Sample records for sepsis outcome acute

  1. Post–Acute Care Use and Hospital Readmission after Sepsis

    PubMed Central

    Jones, Tiffanie K.; Fuchs, Barry D.; Small, Dylan S.; Halpern, Scott D.; Hanish, Asaf; Umscheid, Craig A.; Baillie, Charles A.; Kerlin, Meeta Prasad; Gaieski, David F.

    2015-01-01

    Rationale: The epidemiology of post–acute care use and hospital readmission after sepsis remains largely unknown. Objectives: To examine the rate of post–acute care use and hospital readmission after sepsis and to examine risk factors and outcomes for hospital readmissions after sepsis. Methods: In an observational cohort study conducted in an academic health care system (2010–2012), we compared post–acute care use at discharge and hospital readmission after 3,620 sepsis hospitalizations with 108,958 nonsepsis hospitalizations. We used three validated, claims-based approaches to identify sepsis and severe sepsis. Measurements and Main Results: Post–acute care use at discharge was more likely after sepsis, driven by skilled care facility placement (35.4% after sepsis vs. 15.8%; P < 0.001), with the highest rate observed after severe sepsis. Readmission rates at 7, 30, and 90 days were higher postsepsis (P < 0.001). Compared with nonsepsis hospitalizations (15.6% readmitted within 30 d), the increased readmission risk was present regardless of sepsis severity (27.3% after sepsis and 26.0–26.2% after severe sepsis). After controlling for presepsis characteristics, the readmission risk was found to be 1.51 times greater (95% CI, 1.38–1.66) than nonsepsis hospitalizations. Readmissions after sepsis were more likely to result in death or transition to hospice care (6.1% vs. 13.3% after sepsis; P < 0.001). Independent risk factors associated with 30-day readmissions after sepsis hospitalizations included age, malignancy diagnosis, hospitalizations in the year prior to the index hospitalization, nonelective index admission type, one or more procedures during the index hospitalization, and low hemoglobin and high red cell distribution width at discharge. Conclusions: Post–acute care use and hospital readmissions were common after sepsis. The increased readmission risk after sepsis was observed regardless of sepsis severity and was associated with

  2. Clinical profile and outcomes of acute cardiorenal syndrome type-5 in sepsis: An eight-year cohort study.

    PubMed

    Vallabhajosyula, Saraschandra; Sakhuja, Ankit; Geske, Jeffrey B; Kumar, Mukesh; Kashyap, Rahul; Kashani, Kianoush; Jentzer, Jacob C

    2018-01-01

    To evaluate the clinical features and outcomes of acute cardiorenal syndrome type-5 in patients with severe sepsis and septic shock. Historical cohort study of all adult patients with severe sepsis and septic shock admitted to the intensive care units (ICU) at Mayo Clinic Rochester from January 1, 2007 through December 31, 2014. Patients with prior renal or cardiac dysfunction were excluded. Patients were divided into groups with and without cardiorenal syndrome type-5. Acute Kidney Injury (AKI) was defined by both serum creatinine and urine output criteria of the AKI Network and the cardiac injury was determined by troponin-T levels. Outcomes included in-hospital mortality, ICU and hospital length of stay, and one-year survival. Of 602 patients meeting the study inclusion criteria, 430 (71.4%) met criteria for acute cardiorenal syndrome type-5. Patients with cardiorenal syndrome type-5 had higher severity of illness, greater vasopressor and mechanical ventilation use. Cardiorenal syndrome type-5 was associated higher unadjusted in-hospital mortality, ICU and hospital lengths of stay, and lower one-year survival. When adjusted for age, gender, severity of illness and mechanical ventilation, cardiorenal syndrome type-5 was independently associated with 1.7-times greater odds of in-hospital mortality (p = .03), but did not predict one-year survival (p = .06) compared to patients without cardiorenal syndrome. In sepsis, acute cardiorenal syndrome type-5 is associated with worse in-hospital mortality compared to patients without cardiorenal syndrome.

  3. Acute Kidney Injury in Pediatric Severe Sepsis: An Independent Risk Factor for Death and New Disability.

    PubMed

    Fitzgerald, Julie C; Basu, Rajit K; Akcan-Arikan, Ayse; Izquierdo, Ledys M; Piñeres Olave, Byron E; Hassinger, Amanda B; Szczepanska, Maria; Deep, Akash; Williams, Duane; Sapru, Anil; Roy, Jason A; Nadkarni, Vinay M; Thomas, Neal J; Weiss, Scott L; Furth, Susan

    2016-12-01

    The prevalence of septic acute kidney injury and impact on functional status of PICU survivors are unknown. We used data from an international prospective severe sepsis study to elucidate functional outcomes of children suffering septic acute kidney injury. Secondary analysis of patients in the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study: acute kidney injury was defined on the study day using Kidney Disease Improving Global Outcomes definitions. Patients with no acute kidney injury or stage 1 acute kidney injury ("no/mild acute kidney injury") were compared with those with stage 2 or 3 acute kidney injury ("severe acute kidney injury"). The primary outcome was a composite of death or new moderate disability at discharge defined as a Pediatric Overall Performance Category score of 3 or higher and increased by 1 from baseline. One hundred twenty-eight PICUs in 26 countries. Children with severe sepsis in the Sepsis PRevalence, OUtcomes, and Therapies study. None. One hundred two (21%) of 493 patients had severe acute kidney injury. More than twice as many patients with severe acute kidney injury died or developed new moderate disability compared with those with no/mild acute kidney injury (64% vs 30%; p < 0.001). Severe acute kidney injury was independently associated with death or new moderate disability (adjusted odds ratio, 2.5; 95% CI, 1.5-4.2; p = 0.001) after adjustment for age, region, baseline disability, malignancy, invasive mechanical ventilation, albumin administration, and the pediatric logistic organ dysfunction score. In a multinational cohort of critically ill children with severe sepsis and high mortality rates, septic acute kidney injury is independently associated with further increased death or new disability.

  4. Sepsis and Acute Kidney Injury.

    PubMed

    Bilgili, Beliz; Haliloğlu, Murat; Cinel, İsmail

    2014-12-01

    Acute kindney injury (AKI) is a clinical syndrome which is generally defined as an abrupt decline in glomerular filtration rate, causing accumulation of nitrogenous products and rapid development of fluid, electrolyte and acid base disorders. In intensive care unit sepsis and septic shock are leading causes of AKI. Sepsis-induced AKI literally acts as a biologic indicator of clinical deterioration. AKI triggers variety of immune, inflammatory, metabolic and humoral patways; ultimately leading distant organ dysfunction and increases morbidity and mortality. Serial mesurements of creatinine and urine volume do not make it possible to diagnose AKI at early stages. Serum creatinine influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reason we need new markers, and many biomarkers in the diagnosis of early AKI activity is assessed. Historically "Risk-Injury-Failure-Loss-Endstage" (RIFLE), "Acute Kidney Injury Netwok" (AKIN) and "The Kidney Disease/ Improving Global Outcomes" (KDIGO) classification systems are used for diagnosing easily in clinical practice and research and grading disease. Classifications including diagnostic criteria are formed for the identification of AKI. Neutrophil gelatinase associated lipocalin (NGAL), cystatin-C (Cys-C), kidney injury molecule-1 (KIM-1) and also "cell cycle arrest" molecules has been concerned for clinical use. In this review the pathophysiology of AKI, with the relationship of sepsis and the importance of early diagnosis of AKI is evaluated.

  5. Clinical Characteristics and Outcomes of Sepsis-Related vs Non-Sepsis-Related ARDS

    PubMed Central

    Sheu, Chau-Chyun; Gong, Michelle N.; Zhai, Rihong; Chen, Feng; Bajwa, Ednan K.; Clardy, Peter F.; Gallagher, Diana C.; Thompson, B. Taylor

    2010-01-01

    Background: ARDS may occur after either septic or nonseptic injuries. Sepsis is the major cause of ARDS, but little is known about the differences between sepsis-related and non-sepsis-related ARDS. Methods: A total of 2,786 patients with ARDS-predisposing conditions were enrolled consecutively into a prospective cohort, of which 736 patients developed ARDS. We defined sepsis-related ARDS as ARDS developing in patients with sepsis and non-sepsis-related ARDS as ARDS developing after nonseptic injuries, such as trauma, aspiration, and multiple transfusions. Patients with both septic and nonseptic risks were excluded from analysis. Results: Compared with patients with non-sepsis-related ARDS (n = 62), patients with sepsis-related ARDS (n = 524) were more likely to be women and to have diabetes, less likely to have preceding surgery, and had longer pre-ICU hospital stays and higher APACHE III (Acute Physiology and Chronic Health Evaluation III) scores (median, 78 vs 65, P < .0001). There were no differences in lung injury score, blood pH, Pao2/Fio2 ratio, and Paco2 on ARDS diagnosis. However, patients with sepsis-related ARDS had significantly lower Pao2/Fio2 ratios than patients with non-sepsis-related ARDS patients on ARDS day 3 (P = .018), day 7 (P = .004), and day 14 (P = .004) (repeated-measures analysis, P = .011). Compared with patients with non-sepsis-related ARDS, those with sepsis-related had a higher 60-day mortality (38.2% vs 22.6%; P = .016), a lower successful extubation rate (53.6% vs 72.6%; P = .005), and fewer ICU-free days (P = .0001) and ventilator-free days (P = .003). In multivariate analysis, age, APACHE III score, liver cirrhosis, metastatic cancer, admission serum bilirubin and glucose levels, and treatment with activated protein C were independently associated with 60-day ARDS mortality. After adjustment, sepsis-related ARDS was no longer associated with higher 60-day mortality (hazard ratio, 1.26; 95% CI, 0.71-2.22). Conclusion: Sepsis

  6. Clinical course of sepsis in children with acute leukemia admitted to the pediatric intensive care unit.

    PubMed

    Singer, Kanakadurga; Subbaiah, Perla; Hutchinson, Raymond; Odetola, Folafoluwa; Shanley, Thomas P

    2011-11-01

    To describe the clinical course, resource use, and mortality of patients with leukemia admitted to the pediatric intensive care unit with sepsis and nonsepsis diagnoses over a 10-yr period. Retrospective analysis. Tertiary medical-surgical pediatric intensive care unit at C.S. Mott Children's Hospital, University of Michigan. All patients with leukemia admitted to the pediatric intensive care unit from January 1, 1998, to December 31, 2008. None; chart review. Clinical course was characterized by demographics, leukemia diagnosis, phase of therapy, leukocyte count on admission, presence of sepsis, steroid administration, intensity of care, and Pediatric Risk of Mortality score on admission to the pediatric intensive care unit. The primary outcome was survival to pediatric intensive care unit discharge. Among 68 single admissions to the pediatric intensive care unit with leukemia during the study period, 33 (48.5%) were admitted with sepsis. Admission to the pediatric intensive care unit for sepsis was associated with greater compromise of hemodynamic and renal function and use of stress dose steroids (p = .016), inotropic and/or vasopressor drugs (p = .01), and renal replacement therapy (p = .028) than nonsepsis admission. There was higher mortality among children with sepsis than other diagnoses (52% vs. 17%, p = .004). Also, mortality among children with sepsis was higher among those with acute lymphoblastic leukemia (60% vs. 44%) compared with acute myelogenous leukemia. Administration of stress dose steroids was associated with higher mortality (50% vs. 17%, p = .005) and neutropenia. Patients with acute lymphoblastic leukemia and sepsis showed the greatest mortality and resource use. Patients with acute leukemia and sepsis had a much higher mortality rate compared with previously described sepsis mortality rates for the general pediatric intensive care unit patient populations. Patients who received steroids had an increased mortality rate, but given the

  7. A Sepsis-related Diagnosis Impacts Interventions and Predicts Outcomes for Emergency Patients with Severe Sepsis.

    PubMed

    Kim, Mitchell; Watase, Taketo; Jablonowski, Karl D; Gatewood, Medley O; Henning, Daniel J

    2017-10-01

    Many patients meeting criteria for severe sepsis are not given a sepsis-related diagnosis by emergency physicians (EP). This study 1) compares emergency department (ED) interventions and in-hospital outcomes among patients with severe sepsis, based on the presence or absence of sepsis-related diagnosis, and 2) assesses how adverse outcomes relate to three-hour sepsis bundle completion among patients fulfilling severe sepsis criteria but not given a sepsis-related diagnosis. We performed a retrospective cohort study using patients meeting criteria for severe sepsis at two urban, academic tertiary care centers from March 2015 through May 2015. We included all ED patients with the following: 1) the 1992 Consensus definition of severe sepsis, including two or more systemic inflammatory response syndrome criteria and evidence of organ dysfunction; or 2) physician diagnosis of severe sepsis or septic shock. We excluded patients transferred to or from another hospital and those <18 years old. Patients with an EP-assigned sepsis diagnosis created the "Physician Diagnosis" group; the remaining patients composed the "Consensus Criteria" group. The primary outcome was in-hospital mortality. Secondary outcomes included completed elements of the current three-hour sepsis bundle; non-elective intubation; vasopressor administration; intensive care unit (ICU) admission from the ED; and transfer to the ICU in < 24 hours. We compared proportions of each outcome between groups using the chi-square test, and we also performed a stratified analysis using chi square to assess the association between failure to complete the three-hour bundle and adverse outcomes in each group. Of 418 patients identified with severe sepsis we excluded 54, leaving 364 patients for analysis: 121 "Physician Diagnosis" and 243 "Consensus Criteria." The "Physician Diagnosis" group had a higher in-hospital mortality (12.4% vs 3.3%, P < 0.01) and compliance with the three-hour sepsis bundle (52.1% vs 20.2%, P

  8. Sepsis associated with hematological malignancies: prophylaxis of Pseudomonas aeruginosa sepsis.

    PubMed

    Sakamoto, M; Saruta, K; Nakazawa, Y; Shindo, N; Maezawa, H; Yoshikawa, K; Yoshida, M; Shiba, K; Sakai, O; Saito, A

    1996-02-01

    Underlying diseases, pathogenic bacteria, clinical background and outcome were studied during 91 febrile episodes complicated by sepsis in 55 patients with hematological malignancies, who had been admitted to our hospital (Jikei University Kashiwa Hospital) between January 1990 and December 1994. Particularly in patients with P. aeruginosa sepsis, we compared the prophylactic effect of ciprofloxacin (CPFX) alone with that of the combination of polymyxin B (PL-B) plus kanamycin (KM). The major underlying diseases were acute myelocytic leukemia and malignant lymphoma, followed by myelodysplastic syndrome, acute lymphocytic leukemia and chronic myelocytic leukemia. Nearly two-thirds of the pathogenic microorganisms isolated were gram-positive bacteria (including coagulase-negative staphylococci and Staphylococcus aureus); approximately one-quarter were gram-negative bacteria (such as Pseudomonas aeruginosa), and the remainder were fungi. These microorganisms usually induced sepsis when granulocyte counts were decreased. Sepsis was a direct cause of death in about 60% of the patients and P. aeruginosa sepsis had the worst outcome. Oral administration of CPFX was more effective than PL-B plus KM in preventing P. aeruginosa sepsis. The difference in effectiveness might depend on the absorption profile of the drugs.

  9. Stem cells in sepsis and acute lung injury.

    PubMed

    Cribbs, Sushma K; Matthay, Michael A; Martin, Greg S

    2010-12-01

    Sepsis and acute lung injury continue to be major causes of morbidity and mortality worldwide despite advances in our understanding of pathophysiology and the discovery of new management strategies. Recent investigations show that stem cells may be beneficial as prognostic biomarkers and novel therapeutic strategies in these syndromes. This article reviews the potential use of endogenous adult tissue-derived stem cells in sepsis and acute lung injury as prognostic markers and also as exogenous cell-based therapy. A directed systematic search of the medical literature using PubMed and OVID, with particular emphasis on the time period after 2002, was done to evaluate topics related to 1) the epidemiology and pathophysiology of sepsis and acute lung injury; and 2) the definition, characterization, and potential use of stem cells in these diseases. DATA SYNTHESIS AND FINDINGS: When available, preferential consideration was given to prospective nonrandomized clinical and preclinical studies. Stem cells have shown significant promise in the field of critical care both for 1) prognostic value and 2) treatment strategies. Although several recent studies have identified the potential benefit of stem cells in sepsis and acute lung injury, further investigations are needed to more completely understand stem cells and their potential prognostic and therapeutic value.

  10. Severe sepsis in pre-hospital emergency care: analysis of incidence, care, and outcome.

    PubMed

    Seymour, Christopher W; Rea, Thomas D; Kahn, Jeremy M; Walkey, Allan J; Yealy, Donald M; Angus, Derek C

    2012-12-15

    Severe sepsis is common and highly morbid, yet the epidemiology of severe sepsis at the frontier of the health care system-pre-hospital emergency care-is unknown. We examined the epidemiology of pre-hospital severe sepsis among emergency medical services (EMS) encounters, relative to acute myocardial infarction and stroke. Retrospective study using a community-based cohort of all nonarrest, nontrauma King County EMS encounters from 2000 to 2009 who were transported to a hospital. Overall incidence rate of hospitalization with severe sepsis among EMS encounters, as well as pre-hospital characteristics, admission diagnosis, and outcomes. Among 407,176 EMS encounters, we identified 13,249 hospitalizations for severe sepsis, of whom 2,596 died in the hospital (19.6%). The crude incidence rate of severe sepsis was 3.3 per 100 EMS encounters, greater than for acute myocardial infarction or stroke (2.3 per 100 and 2.2 per 100 EMS encounters, respectively). More than 40% of all severe sepsis hospitalizations arrived at the emergency department after EMS transport, and 80% of cases were diagnosed on admission. Pre-hospital care intervals, on average, exceeded 45 minutes for those hospitalized with severe sepsis. One-half or fewer of patients with severe sepsis were transported by paramedics (n = 7,114; 54%) or received pre-hospital intravenous access (n = 4,842; 37%). EMS personnel care for a substantial and increasing number of patients with severe sepsis, and spend considerable time on scene and during transport. Given the emphasis on rapid diagnosis and intervention for sepsis, the pre-hospital interval may represent an important opportunity for recognition and care of sepsis.

  11. Interaction Effects of Acute Kidney Injury, Acute Respiratory Failure, and Sepsis on 30-Day Postoperative Mortality in Patients Undergoing High-Risk Intraabdominal General Surgical Procedures.

    PubMed

    Kim, Minjae; Brady, Joanne E; Li, Guohua

    2015-12-01

    Acute kidney injury (AKI), acute respiratory failure, and sepsis are distinct but related pathophysiologic processes. We hypothesized that these 3 processes may interact to synergistically increase the risk of short-term perioperative mortality in patients undergoing high-risk intraabdominal general surgery procedures. We performed a retrospective, observational cohort study of data (2005-2011) from the American College of Surgeons-National Surgical Quality Improvement Program, a high-quality surgical outcomes data set. High-risk procedures were those with a risk of AKI, acute respiratory failure, or sepsis greater than the average risk in all intraabdominal general surgery procedures. The effects of AKI, acute respiratory failure, and sepsis on 30-day mortality were assessed using a Cox proportional hazards model. Additive interactions were assessed with the relative excess risk due to interaction. Of 217,994 patients, AKI, acute respiratory failure, and sepsis developed in 1.3%, 3.7%, and 6.8%, respectively. The 30-day mortality risk with sepsis, acute respiratory failure, and AKI were 11.4%, 24.1%, and 25.1%, respectively, compared with 0.85% without these complications. The adjusted hazard ratios and 95% confidence intervals for a single complication (versus no complication) on mortality were 7.24 (6.46-8.11), 10.8 (8.56-13.6), and 14.2 (12.8-15.7) for sepsis, AKI, and acute respiratory failure, respectively. For 2 complications, the adjusted hazard ratios were 30.8 (28.0-33.9), 42.6 (34.3-52.9), and 65.2 (53.9-78.8) for acute respiratory failure/sepsis, AKI/sepsis, and acute respiratory failure/AKI, respectively. Finally, the adjusted hazard ratio for all 3 complications was 105 (92.8-118). Positive additive interactions, indicating synergism, were found for each combination of 2 complications. The relative excess risk due to interaction for all 3 complications was not statistically significant. In high-risk general surgery patients, the development of AKI

  12. Management of acute perianal sepsis in neutropenic patients with hematological malignancy.

    PubMed

    Baker, B; Al-Salman, M; Daoud, F

    2014-04-01

    In neutropenic patients with acute perianal sepsis in the setting of hematological malignancy, the classical clinical features of abscess formation are lacking. Additionally, the role of surgical intervention is not well established. In this review, we discuss the challenges and controversy regarding diagnosis and optimal management when clear surgical guidelines are absent. In the literature, there is great diversity in the surgical approach to these patients, which leads to a high percentage of diagnostic errors, risks of complications, and unnecessary interventions. We review the literature and assess whether surgical intervention produces better outcomes than a non-surgical approach. Studies published on perianal sepsis in neutropenic cancer patients were identified by searching PubMed using the following key words: "perianal sepsis/abscesses, anorectal sepsis/abscess, neutropenia, hematological malignancy, cancer". No randomized or prospective studies on the management of acute perianal sepsis in hematological malignancies were found. The largest retrospective study and most comprehensive clinical data demonstrated that 42% of patients were treated successfully without surgical intervention and without morbidity or mortality related to treatment chosen. Small retrospective studies advocated surgical intervention, while the majority of successes were in a non-operative treatment. It is difficult to formulate a conclusion given the small retrospective series on management of neutropenic patients with hematological malignancies. While there is no evidence mandating a routine surgical approach in this category of patients, non-surgical management including careful follow-up to determine whether the patient's condition is deteriorating or treatment has failed is an acceptable approach in selected patients without pathognomonic features of abscess. Comprehensive and well-designed prospective studies are needed to firmly establish the guidelines of treatment

  13. The Immune System’s Role in Sepsis Progression, Resolution and Long-Term Outcome

    PubMed Central

    Delano, Matthew J.; Ward, Peter A.

    2016-01-01

    SUMMARY Sepsis occurs when an infection exceeds local tissue containment and induces a series of dysregulated physiologic responses that result in organ dysfunction. A subset of patients with sepsis progress to septic shock, defined by profound circulatory, cellular, and metabolic abnormalities, and associated with a greater mortality. Historically, sepsis-induced organ dysfunction and lethality were attributed to the complex interplay between the initial inflammatory and later anti-inflammatory responses. With advances in intensive care medicine and goal-directed interventions, early 30-day sepsis mortality has diminished, only to steadily escalate long after “recovery” from acute events. Since so many sepsis survivors succumb later to persistent, recurrent, nosocomial and secondary infections, many investigators have turned their attention to the long-term sepsis-induced alterations in cellular immune function. Sepsis clearly alters the innate and adaptive immune responses for sustained periods of time after clinical recovery, with immune suppression, chronic inflammation, and persistence of bacterial representing such alterations. Understanding that sepsis-associated immune cell defects correlate with long-term mortality, more investigations have centered on the potential for immune modulatory therapy to improve long term patient outcomes. These efforts are focused on more clearly defining and effectively reversing the persistent immune cell dysfunction associated with long-term sepsis mortality. PMID:27782333

  14. Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study.

    PubMed

    Weiss, Scott L; Fitzgerald, Julie C; Pappachan, John; Wheeler, Derek; Jaramillo-Bustamante, Juan C; Salloo, Asma; Singhi, Sunit C; Erickson, Simon; Roy, Jason A; Bush, Jenny L; Nadkarni, Vinay M; Thomas, Neal J

    2015-05-15

    Limited data exist about the international burden of severe sepsis in critically ill children. To characterize the global prevalence, therapies, and outcomes of severe sepsis in pediatric intensive care units to better inform interventional trials. A point prevalence study was conducted on 5 days throughout 2013-2014 at 128 sites in 26 countries. Patients younger than 18 years of age with severe sepsis as defined by consensus criteria were included. Outcomes were severe sepsis point prevalence, therapies used, new or progressive multiorgan dysfunction, ventilator- and vasoactive-free days at Day 28, functional status, and mortality. Of 6,925 patients screened, 569 had severe sepsis (prevalence, 8.2%; 95% confidence interval, 7.6-8.9%). The patients' median age was 3.0 (interquartile range [IQR], 0.7-11.0) years. The most frequent sites of infection were respiratory (40%) and bloodstream (19%). Common therapies included mechanical ventilation (74% of patients), vasoactive infusions (55%), and corticosteroids (45%). Hospital mortality was 25% and did not differ by age or between developed and resource-limited countries. Median ventilator-free days were 16 (IQR, 0-25), and vasoactive-free days were 23 (IQR, 12-28). Sixty-seven percent of patients had multiorgan dysfunction at sepsis recognition, with 30% subsequently developing new or progressive multiorgan dysfunction. Among survivors, 17% developed at least moderate disability. Sample sizes needed to detect a 5-10% absolute risk reduction in outcomes within interventional trials are estimated between 165 and 1,471 [corrected] patients per group. Pediatric severe sepsis remains a burdensome public health problem, with prevalence, morbidity, and mortality rates similar to those reported in critically ill adult populations. International clinical trials targeting children with severe sepsis are warranted.

  15. Global Epidemiology of Pediatric Severe Sepsis: The Sepsis Prevalence, Outcomes, and Therapies Study

    PubMed Central

    Weiss, Scott L.; Pappachan, John; Wheeler, Derek; Jaramillo-Bustamante, Juan C.; Salloo, Asma; Singhi, Sunit C.; Erickson, Simon; Roy, Jason A.; Bush, Jenny L.; Nadkarni, Vinay M.; Thomas, Neal J.

    2015-01-01

    Rationale: Limited data exist about the international burden of severe sepsis in critically ill children. Objectives: To characterize the global prevalence, therapies, and outcomes of severe sepsis in pediatric intensive care units to better inform interventional trials. Methods: A point prevalence study was conducted on 5 days throughout 2013–2014 at 128 sites in 26 countries. Patients younger than 18 years of age with severe sepsis as defined by consensus criteria were included. Outcomes were severe sepsis point prevalence, therapies used, new or progressive multiorgan dysfunction, ventilator- and vasoactive-free days at Day 28, functional status, and mortality. Measurements and Main Results: Of 6,925 patients screened, 569 had severe sepsis (prevalence, 8.2%; 95% confidence interval, 7.6–8.9%). The patients’ median age was 3.0 (interquartile range [IQR], 0.7–11.0) years. The most frequent sites of infection were respiratory (40%) and bloodstream (19%). Common therapies included mechanical ventilation (74% of patients), vasoactive infusions (55%), and corticosteroids (45%). Hospital mortality was 25% and did not differ by age or between developed and resource-limited countries. Median ventilator-free days were 16 (IQR, 0–25), and vasoactive-free days were 23 (IQR, 12–28). Sixty-seven percent of patients had multiorgan dysfunction at sepsis recognition, with 30% subsequently developing new or progressive multiorgan dysfunction. Among survivors, 17% developed at least moderate disability. Sample sizes needed to detect a 5–10% absolute risk reduction in outcomes within interventional trials are estimated between 165 and 1,437 patients per group. Conclusions: Pediatric severe sepsis remains a burdensome public health problem, with prevalence, morbidity, and mortality rates similar to those reported in critically ill adult populations. International clinical trials targeting children with severe sepsis are warranted. PMID:25734408

  16. Adaptation of a Biomarker-Based Sepsis Mortality Risk Stratification Tool for Pediatric Acute Respiratory Distress Syndrome.

    PubMed

    Yehya, Nadir; Wong, Hector R

    2018-01-01

    The original Pediatric Sepsis Biomarker Risk Model and revised (Pediatric Sepsis Biomarker Risk Model-II) biomarker-based risk prediction models have demonstrated utility for estimating baseline 28-day mortality risk in pediatric sepsis. Given the paucity of prediction tools in pediatric acute respiratory distress syndrome, and given the overlapping pathophysiology between sepsis and acute respiratory distress syndrome, we tested the utility of Pediatric Sepsis Biomarker Risk Model and Pediatric Sepsis Biomarker Risk Model-II for mortality prediction in a cohort of pediatric acute respiratory distress syndrome, with an a priori plan to revise the model if these existing models performed poorly. Prospective observational cohort study. University affiliated PICU. Mechanically ventilated children with acute respiratory distress syndrome. Blood collection within 24 hours of acute respiratory distress syndrome onset and biomarker measurements. In 152 children with acute respiratory distress syndrome, Pediatric Sepsis Biomarker Risk Model performed poorly and Pediatric Sepsis Biomarker Risk Model-II performed modestly (areas under receiver operating characteristic curve of 0.61 and 0.76, respectively). Therefore, we randomly selected 80% of the cohort (n = 122) to rederive a risk prediction model for pediatric acute respiratory distress syndrome. We used classification and regression tree methodology, considering the Pediatric Sepsis Biomarker Risk Model biomarkers in addition to variables relevant to acute respiratory distress syndrome. The final model was comprised of three biomarkers and age, and more accurately estimated baseline mortality risk (area under receiver operating characteristic curve 0.85, p < 0.001 and p = 0.053 compared with Pediatric Sepsis Biomarker Risk Model and Pediatric Sepsis Biomarker Risk Model-II, respectively). The model was tested in the remaining 20% of subjects (n = 30) and demonstrated similar test characteristics. A validated, biomarker

  17. Infection Rate and Acute Organ Dysfunction Risk as Explanations for Racial Differences in Severe Sepsis

    PubMed Central

    Mayr, Florian B.; Yende, Sachin; Linde-Zwirble, Walter T.; Peck-Palmer, Octavia M.; Barnato, Amber E.; Weissfeld, Lisa A.; Angus, Derek C.

    2013-01-01

    Context Severe sepsis, defined as infection complicated by acute organ dysfunction, occurs more frequently and leads to more deaths in black than in white individuals. The optimal approach to minimize these disparities is unclear. Objective To determine the extent to which higher severe sepsis rates in black than in white patients are due to higher infection rates or to a higher risk of acute organ dysfunction. Design, Setting, and Participants Analysis of infection-related hospitalizations from the 2005 hospital discharge data of 7 US states and infection-related emergency department visits from the 2003-2007 National Hospital Ambulatory Care Survey. Main Outcome Measure Age- and sex-standardized severe sepsis and infection hospitalization rates and the risk of acute organ dysfunction. Results Of 8 661 227 non–childbirth-related discharges, 2 261 857 were associated with an infection, and of these, 381 787 (16.8%) had severe sepsis. Black patients had a 67% higher age- and sex-standardized severe sepsis rate than did white patients (9.4; 95% confidence interval [CI], 9.3-9.5 vs 5.6; 95% CI, 5.6-5.6 per 1000 population; P<.001) and 80% higher standardized mortality (1.8, 95% CI, 1.8-1.9 vs 1.0, 95% CI, 1.0-1.1 per 1000 population; P<.001). The higher severe sepsis rate was explained by both a higher infection rate in black patients (47.3; 95% CI, 47.1-47.4 vs 34.0; 95% CI, 33.9-34.0 per 1000 population; incidence rate ratio, 1.39; P<.001) and a higher risk of developing acute organ dysfunction (age- and sex-adjusted odds ratio [OR],1.29; 95% CI, 1.27-1.30; P<.001). Differences in infection presented broadly across different sites and etiology of infection and for community- and hospital-acquired infections and occurred despite a lower likelihood of being admitted for infection from the emergency department (adjusted OR, 0.70; 95% CI, 0.64-0.76; P<.001). The higher risk of organ dysfunction persisted but was attenuated after adjusting for age, sex, comorbid

  18. Pulmonary vs Nonpulmonary Sepsis and Mortality in Acute Lung Injury

    PubMed Central

    Sevransky, Jonathan E.; Martin, Greg S.; Mendez-Tellez, Pedro; Shanholtz, Carl; Brower, Roy; Pronovost, Peter J.; Needham, Dale M.

    2010-01-01

    Background Acute lung injury (ALI) is a frequent complication of sepsis. It is unclear if a pulmonary vs nonpulmonary source of sepsis affects mortality in patients with sepsis-induced ALI. Methods Two hundred eighty-eight consecutive patients with sepsis-induced ALI from 14 ICUs at four hospitals in Baltimore,MDwere prospectively classified as having a pulmonary vs nonpulmonary source of sepsis. Multiple logistic regression was conducted to evaluate the independent association of a pulmonary vs nonpulmonary source of sepsis with inpatient mortality. Results In an unadjusted analysis, in-hospital mortality was lower for pulmonary vs nonpulmonary source of sepsis (42% vs 66%, p < 0.0001). Patients with pulmonary sepsis had lower acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores, shorter ICU stays prior to the development of ALI, and higher lung injury scores. In the adjusted analysis, several factors were predictive of mortality: age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01 to 1.06), Charlson comorbidity index (OR, 1.15; 95% CI, 1.02 to 1.30), ICU length of stay prior to ALI diagnosis (OR, 1.19; 95% CI, 1.01 to 1.39), APACHE II score (OR, 1.07; 95% CI, 1.03 to 1.12), lung injury score (OR, 1.64; 95% CI, 1.11 to 2.43), SOFA score (OR, 1.15; 95% CI, 1.06 to 1.26), and cumulative fluid balance in the first 7 days after ALI diagnosis (OR, 1.06; 95% CI, 1.03 to 1.10). A pulmonary vs nonpulmonary source of sepsis was not independently associated with mortality (OR, 0.72; 95% CI, 0.38 to 1.35). Conclusions Although lower mortality was observed for ALI patients with a pulmonary vs nonpulmonary source of sepsis, this finding is likely due to a lower severity of illness in those with pulmonary sepsis. Pulmonary vs nonpulmonary source of sepsis was not independently predictive of mortality for patients with ALI. PMID:18641112

  19. Acute kidney injury following rhabdomyolysis and sepsis after non-poisonous desert monitor bite.

    PubMed

    Gupta, Poonam; Verma, Pradeep Kumar

    2017-10-01

    The desert monitor, Varanus griseus , is a species of desert monitor lizard found in North-Western India. They are believed to be non-poisonous. We report a case of Indian desert monitor bite leading to acute renal failure following rhabdomyolysis and severe sepsis. Prompt diagnosis and treatment resulted in the favourable outcome. This is author's intent to highlight the complication that may occur after Indian desert monitor bite.

  20. Anaesthetic management of patients with severe sepsis.

    PubMed

    Eissa, D; Carton, E G; Buggy, D J

    2010-12-01

    Severe sepsis, a syndrome characterized by systemic inflammation and acute organ dysfunction in response to infection, is a major healthcare problem affecting all age groups throughout the world. Anaesthetists play a central role in the multidisciplinary management of patients with severe sepsis from their initial deterioration at ward level, transfer to the diagnostic imaging suite, and intraoperative management for emergency surgery. The timely administration of appropriate i.v. antimicrobial therapy is a crucial step in the care of patients with severe sepsis who may require surgery to control the source of sepsis. Preoperative resuscitation, aimed at optimizing major organ perfusion, is based on judicious use of fluids, vasopressors, and inotropes. Intraoperative anaesthesia management requires careful induction and maintenance of anaesthesia, optimizing intravascular volume status, avoidance of lung injury during mechanical ventilation, and ongoing monitoring of arterial blood gases, lactate concentration, haematological and renal indices, and electrolyte levels. Postoperative care overlaps with ongoing management of the severe sepsis syndrome patient in the intensive care unit. These patients are by definition, high risk, already requiring multiple supports, and require experienced and skilful decision-making to optimize their chances of a favourable outcome. Similar to acute myocardial infarction, stroke, or acute trauma, the initial hours (golden hours) of clinical management of severe sepsis represent an important opportunity to reduce morbidity and mortality. Rapid clinical assessment, resuscitation and surgical management by a focused multidisciplinary team, and early effective antimicrobial therapy are the key components to improved patient outcome.

  1. Neutrophil apoptosis: a marker of disease severity in sepsis and sepsis-induced acute respiratory distress syndrome

    PubMed Central

    Fialkow, Léa; Fochesatto Filho, Luciano; Bozzetti, Mary C; Milani, Adriana R; Rodrigues Filho, Edison M; Ladniuk, Roberta M; Pierozan, Paula; de Moura, Rafaela M; Prolla, João C; Vachon, Eric; Downey, Gregory P

    2006-01-01

    Introduction Apoptosis of neutrophils (polymorphonuclear neutrophils [PMNs]) may limit inflammatory injury in sepsis and acute respiratory distress syndrome (ARDS), but the relationship between the severity of sepsis and extent of PMN apoptosis and the effect of superimposed ARDS is unknown. The objective of this study was to correlate neutrophil apoptosis with the severity of sepsis and sepsis-induced ARDS. Methods A prospective cohort study was conducted in intensive care units of three tertiary hospitals in Porto Alegre, southern Brazil. Fifty-seven patients with sepsis (uncomplicated sepsis, septic shock, and sepsis-induced ARDS) and 64 controls were enrolled. Venous peripheral blood was collected from patients with sepsis within 24 hours of diagnosis. All surgical groups, including controls, had their blood drawn 24 hours after surgery. Control patients on mechanical ventilation had blood collected within 24 hours of initiation of mechanical ventilation. Healthy controls were blood donors. Neutrophils were isolated, and incubated ex vivo, and apoptosis was determined by light microscopy on cytospun preparations. The differences among groups were assessed by analysis of variance with Tukeys. Results In medical patients, the mean percentage of neutrophil apoptosis (± standard error of the mean [SEM]) was lower in sepsis-induced ARDS (28% ± 3.3%; n = 9) when compared with uncomplicated sepsis (57% ± 3.2%; n = 8; p < 0.001), mechanical ventilation without infection, sepsis, or ARDS (53% ± 3.0%; n = 11; p < 0.001) and healthy controls (69% ± 1.1%; n = 33; p < 0.001) but did not differ from septic shock (38% ± 3.7%; n = 12; p = 0.13). In surgical patients with sepsis, the percentage of neutrophil apoptosis was lower for all groups when compared with surgical controls (52% ± 3.6%; n = 11; p < 0.001). Conclusion In medical patients with sepsis, neutrophil apoptosis is inversely proportional to the severity of sepsis and thus may be a marker of the severity of

  2. Role of kidney injury in sepsis.

    PubMed

    Doi, Kent

    2016-01-01

    Kidney injury, including acute kidney injury (AKI) and chronic kidney disease (CKD), has become very common in critically ill patients treated in ICUs. Many epidemiological studies have revealed significant associations of AKI and CKD with poor outcomes of high mortality and medical costs. Although many basic studies have clarified the possible mechanisms of sepsis and septic AKI, translation of the obtained findings to clinical settings has not been successful to date. No specific drug against human sepsis or AKI is currently available. Remarkable progress of dialysis techniques such as continuous renal replacement therapy (CRRT) has enabled control of "uremia" in hemodynamically unstable patients; however, dialysis-requiring septic AKI patients are still showing unacceptably high mortality of 60-80 %. Therefore, further investigations must be conducted to improve the outcome of sepsis and septic AKI. A possible target will be remote organ injury caused by AKI. Recent basic studies have identified interleukin-6 and high mobility group box 1 (HMGB1) as important mediators for acute lung injury induced by AKI. Another target is the disease pathway that is amplified by pre-existing CKD. Vascular endothelial growth factor and HMGB1 elevations in sepsis were demonstrated to be amplified by CKD in CKD-sepsis animal models. Understanding the role of kidney injury as an amplifier in sepsis and multiple organ failure might support the identification of new drug targets for sepsis and septic AKI.

  3. Acute Kidney Injury in Pediatric Severe Sepsis, An Independent Risk Factor for Death and New Disability

    PubMed Central

    Fitzgerald, Julie C.; Basu, Rajit; Akcan-Arikan, Ayse; Izquierdo, Ledys M.; Piñeres Olave, Byron E.; Hassinger, Amanda B.; Szczepanska, Maria; Deep, Akash; Williams, Duane; Sapru, Anil; Roy, Jason A.; Nadkarni, Vinay M.; Thomas, Neal J.; Weiss, Scott L.; Furth, Susan

    2017-01-01

    Objective The prevalence of septic acute kidney injury (AKI) and impact on functional status of pediatric intensive care unit (PICU) survivors are unknown. We utilized data from an international prospective severe sepsis study to elucidate functional outcomes of children suffering septic AKI. Design Secondary analysis of patients in the Sepsis PRevalence, OUtcomes, and Therapies (SPROUT) point prevalence study. AKI was defined on the study day using Kidney Disease Improving Global Outcomes definitions. Patients with no AKI or stage 1 AKI (“No/mild AKI”) were compared to those with stage 2 or 3 AKI (“Severe AKI”). The primary outcome was a composite of death or new moderate disability at discharge defined as a Pediatric Overall Performance Category score of 3 or higher, and increased by 1 from baseline. Setting 128 PICUs in 26 countries. Patients Children with severe sepsis in the SPROUT study. Interventions None Measurements and Main Results One hundred two (21%) of 493 patients had Severe AKI. More than twice as many patients with Severe AKI died or developed new moderate disability compared to those with No/mild AKI (64% vs. 30%, p<0.001). Severe AKI was independently associated with death or new moderate disability (adjusted OR 2.5, 95% CI 1.5, 4.2; p=0.001) after adjustment for age, region, baseline disability, malignancy, invasive mechanical ventilation, albumin administration, and the pediatric logistic organ dysfunction score. Conclusions In a multi-national cohort of critically ill children with severe sepsis and high mortality rates, septic AKI is independently associated with further increased death or new disability. PMID:27513354

  4. A patient cohort on long-term sequelae of sepsis survivors: study protocol of the Mid-German Sepsis Cohort.

    PubMed

    Scherag, André; Hartog, Christiane S; Fleischmann, Carolin; Ouart, Dominique; Hoffmann, Franziska; König, Christian; Kesselmeier, Miriam; Fiedler, Sandra; Philipp, Monique; Braune, Anke; Eichhorn, Cornelia; Gampe, Christin; Romeike, Heike; Reinhart, Konrad

    2017-08-23

    An increasing number of patients survive sepsis; however, we lack valid data on the long-term impact on morbidity from prospective observational studies. Therefore, we designed an observational cohort to quantify mid-term and long-term functional disabilities after intensive care unit (ICU)-treated sepsis. Ultimately, findings for the Mid-German Sepsis Cohort (MSC) will serve as basis for the implementation of follow-up structures for patients with sepsis and help to increase quality of care for sepsis survivors. All patients surviving ICU-treated sepsis are eligible and are recruited from five study centres in Germany (acute care hospital setting in Jena, Halle/Saale, Leipzig, Bad Berka, Erfurt; large long-term acute care hospital and rehabilitation setting in Klinik Bavaria Kreischa). Screening is performed by trained study nurses. Data are collected on ICU management of sepsis. On written informed consent provided by patients or proxies, follow-up is carried out by trained research staff at 3, 6 and 12 months and yearly thereafter. The primary outcome is functional disability as assessed by (instrumental) activities of daily living. Other outcomes cover domains like mortality, cognitive, emotional and physical impairment, and resource use. The estimated sample size of 3000 ICU survivors is calculated to allow detection of relevant changes in the primary outcome in sepsis survivors longitudinally. The study is conducted according to the current version of the Declaration of Helsinki and has been approved by four local/federal responsible institutional ethics committees and by the respective federal data protection commissioners. Results of MSC will be fed back to the patients and published in peer-reviewed journals. German Clinical Trials Registry DRKS00010050. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. Effect of Acetaminophen on the Prevention of Acute Kidney Injury in Patients With Sepsis.

    PubMed

    Patanwala, Asad E; Aljuhani, Ohoud; Bakhsh, Hussain; Erstad, Brian L

    2018-01-01

    Acute kidney injury (AKI) commonly occurs in patients with sepsis. Acetaminophen (APAP) has been shown to inhibit lipid peroxidation and, thus, may be renal protective in patients with sepsis. The objective of this study was to determine the effect of APAP on AKI in patients with sepsis. This was a retrospective cohort study conducted at 2 affiliated academic medical centers in the United States. Adult patients who were admitted to the intensive care unit with a diagnosis of severe sepsis were included. Patients were categorized based on whether APAP was received within the first 7 days of hospitalization (APAP or no APAP groups). The primary outcome measure was occurrence or increase in AKI stage from admission. Multivariate logistic regression analyses were used to adjust for potential confounders. There were 238 patients who were included in the study cohort. Of these, 122 received APAP and 116 did not receive APAP. AKI or exacerbation occurred in 16.4% (n = 20) of patients in the APAP group and 19.8% (n = 23) of patients in the no APAP group ( P = 0.505). After adjusting for the most important confounders, there was no significant association between APAP use and AKI (odds ratio = 1.2; 95% CI = 0.6-2.4; P = 0.639). APAP use in critically ill patients with sepsis may not reduce the occurrence or exacerbation of AKI.

  6. Crystalloid Fluid Choice and Clinical Outcomes in Pediatric Sepsis: A Matched Retrospective Cohort Study

    PubMed Central

    Weiss, Scott L.; Keele, Luke; Balamuth, Fran; Vendetti, Neika; Ross, Rachael; Fitzgerald, Julie C.; Gerber, Jeffrey S.

    2017-01-01

    Objective To test the hypothesis that resuscitation with balanced fluids (lactated Ringer [LR]) is associated with improved outcomes compared with normal saline (NS) in pediatric sepsis. Study design We performed matched analyses using data from 12 529 patients <18 years of age with severe sepsis/septic shock at 382 US hospitals between 2000 and 2013 to compare outcomes with vs without LR as part of initial resuscitation. Patients receiving LR were matched 1:1 to patients receiving only NS (NS group), including separate matches for any (LR-any group) or exclusive (LR-only group) LR use. Outcomes included 30-day hospital mortality, acute kidney injury, new dialysis, and length of stay. Results The LR-any group was older, received larger crystalloid volumes, and was less likely to have malignancies than the NS group. After matching, mortality was not different between LR-any (7.2%) and NS (7.9%) groups (risk ratio 0.99, 95% CI 0.98, 1.01; P = .20). There were no differences in secondary outcomes except longer hospital length of stay in LR-any group (absolute difference 2.4, 95% CI 1.4, 5.0 days; P < .001). Although LR was preferentially used as adjunctive fluid with large-volume resuscitation or first-line fluid in patients with lower illness severity, outcomes were not different after matching stratified by volume and proportionate LR utilization, including for patients in the LR-only group. Conclusions Balanced fluid resuscitation with LR was not associated with improved outcomes compared with NS in pediatric sepsis. Although the current practice of NS resuscitation is justified, selective LR use necessitates a prospective trial to definitively determine comparative effectiveness among crystalloids. PMID:28063688

  7. Mitochondrial Function in Sepsis

    PubMed Central

    Arulkumaran, Nishkantha; Deutschman, Clifford S.; Pinsky, Michael R.; Zuckerbraun, Brian; Schumacker, Paul T.; Gomez, Hernando; Gomez, Alonso; Murray, Patrick; Kellum, John A.

    2015-01-01

    Mitochondria are an essential part of the cellular infrastructure, being the primary site for high energy adenosine triphosphate (ATP) production through oxidative phosphorylation. Clearly, in severe systemic inflammatory states, like sepsis, cellular metabolism is usually altered and end organ dysfunction not only common but predictive of long term morbidity and mortality. Clearly, interest is mitochondrial function both as a target for intracellular injury and response to extrinsic stress have been a major focus of basic science and clinical research into the pathophysiology of acute illness. However, mitochondria have multiple metabolic and signaling functions that may be central in both the expression of sepsis and its ultimate outcome. In this review, the authors address five primary questions centered on the role of mitochondria in sepsis. This review should be used as both a summary source in placing mitochondrial physiology within the context of acute illness and as a focal point for addressing new research into diagnostic and treatment opportunities these insights provide. PMID:26871665

  8. MITOCHONDRIAL FUNCTION IN SEPSIS.

    PubMed

    Arulkumaran, Nishkantha; Deutschman, Clifford S; Pinsky, Michael R; Zuckerbraun, Brian; Schumacker, Paul T; Gomez, Hernando; Gomez, Alonso; Murray, Patrick; Kellum, John A

    2016-03-01

    Mitochondria are an essential part of the cellular infrastructure, being the primary site for high-energy adenosine triphosphate production through oxidative phosphorylation. Clearly, in severe systemic inflammatory states, like sepsis, cellular metabolism is usually altered, and end organ dysfunction is not only common, but also predictive of long-term morbidity and mortality. Clearly, interest is mitochondrial function both as a target for intracellular injury and response to extrinsic stress have been a major focus of basic science and clinical research into the pathophysiology of acute illness. However, mitochondria have multiple metabolic and signaling functions that may be central in both the expression of sepsis and its ultimate outcome. In this review, the authors address five primary questions centered on the role of mitochondria in sepsis. This review should be used both as a summary source in placing mitochondrial physiology within the context of acute illness and as a focal point for addressing new research into diagnostic and treatment opportunities these insights provide.

  9. Epidemiologic features, risk factors, and outcome of sepsis in stroke patients treated on a neurologic intensive care unit.

    PubMed

    Berger, Benjamin; Gumbinger, Christoph; Steiner, Thorsten; Sykora, Marek

    2014-04-01

    Because of the immune-suppressive effect of cerebral damage, stroke patients are at high risk for infections. These might result in sepsis, which is the major contributor to intensive care unit (ICU) mortality. Although there are numerous studies on infections in stroke patients, the role of sepsis as a poststroke complication is unknown. We retrospectively analyzed incidence of and risk factors for sepsis acquisition as well as outcome parameters of 238 patients with ischemic or hemorrhagic strokes consecutively admitted to the neurologic ICU in a tertiary university hospital between January 1, 2009, and December 31, 2010. Basic demographic and clinical data including microbiological parameters as well as factors describing stroke severity (eg, lesion volume and National Institute of Health stroke scale score) were recorded and included into the analysis. The diagnosis of sepsis was based on the criteria of the German Sepsis Society. We identified 30 patients (12.6%) with sepsis within the first 7 days from stroke onset. The lungs were the most frequent source of infection (93.3%), and gram-positive organisms were dominating the microbiologic spectrum (52.4%). Comorbidities (chronic obstructive pulmonary disease and immunosuppressive disorders) and Simplified Acute Physiology Score II but none of the factors describing stroke severity were independent predictors of sepsis acquisition. Sepsis was associated with a significantly worse prognosis, leading to a 2-fold increased mortality rate during in-hospital care (36.7% vs 18.8%) and after 3 months (56.5% vs 28.5%), but only in the subgroup of supratentorial hemorrhages, it was an independent predictor of in-hospital and 3-month mortality. Other factors significantly associated with death in a multivariate analysis were chronic obstructive pulmonary disease, malignancies (in-hospital mortality only), and Simplified Acute Physiology Score II (3-month mortality only) for ischemia and heart failure (in

  10. Performance of Quick Sequential (Sepsis Related) and Sequential (Sepsis Related) Organ Failure Assessment to Predict Mortality in Patients with Acute Pyelonephritis Associated with Upper Urinary Tract Calculi.

    PubMed

    Fukushima, Hiroshi; Kobayashi, Masaki; Kawano, Keizo; Morimoto, Shinji

    2018-06-01

    The Third International Consensus Definitions for Sepsis and Septic Shock Task Force proposed a new definition of sepsis based on the SOFA (Sequential [Sepsis-related] Organ Failure Assessment) score and introduced a novel scoring system, quickSOFA, to screen patients at high risk for sepsis. However, the clinical usefulness of these systems is unclear. Therefore, we investigated predictive performance for mortality in patients with acute pyelonephritis associated with upper urinary tract calculi. This retrospective study included 141 consecutive patients who were clinically diagnosed with acute pyelonephritis associated with upper urinary tract calculi outside the intensive care unit. We evaluated the performance of the quickSOFA, SOFA and SIRS (systemic inflammatory response syndrome) scores to predict in-hospital mortality and intensive care unit admission using the AUC of the ROC curve, net reclassification, integrated discrimination improvements and decision curve analysis. A total of 11 patients (8%) died in the hospital and 26 (18%) were admitted to the intensive care unit. The AUC of quickSOFA to predict in-hospital mortality and intensive care unit admission was significantly greater than that of SIRS (each p <0.001) and comparable to that of SOFA (p = 0.47 and 0.57, respectively). When incorporated into the baseline model consisting of patient age, gender and the Charlson Comorbidity Index, quickSOFA and SOFA provided a greater change in AUC, and in net classification and integrated discrimination improvements than SIRS for each outcome. Decision curve analyses revealed that the quickSOFA and SOFA incorporated models showed a superior net benefit compared to the SIRS incorporated model for most examined probabilities of the 2 outcomes. The in-hospital mortality rate of patients with a quickSOFA score of 2 or greater and a SOFA score of 7 or greater, which were the optimal cutoffs determined by the Youden index, was 18% and 28%, respectively. SOFA and

  11. Cerebral imaging and neurodevelopmental outcome after entero- and human parechovirus sepsis in young infants.

    PubMed

    de Jong, Eveline P; Holscher, Herma C; Steggerda, Sylke J; Van Klink, Jeanine M M; van Elzakker, Erika P M; Lopriore, Enrico; Walther, Frans J; Brus, Frank

    2017-12-01

    Enterovirus (EV) and human parechovirus (HPeV) are major causes of sepsis-like illness in infants under 90 days of age and have been identified as neurotropic. Studies about acute and long-term neurodevelopment in infants with sepsis-like illness without the need for intensive care are few. This study investigates cerebral imaging and neurodevelopmental outcome following EV and HPeV infection in these infants. We studied infants under 90 days of age who were admitted to a medium care unit with proven EV- or HPeV-induced sepsis-like illness. In addition to standard care, we did a cerebral ultrasound and cerebral magnetic resonance imaging (MRI), as well as neurodevelopmental follow-up at 6 weeks and 6 months and Bayley Scale of Infant and Toddler Development 3rd edition (BSID-III) investigation at 1 year of age. Twenty-six infants, 22 with EV and 4 with HPeV, were analysed. No abnormalities were detected at cerebral imaging. At 1 year of age, two infants had a moderate delay on both the motor and cognitive scale, one on the cognitive scale only and three others on the gross motor scale only. Although our study population, especially the number of HPeV positive infants is small, our study shows that these infants do not seem to develop severe neurodevelopmental delay and neurologic sequelae more often than the normal Dutch population. Follow-up to school age allows for more reliable assessments of developmental outcome and is recommended for further studies to better assess outcome. What is known: • Enterovirus and Human Parechovirus infections are a major cause of sepsis-like illness in young infants. • After intensive care treatment for EV or HPeV infection, white matter abnormalities and neurodevelopmental delay have been described. What is new: • In our 'medium care' population, no abnormalities at cerebral imaging after EV- or HPeV-induced sepsis-like illness have been found. • At 1 year of age, infants who had EV- or HPeV-induced sepsis

  12. Crystalloid Fluid Choice and Clinical Outcomes in Pediatric Sepsis: A Matched Retrospective Cohort Study.

    PubMed

    Weiss, Scott L; Keele, Luke; Balamuth, Fran; Vendetti, Neika; Ross, Rachael; Fitzgerald, Julie C; Gerber, Jeffrey S

    2017-03-01

    To test the hypothesis that resuscitation with balanced fluids (lactated Ringer [LR]) is associated with improved outcomes compared with normal saline (NS) in pediatric sepsis. We performed matched analyses using data from 12 529 patients <18 years of age with severe sepsis/septic shock at 382 US hospitals between 2000 and 2013 to compare outcomes with vs without LR as part of initial resuscitation. Patients receiving LR were matched 1:1 to patients receiving only NS (NS group), including separate matches for any (LR-any group) or exclusive (LR-only group) LR use. Outcomes included 30-day hospital mortality, acute kidney injury, new dialysis, and length of stay. The LR-any group was older, received larger crystalloid volumes, and was less likely to have malignancies than the NS group. After matching, mortality was not different between LR-any (7.2%) and NS (7.9%) groups (risk ratio 0.99, 95% CI 0.98, 1.01; P = .20). There were no differences in secondary outcomes except longer hospital length of stay in LR-any group (absolute difference 2.4, 95% CI 1.4, 5.0 days; P < .001). Although LR was preferentially used as adjunctive fluid with large-volume resuscitation or first-line fluid in patients with lower illness severity, outcomes were not different after matching stratified by volume and proportionate LR utilization, including for patients in the LR-only group. Balanced fluid resuscitation with LR was not associated with improved outcomes compared with NS in pediatric sepsis. Although the current practice of NS resuscitation is justified, selective LR use necessitates a prospective trial to definitively determine comparative effectiveness among crystalloids. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. The Prehospital Sepsis Project: out-of-hospital physiologic predictors of sepsis outcomes.

    PubMed

    Baez, Amado Alejandro; Hanudel, Priscilla; Wilcox, Susan Renee

    2013-12-01

    Severe sepsis and septic shock are common, expensive and often fatal medical problems. The care of the critically sick and injured often begins in the prehospital setting; there is limited data available related to predictors and interventions specific to sepsis in the prehospital arena. The objective of this study was to assess the predictive effect of physiologic elements commonly reported in the out-of-hospital setting in the outcomes of patients transported with sepsis. This was a cross-sectional descriptive study. Data from the years 2004-2006 were collected. Adult cases (≥18 years of age) transported by Emergency Medical Services to a major academic center with the diagnosis of sepsis as defined by ICD-9-CM diagnostic codes were included. Descriptive statistics and standard deviations were used to present group characteristics. Chi-square was used for statistical significance and odds ratio (OR) to assess strength of association. Statistical significance was set at the .05 level. Physiologic variables studied included mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR) and shock index (SI). Sixty-three (63) patients were included. Outcome variables included a mean hospital length of stay (HLOS) of 13.75 days (SD = 9.97), mean ventilator days of 4.93 (SD = 7.87), in-hospital mortality of 22 out of 63 (34.9%), and mean intensive care unit length-of-stay (ICU-LOS) of 7.02 days (SD = 7.98). Although SI and RR were found to predict intensive care unit (ICU) admissions, [OR 5.96 (CI, 1.49-25.78; P = .003) and OR 4.81 (CI, 1.16-21.01; P = .0116), respectively] none of the studied variables were found to predict mortality (MAP <65 mmHg: P = .39; HR >90: P = .60; RR >20 P = .11; SI >0.7 P = .35). This study demonstrated that the out-of-hospital shock index and respiratory rate have high predictability for ICU admission. Further studies should include the development of an out-of-hospital sepsis score.

  14. SIRT1 inhibition during the hypoinflammatory phenotype of sepsis enhances immunity and improves outcome

    PubMed Central

    Vachharajani, Vidula T.; Liu, Tiefu; Brown, Candice M.; Wang, Xianfeng; Buechler, Nancy L.; Wells, Jonathan David; Yoza, Barbara K.; McCall, Charles E.

    2014-01-01

    Mechanism-based sepsis treatments are unavailable, and their incidence is rising worldwide. Deaths occur during the early acute phase of hyperinflammation or subsequent postacute hypoinflammatory phase with sustained organ failure. The acute sepsis phase shifts rapidly, and multiple attempts to treat early excessive inflammation have uniformly failed. We reported in a sepsis cell model and human sepsis blood leukocytes that nuclear NAD+ sensor SIRT1 deacetylase remodels chromatin at specific gene sets to switch the acute-phase proinflammatory response to hypoinflammatory. Importantly, SIRT1 chromatin reprogramming is reversible, suggesting that inhibition of SIRT1 might reverse postacute-phase hypoinflammation. We tested this concept in septic mice, using the highly specific SIRT1 inhibitor EX-527, a small molecule that closes the NAD+ binding site of SIRT1. Strikingly, when administered 24 h after sepsis, all treated animals survived, whereas only 40% of untreated mice survived. EX-527 treatment reversed the inability of leukocytes to adhere at the small intestine MVI, reversed in vivo endotoxin tolerance, increased leukocyte accumulation in peritoneum, and improved peritoneal bacterial clearance. Mechanistically, the SIRT1 inhibitor restored repressed endothelial E-selectin and ICAM-1 expression and PSGL-1 expression on the neutrophils. Systemic benefits of EX-527 treatment included stabilized blood pressure, improved microvascular blood flow, and a shift toward proimmune macrophages in spleen and bone marrow. Our findings reveal that modifying the SIRT1 NAD+ axis may provide a novel way to treat sepsis in its hypoinflammatory phase. PMID:25001863

  15. Clinical outcome comparison of patients with septic shock defined by the new sepsis-3 criteria and by previous criteria

    PubMed Central

    Ryoo, Seung Mok; Kang, Gu Hyun; Shin, Tae Gun; Hwang, Sung Yeon; Kim, Kyuseok; Jo, You Hwan; Park, Yoo Seok; Choi, Sung-Hyuk; Yoon, Young Hoon; Kwon, Woon Yong; Suh, Gil Joon; Lim, Tae Ho; Han, Kap Su; Choi, Han Sung; Chung, Sung Phil

    2018-01-01

    Background We compared the clinical characteristics and outcomes between the new definition of sepsis-3 septic shock and the definition previously used from 1991 until recently. Methods We conducted an observational study using a prospective, multi-center registry of septic shock from October 2015 to February 2017. Registry data were collected by 10 emergency departments (EDs) in tertiary hospitals that are members of the Korean Shock Society. Data on septic shock patients who met the previous septic shock definition were collected. The patients were divided into a sepsis-3 defined septic shock group, made up of those who met the new criteria for refractory hypotension with hyperlactatemia, and a group of those who met only the 1991 definition for septic shock. The primary outcome was 90-day mortality, and secondary outcomes were 28-day mortality and in-hospital mortality. Results Of all 1,028 included patients, 574 (55.8%) met the septic shock criteria for sepsis-3, leaving 454 patients who met only the previous definition. Those who met the sepsis-3 criteria demonstrated higher comorbidity than those who met the previous definition (83.1% vs. 75.3%, P<0.01), but there was no difference in infection focus. The sequential organ failure assessment (SOFA) (initial/maximal), the acute physiology, and the chronic health evaluation II scores were significantly higher in for those who met the sepsis-3 criteria [6.5±3.1 vs. 5.0±2.9, 9.3±3.8 vs. 6.6±3.4, and 20.0 (15.0–26.0) vs. 15.0 (10.0–20.3), respectively; P<0.01]. The 90-day mortality was significantly higher in the sepsis-3 group (32.1% vs. 23.3%; P<0.01). In-hospital and 28-day mortality were also higher in the sepsis-3 group (26.8% vs. 17.1% and 25.1% vs. 16.5%, respectively; P<0.01). Conclusions The new definition of septic shock successfully selected patients with greater severities and worse outcomes. PMID:29607156

  16. Muscle Mass Depletion Associated with Poor Outcome of Sepsis in the Emergency Department.

    PubMed

    Lee, YoonJe; Park, Hyun Kyung; Kim, Won Young; Kim, Myung Chun; Jung, Woong; Ko, Byuk Sung

    2018-05-08

    Muscle mass depletion has been suggested to predict morbidity and mortality in various diseases. However, it is not well known whether muscle mass depletion is associated with poor outcome in sepsis. We hypothesized that muscle mass depletion is associated with poor outcome in sepsis. Retrospective observational study was conducted in an emergency department during a 9-year period. Medical records of 627 patients with sepsis were reviewed. We divided the patients into 2 groups according to 28-day mortality and compared the presence of muscle mass depletion assessed by the cross-sectional area of the psoas muscle at the level of the third lumbar vertebra on abdomen CT scans. Univariate and multivariate logistic regression analyses were conducted to examine the association of scarcopenia on the outcome of sepsis. A total of 274 patients with sepsis were finally included in the study: 45 (16.4%) did not survive on 28 days and 77 patients (28.1%) were identified as having muscle mass depletion. The presence of muscle mass depletion was independently associated with 28-day mortality on multivariate logistic analysis (OR 2.79; 95% CI 1.35-5.74, p = 0.01). Muscle mass depletion evaluated by CT scan was associated with poor outcome of sepsis patients. Further studies on the appropriateness of specific treatment for muscle mass depletion with sepsis are needed. © 2018 S. Karger AG, Basel.

  17. The impact of a multifaceted intervention including sepsis electronic alert system and sepsis response team on the outcomes of patients with sepsis and septic shock.

    PubMed

    Arabi, Yaseen M; Al-Dorzi, Hasan M; Alamry, Ahmed; Hijazi, Ra'ed; Alsolamy, Sami; Al Salamah, Majid; Tamim, Hani M; Al-Qahtani, Saad; Al-Dawood, Abdulaziz; Marini, Abdellatif M; Al Ehnidi, Fatimah H; Mundekkadan, Shihab; Matroud, Amal; Mohamed, Mohamed S; Taher, Saadi

    2017-12-01

    Compliance with the clinical practice guidelines of sepsis management has been low. The objective of our study was to describe the results of implementing a multifaceted intervention including an electronic alert (e-alert) with a sepsis response team (SRT) on the outcome of patients with sepsis and septic shock presenting to the emergency department. This was a pre-post two-phased implementation study that consisted of a pre-intervention phase (January 01, 2011-September 24, 2012), intervention phase I (multifaceted intervention including e-alert, from September 25, 2012-March 03, 2013) and intervention phase II when SRT was added (March 04, 2013-October 30, 2013) in a 900-bed tertiary-care academic hospital. We recorded baseline characteristics and processes of care in adult patients presenting with sepsis or septic shock. The primary outcome measures were hospital mortality. Secondary outcomes were the need for mechanical ventilation and length of stay in the intensive unit and in the hospital. After implementing the multifaceted intervention including e-alert and SRT, cases were identified with less severe clinical and laboratory abnormalities and the processes of care improved. When adjusted to propensity score, the interventions were associated with reduction in hospital mortality [for intervention phase II compared to pre-intervention: adjusted odds ratio (aOR) 0.71, 95% CI 0.58-0.85, p = 0.003], reduction in the need for mechanical ventilation (aOR 0.45, 95% CI 0.37-0.55, p < 0.0001) and reduction in ICU LOS and hospital LOS for all patients as well as ICU LOS for survivors. Implementing a multifaceted intervention including sepsis e-alert with SRT was associated with earlier identification of sepsis, increase in compliance with sepsis resuscitation bundle and reduction in the need for mechanical ventilation and reduction in hospital mortality and LOS.

  18. ACUTE DIALYSIS QUALITY INITIATIVE (ADQI) XIV SEPSIS PHENOTYPES AND TARGETS FOR BLOOD PURIFICATION IN SEPSIS: THE BOGOTÁ CONSENSUS.

    PubMed

    Kellum, John A; Gómez, Hernando; Gómez, Alonso; Murray, Patrick; Ronco, Claudio

    2016-03-01

    Despite widespread use, there is currently no consensus on how extracorporeal blood purification therapies should be applied or studied in patients with sepsis. One major obstacle has been the lack of clear descriptions of specific sepsis phenotypes tied to mechanisms that would permit the identification of molecular targets. Current evidence suggests that sepsis-related morbidity and mortality involve widely different clinical phenotypes that variably include mitochondrial dysfunction, abnormalities of vascular biology including endothelial dysfunction and coagulopathy, epithelial dysfunction, and immune suppression and dysregulation. While most cases of sepsis involve some element of all of these pathobiologic processes, the magnitude of each varies greatly from patient to patient in part as a result of the pathogen and in part related to host-specific factors. Thus, the purpose of the fourteenth international consensus conference of acute dialysis quality initiative was to develop consensus for a conceptual model of sepsis-induced organ failure that can be treated by extracorporeal blood purification and possibly also with drugs or other therapies. We assembled a group of experts from around the world and used a modified Delphi method to reach consensus. Specific findings and recommendations for future research are provided in the four accompanying papers.

  19. Management of Acute Respiratory Failure in the Patient with Sepsis or Septic Shock.

    PubMed

    Moore, Sarah; Weiss, Brian; Pascual, Jose L; Kaplan, Lewis J

    Sepsis and septic shock are each commonly accompanied by acute respiratory failure and the need for invasive as well as non-invasive ventilation throughout a patient's intensive care unit course. We explore the underpinnings of acute respiratory failure of pulmonary as well as non-pulmonary origin in the context of invasive and non-invasive management approaches. Both pharmacologic and non-pharmacologic adjuncts to ventilatory and oxygenation support are highlighted as well. Finally, rescue modalities are positioned within the intensivist's armamentarium for global care of support of the critically ill or injured patient with sepsis or septic shock.

  20. Procalcitonin levels in sepsis and its association with clinical outcome in southern India.

    PubMed

    Rebello, Alex; Thabah, Molly Mary; Dutta, Tarun Kumar; Bobby, Zachariah; Harish, B N; Mehalingam, Vadivelan

    2017-10-01

    Procalcitonin has been found to be a good marker for the diagnosis of sepsis. However, data on procalcitonin levels to predict the clinical outcome in patients with sepsis are limited. The aim of our study was to estimate serum procalcitonin levels in patients with sepsis and to identify its relationship with the clinical outcome. This was a prospective observational study conducted on 112 patients with sepsis admitted to the medical wards and medical intensive care unit of a tertiary care teaching hospital. Serum procalcitonin was measured at baseline before antibiotic administration and on day 5. The clinical outcome studied was death or survival on day 28. Baseline mean serum procalcitonin was highest in patients with septic shock and lowest in patients having sepsis without organ dysfunction. Mean values of procalcitonin at baseline and on day 5 were significantly higher in non-survivors when compared with survivors. There was a significant difference in the change in procalcitonin levels from baseline to day 5 between survivors and non-survivors, with survivors having declining values on day 5 while non-survivors had increasing values from baseline. The baseline APACHE II and SOFA scores also showed a significant correlation with the baseline procalcitonin level. Declining values of procalcitonin therefore indicate a favourable clinical outcome in patients with sepsis.

  1. The Ratio of Arginine to Dimethylarginines is Reduced and Predicts Outcomes in Patients with Severe Sepsis

    PubMed Central

    Gough, Michael S.; Morgan, Mary Anne M.; Mack, Cynthia M.; Darling, Denise C.; Frasier, Lauren M.; Doolin, Kathleen P.; Apostolakos, Michael J.; Stewart, Judith C.; Graves, Brian T.; Arning, Erland; Bottiglieri, Teodoro; Mooney, Robert A.; Frampton, Mark W.; Pietropaoli, Anthony P.

    2011-01-01

    Objective Arginine deficiency may contribute to microvascular dysfunction, but previous studies suggest that arginine supplementation may be harmful in sepsis. Systemic arginine availability can be estimated by measuring the ratio of arginine to its endogenous inhibitors, asymmetric and symmetric dimethylarginine. We hypothesized that the arginine to dimethylarginine (Arg/DMA) ratio is reduced in patients with severe sepsis and associated with severity of illness and outcomes. Design Case-control and prospective cohort study Setting Medical and surgical intensive care units of an academic medical center Patients and Subjects 109 severe sepsis and 50 control subjects Measurements and Main Results Plasma and urine were obtained in control subjects and within 48 hours of diagnosis in severe sepsis patients. The Arg/DMA ratio was higher in control subjects vs. sepsis patients ((median = 95 [inter-quartile range = 85 – 114]) vs. 34 [24 – 48], p < 0.001), and in hospital survivors vs. non-survivors ((39 [26 – 52]) vs. 27 [19 – 32], p = 0.004). The Arg/DMA ratio was correlated with Acute Physiology and Chronic Health Evaluation II score (Spearman’s correlation coefficient [rho] = − 0.40, p < 0.001) and organ-failure free days (rho = 0.30, p = 0.001). A declining Arg/DMA ratio was independently associated with hospital mortality (odds ratio =1.63 per quartile, 95% confidence interval [CI] = 1.00 – 2.65, p = 0.048) and risk of death over 6 months (hazard ratio = 1.41 per quartile, 95% CI = 1.01 – 1.98, p = 0.043). The Arg/DMA ratio was correlated with the urinary nitrate to creatinine ratio (rho = 0.46, p < 0.001). Conclusions The Arg/DMA ratio is associated with severe sepsis, severity of illness, and clinical outcomes. The Arg/DMA ratio may be a useful biomarker, and interventions designed to augment systemic arginine availability in severe sepsis may still be worthy of investigation. PMID:21378552

  2. Changing Definitions of Sepsis

    PubMed Central

    Gül, Fethi; Arslantaş, Mustafa Kemal; Cinel, İsmail; Kumar, Anand

    2017-01-01

    Sepsis is one of the main causes of morbidity and mortality in critically ill patients despite the use of modern antibiotics and resuscitation therapies. Outcomes in sepsis have improved overall, probably because of an enhanced focus on early diagnosis and other improvements in supportive care, but mortality rates still remain unacceptably high. The diagnosis and definition of sepsis is a critical problem due to the heterogeneity of this disease process. Although it is apparent that much more needs to be done to advance our understanding, sepsis and related terms remain difficult to define. A 1991 consensus conference developed initial definitions that systemic inflammatory response syndrome (SIRS) to infection would be called sepsis. Definitions of sepsis and septic shock were revised in 2001 to incorporate the threshold values for organ damage. In early 2016, the new definitions of sepsis and septic shock have changed dramatically. Sepsis is now defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The consensus document describes organ dysfunction as an acute increase in total Sequential Organ Failure Assessment (SOFA) score two points consequently to the infection. A significant change in the new definitions is the elimination of any mention of SIRS. The Sepsis-3 Task Force also introduced a new bedside index, called the qSOFA, to identify outside of critical care units patients with suspected infection who are likely to develop sepsis. Recently updated the consensus definitions improved specificity compared with the previous descriptions. PMID:28752002

  3. Functional outcomes in pediatric severe sepsis: further analysis of the researching severe sepsis and organ dysfunction in children: a global perspective trial.

    PubMed

    Farris, Reid W D; Weiss, Noel S; Zimmerman, Jerry J

    2013-11-01

    To evaluate risk factors for poor functional outcome in 28-day survivors after an episode of severe sepsis. Retrospective cohort study examining data from the Researching Severe Sepsis and Organ Dysfunction in Children: A Global Perspective trial (NCT00049764). One hundred and four pediatric centers in 18 countries. Children with severe sepsis who required both vasoactive-inotropic infusions and mechanical ventilation and who survived to 28 days (n = 384). None. Poor functional outcome was defined as a Pediatric Overall Performance Category score greater than or equal to 3 and an increase from baseline when measured 28 days after trial enrollment. Median Pediatric Overall Performance Category at enrollment was 1 (interquartile range, 1-2). Median Pediatric Overall Performance Category at 28 days was 2 (interquartile range, 1-4). Thirty-four percent of survivors had decline in their functional status at 28 days, and 18% were determined to have a "poor" functional outcome. Hispanic ethnicity was associated with poor functional outcome compared to the white referent group (risk ratio = 1.9; 95% CI: 1.0-3.0). Clinical factors associated with increased risk of poor outcome included CNS and intra-abdominal infection sources compared to the lung infection referent category (risk ratio = 3.3; 95% CI: 1.4-5.6 and 2.4; 95% CI: 1.0-4.5, respectively); a history of recent trauma (risk ratio = 3.9; 95% CI: 1.4-5.4); receipt of cardiopulmonary resuscitation prior to enrollment (risk ratio = 5.1; 95% CI: 2.9-5.7); and baseline Pediatric Risk of Mortality III score of 20-29 (risk ratio = 2.8; 95% CI: 1.2-5.2) and Pediatric Risk of Mortality III greater than or equal to 30 (risk ratio = 4.5; 95% CI: 1.6-8.0) compared to the referent group with Pediatric Risk of Mortality III scores of 0-9. In this sample of 28-day survivors of pediatric severe sepsis diminished functional status was common. This analysis provides evidence that particular patient characteristics and aspects of an

  4. Initial management of pneumonia and sepsis: factors associated with improved outcome.

    PubMed

    Menéndez, R; Torres, A; Reyes, S; Zalacain, R; Capelastegui, A; Aspa, J; Borderías, L; Martín-Villasclaras, J J; Bello, S; Alfageme, I; de Castro, F R; Rello, J; Molinos, L; Ruiz-Manzano, J

    2012-01-01

    Processes of care and adherence to guidelines have been associated with improved survival in community-acquired pneumonia (CAP). In sepsis, bundles of processes of care have also increased survival. We aimed to audit compliance with guideline-recommended processes of care and its impact on outcome in hospitalised CAP patients with sepsis. We prospectively studied 4,137 patients hospitalised with CAP in 13 hospitals. The processes of care evaluated were adherence to antibiotic prescription guidelines, first dose within 6 h and oxygen assessment. Outcome measures were mortality and length of stay (LOS). Oxygen assessment was measured in 3,745 (90.5%) patients; 3,024 (73.1%) patients received antibiotics according to guidelines and 3,053 (73.8%) received antibiotics within 6 h. In CAP patients with sepsis, the strongest independent factor for survival was antibiotic adherence (OR 0.4). In severe sepsis, only compliance to antibiotic adherence plus first dose within 6 h was associated with lower mortality (OR 0.60), adjusted for fine prognostic scale and hospital. Antibiotic adherence was related to shorter hospital stay. In sepsis, antibiotic adherence is the strongest protective factor of care associated with survival and LOS. In severe sepsis, combined antibiotic adherence and first dose within 6 h may reduce mortality.

  5. Predictive Validity of Sepsis-3 Definitions and Sepsis Outcomes in Critically Ill Patients: A Cohort Study in 49 ICUs in Argentina.

    PubMed

    Estenssoro, Elisa; Kanoore Edul, Vanina S; Loudet, Cecilia I; Osatnik, Javier; Ríos, Fernando G; Vázquez, Daniela N; Pozo, Mario O; Lattanzio, Bernardo; Pálizas, Fernando; Klein, Francisco; Piezny, Damián; Rubatto Birri, Paolo N; Tuhay, Graciela; Díaz, Anatilde; Santamaría, Analía; Zakalik, Graciela; Dubin, Arnaldo

    2018-05-08

    The new Sepsis-3 definitions have been scarcely assessed in low- and middle-income countries; besides, regional information of sepsis outcomes is sparse. Our objective was to evaluate Sepsis-3 definition performance in Argentina. Cohort study of 3-month duration beginning on July 1, 2016. Forty-nine ICUs. Consecutive patients admitted to the ICU with suspected infection that triggered blood cultures and antibiotic administration. None. Patients were classified as having infection, sepsis (infection + change in Sequential Organ Failure Assessment ≥ 2 points), and septic shock (vasopressors + lactate > 2 mmol/L). Patients on vasopressors and lactate less than or equal to 2 mmol/L (cardiovascular dysfunction) were analyzed separately, as those on vasopressors without serum lactate measurement. Systemic inflammatory response syndrome was also recorded. Main outcome was hospital mortality. Of 809 patients, 6% had infection, 29% sepsis, 20% cardiovascular dysfunction, 40% septic shock, and 3% received vasopressors with lactate unmeasured. Hospital mortality was 13%, 20%, 39%, 51%, and 41%, respectively (p = 0.000). Independent predictors of outcome were lactate, Sequential Organ Failure Assessment score, comorbidities, prior duration of symptoms (hr), mechanical ventilation requirement, and infection by highly resistant microorganisms. Area under the receiver operating characteristic curves for mortality for systemic inflammatory response syndrome and Sequential Organ Failure Assessment were 0.53 (0.48-0.55) and 0.74 (0.69-0.77), respectively (p = 0.000). Increasing severity of Sepsis-3 categories adequately tracks mortality; cardiovascular dysfunction subgroup, not included in Sepsis-3, has distinct characteristics. Sequential Organ Failure Assessment score shows adequate prognosis accuracy-contrary to systemic inflammatory response syndrome. This study supports the predictive validity of Sepsis-3 definitions.

  6. Sepsis and acute respiratory distress syndrome requiring extracorporeal life support in an adolescent with mild cystic fibrosis.

    PubMed

    Faricy, Lauren Elizabeth; Church, Gwynne

    2017-01-01

    Outcomes for invasive mechanical ventilation and extracorporeal membrane oxygenation (ECMO) to treat acute respiratory failure in patients with mild cystic fibrosis (CF) lung disease are not known. We present a case of the successful use of ECMO to treat acute respiratory failure secondary to staphylococcal sepsis in an adolescent CF patient with previously normal lung function. Her post-ECMO course was notable for severe airflow obstruction, hypoxemia, deconditioning, and growth failure. She had significantly improved at six months follow-up, though she continued to have moderate airflow obstruction on pulmonary function testing. This case illustrates that ECMO and prolonged intubation can prolong life in CF patients with mild lung disease who present with potentially reversible acute respiratory failure, though they are associated with significant morbidity.

  7. Biology of sepsis: its relevance to pediatric nephrology.

    PubMed

    Blatt, Neal B; Srinivasan, Sushant; Mottes, Theresa; Shanley, Maureen M; Shanley, Thomas P

    2014-12-01

    Because of its multi-organ involvement, the syndrome of sepsis provides clinical challenges to a wide variety of health care providers. While multi-organ dysfunction triggered by sepsis requires general supportive critical care provided by intensivists, the impact of sepsis on renal function and the ability of renal replacement therapies to modulate its biologic consequences provide a significant opportunity for pediatric nephrologists and related care providers to impact outcomes. In this review, we aim to highlight newer areas of understanding of the pathobiology of sepsis with special emphasis on those aspects of particular interest to pediatric nephrology. As such, we aim to: (1) review the definition of sepsis and discuss advances in our mechanistic understanding of sepsis; (2) review current hypotheses regarding sepsis-induced acute kidney injury (AKI) and describe its epidemiology based on evolving definitions of AKI; (3) review the impact of renal failure on the immune system, highlighting the sepsis risk in this cohort and strategies that might minimize this risk; (4) review how renal replacement therapeutic strategies may impact sepsis-induced AKI outcomes. By focusing the review on these specific areas, we have omitted other important areas of the biology of sepsis and additional interactions with renal function from this discussion; however, we have aimed to provide a comprehensive list of references that provide contemporary reviews of these additional areas.

  8. AP214, an analogue of α-melanocyte-stimulating hormone, ameliorates sepsis-induced acute kidney injury and mortality

    PubMed Central

    Doi, Kent; Hu, Xuzhen; Yuen, Peter S.T.; Leelahavanichkul, Asada; Yasuda, Hideo; Kim, Soo Mi; Schnermann, Jürgen; Jonassen, Thomas E.N.; Frøkiær, Jørgen; Nielsen, Søren; Star, Robert A.

    2008-01-01

    Sepsis remains a serious problem in critically ill patients with the mortality increasing to over half when there is attendant acute kidney injury. α-Melanocyte-stimulating hormone is a potent anti-inflammatory cytokine that inhibits many forms of inflammation including that with acute kidney injury. We tested whether a new α-melanocyte-stimulating hormone analogue (AP214), which has increased binding affinity to melanocortin receptors, improves sepsis-induced kidney injury and mortality using a cecal ligation and puncture mouse model. In the lethal cecal ligation-puncture model of sepsis, severe hypotension and bradycardia resulted and AP214 attenuated acute kidney injury of the lethal model with a bell-shaped dose-response curve. An optimum AP214 dose reduced acute kidney injury even when it was administered 6 hr after surgery and it significantly improved blood pressure and heart rate. AP214 reduced serum TNF-α and IL-10 levels with a bell-shaped dose-response curve. Additionally; NF-κB activation in the kidney and spleen, and splenocyte apoptosis were decreased by the treatment. AP214 significantly improved survival in both lethal and sublethal models. We have shown that AP214 improves hemodynamic failure, acute kidney injury, mortality and splenocyte apoptosis attenuating pro- and anti-inflammatory actions due to sepsis. PMID:18354376

  9. Recent advances in the pathogenetic mechanisms of sepsis-associated acute kidney injury.

    PubMed

    Fani, Filippo; Regolisti, Giuseppe; Delsante, Marco; Cantaluppi, Vincenzo; Castellano, Giuseppe; Gesualdo, Loreto; Villa, Gianluca; Fiaccadori, Enrico

    2018-06-01

    Sepsis is a serious medical condition that can lead to multi-organ failure and shock, and it is associated with increased mortality. Acute kidney injury (AKI) is a frequent complication of sepsis in critically ill patients, and often requires renal replacement therapy. The pathophysiology of AKI in sepsis has not yet been fully defined. In the past, classic theories were mainly focused on systemic hemodynamic derangements, underscoring the key role of whole kidney hypoperfusion due to reduced renal blood flow. However, a growing body of experimental and clinical evidence now shows that, at least in the early phase of sepsis-associated AKI, renal blood flow is normal, or even increased. This could suggest a dissociation between renal blood flow and kidney function. In addition, the scant data available from kidney biopsies in human studies do not support diffuse acute tubular necrosis as the predominant lesion. Instead, increasing importance is now attributed to kidney damage resulting from a complex interaction between immunologic mechanisms, inflammatory cascade activation, and deranged coagulation pathways, leading to microvascular dysfunction, endothelial damage, leukocyte/platelet activation with the formation of micro-thrombi, epithelial tubular cell injury and dysfunction. Moreover, the same processes, through maladaptive responses leading to fibrosis acting from the very beginning, may set the stage for progression to chronic kidney disease in survivors from sepsis-associated AKI episodes. The aim of this narrative review is to summarize and discuss the latest evidence on the pathophysiological mechanisms involved in septic AKI, based on the most recent data from the literature.

  10. Alkaline phosphatase for treatment of sepsis-induced acute kidney injury: a prospective randomized double-blind placebo-controlled trial

    PubMed Central

    2012-01-01

    Introduction To evaluate whether alkaline phosphatase (AP) treatment improves renal function in sepsis-induced acute kidney injury (AKI), a prospective, double-blind, randomized, placebo-controlled study in critically ill patients with severe sepsis or septic shock with evidence of AKI was performed. Methods Thirty-six adult patients with severe sepsis or septic shock according to Systemic Inflammatory Response Syndrome criteria and renal injury defined according to the AKI Network criteria were included. Dialysis intervention was standardized according to Acute Dialysis Quality Initiative consensus. Intravenous infusion of alkaline phosphatase (bolus injection of 67.5 U/kg body weight followed by continuous infusion of 132.5 U/kg/24 h for 48 hours, or placebo) starting within 48 hours of AKI onset and followed up to 28 days post-treatment. The primary outcome variable was progress in renal function variables (endogenous creatinine clearance, requirement and duration of renal replacement therapy, RRT) after 28 days. The secondary outcome variables included changes in circulating inflammatory mediators, urinary excretion of biomarkers of tubular injury, and safety. Results There was a significant (P = 0.02) difference in favor of AP treatment relative to controls for the primary outcome variable. Individual renal parameters showed that endogenous creatinine clearance (baseline to Day 28) was significantly higher in the treated group relative to placebo (from 50 ± 27 to 108 ± 73 mL/minute (mean ± SEM) for the AP group; and from 40 ± 37 to 65 ± 30 mL/minute for placebo; P = 0.01). Reductions in RRT requirement and duration did not reach significance. The results in renal parameters were supported by significantly more pronounced reductions in the systemic markers C-reactive protein, Interleukin-6, LPS-binding protein and in the urinary excretion of Kidney Injury Molecule-1 and Interleukin-18 in AP-treated patients relative to placebo. The Drug Safety Monitoring

  11. Acute Oncology Care: A narrative review of the acute management of neutropenic sepsis and immune-related toxicities of checkpoint inhibitors.

    PubMed

    Knight, Thomas; Ahn, Shin; Rice, Terry W; Cooksley, Tim

    2017-11-01

    Cancer care has become increasingly specialized and advances in therapy have resulted in a larger number of patients receiving care. There has been a significant increase in the number of patients presenting with cancer related emergencies including treatment toxicities and those directly related to the malignancy. Suspected neutropenic sepsis is an acute medical emergency and empirical antibiotic therapy should be administered immediately. The goal of empirical therapy is to cover the most likely pathogens that will cause life-threatening infections in neutropenic patients. Patients with febrile neutropenia are a heterogeneous group with only a minority of treated patients developing significant medical complications. Outpatient management of low risk febrile neutropenia patients identified by the MASCC score is a safe and effective strategy. Immunotherapy with "checkpoint inhibitors" has significantly improved outcomes for patients with metastatic melanoma and evidence of benefit in a wide range of malignancies is developing. Despite these clinical benefits a number of immune related adverse events have been recognised which can affect virtually all organ systems and are potentially fatal. The timing of the onset of the adverse events is dependent on the organ system affected and unlike anti-neoplastic therapy can be delayed significantly after initiation or completion of therapy. The field of Acute Oncology is changing rapidly. Alongside, the traditional challenge of neutropenic sepsis there are many emerging toxicities. Further research into the optimal management, strategies and pathways of acutely unwell patients with cancer is required. Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  12. Reduced production of creatinine limits its use as marker of kidney injury in sepsis.

    PubMed

    Doi, Kent; Yuen, Peter S T; Eisner, Christoph; Hu, Xuzhen; Leelahavanichkul, Asada; Schnermann, Jürgen; Star, Robert A

    2009-06-01

    Although diagnosis and staging of acute kidney injury uses serum creatinine, acute changes in creatinine lag behind both renal injury and recovery. The risk for mortality increases when acute kidney injury accompanies sepsis; therefore, we sought to explore the limitations of serum creatinine in this setting. In mice, induction of sepsis by cecal ligation and puncture in bilaterally nephrectomized mice increased markers of nonrenal organ injury and serum TNF-alpha. Serum creatinine, however, was significantly lower in septic animals than in animals subjected to bilateral nephrectomy and sham cecal ligation and puncture. Under these conditions treatment with chloroquine decreased nonrenal organ injury markers but paradoxically increased serum creatinine. Sepsis dramatically decreased production of creatinine in nephrectomized mice, without changes in body weight, hematocrit, or extracellular fluid volume. In conclusion, sepsis reduces production of creatinine, which blunts the increase in serum creatinine after sepsis, potentially limiting the early detection of acute kidney injury. This may partially explain why small absolute increases in serum creatinine levels are associated with poor clinical outcomes. These data support the need for new biomarkers that provide better measures of renal injury, especially in patients with sepsis.

  13. [Value of sepsis single-disease manage system in predicting mortality in patients with sepsis].

    PubMed

    Chen, J; Wang, L H; Ouyang, B; Chen, M Y; Wu, J F; Liu, Y J; Liu, Z M; Guan, X D

    2018-04-03

    Objective: To observe the effect of sepsis single-disease manage system on the improvement of sepsis treatment and the value in predicting mortality in patients with sepsis. Methods: A retrospective study was conducted. Patients with sepsis admitted to the Department of Surgical Intensive Care Unit of Sun Yat-Sen University First Affiliated Hospital from September 22, 2013 to May 5, 2015 were enrolled in this study. Sepsis single-disease manage system (Rui Xin clinical data manage system, China data, China) was used to monitor 25 clinical quality parameters, consisting of timeliness, normalization and outcome parameters. Based on whether these quality parameters could be completed or not, the clinical practice was evaluated by the system. The unachieved quality parameter was defined as suspicious parameters, and these suspicious parameters were used to predict mortality of patients with receiver operating characteristic curve (ROC). Results: A total of 1 220 patients with sepsis were enrolled, included 805 males and 415 females. The mean age was (59±17) years, and acute physiology and chronic health evaluation (APACHE Ⅱ) scores was 19±8. The area under ROC curve of total suspicious numbers for predicting 28-day mortality was 0.70; when the suspicious parameters number was more than 6, the sensitivity was 68.0% and the specificity was 61.0% for predicting 28-day mortality. In addition, the area under ROC curve of outcome suspicious number for predicting 28-day mortality was 0.89; when the suspicious outcome parameters numbers was more than 1, the sensitivity was 88.0% and the specificity was 78.0% for predicting 28-day mortality. Moreover, the area under ROC curve of total suspicious number for predicting 90-day mortality was 0.73; when the total suspicious parameters number was more than 7, the sensitivity was 60.0% and the specificity was 74.0% for predicting 90-day mortality. Finally, the area under ROC curve of outcome suspicious numbers for predicting 90

  14. Hypothermia in the sepsis syndrome and clinical outcome. The Methylprednisolone Severe Sepsis Study Group.

    PubMed

    Clemmer, T P; Fisher, C J; Bone, R C; Slotman, G J; Metz, C A; Thomas, F O

    1992-10-01

    To evaluate the consequences of clinical hypothermia associated with sepsis syndrome and septic shock. Analysis of data from a multi-institutional, randomized, placebo-controlled, prospective study with predetermined end-point analysis of development of shock, recovery from shock, hospital length of stay, and death. Multi-institutional medical and surgical ICUs. Patients meeting predetermined criteria for severe sepsis syndrome. Appropriate sepsis and shock care with 50% of patients receiving methylprednisolone and 50% receiving placebo. The occurrence rate of hypothermia (< 35.5 degrees C) is 9% in this population. When compared with febrile patients, hypothermic patients had a higher frequency of central nervous system dysfunction (88% vs. 60%), increased serum bilirubin concentration (35% vs. 15%), prolonged prothrombin times (50% vs. 23%), shock (94% vs. 61%), failure to recover from shock (66% vs. 26%), and death (62% vs. 26%). The hypothermic patients were also more likely to be classified as having a rapidly or ultimately fatal disease upon study admission. This prospective study confirms that hypothermia associated with sepsis syndrome has a significant relationship to outcome manifest by increased frequency of shock and death from shock. This finding is in sharp contrast to the protective effects of induced hypothermia in septic animals and perhaps man.

  15. Acute ethanol intoxication suppresses pentraxin 3 expression in a mouse sepsis model involving cecal ligation and puncture.

    PubMed

    Kasuda, Shogo; Kudo, Risa; Yuui, Katsuya; Sakurai, Yoshihiko; Hatake, Katsuhiko

    2017-11-01

    Acute ethanol intoxication impairs immunological reactions and increases the risk of sepsis; however, the underlying mechanism remains unclear. Pentraxin (PTX) 3 is a humoral pattern recognition receptor whose levels rapidly increase in response to inflammation. PTX3 production is triggered by tumor necrosis factor (TNF)-α and is mediated by c-Jun N-terminal kinase (JNK). As PTX3 exerts protective effects against sepsis as well as acute lung injury, we investigated whether acute ethanol exposure exacerbates sepsis by altering PTX3 expression. Sepsis was induced in C57/BL6 mice by cecal ligation and puncture (CLP) after ethanol/saline administration. Survival rates were significantly lower in ethanol-treated than in saline-treated mice. Increased vascular permeability and attenuation of PTX3 expression were observed in the lungs of ethanol-treated mice 4 h after CLP. Concomitant with a delayed increase of plasma TNF-α in ethanol-treated mice, plasma PTX3 was also suppressed in the early phase of sepsis. Although TNF-α level in ethanol-treated mice exceeded that in saline-treated mice 16 h after CLP, PTX3 levels were still suppressed in the former group. JNK phosphorylation in lung tissue was suppressed in both groups 4 and 16 h after CLP. Furthermore, JNK phosphorylation in ethanol-treated human umbilical vein endothelial cells was suppressed even in the presence of exogenous TNF-α, resulting in inhibition of PTX3 mRNA and protein expression. Our results suggest that ethanol suppresses de novo PTX3 synthesis via two mechanisms - i.e., suppression of TNF-α production and inhibition of JNK phosphorylation. PTX3 suppression may therefore contribute to exacerbation of sepsis in acute ethanol intoxication. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Chloroquine and inhibition of Toll-like receptor 9 protect from sepsis-induced acute kidney injury

    PubMed Central

    Yasuda, Hideo; Leelahavanichkul, Asada; Tsunoda, Shinichiro; Dear, James W.; Takahashi, Yoshiyuki; Ito, Shuichi; Hu, Xuzhen; Zhou, Hua; Doi, Kent; Childs, Richard; Klinman, Dennis M.; Yuen, Peter S.T.; Star, Robert A.

    2008-01-01

    Mortality from sepsis has remained high despite recent advances in supportive and targeted therapies. Toll-like receptors (TLRs) sense bacterial products and stimulate pathogenic innate immune responses. Mice deficient in the common adapter protein MyD88, downstream from most TLRs, have reduced mortality and acute kidney injury (AKI) from polymicrobial sepsis. However, the identity of the TLR(s) responsible for the host response to polymicrobial sepsis is unknown. Here, we show that chloroquine, an inhibitor of endocytic TLRs (TLR3, 7, 8, 9), improves sepsis-induced mortality and acute kidney injury in a clinically relevant polymicrobial sepsis mouse model, even when administered 6h after the septic insult. Chloroquine administration attenuated the decline in renal function, splenic apoptosis, serum markers of damage to other organs, and prototypical serum pro- and anti-inflammatory cytokines TNF-alpha and IL-10. An oligodeoxynucleotide inhibitor (H154) of TLR9 and TLR9-deficient mice mirror the actions of chloroquine in all functional parameters that we tested. In addition, chloroquine decreased TLR9 protein abundance in spleen, further suggesting that TLR9 signaling may be a major target for the protective actions of chloroquine. Our findings indicate that chloroquine improves survival by inhibiting multiple pathways leading to polymicrobial sepsis, and that chloroquine and TLR9 inhibitors represent viable broad-spectrum and targeted therapeutic strategies, respectively, that are promising candidates for further clinical development. PMID:18305095

  17. Immunotherapy in the management of sepsis.

    PubMed Central

    Fagan, E. A.; Singer, M.

    1995-01-01

    The pathophysiological effects of severe sepsis, septic shock and related syndromes result from tissues damaged by the uncontrolled production of the mediators of inflammation. Early deaths are related primarily to the acute effects of the systemic inflammatory response. Later deaths are related more closely to the consequences of multiple organ dysfunction. Monoclonal antibodies and other immunotherapies have been developed against bacterial products, cytokines and other mediators involved in this systemic inflammatory response. Immunotherapies may improve outcome in the critically ill with sepsis if used early and as part of the therapeutic regimen of antimicrobial agents and intensive care support. PMID:7724438

  18. A Multidisciplinary Sepsis Program Enabled by a Two-Stage Clinical Decision Support System: Factors That Influence Patient Outcomes.

    PubMed

    Amland, Robert C; Haley, James M; Lyons, Jason J

    2016-11-01

    Sepsis is an inflammatory response triggered by infection, with risk of in-hospital mortality fueled by disease progression. Early recognition and intervention by multidisciplinary sepsis programs may reverse the inflammatory response among at-risk patient populations, potentially improving outcomes. This retrospective study of a sepsis program enabled by a 2-stage sepsis Clinical Decision Support (CDS) system sought to evaluate the program's impact, identify early indicators that may influence outcomes, and uncover opportunities for quality improvement. Data encompassed 16 527 adult hospitalizations from 2014 and 2015. Of 2108 non-intensive care unit patients screened-in by sepsis CDS, 97% patients were stratified by 177 providers. Risk of adverse outcome improved 30% from baseline to year end, with gains materializing and stabilizing at month 7 after sepsis program go-live. Early indicators likely to influence outcomes include patient age, recent hospitalization, electrolyte abnormalities, hypovolemic shock, hypoxemia, patient location when sepsis CDS activated, and specific alert patterns. © The Author(s) 2015.

  19. Ethnicity and sepsis characteristics and outcomes. Population based study.

    PubMed

    Karp, Galia; Perl, Yael; Fuchs, Lior; Almog, Yaniv; Klein, Moti; Vodonos, Alina; Dreiher, Jacob; Talmor, Daniel; Codish, Shlomi; Novack, Victor

    2013-01-01

    Two distinct ethnic groups live in Southern Israel: urban Jews and rural Bedouin Arabs. These groups differ in their socioeconomic status, culture and living environment, and are treated in a single regional tertiary care hospital. We hypothesized that these two ethnic groups have different patterns of sepsis-related intensive care admissions. The study included all adult patients admitted to the Soroka University Medical Center Intensive Care Units between January 2002 and December 2008, with a diagnosis of sepsis. Demographic data, medical history, and hospitalization and outcomes data were obtained. Primary outcome was all-cause mortality. Jewish patients admitted to the ICU (1343, 87%) were on average 17 years older than Bedouin Arabs (199, 13%). For the population <65 years, Bedouin Arabs had slightly higher age-adjusted prevalence of ICU sepsis admissions than Jewish patients (39.5 vs. 43.0, p=0.25), while for the population >65 years there was a reverse trend (21.8 vs. 19.8 p=0.49). There were no differences in the type of organ failure, sepsis severity or length of hospitalization between the two groups. Twenty eight days/in-hospital mortality was 33.9% in Bedouin Arabs vs. 45.5% in Jews, p=0.004. Following adjustment for comorbidities, age and severity of the disease, survival was unrelated to ethnicity, both at 28 days (odds ratio for Bedouin Arabs 0.86, 95% CI 0.66-1.24) and following hospital discharge (hazard ratio 0.86, 95% 0.67-1.09). Sepsis-related ICU admissions are more prevalent among Bedouin Arabs at younger age compared with the Jewish population. Adjusted for confounders, ethnicity does not influence prognosis. Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  20. Septic arthritis associated with systemic sepsis.

    PubMed

    Jung, Sung-Weon; Kim, Dong-Hee; Shin, Sung-Jin; Kang, Byoung-Youl; Eho, Yil-Ju; Yang, Seong-Wook

    2018-01-01

    Septic arthritis presents with good joint function, but sometimes leads to poor outcomes. Concurrent systemic sepsis has been regarded as the poor outcome, and the exact cause remains unclear. This paper was performed to identify factors associated with concurrent systemic sepsis and to research results to predict poor outcomes in patients with septic arthritis. Laboratory and medical data were reviewed for 137 adults with acute septic arthritis who underwent open or arthroscopic surgical debridement at our institution between January 2005 and December 2014. The patients were divided according to whether they had septic arthritis alone (Group A) or in combination with systemic sepsis (Group B). Systemic sepsis was defined as two more systemic inflammatory signs in response to an infectious process. Patient characteristics, laboratory findings, synovial fluid findings and cultures, and surgical results were compared between two groups. Of the 137 patients, 41 (29.9%) had initial systemic sepsis at the diagnosis of septic arthritis. Independent t test revealed that duration of prodromal symptom (p = 0.012), serum neutrophil percent (p = 0.008), C-reactive protein (p = 0.001), Charlson comorbidity index (p = 0.001), positive culture in synovial fluid (p = 0.001), and methicillin-sensitive Staphylococcus aureus (MSSA) isolate in synovial fluid (p = 0.001) had significant correlations with the group B. Repeated debridement was performed for those who had recurrence of infection, and this procedure was more often in group B (23 versus 21 joints, 23.9 versus 51.2%, p = 0.012). Progression of arthritis occurred more often in group B (16 versus 17 joints, 16.7 versus 41.5%, p = 0.001). Septic arthritis combined with systemic sepsis was related to duration of prodromal symptom, serum neutrophil percent, C-reactive protein, Charlson comorbidity index, positive culture in synovial fluid, and a MSSA isolate in synovial fluid. Concurrent systemic sepsis led to

  1. Serum amyloid A in the diagnosis of feline sepsis.

    PubMed

    Troìa, Roberta; Gruarin, Marta; Foglia, Armando; Agnoli, Chiara; Dondi, Francesco; Giunti, Massimo

    2017-11-01

    Systemic inflammatory response syndrome (SIRS) and sepsis can be challenging to diagnose in cats. Retrospectively, we investigated the diagnostic and prognostic potential of serum amyloid A (SAA), a major feline acute-phase protein (APP), in a population of critically ill cats with SIRS related to trauma or sepsis. A total of 56 SIRS cats (trauma n = 27; sepsis n = 29) were included and compared with healthy controls ( n = 18). SAA concentration was significantly increased in SIRS cats compared to controls, confirming its potential for the detection of systemic inflammation in this species. Significantly higher values of SAA were detected in cats belonging to the sepsis group; however, according to the results of the receiver operating characteristic curve analysis, the value of using SAA (>81 mg/L) to discriminate septic cats was only moderate (AUC = 0.76). Additionally, cats with sepsis had significantly higher serum bilirubin concentrations and toxic neutrophil changes compared to the trauma group. Overall, 38 of 56 cats were survivors; 18 of 56 were non-survivors, with 83% of the non-survivors (15 of 18) belonging to the sepsis group. Serum bilirubin concentration, but not SAA, was able to predict outcome. Prospective studies are needed to assess the potential of SAA in the diagnosis of feline sepsis and outcome prediction.

  2. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

    PubMed

    Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed; Levy, Mitchell M; Antonelli, Massimo; Ferrer, Ricard; Kumar, Anand; Sevransky, Jonathan E; Sprung, Charles L; Nunnally, Mark E; Rochwerg, Bram; Rubenfeld, Gordon D; Angus, Derek C; Annane, Djillali; Beale, Richard J; Bellinghan, Geoffrey J; Bernard, Gordon R; Chiche, Jean-Daniel; Coopersmith, Craig; De Backer, Daniel P; French, Craig J; Fujishima, Seitaro; Gerlach, Herwig; Hidalgo, Jorge Luis; Hollenberg, Steven M; Jones, Alan E; Karnad, Dilip R; Kleinpell, Ruth M; Koh, Younsuk; Lisboa, Thiago Costa; Machado, Flavia R; Marini, John J; Marshall, John C; Mazuski, John E; McIntyre, Lauralyn A; McLean, Anthony S; Mehta, Sangeeta; Moreno, Rui P; Myburgh, John; Navalesi, Paolo; Nishida, Osamu; Osborn, Tiffany M; Perner, Anders; Plunkett, Colleen M; Ranieri, Marco; Schorr, Christa A; Seckel, Maureen A; Seymour, Christopher W; Shieh, Lisa; Shukri, Khalid A; Simpson, Steven Q; Singer, Mervyn; Thompson, B Taylor; Townsend, Sean R; Van der Poll, Thomas; Vincent, Jean-Louis; Wiersinga, W Joost; Zimmerman, Janice L; Dellinger, R Phillip

    2017-03-01

    To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

  3. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

    PubMed

    Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed; Levy, Mitchell M; Antonelli, Massimo; Ferrer, Ricard; Kumar, Anand; Sevransky, Jonathan E; Sprung, Charles L; Nunnally, Mark E; Rochwerg, Bram; Rubenfeld, Gordon D; Angus, Derek C; Annane, Djillali; Beale, Richard J; Bellinghan, Geoffrey J; Bernard, Gordon R; Chiche, Jean-Daniel; Coopersmith, Craig; De Backer, Daniel P; French, Craig J; Fujishima, Seitaro; Gerlach, Herwig; Hidalgo, Jorge Luis; Hollenberg, Steven M; Jones, Alan E; Karnad, Dilip R; Kleinpell, Ruth M; Koh, Younsuck; Lisboa, Thiago Costa; Machado, Flavia R; Marini, John J; Marshall, John C; Mazuski, John E; McIntyre, Lauralyn A; McLean, Anthony S; Mehta, Sangeeta; Moreno, Rui P; Myburgh, John; Navalesi, Paolo; Nishida, Osamu; Osborn, Tiffany M; Perner, Anders; Plunkett, Colleen M; Ranieri, Marco; Schorr, Christa A; Seckel, Maureen A; Seymour, Christopher W; Shieh, Lisa; Shukri, Khalid A; Simpson, Steven Q; Singer, Mervyn; Thompson, B Taylor; Townsend, Sean R; Van der Poll, Thomas; Vincent, Jean-Louis; Wiersinga, W Joost; Zimmerman, Janice L; Dellinger, R Phillip

    2017-03-01

    To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

  4. Hydrocortisone treatment in early sepsis-associated acute respiratory distress syndrome: results of a randomized controlled trial.

    PubMed

    Tongyoo, Surat; Permpikul, Chairat; Mongkolpun, Wasineenart; Vattanavanit, Veerapong; Udompanturak, Suthipol; Kocak, Mehmet; Meduri, G Umberto

    2016-10-15

    Authors of recent meta-analyses have reported that prolonged glucocorticoid treatment is associated with significant improvements in patients with severe pneumonia or acute respiratory distress syndrome (ARDS) of multifactorial etiology. A prospective randomized trial limited to patients with sepsis-associated ARDS is lacking. The objective of our study was to evaluate the efficacy of hydrocortisone treatment in sepsis-associated ARDS. In this double-blind, single-center (Siriraj Hospital, Bangkok), randomized, placebo-controlled trial, we recruited adult patients with severe sepsis within 12 h of their meeting ARDS criteria. Patients were randomly assigned (1:1 ratio) to receive either hydrocortisone 50 mg every 6 h or placebo. The primary endpoint was 28-day all-cause mortality; secondary endpoints included survival without organ support on day 28. Over the course of 4 years, 197 patients were randomized to either hydrocortisone (n = 98) or placebo (n = 99) and were included in this intention-to-treat analysis. The treatment group had significant improvement in the ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen and lung injury score (p = 0.01), and similar timing to removal of vital organ support (HR 0.74, 95 % CI 0.51-1.07; p = 0.107). After adjustment for significant covariates, day 28 survival was similar for the whole group (HR 0.80, 95 % CI 0.46-1.41; p = 0.44) and for the larger subgroup (n = 126) with Acute Physiology and Chronic Health Evaluation II score <25 (HR 0.57, 95 % CI 0.24-1.36; p = 0.20). With the exception of hyperglycemia (80.6 % vs. 67.7 %; p = 0.04), the rate of adverse events was similar. Hyperglycemia had no impact on outcome. In sepsis-associated ARDS, hydrocortisone treatment was associated with a significant improvement in pulmonary physiology, but without a significant survival benefit. ClinicalTrials.gov identifier NCT01284452 . Registered on 18 January

  5. High Levels of Morbidity and Mortality Among Pediatric Hematopoietic Cell Transplant Recipients With Severe Sepsis: Insights From the Sepsis PRevalence, OUtcomes, and Therapies International Point Prevalence Study.

    PubMed

    Lindell, Robert B; Gertz, Shira J; Rowan, Courtney M; McArthur, Jennifer; Beske, Florian; Plunkett, Adrian; Weiss, Scott L; Thomas, Neal J; Nadkarni, Vinay M; Fitzgerald, Julie C

    2017-12-01

    Pediatric severe sepsis is a major cause of morbidity and mortality worldwide, and hematopoietic cell transplant patients represent a high-risk population. We assessed the epidemiology of severe sepsis in hematopoietic cell transplant patients, describing patient outcomes compared with children with no history of hematopoietic cell transplant. Secondary analysis of the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study, comparing demographics, sepsis etiology, illness severity, organ dysfunction, and sepsis-related treatments in patients with and without hematopoietic cell transplant. The primary outcome was hospital mortality. Multivariable logistic regression models were used to determine adjusted differences in mortality. International; 128 PICUs in 26 countries. Pediatric patients with severe sepsis prospectively identified over a 1-year period. None. In patients with severe sepsis, 37/567 (6.5%) had a history of hematopoietic cell transplant. Compared with patients without hematopoietic cell transplant, hematopoietic cell transplant patients had significantly higher hospital mortality (68% vs 23%; p < 0.001). Hematopoietic cell transplant patients were more likely to have hospital acquired sepsis and had more preexisting renal and hepatic dysfunction than non-hematopoietic cell transplant patients with severe sepsis. History of hematopoietic cell transplant, renal replacement therapy, admission from inpatient floor, and number of organ dysfunctions at severe sepsis recognition were independently associated with hospital mortality in multivariable analysis; hematopoietic cell transplant conferred the highest odds of mortality (odds ratio, 4.00; 95% CI, 1.78-8.98). In secondary analysis of hematopoietic cell transplant patients compared with other immunocompromised patients with severe sepsis, history of hematopoietic cell transplant remained independently associated with hospital mortality (odds ratio, 3.03; 95% CI, 1.11-8.27). In an

  6. Treatment of Pediatric Septic Shock With the Surviving Sepsis Campaign Guidelines and PICU Patient Outcomes.

    PubMed

    Workman, Jennifer K; Ames, Stefanie G; Reeder, Ron W; Korgenski, E Kent; Masotti, Susan M; Bratton, Susan L; Larsen, Gitte Y

    2016-10-01

    The Surviving Sepsis Campaign recommends rapid recognition and treatment of severe sepsis and septic shock. Few reports have evaluated the impact of these recommendations in pediatrics. We sought to determine if outcomes in patients who received initial care compliant with the Surviving Sepsis Campaign time goals differed from those treated more slowly. Single center retrospective cohort study. Emergency department and PICU at an academic children's hospital. Three hundred twenty-one patients treated for septic shock in the emergency department and admitted directly to the PICU. None. The exposure was receipt of emergency department care compliant with the Surviving Sepsis Campaign recommendations (delivery of IV fluids, IV antibiotics, and vasoactive infusions within 1 hr of shock recognition). The primary outcome was development of new or progressive multiple organ dysfunction syndrome. Secondary outcomes included mortality, need for mechanical ventilation or vasoactive medications, and hospital and PICU length of stay. Of the 321 children studied, 117 received Surviving Sepsis Campaign compliant care in the emergency department and 204 did not. New or progressive multiple organ dysfunction syndrome developed in nine of the patients (7.7%) who received Surviving Sepsis Campaign compliant care and 25 (12.3%) who did not (p = 0.26). There were 17 deaths; overall mortality rate was 5%. There were no significant differences between groups in any of the secondary outcomes. Although only 36% of patients met the Surviving Sepsis Campaign guideline recommendation of bundled care within 1 hour of shock recognition, 75% of patients received the recommended interventions in less than 3 hours. Treatment for pediatric septic shock in compliance with the Surviving Sepsis Campaign recommendations was not associated with better outcomes compared with children whose initial therapies in the emergency department were administered more slowly. However, all patients were treated

  7. Profile, risk factors and outcome of acute kidney injury in paediatric acute-on-chronic liver failure.

    PubMed

    Lal, Bikrant B; Alam, Seema; Sood, Vikrant; Rawat, Dinesh; Khanna, Rajeev

    2018-01-11

    There are no studies on acute kidney injury in paediatric acute-on-chronic liver failure. This study was planned with aim to describe the clinical presentation and outcome of acute kidney injury among paediatric acute-on-chronic liver failure patients. Data of all children 1-18 years of age presenting with acute chronic liver failure (Asia pacific association for the study of the liver definition) was reviewed. Acute kidney injury was defined as per Kidney Diseases-Improving Global Outcomes guidelines. Poor outcome was defined as death or need for liver transplant within 3 months of development of acute kidney injury. A total of 84 children with acute-on-chronic liver failure were presented to us in the study period. Acute kidney injury developed in 22.6% of patients with acute-on-chronic liver failure. The median duration from acute-on-chronic liver failure to development of acute kidney injury was 4 weeks (Range: 2-10 weeks). The causes of acute kidney injury were hepatorenal syndrome (31.6%), sepsis (31.6%), nephrotoxic drugs (21%), dehydration (10.5%) and bile pigment related acute tubular necrosis in one patient. On univariate analysis, higher baseline bilirubin, higher international normalized ratio, higher paediatric end stage liver disease, presence of systemic inflammatory response syndrome and presence of spontaneous bacterial peritonitis had significant association with presence of acute kidney injury. On logistic regression analysis, presence of systemic inflammatory response syndrome (adjusted OR: 8.659, 95% CI: 2.18-34.37, P = .002) and higher baseline bilirubin (adjusted OR: 1.07, 95% CI: 1.008-1.135, P = .025) were independently associated with presence of acute kidney injury. Of the patients with acute kidney injury, 5(26.3%) survived with native liver, 10(52.6%) died and 4 (21.1%) underwent liver transplantation. Acute kidney injury developed in 22.6% of children with acute-on-chronic liver failure. Bilirubin more than 17.7 mg/dL and

  8. Superantigens are critical for Staphylococcus aureus Infective endocarditis, sepsis, and acute kidney injury.

    PubMed

    Salgado-Pabón, Wilmara; Breshears, Laura; Spaulding, Adam R; Merriman, Joseph A; Stach, Christopher S; Horswill, Alexander R; Peterson, Marnie L; Schlievert, Patrick M

    2013-08-20

    Infective endocarditis and kidney infections are serious complications of Staphylococcus aureus sepsis. We investigated the role of superantigens (SAgs) in the development of lethal sepsis, infective endocarditis, and kidney infections. SAgs cause toxic shock syndrome, but it is unclear if SAgs contribute to infective endocarditis and kidney infections secondary to sepsis. We show in the methicillin-resistant S. aureus strain MW2 that lethal sepsis, infective endocarditis, and kidney infections in rabbits are critically dependent on high-level SAgs. In contrast, the isogenic strain lacking staphylococcal enterotoxin C (SEC), the major SAg in this strain, is attenuated in virulence, while complementation restores disease production. SAgs' role in infective endocarditis appears to be both superantigenicity and direct endothelial cell stimulation. Maintenance of elevated blood pressure by fluid therapy significantly protects from infective endocarditis, possibly through preventing bacterial accumulation on valves and increased SAg elimination. These data should facilitate better methods to manage these serious illnesses. The Centers for Disease Control and Prevention reported in 2007 that Staphylococcus aureus is the most significant cause of serious infectious diseases in the United States (R. M. Klevens, M. A. Morrison, J. Nadle, S. Petit, K. Gershman, et al., JAMA 298:1763-1771, 2007). Among these infections are sepsis, infective endocarditis, and acute kidney injury. Infective endocarditis occurs in 30 to 60% of patients with S. aureus bacteremia and carries a mortality rate of 40 to 50%. Over the past decades, infective endocarditis outcomes have not improved, and infection rates are steadily increasing (D. H. Bor, S. Woolhandler, R. Nardin, J. Brusch, D. U. Himmelstein, PLoS One 8:e60033, 2013). There is little understanding of the S. aureus virulence factors that are key for infective endocarditis development and kidney abscess formation. We demonstrate that

  9. Clinical review: Extracorporeal blood purification in severe sepsis

    PubMed Central

    Venkataraman, Ramesh; Subramanian, Sanjay; Kellum, John A

    2003-01-01

    Sepsis and septic shock are the leading causes of acute renal failure, multiple organ system dysfunction, and death in the intensive care unit. The pathogenesis of sepsis is complex and comprises a mosaic of interconnected pathways. Several attempts to improve patient outcomes by targeting specific components of this network have been unsuccessful. For these reasons, the ideal immunomodulating strategy would be one that restores immunologic stability rather than blindly inhibiting or stimulating one or another component of this complex network. Hence, the recent focus of immunomodulatory therapy in sepsis has shifted to nonspecific methods of influencing the entire inflammatory response without suppressing it. Here, we discuss the various modalities of extracorporeal blood purification, the existing evidence, and future prospects. PMID:12720560

  10. Pediatric Sepsis

    PubMed Central

    Mathias, Brittany; Mira, Juan; Larson, Shawn D.

    2016-01-01

    Purpose of Review Sepsis is the leading cause of pediatric death worldwide. In the United States alone, there are 72,000 children hospitalized for sepsis annually with a reported mortality rate of 25% and an economic cost estimated to be $4.8 billion. However, it is only recently that the definition and management of pediatric sepsis has been recognized as being distinct from adult sepsis. Recent Findings The definition of pediatric sepsis is currently in a state of evolution and there is a large disconnect between the clinical and research definitions of sepsis which impacts the application of research findings into clinical practice. Despite this, it is the speed of diagnosis and the timely implementation of current treatment guidelines that has been shown to improve outcomes. However, adherence to treatment guidelines is currently low and it is only through the implementation of protocols that improved care and outcomes have been demonstrated. Summary Current management of pediatric sepsis is largely based on adaptations from adult sepsis treatment; however, distinct physiology demands more prospective pediatric trials to tailor management to the pediatric population. Adherence to current and emerging practice guidelines will require that protocolized care pathways become commonplace. PMID:26983000

  11. Pediatric sepsis.

    PubMed

    Mathias, Brittany; Mira, Juan C; Larson, Shawn D

    2016-06-01

    Sepsis is the leading cause of pediatric death worldwide. In the United States alone, there are 72 000 children hospitalized for sepsis annually with a reported mortality rate of 25% and an economic cost estimated to be $4.8 billion. However, it is only recently that the definition and management of pediatric sepsis has been recognized as being distinct from adult sepsis. The definition of pediatric sepsis is currently in a state of evolution, and there is a large disconnect between the clinical and research definitions of sepsis which impacts the application of research findings into clinical practice. Despite this, it is the speed of diagnosis and the timely implementation of current treatment guidelines that has been shown to improve outcomes. However, adherence to treatment guidelines is currently low and it is only through the implementation of protocols that improved care and outcomes have been demonstrated. The current management of pediatric sepsis is largely based on adaptations from adult sepsis treatment; however, distinct physiology demands more prospective pediatric trials to tailor management to the pediatric population. Adherence to current and emerging practice guidelines will require that protocolized care pathways become a commonplace.

  12. Effect of dextran-70 on outcome in severe sepsis; a propensity-score matching study.

    PubMed

    Bentzer, Peter; Broman, Marcus; Kander, Thomas

    2017-07-06

    Albumin may be beneficial in patients with septic shock but availability is limited and cost is high. The objective of the present study was to investigate if the use of dextran-70 in addition to albumin and crystalloids influences organ failure or mortality in patients with severe sepsis or septic shock. Patients with severe sepsis or septic shock (n = 778) admitted to a university hospital intensive care unit (ICU) between 2007 and 2015 that received dextran-70 during resuscitation were propensity score matched to controls at a 1 to 1 ratio. Outcomes were highest acute kidney injury network (AKIN) score the first 10 days in the ICU, use of renal replacement therapy, days alive and free of organ support the first 28 days after admission to ICU, mortality and events of severe bleeding. Outcomes were assessed using paired hypothesis testing. Propensity score matching resulted in two groups of patients with 245 patients in each group. The dextran group received a median volume of 1483 ml (interquartile range, 1000-2000 ml) of dextran-70 during the ICU stay. Highest AKIN score did not differ between the control- and dextran groups (1 (0-3) versus 2 (0-3), p = 0.06). Incidence of renal replacement therapy in the control- and dextran groups was similar (19% versus 22%, p = 0.42, absolute risk reduction -2.9% [95% CI: -9.9 to 4.2]). Days alive and free of renal replacement, vasopressors and mechanical ventilation did not differ between the control- and dextran groups. The 180-day mortality was 50.2% in the control group and 41.6% in the dextran group (p = 0.046, absolute risk reduction 8.6% [-0.2 to 17.4]). Fraction of patients experiencing a severe bleeding in the first 10 days in the ICU did not differ between the control and dextran groups (14% versus 18%, p = 0.21). There is a paucity of high quality data regarding effects of dextran solutions on outcome in sepsis. In the present study, propensity score matching was used in attempt to reduce bias. No

  13. Alkaline phosphatase as a treatment of sepsis-associated acute kidney injury.

    PubMed

    Peters, Esther; van Elsas, Andrea; Heemskerk, Suzanne; Jonk, Luigi; van der Hoeven, Johannes; Arend, Jacques; Masereeuw, Rosalinde; Pickkers, Peter

    2013-01-01

    Currently there are no pharmacological therapies licensed to treat sepsis-associated acute kidney injury (AKI). Considering the high incidence and mortality of sepsis-associated AKI, there is an urgent medical need to develop effective pharmacological interventions. Two phase II clinical trials recently demonstrated beneficial effects of the enzyme alkaline phosphatase (AP). In critically ill patients with sepsis-associated AKI, treatment with AP reduced the urinary excretion of tubular injury biomarkers and plasma markers of inflammation, which was associated with improvement of renal function. The dephosphorylating enzyme, AP, is endogenously present in the renal proximal tubule apical membrane but becomes depleted during ischemia-induced AKI, thereby possibly contributing to further renal damage. The exact mechanism of action of AP in AKI is unknown, but might be related to detoxification of circulating lipopolysaccharide and other proinflammatory mediators that lose their proinflammatory effects after dephosphorylation. Alternatively, tissue damage associated with systemic inflammation might be attenuated by an AP-mediated effect on adenosine metabolism. Adenosine is a signaling molecule that has been shown to protect the body from inflammation-induced tissue injury, which is derived through dephosphorylation of ATP. In this Perspectives article, we discuss the clinical activity of AP and its putative molecular modes of action, and we speculate on its use to treat and possibly prevent sepsis-associated AKI.

  14. Predictive factors of mortality in pediatric patients with acute renal injury associated with sepsis.

    PubMed

    Riyuzo, Marcia C; Silveira, Liciana V de A; Macedo, Célia S; Fioretto, José R

    To evaluate the prognosis factors of children with sepsis and acute kidney injury. This was a retrospective study of children with sepsis and acute kidney injury that were admitted to the pediatric intensive care unit (PICU) of a tertiary hospital. A multivariate analysis was performed to compare risk factors for mortality. Seventy-seven children (47 males) were retrospectively studied, median age of 4 months. Mean length of hospital stay was 7.33±0.16 days, 68.9% of patients received mechanical ventilation, 25.9% had oligo-anuria, and peritoneal dialysis was performed in 42.8%. The pRIFLE criteria were: injury (5.2%) and failure (94.8%), and the staging system criteria were: stage 1 (14.3%), stage 2 (29.9%), and stage 3 (55.8%). The mortality rate was 33.7%. In the multivariate analysis, the risk factors for mortality were PICU length of stay (OR=0.615, SE=0.1377, 95% CI=0.469-0.805, p=0.0004); invasive mechanical ventilation (OR=14.599, SE=1.1178, 95% CI=1.673-133.7564, p=0.0155); need for dialysis (OR=9.714, SE=0.8088, 95% CI=1.990-47.410, p=0.0049), and hypoalbuminemia (OR=10.484, SE=1.1147, 95% CI=1.179-93.200, p=0.035). The risk factors for mortality in children with acute kidney injury were associated with sepsis severity. Copyright © 2016. Published by Elsevier Editora Ltda.

  15. Plasma Neutrophil Gelatinase-Associated Lipocalin diagnosed acute kidney injury in patients with systemic inflammatory disease and sepsis.

    PubMed

    Md Ralib, Azrina; Mat Nor, Mohd Basri; Pickering, John W

    2017-05-01

    Sepsis is the leading cause of intensive care unit (ICU) admission. Plasma Neutrophil Gelatinase Associated-Lipocalin (NGAL) is a promising biomarker for acute kidney injury (AKI) detection; however, it is also increased with inflammation and few studies have been conducted in non-Caucasian populations and/or in developing economies. Therefore, we evaluated plasma NGAL's diagnostic performance in the presence of sepsis and systemic inflammatory response syndrome (SIRS) in a Malaysian ICU cohort. This is a prospective observational study on patients with SIRS. Plasma creatinine (pCr) and NGAL were measured on ICU admission. Patients were classified according to the occurrence of AKI and sepsis. Of 225 patients recruited, 129 (57%) had sepsis of whom 67 (52%) also had AKI. 96 patients (43%) had non-infectious SIRS, of whom 20 (21%) also had AKI. NGAL concentrations were higher in AKI patients within both the sepsis and non-infectious SIRS cohorts (both P < 0.0001). The diagnostic area under curve for AKI was 0.81 (95%CI: 0.74 to 0.87). The optimal cut-off was higher in sepsis compared to non-infectious SIRS patients (454 versus 176 ng/mL). Addition of NGAL to a clinical model comprising age, pCr, medical admission category and SAPS II score increased the mean risk of those with AKI by 4% and reduced the mean risk of those without AKI by 3%. Acute kidney injury is more common with sepsis than non-infectious SIRS. Plasma NGAL was diagnostic of AKI in both subgroups. The optimal cut-off for diagnosing AKI was higher in sepsis than in non-infectious SIRS. Addition of plasma NGAL improved the clinical model used to diagnose AKI. © 2016 Asian Pacific Society of Nephrology.

  16. The outcomes of children with pediatric acute respiratory distress syndrome: proceedings from the Pediatric Acute Lung Injury Consensus Conference.

    PubMed

    Quasney, Michael W; López-Fernández, Yolanda M; Santschi, Miriam; Watson, R Scott

    2015-06-01

    To provide additional details and evidence behind the recommendations for outcomes assessment of patients with pediatric acute respiratory distress syndrome from the Pediatric Acute Lung Injury Consensus Conference. Consensus conference of experts in pediatric acute lung injury. A panel of 27 experts met over the course of 2 years to develop a taxonomy to define pediatric acute respiratory distress syndrome and to make recommendations regarding treatment and research priorities. The outcomes subgroup comprised four experts. When published data were lacking, a modified Delphi approach emphasizing strong professional agreement was used. The Pediatric Acute Lung Injury Consensus Conference experts developed and voted on a total of 151 recommendations addressing the topics related to pediatric acute respiratory distress syndrome, seven of which related to outcomes after pediatric acute respiratory distress syndrome. All seven recommendations had strong agreement. Children with acute respiratory distress syndrome continue to have a high mortality, specifically, in relation to certain comorbidities and etiologies related to pediatric acute respiratory distress syndrome. Comorbid conditions, such as an immunocompromised state, increase the risk of mortality even further. Likewise, certain etiologies, such as non-pulmonary sepsis, also place children at a higher risk of mortality. Significant long-term effects were reported in adult survivors of acute respiratory distress syndrome: diminished lung function and exercise tolerance, reduced quality of life, and diminished neurocognitive function. Little knowledge of long-term outcomes exists in children who survive pediatric acute respiratory distress syndrome. Characterization of the longer term consequences of pediatric acute respiratory distress syndrome in children is vital to help identify opportunities for improved therapeutic and rehabilitative strategies that will lessen the long-term burden of pediatric acute

  17. Baicalin Inhibits Renal Cell Apoptosis and Protects Against Acute Kidney Injury in Pediatric Sepsis

    PubMed Central

    Zhu, Yanping; Fu, Yanxia; Lin, Hairong

    2016-01-01

    Background Pediatric sepsis has high morbidity in children, may lead to acute kidney injury (AKI), and further aggravate the disease. Baicalin is a kind of flavonoid in Scutellaria baicalensis Georgi and has been reported to protect against several diseases, but its roles in septic AKI remain unclear. This study aimed to uncover the effects of baicalin in AKI during pediatric sepsis. Material/Methods Blood urea nitrogen (BUN) and serum creatinine (Cr) levels were detected in 50 pediatric patients, who underwent basic therapy with or without baicalin adjunctive therapy. Mouse sepsis models were constructed by cecal ligation and puncture (CLP) and treated with baicalin intragastrically, after which BUN and Cr examination, TUNEL apoptosis assay, and expression analyses of BAX and BCL2 were performed. Results Baicalin adjunctive therapy significantly decreased BUN and Cr levels in pediatric sepsis patients (P<0.05). CLP led to elevated BUN and Cr levels in the mouse model (P<0.01), indicating kidney injury accompanied by sepsis. Baicalin decreased BUN and Cr levels (P<0.05), and reduced the apoptotic cell percent in the renal tissue (P<0.05) of the CLP model. It inhibited BAX and promoted BCL2 in the renal tissue, which was consistent with cell apoptosis changes. Conclusions Baicalin is capable of suppressing renal cell apoptosis and protecting against AKI in pediatric sepsis. This study provides a potential adjunctive therapy for treating AKI in pediatric sepsis, and further research is necessary to reveal its deeper mechanisms. PMID:28013315

  18. Baicalin Inhibits Renal Cell Apoptosis and Protects Against Acute Kidney Injury in Pediatric Sepsis.

    PubMed

    Zhu, Yanping; Fu, Yanxia; Lin, Hairong

    2016-12-25

    BACKGROUND Pediatric sepsis has high morbidity in children, may lead to acute kidney injury (AKI), and further aggravate the disease. Baicalin is a kind of flavonoid in Scutellaria baicalensis Georgi and has been reported to protect against several diseases, but its roles in septic AKI remain unclear. This study aimed to uncover the effects of baicalin in AKI during pediatric sepsis. MATERIAL AND METHODS Blood urea nitrogen (BUN) and serum creatinine (Cr) levels were detected in 50 pediatric patients, who underwent basic therapy with or without baicalin adjunctive therapy. Mouse sepsis models were constructed by cecal ligation and puncture (CLP) and treated with baicalin intragastrically, after which BUN and Cr examination, TUNEL apoptosis assay, and expression analyses of BAX and BCL2 were performed. RESULTS Baicalin adjunctive therapy significantly decreased BUN and Cr levels in pediatric sepsis patients (P<0.05). CLP led to elevated BUN and Cr levels in the mouse model (P<0.01), indicating kidney injury accompanied by sepsis. Baicalin decreased BUN and Cr levels (P<0.05), and reduced the apoptotic cell percent in the renal tissue (P<0.05) of the CLP model. It inhibited BAX and promoted BCL2 in the renal tissue, which was consistent with cell apoptosis changes. CONCLUSIONS Baicalin is capable of suppressing renal cell apoptosis and protecting against AKI in pediatric sepsis. This study provides a potential adjunctive therapy for treating AKI in pediatric sepsis, and further research is necessary to reveal its deeper mechanisms.

  19. Temporally Distinct Regulation of Pathways Contributing to Cardiac Proteostasis During the Acute and Recovery Phases of Sepsis.

    PubMed

    Crowell, Kristen T; Moreno, Samantha; Steiner, Jennifer L; Coleman, Catherine S; Soybel, David I; Lang, Charles H

    2017-12-13

    Cardiac dysfunction is a common manifestation of sepsis and is associated with early increases in inflammation and decreases in myocardial protein synthesis. However, little is known regarding the molecular mechanisms regulating protein homeostasis during the recovery phase after the removal of the septic nidus. Therefore, the purpose of this study was to investigate diverse signal transduction pathways that regulate myocardial protein synthesis and degradation. Adult male C57BL/6 mice were used to identify potential mechanisms mediating the acute (24 h) effect of cecal ligation and puncture (CLP) as well as long-term changes that manifest during the chronic (10 d) recovery phase. Acutely, sepsis decreased cardiac protein synthesis that was associated with reduced phosphorylation of S6K1/S6 but not 4E-BP1. Sepsis also decreased proteasome activity, although with no change in MuRF1 and atrogin-1 mRNA expression. Sepsis acutely increased apoptosis (increased caspase-3 and PARP cleavage), autophagosome formation (increased LC3B-II), and canonical inflammasome activity (increased NLRP3, TMS1, cleaved caspase-1). In contrast, during the recovery phase, independent of a difference in food consumption, global protein synthesis was increased, the early repression in proteasome activity was restored to basal levels, while stimulation of apoptosis, autophagosome formation and the canonical inflammasome pathway had abated. However, during recovery there was a selective stimulation of the non-canonical inflammasome pathway as evidenced by activation of caspase-11 with cleavage of Gasdermin D. These data demonstrate a temporally distinct homeostatic shift in the cardiac proteostatic response to acute infection and recovery.

  20. Sepsis-induced acute kidney injury in patients with cirrhosis.

    PubMed

    Angeli, Paolo; Tonon, Marta; Pilutti, Chiara; Morando, Filippo; Piano, Salvatore

    2016-01-01

    Acute kidney injury (AKI) is a common and life-threatening complication in patients with cirrhosis. Recently, new criteria for the diagnosis of AKI have been proposed in patients with cirrhosis by the International Club of Ascites. Almost all types of bacterial infections can induce AKI in patients with cirrhosis representing its most common precipitating event. The bacterial infection-induced AKI usually meets the diagnostic criteria of hepatorenal syndrome (HRS). Well in keeping with the "splanchnic arterial vasodilation hypothesis", it has been stated that HRS develops as a consequence of a severe reduction of effective circulating volume related to splanchnic arterial vasodilation and to an inadequate cardiac output. Nevertheless, the role of bacterial infections in precipitating organ failures, including renal failure, is enhanced when their course is characterized by the development of a systemic inflammatory response syndrome (SIRS), thus, when sepsis occurs. Sepsis has been shown to be capable to induce "per se" AKI in animals as well as in patients conditioning also the features of renal damage. This observation suggests that when precipitated by sepsis, the pathogenesis and the clinical course of AKI also in patients with cirrhosis may differentiate to a certain extent from AKI with another or no precipitating factor. The purpose of this review is to describe the features of AKI precipitated by bacterial infections and to highlight whether infection and/or the development of SIRS may influence its clinical course, and, in particular, the response to treatment.

  1. Treatment outcomes after implementation of an adapted WHO protocol for severe sepsis and septic shock in Haiti.

    PubMed

    Papali, Alfred; Eoin West, T; Verceles, Avelino C; Augustin, Marc E; Nathalie Colas, L; Jean-Francois, Carl H; Patel, Devang M; Todd, Nevins W; McCurdy, Michael T

    2017-10-01

    The World Health Organization (WHO) has developed a simplified algorithm specific to resource-limited settings for the treatment of severe sepsis emphasizing early fluids and antibiotics. However, this protocol's clinical effectiveness is unknown. We describe patient outcomes before and after implementation of an adapted WHO severe sepsis protocol at a community hospital in Haiti. Using a before-and-after study design, we retrospectively enrolled 99 adult Emergency Department patients with severe sepsis from January through March 2012. After protocol implementation in January 2014, we compared outcomes to 67 patients with severe sepsis retrospectively enrolled from February to April 2014. We defined sepsis according to the WHO's Integrated Management of Adult Illness guidelines and severe sepsis as sepsis plus organ dysfunction. After protocol implementation, quantity of fluid administered increased and the physician's differential diagnoses more often included sepsis. Patients were more likely to have follow-up vital signs taken sooner, a radiograph performed, and a lactic acid tested. There were no improvements in mortality, time to fluids or antimicrobials. Use of a simplified sepsis protocol based primarily on physiologic parameters allows for substantial improvements in process measures in the care of severely septic patients in a resource-constrained setting. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Association of Gender With Outcome and Host Response in Critically Ill Sepsis Patients.

    PubMed

    van Vught, Lonneke A; Scicluna, Brendon P; Wiewel, Maryse A; Hoogendijk, Arie J; Klein Klouwenberg, Peter M C; Ong, David S Y; Cremer, Olaf L; Horn, Janneke; Franitza, Marek; Toliat, Mohammad R; Nürnberg, Peter; Bonten, Marc M J; Schultz, Marcus J; van der Poll, Tom

    2017-11-01

    To determine the association of gender with the presentation, outcome, and host response in critically ill patients with sepsis. A prospective observational cohort study in the ICU of two tertiary hospitals between January 2011 and January 2014. All consecutive critically ill patients admitted with sepsis, involving 1,815 admissions (1,533 patients). The host response was evaluated on ICU admission by measuring 19 plasma biomarkers reflecting organ systems implicated in sepsis pathogenesis (1,205 admissions) and by applying genome-wide blood gene expression profiling (582 admissions). Sepsis patients admitted to the ICU were more frequently males (61.0%; p < 0.0001 vs females). Baseline characteristics were not different between genders. Urosepsis was more common in females; endocarditis and mediastinitis in men. Disease severity was similar throughout ICU stay. Mortality was similar up to 1 year after ICU admission, and gender was not associated with 90-day mortality in multivariate analyses in a variety of subgroups. Although plasma proteome analyses (including systemic inflammatory and cytokine responses, and activation of coagulation) were largely similar between genders, females showed enhanced endothelial cell activation; this difference was virtually absent in patients more than 55 years old. More than 80% of the leukocyte blood gene expression response was similar in male and female patients. The host response and outcome in male and female sepsis patients requiring ICU admission are largely similar.

  3. Sepsis

    PubMed Central

    Karnatovskaia, Lioudmila V.; Festic, Emir

    2012-01-01

    Sepsis represents a major challenge in medicine. It begins as a systemic response to infection that can affect virtually any organ system, including the central and peripheral nervous systems. Akin to management of stroke, early recognition and treatment of sepsis are just as crucial to a successful outcome. Sepsis can precipitate myasthenic crisis and lead to encephalopathy and critical illness neuropathy. Stroke and traumatic brain injury can predispose a patient to develop sepsis, whereas Guillain-Barré syndrome is similarly not uncommon following infection. This review article will first describe the essential principles of sepsis recognition, pathophysiology, and management and will then briefly cover the neurologic aspects associated with sepsis. Vigilant awareness of the clinical features of sepsis and timeliness of intervention can help clinicians prevent progression of this disease to a multisystem organ failure, which can be difficult to reverse even after the original source of infection is under control. PMID:23983879

  4. Trend and outcome of sepsis in children: A nationwide cohort study.

    PubMed

    Yo, Chia-Hung; Hsu, Tzu-Chun; Gabriel Lee, Meng-Tse; Porta, Lorenzo; Tsou, Po-Yang; Wang, Yu-Hsun; Lee, Wan-Chien; Chen, Szu-Ta; Lee, Chien-Chang

    2018-02-09

    The aim of this study was to investigate the trend of incidence and outcome of paediatric sepsis in a population-based database. Children with sepsis were identified from the 23 million nationwide health insurance claims database of Taiwan. Sepsis was defined by the presence of single ICD-9 code for severe sepsis or septic shock or a combination of ICD-9 codes for infection and organ dysfunction. We analysed the trend of incidence, mortality and source of infection in three age groups: infant (28 days to 1 year), child (1-9 years) and adolescent (10-18 years). From 2002 to 2012, we identified 38 582 paediatric patients with sepsis, of which 21.3% were infants, 52.8% were children and 25.8% were adolescents. The incidence of sepsis was 336.4 cases per 100 000 population in infants, 3.3 times higher than in children (101.5/100 000 cases) and 7.3 times higher than in adolescents (46.2/100 000 cases). While sepsis incidence decreased from 598.0 to 336.4 cases per 100 000 people in the infant population, it remained relatively unchanged in children and adolescents. For 90-day mortality, there were significant decreases in all three age groups (absolute decrease of 5.0% for infants, 3.7% for children and 14.4% for the adolescents). In the infant population, we observed a decrease in the incidence of lower respiratory tract infections, while the incidence of urinary tract infections remained unchanged. The incidence and mortality of sepsis among paediatric patients have decreased substantially between 2002 and 2012, especially among infants. The widespread use of Haemophilus influenzae and pneumococcal vaccines in infants could be a possible explanation. © 2018 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

  5. Appropriate antibiotic therapy improves Ureaplasma sepsis outcome in the neonatal mouse.

    PubMed

    Weisman, Leonard E; Leeming, Angela H; Kong, Lingkun

    2012-11-01

    Ureaplasma causes sepsis in human neonates. Although erythromycin has been the standard treatment, it is not always effective. No published reports have evaluated Ureaplasma sepsis in a neonatal model. We hypothesized that appropriate antibiotic treatment improves Ureaplasma sepsis in a neonatal mouse model. Two ATCC strains and two clinical strains of Ureaplasma were evaluated in vitro for antibiotic minimum inhibitory concentration (MIC). In addition, FVB albino mice pups infected with Ureaplasma were randomly assigned to saline, erythromycin, or azithromycin therapy and survival, quantitative blood culture, and growth were evaluated. MICs ranged from 0.125 to 62.5 µg/ml and 0.25 to 1.0 µg/ml for erythromycin and azithromycin, respectively. The infecting strain and antibiotic selected for treatment appeared to affect survival and bacteremia, but only the infecting strain affected growth. Azithromycin improved survival and bacteremia against each strain, whereas erythromycin was effective against only one of four strains. We have established a neonatal model of Ureaplasma sepsis and observed that treatment outcome is related to infecting strain and antibiotic treatment. We speculate that appropriate antibiotic selection and dosing are required for effective treatment of Ureaplasma sepsis in neonates, and this model could be used to further evaluate these relationships.

  6. Improving Outcomes in Patients With Sepsis.

    PubMed

    Armen, Scott B; Freer, Carol V; Showalter, John W; Crook, Tonya; Whitener, Cynthia J; West, Cheri; Terndrup, Thomas E; Grifasi, Marissa; DeFlitch, Christopher J; Hollenbeak, Christopher S

    2016-01-01

    Sepsis mortality may be improved by early recognition and appropriate treatment based on evidence-based guidelines. An intervention was developed that focused on earlier identification of sepsis, early antimicrobial administration, and an educational program that was disseminated throughout all hospital units and services. There were 1331 patients with sepsis during the intervention period and 1401 patients with sepsis during the control period. After controlling for expected mortality, patients in the intervention period had 30% lower odds of dying (odds ratio = 0.70, 95% confidence interval [CI] = 0.57 to 0.84). They also had 1.07 fewer days on average in the intensive care unit (95% CI = -1.98 to -0.16), 2.15 fewer hospital days (95% CI = -3.45 to -0.86), and incurred on average $1949 less in hospital costs, although the effect on costs was not statistically significant. Continued incremental improvement and sustainment is anticipated through organizational oversight, continued education, and initiation of an automated electronic sepsis alert function. © The Author(s) 2014.

  7. Improving Outcomes in Patients With Sepsis

    PubMed Central

    Armen, Scott B.; Freer, Carol V.; Showalter, John W.; Crook, Tonya; Whitener, Cynthia J.; West, Cheri; Terndrup, Thomas E.; Grifasi, Marissa; DeFlitch, Christopher J.; Hollenbeak, Christopher S.

    2017-01-01

    Sepsis mortality may be improved by early recognition and appropriate treatment based on evidence-based guidelines. An intervention was developed that focused on earlier identification of sepsis, early antimicrobial administration, and an educational program that was disseminated throughout all hospital units and services. There were 1331 patients with sepsis during the intervention period and 1401 patients with sepsis during the control period. After controlling for expected mortality, patients in the intervention period had 30% lower odds of dying (odds ratio = 0.70, 95% confidence interval [CI] = 0.57 to 0.84). They also had 1.07 fewer days on average in the intensive care unit (95% CI = −1.98 to −0.16), 2.15 fewer hospital days (95% CI = −3.45 to −0.86), and incurred on average $1949 less in hospital costs, although the effect on costs was not statistically significant. Continued incremental improvement and sustainment is anticipated through organizational oversight, continued education, and initiation of an automated electronic sepsis alert function. PMID:25216849

  8. Trends in the epidemiology of pediatric severe sepsis*.

    PubMed

    Hartman, Mary E; Linde-Zwirble, Walter T; Angus, Derek C; Watson, R Scott

    2013-09-01

    In the past decade, guidelines have been developed for the early detection and management of severe sepsis in children and neonates. However, severe sepsis continues to be a significant U.S. healthcare problem, accounting for over 720,000 annual hospitalizations. Large-scale epidemiologic studies of severe sepsis continue to be limited, particularly in children. We present data from 1995, 2000, and 2005 in seven U.S. states, examining how case mix, outcome, and resource use for pediatric severe sepsis have changed over time. We constructed a database including all acute-care hospitalizations for children in the seven states. For each case, we extracted data on demographic characteristics; the principal diagnosis, up to six secondary diagnoses, and six procedures as classified by the International Classification of Diseases, 9th Revision, Clinical Modification codes; and in-hospital fatality. We identified patients with severe sepsis using International Classification of Diseases, 9th Revision, Clinical Modification codes for both infection and acute organ failure. Retrospective observational cohort dataset from seven U.S. states from 1995, 2000, and 2005. Children in the U.S. 0-19 years old. None. In 2005, 17,542 children were hospitalized with severe sepsis in the seven states; there was an 81% increase in pediatric severe sepsis cases since 1995 and a 45% increase since 2000. This corresponded to an increase in prevalence from 0.56 to 0.89 cases per 1,000 pediatric population. Between 1995 and 2005, the prevalence of severe sepsis in newborns more than doubled, from 4.5 to 9.7 cases per 1,000 births. The most common infecting organisms in all 3 years were Staphylococcus species. From 1995 to 2005, the case-fatality rate decreased from 10.3% to 8.9%. Case fatality associated with Staphylococcus aureus increased, whereas fatality associated with Streptococcus pneumoniae decreased by 75%. Nationally, there were 75,255 pediatric hospitalizations in 2005 involving

  9. Liver proteomics for therapeutic drug discovery: inhibition of the cyclophilin receptor CD147 attenuates sepsis-induced acute renal failure

    PubMed Central

    Dear, James W.; Leelahavanichkul, Asada; Aponte, Angel; Hu, Xuzhen; Constant, Stephanie L.; Hewitt, Stephen M.; Yuen, Peter S.T.; Star, Robert A.

    2008-01-01

    Objective Sepsis-induced multi-organ failure continues to have a high mortality. The liver is an organ central to the disease pathogenesis. The objective of this study was to identify the liver proteins that change in abundance with sepsis and, therefore, identify new drug targets. Design Proteomic discovery study and drug target validation Setting Research institute laboratory Subjects Three month old C57BL/6 mice Interventions We used a mouse model of sepsis based on cecal ligation and puncture (CLP) but with fluid and antibiotic resuscitation. Liver proteins that changed in abundance were identified by difference in-gel electrophoresis (DIGE). We compared liver proteins from 6 hr post-CLP to sham-operated mice (‘early proteins’) and 24 hr post-CLP with 6 hr post-CLP (‘late proteins’). Proteins that changed in abundance were identified by tandem mass spectrometry. We then inhibited the receptor for one protein and determined the effect on sepsis-induced organ dysfunction. Results The liver proteins that changed in abundance after sepsis had a range of functions such as acute phase proteins, coagulation, ER stress, oxidative stress, apoptosis, mitochondrial proteins and nitric oxide metabolism. We found that cyclophilin increased in abundance after CLP. When the receptor for this protein, CD147, was inhibited sepsis-induced renal dysfunction was reduced. There was also a significant reduction in serum cytokine production when CD147 was inhibited. Conclusion By applying proteomics to a clinically relevant mouse model of sepsis we identified a number of novel proteins that changed in abundance. The inhibition of the receptor for one of these proteins, cyclophilin, attenuated sepsis-induced acute renal failure. The application of proteomics to sepsis research can facilitate the discovery of new therapeutic targets. PMID:17944020

  10. Astilbin alleviates sepsis-induced acute lung injury by inhibiting the expression of macrophage inhibitory factor in rats.

    PubMed

    Zhang, Hong-Bo; Sun, Li-Chao; Zhi, Li-da; Wen, Qian-Kuan; Qi, Zhi-Wei; Yan, Sheng-Tao; Li, Wen; Zhang, Guo-Qiang

    2017-10-01

    Sepsis is a systemic inflammatory response syndrome caused by severe infections. Astilbin is a dihydroflavonol derivative found in many medicinal and food plants with multiple pharmacological functions. To investigate the effects of astilbin on sepsis-induced acute lung injury (ALI), cecal ligation and puncture was performed on rats to establish a sepsis-induced ALI model; these rats were then treated with astilbin at different concentrations. Lung injury scores, including lung wet/dry ratio, protein leakage, myeloperoxidase activity, and inflammatory cell infiltration were determined to evaluate the effects of astilbin on sepsis-induced ALI. We found that astilbin treatment significantly attenuates sepsis-induced lung injury and improves survival rate, lung injury scores, lung wet/dry ratio, protein leakage, myeloperoxidase activity, and inflammatory cell infiltration. Astilbin treatment also dramatically decreased the production of inflammatory cytokines and chemokines in bronchoalveolar lavage fluid. Further, astilbin treatment inhibited the expression and production of macrophage inhibitory factor (MIF), which inhibits the inflammatory response. Collectively, these data suggest that astilbin has a protective effect against sepsis-induced ALI by inhibiting MIF-mediated inflammatory responses. This study provides a molecular basis for astilbin as a new medical treatment for sepsis-induced ALI.

  11. Jack of All Trades: Pleiotropy and the application of Chemically Modified Tetracycline -3 in Sepsis and the Acute Respiratory Distress Syndrome (ARDS)

    PubMed Central

    Roy, Shreyas K.; Kendrick, Daniel; Sadowitz, Benjamin D.; Gatto, Louis; Snyder, Kathleen; Satalin, Joshua M.; Golub, Lorne M.; Nieman, Gary

    2011-01-01

    Sepsis is a disease process that has humbled the medical profession for centuries with its resistance to therapy, relentless mortality, and pathophysiologic complexity. Despite 30 years of aggressive, concerted, well-resourced efforts the biomedical community has been unable to reduce the mortality of sepsis from 30%, nor the mortality of septic shock from greater than 50%. In the last decade only one new drug for sepsis has been brought to the market, drotrecogin alfa-activated (Xigris™), and the success of this drug has been limited by patient safety issues. Clearly a new agent is desperately needed. The advent of recombinant human immune modulators held promise but the outcomes of clinical trials using biologics that target single immune mediators have been disappointing. The complex pathophysiology of the systemic inflammatory response syndrome (SIRS) is self-amplifying and redundant at multiple levels. In this review we argue that perhaps pharmacologic therapy for sepsis will only be successful if it addresses this pathophysiologic complexity; the drug would have to be pleiotropic, working on many components of the inflammatory cascade at once. In this context, therapy that targets any single inflammatory mediator will not adequately address the complexity of SIRS. We propose that Chemically Modified Tetracycline-3, CMT-3 (or COL-3), a non-antimicrobial modified tetracycline with pleiotropic anti-inflammatory properties, is an excellent agent for the management of sepsis and its associated complication of the Acute Respiratory Distress Syndrome (ARDS). The purpose of this review is threefold: 1) to examine the shortcomings of current approaches to treatment of sepsis and ARDS in light of their pathophysiology, 2) to explore the application of COL-3 in ARDS and sepsis, and finally 3) to elucidate the mechanisms of COL-3 that may have potential therapeutic benefit in ARDS and sepsis. PMID:21767646

  12. Effect of aphasia on acute stroke outcomes

    PubMed Central

    Boehme, Amelia K.; Martin-Schild, Sheryl; Marshall, Randolph S.

    2016-01-01

    Objective: To determine the independent effects of aphasia on outcomes during acute stroke admission, controlling for total NIH Stroke Scale (NIHSS) scores and loss of consciousness. Methods: Data from the Tulane Stroke Registry were used from July 2008 to December 2014 for patient demographics, NIHSS scores, length of stay (LOS), complications (sepsis, deep vein thrombosis), and discharge modified Rankin Scale (mRS) score. Aphasia was defined as a score >1 on question 9 on the NIHSS on admission and hemiparesis as >1 on questions 5 or 6. Results: Among 1,847 patients, 866 (46%) had aphasia on admission. Adjusting for NIHSS score and inpatient complications, those with aphasia had a 1.22 day longer LOS than those without aphasia, whereas those with hemiparesis (n = 1,225) did not have any increased LOS compared to those without hemiparesis. Those with aphasia had greater odds of having a complication (odds ratio [OR] 1.44, confidence interval [CI] 1.07–1.93, p = 0.0174) than those without aphasia, which was equivalent to those having hemiparesis (OR 1.47, CI 1.09–1.99, p = 0.0137). Controlling for NIHSS scores, aphasia patients had higher odds of discharge mRS 3–6 (OR 1.42 vs 1.15). Conclusion: Aphasia is independently associated with increased LOS and complications during the acute stroke admission, adding $2.16 billion annually to US acute stroke care. The presence of aphasia was more likely to produce a poor functional outcome than hemiparesis. These data suggest that further research is necessary to determine whether establishing adaptive communication skills can mitigate its consequences in the acute stroke setting. PMID:27765864

  13. Effect of aphasia on acute stroke outcomes.

    PubMed

    Boehme, Amelia K; Martin-Schild, Sheryl; Marshall, Randolph S; Lazar, Ronald M

    2016-11-29

    To determine the independent effects of aphasia on outcomes during acute stroke admission, controlling for total NIH Stroke Scale (NIHSS) scores and loss of consciousness. Data from the Tulane Stroke Registry were used from July 2008 to December 2014 for patient demographics, NIHSS scores, length of stay (LOS), complications (sepsis, deep vein thrombosis), and discharge modified Rankin Scale (mRS) score. Aphasia was defined as a score >1 on question 9 on the NIHSS on admission and hemiparesis as >1 on questions 5 or 6. Among 1,847 patients, 866 (46%) had aphasia on admission. Adjusting for NIHSS score and inpatient complications, those with aphasia had a 1.22 day longer LOS than those without aphasia, whereas those with hemiparesis (n = 1,225) did not have any increased LOS compared to those without hemiparesis. Those with aphasia had greater odds of having a complication (odds ratio [OR] 1.44, confidence interval [CI] 1.07-1.93, p = 0.0174) than those without aphasia, which was equivalent to those having hemiparesis (OR 1.47, CI 1.09-1.99, p = 0.0137). Controlling for NIHSS scores, aphasia patients had higher odds of discharge mRS 3-6 (OR 1.42 vs 1.15). Aphasia is independently associated with increased LOS and complications during the acute stroke admission, adding $2.16 billion annually to US acute stroke care. The presence of aphasia was more likely to produce a poor functional outcome than hemiparesis. These data suggest that further research is necessary to determine whether establishing adaptive communication skills can mitigate its consequences in the acute stroke setting. © 2016 American Academy of Neurology.

  14. Diagnosis and management of sepsis

    NASA Astrophysics Data System (ADS)

    Arifin

    2018-03-01

    Sepsis is the life-threatening condition with organ dysfunction caused by dysregulated host response to the infection. Septic shock is part of sepsis where circulatory abnormalities and cellular metabolism occur. Sepsis and septic shock are still a problem in the world, where one in four people with sepsis will die. As well as any trauma case, acute myocardial infarction, or stroke, early identification and appropriate treatment of sepsis immediately after sepsis will improve the prognosis of the patient. Comprehensive management of septic patients is required, ranging from infection controls that include antibiotic administration and infection source control as well as hemodynamic stabilization that included fluid resuscitation and vasoactive drug delivery.

  15. Potentially modifiable factors contributing to sepsis-associated encephalopathy.

    PubMed

    Sonneville, Romain; de Montmollin, Etienne; Poujade, Julien; Garrouste-Orgeas, Maïté; Souweine, Bertrand; Darmon, Michael; Mariotte, Eric; Argaud, Laurent; Barbier, François; Goldgran-Toledano, Dany; Marcotte, Guillaume; Dumenil, Anne-Sylvie; Jamali, Samir; Lacave, Guillaume; Ruckly, Stéphane; Mourvillier, Bruno; Timsit, Jean-François

    2017-08-01

    Identifying modifiable factors for sepsis-associated encephalopathy may help improve patient care and outcomes. We conducted a retrospective analysis of a prospective multicenter database. Sepsis-associated encephalopathy (SAE) was defined by a score on the Glasgow coma scale (GCS) <15 or when features of delirium were noted. Potentially modifiable risk factors for SAE at ICU admission and its impact on mortality were investigated using multivariate logistic regression analysis and Cox proportional hazard modeling, respectively. We included 2513 patients with sepsis at ICU admission, of whom 1341 (53%) had sepsis-associated encephalopathy. After adjusting for baseline characteristics, site of infection, and type of admission, the following factors remained independently associated with sepsis-associated encephalopathy: acute renal failure [adjusted odds ratio (aOR) = 1.41, 95% confidence interval (CI) 1.19-1.67], hypoglycemia <3 mmol/l (aOR = 2.66, 95% CI 1.27-5.59), hyperglycemia >10 mmol/l (aOR = 1.37, 95% CI 1.09-1.72), hypercapnia >45 mmHg (aOR = 1.91, 95% CI 1.53-2.38), hypernatremia >145 mmol/l (aOR = 2.30, 95% CI 1.48-3.57), and S. aureus (aOR = 1.54, 95% CI 1.05-2.25). Sepsis-associated encephalopathy was associated with higher mortality, higher use of ICU resources, and longer hospital stay. After adjusting for age, comorbidities, year of admission, and non-neurological SOFA score, even mild alteration of mental status (i.e., a score on the GCS of 13-14) remained independently associated with mortality (adjusted hazard ratio = 1.38, 95% CI 1.09-1.76). Acute renal failure and common metabolic disturbances represent potentially modifiable factors contributing to sepsis-associated encephalopathy. However, a true causal relationship has yet to be demonstrated. Our study confirms the prognostic significance of mild alteration of mental status in patients with sepsis.

  16. Fetal optimization during maternal sepsis: relevance and response of the obstetric anesthesiologist.

    PubMed

    Chau, Anthony; Tsen, Lawrence C

    2014-06-01

    In many labor and delivery units, the obstetric anesthesiologist is often responsible for managing and stabilizing the acutely septic parturient. The management of maternal sepsis has been summarized previously; this study will focus on the implications of maternal sepsis on the fetus, and ways to optimize fetal outcomes. Although the complex pathophysiology of sepsis is being better understood, the incidence of maternal severe sepsis and deaths continues to increase. The differential sensitivities of systemic and uterine vasculature to catecholamines during pregnancy and the role of fetal inflammatory responses have recently been further elucidated. Additional investigations on methods of fetal monitoring are needed to assist in early identification of the compromised fetus. Despite decades of research, management of a septic parturient and her fetus, including the most appropriate resuscitation fluids, vasopressors and hemodynamic monitoring systems to maximize maternal and fetal outcomes, remain controversial. In the setting of maternal sepsis, fetal optimization is frequently best accomplished by meeting maternal hemodynamic, oxygenization, and infection treatment goals. Understanding the circulatory and pathophysiologic changes that occur within the uteroplacental unit and fetus is essential to identifying and resolving potential conflicts between maternal and fetal management goals.

  17. Role of acute ethanol exposure and TLR4 in early events of sepsis in a mouse model

    PubMed Central

    Bhatty, Minny; Jan, Basit L; Tan, Wei; Pruett, Stephen B; Nanduri, Bindu

    2011-01-01

    Sepsis is a major cause of death worldwide. The associated risks and mortality are known to significantly increase on exposure to alcohol (chronic or acute). The underlying mechanisms of the association of acute ethanol ingestion and poor prognosis of sepsis are largely unknown. The study described here was designed to determine in detail the role of ethanol and TLR4 in the pathogenesis of the sepsis syndrome. The effects of acute ethanol exposure and TLR4 on bacterial clearance, spleen cell numbers, peritoneal macrophage numbers, and cytokine production were evaluated using wild type and TLR4 hypo-responsive mice treated with ethanol and then challenged with a non pathogenic strain of Escherichia. coli (E. coli). Ethanol treated mice exhibited a decreased clearance of bacteria and produced lesser amounts of most pro-inflammatory cytokines in both strains of mice at two hours after challenge. Neither ethanol treatment nor a hypo-responsive TLR4 had significant effects on the cell numbers in the peritoneal cavity and spleen 2 hours post infection. The suppressive effect of acute ethanol exposure on cytokine and chemokine production was more pronounced in the wild type mice, but the untreated hyporesponsive mice produced less of most cytokines than untreated wild type mice. The major conclusion of this study is that acute ethanol exposure suppresses pro-inflammatory cytokine production and that a hypo-responsive TLR4 (in C3H/HeJ mice) decreases pro-inflammatory cytokine levels but the cytokines and other mediators induced through other receptors are sufficient to ultimately clear the infection but not enough to induce lethal septic shock. In addition, results reported here demonstrate previously unknown effects of acute ethanol exposure on LIF (leukemia inhibitory factor) and eotaxin and provide the first evidence that IL-9 is induced through TLR4 in vivo. PMID:21872420

  18. Pediatric severe sepsis: current trends and outcomes from the Pediatric Health Information Systems database.

    PubMed

    Ruth, Amanda; McCracken, Courtney E; Fortenberry, James D; Hall, Matthew; Simon, Harold K; Hebbar, Kiran B

    2014-11-01

    To 1) describe the characteristics and outcomes over time of PICU patients with severe sepsis within the dedicated U.S. children's hospitals, 2) identify patient subgroups at risk for mortality from pediatric severe sepsis, and 3) describe overall pediatric severe sepsis resource utilization. Retrospective review of a prospectively collected multi-institutional children's hospital database. PICUs in 43 U.S. children's hospitals. PICU patients from birth to younger than 19 years were identified with severe sepsis by modified Angus criteria and International Classification of Diseases, 9th Revision, codes for severe sepsis and septic shock. None. Data from the Pediatric Health Information System database collected by the Children's Hospital Association from 2004 to 2012. Pediatric severe sepsis was defined by 1) International Classification of Diseases, 9th Revision, codes reflecting severe sepsis and septic shock and 2) International Classification of Diseases, 9th Revision, codes of infection and organ dysfunction as defined by modified Angus criteria. From 2004 to 2012, 636,842 patients were identified from 43 hospitals. Pediatric severe sepsis prevalence was 7.7% (49,153) with an associated mortality rate of 14.4%. Age less than 1 year (vs age 10 to < 19) (odds ratio, 1.4), underlying cardiovascular condition (odds ratio, 1.4) and multiple organ dysfunction, conferred higher odds of mortality. Resource burden was significant with median hospital length of stay of 17 days (interquartile range, 8-36 d) and PICU length of stay of 7 days (interquartile range, 2-17 d), with median cost/day of $4,516 and median total hospitalization cost of $77,446. There was a significant increase in the severe sepsis prevalence rate from 6.2% to 7.7% from 2004 to 2012 (p < 0.001) and a significant decrease in mortality from 18.9% to 12.0% (p < 0.001). Center mortality was negatively correlated with prevalence (rs = -0.48) and volume (rs = -0.39) and positively correlated with cost

  19. Myeloperoxidase-derived 2-chlorofatty acids contribute to human sepsis mortality via acute respiratory distress syndrome.

    PubMed

    Meyer, Nuala J; Reilly, John P; Feng, Rui; Christie, Jason D; Hazen, Stanley L; Albert, Carolyn J; Franke, Jacob D; Hartman, Celine L; McHowat, Jane; Ford, David A

    2017-12-07

    Sepsis-associated acute respiratory distress syndrome (ARDS) is characterized by neutrophilic inflammation and poor survival. Since neutrophil myeloperoxidase (MPO) activity leads to increased plasma 2-chlorofatty acid (2-ClFA) levels, we hypothesized that plasma concentrations of 2-ClFAs would associate with ARDS and mortality in subjects with sepsis. In sequential consenting patients with sepsis, free 2-ClFA levels were significantly associated with ARDS, and with 30-day mortality, for each log increase in free 2-chlorostearic acid. Plasma MPO was not associated with either ARDS or 30-day mortality but was correlated with 2-ClFA levels. Addition of plasma 2-ClFA levels to the APACHE III score improved prediction for ARDS. Plasma 2-ClFA levels correlated with plasma levels of angiopoietin-2, E selectin, and soluble thrombomodulin. Endothelial cells treated with 2-ClFA responded with increased adhesion molecule surface expression, increased angiopoietin-2 release, and dose-dependent endothelial permeability. Our results suggest that 2-ClFAs derived from neutrophil MPO-catalyzed oxidation contribute to pulmonary endothelial injury and have prognostic utility in sepsis-associated ARDS.

  20. Methionine Metabolites in Patients With Sepsis.

    PubMed

    Wexler, Orren; Gough, Michael S; Morgan, Mary Anne M; Mack, Cynthia M; Apostolakos, Michael J; Doolin, Kathleen P; Mooney, Robert A; Arning, Erland; Bottiglieri, Teodoro; Pietropaoli, Anthony P

    2018-01-01

    Sepsis is characterized by microvascular dysfunction and thrombophilia. Several methionine metabolites may be relevant to this sepsis pathophysiology. S-adenosylmethionine (SAM) serves as the methyl donor for trans-methylation reactions. S-adenosylhomocysteine (SAH) is the by-product of these reactions and serves as the precursor to homocysteine. Relationships between plasma total homocysteine concentrations (tHcy) and vascular disease and thrombosis are firmly established. We hypothesized that SAM, SAH, and tHcy levels are elevated in patients with sepsis and associated with mortality. This was a combined case-control and prospective cohort study consisting of 109 patients with sepsis and 50 control participants without acute illness. The study was conducted in the medical and surgical intensive care units of the University of Rochester Medical Center. Methionine, SAM, SAH, and tHcy concentrations were compared in patients with sepsis versus control participants and in sepsis survivors versus nonsurvivors. Patients with sepsis had significantly higher plasma SAM and SAH concentrations than control participants (SAM: 164 [107-227] vs73 [59-87 nM], P < .001; SAH: 99 [60-165] vs 35 [28-45] nM, P < .001). In contrast, plasma tHcy concentrations were lower in sepsis patients compared to healthy control participants (4 [2-6]) vs 7 [5-9] μM; P = .04). In multivariable analysis, quartiles of SAM, SAH, and tHcy were independently associated with sepsis ( P = .006, P = .05, and P < .001, respectively). Sepsis nonsurvivors had significantly higher plasma SAM and SAH concentrations than survivors (SAM: 223 [125-260] vs 136 [96-187] nM; P = .01; SAH: 139 [81-197] vs 86 [55-130] nM, P = .006). Plasma tHcy levels were similar in survivors vs nonsurvivors. The associations between SAM or SAH and hospital mortality were no longer significant after adjusting for renal dysfunction. Methionine metabolite concentrations are abnormal in sepsis and linked with clinical outcomes

  1. Decreased ADAMTS 13 Activity is Associated With Disease Severity and Outcome in Pediatric Severe Sepsis

    PubMed Central

    Lin, Jainn-Jim; Chan, Oi-Wa; Hsiao, Hsiang-Ju; Wang, Yu; Hsia, Shao-Hsuan; Chiu, Cheng-Hsun

    2016-01-01

    Abstract Decreased ADAMTS 13 activity has been reported in severe sepsis and in sepsis-induced disseminated intravascular coagulation. This study aimed to investigate the role of ADAMTS 13 in different pediatric sepsis syndromes and evaluate its relationship with disease severity and outcome. We prospectively collected cases of sepsis treated in a pediatric intensive care unit, between July 2012 and June 2014 in Chang Gung Children's Hospital in Taoyuan, Taiwan. Clinical characteristics and ADAMTS-13 activity were analyzed. All sepsis syndromes had decreased ADAMTS 13 activity on days 1 and 3 of admission compared to healthy controls. Patients with septic shock had significantly decreased ADAMTS 13 activity on days 1 and 3 compared to those with sepsis and severe sepsis. There was a significant negative correlation between ADAMTS 13 activity on day 1 and day 1 PRISM-II, PELOD, P-MOD, and DIC scores. Patients with mortality had significantly decreased ADAMTS 13 activity on day 1 than survivors, but not on day 3. Different pediatric sepsis syndromes have varying degrees of decreased ADAMTS 13 activity. ADAMTS 13 activity is strongly negatively correlated with disease severity of pediatric sepsis syndrome, whereas decreased ADAMTS 13 activity on day 1 is associated with increased risk of mortality. PMID:27100422

  2. Decreased ADAMTS 13 Activity is Associated With Disease Severity and Outcome in Pediatric Severe Sepsis.

    PubMed

    Lin, Jainn-Jim; Chan, Oi-Wa; Hsiao, Hsiang-Ju; Wang, Yu; Hsia, Shao-Hsuan; Chiu, Cheng-Hsun

    2016-04-01

    Decreased ADAMTS 13 activity has been reported in severe sepsis and in sepsis-induced disseminated intravascular coagulation. This study aimed to investigate the role of ADAMTS 13 in different pediatric sepsis syndromes and evaluate its relationship with disease severity and outcome. We prospectively collected cases of sepsis treated in a pediatric intensive care unit, between July 2012 and June 2014 in Chang Gung Children's Hospital in Taoyuan, Taiwan. Clinical characteristics and ADAMTS-13 activity were analyzed. All sepsis syndromes had decreased ADAMTS 13 activity on days 1 and 3 of admission compared to healthy controls. Patients with septic shock had significantly decreased ADAMTS 13 activity on days 1 and 3 compared to those with sepsis and severe sepsis. There was a significant negative correlation between ADAMTS 13 activity on day 1 and day 1 PRISM-II, PELOD, P-MOD, and DIC scores. Patients with mortality had significantly decreased ADAMTS 13 activity on day 1 than survivors, but not on day 3. Different pediatric sepsis syndromes have varying degrees of decreased ADAMTS 13 activity. ADAMTS 13 activity is strongly negatively correlated with disease severity of pediatric sepsis syndrome, whereas decreased ADAMTS 13 activity on day 1 is associated with increased risk of mortality.

  3. Defining and measuring suspicion of sepsis: an analysis of routine data.

    PubMed

    Inada-Kim, Matthew; Page, Bethan; Maqsood, Imran; Vincent, Charles

    2017-06-09

    To define the target population of patients who have suspicion of sepsis (SOS) and to provide a basis for assessing the burden of SOS, and the evaluation of sepsis guidelines and improvement programmes. Retrospective analysis of routinely collected hospital administrative data. Secondary care, eight National Health Service (NHS) Acute Trusts. Hospital Episode Statistics data for 2013-2014 was used to identify all admissions with a primary diagnosis listed in the 'suspicion of sepsis' (SOS) coding set. The SOS coding set consists of all bacterial infective diagnoses. We identified 47 475 admissions with SOS, equivalent to a rate of 17 admissions per 1000 adults in a given year. The mortality for this group was 7.2% during their acute hospital admission. Urinary tract infection was the most common diagnosis and lobar pneumonia was associated with the most deaths. A short list of 10 diagnoses can account for 85% of the deaths. Patients with SOS can be identified in routine administrative data. It is these patients who should be screened for sepsis and are the target of programmes to improve the detection and treatment of sepsis. The effectiveness of such programmes can be evaluated by examining the outcomes of patients with SOS. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. A prospective, observational registry of patients with severe sepsis: the Canadian Sepsis Treatment and Response Registry.

    PubMed

    Martin, Claudio M; Priestap, Fran; Fisher, Harold; Fowler, Robert A; Heyland, Daren K; Keenan, Sean P; Longo, Christopher J; Morrison, Teresa; Bentley, Diane; Antman, Neil

    2009-01-01

    To determine the location of acquisition, timing, and outcomes associated with severe sepsis in community and teaching hospital critical care units. Prospective, observational study. Twelve Canadian community and teaching hospital critical care units. All patients admitted between March 17, 2003, and November 30, 2004 to the study critical care units with at least a 24-hr length of stay or severe sepsis identified during the first 24 hrs. Daily monitoring for severe sepsis. We recorded data describing characteristics of patients, infections, systemic responses, and organ dysfunction. Severe sepsis occurred in 1238 patients (overall rate, 19.0%; range, 8.2%-35.3%). Hospital mortality was 38.1% (95% confidence interval [CI]: 35.4-40.8). Median intensive care unit length of stay was 10.3 days (interquartile range: 5.5, 17.9). Variables associated with mortality in multivariable analysis included age (odds ratio [OR] by decade 1.50; 95% CI: 1.36-1.65), acquisition location of severe sepsis (with community as the reference-hospital [OR: 1.69; CI: 1.16-2.46], early intensive care unit [OR: 2.15; CI: 1.42-3.25], late intensive care unit [OR: 2.65; CI: 1.82-3.87]), late intensive care unit (OR: 2.65; CI: 1.82-3.87), any comorbidity (OR: 1.42; CI: 1.04-1.93), chronic renal failure (OR: 2.03; CI: 1.10-3.76), oliguria (OR: 1.34; CI: 1.02-1.76), thrombocytopenia (OR: 2.12; CI: 1.43-3.13), metabolic acidosis (OR: 1.54; CI: 1.13-2.10), Multiple Organ Dysfunction Score (OR: 1.15; CI: 1.09-1.21) and Acute Physiology and Chronic Health Evaluation II predicted risk (OR: 3.75; CI: 2.08-6.76). These data confirm that sepsis is common and has high mortality in general intensive care unit populations. Our results can inform healthcare system planning and clinical study designs. Modifiable variables associated with worse outcomes, such as nosocomial infection (hospital acquisition), and metabolic acidosis indicate potential targets for quality improvement initiatives that could decrease

  5. Enrichment of the lung microbiome with gut bacteria in sepsis and the acute respiratory distress syndrome.

    PubMed

    Dickson, Robert P; Singer, Benjamin H; Newstead, Michael W; Falkowski, Nicole R; Erb-Downward, John R; Standiford, Theodore J; Huffnagle, Gary B

    2016-07-18

    Sepsis and the acute respiratory distress syndrome (ARDS) are major causes of mortality without targeted therapies. Although many experimental and clinical observations have implicated gut microbiota in the pathogenesis of these diseases, culture-based studies have failed to demonstrate translocation of bacteria to the lungs in critically ill patients. Here, we report culture-independent evidence that the lung microbiome is enriched with gut bacteria both in a murine model of sepsis and in humans with established ARDS. Following experimental sepsis, lung communities were dominated by viable gut-associated bacteria. Ecological analysis identified the lower gastrointestinal tract, rather than the upper respiratory tract, as the likely source community of post-sepsis lung bacteria. In bronchoalveolar lavage fluid from humans with ARDS, gut-specific bacteria (Bacteroides spp.) were common and abundant, undetected by culture and correlated with the intensity of systemic inflammation. Alveolar TNF-α, a key mediator of alveolar inflammation in ARDS, was significantly correlated with altered lung microbiota. Our results demonstrate that the lung microbiome is enriched with gut-associated bacteria in sepsis and ARDS, potentially representing a shared mechanism of pathogenesis in these common and lethal diseases.

  6. THE ENDOTHELIUM IN SEPSIS

    PubMed Central

    Ince, Can; Mayeux, Philip R.; Nguyen, Trung; Gomez, Hernando; Kellum, John A.; Ospina-Tascón, Gustavo A.; Hernandez, Glenn; Murray, Patrick; De Backer, Daniel

    2017-01-01

    Sepsis affects practically all aspects of endothelial cell (EC) function and is thought to be the key factor in the progression from sepsis to organ failure. Endothelial functions affected by sepsis include vasoregulation, barrier function, inflammation, and hemostasis. These are among other mechanisms often mediated by glycocalyx shedding, such as abnormal nitric oxide metabolism, up-regulation of reactive oxygen species generation due to down-regulation of endothelial-associated antioxidant defenses, transcellular communication, proteases, exposure of adhesion molecules, and activation of tissue factor. This review covers current insight in EC-associated hemostatic responses to sepsis and the EC response to inflammation. The endothelial cell lining is highly heterogeneous between different organ systems and consequently also in its response to sepsis. In this context, we discuss the response of the endothelial cell lining to sepsis in the kidney, liver, and lung. Finally, we discuss evidence as to whether the EC response to sepsis is adaptive or maladaptive. This study is a result of an Acute Dialysis Quality Initiative XIV Sepsis Workgroup meeting held in Bogota, Columbia, between October 12 and 15, 2014. PMID:26871664

  7. The potential of alkaline phosphatase as a treatment for sepsis-associated acute kidney injury.

    PubMed

    Peters, Esther; Masereeuw, Rosalinde; Pickkers, Peter

    2014-01-01

    Sepsis-associated acute kidney injury (AKI) is associated with a high attributable mortality and an increased risk of developing chronic kidney failure in survivors. As a successful therapy is, as yet, unavailable, a pharmacological treatment option is clearly warranted. Recently, two small phase II clinical trials demonstrated beneficial renal effects of bovine-derived alkaline phosphatase administration in critically ill patients with sepsis-associated AKI. The rationale behind the renal protective effects remains to be fully elucidated, but is likely to be related to dephosphorylation and thereby detoxification of detrimental molecules involved in the pathogenesis of sepsis-associated AKI. A potent candidate target molecule might be endotoxin (lipopolysaccharide) from the cell wall of Gram-negative bacteria, which is associated with the development of sepsis and becomes nontoxic after being dephosphorylated by alkaline phosphatase. Another target of alkaline phosphatase could be adenosine triphosphate, a proinflammatory mediator released during cellular stress, which can be converted by alkaline phosphatase into the tissue-protective and anti-inflammatory molecule adenosine. Human recombinant alkaline phosphatase, a recently developed replacement for bovine-derived alkaline phosphatase, has shown promising results in the preclinical phase. As its safety and tolerability were recently confirmed in a phase I clinical trial, the renal protective effect of human recombinant alkaline phosphatase in sepsis-associated AKI shall be investigated in a multicenter phase II clinical trial starting at the end of this year. 2014 S. Karger AG, Basel.

  8. Construction and management of ARDS/sepsis registry with REDCap.

    PubMed

    Pang, Xiaoqing; Kozlowski, Natascha; Wu, Sulong; Jiang, Mei; Huang, Yongbo; Mao, Pu; Liu, Xiaoqing; He, Weiqun; Huang, Chaoyi; Li, Yimin; Zhang, Haibo

    2014-09-01

    The study aimed to construct and manage an acute respiratory distress syndrome (ARDS)/sepsis registry that can be used for data warehousing and clinical research. The workflow methodology and software solution of research electronic data capture (REDCap) was used to construct the ARDS/sepsis registry. Clinical data from ARDS and sepsis patients registered to the intensive care unit (ICU) of our hospital formed the registry. These data were converted to the electronic case report form (eCRF) format used in REDCap by trained medical staff. Data validation, quality control, and database management were conducted to ensure data integrity. The clinical data of 67 patients registered to the ICU between June 2013 and December 2013 were analyzed. Of the 67 patients, 45 (67.2%) were classified as sepsis, 14 (20.9%) as ARDS, and eight (11.9%) as sepsis-associated ARDS. The patients' information, comprising demographic characteristics, medical history, clinical interventions, daily assessment, clinical outcome, and follow-up data, was properly managed and safely stored in the ARDS/sepsis registry. Data efficiency was guaranteed by performing data collection and data entry twice weekly and every two weeks, respectively. The ARDS/sepsis database that we constructed and manage with REDCap in the ICU can provide a solid foundation for translational research on the clinical data of interest, and a model for development of other medical registries in the future.

  9. Osthole protects sepsis-induced acute kidney injury via down-regulating NF-κB signal pathway

    PubMed Central

    Qu, Hong-lin; Zhang, Yue-juan; Wang, Xue-kai; Fan, Hua-Ying

    2017-01-01

    BACKGROUND AND PURPOSE As a natural coumarin derivative from the Cnidium monnieri(L)Cusson fruit, osthole consists of 7-methoxy-8-isopentenoxy-coumarin. The purpose of this research is to study the mechanism and effect of osthole on sepsis-induced acute kidney injury. EXPERIMENTAL APPROACH The protective effect of osthole on mouse macrophage RAW 264.7 and HK-2 cells induced by LPS in vitro and on acute kidney injury model induced by sepsis and established by puncture and cecal ligation (CLP) in vivo were tested. KEY RESULTS Osthole (20, 40 mg·kg−1) group can greatly attenuate the changes of the score and kidney histopathology damage and enhance the survival time of septic mice. After the CLP surgery, degrees of SCr and BUN related to kidney injury were upregulated. The concentrations of SCr and BUN can be greatly reduced by treatment with osthole. Furthermore, osthole could increase bacterial killing activity and phagocytic activities of macrophages impaired after CLP partly and attenuate blood bacterial counts and leukocyte infiltration markedly. Furthermore, osthole can suppress NF-κB signal pathway through the inhibition of the nuclear translocation by regulating phosphorylation of IκBα and IKKβ and hinder the production of chemoattractant (MCP-1 and IL-8) and proinflammatory cytokines (TNF-α, IL-1β and IL-6). CONCLUSION AND IMPLICATIONS Mainly because of its immunomodulatory properties and anti-inflammatory activity, which might be closely associated with suppression of the stimulation of the NF-κB signal pathway, osthole has protective effect on sepsis-induced kidney injury. It can be seen from such evidence that osthole can be potentially applied in the treatment of acute kidney injury. PMID:27902475

  10. Osthole protects sepsis-induced acute kidney injury via down-regulating NF-κB signal pathway.

    PubMed

    Yu, Chen; Li, Peng; Qi, Dong; Wang, Lei; Qu, Hong-Lin; Zhang, Yue-Juan; Wang, Xue-Kai; Fan, Hua-Ying

    2017-01-17

    As a natural coumarin derivative from the Cnidium monnieri(L)Cusson fruit, osthole consists of 7-methoxy-8-isopentenoxy-coumarin. The purpose of this research is to study the mechanism and effect of osthole on sepsis-induced acute kidney injury. The protective effect of osthole on mouse macrophage RAW 264.7 and HK-2 cells induced by LPS in vitro and on acute kidney injury model induced by sepsis and established by puncture and cecal ligation (CLP) in vivo were tested. Osthole (20, 40 mg·kg-1) group can greatly attenuate the changes of the score and kidney histopathology damage and enhance the survival time of septic mice. After the CLP surgery, degrees of SCr and BUN related to kidney injury were upregulated. The concentrations of SCr and BUN can be greatly reduced by treatment with osthole. Furthermore, osthole could increase bacterial killing activity and phagocytic activities of macrophages impaired after CLP partly and attenuate blood bacterial counts and leukocyte infiltration markedly. Furthermore, osthole can suppress NF-κB signal pathway through the inhibition of the nuclear translocation by regulating phosphorylation of IκBα and IKKβ and hinder the production of chemoattractant (MCP-1 and IL-8) and proinflammatory cytokines (TNF-α, IL-1β and IL-6). Mainly because of its immunomodulatory properties and anti-inflammatory activity, which might be closely associated with suppression of the stimulation of the NF-κB signal pathway, osthole has protective effect on sepsis-induced kidney injury. It can be seen from such evidence that osthole can be potentially applied in the treatment of acute kidney injury.

  11. Inadequate vitamin D levels are associated with culture positive sepsis and poor outcomes in paediatric intensive care.

    PubMed

    Onwuneme, Chike; Carroll, Aoife; Doherty, Dermot; Bruell, Heike; Segurado, Ricardo; Kilbane, Mark; Murphy, Nuala; McKenna, Malachi J; Molloy, Eleanor J

    2015-10-01

    This study aimed to assess vitamin D status, and its determinants, in paediatric patients with suspected sepsis who were admitted to a paediatric intensive care unit (PICU). We also investigated the association between vitamin D status and clinical outcomes. Serum 25-hydroxy vitamin D (25OHD) and clinical determinants were prospectively assessed in children with suspected sepsis (<12 years old) admitted to the PICU. The relationship between 25OHD and clinical outcomes was evaluated. Vitamin D status was also assessed in control children of a similar age. We enrolled 120 children with suspected sepsis admitted to the PICU and 30 paediatric controls. 25OHD was <50 nmol/L in 59% of the children admitted to the PICU and 25OHD was lower than in the controls (47 ± 29 vs 66 ± 26 nmol/L, p < 0.001). After adjusting for potential confounders, 25OHD was strongly associated with culture positive sepsis (p < 0.001), the paediatric index of mortality (p = 0.026) and the duration of mechanical ventilation (p = 0.008). There was a negative correlation between 25OHD and C-reactive protein (CRP): each 0.1% decrease in 25OHD increased CRP (p = 0.04). Children admitted to the PICU with suspected sepsis had lower 25OHD than controls and inadequate 25OHD status was associated with confirmed sepsis and poor outcomes. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  12. Validation of the Sepsis Severity Score Compared with Updated Severity Scores in Predicting Hospital Mortality in Sepsis Patients.

    PubMed

    Khwannimit, Bodin; Bhurayanontachai, Rungsun; Vattanavanit, Veerapong

    2017-06-01

    Recently, the Sepsis Severity Score (SSS) was constructed to predict mortality in sepsis patients. The aim of this study was to compare performance of the SSS with the Acute Physiology and Chronic Health Evaluation (APACHE) II-IV, Simplified Acute Physiology Score (SAPS) II, and SAPS 3 scores in predicting hospital outcome in sepsis patients. A retroprospective analysis was conducted in the medical intensive care unit of a tertiary university hospital. A total of 913 patients were enrolled; 476 of these patients (52.1%) had septic shock. The median SSS was 80 (range 20-137). The SSS presented good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.892. However, the AUC of the SSS did not differ significantly from that of APACHE II (P = 0.07), SAPS II (P = 0.06), and SAPS 3 (P = 0.11). The APACHE IV score showed the best discrimination with an AUC of 0.948 and the overall performance by a Brier score of 0.096. The AUC of the APACHE IV score was statistically greater than the SSS, APACHE II, SAPS II, and SAPS 3 (P <0.0001 for all) and APACHE III (P = 0.0002). The calibration of all scores was poor with the Hosmer-Lemeshow goodness-of-fit H test <0.05. The SSS provided as good discrimination as the APACHE II, SAPS II, and SAPS 3 scores. However, the APACHE IV score had the best discrimination and overall performance in our sepsis patients. The SSS needs to be adapted and modified with new parameters to improve its performance.

  13. Congenital and nosocomial sepsis in infants born in a regional perinatal unit: cause, outcome, and white blood cell response.

    PubMed

    Ohlsson, A; Vearncombe, M

    1987-02-01

    The incidence, cause, and outcome of sepsis and the white blood cell response were studied in 6315 infants born in a regional perinatal unit. The incidence of neonatal sepsis was 6.5 per 1000 live births. Congenital sepsis (12 cases) was overwhelming, with associated maternal infection (92%), neutropenia (75%), and high rate of mortality (50%). The most common organism was Escherichia coli (58%). Gestational age and birth weight were similar in survivors and nonsurvivors. There was a strong correlation between total white blood cell count and both mature and immature neutrophil counts in survivors but this correlation decreased substantially in neonates that died. Analysis of variance indicated that the means for polymorphonuclear leukocyte and immature neutrophil counts were significantly higher in survivors. Nosocomial sepsis (38 cases) occurred in premature low birth weight infants receiving invasive, intensive care. The most common organism was Staphylococcus epidermidis (76%). Total white blood cell, polymorphonuclear leukocyte, and immature neutrophil counts rose significantly in response to sepsis. None died. Prevention of congenital sepsis requires methods to detect early maternal-fetal infection. Providing granulocytes to neutropenic neonates with congenital sepsis might improve outcome.

  14. Liver - guardian, modifier and target of sepsis.

    PubMed

    Strnad, Pavel; Tacke, Frank; Koch, Alexander; Trautwein, Christian

    2017-01-01

    Sepsis and septic shock are characterized by life-threatening organ dysfunction caused by a dysregulated host response to infection. The liver has a central role during sepsis, and is essential to the regulation of immune defence during systemic infections by mechanisms such as bacterial clearance, acute-phase protein or cytokine production and metabolic adaptation to inflammation. However, the liver is also a target for sepsis-related injury, including hypoxic hepatitis due to ischaemia and shock, cholestasis due to altered bile metabolism, hepatocellular injury due to drug toxicity or overwhelming inflammation, as well as distinct pathologies such as secondary sclerosing cholangitis in critically ill patients. Hence, hepatic dysfunction substantially impairs the prognosis of sepsis and serves as a powerful independent predictor of mortality in the intensive care unit. Sepsis is particularly problematic in patients with liver cirrhosis (who experience increased bacterial translocation from the gut and impaired microbial defence) as it can trigger acute-on-chronic liver failure - a syndrome with high short-term mortality. Here, we review the importance of the liver as a guardian, modifier and target of sepsis, the factors that contribute to sepsis in patients with liver cirrhosis and new therapeutic strategies.

  15. Sepsis and septic shock

    PubMed Central

    Hotchkiss, Richard S.; Moldawer, Lyle L.; Opal, Steven M.; Reinhart, Konrad; Turnbull, Isaiah R.; Vincent, Jean-Louis

    2017-01-01

    For more than two decades, sepsis was defined as a microbial infection that produces fever (or hypothermia), tachycardia, tachypnoea and blood leukocyte changes. Sepsis is now increasingly being considered a dysregulated systemic inflammatory and immune response to microbial invasion that produces organ injury for which mortality rates are declining to 15–25%. Septic shock remains defined as sepsis with hyperlactataemia and concurrent hypotension requiring vasopressor therapy, with in-hospital mortality rates approaching 30–50%. With earlier recognition and more compliance to best practices, sepsis has become less of an immediate life-threatening disorder and more of a long-term chronic critical illness, often associated with prolonged inflammation, immune suppression, organ injury and lean tissue wasting. Furthermore, patients who survive sepsis have continuing risk of mortality after discharge, as well as long-term cognitive and functional deficits. Earlier recognition and improved implementation of best practices have reduced in-hospital mortality, but results from the use of immunomodulatory agents to date have been disappointing. Similarly, no biomarker can definitely diagnose sepsis or predict its clinical outcome. Because of its complexity, improvements in sepsis outcomes are likely to continue to be slow and incremental. PMID:28117397

  16. New-Onset Heart Failure and Mortality in Hospital Survivors of Sepsis-Related Left Ventricular Dysfunction.

    PubMed

    Vallabhajosyula, Saraschandra; Jentzer, Jacob C; Geske, Jeffrey B; Kumar, Mukesh; Sakhuja, Ankit; Singhal, Akhil; Poterucha, Joseph T; Kashani, Kianoush; Murphy, Joseph G; Gajic, Ognjen; Kashyap, Rahul

    2018-02-01

    The association between new-onset left ventricular (LV) dysfunction during sepsis with long-term heart failure outcomes is lesser understood. Retrospective cohort study of all adult patients with severe sepsis and septic shock between 2007 and 2014 who underwent echocardiography within 72 h of admission to the intensive care unit. Patients with prior heart failure, LV dysfunction, and structural heart disease were excluded. LV systolic dysfunction was defined as LV ejection fraction <50% and LV diastolic dysfunction as ≥grade II. Primary composite outcome included new hospitalization for acute decompensated heart failure and all-cause mortality at 2-year follow-up. Secondary outcomes included persistent LV dysfunction, and hospital mortality and length of stay. During this 8-year period, 434 patients with 206 (48%) patients having LV dysfunction were included. The two groups had similar baseline characteristics, but those with LV dysfunction had worse function as demonstrated by worse LV ejection fraction, cardiac index, and LV diastolic dysfunction. In the 331 hospital survivors, new-onset acute decompensated heart failure hospitalization did not differ between the two cohorts (15% vs. 11%). The primary composite outcome was comparable at 2-year follow-up between the groups with and without LV dysfunction (P = 0.24). Persistent LV dysfunction was noted in 28% hospital survivors on follow-up echocardiography. Other secondary outcomes were similar between the two groups. In patients with severe sepsis and septic shock, the presence of new-onset LV dysfunction did not increase the risk of long-term adverse heart failure outcomes.

  17. Urgent care in gynaecology: resuscitation and management of sepsis and acute blood loss.

    PubMed

    Fischerova, Daniela

    2009-10-01

    Sepsis and/or acute blood loss can be encoutered as an emergency condition in gynaecology, especially in women with ectopic pregnancy/miscarriage, acute pelvic inflammatory disease (PID)/tuboovarian abscesses, post-puerperal sepsis/haemorrhage and even in postoperative scenarios. If underestimated or suboptimally treated, both can lead to an inadequate tissue perfusion (defined as shock) and the development of multi-organ failure. Morbidity and mortality after development of one of the shock syndromes (septic or haemorrhagic) correlates directly with the duration and severity of the malperfusion. The patient's prognosis depends on a prompt diagnosis of the presence of shock and immediate resuscitation to predefined physiological end-points, often before the cause of the shock has been identified. In septic shock, hypotension is primarily treated with fluid administration and eventually vasopressors, if required, in order to improve the circulation. Timely administration of antibiotics, control of infectious foci, appropriate use of corticoids and recombinant human activated protein C, tight glucose control, prophylaxis of deep vein thrombosis and stress ulcer prevention complete the therapy of septic shock. In haemorrhagic shock, the treatment primarily involves controlling haemorrhage, reversal of possible coagulopathy and administration of sufficient volumes of fluids and blood products to restore normal tissue perfusion.

  18. Physical exercise induces specific adaptations resulting in reduced organ injury and mortality during severe polymicrobial sepsis.

    PubMed

    Sossdorf, Maik; Fischer, Jacqueline; Meyer, Stefan; Dahlke, Katja; Wissuwa, Bianka; Seidel, Carolin; Schrepper, Andrea; Bockmeyer, Clemens L; Lupp, Amelie; Neugebauer, Sophie; Schmerler, Diana; Rödel, Jürgen; Claus, Ralf A; Otto, Gordon P

    2013-10-01

    High physical activity levels are associated with wide-ranging health benefits, disease prevention, and longevity. In the present study, we examined the impact of regular physical exercise on the severity of organ injury and survival probability, as well as characteristics of the systemic immune and metabolic response during severe polymicrobial sepsis. Animal study. University laboratory. Male C57BL/6N mice. Mice were trained for 6 weeks by treadmill and voluntary wheel running or housed normally. Polymicrobial sepsis in mice was induced by injection of fecal slurry. Subsequently, mice were randomized into the following groups: healthy controls, 6 hours postsepsis, and 24 hours postsepsis. Blood and organ samples were collected and investigated by measuring clinical chemistry variables, cytokines, plasma metabolites, and bacterial clearance. Organ morphology and damage were characterized by histological staining. Physical exercise improved survival and the ability of bacterial clearance in blood and organs. The release of pro- and anti-inflammatory cytokines, including interleukin-6 and interleukin-10, was diminished in trained compared to untrained mice during sepsis. The sepsis-associated acute kidney tubular damage was less pronounced in pretrained animals. By metabolic profiling and regression analysis, we detected lysophosphatidylcholine 14:0, tryptophan, as well as pimelylcarnitine linked with levels of neutrophil gelatinase-associated lipocalin representing acute tubular injury (corrected R=0.910; p<0.001). We identified plasma lysophosphatidylcholine 16:0, lysophosphatidylcholine 17:0, and lysophosphatidylcholine 18:0 as significant metabolites discriminating between trained and untrained mice during sepsis. Regular physical exercise reduces sepsis-associated acute kidney injury and death. As a specific mechanism of exercise-induced adaptation, we identified various lysophosphatidylcholines that might function as surrogate for improved outcome in sepsis.

  19. Defining sepsis on the wards: results of a multi-centre point-prevalence study comparing two sepsis definitions.

    PubMed

    Szakmany, T; Pugh, R; Kopczynska, M; Lundin, R M; Sharif, B; Morgan, P; Ellis, G; Abreu, J; Kulikouskaya, S; Bashir, K; Galloway, L; Al-Hassan, H; Grother, T; McNulty, P; Seal, S T; Cains, A; Vreugdenhil, M; Abdimalik, M; Dennehey, N; Evans, G; Whitaker, J; Beasant, E; Hall, C; Lazarou, M; Vanderpump, C V; Harding, K; Duffy, L; Guerrier Sadler, A; Keeling, R; Banks, C; Ng, S W Y; Heng, S Y; Thomas, D; Puw, E W; Otahal, I; Battle, C; Minik, O; Lyons, R A; Hall, J E

    2018-02-01

    Our aim was to prospectively determine the predictive capabilities of SEPSIS-1 and SEPSIS-3 definitions in the emergency departments and general wards. Patients with National Early Warning Score (NEWS) of 3 or above and suspected or proven infection were enrolled over a 24-h period in 13 Welsh hospitals. The primary outcome measure was mortality within 30 days. Out of the 5422 patients screened, 431 fulfilled inclusion criteria and 380 (88%) were recruited. Using the SEPSIS-1 definition, 212 patients had sepsis. When using the SEPSIS-3 definitions with Sequential Organ Failure Assessment (SOFA) score ≥ 2, there were 272 septic patients, whereas with quickSOFA score ≥ 2, 50 patients were identified. For the prediction of primary outcome, SEPSIS-1 criteria had a sensitivity (95%CI) of 65% (54-75%) and specificity of 47% (41-53%); SEPSIS-3 criteria had a sensitivity of 86% (76-92%) and specificity of 32% (27-38%). SEPSIS-3 and SEPSIS-1 definitions were associated with a hazard ratio (95%CI) 2.7 (1.5-5.6) and 1.6 (1.3-2.5), respectively. Scoring system discrimination evaluated by receiver operating characteristic curves was highest for Sequential Organ Failure Assessment score (0.69 (95%CI 0.63-0.76)), followed by NEWS (0.58 (0.51-0.66)) (p < 0.001). Systemic inflammatory response syndrome criteria (0.55 (0.49-0.61)) and quickSOFA score (0.56 (0.49-0.64)) could not predict outcome. The SEPSIS-3 definition identified patients with the highest risk. Sequential Organ Failure Assessment score and NEWS were better predictors of poor outcome. The Sequential Organ Failure Assessment score appeared to be the best tool for identifying patients with high risk of death and sepsis-induced organ dysfunction. © 2017 The Association of Anaesthetists of Great Britain and Ireland.

  20. Adult sepsis - A nationwide study of trends and outcomes in a population of 23 million people.

    PubMed

    Lee, Chien-Chang; Yo, Chia-Hung; Lee, Meng-Tse Gabriel; Tsai, Kuang-Chau; Lee, Shih-Hao; Chen, Yueh-Sheng; Lee, Wan-Chien; Hsu, Tzu-Chun; Lee, Sie-Hue; Chang, Shy-Shin

    2017-11-01

    To determine the trend of incidence and outcome of sepsis based on a nationwide administrative database. We analyzed the incidence and mortality of both emergency department treated and hospital treated sepsis from 2002 through 2012 using the entire health insurance claims data of Taiwan. The national health insurance covers 99% of residents in Taiwan. Sepsis patients were identified using a set of validated ICD-9CM codes conforming to the sepsis-3 definition. The 30-day all-cause mortality was verified by linked death certificate database. During the 11-year study period, a total of 1,259,578 episodes of sepsis was identified. The mean incidence rate was 639 per 100,000 person-years, increasing from 637.8/100,000 persons in 2002 to 772.1/100,000 persons in 2012 (annual increase: 1.9%). The mortality rate, however, has decreased from 27.8% in 2002 to 22.8% in 2012 (annual decrease: 0.45%). The trend of incidence and mortality did not change after standardization by age and gender using 2002 as the reference standard. We showed that the incidence of sepsis has increased while the mortality has decreased in Taiwan. Despite the decreasing trend in sepsis mortality, the total number of sepsis mortality remains increasing due to the rapid increase in sepsis incidence. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  1. Update on pediatric sepsis: a review.

    PubMed

    Kawasaki, Tatsuya

    2017-01-01

    Sepsis is one of the leading causes of mortality among children worldwide. Unfortunately, however, reliable evidence was insufficient in pediatric sepsis and many aspects in clinical practice actually depend on expert consensus and some evidence in adult sepsis. More recent findings have given us deep insights into pediatric sepsis since the publication of the Surviving Sepsis Campaign guidelines 2012. New knowledge was added regarding the hemodynamic management and the timely use of antimicrobials. Quality improvement initiatives of pediatric "sepsis bundles" were reported to be successful in clinical outcomes by several centers. Moreover, a recently published global epidemiologic study (the SPROUT study) did not only reveal the demographics, therapeutic interventions, and prognostic outcomes but also elucidated the inappropriateness of the current definition of pediatric sepsis. With these updated knowledge, the management of pediatric sepsis would be expected to make further progress. In addition, it is meaningful that the fundamental data on which future research should be based were established through the SPROUT study.

  2. Reprioritization of hepatic plasma protein release in trauma and sepsis.

    PubMed

    Sganga, G; Siegel, J H; Brown, G; Coleman, B; Wiles, C E; Belzberg, H; Wedel, S; Placko, R

    1985-02-01

    We studied the temporal pattern of seven hepatic synthesized plasma proteins in 26 severely injured patients beginning in the immediate posttrauma period. Clinical sepsis developed in ten patients between three and eight days after injury, and 16 patients had nonseptic courses. In the initial five days after injury, except for albumin, all acute-phase protein levels rose. However, if sepsis developed, C-reactive protein, fibrinogen, ceruloplasmin, and alpha 1-antitrypsin levels continued to be elevated after the initial five posttrauma days, while transferrin, albumin, and alpha 2-macroglobulin levels fell. This differential response became more extreme as sepsis progressed. Covariance analysis of the regression of the five true acute-phase hepatic proteins on C-reactive protein showed that, when sepsis occurred after major traumatic injury, the C-reactive protein rise was associated with a significant reprioritization of hepatic acute-phase plasma protein release. This reprioritization response seems to be both a predictor of sepsis as well as a measure of the adequacy of the host response to trauma and sepsis.

  3. Sepsis in acute myeloid leukaemia patients receiving high-dose chemotherapy: no impact of chitotriosidase and mannose-binding lectin polymorphisms.

    PubMed

    Klostergaard, Anja; Steffensen, Rudi; Møller, Jens K; Peterslund, Niels; Juhl-Christensen, Caroline; Mølle, Ingolf

    2010-07-01

    Infections after chemotherapy often cause significant morbidity in patients with acute myeloid leukaemia (AML). Chitotriosidase (CHIT) and mannose-binding lectin (MBL) are part of the innate immune system. Polymorphism in the CHIT-coding gene (CHIT1) may be associated with Gram-negative sepsis in children with AML, and polymorphism in the MBL-coding gene (MBL2) seems to modify the risk of infections in several patient groups. The purpose of this study was to investigate the possible associations between polymorphisms in CHIT1, MBL2 and sepsis in adult patients treated with high-dose chemotherapy for AML. We included 190 patients treated with 526 cycles of chemotherapy. The follow-up period was 6 months from the diagnosis of AML. Prophylactic antibiotics were not used. We identified 604 febrile episodes with 246 episodes of sepsis. Thirty-two patients (17%) either died from infection or infection was a major concomitant factor for death. No significant associations between CHIT1 polymorphism and sepsis (P = 0.85) or death caused by sepsis (P = 0.14) were found. Furthermore, no significant associations between MBL2 polymorphism and sepsis (P = 0.76) or death caused by sepsis (P = 0.24) were observed. The severe and long-lasting neutropenia and mucositis after chemotherapy may explain why the MBL system does not protect against sepsis in patients with AML. Replacement therapy with recombinant MBL is not likely to decrease the risk of sepsis in patients with AML.

  4. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008

    PubMed Central

    Levy, Mitchell M.; Carlet, Jean M.; Bion, Julian; Parker, Margaret M.; Jaeschke, Roman; Reinhart, Konrad; Angus, Derek C.; Brun-Buisson, Christian; Beale, Richard; Calandra, Thierry; Dhainaut, Jean-Francois; Gerlach, Herwig; Harvey, Maurene; Marini, John J.; Marshall, John; Ranieri, Marco; Ramsay, Graham; Sevransky, Jonathan; Thompson, B. Taylor; Townsend, Sean; Vender, Jeffrey S.; Zimmerman, Janice L.; Vincent, Jean-Louis

    2007-01-01

    stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B). Conclusion There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients. PMID:18058085

  5. Diminished neutrophil extracellular trap (NET) formation is a novel innate immune deficiency induced by acute ethanol exposure in polymicrobial sepsis, which can be rescued by CXCL1

    PubMed Central

    Jin, Liliang; Batra, Sanjay

    2017-01-01

    Polymicrobial sepsis is the result of an exaggerated host immune response to bacterial pathogens. Animal models and human studies demonstrate that alcohol intoxication is a key risk factor for sepsis-induced mortality. Multiple chemokines, such as CXCL1, CXCL2 and CXCL5 are critical for neutrophil recruitment and proper function of neutrophils. However, it is not quite clear the mechanisms by which acute alcohol suppresses immune responses and whether alcohol-induced immunosuppression can be rescued by chemokines. Thus, we assessed whether acute ethanol challenge via gavage diminishes antibacterial host defense in a sepsis model using cecal ligation and puncture (CLP) and whether this immunosuppression can be rescued by exogenous CXCL1. We found acute alcohol intoxication augments mortality and enhances bacterial growth in mice following CLP. Ethanol exposure impairs critical antibacterial functions of mouse and human neutrophils including reactive oxygen species production, neutrophil extracellular trap (NET) formation, and NET-mediated killing in response to both Gram-negative (E. coli) and Gram-positive (Staphylococcus aureus) pathogens. As compared with WT (C57Bl/6) mice, CXCL1 knockout mice display early mortality following acute alcohol exposure followed by CLP. Recombinant CXCL1 (rCXCL1) in acute alcohol challenged CLP mice increases survival, enhances bacterial clearance, improves neutrophil recruitment, and enhances NET formation (NETosis). Recombinant CXCL1 (rCXCL1) administration also augments bacterial killing by alcohol-treated and E. coli- and S. aureus-infected neutrophils. Taken together, our data unveils novel mechanisms underlying acute alcohol-induced dysregulation of the immune responses in polymicrobial sepsis, and CXCL1 is a critical mediator to rescue alcohol-induced immune dysregulation in polymicrobial sepsis. PMID:28922428

  6. Acute Kidney Injury in Critically Ill Patients with Sepsis: Clinical Characteristics and Outcomes.

    PubMed

    Zhi, De-Yuan; Lin, Jin; Zhuang, Hai-Zhou; Dong, Lei; Ji, Xiao-Jun; Guo, Dong-Cheng; Yang, Xiao-Wei; Liu, Shuai; Yue, Zu; Yu, Shu-Jing; Duan, Mei-Li

    2018-04-25

    The objectives of this study were to examine the clinical profile of critically ill patients with septic acute kidney injury (AKI) and to investigate clinical characteristics associated with the outcome of patients. Data from 582 critically ill patients were collected and retrospectively reviewed. Patients were divided into two groups: without AKI development and with AKI development. Baseline characteristics, laboratory, and other clinical data were compared between these two groups, and correlations between the characteristics and AKI development were examined. Patients with AKI development were further divided into two groups according to the survival outcome, and variables associated with the outcome were determined. AKI was developed in 54.12% (n = 315) of patients, and these patients had blood pressure, SOFA score, APACHE II score, GCS, and various blood chemistry and hematology characteristics significantly different from the patients without AKI. Demographic characteristics (e.g. age and weight) were comparable between the two groups of patients. Among the 315 patients with AKI, 136 of them died during the study period. Multivariate logistic regression analysis revealed that the outcome of patients was associated with lung infection, coagulation system dysfunction, staphylococcus aureus infection, and use of various treatments (epinephrine, norepinephrine, and the use of mechanical ventilation) after AKI development. AKI occurred in approximately half of the critically ill patients admitted to ICU. The site and type of infections, as well as the use of vasopressor agents, were associated with the outcome.

  7. Risk factors and outcomes of sepsis-induced myocardial dysfunction and stress-induced cardiomyopathy in sepsis or septic shock

    PubMed Central

    Jeong, Han Saem; Lee, Tae Hyub; Bang, Cho Hee; Kim, Jong-Ho; Hong, Soon Jun

    2018-01-01

    Abstract While both sepsis-induced myocardial dysfunction (SIMD) and stress-induced cardiomyopathy (SICMP) are common in patients with sepsis, the pathogenesis of the 2 diseases is different, and they require different treatment strategies. Thus, we aimed to investigate risk factors and outcomes between the 2 diseases. This retrospective study enrolled patients diagnosed with sepsis or septic shock, admitted to intensive care unit via emergency department in Korea University Anam Hospital, and who underwent transthoracic echocardiography within the first 24 hours of admission. In all, 25 patients with SIMD and 27 patients with SICMP were enrolled. Chronic obstructive pulmonary disease and a history of heart failure (HF) were more prevalent in both the SIMD and SICMP groups than in the control group. In the SIMD and SICMP groups, levels of inflammatory cytokines were similar. Serum troponin level was significantly elevated in the SICMP and SIMD group compared to the control group. N-terminal pro-brain natriuretic peptide (NT pro-BNP) level was significantly elevated in the SIMD group compared to the SICMP group or control group. The in-hospital mortality rate in the SIMD and SICMP group was about 40%, showing increased trends compared with the control group. The in-hospital mortality rate was significantly increased in SIMD group with EF<30% than in SICMP group with EF<30%. In multiple logistic regression analysis, a past history of diabetes mellitus (DM) and HF was significantly associated with the incidence of SIMD. Younger age, elevated levels of NT pro-BNP, and positive result of blood culture also showed significant odds ratio regard to the occurrence of SIMD. However, only elevated lactate and troponin level were positively associated with the incidence of SICMP. The SIMD and SICMP had different risk factors. The risk factors of SIMD were younger age, history of DM, history of HF, elevated NT pro-BNP, and positive result of blood culture. The elevated levels

  8. Effects of peroxisome proliferator-activated receptor-β/δ on sepsis induced acute lung injury.

    PubMed

    Wang, Cairui; Zhou, Guopeng; Zeng, Zeng

    2014-01-01

    Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the first steps in the development of multiple organ failure induced by sepsis. A systemic excessive inflammatory reaction is currently the accepted mechanism of the pathogenesis of sepsis. Several studies have suggested a protective role of the peroxisome proliferator activated receptor-β/δ (PPAR-β/δ) in related inflammatory diseases. But the role of PPARβ/δ in ALI remains uncertain. The aim of this study was to investigate the role and possible mechanism of PPARβ/δ in ALI induced by sepsis. Cecal ligation and puncture (CLP) was used as a sepsis model. Rats were randomly divided into four groups, the control group (CON, n = 6), sham-operation group (SHAM, n = 12), cecal ligation and puncture group (CLP, n = 30), GW501516 group (CLP+GW, n = 25), which underwent CLP and were subcutaneously injected with the PPAR-β/δ agonist GW501516 (0.05 mg/100 g body weight). Survival was monitored to 24 hours after operation. Blood pressure, serum creatinine, blood urea nitrogen, aspartate aminotrasferase and alanine aminotrasferase were measured after CLP. Concentrations of tumor necrosis factor α (TNF-α) and interleukin (IL)-1β in serum were detected by enzyme linked immunosorbent assay (ELISA) kits. Lung tissue samples were stained with H&E and scored according to the degree of inflammation. Bacterial colonies were counted in the peritoneal fluid. Alveolar macrophages were cultured and incubated with GW501516 (0.15 µmol/L) and PPARβ/δ adenovirus and then treated with Lipopolysaccharide (2 µg/ml) for 2 hours. The TNF-α, IL-1β and IL-6 RNA in lung and alveolar macrophages were determined by real-time PCR. Phosphorylation of signal transducer and activator of transcription 3 (STAT3) in lung and alveolar macrophages was detected by Western blotting. GW501516 significantly increased the survival of septic rats, decreased histological damage of the lungs, reduced inflammatory cytokines in

  9. Management and outcomes of severe dengue patients presenting with sepsis in a tropical country.

    PubMed

    Teparrukkul, Prapit; Hantrakun, Viriya; Day, Nicholas P J; West, T Eoin; Limmathurotsakul, Direk

    2017-01-01

    Dengue is a common cause of infection in adults in tropical countries. Sepsis is a syndrome of systemic manifestations induced by infection of any organisms; including bacterial, fungal and viral agents. Here, we investigated the diagnosis, management and outcomes of dengue patients presenting with sepsis in a prospective study of community-acquired sepsis in Thailand. From June to December 2015, 874 adult patients (age≥18 years) with suspected or documented community-acquired infection, with ≥3 diagnostic criteria for sepsis according to the Surviving Sepsis Campaign 2012, and within 24 hours of admission were evaluated. Serum was stored and later tested for dengue PCR assays. A total of 126 patients had dengue PCR assays positive (2 DENV-1, 12 DENV-2, 24 DENV-3 and 88 DENV-4), and 5 of them (4%) died. We found that attending physicians suspected dengue infection on admission in 84 patients (67%), and recorded dengue infection as the final diagnosis in 96 patients (76%). Four of five fatal cases were diagnosed and treated as septic shock not due to dengue. In multivariable analysis, there was a trend showing that age≥60 years, hypoxemia and misdiagnosis of dengue by attending physicians were associated with 28-day mortality. A number of adult patients who died of dengue are misdiagnosed as severe sepsis and septic shock. Diagnosis of dengue based on clinical features alone is difficult. Rapid diagnostic tests for dengue may need to be routinely used in adult patients presenting with sepsis and septic shock in tropical countries. This approach could improve diagnosis and management of those patients.

  10. Early and innovative interventions for severe sepsis and septic shock: taking advantage of a window of opportunity

    PubMed Central

    Rivers, Emanuel P.; McIntyre, Lauralyn; Morro, David C.; Rivers, Kandis K.

    2005-01-01

    The pathogenic, diagnostic and therapeutic landscape of sepsis is no longer confined to the intensive care unit: many patients from other portals of entry to care, both outside and within the hospital, progress to severe disease. Approaches that have led to improved outcomes with other diseases (e.g., acute myocardial infarction, stroke and trauma) can now be similarly applied to sepsis. Improved understanding of the pathogenesis of severe sepsis and septic shock has led to the development of new therapies that place importance on early identification and aggressive management. This review emphasizes approaches to the early recognition, diagnosis and therapeutic management of sepsis, giving the clinician the most contemporary and practical approaches with which to treat these patients. PMID:16247103

  11. Sepsis Patients with First and Second-Hit Infections Show Different Outcomes Depending on the Causative Organism

    PubMed Central

    Morgan, Matt P.; Szakmany, Tamas; Power, Sarah G.; Olaniyi, Patrick; Hall, Judith E.; Rowan, Kathy; Eberl, Matthias

    2016-01-01

    Objective: With improving rates of initial survival in severe sepsis, second-hit infections that occur following resolution of the primary insult carry an increasing burden of morbidity. However, despite the clinical relevance of these infections, no data are available on differential outcomes in patients with first and second-hit infections depending on the nature of the causative organism. This study aims to explore any differences in these subgroups. Design: In a retrospective, observational cohort study, the United Kingdom Intensive Care National Audit & Research Centre (ICNARC) database was used to explore the outcomes of patient with first-hit infections leading to sepsis, and sepsis patients with second-hit infections grouped according to the Gram status of the causative organism. Setting: General critical care units in England, Wales, and Northern Ireland participating in the ICNARC programme between 1 January, 2007 and 30 June, 2012. Patients: Patient groups analyzed included 2119 patients with and 1319 patients without sepsis who developed an intensive care unit acquired infection in blood. Subgroups included patients with trauma, emergency neurosurgery, elective surgery, and cardiogenic shock. Measurements and main results: Gram-negative organisms were associated with poorer outcomes in first-hit infections. The 90-day mortality of patients who developed a Gram-negative infection was 43.6% following elective surgery and 27.9% following trauma. This compared with a mortality of 25.6 and 20.6%, respectively, in Gram-positive infections. Unexpectedly, an inverse relationship between Gram status and mortality was observed in second-hit infections. Patients with an initial diagnosis of sepsis who developed secondary infections caused by Gram-negative organisms had a 90-day mortality of 40.4%, compared with 43.6% in Gram-positive infections. Conclusions: Our study identifies a fundamental difference in patient outcomes between first-hit and second

  12. Sepsis Patients with First and Second-Hit Infections Show Different Outcomes Depending on the Causative Organism.

    PubMed

    Morgan, Matt P; Szakmany, Tamas; Power, Sarah G; Olaniyi, Patrick; Hall, Judith E; Rowan, Kathy; Eberl, Matthias

    2016-01-01

    With improving rates of initial survival in severe sepsis, second-hit infections that occur following resolution of the primary insult carry an increasing burden of morbidity. However, despite the clinical relevance of these infections, no data are available on differential outcomes in patients with first and second-hit infections depending on the nature of the causative organism. This study aims to explore any differences in these subgroups. In a retrospective, observational cohort study, the United Kingdom Intensive Care National Audit & Research Centre (ICNARC) database was used to explore the outcomes of patient with first-hit infections leading to sepsis, and sepsis patients with second-hit infections grouped according to the Gram status of the causative organism. General critical care units in England, Wales, and Northern Ireland participating in the ICNARC programme between 1 January, 2007 and 30 June, 2012. Patient groups analyzed included 2119 patients with and 1319 patients without sepsis who developed an intensive care unit acquired infection in blood. Subgroups included patients with trauma, emergency neurosurgery, elective surgery, and cardiogenic shock. Gram-negative organisms were associated with poorer outcomes in first-hit infections. The 90-day mortality of patients who developed a Gram-negative infection was 43.6% following elective surgery and 27.9% following trauma. This compared with a mortality of 25.6 and 20.6%, respectively, in Gram-positive infections. Unexpectedly, an inverse relationship between Gram status and mortality was observed in second-hit infections. PATIENTS with an initial diagnosis of sepsis who developed secondary infections caused by Gram-negative organisms had a 90-day mortality of 40.4%, compared with 43.6% in Gram-positive infections. Our study identifies a fundamental difference in patient outcomes between first-hit and second-hit bacterial infections, which may be due to genetic, microbiological, immunological, and

  13. Age, exercise, and the outcome of sepsis.

    PubMed

    Banerjee, Debasree; Opal, Steven M

    2017-11-23

    We report on the increasingly important need to diagnose and care for the elderly with sepsis as a distinct patient population. We share an overview of age-related changes in sepsis physiology and the potential role of exercise.See related research by Tyml et al., https://ccforum.biomedcentral.com/articles/10.1186/s13054-017-1783-1.

  14. Prediction about severity and outcome of sepsis by pro-atrial natriuretic peptide and pro-adrenomedullin.

    PubMed

    Wang, Rui-lan; Kang, Fu-xin

    2010-06-01

    Measurement of biomarkers is a potential approach to early prediction of the risk of mortality in patients with sepsis. The aim of the present study was to evaluate the prognostic value of pro-atrial natriuretic peptide (pro-ANP) and pro-adrenomedullin (pro-ADM) levels in a cohort of medical intensive care patients and to compare it with that of other known biomarkers and physiological scores. Blood samples of 51 consecutive critically ill patients admitted to the intensive care unit and 53 age-matched healthy control people were evaluated in this prospective study. The prognostic value of pro-ANP and pro-ADM levels was compared with that of acute physiology and chronic health evaluation (APACHE) II scores and various biomarkers such as C-reactive protein, interleukin-6 and procalcitonin. Pro-ANP and pro-ADM were detected by a new sandwich immunoassay. On admission, 25 patients had systemic inflammatory response syndrome (SIRS), 12 sepsis, 9 severe sepsis and 5 septic shock. At that time, the median levels (ng/ml) of pro-ANP and pro-ADM were 87.22 and 0.34 respectively in patients with SIRS, 1533.30 and 2.23 in those with sepsis, 1098.73 and 4.57 in those with severe sepsis, and 1933.94 and 8.21 in those with septic shock. With the increasing severity of disease, the levels of pro-ANP and pro-ADM were gradually increased. On admission, the circulating levels of pro-ANP and pro-ADM in patients with sepsis, severe sepsis, or septic shock were significantly higher in non-survivors than in survivors (P less than 0.05). In a receiver operating characteristic curve analysis for the survival of patients with sepsis, the areas under the curve (AUCs) for pro-ANP and pro-ADM were 0.89 and 0.87 respectively, which was similar to the AUCs for procalcitonin and APACHE II scores. Pro-ANP and pro-ADM are valuable biomarkers for prediction of severity of septic patients.

  15. The epidemiology of sepsis in Brazilian intensive care units (the Sepsis PREvalence Assessment Database, SPREAD): an observational study.

    PubMed

    Machado, Flavia R; Cavalcanti, Alexandre Biasi; Bozza, Fernando Augusto; Ferreira, Elaine M; Angotti Carrara, Fernanda Sousa; Sousa, Juliana Lubarino; Caixeta, Noemi; Salomao, Reinaldo; Angus, Derek C; Pontes Azevedo, Luciano Cesar

    2017-11-01

    The sepsis burden on acute care services in middle-income countries is a cause for concern. We estimated incidence, prevalence, and mortality of sepsis in adult Brazilian intensive care units (ICUs) and association of ICU organisational factors with outcome. We did a 1-day point prevalence study with follow-up of patients in ICU with sepsis in a nationally representative pseudo-random sample. We produced a sampling frame initially stratified by geographical region. Each stratum was then stratified by hospitals' main source of income (serving general public vs privately insured individuals) and ICU size (ten or fewer beds vs more than ten beds), finally generating 40 strata. In each stratum we selected a random sample of ICUs so as to enrol the total required beds in 1690 Brazilian adult ICUs. We followed up patients until hospital discharge censored at 60 days, estimated incidence from prevalence and length of stay, and generated national estimates. We assessed mortality prognostic factors using random-effects logistic regression models. On Feb 27, 2014, 227 (72%) of 317 ICUs that were randomly selected provided data on 2632 patients, of whom 794 had sepsis (30·2 septic patients per 100 ICU beds, 95% CI 28·4-31·9). The ICU sepsis incidence was 36·3 per 1000 patient-days (95% CI 29·8-44·0) and mortality was observed in 439 (55·7%) of 788 patients (95% CI 52·2-59·2). Low availability of resources (odds ratio [OR] 1·67, 95% CI 1·02-2·75, p=0·045) and adequacy of treatment (OR 0·56, 0·37-0·84, p=0·006) were independently associated with mortality. The projected incidence rate is 290 per 100 000 population (95% CI 237·9-351·2) of adult cases of ICU-treated sepsis per year, which yields about 420 000 cases annually, of whom 230 000 die in hospital. The incidence, prevalence, and mortality of ICU-treated sepsis is high in Brazil. Outcome varies considerably, and is associated with access to adequate resources and treatment. Our results show the

  16. Blockage of glycolysis by targeting PFKFB3 alleviates sepsis-related acute lung injury via suppressing inflammation and apoptosis of alveolar epithelial cells.

    PubMed

    Gong, Yuanqi; Lan, Haibing; Yu, Zhihong; Wang, Meng; Wang, Shu; Chen, Yu; Rao, Haiwei; Li, Jingying; Sheng, Zhiyong; Shao, Jianghua

    2017-09-16

    Sepsis-related acute lung injury (ALI) is characterized by excessive lung inflammation and apoptosis of alveolar epithelial cells resulting in acute hypoxemic respiratory failure. Recent studies indicated that anaerobic glycolysis play an important role in sepsis. However, whether inhibition of aerobic glycolysis exhibits beneficial effect on sepsis-induced ALI is not known. In vivo, a cecal ligation and puncture (CLP)-induced ALI mouse model was set up and mice treated with glycolytic inhibitor 3PO after CLP. The mice treated with the 3PO ameliorated the survival rate, histopathological changes, lung inflammation, lactate increased and lung apoptosis of mice with CLP-induced sepsis. In vitro, the exposure of human alveolar epithelial A549 cells to lipopolysaccharide (LPS) resulted in cell apoptosis, inflammatory cytokine production, enhanced glycolytic flux and reactive oxygen species (ROS) increased. While these changes were attenuated by 3PO treatment. Sequentially, treatment of A549 cells with lactate caused cell apoptosis and enhancement of ROS. Pretreatment with N-acetylcysteine (NAC) significantly lowered LPS and lactate-induced the generation of ROS and cell apoptosis in A549 cells. Therefore, these results indicate that anaerobic glycolysis may be an important contributor in cell apoptosis of sepsis-related ALI. Moreover, LPS specifically induces apoptotic insults to A549 cell through lactate-mediated enhancement of ROS. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Clinical impact of sepsis at admission to the ICU of a private hospital in Salvador, Brazil.

    PubMed

    Juncal, Verena Ribeiro; Britto Neto, Lelivaldo Antonio de; Camelier, Aquiles Assunção; Messeder, Octavio Henrique Coelho; Farias, Augusto Manoel de Carvalho

    2011-01-01

    To describe the clinical characteristics, laboratory data, and clinical outcomes of patients with and without sepsis admitted to the ICU of a private hospital in the city of Salvador, Brazil, and to identify clinical variables related to a worse prognosis in those with sepsis. This was a longitudinal study including all patients admitted to the general ICU of the Hospital Português, in the city of Salvador, Brazil, between June of 2008 and March of 2009. At ICU admission, two groups of patients were identified: with sepsis and without sepsis. Epidemiological, clinical and laboratory data were collected, and the Acute Physiology and Chronic Health Evaluation II (APACHE II) score was calculated. Of the 144 patients in the study, 29 (20.1%) had sepsis. Among the patients with sepsis, males accounted for 55.2%, the mean age was 73.1 ± 14.6 years, and the mean APACHE II score was 23.8 ± 9.1, compared with 36.3%, 68.7 ± 17.7 years, and 18.4 ± 9.5, respectively, among those without sepsis. There were significant associations between a diagnosis of sepsis and the following variables: APACHE II score; in-hospital mortality; ICU mortality; HR; mean arterial pressure; hematocrit level; white blood cell count; and antibiotic use. The use of life support measures and lower hematocrit levels were associated with a worse prognosis in the patients with sepsis. The patients diagnosed with sepsis presented worse clinical outcomes, probably due to their greater severity. Hematocrit level was the only variable that was a predictor of mortality risk in the patients with sepsis.

  18. Etiology and outcome of acute renal failure in pregnancy.

    PubMed

    Hassan, Irfana; Junejo, Abdul Manan; Dawani, Manohar Lal

    2009-11-01

    To determine the etiology and outcome of Acute Renal Failure (ARF) in pregnancy. A case series. Nephrology Department of the Jinnah Postgraduate Medical Centre, Karachi, from August 2007 to July 2008. Pregnant women who were healthy previously and had developed ARF, diagnosed on oliguria (urine output <400 ml/day) and mounting azotemia (serum creatinine > 2 mg%) were included in the study. Percutaneous renal biopsy was performed for delayed recovery, i.e. after three weeks. Patients were followed up for a period of 6 months. Percentages were calculated for qualitative variables i.e. causes of ARF, mortality, morbidity and outcome in form of complete recovery, partial recovery, demise and non-recovery. A total of 43 patients with pregnancy-related ARF were included in the study. The puerperal group comprised 36 patients (83.7%). Haemorrhage was the etiology for ARF in 25 (58.1%), antepartum haemorrhage APH in 8 (18.6%) and postpartum haemorrhage PPH in 16 (37.2%) of patients. In 12 (27.9%), puerperal sepsis was the etiological factor, while 4 (9.3%) patients had DIC on presentation. Pre-eclampsia, eclampsia and HELLP syndrome accounted for 5 (11.6%). While 1 (2.3%) was diagnosed with hemolytic uremic syndrome and another one was diagnosed as ARF secondary to hypotension produced by hyperemesis gravidarum. Renal biopsy was performed in 31 patients showing that 10 had acute cortical necrosis and 21 had acute tubular necrosis. Maternal mortality was 16.2% (n=7). Of the 36 (83.7%) surviving patients, 18 (41.4%) had complete recovery of renal function; 12 (27.9%) had partial recovery; and 6 (13.9%) required chronic dialysis. Pregnancy-related ARF was associated with poor outcome. Antepartum and postpartum haemorrhage were the most common cause of ARF in pregnancy.

  19. Gene Variations in the Protein C and Fibrinolytic Pathway: Relevance for Severity and Outcome in Pediatric Sepsis.

    PubMed

    Boeddha, Navin P; Emonts, Marieke; Cnossen, Marjon H; de Maat, Moniek P; Leebeek, Frank W; Driessen, Gertjan J; Hazelzet, Jan A

    2017-02-01

    The host response to infection involves complex interplays between inflammation, coagulation, and fibrinolysis. Deregulation of hemostasis and fibrinolysis are major causes of critical illness and important determinants of outcome in severe sepsis. The hemostatic responses to infection vary widely between individuals, and are in part explained by polymorphisms in genes responsible for the protein C and fibrinolytic pathway. This review gives an overview of genetic polymorphisms in the protein C and fibrinolytic pathway associated with susceptibility and severity of pediatric sepsis. In addition, genetic polymorphisms associated with adult sepsis and other pediatric thromboembolic disorders are discussed, as these polymorphisms might be candidates for future molecular genetic research in pediatric sepsis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  20. Predictive Value of IL-8 for Sepsis and Severe Infections after Burn Injury - A Clinical Study

    PubMed Central

    Kraft, Robert; Herndon, David N; Finnerty, Celeste C; Cox, Robert A; Song, Juquan; Jeschke, Marc G

    2014-01-01

    The inflammatory response induced by burn injury contributes to increased incidence of infections, sepsis, organ failure, and mortality. Thus, monitoring post-burn inflammation is of paramount importance but so far there are no reliable biomarkers available to monitor and/or predict infectious complications after burn. As IL-8 is a major mediator for inflammatory responses, the aim of our study was to determine whether IL-8 expression can be used to predict post-burn sepsis, infections, and mortality other outcomes post-burn. Plasma cytokines, acute phase proteins, constitutive proteins, and hormones were analyzed during the first 60 days post injury from 468 pediatric burn patients. Demographics and clinical outcome variables (length of stay, infection, sepsis, multiorgan failure (MOF), and mortality were recorded. A cut-off level for IL-8 was determined using receiver operating characteristic (ROC) analysis. Statistical significance is set at (p<0.05). ROC analysis identified a cut-off level of 234 pg/ml for IL-8 for survival. Patients were grouped according to their average IL-8 levels relative to this cut off and stratified into high (H) (n=133) and low (L) (n=335) groups. In the L group, regression analysis revealed a significant predictive value of IL-8 to percent of total body surface area (TBSA) burned and incidence of MOF (p<0.001). In the H group IL-8 levels were able to predict sepsis (p<0.002). In the H group, elevated IL-8 was associated with increased inflammatory and acute phase responses compared to the L group (p<0.05). High levels of IL-8 correlated with increased MOF, sepsis, and mortality. These data suggest that serum levels of IL-8 may be a valid biomarker for monitoring sepsis, infections, and mortality in burn patients. PMID:25514427

  1. Knowledge and recognition of SIRS and sepsis among pediatric nurses.

    PubMed

    Jeffery, Alvin D; Mutsch, Karen Steffen; Knapp, Lisa

    2014-01-01

    A large amount of research demonstrates the importance of key interventions in reducing mortality rates of pediatric patients with sepsis (Dellinger et al., 2008). Assessment and recognition of declining status must occur for interventions to be initiated. Of health care practitioners, nurses typically spend the most time with patients, and they must be knowledgeable in recognizing the systemic inflammatory response syndrome and sepsis while also being aware of the importance of prompt intervention. The literature does not discuss pediatric nurses' knowledge of systemic inflammatory response syndrome (SIRS)/sepsis recognition. The purpose of this study was to assess the knowledge of acute and critical care pediatric nurses of SIRS diagnostic criteria, sepsis guidelines, and the importance of SIRS recognition. This cross-sectional, quantitative, correlational descriptive study included 242 acute and critical care pediatric nurses at a 490-bed urban pediatric hospital. Participants completed an original questionnaire with face and content validity regarding SIRS criteria, sepsis guidelines, priority interventions, and attitude toward the importance of SIRS recognition. Findings demonstrated a significant knowledge deficit among participants in several key areas of SIRS/sepsis recognition. The mean score was 60.8% ± 7.4%. Item analyses demonstrated nurses easily recognize septic shock but have difficulty recognizing patients in earlier stages of the sepsis continuum. Significant confusion was evident regarding the role of blood pressure and serum lactic acid levels in diagnosing sepsis. It is recommended that an educational intervention be created for acute and critical care pediatric nurses to aid them in recognizing sepsis in its earlier stages.

  2. Assessment of mortality by qSOFA in patients with sepsis outside ICU: A post hoc subgroup analysis by the Japanese Association for Acute Medicine Sepsis Registry Study Group.

    PubMed

    Umemura, Yutaka; Ogura, Hiroshi; Gando, Satoshi; Kushimoto, Shigeki; Saitoh, Daizoh; Mayumi, Toshihiko; Fujishima, Seitaro; Abe, Toshikazu; Ikeda, Hiroto; Kotani, Joji; Miki, Yasuo; Shiraishi, Shin-Ichiro; Shiraishi, Atsushi; Suzuki, Koichiro; Suzuki, Yasushi; Takeyama, Naoshi; Takuma, Kiyotsugu; Tsuruta, Ryosuke; Yamaguchi, Yoshihiro; Yamashita, Norio; Aikawa, Naoki

    2017-11-01

    Quick sequential organ failure assessment (qSOFA) was proposed in the new sepsis definition (Sepsis-3). Although qSOFA was created to identify patients with suspected infection and likely to have poor outcomes, the clinical utility of qSOFA to screen sepsis has not been fully evaluated. We investigated the number of patients diagnosed as having severe sepsis who could not be identified by the qSOFA criteria and what clinical signs could complement the qSOFA score. This retrospective analysis of a multicenter prospective registry included adult patients with severe sepsis diagnosed outside the intensive care unit (ICU) by conventional criteria proposed in 2003. We conducted receiver operating characteristic (ROC) analyses to assess the predictive value for in-hospital mortality and compared clinical characteristics between survivors and non-survivors with qSOFA score ≤ 1 point (qSOFA-negative). Among 387 eligible patients, 63 (16.3%) patients were categorized as qSOFA-negative, and 10 (15.9%) of these patients died. The area under the ROC curve for the qSOFA score was 0.615, which was superior to that for the systemic inflammatory response syndrome score (0.531, P = 0.019) but inferior to that for the SOFA score (0.702, P = 0.005). Multivariate logistic regression analysis showed that hypothermia might be associated with poor outcome independently of qSOFA criteria. Our findings suggested that qSOFA had a suboptimal level of predictive value outside the ICU and could not identify 16.3% of patients who were once actually diagnosed with sepsis. Hypothermia might be associated with an increased risk of death that cannot be identified by qSOFA. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  3. Sepsis 2018: Definitions and Guideline Changes.

    PubMed

    Napolitano, Lena M

    Sepsis is a global healthcare issue and continues to be the leading cause of death from infection. Early recognition and diagnosis of sepsis is required to prevent the transition into septic shock, which is associated with a mortality rate of 40% or more. New definitions for sepsis and septic shock (Third International Consensus Definitions for Sepsis and Septic Shock [Sepsis-3]) have been developed. A new screening tool for sepsis (quick Sequential Organ Failure Assessment [qSOFA]) has been proposed to predict the likelihood of poor outcome in out-of-intensive care unit (ICU) patients with clinical suspicion of sepsis. The Surviving Sepsis Campaign Guidelines were recently updated and include greater evidence-based recommendations for treatment of sepsis in attempts to reduce sepsis-associated mortality. This review discusses the new Sepsis-3 definitions and guidelines.

  4. Role of presepsin for the evaluation of sepsis in the emergency department.

    PubMed

    Pizzolato, Elisa; Ulla, Marco; Galluzzo, Claudia; Lucchiari, Manuela; Manetta, Tilde; Lupia, Enrico; Mengozzi, Giulio; Battista, Stefania

    2014-10-01

    Sepsis, severe sepsis and septic shock are among the most common conditions handled in the emergency department (ED). According to new Sepsis Guidelines, early diagnosis and treatment are the keys to improve survival. Plasma C-reactive protein (CRP) and procalcitonin (PCT) levels, when associated with documented or suspected infection, are now part of the definitions of sepsis. Blood culture is the gold standard method for detecting microorganisms but it requires too much time for results to be known. Sensitive biomarkers are required for early diagnosis and as indexes of prognosis sepsis. CRP is one of the acute phase proteins synthesized by the liver: it has a great sensitivity but a very poor specificity for bacterial infections. Moreover, the evolution of sepsis does not correlate with CRP plasma changes. In recent years PCT has been widely used for sepsis differential diagnosis, because of its close correlation with infections, but it still retains some limitations and false positivity (such as in multiple trauma and burns). Soluble CD14 subtype (sCD14-ST), also known as presepsin, is a novel and promising biomarker that has been shown to increase significantly in patients with sepsis, in comparison to the healthy population. Studies pointed out the capability of this biomarker for diagnosing sepsis, assessing the severity of the disease and providing a prognostic evaluation of patient outcome. In this mini review we mainly focused on presepsin: we evaluate its diagnostic and prognostic roles in patients presenting to the ED with systemic inflammatory response syndrome (SIRS), suspected sepsis or septic shock.

  5. A Valuable Tool in Predicting Poor Outcome due to Sepsis in Pediatric Intensive Care Unit: Tp-e/QT Ratio.

    PubMed

    Ozdemir, Rahmi; Isguder, Rana; Kucuk, Mehmet; Karadeniz, Cem; Ceylan, Gokhan; Katipoglu, Nagehan; Yilmazer, Murat Muhtar; Yozgat, Yilmaz; Mese, Timur; Agin, Hasan

    2016-10-01

    To assess the feasibility of 12-lead electrocardiographic (ECG) measures such as P wave dispersion (PWd), QT interval, QT dispersion (QTd), Tp-e interval, Tp-e/QT and Tp-e/QTc ratio in predicting poor outcome in patients diagnosed with sepsis in pediatric intensive care unit (PICU). Ninety-three patients diagnosed with sepsis, severe sepsis or septic shock and 103 age- and sex-matched healthy children were enrolled into the study. PWd, QT interval, QTd, Tp-e interval and Tp-e/QT, Tp-e/QTc ratios were obtained from a 12-lead electrocardiogram. PWd, QTd, Tp-e interval and Tp-e/QT, Tp-e/QTc ratios were significantly higher in septic patients compared with the controls. During the study period, 41 patients had died. In multivariate logistic regression analyses, only Tp-e/QT ratio was found to be an independent predictor of mortality. The ECG measurements can predict the poor outcome in patients with sepsis. The Tp-e/QT ratio may be a valuable tool in predicting mortality for patients with sepsis in the PICU. © The Author [2016]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Emphysema induced by elastase alters the mRNA relative levels from DNA repair genes in acute lung injury in response to sepsis induced by lipopolysaccharide administration in Wistar rats.

    PubMed

    Sergio, Luiz Philippe S; Lucinda, Leda M F; Reboredo, Maycon M; de Paoli, Flavia; Fonseca, Lídia M C; Pinheiro, Bruno V; Mencalha, Andre L; Fonseca, Adenilson S

    2018-03-01

    Purpose/Aim of the study: Patients suffering from chronic obstructive pulmonary disease (COPD) in association with acute respiratory distress syndrome (ARDS) present oxidative stress in lung cells, with production of free radicals and DNA lesions in pulmonary and adjacent cells. Once the DNA molecule is damaged, a set of enzymatic mechanisms are trigged to preserve genetic code integrity and cellular homeostasis. These enzymatic mechanisms include the base and the nucleotide excision repair pathways, as well as telomere regulation. Thus, the aim of this work was to evaluate the mRNA levels from APEX1, ERCC2, TP53, and TRF2 genes in lung tissue from Wistar rats affected by acute lung injury in response to sepsis and emphysema. Adult male Wistar rats were randomized into 4 groups (n = 6, for each group): control, emphysema, sepsis, and emphysema with sepsis. Pulmonary emphysema was induced by intratracheal instillation of elastase (12 IU/animal) and sepsis induced by intraperitoneal Escherichia coli lipopolysaccharide (LPS) injection (10 mg/kg). Lungs were removed, and samples were withdrawn for histological analysis and total RNA extraction, cDNA synthesis, and mRNA level evaluation by real time quantitative polymerase chain reaction. Data show acute lung injury by LPS and emphysema by elastase and that APEX1, ERCC2, TP53, and TRF2 mRNA levels are increased significantly (p < 0.01) in emphysema with sepsis group. Our results suggest that alteration in mRNA levels from DNA repair and genomic stability could be part of cell response to acute lung injury in response to emphysema and sepsis.

  7. Comparable increase of B-type natriuretic peptide and amino-terminal pro-B-type natriuretic peptide levels in patients with severe sepsis, septic shock, and acute heart failure.

    PubMed

    Rudiger, Alain; Gasser, Stefan; Fischler, Manuel; Hornemann, Thorsten; von Eckardstein, Arnold; Maggiorini, Marco

    2006-08-01

    B-type natriuretic peptide (BNP) and N-terminal pro-BNP measurements are used for the diagnosis of congestive heart failure (HF). However, the diagnostic value of these tests is unknown under septic conditions. We compared patients with severe sepsis or septic shock and patients with acute HF to unravel the influence of the underlying diagnosis on BNP and N-terminal pro-BNP levels. Prospective, clinical study. Academic medical intensive care unit (ICU). A total of 249 consecutive patients were screened for the diagnosis of sepsis or HF. Sepsis was defined according to published guidelines. HF was diagnosed in the presence of an underlying heart disease and congestive HF, pulmonary edema, or cardiogenic shock. BNP and N-terminal pro-BNP were measured from blood samples that were drawn daily for routine analysis. We identified 24 patients with severe sepsis or septic shock and 51 patients with acute HF. At admission, the median (range) BNP and N-terminal pro-BNP levels were 572 (13-1,300) and 6,526 (198-70,000) ng/L in patients with sepsis and 581 (6-1,300) and 4,300 (126-70,000) ng/L in patients with HF. The natriuretic peptide levels increased during the ICU stay, but the differences between the groups were not significant. Nine patients with sepsis and eight patients with HF were monitored with a pulmonary artery catheter. Mean (sd) pulmonary artery occlusion pressure were 16 (4.2) and 22 (5.3) mm Hg (p = .02), and cardiac indexes were 4.6 (2.8) and 2.2 (0.6) L/min/m (p = .03) in patients with sepsis and HF, respectively. Despite these clear hemodynamic differences BNP and N-terminal pro-BNP levels were not statistically different between the two groups. In patients with severe sepsis or septic shock, BNP and N-terminal pro-BNP values are highly elevated and, despite significant hemodynamic differences, comparable with those found in acute HF patients. It remains to be determined how elevations of natriuretic peptide levels are linked to inflammation and sepsis

  8. Soluble Triggering Receptor Expressed on Myeloid Cells-1 as a Novel Marker for Abdominal Sepsis.

    PubMed

    Song, Xiaofei; Song, Yucheng; Zhang, Xuedong; Xue, Huanzhou

    2017-07-01

    The aim of the study was to investigate the concentration and diagnostic significance of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in acute abdominal conditions. Plasma specimens were obtained from 68 patients with abdominal sepsis, 60 patients with systemic inflammatory response syndrome (SIRS), and 60 healthy individuals. The sepsis group was divided into the survival and death groups according to the 28-d outcome. Plasma sTREM-1, procalcitonin (PCT), C-reactive protein (CRP), and white blood cell (WBC) count were measured. A receiver operating characteristic curve (ROC) was used to compare the diagnostic values of sTREM-1, PCT, CRP, and WBC count. In addition, the correlation between plasma sTREM-1 and the Acute Physiology and Chronic Health Evaluation (APACHE) II score in the sepsis group was assessed by Spearman correlation analysis. The plasma concentration of sTREM-1 in the sepsis group was significantly higher than that in the SIRS and healthy groups (both p < 0.001). Also, the plasma concentration of sTREM-1 in the death group was markedly higher than that in the survival group. The ROC for the diagnosis of sepsis vs. SIRS showed that the area under the curve of sTREM-1 (0.82) was greater than that of PCT (0.77), CRP (0.72), and WBC count (0.70). Additionally, in the sepsis group, the plasma sTREM-1 concentration correlated positively with the APACHE II score (r = 0.41; p < 0.05). The plasma concentration of sTREM-1 may be a significantly sensitive and useful indicator for the rapid diagnosis of abdominal sepsis.

  9. Sepsis in Older Adults.

    PubMed

    Rowe, Theresa A; McKoy, June M

    2017-12-01

    Sepsis disproportionally affects older adults with more than 60% of sepsis diagnoses attributed to adults aged 65 years and older. Identifying, diagnosing, and treating sepsis in older individuals remain a challenge for clinicians, and few studies focus specifically on older adults with multiple medical comorbidities. Principles guiding management of sepsis for older adults are generally the same as in younger adults; however, unique considerations particularly pertinent to the care older adults include antimicrobial selection and dosing, delirium management, and goals of care discussions. Other factors, such as medical comorbidities, cognitive impairment, and functional status, impact outcomes more than age alone. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Immunosuppression after Sepsis: Systemic Inflammation and Sepsis Induce a Loss of Naïve T-Cells but No Enduring Cell-Autonomous Defects in T-Cell Function

    PubMed Central

    Markwart, Robby; Condotta, Stephanie A.; Requardt, Robert P.; Borken, Farina; Schubert, Katja; Weigel, Cynthia; Bauer, Michael; Griffith, Thomas S.; Förster, Martin; Brunkhorst, Frank M.; Badovinac, Vladimir P.; Rubio, Ignacio

    2014-01-01

    Sepsis describes the life-threatening systemic inflammatory response (SIRS) of an organism to an infection and is the leading cause of mortality on intensive care units (ICU) worldwide. An acute episode of sepsis is characterized by the extensive release of cytokines and other mediators resulting in a dysregulated immune response leading to organ damage and/or death. This initial pro-inflammatory burst often transits into a state of immune suppression characterised by loss of immune cells and T-cell dysfunction at later disease stages in sepsis survivors. However, despite these appreciations, the precise nature of the evoked defect in T-cell immunity in post-acute phases of SIRS remains unknown. Here we present an in-depth functional analysis of T-cell function in post-acute SIRS/sepsis. We document that T-cell function is not compromised on a per cell basis in experimental rodent models of infection-free SIRS (LPS or CpG) or septic peritonitis. Transgenic antigen-specific T-cells feature an unaltered cytokine response if challenged in vivo and ex vivo with cognate antigens. Isolated CD4+/CD8+ T-cells from post-acute septic animals do not exhibit defects in T-cell receptor-mediated activation at the the level of receptor-proximal signalling, activation marker upregulation or expansion. However, SIRS/sepsis induced transient lymphopenia and gave rise to an environment of immune attenuation at post acute disease stages. Thus, systemic inflammation has an acute impact on T-cell numbers and adaptive immunity, but does not cause major cell-autonomous enduring functional defects in T-cells. PMID:25541945

  11. Sepsis and Septic Shock Strategies.

    PubMed

    Armstrong, Bracken A; Betzold, Richard D; May, Addison K

    2017-12-01

    Three therapeutic principles most substantially improve organ dysfunction and survival in sepsis: early, appropriate antimicrobial therapy; restoration of adequate cellular perfusion; timely source control. The new definitions of sepsis and septic shock reflect the inadequate sensitivity, specify, and lack of prognostication of systemic inflammatory response syndrome criteria. Sequential (sepsis-related) organ failure assessment more effectively prognosticates in sepsis and critical illness. Inadequate cellular perfusion accelerates injury and reestablishing perfusion limits injury. Multiple organ systems are affected by sepsis and septic shock and an evidence-based multipronged approach to systems-based therapy in critical illness results in improve outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. [Procalcitonin as a predictor of trauma severity and post-traumatic sepsis in children].

    PubMed

    Liu, Shao-Feng; Yuan, Gao-Pin; Yang, Jian; He, Tao-Zhen; Feng, Hai-Huan; Liu, Min

    2012-09-01

    To determine the association of procalcitonin (PCT) with trauma severity and post traumatic sepsis in children. The blood samples of 30 children with acute trauma in a Pediatric unit were collected for four consecutive days. The levels of PCT, IL-6, CRP and WBC were measured. The pediatric trauma score (PTS), length of stay in hospital, incidence of sepsis and clinical outcomes of the children were recorded. The value of PCT for predicting prognosis of children with trauma was compared with other inflammatory markers. Plasma PCT levels increased significantly in the patients in our study. Sepsis occurred in 23.33% of the patients. The patients with sepsis had higher levels of PCT than those with and without systemic inflammatory response syndrome (SIRS) and the healthy controls (P < 0.05). The peak level of PCT emerged on day 2 after trauma. The plasma PCT levels were positively correlated with trauma severity. The level of PCT on day 2 was an independent predictor for post-trauma sepsis and SIRS. Plasma PCT levels increase markedly in post trauma children. Plasma PCT of day 2 after trauma is an independent predictor of post-traumatic sepsis and SIRS complications. There is a significant correlation between the severity of injury and plasma PCT.

  13. Clinical outcome of critically ill patients with thrombocytopenia and hypophosphatemia in the early stage of sepsis.

    PubMed

    Brotfain, Evgeni; Schwartz, Andrei; Boniel, Avi; Koyfman, Leonid; Boyko, Matthew; Kutz, Ruslan; Klein, Moti

    2016-01-01

    Hypophosphatemia and thrombocytopenia may both be independent risk factors for the development of multiple organ failure and correlate well with the severity of sepsis. In the present study we wanted to analyze the potential clinical role and prognostic significance of both early hypophosphatemia and thrombocytopenia on clinical outcomes of critically ill ICU patients with severe sepsis. We analyzed the clinical data, including the outcome of critically ill ICU patients with severe sepsis who presented during a 5 year period with early hypophosphatemia and thrombocytopenia.This study was retrospective and single centre. All clinical and laboratory data was collected from the patients' ICU and hospital electronic records. All laboratory measurements were done on admission and during the ICU stay. The included patients were distributed into one of three study groups based on the presence of hypophosphatemia and/or thrombocytopenia during the first 24 hours of admission to the ICU: group 1 - early hypophosphatemia; group 2 - early hypophosphatemia and thrombocytopenia and group 3 - early thrombocytopenia. The ICU mortality rate was significantly higher in groups 2 and 3 (25.9% and 22% vs. 9.3%, respectively, P = 0.034). An APACHE II > 27, a TISS > 25 following the first 24 hours of ICU stay , an age higher than 70, male gender and total parenteral nutrition were independent predictors of ICU and hospital mortality in this study population. It may be considered that hypophosphatemia and thrombocytopenia in the early stage of sepsis, even when severe and coexisting, reflect the degree of initial illness severity of sepsis. However, further investigations need to be done for a better understanding of the potential clinical role of these features in the septic critically ill population.

  14. Immune cell phenotype and function in sepsis

    PubMed Central

    Rimmelé, Thomas; Payen, Didier; Cantaluppi, Vincenzo; Marshall, John; Gomez, Hernando; Gomez, Alonso; Murray, Patrick; Kellum, John A.

    2015-01-01

    Cells of the innate and adaptive immune systems play a critical role in the host response to sepsis. Moreover, their accessibility for sampling and their capacity to respond dynamically to an acute threat increases the possibility that leukocytes might serve as a measure of a systemic state of altered responsiveness in sepsis. The working group of the 14th Acute Dialysis Quality Initiative (ADQI) conference sought to obtain consensus on the characteristic functional and phenotypic changes in cells of the innate and adaptive immune system in the setting of sepsis. Techniques for the study of circulating leukocytes were also reviewed and the impact on cellular phenotypes and leukocyte function of non extracorporeal treatments and extracorporeal blood purification therapies proposed for sepsis was analyzed. A large number of alterations in the expression of distinct neutrophil and monocyte surface markers have been reported in septic patients. The most consistent alteration seen in septic neutrophils is their activation of a survival program that resists apoptotic death. Reduced expression of HLA-DR is a characteristic finding on septic monocytes but monocyte antimicrobial function does not appear to be significantly altered in sepsis. Regarding adaptive immunity, sepsis-induced apoptosis leads to lymphopenia in patients with septic shock and it involves all types of T cells (CD4, CD8 and Natural Killer) except T regulatory cells, thus favoring immunosuppression. Finally, numerous promising therapies targeting the host immune response to sepsis are under investigation. These potential treatments can have an effect on the number of immune cells, the proportion of cell subtypes and the cell function. PMID:26529661

  15. IMMUNE CELL PHENOTYPE AND FUNCTION IN SEPSIS.

    PubMed

    Rimmelé, Thomas; Payen, Didier; Cantaluppi, Vincenzo; Marshall, John; Gomez, Hernando; Gomez, Alonso; Murray, Patrick; Kellum, John A

    2016-03-01

    Cells of the innate and adaptive immune systems play a critical role in the host response to sepsis. Moreover, their accessibility for sampling and their capacity to respond dynamically to an acute threat increases the possibility that leukocytes might serve as a measure of a systemic state of altered responsiveness in sepsis.The working group of the 14th Acute Dialysis Quality Initiative (ADQI) conference sought to obtain consensus on the characteristic functional and phenotypic changes in cells of the innate and adaptive immune system in the setting of sepsis. Techniques for the study of circulating leukocytes were also reviewed and the impact on cellular phenotypes and leukocyte function of nonextracorporeal treatments and extracorporeal blood purification therapies proposed for sepsis was analyzed.A large number of alterations in the expression of distinct neutrophil and monocyte surface markers have been reported in septic patients. The most consistent alteration seen in septic neutrophils is their activation of a survival program that resists apoptotic death. Reduced expression of HLA-DR is a characteristic finding on septic monocytes, but monocyte antimicrobial function does not appear to be significantly altered in sepsis. Regarding adaptive immunity, sepsis-induced apoptosis leads to lymphopenia in patients with septic shock and it involves all types of T cells (CD4, CD8, and Natural Killer) except T regulatory cells, thus favoring immunosuppression. Finally, numerous promising therapies targeting the host immune response to sepsis are under investigation. These potential treatments can have an effect on the number of immune cells, the proportion of cell subtypes, and the cell function.

  16. The impact of hospital-onset Clostridium difficile infection on outcomes of hospitalized patients with sepsis.

    PubMed

    Lagu, Tara; Stefan, Mihaela S; Haessler, Sarah; Higgins, Thomas L; Rothberg, Michael B; Nathanson, Brian H; Hannon, Nicholas S; Steingrub, Jay S; Lindenauer, Peter K

    2014-07-01

    To examine the impact of hospital-onset Clostridium difficile infection (HOCDI) on the outcomes of patients with sepsis. Most prior studies that have addressed this issue lacked adequate matching to controls, suffered from small sample size, or failed to consider time to infection. Retrospective cohort study. We identified adults with a principal or secondary diagnosis of sepsis who received care at 1 of the institutions that participated in a large multihospital database between July 1, 2004 and December 31, 2010. Among eligible patients with sepsis, we identified patients who developed HOCDI during their hospital stay. We used propensity matching and date of diagnosis to match cases to patients without Clostridium difficile infections and compared outcomes between the 2 groups. Of 218,915 sepsis patients, 2368 (1.08%) developed HOCDI. Unadjusted in-hospital mortality was significantly higher in HOCDI patients than controls (25% vs 10%, P < 0.001). After multivariate adjustment, in-hospital mortality rate was 24% in cases vs. 15% in controls. In an analysis limited to survivors, adjusted length of stay (LOS) among cases with Clostridium difficile infections was 5.1 days longer than controls (95% confidence interval: 4.4-5.8) and the median-adjusted cost increase was $4916 (P < 0.001). After rigorous adjustment for time to diagnosis and presenting severity, hospital-acquired Clostridium difficile infection was associated with increased mortality, LOS, and cost. Our results can be used to assess the cost-effectiveness of prevention programs and suggest that efforts directed toward high-risk patient populations are needed. © 2014 Society of Hospital Medicine.

  17. New criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: a retrospective analysis of a nationwide survey.

    PubMed

    Iba, Toshiaki; Nisio, Marcello Di; Levy, Jerrold H; Kitamura, Naoya; Thachil, Jecko

    2017-09-27

    Recent clinical studies have shown that anticoagulant therapy might be effective only in specific at-risk subgroups of patients with sepsis and coagulation dysfunction. The definition of sepsis was recently modified, and as such, old scoring systems may no longer be appropriate for the diagnosis of sepsis-associated coagulopathy. The aim of this study was to evaluate prognostic factors in patients diagnosed with sepsis and coagulopathy according to the new sepsis definition and assess their accuracy in comparison with existing models. Retrospective analysis of the nationwide survey for recombinant human soluble thrombomodulin. General emergency and critical care centres in secondary and tertiary care hospitals. We evaluated the prognostic value of the newly proposed diagnostic criteria for sepsis-induced coagulopathy (SIC). A total of 1498 Japanese patients with sepsis and coagulopathy complications who were treated with recombinant thrombomodulin were analysed in this study. The platelet count, prothrombin time (PT) ratio, fibrinogen/fibrin degradation products, systemic inflammatory response syndrome score and Sequential Organ Failure Assessment (SOFA) score obtained just before the start of treatment were examined in relation to the 28-day mortality rate. The platelet count, PT ratio and total SOFA were independent predictors of a fatal outcome in a logistic regression model. A SIC score was defined using the three above-mentioned variables with a positivity threshold of 4 points or more. The SIC score predicted higher 28-day mortality rate compared with the current Japanese Association for Acute Medicine-disseminated intravascular coagulation score (38.4%vs34.7%). The SIC score is based on readily available parameters, is easy to calculate and has a high predictive value for 28-day mortality. Future studies are warranted to evaluate whether the SIC score may guide the decision to initiate anticoagulant therapy. © Article author(s) (or their employer(s) unless

  18. Measurement of Mitochondrial Respiration and Motility in Acute Care: Sepsis, Trauma, and Poisoning.

    PubMed

    Jang, David H; Greenwood, John C; Spyres, Meghan B; Eckmann, David M

    2017-01-01

    Metabolic biomarkers have potentially wider use in disease diagnosis and prognosis as well as in monitoring disease response to treatment. While biomarkers such as interleukins, microRNA, and lactate have been proposed for disease surveillance, there are still conflicting results regarding their clinical utility. Treatment of commonly encountered disease of acute care such as sepsis, trauma, and poisoning often relies on clinical diagnosis and therapy guided by use of surrogate markers of illness severity. The measurement of mitochondrial function, including respiration and motility, may offer superior alternatives to such markers. Assessing mitochondrial function in a clinical context has the potential to impact the area of acute care in terms of diagnosis, prognosis, and treatment. The study of mitochondrial bioenergetics has become critical in understanding the pathophysiology and treatment of complex diseases such as diabetes and cardiovascular disorders. © The Author(s) 2016.

  19. Concise Review: Mesenchymal Stromal Cell‐Based Approaches for the Treatment of Acute Respiratory Distress and Sepsis Syndromes

    PubMed Central

    Soeder, Yorick; Dahlke, Marc H.

    2017-01-01

    Abstract Despite extensive research on candidate pharmacological treatments and a significant and increasing prevalence, sepsis syndrome, and acute respiratory distress syndrome (ARDS) remain areas of unmet clinical need. Preclinical studies examining mesenchymal stromal cell (MSCs) based‐therapies have provided compelling evidence of potential benefit; however, the precise mechanism by which MSCs exert a therapeutic influence, and whether MSC application is efficacious in humans, remains unknown. Detailed evaluation of the limited number of human trials so far completed is further hampered as a result of variations in trial design and biomarker selection. This review provides a concise summary of current preclinical and clinical knowledge of MSCs as a cell therapy for sepsis syndrome and ARDS. The challenges of modeling such heterogeneous and rapidly progressive disease states are considered and we discuss how lessons from previous studies of pharmacological treatments for sepsis syndrome and ARDS might be used to inform and refine the design of the next generation of MSC clinical trials. Stem Cells Translational Medicine 2017;6:1141–1151 PMID:28186706

  20. Alkaline phosphatase: a possible treatment for sepsis-associated acute kidney injury in critically ill patients.

    PubMed

    Peters, Esther; Heemskerk, Suzanne; Masereeuw, Rosalinde; Pickkers, Peter

    2014-06-01

    Acute kidney injury (AKI) is a common disease in the intensive care unit and accounts for high morbidity and mortality. Sepsis, the predominant cause of AKI in this setting, involves a complex pathogenesis in which renal inflammation and hypoxia are believed to play an important role. A new therapy should be aimed at targeting both these processes, and the enzyme alkaline phosphatase, with its dual mode of action, might be a promising candidate. First, alkaline phosphatase is able to reduce inflammation through dephosphorylation and thereby detoxification of endotoxin (lipopolysaccharide), which is an important mediator of sepsis. Second, adenosine triphosphate, released during cellular stress caused by inflammation and hypoxia, has detrimental effects but can be converted by alkaline phosphatase into adenosine with anti-inflammatory and tissue-protective effects. These postulated beneficial effects of alkaline phosphatase have been confirmed in animal experiments and two phase 2a clinical trials showing that kidney function improved in critically ill patients with sepsis-associated AKI. Because renal inflammation and hypoxia also are observed commonly in AKI induced by other causes, it would be of interest to investigate the therapeutic effect of alkaline phosphatase in these nephropathies as well. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  1. Gene expression profiles analysis identifies key genes for acute lung injury in patients with sepsis.

    PubMed

    Guo, Zhiqiang; Zhao, Chuncheng; Wang, Zheng

    2014-09-26

    To identify critical genes and biological pathways in acute lung injury (ALI), a comparative analysis of gene expression profiles of patients with ALI + sepsis compared with patients with sepsis alone were performed with bioinformatic tools. GSE10474 was downloaded from Gene Expression Omnibus, including a collective of 13 whole blood samples with ALI + sepsis and 21 whole blood samples with sepsis alone. After pre-treatment with robust multichip averaging (RMA) method, differential analysis was conducted using simpleaffy package based upon t-test and fold change. Hierarchical clustering was also performed using function hclust from package stats. Beisides, functional enrichment analysis was conducted using iGepros. Moreover, the gene regulatory network was constructed with information from Kyoto Encyclopedia of Genes and Genomes (KEGG) and then visualized by Cytoscape. A total of 128 differentially expressed genes (DEGs) were identified, including 47 up- and 81 down-regulated genes. The significantly enriched functions included negative regulation of cell proliferation, regulation of response to stimulus and cellular component morphogenesis. A total of 27 DEGs were significantly enriched in 16 KEGG pathways, such as protein digestion and absorption, fatty acid metabolism, amoebiasis, etc. Furthermore, the regulatory network of these 27 DEGs was constructed, which involved several key genes, including protein tyrosine kinase 2 (PTK2), v-src avian sarcoma (SRC) and Caveolin 2 (CAV2). PTK2, SRC and CAV2 may be potential markers for diagnosis and treatment of ALI. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5865162912987143.

  2. Bacillus cereus causing fulminant sepsis and hemolysis in two patients with acute leukemia.

    PubMed

    Arnaout, M K; Tamburro, R F; Bodner, S M; Sandlund, J T; Rivera, G K; Pui, C H; Ribeiro, R C

    1999-01-01

    Hemolysis is so rarely associated with Bacillus cereus sepsis that only two very well documented cases have been reported. This article reports two unusual cases of Bacillus cereus sepsis with massive intravascular hemolysis in patients who had acute lymphoblastic leukemia (ALL). A 20-year-old woman who was 9 weeks pregnant experienced a relapse of ALL. A therapeutic abortion was performed. During week 4 of reinduction the patient had abdominal pain, nausea, and vomiting, with severe neutropenia but no fever. Her condition deteriorated rapidly with cardiovascular collapse, acute massive intravascular hemolysis, and death within hours of the onset of symptoms. Blood cultures were positive for Bacillus cereus. Postmortem histologic examination and cultures revealed Bacillus cereus and Candida albicans in multiple organs. The second patient, a 10-year-old girl, presented with relapsed T-cell ALL. In the second week of reinduction, she had abdominal pain followed by hypotension. Again, no fever was noted. Laboratory studies showed intravascular hemolysis 12 hours after admission. Aggressive support was promptly initiated. Despite disseminated intravascular coagulation; cardiovascular, hepatic, and renal failure; and multiple intracerebral hypodense lesions believed to be infarcts, the patient recovered fully and resumed reinduction therapy. Bacillus cereus infection can have a fulminant clinical course that may be complicated by massive intravascular hemolysis. This pathogen should be suspected in immunosuppressed patients who experience gastrointestinal symptoms and should not be precluded by the absence of fever, especially if steroids such as dexamethasone are being given. Exchange transfusion may be lifesaving in Bacillus cereus septicemia associated with massive hemolysis.

  3. Triage sepsis alert and sepsis protocol lower times to fluids and antibiotics in the ED.

    PubMed

    Hayden, Geoffrey E; Tuuri, Rachel E; Scott, Rachel; Losek, Joseph D; Blackshaw, Aaron M; Schoenling, Andrew J; Nietert, Paul J; Hall, Greg A

    2016-01-01

    Early identification of sepsis in the emergency department (ED), followed by adequate fluid hydration and appropriate antibiotics, improves patient outcomes. We sought to measure the impact of a sepsis workup and treatment protocol (SWAT) that included an electronic health record (EHR)-based triage sepsis alert, direct communication, mobilization of resources, and standardized order sets. We conducted a retrospective, quasiexperimental study of adult ED patients admitted with suspected sepsis, severe sepsis, or septic shock. We defined a preimplementation (pre-SWAT) group and a postimplementation (post-SWAT) group and further broke these down into SWAT A (septic shock) and SWAT B (sepsis with normal systolic blood pressure). We performed extensive data comparisons in the pre-SWAT and post-SWAT groups, including demographics, systemic inflammatory response syndrome criteria, time to intravenous fluids bolus, time to antibiotics, length-of-stay times, and mortality rates. There were 108 patients in the pre-SWAT group and 130 patients in the post-SWAT group. The mean time to bolus was 31 minutes less in the postimplementation group, 51 vs 82 minutes (95% confidence interval, 15-46; P value < .01). The mean time to antibiotics was 59 minutes less in the postimplementation group, 81 vs 139 minutes (95% confidence interval, 44-74; P value < .01). Segmented regression modeling did not identify secular trends in these outcomes. There was no significant difference in mortality rates. An EHR-based triage sepsis alert and SWAT protocol led to a significant reduction in the time to intravenous fluids and time to antibiotics in ED patients admitted with suspected sepsis, severe sepsis, and septic shock. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Barriers to implementing the Sepsis Six guidelines in an acute hospital setting.

    PubMed

    Breen, Sarah-Jane; Rees, Sharon

    2018-05-10

    To identify the barriers to implementation of the Sepsis Six pathway. Research has suggested that compliance with the Sepsis Six pathway remains low. A convenience sample of doctors and nurses from one emergency department, two medical wards and two surgical wards were asked to complete a survey questionnaire. Data from 108 respondents were available for analysis. Doctors and nurses agreed that lack of sepsis recognition during observation rounds and failure to associate sepsis with deranged temperature and blood results acted as barriers to the identification of sepsis. Doctors and nurses agreed that nursing delays and knowledge deficits were the top barriers leading to delay in sepsis treatment. Knowledge deficits, lack of resources and practical issues were barriers identified in this survey. This will inform the educational and process needs of both doctors and nurses in order to improve sepsis care.

  5. The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults.

    PubMed

    McGill, F; Heyderman, R S; Michael, B D; Defres, S; Beeching, N J; Borrow, R; Glennie, L; Gaillemin, O; Wyncoll, D; Kaczmarski, E; Nadel, S; Thwaites, G; Cohen, J; Davies, N W S; Miller, A; Rhodes, A; Read, R C; Solomon, T

    2016-04-01

    Bacterial meningitis and meningococcal sepsis are rare conditions with high case fatality rates. Early recognition and prompt treatment saves lives. In 1999 the British Infection Society produced a consensus statement for the management of immunocompetent adults with meningitis and meningococcal sepsis. Since 1999 there have been many changes. We therefore set out to produce revised guidelines which provide a standardised evidence-based approach to the management of acute community acquired meningitis and meningococcal sepsis in adults. A working party consisting of infectious diseases physicians, neurologists, acute physicians, intensivists, microbiologists, public health experts and patient group representatives was formed. Key questions were identified and the literature reviewed. All recommendations were graded and agreed upon by the working party. The guidelines, which for the first time include viral meningitis, are written in accordance with the AGREE 2 tool and recommendations graded according to the GRADE system. Main changes from the original statement include the indications for pre-hospital antibiotics, timing of the lumbar puncture and the indications for neuroimaging. The list of investigations has been updated and more emphasis is placed on molecular diagnosis. Approaches to both antibiotic and steroid therapy have been revised. Several recommendations have been given regarding the follow-up of patients. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Resuscitation With Balanced Fluids Is Associated With Improved Survival in Pediatric Severe Sepsis.

    PubMed

    Emrath, Elizabeth T; Fortenberry, James D; Travers, Curtis; McCracken, Courtney E; Hebbar, Kiran B

    2017-07-01

    To evaluate outcomes in patients receiving balanced fluids for resuscitation in pediatric severe sepsis. Observational cohort review of prospectively collected data from a large administrative database. PICUs from 43 children's hospitals. PICU patients diagnosed with severe sepsis. None. We reviewed data from the Pediatric Health Information System database from 2004 to 2012. Children with pediatric severe sepsis receiving balanced fluids for resuscitation in the first 24 and 72 hours of treatment were compared to those receiving unbalanced fluids. Thirty-six thousand nine hundred eight patients met entry criteria for analysis. Two thousand three hundred ninety-eight patients received exclusively balanced fluids at 24 hours and 1,641 at 72 hours. After propensity matching, the 72-hour balanced fluids group had lower mortality (12.5% vs 15.9%; p = 0.007; odds ratio, 0.76; 95% CI, 0.62-0.93), lower prevalence of acute kidney injury (16.0% vs 19.2%; p = 0.028; odds ratio, 0.82; 95% CI, 0.68-0.98), and fewer vasoactive infusion days (3.0 vs 3.3 d; p < 0.001) when compared with the unbalanced fluids group. In this retrospective analysis carried out by propensity matching, exclusive use of balanced fluids in pediatric severe sepsis patients for the first 72 hours of resuscitation was associated with improved survival, decreased prevalence of acute kidney injury, and shorter duration of vasoactive infusions when compared with exclusive use of unbalanced fluids.

  7. Acute-on-chronic Liver Failure.

    PubMed

    Sarin, Shiv Kumar; Choudhury, Ashok

    2016-12-01

    Acute-on-chronic liver failure (ACLF) is a distinct entity that differs from acute liver failure and decompensated cirrhosis in timing, presence of treatable acute precipitant, and course of disease, with a potential for self-recovery. The core concept is acute deterioration of existing liver function in a patient of chronic liver disease with or without cirrhosis in response to an acute insult. The insult should be a hepatic one and presentation in the form of liver failure (jaundice, encephalopathy, coagulopathy, ascites) with or without extrahepatic organ failure in a defined time frame. ACLF is characterized by a state of deregulated inflammation. Initial cytokine burst presenting as SIRS, progression to CARS and associated immunoparalysis leads to sepsis and multi-organ failure. Early identification of the acute insult and mitigation of the same, use of nucleoside analogue in HBV-ACLF, steroid in severe alcoholic hepatitis, steroid in severe autoimmune hepatitis and/or bridging therapy lead to recovery, with a 90-day transplant-free survival rate of up to 50 %. First-week presentation is crucial concerning SIRS/sepsis, development, multiorgan failure and consideration of transplant. A protocol-based multi-disciplinary approach including critical care hepatology, early liver transplant before multi-organ involvement, or priority for organ allocation may improve the outcome. Presentation with extrahepatic organ involvement or inclusion of sepsis as an acute insult in definition restricts the therapy, i.e., liver transplant or bridging therapy, and needs serious consideration. Augmentation of regeneration, cell-based therapy, immunotherapy, and gut microbiota modulation are the emerging areas and need further research.

  8. An unusual case of sepsis and petechial rash.

    PubMed

    Gardner, Christina

    2017-05-01

    This article describes a man who presented to the ED in acute distress with signs and symptoms of sepsis, pneumonia, and a new petechial rash on his chest. He was eventually diagnosed with Rocky Mountain spotted fever. Aggressive treatment of sepsis and timely administration of empiric antibiotics were lifesaving in this situation.

  9. Epidemiology and Changes in Mortality of Sepsis After the Implementation of Surviving Sepsis Campaign Guidelines.

    PubMed

    Herrán-Monge, Rubén; Muriel-Bombín, Arturo; García-García, Marta M; Merino-García, Pedro A; Martínez-Barrios, Miguel; Andaluz, David; Ballesteros, Juan Carlos; Domínguez-Berrot, Ana María; Moradillo-Gonzalez, Susana; Macías, Santiago; Álvarez-Martínez, Braulio; Fernández-Calavia, M José; Tarancón, Concepción; Villar, Jesús; Blanco, Jesús

    2017-01-01

    To determine the epidemiology and outcome of severe sepsis and septic shock after 9 years of the implementation of the Surviving Sepsis Campaign (SSC) and to build a mortality prediction model. This is a prospective, multicenter, observational study performed during a 5-month period in 2011 in a network of 11 intensive care units (ICUs). We compared our findings with those obtained in the same ICUs in a study conducted in 2002. The current cohort included 262 episodes of severe sepsis and/or septic shock, and the 2002 cohort included 324. The prevalence was 14% (95% confidence interval: 12.5-15.7) with no differences to 2002. The population-based incidence was 31 cases/100 000 inhabitants/year. Patients in 2011 had a significantly lower Acute Physiology and Chronic Health Evaluation II (APACHE II; 21.9 ± 6.6 vs 25.5 ± 7.07), Logistic Organ Dysfunction Score (5.6 ± 3.2 vs 6.3 ± 3.6), and Sequential Organ Failure Assessment (SOFA) scores on day 1 (8 ± 3.5 vs 9.6 ± 3.7; P < .01). The main source of infection was intraabdominal (32.5%) although microbiologic isolation was possible in 56.7% of cases. The 2011 cohort had a marked reduction in 48-hour (7% vs 14.8%), ICU (27.2% vs 48.2%), and in-hospital (36.7% vs 54.3%) mortalities. Most relevant factors associated with death were APACHE II score, age, previous immunosuppression and liver insufficiency, alcoholism, nosocomial infection, and Delta SOFA score. Although the incidence of sepsis/septic shock remained unchanged during a 10-year period, the implementation of the SSC guidelines resulted in a marked decrease in the overall mortality. The lower severity of patients on ICU admission and the reduced early mortality suggest an improvement in early diagnosis, better initial management, and earlier antibiotic treatment.

  10. Myocardial Injury in Patients With Sepsis and Its Association With Long-Term Outcome.

    PubMed

    Frencken, Jos F; Donker, Dirk W; Spitoni, Cristian; Koster-Brouwer, Marlies E; Soliman, Ivo W; Ong, David S Y; Horn, Janneke; van der Poll, Tom; van Klei, Wilton A; Bonten, Marc J M; Cremer, Olaf L

    2018-02-01

    Sepsis is frequently complicated by the release of cardiac troponin, but the clinical significance of this myocardial injury remains unclear. We studied the associations between troponin release during sepsis and 1-year outcomes. We enrolled consecutive patients with sepsis in 2 Dutch intensive care units between 2011 and 2013. Subjects with a clinically apparent cause of troponin release were excluded. High-sensitivity cardiac troponin I (hs-cTnI) concentration in plasma was measured daily during the first 4 intensive care unit days, and multivariable Cox regression analysis was used to model its association with 1-year mortality while adjusting for confounding. In addition, we studied cardiovascular morbidity occurring during the first year after hospital discharge. Among 1258 patients presenting with sepsis, 1124 (89%) were eligible for study inclusion. Hs-cTnI concentrations were elevated in 673 (60%) subjects on day 1, and 755 (67%) ever had elevated levels in the first 4 days. Cox regression analysis revealed that high hs-cTnI concentrations were associated with increased death rates during the first 14 days (adjusted hazard ratio, 1.72; 95% confidence interval, 1.14-2.59 and hazard ratio, 1.70; 95% confidence interval, 1.10-2.62 for hs-cTnI concentrations of 100-500 and >500 ng/L, respectively) but not thereafter. Furthermore, elevated hs-cTnI levels were associated with the development of cardiovascular disease among 200 hospital survivors who were analyzed for this end point (adjusted subdistribution hazard ratio, 1.25; 95% confidence interval, 1.04-1.50). Myocardial injury occurs in the majority of patients with sepsis and is independently associated with early-but not late-mortality, as well as postdischarge cardiovascular morbidity. © 2018 American Heart Association, Inc.

  11. Cardiovascular response to dobutamine stress predicts outcome in severe sepsis and septic shock.

    PubMed

    Kumar, Anand; Schupp, Elizabeth; Bunnell, Eugene; Ali, Amjad; Milcarek, Barry; Parrillo, Joseph E

    2008-01-01

    During septic shock, resistance to the haemodynamic effects of catecholamine vasopressors and inotropes is a well-recognised marker of mortality risk. However, the specific cardiovascular or metabolic response elements that are most closely associated with outcome have not been well defined. The objective of this study was to assess cardiovascular and metabolic responses to dobutamine as correlates of outcome in patients with severe sepsis or septic shock. A prospective, non-randomised, non-blinded interventional study of graded dobutamine challenge (0, 5, 10, and 15 mug/kg/min) in adult patients who had undergone pulmonary artery catheterisation within 48 hours of onset of severe sepsis or septic shock (8 survivors/15 non-survivors) was performed. Radionuclide cineangiography during graded infusion was used to determine biventricular ejection fractions at each increment of dobutamine. In univariate analysis, a variety of cardiovascular or haemodynamic and oxygen transport or metabolic variables (at the point of maximum cardiac index response for a given subject) were associated with survival including: increased stroke volume index (p = 0.0003); right ventricular end-diastolic volume index (p = 0.0047); left ventricular stroke work index (p = 0.0054); oxygen delivery index (p = 0.0084); cardiac index (p = 0.0093); systolic blood pressure/left ventricular end-systolic volume index ratio (p = 0.0188); left ventricular ejection fraction (p = 0.0160); venous oxygen content (p = 0.0208); mixed venous oxygen saturation (p = 0.0234); pulse pressure (p = 0.0403); decreased pulmonary artery diastolic pressure (p = 0.0133); systemic vascular resistance index (p = 0.0154); extraction ratio (p = 0.0160); and pulmonary vascular resistance index (p = 0.0390). Increases of stroke volume index of greater than or less than 8.5 mL/m2 were concordant with survival or death in 21 of 23 cases. Multivariate profile construction showed stroke volume index as the dominant discriminating

  12. Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain.

    PubMed

    Ferrer, Ricard; Artigas, Antonio; Levy, Mitchell M; Blanco, Jesús; González-Díaz, Gumersindo; Garnacho-Montero, José; Ibáñez, Jordi; Palencia, Eduardo; Quintana, Manuel; de la Torre-Prados, María Victoria

    2008-05-21

    Concern exists that current guidelines for care of patients with severe sepsis and septic shock are followed variably, possibly due to a lack of adequate education. To determine whether a national educational program based on the Surviving Sepsis Campaign guidelines affected processes of care and hospital mortality for severe sepsis. Before and after design in 59 medical-surgical intensive care units (ICUs) located throughout Spain. All ICU patients were screened daily and enrolled if they fulfilled severe sepsis or septic shock criteria. A total of 854 patients were enrolled in the preintervention period (November-December 2005), 1465 patients during the postintervention period (March-June 2006), and 247 patients during the long-term follow-up period 1 year later (November-December 2006) in a subset of 23 ICUs. The educational program consisted of training physicians and nursing staff from the emergency department, wards, and ICU in the definition, recognition, and treatment of severe sepsis and septic shock as outlined in the guidelines. Treatment was organized in 2 bundles: a resuscitation bundle (6 tasks to begin immediately and be accomplished within 6 hours) and a management bundle (4 tasks to be completed within 24 hours). Hospital mortality, differences in adherence to the bundles' process-of-care variables, ICU mortality, 28-day mortality, hospital length of stay, and ICU length of stay. Patients included before and after the intervention were similar in terms of age, sex, and Acute Physiology and Chronic Health Evaluation II score. At baseline, only 3 process-of-care measurements (blood cultures before antibiotics, early administration of broad-spectrum antibiotics, and mechanical ventilation with adequate inspiratory plateau pressure) we had compliance rates higher than 50%. Patients in the postintervention cohort had a lower risk of hospital mortality (44.0% vs 39.7%; P = .04). The compliance with process-of-care variables also improved after the

  13. Evaluation of risk factors and development of acute kidney injury in aneurysmal subarachnoid hemorrhage, head injury, and severe sepsis/septic shock patients during ICU treatment.

    PubMed

    Kamar, Ceren; Ali, Achmet; Altun, Demet; Orhun, Günseli; Sabancı, Akın; Sencer, Altay; Akıncı, İbrahim Özkan

    2017-01-01

    There are few studies examining development of acute kidney injury (AKI) in the various types of patients in intensive care units (ICUs). Presently described is evaluation of risk factors and development of AKI in different groups of ICU patients. Present study was performed in 3 different ICUs. Development of AKI was measured using Acute Kidney Injury Network (AKIN) classification system. Total of 300 patients who were treated in trauma, neurosurgery, or general ICU departments (due to head injury, aneurysmal subarachnoid hemorrhage [aSAH], or severe sepsis/septic shock, respectively) were assessed for incidence, risk factors, and development of AKI. AKI did not develop in aSAH patients when evaluated based on serum creatinine level; however, it was observed in 5% of aSAH patients according to volume adjusted creatinine (VACr) level. AKI developed in 76% of sepsis group, and in 20% of head injury group, based on AKIN classification, according to both serum and VACr levels. Incidence of AKI was significantly higher in sepsis group (p<0.001). Only use of vasopressor was significantly related to AKI development in sepsis and head injury groups. Mortality rate was 8%, 22%, and 42% in aSAH, head injury, and sepsis groups, respectively. AKI development and vasopressor use were significantly related to mortality in sepsis group. Despite similar characteristics and risk factors, there were fewer instances of AKI in aSAH group. Hypertension or hydration therapy used to treat vasospasm and polyuria due to cerebral salt-wasting syndrome may prevent aSAH patients from developing AKI.

  14. Risk of acute stroke after hospitalization for sepsis: A case-crossover study

    PubMed Central

    Boehme, Amelia K.; Ranawat, Purnima; Luna, Jorge; Kamel, Hooman; Elkind, Mitchell S. V.

    2017-01-01

    Background and Purpose Infections have been found to increase the risk of stroke over the short-term. We hypothesized that stroke risk would be highest shortly after a sepsis hospitalization, but that the risk would decrease, yet remain up to 1-year after sepsis. Methods This case-crossover analysis utilized data obtained from the California State Inpatient Database of the Healthcare Cost and Utilization Project (HCUP). All stroke admissions were included. Exposure was defined as hospitalization for sepsis or septicemia 180, 90, 30 or 15 days before stroke (risk period) or similar time intervals exactly 1 or 2 years before stroke (control period). Conditional logistic regression was used to calculate the odds ratio and 95% confidence interval (OR, 95% CI) for the association between sepsis/septicemia and ischemic or hemorrhagic stroke. Results Ischemic (n=37,377) and hemorrhagic (n=12,817) strokes that occurred in 2009 were extracted where 3188 (8.5%) ischemic and 1101 (8.6%) hemorrhagic stroke patients had sepsis. Sepsis within 15 days prior to the stroke placed patients at the highest risk of ischemic (OR 28.36, 95% CI 20.02 –40.10) and hemorrhagic stroke (OR 12.10, 95% CI 7.54–19.42); however while the risk decreased, it remained elevated 181- 365 days after sepsis for ischemic (OR 2.59, 95%CI 2.20–3.06) and hemorrhagic (O 3.92, 95%CI 3.29–4.69) strokes. There was an interaction with age (p=0.0006); risk of developing an ischemic stroke within 180 days of hospitalization for sepsis increased 18% with each 10-year decrease in age. Conclusion Risk of stroke is high after sepsis, and this risk persists for up to a year. Younger sepsis patients have a particularly increased risk of stroke after sepsis. PMID:28196938

  15. Blocking Cyclic Adenosine Diphosphate Ribose-mediated Calcium Overload Attenuates Sepsis-induced Acute Lung Injury in Rats

    PubMed Central

    Peng, Qian-Yi; Zou, Yu; Zhang, Li-Na; Ai, Mei-Lin; Liu, Wei; Ai, Yu-Hang

    2016-01-01

    Background: Acute lung injury (ALI) is a common complication of sepsis that is associated with high mortality. Intracellular Ca2+ overload plays an important role in the pathophysiology of sepsis-induced ALI, and cyclic adenosine diphosphate ribose (cADPR) is an important regulator of intracellular Ca2+ mobilization. The cluster of differentiation 38 (CD38)/cADPR pathway has been found to play roles in multiple inflammatory processes but its role in sepsis-induced ALI is still unknown. This study aimed to investigate whether the CD38/cADPR signaling pathway is activated in sepsis-induced ALI and whether blocking cADPR-mediated calcium overload attenuates ALI. Methods: Septic rat models were established by cecal ligation and puncture (CLP). Rats were divided into the sham group, the CLP group, and the CLP+ 8-bromo-cyclic adenosine diphosphate ribose (8-Br-cADPR) group. Nicotinamide adenine dinucleotide (NAD+), cADPR, CD38, and intracellular Ca2+ levels in the lung tissues were measured at 6, 12, 24, and 48 h after CLP surgery. Lung histologic injury, tumor necrosis factor (TNF)-α, malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activities were measured. Results: NAD+, cADPR, CD38, and intracellular Ca2+ levels in the lungs of septic rats increased significantly at 24 h after CLP surgery. Treatment with 8-Br-cADPR, a specific inhibitor of cADPR, significantly reduced intracellular Ca2+ levels (P = 0.007), attenuated lung histological injury (P = 0.023), reduced TNF-α and MDA levels (P < 0.001 and P = 0.002, respectively) and recovered SOD activity (P = 0.031) in the lungs of septic rats. Conclusions: The CD38/cADPR pathway is activated in the lungs of septic rats, and blocking cADPR-mediated calcium overload with 8-Br-cADPR protects against sepsis-induced ALI. PMID:27411462

  16. The new sepsis definition: limitations and contribution to research and diagnosis of sepsis.

    PubMed

    Verdonk, Franck; Blet, Alice; Mebazaa, Alexandre

    2017-04-01

    Based on recent clinical, epidemiological, and pathophysiological data, a third international consensus conference was carried out to define new criteria of sepsis in February 2016. This review presents the different items of this new definition, their limitations and their contribution to research and diagnosis of sepsis, in comparison with the previous definitions. Incidence, management, and pathophysiological knowledge of sepsis have improved over the past 20 years. However, sepsis still evolves to a mortal outcome, in one case out of five, with no new recent or specific therapy showing its efficacy on the patient's prognosis. These findings have led to the development of new definition. The new definition of sepsis incorporates relevant clinical and biological criteria such as SOFA score or serum lactate levels. It no longer takes into account the items of the systemic inflammatory response syndrome, which present a lack of specificity. It also simplifies the different stages of severity by deleting the term of 'severe sepsis' and by defining septic shock as a subset of sepsis. This definition, endorsed by only two international societies of intensive care, has some limitations and so merits prospective validation at different levels.

  17. Low power infrared laser modifies the morphology of lung affected with acute injury induced by sepsis

    NASA Astrophysics Data System (ADS)

    Sergio, L. P. S.; Trajano, L. A. S. N.; Thomé, A. M. C.; Mencalha, A. L.; Paoli, F.; Fonseca, A. S.

    2018-06-01

    Acute lung injury (ALI) is a potentially fatal disease characterized by uncontrolled hyperinflammatory responses in the lungs as a consequence of sepsis. ALI is divided into two sequential and time-dependent phases, exudative and fibroproliferative phases, with increased permeability of the alveolar barrier, causing edema and inflammation. However, there are no specific treatments for ALI. Low-power lasers have been successfully used in the resolution of acute inflammatory processes. The aim of this study was to evaluate the effects of low-power infrared laser exposure on alveolus and interalveolar septa of Wistar rats affected by ALI-induced by sepsis. Laser fluences, power, and the emission mode were those used in clinical protocols for the treatment of acute inflammation. Adult male Wistar rats were randomized into six groups: control, 10 J cm‑2, 20 J cm‑2, ALI, ALI  +  10 J cm‑2, and ALI  +  20 J cm‑2. ALI was induced by intraperitoneal Escherichia coli lipopolysaccharide (LPS). Lungs were removed and processed for hematoxylin–eosin staining. Morphological alterations induced by LPS in lung tissue were quantified by morphometry with a 32-point cyclic arcs test system in Stepanizer. Data showed that exposure to low-power infrared laser in both fluences reduced the thickening of interalveolar septa in lungs affected by ALI, increasing the alveolar space; however, inflammatory infiltrate was still observed. Our research showed that exposure to low-power infrared laser improves the lung parenchyma in Wistar rats affected by ALI, which could be an alternative approach for treatment of inflammatory lung injuries.

  18. Blood transfusion improves renal oxygenation and renal function in sepsis-induced acute kidney injury in rats.

    PubMed

    Zafrani, Lara; Ergin, Bulent; Kapucu, Aysegul; Ince, Can

    2016-12-20

    The effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury. Twenty-seven Wistar albino rats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 7), a LPS group that received fluid resuscitation (n = 7), and a LPS group that received blood transfusion (n = 7). The mean arterial blood pressure, renal blood flow, and renal microvascular oxygenation within the kidney cortex were recorded. Acute kidney injury was assessed using the serum creatinine levels, metabolic cost, and histopathological lesions. Nitrosative stress (expression of endothelial (eNOS) and inducible nitric oxide synthase (iNOS)) within the kidney was assessed by immunohistochemistry. Hemoglobin levels, pH, serum lactate levels, and liver enzymes were measured. Fluid resuscitation and blood transfusion both significantly improved the mean arterial pressure and renal blood flow after LPS infusion. Renal microvascular oxygenation, serum creatinine levels, and tubular damage significantly improved in the LPS group that received blood transfusion compared to the group that received fluids. Moreover, the renal expression of eNOS was markedly suppressed under endotoxin challenge. Blood transfusion, but not fluid resuscitation, was able to restore the renal expression of eNOS. However, there were no significant differences in lactic acidosis or liver function between the two groups. Blood transfusion significantly improved renal function in endotoxemic rats. The specific beneficial effect of blood transfusion on the kidney could have been mediated in part by the improvements in renal microvascular oxygenation and sepsis-induced endothelial dysfunction via the restoration of eNOS expression within the kidney.

  19. HbA1c is outcome predictor in diabetic patients with sepsis.

    PubMed

    Gornik, Ivan; Gornik, Olga; Gasparović, Vladimir

    2007-07-01

    We have investigated predictive value of HbA1c for hospital mortality and length of stay (LOS) in patients with type 2 diabetes admitted because of sepsis. A prospective observational study was implemented in a university hospital, 286 patients with type 2 diabetes admitted with sepsis were included. Leukocyte count, CRP, admission plasma glucose, APACHE II and SOFA score were noted at admission, HbA1c was measured on the first day following admission. Hospital mortality and hospital length of stay (LOS) were the outcome measures. Admission HbA1c was significantly lower in surviving patients than in non-survivors (median 8.2% versus 9.75%, respectively; P<0.001). There was a significant correlation between admission HbA1c and hospital LOS of surviving patients (r=0.29; P<0.001). Logistic regression showed that HbA1c is an independent predictor of hospital mortality (odds ratio 1.36), together with female sex (OR 2.24), APACHE II score (OR 1.08) and SOFA score (OR 1.28). Multiple regression showed that HbA1c and APACHE II score are independently related to hospital LOS. According to our results, HbA1c is an independent predictive factor for hospital mortality and hospital LOS of diabetic patients with sepsis.

  20. Long-term risk of seizures in adult survivors of sepsis.

    PubMed

    Reznik, Michael E; Merkler, Alexander E; Mahta, Ali; Murthy, Santosh B; Claassen, Jan; Kamel, Hooman

    2017-10-03

    To examine the association between sepsis and the long-term risk of seizures. We conducted a retrospective population-based cohort study using administrative claims data from all emergency department visits and hospitalizations at nonfederal acute care hospitals in California, Florida, and New York from 2005 to 2013. Using previously validated diagnosis codes, we identified all adult patients hospitalized with sepsis. Our outcome was any emergency department visit or hospitalization for seizure. Poisson regression and demographic data were used to calculate age-, sex-, and race-standardized incidence rate ratios (IRR). To confirm our findings, we used a matched cohort of hospitalized patients without sepsis for comparison and additionally assessed claims data from a nationally representative 5% sample of Medicare beneficiaries. We identified 842,735 patients with sepsis. The annual incidence of seizure was 1.29% (95% confidence interval [CI] 1.27%-1.30%) in patients with sepsis vs 0.16% (95% CI 0.16%-0.16%) in the general population (IRR 4.98; 95% CI 4.92-5.04). A secondary analysis using matched hospitalized patients confirmed these findings (IRR 4.33; 95% CI 4.13-4.55), as did a separate analysis of Medicare beneficiaries, in whom we found a similar strength of association (IRR 2.72; 95% CI 2.60-2.83), as we did in patients ≥65 years of age in our primary statewide data (IRR 2.83; 95% CI 2.78-2.88). We found that survivors of sepsis faced a significantly higher long-term risk of seizures than both the general population and other hospitalized patients. Our findings suggest that sepsis is associated with pathways that lead to permanent neurologic sequelae. © 2017 American Academy of Neurology.

  1. Quality improvement in pediatric sepsis.

    PubMed

    Melendez, Elliot; Bachur, Richard

    2015-06-01

    Although there is abundant literature detailing the impact of quality improvement in adult sepsis, the pediatric literature is lacking. Despite consensus definitions for sepsis, which patients along the sepsis spectrum should receive aggressive management and the exact onset of sepsis ('time zero') are not clearly established. In the adult emergency department (ED), sepsis onset is defined as the time of entry into the ED; however, this definition cannot be applied to hospitalized patients or patients who evolve during their ED course. Since the time of sepsis onset will dictate the timeliness of subsequent process measures, the variable definitions in the literature make it difficult to generalize findings among prior studies. Despite the variation in defining time zero, aggressive fluid administration, timely antibiotics, and compliance with sepsis bundles have been shown to improve mortality and to reduce hospital and intensive care length of stay. In addition, early identification tools show promise in beginning to define sepsis onset and retrospective search tools may allow improved case finding of those children of concern for sepsis. Quality improvement in pediatric sepsis is evolving. As we continue to define quality measures, we must standardize the definition of sepsis onset. This definition should be applicable to any treatment venue to ensure measures can be evaluated across all settings. In addition, we must delineate which patients along the sepsis spectrum should be candidates for timely interventions and standardize other outcome measures beyond mortality.

  2. THE IMPACT OF AGE ON THE INNATE IMMUNE RESPONSE AND OUTCOMES AFTER SEVERE SEPSIS/SEPTIC SHOCK IN TRAUMA AND SURGICAL INTENSIVE CARE UNIT PATIENTS.

    PubMed

    Brakenridge, Scott C; Efron, Philip A; Stortz, Julie A; Ozrazgat-Baslanti, Teczan; Ghita, Gabriela; Wang, Zhongkai; Bihorac, Azra; Mohr, Alicia M; Brumback, Babette A; Moldawer, Lyle L; Moore, Frederick A

    2018-04-02

    Advancing age is a strong risk factor for adverse outcomes across multiple disease processes. However, septic surgical and trauma patients are unique in they incur two or more inflammatory insults. The effects of advanced age on sepsis pathophysiology and outcomes remain unclear. We performed a single center, prospective observational cohort study of Surgical ICU patients with severe sepsis/septic shock. Peripheral blood was collected for genomic, cytokine and biomarker analysis at 0.5, 1, 4, 7, 14, 21 and 28 days after sepsis onset. Based on sensitivity analysis, cohorts were defined as "young" (<55 years) and "aged" (≥55 years). We compared age-defined cohorts to determine differences in patient characteristics, biomarker profiles and clinical outcomes. The cohort included 173 patients with severe sepsis (n=93; 53.8%) or septic shock (n=80; 46.2%), with a mean age of 60.9 (±14.5) years. Intra-abdominal sepsis was the leading source (n=81; 46.8%), followed by NSTI (n=33, 19.1%) and pneumonia (n=30; 17.3%). Aged patients had a higher comorbidity burden, but were otherwise similar to the young cohort. The aged cohort had a higher severity of early physiologic derangement (median APACHE II, 23 vs 18, p=0.002), greater incidence of multiple organ failure (MOF; 64.3% vs 40.4%, p=0.006), and hospital mortality (15.9% vs 2.1%, p=0.016). Six-month mortality was significantly higher in the aged as compared to young cohort (31% vs 9%, p=0.003). Aged septic patients biomarker trajectories suggestive of persistent immunosuppression (Absolute lymphocyte count, sPDL-1) and catabolism (Urine 3MH-Cr ratio, IGF, IGF1BP3, albumin) out to 28 days after sepsis. Aged, critically ill surgical patients have greater organ dysfunction, and incidence of adverse clinical outcomes after sepsis. Biomarker profiles suggest an immunophenotype of persistent immunosuppression and catabolism. Advanced age may necessitate novel therapeutic strategies to promote multi-system organ recovery and

  3. Risk factors and outcomes of sepsis-induced myocardial dysfunction and stress-induced cardiomyopathy in sepsis or septic shock: A comparative retrospective study.

    PubMed

    Jeong, Han Saem; Lee, Tae Hyub; Bang, Cho Hee; Kim, Jong-Ho; Hong, Soon Jun

    2018-03-01

    While both sepsis-induced myocardial dysfunction (SIMD) and stress-induced cardiomyopathy (SICMP) are common in patients with sepsis, the pathogenesis of the 2 diseases is different, and they require different treatment strategies. Thus, we aimed to investigate risk factors and outcomes between the 2 diseases.This retrospective study enrolled patients diagnosed with sepsis or septic shock, admitted to intensive care unit via emergency department in Korea University Anam Hospital, and who underwent transthoracic echocardiography within the first 24 hours of admission.In all, 25 patients with SIMD and 27 patients with SICMP were enrolled. Chronic obstructive pulmonary disease and a history of heart failure (HF) were more prevalent in both the SIMD and SICMP groups than in the control group. In the SIMD and SICMP groups, levels of inflammatory cytokines were similar. Serum troponin level was significantly elevated in the SICMP and SIMD group compared to the control group. N-terminal pro-brain natriuretic peptide (NT pro-BNP) level was significantly elevated in the SIMD group compared to the SICMP group or control group. The in-hospital mortality rate in the SIMD and SICMP group was about 40%, showing increased trends compared with the control group. The in-hospital mortality rate was significantly increased in SIMD group with EF<30% than in SICMP group with EF<30%. In multiple logistic regression analysis, a past history of diabetes mellitus (DM) and HF was significantly associated with the incidence of SIMD. Younger age, elevated levels of NT pro-BNP, and positive result of blood culture also showed significant odds ratio regard to the occurrence of SIMD. However, only elevated lactate and troponin level were positively associated with the incidence of SICMP.The SIMD and SICMP had different risk factors. The risk factors of SIMD were younger age, history of DM, history of HF, elevated NT pro-BNP, and positive result of blood culture. The elevated levels of lactate

  4. Epidemiology and Outcome of Severe Sepsis and Septic Shock in Intensive Care Units in Mainland China

    PubMed Central

    Zhou, Jianfang; Qian, Chuanyun; Zhao, Mingyan; Yu, Xiangyou; Kang, Yan; Ma, Xiaochun; Ai, Yuhang; Xu, Yuan; Liu, Dexin; An, Youzhong; Wu, Dawei; Sun, Renhua; Li, Shusheng; Hu, Zhenjie; Cao, Xiangyuan; Zhou, Fachun; Jiang, Li; Lin, Jiandong; Mao, Enqiang; Qin, Tiehe; He, Zhenyang; Zhou, Lihua; Du, Bin

    2014-01-01

    Introduction Information about sepsis in mainland China remains scarce and incomplete. The purpose of this study was to describe the epidemiology and outcome of severe sepsis and septic shock in mixed ICU in mainland China, as well as the independent predictors of mortality. Methods We performed a 2-month prospective, observational cohort study in 22 closed multi-disciplinary intensive care units (ICUs). All admissions into those ICUs during the study period were screened and patients with severe sepsis or septic shock were included. Results A total of 484 patients, 37.3 per 100 ICU admissions were diagnosed with severe sepsis (n = 365) or septic shock (n = 119) according to clinical criteria and included into this study. The most frequent sites of infection were the lung and abdomen. The overall ICU and hospital mortality rates were 28.7% (n = 139) and 33.5% (n = 162), respectively. In multivariate analyses, APACHE II score (odds ratio[OR], 1.068; 95% confidential interval[CI], 1.027–1.109), presence of ARDS (OR, 2.676; 95%CI, 1.691–4.235), bloodstream infection (OR, 2.520; 95%CI, 1.142–5.564) and comorbidity of cancer (OR, 2.246; 95%CI, 1.141–4.420) were significantly associated with mortality. Conclusions Our results indicated that severe sepsis and septic shock were common complications in ICU patients and with high mortality in China, and can be of help to know more about severe sepsis and septic shock in China and to improve characterization and risk stratification in these patients. PMID:25226033

  5. Neutrophil dysregulation during sepsis: an overview and update.

    PubMed

    Shen, Xiao-Fei; Cao, Ke; Jiang, Jin-Peng; Guan, Wen-Xian; Du, Jun-Feng

    2017-09-01

    Sepsis remains a leading cause of death worldwide, despite advances in critical care, and understanding of the pathophysiology and treatment strategies. No specific therapy or drugs are available for sepsis. Neutrophils play a critical role in controlling infection under normal conditions, and it is suggested that their migration and antimicrobial activity are impaired during sepsis which contribute to the dysregulation of immune responses. Recent studies further demonstrated that interruption or reversal of the impaired migration and antimicrobial function of neutrophils improves the outcome of sepsis in animal models. In this review, we provide an overview of the associated mediators and signal pathways involved which govern the survival, migration and antimicrobial function of neutrophils in sepsis, and discuss the potential of neutrophils as a target to specifically diagnose and/or predict the outcome of sepsis. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  6. SIRS score on admission and initial concentration of IL-6 as severe acute pancreatitis outcome predictors.

    PubMed

    Gregoric, Pavle; Pavle, Gregoric; Sijacki, Ana; Ana, Sijacki; Stankovic, Sanja; Sanja, Stankovic; Radenkovic, Dejan; Dejan, Radenkovic; Ivancevic, Nenad; Nenad, Ivancevic; Karamarkovic, Aleksandar; Aleksandar, Karamarkovic; Popovic, Nada; Nada, Popovic; Karadzic, Borivoje; Borivoje, Karadzic; Stijak, Lazar; Stefanovic, Branislav; Branislav, Stefanovic; Milosevic, Zoran; Zoran, Milosević; Bajec, Djordje; Djordje, Bajec

    2010-01-01

    Early recognition of severe form of acute pancreatitis is important because these patients need more agressive diagnostic and therapeutical approach an can develope systemic complications such as: sepsis, coagulopathy, Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS), Multiple Organ Dysfunction Syndrome (MODS), Multiple Organ Failure (MOF). To determine role of the combination of Systemic Inflammatory Response Syndrome (SIRS) score and serum Interleukin-6 (IL-6) level on admission as predictor of illness severity and outcome of Severe Acute Pancreatitis (SAP). We evaluated 234 patients with first onset of SAP appears in last twenty four hours. A total of 77 (33%) patients died. SIRS score and serum IL-6 concentration were measured in first hour after admission. In 105 patients with SIRS score 3 and higher, initial measured IL-6 levels were significantly higher than in the group of remaining 129 patients (72 +/- 67 pg/mL, vs 18 +/- 15 pg/mL). All nonsurvivals were in the first group, with SIRS score 3 and 4 and initial IL-6 concentration 113 +/- 27 pg/mL. The values of C-reactive Protein (CRP) measured after 48h, Acute Physiology and Chronic Health Evaluation (APACHE II) score on admission and Ranson score showed the similar correlation, but serum amylase level did not correlate significantly with Ranson score, IL-6 concentration and APACHE II score. The combination of SIRS score on admission and IL-6 serum concentration can be early, predictor of illness severity and outcome in SAP.

  7. Trends and disparities in sepsis hospitalisations in Victoria, Australia.

    PubMed

    Ore, Timothy

    2016-11-01

    Objective The aim of the present study was to determine the clinical and epidemiological characteristics of patients with sepsis admitted to hospitals in Victoria, Australia, during the period 2004-14. The data include incidence, severity and mortality. Methods In all, 44222 sepsis hospitalisations were identified between 2004-05 and 2013-14 from the Victorian Admitted Episodes Dataset. The dataset contains clinical and demographic information on all admissions to acute public and private hospitals. Using the International Classification of Diseases (10th Revision) Australian Modification codes, incidence rates, severity of disease and mortality were calculated. Results Sepsis hospitalisation rates per 10000 population increased significantly (P<0.01) over the period, from 6.9 (95% confidence interval (CI) 5.6-7.8) to 10.0 (95% CI 9.1-11.1), an annual growth rate of 3.8%. The age-standardised in-hospital death rates per 100000 population grew significantly (P<0.01) from 9.2 (95% CI 7.8-10.4) in 2004-05 to 13.0 (95% CI 11.7-14.6) in 2013-14, an annual growth rate of 3.1%. Among people under 45 years of age, the 0-4 years age group had the highest hospitalisation rate (3.0 per 10000 population; 95% CI 2.7-3.4). Nearly half (46.2%) of all sepsis hospitalisations were among patients born overseas, with a rate of 14.5 per 10000 population (95% CI 12.4-16.2) in that group compared with a rate of 5.9 per 10000 population (95% CI 5.3-6.7) for patients born in Australia. The age-standardised sepsis hospitalisation rate was 2.6-fold greater in the lowest compared with highest socioeconomic areas (12.7 per 10000 population (95% CI 11.2-13.8) vs 4.8 per 10000 population (95% CI 4.1-5.7), respectively). Conclusion This paper shows a significant upward trend in both sepsis separation rates and in-hospital death rates over the period; unlike sepsis, in-hospital death rates from all diagnoses fell over the same period. The results can be used to stimulate review of clinical

  8. Sequential Actions of SIRT1-RELB-SIRT3 Coordinate Nuclear-Mitochondrial Communication during Immunometabolic Adaptation to Acute Inflammation and Sepsis*

    PubMed Central

    Liu, Tie Fu; Vachharajani, Vidula; Millet, Patrick; Bharadwaj, Manish S.; Molina, Anthony J.; McCall, Charles E.

    2015-01-01

    We reported that NAD+-dependent SIRT1, RELB, and SIRT6 nuclear proteins in monocytes regulate a switch from the glycolysis-dependent acute inflammatory response to fatty acid oxidation-dependent sepsis adaptation. We also found that disrupting SIRT1 activity during adaptation restores immunometabolic homeostasis and rescues septic mice from death. Here, we show that nuclear SIRT1 guides RELB to differentially induce SIRT3 expression and also increases mitochondrial biogenesis, which alters bioenergetics during sepsis adaptation. We constructed this concept using TLR4-stimulated THP1 human promonocytes, a model that mimics the initiation and adaptation stages of sepsis. Following increased expression, mitochondrial SIRT3 deacetylase activates the rate-limiting tricarboxylic acid cycle (TCA) isocitrate dehydrogenase 2 and superoxide dismutase 2, concomitant with increases in citrate synthase activity. Mitochondrial oxygen consumption rate increases early and decreases during adaptation, parallel with modifications to membrane depolarization, ATP generation, and production of mitochondrial superoxide and whole cell hydrogen peroxide. Evidence of SIRT1-RELB induction of mitochondrial biogenesis included increases in mitochondrial mass, mitochondrial-to-nuclear DNA ratios, and both nuclear and mitochondrial encoded proteins. We confirmed the SIRT-RELB-SIRT3 adaptation link to mitochondrial bioenergetics in both TLR4-stimulated normal and sepsis-adapted human blood monocytes and mouse splenocytes. We also found that SIRT1 inhibition ex vivo reversed the sepsis-induced changes in bioenergetics. PMID:25404738

  9. Arterial to end-tidal carbon dioxide tension difference (CO2 gap) as a prognostic marker for adverse outcomes in emergency department patients presenting with suspected sepsis.

    PubMed

    Shetty, Amith; Sparenberg, Sebastian; Adams, Kristian; Selvedran, Selwyn; Tang, Benjamin; Hanna, Kim; Iredell, Jonathan

    2018-05-13

    The arterial to end-tidal carbon dioxide tension difference (CO 2 gap) correlates with physiologic dead space. The prognostic value of increased CO 2 gap in trauma and respiratory distress patients is documented. Transpulmonary arteriovenous shunting is identified as a predictor of mortality in non-pulmonary sepsis. We set out to investigate the prognostic value of the CO 2 gap in a pilot study of patients with suspected sepsis from non-respiratory causes. Patients presenting to tertiary Australian ED with suspected sepsis (n = 215) underwent near-simultaneous end-tidal carbon dioxide and partial pressure of carbon dioxide measurements. We investigated the correlation of CO 2 gap levels with the primary outcome of in-hospital mortality (IHM) and secondary outcomes of sepsis (ΔSOFA ≥2) and IHM and/or intensive care unit stay ≥72 h (IHM/ICU72h) in patients with sepsis because of non-respiratory causes. Among patients included in the analysis (n = 165), the CO 2 gap showed modest positive correlation with qSOFA (ρ = 0.39) and weak positive correlation with SOFA scores (ρ = 0.29) (both P < 0.01). The CO 2 gap had modest predictive value for primary outcome (IHM), area under receiver operating curve (AUROC 0.85, 95% confidence interval [CI] 0.78-0.90) and IHM/ICU72h outcome (AUROC 0.80, 95% CI 0.73-0.86), but lower predictive value for sepsis outcome (AUROC 0.64, 95% CI 0.55-0.71) (all P < 0.001). We report modest test performance for primary outcome at CO 2 gap ≥5 and ≥10 mmHg cut-offs. In this pilot study of patients with suspected sepsis from non-respiratory causes, an increased CO 2 gap demonstrates value in risk stratification and needs to be further evaluated and compared to other existent biomarkers. © 2018 Australasian College for Emergency Medicine & Australasian Society for Emergency Medicine.

  10. Incidence and Trends of Sepsis in US Hospitals Using Clinical vs Claims Data, 2009-2014

    PubMed Central

    Dantes, Raymund; Epstein, Lauren; Murphy, David J.; Seymour, Christopher W.; Iwashyna, Theodore J.; Kadri, Sameer S.; Angus, Derek C.; Danner, Robert L.; Fiore, Anthony E.; Jernigan, John A.; Martin, Greg S.; Septimus, Edward; Warren, David K.; Karcz, Anita; Chan, Christina; Menchaca, John T.; Wang, Rui; Gruber, Susan; Klompas, Michael

    2017-01-01

    Importance Estimates from claims-based analyses suggest that the incidence of sepsis is increasing and mortality rates from sepsis are decreasing. However, estimates from claims data may lack clinical fidelity and can be affected by changing diagnosis and coding practices over time. Objective To estimate the US national incidence of sepsis and trends using detailed clinical data from the electronic health record (EHR) systems of diverse hospitals. Design, Setting, and Population Retrospective cohort study of adult patients admitted to 409 academic, community, and federal hospitals from 2009-2014. Exposures Sepsis was identified using clinical indicators of presumed infection and concurrent acute organ dysfunction, adapting Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria for objective and consistent EHR-based surveillance. Main Outcomes and Measures Sepsis incidence, outcomes, and trends from 2009-2014 were calculated using regression models and compared with claims-based estimates using International Classification of Diseases, Ninth Revision, Clinical Modification codes for severe sepsis or septic shock. Case-finding criteria were validated against Sepsis-3 criteria using medical record reviews. Results A total of 173 690 sepsis cases (mean age, 66.5 [SD, 15.5] y; 77 660 [42.4%] women) were identified using clinical criteria among 2 901 019 adults admitted to study hospitals in 2014 (6.0% incidence). Of these, 26 061 (15.0%) died in the hospital and 10 731 (6.2%) were discharged to hospice. From 2009-2014, sepsis incidence using clinical criteria was stable (+0.6% relative change/y [95% CI, −2.3% to 3.5%], P = .67) whereas incidence per claims increased (+10.3%/y [95% CI, 7.2% to 13.3%], P < .001). In-hospital mortality using clinical criteria declined (−3.3%/y [95% CI, −5.6% to −1.0%], P = .004), but there was no significant change in the combined outcome of death or discharge to hospice (

  11. Acute Respiratory Failure in Cardiac Transplant Recipients.

    PubMed

    Komurcu, Ozgur; Ozdemirkan, Aycan; Camkiran Firat, Aynur; Zeyneloglu, Pinar; Sezgin, Atilla; Pirat, Arash

    2015-11-01

    This study sought to evaluate the incidence, risk factors, and outcomes of acute respiratory failure in cardiac transplant recipients. Cardiac transplant recipients >15 years of age and readmitted to the intensive care unit after cardiac transplant between 2005 and 2015 were included. Thirty-nine patients were included in the final analyses. Patients with acute respiratory failure and without acute respiratory failure were compared. The most frequent causes of readmission were routine intensive care unit follow-up after endomyocardial biopsy, heart failure, sepsis, and pneumonia. Patients who were readmitted to the intensive care unit were further divided into 2 groups based on presence of acute respiratory failure. Patients' ages and body weights did not differ between groups. The groups were not different in terms of comorbidities. The admission sequential organ failure assessment scores were higher in patients with acute respiratory failure. Patients with acute respiratory failure were more likely to use bronchodilators and n-acetylcysteine before readmission. Mean peak inspiratory pressures were higher in patients in acute respiratory failure. Patients with acute respiratory failure developed sepsis more frequently and they were more likely to have hypotension. Patients with acute respiratory failure had higher values of serum creatinine before admission to intensive care unit and in the first day of intensive care unit. Patients with acute respiratory failure had more frequent bilateral opacities on chest radiographs and positive blood and urine cultures. Duration of intensive care unit and hospital stays were not statistically different between groups. Mortality in patients with acute respiratory failure was 76.5% compared with 0% in patients without acute respiratory failure. A significant number of cardiac transplant recipients were readmitted to the intensive care unit. Patients presenting with acute respiratory failure on readmission more frequently

  12. Oral supplementation with ursolic acid ameliorates sepsis-induced acute kidney injury in a mouse model by inhibiting oxidative stress and inflammatory responses

    PubMed Central

    Zhang, Zhenyu; Zhang, Hong; Chen, Rui; Wang, Zhong

    2018-01-01

    Ursolic acid (UA) as a multiple bioactive native compound has recently been demonstrated to treat sepsis in animal models. However, the beneficial effects of UA in sepsis-induced acute kidney injury (AKI) are not completely understood. In the present study, the effect of UA on sepsis-induced AKI in cecal ligation and puncture (CLP) surgery mice was investigated. Renal histomorphological analysis was performed by hematoxylin and eosin staining. The expression of inflammatory markers in the kidney of septic mice was measured by reverse transcription-quantitative polymerase chain reaction and western blotting. The results demonstrated that UA administration improved survival in septic mice induced by CLP surgery. The treatment with UA revealed protection against AKI induced by CLP surgery, including the alleviation of glomerular damage and vacuolization in the proximal tubules. In addition, the effects of UA on oxidative stress and inflammation in septic mice were determined. The findings suggested that UA may protect against sepsis-induced AKI by inhibiting reactive oxygen species and inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1β and IL-6, in the kidney from septic mice. Finally, UA inhibited CLP-induced activation of nuclear factor-κB signaling in the kidney from septic mice. The findings of the present study demonstrated that UA may be used as a potential therapeutic agent for complications of sepsis, especially for sepsis-induced AKI. PMID:29568928

  13. Assessment of Sepsis-3 criteria and quick SOFA in patients with cirrhosis and bacterial infections.

    PubMed

    Piano, Salvatore; Bartoletti, Michele; Tonon, Marta; Baldassarre, Maurizio; Chies, Giada; Romano, Antonietta; Viale, Pierluigi; Vettore, Elia; Domenicali, Marco; Stanco, Marialuisa; Pilutti, Chiara; Frigo, Anna Chiara; Brocca, Alessandra; Bernardi, Mauro; Caraceni, Paolo; Angeli, Paolo

    2017-08-31

    Patients with cirrhosis have a high risk of sepsis, which confers a poor prognosis. The systemic inflammatory response syndrome (SIRS) criteria have several limitations in cirrhosis. Recently, new criteria for sepsis (Sepsis-3) have been suggested in the general population (increase of Sequential Organ Failure Assessment (SOFA) ≥2 points from baseline). Outside the intensive care unit (ICU), the quick SOFA (qSOFA (at least two among alteration in mental status, systolic blood pressure ≤100 mm Hg or respiratory rate ≥22/min)) was suggested to screen for sepsis. These criteria have never been evaluated in patients with cirrhosis. The aim of the study was to assess the ability of Sepsis-3 criteria in predicting in-hospital mortality in patients with cirrhosis and bacterial/fungal infections. 259 consecutive patients with cirrhosis and bacterial/fungal infections were prospectively included. Demographic, laboratory and microbiological data were collected at diagnosis of infection. Baseline SOFA was assessed using preadmission data. Patients were followed up until death, liver transplantation or discharge. Findings were externally validated (197 patients). Sepsis-3 and qSOFA had significantly greater discrimination for in-hospital mortality (area under the receiver operating characteristic (AUROC)=0.784 and 0.732, respectively) than SIRS (AUROC=0.606) (p<0.01 for both). Similar results were observed in the validation cohort. Sepsis-3 (subdistribution HR (sHR)=5.47; p=0.006), qSOFA (sHR=1.99; p=0.020), Chronic Liver Failure Consortium Acute Decompensation score (sHR=1.05; p=0.001) and C reactive protein (sHR=1.01;p=0.034) were found to be independent predictors of in-hospital mortality. Patients with Sepsis-3 had higher incidence of acute-on-chronic liver failure, septic shock and transfer to ICU than those without Sepsis-3. Sepsis-3 criteria are more accurate than SIRS criteria in predicting the severity of infections in patients with cirrhosis. qSOFA is a

  14. Acute peritoneal dialysis in neonates with acute kidney injury and hypernatremic dehydration.

    PubMed

    Yildiz, Nurdan; Erguven, Müferet; Yildiz, Metin; Ozdogan, Tutku; Turhan, Pinar

    2013-01-01

    We aimed to evaluate the efficacy of acute peritoneal dialysis (PD) and clinical outcomes in neonates with acute kidney injury (AKI) and hypernatremic dehydration. ♢ The medical records of 15 neonates with AKI and hypernatremic dehydration who were treated with acute PD were reviewed. The diagnoses were AKI with hypernatremic dehydration with or without sepsis in 13 patients and AKI with hypernatremia and congenital nephropathy in 2 patients. The main indications for PD were AKI with some combination of oligoanuria, azotemia, hyperuricemia, and metabolic acidosis unresponsive to initial intensive medical treatment. ♢ The mean age of the patients at dialysis initiation was 11.9 ± 9 days, and the mean duration of PD was 6.36 ± 4.8 days. In 7 patients (46.7%), hypotension required the use of vasopressors, and in 6 patients (40%), mechanical ventilation was required. Peritoneal dialysis-related complications occurred in 7 patients (46.7%), the most common being catheter malfunction (n = 6). Four episodes of peritonitis occurred in the 15 patients (26.7%), 2 episodes in patients with congenital renal disease and 2 episodes in patients with sepsis and multiorgan failure, who did not survive. Congenital renal disease, septicemia, and the need for mechanical ventilation were important factors influencing patient survival. All patients with no pre-existing renal disease or sepsis recovered their renal function and survived. ♢ In neonates with AKI and hypernatremic dehydration, PD is safe and successful, and in patients without congenital renal disease or sepsis, the prognosis is good. Peritoneal dialysis should be the treatment of choice in neonates with AKI and hypernatremic dehydration who do not respond to appropriate medical treatment.

  15. The costs and cost-effectiveness of an integrated sepsis treatment protocol.

    PubMed

    Talmor, Daniel; Greenberg, Dan; Howell, Michael D; Lisbon, Alan; Novack, Victor; Shapiro, Nathan

    2008-04-01

    Sepsis is associated with high mortality and treatment costs. International guidelines recommend the implementation of integrated sepsis protocols; however, the true cost and cost-effectiveness of these are unknown. To assess the cost-effectiveness of an integrated sepsis protocol, as compared with conventional care. Prospective cohort study of consecutive patients presenting with septic shock and enrolled in the institution's integrated sepsis protocol. Clinical and economic outcomes were compared with a historical control cohort. Beth Israel Deaconess Medical Center. Overall, 79 patients presenting to the emergency department with septic shock in the treatment cohort and 51 patients in the control group. An integrated sepsis treatment protocol incorporating empirical antibiotics, early goal-directed therapy, intensive insulin therapy, lung-protective ventilation, and consideration for drotrecogin alfa and steroid therapy. In-hospital treatment costs were collected using the hospital's detailed accounting system. The cost-effectiveness analysis was performed from the perspective of the healthcare system using a lifetime horizon. The primary end point for the cost-effectiveness analysis was the incremental cost per quality-adjusted life year gained. Mortality in the treatment group was 20.3% vs. 29.4% in the control group (p = .23). Implementing an integrated sepsis protocol resulted in a mean increase in cost of approximately $8,800 per patient, largely driven by increased intensive care unit length of stay. Life expectancy and quality-adjusted life years were higher in the treatment group; 0.78 and 0.54, respectively. The protocol was associated with an incremental cost of $11,274 per life-year saved and a cost of $16,309 per quality-adjusted life year gained. In patients with septic shock, an integrated sepsis protocol, although not cost-saving, appears to be cost-effective and compares very favorably to other commonly delivered acute care interventions.

  16. Candidate genes and pathogenesis investigation for sepsis-related acute respiratory distress syndrome based on gene expression profile.

    PubMed

    Wang, Min; Yan, Jingjun; He, Xingxing; Zhong, Qiang; Zhan, Chengye; Li, Shusheng

    2016-04-18

    Acute respiratory distress syndrome (ARDS) is a potentially devastating form of acute inflammatory lung injury as well as a major cause of acute respiratory failure. Although researchers have made significant progresses in elucidating the pathophysiology of this complex syndrome over the years, the absence of a universal detail disease mechanism up until now has led to a series of practical problems for a definitive treatment. This study aimed to predict some genes or pathways associated with sepsis-related ARDS based on a public microarray dataset and to further explore the molecular mechanism of ARDS. A total of 122 up-regulated DEGs and 91 down-regulated differentially expressed genes (DEGs) were obtained. The up- and down-regulated DEGs were mainly involved in functions like mitotic cell cycle and pathway like cell cycle. Protein-protein interaction network of ARDS analysis revealed 20 hub genes including cyclin B1 (CCNB1), cyclin B2 (CCNB2) and topoisomerase II alpha (TOP2A). A total of seven transcription factors including forkhead box protein M1 (FOXM1) and 30 target genes were revealed in the transcription factor-target gene regulation network. Furthermore, co-cited genes including CCNB2-CCNB1 were revealed in literature mining for the relations ARDS related genes. Pathways like mitotic cell cycle were closed related with the development of ARDS. Genes including CCNB1, CCNB2 and TOP2A, as well as transcription factors like FOXM1 might be used as the novel gene therapy targets for sepsis related ARDS.

  17. Methods for reducing sepsis mortality in emergency departments and inpatient units.

    PubMed

    Doerfler, Martin E; D'Angelo, John; Jacobsen, Diane; Jarrett, Mark P; Kabcenell, Andrea I; Masick, Kevin D; Parmentier, Darlene; Nelson, Karen L; Stier, Lori

    2015-05-01

    As part of a zero-tolerance approach to preventable deaths, North Shore-LIJ Health System (North Shore-LIJ) leadership prioritized a major patient safety initiative to reduce sepsis mortality in 2009 across 10 acute care hospitals (an 11th joined later). At baseline (2008), approximately 3,500 patients were discharged with a diagnosis of sepsis, which ranked as the top All Patient Refined Diagnosis-Related Group by number of deaths (N = 883). Initially, the focus was sepsis recognition and treatment in the emergency departments (EDs). North Shore-LIJ, the 14th largest health care system in the United States, cares for individuals at every stage of life at 19 acute care and specialty hospitals and more than 400 outpatient physician practice sites throughout New York City and the greater New York metropolitan area. The health system launched a strategic partnership with the Institute for Healthcare Improvement (IHI) in August 2011 to accelerate the pace of sepsis improvement. Throughout the course of the initiative, North Shore-LIJ collaborated with many local, state, national, and international organizations to test innovative ideas, share evidence-based best practices, and, more recently, to raise public awareness. North Shore-LIJ reduced overall sepsis mortality by approximately 50% in a six-year period (2008-2013; sustained through 2014) and increased compliance with sepsis resuscitation bundle elements in the EDs and inpatient units in the 11 acute care hospitals. Improvements were achieved by engaging leadership; fostering interprofessional collaboration, collaborating with other leading health care organizations; and developing meaningful, real-time metrics for all levels of staff.

  18. Management of sepsis: a 47-year-old woman with an indwelling intravenous catheter and sepsis.

    PubMed

    Angus, Derek C

    2011-04-13

    Severe sepsis is the term used to describe the host response to infection when complicated by acute organ dysfunction. Severe sepsis occurs in more than 750,000 individuals in the United States each year, with a hospital mortality of about 30%. Although the classic presentation is of florid shock with frank hypotension, fever, and elevated white blood cell count, many patients can present with cryptogenic shock (shock without hypotension) with more subtle signs of vital organ compromise. Using the case of Ms C, a 47-year-old woman with short gut syndrome and an indwelling intravenous catheter who developed an episode of severe sepsis secondary to a central line infection, treatment of sepsis is discussed. Management consists of prompt intervention with broad-spectrum antibiotics and fluid resuscitation, even in the absence of hypotension, and institution of a variety of strategies in the emergency setting to prevent development or worsening of vital organ dysfunction. Although advances in understanding the host immune response have fueled considerable interest in immunomodulatory therapy, the role of such agents in clinical practice remains limited and controversial.

  19. Plasma Glycoproteomics Reveals Sepsis Outcomes Linked to Distinct Proteins in Common Pathways

    PubMed Central

    DeLeon-Pennell, Kristine Y.; Nguyen, Nguyen T.; de Castro Brás, Lisandra E.; Flynn, Elizabeth R.; Cannon, Presley L.; Griswold, Michael E.; Jin, Yu-Fang; Puskarich, Michael A.; Jones, Alan E.; Lindsey, Merry L.

    2015-01-01

    Objective Sepsis remains a predominant cause of mortality in the ICU, yet strategies to increase survival have proved largely unsuccessful. This study aimed to identify proteins linked to sepsis outcomes using a glycoproteomic approach to target extracellular proteins that trigger downstream pathways and direct patient outcomes. Design Plasma was obtained from the LacTATEs cohort. N-linked plasma glycopeptides were quantified by solid-phase extraction coupled with mass spectrometry. Glycopeptides were assigned to proteins using RefSeq and visualized in a heat map. Protein differences were validated by immunoblotting, and proteins were mapped for biological processes using Database for Annotation, Visualization and Integrated Discovery and for functional pathways using Kyoto Encyclopedia of Genes and Genomes databases. Setting Hospitalized care. Measurements and Main Results A total of 501 glycopeptides corresponding to 234 proteins were identified. Of these, 66 glycopeptides were unique to the survivor group and corresponded to 54 proteins, 60 were unique to the nonsurvivor group and corresponded to 43 proteins, and 375 were common responses between groups and corresponded to 137 proteins. Immunoblotting showed that nonsurvivors had increased total kininogen; decreased total cathepsin-L1, vascular cell adhesion molecule, periostin, and neutrophil gelatinase–associated lipocalin; and a two-fold decrease in glycosylated clusterin (all p < 0.05). Kyoto Encyclopedia of Genes and Genomes analysis identified six enriched pathways. Interestingly, survivors relied on the extrinsic pathway of the complement and coagulation cascade, whereas nonsurvivors relied on the intrinsic pathway. Conclusion This study identifies proteins linked to patient outcomes and provides insight into unexplored mechanisms that can be investigated for the identification of novel therapeutic targets. (Crit Care Med 2015; XX:00–00) PMID:26086942

  20. Marginal dietary zinc deprivation augments sepsis-induced alterations in skeletal muscle TNF-α but not protein synthesis.

    PubMed

    Crowell, Kristen T; Kelleher, Shannon L; Soybel, David I; Lang, Charles H

    2016-11-01

    Severe zinc deficiency is associated with an increased systemic inflammatory response and mortality after sepsis. However, the impact of mild zinc deficiency, which is more common in populations with chronic illnesses and sepsis, is unknown. In this study, we hypothesized that marginal dietary Zn deprivation (ZM) would amplify tissue inflammation and exacerbate the sepsis-induced decrease in muscle protein synthesis. Adult male C57BL/6 mice were fed a zinc-adequate (ZA) or ZM diet (30 or 10 mg Zn/kg, respectively) over 4 weeks, peritonitis was induced by cecal ligation and puncture (CLP), and mice were examined at either 24 h (acute) or 5 days (chronic) post-CLP Acute sepsis decreased the in vivo rate of skeletal muscle protein synthesis and the phosphorylation of the mTOR substrate 4E-BP1. Acutely, sepsis increased TNF-α and IL-6 mRNA in muscle, and the increase in TNF-α was significantly greater in ZM mice. However, muscle protein synthesis and 4E-BP1 phosphorylation returned to baseline 5 days post-CLP in both ZA and ZM mice. Protein degradation via markers of the ubiquitin proteasome pathway was increased in acute sepsis, yet only MuRF1 mRNA was increased in chronic sepsis and ZM amplified this elevation. Our data suggest that mild zinc deficiency increases TNF-α in muscle acutely after sepsis but does not significantly modulate the rate of muscle protein synthesis. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  1. Clinical outcomes and mortality before and after implementation of a pediatric sepsis protocol in a limited resource setting: A retrospective cohort study in Bangladesh

    PubMed Central

    Axelrod, David M.; Chisti, Mohammod J.; Kache, Saraswati

    2017-01-01

    Background Pediatric sepsis has a high mortality rate in limited resource settings. Sepsis protocols have been shown to be a cost-effective strategy to improve morbidity and mortality in a variety of populations and settings. At Dhaka Hospital in Bangladesh, mortality from pediatric sepsis in high-risk children previously approached 60%, which prompted the implementation of an evidenced-based protocol in 2010. The clinical effectiveness of this protocol had not been measured. We hypothesized that implementation of a pediatric sepsis protocol improved clinical outcomes, including reducing mortality and length of hospital stay. Materials and methods This was a retrospective cohort study of children 1–59 months old with a diagnosis of sepsis, severe sepsis or septic shock admitted to Dhaka Hospital from 10/25/2009-10/25/2011. The primary outcome was inpatient mortality pre- and post-protocol implementation. Secondary outcomes included fluid overload, heart failure, respiratory insufficiency, length of hospital stay, and protocol compliance, as measured by antibiotic and fluid bolus administration within 60 minutes of hospital presentation. Results 404 patients were identified by a key-word search of the electronic medical record; 328 patients with a primary diagnosis of sepsis, severe sepsis, or septic shock were included (143 pre- and185 post-protocol) in the analysis. Pre- and post-protocol mortality were similar and not statistically significant (32.17% vs. 34.59%, p = 0.72). The adjusted odds ratio (AOR) for post-protocol mortality was 1.55 (95% CI, 0.88–2.71). The odds for developing fluid overload were significantly higher post-protocol (AOR 3.45, 95% CI, 2.04–5.85), as were the odds of developing heart failure (AOR 4.52, 95% CI, 1.43–14.29) and having a longer median length of stay (AOR 1.81, 95% CI 1.10–2.96). There was no statistically significant difference in respiratory insufficiency (pre- 65.7% vs. post- 70.3%, p = 0.4) or antibiotic

  2. Clinical outcomes and mortality before and after implementation of a pediatric sepsis protocol in a limited resource setting: A retrospective cohort study in Bangladesh.

    PubMed

    Kortz, Teresa Bleakly; Axelrod, David M; Chisti, Mohammod J; Kache, Saraswati

    2017-01-01

    Pediatric sepsis has a high mortality rate in limited resource settings. Sepsis protocols have been shown to be a cost-effective strategy to improve morbidity and mortality in a variety of populations and settings. At Dhaka Hospital in Bangladesh, mortality from pediatric sepsis in high-risk children previously approached 60%, which prompted the implementation of an evidenced-based protocol in 2010. The clinical effectiveness of this protocol had not been measured. We hypothesized that implementation of a pediatric sepsis protocol improved clinical outcomes, including reducing mortality and length of hospital stay. This was a retrospective cohort study of children 1-59 months old with a diagnosis of sepsis, severe sepsis or septic shock admitted to Dhaka Hospital from 10/25/2009-10/25/2011. The primary outcome was inpatient mortality pre- and post-protocol implementation. Secondary outcomes included fluid overload, heart failure, respiratory insufficiency, length of hospital stay, and protocol compliance, as measured by antibiotic and fluid bolus administration within 60 minutes of hospital presentation. 404 patients were identified by a key-word search of the electronic medical record; 328 patients with a primary diagnosis of sepsis, severe sepsis, or septic shock were included (143 pre- and185 post-protocol) in the analysis. Pre- and post-protocol mortality were similar and not statistically significant (32.17% vs. 34.59%, p = 0.72). The adjusted odds ratio (AOR) for post-protocol mortality was 1.55 (95% CI, 0.88-2.71). The odds for developing fluid overload were significantly higher post-protocol (AOR 3.45, 95% CI, 2.04-5.85), as were the odds of developing heart failure (AOR 4.52, 95% CI, 1.43-14.29) and having a longer median length of stay (AOR 1.81, 95% CI 1.10-2.96). There was no statistically significant difference in respiratory insufficiency (pre- 65.7% vs. post- 70.3%, p = 0.4) or antibiotic administration between the cohorts (pre- 16.08% vs. post- 12

  3. The characteristics and impact of source of infection on sepsis-related ICU outcomes.

    PubMed

    Jeganathan, Niranjan; Yau, Stephen; Ahuja, Neha; Otu, Dara; Stein, Brian; Fogg, Louis; Balk, Robert

    2017-10-01

    Source of infection is an independent predictor of sepsis-related mortality. To date, studies have failed to evaluate differences in septic patients based on the source of infection. Retrospective study of all patients with sepsis admitted to the ICU of a university hospital within a 12month time period. Sepsis due to intravascular device and multiple sources had the highest number of positive blood cultures and microbiology whereas lung and abdominal sepsis had the least. The observed hospital mortality was highest for sepsis due to multiple sources and unknown cause, and was lowest when due to abdominal, genitourinary (GU) or skin/soft tissue. Patients with sepsis due to lungs, unknown and multiple sources had the highest rates of multi-organ failure, whereas those with sepsis due to GU and skin/soft tissue had the lowest rates. Those with multisource sepsis had a significantly higher median ICU length of stay and hospital cost. There are significant differences in patient characteristics, microbiology positivity, organs affected, mortality, length of stay and cost based on the source of sepsis. These differences should be considered in future studies to be able to deliver personalized care. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. A model-specific role of microRNA-223 as a mediator of kidney injury during experimental sepsis.

    PubMed

    Colbert, James F; Ford, Joshay A; Haeger, Sarah M; Yang, Yimu; Dailey, Kyrie L; Allison, Kristen C; Neudecker, Viola; Evans, Christopher M; Richardson, Vanessa L; Brodsky, Kelley S; Faubel, Sarah; Eltzschig, Holger K; Schmidt, Eric P; Ginde, Adit A

    2017-08-01

    Sepsis outcomes are heavily dependent on the development of septic organ injury, but no interventions exist to interrupt or reverse this process. microRNA-223 (miR-223) is known to be involved in both inflammatory gene regulation and host-pathogen interactions key to the pathogenesis of sepsis. The goal of this study was to determine the role of miR-223 as a mediator of septic kidney injury. Using miR-223 knockout mice and multiple models of experimental sepsis, we found that miR-223 differentially influences acute kidney injury (AKI) based on the model used. In the absence of miR-223, mice demonstrated exaggerated AKI in sterile models of sepsis (LPS injection) and attenuated AKI in a live-infection model of sepsis (cecal ligation and puncture). We demonstrated that miR-223 expression is induced in kidney homogenate after cecal ligation and puncture, but not after LPS or fecal slurry injection. We investigated additional potential mechanistic explanations including differences in peritoneal bacterial clearance and host stool virulence. Our findings highlight the complex role of miR-223 in the pathogenesis of septic kidney injury, as well as the importance of differences in experimental sepsis models and their consequent translational applicability. Copyright © 2017 the American Physiological Society.

  5. The evolutionary logic of sepsis.

    PubMed

    Rózsa, Lajos; Apari, Péter; Sulyok, Mihály; Tappe, Dennis; Bodó, Imre; Hardi, Richárd; Müller, Viktor

    2017-11-01

    The recently proposed Microbiome Mutiny Hypothesis posits that members of the human microbiome obtain information about the host individuals' health status and, when host survival is compromised, switch to an intensive exploitation strategy to maximize residual transmission. In animals and humans, sepsis is an acute systemic reaction to microbes invading the normally sterile body compartments. When induced by formerly mutualistic or neutral microbes, possibly in response to declining host health, sepsis appears to fit the 'microbiome mutiny' scenario except for its apparent failure to enhance transmission of the causative organisms. We propose that the ability of certain species of the microbiome to induce sepsis is not a fortuitous side effect of within-host replication, but rather it might, in some cases, be the result of their adaptive evolution. Whenever host health declines, inducing sepsis can be adaptive for those members of the healthy human microbiome that are capable of colonizing the future cadaver and spread by cadaver-borne transmission. We hypothesize that such microbes might exhibit switches along the 'mutualist - lethal pathogen - decomposer - mutualist again' scenario, implicating a previously unsuspected, surprising level of phenotypic plasticity. This hypothesis predicts that those species of the healthy microbiome that are recurring causative agents of sepsis can participate in the decomposition of cadavers, and can be transmitted as soil-borne or water-borne infections. Furthermore, in individual sepsis cases, the same microbial clones that dominate the systemic infection that precipitates sepsis, should also be present in high concentration during decomposition following death: this prediction is testable by molecular fingerprinting in experimentally induced animal models. Sepsis is a leading cause of human death worldwide. If further research confirms that some cases of sepsis indeed involve the 'mutiny' (facultative phenotypic switching) of

  6. Animal models of sepsis.

    PubMed

    Fink, Mitchell P

    2014-01-01

    Sepsis remains a common, serious, and heterogeneous clinical entity that is difficult to define adequately. Despite its importance as a public health problem, efforts to develop and gain regulatory approval for a specific therapeutic agent for the adjuvant treatment of sepsis have been remarkably unsuccessful. One step in the critical pathway for the development of a new agent for adjuvant treatment of sepsis is evaluation in an appropriate animal model of the human condition. Unfortunately, the animal models that have been used for this purpose have often yielded misleading findings. It is likely that there are multiple reasons for the discrepancies between the results obtained in tests of pharmacological agents in animal models of sepsis and the outcomes of human clinical trials. One of important reason may be that the changes in gene expression, which are triggered by trauma or infection, are different in mice, a commonly used species for preclinical testing, and humans. Additionally, many species, including mice and baboons, are remarkably resistant to the toxic effects of bacterial lipopolysaccharide, whereas humans are exquisitely sensitive. New approaches toward the use of animals for sepsis research are being investigated. But, at present, results from preclinical studies of new therapeutic agents for sepsis must be viewed with a degree of skepticism.

  7. Reporting of Sepsis Cases for Performance Measurement Versus for Reimbursement in New York State.

    PubMed

    Prescott, Hallie C; Cope, Tara M; Gesten, Foster C; Ledneva, Tatiana A; Friedrich, Marcus E; Iwashyna, Theodore J; Osborn, Tiffany M; Seymour, Christopher W; Levy, Mitchell M

    2018-05-01

    Under "Rory's Regulations," New York State Article 28 acute care hospitals were mandated to implement sepsis protocols and report patient-level data. This study sought to determine how well cases reported under state mandate align with discharge records in a statewide administrative database. Observational cohort study. First 27 months of mandated sepsis reporting (April 1, 2014, to June 30, 2016). Hospitalizations with sepsis at New York State Article 28 acute care hospitals. Sepsis regulations with mandated reporting. We compared cases reported to the New York State Department of Health Sepsis Clinical Database with discharge records in the Statewide Planning and Research Cooperative System database. We classified discharges as 1) "coded sepsis discharges"-a diagnosis code for severe sepsis or septic shock and 2) "possible sepsis discharges," using Dombrovskiy and Angus criteria. Of 111,816 sepsis cases reported to the New York State Department of Health Sepsis Clinical Database, 105,722 (94.5%) were matched to discharge records in Statewide Planning and Research Cooperative System. The percentage of coded sepsis discharges reported increased from 67.5% in the first quarter to 81.3% in the final quarter of the study period (mean, 77.7%). Accounting for unmatched cases, as many as 82.7% of coded sepsis discharges were potentially reported, whereas at least 17.3% were unreported. Compared with unreported discharges, reported discharges had higher rates of acute organ dysfunction (e.g., cardiovascular dysfunction 63.0% vs 51.8%; p < 0.001) and higher in-hospital mortality (30.2% vs 26.1%; p < 0.001). Hospital characteristics (e.g., number of beds, teaching status, volume of sepsis cases) were similar between hospitals with a higher versus lower percent of discharges reported, p values greater than 0.05 for all. Hospitals' percent of discharges reported was not correlated with risk-adjusted mortality of their submitted cases (Pearson correlation coefficient 0.11; p

  8. Diagnostic value of Pentraxin-3 in patients with sepsis and septic shock in accordance with latest sepsis-3 definitions.

    PubMed

    Hamed, Sonja; Behnes, Michael; Pauly, Dominic; Lepiorz, Dominic; Barre, Max; Becher, Tobias; Lang, Siegfried; Akin, Ibrahim; Borggrefe, Martin; Bertsch, Thomas; Hoffmann, Ursula

    2017-08-09

    Pentraxin-3 (PTX-3) is an acute-phase protein involved in inflammatory and infectious processes. This study assesses its diagnostic and prognostic value in patients with sepsis or septic shock in a medical intensive care unit (ICU). The study includes 213 ICU patients with clinical criteria of sepsis and septic shock. 77 donors served as controls. Plasma levels of PTX-3, procalcitonin (PCT) and interleukin-6 were measured on day 1, 3 and 8. PTX-3 correlated with higher lactate levels as well as with APACHE II and SOFA scores (p = 0.0001). PTX-3 levels of patients with sepsis or septic shock were consistently significantly higher than in the control group (p ≤ 0.001). Plasma levels were able to discriminate sepsis and septic shock significantly on day 1, 3 and 8 (range of AUC 0.73-0.92, p = 0.0001). Uniform cut-off levels were defined at ≥5 ng/ml for at least sepsis, ≥9 ng/ml for septic shock (p = 0.0001). PTX-3 reveals diagnostic value for sepsis and septic shock during the first week of intensive care treatment, comparable to interleukin-6 according to latest Sepsis-3 definitions. NCT01535534 . Registered 14.02.2012.

  9. A simple scoring system based on neutrophil count in sepsis patients.

    PubMed

    Ueda, Takahiro; Aoyama-Ishikawa, Michiko; Nakao, Atsunori; Yamada, Taihei; Usami, Makoto; Kotani, Joji

    2014-03-01

    The assessment of critically ill patients is often a challenge for clinicians. There are a number of scoring systems such as Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA) and C-reactive protein test (CRP), which have been shown to correlate with outcome in a variety of Intensive Care Unit (ICU) patients. Therefore, use of repeated measures of these preexisting scores over time is a reasonable attempt to assess the severity of organ dysfunction and predict outcome in critically ill patients. Several reports suggest that the neutrophil is a useful marker of sepsis. However, since both a large number and a small number of neutrophils indicate a severe situation, neutrophil count is difficult to use to directly predict patients'. We proposed a novel scoring system identify predictive factors using a simple blood cell count that may be associated with mortality in ICU patients. Our novel scoring system (n-score) was calculated as follows: ranges of neutrophils of 0-4999 cells/mm(3) and 5000-9999 cells/mm(3) were defined as 3 and 1 points, respectively. When the neutrophil count was over 10,000 cells/mm(3), the score was calculated by dividing the number of cells by 10,000. Then, 1 or 2 points were added when patients were female or male, respectively. We hypothesize that n-score may be a simple and easy scoring system to estimate mortality of the patients with sepsis and severe sepsis/septic shock without requirement of special methods or special measuring equipment, and may be as reliable as the APACHE II score or SOFA score. The retrospective evaluation was conducted at the Department of Emergency, Disaster and Critical Care Medicine at the Hyogo College of Medicine. Seventy-seven patients who were admitted to the emergency center and diagnosed sepsis or severe sepsis/septic shock between June 2007 and December 2012 and gave informed consent were enrolled. The n-score was significantly higher in non

  10. Sleep apnoea patients have higher mortality when confronting sepsis.

    PubMed

    Huang, Chien-Yu; Chen, Yung-Tai; Wu, Li-An; Liu, Chia-Jen; Chang, Shi-Chuan; Perng, Diahn-Warng; Chen, Yuh-Min; Chen, Tzeng-Ji; Lee, Yu-Chin; Chou, Kun-Ta

    2014-01-01

    Sleep is essential for the maintenance of an intact immune function. Patients with sleep apnoea experience frequent sleep interruption due to apnoea-related arousals, possibly adversely impacting their immunity and affecting their outcomes when confronting sepsis. This case-control study aimed to compare the outcomes of sepsis patients with and without sleep apnoea. From 2000 to 2009, 168 sleep apnoea patients who were first admitted for sepsis were identified from the Taiwan National Health Insurance Research Database. Also, 672 sepsis patients without sleep apnoea, who were matched by age, gender and Charlson's comorbidity index scores, served as controls. Hospital outcomes of the two groups were compared. Binary logistic regression was employed for multivariate analysis. The mortality rates of sepsis patients with and without sleep apnoea were 60.1% and 47.9%, respectively (P = 0. 005). After multivariate adjustment, sleep apnoea (OR: 1.805, 95% CI: 1.227-2.656, P = 0.003), presence of shock (OR: 3.600, 95% CI: 2.144-6.046, P < 0.001) and number of organs with dysfunction (OR: 1.591, 95% CI: 1.087-2.329, P = 0.017) were found to be independently associated with mortality. Sleep apnoea patients who needed continuous positive airway pressure treatment had an even higher risk of mortality. Sepsis patients with sleep apnoea may have poorer hospital outcomes than those without sleep apnoea. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

  11. Age-related differences in biomarkers of acute inflammation during hospitalization for sepsis.

    PubMed

    Ginde, Adit A; Blatchford, Patrick J; Trzeciak, Stephen; Hollander, Judd E; Birkhahn, Robert; Otero, Ronny; Osborn, Tiffany M; Moretti, Eugene; Nguyen, H Bryant; Gunnerson, Kyle J; Milzman, David; Gaieski, David F; Goyal, Munish; Cairns, Charles B; Rivers, Emanuel P; Shapiro, Nathan I

    2014-08-01

    The authors aimed to evaluate age-related differences in inflammation biomarkers during the first 72 h of hospitalization for sepsis. This was a secondary analysis of a prospective observational cohort of adult patients (n = 855) from 10 urban academic emergency departments with confirmed infection and two or more systemic inflammatory response syndrome criteria. Six inflammation-related biomarkers were analyzed-chemokine (CC-motif) ligand-23, C-reactive protein, interleukin-1 receptor antagonist, neutrophil gelatinase-associated lipocalin (NGAL), peptidoglycan recognition protein, and tumor necrosis factor receptor-1a (TNFR-1a)-measured at presentation and 3, 6, 12, 24, 48, or 72 h later. The median age was 56 (interquartile range, 43 - 72) years, and sepsis severity was 38% sepsis, 16% severe sepsis without shock, and 46% septic shock; the overall 30-day mortality was 12%. Older age was associated with higher sepsis severity: 41% of subjects aged 18 to 34 years had severe sepsis or septic shock compared with 71% for those aged 65 years or older (P < 0.001). In longitudinal models adjusting for demographics, comorbidities, and infection source, older age was associated with higher baseline values for chemokine (CC-motif) ligand-23, interleukin-1 receptor antagonist, NGAL, and TNFR-1a (all P < 0.05). However, older adults had higher mean values during the entire 72-h period only for NGAL and TNFR-1a and higher final 72-h values only for TNFR-1a. Adjustment or stratification by sepsis severity did not change the age-inflammation associations. Although older adults had higher levels of inflammation at presentation and an increased incidence of severe sepsis and septic shock, these age-related differences in inflammation largely resolved during the first 72 h of hospitalization.

  12. Impact of statin therapy on mortality in patients with sepsis-associated acute respiratory distress syndrome (ARDS) depends on ARDS severity: a prospective observational cohort study.

    PubMed

    Mansur, Ashham; Steinau, Maximilian; Popov, Aron Frederik; Ghadimi, Michael; Beissbarth, Tim; Bauer, Martin; Hinz, José

    2015-06-01

    Previous investigations have presumed a potential therapeutic effect of statin therapy in patients with acute respiratory distress syndrome (ARDS). Statins are expected to attenuate inflammation in the lungs of patients with ARDS due to their anti-inflammatory effects. Clinical investigations of the role of statin therapy have revealed contradictory results. This study aimed to investigate whether pretreatment and continuous therapy with statins in patients with sepsis-associated ARDS are associated with 28-day survival according to disease severity (mild, moderate, or severe). Patients with sepsis-associated ARDS from the surgical intensive care were enrolled in this prospective observational investigation. ARDS was classified into three groups (mild, moderate, and severe); 28-day mortality was recorded as the primary outcome variable and organ failure was recorded as secondary outcome variable. Sequential Organ Failure Assessment scores and the requirements for organ support were evaluated throughout the observational period to assess organ failure. 404 patients with sepsis-associated ARDS were enrolled in this investigation. The distribution of the ARDS subgroups was 13 %, 59 %, and 28 % for mild, moderate, and severe disease, respectively. Statin therapy improved 28-day survival exclusively in the patients with severe ARDS compared with patients without statin therapy (88.5 % and 62.5 %, respectively; P = 0.0193). To exclude the effects of several confounders, we performed multivariate Cox regression analysis, which showed that statin therapy remained a significant covariate for mortality (hazard ratio, 5.46; 95 % CI, 1.38-21.70; P = 0.0156). Moreover, after carrying a propensity score-matching in the severe ARDS cohort, Kaplan-Meier survival analysis confirmed the improved 28-day survival among patients with statin therapy (P = 0.0205). Patients with severe ARDS who received statin therapy had significantly more vasopressor-free days compared with those

  13. Cytokine Profiles during Invasive Nontyphoidal Salmonella Disease Predict Outcome in African Children.

    PubMed

    Gilchrist, James J; Heath, Jennifer N; Msefula, Chisomo L; Gondwe, Esther N; Naranbhai, Vivek; Mandala, Wilson; MacLennan, Jenny M; Molyneux, Elizabeth M; Graham, Stephen M; Drayson, Mark T; Molyneux, Malcolm E; MacLennan, Calman A

    2016-07-01

    Nontyphoidal Salmonella is a leading cause of sepsis in African children. Cytokine responses are central to the pathophysiology of sepsis and predict sepsis outcome in other settings. In this study, we investigated cytokine responses to invasive nontyphoidal Salmonella (iNTS) disease in Malawian children. We determined serum concentrations of 48 cytokines with multiplexed immunoassays in Malawian children during acute iNTS disease (n = 111) and in convalescence (n = 77). Principal component analysis and logistic regression were used to identify cytokine signatures of acute iNTS disease. We further investigated whether these responses are altered by HIV coinfection or severe malnutrition and whether cytokine responses predict inpatient mortality. Cytokine changes in acute iNTS disease were associated with two distinct cytokine signatures. The first is characterized by increased concentrations of mediators known to be associated with macrophage function, and the second is characterized by raised pro- and anti-inflammatory cytokines typical of responses reported in sepsis secondary to diverse pathogens. These cytokine responses were largely unaltered by either severe malnutrition or HIV coinfection. Children with fatal disease had a distinctive cytokine profile, characterized by raised mediators known to be associated with neutrophil function. In conclusion, cytokine responses to acute iNTS infection in Malawian children are reflective of both the cytokine storm typical of sepsis secondary to diverse pathogens and the intramacrophage replicative niche of NTS. The cytokine profile predictive of fatal disease supports a key role of neutrophils in the pathogenesis of NTS sepsis. Copyright © 2016 Gilchrist et al.

  14. Epidemiology of sepsis in intensive care units in Turkey: a multicenter, point-prevalence study.

    PubMed

    Baykara, Nur; Akalın, Halis; Arslantaş, Mustafa Kemal; Hancı, Volkan; Çağlayan, Çiğdem; Kahveci, Ferda; Demirağ, Kubilay; Baydemir, Canan; Ünal, Necmettin

    2018-04-16

    The prevalence and mortality of sepsis are largely unknown in Turkey, a country with high antibiotic resistance. A national, multicenter, point-prevalence study was conducted to determine the prevalence, causative microorganisms, and outcome of sepsis in intensive care units (ICUs) in Turkey. A total of 132 ICUs from 94 hospitals participated. All patients (aged > 18 years) present at the participating ICUs or admitted for any duration within a 24-h period (08:00 on January 27, 2016 to 08:00 on January 28, 2016) were included. The presence of systemic inflammatory response syndrome (SIRS), severe sepsis, and septic shock were assessed and documented based on the consensus criteria of the American College of Chest Physicians and Society of Critical Care Medicine (SEPSIS-I) in infected patients. Patients with septic shock were also assessed using the SEPSIS-III definitions. Data regarding demographics, illness severity, comorbidities, microbiology, therapies, length of stay, and outcomes (dead/alive during 30 days) were recorded. Of the 1499 patients included in the analysis, 237 (15.8%) had infection without SIRS, 163 (10.8%) had infection with SIRS, 260 (17.3%) had severe sepsis without shock, and 203 (13.5%) had septic shock. The mortality rates were higher in patients with severe sepsis (55.7%) and septic shock (70.4%) than those with infection alone (24.8%) and infection + SIRS (31.2%) (p < 0.001). According to SEPSIS-III, 104 (6.9%) patients had septic shock (mortality rate, 75.9%). The respiratory system (71.6%) was the most common site of infection, and Acinetobacter spp. (33.7%) were the most common isolated pathogen. Approximately, 74.9%, 39.1%, and 26.5% of Acinetobacter, Klebsiella, and Pseudomonas spp. isolates, respectively, were carbapenem-resistant, which was not associated with a higher mortality risk. Age, acute physiology and chronic health evaluation II score at ICU admission, sequential organ failure assessment score on study day, solid organ

  15. A Unified Theory of Sepsis-Induced Acute Kidney Injury: Inflammation, microcirculatory dysfunction, bioenergetics and the tubular cell adaptation to injury

    PubMed Central

    Gomez, Hernando; Ince, Can; De Backer, Daniel; Pickkers, Peter; Payen, Didier; Hotchkiss, John; Kellum, John A.

    2014-01-01

    Given that the leading clinical conditions associated with Acute kidney injury (AKI), namely, sepsis, major surgery, heart failure and hypovolemia, are all associated with shock, it is tempting to attribute all AKI to ischemia on the basis of macro-hemodynamic changes. However, an increasing body of evidence has suggested that in many patients, AKI can occur in the absence of overt signs of global renal hypoperfusion. Indeed, sepsis-induced AKI can occur in the setting of normal or even increased renal blood flow. Accordingly, renal injury may not be entirely explained solely on the basis of the classic paradigm of hypoperfusion, and thus other mechanisms must come into play. Herein, we put forward a “unifying theory” to explain the interplay between inflammation and oxidative stress, microvascular dysfunction, and the adaptive response of the tubular epithelial cell to the septic insult. We propose that this response is mostly adaptive in origin, that it is driven by mitochondria and that it ultimately results in and explains the clinical phenotype of sepsis induced AKI. PMID:24346647

  16. Pediatric Sepsis Endotypes Among Adults With Sepsis.

    PubMed

    Wong, Hector R; Sweeney, Timothy E; Hart, Kimberly W; Khatri, Purvesh; Lindsell, Christopher J

    2017-12-01

    Recent transcriptomic studies describe two subgroups of adults with sepsis differentiated by a sepsis response signature. The implied biology and related clinical associations are comparable with recently reported pediatric sepsis endotypes, labeled "A" and "B." We classified adults with sepsis using the pediatric endotyping strategy and the sepsis response signature and determined how endotype assignment, sepsis response signature membership, and age interact with respect to mortality. Retrospective analysis of publically available transcriptomic data representing critically ill adults with sepsis from which the sepsis response signature groups were derived and validated. Multiple ICUs. Adults with sepsis. None. Transcriptomic data were conormalized into a single dataset yielding 549 unique cases with sepsis response signature assignments. Each subject was assigned to endotype A or B using the expression data for the 100 endotyping genes. There were 163 subjects (30%) assigned to endotype A and 386 to endotype B. There was a weak, positive correlation between endotype assignment and sepsis response signature membership. Mortality rates were similar between patients assigned endotype A and those assigned endotype B. A multivariable logistic regression model fit to endotype assignment, sepsis response signature membership, age, and the respective two-way interactions revealed that endotype A, sepsis response signature 1 membership, older age, and the interactions between them were associated with mortality. Subjects coassigned to endotype A, and sepsis response signature 1 had the highest mortality. Combining the pediatric endotyping strategy with sepsis response signature membership might provide complementary, age-dependent, biological, and prognostic information.

  17. Resveratrol protects against early polymicrobial sepsis-induced acute kidney injury through inhibiting endoplasmic reticulum stress-activated NF-κB pathway

    PubMed Central

    Wang, Nian; Mao, Li; Yang, Liu; Zou, Jiang; Liu, Ke; Liu, Meidong; Zhang, Huali; Xiao, Xianzhong; Wang, Kangkai

    2017-01-01

    Resveratrol, a polyphenol compound derived from various edible plants, protects against sepsis-induced acute kidney injury (AKI) via its anti-inflammatory activity, but the underlying mechanisms remain largely unknown. In this study, a rat model of sepsis was established by cecal ligation and puncture (CLP), 30 mg/kg resveratrol was intraperitoneally administrated immediately after the CLP operation. HK-2 cells treated by 1 μg/ml lipopolysaccharide, 0.2 μM tunicamycin, 2.5 mM irestatin 9389 and 20 μM resveratrol were used for in vitro study. The results demonstrated that resveratrol significantly improved the renal function and tubular epithelial cell injury and enhanced the survival rate of CLP-induced rat model of sepsis, which was accompanied by a substantial decrease of the serum content and renal mRNA expressions of TNF-α, IL-1β and IL-6. In addition, resveratrol obviously relieved the endoplasmic reticulum stress, inhibited the phosphorylation of inositol-requiring enzyme 1(IRE1) and nuclear factor-κB (NF-κB) in the kidney. In vitro studies showed that resveratrol enhanced the cell viability, reduced the phosphorylation of NF-κB and production of inflammatory factors in lipopolysaccharide and tunicamycin-induced HK-2 cells through inhibiting IRE1 activation. Taken together, administration of resveratrol as soon as possible after the onset of sepsis could protect against septic AKI mainly through inhibiting IRE1-NF-κB pathway-triggered inflammatory response in the kidney. Resveratrol might be a readily translatable option to improve the prognosis of sepsis. PMID:28430592

  18. Fluids and sepsis: changing the paradigm of fluid therapy: a case report.

    PubMed

    Hariyanto, Hori; Yahya, Corry Quando; Widiastuti, Monika; Wibowo, Primartanto; Tampubolon, Oloan Eduard

    2017-02-04

    Over the past 16 years, sepsis management has been guided by large-volume fluid administration to achieve certain hemodynamic optimization as advocated in the Rivers protocol. However, the safety of such practice has been questioned because large-volume fluid administration is associated with fluid overload and carries the worst outcome in patients with sepsis. Researchers in multiple studies have declared that using less fluid leads to increased survival, but they did not describe how to administer fluids in a timely and appropriate manner. An 86-year-old previously healthy Sundanese man was admitted to the intensive care unit at our institution with septic shock, acute kidney injury, and respiratory distress. Standard care was implemented during his initial care in the high-care unit; nevertheless, his condition worsened, and he was transferred to the intensive care unit. We describe the timing of fluid administration and elaborate on the amount of fluids needed using a conservative fluid regimen in a continuum of resuscitated sepsis. Because fluid depletion in septic shock is caused by capillary leak and pathologic vasoplegia, continuation of fluid administration will drive intravascular fluid into the interstitial space, thereby producing marked tissue edema and disrupting vital oxygenation. Thus, fluids have the power to heal or kill. Therefore, management of patients with sepsis should entail early vasopressors with adequate fluid resuscitation followed by a conservative fluid regimen.

  19. Three Hypothetical Inflammation Pathobiology Phenotypes and Pediatric Sepsis-Induced Multiple Organ Failure Outcome.

    PubMed

    Carcillo, Joseph A; Halstead, E Scott; Hall, Mark W; Nguyen, Trung C; Reeder, Ron; Aneja, Rajesh; Shakoory, Bita; Simon, Dennis

    2017-06-01

    We hypothesize that three inflammation pathobiology phenotypes are associated with increased inflammation, proclivity to develop features of macrophage activation syndrome, and multiple organ failure-related death in pediatric severe sepsis. Prospective cohort study comparing children with severe sepsis and any of three phenotypes: 1) immunoparalysis-associated multiple organ failure (whole blood ex vivo tumor necrosis factor response to endotoxin < 200 pg/mL), 2) thrombocytopenia-associated multiple organ failure (new onset thrombocytopenia with acute kidney injury and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 activity < 57%), and/or 3) sequential multiple organ failure with hepatobiliary dysfunction (respiratory distress followed by liver dysfunction with soluble Fas ligand > 200 pg/mL), to those without any of these phenotypes. Tertiary children's hospital PICU. One hundred consecutive severe sepsis admissions. Clinical data were recorded daily, and blood was collected twice weekly. Multiple organ failure developed in 75 cases and eight died. Multiple organ failure cases with any of the three inflammation phenotypes (n = 37) had higher inflammation (C-reactive protein, p = 0.009 and ferritin, p < 0.001) than multiple organ failure cases without any of these phenotypes (n = 38) or cases with only single organ failure (n = 25). Development of features of macrophage activation syndrome and death were more common among multiple organ failure cases with any of the phenotypes (macrophage activation syndrome: 10/37, 27%; death: 8/37, 22%) compared to multiple organ failure cases without any phenotype (macrophage activation syndrome: 1/38, 3%; p = 0.003 and death: 0/38, 0%; p = 0.002). Our approach to phenotype categorization remains hypothetical, and the phenotypes identified need to be confirmed in multicenter studies of pediatric multiple organ dysfunction syndrome.

  20. Systolic blood pressure variability in patients with early severe sepsis or septic shock: a prospective cohort study.

    PubMed

    Tang, Yi; Sorenson, Jeff; Lanspa, Michael; Grissom, Colin K; Mathews, V J; Brown, Samuel M

    2017-06-17

    Severe sepsis and septic shock are often lethal syndromes, in which the autonomic nervous system may fail to maintain adequate blood pressure. Heart rate variability has been associated with outcomes in sepsis. Whether systolic blood pressure (SBP) variability is associated with clinical outcomes in septic patients is unknown. The propose of this study is to determine whether variability in SBP correlates with vasopressor independence and mortality among septic patients. We prospectively studied patients with severe sepsis or septic shock, admitted to an intensive care unit (ICU) with an arterial catheter. We analyzed SBP variability on the first 5-min window immediately following ICU admission. We performed principal component analysis of multidimensional complexity, and used the first principal component (PC 1 ) as input for Firth logistic regression, controlling for mean systolic pressure (SBP) in the primary analyses, and Acute Physiology and Chronic Health Evaluation (APACHE) II score or NEE dose in the ancillary analyses. Prespecified outcomes were vasopressor independence at 24 h (primary), and 28-day mortality (secondary). We studied 51 patients, 51% of whom achieved vasopressor independence at 24 h. Ten percent died at 28 days. PC 1 represented 26% of the variance in complexity measures. PC 1 was not associated with vasopressor independence on Firth logistic regression (OR 1.04; 95% CI: 0.93-1.16; p = 0.54), but was associated with 28-day mortality (OR 1.16, 95% CI: 1.01-1.35, p = 0.040). Early SBP variability appears to be associated with 28-day mortality in patients with severe sepsis and septic shock.

  1. Beneficial effects of Red Light-Emitting Diode treatment in experimental model of acute lung injury induced by sepsis.

    PubMed

    Costa, Silvia Goes; Barioni, Éric Diego; Ignácio, Aline; Albuquerque, Juliana; Câmara, Niels Olsen Saraiva; Pavani, Christiane; Vitoretti, Luana Beatriz; Damazo, Amílcar Sabino; Farsky, Sandra Helena Poliselli; Lino-Dos-Santos-Franco, Adriana

    2017-10-04

    Sepsis is a severe disease with a high mortality index and it is responsible for the development of acute lung injury (ALI). We evaluated the effects of light-emitting diode (LED) on ALI induced by sepsis. Balb-c mice were injected with lipopolysaccharide or saline and then irradiated or not with red LED on their tracheas and lungs for 150 s, 2 and 6 h after LPS injections. The parameters were investigated 24 h after the LPS injections. Red LED treatment reduced neutrophil influx and the levels of interleukins 1β, 17 A and, tumor necrosis factor-α; in addition to enhanced levels of interferon γ in the bronchoalveolar fluid. Moreover, red LED treatment enhanced the RNAm levels of IL-10 and IFN-γ. It also partially reduced the elevated oxidative burst and enhanced apoptosis, but it did not alter the translocation of nuclear factor κB, the expression of toll-like receptor 4 (TLR4), as well as, oedema or mucus production in their lung tissues. Together, our data has shown the beneficial effects of short treatment with LED on ALI that are caused by gram negative bacterial infections. It is suggested that LED applications are an inexpensive and non-invasive additional treatment for sepsis.

  2. Inhibition of nuclear factor of activated T cells (NFAT) c3 activation attenuates acute lung injury and pulmonary edema in murine models of sepsis

    PubMed Central

    Karpurapu, Manjula; Lee, Yong Gyu; Qian, Ziqing; Wen, Jin; Ballinger, Megan N.; Rusu, Luiza; Chung, Sangwoon; Deng, Jing; Qian, Feng; Reader, Brenda F.; Nirujogi, Teja Srinivas; Park, Gye Young; Pei, Dehua; Christman, John W.

    2018-01-01

    Specific therapies targeting cellular and molecular events of sepsis induced Acute Lung Injury (ALI) pathogenesis are lacking. We have reported a pivotal role for Nuclear Factors of Activated T cells (NFATc3) in regulating macrophage phenotype during sepsis induced ALI and subsequent studies demonstrate that NFATc3 transcriptionally regulates macrophage CCR2 and TNFα gene expression. Mouse pulmonary microvascular endothelial cell monolayer maintained a tighter barrier function when co-cultured with LPS stimulated NFATc3 deficient macrophages whereas wild type macrophages caused leaky monolayer barrier. More importantly, NFATc3 deficient mice showed decreased neutrophilic lung inflammation, improved alveolar capillary barrier function, arterial oxygen saturation and survival benefit in lethal CLP sepsis mouse models. In addition, survival of wild type mice subjected to the lethal CLP sepsis was not improved with broad-spectrum antibiotics, whereas the survival of NFATc3 deficient mice was improved to 40–60% when treated with imipenem. Passive adoptive transfer of NFATc3 deficient macrophages conferred protection against LPS induced ALI in wild type mice. Furthermore, CP9-ZIZIT, a highly potent, cell-permeable peptide inhibitor of Calcineurin inhibited NFATc3 activation. CP9-ZIZIT effectively reduced sepsis induced inflammatory cytokines and pulmonary edema in mice. Thus, this study demonstrates that inhibition of NFATc3 activation by CP9-ZIZIT provides a potential therapeutic option for attenuating sepsis induced ALI/pulmonary edema. PMID:29535830

  3. Hemodynamic variables and progression of acute kidney injury in critically ill patients with severe sepsis: data from the prospective observational FINNAKI study

    PubMed Central

    2013-01-01

    Introduction Knowledge of the association of hemodynamics with progression of septic acute kidney injury (AKI) is limited. However, some recent data suggest that mean arterial pressure (MAP) exceeding current guidelines (60–65 mmHg) may be needed to prevent AKI. We hypothesized that higher MAP during the first 24 hours in the intensive care unit (ICU), would be associated with a lower risk of progression of AKI in patients with severe sepsis. Methods We identified 423 patients with severe sepsis and electronically recorded continuous hemodynamic data in the prospective observational FINNAKI study. The primary endpoint was progression of AKI within the first 5 days of ICU admission defined as new onset or worsening of AKI by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We evaluated the association of hemodynamic variables with this endpoint. We included 53724 10-minute medians of MAP in the analysis. We analysed the ability of time-adjusted MAP to predict progression of AKI by receiver operating characteristic (ROC) analysis. Results Of 423 patients, 153 (36.2%) had progression of AKI. Patients with progression of AKI had significantly lower time-adjusted MAP, 74.4 mmHg [68.3-80.8], than those without progression, 78.6 mmHg [72.9-85.4], P < 0.001. A cut-off value of 73 mmHg for time-adjusted MAP best predicted the progression of AKI. Chronic kidney disease, higher lactate, higher dose of furosemide, use of dobutamine and time-adjusted MAP below 73 mmHg were independent predictors of progression of AKI. Conclusions The findings of this large prospective multicenter observational study suggest that hypotensive episodes (MAP under 73 mmHg) are associated with progression of AKI in critically ill patients with severe sepsis. PMID:24330815

  4. Validation of the Vasoactive-Inotropic Score in Pediatric Sepsis*

    PubMed Central

    Tong, Suhong; Deakyne, Sara J.; Davidson, Jesse A.; Scott, Halden F.

    2017-01-01

    Objectives: To assess the validity of Vasoactive-Inotropic Score as a scoring system for cardiovascular support and surrogate outcome in pediatric sepsis. Design: Secondary retrospective analysis of a single-center sepsis registry. Setting: Freestanding children’s hospital and tertiary referral center. Patients: Children greater than 60 days and less than 18 years with sepsis identified in the emergency department between January 2012 and June 2015 treated with at least one vasoactive medication within 48 hours of admission to the PICU. Interventions: None. Measurements and Main Results: Vasoactive-Inotropic Score was abstracted at 6, 12, 24, and 48 hours post ICU admission. Primary outcomes were ventilator days and ICU length of stay. The secondary outcome was a composite outcome of cardiac arrest/extracorporeal membrane oxygenation/in-hospital mortality. One hundred thirty-eight patients met inclusion criteria. Most common infectious sources were pneumonia (32%) and bacteremia (23%). Thirty-three percent were intubated and mortality was 6%. Of the time points assessed, Vasoactive-Inotropic Score at 48 hours showed the strongest correlation with ICU length of stay (r = 0.53; p < 0.0001) and ventilator days (r = 0.52; p < 0.0001). On multivariable analysis, Vasoactive-Inotropic Score at 48 hours was a strong independent predictor of primary outcomes and intubation. For every unit increase in Vasoactive-Inotropic Score at 48 hours, there was a 13% increase in ICU length of stay (p < 0.001) and 8% increase in ventilator days (p < 0.01). For every unit increase in Vasoactive-Inotropic Score at 12 hours, there was a 14% increase in odds of having the composite outcome (p < 0.01). Conclusions: Vasoactive-Inotropic Score in pediatric sepsis patients is independently associated with important clinically relevant outcomes including ICU length of stay, ventilator days, and cardiac arrest/extracorporeal membrane oxygenation/mortality. Vasoactive-Inotropic Score may be a

  5. Validation of the Vasoactive-Inotropic Score in Pediatric Sepsis.

    PubMed

    McIntosh, Amanda M; Tong, Suhong; Deakyne, Sara J; Davidson, Jesse A; Scott, Halden F

    2017-08-01

    To assess the validity of Vasoactive-Inotropic Score as a scoring system for cardiovascular support and surrogate outcome in pediatric sepsis. Secondary retrospective analysis of a single-center sepsis registry. Freestanding children's hospital and tertiary referral center. Children greater than 60 days and less than 18 years with sepsis identified in the emergency department between January 2012 and June 2015 treated with at least one vasoactive medication within 48 hours of admission to the PICU. None. Vasoactive-Inotropic Score was abstracted at 6, 12, 24, and 48 hours post ICU admission. Primary outcomes were ventilator days and ICU length of stay. The secondary outcome was a composite outcome of cardiac arrest/extracorporeal membrane oxygenation/in-hospital mortality. One hundred thirty-eight patients met inclusion criteria. Most common infectious sources were pneumonia (32%) and bacteremia (23%). Thirty-three percent were intubated and mortality was 6%. Of the time points assessed, Vasoactive-Inotropic Score at 48 hours showed the strongest correlation with ICU length of stay (r = 0.53; p < 0.0001) and ventilator days (r = 0.52; p < 0.0001). On multivariable analysis, Vasoactive-Inotropic Score at 48 hours was a strong independent predictor of primary outcomes and intubation. For every unit increase in Vasoactive-Inotropic Score at 48 hours, there was a 13% increase in ICU length of stay (p < 0.001) and 8% increase in ventilator days (p < 0.01). For every unit increase in Vasoactive-Inotropic Score at 12 hours, there was a 14% increase in odds of having the composite outcome (p < 0.01). Vasoactive-Inotropic Score in pediatric sepsis patients is independently associated with important clinically relevant outcomes including ICU length of stay, ventilator days, and cardiac arrest/extracorporeal membrane oxygenation/mortality. Vasoactive-Inotropic Score may be a useful surrogate outcome in pediatric sepsis.

  6. A quality improvement project to improve the Medicare and Medicaid Services (CMS) sepsis bundle compliance rate in a large healthcare system.

    PubMed

    Raschke, Robert A; Groves, Robert H; Khurana, Hargobind S; Nikhanj, Nidhi; Utter, Ethel; Hartling, Didi; Stoffer, Brenda; Nunn, Kristina; Tryon, Shona; Bruner, Michelle; Calleja, Maria; Curry, Steven C

    2017-01-01

    Sepsis is a leading cause of mortality and morbidity in hospitalised patients. The Centers for Medicare and Medicaid Services (CMS) mandated that US hospitals report sepsis bundle compliance rate as a quality process measure in October 2015. The specific aim of our study was to improve the CMS sepsis bundle compliance rate from 30% to 40% across 20 acute care hospitals in our healthcare system within 1 year. The study included all adult inpatients with sepsis sampled according to CMS specifications from October 2015 to September 2016. The CMS sepsis bundle compliance rate was tracked monthly using statistical process control charting. A baseline rate of 28.5% with 99% control limits was established. We implemented multiple interventions including computerised decision support systems (CDSSs) to increase compliance with the most commonly missing bundle elements. Compliance reached 42% (99% statistical process control limits 18.4%-38.6%) as CDSS was implemented system-wide, but this improvement was not sustained after CMS changed specifications of the outcome measure. Difficulties encountered elucidate shortcomings of our study methodology and of the CMS sepsis bundle compliance rate as a quality process measure.

  7. Targeting macrophage immunometabolism: Dawn in the darkness of sepsis.

    PubMed

    Kumar, V

    2018-05-01

    Sepsis is known since the time (470 BC) of great Greek physician, Hippocrates. Advancement in modern medicine and establishment of separate branches of medical science dealing with sepsis research have improved its outcome. However, mortality associated with sepsis still remains higher (25-30%) that further increases to 40-50% in the presence of septic shock. For example, sepsis-associated deaths account more in comparison to deaths-associated with myocardial-infarction and certain cancers (i.e. breast and colorectal cancer). However, it is now well established that profound activation of innate immune cells including macrophages play a very important role in the immunopathogenesis of sepsis. Macrophages are sentinel cells of the innate immune system with their location varying from peripheral blood to various target organs including lungs, liver, brain, kidneys, skin, testes, vascular endothelium etc. Thus, profound and dysregulated activation of these cells during sepsis can directly impact the outcome of sepsis. However, the emergence of the concept of immunometabolism as a major controller of immune response has raised a new hope for identifying new targets for immunomodulatory therapeutic approaches. Thus this present review starts with an introduction of sepsis as a major medical problem worldwide and signifies the role of dysregulated innate immune response including macrophages in its immunopathogenesis. Thereafter, subsequent sections describe changes in immunometabolic stage of macrophages (both M1 and M2) during sepsis. The article ends with the discussion of novel macrophage-specific therapeutic targets targeting their immunometabolism during sepsis and epigenetic regulation of macrophage immunometabolism and vice versa. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

    PubMed Central

    Singer, Mervyn; Deutschman, Clifford S.; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig M.; Hotchkiss, Richard S.; Levy, Mitchell M.; Marshall, John C.; Martin, Greg S.; Opal, Steven M.; Rubenfeld, Gordon D.; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C.

    2016-01-01

    greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less. CONCLUSIONS AND RELEVANCE These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis. PMID:26903338

  9. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

    PubMed

    Singer, Mervyn; Deutschman, Clifford S; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R; Chiche, Jean-Daniel; Coopersmith, Craig M; Hotchkiss, Richard S; Levy, Mitchell M; Marshall, John C; Martin, Greg S; Opal, Steven M; Rubenfeld, Gordon D; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C

    2016-02-23

    can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less. These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.

  10. Premise for Standardized Sepsis Models.

    PubMed

    Remick, Daniel G; Ayala, Alfred; Chaudry, Irshad; Coopersmith, Craig M; Deutschman, Clifford; Hellman, Judith; Moldawer, Lyle; Osuchowski, Marcin

    2018-06-05

    Sepsis morbidity and mortality exacts a toll on patients and contributes significantly to healthcare costs. Preclinical models of sepsis have been used to study disease pathogenesis and test new therapies, but divergent outcomes have been observed with the same treatment even when using the same sepsis model. Other disorders such as diabetes, cancer, malaria, obesity and cardiovascular diseases have used standardized, preclinical models that allow laboratories to compare results. Standardized models accelerate the pace of research and such models have been used to test new therapies or changes in treatment guidelines. The National Institutes of Health (NIH) mandated that investigators increase data reproducibility and the rigor of scientific experiments and has also issued research funding announcements about the development and refinement of standardized models. Our premise is that refinement and standardization of preclinical sepsis models may accelerate the development and testing of potential therapeutics for human sepsis, as has been the case with preclinical models for other disorders. As a first step towards creating standardized models, we suggest 1) standardizing the technical standards of the widely used cecal ligation and puncture model and 2) creating a list of appropriate organ injury and immune dysfunction parameters. Standardized sepsis models could enhance reproducibility and allow comparison of results between laboratories and may accelerate our understanding of the pathogenesis of sepsis.

  11. Sepsis

    MedlinePlus

    ... its early stage, before it becomes more dangerous. Sepsis To be diagnosed with sepsis, you must exhibit ... rate higher than 20 breaths a minute Severe sepsis Your diagnosis will be upgraded to severe sepsis ...

  12. Pediatric severe sepsis in U.S. children's hospitals.

    PubMed

    Balamuth, Fran; Weiss, Scott L; Neuman, Mark I; Scott, Halden; Brady, Patrick W; Paul, Raina; Farris, Reid W D; McClead, Richard; Hayes, Katie; Gaieski, David; Hall, Matt; Shah, Samir S; Alpern, Elizabeth R

    2014-11-01

    To compare the prevalence, resource utilization, and mortality for pediatric severe sepsis identified using two established identification strategies. Observational cohort study from 2004 to 2012. Forty-four pediatric hospitals contributing data to the Pediatric Health Information Systems database. Children 18 years old or younger. We identified patients with severe sepsis or septic shock by using two International Classification of Diseases, 9th edition, Clinical Modification-based coding strategies: 1) combinations of International Classification of Diseases, 9th edition, Clinical Modification codes for infection plus organ dysfunction (combination code cohort); 2) International Classification of Diseases, 9th edition, Clinical Modification codes for severe sepsis and septic shock (sepsis code cohort). Outcomes included prevalence of severe sepsis, as well as hospital and ICU length of stay, and mortality. Outcomes were compared between the two cohorts examining aggregate differences over the study period and trends over time. The combination code cohort identified 176,124 hospitalizations (3.1% of all hospitalizations), whereas the sepsis code cohort identified 25,236 hospitalizations (0.45%), a seven-fold difference. Between 2004 and 2012, the prevalence of sepsis increased from 3.7% to 4.4% using the combination code cohort and from 0.4% to 0.7% using the sepsis code cohort (p < 0.001 for trend in each cohort). Length of stay (hospital and ICU) and costs decreased in both cohorts over the study period (p < 0.001). Overall, hospital mortality was higher in the sepsis code cohort than the combination code cohort (21.2% [95% CI, 20.7-21.8] vs 8.2% [95% CI, 8.0-8.3]). Over the 9-year study period, there was an absolute reduction in mortality of 10.9% (p < 0.001) in the sepsis code cohort and 3.8% (p < 0.001) in the combination code cohort. Prevalence of pediatric severe sepsis increased in the studied U.S. children's hospitals over the past 9 years, whereas

  13. Apoptosis-induced lymphopenia in sepsis and other severe injuries.

    PubMed

    Girardot, Thibaut; Rimmelé, Thomas; Venet, Fabienne; Monneret, Guillaume

    2017-02-01

    Sepsis and other acute injuries such as severe trauma, extensive burns, or major surgeries, are usually followed by a period of marked immunosuppression. In particular, while lymphocytes play a pivotal role in immune response, their functions and numbers are profoundly altered after severe injuries. Apoptosis plays a central role in this process by affecting immune response at various levels. Indeed, apoptosis-induced lymphopenia duration and depth have been associated with higher risk of infection and mortality in various clinical settings. Therapies modulating apoptosis represent an interesting approach to restore immune competence after acute injury, although their use in clinical practice still presents several limitations. After briefly describing the apoptosis process in physiology and during severe injuries, we will explore the immunological consequences of injury-induced lymphocyte apoptosis, and describe associations with clinically relevant outcomes in patients. Therapeutic perspectives targeting apoptosis will also be discussed.

  14. Comparative study of single/combination use of Huang-Lian-Jie-Du decoction and berberine on their protection on sepsis induced acute liver injury by NMR metabolic profiling.

    PubMed

    Lv, Yan; Wang, Junsong; Xu, Dingqiao; Liao, Shanting; Li, Pei; Zhang, Qian; Yang, Minghua; Kong, Lingyi

    2017-10-25

    Sepsis is a serious clinical disease with a high mortality rate all around the world. Liver organ dysfunction is an important sign for the severity and outcome of sepsis in patients. In this study, 1 H NMR-based metabolomics approach and biochemical assays were applied to investigate the metabolic profiling for cecal ligation and puncture (CLP) induced acute liver injury, the therapeutical effect of single/combination use of Huang-Lian-Jie-Du decoction (HLJDD) and berberine, and the interaction of them. Metabolomics analysis revealed significant perturbations in livers of septic rats, which could be ameliorated by HLJDD, berberine and their combination treatment. Berberine could better rectified glycolysis and nucleic acid metabolism in the liver. HLJDD had exceptional better anti-inflammatory, antibacterial and antioxidative effects than berberine. The interaction of berberine and HLJDD could further strengthen the anti-inflammation and anti-oxidation, but with poor effect on amino acids metabolism. These findings highlighted the feasibility of the integrated NMR based metabolomics approach to understand the pathogenesis of diseases, the action mechanisms of therapy and the herb-drug interaction. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Incorporating Interprofessional Evidenced-Based Sepsis Simulation Education for Certified Nursing Assistants (CNAs) and Licensed Care Providers Within Long-term Care Settings for Process and Quality Improvement.

    PubMed

    Mihaljevic, Susan E; Howard, Valerie M

    2016-01-01

    Improving resident safety and quality of care by maximizing interdisciplinary communication among long-term care providers is essential in meeting the goals of the United States' Federal Health care reform. The new Triple Aim goals focus on improved patient outcomes, increasing patient satisfaction, and decreased health care costs, thus providing consumers with quality, efficient patient-focused care. Within the United States, sepsis is the 10th leading cause of death with a 28.6% mortality rate in the elderly, increasing to 40% to 60% in septic shock. As a result of the Affordable Care Act, the Centers for Medicare & Medicaid services supported the Interventions to Reduce Acute Care Transfers 3.0 program to improve health care quality and prevent avoidable rehospitalization by improving assessment, documentation, and communication among health care providers. The Interventions to Reduce Acute Care Transfers 3.0 tools were incorporated in interprofessional sepsis simulations throughout 19 long-term care facilities to encourage the early recognition of sepsis symptoms and prompt communication of sepsis symptoms among interdisciplinary teams. As a result of this simulation training, many long-term care organizations have adopted the STOP and WATCH and SBAR tools as a venue to communicate resident condition changes.

  16. Stress disorders following prolonged critical illness in survivors of severe sepsis.

    PubMed

    Wintermann, Gloria-Beatrice; Brunkhorst, Frank Martin; Petrowski, Katja; Strauss, Bernhard; Oehmichen, Frank; Pohl, Marcus; Rosendahl, Jenny

    2015-06-01

    To examine the frequency of acute stress disorder and posttraumatic stress disorder in chronically critically ill patients with a specific focus on severe sepsis, to classify different courses of stress disorders from 4 weeks to 6 months after transfer from acute care hospital to postacute rehabilitation, and to identify patients at risk by examining the relationship between clinical, demographic, and psychological variables and stress disorder symptoms. Prospective longitudinal cohort study, three assessment times within 4 weeks, 3 months, and 6 months after transfer to postacute rehabilitation. Patients were consecutively enrolled in a large rehabilitation hospital (Clinic Bavaria, Kreischa, Germany) admitted for ventilator weaning from acute care hospitals. We included 90 patients with admission diagnosis critical illness polyneuropathy or critical illness myopathy with or without severe sepsis, age between 18 and 70 years with a length of ICU stay greater than 5 days. None. Acute stress disorder and posttraumatic stress disorder were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, criteria by a trained and experienced clinical psychologist using a semistructured clinical interview for Diagnostic and Statistical Manual of Mental Disorders. We further administered the Acute Stress Disorder Scale and the Posttraumatic Symptom Scale-10 to assess symptoms of acute stress disorder and posttraumatic stress disorder. Three percent of the patients had an acute stress disorder diagnosis 4 weeks after transfer to postacute rehabilitation. Posttraumatic stress disorder was found in 7% of the patients at 3-month follow-up and in 12% after 6 months, respectively. Eighteen percent of the patients showed a delayed onset of posttraumatic stress disorder. Sepsis turned out to be a significant predictor of posttraumatic stress disorder symptoms at 3-month follow-up. A regular screening of post-ICU patients after discharge from

  17. Bilateral adrenal hemorrhage in the background of Escherichia coli sepsis: a case report.

    PubMed

    Khwaja, Jahanzaib

    2017-03-17

    Sepsis is a syndrome of life-threatening organ dysfunction caused by a dysregulated host response to infection. It can have devastating consequences, including bilateral adrenal hemorrhage, particularly in patients at high thrombotic risk, such as those with antiphospholipid syndrome and those on long-term anticoagulation. A 49-year-old white woman re-presented to hospital with a history suggestive of sepsis. She had a medical background of primary antiphospholipid syndrome on lifelong warfarin. Ten days prior to this presentation, she had been hospitalized following Escherichia coli bacteremia, commenced on intravenous antibiotics, and discharged 2 days later with a prescribed 5-day course of oral amoxicillin. On readmission, she had ongoing fever, myalgia, malaise, and hypotension. Investigations revealed anemia with thrombocytopenia, hyponatremia, and acute-on-chronic kidney injury. Despite treatment for urosepsis, she became tachypneic, clammy, light-headed, drowsy, and hypothermic. Computed tomography revealed bilateral adrenal hemorrhage, and biochemical examination confirmed hypoadrenalism. Following discharge, she had persistent renal and hepatic injury lasting 3 months. Early identification, intensive monitoring, and aggressive support may reduce the acquired thrombotic risk and avoid potentially life-threatening outcomes of sepsis.

  18. Oxidative stress biomarkers in pediatric sepsis: a prospective observational pilot study.

    PubMed

    Molina, Víctor; von Dessauer, Bettina; Rodrigo, Ramón; Carvajal, Cristian

    2017-11-01

    Oxidative stress is known to participate in the progression of sepsis. Definite data regarding the behavior of oxidative stress biomarkers in pediatric sepsis is still lacking. This study hypothesized that oxidative stress occurs in pediatric sepsis and that the magnitude of the redox derangement is associated with worse clinical progression. Forty-two previously healthy pediatric patients with sepsis and a group of control subjects were included. Oxidative stress and inflammatory activity biomarkers were determined in blood samples. Patients were prospectively followed until their discharge or death. Patients with non-severe and severe sepsis showed higher levels of plasmatic antioxidant capacity, lower erythrocyte thiol index, lower superoxide dismutase and catalase activities, higher glutathione peroxidase activity, and higher plasmatic F 2 -isoprostanes concentration than controls. Patients with severe sepsis had higher NF-kappaB activation than those with non-severe sepsis. Although we observed changes in some biomarkers in patients with worse clinical evolution, the explored biomarkers did not correlate with clinical estimators of outcome. Oxidative stress occurs in pediatric sepsis, resulting in oxidative damage. The explored biomarkers are not useful as outcome predictors in the studied population. The behavior of these biomarkers still needs to be addressed in broader groups of pediatric patients with sepsis.

  19. Delay Within the 3-Hour Surviving Sepsis Campaign Guideline on Mortality for Patients With Severe Sepsis and Septic Shock.

    PubMed

    Pruinelli, Lisiane; Westra, Bonnie L; Yadav, Pranjul; Hoff, Alexander; Steinbach, Michael; Kumar, Vipin; Delaney, Connie W; Simon, Gyorgy

    2018-04-01

    To specify when delays of specific 3-hour bundle Surviving Sepsis Campaign guideline recommendations applied to severe sepsis or septic shock become harmful and impact mortality. Retrospective cohort study. One health system composed of six hospitals and 45 clinics in a Midwest state from January 01, 2011, to July 31, 2015. All adult patients hospitalized with billing diagnosis of severe sepsis or septic shock. Four 3-hour Surviving Sepsis Campaign guideline recommendations: 1) obtain blood culture before antibiotics, 2) obtain lactate level, 3) administer broad-spectrum antibiotics, and 4) administer 30 mL/kg of crystalloid fluid for hypotension (defined as "mean arterial pressure" < 65) or lactate (> 4). To determine the effect of t minutes of delay in carrying out each intervention, propensity score matching of "baseline" characteristics compensated for differences in health status. The average treatment effect in the treated computed as the average difference in outcomes between those treated after shorter versus longer delay. To estimate the uncertainty associated with the average treatment effect in the treated metric and to construct 95% CIs, bootstrap estimation with 1,000 replications was performed. From 5,072 patients with severe sepsis or septic shock, 1,412 (27.8%) had in-hospital mortality. The majority of patients had the four 3-hour bundle recommendations initiated within 3 hours. The statistically significant time in minutes after which a delay increased the risk of death for each recommendation was as follows: lactate, 20.0 minutes; blood culture, 50.0 minutes; crystalloids, 100.0 minutes; and antibiotic therapy, 125.0 minutes. The guideline recommendations showed that shorter delays indicates better outcomes. There was no evidence that 3 hours is safe; even very short delays adversely impact outcomes. Findings demonstrated a new approach to incorporate time t when analyzing the impact on outcomes and provide new evidence for clinical practice

  20. May thrombopoietin be a useful marker of sepsis severity assessment in patients with SIRS entering the emergency department?

    PubMed

    Segre, Elisabetta; Pigozzi, Luca; Lison, Davide; Pivetta, Emanuele; Bosco, Ornella; Vizio, Barbara; Suppo, Umberto; Turvani, Fabrizio; Morello, Fulvio; Battista, Stefania; Moiraghi, Corrado; Montrucchio, Giuseppe; Lupia, Enrico

    2014-10-01

    Thrombopoietin (TPO), a growth factor primarily involved in regulating thrombopoiesis, has been recently implicated in the pathogenesis of sepsis. TPO levels are, indeed, greatly increased in patients with sepsis compared to control subjects, and correlate with sepsis severity. The aim of this study was to evaluate TPO as predictive biomarker of sepsis and of sepsis severity in patients entering the emergency department (ED) with systemic inflammatory response syndrome (SIRS). This was a prospective observational study. Ours is a sub-study of the 'Need-speed trial', a multi-center observational study involving six Italian centers affiliated to the GREAT Italian Network. TPO was measured by ELISA. We enrolled 13 patients with SIRS (6 with acute pancreatitis, 3 with acute heart failure, 1 with pulmonary embolism, and 3 with allergic reactions), and 40 patients with sepsis, eight of whom had severe sepsis and three septic shock. TPO was significantly higher in patients with sepsis than with SIRS. In addition, TPO was higher in patients with severe sepsis than with sepsis, and in patients with septic shock than with severe sepsis, although these differences did not reach the statistical significance. Our preliminary results suggest that TPO may have the potential to be considered a promising early biomarker for both the diagnosis of sepsis and the assessment of sepsis severity in patients with SIRS entering the ED.

  1. Implications of the new sepsis definition on research and practice.

    PubMed

    Peach, Brian C

    2017-04-01

    The Society of Critical-Care Medicine and the European Society of Intensive Care Medicine recently announced a marked change in the sepsis definition. A task force of 19 sepsis clinicians and researchers made the change based on advances in the pathobiological understanding of the septic process. The task force determined that there were numerous justifications for a revision of the sepsis definition, which are outlined in this article. The systemic inflammatory response criteria have been replaced by the Sequential Organ Failure Assessment (SOFA) score in the newly operationalized definition (Singer et al., 2016). In addition to the definition change, the task force recommended using the new quick SOFA (qSOFA) score in non-ICU settings, as a risk stratification tool to identify patients who may be septic or be at risk of developing sepsis. The change in definition will likely have a negative impact on sepsis research in the short-term as hospitals adjust their coding for the new definition, but may result in less misclassification bias and improved research data in the long-term. While the intent of the SCCM/ESICM task force was to better define sepsis for coding and epidemiological research purposes, there is the potential for improved patient outcomes if clinicians are better able to differentiate between sepsis and inflammatory events. The qSOFA tool may also aid clinicians in recognizing sepsis in a quicker manner, leading to more timely treatment, and potentially better outcomes. While the new operationalized Sepsis-3 definition appears on the surface to be an improvement over the previous iterations, it remains to be seen if research data will be more robust using the new criteria. There is the potential for better patient outcomes if clinicians are better able to differentiate sepsis from inflammatory events with the new definition, and if sepsis cases are recognized sooner with qSOFA. Future research on the impact of this definition change on research and

  2. [Frequency, etiology, and outcomes of acute renal failure (data of Kaunas University of Medicine Hospital in 1995-2006)].

    PubMed

    Skarupskiene, Inga; Kuzminskis, Vytautas; Ziginskiene, Edita

    2007-01-01

    The aim of this study was to determine the frequency, etiology, and outcomes of acute renal failure. We retrospectively collected data on all patients (n=1653) who received renal replacement therapy for acute renal failure at the Kaunas University of Medicine Hospital during 1995-2006. The number of patients with acute renal failure increased nine times during the 11-year period. The mean age of patients was 59.76+/-17.52 years and increased from 44.97+/-17.1 years in 1995 to 62.84+/-16.49 years in 2006. The most common causes of acute renal failure were renal (n=646, 39%), prerenal (n=380, 23%), and obstructive (n=145, 9%). The renal replacement therapy was discontinued because of recovery of renal function in 49.9% of cases. The overall hospital mortality rate was 45.1%. Renal function did not recover in 6.7% of patients. The mortality rate over the 11-year period varied from 37.8 to 57.5%. The highest mortality rate was in the neurosurgical (62.3%) and cardiac surgical (61.8%) intensive care units. High mortality rate (more than 50%) was in the groups of patients with acute renal failure that was caused by hepatorenal syndrome, shock, sepsis, and reduced cardiac output.

  3. Epidemiology and outcome analysis of sepsis and organ dysfunction/failure after burns.

    PubMed

    Belba, Monika Kristaq; Petrela, Elizana Ylber; Belba, Amy Gjergji

    2017-09-01

    The aim of this prospective study in adult population is to give frequency data (prevalence, incidence) of burn wound sepsis and its consequences (organ dysfunction/failure); to analyze the evolution of the SOFA cumulative score during the disease and relationship between the SOFA score in the 3rd, 7th, 14th and 21th day after burn with mortality. A prospective cohort study was performed among adult patients (age ≥20 years) admitted in the ICU, with major and moderate burns. Sepsis, organ dysfunction, organ failure and mortality were calculated as Cumulative Incidence (CI) and as Incidence rate (IR). Data from patients with sepsis were compared with those without sepsis. Evaluation of SOFA evolution was done with delta score and the influence of the SOFA score in mortality was calculated with AUC of the ROC curve. Period prevalence of sepsis in our adult burned population was 26%. Incidence proportion as CI was 0.3 or 30 patients per 100 adults. Incidence rate (IR) was 6 patients with sepsis per 100 patient-years. Overall morbidity was 88.1% while overall mortality was 11.9%. Mortality in patients with sepsis was 34.4%. Incidence of MOD was 63% while incidence of MOF was 37%. Respective mortality as CI was 7% and 81% while mortality rate as IR was 1.4 per 100 patient-years in patients with MOD and 16.2 per 100 patient-years in patients with MOF. SOFA-3 should be considered a "reliable indicator" at separating survivors from non survivors and SOFA 7, 14, and 21 should be considered excellent in predicting mortality. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

  4. The Surviving Sepsis Campaign: Where have we been and where are we going?

    PubMed

    Dellinger, R Phillip

    2015-04-01

    The Surviving Sepsis Campaign develops and promotes evidence-based guidelines and performance-improvement practices aimed at reducing deaths from sepsis worldwide. The most recent guidelines, published in 2013, provide detailed management strategies for acute care, fluid resuscitation, and vasopressor use. In addition, the campaign has developed simple, short protocols for what to do within 3 and 6 hours of recognition of sepsis. These protocols are associated with reduced mortality rates. Copyright © 2015 Cleveland Clinic.

  5. Culture-positive sepsis in neonatal camelids: 21 cases.

    PubMed

    Dolente, Brett A; Lindborg, Susan; Palmer, Jonathan E; Wilkins, Pamela A

    2007-01-01

    There is limited literature on neonatal bacterial sepsis in New World (NW) camelids. Bacterial culture-positive crias have clinical differences based on the specific bacterial genera isolated. Bacterial culture-positive NW camelid crias <21 days of age from 1990 to 2005 were included. Historic physical examination and cliniopathologic data were retrieved from medical records as were the identity and antibiograms of bacterial isolates. Cases were categorized by outcome (survival versus nonsurvival) and type of sepsis (gram-negative or gram-positive). Kruskal-Wallis and chi-square testing were used to evaluate differences between groups. Twenty-one crias met the inclusion criteria. Median age was 2 days. Failure of passive transfer was common. There were few differences identified on the basis of outcome or type of sepsis. Crias without gastrointestinal or central nervous system involvement survived in greater numbers. Forty-six percent of isolates were gram-positive. The most common isolates were the following: Escherichia coli, Enterococcus spp., Listeria monocytogenes, and Citrobacter spp. Overall survival was 67% (14/21). Crias with sepsis do not appear to present with major biochemical, hematologic, or blood gas abnormalities, potentially complicating diagnosis. Affected crias may not have localizing signs at presentation and are not usually febrile, although hypothermia, tachypnea, and tachycardia are relatively common. Total protein concentration was not a substitute for immunoglobulin G measurement in septic crias in this study. Familiarity with the clinical presentation and common pathogens isolated should improve early recognition and treatment and ultimately outcome of crias with sepsis.

  6. Pediatric Severe Sepsis in US Children’s Hospitals

    PubMed Central

    Balamuth, Fran; Weiss, Scott L.; Neuman, Mark I.; Scott, Halden; Brady, Patrick W.; Paul, Raina; Farris, Reid W.D.; McClead, Richard; Hayes, Katie; Gaieski, David; Hall, Matt; Shah, Samir S.; Alpern, Elizabeth R.

    2014-01-01

    Objective To compare the prevalence, resource utilization, and mortality for pediatric severe sepsis identified using two established identification strategies. Design Observational cohort study from 2004–2012. Setting Forty-four pediatric hospitals contributing data to the Pediatric Health Information Systems database. Patients Children ≤18 years of age. Measurements and Main Results We identified patients with severe sepsis or septic shock by using two International Classification of Diseases, 9th edition-Clinical Modification (ICD9-CM) based coding strategies: 1) combinations of ICD9-CM codes for infection plus organ dysfunction (combination code cohort); 2) ICD9-CM codes for severe sepsis and septic shock (sepsis code cohort). Outcomes included prevalence of severe sepsis, as well as hospital and intensive care unit (ICU) length of stay (LOS), and mortality. Outcomes were compared between the two cohorts examining aggregate differences over the study period and trends over time. The combination code cohort identified, 176,124 hospitalizations (3.1% of all hospitalizations), while the sepsis code cohort identified 25,236 hospitalizations (0.45%), a 7-fold difference. Between 2004 and 2012, the prevalence of sepsis increased from 3.7% to 4.4% using the combination code cohort and from 0.4% to 0.7% using the sepsis code cohort (p<0.001 for trend in each cohort). LOS (hospital and ICU) and costs decreased in both cohorts over the study period (p<0.001). Overall hospital mortality was higher in the sepsis code cohort than the combination code cohort (21.2%, (95% CI: 20.7–21.8 vs. 8.2%,(95% CI: 8.0–8.3). Over the 9 year study period, there was an absolute reduction in mortality of 10.9% (p<0.001) in the sepsis code cohort and 3.8% (p<0.001) in the combination code cohort. Conclusions Prevalence of pediatric severe sepsis increased in the studied US children’s hospitals over the past 9 years, though resource utilization and mortality decreased. Epidemiologic

  7. Clinical, laboratory, and hemostatic findings in cats with naturally occurring sepsis.

    PubMed

    Klainbart, Sigal; Agi, Limor; Bdolah-Abram, Tali; Kelmer, Efrat; Aroch, Itamar

    2017-11-01

    OBJECTIVE To characterize clinical and laboratory findings in cats with naturally occurring sepsis, emphasizing hemostasis-related findings, and evaluate these variables for associations with patient outcomes. DESIGN Prospective, observational, clinical study. ANIMALS 31 cats with sepsis and 33 healthy control cats. PROCEDURES Data collected included history; clinical signs; results of hematologic, serum biochemical, and hemostatic tests; diagnosis; and outcome (survival vs death during hospitalization or ≤ 30 days after hospital discharge). Differences between cats with and without sepsis and associations between variables of interest and death were analyzed statistically. RESULTS The sepsis group included cats with pyothorax (n = 10), septic peritonitis (7), panleukopenia virus infection (5), bite wounds (5), abscesses and diffuse cellulitis (3), and pyometra (1). Common clinical abnormalities included dehydration (21 cats), lethargy (21), anorexia (18), pale mucous membranes (15), and dullness (15). Numerous clinicopathologic abnormalities were identified in cats with sepsis; novel findings included metarubricytosis, hypertriglyceridemia, and high circulating muscle enzyme activities. Median activated partial thromboplastin time and plasma D-dimer concentrations were significantly higher, and total protein C and antithrombin activities were significantly lower, in the sepsis group than in healthy control cats. Disseminated intravascular coagulopathy was uncommon (4/22 [18%] cats with sepsis). None of the clinicopathologic abnormalities were significantly associated with death on multivariate analysis. CONCLUSIONS AND CLINICAL RELEVANCE Cats with sepsis had multiple hematologic, biochemical, and hemostatic abnormalities on hospital admission, including several findings suggestive of hemostatic derangement. Additional research including larger numbers of cats is needed to further investigate these findings and explore associations with outcome.

  8. Proenkephalin, Neutrophil Gelatinase-Associated Lipocalin, and Estimated Glomerular Filtration Rates in Patients With Sepsis.

    PubMed

    Kim, Hanah; Hur, Mina; Lee, Seungho; Marino, Rossella; Magrini, Laura; Cardelli, Patrizia; Struck, Joachim; Bergmann, Andreas; Hartmann, Oliver; Di Somma, Salvatore

    2017-09-01

    Proenkephalin (PENK) has been suggested as a novel biomarker for kidney function. We investigated the diagnostic and prognostic utility of plasma PENK in comparison with neutrophil gelatinase-associated lipocalin (NGAL) and estimated glomerular filtration rates (eGFR) in septic patients. A total of 167 septic patients were enrolled: 99 with sepsis, 37 with septic shock, and 31 with suspected sepsis. PENK and NGAL concentrations were measured and GFR was estimated by using the isotope dilution mass spectrometry traceable-Modification of Diet in Renal Disease (MDRD) Study and three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations: CKD-EPI(Cr), CDK-EPI(CysC), and CKD-EPI(Cr-CysC). The PENK, NGAL, and eGFR results were compared according to sepsis severity, presence or absence of acute kidney injury (AKI), and clinical outcomes. The PENK, NGAL, and eGFR results were significantly associated with sepsis severity and differed significantly between patients with and without AKI only in the sepsis group (all P<0.05). PENK was superior to NGAL in predicting AKI (P=0.022) and renal replacement therapy (RRT) (P=0.0085). Regardless of the variable GFR category by the different eGFR equations, PENK showed constant and significant associations with all eGFR equations. Unlike NGAL, PENK was not influenced by inflammation and predicted the 30-day mortality. PENK is a highly sensitive and objective biomarker of AKI and RRT and is useful for prognosis prediction in septic patients. With its diagnostic robustness and predictive power for survival, PENK constitutes a promising biomarker in critical care settings including sepsis. © The Korean Society for Laboratory Medicine

  9. Haplotypes composed of minor frequency single nucleotide polymorphisms of the TNF gene protect from progression into sepsis: A study using the new sepsis classification.

    PubMed

    Retsas, Theodoros; Huse, Klaus; Lazaridis, Lazaros-Dimitrios; Karampela, Niki; Bauer, Michael; Platzer, Matthias; Kolonia, Virginia; Papageorgiou, Eirini; Giamarellos-Bourboulis, Evangelos J; Dimopoulos, George

    2018-02-01

    Several articles have provided conflicting results regarding the role of single nucleotide polymorphisms (SNPs) in the promoter region of the TNF gene in susceptibility to sepsis. Former articles have been based on previous definitions of sepsis. This study investigated the influence of TNF haplotypes on the development of sepsis using the new Sepsis-3 definitions. DNA was isolated from patients suffering from infection and systemic inflammatory response syndrome. Haplotyping was performed for six SNPs of TNF. The serum levels of tumour necrosis factor alpha (TNF-α) of these patients were measured using an enzyme immunosorbent assay. Patients were classified into infection and sepsis categories using the Sepsis-3 definitions. Associations between the TNF haplotypes and the clinical characteristics and serum TNF-α levels of the patients were examined. The most common TNF haplotype h1 was composed of major alleles of the studied SNPs. Carriage of haplotypes composed of minor frequency alleles was associated with a lower risk of developing sepsis (odds ratio 0.41, 95% confidence interval 0.19-0.88, p=0.022), but this did not affect the 28-day outcome. Serum TNF-α levels were significantly higher among patients homozygous for h1 haplotypes who developed sepsis compared to infection (p=0.032); a similar result was not observed for patients carrying other haplotypes. Haplotypes containing minor frequency SNP alleles of TNF protect against the development of sepsis without affecting the outcome. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  10. Pediatric Acute Lung Injury Epidemiology and Natural History study: Incidence and outcome of the acute respiratory distress syndrome in children.

    PubMed

    López-Fernández, Yolanda; Azagra, Amelia Martínez-de; de la Oliva, Pedro; Modesto, Vicent; Sánchez, Juan I; Parrilla, Julio; Arroyo, María José; Reyes, Susana Beatriz; Pons-Ódena, Martí; López-Herce, Jesús; Fernández, Rosa Lidia; Kacmarek, Robert M; Villar, Jesús

    2012-12-01

    The incidence and outcome of the acute respiratory distress syndrome in children are not well-known, especially under current ventilatory practices. The goal of this study was to determine the incidence, etiology, and outcome of acute respiratory distress syndrome in the pediatric population in the setting of lung protective ventilation. A 1-yr, prospective, multicenter, observational study in 12 geographical areas of Spain (serving a population of 3.77 million ≤ 15 yrs of age) covered by 21 pediatric intensive care units. All consecutive pediatric patients receiving invasive mechanical ventilation and meeting American-European Consensus Criteria for acute respiratory distress syndrome. None. Data on ventilatory management, gas exchange, hemodynamics, and organ dysfunction were collected. A total of 146 mechanically ventilated patients fulfilled the acute respiratory distress syndrome definition, representing a incidence of 3.9/100,000 population ≤ 15 yrs of age/yr. Pneumonia and sepsis were the most common causes of acute respiratory distress syndrome. At the time of meeting acute respiratory distress syndrome criteria, mean PaO2/FIO2 was 99 mm Hg ± 41 mm Hg, mean tidal volume was 7.6 mL/kg ± 1.8 mL/kg predicted body weight, mean plateau pressure was 27 cm H2O ± 6 cm H2O, and mean positive end-expiratory pressure was 8.9 cm ± 2.9 cm H2O. Overall pediatric intensive care unit and hospital mortality were 26% (95% confidence interval 19.6-33.7) and 27.4% (95% confidence interval 20.8-35.1), respectively. At 24 hrs, after the assessment of oxygenation under standard ventilatory settings, 118 (80.8%) patients continued to meet acute respiratory distress syndrome criteria (PaO2/FIO2 104 mm Hg ± 36 mm Hg; pediatric intensive care units mortality 30.5%), whereas 28 patients (19.2%) had a PaO2/FIO2 >200 mm Hg (pediatric intensive care units mortality 7.1%) (p = .014). This is the largest study to estimate prospectively the pediatric population-based acute

  11. Implementation of an Inpatient Pediatric Sepsis Identification Pathway.

    PubMed

    Bradshaw, Chanda; Goodman, Ilyssa; Rosenberg, Rebecca; Bandera, Christopher; Fierman, Arthur; Rudy, Bret

    2016-03-01

    Early identification and treatment of severe sepsis and septic shock improves outcomes. We sought to identify and evaluate children with possible sepsis on a pediatric medical/surgical unit through successful implementation of a sepsis identification pathway. The sepsis identification pathway, a vital sign screen and subsequent physician evaluation, was implemented in October 2013. Quality improvement interventions were used to improve physician and nursing adherence with the pathway. We reviewed charts of patients with positive screens on a monthly basis to assess for nursing recognition/physician notification, physician evaluation for sepsis, and subsequent physician diagnosis of sepsis and severe sepsis/septic shock. Adherence data were analyzed on a run chart and statistical process control p-chart. Nursing and physician pathway adherence of >80% was achieved over a 6-month period and sustained for the following 6 months. The direction of improvements met standard criteria for special causes. Over a 1-year period, there were 963 admissions to the unit. Positive screens occurred in 161 (16.7%) of these admissions and 38 (23.5%) of these had a physician diagnosis of sepsis, severe sepsis, or septic shock. One patient with neutropenia and septic shock had a negative sepsis screen due to lack of initial fever. Using quality improvement methodology, we successfully implemented a sepsis identification pathway on our pediatric unit. The pathway provided a standardized process to identify and evaluate children with possible sepsis requiring timely evaluation and treatment. Copyright © 2016 by the American Academy of Pediatrics.

  12. C-Reactive Protein and Hemogram Parameters for the Non-Sepsis Systemic Inflammatory Response Syndrome and Sepsis: What Do They Mean?

    PubMed

    Gucyetmez, Bulent; Atalan, Hakan K

    2016-01-01

    Sepsis is one of the most common reasons of increased mortality and morbidity in the intensive care unit. The changes in CRP levels and hemogram parameters and their combinations may help to distinguish sepsis from non-sepsis SIRS. The aim of this study is to investigate the CRP and hemogram parameters as an indicator of sepsis. A total of 2777 patients admitted to the ICU of two centers between 2006-2013 were evaluated retrospectively. The patients were diagnosed as SIRS (-), non-sepsis SIRS and sepsis. The patients who were under 18 years old, re-admitted, diagnosed with hematological disease, on corticosteroid and immunosuppressive therapy, SIRS (-), culture negative, undocumented laboratory values and outcomes were excluded. 1257 patients were divided into 2 groups as non-sepsis SIRS and sepsis. The patients' demographic data, CRP levels, hemogram parameters, length of ICU stay and mortality were recorded. 1257 patients were categorized as non-sepsis SIRS (816, 64.9%) and sepsis (441, 35.1%). In the multivariate analysis, the likelihood of sepsis was increased 3.2 (2.2-4.6), 1.7 (1.2-2.4), 1.6 (1.2-2.1), 2.3 (1.4-3.8), 1.5 (1.1-2.1) times by the APACHE II≥13, SOFA score≥4, CRP≥4.0, LymC<0.45 and PLTC<150 respectively (p<0.001 p = 0.007 p = 0.004 p<0.001 p = 0.027). The likelihood of sepsis was increased 18.1 (8.4-38.7) times by the combination of CRP≥4.0, lymC<0.45 and PLTC<150 (P<0.001). While WBCC, NeuC, Neu%, NLCR and EoC are far from being the indicators to distinguish sepsis from non-sepsis SIRS, the combinations of CRP, LymC and PLTC can be used to determine the likelihood of sepsis.

  13. Pharmacist involvement in a multidisciplinary initiative to reduce sepsis-related mortality.

    PubMed

    Beardsley, James R; Jones, Catherine M; Williamson, John; Chou, Jason; Currie-Coyoy, Margaret; Jackson, Teresa

    2016-02-01

    Pharmacy department contributions to a medical center's broad initiative to improve sepsis care outcomes are described. Timely and appropriate antimicrobial therapy is a key factor in optimizing treatment outcomes in patients with severe sepsis or septic shock. The inpatient pharmacy at Wake Forest Baptist Health implemented standardized processes to reduce order turnaround time and facilitate prompt antibiotic administration as part of the hospital's multidisciplinary "Code Sepsis" initiative. The program includes (1) nurse-conducted screening for sepsis using a standard assessment instrument, (2) pager alerts notifying rapid-response, pharmacy, and other personnel of cases of suspected sepsis, (3) activation of an electronic order set including guideline-based antibiotic therapy recommendations based on local pathogen patterns, and (4) a protocol allowing pharmacists to select an antibiotic regimen if providers are busy with other patient care duties. Assessments conducted during and after implementation of the Code Sepsis initiative showed improvements in key program metrics. The mean ± S.D. time from receipt of a Code Sepsis page to antibiotic delivery was reduced to 14.1 ± 13.7 minutes, the mean time from identification of suspected sepsis to antibiotic administration was reduced to 31 minutes in the hospital's intensive care units and to 51 minutes in non-critical care units, and the institution's performance on a widely used measure of sepsis-related mortality improved dramatically. Implementation of the Code Sepsis initiative was associated with reductions in order turnaround time, time to antibiotic administration, and sepsis-related mortality. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  14. Multicentric Standardized Flow Cytometry Routine Assessment of Patients With Sepsis to Predict Clinical Worsening.

    PubMed

    Daix, Thomas; Guerin, Estelle; Tavernier, Elsa; Mercier, Emmanuelle; Gissot, Valérie; Hérault, Olivier; Mira, Jean-Paul; Dumas, Florence; Chapuis, Nicolas; Guitton, Christophe; Béné, Marie C; Quenot, Jean-Pierre; Tissier, Cindy; Guy, Julien; Piton, Gaël; Roggy, Anne; Muller, Grégoire; Legac, Éric; de Prost, Nicolas; Khellaf, Mehdi; Wagner-Ballon, Orianne; Coudroy, Rémi; Dindinaud, Elodie; Uhel, Fabrice; Roussel, Mikaël; Lafon, Thomas; Jeannet, Robin; Vargas, Frédéric; Fleureau, Catherine; Roux, Mickaël; Allou, Kaoutar; Vignon, Philippe; Feuillard, Jean; François, Bruno

    2018-04-26

    In this study, we primarily sought to assess the ability of flow cytometry to predict early clinical deterioration and overall survival in patients with sepsis admitted in the ED and ICU. Patients admitted for community-acquired acute sepsis from 11 hospital centers were eligible. Early (day 7) and late (day 28) deaths were notified. Levels of CD64 pos granulocytes, CD16 pos monocytes, CD16 dim immature granulocytes (IGs), and T and B lymphocytes were assessed by flow cytometry using an identical, cross-validated, robust, and simple consensus standardized protocol in each center. Among 1,062 patients screened, 781 patients with confirmed sepsis were studied (age, 67 ± 48 years; Simplified Acute Physiology Score II, 36 ± 17; Sequential Organ Failure Assessment, 5 ± 4). Patients were divided into three groups (sepsis, severe sepsis, and septic shock) on day 0 and on day 2. On day 0, patients with sepsis exhibited increased levels of CD64 pos granulocytes, CD16 pos monocytes, and IGs with T-cell lymphopenia. Clinical severity was associated with higher percentages of IGs and deeper T-cell lymphopenia. IG percentages tended to be higher in patients whose clinical status worsened on day 2 (35.1 ± 35.6 vs 43.5 ± 35.2, P = .07). Increased IG percentages were also related to occurrence of new organ failures on day 2. Increased IG percentages, especially when associated with T-cell lymphopenia, were independently associated with early (P < .01) and late (P < .01) death. Increased circulating IGs at the acute phase of sepsis are linked to clinical worsening, especially when associated with T-cell lymphopenia. Early flow cytometry could help clinicians to target patients at high risk of clinical deterioration. ClinicalTrials.gov; No.: NCT01995448; URL: www.clinicaltrials.gov. Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  15. Automated Detection of Sepsis Using Electronic Medical Record Data: A Systematic Review.

    PubMed

    Despins, Laurel A

    Severe sepsis and septic shock are global issues with high mortality rates. Early recognition and intervention are essential to optimize patient outcomes. Automated detection using electronic medical record (EMR) data can assist this process. This review describes automated sepsis detection using EMR data. PubMed retrieved publications between January 1, 2005 and January 31, 2015. Thirteen studies met study criteria: described an automated detection approach with the potential to detect sepsis or sepsis-related deterioration in real or near-real time; focused on emergency department and hospitalized neonatal, pediatric, or adult patients; and provided performance measures or results indicating the impact of automated sepsis detection. Detection algorithms incorporated systemic inflammatory response and organ dysfunction criteria. Systems in nine studies generated study or care team alerts. Care team alerts did not consistently lead to earlier interventions. Earlier interventions did not consistently translate to improved patient outcomes. Performance measures were inconsistent. Automated sepsis detection is potentially a means to enable early sepsis-related therapy but current performance variability highlights the need for further research.

  16. [Relationship between highly sensitive cardiac troponin T and sepsis and outcome in critically ill patients].

    PubMed

    Wang, T T; Jiang, L

    2017-10-01

    Objective: To investigate the prognostic value of highly sensitive cardiac Troponin T (hs-cTn T) for sepsis in critically ill patients. Methods: Patients estimated to stay in the ICU of Fuxing Hospital for more than 24h were enrolled at from March 2014 to December 2014. Serum hs-cTn T was tested within two hours. Univariate and multivariate linear regression analyses were used to determine the association of variables with the hs-cTn T. Multivariable logistic regression analysis was used to evaluate the risk factors of 28-day mortality. Results: A total of 125 patients were finally enrolled including 68 patients with sepsis and 57 without. The levels of hs-cTn T in sepsis and non-sepsis groups were significantly different[52.0(32.5, 87.5) ng/L vs 14.0(6.5, 29.0) ng/L respectively, P <0.001]. In sepsis group, hs-cTn T among common sepsis, severe sepsis and septic shock were similar. Hs-cTn T was significantly higher in non-survivors than survivors [27(13, 52)ng/L vs 44.5(28.8, 83.5)ng/L, P <0.001]. Age, sepsis, serum creatinine were independent risk factors affecting hs-cTn T by multivariate linear regression analyses. But hs-cTn T was not a risk factor for death. Conclusion: Patients with sepsis had higher serum hs-cTn T than those without sepsis. but it was not found to be associated with the severity of sepsis.

  17. A rational approach to fluid therapy in sepsis.

    PubMed

    Marik, P; Bellomo, R

    2016-03-01

    Aggressive fluid resuscitation to achieve a central venous pressure (CVP) greater than 8 mm Hg has been promoted as the standard of care, in the management of patients with severe sepsis and septic shock. However recent clinical trials have demonstrated that this approach does not improve the outcome of patients with severe sepsis and septic shock. Pathophysiologically, sepsis is characterized by vasoplegia with loss of arterial tone, venodilation with sequestration of blood in the unstressed blood compartment and changes in ventricular function with reduced compliance and reduced preload responsiveness. These data suggest that sepsis is primarily not a volume-depleted state and recent evidence demonstrates that most septic patients are poorly responsive to fluids. Furthermore, almost all of the administered fluid is sequestered in the tissues, resulting in severe oedema in vital organs and, thereby, increasing the risk of organ dysfunction. These data suggest that a physiologic, haemodynamically guided conservative approach to fluid therapy in patients with sepsis would be prudent and would likely reduce the morbidity and improve the outcome of this disease. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. The Effect of Sepsis on the Erythrocyte

    PubMed Central

    Bateman, Ryon M.; Sharpe, Michael D.; Singer, Mervyn; Ellis, Christopher G.

    2017-01-01

    Sepsis induces a wide range of effects on the red blood cell (RBC). Some of the effects including altered metabolism and decreased 2,3-bisphosphoglycerate are preventable with appropriate treatment, whereas others, including decreased erythrocyte deformability and redistribution of membrane phospholipids, appear to be permanent, and factors in RBC clearance. Here, we review the effects of sepsis on the erythrocyte, including changes in RBC volume, metabolism and hemoglobin’s affinity for oxygen, morphology, RBC deformability (an early indicator of sepsis), antioxidant status, intracellular Ca2+ homeostasis, membrane proteins, membrane phospholipid redistribution, clearance and RBC O2-dependent adenosine triphosphate efflux (an RBC hypoxia signaling mechanism involved in microvascular autoregulation). We also consider the causes of these effects by host mediated oxidant stress and bacterial virulence factors. Additionally, we consider the altered erythrocyte microenvironment due to sepsis induced microvascular dysregulation and speculate on the possible effects of RBC autoxidation. In future, a better understanding of the mechanisms involved in sepsis induced erythrocyte pathophysiology and clearance may guide improved sepsis treatments. Evidence that small molecule antioxidants protect the erythrocyte from loss of deformability, and more importantly improve septic patient outcome suggest further research in this area is warranted. While not generally considered a critical factor in sepsis, erythrocytes (and especially a smaller subpopulation) appear to be highly susceptible to sepsis induced injury, provide an early warning signal of sepsis and are a factor in the microvascular dysfunction that has been associated with organ dysfunction. PMID:28885563

  19. The Effect of Sepsis on the Erythrocyte.

    PubMed

    Bateman, Ryon M; Sharpe, Michael D; Singer, Mervyn; Ellis, Christopher G

    2017-09-08

    Sepsis induces a wide range of effects on the red blood cell (RBC). Some of the effects including altered metabolism and decreased 2,3-bisphosphoglycerate are preventable with appropriate treatment, whereas others, including decreased erythrocyte deformability and redistribution of membrane phospholipids, appear to be permanent, and factors in RBC clearance. Here, we review the effects of sepsis on the erythrocyte, including changes in RBC volume, metabolism and hemoglobin's affinity for oxygen, morphology, RBC deformability (an early indicator of sepsis), antioxidant status, intracellular Ca 2+ homeostasis, membrane proteins, membrane phospholipid redistribution, clearance and RBC O₂-dependent adenosine triphosphate efflux (an RBC hypoxia signaling mechanism involved in microvascular autoregulation). We also consider the causes of these effects by host mediated oxidant stress and bacterial virulence factors. Additionally, we consider the altered erythrocyte microenvironment due to sepsis induced microvascular dysregulation and speculate on the possible effects of RBC autoxidation. In future, a better understanding of the mechanisms involved in sepsis induced erythrocyte pathophysiology and clearance may guide improved sepsis treatments. Evidence that small molecule antioxidants protect the erythrocyte from loss of deformability, and more importantly improve septic patient outcome suggest further research in this area is warranted. While not generally considered a critical factor in sepsis, erythrocytes (and especially a smaller subpopulation) appear to be highly susceptible to sepsis induced injury, provide an early warning signal of sepsis and are a factor in the microvascular dysfunction that has been associated with organ dysfunction.

  20. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012.

    PubMed

    Dellinger, R P; Levy, Mitchell M; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M; Sevransky, Jonathan E; Sprung, Charles L; Douglas, Ivor S; Jaeschke, Roman; Osborn, Tiffany M; Nunnally, Mark E; Townsend, Sean R; Reinhart, Konrad; Kleinpell, Ruth M; Angus, Derek C; Deutschman, Clifford S; Machado, Flavia R; Rubenfeld, Gordon D; Webb, Steven; Beale, Richard J; Vincent, Jean-Louis; Moreno, Rui

    2013-02-01

    respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5-10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C). Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.

  1. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.

    PubMed

    Dellinger, R Phillip; Levy, Mitchell M; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M; Sevransky, Jonathan E; Sprung, Charles L; Douglas, Ivor S; Jaeschke, Roman; Osborn, Tiffany M; Nunnally, Mark E; Townsend, Sean R; Reinhart, Konrad; Kleinpell, Ruth M; Angus, Derek C; Deutschman, Clifford S; Machado, Flavia R; Rubenfeld, Gordon D; Webb, Steven A; Beale, Richard J; Vincent, Jean-Louis; Moreno, Rui

    2013-02-01

    continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5 to 10 mins (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C). Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.

  2. Shenfu injection for improving cellular immunity and clinical outcome in patients with sepsis or septic shock.

    PubMed

    Zhang, Ning; Liu, Jianhua; Qiu, Zeliang; Ye, Yiping; Zhang, Jian; Lou, Tianzheng

    2017-01-01

    To assess the efficacy of Shenfu injection (SFI) for enhancing cellular immunity and improving the clinical outcomes of patients with septic shock. Patients with sepsis were randomly assigned to receive either SFI at a dose of 100mL every 24hours for 7 consecutive days or a placebo in addition to conventional therapy. The immunologic parameters were collected on days 1, 3, and 7 after the above treatments, and the clinical outcomes were updated for 28days. Of these160 patients, 3 were excluded from the analysis due to protocol violation and withdrawal of consent; thus, 157 completed the study (78 in the SFI group and 79 in the placebo group). We found that SFI increased both CD4 + and CD8 + T cells in peripheral blood and up-regulated HLA-DR expression in monocytes (P<.05). Furthermore, SFI was also found to restore ex vivo monocytic tumor necrosis factor α and interleukin 6 proinflammatory cytokine release in response to the endotoxin (P<.05). Importantly, the SFI group showed better clinical outcomes than did the placebo group in terms of the duration of vasopressor use (P=.008), Acute Physiology and Chronic Health Evaluation II score (P=.034), Marshall score (P=.01), and length of intensive care unit stay (10.5±3.2 vs 12.2±2.8days; P=.012). However, the 28-day mortality rate was not significantly different between the SFI (20.5%; 16/78) and placebo groups (27.8%; -22/79; P=.28). These findings suggest that SFI can enhance the cellular immunity of patients with septic shock and could be a promising adjunctive treatment for patients with septic shock. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. The Epidemiology of Hospital Death Following Pediatric Severe Sepsis: When, Why, and How Children With Sepsis Die.

    PubMed

    Weiss, Scott L; Balamuth, Fran; Hensley, Josey; Fitzgerald, Julie C; Bush, Jenny; Nadkarni, Vinay M; Thomas, Neal J; Hall, Mark; Muszynski, Jennifer

    2017-09-01

    The epidemiology of in-hospital death after pediatric sepsis has not been well characterized. We investigated the timing, cause, mode, and attribution of death in children with severe sepsis, hypothesizing that refractory shock leading to early death is rare in the current era. Retrospective observational study. Emergency departments and ICUs at two academic children's hospitals. Seventy-nine patients less than 18 years old treated for severe sepsis/septic shock in 2012-2013 who died prior to hospital discharge. None. Time to death from sepsis recognition, cause and mode of death, and attribution of death to sepsis were determined from medical records. Organ dysfunction was assessed via daily Pediatric Logistic Organ Dysfunction-2 scores for 7 days preceding death with an increase greater than or equal to 5 defined as worsening organ dysfunction. The median time to death was 8 days (interquartile range, 1-12 d) with 25%, 35%, and 49% of cumulative deaths within 1, 3, and 7 days of sepsis recognition, respectively. The most common cause of death was refractory shock (34%), then multiple organ dysfunction syndrome after shock recovery (27%), neurologic injury (19%), single-organ respiratory failure (9%), and nonseptic comorbidity (6%). Early deaths (≤ 3 d) were mostly due to refractory shock in young, previously healthy patients while multiple organ dysfunction syndrome predominated after 3 days. Mode of death was withdrawal in 72%, unsuccessful cardiopulmonary resuscitation in 22%, and irreversible loss of neurologic function in 6%. Ninety percent of deaths were attributable to acute or chronic manifestations of sepsis. Only 23% had a rise in Pediatric Logistic Organ Dysfunction-2 that indicated worsening organ dysfunction. Refractory shock remains a common cause of death in pediatric sepsis, especially for early deaths. Later deaths were mostly attributable to multiple organ dysfunction syndrome, neurologic, and respiratory failure after life-sustaining therapies

  4. THE EPITHELIUM AS A TARGET IN SEPSIS.

    PubMed

    Chawla, Lakhmir S; Fink, Mitchell; Goldstein, Stuart L; Opal, Steven; Gómez, Alonso; Murray, Patrick; Gómez, Hernando; Kellum, John A

    2016-03-01

    Organ dysfunction induced by sepsis has been consistently associated with worse outcome and death. Regardless of the organ compromised, epithelial dysfunction is present throughout the body, affecting those organs that contain epithelia like the skin, lungs, liver, gut, and kidneys. Despite their obvious differences, sepsis seems to alter common features of all epithelia, such as barrier function and vectorial ion transport. Such alterations in the lung, the gut, and the kidney have direct implications that may explain the profound organ functional impairments in the absence of overt cell death. Epithelial injury in this context is not only an explanatory real pathophysiologic event, but also represents a source of biomarkers that have been explored to identify organ compromise earlier, predict outcome, and even to test novel therapeutic interventions such as blood purification. However, this remains largely experimental, and despite promising results, work is still required to better understand the response of the epithelial cells to sepsis, to define their role in adaptation to insults, to comprehend the interorgan cross-talk that occurs in these circumstances, and to exploit these aspects in pursuit of targeted therapies like blood purification, which may improve outcome for these patients in the future.

  5. Impact of an emergency department electronic sepsis surveillance system on patient mortality and length of stay.

    PubMed

    Austrian, Jonathan S; Jamin, Catherine T; Doty, Glenn R; Blecker, Saul

    2018-05-01

    The purpose of this study was to determine whether an electronic health record-based sepsis alert system could improve quality of care and clinical outcomes for patients with sepsis. We performed a patient-level interrupted time series study of emergency department patients with severe sepsis or septic shock between January 2013 and April 2015. The intervention, introduced in February 2014, was a system of interruptive sepsis alerts triggered by abnormal vital signs or laboratory results. Primary outcomes were length of stay (LOS) and in-hospital mortality; other outcomes included time to first lactate and blood cultures prior to antibiotics. We also assessed sensitivity, positive predictive value (PPV), and clinician response to the alerts. Mean LOS for patients with sepsis decreased from 10.1 to 8.6 days (P < .001) following alert introduction. In adjusted time series analysis, the intervention was associated with a decreased LOS of 16% (95% CI, 5%-25%; P = .007, with significance of α = 0.006) and no change thereafter (0%; 95% CI, -2%, 2%). The sepsis alert system had no effect on mortality or other clinical or process measures. The intervention had a sensitivity of 80.4% and a PPV of 14.6%. Alerting based on simple laboratory and vital sign criteria was insufficient to improve sepsis outcomes. Alert fatigue due to the low PPV is likely the primary contributor to these results. A more sophisticated algorithm for sepsis identification is needed to improve outcomes.

  6. Antioxidants that protect mitochondria reduce interleukin-6 and oxidative stress, improve mitochondrial function, and reduce biochemical markers of organ dysfunction in a rat model of acute sepsis

    PubMed Central

    Lowes, D. A.; Webster, N. R.; Murphy, M. P.; Galley, H. F.

    2013-01-01

    Background Sepsis-induced organ failure is the major cause of death in critical care units, and is characterized by a massive dysregulated inflammatory response and oxidative stress. We investigated the effects of treatment with antioxidants that protect mitochondria (MitoQ, MitoE, or melatonin) in a rat model of lipopolysaccharide (LPS) plus peptidoglycan (PepG)-induced acute sepsis, characterized by inflammation, mitochondrial dysfunction and early organ damage. Methods Anaesthetized and ventilated rats received an i.v. bolus of LPS and PepG followed by an i.v. infusion of MitoQ, MitoE, melatonin, or saline for 5 h. Organs and blood were then removed for determination of mitochondrial and organ function, oxidative stress, and key cytokines. Results MitoQ, MitoE, or melatonin had broadly similar protective effects with improved mitochondrial respiration (P<0.002), reduced oxidative stress (P<0.02), and decreased interleukin-6 levels (P=0.0001). Compared with control rats, antioxidant-treated rats had lower levels of biochemical markers of organ dysfunction, including plasma alanine amino-transferase activity (P=0.02) and creatinine concentrations (P<0.0001). Conclusions Antioxidants that act preferentially in mitochondria reduce mitochondrial damage and organ dysfunction and decrease inflammatory responses in a rat model of acute sepsis. PMID:23381720

  7. Implications of the new international sepsis guidelines for nursing care.

    PubMed

    Kleinpell, Ruth; Aitken, Leanne; Schorr, Christa A

    2013-05-01

    Sepsis is a serious worldwide health care condition that is associated with high mortality rates, despite improvements in the ability to manage infection. New guidelines for the management of sepsis were recently released that advocate for implementation of care based on evidence-based practice for both adult and pediatric patients. Critical care nurses are directly involved in the assessment of patients at risk for developing sepsis and in the treatment of patients with sepsis and can, therefore, affect outcomes for critically ill patients. Nurses' knowledge of the recommendations in the new guidelines can help to ensure that patients with sepsis receive therapies that are based on the latest scientific evidence. This article presents an overview of new evidence-based recommendations for the treatment of adult patients with sepsis, highlighting the role of critical care nurses.

  8. Superantigens Are Critical for Staphylococcus aureus Infective Endocarditis, Sepsis, and Acute Kidney Injury

    PubMed Central

    Salgado-Pabón, Wilmara; Breshears, Laura; Spaulding, Adam R.; Merriman, Joseph A.; Stach, Christopher S.; Horswill, Alexander R.; Peterson, Marnie L.; Schlievert, Patrick M.

    2013-01-01

    ABSTRACT Infective endocarditis and kidney infections are serious complications of Staphylococcus aureus sepsis. We investigated the role of superantigens (SAgs) in the development of lethal sepsis, infective endocarditis, and kidney infections. SAgs cause toxic shock syndrome, but it is unclear if SAgs contribute to infective endocarditis and kidney infections secondary to sepsis. We show in the methicillin-resistant S. aureus strain MW2 that lethal sepsis, infective endocarditis, and kidney infections in rabbits are critically dependent on high-level SAgs. In contrast, the isogenic strain lacking staphylococcal enterotoxin C (SEC), the major SAg in this strain, is attenuated in virulence, while complementation restores disease production. SAgs’ role in infective endocarditis appears to be both superantigenicity and direct endothelial cell stimulation. Maintenance of elevated blood pressure by fluid therapy significantly protects from infective endocarditis, possibly through preventing bacterial accumulation on valves and increased SAg elimination. These data should facilitate better methods to manage these serious illnesses. PMID:23963178

  9. The recognition and management of sepsis and septic shock: a guide for non-intensivists.

    PubMed

    Keeley, Alexander; Hine, Paul; Nsutebu, Emmanuel

    2017-10-01

    Sepsis is common, often fatal and requires rapid interventions to improve outcomes. While the optimal management of sepsis in the intensive care setting is the focus of extensive research interest, the mainstay of the recognition and initial management of sepsis will occur outside the intensive care setting. Therefore, it is key that institutions and clinicians remain well informed of the current updates in sepsis management and continue to use them to deliver appropriate and timely interventions to enhance patient survival. This review discusses the latest updates in sepsis care including the new consensus definition of sepsis, the outcome of the proCESS, ProMISe and ARISE trials of early goal directed therapy (EGDT), and the most recent guidelines from the Surviving Sepsis Campaign. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. Immunoparalysis: Clinical and immunological associations in SIRS and severe sepsis patients.

    PubMed

    Papadopoulos, Panagiotis; Pistiki, Aikaterini; Theodorakopoulou, Maria; Christodoulopoulou, Theodora; Damoraki, Georgia; Goukos, Dimitris; Briassouli, Efrossini; Dimopoulou, Ioanna; Armaganidis, Apostolos; Nanas, Serafim; Briassoulis, George; Tsiodras, Sotirios

    2017-04-01

    This study was designed to identify changes in the monocytic membrane marker HLA-DR and heat shock proteins (HSPs) in relation to T-regulatory cells (T-regs) and other immunological marker changes in patients with systemic inflammatory response syndrome (SIRS) or sepsis/septic shock. Healthy volunteers, intensive care unit (ICU) patients with SIRS due to head injury and ICU patients with severe sepsis/septic shock were enrolled in the current study. Determination of CD14+/HLA-DR+ cells, intracellular heat-shock proteins and other immunological parameters were performed by flow cytometry and RT-PCR techniques as appropriate. Univariate and multivariate analysis examined associations of CD14/HLA-DR, HSPs, T-regs and suppressor of cytokine signalling (SOCS) proteins with SIRS, sepsis and outcome. Fifty patients (37 with severe sepsis and 13 with SIRS) were enrolled, together with 20 healthy volunteers used as a control group. Compared to healthy individuals, patients with SIRS and severe sepsis showed progressive decline of their CD14/HLA-DR expression (0% to 7.7% to 50% within each study subpopulation, p<0.001). Mean fluorescent intensity (MFI) levels of HSP70 and HSP90 on monocytes and polymorphonuclear cells were significantly higher in SIRS patients compared to controls and fell significantly in severe sepsis/septic shock patients (p<0.05 for all comparisons). There was no statistically significant difference between subgroups for levels of T-regulatory cells or relative copies of Suppressor of Cytokine Signalling 3 (SOCS3) proteins. In univariate models percent of CD14/HLA-DR was associated with mortality (OR: 1.8 95%CI 1.02-3.2, p=0.05), while in multivariate models after adjusting for CD14/HLA-DR only younger age and lower Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were associated with increased chances of survival (beta -0.05, OR 0.9, 95% CI 0.9-0.99, p=0.038 for age and beta -0.11, OR 0.89, 95% CI 0.8-0.99, p=0.037 for APACHE II

  11. SPECTRUM OF DISEASE AND OUTCOME OF PRIMARY AMPUTATION FOR DIABETIC FOOT SEPSIS.

    PubMed

    Cheddie, S; Manneh, C; Zulu, H

    2017-09-01

    Guillotine amputation for diabetic foot sepsis followed by an elective refashioning of the stump is regarded as standard practice. Primary amputation is associated with higher reamputation rates. A prospective cohort study of 85 patients who underwent surgery for diabetic foot sepsis from 2014 to 2016 at Madadeni Provincial Hospital, KwaZulu-Natal was done. Ethical approval was granted. The Wagner classification (Wag) was used to classify disease severity. Outcome measures included length of hospital stay, mortality and re-amputation rates. Of the 85 patients, females (n=45) accounted for 53% of admissions. The mean age was 61 years (range: 29 to 80 years). The majority of patients were African, n=75 (88%). Only 1 patient presented with diabetic ketoacidosis and 18 (21%) presented with renal failure. Most patients presented with advanced disease: [Wag 5, n=66 (78%); Wag 4, n=12 (14%); Wag 3, n=5 (6%); Wag 2, n=2 (2%)]. The levels of vascular occlusion included aortoiliac disease n=2 (2%), femoro-popliteal disease n=18 (21%), tibio-peroneal disease n=65 (76%). Radiographic features included normal findings n=60 (71%); gas gangrene n=11 (13%), osteitis n=8 (9%). The following amputations were done: AKA, n=29 (34%); BKA, n=39 (46%); TMA, n=8 (9%); Toe-ectomy, n=5 (6%) and Debridement, n=4 (5%). The re-amputation rate to above knee amputation was n= 3/39 (8%). All AKA stumps healed well. The overall in-hospital mortality was n=5 (6%) and mean length of hospital stay was 7.8 days ±3.83. The majority of patients presented with advanced disease requiring a major amputation. A definitive one stage primary amputation is a safe and effective procedure for diabetic foot sepsis and is associated with a low re-amputation rate, length of hospital stay and mortality. A guillotine amputation should be reserved for physiologically unstable patients.

  12. MiRNA-21 has effects to protect kidney injury induced by sepsis.

    PubMed

    Fu, Dian; Dong, Jie; Li, Ping; Tang, Chaopeng; Cheng, Wen; Xu, Zhenyu; Zhou, Wenquan; Ge, Jingping; Xia, Chen; Zhang, Zhengyu

    2017-10-01

    To investigate the miRNA-21 over-expression in the acute kidney injury induced by sepsis, we developed a sepsis induced in vitro model by lip polysaccharide (LPS) and in vovo model by cecal ligation and puncture (CLP) surgery. LPS or CLP surgery induced kidney cell apoptosis increasing. However, the kidney injury indexes of miRNA groups which were transfected with miRNA-21 were significantly suppressed. In further study, the relative proteins expressions were evaluated to explain the miRNA-21 mechanism to improve sepsis induced kidney cell apoptosis. The results were shown that miRNA-21 over-expression had effects to protect kidney cell apoptosis induced by sepsis via PTEN/PI3K/AKT signaling pathway. Copyright © 2017. Published by Elsevier Masson SAS.

  13. Hospital Variation in Risk-Adjusted Pediatric Sepsis Mortality.

    PubMed

    Ames, Stefanie G; Davis, Billie S; Angus, Derek C; Carcillo, Joseph A; Kahn, Jeremy M

    2018-05-01

    With continued attention to pediatric sepsis at both the clinical and policy levels, it is important to understand the quality of hospitals in terms of their pediatric sepsis mortality. We sought to develop a method to evaluate hospital pediatric sepsis performance using 30-day risk-adjusted mortality and to assess hospital variation in risk-adjusted sepsis mortality in a large state-wide sample. Retrospective cohort study using administrative claims data. Acute care hospitals in the state of Pennsylvania from 2011 to 2013. Patients between the ages of 0-19 years admitted to a hospital with sepsis defined using validated International Classification of Diseases, Ninth revision, Clinical Modification, diagnosis and procedure codes. None. During the study period, there were 9,013 pediatric sepsis encounters in 153 hospitals. After excluding repeat visits and hospitals with annual patient volumes too small to reliably assess hospital performance, there were 6,468 unique encounters in 24 hospitals. The overall unadjusted mortality rate was 6.5% (range across all hospitals: 1.5-11.9%). The median number of pediatric sepsis cases per hospital was 67 (range across all hospitals: 30-1,858). A hierarchical logistic regression model for 30-day risk-adjusted mortality controlling for patient age, gender, emergency department admission, infection source, presence of organ dysfunction at admission, and presence of chronic complex conditions showed good discrimination (C-statistic = 0.80) and calibration (slope and intercept of calibration plot: 0.95 and -0.01, respectively). The hospital-specific risk-adjusted mortality rates calculated from this model varied minimally, ranging from 6.0% to 7.4%. Although a risk-adjustment model for 30-day pediatric sepsis mortality had good performance characteristics, the use of risk-adjusted mortality rates as a hospital quality measure in pediatric sepsis is not useful due to the low volume of cases at most hospitals. Novel metrics to

  14. Diagnostic accuracy and effectiveness of automated electronic sepsis alert systems: A systematic review.

    PubMed

    Makam, Anil N; Nguyen, Oanh K; Auerbach, Andrew D

    2015-06-01

    Although timely treatment of sepsis improves outcomes, delays in administering evidence-based therapies are common. To determine whether automated real-time electronic sepsis alerts can: (1) accurately identify sepsis and (2) improve process measures and outcomes. We systematically searched MEDLINE, Embase, The Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature from database inception through June 27, 2014. Included studies that empirically evaluated 1 or both of the prespecified objectives. Two independent reviewers extracted data and assessed the risk of bias. Diagnostic accuracy of sepsis identification was measured by sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratio (LR). Effectiveness was assessed by changes in sepsis care process measures and outcomes. Of 1293 citations, 8 studies met inclusion criteria, 5 for the identification of sepsis (n = 35,423) and 5 for the effectiveness of sepsis alerts (n = 6894). Though definition of sepsis alert thresholds varied, most included systemic inflammatory response syndrome criteria ± evidence of shock. Diagnostic accuracy varied greatly, with PPV ranging from 20.5% to 53.8%, NPV 76.5% to 99.7%, LR+ 1.2 to 145.8, and LR- 0.06 to 0.86. There was modest evidence for improvement in process measures (ie, antibiotic escalation), but only among patients in non-critical care settings; there were no corresponding improvements in mortality or length of stay. Minimal data were reported on potential harms due to false positive alerts. Automated sepsis alerts derived from electronic health data may improve care processes but tend to have poor PPV and do not improve mortality or length of stay. © 2015 Society of Hospital Medicine.

  15. Diagnostic Accuracy and Effectiveness of Automated Electronic Sepsis Alert Systems: A Systematic Review

    PubMed Central

    Makam, Anil N.; Nguyen, Oanh K.; Auerbach, Andrew D.

    2015-01-01

    Background Although timely treatment of sepsis improves outcomes, delays in administering evidence-based therapies are common. Purpose To determine whether automated real-time electronic sepsis alerts can: 1) accurately identify sepsis, and 2) improve process measures and outcomes. Data Sources We systematically searched MEDLINE, Embase, The Cochrane Library, and CINAHL from database inception through June 27, 2014. Study Selection Included studies that empirically evaluated one or both of the prespecified objectives. Data Extraction Two independent reviewers extracted data and assessed the risk of bias. Diagnostic accuracy of sepsis identification was measured by sensitivity, specificity, positive (PPV) and negative predictive values (NPV) and likelihood ratios (LR). Effectiveness was assessed by changes in sepsis care process measures and outcomes. Data Synthesis Of 1,293 citations, 8 studies met inclusion criteria, 5 for the identification of sepsis (n=35,423) and 5 for the effectiveness of sepsis alerts (n=6,894). Though definition of sepsis alert thresholds varied, most included systemic inflammatory response syndrome criteria ± evidence of shock. Diagnostic accuracy varied greatly, with PPV ranging from 20.5-53.8%, NPV 76.5-99.7%; LR+ 1.2-145.8; and LR- 0.06-0.86. There was modest evidence for improvement in process measures (i.e., antibiotic escalation), but only among patients in non-critical care settings; there were no corresponding improvements in mortality or length of stay. Minimal data were reported on potential harms due to false positive alerts. Conclusions Automated sepsis alerts derived from electronic health data may improve care processes but tend to have poor positive predictive value and do not improve mortality or length of stay. PMID:25758641

  16. Evaluation of management and surgical outcomes in pregnancies complicated by acute cholecystitis.

    PubMed

    El-Messidi, Amira; Alsarraj, Ghazi; Czuzoj-Shulman, Nicholas; Mishkin, Daniel S; Abenhaim, Haim Arie

    2018-01-25

    To evaluate the management of pregnancies complicated by acute cholecystitis (AC) and determine whether pregnant women are more likely to have medical and surgical complications. We carried out a population-based matched cohort study using the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample from 2003 to 2011. Pregnant women with AC were age matched to non-pregnant women with AC on a 1:5 ratio. Management and outcomes were compared using descriptive analysis and conditional logistic regression. There were 11,835 pregnant women admitted with AC who were age matched to 59,175 non-pregnant women. As compared to non-pregnant women, women with AC were more commonly managed conservatively, odds ratio (OR) 6.1 (5.8-6.4). As compared to non-pregnant women, pregnant women with AC more commonly developed sepsis [OR 1.4 (1.0-1.9)], developed venous thromboembolism [OR 8.7 (4.3-17.8)] and had bowel obstruction [OR 1.3 (1.1-1.6)]. Among pregnant women with AC, surgical management was associated with a small but significant increased risk of septic shock and bile leak. AC, in the context of pregnancy, is associated with an increased risk of adverse outcomes. Although the literature favors early surgical intervention, pregnancies with AC appear to be more commonly managed conservatively with overall comparable outcomes to surgically managed AC. Conservative management may have a role in select pregnant women with AC.

  17. [Sepsis caused by Fusobacterium necrophorum (Lemierre syndrome): a rare complication of acute pharyngotonsilitis].

    PubMed

    Perović, Marta; Maretić, Tomislav; Begovac, Josip

    2006-12-01

    Lemierre syndrome is defined as an acute pharyngotonsillar infection that has spread into the lateral pharyngeal space causing thrombophlebitis of the internal jugular vein with consecutive metastatic emboli. The syndrome is most often caused by Fusobacterium (F.) necrophorum and usually involves young, previously healthy people. We present a healthy 20-year-old man who suddenly developed with high fever and sore throat followed by dyspnea, tachypnea and cough on the third day of illness. His condition worsened despite outpatient intramuscular penicillin therapy (1600 000 IU/day). He was admitted to Dr. Fran Mihaljević University Hospital for Infectious Diseases, Zagreb, on the sixth day of his illness with clinical signs of sepsis. Chest radiograph showed bilateral multiple infiltrates. F. necrophorum was isolated from blood culture. Swelling of the neck was also observed on the fourteenth day of illness, however, thrombophlebitis of the jugular vein was not diagnosed on ultrasound examination. The patient was treated with clindamycin for five weeks and recovered completely.

  18. Comparison of complication outcomes in acute pancreatitis following ERCP and conservative management at UKM medical centre: a six years retrospective study.

    PubMed

    Zamri, Z; Razman, J

    2012-11-01

    Acute pancreatitis is one of the common reasons for surgical admission. It is a potentially lethal disease that is increasing in its incidence. The most common causes of acute pancreatitis is from gallstones and alcohol. Other causes of acute pancreatitis include hypertriglyceridaemia, hyperparathyroidism, pancreatic malignancy, Endoscopic retrograde cholangiopancreatography (ERCP), trauma, infectious agents, drugs, autoimmunity, and hereditary. The treatment of acute pancreatitis is mainly supportive. The complication of ERCP in acute pancreatitis can be divided into local complication (pancreatic abscess, pseudocyst), systemic complications (renal failure, respiratory failure, cardiogenic shock) and biliary sepsis (acute cholangitis and acute cholecystitis). However, early ERCP and possible sphincterotomy should be kept in mind for patients with severe disease and biliary obstruction who are not improving with medical therapy. This study is done to compare the complication rate of ERCP and conservative management in acute pancreatitis for past 6 years in Pusat Perubatan UKM. The study is conducted retrospectively and the study population was from January 2003 until December 2008. About 100 patients involving 51 males and 49 females were included in this study. All of them were diagnosed acute pancreatitis based on the serum amylase level of 4 times than normal value detected from Chemistry Pathology record, Pathology Department, PPUKM. Then, data were collected from the patient's file which include the demographic data and patient clinical presentation, ultrasound finding, either patient went for ERCP within 72 hours or not. If ERCP not done within 72 hours of admission then it will considered that the patient is under conservative management. From 100 patients that involved in this study about 44% was Malay, 36 % was Chinese, 18 % was Indian and the other 2 % was from other origin. There were 28 cases (28%) where ERCP was done within 72 hours, and the other 72

  19. The Impact of Timing of Antibiotics on Outcomes in Severe Sepsis and Septic Shock: A Systematic Review and Meta-analysis

    PubMed Central

    Sterling, Sarah A.; Miller, W. Ryan; Pryor, Jason; Puskarich, Michael A.; Jones, Alan E.

    2015-01-01

    Objectives We sought to systematically review and meta-analyze the available data on the association between timing of antibiotic administration and mortality in severe sepsis and septic shock. Data Sources and Study Selection A comprehensive search was performed using a pre-defined protocol. Inclusion criteria: adult patients with severe sepsis or septic shock, reported time to antibiotic administration in relation to ED triage and/or shock recognition, and mortality. Exclusion criteria: immunosuppressed populations, review article, editorial, or non-human studies. Data Extraction Two reviewers screened abstracts with a third reviewer arbitrating. The effect of time to antibiotic administration on mortality was based on current guideline recommendations: 1) administration within 3 hours of ED triage; 2) administration within 1 hour of severe sepsis/septic shock recognition. Odds Ratios (OR) were calculated using a random effect model. The primary outcome was mortality. Data Synthesis 1123 publications were identified and 11 were included in the analysis. Among the 11 included studies, 16,178 patients were evaluable for antibiotic administration from ED triage. Patients who received antibiotics more than 3 hours after ED triage (< 3 hours reference), had a pooled OR for mortality of 1.16 (0.92 to 1.46, p = 0.21). A total of 11,017 patients were evaluable for antibiotic administration from severe sepsis/septic shock recognition. Patients who received antibiotics more than 1 hour after severe sepsis/shock recognition (< 1 hour reference) had a pooled OR for mortality of 1.46 (0.89 to 2.40, p = 0.13). There was no increased mortality in the pooled ORs for each hourly delay from <1 to >5 hours in antibiotic administration from severe sepsis/shock recognition. Conclusion Using the available pooled data we found no significant mortality benefit of administering antibiotics within 3 hours of ED triage or within 1 hour of shock recognition in severe sepsis and septic shock

  20. [Pharmaconutrition with parenteral selenium in sepsis].

    PubMed

    Langlois, P L; de Oliveira Figliolino, L F; Hardy, G; Manzanares, W

    2014-04-01

    Critical illness is characterized by oxidative stress which leads to multiple organ failure, and sepsis-related organ dysfunction remains the most common cause of death in the intensive care unit. Over the last 2 decades, different antioxidant therapies have been developed to improve outcomes in septic patients. According to recent evidence, selenium therapy should be considered the cornerstone of the antioxidant strategies. Selenium given as selenious acid or sodium selenite should be considered as a drug or pharmaconutrient with prooxidant and cytotoxic effects when a loading dose in intravenous bolus form is administered, particularly in the early stage of severe sepsis/septic shock. To date, several phase ii trials have demonstrated that selenium therapy may be able to decrease mortality, improve organ dysfunction and reduce infections in critically ill septic patients. The effect of selenium therapy in sepsis syndrome must be confirmed by large, well designed phase iii clinical trials. The purpose of this review is to discuss current evidence on selenium pharmaconutrition in sepsis syndrome. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  1. Assessment of Clinical Criteria for Sepsis

    PubMed Central

    Seymour, Christopher W.; Liu, Vincent X.; Iwashyna, Theodore J.; Brunkhorst, Frank M.; Rea, Thomas D.; Scherag, André; Rubenfeld, Gordon; Kahn, Jeremy M.; Shankar-Hari, Manu; Singer, Mervyn; Deutschman, Clifford S.; Escobar, Gabriel J.; Angus, Derek C.

    2016-01-01

    IMPORTANCE The Third International Consensus Definitions Task Force defined sepsis as “life-threatening organ dysfunction due to a dysregulated host response to infection.” The performance of clinical criteria for this sepsis definition is unknown. OBJECTIVE To evaluate the validity of clinical criteria to identify patients with suspected infection who are at risk of sepsis. DESIGN, SETTINGS, AND POPULATION Among 1.3 million electronic health record encounters from January 1, 2010, to December 31, 2012, at 12 hospitals in southwestern Pennsylvania, we identified those with suspected infection in whom to compare criteria. Confirmatory analyses were performed in 4 data sets of 706 399 out-of-hospital and hospital encounters at 165 US and non-US hospitals ranging from January 1, 2008, until December 31, 2013. EXPOSURES Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score, systemic inflammatory response syndrome (SIRS) criteria, Logistic Organ Dysfunction System (LODS) score, and a new model derived using multivariable logistic regression in a split sample, the quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA) score (range, 0–3 points, with 1 point each for systolic hypotension [≤100 mm Hg], tachypnea [≥22/min], or altered mentation). MAIN OUTCOMES AND MEASURES For construct validity, pairwise agreement was assessed. For predictive validity, the discrimination for outcomes (primary: in-hospital mortality; secondary: in-hospital mortality or intensive care unit [ICU] length of stay ≥3 days) more common in sepsis than uncomplicated infection was determined. Results were expressed as the fold change in outcome over deciles of baseline risk of death and area under the receiver operating characteristic curve (AUROC). RESULTS In the primary cohort, 148 907 encounters had suspected infection (n = 74 453 derivation; n = 74 454 validation), of whom 6347 (4%) died. Among ICU encounters in the validation cohort (n = 7932 with suspected

  2. Procalcitonin decrease over 72 hours in US critical care units predicts fatal outcome in sepsis patients

    PubMed Central

    2013-01-01

    Introduction Close monitoring and repeated risk assessment of sepsis patients in the intensive care unit (ICU) is important for decisions regarding care intensification or early discharge to the ward. We studied whether considering plasma kinetics of procalcitonin, a biomarker of systemic bacterial infection, over the first 72 critical care hours improved mortality prognostication of septic patients from two US settings. Methods This retrospective analysis included consecutively treated eligible adults with a diagnosis of sepsis from critical care units in two independent institutions in Clearwater, FL and Chicago, IL. Cohorts were used for derivation or validation to study the association between procalcitonin change over the first 72 critical care hours and mortality. Results ICU/in-hospital mortality rates were 29.2%/31.8% in the derivation cohort (n = 154) and 17.6%/29.4% in the validation cohort (n = 102). In logistic regression analysis of both cohorts, procalcitonin change was strongly associated with ICU and in-hospital mortality independent of clinical risk scores (Acute Physiology, Age and Chronic Health Evaluation IV or Simplified Acute Physiology Score II), with area under the curve (AUC) from 0.67 to 0.71. When procalcitonin decreased by at least 80%, the negative predictive value for ICU/in-hospital mortality was 90%/90% in the derivation cohort, and 91%/79% in the validation cohort. When procalcitonin showed no decrease or increased, the respective positive predictive values were 48%/48% and 36%/52%. Discussion In septic patients, procalcitonin kinetics over the first 72 critical care hours provide prognostic information beyond that available from clinical risk scores. If these observations are confirmed, procalcitonin monitoring may assist physician decision-making regarding care intensification or early transfer from the ICU to the floor. PMID:23787145

  3. Adjunctive treatment of abdominal catastrophes and sepsis with direct peritoneal resuscitation: indications for use in acute care surgery.

    PubMed

    Smith, Jason W; Neal Garrison, R; Matheson, Paul J; Harbrecht, Brian G; Benns, Matthew V; Franklin, Glen A; Miller, Keith R; Bozeman, Matthew C; David Richardson, J

    2014-09-01

    The success of damage-control surgery (DCS) for the treatment of trauma has led to its use in other surgical problems such as abdominal sepsis. Previous studies using direct peritoneal resuscitation (DPR) for the treatment of trauma have yielded promising results. We present the results of the application of this technique to patients experiencing abdominal sepsis. We enrolled 88 DCS patients during a 5 year-period (January 2008 to December 2012) into a propensity-matched study to evaluate the utility of using DPR in addition to standard resuscitation. DPR consisted of peritoneal lavage with 2.5% DELFLEX, and abdominal closure was standardized across both groups. Patients were matched using Acute Physiology and Chronic Health Evaluation II (APACHE II) variables. Univariate and multivariate analyses were performed. There were no differences between the control and experimental groups with regard to age, sex, ethnicity, or APACHE II at 24 hours. Indications for damage control included pancreatitis, perforated hollow viscous, bowel obstruction, and ischemic enterocolitis. Patients undergoing DPR had both a higher rate of (68% vs. 43%, p < 0.03) and a shorter time to definitive fascial closure (5.9 [3.2] days vs. 7.7 [4.1] days, p < 0.02). DPR patients had a decreased APACHE II and Sequential Organ Failure Assessment (SOFA) score compared with the controls at 48 hours. In addition, DPR patients had fewer abdominal complications compared with the controls (RR, 0.57; 95% confidence interval, 0.32-1.01; p = 0.038). Ventilator days and intensive care unit length of stay were both significantly reduced in the DPR group. The DPR group showed a lower overall mortality at 30 days (16% vs. 27%, p = 0.15). DPR reduces time to definitive abdominal closure, increases primary fascial closure, and reduces intra-abdominal complications following DCS. DPR may also attenuate progressive physiologic injury as demonstrated by a reduction in 48-hour intensive care unit severity scores. As

  4. An epidemiologic survey of pediatric sepsis in regional hospitals in China.

    PubMed

    Wang, Yuanyuan; Sun, Bo; Yue, Hongni; Lin, Xiaofei; Li, Bing; Yang, Xiaochun; Shan, Chunming; Fan, Yujin; Dong, Maotian; Zhang, Yixing; Lin, Wenlong; Zuo, Xiaofeng; Su, Ping; Heng, Yongbo; Xu, Jinzhong; Kissoon, Niranjan

    2014-11-01

    To determine the prevalence, treatment, and outcomes of sepsis at regional hospitals in Huai'an, Jiangsu, China. Prospective data registry using a descriptive clinical epidemiologic approach through a collaborative network. Pediatric departments in 11 regional city and county referral hospitals serving 843,000 children (exclusive of neonates). All admissions (n = 27,836) of patients from 28 days to 15 years old from September 1, 2010, to August 31, 2011. None. A total of 1,530 patients met the 2005 international consensus definition of sepsis, corresponding to an estimated incidence of 181/100,000 children, with 80% under 5 years old, and in 10% (153), severe sepsis or septic shock developed. The overall case fatality rate for sepsis was 3.5% (53/1,530) or 34.6% (53/153) in those in whom severe sepsis or septic shock developed. Treatment varied widely and in many instances did not conform to international guidelines as reflected by inadequate use of antibiotics, corticosteroids, vasoactive agents, and inotropes. We first report the prevalence and outcome of pediatric sepsis based on a regional hospital network in China. The diverse treatment approaches and practice at low-level clinics suggest the need for clinical implementation of internationally recognized strategy to improve the care standard in resource-limited regional hospitals.

  5. Neuroanatomy and Physiology of Brain Dysfunction in Sepsis.

    PubMed

    Mazeraud, Aurelien; Pascal, Quentin; Verdonk, Franck; Heming, Nicholas; Chrétien, Fabrice; Sharshar, Tarek

    2016-06-01

    Sepsis-associated encephalopathy (SAE), a complication of sepsis, is often complicated by acute and long-term brain dysfunction. SAE is associated with electroencephalogram pattern changes and abnormal neuroimaging findings. The major processes involved are neuroinflammation, circulatory dysfunction, and excitotoxicity. Neuroinflammation and microcirculatory alterations are diffuse, whereas excitotoxicity might occur in more specific structures involved in the response to stress and the control of vital functions. A dysfunction of the brainstem, amygdala, and hippocampus might account for the increased mortality, psychological disorders, and cognitive impairment. This review summarizes clinical and paraclinical features of SAE and describes its mechanisms at cellular and structural levels. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. AspiriN To Inhibit SEPSIS (ANTISEPSIS) randomised controlled trial protocol.

    PubMed

    Eisen, Damon P; Moore, Elizabeth M; Leder, Karin; Lockery, Jessica; McBryde, Emma S; McNeil, John J; Pilcher, David; Wolfe, Rory; Woods, Robyn L

    2017-01-20

    Sepsis is a leading global cause of morbidity and mortality, and is more common at the extremes of age. Moreover, the cost of in-hospital care for elderly patients with sepsis is significant. There are indications from experimental and observational studies that aspirin may reduce inflammation associated with infection. This paper describes the rationale and design of the AspiriN To Inhibit SEPSIS (ANTISEPSIS) trial, a substudy of ASPirin in Reducing Events in the Elderly (ASPREE). ANTISEPSIS primarily aims to determine whether low-dose aspirin reduces sepsis-related deaths in older people. Additionally, it will assess whether low-dose aspirin reduces sepsis-related hospitalisations and sepsis-related Intensive Care Unit (ICU) admissions. ASPREE is a double-blinded, randomised, placebo-controlled primary prevention trial that will determine whether daily low-dose aspirin extends disability-free longevity in 19 000 healthy older people recruited in Australia and the USA. The ANTISEPSIS substudy involves additional ASPREE trial data collection to assess the impact of daily low-dose aspirin on sepsis-related events in the 16 703 ASPREE participants aged 70 years and over, recruited in Australia. The intervention is a daily 100 mg dose of enteric-coated aspirin versus matching placebo, with 1:1 randomisation. The primary outcome for the ANTISEPSIS substudy is the incidence of sepsis-related death in eligible patients. The incidence of sepsis-related hospital and ICU admissions are secondary outcomes. ANTISEPSIS is to be conducted between 2012 and 2018. This substudy will determine whether aspirin, an inexpensive and accessible therapy, safely reduces sepsis-related deaths and hospitalisations in older Australians. If shown to be the case, this would have profound effects on the health of older Australians. Pre-results, ACTRN12613000349741. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go

  7. Drotrecogin alfa (activated): a novel therapeutic strategy for severe sepsis

    PubMed Central

    Pastores, S

    2003-01-01

    Recent studies have highlighted the close link between activation of the coagulation system and the inflammatory response in the pathophysiology of severe sepsis. The protein C anticoagulant pathway plays an integral part in modulating the coagulation and inflammatory responses to infection. In patients with sepsis, endogenous protein C levels are decreased, shifting the balance toward greater systemic inflammation, coagulation, and cell death. On the basis of a single large randomised phase 3 trial, drotrecogin alfa (activated), a recombinant form of human activated protein C, was recently approved for the treatment of adult patients with severe sepsis and a high risk of death. Since its approval, several questions have been raised regarding the appropriate use of this agent. Given the increased risk of serious bleeding and the high cost of treatment, drotrecogin alfa (activated) should be reserved at this time for the most acutely ill patients with severe sepsis who meet the criteria that were used in the phase 3 trial. PMID:12566544

  8. A blueprint for a sepsis protocol.

    PubMed

    Shapiro, Nathan I; Howell, Michael; Talmor, Daniel

    2005-04-01

    Despite numerous advances in medicine, sepsis remains an unconquered challenge. Although outcomes have improved slightly over decades, the unacceptably high mortality rate of 30%-50% for severe sepsis and septic shock continues. However, after years of unsuccessful clinical trials, several investigations over the last few years have reported survival benefit in the treatment of sepsis. Physicians now have several proven therapies to treat sepsis, but have yet to implement them on a widespread, systematic basis. This led 11 international professional societies spanning multiple specialties and continents to come together to create the Surviving Sepsis Campaign. The product of their work is an international effort organized to improve care of patients with sepsis and includes consensus, evidence-based guidelines for care that improves survival in septic patients, and an action plan for change. Given the clear role of early identification and treatment in stopping the sepsis cascade, therapy must start early in the emergency department (ED) and continue throughout the hospital course. The first of the recommendations by the Surviving Sepsis Campaign is the aggressive resuscitation strategy of early goal-directed therapy (EGDT). EGDT is reported to reduce absolute mortality by a staggering 16%. The use of recombinant activated protein C was demonstrated to confer a 6% absolute survival benefit. Steroid supplementation in adrenal insufficiency produced a 10% benefit. Additionally, early and appropriate use of antibiotics remains a cornerstone of therapy. Although no randomized trial will be performed, the effects are undisputed. Finally, although predominantly intensive care unit therapies, tight glucose control and low-tidal-volume ventilation strategies have also led to improved survival. Armed with these new therapies, the medical community must rise to this call to action. Clinicians must change the approach to this disease, as well as the way the septic patient is

  9. Basic and advanced echocardiographic evaluation of myocardial dysfunction in sepsis and septic shock.

    PubMed

    Vallabhajosyula, S; Pruthi, S; Shah, S; Wiley, B M; Mankad, S V; Jentzer, J C

    2018-01-01

    Sepsis continues to be a leading cause of mortality and morbidity in the intensive care unit. Cardiovascular dysfunction in sepsis is associated with worse short- and long-term outcomes. Sepsis-related myocardial dysfunction is noted in 20%-65% of these patients and manifests as isolated or combined left or right ventricular systolic or diastolic dysfunction. Echocardiography is the most commonly used modality for the diagnosis of sepsis-related myocardial dysfunction. With the increasing use of ultrasonography in the intensive care unit, there is a renewed interest in sepsis-related myocardial dysfunction. This review summarises the current scope of literature focused on sepsis-related myocardial dysfunction and highlights the use of basic and advanced echocardiographic techniques for the diagnosis of sepsis-related myocardial dysfunction and the management of sepsis and septic shock.

  10. Managing sepsis: Electronic recognition, rapid response teams, and standardized care save lives.

    PubMed

    Guirgis, Faheem W; Jones, Lisa; Esma, Rhemar; Weiss, Alice; McCurdy, Kaitlin; Ferreira, Jason; Cannon, Christina; McLauchlin, Laura; Smotherman, Carmen; Kraemer, Dale F; Gerdik, Cynthia; Webb, Kendall; Ra, Jin; Moore, Frederick A; Gray-Eurom, Kelly

    2017-08-01

    Sepsis can lead to poor outcomes when treatment is delayed or inadequate. The purpose of this study was to evaluate outcomes after initiation of a hospital-wide sepsis alert program. Retrospective review of patients ≥18years treated for sepsis. There were 3917 sepsis admissions: 1929 admissions before, and 1988 in the after phase. Mean age (57.3 vs. 57.1, p=0.94) and Charlson Comorbidity Scores (2.52 vs. 2.47, p=0.35) were similar between groups. Multivariable analyses identified significant reductions in the after phase for odds of death (OR 0.62, 95% CI 0.39-0.99, p=0.046), mean intensive care unit LOS (2.12days before, 95%CI 1.97, 2.34; 1.95days after, 95%CI 1.75, 2.06; p<0.001), mean overall hospital LOS (11.7days before, 95% CI 10.9, 12.7days; 9.9days after, 95% CI 9.3, 10.6days, p<0.001), odds of mechanical ventilation use (OR 0.62, 95% CI 0.39, 0.99, p=0.007), and total charges with a savings of $7159 per sepsis admission (p=0.036). There was no reduction in vasopressor use (OR 0.89, 95% CI 0.75, 0.1.06, p=0.18). A hospital-wide program utilizing electronic recognition and RRT intervention resulted in improved outcomes in patients with sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Outcomes of the Surviving Sepsis Campaign in intensive care units in the USA and Europe: a prospective cohort study.

    PubMed

    Levy, Mitchell M; Artigas, Antonio; Phillips, Gary S; Rhodes, Andrew; Beale, Richard; Osborn, Tiffany; Vincent, Jean-Louis; Townsend, Sean; Lemeshow, Stanley; Dellinger, R Phillip

    2012-12-01

    Mortality from severe sepsis and septic shock differs across continents, countries, and regions. We aimed to use data from the Surviving Sepsis Campaign (SSC) to compare models of care and outcomes for patients with severe sepsis and septic shock in the USA and Europe. The SSC was introduced into more than 200 sites in Europe and the USA. All patients identified with severe sepsis and septic shock in emergency departments or hospital wards and admitted to intensive care units (ICUs), and those with sepsis in ICUs were entered into the SSC database. Patients entered into the database from its launch in January, 2005, through January, 2010, in units with at least 20 patients and 3 months of enrolment of patients were included in this analysis. Patients included in the cohort were limited to those entered in the first 4 years at every site. We used random-effects logistic regression to estimate the hospital mortality odds ratio (OR) for Europe relative to the USA. We used random-effects linear regression to find the relation between lengths of stay in hospital and ICU and geographic region. 25 375 patients were included in the cohort. The USA included 107 sites with 18 766 (74%) patients, and Europe included 79 hospital sites with 6609 (26%) patients. In the USA, 12 218 (65·1%) were admitted to the ICU from the emergency department whereas in Europe, 3405 (51·5%) were admitted from the wards. The median stay on the hospital wards before ICU admission was longer in Europe than in the USA (1·0 vs 0·1 days, difference 0·9, 95% CI 0·8-0·9). Raw hospital mortality was higher in Europe than in the USA (41·1%vs 28·3%, difference 12·8, 95% CI 11·5-14·7). The median length of stay in ICU (7·8 vs 4·2 days, 3·6, 3·3-3·7) and hospital (22·8 vs 10·5 days, 12·3, 11·9-12·8) was longer in Europe than in the USA. Adjusted mortality in Europe was not significantly higher than that in the USA (32·3%vs 31·3%, 1·0, -1·7 to 3·7, p=0·468). Complete compliance

  12. Sepsis-induced morbidity in mice: effects on body temperature, body weight, cage activity, social behavior and cytokines in brain

    PubMed Central

    Granger, Jill I.; Ratti, Pietro-Luca; Datta, Subhash C.; Raymond, Richard M.; Opp, Mark R.

    2012-01-01

    Infection negatively impacts mental health, as evidenced by the lethargy, malaise, and cognitive deficits experienced during illness. These changes in central nervous system processes, collectively termed sickness behavior, have been shown in animal models to be mediated primarily by the actions of cytokines in brain. Most studies of sickness behavior to date have used bolus injection of bacterial lipopolysaccharide (LPS) or selective administration of the proinflammatory cytokines interleukin-1β (IL-1β) or IL-6 as the immune challenge. Such models, although useful for determining mechanisms responsible for acute changes in physiology and behavior, do not adequately represent the more complex effects on central nervous system (CNS) processes of a true infection with replicating pathogens. In the present study, we used the cecal ligation and puncture (CLP) model to quantify sepsis-induced alterations in several facets of physiology and behavior of mice. We determined the impact of sepsis on cage activity, body temperature, food and water consumption and body weights of mice. Because cytokines are critical mediators of changes in behavior and temperature regulation during immune challenge, we also quantified sepsis-induced alterations in cytokine mRNA and protein in brain during the acute period of sepsis onset. We now report that cage activity and temperature regulation in mice that survive are altered for up to 23 days after sepsis induction. Food and water consumption are transiently reduced, and body weight is lost during sepsis. Furthermore, sepsis decreases social interactions for 24 – 48 hours. Finally, mRNA and protein for IL-1β, IL-6, and tumor necrosis factor-α (TNFα) are upregulated in the hypothalamus, hippocampus, and brain stem during sepsis onset, from 6–72 hour post sepsis induction. Collectively, these data indicate that sepsis not only acutely alters physiology, behavior and cytokine profiles in brain, but that some brain functions are

  13. Antibiotic prophylaxis with teicoplanin on alternate days reduces rate of viridans sepsis and febrile neutropenia in pediatric patients with acute myeloid leukemia.

    PubMed

    Boztug, Heidrun; Mühlegger, Nora; Pötschger, Ulrike; Attarbaschi, Andishe; Peters, Christina; Mann, Georg; Dworzak, Michael

    2017-01-01

    Intensive chemotherapy directed against acute myeloid leukemia of childhood is followed by profound neutropenia and high risk for bacterial and fungal infections, including viridans group streptococci as a common cause for gram-positive septicemia. Few retrospective studies have shown the efficacy of various antibiotic prophylactic regimens in children. We retrospectively studied 50 pediatric patients treated on the AML-BFM 2004 protocol between 2005 and 2015 at St. Anna Children's Hospital and assessed the effect of antibiotic prophylaxis on the frequency of febrile neutropenia and bacterial sepsis. Fifty pediatric patients underwent 199 evaluable chemotherapy cycles. Viridans sepsis occurred after none of 98 cycles with prophylactic administration of teicoplanin/vancomycin in comparison to 12 cases of viridans sepsis among 79 cycles without systemic antibacterial prophylaxis (0 vs. 15 %, p < 0.0001). In addition, there were significantly fewer episodes of febrile neutropenia in the teicoplanin/vancomycin group (44 % vs. no prophylaxis 82 %, p < 0.0001). Severity of infection seemed to be worse when no antibiotic prophylaxis had been administered with a higher rate of intensive care unit treatment (0/98, 0 %, vs. 4/79, 5 %, p = 0.038). So far, no increase of vancomycin-resistant enterococcus isolates in surveillance cultures was noticed. Antibiotic prophylaxis with teicoplanin (or vancomycin) appears safe and feasible and resulted in eradication of viridans sepsis and decreased incidence of febrile neutropenia in pediatric AML patients. The possibility to administer teicoplanin on alternate days on an outpatient basis or at home could contribute to patient's quality of life and decrease health care costs.

  14. Epidemiology and outcomes of acute encephalitis.

    PubMed

    Venkatesan, Arun

    2015-06-01

    This review seeks to describe recent advances in the epidemiology, outcomes, and prognostic factors in acute encephalitis. Infectious causes continue to account for the largest proportion of encephalitis cases in which a cause is identified, although autoimmune causes are increasingly recognized. Type-A gamma-aminobutyric acid (GABAa) receptor antibodies have been recently identified in encephalitis with refractory seizures, whereas the roles of antibodies to the glycine receptor and dipeptidyl peptidase-like protein 6 have been defined in progressive encephalomyelitis with rigidity and myoclonus. Recent findings in the US cases of encephalomyelitis presenting with acute flaccid paralysis raise the possibility that enterovirus D68, a common respiratory pathogen, may cause central nervous system disease. Mortality from acute encephalitis occurs in about 10% of cases, with a large proportion of survivors suffering from cognitive or physical disability. In addition to delay in institution of appropriate antiviral or immune therapy, several potentially reversible factors associated with poor prognosis have been identified, including cerebral edema, status epilepticus, and thrombocytopenia. Encephalitis imposes a significant worldwide health burden and is associated with poor outcomes. Supportive treatment and early institution of therapy may improve outcomes. Careful neurocognitive assessment of survivors of encephalitis is needed to better define long-term outcomes.

  15. Therapeutic mild hypothermia improves early outcomes in rats subjected to severe sepsis.

    PubMed

    Ding, Wu; Shen, Yuehong; Li, Qiang; Jiang, Shouyin; Shen, Huahao

    2018-04-15

    Therapeutic hypothermia has shown beneficial effects in sepsis. This study focused on its mechanism. Sixteen male Sprague-Dawley rats underwent cecal ligation and perforation and subsequently were treated with either hypothermia (HT; body temperature cooled and maintained at 34 °C by ice pad for 10 h; n = 8) or normothermia (NT; n = 8). Three additional rats underwent sham surgery. The body temperatures of the sham-operated and NT groups were maintained at 38 °C with a thermal pad. After the hypothermia treatment, the HT rats were rewarmed for 2 h. The groups were compared for circulating cytokines (IL-6, IL-10), lactate, high mobility group box-1 protein (HMGB1), and lung and intestinal lesions. Animals were observed for 24 h. Compared with the sham-operated group, the 2 sepsis group rats had significantly higher circulating IL-6, HMGB1, and lactate levels, and tissue injury. In the HT rats, the levels of IL-6, HMGB1, and lactate, the lung wet-to-dry ratio, and lung and intestinal damage were significantly lower than that of the NT group. Circulating IL-10 levels increased significantly after 12 h in the sepsis groups compared with sham animals, while that of the NT and HT groups were comparable. The survival rates of the NT and HT rats were also comparable. Therapeutic hypothermia in a rat model of sepsis was associated with lower levels of circulating IL-6 and HMGB1, and less capillary leakage and tissue edema. These results suggest that mild hypothermia has potential as a therapy in sepsis. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Sepsis Fact Sheet

    MedlinePlus

    ... News & Meetings Science Education About NIGMS NIGMS Home > Science Education > Sepsis Sepsis Tagline (Optional) Middle/Main Content Area PDF Version (392 KB) En español Other Fact Sheets What is sepsis? Sepsis is a serious ...

  17. Sepsis (For Parents)

    MedlinePlus

    ... Staying Safe Videos for Educators Search English Español Sepsis KidsHealth / For Parents / Sepsis What's in this article? ... When to Call the Doctor Print What Is Sepsis? Sepsis is when the immune system responds to ...

  18. A Data Mining Approach to Determine Sepsis Guideline Impact on Inpatient Mortality and Complications.

    PubMed

    Pruinelli, Lisiane; Yadav, Pranjul; Hangsleben, Andrew; Johnson, Jakob; Dey, Sanjoy; McCarty, Maribet; Kumar, Vipin; Delaney, Connie W; Steinbach, Michael; Westra, Bonnie L; Simon, György J

    2016-01-01

    Sepsis incidents have doubled from 2000 through 2008, and hospitalizations for these diagnoses have increased by 70%. The use of the Surviving Sepsis Campaign (SSC) guidelines can lead to earlier diagnosis and treatment; however, the effectiveness of the SSC guidelines in preventing complications for this population is unclear. The overall purpose of this study was to apply SSC guideline recommendations to EHR data for patients with severe sepsis or septic shock and determine guideline compliance as well as its impact on inpatient mortality and sepsis complications. Propensity Score Matching in conjuction with Bootstrap Simulation were used to match patients with and without exposure to the SSC recommendations. Findings showed that EHR data could be used to estimate compliance with SSC recommendations as well as the effect of compliance on outcomes. Compliance with guideline recommendations ranged from 9% to 100%. For individual recommendations with sufficient data, association with outcomes varied. Checking lactate influenced four outcomes; however, two were negative and two positive. Use of a ventilator for patients with respiratory distress had a positive association with three outcomes.

  19. Pediatric Sepsis.

    PubMed

    Prusakowski, Melanie K; Chen, Audrey P

    2017-02-01

    Pediatric sepsis is distinct from adult sepsis in its definitions, clinical presentations, and management. Recognition of pediatric sepsis is complicated by the various pediatric-specific comorbidities that contribute to its mortality and the age- and development-specific vital sign and clinical parameters that obscure its recognition. This article outlines the clinical presentation and management of sepsis in neonates, infants, and children, and highlights some key populations who require specialized care. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Lung Transcriptomics during Protective Ventilatory Support in Sepsis-Induced Acute Lung Injury

    PubMed Central

    Acosta-Herrera, Marialbert; Lorenzo-Diaz, Fabian; Pino-Yanes, Maria; Corrales, Almudena; Valladares, Francisco; Klassert, Tilman E.; Valladares, Basilio; Slevogt, Hortense; Ma, Shwu-Fan

    2015-01-01

    Acute lung injury (ALI) is a severe inflammatory process of the lung. The only proven life-saving support is mechanical ventilation (MV) using low tidal volumes (LVT) plus moderate to high levels of positive end-expiratory pressure (PEEP). However, it is currently unknown how they exert the protective effects. To identify the molecular mechanisms modulated by protective MV, this study reports transcriptomic analyses based on microarray and microRNA sequencing in lung tissues from a clinically relevant animal model of sepsis-induced ALI. Sepsis was induced by cecal ligation and puncture (CLP) in male Sprague-Dawley rats. At 24 hours post-CLP, septic animals were randomized to three ventilatory strategies: spontaneous breathing, LVT (6 ml/kg) plus 10 cmH2O PEEP and high tidal volume (HVT, 20 ml/kg) plus 2 cmH2O PEEP. Healthy, non-septic, non-ventilated animals served as controls. After 4 hours of ventilation, lung samples were obtained for histological examination and gene expression analysis using microarray and microRNA sequencing. Validations were assessed using parallel analyses on existing publicly available genome-wide association study findings and transcriptomic human data. The catalogue of deregulated processes differed among experimental groups. The ‘response to microorganisms’ was the most prominent biological process in septic, non-ventilated and in HVT animals. Unexpectedly, the ‘neuron projection morphogenesis’ process was one of the most significantly deregulated in LVT. Further support for the key role of the latter process was obtained by microRNA studies, as four species targeting many of its genes (Mir-27a, Mir-103, Mir-17-5p and Mir-130a) were found deregulated. Additional analyses revealed 'VEGF signaling' as a central underlying response mechanism to all the septic groups (spontaneously breathing or mechanically ventilated). Based on this data, we conclude that a co-deregulation of 'VEGF signaling' along with 'neuron projection

  1. Comparison of Pediatric Severe Sepsis Managed in U.S. and European ICUs.

    PubMed

    Giuliano, John S; Markovitz, Barry P; Brierley, Joe; Levin, Richard; Williams, Gary; Lum, Lucy Chai See; Dorofaeff, Tavey; Cruces, Pablo; Bush, Jenny L; Keele, Luke; Nadkarni, Vinay M; Thomas, Neal J; Fitzgerald, Julie C; Weiss, Scott L

    2016-06-01

    Pediatric severe sepsis remains a significant global health problem without new therapies despite many multicenter clinical trials. We compared children managed with severe sepsis in European and U.S. PICUs to identify geographic variation, which may improve the design of future international studies. We conducted a secondary analysis of the Sepsis PRevalence, OUtcomes, and Therapies study. Data about PICU characteristics, patient demographics, therapies, and outcomes were compared. Multivariable regression models were used to determine adjusted differences in morbidity and mortality. European and U.S. PICUs. Children with severe sepsis managed in European and U.S. PICUs enrolled in the Sepsis PRevalence, OUtcomes, and Therapies study. None. European PICUs had fewer beds (median, 11 vs 24; p < 0.001). European patients were younger (median, 1 vs 6 yr; p < 0.001), had higher severity of illness (median Pediatric Index of Mortality-3, 5.0 vs 3.8; p = 0.02), and were more often admitted from the ward (37% vs 24%). Invasive mechanical ventilation, central venous access, and vasoactive infusions were used more frequently in European patients (85% vs 68%, p = 0.002; 91% vs 82%, p = 0.05; and 71% vs 50%; p < 0.001, respectively). Raw morbidity and mortality outcomes were worse for European compared with U.S. patients, but after adjusting for patient characteristics, there were no significant differences in mortality, multiple organ dysfunction, disability at discharge, length of stay, or ventilator/vasoactive-free days. Children with severe sepsis admitted to European PICUs have higher severity of illness, are more likely to be admitted from hospital wards, and receive more intensive care therapies than in the United States. The lack of significant differences in morbidity and mortality after adjusting for patient characteristics suggests that the approach to care between regions, perhaps related to PICU bed availability, needs to be considered in the design of future

  2. Comparison of Pediatric Severe Sepsis Managed in U.S. and European ICUs

    PubMed Central

    Giuliano, John S.; Markovitz, Barry P.; Brierley, Joe; Levin, Richard; Williams, Gary; Lum, Lucy Chai See; Dorofaeff, Tavey; Cruces, Pablo; Bush, Jenny L.; Keele, Luke; Nadkarni, Vinay M.; Thomas, Neal J.; Fitzgerald, Julie C.; Weiss, Scott L.

    2017-01-01

    Objectives Pediatric severe sepsis remains a significant global health problem without new therapies despite many multicenter clinical trials. We compared children managed with severe sepsis in European and U.S. PICUs to identify geographic variation, which may improve the design of future international studies. Design We conducted a secondary analysis of the Sepsis PRevalence, OUtcomes, and Therapies study. Data about PICU characteristics, patient demographics, therapies, and outcomes were compared. Multivariable regression models were used to determine adjusted differences in morbidity and mortality. Setting European and U.S. PICUs. Patients Children with severe sepsis managed in European and U.S. PICUs enrolled in the Sepsis PRevalence, OUtcomes, and Therapies study. Interventions None. Measurements and Main Results European PICUs had fewer beds (median, 11 vs 24; p < 0.001). European patients were younger (median, 1 vs 6 yr; p < 0.001), had higher severity of illness (median Pediatric Index of Mortality −3, 5.0 vs 3.8; p = 0.02), and were more often admitted from the ward (37% vs 24%). Invasive mechanical ventilation, central venous access, and vasoactive infusions were used more frequently in European patients (85% vs 68%, p = 0.002; 91% vs 82%, p = 0.05; and 71% vs 50%; p < 0.001, respectively). Raw morbidity and mortality outcomes were worse for European compared with U.S. patients, but after adjusting for patient characteristics, there were no significant differences in mortality, multiple organ dysfunction, disability at discharge, length of stay, or ventilator/vasoactive-free days. Conclusions Children with severe sepsis admitted to European PICUs have higher severity of illness, are more likely to be admitted from hospital wards, and receive more intensive care therapies than in the United States. The lack of significant differences in morbidity and mortality after adjusting for patient characteristics suggests that the approach to care between regions

  3. Feasibility of modified surviving sepsis campaign guidelines in a resource-restricted setting based on a cohort study of severe S. aureus sepsis [corrected].

    PubMed

    Mahavanakul, Weera; Nickerson, Emma K; Srisomang, Pramot; Teparrukkul, Prapit; Lorvinitnun, Pichet; Wongyingsinn, Mingkwan; Chierakul, Wirongrong; Hongsuwan, Maliwan; West, T Eoin; Day, Nicholas P; Limmathurotsakul, Direk; Peacock, Sharon J

    2012-01-01

    The Surviving Sepsis Campaign (SSC) guidelines describe best practice for the management of severe sepsis and septic shock in developed countries, but most deaths from sepsis occur where healthcare is not sufficiently resourced to implement them. Our objective was to define the feasibility and basis for modified guidelines in a resource-restricted setting. We undertook a detailed assessment of sepsis management in a prospective cohort of patients with severe sepsis caused by a single pathogen in a 1,100-bed hospital in lower-middle income Thailand. We compared their management with the SSC guidelines to identify care bundles based on existing capabilities or additional activities that could be undertaken at zero or low cost. We identified 72 patients with severe sepsis or septic shock associated with S. aureus bacteraemia, 38 (53%) of who died within 28 days. One third of patients were treated in intensive care units (ICUs). Numerous interventions described by the SSC guidelines fell within existing capabilities, but their implementation was highly variable. Care available to patients on general wards covered the fundamental principles of sepsis management, including non-invasive patient monitoring, antimicrobial administration and intravenous fluid resuscitation. We described two additive care bundles, one for general wards and the second for ICUs, that if consistently performed would be predicted to improve outcome from severe sepsis. It is feasible to implement modified sepsis guidelines that are scaled to resource availability, and that could save lives prior to the publication of international guidelines for developing countries.

  4. Sepsis

    MedlinePlus

    Septicemia; Sepsis syndrome; Systemic inflammatory response syndrome; SIRS; Septic shock ... The symptoms of sepsis are not caused by the germs themselves. Instead, chemicals the body releases cause the response. A bacterial infection anywhere ...

  5. Hospitalized cancer patients with severe sepsis: analysis of incidence, mortality, and associated costs of care

    PubMed Central

    Williams, Mark D; Braun, Lee Ann; Cooper, Liesl M; Johnston, Joseph; Weiss, Richard V; Qualy, Rebecca L; Linde-Zwirble, Walter

    2004-01-01

    Introduction Infection is an important complication in cancer patients, which frequently leads to or prolongs hospitalization, and can also lead to acute organ dysfunction (severe sepsis) and eventually death. While cancer patients are known to be at higher risk for infection and subsequent complications, there is no national estimate of the magnitude of this problem. Our objective was to identify cancer patients with severe sepsis and to project these numbers to national levels. Methods Data for all 1999 hospitalizations from six states (Florida, Massachusetts, New Jersey, New York, Virginia, and Washington) were merged with US Census data, Centers for Disease Control vital statistics and National Cancer Institute, Surveillance, Epidemiology, and End Results initiative cancer prevalence data. Malignant neoplasms were identified by International Classification of Disease (ninth revision, clinical modification) (ICD-9-CM) codes (140–208), and infection and acute organ failure were identified from ICD-9-CM codes following Angus and colleagues. Cases were identified as a function of age and were projected to national levels. Results There were 606,176 cancer hospitalizations identified, with severe sepsis present in 29,795 (4.9%). Projecting national estimates for the US population, cancer patients account for 126,209 severe sepsis cases annually, or 16.4 cases per 1000 people with cancer per year. The inhospital mortality for cancer patients with severe sepsis was 37.8%. Compared with the overall population, cancer patients are much more likely to be hospitalized (relative risk, 2.77; 95% confidence interval, 2.77–2.78) and to be hospitalized with severe sepsis (relative risk, 3.96; 95% confidence interval, 3.94–3.99). Overall, severe sepsis is associated with 8.5% (46,729) of all cancer deaths at a cost of $3.4 billion per year. Conclusion Severe sepsis is a common, deadly, and costly complication in cancer patients. PMID:15469571

  6. Hospitalized cancer patients with severe sepsis: analysis of incidence, mortality, and associated costs of care.

    PubMed

    Williams, Mark D; Braun, Lee Ann; Cooper, Liesl M; Johnston, Joseph; Weiss, Richard V; Qualy, Rebecca L; Linde-Zwirble, Walter

    2004-10-01

    Infection is an important complication in cancer patients, which frequently leads to or prolongs hospitalization, and can also lead to acute organ dysfunction (severe sepsis) and eventually death. While cancer patients are known to be at higher risk for infection and subsequent complications, there is no national estimate of the magnitude of this problem. Our objective was to identify cancer patients with severe sepsis and to project these numbers to national levels. Data for all 1999 hospitalizations from six states (Florida, Massachusetts, New Jersey, New York, Virginia, and Washington) were merged with US Census data, Centers for Disease Control vital statistics and National Cancer Institute, Surveillance, Epidemiology, and End Results initiative cancer prevalence data. Malignant neoplasms were identified by International Classification of Disease (ninth revision, clinical modification) (ICD-9-CM) codes (140-208), and infection and acute organ failure were identified from ICD-9-CM codes following Angus and colleagues. Cases were identified as a function of age and were projected to national levels. There were 606,176 cancer hospitalizations identified, with severe sepsis present in 29,795 (4.9%). Projecting national estimates for the US population, cancer patients account for 126,209 severe sepsis cases annually, or 16.4 cases per 1000 people with cancer per year. The inhospital mortality for cancer patients with severe sepsis was 37.8%. Compared with the overall population, cancer patients are much more likely to be hospitalized (relative risk, 2.77; 95% confidence interval, 2.77-2.78) and to be hospitalized with severe sepsis (relative risk, 3.96; 95% confidence interval, 3.94-3.99). Overall, severe sepsis is associated with 8.5% (46,729) of all cancer deaths at a cost of 3.4 billion dollars per year. Severe sepsis is a common, deadly, and costly complication in cancer patients.

  7. DcR3, a new biomarker for sepsis, correlates with infection severity and procalcitonin.

    PubMed

    Gao, Liqin; Yang, Bin; Zhang, Hairong; Ou, Qishui; Lin, Yulan; Zhang, Mei; Zhang, Zhenhuan; Kim, Sunghee; Wu, Bing; Wang, Zeng; Fu, Lengxi; Lin, Jingan; Chen, Ruiqing; Lan, Ruilong; Chen, Junying; Chen, Wei; Chen, Long; Zhang, Hengshan; Han, Deping; Chen, Jingrong; Okunieff, Paul; Lin, Jianhua; Zhang, Lurong

    2018-02-16

    Early diagnosis of sepsis is critical for successful treatment. The clinical value of DcR3 in early diagnosis of sepsis was determined in a dynamic follow-up study. Alterations in plasma levels of DcR3, PCT, CRP, and IL-6 were measured by ELISA and compared among patients with sepsis ( n = 134), SIRS ( n = 60) and normal adults ( n = 50). Correlations and dynamic patterns among the biomarkers, APACHE II scores, clinical outcomes, and pathogens were also examined. Plasma DcR3 was significantly increased in sepsis compared to SIRS and normal adults (median 3.87 vs. 1.28 and 0.17 ng/ml). The elevated DcR3 could be detected in 97.60% sepsis patients 1-2 days prior to the result of blood culture reported. For diagnosis of sepsis, the sensitivity was 97.69% and specificity 98.04%; and for differential diagnosis of sepsis from SIRS, the sensitivity was 90.77% and specificity 98.40%. DcR3 level was positively correlated with severity of sepsis ( r s = 0.82). In 41 patients who died of sepsis, DcR3 elevated as early as 1-2 days before blood culture and peaked on day 3 after blood culture performed. In 90% of sepsis patients, the dynamic alteration pattern of DcR3 was identical to that of PCT, while pattern of 10% patients differed in which clinical data was consistent with DcR3. In 13% sepsis patients, while PCT remained normal, DcR3 levels were at a high level. DcR3 levels had no difference among various pathogens infected. DcR3, a new biomarker, will aid in early diagnosis of sepsis and monitoring its outcome, especially when sepsis patients were PCT negative.

  8. Comparison of oxidative stress & leukocyte activation in patients with severe sepsis & burn injury

    PubMed Central

    Mühl, Diana; Woth, Gábor; Drenkovics, Livia; Varga, Adrienn; Ghosh, Subhamay; Csontos, Csaba; Bogár, Lajos; Wéber, György; Lantos, János

    2011-01-01

    Background & objectives: We evaluated pro- and anti-oxidant disturbances in sepsis and non-sepsis burn patients with systemic inflammatory response syndrome (SIRS). Adhesion molecules and inflammation markers on leukocytes were also analyzed. We hypothesized that oxidative stress and leukocyte activation markers can lead to the severity of sepsis. Methods: In 28 severe sepsis and 27 acute burn injury patients blood samples were collected at admission and 4 days consecutively. Oxidative stress markers: production of reactive oxygen species (ROS), myeloperoxidase, malondialdehyde and endogenous antioxidants: plasma protein sulphydryl groups, reduced glutathione, superoxide dismutase and catalase were measured. Flow cytometry was used to determine CD11a, CD14, CD18, CD49d and CD97 adhesion molecules on leukocytes. Procalcitonin, C-reactive protein, fibrinogen, platelet count and lactate were also analyzed. Results: Pro-oxidant parameters were significantly elevated in sepsis patients at admission, ROS intensity increased in burn patients until the 5th day. Endogenous antioxidant levels except catalase showed increased levels after burn trauma compared to sepsis. Elevated granulocyte activation and suppressed lymphocyte function were found at admission and early activation of granulocytes caused by increasing activation/migration markers in sepsis. Leukocyte adhesion molecule expression confirmed the suppressed lymphocyte and monocyte function in sepsis. Interpretation & conclusions: Severe sepsis is accompanied by oxidative stress and pathological leukocyte endothelial cell interactions. The laboratory parameters used for the evaluation of sepsis and several markers of pro- and antioxidant status were different between sepsis and non-sepsis burn patients. The tendency of changes in these parameters may refer to major oxidative stress in sepsis and developing SIRS in burns. PMID:21808137

  9. Molecular Regulatory Pathways Link Sepsis With Metabolic Syndrome: Non-coding RNA Elements Underlying the Sepsis/Metabolic Cross-Talk.

    PubMed

    Meydan, Chanan; Bekenstein, Uriya; Soreq, Hermona

    2018-01-01

    Sepsis and metabolic syndrome (MetS) are both inflammation-related entities with high impact for human health and the consequences of concussions. Both represent imbalanced parasympathetic/cholinergic response to insulting triggers and variably uncontrolled inflammation that indicates shared upstream regulators, including short microRNAs (miRs) and long non-coding RNAs (lncRNAs). These may cross talk across multiple systems, leading to complex molecular and clinical outcomes. Notably, biomedical and RNA-sequencing based analyses both highlight new links between the acquired and inherited pathogenic, cardiac and inflammatory traits of sepsis/MetS. Those include the HOTAIR and MIAT lncRNAs and their targets, such as miR-122, -150, -155, -182, -197, -375, -608 and HLA-DRA. Implicating non-coding RNA regulators in sepsis and MetS may delineate novel high-value biomarkers and targets for intervention.

  10. Predictors of Outcome in Modern Surgery for Lung Abscess.

    PubMed

    Schweigert, Michael; Solymosi, Norbert; Dubecz, Attila; John, Joseph; West, Doug; Boenisch, Paul Leonhard; Karmy-Jones, Riyad; Ospina, Carlos F Giraldo; Almeida, Ana Beatriz; Witzigmann, Helmut; Stein, Hubert J

    2017-10-01

    Background  Surgery for lung abscess is a challenging task. Timing and indications for surgery are not well established. Identification of predictors of outcome could help to clarify the role of surgery. Methods  Patients who underwent major thoracic surgery for infectious lung abscess were identified at six centers for general thoracic surgery in Germany, Spain, the United Kingdom, and the United States. Study period was 2000 to 2016. Results  There were 91 patients. Pulmonary sepsis (48), pleural empyema (43), persistent air leakage (25), acute renal failure (12), and respiratory failure with mechanical ventilation (25) were already preoperatively present. The mean Charlson index of comorbidity was 3.0 (median: 2.0; interquartile range: 3). Procedures were segmentectomy (18), lobectomy (58), and pneumonectomy (15). The 30-day mortality following surgery was 13/91.Preoperative sepsis (odds ratio [OR]: 13.69; 95% confidence interval [CI]: 1.86-610.53; p  < 0.01), preoperative persistent air leak (OR: 13.46, 95% CI: 3.00-85.37, p  < 0.01), respiratory failure (OR: 5.60; 95% CI: 1.41-24.84; p  < 0.01), acute renal failure (OR: 6.15 ; 95% CI: 1.24-29.56 ; p  = 0.01), and Charlson index of comorbidity ≥ 3 (OR: 7.19 ; 95% CI: 1.43-71.21 ; p  < 0.01) are associated with higher mortality, whereas age > 70 years ( p  = 0.46) and the extent of pulmonary resection (segmentectomy, lobectomy, pneumonectomy) have no significant influence on mortality. Patients with fatal outcome have significantly higher Charlson index of comorbidity ( p  < 0.01). Conclusions  Delayed referral for surgery is common. Significant predictors for fatal outcome are pulmonary sepsis, septic complications (air leak, pleural empyema), septic organ failure (respiratory, acute renal failure), and preexisting comorbidity (Charlson index of comorbidity ≥ 3). The extent of surgical resection shows no significant influence. Georg Thieme Verlag KG Stuttgart

  11. Acute kidney injury and cardiovascular outcomes in acute severe hypertension.

    PubMed

    Szczech, Lynda A; Granger, Christopher B; Dasta, Joseph F; Amin, Alpesh; Peacock, W Frank; McCullough, Peter A; Devlin, John W; Weir, Matthew R; Katz, Jason N; Anderson, Frederick A; Wyman, Allison; Varon, Joseph

    2010-05-25

    Little is known about the association of kidney dysfunction and outcome in acute severe hypertension. This study aimed to measure the association between baseline chronic kidney disease (estimated glomerular filtration rate), acute kidney injury (AKI, decrease in estimated glomerular filtration rate > or =25% from baseline) and outcome in patients hospitalized with acute severe hypertension. The Studying the Treatment of Acute Hypertension (STAT) registry enrolled patients with acute severe hypertension, defined as > or =1 blood pressure measurement >180 mm Hg systolic and/or >110 mm Hg diastolic and treated with intravenous antihypertensive therapy. Data were compared across groups categorized by admission estimated glomerular filtration rate and AKI during admission. On admission, 79% of the cohort (n=1566) had at least mild chronic kidney disease (estimated glomerular filtration rate <60 mL/min in 46%, <30 mL/min in 22%). Chronic kidney disease patients were more likely to develop heart failure (P<0.0001), non-ST-elevation myocardial infarction (P=0.003), and AKI (P<0.007). AKI patients were at greater risk of heart failure and cardiac arrest (P< or =0.0001 for both). Subjects with AKI experienced higher mortality at 90 days (P=0.003). Any acute loss of estimated glomerular filtration rate during hospitalization was independently associated with an increased risk of death (odds ratio, 1.05; P=0.03 per 10-mL/min decline). Other independent predictors of mortality included increasing age (P<0.0001), male gender (P=0.016), white versus black race (P=0.003), and worse baseline kidney function (P=0.003). Chronic kidney disease is a common comorbidity among patients admitted with acute severe hypertension, and AKI is a frequent form of acute target organ dysfunction, particularly in those with baseline chronic kidney disease. Any degree of AKI is associated with a greater risk of morbidity and mortality.

  12. The diagnosis of sepsis revisited - a challenge for young medical scientists in the 21st century

    PubMed Central

    2014-01-01

    In 1991, a well-meaning consensus group of thought leaders derived a simple definition for sepsis which required the breach of only a few static thresholds. More than 20 years later, this simple definition has calcified to become the gold standard for sepsis protocols and research. Yet sepsis clearly comprises a complex, dynamic, and relational distortion of human life. Given the profound scope of the loss of life worldwide, there is a need to disengage from the simple concepts of the past. There is an acute need to develop 21st century approaches which engage sepsis in its true form, as a complex, dynamic, and relational pattern of death. PMID:24383420

  13. Circulating Endothelial Cells and Endothelial Progenitor Cells in Pediatric Sepsis.

    PubMed

    Zahran, Asmaa Mohamad; Elsayh, Khalid Ibrahim; Mohamad, Ismail Lotfy; Hassan, Gamal Mohamad; Abdou, Madleen Adel A

    2016-03-01

    The aim of the study was to measure the number of circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPs) in pediatric patients with sepsis and correlating it with the severity of the disease and its outcome. The study included 19 children with sepsis, 26 with complicated sepsis, and 30 healthy controls. The patients were investigated within 48 hours of pediatric intensive care unit admission together with flow cytometric detection of CECs and CEPs. The levels of both CECs and CEPs were significantly higher in patient with sepsis and complicated sepsis than the controls. The levels of CECs were higher in patients with complicated sepsis, whereas the levels of CEPs were lower in patients with complicated sepsis. Comparing the survival and nonsurvival septic patients, the levels of CEPs were significantly higher in the survival than in nonsurvival patients, whereas the levels of CECs were significantly lower in the survival than in nonsurvival patients. Serum albumin was higher in survival than in nonsurvival patients. Estimation of CECs and CEPs and their correlation with other parameters such as serum albumen could add important information regarding prognosis in septic pediatric patients.

  14. Role of Admission Troponin-T and Serial Troponin-T Testing in Predicting Outcomes in Severe Sepsis and Septic Shock.

    PubMed

    Vallabhajosyula, Saraschandra; Sakhuja, Ankit; Geske, Jeffrey B; Kumar, Mukesh; Poterucha, Joseph T; Kashyap, Rahul; Kashani, Kianoush; Jaffe, Allan S; Jentzer, Jacob C

    2017-09-09

    Troponin-T elevation is seen commonly in sepsis and septic shock patients admitted to the intensive care unit. We sought to evaluate the role of admission and serial troponin-T testing in the prognostication of these patients. This was a retrospective cohort study from 2007 to 2014 on patients admitted to the intensive care units at the Mayo Clinic with severe sepsis and septic shock. Elevated admission troponin-T and significant delta troponin-T were defined as ≥0.01 ng/mL and ≥0.03 ng/mL in 3 hours, respectively. The primary outcome was in-hospital mortality. Secondary outcomes included 1-year mortality and lengths of stay. During this 8-year period, 944 patients met the inclusion criteria with 845 (90%) having an admission troponin-T ≥0.01 ng/mL. Serial troponin-T values were available in 732 (78%) patients. Elevated admission troponin-T was associated with older age, higher baseline comorbidity, and severity of illness, whereas significant delta troponin-T was associated with higher severity of illness. Admission log 10 troponin-T was associated with unadjusted in-hospital (odds ratio 1.6; P =0.003) and 1-year mortality (odds ratio 1.3; P =0.04), but did not correlate with length of stay. Elevated delta troponin-T and log 10 delta troponin-T were not significantly associated with any of the primary or secondary outcomes. Admission log 10 troponin-T remained an independent predictor of in-hospital mortality (odds ratio 1.4; P =0.04) and 1-year survival (hazard ratio 1.3; P =0.008). In patients with sepsis and septic shock, elevated admission troponin-T was associated with higher short- and long-term mortality. Routine serial troponin-T testing did not add incremental prognostic value in these patients. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  15. The Effect of Hospital Volume on Mortality in Patients Admitted with Severe Sepsis

    PubMed Central

    Shahul, Sajid; Hacker, Michele R.; Novack, Victor; Mueller, Ariel; Shaefi, Shahzad; Mahmood, Bilal; Ali, Syed Haider; Talmor, Daniel

    2014-01-01

    Importance The association between hospital volume and inpatient mortality for severe sepsis is unclear. Objective To assess the effect of severe sepsis case volume and inpatient mortality. Design Setting and Participants Retrospective cohort study from 646,988 patient discharges with severe sepsis from 3,487 hospitals in the Nationwide Inpatient Sample from 2002 to 2011. Exposures The exposure of interest was the mean yearly sepsis case volume per hospital divided into tertiles. Main Outcomes and Measures Inpatient mortality. Results Compared with the highest tertile of severe sepsis volume (>60 cases per year), the odds ratio for inpatient mortality among persons admitted to hospitals in the lowest tertile (≤10 severe sepsis cases per year) was 1.188 (95% CI: 1.074–1.315), while the odds ratio was 1.090 (95% CI: 1.031–1.152) for patients admitted to hospitals in the middle tertile. Similarly, improved survival was seen across the tertiles with an adjusted inpatient mortality incidence of 35.81 (95% CI: 33.64–38.03) for hospitals with the lowest volume of severe sepsis cases and a drop to 32.07 (95% CI: 31.51–32.64) for hospitals with the highest volume. Conclusions and Relevance We demonstrate an association between a higher severe sepsis case volume and decreased mortality. The need for a systems-based approach for improved outcomes may require a high volume of severely septic patients. PMID:25264788

  16. Association of Fluid Accumulation with Clinical Outcomes in Critically Ill Children with Severe Sepsis

    PubMed Central

    Chen, Jiao; Li, Xiaozhong; Bai, Zhenjiang; Fang, Fang; Hua, Jun; Li, Ying; Pan, Jian; Wang, Jian; Feng, Xing; Li, Yanhong

    2016-01-01

    Objective To evaluate whether early and acquired daily fluid overload (FO), as well as fluctuations in fluid accumulation, were associated with adverse outcomes in critically ill children with severe sepsis. Methods This study enrolled 202 children in a pediatric intensive care unit (PICU) with severe sepsis. Early fluid overload was defined as ≥5% fluid accumulation occurring in the first 24 hours of PICU admission. The maximum daily fluid accumulation ≥5% occurring during the next 6 days in patients with at least 48 hours of PICU stay was defined as PICU-acquired daily fluid overload. The fluctuation in fluid accumulation was calculated as the difference between the maximum and the minimum daily fluid accumulation obtained during the first 7 days after admission. Results Of the 202 patients, 61 (30.2%) died during PICU stay. Among all patients, 41 (20.3%) experienced early fluid overload, including 9 with a FO ≥10%. Among patients with at least 48 hours of PICU stay (n = 154), 36 (23.4%) developed PICU-acquired daily fluid overload, including 2 with a FO ≥10%. Both early fluid overload (AOR = 1.20; 95% CI 1.08–1.33; P = 0.001; n = 202) and PICU-acquired daily fluid overload (AOR = 5.47 per log increase; 95% CI 1.15–25.96; P = 0.032; n = 154) were independent risk factors associated with mortality after adjusting for age, illness severity, etc. However, fluctuations in fluid accumulation were not associated with mortality after adjustment. Length of PICU stay increased with greater fluctuations in fluid accumulation in all patients with at least 48 hours of PICU stay (FO <5%, 5%-10% vs. ≥10%: 4 [3–8], 7 [4–11] vs. 10 [6–16] days; P <0.001; n = 154) and in survivors (4 [3–8], 7 [5–11] vs. 10 [5–15] days; P <0.001; n = 121). Early fluid overload achieved an area under-the-receiver-operating-characteristic curve of 0.74 (95% CI 0.65–0.82; P <0.001; n = 202) for predicting mortality in patients with severe sepsis, with a sensitivity of 67

  17. Role of pancreatic fat in the outcomes of pancreatitis.

    PubMed

    Acharya, Chathur; Navina, Sarah; Singh, Vijay P

    2014-01-01

    The role of obesity in relation to various disease processes is being increasingly studied, with reports over the last several years increasingly mentioning its association with worse outcomes in acute disease. Obesity has also gained recognition as a risk factor for severe acute pancreatitis (SAP).The mortality in SAP may be as high as 30% and is usually attributable to multi system organ failure (MSOF) earlier in the disease, and complications of necrotizing pancreatitis later [9-11]. To date there is no specific treatment for acute pancreatitis (AP) and the management is largely expectant and supportive. Obesity in general has also been associated with poor outcomes in sepsis and other pathological states including trauma and burns. With the role of unsaturated fatty acids (UFA) as propagators in SAP having recently come to light and with the recognition of acute lipotoxicity, there is now an opportunity to explore different strategies to reduce the mortality and morbidity in SAP and potentially other disease states associated with such a pathophysiology. In this review we will discuss the role of fat and implications of the consequent acute lipotoxicity on the outcomes of acute pancreatitis in lean and obese states and during acute on chronic pancreatitis. Copyright © 2014 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  18. ROLE OF PANCREATIC FAT IN THE OUTCOMES OF PANCREATITIS

    PubMed Central

    Acharya, Chathur; Navina, Sarah; Singh, Vijay P.

    2014-01-01

    The role of obesity in relation to various disease processes is being increasingly studied, with reports over the last several years increasingly mentioning its association with worse outcomes in acute disease. Obesity has also gained recognition as a risk factor for severe acute pancreatitis (SAP) [1–8]. The mortality in SAP may be as high as 30% and is usually attributable to multi system organ failure (MSOF) earlier in the disease, and complications of necrotizing pancreatitis later [9–11]. To date there is no specific treatment for acute pancreatitis (AP) and the management is largely expectant and supportive. Obesity in general has also been associated with poor outcomes in sepsis and other pathological states including trauma and burns [12–14]. With the role of unsaturated fatty acids (UFA) as propagators in SAP having recently come to light [15] and with the recognition of acute lipotoxicity, there is now an opportunity to explore different strategies to reduce the mortality and morbidity in SAP and potentially other disease states associated with such a pathophysiology. In this review we will discuss the role of fat and implications of the consequent acute lipotoxicity on the outcomes of acute pancreatitis in lean and obese states and during acute on chronic pancreatitis. PMID:25278311

  19. Carbapenem resistance, inappropriate empiric treatment and outcomes among patients hospitalized with Enterobacteriaceae urinary tract infection, pneumonia and sepsis.

    PubMed

    Zilberberg, Marya D; Nathanson, Brian H; Sulham, Kate; Fan, Weihong; Shorr, Andrew F

    2017-04-17

    Drug resistance among gram-negative pathogens is a risk factor for inappropriate empiric treatment (IET), which in turn increases the risk for mortality. We explored the impact of carbapenem-resistant Enterobacteriaceae (CRE) on the risk of IET and of IET on outcomes in patients with Enterobacteriaceae infections. We conducted a retrospective cohort study in Premier Perspective database (2009-2013) of 175 US hospitals. We included all adult patients with community-onset culture-positive urinary tract infection (UTI), pneumonia, or sepsis as a principal diagnosis, or as a secondary diagnosis in the setting of respiratory failure, treated with antibiotics within 2 days of admission. We employed regression modeling to compute adjusted association of presence of CRE with risk of receiving IET, and of IET on hospital mortality, length of stay (LOS) and costs. Among 40,137 patients presenting to the hospital with an Enterobacteriaceae UTI, pneumonia or sepsis, 1227 (3.1%) were CRE. In both groups, the majority of the cases were UTI (51.4% CRE and 54.3% non-CRE). Those with CRE were younger (66.6+/-15.3 vs. 69.1+/-15.9 years, p < 0.001), and more likely to be African-American (19.7% vs. 14.0%, p < 0.001) than those with non-CRE. Both chronic (Charlson score 2.0+/-2.0 vs. 1.9+/-2.1, p = 0.009) and acute (by day 2: ICU 56.3% vs. 30.4%, p < 0.001, and mechanical ventilation 35.8% vs. 11.7%, p < 0.001) illness burdens were higher among CRE than non-CRE subjects, respectively. CRE patients were 3× more likely to receive IET than non-CRE (46.5% vs. 11.8%, p < 0.001). In a regression model CRE was a strong predictor of receiving IET (adjusted relative risk ratio 3.95, 95% confidence interval 3.5 to 4.5, p < 0.001). In turn, IET was associated with an adjusted rise in mortality of 12% (95% confidence interval 3% to 23%), and an excess of 5.2 days (95% confidence interval 4.8, 5.6, p < 0.001) LOS and $10,312 (95% confidence interval $9497, $11,126, p < 0

  20. Oral supplementation with ursolic acid ameliorates sepsis-induced acute kidney injury in a mouse model by inhibiting oxidative stress and inflammatory responses.

    PubMed

    Zhang, Zhenyu; Zhang, Hong; Chen, Rui; Wang, Zhong

    2018-05-01

    Ursolic acid (UA) as a multiple bioactive native compound has recently been demonstrated to treat sepsis in animal models. However, the beneficial effects of UA in sepsis‑induced acute kidney injury (AKI) are not completely understood. In the present study, the effect of UA on sepsis‑induced AKI in cecal ligation and puncture (CLP) surgery mice was investigated. Renal histomorphological analysis was performed by hematoxylin and eosin staining. The expression of inflammatory markers in the kidney of septic mice was measured by reverse transcription‑quantitative polymerase chain reaction and western blotting. The results demonstrated that UA administration improved survival in septic mice induced by CLP surgery. The treatment with UA revealed protection against AKI induced by CLP surgery, including the alleviation of glomerular damage and vacuolization in the proximal tubules. In addition, the effects of UA on oxidative stress and inflammation in septic mice were determined. The findings suggested that UA may protect against sepsis‑induced AKI by inhibiting reactive oxygen species and inflammatory cytokines, including tumor necrosis factor‑α, interleukin (IL)‑1β and IL‑6, in the kidney from septic mice. Finally, UA inhibited CLP‑induced activation of nuclear factor‑κB signaling in the kidney from septic mice. The findings of the present study demonstrated that UA may be used as a potential therapeutic agent for complications of sepsis, especially for sepsis-induced AKI.

  1. Biomarker and Drug Target Discovery Using Proteomics in a New Rat Model of Sepsis-Induced Acute Renal Failure

    PubMed Central

    Holly, Mikaela K.; Dear, James W.; Hu, Xuzhen; Schechter, Alan N.; Gladwin, Mark T.; Hewitt, Stephen M.; Yuen, Peter S.T.; Star, Robert A.

    2008-01-01

    Background Sepsis is one of the common causes of acute renal failure (ARF). The objective of this study was to identify new biomarkers and therapeutic targets. We present a new rat model of sepsis-induced ARF based on cecal ligation and puncture (CLP). We used this model to find urinary proteins which may be potential biomarkers and/or drug targets. Methods Aged rats were treated with fluids and antibiotics after CLP. Urinary proteins from septic rats without ARF and urinary proteins from septic rats with ARF were compared by difference in-gel electrophoresis (DIGE). Results CLP surgery elevated IL-6 and IL-10 serum cytokines and blood nitrite compared with sham-operated rats. However there was a range of serum creatinine values at 24 hrs (0.4–2.3 mg/dL) and only 24% developed ARF. Histology confirmed renal injury in these rats. 49% of rats did not develop ARF. Rats without ARF also had less liver injury. The mortality rate at 24 hrs was 27% but was increased by housing the post-surgery rats in metabolic cages. Creatinine clearance and urine output 2–8 hours after CLP was significantly reduced in rats which died within 24 hours. Using DIGE we identified changes in a number of urinary proteins including albumin, brush-border enzymes (eg., meprin-1-alpha) and serine protease inhibitors. The meprin-1-alpha inhibitor actinonin prevented ARF in aged mice. Conclusion In summary we describe a new rat model of sepsis-induced ARF which has a heterogeneous response similar to humans. This model allowed us to use DIGE to find changes in urinary proteins and this approach identified a potential biomarker and drug target – meprin-1-alpha. PMID:16760904

  2. Computer versus paper system for recognition and management of sepsis in surgical intensive care.

    PubMed

    Croft, Chasen A; Moore, Frederick A; Efron, Philip A; Marker, Peggy S; Gabrielli, Andrea; Westhoff, Lynn S; Lottenberg, Lawrence; Jordan, Janeen; Klink, Victoria; Sailors, R Matthew; McKinley, Bruce A

    2014-02-01

    A system to provide surveillance, diagnosis, and protocolized management of surgical intensive care unit (SICU) sepsis was undertaken as a performance improvement project. A system for sepsis management was implemented for SICU patients using paper followed by a computerized system. The hypothesis was that the computerized system would be associated with improved process and outcomes. A system was designed to provide early recognition and guide patient-specific management of sepsis including (1) modified early warning signs-sepsis recognition score (MEWS-SRS; summative point score of ranges of vital signs, mental status, white blood cell count; after every 4 hours) by bedside nurse; (2) suspected site assessment (vascular access, lung, abdomen, urinary tract, soft tissue, other) at bedside by physician or extender; (3) sepsis management protocol (replicable, point-of-care decisions) at bedside by nurse, physician, and extender. The system was implemented first using paper and then a computerized system. Sepsis severity was defined using standard criteria. In January to May 2012, a paper system was used to manage 77 consecutive sepsis encounters (3.9 ± 0.5 cases per week) in 65 patients (77% male; age, 53 ± 2 years). In June to December 2012, a computerized system was used to manage 132 consecutive sepsis encounters (4.4 ± 0.4 cases per week) in 119 patients (63% male; age, 58 ± 2 years). MEWS-SRS elicited 683 site assessments, and 201 had sepsis diagnosis and protocol management. The predominant site of infection was abdomen (paper, 58%; computer, 53%). Recognition of early sepsis tended to occur more using the computerized system (paper, 23%; computer, 35%). Hospital mortality rate for surgical ICU sepsis (paper, 20%; computer, 14%) was less with the computerized system. A computerized sepsis management system improves care process and outcome. Early sepsis is recognized and managed with greater frequency compared with severe sepsis or septic shock. The system

  3. Prevention of neonatal late-onset sepsis: a randomised controlled trial.

    PubMed

    Alcock, Gary; Liley, Helen G; Cooke, Lucy; Gray, Peter H

    2017-04-04

    Late-onset sepsis (LOS), defined as sepsis occurring after 48 h of age causes substantial mortality and morbidity in very low birth weight infants. Risk factors for LOS include immaturity, intravascular catheters, mechanical ventilation, and prolonged parenteral nutrition (PN). Little attention has been paid to studying the effects of PN administration methods. The aim of the study was to compare a bundle of measures for PN line management incorporating a strict aseptic technique with standard line management on LOS in very low birth weight infants. Infants <1500 g birth weight who required PN were randomised to either a bundle of a strict aseptic technique for line management together with single use intravascular catheter for PN or a standard technique. The primary outcome was the incidence of LOS in the first 28 days of life. Secondary outcomes were mortality, neonatal morbidities and developmental outcome at 12 months of age. There were 126 infants in the aseptic technique group and 123 in the standard technique group. Forty (31.8%) infants in the aseptic technique group and 36 (29.3%) in the standard technique group had an episode of sepsis (p = 0.77). This corresponds to incidences of 15.8 and 14.2 episodes of sepsis per 1000 patient days respectively. Subgroup analyses for infants <1000 g also revealed no difference in the rate of sepsis between the intervention and control groups. (p = 0.43). There were no significant differences in secondary outcomes and development between the groups. A bundle of measures including strict aseptic technique for parenteral nutrition line management did not result in a reduction in LOS when compared to a standard technique. There is no evidence to recommend this as routine practice. Interdisciplinary Maternal Perinatal Australasian Collaborative Trials (IMPACT) Network, TRN registration number: PT0363. Date: 06/03/2001; Australian New Zealand Clinical Trials Registry (ANZCTR), TRN registration number: ACTRN

  4. Successful treatment of Chromobacterium violaceum sepsis in South Africa.

    PubMed

    Bosch, F J; Badenhorst, L; Le Roux, J A; Louw, V J

    2008-10-01

    Chromobacterium violaceum sepsis is extremely rare and usually fatal. A very few cases of C. violaceum infection have been reported from Africa, but never from South Africa. As far as could be ascertained, this infection has never been reported in a patient with leukaemia. We describe what we believe to be the first such case of C. violaceum sepsis, in a 16-year-old female patient with acute biphenotypic leukaemia, which developed during the neutropenic phase after intensive chemotherapy. The infection was due to a non-pigmented strain of C. violaceum and was associated with a co-infection with Candida parapsilosis; both were successfully treated using broad-spectrum antibiotics, antifungals and removal of a Hickman line.

  5. Calpastatin Controls Polymicrobial Sepsis by Limiting Procoagulant Microparticle Release

    PubMed Central

    Gerotziafas, Grigoris; Byrnes, Colleen; Hu, Xuzhen; Perez, Joelle; Lévi, Charlène; Placier, Sandrine; Letavernier, Emmanuel; Leelahavanichkul, Asada; Haymann, Jean-philippe; Elalamy, Ismail; Miller, Jeffrey L.; Star, Robert A.; Yuen, Peter S. T.; Baud, Laurent

    2012-01-01

    Rationale: Sepsis, a leading cause of death worldwide, involves widespread activation of inflammation, massive activation of coagulation, and lymphocyte apoptosis. Calpains, calcium-activated cysteine proteases, have been shown to increase inflammatory reactions and lymphocyte apoptosis. Moreover, calpain plays an essential role in microparticle release. Objectives: We investigated the contribution of calpain in eliciting tissue damage during sepsis. Methods: To test our hypothesis, we induced polymicrobial sepsis by cecal ligation and puncture in wild-type (WT) mice and transgenic mice expressing high levels of calpastatin, a calpain-specific inhibitor. Measurements and Main Results: In WT mice, calpain activity increased transiently peaking at 6 hours after cecal ligation and puncture surgery. Calpastatin overexpression improved survival, organ dysfunction (including lung, kidney, and liver damage), and lymphocyte apoptosis. It decreased the sepsis-induced systemic proinflammatory response and disseminated intravascular coagulation, by reducing the number of procoagulant circulating microparticles and therefore delaying thrombin generation. The deleterious effect of microparticles in this model was confirmed by transferring microparticles from septic WT to septic transgenic mice, worsening their survival and coagulopathy. Conclusions: These results demonstrate an important role of the calpain/calpastatin system in coagulation/inflammation pathways during sepsis, because calpain inhibition is associated with less severe disseminated intravascular coagulation and better overall outcomes in sepsis. PMID:22268136

  6. Soluble RAGE as a severity marker in community acquired pneumonia associated sepsis

    PubMed Central

    2012-01-01

    Background Community-acquired pneumonia (CAP) is considered the most important cause of death from infectious disease in developed countries. Severity assessment scores partially address the difficulties in identifying high-risk patients. A lack of specific and valid pathophysiologic severity markers affect early and effective sepsis therapy. HMGB-1, sRAGE and RAGE have been involved in sepsis and their potential as severity markers has been proposed. The aim of this study was to evaluate HMGB-1, RAGE and sRAGE levels in patients with CAP-associated sepsis and determine their possible association with clinical outcome. Method We evaluated 33 patients with CAP-associated sepsis admitted to the emergency room and followed in the medical wards. Severity assessment scores (CURB-65, PSI, APACHE II, SOFA) and serologic markers (HMGB-1, RAGE, sRAGE) were evaluated on admission. Results Thirty patients with a diagnosis of CAP-associated sepsis were enrolled in the study within 24 hours after admission. Fourteen (46.6%) had pandemic (H1N1) influenza A virus, 2 (6.6%) had seasonal influenza A and 14 other diagnoses. Of the patients in the study group, 16 (53.3%) had a fatal outcome. ARDS was observed in 17 (56.6%) and a total of 22 patients had severe sepsis on admission (73%). The SOFA score showed the greatest difference between surviving and non-surviving groups (P = .003) with similar results in ARDS patients (P = .005). sRAGE levels tended to be higher in non-surviving (P = .058) and ARDS patients (P = .058). Logistic regression modeling demonstrated that SOFA (P = .013) and sRAGE (P = .05) were the only variables that modified the probability of a fatal outcome. Conclusion The association of elevated sRAGE with a fatal outcome suggests that it may have an independent causal effect in CAP. SOFA scores were the only clinical factor with the ability to identify surviving and ARDS patients. PMID:22264245

  7. Systemic bioinformatics analysis of skeletal muscle gene expression profiles of sepsis

    PubMed Central

    Yang, Fang; Wang, Yumei

    2018-01-01

    Sepsis is a type of systemic inflammatory response syndrome with high morbidity and mortality. Skeletal muscle dysfunction is one of the major complications of sepsis that may also influence the outcome of sepsis. The aim of the present study was to explore and identify potential mechanisms and therapeutic targets of sepsis. Systemic bioinformatics analysis of skeletal muscle gene expression profiles from the Gene Expression Omnibus was performed. Differentially expressed genes (DEGs) in samples from patients with sepsis and control samples were screened out using the limma package. Differential co-expression and coregulation (DCE and DCR, respectively) analysis was performed based on the Differential Co-expression Analysis package to identify differences in gene co-expression and coregulation patterns between the control and sepsis groups. Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways of DEGs were identified using the Database for Annotation, Visualization and Integrated Discovery, and inflammatory, cancer and skeletal muscle development-associated biological processes and pathways were identified. DCE and DCR analysis revealed several potential therapeutic targets for sepsis, including genes and transcription factors. The results of the present study may provide a basis for the development of novel therapeutic targets and treatment methods for sepsis. PMID:29805480

  8. Clinical Significance of Tissue Factor and CD13 Double-Positive Microparticles in Sirs Patients with Trauma and Severe Sepsis.

    PubMed

    Matsumoto, Hisatake; Yamakawa, Kazuma; Ogura, Hiroshi; Koh, Taichin; Matsumoto, Naoya; Shimazu, Takeshi

    2017-04-01

    Activated immune cells such as monocytes are key factors in systemic inflammatory response syndrome (SIRS) following trauma and sepsis. Activated monocytes induce almost all tissue factor (TF) expression contributing to inflammation and coagulation. TF and CD13 double-positive microparticles (TF/CD13MPs) are predominantly released from these activated monocytes. This study aimed to evaluate TF/CD13MPs and assess their usefulness as a biomarker of pathogenesis in early SIRS following trauma and sepsis. This prospective study comprising 24 trauma patients, 25 severe sepsis patients, and 23 healthy controls was conducted from November 2012 to February 2015. Blood samples were collected from patients within 24 h after injury and diagnosis of severe sepsis and from healthy controls. Numbers of TF/CD13MPs were measured by flow cytometry immediately thereafter. Injury Severity Score (ISS) and Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were calculated at patient enrollment. APACHE II and SOFA scores and International Society of Thrombosis and Haemostasis (ISTH) overt disseminated intravascular coagulation (DIC) diagnostic criteria algorithm were calculated at the time of enrollment of severe sepsis patients. Numbers of TF/CD13MPs were significantly increased in both trauma and severe sepsis patients versus controls and correlated significantly with ISS and APACHE II score in trauma patients and with APACHE II and ISTH DIC scores in severe sepsis patients. Increased numbers of TF/CD13MPs correlated significantly with severities in the acute phase in trauma and severe sepsis patients, suggesting that TF/CD13MPs are important in the pathogenesis of early SIRS following trauma and sepsis.

  9. Human granulocyte colony-stimulating factor may improve outcome attributable to neonatal sepsis complicated by neutropenia.

    PubMed

    Kocherlakota, P; La Gamma, E F

    1997-07-01

    To determine whether adjunctive therapy with recombinant human granulocyte colony-stimulating factor (rhG-CSF) could reverse sepsis-associated neonatal neutropenia and improve neonatal survival compared with conventional therapy in a phase I/II-type trial. An intravenous infusion of rhG-CSF (10 microg/kg/d x 3 d) was administered to 14 septic neutropenic neonates. Neutrophilic responses and outcome of these neonates were compared with 11 concurrently treated, retrospectively selected, case-matched control septic patients identified by using a search of medical records coded for sepsis with neutropenia (>/=24 hours). Seven neonates with early-onset sepsis with neutropenia at birth and seven neonates with late-onset sepsis plus neutropenia (all with necrotizing enterocolitis) were entered in the rhG-CSF treatment group. Results were compared with a conventional therapy control group (five early onset, six late onset). No significant differences existed in the birth weight, gestational age, use of antibiotic therapy, magnitude of respiratory support, severity of metabolic acidosis, use of vasopressors, or other supportive therapy between the two groups. In the rhG-CSF-treated group and in the conventionally treated control group, the absolute neutrophil count (ANC) (mean +/- SEM) was 585 +/- 138 and 438 +/- 152, respectively. The ANC increased to more than baseline in the rhG-CSF-treated group by 10-fold versus 2-fold at 24 hours, 18-fold versus 4-fold at 48 hours, 24-fold versus 5-fold at 72 hours (significant by one-way analysis of variance in the rhG-CSF group only), and 29-fold versus 16-fold at 7 to 10 days when compared with the conventional therapy group. There were no nonresponders in the rhG-CSF group by 24 hours after the first dose of study drug. Monocyte cell counts also increased significantly in both groups by 7 days after entry into this protocol but remained within normal range for age. No clinically significant effect on lymphocytes, erythrocytes, or

  10. Role of Cytokines as a Double-edged Sword in Sepsis

    PubMed Central

    CHAUDHRY, HINA; ZHOU, JUHUA; ZHONG, YIN; ALI, MIR MUSTAFA; MCGUIRE, FRANKLIN; NAGARKATTI, PRAKASH S.; NAGARKATTI, MITZI

    2014-01-01

    Background Sepsis is a deadly immunological disorder and its pathophysiology is still poorly understood. We aimed to determine if specific pro-inflammatory and anti-inflammatory cytokines can be used as diagnostic and therapeutic targets for sepsis. Materials and Methods Recent publications in the MEDLINE database were searched for articles regarding the clinical significance of inflammatory cytokines in sepsis. Results In response to pathogen infection, pro-inflammatory cytokines [interleukin-6 (IL-6), IL-8, IL-18 and tumor necrosis factor-α (TNF-α)] and anti-inflammatory cytokine (IL-10) increased in patients with sepsis. Importantly, a decrease in IL-6 was associated with a better prognosis and overproduction of IL-10 was found to be the main predictor of severity and fatal outcome. Conclusion Both pro-inflammatory and anti-inflammatory cytokines constitute a double-edged sword in sepsis; on one hand they are critical to eliminate the infection while on the other, excessive production can cause tissue and organ damage. Increase in cytokines such as IL-6, Il-8, IL-10, IL-18 and TNF-α may have implications in diagnosis and treatment of sepsis. PMID:24292568

  11. Screening for sepsis in general hospitalized patients: a systematic review.

    PubMed

    Alberto, L; Marshall, A P; Walker, R; Aitken, L M

    2017-08-01

    Sepsis is a condition widely observed outside critical care areas. To examine the application of sepsis screening tools for early recognition of sepsis in general hospitalized patients to: (i) identify the accuracy of these tools; (ii) determine the outcomes associated with their implementation; and (iii) describe the implementation process. A systematic review method was used. PubMed, CINAHL, Cochrane, Scopus, Web of Science, and Embase databases were systematically searched for primary articles, published from January 1990 to June 2016, that investigated screening tools or alert mechanisms for early identification of sepsis in adult general hospitalized patients. The review protocol was registered with PROSPERO (CRD42016042261). More than 8000 citations were screened for eligibility after duplicates had been removed. Six articles met the inclusion criteria testing two types of sepsis screening tools. Electronic tools can capture, recognize abnormal variables, and activate an alert in real time. However, accuracy of these tools was inconsistent across studies with only one demonstrating high specificity and sensitivity. Paper-based, nurse-led screening tools appear to be more sensitive in the identification of septic patients but were only studied in small samples and particular populations. The process of care measures appears to be enhanced; however, demonstrating improved outcomes is more challenging. Implementation details are rarely reported. Heterogeneity of studies prevented meta-analysis. Clinicians, researchers and health decision-makers should consider these findings and limitations when implementing screening tools, research or policy on sepsis recognition in general hospitalized patients. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  12. Red cell distribution width and its association with mortality in neonatal sepsis.

    PubMed

    Martin, Snehal L; Desai, Saumil; Nanavati, Ruchi; Colah, Roshan B; Ghosh, Kanjaksha; Mukherjee, Malay B

    2018-01-08

    Neonatal sepsis is a major cause of mortality in the developing countries. However, with current severity scores and laboratory parameters, predicting outcomes of neonatal sepsis is a serious challenge. Red cell distribution width (RDW) is a readily available pragmatic means to predict outcomes of various comorbidities in adults and children, without causing any additional blood loss. However, its utility in neonates remains unexplored. Hence, the objective of the present study was to evaluate the association of RDW with neonatal sepsis and its role as a predictive marker for mortality. This Prospective observational study was carried out in a Level IIIB NICU for a period of 3 years. It involved comparison of RDW values of septic neonates with those of controls (matched for gestational age and birth weight) with an equal allocation ratio. A total of 251 septic neonates along with 251 controls >28 weeks of gestational age were enrolled. The RDW was derived from complete blood count done within first 6 hours of life. After arranging the RDW (median; interquartile range (IQR)), the values were categorized as those above the 50th percentile i.e. ≥20% and those below the 50th percentile i.e. <20%. The cumulative survival rates of the above two groups were assessed using the Kaplan-Meier curve and the log rank test. RDW levels were significantly higher among the neonatal sepsis cases (19.90%) as compared to the controls (18.90%) with a p value of < .001. RDW was significantly higher amongst the nonsurvivors than survivors (p < .003). Kaplan-Meier curve showed that septic neonates having RDW values ≥20% had significantly increased mortality (p < .02) with a hazard ratio of 0.5. High RDW is associated with neonatal sepsis and is an independent outcome predictor for mortality associated with neonatal sepsis.

  13. Role of probiotics in the prevention of the enteric colonization by Candida in preterm newborns: incidence of late-onset sepsis and neurological outcome.

    PubMed

    Romeo, M G; Romeo, D M; Trovato, L; Oliveri, S; Palermo, F; Cota, F; Betta, P

    2011-01-01

    To evaluate the efficacy of probiotics in the prevention of gastrointestinal colonization by Candida species, of late-onset sepsis and neurological outcome in preterm newborns. A prospective study was conducted in 249 preterms who were subdivided into three groups: one group (n=83) was supplemented with Lactobacillus (L.) reuteri, one group with L. rhamnosus (n=83) and the other with no supplementation (n=83). The fungal colonization in the gastrointestinal tract, the late onset of sepsis and clinical parameters were recorded. A neurological structured assessment was further performed at 1 year of age. Candida stool colonization was significantly higher (P<0.01) in the control group than in the groups treated with probiotics. The L. reuteri group presented a significantly higher reduction in gastrointestinal symptoms than did the L. rhamnosus and control groups. Infants treated with probiotics showed a statistically significant lower incidence of abnormal neurological outcome than did the control group. The use of both probiotics seems to be effective in the prevention of gastrointestinal colonization by Candida, in the protection from late-onset sepis and in reducing abnormal neurological outcomes in preterms.

  14. Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis.

    PubMed

    Weiss, Scott L; Fitzgerald, Julie C; Balamuth, Fran; Alpern, Elizabeth R; Lavelle, Jane; Chilutti, Marianne; Grundmeier, Robert; Nadkarni, Vinay M; Thomas, Neal J

    2014-11-01

    Delayed antimicrobials are associated with poor outcomes in adult sepsis, but data relating antimicrobial timing to mortality and organ dysfunction in pediatric sepsis are limited. We sought to determine the impact of antimicrobial timing on mortality and organ dysfunction in pediatric patients with severe sepsis or septic shock. Retrospective observational study. PICU at an academic medical center. One hundred thirty patients treated for severe sepsis or septic shock. None. We determined if hourly delays from sepsis recognition to initial and first appropriate antimicrobial administration were associated with PICU mortality (primary outcome); ventilator-free, vasoactive-free, and organ failure-free days; and length of stay. Median time from sepsis recognition to initial antimicrobial administration was 140 minutes (interquartile range, 74-277 min) and to first appropriate antimicrobial was 177 minutes (90-550 min). An escalating risk of mortality was observed with each hour delay from sepsis recognition to antimicrobial administration, although this did not achieve significance until 3 hours. For patients with more than 3-hour delay to initial and first appropriate antimicrobials, the odds ratio for PICU mortality was 3.92 (95% CI, 1.27-12.06) and 3.59 (95% CI, 1.09-11.76), respectively. These associations persisted after adjustment for individual confounders and a propensity score analysis. After controlling for severity of illness, the odds ratio for PICU mortality increased to 4.84 (95% CI, 1.45-16.2) and 4.92 (95% CI, 1.30-18.58) for more than 3-hour delay to initial and first appropriate antimicrobials, respectively. Initial antimicrobial administration more than 3 hours was also associated with fewer organ failure-free days (16 [interquartile range, 1-23] vs 20 [interquartile range, 6-26]; p = 0.04). Delayed antimicrobial therapy was an independent risk factor for mortality and prolonged organ dysfunction in pediatric sepsis.

  15. A Validation Argument for a Simulation-Based Training Course Centered on Assessment, Recognition, and Early Management of Pediatric Sepsis.

    PubMed

    Geis, Gary L; Wheeler, Derek S; Bunger, Amy; Militello, Laura G; Taylor, Regina G; Bauer, Jerome P; Byczkowski, Terri L; Kerrey, Benjamin T; Patterson, Mary D

    2018-02-01

    Early recognition of sepsis remains one of the greatest challenges in medicine. Novice clinicians are often responsible for the recognition of sepsis and the initiation of urgent management. The aim of this study was to create a validity argument for the use of a simulation-based training course centered on assessment, recognition, and early management of sepsis in a laboratory-based setting. Five unique simulation scenarios were developed integrating critical sepsis cues identified through qualitative interviewing. Scenarios were piloted with groups of novice, intermediate, and expert pediatric physicians. The primary outcome was physician recognition of sepsis, measured with an adapted situation awareness global assessment tool. Secondary outcomes were physician compliance with pediatric advanced life support (PALS) guidelines and early sepsis management (ESM) recommendations, measured by two internally derived tools. Analysis compared recognition of sepsis by levels of expertise and measured association of sepsis recognition with the secondary outcomes. Eighteen physicians were recruited, six per study group. Each physician completed three sepsis simulations. Sepsis was recognized in 19 (35%) of 54 simulations. The odds that experts recognized sepsis was 2.6 [95% confidence interval (CI) = 0.5-13.8] times greater than novices. Adjusted for severity, for every point increase in the PALS global performance score, the odds that sepsis was recognized increased by 11.3 (95% CI = 3.1-41.4). Similarly, the odds ratio for the PALS checklist score was 1.5 (95% CI = 0.8-2.6). Adjusted for severity and level of expertise, the odds of recognizing sepsis was associated with an increase in the ESM checklist score of 1.8 (95% CI = 0.9-3.6) and an increase in ESM global performance score of 4.1 (95% CI = 1.7-10.0). Although incomplete, evidence from initial testing suggests that the simulations of pediatric sepsis were sufficiently valid to justify their use in training novice

  16. Sepsis: Multiple Abnormalities, Heterogeneous Responses, and Evolving Understanding

    PubMed Central

    Iskander, Kendra N.; Osuchowski, Marcin F.; Stearns-Kurosawa, Deborah J.; Kurosawa, Shinichiro; Stepien, David; Valentine, Catherine

    2013-01-01

    Sepsis represents the host's systemic inflammatory response to a severe infection. It causes substantial human morbidity resulting in hundreds of thousands of deaths each year. Despite decades of intense research, the basic mechanisms still remain elusive. In either experimental animal models of sepsis or human patients, there are substantial physiological changes, many of which may result in subsequent organ injury. Variations in age, gender, and medical comorbidities including diabetes and renal failure create additional complexity that influence the outcomes in septic patients. Specific system-based alterations, such as the coagulopathy observed in sepsis, offer both potential insight and possible therapeutic targets. Intracellular stress induces changes in the endoplasmic reticulum yielding misfolded proteins that contribute to the underlying pathophysiological changes. With these multiple changes it is difficult to precisely classify an individual's response in sepsis as proinflammatory or immunosuppressed. This heterogeneity also may explain why most therapeutic interventions have not improved survival. Given the complexity of sepsis, biomarkers and mathematical models offer potential guidance once they have been carefully validated. This review discusses each of these important factors to provide a framework for understanding the complex and current challenges of managing the septic patient. Clinical trial failures and the therapeutic interventions that have proven successful are also discussed. PMID:23899564

  17. Lactate Clearance and Normalization and Prolonged Organ Dysfunction in Pediatric Sepsis.

    PubMed

    Scott, Halden F; Brou, Lina; Deakyne, Sara J; Fairclough, Diane L; Kempe, Allison; Bajaj, Lalit

    2016-03-01

    To evaluate whether lactate clearance and normalization during emergency care of pediatric sepsis is associated with lower rates of persistent organ dysfunction. This was a prospective cohort study of 77 children <18 years of age in the emergency department with infection and acute organ dysfunction per consensus definitions. In consented patients, lactate was measured 2 and/or 4 hours after an initial lactate; persistent organ dysfunction was assessed through laboratory and physician evaluation at 48 hours. A decrease of ≥ 10% from initial to final level was considered lactate clearance; a final level < 2 mmol/L was considered lactate normalization. Relative risk (RR) with 95% CIs, adjusted in a log-binomial model, was used to evaluate associations between lactate clearance/normalization and organ dysfunction. Lactate normalized in 62 (81%) patients and cleared in 70 (91%). The primary outcome, persistent 48-hour organ dysfunction, was present in 32 (42%). Lactate normalization was associated with decreased risk of persistent organ dysfunction (RR 0.46, 0.29-0.73; adjusted RR 0.47, 0.29-0.78); lactate clearance was not (RR 0.70, 0.35-1.41; adjusted RR 0.75, 0.38-1.50). The association between lactate normalization and decreased risk of persistent organ dysfunction was retained in the subgroups with initial lactate ≥ 2 mmol/L and hypotension. In children with sepsis and organ dysfunction, lactate normalization within 4 hours was associated with decreased persistent organ dysfunction. Serial lactate level measurement may provide a useful prognostic tool during the first hours of resuscitation in pediatric sepsis. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Totem and taboo: fluids in sepsis.

    PubMed

    Hilton, Andrew K; Bellomo, Rinaldo

    2011-01-01

    The need for early, rapid, and substantial fluid resuscitation in septic patients has long been an article of faith in the intensive care community, a tribal totem that is taboo to question. The results of a recent multicenter trial in septic children in Africa, published in The New England Journal of Medicine, powerfully challenge the fluid paradigm. The salient aspects of the trial need to be understood and reflected upon. In this commentary, we discuss the background to and findings of the trial and explain why they will likely trigger a re-evaluation of our thinking about fluids in sepsis, a re-evaluation that is already happening in the treatment of acute respiratory distress syndrome and acute kidney injury and in postoperative care.

  19. Totem and Taboo: Fluids in sepsis

    PubMed Central

    2011-01-01

    The need for early, rapid, and substantial fluid resuscitation in septic patients has long been an article of faith in the intensive care community, a tribal totem that is taboo to question. The results of a recent multicenter trial in septic children in Africa, published in The New England Journal of Medicine, powerfully challenge the fluid paradigm. The salient aspects of the trial need to be understood and reflected upon. In this commentary, we discuss the background to and findings of the trial and explain why they will likely trigger a re-evaluation of our thinking about fluids in sepsis, a re-evaluation that is already happening in the treatment of acute respiratory distress syndrome and acute kidney injury and in postoperative care. PMID:21672278

  20. New or Progressive Multiple Organ Dysfunction Syndrome in Pediatric Severe Sepsis: A Sepsis Phenotype With Higher Morbidity and Mortality.

    PubMed

    Lin, John C; Spinella, Philip C; Fitzgerald, Julie C; Tucci, Marisa; Bush, Jenny L; Nadkarni, Vinay M; Thomas, Neal J; Weiss, Scott L

    2017-01-01

    To describe the epidemiology, morbidity, and mortality of new or progressive multiple organ dysfunction syndrome in children with severe sepsis. Secondary analysis of a prospective, cross-sectional, point prevalence study. International, multicenter PICUs. Pediatric patients with severe sepsis identified on five separate days over a 1-year period. None. Of 567 patients from 128 PICUs in 26 countries enrolled, 384 (68%) developed multiple organ dysfunction syndrome within 7 days of severe sepsis recognition. Three hundred twenty-seven had multiple organ dysfunction syndrome on the day of sepsis recognition. Ninety-one of these patients developed progressive multiple organ dysfunction syndrome, whereas an additional 57 patients subsequently developed new multiple organ dysfunction syndrome, yielding a total proportion with severe sepsis-associated new or progressive multiple organ dysfunction syndrome of 26%. Hospital mortality in patients with progressive multiple organ dysfunction syndrome was 51% compared with patients with new multiple organ dysfunction syndrome (28%) and those with single-organ dysfunction without multiple organ dysfunction syndrome (10%) (p < 0.001). Survivors of new or progressive multiple organ dysfunction syndrome also had a higher frequency of moderate to severe disability defined as a Pediatric Overall Performance Category score of greater than or equal to 3 and an increase of greater than or equal to 1 from baseline: 22% versus 29% versus 11% for progressive, new, and no multiple organ dysfunction syndrome, respectively (p < 0.001). Development of new or progressive multiple organ dysfunction syndrome is common (26%) in severe sepsis and is associated with a higher risk of morbidity and mortality than severe sepsis without new or progressive multiple organ dysfunction syndrome. Our data support the use of new or progressive multiple organ dysfunction syndrome as an important outcome in trials of pediatric severe sepsis although efforts

  1. Early versus late pre-intensive care unit admission broad spectrum antibiotics for severe sepsis in adults.

    PubMed

    Siddiqui, Shahla; Razzak, Junaid

    2010-10-06

    Severe sepsis and septic shock have recently emerged as particularly acute and lethal challenges amongst critically ill patients presenting to the emergency department (ED). There are no existing data on the current practices of management of patients with severe sepsis comparing early versus late administration of appropriate broad spectrum antibiotics as part of the early goal-directed therapy that is commenced in the first few hours of presentation. To assess the difference in outcomes with early compared to late administration of antibiotics in patients with severe sepsis in the pre-intensive care unit (ICU) admission period. We defined early as within one hour of presentation to the ED. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2009); MEDLINE (1990 to February 2010); EMBASE (1990 to February 2010); and ISI web of Science (February 2010). We also searched for relevant ongoing trials in specific websites such as www.controlled-trials.com; www.clinicalstudyresults.org; and www.update-software.com. We searched the reference lists of articles. There were no constraints based on language or publication status. We planned to include randomized controlled trials of early versus late broad spectrum antibiotics in adult patients with severe sepsis in the ED, prior to admission to the intensive care unit. Two authors independently assessed articles for inclusion. We found no studies that satisfied the inclusion criteria. Based on this review we are unable to make a recommendation on the early or late use of broad spectrum antibiotics in adult patients with severe sepsis in the ED pre-ICU admission. There is a need to do large prospective double blinded randomized controlled trials on the efficacy of early (within one hour) versus late broad spectrum antibiotics in adult severe sepsis patients. Since it makes sense to start antibiotics as soon as possible in this group of seriously ill patients, administering

  2. Thrombopoietin as Early Biomarker of Disease Severity in Patients With Acute Pancreatitis.

    PubMed

    Lupia, Enrico; Pigozzi, Luca; Pivetta, Emanuele; Bosco, Ornella; Vizio, Barbara; Loiacono, Maria; Lucchiari, Manuela; Battista, Stefania; Morello, Fulvio; Moiraghi, Corrado; Mengozzi, Giulio; Montrucchio, Giuseppe

    2017-02-01

    To study the concentrations of thrombopoietin (TPO), a growth factor recently involved in the pathogenesis of experimental acute pancreatitis (AP), and its potential role as an early diagnostic and prognostic biomarker in patients with AP. Thrombopoietin was measured in 44 AP patients, 18 patients with nonpancreatic acute abdominal pain, and 18 healthy volunteers. Acute pancreatitis severity was classified on the basis of the 2012 International Atlanta Symposium on Acute Pancreatitis criteria. Thrombopoietin levels did not differ between AP patients and control subjects, whereas these were higher in patients with moderately severe or severe AP compared with those with mild AP. Receiver operating characteristic curve analysis of TPO for severe AP diagnosis showed an area under the curve of 0.80. A cutoff value of 31.48 pg/mL showed the highest sensitivity, allowing to rule out severe AP when TPO was lower, whereas TPO higher than 98.23 pg/mL was associated with severe AP with high specificity (93.5%). Furthermore, TPO levels were greater in AP patients developing organ dysfunction or sepsis and in nonsurvivors compared with survivors. Our data provide the first evidence for TPO as potential early prognostic biomarker in AP patients. High TPO levels at hospital admission may predict organ dysfunction, sepsis, and fatal outcome in AP patients.

  3. Choice of Fluid Therapy in the Initial Management of Sepsis, Severe Sepsis, and Septic Shock.

    PubMed

    Chang, Ronald; Holcomb, John B

    2016-07-01

    Sepsis results in disruption of the endothelial glycocalyx layer and damage to the microvasculature, resulting in interstitial accumulation of fluid and subsequently edema. Fluid resuscitation is a mainstay in the initial treatment of sepsis, but the choice of fluid is unclear. The ideal resuscitative fluid is one that restores intravascular volume while minimizing edema; unfortunately, edema and edema-related complications are common consequences of current resuscitation strategies. Crystalloids are recommended as first-line therapy, but the type of crystalloid is not specified. There is increasing evidence that normal saline is associated with increased mortality and kidney injury; balanced crystalloids may be a safer alternative. Albumin is similar to crystalloids in terms of outcomes in the septic population but is costlier. Hydroxyethyl starches appear to increase mortality and kidney injury in the critically ill and are no longer indicated in these patients. In the trauma population, the shift to plasma-based resuscitation with decreased use of crystalloid and colloid in the treatment of hemorrhagic shock has led to decreased inflammatory and edema-mediated complications. Studies are needed to determine if these benefits also occur with a similar resuscitation strategy in the setting of sepsis.

  4. In Search of a Cure for Sepsis: Taming the Monster in Critical Care Medicine.

    PubMed

    Okeke, Emeka B; Uzonna, Jude E

    2016-01-01

    In spite of over half a century of research, sepsis still constitutes a major problem in health care delivery. Although advances in research have significantly increased our knowledge of the pathogenesis of sepsis and resulted in better prognosis and improved survival outcome, sepsis still remains a major challenge in modern medicine with an increase in occurrence predicted and a huge socioeconomic burden. It is generally accepted that sepsis is due to an initial hyperinflammatory response. However, numerous efforts aimed at targeting the proinflammatory cytokine network have been largely unsuccessful and the search for novel potential therapeutic targets continues. Recent studies provide compelling evidence that dysregulated anti-inflammatory responses may also contribute to sepsis mortality. Our previous studies on the role of regulatory T cells and phosphoinositide 3-kinases in sepsis highlight immunological approaches that could be explored for sepsis therapy. In this article, we review the current and emerging concepts in sepsis, highlight novel potential therapeutic targets and immunological approaches for sepsis treatment and propose a biphasic treatment approach for management of the condition. © 2016 S. Karger AG, Basel.

  5. Interleukin-10-1082 promoter polymorphism in association with cytokine production and sepsis susceptibility.

    PubMed

    Stanilova, Spaska A; Miteva, Lyuba D; Karakolev, Zhivko T; Stefanov, Chavdar S

    2006-02-01

    To investigate the -1082 (A/G) polymorphism in the promoter of the IL-10 gene in terms of IL-10 production from stimulated peripheral blood mononuclear cells (PBMC) and to evaluate the relationship of this polymorphism with susceptibility to severe sepsis and the outcome of the disease. Case-control study. Research laboratory of Molecular Biology and Immunology and University Hospital ICU, Faculty of Medicine, Trakia University. A total of 53 healthy volunteers and 33 patients in ICU meeting the criteria for severe sepsis were included. The amplification refractory mutation system PCR was used for IL-10-1082 polymorphism detection. Isolated PBMC were stimulated with either C3-binding glycoprotein (C3bgp), lipopolysaccharide (LPS), phytohemagglutinin (PHA),or pokeweed mitogen (PWM). IL-10 production was measured in culture supernatants. The AA genotype was associated with lower IL-10 production in LPS-, PHA- or PWM-stimulated healthy PBMC. Patients with severe sepsis had significant elevation of A allele, compared with healthy controls (74.2% vs 52.8%; p=0.0062). Carriage of at least one copy of IL-10-1082 G allele in sepsis patients and in healthy controls resulted in a statistically significant increase in IL-10 production from stimulated PBMC. Surviving sepsis patients had a significant decrease of IL-10-1082 allele G frequency, compared with controls (17% vs 47.2%; p=0.012). An association between increased IL-10 production and poor outcome from sepsis was observed. The A allele of the -1082 polymorphism in the interleukin-10 gene promoter is associated with sepsis susceptibility, whereas G allele is associated with higher stimulated interleukin-10 production and increased mortality in severe sepsis.

  6. Acute and long-term dysphagia in critically ill patients with severe sepsis: results of a prospective controlled observational study.

    PubMed

    Zielske, Joerg; Bohne, Silvia; Brunkhorst, Frank M; Axer, Hubertus; Guntinas-Lichius, Orlando

    2014-11-01

    Dysphagia is a major risk factor for morbidity and mortality in critically ill patients treated in intensive care units (ICUs). Structured otorhinolaryngological data on dysphagia in ICU survivors with severe sepsis are missing. In a prospective study, 30 ICU patients with severe sepsis and thirty without sepsis as control group were examined using bedside fiberoptic endoscopic evaluation of swallowing after 14 days in the ICU (T1) and 4 months after onset of critical illness (T2). Swallowing dysfunction was assessed using the Penetration-Aspiration Scale (PAS). The Functional Oral Intake Scale was applied to evaluate the diet needed. Primary endpoint was the burden of dysphagia defined as PAS score >5. At T1, 19 of 30 severe sepsis patients showed aspiration with a PAS score >5, compared to 7 of 30 in critically ill patients without severe sepsis (p = 0.002). Severe sepsis and tracheostomy were independent risk factors for severe dysphagia with aspiration (PAS > 5) at T1 (p = 0.042 and 0.006, respectively). 4-month mortality (T2) was 57 % in severe sepsis patients compared to 20 % in patients without severe sepsis (p = 0.006). At T2, more severe sepsis survivors were tracheostomy-dependent and needed more often tube or parenteral feeding (p = 0.014 and p = 0.040, respectively). Multivariate analysis revealed tracheostomy at T1 as independent risk factor for severe dysphagia at T2 (p = 0.030). Severe sepsis appears to be a relevant risk factor for long-term dysphagia. An otorhinolaryngological evaluation of dysphagia at ICU discharge is mandatory for survivors of severe critical illness to plan specific swallowing rehabilitation programs.

  7. Comparing Quick Sequential Organ Failure Assessment Scores to End-tidal Carbon Dioxide as Mortality Predictors in Prehospital Patients with Suspected Sepsis.

    PubMed

    Hunter, Christopher L; Silvestri, Salvatore; Ralls, George; Stone, Amanda; Walker, Ayanna; Mangalat, Neal; Papa, Linda

    2018-05-01

    Early identification of sepsis significantly improves outcomes, suggesting a role for prehospital screening. An end-tidal carbon dioxide (ETCO 2 ) value ≤ 25 mmHg predicts mortality and severe sepsis when used as part of a prehospital screening tool. Recently, the Quick Sequential Organ Failure Assessment (qSOFA) score was also derived as a tool for predicting poor outcomes in potentially septic patients. We conducted a retrospective cohort study among patients transported by emergency medical services to compare the use of ETCO 2 ≤ 25 mmHg with qSOFA score of ≥ 2 as a predictor of mortality or diagnosis of severe sepsis in prehospital patients with suspected sepsis. By comparison of receiver operator characteristic curves, ETCO 2 had a higher discriminatory power to predict mortality, sepsis, and severe sepsis than qSOFA. Both non-invasive measures were easily obtainable by prehospital personnel, with ETCO 2 performing slightly better as an outcome predictor.

  8. Early outcome of early-goal directed therapy for patients with sepsis or septic shock: a systematic review and meta-analysis of randomized controlled trials.

    PubMed

    Chen, Xiaofan; Zhu, Weifeng; Tan, Jing; Nie, Heyun; Liu, Liangming; Yan, Dongmei; Zhou, Xu; Sun, Xin

    2017-04-18

    Various trials and meta-analyses have reported conflicting results concerning the application of early goal-directed therapy (EGDT) for sepsis and septic shock. The aim of this study was to update the evidence by performing a systematic review and meta-analysis. Multiple databases were searched from initial through August, 2016 for randomized controlled trials (RCTs) which investigated the associations between the use of EGDT and mortality in patients with sepsis or septic shock. Meta-analysis was performed using random-effects model and heterogeneity was examined through subgroup analyses. The primary outcome of interest was patient all-cause mortality including hospital or ICU mortality. Seventeen RCTs including 6207 participants with 3234 in the EGDT group and 2973 in the control group were eligible for this study. Meta-analysis showed that EGDT did not significantly reduce hospital or intensive care unit (ICU) mortality (relative risk [RR] 0.89, 95% CI 0.78 to 1.02) compared with control group for patients with sepsis or septic shock. The findings of subgroup analyses stratified by study region, number of research center, year of enrollment, clinical setting, sample size, timing of EGDT almost remained constant with that of the primary analysis. Our findings provide evidence that EGDT offers neutral survival effects for patients with sepsis or septic shock. Further meta-analyses based on larger well-designed RCTs or individual patient data meta-analysis are required to explore the survival benefits of EDGT in patients with sepsis or septic shock.

  9. Symptoms of depression in survivors of severe sepsis: a prospective cohort study of older Americans.

    PubMed

    Davydow, Dimitry S; Hough, Catherine L; Langa, Kenneth M; Iwashyna, Theodore J

    2013-09-01

    To examine if incident severe sepsis is associated with increased risk of subsequent depressive symptoms and to assess which patient characteristics are associated with increased risk of depressive symptoms. Prospective longitudinal cohort study. Population-based cohort of older U.S. adults interviewed as part of the Health and Retirement Study (1998-2006). A total of 439 patients who survived 471 hospitalizations for severe sepsis and completed at least one follow-up interview. Depressive symptoms were assessed with a modified version of the Center for Epidemiologic Studies Depression Scale. Severe sepsis was identified using a validated algorithm in Medicare claims. The point prevalence of substantial depressive symptoms was 28% at a median of 1.2 years before sepsis, and remained 28% at a median of 0.9 years after sepsis. Neither incident severe sepsis (relative risk [RR]: 1.00; 95% confidence interval [CI]: 0.73, 1.34) nor severe sepsis-related clinical characteristics were significantly associated with subsequent depressive symptoms. These results were robust to potential threats from missing data or alternative outcome definitions. After adjustment, presepsis substantial depressive symptoms (RR: 2.20; 95% CI: 1.66, 2.90) and worse postsepsis functional impairment (RR: 1.08 per new limitation; 95% CI: 1.03, 1.13) were independently associated with substantial depressive symptoms after sepsis. The prevalence of substantial depressive symptoms in severe sepsis survivors is high but is not increased relative to their presepsis levels. Identifying this large subset of severe sepsis survivors at increased risk for major depression, and beginning interventions before hospital discharge, may improve outcomes. Copyright © 2013 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  10. Increased expression of the interleukin 1 receptor on blood neutrophils of humans with the sepsis syndrome.

    PubMed Central

    Fasano, M B; Cousart, S; Neal, S; McCall, C E

    1991-01-01

    Because of the potential importance of interleukin 1 (IL-1) in modulating inflammation and the observations that human blood neutrophils (PMN) express IL-1 receptors (IL-1R) and synthesize IL-1 alpha and IL-1 beta, we studied the IL-1R on blood PMN from a group of patients with the sepsis syndrome. We report a marked enhancement in the sites per cell of IL-1R expressed on sepsis-PMN of 25 consecutively studied patients compared to 20 controls (patient mean = 9,329 +/- 2,212 SE; control mean = 716 +/- 42 SE, respectively). There was no demonstrable difference in the Kd of IL-1R on sepsis-PMN (approximately 1 nM) as determined by saturation curves of 125I-IL-1 alpha binding and the IL-1R on sepsis-PMN had an apparent Mr approximately 68,000, a value like that of normal PMN. Cytofluorographic analysis indicated that the sepsis-PMN phenotype is a single homogeneous population with respect to IL-1R expression. In contrast, expression of the membrane complement receptor CR3 is not increased on sepsis-PMN. Similar increases in expression of IL-1R were not observed in various other inflammatory processes, including acute disseminated inflammation and organ failure not caused by infection, acute infection without organ failure, and immunopathologies such as active systemic lupus erythematosus and rheumatoid arthritis. Enhanced expression of IL-1R was not related simply to the state of myeloid stimulation. Increased expression of IL-1R on normal PMN was induced in vitro by incubating cells with recombinant human granulocyte-macrophage/colony-stimulating factor for 18 h and this response was inhibited by cycloheximide, suggesting the possibility that de novo synthesis of IL-1R might occur in PMN during the sepsis syndrome. Images PMID:1834697

  11. Long non-coding RNA NEAT1 plays an important role in sepsis-induced acute kidney injury by targeting miR-204 and modulating the NF-κB pathway.

    PubMed

    Chen, Yi; Qiu, Jialing; Chen, Bin; Lin, Youping; Chen, Yulan; Xie, Guojin; Qiu, Junming; Tong, Huasheng; Jiang, Dongxin

    2018-06-01

    This study aimed to explore the role of long non-coding RNA NEAT1 in sepsis-induced acute kidney injury (AKI). The expression levels of NEAT1 in sepsis-induced AKI patients were detected. The rat mesangial cells (RMCs) were treated with lipopolysaccharide (LPS) to induce cell injury. Then, the effects of NEAT1 suppression on the cell viability, apoptosis, cytokines expression, and oxidative stress in the LPS-stimulated RMCs were tested. The regulatory miRNA of NEAT1, as well as the target genes of this miRNA, were investigated. Moreover, the regulatory relationship between NEAT1 and the NF-κB pathway was explored. The results demonstrated that NEAT1 was significantly upregulated in the sepsis-induced AKI patients. Moreover, the upregulation of NEAT1 was associated with the serious degrees of AKI in sepsis patients. In addition, the suppression of NEAT1 alleviated LPS-induced injury in RMCs. MiR-204 was negatively regulated by NEAT1. Suppression of NEAT1 alleviated LPS-induced injury by overexpression of miR-204. Moreover, IL-6R was a target of miR-204, and the effects of the suppression of NEAT1 on LPS-induced cell injury were caused by inactivating the NF-κB pathway. In conclusion, upregulation of NEAT1 may aggravate the LPS-induced injury by targeting miR-204 and activating the NF-κB pathway. NEAT1 may serve as an important diagnostic marker and therapeutic target in sepsis-induced AKI. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. An international sepsis survey: a study of doctors' knowledge and perception about sepsis

    PubMed Central

    Poeze, Martijn; Ramsay, Graham; Gerlach, Herwig; Rubulotta, Francesca; Levy, Mitchel

    2004-01-01

    Background To be able to diagnose and treat sepsis better it is important not only to improve the knowledge about definitions and pathophysiology, but also to gain more insight into specialists' perception of, and attitude towards, the current diagnosis and treatment of sepsis. Methods The study was conducted as a prospective, international survey by structured telephone interview. The subjects were intensive care physicians and other specialist physicians caring for intensive care unit (ICU) patients. Results The 1058 physicians who were interviewed (including 529 intensivists) agreed that sepsis is a leading cause of death on the ICU and that the incidence of sepsis is increasing, but that the symptoms of sepsis can easily be misattributed to other conditions. Physicians were concerned that this could lead to under-reporting of sepsis. Two-thirds (67%) were concerned that a common definition is lacking and 83% said it is likely that sepsis is frequently missed. Not more than 17% agreed on any one definition. Conclusion There is a general awareness about the inadequacy of the current definitions of sepsis. Physicians caring for patients with sepsis recognise the difficulty of defining and diagnosing sepsis and are aware that they miss the diagnosis frequently. PMID:15566585

  13. Lymphocyte integrin expression differences between SIRS and sepsis patients.

    PubMed

    Heffernan, D S; Monaghan, S F; Ayala, Alfred

    2017-11-01

    Systemic Inflammatory Response Syndrome (SIRS) and sepsis remain leading causes of death. Despite many similarities, the two entities are very distinct clinically and immunologically. T-Lymphocytes play a key pivotal role in the pathogenesis and ultimately outcome following both SIRS and sepsis. Integrins are essential in the trafficking and migration of lymphocytes. They also serve vital roles in efficient wound healing and clearance of infections. Here, we investigate whether integrin expression, specifically β1 (CD29) and β2 (CD18), are disrupted in SIRS and sepsis, and assess differences in integrin expression between these two critically ill clinical categories. T-Lymphocytes were isolated from whole blood collected from ICU patients exhibiting SIRS or sepsis. Samples were analyzed for CD18 (β2) and CD29 (β1) on CD3 + T cells through flow cytometry. Septic patients were stratified into either exclusively abdominal or non-abdominal sources of sepsis. CD18 was almost ubiquitously expressed on CD3 + T cells irrespective of clinical condition. However, CD29 (β1 integrin) was lowest in SIRS patients (20.4% of CD3 + T cells) when compared with either septic patients (35.5%) or healthy volunteers (54.1%). Furthermore, there was evidence of compartmentalization in septic patients, where abdominal sources had a greater percentage of CD3 + CD29 + T cells (41.7%) when compared with those with non-abdominal sources (29.5%). Distinct differences in T-cell integrin expression exists between patients in SIRS versus sepsis, as well as relative to the source of sepsis. Further work is needed to understand cause and effect relative to the progression from SIRS into sepsis.

  14. Personalized identification of differentially expressed pathways in pediatric sepsis.

    PubMed

    Li, Binjie; Zeng, Qiyi

    2017-10-01

    Sepsis is a leading killer of children worldwide with numerous differentially expressed genes reported to be associated with sepsis. Identifying core pathways in an individual is important for understanding septic mechanisms and for the future application of custom therapeutic decisions. Samples used in the study were from a control group (n=18) and pediatric sepsis group (n=52). Based on Kauffman's attractor theory, differentially expressed pathways associated with pediatric sepsis were detected as attractors. When the distribution results of attractors are consistent with the distribution of total data assessed using support vector machine, the individualized pathway aberrance score (iPAS) was calculated to distinguish differences. Through attractor and Kyoto Encyclopedia of Genes and Genomes functional analysis, 277 enriched pathways were identified as attractors. There were 81 pathways with P<0.05 and 59 pathways with P<0.01. Distribution outcomes of screened attractors were mostly consistent with the total data demonstrated by the six classifying parameters, which suggested the efficiency of attractors. Cluster analysis of pediatric sepsis using the iPAS method identified seven pathway clusters and four sample clusters. Thus, in the majority pediatric sepsis samples, core pathways can be detected as different from accumulated normal samples. In conclusion, a novel procedure that identified the dysregulated attractors in individuals with pediatric sepsis was constructed. Attractors can be markers to identify pathways involved in pediatric sepsis. iPAS may provide a correlation score for each of the signaling pathways present in an individual patient. This process may improve the personalized interpretation of disease mechanisms and may be useful in the forthcoming era of personalized medicine.

  15. Evaluation of procalcitonin for diagnosis of neonatal sepsis of vertical transmission

    PubMed Central

    López Sastre, José B; Solís, David Pérez; Serradilla, Vicente Roqués; Colomer, Belén Fernández; Cotallo, Gil D Coto

    2007-01-01

    Background The results of recent studies suggest the usefulness of PCT for early diagnosis of neonatal sepsis, with varying results. The aim of this prospective multicenter study was to determine the behavior of serum PCT concentrations in both uninfected and infected neonates, and to assess the value of this marker for diagnosis of neonatal sepsis of vertical transmission. Methods PCT was measured in 827 blood samples collected prospectively from 317 neonates admitted to 13 acute-care teaching hospitals in Spain over one year. Serum PCT concentrations were determined by a specific immunoluminometric assay. The diagnostic efficacy of PCT at birth and within 12–24 h and 36–48 h of life was evaluated calculating the sensitivity, specificity, and likelihood ratio of positive and negative results. Results 169 asymptomatic newborns and 148 symptomatic newborns (confirmed vertical sepsis: 31, vertical clinical sepsis: 38, non-infectious diseases: 79) were studied. In asymptomatic neonates, PCT values at 12–24 h were significantly higher than at birth and at 36–48 h of life. Resuscitation at birth and chorioamnionitis were independently associated to PCT values. Neonates with confirmed vertical sepsis showed significantly higher PCT values than those with clinical sepsis. PCT thresholds for the diagnosis of sepsis were 0.55 ng/mL at birth (sensitivity 75.4%, specificity 72.3%); 4.7 ng/mL within 12–24 h of life (sensitivity 73.8%, specificity 80.8%); and 1.7 ng/mL within 36–48 h of life (sensitivity 77.6%, specificity 79.2%). Conclusion Serum PCT was moderately useful for the detection of sepsis of vertical transmission, and its reliability as a maker of bacterial infection requires specific cutoff values for each evaluation point over the first 48 h of life. PMID:17324267

  16. The efficacy of procalcitonin as a biomarker in the management of sepsis: slaying dragons or tilting at windmills?

    PubMed

    Sridharan, Prasanna; Chamberlain, Ronald S

    2013-12-01

    Sepsis is defined as systemic inflammatory response syndrome (SIRS) in the context of an underlying infectious process, and is associated with high rates of morbidity and mortality, particularly when initial therapy is delayed. Numerous biomarkers, including but not limited to cytokines (interleukins-2 and -6 [IL-2, IL-6] and tumor necrosis factor-α [TNF-α]), leukotrienes, acute-phase proteins (C-reactive protein [CRP]), and adhesion molecules, have been evaluated and rejected as unsuitable for the diagnosis of sepsis, predicting its severity, and guiding its treatment. Most recently, procalcitonin (PCT) has been suggested as a novel biomarker that may be useful in guiding therapeutic decision making in the management of sepsis. This article assesses critically the published literature on the clinical utility of PCT concentrations for guiding the treatment of sepsis in adult patients. A comprehensive search of all published studies of the use of serum concentrations of PCT to guide the treatment of sepsis in adult patients (1996 to 2011) was conducted with PubMed and Google Scholar. The search focused on the value of PCT concentrations to guide the diagnosis, prognosis, monitoring, and escalation and de-escalation of antbiotic therapy in these patients. Keywords searched included "procalcitonin," "sepsis," "sepsis biomarker," "sepsis diagnosis," "sepsis prognosis," "sepsis mortality," "antibiotic escalation," "antibiotic de-escalation," "antibiotic duration," and "antimicrobial stewardship." Forty-six trials evaluating the efficacy of PCT concentrations in diagnosing sepsis have been published, with 39 of these trials yielding positive results and 7 yielding negative results. Wanner et al. published the largest study (n=405) demonstrating that peak PCT concentrations occur early after injury in both patients with sepsis and those with multiple organ dysfunction syndrome (MODS). Among 17 trials assessing the prognostic value of PCT concentrations with regard to

  17. Colostomy for Perianal Sepsis With Ecthyma Gangrenosum in Immunocompromised Children.

    PubMed

    Vuille-dit-Bille, Raphael N; Berger, Christoph; Meuli, Martin; Grotzer, Michael A

    2016-01-01

    Perianal sepsis with ecthyma gangrenosum is a severe and potentially mutilating complication in immunocompromised children. Therapies include antimicrobial treatment, incision and drainage, generous tissue debridement, and skin transplantation. We describe 3 children with acute lymphoblastic leukemia having sepsis with Pseudomonas aeruginosa in febrile neutropenia and severe perianal infections treated relatively early with a protective colostomy. Indications for colostomy were nonhealing wounds, and ceaseless pain. All patients showed a rapid reduction of pain. Complete wound healing was seen in 2 patients, and considerable pain reduction and increased quality of life were seen in a third patient during palliative care. These results suggest that a protective colostomy should be considered early in the management of immunocompromised children with ecthyma gangrenosum.

  18. Systematic review of use of β-blockers in sepsis.

    PubMed

    Chacko, Cyril Jacob; Gopal, Shameer

    2015-01-01

    We proposed a review of present literature and systematic analysis of present literature to summarize the evidence on the use of β-blockers on the outcome of a patient with severe sepsis and septic shock. Medline, EMBASE, Cochrane Library were searched from 1946 to December 2013. The bibliography of all relevant articles was hand searched. Full-text search of the grey literature was done through the medical institution database. The database search identified a total of 1241 possible studies. The citation list was hand searched by both the authors. A total of 9 studies were identified. Most studies found a benefit from β-blocker administration in sepsis. This included improved heart rate (HR) control, decreased mortality and improvement in acid-base parameters. Chronic β-blocker usage in sepsis was also associated with improved mortality. The administration of β-blockers during sepsis was associated with better control of HR. The methodological quality of all the included studies, however, was poor. There is insufficient evidence to justify the routine use of β-blockers in sepsis. A large adequately powered multi-centered randomized controlled clinical trial is required to address the question on the efficacy of β-blocker usage in sepsis. This trial should also consider a number of important questions including the choice of β-blocker used, optimal dosing, timing of intervention, duration of intervention and discontinuation of the drug. Until such time based on the available evidence, there is no place for the use of β-blockers in sepsis in current clinical practice.

  19. Isoliquiritigenin protects against sepsis-induced lung and liver injury by reducing inflammatory responses.

    PubMed

    Chen, Xiong; Cai, Xueding; Le, Rongrong; Zhang, Man; Gu, Xuemei; Shen, Feixia; Hong, Guangliang; Chen, Zimiao

    2018-02-05

    Sepsis, one of the most fatal diseases worldwide, often leads to multiple organ failure, mainly due to uncontrolled inflammatory responses. Despite accumulating knowledge obtained in recent years, effective drugs to treat sepsis in the clinic are still urgently needed. Isoliquiritigenin (ISL), a chalcone compound, has been reported to exert anti-inflammatory properties. However, little is known about the effects of ISL on sepsis and its related complications. In this study, we investigated the potential protective effects of ISL on lipopolysaccharide (LPS)-induced injuries and identified the mechanisms underlying these effects. ISL inhibited inflammatory cytokine expression in mouse primary peritoneal macrophages (MPMs) exposed to LPS. In an acute lung injury (ALI) mouse model, ISL prevented LPS-induced structural damage and inflammatory cell infiltration. Additionally, pretreatment with ISL attenuated sepsis-induced lung and liver injury, accompanied by a reduction in inflammatory responses. Moreover, these protective effects were mediated by the nuclear factor kappa B (NF-κB) pathway-mediated inhibition of inflammatory responses in vitro and in vivo. Our study suggests that ISL may be a potential therapeutic agent for sepsis-induced injuries. Copyright © 2017. Published by Elsevier Inc.

  20. T helper type 2-polarized invariant natural killer T cells reduce disease severity in acute intra-abdominal sepsis

    PubMed Central

    Anantha, R V; Mazzuca, D M; Xu, S X; Porcelli, S A; Fraser, D D; Martin, C M; Welch, I; Mele, T; Haeryfar, S M M; McCormick, J K

    2014-01-01

    Sepsis is characterized by a severe systemic inflammatory response to infection that is associated with high morbidity and mortality despite optimal care. Invariant natural killer T (iNK T) cells are potent regulatory lymphocytes that can produce pro- and/or anti-inflammatory cytokines, thus shaping the course and nature of immune responses; however, little is known about their role in sepsis. We demonstrate here that patients with sepsis/severe sepsis have significantly elevated proportions of iNK T cells in their peripheral blood (as a percentage of their circulating T cells) compared to non-septic patients. We therefore investigated the role of iNK T cells in a mouse model of intra-abdominal sepsis (IAS). Our data show that iNK T cells are pathogenic in IAS, and that T helper type 2 (Th2) polarization of iNK T cells using the synthetic glycolipid OCH significantly reduces mortality from IAS. This reduction in mortality is associated with the systemic elevation of the anti-inflammatory cytokine interleukin (IL)-13 and reduction of several proinflammatory cytokines within the spleen, notably interleukin (IL)-17. Finally, we show that treatment of sepsis with OCH in mice is accompanied by significantly reduced apoptosis of splenic T and B lymphocytes and macrophages, but not natural killer cells. We propose that modulation of iNK T cell responses towards a Th2 phenotype may be an effective therapeutic strategy in early sepsis. PMID:24965554

  1. Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study.

    PubMed

    Marik, Paul E; Khangoora, Vikramjit; Rivera, Racquel; Hooper, Michael H; Catravas, John

    2017-06-01

    The global burden of sepsis is estimated as 15 to 19 million cases annually, with a mortality rate approaching 60% in low-income countries. In this retrospective before-after clinical study, we compared the outcome and clinical course of consecutive septic patients treated with intravenous vitamin C, hydrocortisone, and thiamine during a 7-month period (treatment group) with a control group treated in our ICU during the preceding 7 months. The primary outcome was hospital survival. A propensity score was generated to adjust the primary outcome. There were 47 patients in both treatment and control groups, with no significant differences in baseline characteristics between the two groups. The hospital mortality was 8.5% (4 of 47) in the treatment group compared with 40.4% (19 of 47) in the control group (P < .001). The propensity adjusted odds of mortality in the patients treated with the vitamin C protocol was 0.13 (95% CI, 0.04-0.48; P = .002). The Sepsis-Related Organ Failure Assessment score decreased in all patients in the treatment group, with none developing progressive organ failure. All patients in the treatment group were weaned off vasopressors, a mean of 18.3 ± 9.8 h after starting treatment with the vitamin C protocol. The mean duration of vasopressor use was 54.9 ± 28.4 h in the control group (P < .001). Our results suggest that the early use of intravenous vitamin C, together with corticosteroids and thiamine, are effective in preventing progressive organ dysfunction, including acute kidney injury, and in reducing the mortality of patients with severe sepsis and septic shock. Additional studies are required to confirm these preliminary findings. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  2. Alkalosis in Critically Ill Patients with Severe Sepsis and Septic Shock

    PubMed Central

    Jazrawi, Allan; Miller, Jan; Baigi, Amir; Chew, Michelle

    2017-01-01

    Introduction Although metabolic alkalosis is a common occurrence in intensive care units (ICUs), no study has evaluated its prevalence or outcomes in patients with severe sepsis or septic shock. Methods This is a retrospective cohort study of critically ill patients suffering from severe sepsis and septic shock admitted to the ICUs of Halmstad and Varberg County hospitals. From 910 patient records, 627 patients met the inclusion criteria. We investigated the relationship between metabolic alkalosis and mortality. Further, we studied the relationship between metabolic alkalosis and ICU length of stay (LOS). Results Metabolic alkalosis was associated with decreased 30-day and 12-month mortalities. This effect was however lost when a multivariate analysis was conducted, correcting for age, gender, pH on admission, base excess (BE) on admission, Simplified Acute Physiology Score III (SAPS III) and acute kidney injury (AKI). We then analyzed for any dose-response effect between the severity of metabolic alkalosis and mortality and found no relationship. Bivariate analysis showed that metabolic alkalosis had a significant effect on the length of ICU stay. When adjusting for age, sex, pH at admission, BE at admission, SAPS III and AKI in a multivariate analysis, metabolic alkalosis significantly contributed to prolonged ICU length of stay. In two separate sensitivity analyses pure metabolic alkalosis and late metabolic alkalosis (time of onset >48 hours) were the only significant predictor of increased ICU length of stay. Conclusion Metabolic alkalosis did not have any effect on 30-day and 12-month mortalities after adjusting for age, sex, SAPS III-score, pH and BE on admission and AKI in a multivariate analysis. The presence of metabolic alkalosis was independently associated with an increased ICU length of stay. PMID:28045915

  3. The role of heparin in sepsis: much more than just an anticoagulant.

    PubMed

    Li, Xu; Ma, Xiaochun

    2017-11-01

    Despite progress in antibiotic treatment, mechanical ventilation, fluid resuscitation and blood glucose maintenance, sepsis remains a cause of high mortality in the intensive care unit to date, there are no proven treatment strategies for the routine management of septic patients. The extensive interaction between inflammation and coagulation contributes to the basic pathophysiology of sepsis. Thus, the agents that attenuate the activation of both inflammation and coagulation may improve the outcome in sepsis. Apart from the well-known anticoagulant effects of heparin, it also possesses various immunomodulatory properties and protects glycocalyx from shedding. Hence, heparin seems to be such an agent. Immunothrombosis plays an important role in early host defence against bacterial dissemination, thus the proper timing for anticoagulant therapy should be determined. We review the available experimental and clinical data supporting the use of heparin in sepsis. At this time the use of heparin in the treatment of sepsis is conflicting. Future trials of heparin therapy for sepsis should concentrate on the very severely ill patients, in whom benefit is most likely to be demonstrated. © 2017 John Wiley & Sons Ltd.

  4. Urgent Chemotherapy in Sepsis-Like Shock Related to Hematologic Malignancies.

    PubMed

    Cherruault, Marlène; Le Goff, Marielle; Tamburini, Jérôme; Pène, Frédéric

    2018-05-01

    Hematologic malignancies may result in multiple organ involvement including pulmonary and renal dysfunctions, and the less common acute circulatory failure. We herein addressed the outcome of patients with sepsis-like shock related to aggressive hematologic malignancies. A 10-year (2007-2016) monocenter retrospective study. A medical ICU in a tertiary care center. Patients with circulatory shock requiring vasopressors and who subsequently received chemotherapy. Shock was presumably related to the underlying malignancy after ruling out an ongoing or new-onset infectious process. The extent and time course of organ failures was assessed by a modified Sequential Organ Failure Assessment score devoid of the platelet component. None. Seventeen patients were included, including 13 with non-Hodgkin lymphoma, two with hyperleukocytic acute myeloid leukemia, and two with "Human Herpes virus 8"-associated multicentric Castleman's disease. The following associated conditions prompted urgent administration of chemotherapy: tumor lysis syndrome (n = 10), hemophagocytic lymphohistiocytosis (n = 3), compressive bulky tumor (n = 3), pulmonary involvement (n = 3), and disseminated intravascular coagulation (n = 1). Following the initiation of chemotherapy, a number of patients died rapidly from untractable multiple organ failure. In contrast, chemotherapy led to a fast and dramatic improvement in organ failures in early survivors, as shown by the decrease in the modified Sequential Organ Failure Assessment score. However, the overall outcome was poor since only four and three patients could be discharged alive from the ICU and the hospital, and three and two patients remained alive at 6 months and 1 year. Multiple organ dysfunction syndrome related to hematologic malignancies is associated with a dismal outcome. A chemotherapy trial may provide a fast prognostic assessment of the reversibility of organ failure.

  5. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics.

    PubMed

    Goldstein, Brahm; Giroir, Brett; Randolph, Adrienne

    2005-01-01

    Although general definitions of the sepsis continuum have been published for adults, no such work has been done for the pediatric population. Physiologic and laboratory variables used to define the systemic inflammatory response syndrome (SIRS) and organ dysfunction require modification for the developmental stages of children. An international panel of 20 experts in sepsis and clinical research from five countries (Canada, France, Netherlands, United Kingdom, and United States) was convened to modify the published adult consensus definitions of infection, sepsis, severe sepsis, septic shock, and organ dysfunction for children. Consensus conference. This document describes the issues surrounding consensus on four major questions addressed at the meeting: a) How should the pediatric age groups affected by sepsis be delineated? b) What are the specific definitions of pediatric SIRS, infection, sepsis, severe sepsis, and septic shock? c) What are the specific definitions of pediatric organ failure and the validity of pediatric organ failure scores? d) What are the appropriate study populations and study end points required to successfully conduct clinical trials in pediatric sepsis? Five subgroups first met separately and then together to evaluate the following areas: signs and symptoms of sepsis, cell markers, cytokines, microbiological data, and coagulation variables. All conference participants approved the final draft of the proceedings of the meeting. Conference attendees modified the current criteria used to define SIRS and sepsis in adults to incorporate pediatric physiologic variables appropriate for the following subcategories of children: newborn, neonate, infant, child, and adolescent. In addition, the SIRS definition was modified so that either criteria for fever or white blood count had to be met. We also defined various organ dysfunction categories, severe sepsis, and septic shock specifically for children. Although no firm conclusion was made regarding

  6. Long-term survival and function after suspected gram-negative sepsis.

    PubMed

    Perl, T M; Dvorak, L; Hwang, T; Wenzel, R P

    1995-07-26

    Acute Physiology and Chronic Health Evaluation II score was not a significant predictor of outcome when either model included the simpler McCabe and Jackson classification of underlying disease severity. We compared the health status scores with norms for the general population and found that patients with resolved sepsis reported more physical dysfunction (P < .001), including problems with work and activities of daily living (P = .02), and more poorly perceived general health (P < .01). In contrast, patients' scores for perceived emotional health were higher than those in the general population (P = .004). The mean Barthel score of our patients was 85 (100 = total independence) and the mean Eastern Cooperative Oncology Group score was 0.7 (0 = normal, 4 = 100% bedridden), suggesting that the patients' physical function was not normal. At the onset of suspected gram-negative sepsis, severity of underlying illness and in-hospital use of vasopressors are strong and consistent predictors of short- and long-term survival. Our data validate the McCabe and Jackson severity of illness scoring system for predicting long-term survival after sepsis. Physical dysfunction and more poorly perceived general health occur commonly after sepsis.

  7. Biomarkers of sepsis

    PubMed Central

    2013-01-01

    Sepsis is an unusual systemic reaction to what is sometimes an otherwise ordinary infection, and it probably represents a pattern of response by the immune system to injury. A hyper-inflammatory response is followed by an immunosuppressive phase during which multiple organ dysfunction is present and the patient is susceptible to nosocomial infection. Biomarkers to diagnose sepsis may allow early intervention which, although primarily supportive, can reduce the risk of death. Although lactate is currently the most commonly used biomarker to identify sepsis, other biomarkers may help to enhance lactate’s effectiveness; these include markers of the hyper-inflammatory phase of sepsis, such as pro-inflammatory cytokines and chemokines; proteins such as C-reactive protein and procalcitonin which are synthesized in response to infection and inflammation; and markers of neutrophil and monocyte activation. Recently, markers of the immunosuppressive phase of sepsis, such as anti-inflammatory cytokines, and alterations of the cell surface markers of monocytes and lymphocytes have been examined. Combinations of pro- and anti-inflammatory biomarkers in a multi-marker panel may help identify patients who are developing severe sepsis before organ dysfunction has advanced too far. Combined with innovative approaches to treatment that target the immunosuppressive phase, these biomarkers may help to reduce the mortality rate associated with severe sepsis which, despite advances in supportive measures, remains high. PMID:23480440

  8. Multicentre observational study of adherence to Sepsis Six guidelines in emergency general surgery.

    PubMed

    2017-01-01

    Evidence-based interventions may reduce mortality in surgical patients. This study documented the prevalence of sepsis, adherence to guidelines in its management, and timing of source control in general surgical patients presenting as an emergency. Patients aged 16 years or more presenting with emergency general surgery problems were identified over a 7-day period and then screened for sepsis compliance (using the Sepsis Six standards, devised for severe sepsis) and the timing of source control (whether radiological or surgical). Exploratory analyses examined associations between the mode (emergency department or general practitioner) and time of admission, adherence to the sepsis guidelines, and outcomes (complications or death within 30 days). Of a total of 5067 patients from 97 hospitals across the UK, 911 (18·0 per cent) fulfilled the criteria for sepsis, 165 (3·3 per cent) for severe sepsis and 24 (0·5 per cent) for septic shock. Timely delivery of all Sepsis Six guidelines for patients with severe sepsis was achieved in four patients. For patients with severe sepsis, 17·6-94·5 per cent of individual guidelines within the Sepsis Six were delivered. Oxygen was the criterion most likely to be missed, followed by blood cultures in all sepsis severity categories. Surgery for source control occurred a median of 19·8 (i.q.r. 10·0-35·4) h after diagnosis. Omission of Sepsis Six parameters did not appear to be associated with an increase in morbidity or mortality. Although sepsis was common in general surgical patients presenting as an emergency, adherence to severe sepsis guidelines was incomplete in the majority. Despite this, no evidence of harm was apparent. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

  9. Sepsis and Critical Illness Research Center investigators: protocols and standard operating procedures for a prospective cohort study of sepsis in critically ill surgical patients

    PubMed Central

    Loftus, Tyler J; Mira, Juan C; Ozrazgat-Baslanti, Tezcan; Ghita, Gabriella L; Wang, Zhongkai; Stortz, Julie A; Brumback, Babette A; Bihorac, Azra; Segal, Mark S; Anton, Stephen D; Leeuwenburgh, Christiaan; Mohr, Alicia M; Efron, Philip A; Moldawer, Lyle L; Moore, Frederick A; Brakenridge, Scott C

    2017-01-01

    Introduction Sepsis is a common, costly and morbid cause of critical illness in trauma and surgical patients. Ongoing advances in sepsis resuscitation and critical care support strategies have led to improved in-hospital mortality. However, these patients now survive to enter state of chronic critical illness (CCI), persistent low-grade organ dysfunction and poor long-term outcomes driven by the persistent inflammation, immunosuppression and catabolism syndrome (PICS). The Sepsis and Critical Illness Research Center (SCIRC) was created to provide a platform by which the prevalence and pathogenesis of CCI and PICS may be understood at a mechanistic level across multiple medical disciplines, leading to the development of novel management strategies and targeted therapies. Methods Here, we describe the design, study cohort and standard operating procedures used in the prospective study of human sepsis at a level 1 trauma centre and tertiary care hospital providing care for over 2600 critically ill patients annually. These procedures include implementation of an automated sepsis surveillance initiative, augmentation of clinical decisions with a computerised sepsis protocol, strategies for direct exportation of quality-filtered data from the electronic medical record to a research database and robust long-term follow-up. Ethics and dissemination This study has been registered at ClinicalTrials.gov, approved by the University of Florida Institutional Review Board and is actively enrolling subjects. Dissemination of results is forthcoming. PMID:28765125

  10. Postpartum acute kidney injury: a review of 99 cases.

    PubMed

    Eswarappa, Mahesh; Madhyastha, P Rakesh; Puri, Sonika; Varma, Vijay; Bhandari, Aneesh; Chennabassappa, Gurudev

    2016-07-01

    Postpartum acute kidney injury (PPAKI) constitutes an important cause of obstetric AKI. It is associated with high maternal and fetal mortality in developing nations. The aim of this study is to survey the etiology and outcomes of PPAKI in a tertiary care Indian hospital. Ninety-nine patients, without prior comorbidities, treated for PPAKI, between 2005-2014 at M.S. Ramaiah Medical College, were included for analysis in this retrospective, observational study. AKI was analyzed in terms of maximal stage of renal injury attained as per RIFLE criteria. Outcomes included requirement for renal replacement therapy (RRT), maternal and fetal outcomes. PPAKI constituted 60% of all obstetric AKI cases. Median maternal age was 23 years and 52% of patients were primigravidas. Mean serum creatinine was 4.1 mg/dL. Failure (33%) and injury (31%) were the major categories as per RIFLE criteria. Thirty-nine percent of cases required RRT. Sepsis, particularly puerperal sepsis, was the leading causes of PPAKI (75% of cases) and maternal mortality (94% of deaths). Maternal and fetal mortality were 19% and 22% respectively. The incidence of cortical necrosis was 10.3%. Three patients required long-term RRT. In conclusion, consistent with other Indian literature, we report a high incidence of PPAKI. We found incremental mortality on moving from "Risk" to "Failure" category of RIFLE. PPAKI was associated with high maternal and fetal mortality with sepsis being the leading cause. Our study highlights the need for provision of better quality of maternal care and fetal monitoring to decrease mortality associated with PPAKI in developing countries.

  11. Delayed Antimicrobial Therapy Increases Mortality and Organ Dysfunction Duration in Pediatric Sepsis

    PubMed Central

    Weiss, Scott L.; Fitzgerald, Julie C.; Balamuth, Fran; Alpern, Elizabeth R.; Lavelle, Jane; Chilutti, Marianne; Grundmeier, Robert; Nadkarni, Vinay M.; Thomas, Neal J.

    2014-01-01

    Objectives Delayed antimicrobials are associated with poor outcomes in adult sepsis, but data relating antimicrobial timing to mortality and organ dysfunction in pediatric sepsis are limited. We sought to determine the impact of antimicrobial timing on mortality and organ dysfunction in pediatric patients with severe sepsis or septic shock. Design Retrospective observational study. Setting PICU at an academic medical center. Patients One hundred thirty patients treated for severe sepsis or septic shock. Interventions None. Measurements and Main Results We determined if hourly delays from sepsis recognition to initial and first appropriate antimicrobial administration were associated with PICU mortality (primary outcome); ventilator-free, vasoactive-free, and organ failure–free days; and length of stay. Median time from sepsis recognition to initial antimicrobial administration was 140 minutes (interquartile range, 74–277 min) and to first appropriate antimicrobial was 177 minutes (90–550 min). An escalating risk of mortality was observed with each hour delay from sepsis recognition to antimicrobial administration, although this did not achieve significance until 3 hours. For patients with more than 3-hour delay to initial and first appropriate antimicrobials, the odds ratio for PICU mortality was 3.92 (95% CI, 1.27–12.06) and 3.59 (95% CI, 1.09–11.76), respectively. These associations persisted after adjustment for individual confounders and a propensity score analysis. After controlling for severity of illness, the odds ratio for PICU mortality increased to 4.84 (95% CI, 1.45–16.2) and 4.92 (95% CI, 1.30–18.58) for more than 3-hour delay to initial and first appropriate antimicrobials, respectively. Initial antimicrobial administration more than 3 hours was also associated with fewer organ failure–free days (16 [interquartile range, 1–23] vs 20 [interquartile range, 6–26]; p = 0.04). Conclusions Delayed antimicrobial therapy was an independent

  12. Similar Metabolic, Innate Immunity, and Adipokine Profiles in Adult and Pediatric Sepsis Versus Systemic Inflammatory Response Syndrome-A Pilot Study.

    PubMed

    Tavladaki, Theonymfi; Spanaki, Anna Maria; Dimitriou, Helen; Kondili, Efmorfia; Choulaki, Christianna; Georgopoulos, Dimitris; Briassoulis, George

    2017-11-01

    To examine whether the septic profiles of heat shock protein 72, heat shock protein 90α, resistin, adiponectin, oxygen consumption, CO2 production, energy expenditure, and metabolic pattern, along with illness severity, nutritional, and inflammatory indices, differ between adult and pediatric patients compared with systemic inflammatory response syndrome and healthy controls. To evaluate whether these biomolecules may discriminate sepsis from systemic inflammatory response syndrome in adult and pediatric patients. Prospective cohort study. University ICU and PICU. Seventy-eight adults (sepsis/23; systemic inflammatory response syndrome/23; healthy controls/33), 67 children (sepsis/18; systemic inflammatory response syndrome/23; controls/27), mechanically ventilated. None. Flow cytometry determined mean fluorescence intensity for monocyte or neutrophil heat shock protein expression. Resistin, adiponectin, and extracellular heat shock proteins were measured using enzyme-linked immunosorbent assay; energy expenditure by E-COVX (GE Healthcare). Genomic DNA was extracted with PureLink Genomic DNA kit (Invitrogen, Carlsbad, CA) to detect heat shock protein 72 single nucleotide polymorphisms. Similarly, in adult and pediatric patients, Acute Physiology and Chronic Evaluation-II/Acute Physiology and Pediatric Risk of Mortality-III, Simplified Acute Physiology Score-III, C-reactive protein, lactate, and resistin were higher and myocardial contractility, monocyte heat shock protein 72, oxygen consumption, CO2 production, energy expenditure, metabolic pattern, glucose, and albumin lower in sepsis compared with systemic inflammatory response syndrome or controls (p < 0.05). For discriminating sepsis from systemic inflammatory response syndrome, resistin, extracellular heat shock protein 90α, and lactate achieved a receiver operating characteristic curve greater than 0.80 in children and greater than 0.75 in adults (p < 0.05). In both, adults and children, genotype heat shock

  13. Sepsis and identification of reliable biomarkers for postoperative period prognosis.

    PubMed

    Siloşi, Cristian Adrian; Siloşi, Isabela; Pădureanu, Vlad; Bogdan, Maria; Mogoantă, Stelian Ştefăniţă; Ciurea, Marius Eugen; Cojocaru, Manole; Boldeanu, Lidia; Avrămescu, Carmen Silvia; Boldeanu, Mihail Virgil; Popa, Dragoş George

    2018-01-01

    Sepsis is currently defined as the presence of organ dysfunction occurring as the result of a disturbed host response to a serious infection. Sepsis is one of the most common diseases, which cause mortality and a considerable absorber of healthcare resources. Despite progress in technology and improving knowledge of pathophysiology, the disease mechanism is still poorly understood. At present, diagnosis is based on non-specific physiological criteria and on the late identification of the pathogen. For these reasons, the diagnosis may be uncertain, treatment delayed or an immunomodulatory therapy cannot be established. An early and reliable diagnosis is essential to achieve better outcomes on disease progression. The host response to infection involves hundreds of many mediators of which have been proposed as biomarkers. There is a need for new diagnostic approaches for sepsis, new sepsis biomarkers that can aid in diagnosis, therapeutic decision and monitoring of the response to therapy. The differentiation of sepsis from non-infectious systemic inflammatory response syndrome is difficult, and the search for a highly accurate biomarker of sepsis has become one important objective of the medicine. The goal of our review is to summarize the recent advances on the most commonly studied serum biomarkers, evaluated in clinical and experimental studies, for early diagnosis of sepsis and their informative value in diagnosis, prognosis, or response to therapy. In this context, we have tracked the clinical utility of measuring serum biomarkers, such as procalcitonin, pro- and anti-inflammatory cytokines, C-reactive protein, leptin and their combinations. Currently, has not been identified an ideal biomarker to aid in the diagnosis of sepsis. It is hoped that the discovery of new serum markers, as well as their combinations, will serve for the diagnosis and prognosis of sepsis.

  14. Elevated troponin I levels in acute liver failure: is myocardial injury an integral part of acute liver failure?

    PubMed

    Parekh, Nimisha K; Hynan, Linda S; De Lemos, James; Lee, William M

    2007-06-01

    Although rare instances of cardiac injury or arrhythmias have been reported in acute liver failure (ALF), overall, the heart is considered to be spared in this condition. Troponin I, a sensitive and specific marker of myocardial injury, may be elevated in patients with sepsis and acute stroke without underlying acute coronary syndrome, indicating unrecognized cardiac injury in these settings. We sought to determine whether subclinical cardiac injury might also occur in acute liver failure. Serum troponin I levels were measured in 187 patients enrolled in the US Acute Liver Failure Study Group registry, and correlated with clinical variables and outcomes. Diagnoses were representative of the larger group of >1000 patients thus far enrolled and included 80 with acetaminophen-related injury, 26 with viral hepatitis, 19 with ischemic injury, and 62 others. Overall, 74% of patients had elevated troponin I levels (>0.1 ng/ml). Patients with elevated troponin I levels were more likely to have advanced hepatic coma (grades III or IV) or to die (for troponin I levels >0.1 ng/ml, odds ratio 3.88 and 4.69 for advanced coma or death, respectively). In acute liver failure, subclinical myocardial injury appears to occur more commonly than has been recognized, and its pathogenesis in the context of acute liver failure is unclear. Elevated troponin levels are associated with a significant increase in morbidity and mortality. Measurement of troponin I levels may be helpful in patients with acute liver failure, to detect unrecognized myocardial damage and as a marker of unfavorable outcome.

  15. Incidence, clinical features, and implications on outcomes of neonatal late-onset sepsis with concurrent infectious focus.

    PubMed

    Wu, I-Hsyuan; Tsai, Ming-Horng; Lai, Mei-Yin; Hsu, Lee-Fen; Chiang, Ming-Chou; Lien, Reyin; Fu, Ren-Huei; Huang, Hsuan-Rong; Chu, Shih-Ming; Hsu, Jen-Fu

    2017-07-03

    Neonatal bloodstream infection (BSI) is the most important cause of morbidity and mortality in the neonatal intensive care unit (NICU). Although most neonatal BSIs are primary bacteremia, some are associated with a focus of infection. This distinction is not well characterized. All patients with neonatal late-onset sepsis (LOS) between January 2006 and December 2013 were enrolled. LOS was categorized as a BSI with a concurrent focus of infection if LOS occurred before or within 24 h after the diagnosis of a specific infectious entity, and as "primary bacteremia" if no concurrent focus of infection was identified. Data concerning demographics, hospital course, microbiology, and outcomes were compared via univariate and multivariate analyses. Of 948 episodes of neonatal LOS, 781 (82.4%) were primary bacteremia, whereas 167 (17.6%) were associated with a known focus of infection, including meningitis (n = 51, 5.4%), ventilator-associated pneumonia (VAP) (n = 36, 3.8%), catheter-related bloodstream infections (n = 57, 6.0%), and necrotizing enterocolitis (NEC) (n = 21, 2.2%). The majority of NEC-associated BSIs were caused by gram-negative bacilli (85.7%). Group B streptococcus accounted for nearly one-third of all meningitis cases (29.4%). Although sepsis-attributable mortality was comparable between primary bacteremia and neonatal BSIs with a focus of infection, neonatal BSIs with meningitis, VAP, and NEC had significantly higher rates of infectious complications. The independent risk factors of sepsis-attributable mortality were infectious complications (Odds ratio [OR] 6.98; 95% confidence interval [CI] 3.64-13.39, P < 0.001); history of one or more than one previous episode(s) of BSI (OR 2.40 and 7.40; 95% CI 1.21-4.74 and 3.70-14.78, P = 0.012 and <0.001, respectively); and underlying secondary pulmonary hypertension in neonates (OR 4.77; 95% CI 1.91-11.96, P = 0.001). A considerable proportion of neonatal LOS can be associated with known

  16. Understanding the Inflammatory Cytokine Response in Pneumonia and Sepsis

    PubMed Central

    Kellum, John A.; Kong, Lan; Fink, Mitchell P.; Weissfeld, Lisa A.; Yealy, Donald M.; Pinsky, Michael R.; Fine, Jonathan; Krichevsky, Alexander; Delude, Russell L.; Angus, Derek C.

    2015-01-01

    Background Severe sepsis is common and frequently fatal, and community-acquired pneumonia (CAP) is the leading cause. Although severe sepsis is often attributed to uncontrolled and unbalanced inflammation, evidence from humans with infection syndromes across the breadth of disease is lacking. In this study we describe the systemic cytokine response to pneumonia and determine if specific patterns, including the balance of pro-inflammatory and anti-inflammatory markers, are associated with severe sepsis and death. Methods This is a cohort study of 1886 subjects hospitalized with CAP through the emergency departments in 28 US academic and community hospitals. We defined severe sepsis as CAP complicated by new-onset organ dysfunction, following international consensus conference criteria. We measured plasma tumor necrosis factor, IL-6 (interleukin 6), and IL-10 levels daily for the first week and weekly thereafter. Our main outcome measures were severe sepsis and 90-day mortality. Results A total of 583 patients developed severe sepsis (31%), of whom 149 died (26%). Systemic cytokine level elevation occurred in 82% of all subjects with CAP. Mean cytokine concentrations were highest at presentation, declined rapidly over the first few days, but remained elevated throughout the first week, beyond resolution of clinical signs of infection. Cytokine levels were highest in fatal severe sepsis and lowest in CAP with no severe sepsis. Unbalanced (high/low) cytokine patterns were unusual (4.6%) and not associated with decreased survival. Highest risk of death was with combined high levels of the proinflammatory IL-6 and anti-inflammatory IL-10 cytokine activity (hazard ratio, 20.5; 95% confidence interval, 10.8–39.0) (P<.001). Conclusions The circulating cytokine response to pneumonia is heterogeneous and continues for more than a week after presentation, with considerable overlap between those who do and do not develop severe sepsis. Unbalanced activation is uncommon, and

  17. Application of sepsis definitions to pediatric patients admitted with suspected infections in Uganda

    PubMed Central

    Wiens, Matthew O.; Larson, Charles P.; Kumbakumba, Elias; Kissoon, Niranjan; Ansermino, J. Mark; Singer, Joel; Wong, Hubert; Ndamira, Andrew; Kabakyenga, Jerome; Moschovis, Peter; Kiwanuka, Julius

    2017-01-01

    Objectives Acute infectious diseases are the most common cause of under-5 mortality. However, the hospital burden of non-neonatal pediatric sepsis has not previously been described in the resource poor setting. The objective of this study was to determine the prevalence of sepsis among children 6 months to 5 years of age admitted with proven or suspected infection and to evaluate the presence of sepsis as a predictive tool for mortality during admission. Design In this Prospective cohort study we used the pediatric International Consensus Conference definition of sepsis to determine the prevalence of sepsis among children admitted to the pediatric ward with a proven or suspected infection. The diagnosis of sepsis, as well as each individual component of the sepsis definition, were evaluated for capturing in-hospital mortality. Setting The pediatric ward of two hospitals in Mbarara, Uganda Patients Admitted children between 6 months and 5 years with a confirmed or suspected infection. Interventions None Measurements and Main Results One thousand three hundred and seven (1307) subjects with a confirmed or suspected infection were enrolled and 65 children died (5.0%) during their admission. One thousand one hundred and twenty-one (85.9%) met the systemic inflammatory response syndrome criteria, and therefore were defined as having sepsis. The sepsis criteria captured 61 deaths, demonstrating a sensitivity and specificity of 95% (95% CI 90% – 100%) and 15% (95% CI 13% – 17%), respectively. The most discriminatory individual component of the SIRS criteria was the leukocyte count which alone had a sensitivity of 72% and a specificity of 56% for the identification of mortality in hospital. Conclusions This study is among the first to quantify the burden of non-neonatal pediatric sepsis in children with suspected infection, using the international consensus sepsis definition, in a typical resource constrained setting in Africa. This definition was found to be highly

  18. Application of Sepsis Definitions to Pediatric Patients Admitted With Suspected Infections in Uganda.

    PubMed

    Wiens, Matthew O; Larson, Charles P; Kumbakumba, Elias; Kissoon, Niranjan; Ansermino, J Mark; Singer, Joel; Wong, Hubert; Ndamira, Andrew; Kabakyenga, Jerome; Moschovis, Peter; Kiwanuka, Julius

    2016-05-01

    Acute infectious diseases are the most common cause of under-5 mortality. However, the hospital burden of nonneonatal pediatric sepsis has not previously been described in the resource poor setting. The objective of this study was to determine the prevalence of sepsis among children 6 months to 5 years old admitted with proven or suspected infection and to evaluate the presence of sepsis as a predictive tool for mortality during admission. In this prospective cohort study, we used the pediatric International Consensus Conference definition of sepsis to determine the prevalence of sepsis among children admitted to the pediatric ward with a proven or suspected infection. The diagnosis of sepsis, as well as each individual component of the sepsis definition, was evaluated for capturing in-hospital mortality. The pediatric ward of two hospitals in Mbarara, Uganda. Admitted children between 6 months and 5 years with a confirmed or suspected infection. None. One thousand three hundred seven (1,307) subjects with a confirmed or suspected infection were enrolled, and 65 children died (5.0%) during their admission. One thousand one hundred twenty-one (85.9%) met the systemic inflammatory response syndrome criteria, and therefore, they were defined as having sepsis. The sepsis criteria captured 61 deaths, demonstrating a sensitivity and a specificity of 95% (95% CI, 90-100%) and 15% (95% CI, 13-17%), respectively. The most discriminatory individual component of the systemic inflammatory response syndrome criteria was the leukocyte count, which alone had a sensitivity of 72% and a specificity of 56% for the identification of mortality in hospital. This study is among the first to quantify the burden of nonneonatal pediatric sepsis in children with suspected infection, using the international consensus sepsis definition, in a typical resource-constrained setting in Africa. This definition was found to be highly sensitive in identifying those who died but had very low

  19. Differentiating sepsis from non-infectious systemic inflammation based on microvesicle-bacteria aggregation

    NASA Astrophysics Data System (ADS)

    Herrmann, I. K.; Bertazzo, S.; O'Callaghan, D. J. P.; Schlegel, A. A.; Kallepitis, C.; Antcliffe, D. B.; Gordon, A. C.; Stevens, M. M.

    2015-08-01

    Sepsis is a severe medical condition and a leading cause of hospital mortality. Prompt diagnosis and early treatment has a significant, positive impact on patient outcome. However, sepsis is not always easy to diagnose, especially in critically ill patients. Here, we present a conceptionally new approach for the rapid diagnostic differentiation of sepsis from non-septic intensive care unit patients. Using advanced microscopy and spectroscopy techniques, we measure infection-specific changes in the activity of nano-sized cell-derived microvesicles to bind bacteria. We report on the use of a point-of-care-compatible microfluidic chip to measure microvesicle-bacteria aggregation and demonstrate rapid (<=1.5 hour) and reliable diagnostic differentiation of bacterial infection from non-infectious inflammation in a double-blind pilot study. Our study demonstrates the potential of microvesicle activities for sepsis diagnosis and introduces microvesicle-bacteria aggregation as a potentially useful parameter for making early clinical management decisions.Sepsis is a severe medical condition and a leading cause of hospital mortality. Prompt diagnosis and early treatment has a significant, positive impact on patient outcome. However, sepsis is not always easy to diagnose, especially in critically ill patients. Here, we present a conceptionally new approach for the rapid diagnostic differentiation of sepsis from non-septic intensive care unit patients. Using advanced microscopy and spectroscopy techniques, we measure infection-specific changes in the activity of nano-sized cell-derived microvesicles to bind bacteria. We report on the use of a point-of-care-compatible microfluidic chip to measure microvesicle-bacteria aggregation and demonstrate rapid (<=1.5 hour) and reliable diagnostic differentiation of bacterial infection from non-infectious inflammation in a double-blind pilot study. Our study demonstrates the potential of microvesicle activities for sepsis diagnosis and

  20. A Severe Sepsis Mortality Prediction Model and Score for Use with Administrative Data

    PubMed Central

    Ford, Dee W.; Goodwin, Andrew J.; Simpson, Annie N.; Johnson, Emily; Nadig, Nandita; Simpson, Kit N.

    2016-01-01

    Objective Administrative data is used for research, quality improvement, and health policy in severe sepsis. However, there is not a sepsis-specific tool applicable to administrative data with which to adjust for illness severity. Our objective was to develop, internally validate, and externally validate a severe sepsis mortality prediction model and associated mortality prediction score. Design Retrospective cohort study using 2012 administrative data from five US states. Three cohorts of patients with severe sepsis were created: 1) ICD-9-CM codes for severe sepsis/septic shock, 2) ‘Martin’ approach, and 3) ‘Angus’ approach. The model was developed and internally validated in ICD-9-CM cohort and externally validated in other cohorts. Integer point values for each predictor variable were generated to create a sepsis severity score. Setting Acute care, non-federal hospitals in NY, MD, FL, MI, and WA Subjects Patients in one of three severe sepsis cohorts: 1) explicitly coded (n=108,448), 2) Martin cohort (n=139,094), and 3) Angus cohort (n=523,637) Interventions None Measurements and Main Results Maximum likelihood estimation logistic regression to develop a predictive model for in-hospital mortality. Model calibration and discrimination assessed via Hosmer-Lemeshow goodness-of-fit (GOF) and C-statistics respectively. Primary cohort subset into risk deciles and observed versus predicted mortality plotted. GOF demonstrated p>0.05 for each cohort demonstrating sound calibration. C-statistic ranged from low of 0.709 (sepsis severity score) to high of 0.838 (Angus cohort) suggesting good to excellent model discrimination. Comparison of observed versus expected mortality was robust although accuracy decreased in highest risk decile. Conclusions Our sepsis severity model and score is a tool that provides reliable risk adjustment for administrative data. PMID:26496452

  1. Outcome of infants with unrepaired heart disease admitted to the pediatric intensive care unit: single-center developing country perspective.

    PubMed

    Mohsin, Shazia Samad; Haque, Anwarul; Shaikh, Abdul Sattar; Bano, Surraiya; Hasan, Babar Sultan

    2014-01-01

    Congenital heart disease (CHD) has an incidence of ∼0.8-1%. Outcome of previously diagnosed CHD patients awaiting surgery (either correction or palliation) in a developing country setting is unknown. We strive to determine the outcome of patients with CHD awaiting surgery who present to pediatric intensive care unit (PICU) setting with an acute illness. Retrospective cross-sectional chart review. Pediatric intensive care unit of The Aga Khan University Hospital, Karachi, Pakistan. Medical records of infants (1-12 months) with CHD awaiting surgery presenting to the PICU with an acute illness between January 2009 and June 2012 were included. Newly diagnosed CHD patients, those not requiring PICU admission, and those transferred to another hospital were excluded. A total of 34 infants met the inclusion criteria. Median age at presentation was 5 months. Seventy-four percent of the infants had CHD lesion characterized by increased pulmonary blood flow (shunt lesions). Though none of the patients met the strict criteria for sepsis or pneumonia, 74% were admitted with a diagnosis of pneumonia or sepsis. Only 15% of patient had congestive heart failure as an admitting diagnosis. Oxygen therapy was given to 94% of these patients. Fifty-nine percent of these patients expired during the admission, 95% of those expired had multiorgan dysfunction. Patients with CHD awaiting surgery and who admitted to the PICU with acute illness are at high risk for mortality. Stringent criteria to diagnose pneumonia or sepsis should be used in these patients. © 2013 Wiley Periodicals, Inc.

  2. The clinical utility of fibrin-related biomarkers in sepsis.

    PubMed

    Toh, Julien M H; Ken-Dror, Gie; Downey, Colin; Abrams, Simon T

    2013-12-01

    Sepsis is associated with systemic inflammatory responses and induction of intravascular fibrin formation. Our aim is to investigate whether three fibrin-related markers (FRM) reflect the extent of coagulation activation in vivo and evaluate their clinical usefulness in identifying as well as monitoring patients with sepsis. Fibrin-degradation products (FDP), D-dimer and soluble fibrin monomer assays were measured on plasma samples from patients in the ICU with sepsis (n = 37), systemic inflammatory response syndrome (SIRS) (n = 35) and healthy individuals (n = 15). The levels were correlated with each other and also with fibrinogen, prothrombin time, platelets and antithrombin III. Clinical correlation was also performed for the diagnosis of sepsis and longitudinal monitoring for survival or death.There was strong correlation between the three FRM (r = 0.38-0.93, P < 0.0001) with only fibrin monomer correlating significantly with prothrombin time, fibrinogen and platelet levels. Clinically, all three FRM could discriminate between patients with sepsis, SIRS and healthy individuals with FDP, and D-dimer showing statistical significance (P < 0.05). No FRM predicted outcome from a single measurement but FDP was significantly able to predict patient survival from serial samples [mean FDP (μg/ml) from 35.36 to 21.37 (first to third ICU-day), P < 0.05]. Fibrin monomer appears the most sensitive indicator of coagulation activation, whereas D-dimer and FDP levels can significantly differentiate ICU patients with sepsis from those without. In addition, FDP would be preferable for monitoring with its statistically significant time-dependent prediction of survival or death from sepsis.

  3. Endothelial glycocalyx degradation is more severe in patients with non-pulmonary sepsis compared to pulmonary sepsis and associates with risk of ARDS and other organ dysfunction.

    PubMed

    Murphy, Laura S; Wickersham, Nancy; McNeil, J Brennan; Shaver, Ciara M; May, Addison K; Bastarache, Julie A; Ware, Lorraine B

    2017-10-06

    Disruption of the endothelial glycocalyx contributes to acute lung injury in experimental sepsis but has not been well studied in humans. To study glycocalyx degradation in sepsis-induced ARDS, we measured plasma levels of syndecan-1, a marker for glycocalyx degradation. The present study is a retrospective observational study of 262 ventilated medical ICU patients at risk of ARDS due to severe sepsis and APACHE II ≥ 25. Plasma syndecan-1 was measured at study enrollment. Primary analysis focused on the association between syndecan-1 levels and the development of ARDS, other organ dysfunction (Brussels criteria), or in-hospital mortality. Overall, 135 (52%) patients developed ARDS. In patients with non-pulmonary sepsis, syndecan-1 levels were associated with ARDS (p = 0.05). Regardless of etiology of sepsis, higher syndecan-1 levels were associated with hepatic (p < 0.001), renal (p = 0.003), coagulation (p = 0.001), and circulatory (p = 0.02) failure as well as in-hospital mortality (p = 0.001), and there was a significant association between syndecan-1 levels and the number of vasopressors required in the first 24 h (p < 0.001). In addition, elevated syndecan levels were independently predictive of mortality in multivariable logistic regression adjusted for age and APACHE II score (odds ratio 1.85 per log increase in syndecan-1, 95% CI 1.056-3.241, p = 0.03). The extent of endothelial glycocalyx degradation is associated with non-pulmonary organ dysfunction in subjects with sepsis and is associated with ARDS but only in the subgroup with non-pulmonary sepsis. Measurement of syndecan-1 levels in sepsis patients might be useful for identifying patients at high risk of organ dysfunction and mortality as well as those who could benefit from therapies targeted at protecting or restoring the glycocalyx.

  4. Systemic inflammatory response syndrome-based severe sepsis screening algorithms in emergency department patients with suspected sepsis.

    PubMed

    Shetty, Amith L; Brown, Tristam; Booth, Tarra; Van, Kim Linh; Dor-Shiffer, Daphna E; Vaghasiya, Milan R; Eccleston, Cassanne E; Iredell, Jonathan

    2016-06-01

    Systemic inflammatory response syndrome (SIRS)-based severe sepsis screening algorithms have been utilised in stratification and initiation of early broad spectrum antibiotics for patients presenting to EDs with suspected sepsis. We aimed to investigate the performance of some of these algorithms on a cohort of suspected sepsis patients. We conducted a retrospective analysis on an ED-based prospective sepsis registry at a tertiary Sydney hospital, Australia. Definitions for sepsis were based on the 2012 Surviving Sepsis Campaign guidelines. Numerical values for SIRS criteria and ED investigation results were recorded at the trigger of sepsis pathway on the registry. Performance of specific SIRS-based screening algorithms at sites from USA, Canada, UK, Australia and Ireland health institutions were investigated. Severe sepsis screening algorithms' performance was measured on 747 patients presenting with suspected sepsis (401 with severe sepsis, prevalence 53.7%). Sensitivity and specificity of algorithms to flag severe sepsis ranged from 20.2% (95% CI 16.4-24.5%) to 82.3% (95% CI 78.2-85.9%) and 57.8% (95% CI 52.4-63.1%) to 94.8% (95% CI 91.9-96.9%), respectively. Variations in SIRS values between uncomplicated and severe sepsis cohorts were only minor, except a higher mean lactate (>1.6 mmol/L, P < 0.01). We found the Ireland and JFK Medical Center sepsis algorithms performed modestly in stratifying suspected sepsis patients into high-risk groups. Algorithms with lactate levels thresholds of >2 mmol/L rather than >4 mmol/L performed better. ED sepsis registry-based characterisation of patients may help further refine sepsis definitions of the future. © 2016 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

  5. The role of genetics and antibodies in sepsis

    PubMed Central

    Giamarellos-Bourboulis, Evangelos J.

    2016-01-01

    During the course of sepsis when immunosuppression predominates, the concentrations of circulating immunoglobulins (IGs) are decreased and this is associated with adverse outcomes. The production of IGs as response to invasive bacterial pathogens takes place through a complex pathway starting from the recognition of the antigen (Ag) by innate immune cells that process and present Ags to T cells. The orchestration of T-helper (Th) lymphocyte responses directs specific B cells and ends with the production of IGs by plasma cells. All molecules implicated in this process are encoded by genes bearing single nucleotide polymorphisms (SNPs). Meta-analysis of case-control studies have shown that the carriage of minor frequency SNPs of CD14, TLR2 and TNF is associated with increased sepsis risk. The ambiguity of results of clinical trials studying the clinical efficacy of exogenous IG administration in sepsis suggests that efficacy of treatment should be considered after adjustment for SNPs of all implicated genes in the pathway of IG production. PMID:27713886

  6. The role of genetics and antibodies in sepsis.

    PubMed

    Giamarellos-Bourboulis, Evangelos J; Opal, Steven M

    2016-09-01

    During the course of sepsis when immunosuppression predominates, the concentrations of circulating immunoglobulins (IGs) are decreased and this is associated with adverse outcomes. The production of IGs as response to invasive bacterial pathogens takes place through a complex pathway starting from the recognition of the antigen (Ag) by innate immune cells that process and present Ags to T cells. The orchestration of T-helper (Th) lymphocyte responses directs specific B cells and ends with the production of IGs by plasma cells. All molecules implicated in this process are encoded by genes bearing single nucleotide polymorphisms (SNPs). Meta-analysis of case-control studies have shown that the carriage of minor frequency SNPs of CD14 , TLR2 and TNF is associated with increased sepsis risk. The ambiguity of results of clinical trials studying the clinical efficacy of exogenous IG administration in sepsis suggests that efficacy of treatment should be considered after adjustment for SNPs of all implicated genes in the pathway of IG production.

  7. S100A8/A9 Drives Neuroinflammatory Priming and Protects against Anxiety-like Behavior after Sepsis.

    PubMed

    Denstaedt, Scott J; Spencer-Segal, Joanna L; Newstead, Michael W; Laborc, Klaudia; Zhao, Anne P; Hjelmaas, Alexander; Zeng, Xianying; Akil, Huda; Standiford, Theodore J; Singer, Benjamin H

    2018-05-01

    Sepsis commonly results in acute and chronic brain dysfunction, which dramatically increases the morbidity associated with this common disease. Chronic brain dysfunction in animal models of sepsis survival is linked to persistent neuroinflammation and expression of multiple cytokines. However, we have found previously that microglia predominantly upregulate the damage associated molecule S100A8/A9 after sepsis. In this article, we show that S100A8/A9 is increased in the brains of patients who died of sepsis and that S100A8 is expressed in astrocytes and myeloid cells. Using a mouse model of sepsis survival, we show that S100A8/A9 is persistently expressed in the brain after sepsis. S100A9 expression is necessary for recruitment of neutrophils to the brain and for priming production of reactive oxygen species and TNF-α secretion in microglia and macrophages. However, despite improving these indices of chronic inflammation, S100A9 deficiency results in worsened anxiety-like behavior 2 wk after sepsis. Taken together, these results indicate that S100A8/A9 contributes to several facets of neuroinflammation in sepsis survivor mice, including granulocyte recruitment and priming of microglial-reactive oxygen species and cytokine production, and that these processes may be protective against anxiety behavior in sepsis survivors. Copyright © 2018 by The American Association of Immunologists, Inc.

  8. Pediatric sepsis

    PubMed Central

    Randolph, Adrienne G; McCulloh, Russell J

    2014-01-01

    Sepsis is the leading cause of death in children worldwide. Although the diagnosis and management of sepsis in infants and children is largely influenced by studies done in adults, there are important considerations relevant for pediatrics. This article highlights pediatric-specific issues related to the definition of sepsis and its epidemiology and management. We review how the capacity of the immune system to respond to infection develops over early life. We also bring attention to primary immune deficiencies that should be considered in children recurrently infected with specific types of organisms. The management of pediatric sepsis must be tailored to the child’s age and immune capacity, and to the site, severity, and source of the infection. It is important for clinicians to be aware of infection-related syndromes that primarily affect children. Although children in developed countries are more likely to survive severe infections than adults, many survivors have chronic health impairments. PMID:24225404

  9. New Sepsis Definition (Sepsis-3) and Community-acquired Pneumonia Mortality. A Validation and Clinical Decision-Making Study.

    PubMed

    Ranzani, Otavio T; Prina, Elena; Menéndez, Rosario; Ceccato, Adrian; Cilloniz, Catia; Méndez, Raul; Gabarrus, Albert; Barbeta, Enric; Bassi, Gianluigi Li; Ferrer, Miquel; Torres, Antoni

    2017-11-15

    The Sepsis-3 Task Force updated the clinical criteria for sepsis, excluding the need for systemic inflammatory response syndrome (SIRS) criteria. The clinical implications of the proposed flowchart including the quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA) and SOFA scores are unknown. To perform a clinical decision-making analysis of Sepsis-3 in patients with community-acquired pneumonia. This was a cohort study including adult patients with community-acquired pneumonia from two Spanish university hospitals. SIRS, qSOFA, the Confusion, Respiratory Rate and Blood Pressure (CRB) score, modified SOFA (mSOFA), the Confusion, Urea, Respiratory Rate, Blood Pressure and Age (CURB-65) score, and Pneumonia Severity Index (PSI) were calculated with data from the emergency department. We used decision-curve analysis to evaluate the clinical usefulness of each score and the primary outcome was in-hospital mortality. Of 6,874 patients, 442 (6.4%) died in-hospital. SIRS presented the worst discrimination, followed by qSOFA, CRB, mSOFA, CURB-65, and PSI. Overall, overestimation of in-hospital mortality and miscalibration was more evident for qSOFA and mSOFA. SIRS had lower net benefit than qSOFA and CRB, significantly increasing the risk of over-treatment and being comparable with the "treat-all" strategy. PSI had higher net benefit than mSOFA and CURB-65 for mortality, whereas mSOFA seemed more applicable when considering mortality/intensive care unit admission. Sepsis-3 flowchart resulted in better identification of patients at high risk of mortality. qSOFA and CRB outperformed SIRS and presented better clinical usefulness as prompt tools for patients with community-acquired pneumonia in the emergency department. Among the tools for a comprehensive patient assessment, PSI had the best decision-aid tool profile.

  10. Low Socioeconomic Status Is Associated with Prolonged Times to Assessment and Treatment, Sepsis and Infectious Death in Pediatric Fever in El Salvador

    PubMed Central

    Gavidia, Ronald; Fuentes, Soad L.; Vasquez, Roberto; Bonilla, Miguel; Ethier, Marie-Chantal; Diorio, Caroline; Caniza, Miguela; Howard, Scott C.; Sung, Lillian

    2012-01-01

    Background Infection remains the most common cause of death from toxicity in children with cancer in low- and middle-income countries. Rapid administration of antibiotics when fever develops can prevent progression to sepsis and shock, and serves as an important indicator of the quality of care in children with acute lymphoblastic leukemia and acute myeloid leukemia. We analyzed factors associated with (1) Longer times from fever onset to hospital presentation/antibiotic treatment and (2) Sepsis and infection-related mortality. Method This prospective cohort study included children aged 0–16 years with newly diagnosed acute leukemia treated at Benjamin Bloom Hospital, San Salvador. We interviewed parents/caregivers within one month of diagnosis and at the onset of each new febrile episode. Times from initial fever to first antibiotic administration and occurrence of sepsis and infection-related mortality were documented. Findings Of 251 children enrolled, 215 had acute lymphoblastic leukemia (85.7%). Among 269 outpatient febrile episodes, median times from fever to deciding to seek medical care was 10.0 hours (interquartile range [IQR] 5.0–20.0), and from decision to seek care to first hospital visit was 1.8 hours (IQR 1.0–3.0). Forty-seven (17.5%) patients developed sepsis and 7 (2.6%) died of infection. Maternal illiteracy was associated with longer time from fever to decision to seek care (P = 0.029) and sepsis (odds ratio [OR] 3.06, 95% confidence interval [CI] 1.09–8.63; P = 0.034). More infectious deaths occurred in those with longer travel time to hospital (OR 1.36, 95% CI 1.03–1.81; P = 0.031) and in families with an annual household income sepsis and infectious mortality in pediatric leukemia. Providing additional education to high-risk families

  11. S1PR3 Signaling Drives Bacterial Killing and Is Required for Survival in Bacterial Sepsis.

    PubMed

    Hou, JinChao; Chen, QiXing; Wu, XiaoLiang; Zhao, DongYan; Reuveni, Hadas; Licht, Tamar; Xu, MengLong; Hu, Hu; Hoeft, Andreas; Ben-Sasson, Shmuel A; Shu, Qiang; Fang, XiangMing

    2017-12-15

    Efficient elimination of pathogenic bacteria is a critical determinant in the outcome of sepsis. Sphingosine-1-phosphate receptor 3 (S1PR3) mediates multiple aspects of the inflammatory response during sepsis, but whether S1PR3 signaling is necessary for eliminating the invading pathogens remains unknown. To investigate the role of S1PR3 in antibacterial immunity during sepsis. Loss- and gain-of-function experiments were performed using cell and murine models. S1PR3 levels were determined in patients with sepsis and healthy volunteers. S1PR3 protein levels were up-regulated in macrophages upon bacterial stimulation. S1pr3 -/- mice showed increased mortality and increased bacterial burden in multiple models of sepsis. The transfer of wild-type bone marrow-derived macrophages rescued S1pr3 -/- mice from lethal sepsis. S1PR3-overexpressing macrophages further ameliorated the mortality rate of sepsis. Loss of S1PR3 led to markedly decreased bacterial killing in macrophages. Enhancing endogenous S1PR3 activity using a peptide agonist potentiated the macrophage bactericidal function and improved survival rates in multiple models of sepsis. Mechanically, the reactive oxygen species levels were decreased and phagosome maturation was delayed in S1pr3 -/- macrophages due to impaired recruitment of vacuolar protein-sorting 34 to the phagosomes. In addition, S1RP3 expression levels were elevated in monocytes from patients with sepsis. Higher levels of monocytic S1PR3 were associated with efficient intracellular bactericidal activity, better immune status, and preferable outcomes. S1PR3 signaling drives bacterial killing and is essential for survival in bacterial sepsis. Interventions targeting S1PR3 signaling could have translational implications for manipulating the innate immune response to combat pathogens.

  12. Activation of Invariant Natural Killer T Cells Redirects the Inflammatory Response in Neonatal Sepsis.

    PubMed

    Bolognese, Alexandra C; Yang, Weng-Lang; Hansen, Laura W; Sharma, Archna; Nicastro, Jeffrey M; Coppa, Gene F; Wang, Ping

    2018-01-01

    Sepsis is the third leading cause of death in the neonatal population, due to susceptibility to infection conferred by immaturity of both the innate and adaptive components of the immune system. Invariant natural killer T (iNKT) cells are specialized adaptive immune cells that possess important innate-like characteristics and have not yet been well-studied in septic neonates. We hypothesized that iNKT cells would play an important role in mediating the neonatal immune response to sepsis. To study this, we subjected 5- to 7-day-old neonatal C57BL/6 mice to sepsis by intraperitoneal (i.p.) cecal slurry (CS) injection. Thirty hours prior to or immediately following sepsis induction, pups received i.p. injection of the iNKT stimulator KRN7000 (KRN, 0.2 µg/g) or vehicle. Ten hours after CS injection, blood and tissues were collected for various analyses. Thirty-hour pretreatment with KRN resulted in better outcomes in inflammation, lung injury, and survival, while immediate treatment with KRN resulted in worse outcomes compared to vehicle treatment. We further analyzed the activation status of neonatal iNKT cells for 30 h after KRN administration, and showed a peak in frequency of CD69 expression on iNKT cells and serum IFN-γ levels at 5 and 10 h, respectively. We then used CD1d knockout neonatal mice to demonstrate that KRN acts through the major histocompatibility complex-like molecule CD1d to improve outcomes in neonatal sepsis. Finally, we identified that KRN pretreatment exerts its protective effect by increasing systemic levels of TGF-β1. These findings support the importance of iNKT cells for prophylactic immunomodulation in neonates susceptible to sepsis.

  13. Identification of MicroRNA as Sepsis Biomarker Based on miRNAs Regulatory Network Analysis

    PubMed Central

    Huang, Jie; Sun, Zhandong; Yan, Wenying; Zhu, Yujie; Lin, Yuxin; Chen, Jiajai; Shen, Bairong

    2014-01-01

    Sepsis is regarded as arising from an unusual systemic response to infection but the physiopathology of sepsis remains elusive. At present, sepsis is still a fatal condition with delayed diagnosis and a poor outcome. Many biomarkers have been reported in clinical application for patients with sepsis, and claimed to improve the diagnosis and treatment. Because of the difficulty in the interpreting of clinical features of sepsis, some biomarkers do not show high sensitivity and specificity. MicroRNAs (miRNAs) are small noncoding RNAs which pair the sites in mRNAs to regulate gene expression in eukaryotes. They play a key role in inflammatory response, and have been validated to be potential sepsis biomarker recently. In the present work, we apply a miRNA regulatory network based method to identify novel microRNA biomarkers associated with the early diagnosis of sepsis. By analyzing the miRNA expression profiles and the miRNA regulatory network, we obtained novel miRNAs associated with sepsis. Pathways analysis, disease ontology analysis, and protein-protein interaction network (PIN) analysis, as well as ROC curve, were exploited to testify the reliability of the predicted miRNAs. We finally identified 8 novel miRNAs which have the potential to be sepsis biomarkers. PMID:24809055

  14. Angiopoietin-1, Angiopoietin-2 and Bicarbonate as Diagnostic Biomarkers in Children with Severe Sepsis

    PubMed Central

    Wang, Kun; Bhandari, Vineet; Giuliano, John S.; O′Hern, Corey S.; Shattuck, Mark D.; Kirby, Michael

    2014-01-01

    Severe pediatric sepsis continues to be associated with high mortality rates in children. Thus, an important area of biomedical research is to identify biomarkers that can classify sepsis severity and outcomes. The complex and heterogeneous nature of sepsis makes the prospect of the classification of sepsis severity using a single biomarker less likely. Instead, we employ machine learning techniques to validate the use of a multiple biomarkers scoring system to determine the severity of sepsis in critically ill children. The study was based on clinical data and plasma samples provided by a tertiary care center's Pediatric Intensive Care Unit (PICU) from a group of 45 patients with varying sepsis severity at the time of admission. Canonical Correlation Analysis with the Forward Selection and Random Forests methods identified a particular set of biomarkers that included Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2), and Bicarbonate (HCO) as having the strongest correlations with sepsis severity. The robustness and effectiveness of these biomarkers for classifying sepsis severity were validated by constructing a linear Support Vector Machine diagnostic classifier. We also show that the concentrations of Ang-1, Ang-2, and HCO enable predictions of the time dependence of sepsis severity in children. PMID:25255212

  15. A Multicentre Study of Acute Kidney Injury in Severe Sepsis and Septic Shock: Association with Inflammatory Phenotype and HLA Genotype

    PubMed Central

    Legrand, Matthieu; Gayat, Etienne; Faivre, Valérie; Megarbane, Bruno; Azoulay, Elie; Fieux, Fabienne; Charron, Dominique; Loiseau, Pascale; Busson, Marc

    2012-01-01

    Background To investigate the association between severity of acute kidney injury (AKI) and outcome, systemic inflammatory phenotype and HLA genotype in severe sepsis. Methodology/Principal Findings Prospective multicenter observational study done in 4 intensive care units in two university hospitals. Severe sepsis and septic shock patients with at least 2 organ failures based on the SOFA score were classified: 1) "no AKI", 2) "mild AKI" (grouping stage 1 and 2 of AKIN score) and 3) "severe AKI" (stage 3 of AKIN score). Sequential measurements: The vasopressor dependency index (VDI; dose and types of drugs) to evaluate the association between hemodynamic status and the development of early AKI; plasma levels of IL-10, macrophage migration inhibitory factor (MIF), IL-6 and HLA-DR monocyte expression. Genotyping of the 13 HLA-DRB1 alleles with deduction of presence of HLA-DRB3, -DRB4 and -DRB5 genes. We used multivariate analysis with competitive risk model to study associations. Overall, 176 study patients (146 with septic shock) were classified from AKIN score as "no AKI" (n = 43), "mild AKI" (n = 74) or "severe AKI" (n = 59). The VDI did not differ between groups of AKI. After adjustment, "mild and severe AKI" were an independent risk factor for mortality (HR 2.42 95%CI[1.01-5.83], p = 0.048 and HR 1.99 95%CI[1.30-3.03], p = 0.001 respectively). "Severe AKI" had higher levels of plasma IL-10, MIF and IL-6 compared to “no AKI” and mild AKI (p<0.05 for each), with no difference in mHLA-DR at day 0. HLA-DRB genotyping showed a significantly lower proportion of 4 HLA-DRB alleles among patients requiring renal replacement therapy (RRT) (58%) than in patients with severe AKI who did not receive RRT (84%) (p = 0.004). Conclusions AKI severity is independently associated with mortality and plasma IL-10, MIF or IL-6 levels. Presence of 4 alleles of HLA-DRB in severe AKI patients seems associated with a lower need of RRT. PMID:22701553

  16. Increased expression of neutrophil-related genes in patients with early sepsis-induced ARDS.

    PubMed

    Kangelaris, Kirsten Neudoerffer; Prakash, Arun; Liu, Kathleen D; Aouizerat, Bradley; Woodruff, Prescott G; Erle, David J; Rogers, Angela; Seeley, Eric J; Chu, Jeffrey; Liu, Tom; Osterberg-Deiss, Thomas; Zhuo, Hanjing; Matthay, Michael A; Calfee, Carolyn S

    2015-06-01

    The early sequence of events leading to the development of the acute respiratory distress syndrome (ARDS) in patients with sepsis remains inadequately understood. The purpose of this study was to identify changes in gene expression early in the course of illness, when mechanisms of injury may provide the most relevant treatment and prognostic targets. We collected whole blood RNA in critically ill patients admitted from the Emergency Department to the intensive care unit within 24 h of admission at a tertiary care center. Whole genome expression was compared in patients with sepsis and ARDS to patients with sepsis alone. We selected genes with >1 log2 fold change and false discovery rate <0.25, determined their significance in the literature, and performed pathway analysis. Several genes were upregulated in 29 patients with sepsis with ARDS compared with 28 patients with sepsis alone. The most differentially expressed genes included key mediators of the initial neutrophil response to infection: olfactomedin 4, lipocalin 2, CD24, and bactericidal/permeability-increasing protein. These gene expression differences withstood adjustment for age, sex, study batch, white blood cell count, and presence of pneumonia or aspiration. Pathway analysis demonstrated overrepresentation of genes involved in known respiratory and infection pathways. These data indicate that several neutrophil-related pathways may be involved in the early pathogenesis of sepsis-related ARDS. In addition, identifiable gene expression differences occurring early in the course of sepsis-related ARDS may further elucidate understanding of the neutrophil-related mechanisms in progression to ARDS. Copyright © 2015 the American Physiological Society.

  17. Increased expression of neutrophil-related genes in patients with early sepsis-induced ARDS

    PubMed Central

    Prakash, Arun; Liu, Kathleen D.; Aouizerat, Bradley; Woodruff, Prescott G.; Erle, David J.; Rogers, Angela; Seeley, Eric J.; Chu, Jeffrey; Liu, Tom; Osterberg-Deiss, Thomas; Zhuo, Hanjing; Matthay, Michael A.; Calfee, Carolyn S.

    2015-01-01

    The early sequence of events leading to the development of the acute respiratory distress syndrome (ARDS) in patients with sepsis remains inadequately understood. The purpose of this study was to identify changes in gene expression early in the course of illness, when mechanisms of injury may provide the most relevant treatment and prognostic targets. We collected whole blood RNA in critically ill patients admitted from the Emergency Department to the intensive care unit within 24 h of admission at a tertiary care center. Whole genome expression was compared in patients with sepsis and ARDS to patients with sepsis alone. We selected genes with >1 log2 fold change and false discovery rate <0.25, determined their significance in the literature, and performed pathway analysis. Several genes were upregulated in 29 patients with sepsis with ARDS compared with 28 patients with sepsis alone. The most differentially expressed genes included key mediators of the initial neutrophil response to infection: olfactomedin 4, lipocalin 2, CD24, and bactericidal/permeability-increasing protein. These gene expression differences withstood adjustment for age, sex, study batch, white blood cell count, and presence of pneumonia or aspiration. Pathway analysis demonstrated overrepresentation of genes involved in known respiratory and infection pathways. These data indicate that several neutrophil-related pathways may be involved in the early pathogenesis of sepsis-related ARDS. In addition, identifiable gene expression differences occurring early in the course of sepsis-related ARDS may further elucidate understanding of the neutrophil-related mechanisms in progression to ARDS. PMID:25795726

  18. [Sepsis caused by methicillin-resistant Staphylococcus aureus: the shadow of a persistent threat].

    PubMed

    Sifuentes-Osornio, José; Pérez-Patrigeon, Santiago

    2006-01-01

    Clinical case. This 27 year-old male was referred admitted with severe acute pancreatitis (SAP) after heavy consumption of alcohol and sepsis (bacteremia and multilobar pneumonia) due to methicillin-resistant Staphylococcus aureus (MRSA); he required mechanical ventilation and haemodyalisis, and developed fungemia by fluconazol-resistant Candida albicans. He was treated with caspofungin for 20 days and vancomycin for six weeks, and he was discharged after 51 days of hospitalization. This case shows the painful evolution of a patient admitted to the intensive care unit (ICU) with MRSA sepsis. According to the National Nosocomial Infections Study (USA), S. aureus is the cause of up to 35% of hospital-acquired pneumonia and bacteremia. Using molecular tools (e.g. pulse gel electrophoresis), different families of MRSA have been well described. Use of i.v. catheters, long-term hospitalization, surgery and previous use of antimicrobials are considered major risk factors for MRSA. In Mexico, Alpuche-Aranda, et al (1986) reported a prevalence of 5% in a pediatric hospital. However, a recent report from the National Resistance Network showed a MRSA prevalence of 36% in 2004. In this institution, we observed a rate of MRSA of 100% in the ICU during 2005. This case shows an episode of SAP after heavy alcohol consumption, complicated with severe infections such as candidemia and MRSA sepsis; fortunately he had a favorable outcome after a multidisciplinary and aggressive approach. This case fulfilled all the risk factors for an MRSA infection, in a setting with a very high rate of methicillin-resistance, which compels the medical community to implement adequate and efficacious epidemiological control measures.

  19. Endothelial biomarkers in human sepsis: pathogenesis and prognosis for ARDS

    PubMed Central

    Hendrickson, Carolyn M.; Matthay, Michael A.

    2018-01-01

    Experimental models of sepsis in small and large animals and a variety of in vitro preparations have established several basic mechanisms that drive endothelial injury. This review is focused on what can be learned from the results of clinical studies of plasma biomarkers of endothelial injury and inflammation in patients with sepsis. There is excellent evidence that elevated plasma levels of several biomarkers of endothelial injury, including von Willebrand factor antigen (VWF), angiopoietin-2 (Ang-2), and soluble fms-like tyrosine kinase 1 (sFLT-1), and biomarkers of inflammation, especially interleukin-8 (IL-8) and soluble tumor necrosis factor receptor (sTNFr), identify sepsis patients with a higher mortality. There are also some data that elevated levels of endothelial biomarkers can identify which patients with non-pulmonary sepsis will develop acute respiratory distress syndrome (ARDS). If ARDS patients are divided among those with indirect versus direct lung injury, then there is an association of elevated levels of endothelial biomarkers in indirect injury and markers of inflammation and alveolar epithelial injury in patients with direct lung injury. New research suggests that the combination of biologic and clinical markers may make it possible to segregate patients with ARDS into hypo- versus hyper-inflammatory phenotypes that may have implications for therapeutic responses to fluid therapy. Taken together, the studies reviewed here support a primary role of the microcirculation in the pathogenesis and prognosis of ARDS after sepsis. Biological differences identified by molecular patterns could explain heterogeneity of treatment effects that are not explained by clinical factors alone. PMID:29575977

  20. Development of a novel score for the prediction of hospital mortality in patients with severe sepsis: the use of electronic healthcare records with LASSO regression.

    PubMed

    Zhang, Zhongheng; Hong, Yucai

    2017-07-25

    There are several disease severity scores being used for the prediction of mortality in critically ill patients. However, none of them was developed and validated specifically for patients with severe sepsis. The present study aimed to develop a novel prediction score for severe sepsis. A total of 3206 patients with severe sepsis were enrolled, including 1054 non-survivors and 2152 survivors. The LASSO score showed the best discrimination (area under curve: 0.772; 95% confidence interval: 0.735-0.810) in the validation cohort as compared with other scores such as simplified acute physiology score II, acute physiological score III, Logistic organ dysfunction system, sequential organ failure assessment score, and Oxford Acute Severity of Illness Score. The calibration slope was 0.889 and Brier value was 0.173. The study employed a single center database called Medical Information Mart for Intensive Care-III) MIMIC-III for analysis. Severe sepsis was defined as infection and acute organ dysfunction. Clinical and laboratory variables used in clinical routines were included for screening. Subjects without missing values were included, and the whole dataset was split into training and validation cohorts. The score was coined LASSO score because variable selection was performed using the least absolute shrinkage and selection operator (LASSO) technique. Finally, the LASSO score was evaluated for its discrimination and calibration in the validation cohort. The study developed the LASSO score for mortality prediction in patients with severe sepsis. Although the score had good discrimination and calibration in a randomly selected subsample, external validations are still required.

  1. Cytokines in Sepsis: Potent Immunoregulators and Potential Therapeutic Targets—An Updated View

    PubMed Central

    Bernhagen, Jürgen; Bucala, Richard

    2013-01-01

    Sepsis and septic shock are among the leading causes of death in intensive care units worldwide. Numerous studies on their pathophysiology have revealed an imbalance in the inflammatory network leading to tissue damage, organ failure, and ultimately, death. Cytokines are important pleiotropic regulators of the immune response, which have a crucial role in the complex pathophysiology underlying sepsis. They have both pro- and anti-inflammatory functions and are capable of coordinating effective defense mechanisms against invading pathogens. On the other hand, cytokines may dysregulate the immune response and promote tissue-damaging inflammation. In this review, we address the current knowledge of the actions of pro- and anti-inflammatory cytokines in sepsis pathophysiology as well as how these cytokines and other important immunomodulating agents may be therapeutically targeted to improve the clinical outcome of sepsis. PMID:23853427

  2. Liver maximum capacity (LiMAx) test as a helpful prognostic tool in acute liver failure with sepsis: a case report.

    PubMed

    Buechter, Matthias; Gerken, Guido; Hoyer, Dieter P; Bertram, Stefanie; Theysohn, Jens M; Thodou, Viktoria; Kahraman, Alisan

    2018-06-20

    Acute liver failure (ALF) is a life-threatening entity particularly when infectious complications worsen the clinical course. Urgent liver transplantation (LT) is frequently the only curative treatment. However, in some cases, recovery is observed under conservative treatment. Therefore, prognostic tools for estimating course of the disease are of great clinical interest. Since laboratory parameters sometimes lack sensitivity and specificity, enzymatic liver function measured by liver maximum capacity (LiMAx) test may offer novel and valuable additional information in this setting. We here report the case of a formerly healthy 20-year old male caucasian patient who was admitted to our clinic for ALF of unknown origin in December 2017. Laboratory parameters confirmed the diagnosis with an initial MELD score of 28 points. Likewise, enzymatic liver function was significantly impaired with a value of 147 [> 315] μg/h/kg. Clinical and biochemical analyses for viral-, autoimmune-, or drug-induced hepatitis were negative. Liver synthesis parameters further deteriorated reaching a MELD score of 40 points whilst clinical course was complicated by septic pneumonia leading to severe hepatic encephalopathy grade III-IV, finally resulting in mechanical ventilation of the patient. Interestingly, although clinical course and laboratory data suggested poor outcome, serial LiMAx test revealed improvement of the enzymatic liver function at this time point increasing to 169 μg/h/kg. Clinical condition and laboratory data slowly improved likewise, however with significant time delay of 11 days. Finally, the patient could be dismissed from our clinic after 37 days. Estimating prognosis in patients with ALF is challenging by use of the established scores. In our case, improvement of enzymatic liver function measured by the LiMAx test was the first parameter predicting beneficial outcome in a patient with ALF complicated by sepsis.

  3. Sepsis in Pediatric Cardiac Intensive Care.

    PubMed

    Wheeler, Derek S; Wong, Hector R

    2016-08-01

    In this review, we will discuss risk factors for developing sepsis; the role of biomarkers in establishing an early diagnosis, in monitoring therapeutic efficacy, in stratification, and for the identification of sepsis endotypes; and the pathophysiology and management of severe sepsis and septic shock, with an emphasis on the impact of sepsis on cardiovascular function. MEDLINE and PubMed. There is a lot of excitement in the field of sepsis research today. Scientific advances in the diagnosis and clinical staging of sepsis, as well as a personalized approach to the treatment of sepsis, offer tremendous promise for the future. However, at the same time, it is also evident that sepsis mortality has not improved enough, even with progress in our understanding of the molecular pathophysiology of sepsis.

  4. Healthcare infrastructure capacity to respond to severe acute respiratory infection (SARI) and sepsis in Vietnam: A low-middle income country.

    PubMed

    Dat, Vu Quoc; Long, Nguyen Thanh; Giang, Kim Bao; Diep, Pham Bich; Giang, Ta Hoang; Diaz, Janet V

    2017-12-01

    This study investigated the availability of relevant structural and human resources needed for the clinical management of patients with severe acute respiratory infections and sepsis in critical care units in Vietnam. A questionnaire survey was conducted by purposive sampling of 128 hospitals (36% of total hospitals in surveyed provinces), including 25 provincial and 103 district level hospitals, from 20 provinces in Vietnam. Data on availability of hospital characteristics, structural resources and health care workers was then analyzed. Most hospitals (>80%) reported having 60% of the relevant structural resources. Significant differences were observed between provincial hospitals when compared to district hospitals in regards to availability of central oxygen piping system (78.3% vs 38.7%, p=0.001) mechanical ventilation (100.0% vs 73.6%, p=0.003), mobile x-rays (80.0% vs 29.8%, p<0.001), carbapenem antibiotic (73.9% vs 17.4%, p<0.001) and norepinephrine (95.8% vs 56.3%, p<0.001). There was a limited availability of arterial blood gas analyzers (13.7%), oseltamivir (42.2%) and N95 respirators (54.6%) across all hospitals surveyed. The limited availability of relevant structural and human resources in critical care units around Vietnam makes the implementation of quality critical care to patients with SARI and sepsis, according international guidelines, not universally possible. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Preventing Staphylococcus aureus Sepsis through the Inhibition of Its Agglutination in Blood

    PubMed Central

    McAdow, Molly; Kim, Hwan Keun; DeDent, Andrea C.; Hendrickx, Antoni P. A.; Schneewind, Olaf; Missiakas, Dominique M.

    2011-01-01

    Staphylococcus aureus infection is a frequent cause of sepsis in humans, a disease associated with high mortality and without specific intervention. When suspended in human or animal plasma, staphylococci are known to agglutinate, however the bacterial factors responsible for agglutination and their possible contribution to disease pathogenesis have not yet been revealed. Using a mouse model for S. aureus sepsis, we report here that staphylococcal agglutination in blood was associated with a lethal outcome of this disease. Three secreted products of staphylococci - coagulase (Coa), von Willebrand factor binding protein (vWbp) and clumping factor (ClfA) – were required for agglutination. Coa and vWbp activate prothrombin to cleave fibrinogen, whereas ClfA allowed staphylococci to associate with the resulting fibrin cables. All three virulence genes promoted the formation of thromboembolic lesions in heart tissues. S. aureus agglutination could be disrupted and the lethal outcome of sepsis could be prevented by combining dabigatran-etexilate treatment, which blocked Coa and vWbp activity, with antibodies specific for ClfA. Together these results suggest that the combined administration of direct thrombin inhibitors and ClfA-antibodies that block S. aureus agglutination with fibrin may be useful for the prevention of staphylococcal sepsis in humans. PMID:22028651

  6. Preventing Staphylococcus aureus sepsis through the inhibition of its agglutination in blood.

    PubMed

    McAdow, Molly; Kim, Hwan Keun; Dedent, Andrea C; Hendrickx, Antoni P A; Schneewind, Olaf; Missiakas, Dominique M

    2011-10-01

    Staphylococcus aureus infection is a frequent cause of sepsis in humans, a disease associated with high mortality and without specific intervention. When suspended in human or animal plasma, staphylococci are known to agglutinate, however the bacterial factors responsible for agglutination and their possible contribution to disease pathogenesis have not yet been revealed. Using a mouse model for S. aureus sepsis, we report here that staphylococcal agglutination in blood was associated with a lethal outcome of this disease. Three secreted products of staphylococci--coagulase (Coa), von Willebrand factor binding protein (vWbp) and clumping factor (ClfA)--were required for agglutination. Coa and vWbp activate prothrombin to cleave fibrinogen, whereas ClfA allowed staphylococci to associate with the resulting fibrin cables. All three virulence genes promoted the formation of thromboembolic lesions in heart tissues. S. aureus agglutination could be disrupted and the lethal outcome of sepsis could be prevented by combining dabigatran-etexilate treatment, which blocked Coa and vWbp activity, with antibodies specific for ClfA. Together these results suggest that the combined administration of direct thrombin inhibitors and ClfA-antibodies that block S. aureus agglutination with fibrin may be useful for the prevention of staphylococcal sepsis in humans.

  7. Recent advances in the pathophysiology and molecular basis of sepsis-associated organ dysfunction: Novel therapeutic implications and challenges.

    PubMed

    Hattori, Yuichi; Hattori, Kohshi; Suzuki, Tokiko; Matsuda, Naoyuki

    2017-09-01

    Sepsis is one of the most common reasons for critically ill patients to be admitted to an intensive care unit and, despite advances in overall medical care, it represents a major clinical problem and remains the leading cause of death in the critically ill patient population. Although sepsis has been defined as a systemic inflammatory syndrome, in which there is an identifiable focus of infection, clinical trials aimed at anti-inflammatory therapeutic approaches have largely failed to identify an effective therapeutic target to improve clinical outcomes in sepsis. Very recently, the third international consensus definitions have been advocated for sepsis and septic shock. Thus, sepsis is now defined as life-threatening organ dysfunction due to a dysregulated host response to infection. A better understanding of the molecular mechanisms involved in the pathogenesis of sepsis and its resultant organ failure has been sought, and the development of therapies targeted at preventing or limiting molecular events associated with the progress of fatal organ failure, hence leading to improvement of outcomes, is urgently needed. This review article provides an overview of possible pathogenic mechanisms underlying the development of multiple organ dysfunction in sepsis and discusses pharmacological agents regarded as promising in treatment of this disorder. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Implementation of an Emergency Department Sepsis Bundle and System Redesign: A Process Improvement Initiative.

    PubMed

    McColl, Tamara; Gatien, Mathieu; Calder, Lisa; Yadav, Krishan; Tam, Ryan; Ong, Melody; Taljaard, Monica; Stiell, Ian

    2017-03-01

    In 2008-2009, the Canadian Institute for Health Information reported over 30,000 cases of sepsis hospitalizations in Canada, an increase of almost 4,000 from 2005. Mortality rates from severe sepsis and septic shock continue to remain greater than 30% in Canada and are significantly higher than other critical conditions treated in the emergency department (ED). Our group formed a multidisciplinary sepsis committee, conducted an ED process of care analysis, and developed a quality improvement protocol. The objective of this study was to evaluate the effects of this sepsis management bundle on patient mortality. This before and after study was conducted in two large Canadian tertiary care EDs and included adult patients with suspected severe infection that met at least two systemic inflammatory response syndrome (SIRS) criteria. We studied the implementation of a sepsis bundle including triage flagging, RN medical directive, education campaign, and a modified sepsis protocol. The primary outcomes were 30-day all-cause mortality and sepsis protocol use. We included a total of 167 and 185 patients in the pre- and post-intervention analysis, respectively. Compared to the pre-intervention group, mortality was significantly lower in the post-intervention group (30.7% versus 17.3%; absolute difference, 13.4%; 95% CI 9.8-17.0; p=0.006). There was also a higher rate of sepsis protocol use in the post-intervention group (20.3% versus 80.5%, absolute difference 60.2%; 95% CI 55.1-65.3; p<0.001). Additionally, we found shorter time-intervals from triage to MD assessment, fluid resuscitation, and antibiotic administration as well as lower rates of vasopressor requirements and ICU admission. Interpretation The implementation of our multidisciplinary ED sepsis bundle, including improved early identification and protocolized medical care, was associated with improved time to achieve key therapeutic interventions and a reduction in 30-day mortality. Similar low-cost initiatives

  9. Sepsis in Pediatric Cardiac Intensive Care

    PubMed Central

    Wheeler, Derek S.; Wong, Hector R.

    2016-01-01

    Objectives In this review we will discuss risk factors for developing sepsis; the role of biomarkers in establishing an early diagnosis, monitoring therapeutic efficacy, stratification, and for the identification of sepsis endotypes; and the pathophysiology and management of severe sepsis and septic shock, with an emphasis on the impact of sepsis on cardiovascular function. Data Source MEDLINE, PubMed Conclusion There is a lot of excitement in the field of sepsis research today. Scientific advances in the diagnosis and clinical staging of sepsis, as well as a personalized approach to the treatment of sepsis, offer tremendous promise for the future. However, at the same time, it is also evident that sepsis mortality has not improved enough, even with progress in our understanding of the molecular pathophysiology of sepsis. PMID:27490609

  10. Reducing patient mortality, length of stay and readmissions through machine learning-based sepsis prediction in the emergency department, intensive care unit and hospital floor units

    PubMed Central

    McCoy, Andrea

    2017-01-01

    Introduction Sepsis management is a challenge for hospitals nationwide, as severe sepsis carries high mortality rates and costs the US healthcare system billions of dollars each year. It has been shown that early intervention for patients with severe sepsis and septic shock is associated with higher rates of survival. The Cape Regional Medical Center (CRMC) aimed to improve sepsis-related patient outcomes through a revised sepsis management approach. Methods In collaboration with Dascena, CRMC formed a quality improvement team to implement a machine learning-based sepsis prediction algorithm to identify patients with sepsis earlier. Previously, CRMC assessed all patients for sepsis using twice-daily systemic inflammatory response syndrome screenings, but desired improvements. The quality improvement team worked to implement a machine learning-based algorithm, collect and incorporate feedback, and tailor the system to current hospital workflow. Results Relative to the pre-implementation period, the post-implementation period sepsis-related in-hospital mortality rate decreased by 60.24%, sepsis-related hospital length of stay decreased by 9.55% and sepsis-related 30-day readmission rate decreased by 50.14%. Conclusion The machine learning-based sepsis prediction algorithm improved patient outcomes at CRMC. PMID:29450295

  11. Application of a simplified definition of diastolic function in severe sepsis and septic shock.

    PubMed

    Lanspa, Michael J; Gutsche, Andrea R; Wilson, Emily L; Olsen, Troy D; Hirshberg, Eliotte L; Knox, Daniel B; Brown, Samuel M; Grissom, Colin K

    2016-08-04

    Left ventricular diastolic dysfunction is common in patients with severe sepsis or septic shock, but the best approach to categorization is unknown. We assessed the association of common measures of diastolic function with clinical outcomes and tested the utility of a simplified definition of diastolic dysfunction against the American Society of Echocardiography (ASE) 2009 definition. In this prospective observational study, patients with severe sepsis or septic shock underwent transthoracic echocardiography within 24 h of onset of sepsis (median 4.3 h). We measured echocardiographic parameters of diastolic function and used random forest analysis to assess their association with clinical outcomes (28-day mortality and ICU-free days to day 28) and thereby suggest a simplified definition. We then compared patients categorized by the ASE 2009 definition and our simplified definition. We studied 167 patients. The ASE 2009 definition categorized only 35 % of patients. Random forest analysis demonstrated that the left atrial volume index and deceleration time, central to the ASE 2009 definition, were not associated with clinical outcomes. Our simplified definition used only e' and E/e', omitting the other measurements. The simplified definition categorized 87 % of patients. Patients categorized by either ASE 2009 or our novel definition had similar clinical outcomes. In both definitions, worsened diastolic function was associated with increased prevalence of ischemic heart disease, diabetes, and hypertension. A novel, simplified definition of diastolic dysfunction categorized more patients with sepsis than ASE 2009 definition. Patients categorized according to the simplified definition did not differ from patients categorized according to the ASE 2009 definition in respect to clinical outcome or comorbidities.

  12. Targeting IL-17A attenuates neonatal sepsis mortality induced by IL-18

    PubMed Central

    Wynn, James Lawrence; Wilson, Chris S.; Hawiger, Jacek; Scumpia, Philip O.; Marshall, Andrew F.; Liu, Jin-Hua; Zharkikh, Irina; Wong, Hector R.; Lahni, Patrick; Benjamin, John T.; Plosa, Erin J.; Weitkamp, Jörn-Hendrik; Sherwood, Edward R.; Moldawer, Lyle L.; Ungaro, Ricardo; Baker, Henry V.; Lopez, M. Cecilia; McElroy, Steven J.; Colliou, Natacha; Mohamadzadeh, Mansour; Moore, Daniel Jensen

    2016-01-01

    Interleukin (IL)-18 is an important effector of innate and adaptive immunity, but its expression must also be tightly regulated because it can potentiate lethal systemic inflammation and death. Healthy and septic human neonates demonstrate elevated serum concentrations of IL-18 compared with adults. Thus, we determined the contribution of IL-18 to lethality and its mechanism in a murine model of neonatal sepsis. We find that IL-18–null neonatal mice are highly protected from polymicrobial sepsis, whereas replenishing IL-18 increased lethality to sepsis or endotoxemia. Increased lethality depended on IL-1 receptor 1 (IL-1R1) signaling but not adaptive immunity. In genome-wide analyses of blood mRNA from septic human neonates, expression of the IL-17 receptor emerged as a critical regulatory node. Indeed, IL-18 administration in sepsis increased IL-17A production by murine intestinal γδT cells as well as Ly6G+ myeloid cells, and blocking IL-17A reduced IL-18–potentiated mortality to both neonatal sepsis and endotoxemia. We conclude that IL-17A is a previously unrecognized effector of IL-18–mediated injury in neonatal sepsis and that disruption of the deleterious and tissue-destructive IL-18/IL-1/IL-17A axis represents a novel therapeutic approach to improve outcomes for human neonates with sepsis. PMID:27114524

  13. Chromobacterium Violaceum Sepsis: Rethinking Conventional Therapy to Improve Outcome.

    PubMed

    Richard, Kathleen R; Lovvorn, Joshua J; Oliver, Sara E; Ross, Shannon A; Benner, Kim W; Kong, Michele Y F

    2015-10-19

    Chromobacterium violaceum (C. violaceum) is a facultative anaerobic gram-negative bacterium found in soil and water, especially in tropical and subtropical areas. Although infection in humans is rare, it is associated with significant morbidity. The bacterium is known for its resistance to multiple antimicrobials, and the possibility of relapse and reinfection. Presence of bacteremia, disseminated infection, and ineffective antimicrobial agents are predictors of mortality. We report the case of a previously healthy 11-year-old male with C. violaceum sepsis who was exposed to stagnant water. He presented with severe septic shock and developed multi-organ system failure. Initial presumptive diagnosis was staphylococcal infection secondary to presence of skin abscesses resulting in antibiotic coverage with vancomycin, clindamycin, nafcillin and ceftriaxone. He also had multiple lung and liver abscesses. Once C. violaceum was identified, he received meropenem and ciprofloxacin, and was later discharged on ertapenem and trimethoprim-sulfamethoxazole (TMP-SMX) to complete a total of six months of antibiotics. He was diagnosed with chronic granulomatous disease (CGD) and is currently on prophylactic TMP-SMX and itraconazole. He has not had any relapses since his initial presentation. This case highlights the importance of considering C. violaceum as a relevant human pathogen, and considering it early in temperate regions, particularly in cases of fulminant sepsis associated with multi-organ abscesses. Once C. violaceum is identified, appropriate antimicrobial therapy should be started promptly, and sufficient duration of treatment is necessary for successful therapy.

  14. Correlation analysis of omega-3 fatty acids and mortality of sepsis and sepsis-induced ARDS in adults: data from previous randomized controlled trials.

    PubMed

    Chen, HuaiSheng; Wang, Su; Zhao, Ying; Luo, YuTian; Tong, HuaSheng; Su, Lei

    2018-05-31

    This study aimed to investigate the possible effect of omega-3 fatty acids on reducing the mortality of sepsis and sepsis-induced acute respiratory distress syndrome (ARDS) in adults. Medline, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI) database, WangFang database, and Chinese BioMedical Literature Database from their inception to March 6, 2017, were searched using systematic review researching methods. Five factors were analyzed to investigate the correlation between omega-3 fatty acids (either parenteral or enteral supplementation) and mortality rate. Forty randomized controlled trials (RCTs) were initially included, but only 25 of them assessed mortality. Of these RCTs, nine used enteral nutrition (EN) and 16 used parenteral nutrition (PN). The total mortality rate in the omega-3 fatty acid group was lower than that in the control group. However, the odds ratio (OR) value was not significantly different in the EN or PN subgroup. Eighteen RCTs including 1790 patients with similar severity of sepsis and ARDS were also analyzed. The OR value was not significantly different in the EN or PN subgroup. Omega-3 fatty acids did not show positive effect on improving mortality of sepsis-induced ARDS (p = 0.39). But in EN subgroup, omega-3 fatty acids treatment seemed to have some benefits in reducing mortality rate (p = 0.04). In the RCTs including similar baseline patients, partial correlation analysis found that the concentration ratio of n-6 to n-3 fatty acids had positive correlation with reduction of mortality (RM) (γ = 0.60, P = 0.02), whereas the total number of each RCT had negative correlation with RM (γ = - 0.54, P = 0.05). This review found that omega-3 fatty acid supplementation could reduce the mortality rate of sepsis and sepsis-induced ARDS. However, further investigation based on suitable concentrations and indications is needed to support the findings.

  15. Does Infection Site Matter? A Systematic Review of Infection Site Mortality in Sepsis.

    PubMed

    Motzkus, Christine A; Luckmann, Roger

    2017-09-01

    Sepsis treatment protocols emphasize source control with empiric antibiotics and fluid resuscitation. Previous reviews have examined the impact of infection site and specific pathogens on mortality from sepsis; however, no recent review has addressed the infection site. This review focuses on the impact of infection site on hospital mortality among patients with sepsis. The PubMed database was searched for articles from 2001 to 2014. Studies were eligible if they included (1) one or more statistical models with hospital mortality as the outcome and considered infection site for inclusion in the model and (2) adult patients with sepsis, severe sepsis, or septic shock. Data abstracted included stage of sepsis, infection site, and raw and adjusted effect estimates. Nineteen studies were included. Infection sites most studied included respiratory (n = 19), abdominal (n = 19), genitourinary (n = 18), and skin and soft tissue infections (n = 11). Several studies found a statistically significant lower mortality risk for genitourinary infections on hospital mortality when compared to respiratory infections. Based on studies included in this review, the impact of infection site in patients with sepsis on hospital mortality could not be reliably estimated. Misclassification among infections and disease states remains a serious possibility in studies on this topic.

  16. Serum alpha1 -proteinase inhibitor concentrations in dogs with systemic inflammatory response syndrome or sepsis.

    PubMed

    Heilmann, Romy M; Grützner, Niels; Thames, Brittany E; Steiner, Jörg M; Barr, James W

    2017-11-01

    To determine whether the concentration of serum canine alpha 1 -proteinase inhibitor (cα 1 -PI) has diagnostic or prognostic utility in dogs with sepsis or noninfectious systemic inflammatory response syndrome (SIRS). Prospective, observational study from May to December 2010. University teaching hospital ICU. Sixty-nine client-owned dogs: 19 dogs with SIRS or sepsis and 50 healthy control dogs. None. Serum and plasma samples were collected from dogs with SIRS or sepsis on the day of hospital admission and once on the following 2 days, and on a single day in healthy controls. Patients were assessed using the 10-parameter Acute Patient Physiologic and Laboratory Evaluation (APPLE full ) and 5-parameter (APPLE fast ) score. Serum cα 1 -PI concentrations were measured, compared among groups of dogs, and evaluated for a correlation with the concentration of serum C-reactive protein, plasma interleukin-6, tumor necrosis factor-α, the APPLE scores, and survival to discharge. Serum cα 1 -PI concentrations were significantly lower in dogs with SIRS/sepsis (P < 0.001) than in healthy controls. While day 1 serum cα 1 -PI concentrations did not differ between dogs with SIRS and those with sepsis (P = 0.592), septic dogs had significantly lower serum cα 1 -PI concentrations on days 2 (P = 0.017) and 3 (P = 0.036) than dogs with SIRS. Serum cα 1 -PI concentrations did not differ between survivors and nonsurvivors (P = 1.000), but were inversely correlated with the APPLE full score (ρ = -0.48; P = 0.040) and plasma interleukin-6 concentrations (ρ = -0.50; P = 0.037). These results suggest a role of cα 1 -PI as a negative acute phase protein in dogs. The concentration of serum cα 1 -PI at the time of hospital admission does not have utility to identify dogs with sepsis from those with noninfectious SIRS, but may be a useful surrogate marker for early stratification of illness severity. © Veterinary Emergency and Critical Care Society 2017.

  17. Protocolized treatment is associated with decreased organ dysfunction in pediatric severe sepsis

    PubMed Central

    Balamuth, Fran; Weiss, Scott L.; Fitzgerald, Julie C.; Hayes, Katie; Centkowski, Sierra; Chilutti, Marianne; Grundmeier, Robert W.; Lavelle, Jane; Alpern, Elizabeth R.

    2016-01-01

    Objective To determine whether treatment with a protocolized sepsis guideline in the emergency department (ED) was associated with a lower burden of organ dysfunction (OD) by hospital day 2 compared to non-protocolized usual care in pediatric patients with severe sepsis. Design Retrospective cohort study Setting Tertiary care children’s hospital from January 1, 2012–March 31, 2014. Measurements and Main Results Subjects with international consensus defined severe sepsis and pediatric intensive care unit (PICU) admission within 24 hours of ED arrival were included. The exposure was the use of a protocolized ED sepsis guideline. The primary outcome was complete resolution of OD by hospital day 2. One hundred eighty nine subjects were identified during the study period. Of these, 121 (64%) were treated with the protocolized ED guideline and 68 were not. There were no significant differences between the groups in age, sex, race, number of comorbid conditions, ED triage level, or OD on arrival to the ED. Patients treated with protocolized ED care were more likely to be free of OD on hospital day 2 after controlling for sex, comorbid condition, indwelling central venous catheter, PIM-2 score, and timing of antibiotics and intravenous fluids (adjusted OR 4.2, 95% CI 1.7, 10.4). Conclusions Use of a protocolized ED sepsis guideline was independently associated with resolution of OD by hospital day 2 compared to non-protocolized usual care. These data indicate that morbidity outcomes in children can be improved with the use of protocolized care. PMID:27455114

  18. Protocolized Treatment Is Associated With Decreased Organ Dysfunction in Pediatric Severe Sepsis.

    PubMed

    Balamuth, Fran; Weiss, Scott L; Fitzgerald, Julie C; Hayes, Katie; Centkowski, Sierra; Chilutti, Marianne; Grundmeier, Robert W; Lavelle, Jane; Alpern, Elizabeth R

    2016-09-01

    To determine whether treatment with a protocolized sepsis guideline in the emergency department was associated with a lower burden of organ dysfunction by hospital day 2 compared to nonprotocolized usual care in pediatric patients with severe sepsis. Retrospective cohort study. Tertiary care children's hospital from January 1, 2012, to March 31, 2014. Patients older than 56 days old and younger than 18 years old with international consensus defined severe sepsis and who required PICU admission within 24 hours of emergency department arrival were included. The exposure was the use of a protocolized emergency department sepsis guideline. The primary outcome was complete resolution of organ dysfunction by hospital day 2. One hundred eighty nine subjects were identified during the study period. Of these, 121 (64%) were treated with the protocolized emergency department guideline and 68 were not. There were no significant differences between the groups in age, sex, race, number of comorbid conditions, emergency department triage level, or organ dysfunction on arrival to the emergency department. Patients treated with protocolized emergency department care were more likely to be free of organ dysfunction on hospital day 2 after controlling for sex, comorbid condition, indwelling central venous catheter, Pediatric Index of Mortality-2 score, and timing of antibiotics and IV fluids (adjusted odds ratio, 4.2; 95% CI, 1.7-10.4). Use of a protocolized emergency department sepsis guideline was independently associated with resolution of organ dysfunction by hospital day 2 compared to nonprotocolized usual care. These data indicate that morbidity outcomes in children can be improved with the use of protocolized care.

  19. Pediatric Sepsis Guidelines: Summary for resource-limited countries

    PubMed Central

    Khilnani, Praveen; Singhi, Sunit; Lodha, Rakesh; Santhanam, Indumathi; Sachdev, Anil; Chugh, Krishan; Jaishree, M.; Ranjit, Suchitra; Ramachandran, Bala; Ali, Uma; Udani, Soonu; Uttam, Rajiv; Deopujari, Satish

    2010-01-01

    Justification: Pediatric sepsis is a commonly encountered global issue. Existing guidelines for sepsis seem to be applicable to the developed countries, and only few articles are published regarding application of these guidelines in the developing countries, especially in resource-limited countries such as India and Africa. Process: An expert representative panel drawn from all over India, under aegis of Intensive Care Chapter of Indian Academy of Pediatrics (IAP) met to discuss and draw guidelines for clinical practice and feasibility of delivery of care in the early hours in pediatric patient with sepsis, keeping in view unique patient population and limited availability of equipment and resources. Discussion included issues such as sepsis definitions, rapid cardiopulmonary assessment, feasibility of early aggressive fluid therapy, inotropic support, corticosteriod therapy, early endotracheal intubation and use of positive end expiratory pressure/mechanical ventilation, initial empirical antibiotic therapy, glycemic control, and role of immunoglobulin, blood, and blood products. Objective: To achieve a reasonable evidence-based consensus on the basis of published literature and expert opinion to formulating clinical practice guidelines applicable to resource-limited countries such as India. Recommendations: Pediatric sepsis guidelines are presented in text and flow chart format keeping resource limitations in mind for countries such as India and Africa. Levels of evidence are indicated wherever applicable. It is anticipated that once the guidelines are used and outcomes data evaluated, further modifications will be necessary. It is planned to periodically review and revise these guidelines every 3–5 years as new body of evidence accumulates. PMID:20606908

  20. The Timing of Early Antibiotics and Hospital Mortality in Sepsis.

    PubMed

    Liu, Vincent X; Fielding-Singh, Vikram; Greene, John D; Baker, Jennifer M; Iwashyna, Theodore J; Bhattacharya, Jay; Escobar, Gabriel J

    2017-10-01

    Prior sepsis studies evaluating antibiotic timing have shown mixed results. To evaluate the association between antibiotic timing and mortality among patients with sepsis receiving antibiotics within 6 hours of emergency department registration. Retrospective study of 35,000 randomly selected inpatients with sepsis treated at 21 emergency departments between 2010 and 2013 in Northern California. The primary exposure was antibiotics given within 6 hours of emergency department registration. The primary outcome was adjusted in-hospital mortality. We used detailed physiologic data to quantify severity of illness within 1 hour of registration and logistic regression to estimate the odds of hospital mortality based on antibiotic timing and patient factors. The median time to antibiotic administration was 2.1 hours (interquartile range, 1.4-3.1 h). The adjusted odds ratio for hospital mortality based on each hour of delay in antibiotics after registration was 1.09 (95% confidence interval [CI], 1.05-1.13) for each elapsed hour between registration and antibiotic administration. The increase in absolute mortality associated with an hour's delay in antibiotic administration was 0.3% (95% CI, 0.01-0.6%; P = 0.04) for sepsis, 0.4% (95% CI, 0.1-0.8%; P = 0.02) for severe sepsis, and 1.8% (95% CI, 0.8-3.0%; P = 0.001) for shock. In a large, contemporary, and multicenter sample of patients with sepsis in the emergency department, hourly delays in antibiotic administration were associated with increased odds of hospital mortality even among patients who received antibiotics within 6 hours. The odds increased within each sepsis severity strata, and the increased odds of mortality were greatest in septic shock.

  1. Impact of an electronic sepsis initiative on antibiotic use and health care facility-onset Clostridium difficile infection rates.

    PubMed

    Hiensch, Robert; Poeran, Jashvant; Saunders-Hao, Patricia; Adams, Victoria; Powell, Charles A; Glasser, Allison; Mazumdar, Madhu; Patel, Gopi

    2017-10-01

    Although integrated, electronic sepsis screening and treatment protocols are thought to improve patient outcomes, less is known about their unintended consequences. We aimed to determine if the introduction of a sepsis initiative coincided with increases in broad-spectrum antibiotic use and health care facility-onset (HCFO) Clostridium difficile infection (CDI) rates. We used interrupted time series data from a large, tertiary, urban academic medical center including all adult inpatients on 4 medicine wards (June 2011-July 2014). The main exposure was implementation of the sepsis screening program; the main outcomes were the use of broad-spectrum antibiotics (including 3 that were part of an order set designed for the sepsis initiative) and HCFO CDI rates. Segmented regression analyses compared outcomes in 3 time segments: before (11 months), during (14 months), and after (12 months) implementation of a sepsis initiative. Antibiotic use and HFCO CDI rates increased during the period of implementation and the period after implementation compared with baseline; these increases were highest in the period after implementation (level change, 50.4 days of therapy per 1,000 patient days for overall antibiotic use and 10.8 HCFO CDIs per 10,000 patient days; P < .05). Remarkably, the main drivers of overall antibiotic use were not those included in the sepsis order set. The implementation of an electronic sepsis screening and treatment protocol coincided with increased broad-spectrum antibiotic use and HCFO CDIs. Because these protocols are increasingly used, further study of their unintended consequences is warranted. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  2. Acute salicylate poisoning: risk factors for severe outcome.

    PubMed

    Shively, Rachel M; Hoffman, Robert S; Manini, Alex F

    2017-03-01

    Salicylate poisoning remains a significant public health threat with more than 20,000 exposures reported annually in the United States. We aimed to establish early predictors of severe in-hospital outcomes in Emergency Department patients presenting with acute salicylate poisoning. This was a secondary data analysis of adult salicylate overdoses from a prospective cohort study of acute drug overdoses at two urban university teaching hospitals from 2009 to 2013. Patients were included based on confirmed salicylate ingestion and enrolled consecutively. Demographics, clinical parameters, treatment and disposition were collected from the medical record. Severe outcome was defined as a composite occurrence of acidemia (pH <7.3 or bicarbonate <16 mEq/L), hemodialysis, and/or death. Out of 1997 overdoses screened, 48 patients met inclusion/exclusion criteria. Patient characteristics were 43.8% male, median age 32 (range 18-87), mean initial salicylate concentration 28.1 mg/dL (SD 26.6), and 20.8% classified as severe outcome. Univariate analysis indicated that age, respiratory rate, lactate, coma, and the presence of co-ingestions were significantly associated with severe outcome, while initial salicylate concentration alone had no association. However, when adjusted for salicylate concentration, only age (OR 1.13; 95% CI 1.02-1.26) and respiratory rate (OR 1.29; 95% CI 1.02-1.63) were independent predictors. Additionally, lactate showed excellent test characteristics to predict severe outcome, with an optimal cutpoint of 2.25 mmol/L (78% sensitivity, 67% specificity). In adult Emergency Department patients with acute salicylate poisoning, independent predictors of severe outcome were older age and increased respiratory rate, as well as initial serum lactate, while initial salicylate concentration alone was not predictive.

  3. Characteristics of a Pseudomonas aeruginosa induced porcine sepsis model for multi-organ metabolic flux measurements.

    PubMed

    Ten Have, Gabriella A M; Deutz, Renske C I; Engelen, Mariëlle P K J; Wolfe, Robert R; Deutz, Nicolaas E P

    2018-04-01

    Survival of sepsis is related to loss of muscle mass. Therefore, it is imperative to further define and understand the basic alterations in nutrient metabolism in order to improve targeted sepsis nutritional therapies. We developed and evaluated a controlled hyperdynamic severe sepsis pig model that can be used for in vivo multi-organ metabolic studies in a conscious state. In this catheterized pig model, bacteremia was induced intravenously with 10 9 CFU/h Pseudomonas aeruginosa (PA) in 13 pigs for 18 h. Both the PA and control (nine) animals received fluid resuscitation and were continuously monitored. We examined in detail their hemodynamics, blood gases, clinical chemistry, inflammation, histopathology and organ plasma flows. The systemic inflammatory response (SIRS) diagnostic scoring system was used to determine the clinical septic state. Within 6 h from the start of PA infusion, a septic state developed, as was reflected by hyperthermia and cardiovascular changes. After 12 h of PA infusion, severe sepsis was diagnosed. Disturbed cardiovascular function, decreased portal drained viscera plasma flow (control: 37.6 ± 4.6 mL/kg body weight (bw)/min; PA 20.3 ± 2.6 mL/kg bw/min, P < 0.001), as well as moderate villous injury in the small intestines were observed. No lung, kidney or liver failure was observed. Acute phase C-reactive protein (CRP) and interleukin-6 (IL-6) levels did not change in the PA group. However, significant metabolic changes such as enhanced protein breakdown, hypocalcemia and hypocholesterolemia were found. In conclusion, PA-induced bacteremia in a catheterized pig is a clinically relevant model for acute severe sepsis and enables the study of complex multi-organ metabolisms.

  4. The impact of duration of organ dysfunction on the outcome of patients with severe sepsis and septic shock.

    PubMed

    Freitas, Flávio G R; Salomão, Reinaldo; Tereran, Nathalia; Mazza, Bruno Franco; Assunção, Murillo; Jackiu, Mirian; Fernandes, Haggeas; Machado, Flávia Ribeiro

    2008-08-01

    This study aimed to assess the impact of the duration of organ dysfunction on the outcome of patients with severe sepsis or septic shock. Clinical data were collected from hospital charts of patients with severe sepsis and septic shock admitted to a mixed intensive care unit from November 2003 to February 2004. The duration of organ dysfunction prior to diagnosis was correlated with mortality. Results were considered significant if p<0.05. Fifty-six patients were enrolled. Mean age was 55.6+/-20.7 years, mean APACHE II score was 20.6+/-6.9, and mean SOFA score was 7.9+/-3.7. Thirty-six patients (64.3%) had septic shock. The mean duration of organ dysfunction was 1.9+/-1.9 days. Within the univariate analysis, the variables correlated with hospital mortality were: age (p=0.015), APACHE II (p=0.008), onset outside the intensive care unit (p=0.05), blood glucose control (p=0.05) and duration of organ dysfunction (p=0.0004). In the multivariate analysis, only a duration of organ dysfunction persisting longer than 48 hours correlated with mortality (p=0.004, OR: 8.73 (2.37-32.14)), whereas the APACHE II score remained only a slightly significant factor (p=0.049, OR: 1.11 (1.00-1.23)). Patients who received therapeutic interventions within the first 48 hours after the onset of organ dysfunction exhibited lower mortality (32.1% vs. 82.1%, p=0.0001). These findings suggest that the diagnosis of organ dysfunction is not being made in a timely manner. The time elapsed between the onset of organ dysfunction and initiation of therapeutic intervention can be quite long, and this represents an important determinant of survival in cases of severe sepsis and septic shock.

  5. Parameters of the Endocannabinoid System as Novel Biomarkers in Sepsis and Septic Shock.

    PubMed

    Lafreniere, J Daniel; Lehmann, Christian

    2017-11-01

    Sepsis represents a dysregulated immune response to infection, with a continuum of severity progressing to septic shock. This dysregulated response generally follows a pattern by which an initial hyperinflammatory phase is followed by a state of sepsis-associated immunosuppression. Major challenges in improving sepsis care include developing strategies to ensure early and accurate identification and diagnosis of the disease process, improving our ability to predict outcomes and stratify patients, and the need for novel sepsis-specific treatments such as immunomodulation. Biomarkers offer promise with all three of these challenges and are likely also to be the solution to determining a patient's immune status; something that is critical in guiding effective and safe immunomodulatory therapy. Currently available biomarkers used in sepsis lack sensitivity and specificity, among other significant shortcomings. The endocannabinoid system (ECS) is an emerging topic of research with evidence suggesting a ubiquitous presence on both central and peripheral tissues, including an intrinsic link with immune function. This review will first discuss the state of sepsis biomarkers and lack of available treatments, followed by an introduction to the ECS and a discussion of its potential to provide novel biomarkers and treatments.

  6. Sepsis and Critical Illness Research Center investigators: protocols and standard operating procedures for a prospective cohort study of sepsis in critically ill surgical patients.

    PubMed

    Loftus, Tyler J; Mira, Juan C; Ozrazgat-Baslanti, Tezcan; Ghita, Gabriella L; Wang, Zhongkai; Stortz, Julie A; Brumback, Babette A; Bihorac, Azra; Segal, Mark S; Anton, Stephen D; Leeuwenburgh, Christiaan; Mohr, Alicia M; Efron, Philip A; Moldawer, Lyle L; Moore, Frederick A; Brakenridge, Scott C

    2017-08-01

    Sepsis is a common, costly and morbid cause of critical illness in trauma and surgical patients. Ongoing advances in sepsis resuscitation and critical care support strategies have led to improved in-hospital mortality. However, these patients now survive to enter state of chronic critical illness (CCI), persistent low-grade organ dysfunction and poor long-term outcomes driven by the persistent inflammation, immunosuppression and catabolism syndrome (PICS). The Sepsis and Critical Illness Research Center (SCIRC) was created to provide a platform by which the prevalence and pathogenesis of CCI and PICS may be understood at a mechanistic level across multiple medical disciplines, leading to the development of novel management strategies and targeted therapies. Here, we describe the design, study cohort and standard operating procedures used in the prospective study of human sepsis at a level 1 trauma centre and tertiary care hospital providing care for over 2600 critically ill patients annually. These procedures include implementation of an automated sepsis surveillance initiative, augmentation of clinical decisions with a computerised sepsis protocol, strategies for direct exportation of quality-filtered data from the electronic medical record to a research database and robust long-term follow-up. This study has been registered at ClinicalTrials.gov, approved by the University of Florida Institutional Review Board and is actively enrolling subjects. Dissemination of results is forthcoming. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. Assessment of Diagnostic and Prognostic Role of Copeptin in the Clinical Setting of Sepsis.

    PubMed

    Battista, Stefania; Audisio, Umberto; Galluzzo, Claudia; Maggiorotto, Matteo; Masoero, Monica; Forno, Daniela; Pizzolato, Elisa; Ulla, Marco; Lucchiari, Manuela; Vitale, Annarita; Moiraghi, Corrado; Lupia, Enrico; Settanni, Fabio; Mengozzi, Giulio

    2016-01-01

    The diagnostic and prognostic usefulness of copeptin were evaluated in septic patients, as compared to procalcitonin assessment. In this single centre and observational study 105 patients were enrolled: 24 with sepsis, 25 with severe sepsis, 15 with septic shock, and 41 controls, divided in two subgroups (15 patients with gastrointestinal bleeding and 26 with suspected SIRS secondary to trauma, acute coronary syndrome, and pulmonary embolism). Biomarkers were determined at the first medical evaluation and thereafter 24, 48, and 72 hours after admission. Definitive diagnosis and in-hospital survival rates at 30 days were obtained through analysis of medical records. At entry, copeptin proved to be able to distinguish cases from controls and also sepsis group from septic shock group, while procalcitonin could distinguish also severe sepsis from septic shock group. Areas under the ROC curve for copeptin and procalcitonin were 0.845 and 0.861, respectively. Noteworthy, patients with copeptin concentrations higher than the threshold value (23.2 pmol/L), calculated from the ROC curve, at admission presented higher 30-day mortality. No significant differences were found in copeptin temporal profile among different subgroups. Copeptin showed promising diagnostic and prognostic role in the management of sepsis, together with its possible role in monitoring the response to treatment.

  8. Assessment of Diagnostic and Prognostic Role of Copeptin in the Clinical Setting of Sepsis

    PubMed Central

    Battista, Stefania; Audisio, Umberto; Galluzzo, Claudia; Maggiorotto, Matteo; Masoero, Monica; Forno, Daniela; Pizzolato, Elisa; Ulla, Marco; Lucchiari, Manuela; Vitale, Annarita; Moiraghi, Corrado; Lupia, Enrico; Settanni, Fabio; Mengozzi, Giulio

    2016-01-01

    The diagnostic and prognostic usefulness of copeptin were evaluated in septic patients, as compared to procalcitonin assessment. In this single centre and observational study 105 patients were enrolled: 24 with sepsis, 25 with severe sepsis, 15 with septic shock, and 41 controls, divided in two subgroups (15 patients with gastrointestinal bleeding and 26 with suspected SIRS secondary to trauma, acute coronary syndrome, and pulmonary embolism). Biomarkers were determined at the first medical evaluation and thereafter 24, 48, and 72 hours after admission. Definitive diagnosis and in-hospital survival rates at 30 days were obtained through analysis of medical records. At entry, copeptin proved to be able to distinguish cases from controls and also sepsis group from septic shock group, while procalcitonin could distinguish also severe sepsis from septic shock group. Areas under the ROC curve for copeptin and procalcitonin were 0.845 and 0.861, respectively. Noteworthy, patients with copeptin concentrations higher than the threshold value (23.2 pmol/L), calculated from the ROC curve, at admission presented higher 30-day mortality. No significant differences were found in copeptin temporal profile among different subgroups. Copeptin showed promising diagnostic and prognostic role in the management of sepsis, together with its possible role in monitoring the response to treatment. PMID:27366743

  9. Cytokine profile in severe gram-positive and gram-negative abdominal sepsis

    PubMed Central

    Surbatovic, Maja; Popovic, Nada; Vojvodic, Danilo; Milosevic, Ivan; Acimovic, Gordana; Stojicic, Milan; Veljovic, Milic; Jevdjic, Jasna; Djordjevic, Dragan; Radakovic, Sonja

    2015-01-01

    Sepsis is a principal cause of death in critical care units worldwide and consumes considerable healthcare resources. The aim of our study was to determine whether the early cytokine profile can discriminate between Gram-positive and Gram-negative bacteraemia (GPB and GNB, respectively) and to assess the prognostic value regarding outcome in critically ill patients with severe abdominal sepsis. The outcome measure was hospital mortality. Blood samples were obtained from 165 adult patients with confirmed severe abdominal sepsis. Levels of the proinflammatory mediators TNF-α, IL-8, IL-12 and IFN-γ and the anti-inflammatory mediators IL-1ra, IL-4, IL-10 and TGF-β1 were determined and correlated with the nature of the bacteria isolated from the blood culture and outcome. The cytokine profile in our study indicated that the TNF-α levels were 2-fold, IL-8 were 3.3-fold, IFN-γ were 13-fold, IL-1ra were 1.05-fold, IL-4 were 1.4-fold and IL-10 were 1.83-fold higher in the GNB group compared with the GPB group. The TNF-α levels were 4.7-fold, IL-8 were 4.6-fold, IL-1ra were 1.5-fold and IL-10 were 3.3-fold higher in the non-survivors compared with the survivors. PMID:26079127

  10. Predictors and Outcomes of Dysphagia Screening After Acute Ischemic Stroke.

    PubMed

    Joundi, Raed A; Martino, Rosemary; Saposnik, Gustavo; Giannakeas, Vasily; Fang, Jiming; Kapral, Moira K

    2017-04-01

    Guidelines advocate screening all acute stroke patients for dysphagia. However, limited data are available regarding how many and which patients are screened and how failing a swallowing screen affects patient outcomes. We sought to evaluate predictors of receiving dysphagia screening after acute ischemic stroke and outcomes after failing a screening test. We used the Ontario Stroke Registry from April 1, 2010, to March 31, 2013, to identify patients hospitalized with acute ischemic stroke and determine predictors of documented dysphagia screening and outcomes after failing the screening test, including pneumonia, disability, and death. Among 7171 patients, 6677 patients were eligible to receive dysphagia screening within 72 hours, yet 1280 (19.2%) patients did not undergo documented screening. Patients with mild strokes were significantly less likely than those with more severe strokes to have documented screening (adjusted odds ratio, 0.51; 95% confidence interval [CI], 0.41-0.64). Failing dysphagia screening was associated with poor outcomes, including pneumonia (adjusted odds ratio, 4.71; 95% CI, 3.43-6.47), severe disability (adjusted odds ratio, 5.19; 95% CI, 4.48-6.02), discharge to long-term care (adjusted odds ratio, 2.79; 95% CI, 2.11-3.79), and 1-year mortality (adjusted hazard ratio, 2.42; 95% CI, 2.09-2.80). Associations were maintained in patients with mild strokes. One in 5 patients with acute ischemic stroke did not have documented dysphagia screening, and patients with mild strokes were substantially less likely to have documented screening. Failing dysphagia screening was associated with poor outcomes, including in patients with mild strokes, highlighting the importance of dysphagia screening for all patients with acute ischemic stroke. © 2017 American Heart Association, Inc.

  11. Effect of selective inhibition of renal inducible nitric oxide synthase on renal blood flow and function in experimental hyperdynamic sepsis.

    PubMed

    Ishikawa, Ken; Calzavacca, Paolo; Bellomo, Rinaldo; Bailey, Michael; May, Clive N

    2012-08-01

    Nitric oxide plays an important role in the control of renal blood flow and renal function. In sepsis, increased levels of inducible nitric oxide synthase produce excessive nitric oxide, which may contribute to the development of acute kidney injury. We, therefore, examined the effects of intrarenal infusion of selective inducible nitric oxide synthase inhibitors in a large animal model of hyperdynamic sepsis in which acute kidney injury occurs in the presence of increased renal blood flow. Prospective crossover randomized controlled interventional studies. University-affiliated research institute. Twelve unilaterally nephrectomized Merino ewes. Infusion of a selective (1400W) and a partially selective inducible nitric oxide synthase inhibitor (aminoguanidine) into the renal artery for 2 hrs after the induction of sepsis, and comparison with a nonselective inhibitor (Nω-nitro-L-arginine methyl ester). In sheep with nonhypotensive hyperdynamic sepsis, creatinine clearance halved (32 to 16 mL/min, ratio [95% confidence interval] 0.51 [0.28-0.92]) despite increased renal blood flow (241 to 343 mL/min, difference [95% confidence interval] 102 [78-126]). Infusion of 1400W did not change renal blood flow, urine output, or creatinine clearance, whereas infusion of Nω-nitro-L-arginine methyl ester and a high dose of aminoguanidine normalized renal blood flow, but did not alter creatinine clearance. In hyperdynamic sepsis, intrarenal infusion of a highly selective inducible nitric oxide synthase inhibitor did not reduce the elevated renal blood flow or improve renal function. In contrast, renal blood flow was reduced by infusion of a nonselective NOS inhibitor or a high dose of a partially selective inducible nitric oxide synthase inhibitor. The renal vasodilatation in septic acute kidney injury may be due to nitric oxide derived from the endothelial and neural isoforms of nitric oxide synthase, but their blockade did not restore renal function.

  12. Treatment outcome of selective digestive decontamination and enteral nutrition in patients with severe acute pancreatitis.

    PubMed

    Sawa, Hidehiro; Ueda, Takashi; Takeyama, Yoshifumi; Yasuda, Takeo; Shinzeki, Makoto; Matsumura, Naoki; Nakajima, Takahiro; Matsumoto, Ippei; Fujita, Tsunenori; Ajiki, Tetsuo; Fujino, Yasuhiro; Kuroda, Yoshikazu

    2007-01-01

    Sepsis due to infected pancreatic necrosis is the most serious complication in the late phase of severe acute pancreatitis (SAP). Bacterial translocation from the gut is thought to be the main cause of pancreatic infection. The possibility has recently been reported that selective digestive decontamination (SDD) and enteral nutrition (EN) may alleviate the complications and reduce the mortality rate in patients with SAP. We analyzed the treatment outcome of SDD and EN in patients with SAP. We divided 90 patients with SAP into three groups: SDD(-)EN(-),group A; SDD(+)EN(-), group B; and SDD(+)EN(+), group C. Clinical outcome was analyzed retrospectively. The effect of SDD was compared in groups A and B, and the effect of EN was compared in groups B and C. The background of patients was not significantly different between the groups. SDD reduced the incidence of organ dysfunction (from 70% to 59%) and the mortality rate (from 40% to 28%), but the differences were not significant. EN reduced the incidence of infected pancreatic necrosis (from 31% to 24%) and the frequency of surgery for pancreas (from 28% to 18%), and further reduced the mortality rate (from 28% for SDD to 16%), but the differences were not significant. The peripheral lymphocyte count was significantly increased in patients with EN. SDD and EN did not significantly affect the treatment outcome in SAP. However, the results in this study raise the possibility that SDD and EN may decrease the complications and reduce the mortality rate in SAP. The efficacy of SDD and EN for SAP should be evaluated in a randomized controlled trial.

  13. Treatment With Human Wharton’s Jelly-Derived Mesenchymal Stem Cells Attenuates Sepsis-Induced Kidney Injury, Liver Injury, and Endothelial Dysfunction

    PubMed Central

    Cóndor, José M.; Rodrigues, Camila E.; de Sousa Moreira, Roberto; Canale, Daniele; Volpini, Rildo A.; Shimizu, Maria H.M.; Camara, Niels O.S.; Noronha, Irene de L.

    2016-01-01

    The pathophysiology of sepsis involves complex cytokine and inflammatory mediator networks. Downregulation of endothelial nitric oxide synthase contributes to sepsis-induced endothelial dysfunction. Human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) are known to reduce expression of proinflammatory cytokines and markers of apoptosis. We hypothesized that treatment with WJ-MSCs would protect renal, hepatic, and endothelial function in a cecal ligation and puncture (CLP) model of sepsis in rats. Rats were randomly divided into three groups: sham-operated rats; rats submitted to CLP and left untreated; and rats submitted to CLP and intraperitoneally injected, 6 hours later, with 1 × 106 WJ-MSCs. The glomerular filtration rate (GFR) was measured at 6 and 24 hours after CLP or sham surgery. All other studies were conducted at 24 hours after CLP or sham surgery. By 6 hours, GFR had decreased in the CLP rats. At 24 hours, Klotho renal expression significantly decreased. Treatment with WJ-MSCs improved the GFR; improved tubular function; decreased the CD68-positive cell count; decreased the fractional interstitial area; decreased expression of nuclear factor κB and of cytokines; increased expression of eNOS, vascular endothelial growth factor, and Klotho; attenuated renal apoptosis; ameliorated hepatic function; increased glycogen deposition in the liver; and improved survival. Sepsis-induced acute kidney injury is a state of Klotho deficiency, which WJ-MSCs can attenuate. Klotho protein expression was higher in WJ-MSCs than in human adipose-derived MSCs. Because WJ-MSCs preserve renal and hepatic function, they might play a protective role in sepsis. Significance Sepsis is the leading cause of death in intensive care units. Although many different treatments for sepsis have been tested, sepsis-related mortality rates remain high. It was hypothesized in this study that treatment with human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) would

  14. The association between pre-operative sepsis and 30-day mortality in hip fracture patients-A cohort study.

    PubMed

    Mørch, S S; Tantholdt-Hansen, S; Pedersen, N E; Duus, C L; Petersen, J A; Andersen, C Ø; Jarløv, J O; Meyhoff, C S

    2018-05-24

    Post-operative sepsis considerably increases mortality, but the extent of pre-operative sepsis in hip fracture patients and its consequences are sparsely elucidated. The aim of this study was to assess the association between pre-operative sepsis and 30-day mortality after hip fracture surgery. We conducted a retrospective analysis of data collected among 1894 patients who underwent hip fracture surgery in the Capital Region of Denmark in 2014 (NCT03201679). Data on vital signs, cultures and laboratory data were obtained. Sepsis was defined as a positive culture of any kind and presence of systemic inflammatory response syndrome within 24 hours and was assessed within 72 hours before surgery and 30 days post-operatively. Primary outcome was 30-day mortality. Secondary outcomes included length of hospital stay and admission to intensive care unit. A total of 144 (7.6%) of the hip fracture patients met the criteria for pre-operative sepsis. The 30-day mortality was 13.9% in patients with pre-operative sepsis as compared to 9.0% in those without (OR 1.69, 95% CI [1.00; 2.85], P = .08). Patients with pre-operative sepsis had longer hospital stays (median 10 days vs 9 days, mean difference 2.1 [SD 9.4] days, P = .03), and higher frequency of ICU admission (11.1% vs 2.7%, OR 4.15, 95% CI [2.19; 7.87], P < .0001). Pre-operative sepsis in hip fracture patients was associated with an increased length of hospital stay and tended to increase mortality. Pre-operative sepsis in hip fracture patients merits more intensive surveillance and increased attention to timely treatment. © 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  15. Interprofessional Collaboration to Improve Sepsis Care and Survival Within a Tertiary Care Emergency Department.

    PubMed

    Tedesco, Elizabeth R; Whiteman, Kimberly; Heuston, Melanie; Swanson-Biearman, Brenda; Stephens, Kimberly

    2017-11-01

    Sepsis is a leading cause of death in the United States; however, health care providers struggle with timely recognition, diagnosis, and treatment of patients. Both the Centers for Medicare and Medicaid Services and the National Quality Forum have identified this diagnosis as a priority. Presently, many patients with sepsis are identified late, resulting in significant morbidity and death. In this project, a collaborative, interprofessional approach was created for screening and early identification of ED patients with possible sepsis. The department has 38 beds with annual patient volumes of more than 40,000 visits. Education was provided about the symptoms and treatment of patients with sepsis. A screening and management algorithm tool was instituted that consisted of early identification triggers and how to intervene according to Surviving Sepsis Campaign recommendations. The tool allowed for assessment of the patient by the ED team; the team worked to determine if sepsis was present and the extent of the illness. During the first 4 months after implementation, more than 240 patients were screened, assessed, and treated according to the algorithm. Project outcomes resulted in an increase in staff knowledge of sepsis, a decrease in length of stay by 3 hours, and a significant decrease in mortality when compared with the previous year's coded data. This project demonstrates that sepsis education and team collaboration are an integral part of identifying and treating patients with sepsis. An interprofessional collaborative approach could be implemented in other institutions to combat the life-threatening complications of sepsis. Copyright © 2017 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.

  16. Pulse high-volume haemofiltration for treatment of severe sepsis: effects on hemodynamics and survival

    PubMed Central

    Ratanarat, Ranistha; Brendolan, Alessandra; Piccinni, Pasquale; Dan, Maurizio; Salvatori, Gabriella; Ricci, Zaccaria; Ronco, Claudio

    2005-01-01

    Introduction Severe sepsis is the leading cause of mortality in critically ill patients. Abnormal concentrations of inflammatory mediators appear to be involved in the pathogenesis of sepsis. Based on the humoral theory of sepsis, a potential therapeutic approach involves high-volume haemofiltration (HVHF), which has exhibited beneficial effects in severe sepsis, improving haemodynamics and unselectively removing proinflammatory and anti-inflammatory mediators. However, concerns have been expressed about the feasibility and costs of continuous HVHF. Here we evaluate a new modality, namely pulse HVHF (PHVHF; 24-hour schedule: HVHF 85 ml/kg per hour for 6–8 hours followed by continuous venovenous haemofiltration 35 ml/kg per hour for 16–18 hours). Method Fifteen critically ill patients (seven male; mean Acute Physiology and Chronic Health Evaluation [APACHE] II score 31.2, mean Simplified Acute Physiology Score [SAPS] II 62, and mean Sequential Organ Failure Assessment 14.2) with severe sepsis underwent daily PHVHF. We measured changes in haemodynamic variables and evaluated the dose of noradrenaline required to maintain mean arterial pressure above 70 mmHg during and after pulse therapy at 6 and 12 hours. PHVHF was performed with 250 ml/min blood flow rate. The bicarbonate-based replacement fluid was used at a 1:1 ratio in simultaneous pre-dilution and post-dilution. Results No treatment was prematurely discontinued. Haemodynamics were improved by PHVHF, allowing a significant reduction in noradrenaline dose during and at the end of the PHVHF session; this reduction was maintained at 6 and 12 hours after pulse treatment (P = 0.001). There was also an improvement in systolic blood pressure (P = 0.04). There were no changes in temperature, cardiac index, oxygenation, arterial pH or urine output during the period of observation. The mean daily Kt/V was 1.92. Predicted mortality rates were 72% (based on APACHE II score) and 68% (based on SAPS II score), and the

  17. Serum tenascin-C predicts severity and outcome of acute intracerebral hemorrhage.

    PubMed

    Wang, Lin-Guo; Huangfu, Xue-Qin; Tao, Bo; Zhong, Guan-Jin; Le, Zhou-Di

    2018-06-01

    Tenascin-C is a matricellular protein related to brain injury. We studied serum tenascin-C in acute intracerebral hemorrhage (ICH) and examined the associations with severity and outcome following the acute event. Tenascin-C samples were obtained from 162 patients with acute hemorrhagic stroke and 162 healthy controls. Poor 90-day functional outcome was defined as modified Rankin Scale score > 2. Early neurological deterioration (END) and hematoma growth (HG) were recorded at 24 h. Patients had higher tenascin-C levels than controls. Tenascin-C levels were positively correlated with hematoma volume or National Institutes of Health Stroke Scale score at baseline. Elevated tenascin-C levels were independently associated with END, HG, 90-day mortality and poor functional outcome. Moreover, tenascin-C levels significantly predicted END, HG and 90-day outcomes under receiver operating characteristic curves. An increase in serum tenascin-C level is associated with an adverse outcome in ICH patients, supporting the potential role of serum tenascin-C as a prognostic biomarker for hemorrhagic stroke. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Prophylactic antibiotics reduce morbidity due to septicemia during intensive treatment for pediatric acute myeloid leukemia.

    PubMed

    Kurt, Beth; Flynn, Patricia; Shenep, Jerry L; Pounds, Stanley; Lensing, Shelly; Ribeiro, Raul C; Pui, Ching-Hon; Razzouk, Bassem I; Rubnitz, Jeffrey E

    2008-07-15

    The aim of this study was to determine whether antibiotic prophylaxis during periods of neutropenia reduced streptococcal (S. viridans) sepsis and overall bacterial sepsis. The authors reviewed outcomes of 78 evaluable patients who were consecutively treated for acute myeloid leukemia (AML) from October 2002 through January 2007. Several successive prophylactic antibiotic regimens were used. All patients received antifungal prophylaxis with oral voriconazole. Oral cephalosporins did not significantly reduce the odds of bacterial sepsis (P = .81) or streptococcal (S. viridans) sepsis (P = .90) relative to no prophylaxis. Intravenous (iv) cefepime completely prevented streptococcal (S. viridans) sepsis and reduced the odds of bacterial sepsis 91% (P < .0001) relative to no prophylaxis, but resistant gram-negative bacteria emerged in 2 patients. Vancomycin with oral ciprofloxacin or a cephalosporin reduced the odds of bacterial sepsis by 93% (P < .0001) and streptococcal (S. viridans) sepsis by 99% (P < .0001). The fungal infection rate did not differ significantly between patients who did and did not receive antibiotic prophylaxis (1.0 per 1000 patient-days for both groups). The observed reduction in average hospital days per chemotherapy course for patients given vancomycin regimens or cefepime was 5.7 (P < .0001) and 4.1 (P = .0039) days, respectively. No reduction was observed with oral cephalosporins (P = .10). Furthermore, vancomycin regimens or cefepime were associated with a 20% reduction in healthcare charges (P = .0015) relative to using no antibiotics. One patient, who was on oral cefuroxime alone, died of septicemia. Prophylaxis with intravenous cefepime or a vancomycin regimen, and voriconazole, reduced morbidity in children with AML, and resulted in dramatic decreases in the incidence of septicemia and hospitalization days.

  19. A Multicenter Survey of House Staff Knowledge About Sepsis and the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock".

    PubMed

    Watkins, Richard R; Haller, Nairmeen; Wayde, Melinda; Armitage, Keith B

    2017-01-01

    We aimed to assess the knowledge, attitudes, and perceptions of resident physicians regarding sepsis in general and the Surviving Sepsis Campaign Guidelines in particular. After institutional review board approval, we surveyed internal medicine (IM) and emergency medicine (EM) house staff from 3 separate institutions. House staff were notified of the survey via e-mail from their residency director or chief resident. The survey was Internet-based (using http://www.surveymonkey.com ), voluntary, and anonymous. The Surviving Sepsis Campaign Guidelines were used to develop the survey. The survey was open between December 2015 and April 2016. No incentives for participation were given. Reminder e-mails were sent approximately every 3 to 4 weeks to all eligible participants. Comparisons of responses were evaluated using the N-1 2-proportion test. A total of 133 responses were received. These included 84 from IM house staff, 27 from EM house staff, and 22 who selected "other." Eighty (101/126) percent reported managing at least 1 patient with sepsis in the preceding 30 days, 85% (97/114) rated their knowledge of the Surviving Sepsis Guidelines as "very familiar" or at least "somewhat familiar," and 84% (91/108) believed their training in the diagnosis and management of sepsis was "excellent" or at least "good." However, 43% (47/108) reported not receiving any feedback on their treatment of patients with sepsis in the last 30 days, while 24% (26/108) received feedback once. Both IM and EM house staff received comparable rates of feedback (62% vs 48%, respectively; P = .21). For the 3 questions that directly tested knowledge of the guidelines, the scores of the IM and EM house staff were similar. Notably, <20% of both groups correctly identified diagnostic criteria for sepsis. Additional education of IM and EM house staff on the Surviving Sepsis Campaign Guidelines is warranted, along with more consistent feedback regarding their diagnosis and management of sepsis.

  20. Early lactate clearance is associated with biomarkers of inflammation, coagulation, apoptosis, organ dysfunction and mortality in severe sepsis and septic shock

    PubMed Central

    2010-01-01

    Background Lactate clearance, a surrogate for the magnitude and duration of global tissue hypoxia, is used diagnostically, therapeutically and prognostically. This study examined the association of early lactate clearance with selected inflammatory, coagulation, apoptosis response biomarkers and organ dysfunction scores in severe sepsis and septic shock. Methods Measurements of serum arterial lactate, biomarkers (interleukin-1 receptor antagonist, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-alpha, intercellular adhesion molecule-1, high mobility group box-1, D-Dimer and caspase-3), and organ dysfunction scores (Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology Score II, Multiple Organ Dysfunction Score, and Sequential Organ Failure Assessment) were obtained in conjunction with a prospective, randomized study examining early goal-directed therapy in severe sepsis and septic shock patients presenting to the emergency department (ED). Lactate clearance was defined as the percent change in lactate levels after six hours from a baseline measurement in the ED. Results Two-hundred and twenty patients, age 65.0 +/- 17.1 years, were examined, with an overall lactate clearance of 35.5 +/- 43.1% and in-hospital mortality rate of 35.0%. Patients were divided into four quartiles of lactate clearance, -24.3 +/- 42.3, 30.1 +/- 7.5, 53.4 +/- 6.6, and 75.1 +/- 7.1%, respectively (p < 0.01). The mean levels of all biomarkers and organ dysfunction scores over 72 hours were significantly lower with higher lactate clearance quartiles (p < 0.01). There was a significant decreased in-hospital, 28-day, and 60-day mortality in the higher lactate clearance quartiles (p < 0.01). Conclusions Early lactate clearance as a surrogate for the resolution of global tissue hypoxia is significantly associated with decreased levels of biomarkers, improvement in organ dysfunction and outcome in severe sepsis and septic shock. PMID:20181046

  1. Platelets Induce Apoptosis during Sepsis in a Contact-Dependent Manner That Is Inhibited by GPIIb/IIIa Blockade

    PubMed Central

    Sharron, Matthew; Hoptay, Claire E.; Wiles, Andrew A.; Garvin, Lindsay M.; Geha, Mayya; Benton, Angela S.; Nagaraju, Kanneboyina; Freishtat, Robert J.

    2012-01-01

    Purpose End-organ apoptosis is well-described in progressive sepsis and Multiple Organ Dysfunction Syndrome (MODS), especially where platelets accumulate (e.g. spleen and lung). We previously reported an acute sepsis-induced cytotoxic platelet phenotype expressing serine protease granzyme B. We now aim to define the site(s) of and mechanism(s) by which platelet granzyme B induces end-organ apoptosis in sepsis. Methods End-organ apoptosis in murine sepsis (i.e. polymicrobial peritonitis) was analyzed by immunohistochemistry. Platelet cytotoxicity was measured by flow cytometry following 90 minute ex vivo co-incubation with healthy murine splenocytes. Sepsis progression was measured via validated preclinical murine sepsis score. Measurements and Main Results There was evident apoptosis in spleen, lung, and kidney sections from septic wild type mice. In contrast, there was a lack of TUNEL staining in spleens and lungs from septic granzyme B null mice and these mice survived longer following induction of sepsis than wild type mice. In co-incubation experiments, physical separation of septic platelets from splenocytes by a semi-permeable membrane reduced splenocyte apoptosis to a rate indistinguishable from negative controls. Chemical separation by the platelet GPIIb/IIIa receptor inhibitor eptifibatide decreased apoptosis by 66.6±10.6% (p = 0.008). Mice treated with eptifibatide in vivo survived longer following induction of sepsis than vehicle control mice. Conclusions In sepsis, platelet granzyme B-mediated apoptosis occurs in spleen and lung, and absence of granzyme B slows sepsis progression. This process proceeds in a contact-dependent manner that is inhibited ex vivo and in vivo by the platelet GPIIb/IIIa receptor inhibitor eptifibatide. The GPIIb/IIIa inhibitors and other classes of anti-platelet drugs may be protective in sepsis. PMID:22844498

  2. Temporal trends in the systemic inflammatory response syndrome, sepsis, and medical coding of sepsis.

    PubMed

    Thomas, Benjamin S; Jafarzadeh, S Reza; Warren, David K; McCormick, Sandra; Fraser, Victoria J; Marschall, Jonas

    2015-11-24

    Recent reports using administrative claims data suggest the incidence of community- and hospital-onset sepsis is increasing. Whether this reflects changing epidemiology, more effective diagnostic methods, or changes in physician documentation and medical coding practices is unclear. We performed a temporal-trend study from 2008 to 2012 using administrative claims data and patient-level clinical data of adult patients admitted to Barnes-Jewish Hospital in St. Louis, Missouri. Temporal-trend and annual percent change were estimated using regression models with autoregressive integrated moving average errors. We analyzed 62,261 inpatient admissions during the 5-year study period. 'Any SIRS' (i.e., SIRS on a single calendar day during the hospitalization) and 'multi-day SIRS' (i.e., SIRS on 3 or more calendar days), which both use patient-level data, and medical coding for sepsis (i.e., ICD-9-CM discharge diagnosis codes 995.91, 995.92, or 785.52) were present in 35.3 %, 17.3 %, and 3.3 % of admissions, respectively. The incidence of admissions coded for sepsis increased 9.7 % (95 % CI: 6.1, 13.4) per year, while the patient data-defined events of 'any SIRS' decreased by 1.8 % (95 % CI: -3.2, -0.5) and 'multi-day SIRS' did not change significantly over the study period. Clinically-defined sepsis (defined as SIRS plus bacteremia) and severe sepsis (defined as SIRS plus hypotension and bacteremia) decreased at statistically significant rates of 5.7 % (95 % CI: -9.0, -2.4) and 8.6 % (95 % CI: -4.4, -12.6) annually. All-cause mortality, SIRS mortality, and SIRS and clinically-defined sepsis case fatality did not change significantly during the study period. Sepsis mortality, based on ICD-9-CM codes, however, increased by 8.8 % (95 % CI: 1.9, 16.2) annually. The incidence of sepsis, defined by ICD-9-CM codes, and sepsis mortality increased steadily without a concomitant increase in SIRS or clinically-defined sepsis. Our results highlight the need to develop

  3. [Analysis of the risk factors of acute respiratory distress syndrome of Berlin new definition in patients with sepsis in emergency department].

    PubMed

    Qiao, Liang; Liu, Zhi

    2015-07-01

    To discuss the risk factors of acute respiratory distress syndrome (ARDS) in patients with sepsis in emergency department. 312 patients with sepsis admitted to Department of Emergency of China Medical University Affiliated First Hospital were retrospectively analyzed, and they were divided into two groups according to development of ARDS, which was defined according to the Berlin new definition. The age, gender, vital signs, laboratory results, underlying disease, the mortality in emergency department sepsis (MEDS) score and lung injury prediction score (LIPS) were collected. Univariate analysis was done for each parameter. Statistical significance results were evaluated by multivariate logistic regression analysis. Receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of the parameter for ARDS. The incidence of sepsis-related ARDS was 11.2% (35/312). Within 35 cases of ARDS, there were 10 cases of mild ARDS, 18 cases of moderate ARDS, and 7 cases of severe ARDS. Univariate analysis showed that age (t=-2.134, P=0.035), oxygenation index (t=-4.245, P=0.001), arterial lactate (Lac, t=6.245, P<0.001), drugs for vascular diseases (χ2=4.261, P=0.026), shock (χ2=4.386, P=0.021), MEDS (t=4.021, P=0.045), LIPS (t=5.569, P<0.001), lung infections (χ2=4.289, P=0.025), and mechanical ventilation (χ2=6.245, P=0.001) were related to ARDS. The incidence of ARDS was different in different levels of Lac, which was 5.00% (3/16) at low level of Lac (<2.0 mmol/L), 9.46% (14/148) at middle level of Lac (2.0-3.9 mmol/L) and 17.31% (18/104) at high level of Lac (≥4.0 mmol/L). It was shown by multivariate logistic regression analysis that LIPS [ odds ratio (OR)=5.124, 95% confidence interval (95%CI)=3.642-10.153, P=0.002], Lac (OR=18.180, 95%CI=7.677-32.989, P<0.001) were independent risk factors for ARDS. It was shown by area under ROC (AUC) that the predictive value of LIPS and Lac in ARDS occurrence was significant. AUC of LIPS was 0.725, the

  4. A core outcome set for clinical trials in acute diarrhoea.

    PubMed

    Karas, Jacek; Ashkenazi, Shai; Guarino, Alfredo; Lo Vecchio, Andrea; Shamir, Raanan; Vandenplas, Yvan; Szajewska, Hania

    2015-04-01

    Core outcome sets are the baseline for what should be measured in clinical research and, thus, should serve as a guide for what should be collected and reported. The Consensus Group on Outcome Measures Made in Pediatric Enteral Nutrition Clinical Trials, established in 2012, agreed that consensus on a core set of outcomes with agreed-upon definitions that should be measured and reported in clinical trials was needed. To achieve this goal, six working groups (WGs) were setup, including WG on acute diarrhoea, whose main goal was to develop a core outcome set for trials in acute diarrhoea. The first step identified how published outcomes related to acute diarrhoea were reported. The second focused on the methodology for determining which outcomes to measure in clinical trials. The third employed a two-phase questionnaire study using the Delphi technique to define clinically important outcomes to clinicians and parents. For therapeutic studies, the five most important outcome measures were diarrhoea duration, degree of dehydration, need for hospitalisation (or duration of hospitalisation for inpatients), the proportion of patients recovered by 48 h and adverse effects. The prophylactic core outcome set included prevention of diarrhoea, prevention of dehydration, prevention of hospitalisation and adverse effects. The outcome sets for therapy and prevention can be recommended for use in future trials of patients with gastroenteritis. Their envisioned goal is to decrease study heterogeneity and to ease the comparability of studies. WG's next step is to determine how to measure the outcomes included in the core set. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  5. The Severity of Cecal Ligature and Puncture-Induced Sepsis Correlates with the Degree of Encephalopathy, but the Sepsis Does Not Lead to Acute Activation of Spleen Lymphocytes in Mice.

    PubMed

    Jeremias, I C; Victorino, V J; Machado, J L; Barroso, W A; Ariga, S K; Lima, T M; Soriano, F G

    2016-07-01

    Septic encephalopathy represents the most frequently observed form of encephalopathy in intensive care units. Interactions between the immune and nervous systems have been observed in experimental sepsis. Therefore, the aim of the current study was to characterize the effect of different severities of sepsis on encephalopathy and the inflammatory profile of the spleen. We hypothesized that different grades of sepsis severity would lead to variations in encephalopathy and activation of spleen cells. We induced sepsis of different severities in Balb/c mice by cecal ligature and puncture (CLP). Six and 12 h after CLP induction, behavioral impairment was assessed by the SmithKline/Harwell/Imperial College/Royal Hospital/Phenotype Assessment (SHIRPA) test. The animals were then killed, and the plasma, spleen, and hippocampus were removed. Levels of the encephalopathy marker S100β were measured in plasma. Spleens were weighed and then a characterization of splenic lymphocytes was performed by flow cytometry (cytotoxic T lymphocyte, T helper lymphocytes, B lymphocytes, T regulatory cells, and Th17 cells). Cytokine levels in the spleen and hippocampus were determined by enzyme-linked immunosorbent assay (ELISA), and cytokine levels in plasma were performed with MilliPlex® technology. Our results showed that behavioral impairment as measured by the SHIRPA test and elevation in plasma S100β levels were significant in moderate and severe CLP groups compared to those in the sham control group. Regarding immunological alterations, we were unable to observe changes in the weights of the spleen and the profile of lymphocytes 6 h after CLP. However, several cytokines, including IL-6, IL-10, and IL-1β, were increased in spleen and plasma. In conclusion, we observed variations in encephalopathy as measured by plasma S100β, which were mediated by the severity of sepsis; however, we did not observe a different activation of spleen cells 6 h post-CLP, despite evidence of

  6. Australian Staphylococcus aureus Sepsis Outcome Programme annual report, 2013.

    PubMed

    Coombs, Geoffrey W; Nimmo, Graeme R; Daly, Denise A; Le, Tam T; Pearson, Julie C; Tan, Hui-Leen; Robinson, James O; Collignon, Peter J; McLaws, Mary-Louise; Turnidge, John D

    2014-12-31

    From 1 January to 31 December 2013, around Australia 26 institutions around Australia participated in the Australian Staphylococcal Sepsis Outcome Programme (ASSOP). The aim of ASSOP 2013 was to determine the proportion of Staphylococcus aureus bacteraemia (SAB) isolates in Australia that are antimicrobial resistant, (with particular emphasis on susceptibility to methicillin) and to characterise the molecular epidemiology of the isolates. Overall 19.1% of the 2,010 SAB episodes were methicillin resistant, which is significantly higher than that reported in most European countries. Although the SAB 30-day all cause mortality appears to be decreasing in Australia, methicillin-resistant SAB associated mortality remains high (20.1%) and was significantly higher than methicillin-sensitive SAB associated mortality (13%) (P< 0.0001). With the exception of the ß-lactams and erythromycin, antimicrobial resistance in methicillin sensitive S. aureus remains rare. However, in addition to the ß-lactams, approximately 50% of methicillin-resistant S. aureus (MRSA) were resistant to erythromycin and ciprofloxacin and approximately 20% were resistant to co-trimoxazole, tetracycline and gentamicin. Linezolid, daptomycin and teicoplanin resistance was detected in a small number of S. aureus isolates. Resistance to vancomycin was not detected. Resistance was largely attributable to 2 healthcare associated MRSA clones; ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA). ST22-IV [2B] (EMRSA-15) has now become the predominant healthcare associated clone in Australia. Approximately 60% of methicillin-resistant SAB were due to community associated clones. Although polyclonal, almost 50% of community associated clones were characterised as ST93-IV [2B] (Queensland CA-MRSA) and ST1-IV [2B] (WA1). CA-MRSA, in particular the ST45-V [5C2&5] (WA84) clone, has acquired multiple antimicrobial resistance determinants including ciprofloxacin, erythromycin, clindamycin, gentamicin and

  7. The global maternal sepsis study and awareness campaign (GLOSS): study protocol.

    PubMed

    Bonet, Mercedes; Souza, Joao Paulo; Abalos, Edgardo; Fawole, Bukola; Knight, Marian; Kouanda, Seni; Lumbiganon, Pisake; Nabhan, Ashraf; Nadisauskiene, Ruta; Brizuela, Vanessa; Metin Gülmezoglu, A

    2018-01-30

    will provide data on the frequency of maternal sepsis and uptake of effective diagnostic and therapeutic interventions in obstetrics in different hospitals and countries. We will also be able to explore links between interventions and maternal and perinatal outcomes and identify priority areas for action.

  8. Sepsis and cytomegalovirus: foes or conspirators?

    PubMed

    Mansfield, Sara; Grießl, Marion; Gutknecht, Michael; Cook, Charles H

    2015-06-01

    Cytomegalovirus (CMV) reactivation in non-immune-suppressed critically ill patients is an area of increasing interest. CMV has long been appreciated as a pathogen in immunocompromised hosts. CMV reactivates in approximately one-third of latently infected non-immune-suppressed hosts during critical illness; however, its role as a pathogen in these patients remains unclear. CMV reactivation has been linked to bacterial sepsis and likely results from inflammation, transient immune compromise, and viral epigenetic changes. While CMV may improve immune response to some bacterial infections, other data suggest that CMV induces exaggerated responses to severe infections that may be harmful to latently infected hosts. These results also suggest that previous infection history may explain significant differences seen between human septic responses and murine models of sepsis. While critically ill human hosts clearly have worse outcomes associated with CMV reactivation, determining causality remains an area of investigation, with randomized control trials currently being performed. Here we review the current literature and highlight areas for future investigation.

  9. Comparison of the Performance Between Sepsis-1 and Sepsis-3 in ICUs in China: A Retrospective Multicenter Study.

    PubMed

    Cheng, Baoli; Li, Zhongwang; Wang, Jingya; Xie, Guohao; Liu, Xu; Xu, Zhipeng; Chu, Lihua; Zhao, Jialian; Yao, Yongming; Fang, Xiangming

    2017-09-01

    The definition of sepsis was updated to sepsis-3 in February 2016. However, the performance of the previous and new definition of sepsis remains unclear in China. This was a retrospective multicenter study in six intensive care unit (ICUs) from five university-affiliated hospitals to compare the performance between sepsis-1 and sepsis-3 in China. From May 1, 2016 to June 1, 2016, 496 patients were enrolled consecutively. Data were extracted from the electronic clinical records. We evaluated the performance of sepsis-1 and sepsis-3 by measuring the area under the receiver operating characteristic curves (AUROC) to predict 28-day mortality rates. Of 496 enrolled patients, 186 (37.5%) were diagnosed with sepsis according to sepsis-1, while 175 (35.3%) fulfilled the criteria of sepsis-3. The AUROC of systemic inflammatory response syndrome (SIRS) is significantly smaller than that of sequential organ failure assessment (SOFA) (0.55 [95% confidence interval, 0.46-0.64] vs. 0.69 (95% confidence interval, 0.61-0.77], P = 0.008) to predict 28-day mortality rates of infected patients. Moreover, 5.9% infected patients (11 patients) were diagnosed as sepsis according to sepsis-1 but not to sepsis-3. The APACHE II, SOFA scores, and mortality rate of the 11 patients were significantly lower than of patients whose sepsis was defined by both the previous and new criteria (8.6±3.5 vs. 16.3±6.2, P =  < 0.001; 1 (0-1) vs. 6 (4-8), P = <0.001; 0.0 vs. 33.1%, P = 0.019). In addition, the APACHE II, length of stay in ICU, and 28-day mortality rate of septic patients rose gradually corresponding with the raise in SOFA score (but not the SIRS score). Sepsis-3 performed better than sepsis-1 in the study samples in ICUs in China.

  10. Recent developments and current issues in the epidemiology, diagnosis, and management of bacterial and fungal neonatal sepsis.

    PubMed

    Shane, Andi L; Stoll, Barbara J

    2013-02-01

    Identifying neonates with sepsis is complicated by variability in clinical presentation. The incidence of early onset sepsis (EOS) resulting from invasive group B streptococcal (GBS) infections has been notably reduced by the widespread delivery of intrapartum antibiotic prophylaxis. Rates of EOS attributable to non-GBS etiologies have remained constant, and ampicillin-resistant Escherichia coli has become more prevalent. Late-onset sepsis (LOS) attributable to gram-positive organisms including coagulase-negative Staphylococci and Staphylococcus aureus is associated with increased morbidity and mortality among premature infants. Invasive candidiasis is an emerging cause of LOS, especially among infants who receive broad-spectrum antimicrobial agents. Prophylactic fluconazole administration to very low-birth-weight (VLBW) neonates during the first 6 weeks of life prevents invasive candidiasis in neonatal intensive care units (NICU) with high rates of fungal infections. Targeted fluconazole prophylaxis may be beneficial in VLBW neonates who receive care in NICUs with lower rates of invasive fungal infections. Assessment of immune function, neutrophil markers, acute phase reactants, and utilization of sepsis screening scores may contribute to the management of sepsis. Maternal decolonization, antimicrobial stewardship, early enteral feeding, and optimal infection control practices are potential practical strategies for reducing the burden of neonatal sepsis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  11. Insulin resistance and clinical outcomes after acute ischemic stroke.

    PubMed

    Ago, Tetsuro; Matsuo, Ryu; Hata, Jun; Wakisaka, Yoshinobu; Kuroda, Junya; Kitazono, Takanari; Kamouchi, Masahiro

    2018-04-24

    In this study, we aimed to determine whether insulin resistance is associated with clinical outcomes after acute ischemic stroke. We enrolled 4,655 patients with acute ischemic stroke (aged 70.3 ± 12.5 years, 63.5% men) who had been independent before admission; were hospitalized in 7 stroke centers in Fukuoka, Japan, from April 2009 to March 2015; and received no insulin therapy during hospitalization. The homeostasis model assessment of insulin resistance (HOMA-IR) score was calculated using fasting blood glucose and insulin levels measured 8.3 ± 7.8 days after onset. Study outcomes were neurologic improvement (≥4-point decrease in NIH Stroke Scale score or 0 at discharge), poor functional outcome (modified Rankin Scale score of ≥3 at 3 months), and 3-month prognosis (stroke recurrence and all-cause mortality). Logistic regression analysis was used to evaluate the association of the HOMA-IR score with clinical outcomes. The HOMA-IR score was associated with neurologic improvement (odds ratio, 0.68 [95% confidence interval, 0.56-0.83], top vs bottom quintile) and with poor functional outcome (2.02 [1.52-2.68], top vs bottom quintile) after adjusting for potential confounding factors, including diabetes and body mass index. HOMA-IR was not associated with stroke recurrence or mortality within 3 months of onset. The associations were maintained in nondiabetic or nonobese patients. No heterogeneity was observed according to age, sex, stroke subtype, or stroke severity. These findings suggest that insulin resistance is independently associated with poor functional outcome after acute ischemic stroke apart from the risk of short-term stroke recurrence or mortality. © 2018 American Academy of Neurology.

  12. Inclusion of emergency department patients in early stages of sepsis in a quality improvement programme has the potential to improve survival: a prospective dual-centre study.

    PubMed

    De Groot, Bas; Struyk, Bastiaan; Najafi, Rashed; Halma, Nieke; Pelser, Loekie; Vorst, Denise; Mertens, Bart; Ansems, Annemieke; Rijpsma, Douwe

    2017-09-01

    Sepsis quality improvement programmes typically focus on severe sepsis (ie, with acute organ failure). However, quality of ED care might be improved if these programmes included patients whose progression to severe sepsis could still be prevented (ie, infection without acute organ failure). We compared the impact on mortality of implementing a quality improvement programme among ED patients with a suspected infection with or without acute organ failure. This prospective observational study among ED patients hospitalised with suspected infection was conducted in two hospitals in the Netherlands. After stratification by sepsis category (with or without organ failure), in-hospital mortality was compared between a full compliance ( all quality performance measures achieved) and an incomplete compliance group. Multivariable logistic regression analysis was used to quantify the impact of full compliance on in-hospital mortality, adjusting for disease severity, disposition and hospital. There were 1732 ED patients and 130 deaths. Full compliance was independently associated with approximately two-thirds reduction in the odds of hospital mortality ( adjusted OR of 0.30 (95% CI 0.19 to 0.47), which was similar in patients with and without organ failure. Among the 1379 patients with suspected infection without acute organ failure, there were 64 deaths, 15 (1.1%) in the full compliance group and 49 (3.6%) in the incomplete compliance group (mortality difference 2.5% (95% CI 1.6% to 3.3%)). Among 353 patients with organ failure, there were 66 deaths, 12 (3.4%) in the full compliance compared with 54 (15.3%) in the incomplete compliance group (mortality difference 11.9% (95% CI 8.5% to 15.3%)). Thus, there was a difference of 76 deaths between full and incomplete compliance groups, and 34 (45%) who benefited were those without acute organ failure. Sepsis quality improvement programmes should incorporate ED patients in earlier stages of sepsis given the potential to reduce in

  13. Pharmacological management of sepsis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fletcher, J.R.

    Systemic sepsis continues to be the most-difficult management problem in caring for the combat casualty. The complications of sepsis pervade all areas of injury to soldiers in the field, whether it is mechanical (missiles), thermal (burns), chemical, biological, or radiation injury. With the advent of tactical nuclear weapons, the problem of sepsis will be much higher in future wars than has previously been experienced through the world. The purpose of this chapter is a) to review the data suggesting pharmacological agents that may benefit the septic patient, and b) to emphasize the adjunctive therapies that should be explored in clinicalmore » trials. The pharmacological management of sepsis remains controversial. Most of the drugs utilized clinically treat the symptoms of the disease and are not necessarily directed at fundamental mechanisms that are known to be present in sepsis. A broad data base is emerging, indicating that NSAID should be used in human clinical trials. Prostaglandins are sensitive indicators of cellular injury and may be mediators for a number of vasoactive chemicals. Opiate antagonists and calcium channel blockers require more in-depth data; however, recent studies generate excitement for their potential use in the critically ill patient. Pharmacological effects of antibiotics, in concert with other drugs, suggest an entirely new approach to pharmacological treatment in sepsis. There is no doubt that new treatment modalities or adjunctive therapies must be utilized to alter the poor prognosis of severe sepsis that we have observed in the past 4 decades.« less

  14. Long-term outcomes of acute kidney injury.

    PubMed

    Coca, Steven G

    2010-05-01

    The goal of this review is to summarize the recent plethora of data that relate to long-term outcomes after acute kidney injury (AKI). Surviving patients with AKI are still at high risk for long-term adverse outcomes, even if serum creatinine returns to normal. After adjusting for potential confounders, many recent studies have demonstrated that AKI is independently associated with chronic kidney disease, end-stage renal disease, and premature death. Unfortunately, definitive evidence from randomized controlled trials demonstrating that prevention or treatment of AKI prevents long-term adverse outcomes is not yet available. AKI is clearly a prognostic marker for poor long-term outcomes, but more studies will be needed to determine whether AKI is truly causal and whether or not the risk is modifiable.

  15. Sepsis risk factors in infants with congenital diaphragmatic hernia.

    PubMed

    Levy, Michaël; Le Sache, Nolwenn; Mokhtari, Mostafa; Fagherazzi, Guy; Cuzon, Gaelle; Bueno, Benjamin; Fouquet, Virginie; Benachi, Alexandra; Eleni Dit Trolli, Sergio; Tissieres, Pierre

    2017-12-01

    Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly and remains among the most challenging ICU-managed disease. Beside severe pulmonary hypertension, lung hypoplasia and major abdominal surgery, infective complications remain major determinants of outcome. However, the specific incidence of sepsis as well as associated risk factors is unknown. This prospective, 4-year observational study took place in the pediatric intensive care and neonatal medicine department of the Paris South University Hospitals (Le Kremlin-Bicêtre, France), CDH national referral center and involved 62 neonates with CDH. During their ICU stay, 28 patients (45%) developed 38 sepsis episodes. Ventilator-associated pneumonia (VAP: 23/38; 31.9 VAP per 1000 days of mechanical ventilation) and central line-associated blood stream infections (CLABSI: 5/38; 5.5 per 1000 line days) were the most frequently encountered infections. Multivariate analysis showed that gestational age at birth and intra-thoracic position of liver were significantly associated with the occurrence of sepsis. Infected patients had longer duration of mechanical and noninvasive ventilation (16.2 and 5.8 days, respectively), longer delay to first feeding (1.2 days) and a longer length of stay in ICU (23 days), but there was no difference in mortality. Healthcare-associated infections, and more specifically VAP, are the main infective threat in children with CDH. Sepsis has a significant impact on the duration of ventilator support and ICU length of stay but does not impact mortality. Low gestational age and intra-thoracic localization of the liver are two independent risk factors associated with sepsis.

  16. Chromobacterium Violaceum Sepsis: Rethinking Conventional Therapy to Improve Outcome

    PubMed Central

    Richard, Kathleen R.; Lovvorn, Joshua J.; Oliver, Sara E.; Ross, Shannon A.; Benner, Kim W.; Kong, Michele Y.F.

    2015-01-01

    Patient: Male, 11 Final Diagnosis: Chromobacterium violaceum infection Symptoms: Abscess • fever • rash Medication: — Clinical Procedure: ECMO Specialty: Critical Care Medicine Objective: Rare disease Background: Chromobacterium violaceum (C. violaceum) is a facultative anaerobic gram-negative bacterium found in soil and water, especially in tropical and subtropical areas. Although infection in humans is rare, it is associated with significant morbidity. The bacterium is known for its resistance to multiple antimicrobials, and the possibility of relapse and reinfection. Presence of bacteremia, disseminated infection, and ineffective antimicrobial agents are predictors of mortality. Case Report: We report the case of a previously healthy 11-year-old male with C. violaceum sepsis who was exposed to stagnant water. He presented with severe septic shock and developed multi-organ system failure. Initial presumptive diagnosis was staphylococcal infection secondary to presence of skin abscesses resulting in antibiotic coverage with vancomycin, clindamycin, nafcillin and ceftriaxone. He also had multiple lung and liver abscesses. Once C. violaceum was identified, he received meropenem and ciprofloxacin, and was later discharged on ertapenem and trimethoprim-sulfamethoxazole (TMP-SMX) to complete a total of six months of antibiotics. He was diagnosed with chronic granulomatous disease (CGD) and is currently on prophylactic TMP-SMX and itraconazole. He has not had any relapses since his initial presentation. Conclusions: This case highlights the importance of considering C. violaceum as a relevant human pathogen, and considering it early in temperate regions, particularly in cases of fulminant sepsis associated with multi-organ abscesses. Once C. violaceum is identified, appropriate antimicrobial therapy should be started promptly, and sufficient duration of treatment is necessary for successful therapy. PMID:26477750

  17. Endothelial Progenitor Cell Mobilization in Preterm Infants With Sepsis Is Associated With Improved Survival.

    PubMed

    Siavashi, Vahid; Asadian, Simin; Taheri-Asl, Masoud; Keshavarz, Samaneh; Zamani-Ahmadmahmudi, Mohamad; Nassiri, Seyed Mahdi

    2017-10-01

    Microvascular dysfunction plays a key role in the pathology of sepsis, leading to multi-organ failure, and death. Circulating endothelial progenitor cells (cEPCs) are critically involved in the maintenance of the vascular homeostasis in both physiological and pathological contexts. In this study, concentration of cEPCs in preterm infants with sepsis was determined to recognize whether the EPC mobilization would affect the clinical outcome of infantile sepsis. One hundred and thirty-three preterm infants (81 with sepsis and 52 without sepsis) were enrolled in this study. The release of EPCs in circulation was first quantified. Thereafter, these cells were cultivated and biological features of these cells such as, proliferation and colony forming efficiency were analyzed. The levels of chemoattractant cytokines were also measured in infants. In mouse models of sepsis, effects of VEGF and SDF-1 as well as anti-VEGF and anti-SDF-1 were evaluated in order to shed light upon the role which the EPC mobilization plays in the overall survival of septic animals. Circulating EPCs were significantly higher in preterm infants with sepsis than in the non-sepsis group. Serum levels of VEGF, SDF-1, and Angiopoietin-2 were also higher in preterm infants with sepsis than in control non-sepsis. In the animal experiments, injection of VEGF and SDF-1 prompted the mobilization of EPCs, leading to an improvement in survival whereas injection of anti-VEGF and anti-SDF-1 was associated with significant deterioration of survival. Overall, our results demonstrated the beneficial effects of EPC release in preterm infants with sepsis, with increased mobilization of these cells was associated with improved survival. J. Cell. Biochem. 118: 3299-3307, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. [Diagnostic value of a combination of biomarkers in patients with sepsis and severe sepsis in emergency department].

    PubMed

    Zhao, Yongzhen; Li, Chunsheng

    2014-03-01

    To determine a combination of biomarkers that assure the diagnosis of sepsis and severe sepsis in patients in emergency department (ED). A total of 652 patients with systemic inflammatory response syndrome (SIRS) were enrolled for this prospective study in the ED of Beijing Chaoyang Hospital of the Capital Medical University between March 2010 and March 2013. Eight biomarkers were determined, including levels of procalcitonin (PCT), interleukin-6 (IL-6), D-dimer, C-reactive protein (CRP), brain natriuretic peptide (BNP), white blood cell count (WBC), percentage of immature neutrophil, and platelet count (PLT). Patients were divided into the sepsis group (452 cases) and non-sepsis group (200 cases) according to the diagnostic criteria of sepsis. Then all these patients were stratified into severe sepsis group (190 cases, including septic shock) and non-severe sepsis group (462 cases) according to the diagnosis of severe sepsis. Logistic regression was performed to identify the independent factors for the diagnosis of sepsis and severe sepsis, and the optimal combination of biomarkers was established. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic ability of the combination and the biomarkers.A total of 652 patients with systemic inflammatory response syndrome (SIRS) were enrolled for this prospective study in the ED of Beijing Chaoyang Hospital of the Capital Medical University between March 2010 and March 2013. Eight biomarkers were determined, including levels of procalcitonin (PCT), interleukin-6 (IL-6), D-dimer, C-reactive protein (CRP), brain natriuretic peptide (BNP), white blood cell count (WBC), percentage of immature neutrophil, and platelet count (PLT). Patients were divided into the sepsis group (452 cases) and non-sepsis group (200 cases) according to the diagnostic criteria of sepsis. Then all these patients were stratified into severe sepsis group (190 cases, including septic shock) and non-severe sepsis group (462

  19. Clostridium difficile infection in pediatric acute myeloid leukemia: from the Canadian Infections in Acute Myeloid Leukemia Research Group.

    PubMed

    Price, Victoria; Portwine, Carol; Zelcer, Shayna; Ethier, Marie-Chantal; Gillmeister, Biljana; Silva, Mariana; Schindera, Christina; Yanofsky, Rochelle; Mitchell, David; Johnston, Donna L; Lewis, Victor; Dix, David; Cellot, Sonia; Michon, Bruno; Bowes, Lynette; Stobart, Kent; Brossard, Josee; Beyene, Joseph; Sung, Lillian

    2013-06-01

    The prevalence and severity of Clostridium difficile infection (CDI) has increased over time in adult patients, but little is known about CDI in pediatric cancer. The primary objectives were to describe the incidence and characteristics of CDI in children with de novo acute myeloid leukemia (AML). The secondary objective was to describe factors associated with CDI. We performed a multicenter, retrospective cohort study of children with de novo AML and evaluated CDI. Recurrence, sepsis and infection-related death were examined. Factors associated with CDI were also evaluated. Forty-three CDI occurred in 37 of 341 (10.9%) patients during 42 of 1277 (3.3%) courses of chemotherapy. There were 6 children with multiple episodes of CDI. Three infections were associated with sepsis, and no children died of CDI. Only 2 children had an associated enterocolitis. Both days of broad-spectrum antibiotics (odds ratio 1.03, 95% confidence interval: 1.01 to 1.06; P = 0.003) and at least 1 microbiologically documented sterile site infection (odds ratio 10.81, 95% confidence interval: 5.88 to 19.89; P < 0.0001) were independently associated with CDI. CDI occurred in 11% of children receiving intensive chemotherapy for AML, and outcomes were not severe. CDI is not a prominent issue in pediatric AML in terms of prevalence, incidence or associated outcomes.

  20. Towards a consensus definition of maternal sepsis: results of a systematic review and expert consultation.

    PubMed

    Bonet, Mercedes; Nogueira Pileggi, Vicky; Rijken, Marcus J; Coomarasamy, Arri; Lissauer, David; Souza, João Paulo; Gülmezoglu, Ahmet Metin

    2017-05-30

    There is a need for a clear and actionable definition of maternal sepsis, in order to better assess the burden of this condition, trigger timely and effective treatment and allow comparisons across facilities and countries. The objective of this study was to review maternal sepsis definitions and identification criteria and to report on the results of an expert consultation to develop a new international definition of maternal sepsis. All original and review articles and WHO documents, as well as clinical guidelines providing definitions and/or identification criteria of maternal sepsis were included. A multidisciplinary international panel of experts was surveyed through an online consultation in March-April 2016 on their opinion on the existing sepsis definitions, including new definition of sepsis proposed for the adult population (2016 Third International Consensus Definitions for Sepsis and Septic Shock) and importance of different criteria for identification of maternal sepsis. The definition was agreed using an iterative process in an expert face-to-face consensus development meeting convened by WHO and Jhpiego. Standardizing the definition of maternal sepsis and aligning it with the current understanding of sepsis in the adult population was considered a mandatory step to improve the assessment of the burden of maternal sepsis by the expert panel. The literature review and expert consultation resulted in a new WHO consensus definition "Maternal sepsis is a life-threatening condition defined as organ dysfunction resulting from infection during pregnancy, child-birth, post-abortion, or post-partum period". Plans are in progress to validate the new WHO definition of maternal sepsis in a large international population. The operationalization of the new maternal sepsis definition requires generation of a set of practical criteria to identify women with sepsis. These criteria should enable clinicians to focus on the timely initiation of actionable elements of

  1. Blue Light Enhances Bacterial Clearance and Reduces Organ Injury During Sepsis.

    PubMed

    Lewis, Anthony J; Zhang, Xianghong; Griepentrog, John E; Yuan, Du; Collage, Richard D; Waltz, Paul K; Angus, Derek C; Zuckerbraun, Brian S; Rosengart, Matthew R

    2018-05-04

    The physiology of nearly all mammalian organisms are entrained by light and exhibit circadian rhythm. The data derived from animal studies show that light influences immunity, and these neurophysiologic pathways are maximally entrained by the blue spectrum. Here, we hypothesize that bright blue light reduces acute kidney injury by comparison with either bright red or standard, white fluorescent light in mice subjected to sepsis. To further translational relevance, we performed a pilot clinical trial of blue light therapy in human subjects with appendicitis. Laboratory animal research, pilot human feasibility trial. University basic science laboratory and tertiary care hospital. Male C57BL/6J mice, adult (> 17 yr) patients with acute appendicitis. Mice underwent cecal ligation and puncture and were randomly assigned to a 24-hour photoperiod of bright blue, bright red, or ambient white fluorescent light. Subjects with appendicitis were randomized to receive postoperatively standard care or standard care plus high-illuminance blue light. Exposure to bright blue light enhanced bacterial clearance from the peritoneum, reduced bacteremia and systemic inflammation, and attenuated the degree of acute kidney injury. The mechanism involved an elevation in cholinergic tone that augmented tissue expression of the nuclear orphan receptor REV-ERBα and occurred independent of alterations in melatonin or corticosterone concentrations. Clinically, exposure to blue light after appendectomy was feasible and reduced serum interleukin-6 and interleukin-10 concentrations. Modifying the spectrum of light may offer therapeutic utility in sepsis.

  2. Sirt1 restrains lung inflammasome activation in a murine model of sepsis.

    PubMed

    Gao, Rong; Ma, Zhongsen; Hu, Yuxin; Chen, Jiao; Shetty, Sreerama; Fu, Jian

    2015-04-15

    Excessive inflammation is a major cause of organ damage during sepsis. The elderly are highly susceptible to sepsis-induced organ injury. Sirt1 expression is reduced during aging. In the present study, we investigated the role of Sirt1, a histone deacetylase, in controlling inflammatory responses in a murine sepsis model induced by cecal ligation and puncture (CLP). We examined lung inflammatory signaling in inducible Sirt1 knockout (Sirt1(-/-)) mice and wild-type littermates (Sirt1(+/+)) after CLP. Our results demonstrated that Sirt1 deficiency led to severe lung inflammatory injury. To further investigate molecular mechanisms of Sirt1 regulation of lung inflammatory responses in sepsis, we conducted a series of experiments to assess lung inflammasome activation after CLP. We detected increased lung inflammatory signaling including NF-κB, signal transducer and activator of transcription 3, and ERK1/2 activation in Sirt1(-/-) mice after CLP. Furthermore, inflammasome activity was increased in Sirt1(-/-) mice after CLP, as demonstrated by increased IL-1β and caspase-7 cleavage and activation. Aggravated inflammasome activation in Sirt1(-/-) mice was associated with the increased production of lung proinflammatory mediators, including ICAM-1 and high-mobility group box 1, and further disruption of tight junctions and adherens junctions, as demonstrated by dramatic reduction of lung claudin-1 and vascular endothelial-cadherin expression, which was associated with the upregulation of matrix metallopeptidase 9 expression. In summary, our results suggest that Sirt1 suppresses acute lung inflammation during sepsis by controlling inflammasome activation pathway. Copyright © 2015 the American Physiological Society.

  3. Sepsis in Internal Medicine wards: current knowledge, uncertainties and new approaches for management optimization.

    PubMed

    Zaccone, Vincenzo; Tosoni, Alberto; Passaro, Giovanna; Vallone, Carla Vincenza; Impagnatiello, Michele; Li Puma, Domenica Donatella; De Cosmo, Salvatore; Landolfi, Raffaele; Mirijello, Antonio

    2017-11-01

    Sepsis represents a global health problem in terms of morbidity, mortality, social and economic costs. Although usually managed in Intensive Care Units, sepsis showed an increased prevalence among Internal Medicine wards in the last decade. This is substantially due to the ageing of population and to multi-morbidity. These characteristics represent both a risk factor for sepsis and a relative contra-indication for the admission to Intensive Care Units. Although there is a lack of literature on the management of sepsis in Internal Medicine, the outcome of these patients seems to be gradually improving. This is due to Internists' increased adherence to guidelines and "bundles". The routine use of SOFA score helps physicians in the definition of septic patients, even if the optimal score has still to come. Point-of-care ultrasonography, lactates, procalcitonin and beta-d-glucan are of help for treatment optimization. The purpose of this narrative review is to focus on the management of sepsis in Internal Medicine departments, particularly on crucial concepts regarding diagnosis, risk assessment and treatment. Key Messages Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The prevalence of sepsis is constantly increasing, affecting more hospital patients than any other disease. At least half of patients affected by sepsis are admitted to Internal Medicine wards. Adherence to guidelines, routine use of clinical and lab scores and point-of-care ultrasonography are of help for early recognition of septic patients and treatment optimization.

  4. Differential expression of plasma miR-146a in sepsis patients compared with non-sepsis-SIRS patients.

    PubMed

    Wang, Lina; Wang, Hua-Cheng; Chen, Cha; Zeng, Jianming; Wang, Qian; Zheng, Lei; Yu, Huan-DU

    2013-04-01

    Sepsis is a subtype of systemic inflammatory response syndrome (SIRS), which is characterized by infection. Circulating microRNAs (miRNAs), including miR-150, miR-146a and miR-223, are potential biomarkers of sepsis. In this study, we demonstrated that measuring the relative expression of miR-146a/U6 in plasma, using the 2 -ΔΔCt method, provides a method for differentiating between sepsis and non-sepsis-SIRS. We observed a significant increase in miR-146a expression in the initial cohort of 6 non-sepsis-SIRS patients compared to the 4 sepsis patients (P=0.01) and in the second cohort of 8 non-sepsis-SIRS patients compared to the 10 sepsis patients (P=0.027). Additionally, we identified that sodium citrate and ethylenediaminetetraacetic acid (EDTA) K 2 may be used as anticoagulant reagents. Generation of a standard curve is not necessary in these diagnostic tests, unless the standard of normalization is carefully selected. Thus we provide more detailed guidance for the clinical use of circulating miRNA biomarkers.

  5. Implications of culture positivity in acute pancreatitis: does the source matter?

    PubMed

    Rao, Chalapathi; Bhasin, Deepak Kumar; Rana, Surinder Singh; Gupta, Rajesh; Gautam, Vikas; Singh, Kartar

    2013-05-01

    Sepsis is an important complication and cause of morbidity and mortality in acute pancreatitis (AP). The source of sepsis may be infected pancreatic and peripancreatic collections and/or necrosis or extrapancreatic including infections in the bloodstream or respiratory and urinary tracts. We studied the implications of the source of sepsis on various outcome parameters in AP like persistent organ failure (POF), length of hospital (LOH) stay, and mortality. A retrospective analysis of culture reports of AP patients was done, and the outcome parameters were recorded. Three hundred fifty-seven patients (229 M; age: 40.3 ± 14.04 years) of AP who had detailed culture reports were included. Eighty-four (23.5%) patients had pancreatic (or peripancreatic) source (group 1), 52 (14.6%) patients had other (extrapancreatic) sources (group 2), 20 (5.6%) patients were noted to have positive cultures from sources, which were both pancreatic and extrapancreatic (combined) sources (group 3), while 201 patients had sterile cultures. POF was seen in 147 (48%) patients (group 1: 67.8%; group 2: 65%; group 3: 90%; group 4: 34% [P < 0.001]). The mean LOH stay was 22.1 ± 20.26 days (group 1: 30.2 ± 20.64 days; group 2: 26.4 ± 26.82 days; group 3: 47.3 ± 32.60 days; group 4: 15.2 ± 11.34 days [P < 0.001]). Seventy (19.7%) patients succumbed to their illness (group 1 [22.9%]; group 2 [36.5%]; group 3 [40%]; group 4 [12%] [P < 0.001]). POF and LOH stay were more common in patients with combined pancreatic and extrapancreatic sources of sepsis. Mortality was significantly higher in patients with sepsis (groups 1, 2, 3) compared with sterile groups. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  6. Interleukin-8 in sepsis: relation to shock and inflammatory mediators.

    PubMed Central

    Hack, C E; Hart, M; van Schijndel, R J; Eerenberg, A J; Nuijens, J H; Thijs, L G; Aarden, L A

    1992-01-01

    Because of its neutrophil-activating properties, interleukin-8 (IL-8) may play an important role in the pathophysiology of sepsis. We measured circulating IL-8 levels in 47 patients with clinical sepsis. Levels on admission were elevated in 42 of the 47 patients (89%) and were comparable in patients with gram-positive or gram-negative infections. Patients with shock had significantly higher IL-8 levels than normotensive patients (P = 0.0014, Wilcoxon-Mann-Whitney test), whereas no differences in IL-8 levels were found between patients with or without adult respiratory distress syndrome. Patients who died had higher IL-8 levels on admission than the patients who survived. The largest differences in IL-8 levels between survivors and nonsurvivors was found when only patients with positive cultures were considered (P = 0.0342). IL-8 levels appeared to correlate significantly with lactate levels and inversely with leukocyte and platelet numbers and mean arterial pressure. In addition, the IL-8 level in the sepsis patients was found to correlate significantly with levels of IL-6, elastase-alpha 1-antitrypsin, and C3a. Serial observations revealed that in most patients IL-8 levels decreased, irrespective of the outcome. Thus, our results demonstrate that IL-8 levels are increased in most patients with sepsis and correlate with some important clinical, biochemical, and inflammatory parameters. These findings suggest a role for IL-8 in the pathophysiology of sepsis. PMID:1612748

  7. Outcome of Acute Pancreatic and Peripancreatic Collections Occurring in Patients With Acute Pancreatitis.

    PubMed

    Manrai, Manish; Kochhar, Rakesh; Gupta, Vikas; Yadav, Thakur Deen; Dhaka, Narendra; Kalra, Naveen; Sinha, Saroj K; Khandelwal, Niranjan

    2018-02-01

    To study the outcome of acute collections occurring in patients with acute pancreatitis BACKGROUND:: There are limited data on natural history of acute collections arising after acute pancreatitis (AP). Consecutive patients of AP admitted between July 2011 and December 2012 were evaluated by imaging for development of acute collections as defined by revised Atlanta classification. Imaging was repeated at 1 and 3 months. Spontaneous resolution, evolution, and need for intervention were assessed. Of the 189 patients, 151 patients (79.9%) had acute collections with severe disease and delayed hospitalization being predictors of acute collections. Thirty-six patients had acute interstitial edematous pancreatitis, 8 of whom developed acute peripancreatic fluid collections, of which 1 evolved into pseudocyst. Among the 153 patients with acute necrotizing pancreatitis, 143 (93.4%) developed acute necrotic collection (ANC). Twenty-three of 143 ANC patients died, 21 had resolved collections, whereas 84 developed walled-off necrosis (WON), with necrosis >30% (P = 0.010) and Computed Tomographic Severity Index score ≥7 (P = 0.048) predicting development of WON. Of the 84 patients with WON, 8 expired, 53 patients required an intervention, and 23 were managed conservatively. Independent predictors of any intervention among all patients were Computed Tomographic Severity Index score ≥7 (P < 0.001) and interval between onset of pain to hospitalization >7 days (P = 0.04). Patients with severe AP and delayed hospitalization more often develop acute collections. Pancreatic pseudocysts are a rarity in acute interstitial pancreatitis. A majority of patients with necrotising pancreatitis will develop ANC, more than half of whom will develop WON. Delay in hospitalization and higher baseline necrosis score predict need for intervention.

  8. Role of folate status and methylenetetrahydrofolate reductase genotype on the toxicity and outcome of induction chemotherapy in children with acute lymphoblastic leukemia.

    PubMed

    Roy Moulik, Nirmalya; Kumar, Archana; Agrawal, Suraksha; Awasthi, Shally; Mahdi, Abbas Ali; Kumar, Ashutosh

    2015-05-01

    The effect of serum folate levels and methylenetetrahydrofolate reductase (MTHFR) genotype on complications and outcome of induction chemotherapy in 150 children with acute lymphoblastic leukemia (ALL) was studied. Folate deficiency in 26% at baseline was more common in children with MTHFR 677 mutations. Folate deficient children had a higher incidence of neutropenia (p = 0.03), thrombocytopenia (p = 0.02) and febrile neutropenia (p = 0.01) and higher transfusion requirement during induction compared to folate sufficient children. Sepsis related induction deaths were more frequent in folate deficient children (p = 0.02) during induction. Children with 677 and 1298 mutations had a higher incidence of cytopenias (p = 0.01) and mucositis (p = 0.007), the risks of which increased with concomitant folate deficiency. A significant fall in folate levels was observed post-induction (p = 0.02), most markedly in mutant 677 genotypes. Multivariate analysis revealed associations of baseline folate deficiency with low counts at day 14 (p = 0.001) and MTHFR 1298 mutations with mucositis (p = 0.02).

  9. Sepsis in general surgery: a deadly complication.

    PubMed

    Moore, Laura J; Moore, Frederick A; Jones, Stephen L; Xu, Jiaqiong; Bass, Barbara L

    2009-12-01

    Sepsis is a deadly and potentially preventable complication. A better understanding of sepsis in general surgery patients is needed to help direct resources to those patients at highest risk for death from sepsis. We identified risk factors for sepsis in general surgery patients by using the National Surgical Quality Improvement Project database. Analysis of the database identified 3 major risk factors for both the development of sepsis and death from sepsis in general surgery patients. These risk factors are age older than 60 years, need for emergency surgery, and the presence of comorbid conditions. Risk factors for death from sepsis or septic shock in general surgery patients include age older than 60 years, need for emergency surgery, and the presence of preexisting comorbidities. These findings emphasize the need for early recognition through aggressive sepsis screening and rapid implementation of evidence-based interventions for sepsis and septic shock in general surgery patients with these risk factors.

  10. Dementia in the acute hospital: the prevalence and clinical outcomes of acutely unwell patients with dementia.

    PubMed

    Briggs, R; Dyer, A; Nabeel, S; Collins, R; Doherty, J; Coughlan, T; O'Neill, D; Kennelly, S P

    2017-01-01

    Studies have demonstrated that a significant minority of older persons presenting to acute hospital services are cognitively impaired; however, the impact of dementia on long-term outcomes is less clear. To evaluate the prevalence of dementia, both formally diagnosed and hitherto unrecognised in a cohort of acutely unwell older adults, as well as its impact on both immediate outcomes (length of stay and in-hospital mortality) and 12-month outcomes including readmission, institutionalisation and death. Prospective observational study. 190 patients aged 70 years and over, presenting to acute hospital services underwent a detailed health assessment including cognitive assessment (standardised Mini Mental State Examination, AD8 and Confusion Assessment Method for the Intensive Care Unit). Patients or informants were contacted directly 12 months later to compile 1-year outcome data. Dementia was defined as a score of 2 or more on the AD8 screening test. Dementia was present in over one-third of patients (73/190). Of these patients, 36% (26/73) had a prior documented diagnosis of dementia with the remaining undiagnosed before presentation. The composite outcome of death or readmission to hospital within the following 12 months was more likely to occur in patients with dementia (73% (53/73) vs. 58% (68/117), P = 0.043). This finding persisted after controlling for age, gender, frailty status and medical comorbidities, including stroke and heart disease. A diagnosis of dementia confers an increased risk of either death or further admission within the following 12 months, highlighting the need for better cognitive screening in the acute setting, as well as targeted intervention such as comprehensive geriatric assessment. © The Author 2016. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. A low muscle mass increases mortality in compensated cirrhotic patients with sepsis.

    PubMed

    Lucidi, Cristina; Lattanzi, Barbara; Di Gregorio, Vincenza; Incicco, Simone; D'Ambrosio, Daria; Venditti, Mario; Riggio, Oliviero; Merli, Manuela

    2018-05-01

    Severe infections and muscle wasting are both associated to poor outcome in cirrhosis. A possible synergic effect of these two entities in cirrhotic patients has not been previously investigated. We aimed at analysing if a low muscle mass may deteriorate the outcome of cirrhotic patients with sepsis. Consecutive cirrhotic patients hospitalized for sepsis were enrolled in the study. Patients were classified for the severity of liver impairment (Child-Pugh class) and for the presence of "low muscle mass" (mid-arm muscle circumference<5th percentile). The development of complication during hospitalization and survival was analysed. There were 74 consecutive cirrhotics with sepsis. Forty-three of these patients showed low muscle mass. In patients with and without low muscle mass, severity of liver disease and characteristics of infections were similar. Mortality tended to be higher in patients with low muscle mass (47% vs 26%, P = .06). A multivariate analysis selected low muscle mass (P < .01, HR: 3.2, IC: 1.4-4.8) and Child-Pugh C (P < .01, HR: 3.3, 95% IC: 1.5-4.9) as independent predictors of in-hospital mortality. In Child-Pugh A-B patients, mortality was higher in patients with low muscle mass compared with those without (50% vs 16%; P = .01). The mortality rate and the incidence of complications in malnourished patients classified in Child-Pugh A-B were similar to those Child-Pugh C. Low muscle mass worsen prognosis in cirrhotic patients with severe infections. This is particularly evident in patients with Child A-B cirrhosis in whom the coexistence of low muscle mass and sepsis caused a negative impact on mortality similar to that observable in all Child C patients with sepsis. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Comparison between presepsin and procalcitonin in early diagnosis of neonatal sepsis.

    PubMed

    Iskandar, Agustin; Arthamin, Maimun Z; Indriana, Kristin; Anshory, Muhammad; Hur, Mina; Di Somma, Salvatore

    2018-05-09

    Neonatal sepsis remains worldwide one of the leading causes of morbidity and mortality in both term and preterm infants. Lower mortality rates are related to timely diagnostic evaluation and prompt initiation of empiric antibiotic therapy. Blood culture, as gold standard examination for sepsis, has several limitations for early diagnosis, so that sepsis biomarkers could play an important role in this regard. This study was aimed to compare the value of the two biomarkers presepsin and procalcitonin in early diagnosis of neonatal sepsis. This was a prospective cross-sectional study performed, in Saiful Anwar General Hospital Malang, Indonesia, in 51 neonates that fulfill the criteria of systemic inflammatory response syndrome (SIRS) with blood culture as diagnostic gold standard for sepsis. At reviewer operating characteristic (ROC) curve analyses, using a presepsin cutoff of 706,5 pg/mL, the obtained area under the curve (AUCs) were: sensitivity = 85.7%, specificity = 68.8%, positive predictive value = 85.7%, negative predictive value = 68.8%, positive likelihood ratio = 2.75, negative likelihood ratio = 0.21, and accuracy = 80.4%. On the other hand, with a procalcitonin cutoff value of 161.33 pg/mL the obtained AUCs showed: sensitivity = 68.6%, specificity = 62.5%, positive predictive value = 80%, negative predictive value = 47.6%, positive likelihood ratio = 1.83, the odds ratio negative = 0.5, and accuracy = 66.7%. In early diagnosis of neonatal sepsis, compared with procalcitonin, presepsin seems to provide better early diagnostic value with consequent possible faster therapeutical decision making and possible positive impact on outcome of neonates.

  13. Association of Delayed Antimicrobial Therapy with One-Year Mortality in Pediatric Sepsis.

    PubMed

    Han, Moonjoo; Fitzgerald, Julie C; Balamuth, Fran; Keele, Luke; Alpern, Elizabeth R; Lavelle, Jane; Chilutti, Marianne; Grundmeier, Robert W; Nadkarni, Vinay M; Thomas, Neal J; Weiss, Scott L

    2017-07-01

    Delayed antimicrobial therapy in sepsis is associated with increased hospital mortality, but the impact of antimicrobial timing on long-term outcomes is unknown. We tested the hypothesis that hourly delays to antimicrobial therapy are associated with 1-year mortality in pediatric severe sepsis. Retrospective observational study. Quaternary academic pediatric intensive care unit (PICU) from February 1, 2012 to June 30, 2013. One hundred sixty patients aged ≤21 years treated for severe sepsis. None. We tested the association of hourly delays from sepsis recognition to antimicrobial administration with 1-year mortality using multivariable Cox and logistic regression. Overall 1-year mortality was 24% (39 patients), of whom 46% died after index PICU discharge. Median time from sepsis recognition to antimicrobial therapy was 137 min (IQR 65-287). After adjusting for severity of illness and comorbid conditions, hourly delays up to 3 h were not associated with 1-year mortality. However, increased 1-year mortality was evident in patients who received antimicrobials ≤1 h (aOR 3.8, 95% CI 1.2, 11.7) or >3 h (aOR 3.5, 95% CI 1.3, 9.8) compared with patients who received antimicrobials within 1 to 3 h from sepsis recognition. For the subset of patients who survived index PICU admission, antimicrobial therapy ≤1 h was also associated with increased 1-year mortality (aOR 5.5, 95% CI 1.1, 27.4), while antimicrobial therapy >3 h was not associated with 1-year mortality (aOR 2.2, 95% CI 0.5, 11.0). Hourly delays to antimicrobial therapy, up to 3 h, were not associated with 1-year mortality in pediatric severe sepsis in this study. The finding that antimicrobial therapy ≤1 h from sepsis recognition was associated with increased 1-year mortality should be regarded as hypothesis-generating for future studies.

  14. Persistent inflammation and T cell exhaustion in severe sepsis in the elderly

    PubMed Central

    2014-01-01

    Introduction Sepsis is known as a complex immunological response with hyperinflammation in the acute phase followed by immunosuppression. Although aging is crucial in sepsis, the impact of aging on inflammation and immunosuppression is still unclear. The purpose of this study was to investigate the relationship between inflammation and immunosuppression in aged patients and mice after sepsis. Methods Fifty-five patients with severe sepsis and 30 healthy donors were prospectively enrolled, and 90-day survival was compared between elderly (≥65 years) and adult (18–64 years) septic patients with serial measurement of serum interleukin (IL)-6. Within 24 h after diagnosis of severe sepsis, peripheral blood mononuclear cells were stimulated ex vivo to measure expression of the activation maker CD25 in T cells, IL-2 levels in the supernatant, and proliferation. In the mouse study, young (6–8 weeks) and aged (20–22 months) C57/B6 mice were subjected to cecal ligation and puncture (CLP), and survival was compared after 7 days with serial measurement of serum IL-6. Expression of the negative co-stimulatory molecules, CD25, and IL-2 in CD4+ T cells was measured. Results The survival rate in elderly sepsis patients and aged septic mice was significantly lower than that in adult patients and young septic mice (60% vs. 93% in septic patients, 0% vs. 63% in septic mice, P < 0.05). Serum IL-6 levels in elderly sepsis patients and aged septic mice were persistently higher than those in adult patients and young septic mice. Expression of negative co-stimulatory molecules in CD4+ T cells in the spleen, lymph nodes, and peripheral blood was significantly higher in aged mice than in young mice (P < 0.01). Ex vivo stimulation decreased CD25 expression, IL-2 production, and proliferation to a greater extent in CD4+ T cells from elderly patients and aged septic mice than in those from adult patients and young septic mice. Elderly patients demonstrated increased

  15. Clinical course of sepsis, severe sepsis, and septic shock in a cohort of infected patients from ten Colombian hospitals

    PubMed Central

    2013-01-01

    Background Sepsis has several clinical stages, and mortality rates are different for each stage. Our goal was to establish the evolution and the determinants of the progression of clinical stages, from infection to septic shock, over the first week, as well as their relationship to 7-day and 28-day mortality. Methods This is a secondary analysis of a multicenter cohort of inpatients hospitalized in general wards or intensive care units (ICUs). The general estimating equations (GEE) model was used to estimate the risk of progression and the determinants of stages of infection over the first week. Cox regression with time-dependent covariates and fixed covariates was used to determine the factors related with 7-day and 28-day mortality, respectively. Results In 2681 patients we show that progression to severe sepsis and septic shock increases with intraabdominal and respiratory sources of infection [OR = 1,32; 95%IC = 1,20-1,46 and OR = 1.21, 95%CI = 1,11-1,33 respectively], as well as according to Acute Physiology and Chronic Health Evaluation II (APACHE II) [OR = 1,03; 95%CI = 1,02-1,03] and Sequential Organ Failure Assessment (SOFA) [OR = 1,16; 95%CI = 1,14-1,17] scores. The variables related with first-week mortality were progression to severe sepsis [HR = 2,13; 95%CI = 1,13-4,03] and septic shock [HR = 3,00; 95%CI = 1,50-5.98], respiratory source of infection [HR = 1,76; 95%IC = 1,12-2,77], APACHE II [HR = 1,07; 95% CI = 1,04-1,10] and SOFA [HR = 1,09; 95%IC = 1,04-1,15] scores. Conclusions Intraabdominal and respiratory sources of infection, independently of SOFA and APACHE II scores, increase the risk of clinical progression to more severe stages of sepsis; and these factors, together with progression of the infection itself, are the main determinants of 7-day and 28-day mortality. PMID:23883312

  16. Risk factors and outcomes of acute kidney injury in patients with acute liver failure.

    PubMed

    Tujios, Shannan R; Hynan, Linda S; Vazquez, Miguel A; Larson, Anne M; Seremba, Emmanuel; Sanders, Corron M; Lee, William M

    2015-02-01

    Patients with acute liver failure (ALF) frequently develop renal dysfunction, yet its overall incidence and outcomes have not been fully assessed. We investigated the incidence of acute kidney injury (AKI) among patients with ALF, using defined criteria to identify risk factors and to evaluate its effect on overall outcomes. We performed a retrospective review of data from 1604 patients enrolled in the Acute Liver Failure Study Group, from 1998 through 2010. Patients were classified by the Acute Kidney Injury Network criteria, as well as for etiology of liver failure (acetaminophen-based, ischemic, and all others). Seventy percent of patients with ALF developed AKI, and 30% received renal replacement therapy (RRT). Patients with severe AKI had higher international normalized ratio values than those without renal dysfunction (P < .001), and a higher proportion had advanced-grade coma (coma grades 3 or 4; P < .001) or presented with hypotension requiring vasopressor therapy (P < .001). A greater proportion of patients with acetaminophen-induced ALF had severe kidney injury than of patients with other etiologies of ALF; 34% required RRT, compared with 25% of patients with ALF not associated with acetaminophen or ischemia (P < .002). Of the patients with ALF who were alive at 3 weeks after study entry, significantly fewer with AKI survived for 1 year. Although AKI reduced the overall survival time, more than 50% of patients with acetaminophen-associated or ischemic ALF survived without liver transplantation (even with RRT), compared with 19% of patients with ALF attribute to other causes (P < .001). Only 4% of patients requiring RRT became dependent on dialysis. Based on a retrospective analysis of data from more than 1600 patients, AKI is common in patients with ALF and affects short- and long-term outcomes, but rarely results in chronic kidney disease. Acetaminophen-induced kidney injury is frequent, but patients have better outcomes than those with other forms of

  17. Comparison of the outcome of burn patients using acute-phase plasma base deficit.

    PubMed

    Salehi, S H; As'adi, K; Mousavi, J

    2011-12-31

    Background. In recent years, plasma base deficit has been used as a marker to determine the status of tissue perfusion in trauma patients and also to predict the outcome of these patients. This study was performed to investigate the effect of plasma base deficit in predicting burn patient outcome. Methods. This prospective cohort study was performed from October 2009 to October 2010 in the acute phase of burn patients who were admitted within 6 h post-injury to Motahari Burn Hospital in Iran. The patients were divided into two groups based on the plasma base deficit in the first 24 h post-injury: group A, in which the mean plasma base deficit was less than or equal to -6 (more negative), and group B, in which the mean plasma base deficit greater than -6. Statistical analysis was performed using SPSS v.16 software. Results. Thirty-eight patients were enrolled in each group. The mean plasma base deficit in group A (-7.76 ± 2.18 mmol) was significantly less than that in group B (-1.19 ± 2.82) mmol (p < 0.05). Although there was no significant difference between the mean of fluid resuscitation and urine output in the first 24 h after injury between the two groups (p > 0.05) and despite removal of interfering factors, there were significant differences between the systemic inflammatory response syndrome and the multiple organ dysfunction syndrome score and the percentage of sepsis between the two groups (p < 0.05). The mortality rate in group A (63.2%) was significantly higher than that in group B (36.8%) (p > 0.05). Conclusion. The plasma base deficit can be used as a valuable marker in the resuscitation of burn patients, along with clinical criteria. Physiological indicators (burn percentage, age, and mucosal burns) are not sufficient to predict mortality and morbidity in burn patients, and it is necessary to investigate the role of biochemical markers such as base deficit in determining the final outcome of burn patients.

  18. The Microbiome and Metabolome of Preterm Infant Stool Are Personalized and Not Driven by Health Outcomes, Including Necrotizing Enterocolitis and Late-Onset Sepsis

    PubMed Central

    Wandro, Stephen; Osborne, Stephanie; Enriquez, Claudia; Bixby, Christine; Arrieta, Antonio

    2018-01-01

    ABSTRACT The assembly and development of the gut microbiome in infants have important consequences for immediate and long-term health. Preterm infants represent an abnormal case for bacterial colonization because of early exposure to bacteria and frequent use of antibiotics. To better understand the assembly of the gut microbiota in preterm infants, fecal samples were collected from 32 very low birth weight preterm infants over the first 6 weeks of life. Infant health outcomes included health, late-onset sepsis, and necrotizing enterocolitis (NEC). We characterized bacterial compositions by 16S rRNA gene sequencing and metabolomes by untargeted gas chromatography-mass spectrometry. Preterm infant fecal samples lacked beneficial Bifidobacterium spp. and were dominated by Enterobacteriaceae, Enterococcus, and Staphylococcus organisms due to nearly uniform antibiotic administration. Most of the variance between the microbial community compositions could be attributed to the baby from which the sample derived (permutational multivariate analysis of variance [PERMANOVA] R2 = 0.48, P < 0.001), while clinical status (health, NEC, or late-onset sepsis) and overlapping times in the neonatal intensive care unit (NICU) did not explain a significant amount of variation in bacterial composition. Fecal metabolomes were also found to be unique to the individual (PERMANOVA R2 = 0.43, P < 0.001) and weakly associated with bacterial composition (Mantel statistic r = 0.23 ± 0.05, P < 0.05). No measured metabolites were found to be associated with necrotizing enterocolitis, late-onset sepsis, or a healthy outcome. Overall, preterm infant gut microbial communities were personalized and reflected antibiotic usage. IMPORTANCE Preterm infants face health problems likely related to microbial exposures, including sepsis and necrotizing enterocolitis. However, the role of the gut microbiome in preterm infant health is poorly understood. Microbial colonization differs from that of healthy

  19. The Microbiome and Metabolome of Preterm Infant Stool Are Personalized and Not Driven by Health Outcomes, Including Necrotizing Enterocolitis and Late-Onset Sepsis.

    PubMed

    Wandro, Stephen; Osborne, Stephanie; Enriquez, Claudia; Bixby, Christine; Arrieta, Antonio; Whiteson, Katrine

    2018-06-27

    The assembly and development of the gut microbiome in infants have important consequences for immediate and long-term health. Preterm infants represent an abnormal case for bacterial colonization because of early exposure to bacteria and frequent use of antibiotics. To better understand the assembly of the gut microbiota in preterm infants, fecal samples were collected from 32 very low birth weight preterm infants over the first 6 weeks of life. Infant health outcomes included health, late-onset sepsis, and necrotizing enterocolitis (NEC). We characterized bacterial compositions by 16S rRNA gene sequencing and metabolomes by untargeted gas chromatography-mass spectrometry. Preterm infant fecal samples lacked beneficial Bifidobacterium spp. and were dominated by Enterobacteriaceae , Enterococcus , and Staphylococcus organisms due to nearly uniform antibiotic administration. Most of the variance between the microbial community compositions could be attributed to the baby from which the sample derived (permutational multivariate analysis of variance [PERMANOVA] R 2 = 0.48, P < 0.001), while clinical status (health, NEC, or late-onset sepsis) and overlapping times in the neonatal intensive care unit (NICU) did not explain a significant amount of variation in bacterial composition. Fecal metabolomes were also found to be unique to the individual (PERMANOVA R 2 = 0.43, P < 0.001) and weakly associated with bacterial composition (Mantel statistic r = 0.23 ± 0.05, P < 0.05). No measured metabolites were found to be associated with necrotizing enterocolitis, late-onset sepsis, or a healthy outcome. Overall, preterm infant gut microbial communities were personalized and reflected antibiotic usage. IMPORTANCE Preterm infants face health problems likely related to microbial exposures, including sepsis and necrotizing enterocolitis. However, the role of the gut microbiome in preterm infant health is poorly understood. Microbial colonization differs from that of healthy term

  20. Sepsis in Children: Global Implications of the World Health Assembly Resolution on Sepsis.

    PubMed

    Kissoon, Niranjan; Reinhart, Konrad; Daniels, Ron; Machado, Machado Flavia R; Schachter, Raymond D; Finfer, Simon

    2017-12-01

    Sepsis, worldwide the leading cause of death in children, has now been recognized as the global health emergency it is. On May 26, 2017, the World Health Assembly, the decision-making body of the World Health Organization, adopted a resolution proposed by the Global Sepsis Alliance to improve the prevention, diagnosis, and management of sepsis. To discuss the implications of this resolution for children worldwide. The resolution highlights sepsis as a global threat and urges the 194 United Nations member states to take specific actions and implement appropriate measures to reduce its human and health economic burden. The resolution is a major step toward achieving the targets outlined by the Sustainable Developmental Goals for decreasing mortality in infants and children, but implementing it will require a concerted global effort.

  1. Comparison of QSOFA score and SIRS criteria as screening mechanisms for emergency department sepsis.

    PubMed

    Haydar, Samir; Spanier, Matthew; Weems, Patricia; Wood, Samantha; Strout, Tania

    2017-11-01

    The Quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA) score has been shown to accurately predict mortality in septic patients and is part of recently proposed diagnostic criteria for sepsis. We sought to ascertain the sensitive of the score in diagnosing sepsis, as well as the diagnostic timeliness of the score when compared to traditional systemic inflammatory response syndrome (SIRS) criteria in a population of emergency department (ED) patients treated in the ED, admitted, and subsequently discharged with a diagnosis of sepsis. Electronic health records of 200 patients who were treated for suspected sepsis in our ED and ultimately discharged from our hospital with a diagnosis of sepsis were randomly selected for review from a population of adult ED patients (N=1880). Data extracted included the presence of SIRS criteria and the qSOFA score as well as time required to meet said criteria. In this cohort, 94.5% met SIRS criteria while in the ED whereas only 58.3% met qSOFA. The mean time from arrival to SIRS documentation was 47.1min (95% CI: 36.5-57.8) compared to 84.0min (95% CI: 62.2-105.8) for qSOFA. The median ED "door" to positive SIRS criteria was 12min and 29min for qSOFA. Although qSOFA may be valuable in predicting sepsis-related mortality, it performed poorly as a screening tool for identifying sepsis in the ED. As the time to meet qSOFA criteria was significantly longer than for SIRS, relying on qSOFA alone may delay initiation of evidence-based interventions known to improve sepsis-related outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. A complex endeavour: an ethnographic study of the implementation of the Sepsis Six clinical care bundle.

    PubMed

    Tarrant, Carolyn; O'Donnell, Barbara; Martin, Graham; Bion, Julian; Hunter, Alison; Rooney, Kevin D

    2016-11-16

    Implementation of the 'Sepsis Six' clinical care bundle within an hour of recognition of sepsis is recommended as an approach to reduce mortality in patients with sepsis, but achieving reliable delivery of the bundle has proved challenging. There remains little understanding of the barriers to reliable implementation of bundle components. We examined frontline clinical practice in implementing the Sepsis Six. We conducted an ethnographic study in six hospitals participating in the Scottish Patient Safety Programme Sepsis collaborative. We conducted around 300 h of non-participant observation in emergency departments, acute medical receiving units and medical and surgical wards. We interviewed a purposive sample of 43 members of hospital staff. Data were analysed using a constant comparative approach. Implementation strategies to promote reliable use of the Sepsis Six primarily focused on education, engaging and motivating staff, and providing prompts for behaviour, along with efforts to ensure that equipment required was readily available. Although these strategies were successful in raising staff awareness of sepsis and engagement with implementation, our study identified that completing the bundle within an hour was not straightforward. Our emergent theory suggested that rather than being an apparently simple sequence of six steps, the Sepsis Six actually involved a complex trajectory comprising multiple interdependent tasks that required prioritisation and scheduling, and which was prone to problems of coordination and operational failures. Interventions that involved allocating specific roles and responsibilities for completing the Sepsis Six in ways that reduced the need for coordination and task switching, and the use of process mapping to identify system failures along the trajectory, could help mitigate against some of these problems. Implementation efforts that focus on individual behaviour change to improve uptake of the Sepsis Six should be supplemented

  3. Key process indicators of mortality in the implementation of protocol-driven therapy for severe sepsis.

    PubMed

    Wang, Jiun-Long; Chin, Chun-Shih; Chang, Ming-Chen; Yi, Chi-Yuan; Shih, Sou-Jen; Hsu, Jeng-Yuan; Wu, Chieh-Liang

    2009-10-01

    Severe sepsis and septic shock are life-threatening disorders. Integrating treatments into a bundle strategy has been proposed to facilitate timely resuscitation, but is difficult to implement. We implemented protocol-driven therapy for severe sepsis, and analyzed retrospectively the key process indicators of mortality in managing sepsis. Continuous quality improvement was begun to implement a tailored protocol-driven therapy for sepsis in a 24-bed respiratory intensive care unit (RICU) of Taichung Veterans General Hospital from January 2007 to February 2008. Patients, who were admitted to the RICU directly, or within 24 hours, were enrolled if they met the criteria for severe sepsis and septic shock. Disease severity [Acute Physiology and Chronic Health Evaluation (APACHE) II and lactate level], causes of sepsis, comorbidity and site of sepsis onset were recorded. Process-of-care indicators included resuscitation time (Tr-s), RICU bed availability (Ti-s) and the ratio of completing the elements of the protocol at 1, 2, 4 and 6 hours. The structure and process-of-care indicators reflated to mortality at 7 days after RICU admission and at RICU discharge were identified retrospectively. Eighty-six patients (mean age, 71 +/- 14 years, 72 men, 14 women, APACHE II, 25.0 +/- 7.0) were enrolled. APACHE II scores and lactate levels were higher for mortality than survival at 7 days after RICU admission (p < 0.01). For the process-of-care indicators, Ti-s (562.2 +/- 483.3 vs.1017.3 +/- 557.8 minutes, p = 0.03) and Tr-s (60.7 +/- 207.8 vs. 248.5 +/- 453.1 minutes, p = 0.07) were shorter for survival than mortality at 7 days after RICU admission. The logistic regression study showed that Tr-s was an important indicator. The ratio of completing the elements of protocols at 1, 2, 4 and 6 hours ranged from 70% to 90% and was not related to mortality. Protocol-driven therapy for sepsis was put into clinical practice. Early resuscitation and ICU bed availability were key process

  4. Pediatric sepsis in the developing world: challenges in defining sepsis and issues in post-discharge mortality.

    PubMed

    Wiens, Matthew O; Kumbakumba, Elias; Kissoon, Niranjan; Ansermino, J Mark; Ndamira, Andrew; Larson, Charles P

    2012-01-01

    Sepsis represents the progressive underlying inflammatory pathway secondary to any infectious illness, and ultimately is responsible for most infectious disease-related deaths. Addressing issues related to sepsis has been recognized as an important step towards reducing morbidity and mortality in developing countries, where the majority of the 7.5 million annual deaths in children under 5 years of age are considered to be secondary to sepsis. However, despite its prevalence, sepsis is largely neglected. Application of sepsis definitions created for use in resource-rich countries are neither practical nor feasible in most developing country settings, and alternative definitions designed for use in these settings need to be established. It has also been recognized that the inflammatory state created by sepsis increases the risk of post-discharge morbidity and mortality in developed countries, but exploration of this issue in developing countries is lacking. Research is urgently required to characterize better this potentially important issue.

  5. Costs of postoperative sepsis: the business case for quality improvement to reduce postoperative sepsis in veterans affairs hospitals.

    PubMed

    Vaughan-Sarrazin, Mary S; Bayman, Levent; Cullen, Joseph J

    2011-08-01

    To estimate the incremental costs associated with sepsis as a complication of general surgery, controlling for patient risk factors that may affect costs (eg, surgical complexity and comorbidity) and hospital-level variation in costs. Database analysis. One hundred eighteen Veterans Health Affairs hospitals. A total of 13 878 patients undergoing general surgery during fiscal year 2006 (October 1, 2005, through September 30, 2006). Incremental costs associated with sepsis as a complication of general surgery (controlling for patient risk factors and hospital-level variation of costs), as well as the increase in costs associated with complications that co-occur with sepsis. Costs were estimated using the Veterans Health Affairs Decision Support System, and patient risk factors and postoperative complications were identified in the Veterans Affairs Surgical Quality Improvement Program database. Overall, 564 of 13 878 patients undergoing general surgery developed postoperative sepsis, for a rate of 4.1%. The average unadjusted cost for patients with no sepsis was $24 923, whereas the average cost for patients with sepsis was 3.6 times higher at $88 747. In risk-adjusted analyses, the relative costs were 2.28 times greater for patients with sepsis relative to patients without sepsis (95% confidence interval, 2.19-2.38), with the difference in risk-adjusted costs estimated at $26 972 (ie, $21 045 vs $48 017). Sepsis often co-occurred with other types of complications, most frequently with failure to wean the patient from mechanical ventilation after 48 hours (36%), postoperative pneumonia (31%), and reintubation for respiratory or cardiac failure (29%). Costs were highest when sepsis occurred with pneumonia or failure to wean the patient from mechanical ventilation after 48 hours. Given the high cost of treating sepsis, a business case can be made for quality improvement initiatives that reduce the likelihood of postoperative sepsis.

  6. Prediction of pediatric sepsis mortality within 1 h of intensive care admission.

    PubMed

    Schlapbach, Luregn J; MacLaren, Graeme; Festa, Marino; Alexander, Janet; Erickson, Simon; Beca, John; Slater, Anthony; Schibler, Andreas; Pilcher, David; Millar, Johnny; Straney, Lahn

    2017-08-01

    The definitions of sepsis and septic shock have recently been revised in adults, but contemporary data are needed to inform similar approaches in children. Multicenter cohort study including children <16 years admitted with sepsis or septic shock to ICUs in Australia and New Zealand in the period 2012-2015. We assessed septic shock criteria at ICU admission to define sepsis severity, using 30-day mortality as outcome. Through multivariable logistic regression, a pediatric sepsis score was derived using variables available within 60 min of ICU admission. Of 42,523 pediatric admissions, 4403 children were admitted with invasive infection, including 1697 diagnosed as having sepsis/septic shock on admission. Mortality was 8.5% (144/1697) and 50.7% of deaths occurred within 48 h of admission. The presence of septic shock as defined by the 2005 consensus was sensitive but not specific in predicting mortality (AUC = 0.69; 95% CI 0.65-0.72). Combinations of hypotension, vasopressor therapy, and lactate >2 mmol/l discriminated poorly (AUC <0.60). Multivariate models showed that oxygenation markers, ventilatory support, hypotension, cardiac arrest, serum lactate, pupil responsiveness, and immunosuppression were the best-performing predictors (0.843; 0.811-0.875). We derived a pediatric sepsis score (0.817; 0.779-0.855), and every one-point increase was associated with a 28.5% (23.8-33.2%) increase in the odds of death. Children with a score ≥6 had 19.8% mortality and accounted for 74.3% of deaths. The sepsis score performed comparably when applied to all children admitted with invasive infection (0.810; 0.781-0.840). We observed mortality patterns specific to pediatric sepsis that support the need for specialized definitions of sepsis severity in children. We demonstrated the importance of lactate, cardiovascular, and respiratory derangements at ICU admission for the identification of children with substantially higher risk of sepsis mortality.

  7. Comparison of Two Sepsis Recognition Methods in a Pediatric Emergency Department

    PubMed Central

    Balamuth, Fran; Alpern, Elizabeth R.; Grundmeier, Robert W.; Chilutti, Marianne; Weiss, Scott L.; Fitzgerald, Julie C.; Hayes, Katie; Bilker, Warren; Lautenbach, Ebbing

    2015-01-01

    Objectives To compare the effectiveness of physician judgment and an electronic algorithmic alert to identify pediatric patients with severe sepsis/septic shock in a pediatric emergency department (ED). Methods This was an observational cohort study of patients older than 56 days with fever or hypothermia. All patients were evaluated for potential sepsis in real time by the ED clinical team. An electronic algorithmic alert was retrospectively applied to identify patients with potential sepsis independent of physician judgment. The primary outcome was the proportion of patients correctly identified with severe sepsis/septic shock defined by consensus criteria. Test characteristics were determined and receiver operating characteristic (ROC) curves were compared. Results Of 19,524 eligible patient visits, 88 patients developed consensus-confirmed severe sepsis or septic shock. Physician judgment identified 159, and the algorithmic alert identified 3,301 patients with potential sepsis. Physician judgment had sensitivity of 72.7% (95% CI = 72.1% to 73.4%) and specificity 99.5% (95% CI = 99.4% to 99.6%); the algorithmic alert had sensitivity 92.1% (95% CI = 91.7% to 92.4%), and specificity 83.4% (95% CI = 82.9% to 83.9%) for severe sepsis/septic shock. There was no significant difference in the area under the ROC curve for physician judgment (0.86, 95% CI = 0.81 to 0.91) or the algorithm (0.88, 95% CI = 0.85 to 0.91; p = 0.54). A combination method using either positive physician judgment or an algorithmic alert improved sensitivity to 96.6% and specificity to 83.3%. A sequential approach, in which positive identification by the algorithmic alert was then confirmed by physician judgment, achieved 68.2% sensitivity and 99.6% specificity. Positive and negative predictive values for physician judgment vs. algorithmic alert were 40.3% vs. 2.5% and 99.88 % vs. 99.96%, respectively. Conclusions The electronic algorithmic alert was more sensitive but less specific than

  8. Comparison of Two Sepsis Recognition Methods in a Pediatric Emergency Department.

    PubMed

    Balamuth, Fran; Alpern, Elizabeth R; Grundmeier, Robert W; Chilutti, Marianne; Weiss, Scott L; Fitzgerald, Julie C; Hayes, Katie; Bilker, Warren; Lautenbach, Ebbing

    2015-11-01

    The objective was to compare the effectiveness of physician judgment and an electronic algorithmic alert to identify pediatric patients with severe sepsis/septic shock in a pediatric emergency department (ED). This was an observational cohort study of patients older than 56 days with fever or hypothermia. All patients were evaluated for potential sepsis in real time by the ED clinical team. An electronic algorithmic alert was retrospectively applied to identify patients with potential sepsis independent of physician judgment. The primary outcome was the proportion of patients correctly identified with severe sepsis/septic shock defined by consensus criteria. Test characteristics were determined and receiver operating characteristic (ROC) curves were compared. Of 19,524 eligible patient visits, 88 patients developed consensus-confirmed severe sepsis or septic shock. Physician judgment identified 159 and the algorithmic alert identified 3,301 patients with potential sepsis. Physician judgment had sensitivity of 72.7% (95% confidence interval [CI] = 72.1% to 73.4%) and specificity of 99.5% (95% CI = 99.4% to 99.6%); the algorithmic alert had sensitivity of 92.1% (95% CI = 91.7% to 92.4%) and specificity of 83.4% (95% CI = 82.9% to 83.9%) for severe sepsis/septic shock. There was no significant difference in the area under the ROC curve for physician judgment (0.86, 95% CI = 0.81 to 0.91) or the algorithm (0.88, 95% CI = 0.85 to 0.91; p = 0.54). A combination method using either positive physician judgment or an algorithmic alert improved sensitivity to 96.6% and specificity to 83.3%. A sequential approach, in which positive identification by the algorithmic alert was then confirmed by physician judgment, achieved 68.2% sensitivity and 99.6% specificity. Positive and negative predictive values for physician judgment versus algorithmic alert were 40.3% versus 2.5% and 99.88% versus 99.96%, respectively. The electronic algorithmic alert was more sensitive but less

  9. Endoplasmic Reticulum Stress in Sepsis

    PubMed Central

    Khan, Mohammad Moshahid; Yang, Weng-Lang; Wang, Ping

    2015-01-01

    Sepsis is an enormous public health issue and the leading cause of death in critically ill patients in intensive care units (ICU). Overwhelming inflammation, characterized by cytokine storm, oxidative threats, and neutrophil sequestration is an underlying component of sepsis-associated organ failure. Despite recent advances in sepsis research, there is still no effective treatment available beyond the standard of care and supportive therapy. To reduce sepsis-related mortality, a better understanding of the biological mechanism associated with the sepsis is essential. Endoplasmic reticulum (ER), a subcellular organelle is responsible for the facilitation of protein folding and assembly and involved in several other physiological activities. Under the stress and inflammation condition, ER loses the homeostasis in its function, which is termed as ER stress. During ER stress, unfolded protein response (UPR) is activated to restore ER function to its normal balance. However, once the stress is beyond the compensatory capacity of UPR or protracted, the apoptosis would be initiated by triggering cell injuries, even to cell death. As such, ER stress and UPR are reported to be implicated in several pathological and inflammatory conditions. Although the detrimental role of ER stress during infections has been demonstrated, there is growing evidences that ER stress participate in the pathogenesis of sepsis. In this review, we summarize the current research in the context of ER stress and UPR signaling associated with sepsis and its related clinical conditions, such as trauma- hemorrhage, and ischemia/reperfusion (I/R) injury. We also discuss the potential implication of ER stress as a novel therapeutic target and prognostic marker in patients with sepsis. PMID:26125088

  10. The impact of evidence-based sepsis guidelines on emergency department clinical practice: a pre-post medical record audit.

    PubMed

    Romero, Bernadine; Fry, Margaret; Roche, Michael

    2017-11-01

    To explore the number of patients presenting with sepsis before and after guideline implementation; the impact of sepsis guidelines on triage assessment, emergency department management and time to antibiotics. Sepsis remains one of the leading causes of mortality and morbidity within hospitals. Globally, strategies have been implemented to reduce morbidity and mortality rates, which rely on the early recognition and management of sepsis. To improve patient outcomes, the New South Wales government in Australia introduced sepsis guidelines into emergency departments. However, the impact of the guidelines on clinical practice remains unclear. A 12-month pre-post retrospective randomised medical record audit of adult patients with a sepsis diagnosis. Data were extracted from the emergency department database and paper medical record. Data included patient demographic (age, gender), clinical information (time of arrival, triage code, seen by time, disposition, time to antibiotic, pathology, time to intravenous fluids) and patient assessment data (heart rate, respiratory rate, blood pressure, temperature, oxygen saturations, medication). This study demonstrated a statistically significant 230-minute reduction in time to antibiotics post implementation of the guidelines. The post group (n = 165) received more urgent triage categories (n = 81; 49·1%), a 758-minute reduction in mean time to second litre of intravenous fluids and an improvement in collection of lactate (n = 112, 67·9%), also statistically significant. The findings highlight the impact the guidelines can have on clinician decision-making and behaviour that support best practice and positive patient outcomes. The sepsis guidelines improved the early assessment, recognition and management of patients presenting with sepsis in one tertiary referral emergency department. The use of evidenced-based guidelines can impact clinical decision-making and behaviour, resulting in the translation and support of

  11. Effect of gestational age on the epidemiology of late-onset sepsis in neonatal intensive care units - a review.

    PubMed

    Afonso, Elsa Da Palma; Blot, Stijn

    2017-10-01

    Neonatal sepsis is a major cause of morbidity and mortality. Late-onset sepsis affects a significant percentage of infants admitted to the neonatal intensive care unit (NICU). Most affected newborns are preterm or low birth weight, but late-onset sepsis also affects late preterm and term infants. Understanding how gestational age affects the epidemiology of late-onset sepsis can be of use when defining strategies for its prevention and clinical management in NICU. Areas covered: Available evidence suggests the incidence and mortality of late-onset sepsis is higher in preterm and VLBW infants, but pathogen distribution and risk exposure is similar across all infants admitted to NICU. More research is required for late-onset sepsis in late preterm and term infants admitted to NICU. There is some research insight on the impact of gut bacteria in the epidemiology of Gram-negative sepsis, which could benefit from further dedicated studies. Expert commentary: Understanding the manner in which some infants develop severe sepsis and others don't and what the long-term outcomes are is fundamental to guide management strategies. Further research should focus both on infants' characteristics and on pathogenic processes. The ultimate goal is to be able to design guidelines for prevention and management of sepsis that are adapted to a varied neonatal population.

  12. Pediatric sepsis: actions to decrease sepsis in children.

    PubMed

    Marraro, Giuseppe A

    2009-10-01

    The European Society of Pediatric and Neonatal Intensive Care is the physicians' and nurses' annual meeting that was held in Verona, Italy from 14 to 17 June 2009, and approximately 1000 participants from around the world (84 countries) attended. The Congress gave an opportunity to experts to discuss ongoing research and exchange opinions on the future development of studies to identify optimal supportive, preventive and therapeutic strategies for sepsis. A wide range of topics were discussed and several lectures, oral presentations and posters were dedicated to sepsis and its treatment. High scientific-level topics were presented, and stimulated much interest and discussion.

  13. Patient and hospital correlates of clinical outcomes and resource utilization in severe pediatric sepsis.

    PubMed

    Odetola, Folafoluwa O; Gebremariam, Achamyeleh; Freed, Gary L

    2007-03-01

    Our goal was to describe patient and hospital characteristics associated with in-hospital mortality, length of stay, and charges for critically ill children with severe sepsis. Our study consisted of a retrospective study of children 0 to 19 years of age hospitalized with severe sepsis using the 2003 Kids' Inpatient Database. We generated national estimates of rates of hospitalization and then compared in-hospital mortality, length of stay, and total charges according to patient and hospital characteristics using multivariable regression methods. Severity of illness was measured by using all-patient refined diagnosis-related group severity of illness classification into minor, moderate, major, and extreme severity. There were an estimated 21,448 hospitalizations for severe pediatric sepsis nationally in 2003. The in-hospital mortality rate was 4.2%. Comorbid illness was present in 34% of hospitalized children. Most (70%) of the extremely ill children were admitted to children's hospitals. Length of stay was longer among patients with higher illness severity and nonsurvivors compared with survivors (13.5 vs 8.5 days). Hospitalizations at urban or children's hospitals were also associated with longer length of stay than nonchildren's or rural hospitals, respectively. Higher charges were associated with higher illness severity, and nonsurvivors had 2.5-fold higher total charges than survivors. Also, higher charges were observed among hospitalizations in urban or children's hospitals. In multivariable regression analysis, multiple comorbid illnesses, multiple organ dysfunction, and greater severity of illness were associated with higher odds of mortality and longer length of stay. Higher hospital charges and longer length of stay were observed among transfer hospitalizations and among hospitalizations to children's hospitals and nonchildren's teaching hospitals compared with hospitals, which had neither children's nor teaching status. Mortality from severe pediatric

  14. Positive fluid balance as a major predictor of clinical outcome of patients with sepsis/septic shock after ICU discharge.

    PubMed

    Brotfain, Evgeni; Koyfman, Leonid; Toledano, Ronen; Borer, Abraham; Fucs, Lior; Galante, Ori; Frenkel, Amit; Kutz, Ruslan; Klein, Moti

    2016-11-01

    Sepsis and septic shock continue to be syndromes that carry a high mortality rate worldwide. Early aggressive fluid and vasopressor support have resulted in significant improvement in patient outcomes. The prognostic clinical significance of a positive fluid balance in septic intensive care unit (ICU) patients remains undetermined. We collected data from 297 septic patients hospitalized in our general and medical ICUs at Soroka Medical Center between January 2005 and June 2011 and divided the 4 study groups into the following 4 fluid balances: group 1, patients with fluid balance at discharge from ICU (FBD) less than 10 L; group 2, patients with an FBD of 10 to 20 L; group 3, patients with an FBD of 20 to 30 L; and group 4, patients with FBD in excess of 30 L. The ICU and in-hospital mortality rate was also significantly higher in groups 2 to 4 as compared with group 1 (P < .001 for both ICU and in-hospital mortality). The positive cumulative FBD was found to be an independent predictor of ICU mortality (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02-1.06; P < .001; Table 3) and in-hospital mortality (OR, 1.06; 95% CI, 1.03-1.08; P < .001; Table 5) and also to constitute a risk factor for new organ system dysfunction at hospital discharge (OR, 1.01; 95% CI, 1.01-1.013; P < .001; Table 6) in critically ill patients with severe sepsis/septic shock. Although it is a monocentric retrospective study, we suggest that positive cumulative fluid balance is one of the major factors that can predict the clinical outcome of critically ill patients during their ICU stay and after their discharge from the ICU. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Atorvastatin along with imipenem attenuates acute lung injury in sepsis through decrease in inflammatory mediators and bacterial load.

    PubMed

    Choudhury, Soumen; Kandasamy, Kannan; Maruti, Bhojane Somnath; Addison, M Pule; Kasa, Jaya Kiran; Darzi, Sazad A; Singh, Thakur Uttam; Parida, Subhashree; Dash, Jeevan Ranjan; Singh, Vishakha; Mishra, Santosh Kumar

    2015-10-15

    Lung is one of the vital organs which is affected during the sequential development of multi-organ dysfunction in sepsis. The purpose of the present study was to examine whether combined treatment with atorvastatin and imipenem could attenuate sepsis-induced lung injury in mice. Sepsis was induced by caecal ligation and puncture. Lung injury was assessed by the presence of lung edema, increased vascular permeability, increased inflammatory cell infiltration and cytokine levels in broncho-alveolar lavage fluid (BALF). Treatment with atorvastatin along with imipenem reduced the lung bacterial load and pro-inflammatory cytokines (IL-1β and TNFα) level in BALF. The markers of pulmonary edema such as microvascular leakage and wet-dry weight ratio were also attenuated. This was further confirmed by the reduced activity of MPO and ICAM-1 mRNA expression, indicating the lesser infiltration and adhesion of inflammatory cells to the lungs. Again, expression of mRNA and protein level of iNOS in lungs was also reduced in the combined treatment group. Based on the above findings it can be concluded that, combined treatment with atorvastatin and imipenem dampened the inflammatory response and reduced the bacterial load, thus seems to have promising therapeutic potential in sepsis-induced lung injury in mice. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Alterations in energy substrate metabolism in mice with different degrees of sepsis.

    PubMed

    Irahara, Takayuki; Sato, Norio; Otake, Kosuke; Matsumura, Shigenobu; Inoue, Kazuo; Ishihara, Kengo; Fushiki, Tohru; Yokota, Hiroyuki

    2018-07-01

    Nutritional management is crucial during the acute phase of severe illnesses. However, the appropriate nutritional requirements for patients with sepsis are poorly understood. We investigated alterations in carbohydrate, fat, and protein metabolism in mice with different degrees of sepsis. C57BL/6 mice were divided into three groups: control mice group, administered with saline, and low- and high-dose lipopolysaccharide (LPS) groups, intraperitoneally administered with 1 and 5 mg of LPS/kg, respectively. Rectal temperature, food intake, body weight, and spontaneous motor activity were measured. Indirect calorimetry was performed using a respiratory gas analysis for 120 h, after which carbohydrate oxidation and fatty acid oxidation were calculated. Urinary nitrogen excretion was measured to evaluate protein metabolism. The substrate utilization ratio was recalculated. Plasma and liver carbohydrate and lipid levels were evaluated at 24, 72, and 120 h after LPS administration. Biological reactions decreased significantly in the low- and high-LPS groups. Fatty acid oxidation and protein oxidation increased significantly 24 h after LPS administration, whereas carbohydrate oxidation decreased significantly. Energy substrate metabolism changed from glucose to predominantly lipid metabolism depending on the degree of sepsis, and protein metabolism was low. Plasma lipid levels decreased, whereas liver lipid levels increased at 24 h, suggesting that lipids were transported to the liver as the energy source. Our findings revealed that energy substrate metabolism changed depending on the degree of sepsis. Therefore, in nutritional management, such metabolic alterations must be considered, and further studies on the optimum nutritional intervention during severe sepsis are necessary. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Staphylococcus aureus Sepsis Induces Early Renal Mitochondrial DNA Repair and Mitochondrial Biogenesis in Mice

    PubMed Central

    Bartz, Raquel R.; Fu, Ping; Suliman, Hagir B.; Crowley, Stephen D.; MacGarvey, Nancy Chou; Welty-Wolf, Karen; Piantadosi, Claude A.

    2014-01-01

    Acute kidney injury (AKI) contributes to the high morbidity and mortality of multi-system organ failure in sepsis. However, recovery of renal function after sepsis-induced AKI suggests active repair of energy-producing pathways. Here, we tested the hypothesis in mice that Staphyloccocus aureus sepsis damages mitochondrial DNA (mtDNA) in the kidney and activates mtDNA repair and mitochondrial biogenesis. Sepsis was induced in wild-type C57Bl/6J and Cox-8 Gfp-tagged mitochondrial-reporter mice via intraperitoneal fibrin clots embedded with S. aureus. Kidneys from surviving mice were harvested at time zero (control), 24, or 48 hours after infection and evaluated for renal inflammation, oxidative stress markers, mtDNA content, and mitochondrial biogenesis markers, and OGG1 and UDG mitochondrial DNA repair enzymes. We examined the kidneys of the mitochondrial reporter mice for changes in staining density and distribution. S. aureus sepsis induced sharp amplification of renal Tnf, Il-10, and Ngal mRNAs with decreased renal mtDNA content and increased tubular and glomerular cell death and accumulation of protein carbonyls and 8-OHdG. Subsequently, mtDNA repair and mitochondrial biogenesis was evidenced by elevated OGG1 levels and significant increases in NRF-1, NRF-2, and mtTFA expression. Overall, renal mitochondrial mass, tracked by citrate synthase mRNA and protein, increased in parallel with changes in mitochondrial GFP-fluorescence especially in proximal tubules in the renal cortex and medulla. Sub-lethal S. aureus sepsis thus induces widespread renal mitochondrial damage that triggers the induction of the renal mtDNA repair protein, OGG1, and mitochondrial biogenesis as a conspicuous resolution mechanism after systemic bacterial infection. PMID:24988481

  18. A prospective study of the demographics, management and outcome of patients with acute kidney injury in Cape Town, South Africa.

    PubMed

    Dlamini, Thandiwe A L; Heering, Peter J; Chivese, Tawanda; Rayner, Brian

    2017-01-01

    To study the demographics and outcome of acute kidney injury (AKI) at Groote Schuur Hospital, Cape Town, South Africa. A prospective observational study of AKI fulfilling the Kidney Disease: Improving Global Outcomes definition, from 8 July 2012 to 8 July 2013. Ethics approval was granted by the University of Cape Town Human Research Ethics Committee. Consent was waived because patient data was de-identified and patient management was not adversely affected by the study. A clerking sheet was used for data collection. Patients were reassessed after 3 months. Main outcomes were renal recovery and 3 month mortality. Descriptive statistics and multivariate logistic regression were carried out for risk factors. Over this period there were 10,750 hospital admissions and 366 patients with AKI giving an incidence of 3.4%. Median age was 44 years (IQR 14-82) and 214 (58.5%) were male, with 152 (41.5%) female. Most, 265 (72.4%), had community acquired AKI. Common underlying comorbidities were hypertension (n = 152, 41.5%), diabetes mellitus (n = 65, 17.8%) Human immunodeficiency virus (HIV) (n = 75, 20.6%), heart disease (n = 58, 16.1%), and chronic kidney disease (n = 37, 10.1%). Renal biopsies were performed in 36 (9.8%) patients. In total, 202 (55.2%) patients were in the intensive care unit, and of the whole study population 204 (55.7%) were dialysed. Those admitted to ICU who required dialysis amounted to 145 (39.6%). The overall 3 month mortality was 38.8%. Among the 145 patients dialysed in ICU, there were 71 deaths (49%) at 3 month follow up. Of the 119 patients with follow up serum creatinine, 95 (79.8%) had full renal recovery, and 4 (3.4%) had end-stage renal disease. On multivariate analysis, mechanical ventilation was associated with 3 month mortality (OR 2.46, p-value 0.019, 95% CI 1.41-4.03). Sepsis had a borderline significant association (OR 1.83, P-value 0.066, 95%CI 1.02-3.27), as did prolonged time to dialysis (OR 1.93, p-value 0.08, 095% CI 0

  19. Healthcare Resource Availability, Quality of Care, and Acute Ischemic Stroke Outcomes.

    PubMed

    O'Brien, Emily C; Wu, Jingjing; Zhao, Xin; Schulte, Phillip J; Fonarow, Gregg C; Hernandez, Adrian F; Schwamm, Lee H; Peterson, Eric D; Bhatt, Deepak L; Smith, Eric E

    2017-02-03

    Healthcare resources vary geographically, but associations between hospital-based resources and acute stroke quality and outcomes remain unclear. Using Get With The Guidelines-Stroke and Dartmouth Atlas of Health Care data, we examined associations between healthcare resource availability, stroke care, and outcomes. We categorized hospital referral regions with high-, medium-, or low-resource levels based on the 2006 national per-capita availability median of 6 relevant acute stroke care resources. Using multivariable logistic regression, we examined healthcare resource level and in-hospital quality and outcomes. Of 1 480 308 admitted ischemic stroke patients (2006-2013), 28.8% were hospitalized in low-, 44.4% in medium-, and 26.9% in high-resource hospital referral regions. Quality-of-care/timeliness metrics, adjusted length of stay, and in-hospital mortality were similar across all resource levels. Significant variation exists in regional availability of healthcare resources for acute ischemic stroke treatment, yet among Get With the Guidelines-Stroke hospitals, quality of care and in-hospital outcomes did not differ by regional resource availability. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  20. Impact of the implementation of a Sepsis Code hospital protocol in antibiotic prescription and clinical outcomes in an intensive care unit.

    PubMed

    García-López, L; Grau-Cerrato, S; de Frutos-Soto, A; Bobillo-De Lamo, F; Cítores-Gónzalez, R; Diez-Gutierrez, F; Muñoz-Moreno, M F; Sánchez-Sánchez, T; Gandía-Martínez, F; Andaluz-Ojeda, D

    A study was performed to analyze the impact of an in-hospital Sepsis Code (SC) program on use of antibiotic and clinical outcomes. Quasi-experimental observational retrospective study. Polyvalent 11 beds ICU belonging to a tertiary Universitary hospital. Patients admitted consecutively to the ICU with diagnosis of severe sepsis or septic shock. A post intervention group (POST-SC) (September 2012-August 2013) was compared with a historical group (PRE-SC) used as control (January-December 2010). Antibiotic treatment, therapeutic antibiotic strategy, mortality and length of stay. Antibiotic consumption was expressed as defined daily doses (DDD)/ 100 stays. 42 patients with SS/SS in POST-SC group and 50 patients in PRE-SC group were consecutively recluted and further analyzed. Total antibiotic consumption (DDD) was similar in both groups. Rate of de-escalation therapy was significantly higher in POST-SC group (75% vs 30,8%, p<0,005) while prescription of restricted antibiotics was significantly lower (74% vs 52%, p=0,031). Finally POST-SC patients showed a significantly decrease in hospital and 28 days mortality rates [23% vs 44%, (p=0,035) and 31% vs 56% (p=0,014) respectively] as well as a reduction in ICU length of stay compared to PRE-SC cohort (5 days vs 10,5 days, p=0,05). The implementation of a Sepsis Code-hospital protocol is associated to an improvement in the management of antibiotic therapy with a significant increase in de-escalation therapy and lesser utilization of restricted use antibiotics, as well as a significant reduction in mortality, and a tendency towards shorter ICU length stay. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.