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Sample records for clinical septic shock

  1. Septic Shock

    PubMed Central

    Seymour, Christopher W.; Rosengart, Matthew R.

    2015-01-01

    IMPORTANCE Septic shock is a clinical emergency that occurs in more than 230 000 US patients each year. OBSERVATIONS AND ADVANCES In the setting of suspected or documented infection, septic shock is typically defined in a clinical setting by low systolic (≤90 mm Hg) or mean arterial blood pressure (≤65 mm Hg) accompanied by signs of hypoperfusion (eg, oliguria, hyperlactemia, poor peripheral perfusion, or altered mental status). Focused ultrasonography is recommended for the prompt recognition of complicating physiology (eg, hypovolemia or cardiogenic shock), while invasive hemodynamic monitoring is recommended only for select patients. In septic shock, 3 randomized clinical trials demonstrate that protocolized care offers little advantage compared with management without a protocol. Hydroxyethyl starch is no longer recommended, and debate continues about the role of various crystalloid solutions and albumin. CONCLUSIONS AND RELEVANCE The prompt diagnosis of septic shock begins with obtainment of medical history and performance of a physical examination for signs and symptoms of infection and may require focused ultrasonography to recognize more complex physiologic manifestations of shock. Clinicians should understand the importance of prompt administration of intravenous fluids and vasoactive medications aimed at restoring adequate circulation, and the limitations of protocol-based therapy, as guided by recent evidence. PMID:26284722

  2. Septic Shock

    PubMed Central

    Lansing, Allan M.

    1963-01-01

    Septic shock may be defined as hypotension caused by bacteremia and accompanied by decreased peripheral blood flow, evidenced by oliguria. Clinically, a shaking chill is the warning signal. The immediate cause of hypotension is pooling of blood in the periphery, leading to decreased venous return: later, peripheral resistance falls and cardiac failure may occur. Irreversible shock is comparable to massive reactive hyperemia. Reticuloendothelial failure, histamine release, and toxic hypersensitivity may be factors in the pathogenesis of septic shock. Adrenal failure does not usually occur, but large doses of corticosteroid are employed therapeutically to counteract the effect of histamine release or hypersensitivity to endotoxin. The keys to successful therapy are time, antibiotics, vasopressors, cortisone and correction of acidosis. PMID:14063936

  3. Mycobacterium tuberculosis septic shock.

    PubMed

    Kethireddy, Shravan; Light, R Bruce; Mirzanejad, Yazdan; Maki, Dennis; Arabi, Yaseen; Lapinsky, Stephen; Simon, David; Kumar, Aseem; Parrillo, Joseph E; Kumar, Anand

    2013-08-01

    Septic shock due to Mycobacterium tuberculosis (MTB) is an uncommon but well-recognized clinical syndrome. The objective of this study was to describe the unique clinical characteristics, epidemiologic risk factors, and covariates of survival of patients with MTB septic shock in comparison with other bacterial septic shock. A retrospective nested cohort study was conducted of patients given a diagnosis of MTB septic shock derived from a trinational, 8,670-patient database of patients with septic shock between 1996 and 2007. In the database, 53 patients had been given a diagnosis of MTB shock compared with 5,419 with septic shock associated with isolation of more common bacterial pathogens. Patients with MTB and other bacterial septic shock had in-hospital mortality rates of 79.2% and 49.7%, respectively (P < .0001). Of the cases of MTB shock, all but five patients had recognized respiratory tract involvement. Fifty-five percent of patients (29 of 53) were documented (by direct culture or stain) as having disseminated extrapulmonary involvement. Inappropriate and appropriate initial empirical therapy was delivered in 28 patients (52.8%) and 25 patients (47.2%); survival was 7.1% and 36.0%, respectively (P = .0114). Ten patients (18.9%) did not receive anti-MTB therapy; all died. The median time to appropriate antimicrobial therapy for MTB septic shock was 31.0 h (interquartile range, 18.9-71.9 h). Only 11 patients received anti-MTB therapy within 24 h of documentation of hypotension; six of these (54.5%) survived. Only one of 21 patients (4.8%) who started anti-MTB therapy after 24 h survived (P = .0003 vs < 24 h). Survival differences between these time intervals are not significantly different from those seen with bacterial septic shock due to more common bacterial pathogens. MTB septic shock behaves similarly to bacterial septic shock. As with bacterial septic shock, early appropriate antimicrobial therapy appears to improve mortality.

  4. Clinical review: Vasopressin and terlipressin in septic shock patients

    PubMed Central

    Delmas, Anne; Leone, Marc; Rousseau, Sébastien; Albanèse, Jacques; Martin, Claude

    2005-01-01

    Vasopressin (antidiuretic hormone) is emerging as a potentially major advance in the treatment of septic shock. Terlipressin (tricyl-lysine-vasopressin) is the synthetic, long-acting analogue of vasopressin, and has comparable pharmacodynamic but different pharmacokinetic properties. Vasopressin mediates vasoconstriction via V1 receptor activation on vascular smooth muscle. Septic shock first causes a transient early increase in blood vasopressin concentrations; these concentrations subsequently decrease to very low levels as compared with those observed with other causes of hypotension. Infusions of 0.01–0.04 U/min vasopressin in septic shock patients increase plasma vasopressin concentrations. This increase is associated with reduced need for other vasopressors. Vasopressin has been shown to result in greater blood flow diversion from nonvital to vital organ beds compared with adrenaline (epinephrine). Of concern is a constant decrease in cardiac output and oxygen delivery, the consequences of which in terms of development of multiple organ failure are not yet known. Terlipressin (one or two boluses of 1 mg) has similar effects, but this drug has been used in far fewer patients. Large randomized clinical trials should be conducted to establish the utility of these drugs as therapeutic agents in patients with septic shock. PMID:15774080

  5. Sepsis and septic shock.

    PubMed

    Maloney, Patrick J

    2013-08-01

    Early recognition of sepsis and septic shock in children relies on obtaining an attentive clinical history, accurate vital signs, and a physical examination focused on mental status, work of breathing, and circulatory status. Laboratory tests may support the diagnosis but are not reliable in isolation. The goal of septic shock management is reversal of tissue hypoperfusion. The therapeutic end point is shock reversal. Mortality is significantly better among children when managed appropriately. Every physician who cares for children must strive to have a high level of suspicion and keen clinical acumen for recognizing the rare but potentially seriously ill child.

  6. [Corticosteroids and septic shock].

    PubMed

    Bouletreau, P; Petit, P; Latarjet, J

    1976-01-01

    According to the data in the literature, the authors attempted to sum-up present attitudes on the value of corticoids in the treatment of septic shock. If their cardiovascular effects after a period of enthusiasm, are presently rather controversial, their cellular and sub-cellular actions, on the lysosomal membranes, capillary permeability and perhaps the intimate mechanisms of cellular oxygenation seem to be more real. However, the contra-indications which persist in the results of clinical works have resulted in the fact that the exact place of cortico-steroids in the therapeutic arsenal of septic shock still remains to be specified.

  7. [Severe sepsis and septic shock].

    PubMed

    Tønnesen, Else; Larsen, Kim

    2014-07-07

    Sepsis, severe sepsis and septic shock are syndromes. The incidence of sepsis is as high as 35% and with mortality rates in the intensive care unit from 27% to 54% in sepsis and septic shock, respectively. Many new treatments have been tested but only few have been implemented in clinical practise. The treatment of severe sepsis and septic shock is based on the Surviving Sepsis Campaign guidelines developed by an international expert panel. Early diagnosis, optimization of haemodynamics, rapid identification of focus and adequate antibiotic treatment are the most important strategies.

  8. Septic shock in chronic dialysis patients: clinical characteristics, antimicrobial therapy and mortality.

    PubMed

    Clark, Edward; Kumar, Anand; Langote, Amit; Lapinsky, Stephen; Dodek, Peter; Kramer, Andreas; Wood, Gordon; Bagshaw, Sean M; Wood, Ken; Gurka, Dave; Sood, Manish M

    2016-02-01

    To describe the clinical characteristics and in-hospital mortality of chronic dialysis-dependent end-stage kidney disease patients with septic shock in comparison to septic shock patients not receiving chronic dialysis. Using an international, multicenter database, we conducted a retrospective analysis of data collected from 10,414 patients admitted to the intensive care unit (ICU) with septic shock from 1989 to 2013, of which 800 (7.7 %) were chronic dialysis patients. Data on demographic characteristics, sites of infection, microbial pathogens, antimicrobial usage patterns, and in-hospital mortality were aggregated and compared for chronic dialysis and non-dialysis patients. Multivariate time-varying Cox models with and without propensity score matching were constructed to determine the association between dialysis and in-hospital death. Septic shock secondary to central venous catheter infection, peritonitis, ischemic bowel, and cellulitis was more frequent in chronic dialysis patients. The isolation of resistant organisms (10.7 vs. 7.1 %; p = 0.005) and delays in receiving antimicrobials (6.0 vs. 5.0 h) were more common in chronic dialysis patients than in non-dialysis patients. Delayed appropriate antimicrobial therapy was associated with an increased risk of death in chronic dialysis patients (p < 0.0001). In-hospital death occurred in 54.8 and 49.0 % of chronic dialysis and non-dialysis patients, respectively. After propensity score matching, there was no difference in overall survival between chronic dialysis and non-dialysis patients, but survival in chronic dialysis patients decreased over time compared to non-dialysis patients. The demographic and clinical characteristics of chronic dialysis patients with septic shock differ from those of similar non-dialysis patients. However, there was no significant difference in mortality between the chronic dialysis and non-dialysis patients with septic shock enrolled in this analysis.

  9. Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

    PubMed

    Shankar-Hari, Manu; Phillips, Gary S; Levy, Mitchell L; Seymour, Christopher W; Liu, Vincent X; Deutschman, Clifford S; Angus, Derek C; Rubenfeld, Gordon D; Singer, Mervyn

    2016-02-23

    Septic shock currently refers to a state of acute circulatory failure associated with infection. Emerging biological insights and reported variation in epidemiology challenge the validity of this definition. To develop a new definition and clinical criteria for identifying septic shock in adults. The Society of Critical Care Medicine and the European Society of Intensive Care Medicine convened a task force (19 participants) to revise current sepsis/septic shock definitions. Three sets of studies were conducted: (1) a systematic review and meta-analysis of observational studies in adults published between January 1, 1992, and December 25, 2015, to determine clinical criteria currently reported to identify septic shock and inform the Delphi process; (2) a Delphi study among the task force comprising 3 surveys and discussions of results from the systematic review, surveys, and cohort studies to achieve consensus on a new septic shock definition and clinical criteria; and (3) cohort studies to test variables identified by the Delphi process using Surviving Sepsis Campaign (SSC) (2005-2010; n = 28,150), University of Pittsburgh Medical Center (UPMC) (2010-2012; n = 1,309,025), and Kaiser Permanente Northern California (KPNC) (2009-2013; n = 1,847,165) electronic health record (EHR) data sets. Evidence for and agreement on septic shock definitions and criteria. The systematic review identified 44 studies reporting septic shock outcomes (total of 166,479 patients) from a total of 92 sepsis epidemiology studies reporting different cutoffs and combinations for blood pressure (BP), fluid resuscitation, vasopressors, serum lactate level, and base deficit to identify septic shock. The septic shock-associated crude mortality was 46.5% (95% CI, 42.7%-50.3%), with significant between-study statistical heterogeneity (I2 = 99.5%; τ2 = 182.5; P < .001). The Delphi process identified hypotension, serum lactate level, and vasopressor therapy as variables to

  10. Developing a New Definition and Assessing New Clinical Criteria for Septic Shock

    PubMed Central

    Shankar-Hari, Manu; Phillips, Gary S.; Levy, Mitchell L.; Seymour, Christopher W.; Liu, Vincent X.; Deutschman, Clifford S.; Angus, Derek C.; Rubenfeld, Gordon D.; Singer, Mervyn

    2016-01-01

    IMPORTANCE Septic shock currently refers to a state of acute circulatory failure associated with infection. Emerging biological insights and reported variation in epidemiology challenge the validity of this definition. OBJECTIVE To develop a new definition and clinical criteria for identifying septic shock in adults. DESIGN, SETTING, AND PARTICIPANTS The Society of Critical Care Medicine and the European Society of Intensive Care Medicine convened a task force (19 participants) to revise current sepsis/septic shock definitions. Three sets of studies were conducted: (1) a systematic review and meta-analysis of observational studies in adults published between January 1, 1992, and December 25, 2015, to determine clinical criteria currently reported to identify septic shock and inform the Delphi process; (2) a Delphi study among the task force comprising 3 surveys and discussions of results from the systematic review, surveys, and cohort studies to achieve consensus on a new septic shock definition and clinical criteria; and (3) cohort studies to test variables identified by the Delphi process using Surviving Sepsis Campaign (SSC) (2005–2010; n = 28 150), University of Pittsburgh Medical Center (UPMC) (2010–2012; n = 1 309 025), and Kaiser Permanente Northern California (KPNC) (2009–2013; n = 1 847 165) electronic health record (EHR) data sets. MAIN OUTCOMES AND MEASURES Evidence for and agreement on septic shock definitions and criteria. RESULTS The systematic review identified 44 studies reporting septic shock outcomes (total of 166 479 patients) from a total of 92 sepsis epidemiology studies reporting different cutoffs and combinations for blood pressure (BP), fluid resuscitation, vasopressors, serum lactate level, and base deficit to identify septic shock. The septic shock–associated crude mortality was 46.5% (95%CI, 42.7%–50.3%), with significant between-study statistical heterogeneity (I2 = 99.5%; τ2 = 182.5; P < .001). The Delphi process identified

  11. Acute kidney injury in patients with sepsis and septic shock: risk factors and clinical outcomes.

    PubMed

    Suh, Sang Heon; Kim, Chang Seong; Choi, Joon Seok; Bae, Eun Hui; Ma, Seong Kwon; Kim, Soo Wan

    2013-07-01

    The aim of this study was to investigate clinical characteristics and risk factors of acute kidney injury (AKI) in patients with sepsis and septic shock. Additionally, we explored whether the severity of AKI affects on the clinical outcomes. Data were collected retrospectively in a single center. Among 5680 patients who visited emergency department from January to December 2010, 992 patients with sepsis and septic shock were enrolled. Patients were divided into two groups, patients who developed AKI or not, to compare the baseline characteristics, and laboratory and physiologic data. Patients with AKI were subdivided according to its stages for survival analysis. AKI was developed in 57.7% of patients. Multivariable logistic regression analysis revealed that development of septic AKI was associated with older age, pre-existing chronic kidney disease, use of angiotensin converting enzyme inhibitor or angiotensin receptor blocker, presence of shock, positive blood culture results, and low white blood cell and platelet counts. Hospital mortality was higher in AKI group. Crude Kaplan-Meier survival curves demonstrated reduced 30-day survival rate was significantly associated with the severity of acute kidney injury. The development of septic AKI was associated with poor clinical outcomes. Furthermore, the severity of AKI was associated with increased mortality.

  12. Severe sepsis and septic shock: clinical overview and update on management.

    PubMed

    Cawcutt, Kelly A; Peters, Steve G

    2014-11-01

    Sepsis is among the oldest themes in medicine; however, despite modern advances, it remains a leading cause of death in the United States. Every clinician should be able to recognize the signs and symptoms of sepsis, along with early management strategies, to expeditiously provide appropriate care and decrease resultant morbidity and mortality. This review addresses the definitions, pathogenesis, clinical manifestations, management, and outcomes of patients with sepsis, severe sepsis, and septic shock.

  13. Septic shock in canine babesiosis.

    PubMed

    Matijatko, Vesna; Kis, Ivana; Torti, Marin; Brkljacić, Mirna; Kucer, Nada; Rafaj, Renata Barić; Grden, Darko; Zivicnjak, Tanja; Mrljak, Vladimir

    2009-06-10

    The records of all canine patients (86) that had been diagnosed with babesiosis and that were admitted to the Clinic for Internal Diseases, Faculty of Veterinary Medicine, Zagreb from January 2007 to December 2007 were reviewed retrospectively. All dogs that had been diagnosed with canine babesiosis and that had systemic inflammatory response syndrome (SIRS) followed by multiple organ dysfunction syndrome (MODS), and refractory hypotension, were included in this study. Of 86 patients diagnosed with canine babesiosis that were admitted during the study period, 10 had evidence of septic shock and were included in this study. Seven of the 10 dogs had a level of parasitaemia above 1%, with the highest level being 20.2%, seven of the 10 dogs were anaemic and three of the 10 dogs were leucopoenic. Thrombocytopenia was present in nine dogs. Hypoglycaemia was noted in two dogs, and bilirubinaemia in nine dogs. Four patients had involvement of two organs, five had involvement of three organs, and one had involvement of four organs. The organ that was most frequently involved was the kidney (nine cases). Central nervous system dysfunction was the rarest complication noted (one case). The mortality rate in non-septic shock canine babesiosis was 2.6%. All dogs that developed septic shock died between the first and the fourth day after admission. The 100% mortality rate that is reported here reflects the fact that in cases in which progression of the inflammatory response leads to the development of septic shock, an unfavourable outcome should be expected.

  14. Clinical impact of stress dose steroids in patients with septic shock: insights from the PROWESS-Shock trial.

    PubMed

    Póvoa, Pedro; Salluh, Jorge I F; Martinez, Maria L; Guillamat-Prats, Raquel; Gallup, Dianne; Al-Khalidi, Hussein R; Thompson, B Taylor; Ranieri, V Marco; Artigas, Antonio

    2015-04-28

    The aim of our study was to evaluate the clinical impact of the administration of intravenous steroids, alone or in conjunction with drotrecogin-alfa (activated) (DrotAA), on the outcomes in septic shock patients. We performed a sub-study of the PROWESS-Shock trial (septic shock patients who received fluids and vasopressors above a predefined threshold for at least 4 hours were randomized to receive either DrotAA or placebo for 96 hours). A propensity score for the administration of intravenous steroids for septic shock at baseline was constructed using multivariable logistic regression. Cox proportional hazards model using inverse probability of treatment weighting of the propensity score was used to estimate the effect of intravenous steroids, alone or in conjunction with DrotAA, on 28-day and 90-day all-cause mortality. A total of 1695 patients were enrolled of which 49.5% received intravenous steroids for treatment of septic shock at baseline (DrotAA + steroids N = 436; DrotAA + no steroids N = 414; placebo + steroids N = 403; placebo + no steroids N = 442). The propensity weighted risk of 28-day as well as 90-day mortality in those treated vs. those not treated with steroids did not differ among those randomized to DrotAA vs. placebo (interaction p-value = 0.38 and p = 0.27, respectively) nor was a difference detected within each randomized treatment. Similarly, the course of vasopressor use and cardiovascular SOFA did not appear to be influenced by steroid therapy. In patients with lung infection (N = 744), abdominal infection (N = 510), Gram-positive sepsis (N = 420) and Gram-negative sepsis (N = 461), the propensity weighted risk of 28-day as well as 90-day mortality in those treated vs. those not treated with steroids did not differ among those randomized to DrotAA vs. placebo nor was a difference detected within each randomized treatment. In the present study of septic shock patients, after

  15. [Comparison of clinical assessment and invasive evaluation of hemodynamic parameters in septic shock].

    PubMed

    Vucić, N; Pilas, V

    1995-06-01

    The authors compare, in this prospective study, the accuracy of their own clinical assessment of hemodynamic parameters and severity of disease with the findings obtained by right heart catheterization in 50 patients with septic shock. The purpose of the study was to determine whether Swan-Ganz catheter insertion was necessary in all patients with septic shock. As soon as the diagnosis was established, the value of pulmonary capillary wedge pressure was estimated, as well as presence or absence of pathological uptake/supply dependency in all patients. The latter is an excellent indicator of severity of disease. The accurate assessment was noted in 27 (54%) patients (1. investigator), and in 30 (60%) patients (2. investigator). The sensitivity of detection of pathological uptake/supply dependency amounted to 53% and 65%; specificity was 73% and 79%, respectively. The therapy was altered in 21 patients (42%) after catheter insertion. The results were tested with chi2-test (p < 0.01). The findings of this study warrant catheter insertion in patients with septic shock.

  16. 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

  17. Severe Sepsis and Septic Shock: Timing of Septic Shock Onset Matters.

    PubMed

    Huang, Chun-Ta; Tsai, Yi-Ju; Tsai, Pi-Ru; Yu, Chong-Jen; Ko, Wen-Je

    2016-05-01

    Timing of septic shock onset may play a prognostic role in severe sepsis; however, clinical evidence provides contradictory results. This study aimed to investigate possible associations between timing of onset of septic shock and patient outcome. In a university-affiliated hospital, all patients admitted to the intensive care unit (ICU) for severe sepsis or septic shock from November 2007 to March 2011 were included. The primary outcome of interest was the impact of timing of septic shock onset on in-hospital mortality. We also sought to identify potential factors predicting development of septic shock after ICU admission. In total, 772 patients were identified to have severe sepsis; approximately two-thirds (487/772) of them experienced septic shock and overall in-hospital mortality was 57%. Timing of onset of septic shock was an independent predictor of in-hospital outcome, and there was an increasing trend of in-hospital mortality with later onset of septic shock. In addition, timing of septic shock onset provided further mortality risk stratification in patients with APACHE II scores of less than 20 and 20 to 25. We also found that patients who underwent cardiovascular surgery were more likely to experience septic shock after admission and those receiving neurosurgery were at lower risk of developing septic shock. This study showed the significance of timing of septic shock onset in prognosis among ICU patients with severe sepsis. Timing of shock onset further stratified patients with similar disease severity into different mortality risk groups. These findings deliver useful information regarding risk stratification of septic patients.

  18. Protocol Adherence for Severe Sepsis and Septic Shock Management in the Emergency Department; a Clinical Audit

    PubMed Central

    Alavi-Moghaddam, Mostafa; Anvari, Ali; Soltani Delgosha, Reaza; Kariman, Hamid

    2017-01-01

    Introduction: Although significant development in the field of medicine is achieved, sepsis is still a major issue threatening humans’ lives. This study was aimed to audit the management of severe sepsis and septic shock patients in emergency department (ED) according to the present standard guidelines. Method: This is a prospective audit on approaching adult septic patients who were admitted to ED. The audit checklist was created based on the protocols of Surviving Sepsis Campaign and British Royal College recommendations. The mean knowledge score and the compliance rate of studied measures regarding standard protocols were calculated using SPSS version 21. Results: 30 emergency medicine residents were audited (63.3% male). The mean knowledge score of studied residents regarding standard guidelines were 5.07 ± 1.78 (IQR = 2) in pre education and 8.17 ± 1.31 (IQR = 85) in post education phase (p < 0.001). There was excellent compliance with standard in 4 (22%) studied measures, good in 2 (11%), fair in 1 (6%), weak in 2 (11%), and poor in 9 (50%). 64% of poor compliance measures correlated to therapeutic factors. After training, score of 5 measures including checking vital signs in < 20 minute, central vein pressure measurement in < 1 hour, blood culture request, administration of vasopressor agents, and high flow O2 therapy were improved clinically, but not statistically. Conclusion: The protocol adherence in management of severe sepsis and septic shock for urine output measurement, central venous pressure monitoring, administration of inotrope agents, blood transfusion, intravenous antibiotic and hydration therapy, and high flow O2 delivery were disappointingly low. It seems training workshops and implementation of Clinical audit can improve residents’ adherence to current standard guidelines regarding severe sepsis and septic shock. PMID:28286823

  19. Protocol Adherence for Severe Sepsis and Septic Shock Management in the Emergency Department; a Clinical Audit.

    PubMed

    Alavi-Moghaddam, Mostafa; Anvari, Ali; Soltani Delgosha, Reaza; Kariman, Hamid

    2017-01-01

    Although significant development in the field of medicine is achieved, sepsis is still a major issue threatening humans' lives. This study was aimed to audit the management of severe sepsis and septic shock patients in emergency department (ED) according to the present standard guidelines. This is a prospective audit on approaching adult septic patients who were admitted to ED. The audit checklist was created based on the protocols of Surviving Sepsis Campaign and British Royal College recommendations. The mean knowledge score and the compliance rate of studied measures regarding standard protocols were calculated using SPSS version 21. 30 emergency medicine residents were audited (63.3% male). The mean knowledge score of studied residents regarding standard guidelines were 5.07 ± 1.78 (IQR = 2) in pre education and 8.17 ± 1.31 (IQR = 85) in post education phase (p < 0.001). There was excellent compliance with standard in 4 (22%) studied measures, good in 2 (11%), fair in 1 (6%), weak in 2 (11%), and poor in 9 (50%). 64% of poor compliance measures correlated to therapeutic factors. After training, score of 5 measures including checking vital signs in < 20 minute, central vein pressure measurement in < 1 hour, blood culture request, administration of vasopressor agents, and high flow O2 therapy were improved clinically, but not statistically. The protocol adherence in management of severe sepsis and septic shock for urine output measurement, central venous pressure monitoring, administration of inotrope agents, blood transfusion, intravenous antibiotic and hydration therapy, and high flow O2 delivery were disappointingly low. It seems training workshops and implementation of Clinical audit can improve residents' adherence to current standard guidelines regarding severe sepsis and septic shock.

  20. Clinical relevance of the severe abnormalities of the T cell compartment in septic shock patients

    PubMed Central

    Monserrat, Jorge; de Pablo, Raul; Reyes, Eduardo; Díaz, David; Barcenilla, Hugo; Zapata, Manuel R; De la Hera, Antonio; Prieto, Alfredo; Álvarez-Mon, Melchor

    2009-01-01

    Introduction Given the pivotal role of T lymphocytes in the immune system, patients with septic shock may show T cell abnormalities. We have characterised the T cell compartment in septic shock and assess its clinical implications. Methods T lymphocytes from the peripheral blood of 52 patients with septic shock and 36 healthy control subjects were analysed on admission to the intensive care unit, baseline, and 3, 7, 14 and 28 days later. T cell phenotypes (CD3+CD4+/CD3+CD8+, CD45RA+/CD45RO+, CD62L+/CD28+) were assessed by quantitative flow cytometry. Results CD3+, CD3+CD4+ and CD3+CD8+ lymphocyte counts were significantly lower in patients with septic shock than control subjects. In surviving patients, CD3+CD4+ lymphocytes had normalised after 14 days, yet CD3+CD8+ numbers were still low. Non effector CD45RA+CD45RO- subsets of CD3+CD4+ and CD3+CD8+ were persistently low during patient follow up. CD3+CD8+CD28+ and CD3+CD8+CD62L+ were reduced in patients versus controls and survivors versus nonsurvivors in the first three days. A prediction receptor operative curve revealed that for the CD3+CD8+CD28+ subset, a cutoff of 136 cells/ml showed 70% sensitivity and 100% specificity for predicting death and the area under the curve was 0.84 at admission. Corresponding values for CD3+CD8+CD62L+ were 141 cells/ml, 60% sensitivity, 100% specificity and an area under the curve of 0.75. Conclusions A severe redistribution of T lymphocyte subsets is found in septic shock patients. A different kinetic pattern of T cell subset involvement is observed in surviving and nonsurviving patients, with lower numbers of circulating CD3+CD8+CD28+ and CD3+CD8+CD62L+ associated with a better disease outcome. PMID:19243622

  1. Management of septic shock.

    PubMed Central

    Edwards, J D

    1993-01-01

    There have been important advances in the resuscitation of patients in septic shock in recent years. Survival can be improved by earlier recognition and therefore eradication of the sepsis combined with logical supportive measures. As with any acutely ill patient consultation with intensive care unit staff may be useful. Consultation with the intensive care unit does not necessarily imply the need for admission and mechanical ventilation; helpful advice may be forthcoming. Equally, referral to the intensive care unit does not mean an admission of failure but merely a recognition that additional skills and technical facilities are necessary for the patient's survival. PMID:8324438

  2. [Management of pediatric septic shock].

    PubMed

    Llor, J; Parret, L; Stucki, P; Cotting, J

    2005-06-01

    Septic shock is a frequent admission cause in intensive care unit. In spite of the important progresses in the understanding of his physiopathology, mortality due to septic shock is about 20%. Recently, it has been demonstrated that an early goal-directed therapy permitted to improve the patient prognosis. With a good hemodynamic management and early antibiotherapy, mortality could be reduced.

  3. Mortality Reduction in Septic Shock by Plasma Adsorption (ROMPA): a protocol for a randomised clinical trial

    PubMed Central

    Colomina-Climent, Francisco; Giménez-Esparza, Carola; Portillo-Requena, Cristina; Allegue-Gallego, José Manuel; Galindo-Martínez, María; Mollà-Jiménez, Cristina; Antón-Pascual, José Luis; Rodríguez-Serra, Manuel; Martín-Ruíz, José Luis; Fernández-Arroyo, Pablo Juan; Blasco-Císcar, Eugenia María; Cánovas-Robles, José; Herrera-Murillo, Miguel; González-Hernández, Enrique; Sánchez-Morán, Fernando; Solera-Suárez, Manuel; Torres-Tortajada, Jesús; Nuñez-Martínez, José María; Martín-Langerwerf, David; Herrero-Gutiérrez, Eugenio; Sebastián-Muñoz, Isabel; Palazón-Bru, Antonio; Gil-Guillén, Vicente Francisco

    2016-01-01

    Introduction There is a lack of evidence in the efficacy of the coupled plasma filtration adsorption (CPFA) to reduce the mortality rate in septic shock. To fill this gap, we have designed the ROMPA study (Mortality Reduction in Septic Shock by Plasma Adsorption) to confirm whether treatment with an adequate dose of treated plasma by CPFA could confer a clinical benefit. Methods and analysis Our study is a multicentric randomised clinical trial with a 28-day and 90-day follow-up and allocation ratio 1:1. Its aim is to clarify whether the application of high doses of CPFA (treated plasma ≥0.20 L/kg/day) in the first 3 days after randomisation, in addition to the current clinical practice, is able to reduce hospital mortality in patients with septic shock in intensive care units (ICUs) at 28 and 90 days after initiation of the therapy. The study will be performed in 10 ICUs in the Southeast of Spain which follow the same protocol in this disease (based on the Surviving Sepsis Campaign). Our trial is designed to be able to demonstrate an absolute mortality reduction of 20% (α=0.05; 1−β=0.8; n=190(95×2)). The severity of the process, ensuring the recruitment of patients with a high probability of death (50% in the control group), will be achieved through an adequate stratification by using both severity scores and classical definitions of severe sepsis/septic shock and dynamic parameters. Our centres are fully aware of the many pitfalls associated with previous medical device trials. Trying to reduce these problems, we have developed a training programme to improve the CPFA use (especially clotting problems). Ethics and dissemination The protocol was approved by the Ethics Committees of all the participant centres. The findings of the trial will be disseminated through peer-reviewed journals, as well as national and international conference presentations. Trial registration number NCT02357433; Pre-results. PMID:27406647

  4. American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock.

    PubMed

    Davis, Alan L; Carcillo, Joseph A; Aneja, Rajesh K; Deymann, Andreas J; Lin, John C; Nguyen, Trung C; Okhuysen-Cawley, Regina S; Relvas, Monica S; Rozenfeld, Ranna A; Skippen, Peter W; Stojadinovic, Bonnie J; Williams, Eric A; Yeh, Tim S; Balamuth, Fran; Brierley, Joe; de Caen, Allan R; Cheifetz, Ira M; Choong, Karen; Conway, Edward; Cornell, Timothy; Doctor, Allan; Dugas, Marc-Andre; Feldman, Jonathan D; Fitzgerald, Julie C; Flori, Heidi R; Fortenberry, James D; Graciano, Ana Lia; Greenwald, Bruce M; Hall, Mark W; Han, Yong Yun; Hernan, Lynn J; Irazuzta, Jose E; Iselin, Elizabeth; van der Jagt, Elise W; Jeffries, Howard E; Kache, Saraswati; Katyal, Chhavi; Kissoon, Niranjan Tex; Kon, Alexander A; Kutko, Martha C; MacLaren, Graeme; Maul, Timothy; Mehta, Renuka; Odetola, Fola; Parbuoni, Kristine; Paul, Raina; Peters, Mark J; Ranjit, Suchitra; Reuter-Rice, Karin E; Schnitzler, Eduardo J; Scott, Halden F; Torres, Adalberto; Weingarten-Abrams, Jacki; Weiss, Scott L; Zimmerman, Jerry J; Zuckerberg, Aaron L

    2017-06-01

    The American College of Critical Care Medicine provided 2002 and 2007 guidelines for hemodynamic support of newborn and pediatric septic shock. Provide the 2014 update of the 2007 American College of Critical Care Medicine "Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock." Society of Critical Care Medicine members were identified from general solicitation at Society of Critical Care Medicine Educational and Scientific Symposia (2006-2014). The PubMed/Medline/Embase literature (2006-14) was searched by the Society of Critical Care Medicine librarian using the keywords: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, extracorporeal membrane oxygenation, and American College of Critical Care Medicine guidelines in the newborn and pediatric age groups. The 2002 and 2007 guidelines were widely disseminated, translated into Spanish and Portuguese, and incorporated into Society of Critical Care Medicine and American Heart Association/Pediatric Advanced Life Support sanctioned recommendations. The review of new literature highlights two tertiary pediatric centers that implemented quality improvement initiatives to improve early septic shock recognition and first-hour compliance to these guidelines. Improved compliance reduced hospital mortality from 4% to 2%. Analysis of Global Sepsis Initiative data in resource rich developed and developing nations further showed improved hospital mortality with compliance to first-hour and stabilization guideline recommendations. The major new recommendation in the 2014 update is consideration of institution-specific use of 1) a "recognition bundle" containing a trigger tool for rapid identification of patients with septic shock, 2) a "resuscitation and stabilization bundle" to help adherence to best practice principles, and 3) a "performance bundle" to identify and overcome perceived barriers to the pursuit of best practice principles.

  5. Fluid therapy in septic shock.

    PubMed

    Rivers, Emanuel P; Jaehne, Anja Kathrin; Eichhorn-Wharry, Laura; Brown, Samantha; Amponsah, David

    2010-08-01

    To examine the role of fluid therapy in the pathogenesis of severe sepsis and septic shock. The type, composition, titration, management strategies and complications of fluid administration will be examined in respect to outcomes. Fluids have a critical role in the pathogenesis and treatment of early resuscitation of severe sepsis and septic shock. Although this pathogenesis is evolving, early titrated fluid administration modulates inflammation, improves microvascular perfusion, impacts organ function and outcome. Fluid administration has limited impact on tissue perfusion during the later stages of sepsis and excess fluid is deleterious to outcome. The type of fluid solution does not seem to influence these observations.

  6. [Septic shock secondary to non-congenital chikungunya fever in a young infant: A clinical case].

    PubMed

    Méndez-Domínguez, Nina; Achach-Asaf, Jorge Augusto; Basso-García, Luis Manuel; Quiñones-Pacheco, Yazmín Berenice; Gómez-Carro, Salvador

    2016-01-01

    A chikungunya outbreak took place in the State of Yucatan starting in the second half of 2015 OBJECTIVE: To analyse the clinical course of a case of chikungunya in a previously healthy infant, providing practical evidence to guide future diagnoses and treatment during outbreak seasons in endemic areas Clinical manifestation started with a sudden onset of fever and a diffuse macular-papillary erythema, originally treated in the community with non-steroidal anti-inflammatory drugs. Two days later, the fever relapsed with hypoactivity, severe thrombocytopenia and neutropenia (without lymphopenia), respiratory distress, liver dysfunction, sepsis, followed by septic shock with a fatal outcome. IgM test was positive to chikungunya, while her mother tested negative. Pseudomonas aeruginosa was isolated from the blood culture possible due to contamination, without ruling out the possibility of a mixed origin sepsis. Chikungunya is a disease in which the manifestations in neonates and young infants can be severe, and even fatal. It is important to suspect it in this age group at risk of vector contact, in the presence of fever without apparent source of infection and cutaneous manifestations. It is important to use the antipyretics cautiously, considering the possibility of aggravating the underlying infection, and the potential hepatic and haematological damage. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Judging quality of current septic shock definitions and criteria.

    PubMed

    Shankar-Hari, Manu; Bertolini, Guido; Brunkhorst, Frank M; Bellomo, Rinaldo; Annane, Djillali; Deutschman, Clifford S; Singer, Mervyn

    2015-12-25

    Septic shock definitions are being revisited. We assess the feasibility, reliability, and validity characteristics of the current definitions and criteria of septic shock. Septic shock is conceptualised as cardiovascular dysfunction, tissue perfusion and cellular abnormalities caused by infection. Currently, for feasibility, septic shock is identified at the bedside by using either hypotension or a proxy for tissue perfusion/cellular abnormalities (e.g., hyperlactatemia). We propose that concurrent presence of cardiovascular dysfunction and perfusion/cellular abnormalities could improve validity of septic shock diagnosis, as we are more likely to identify a patient population with all elements of the illness concept. This epidemiological refinement should not affect clinical care and may aid study design to identify illness-specific biomarkers and interventions.

  8. Is this septic shock? A rare case of distributive shock.

    PubMed

    Val-Flores, Luis Silva; Fior, Alberto; Santos, Ana; Reis, Luís; Bento, Luís

    2014-01-01

    The authors report a rare case of shock in a patient without significant clinical history, admitted to the intensive care unit for suspected septic shock. The patient was initially treated with fluid therapy without improvement. A hypothesis of systemic capillary leak syndrome was postulated following the confirmation of severe hypoalbuminemia, hypotension, and hemoconcentration--a combination of three symptoms typical of the disease. The authors discussed the differential diagnosis and also conducted a review of the diagnosis and treatment of the disease.

  9. Is this septic shock? A rare case of distributive shock

    PubMed Central

    Val-Flores, Luis Silva; Fior, Alberto; Santos, Ana; Reis, Luís; Bento, Luís

    2014-01-01

    The authors report a rare case of shock in a patient without significant clinical history, admitted to the intensive care unit for suspected septic shock. The patient was initially treated with fluid therapy without improvement. A hypothesis of systemic capillary leak syndrome was postulated following the confirmation of severe hypoalbuminemia, hypotension, and hemoconcentration - a combination of three symptoms typical of the disease. The authors discussed the differential diagnosis and also conducted a review of the diagnosis and treatment of the disease. PMID:25607273

  10. Massive Organ Inflammation in Experimental and in Clinical Meningococcal Septic Shock.

    PubMed

    Hellerud, Bernt C; Olstad, Ole K; Nielsen, Erik W; Trøseid, Anne-Marie S; Skadberg, Øyvind; Thorgersen, Ebbe B; Vege, Åshild; Mollnes, Tom E; Brandtzæg, Petter

    2015-11-01

    Fulminant meningococcal sepsis is characterized by a massive growth of bacteria in the circulation, regarded as the primary inflammatory site, with no specific solid organ focus. Here we aimed to study the local inflammatory response in organs using a porcine model of fulminant meningococcal septic shock challenged with exponentially increasing doses of heat inactivated Neisseria meningitidis. The results were compared with those obtained in organs post mortem from three patients with lethal meningococcal septic shock. Nine patients with lethal pneumococcal disease and 14 patients with sudden infant death syndrome served as controls. Frozen tissue were thawed, homogenized and prepared for quantification of bacterial DNA by real-time polymerase chain reaction, and key inflammatory mediators were measured by ELISA in the pig material and by multiplex in the human material. In addition, gene expression assayed by Affymetrix gene expression profiling was performed in the pig study. The porcine model revealed a major influx of N. meningitidis in lungs, liver, spleen, and kidneys accompanied with major production of cardinal inflammatory mediators including tumor necrosis factor, interleukin (IL)-1β, IL-6, and IL-8, far exceeding the amount detected in blood. Genes encoding for these mediators revealed a similar profile. By comparing the wild-type with a lipopolysaccharide (LPS) deficient meningococcal strain, we documented that LPS was the dominant group of molecules inducing organ inflammation and was required for IL-8 production. IL-10 production was predominantly stimulated by non-LPS molecules. The massive organ inflammation in the porcine model was present in the three patients dying of meningococcal shock and differed markedly from the patients with lethal pneumococcal infections and sudden infant death syndrome. In conclusion, in meningococcal sepsis, a massive local inflammatory response occurs in specific organs.

  11. Efficacy of coupled plasma filtration adsorption (CPFA) in patients with septic shock: A multicenter randomised controlled clinical trial

    PubMed Central

    Livigni, Sergio; Bertolini, Guido; Rossi, Carlotta; Ferrari, Fiorenza; Giardino, Michele; Pozzato, Marco; Remuzzi, Giuseppe

    2014-01-01

    Objectives Coupled plasma filtration adsorption (CPFA, Bellco, Italy), to remove inflammatory mediators from blood, has been proposed as a novel treatment for septic shock. This multicenter, randomised, non-blinded trial compared CPFA with standard care in the treatment of critically ill patients with septic shock. Design Prospective, multicenter, randomised, open-label, two parallel group and superiority clinical trial. Setting 18 Italian adult, general, intensive care units (ICUs). Participants Of the planned 330 adult patients with septic shock, 192 were randomised to either have CPFA added to the standard care, or not. The external monitoring committee excluded eight ineligible patients who were erroneously included. Interventions CPFA was to be performed daily for 5 days, lasting at least 10 h/day. Primary and secondary outcome measures The primary endpoint was mortality at discharge from the hospital at which the patient last stayed. Secondary endpoints were: 90-day mortality, new organ failures and ICU-free days within 30 days. Results There was no statistical difference in hospital mortality (47.3% controls, 45.1% CPFA; p=0.76), nor in secondary endpoints, namely the occurrence of new organ failures (55.9% vs 56.0%; p=0.99) or free-ICU days during the first 30 days (6.8 vs 7.5; p=0.35). The study was terminated on the grounds of futility. Several patients randomised to CPFA were subsequently found to be undertreated. An a priori planned subgroup analysis showed those receiving a CPFA dose >0.18 L/kg/day had a lower mortality compared with controls (OR 0.36, 95% CI 0.13 to 0.99). Conclusions CPFA did not reduce mortality in patients with septic shock, nor did it positively affect other important clinical outcomes. A subgroup analysis suggested that CPFA could reduce mortality, when a high volume of plasma is treated. Owing to the inherent potential biases of such a subgroup analysis, this result can only be viewed as a hypothesis generator and

  12. Systemic over-release of interleukin-17 in acute kidney injury after septic shock: Clinical and experimental evidence.

    PubMed

    Maravitsa, Panagiota; Adamopoulou, Maria; Pistiki, Aikaterini; Netea, Mihai G; Louis, Konstantinos; Giamarellos-Bourboulis, Evangelos J

    2016-10-01

    In order to investigate the role of T-helper 17 (Th17) cell activation in acute kidney injury (AKI) after septic shock, a two-stage approach was used. Firstly, peripheral blood mononuclear cells (PBMCs) and CD4-lymphocytes were isolated the first 24h after septic shock from 26 patients with AKI and 18 patients with chronic renal disease (CRD) without AKI and stimulated for the release of tumour necrosis factor-alpha (TNFα), interleukin (IL)-10, IL-17, IL-22 and interferon-gamma (IFNγ). Results were compared with 15 healthy volunteers and 13 patients with uncomplicated sepsis. Secondly, a murine model of multiple organ dysfunction (MODS) complicated with AKI and bacterial gut translocation was studied, and IL-10, IL-17, IL-22 and IFNγ were measured in kidney homogenates. IL-17 was the only cytokine produced at greater quantities from PBMCs and CD4-lymphocytes of patients with septic shock and AKI than comparators. When PBMCs of patients with septic shock and AKI were ex-vivo stimulated, intracellular staining for IL-17 was greater in CD3(+)/CD4(+)/CD196(+) cells compared to patients with septic shock and CRD. IL-17 was released at greater amounts from PBMCs of non-survivors by septic shock and AKI but not of septic shock and CRD. In the murine model of MODS, a gradual decrease of IL-17, but not of IL-10, IL-22 and IFNγ, of kidney homogenates was found indicating over-consumption. These results suggest that AKI after septic shock is driven through IL-17 release by Th17 cells; this is gradually consumed in the kidney.

  13. Efficacy of coupled plasma filtration adsorption (CPFA) in patients with septic shock: a multicenter randomised controlled clinical trial.

    PubMed

    Livigni, Sergio; Bertolini, Guido; Rossi, Carlotta; Ferrari, Fiorenza; Giardino, Michele; Pozzato, Marco; Remuzzi, Giuseppe

    2014-01-08

    Coupled plasma filtration adsorption (CPFA, Bellco, Italy), to remove inflammatory mediators from blood, has been proposed as a novel treatment for septic shock. This multicenter, randomised, non-blinded trial compared CPFA with standard care in the treatment of critically ill patients with septic shock. Prospective, multicenter, randomised, open-label, two parallel group and superiority clinical trial. 18 Italian adult, general, intensive care units (ICUs). Of the planned 330 adult patients with septic shock, 192 were randomised to either have CPFA added to the standard care, or not. The external monitoring committee excluded eight ineligible patients who were erroneously included. CPFA was to be performed daily for 5 days, lasting at least 10 h/day. The primary endpoint was mortality at discharge from the hospital at which the patient last stayed. Secondary endpoints were: 90-day mortality, new organ failures and ICU-free days within 30 days. There was no statistical difference in hospital mortality (47.3% controls, 45.1% CPFA; p=0.76), nor in secondary endpoints, namely the occurrence of new organ failures (55.9% vs 56.0%; p=0.99) or free-ICU days during the first 30 days (6.8 vs 7.5; p=0.35). The study was terminated on the grounds of futility. Several patients randomised to CPFA were subsequently found to be undertreated. An a priori planned subgroup analysis showed those receiving a CPFA dose >0.18 L/kg/day had a lower mortality compared with controls (OR 0.36, 95% CI 0.13 to 0.99). CPFA did not reduce mortality in patients with septic shock, nor did it positively affect other important clinical outcomes. A subgroup analysis suggested that CPFA could reduce mortality, when a high volume of plasma is treated. Owing to the inherent potential biases of such a subgroup analysis, this result can only be viewed as a hypothesis generator and should be confirmed in future studies. NCT00332371; ISRCTN24534559.

  14. Angiotensin II in Refractory Septic Shock.

    PubMed

    Antonucci, Elio; Gleeson, Patrick J; Annoni, Filippo; Agosta, Sara; Orlando, Sergio; Taccone, Fabio Silvio; Velissaris, Dimitrios; Scolletta, Sabino

    2017-05-01

    Refractory septic shock is defined as persistently low mean arterial blood pressure despite volume resuscitation and titrated vasopressors/inotropes in patients with a proven or suspected infection and concomitant organ dysfunction. Its management typically requires high doses of catecholamines, which can induce significant adverse effects such as ischemia and arrhythmias. Angiotensin II (Ang II), a key product of the renin-angiotensin-aldosterone system, is a vasopressor agent that could be used in conjunction with other vasopressors to stabilize critically ill patients during refractory septic shock, and reduce catecholamine requirements. However, very few clinical data are available to support Ang II administration in this setting. Here, we review the current literature on this topic to better understand the role of Ang II administration during refractory septic shock, differentiating experimental from clinical studies. We also consider the potential role of exogenous Ang II administration in specific organ dysfunction and possible pitfalls with Ang II in sepsis. Various issues remain unresolved and future studies should investigate important topics such as: the optimal dose and timing of Ang II administration, a comparison between Ang II and the other vasopressors (epinephrine; vasopressin), and Ang II effects on microcirculation.

  15. An alternate pathophysiologic paradigm of sepsis and septic shock

    PubMed Central

    Kumar, Anand

    2014-01-01

    The advent of modern antimicrobial therapy following the discovery of penicillin during the 1940s yielded remarkable improvements in case fatality rate of serious infections including septic shock. Since then, pathogens have continuously evolved under selective antimicrobial pressure resulting in a lack of significant improvement in clinical effectiveness in the antimicrobial therapy of septic shock despite ever more broad-spectrum and potent drugs. In addition, although substantial effort and money has been expended on the development novel non-antimicrobial therapies of sepsis in the past 30 years, clinical progress in this regard has been limited. This review explores the possibility that the current pathophysiologic paradigm of septic shock fails to appropriately consider the primacy of the microbial burden of infection as the primary driver of septic organ dysfunction. An alternate paradigm is offered that suggests that has substantial implications for optimizing antimicrobial therapy in septic shock. This model of disease progression suggests the key to significant improvement in the outcome of septic shock may lie, in great part, with improvements in delivery of existing antimicrobials and other anti-infectious strategies. Recognition of the role of delays in administration of antimicrobial therapy in the poor outcomes of septic shock is central to this effort. However, therapeutic strategies that improve the degree of antimicrobial cidality likely also have a crucial role. PMID:24184742

  16. The Impact of the Sepsis-3 Septic Shock Definition on Previously Defined Septic Shock Patients.

    PubMed

    Sterling, Sarah A; Puskarich, Michael A; Glass, Andrew F; Guirgis, Faheem; Jones, Alan E

    2017-09-01

    The Third International Consensus Definitions Task Force (Sepsis-3) recently recommended changes to the definitions of sepsis. The impact of these changes remains unclear. Our objective was to determine the outcomes of patients meeting Sepsis-3 septic shock criteria versus patients meeting the "old" (1991) criteria of septic shock only. Secondary analysis of two clinical trials of early septic shock resuscitation. Large academic emergency departments in the United States. Patients with suspected infection, more than or equal to two systemic inflammatory response syndrome criteria, and systolic blood pressure less than 90 mm Hg after fluid resuscitation. Patients were further categorized as Sepsis-3 septic shock if they demonstrated hypotension, received vasopressors, and exhibited a lactate greater than 2 mmol/L. We compared in-hospital mortality in patients who met the old definition only with those who met the Sepsis-3 criteria. Four hundred seventy patients were included in the present analysis. Two hundred (42.5%) met Sepsis-3 criteria, whereas 270 (57.4%) met only the old definition. Patients meeting Sepsis-3 criteria demonstrated higher severity of illness by Sequential Organ Failure Assessment score (9 vs 5; p < 0.001) and mortality (29% vs 14%; p < 0.001). Subgroup analysis of 127 patients meeting only the old definition demonstrated significant mortality benefit following implementation of a quantitative resuscitation protocol (35% vs 10%; p = 0.006). In this analysis, 57% of patients meeting old definition for septic shock did not meet Sepsis-3 criteria. Although Sepsis-3 criteria identified a group of patients with increased organ failure and higher mortality, those patients who met the old criteria and not Sepsis-3 criteria still demonstrated significant organ failure and 14% mortality rate.

  17. 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

  18. Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial.

    PubMed

    Gordon, Anthony C; Mason, Alexina J; Thirunavukkarasu, Neeraja; Perkins, Gavin D; Cecconi, Maurizio; Cepkova, Magda; Pogson, David G; Aya, Hollmann D; Anjum, Aisha; Frazier, Gregory J; Santhakumaran, Shalini; Ashby, Deborah; Brett, Stephen J

    2016-08-02

    Norepinephrine is currently recommended as the first-line vasopressor in septic shock; however, early vasopressin use has been proposed as an alternative. To compare the effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock. A factorial (2×2), double-blind, randomized clinical trial conducted in 18 general adult intensive care units in the United Kingdom between February 2013 and May 2015, enrolling adult patients who had septic shock requiring vasopressors despite fluid resuscitation within a maximum of 6 hours after the onset of shock. Patients were randomly allocated to vasopressin (titrated up to 0.06 U/min) and hydrocortisone (n = 101), vasopressin and placebo (n = 104), norepinephrine and hydrocortisone (n = 101), or norepinephrine and placebo (n = 103). The primary outcome was kidney failure-free days during the 28-day period after randomization, measured as (1) the proportion of patients who never developed kidney failure and (2) median number of days alive and free of kidney failure for patients who did not survive, who experienced kidney failure, or both. Rates of renal replacement therapy, mortality, and serious adverse events were secondary outcomes. A total of 409 patients (median age, 66 years; men, 58.2%) were included in the study, with a median time to study drug administration of 3.5 hours after diagnosis of shock. The number of survivors who never developed kidney failure was 94 of 165 patients (57.0%) in the vasopressin group and 93 of 157 patients (59.2%) in the norepinephrine group (difference, -2.3% [95% CI, -13.0% to 8.5%]). The median number of kidney failure-free days for patients who did not survive, who experienced kidney failure, or both was 9 days (interquartile range [IQR], 1 to -24) in the vasopressin group and 13 days (IQR, 1 to -25) in the norepinephrine group (difference, -4 days [95% CI, -11 to 5]). There was less use of renal replacement therapy in the vasopressin group

  19. Efficacy of plasma exchange in septic shock: a case report.

    PubMed

    Sołtysiak, Jolanta; Bartkowska-Śniatkowska, Alicja; Rosada-Kurasińska, Jowita; Lipkowska, Katarzyna; Zachwieja, Jacek

    2014-01-01

    The mortality rate for severe sepsis and septic shock remains high. Additionally, this life-threatening state poses serious difficulties for the treatment of patients. Unfortunately, the mechanism of sepsis is complex and not well understood. In this paper, we present the case of a 2.5-year-old female with septic shock treated with plasma exchange (PE) as a nonstandard therapy. We analysed the medical history of disease, including patient data, physical examination, laboratory tests and treatment. Unexpectedly, we achieved clinical improvement after the first PE. During PE, the dose of catecholamine was reduced. In addition, the level of C-reactive protein seemed to be a better predictor of the efficacy of PE in septic shock compared to procalcitonin. We conclude that PE may improve the survival rate for patients with septic shock. These data could be useful in the search and introduction of new or alternative methods of treatment for critically ill children.

  20. Sepsis and Septic Shock: Lingering Questions.

    PubMed

    Dumont, Tiffany; Francis-Frank, Lyndave; Chong, Josebelo; Balaan, Marvin R

    2016-01-01

    Sepsis and septic shock are major health conditions in the United States, with a high incidence and mortality. The Surviving Sepsis Campaign, which was formed in 2002, formulates guidelines for the management of severe sepsis and septic shock and has actually demonstrated a reduction in mortality with institution of "sepsis bundles." Despite this, some elements of the guidelines have been questioned, and recent data suggest that strict compliance with bundles and protocols may not be necessary. Still, prompt recognition and treatment of sepsis and septic shock remain of utmost importance.

  1. The Effect of Early Goal-Directed Therapy on Outcome in Adult Severe Sepsis and Septic Shock Patients: A Meta-Analysis of Randomized Clinical Trials.

    PubMed

    Xu, Jing-Yuan; Chen, Qi-Hong; Liu, Song-Qiao; Pan, Chun; Xu, Xiu-Ping; Han, Ji-Bin; Xie, Jian-Feng; Huang, Ying-Zi; Guo, Feng-Mei; Yang, Yi; Qiu, Hai-Bo

    2016-08-01

    Whether early goal-directed therapy (EGDT) improves outcome in severe sepsis and septic shock remains unclear. We performed a meta-analysis of existing clinical trials to examine whether EGDT improved outcome in the resuscitation of adult sepsis patients compared with control care. We searched for eligible studies using MEDLINE, Elsevier, Cochrane Central Register of Controlled Trials, and Web of Science databases. Studies were eligible if they compared the effects of EGDT versus control care on mortality in adult patients with severe sepsis and septic shock. Two reviewers extracted data independently. Data including mortality, sample size of the patients with severe sepsis and septic shock, and resuscitation end points were extracted. Data were analyzed using methods recommended by the Cochrane Collaboration Review Manager 4.2 software. Random errors were evaluated by trial sequential analysis (TSA). Nine studies compared EGDT with control care, and 5202 severe sepsis and septic shock patients were included. A nonsignificant trend toward reduction in the longest all-cause mortality was observed in the EGDT group compared with control care (relative risk, 0.89; 99% confidence interval, 0.74-1.07; P = 0.10). However, EGDT significantly reduced intensive care unit mortality in severe sepsis and septic shock patients (relative risk, 0.72; 99% confidence interval, 0.57-0.90; P = 0.0002). TSA indicated lack of firm evidence for a beneficial effect. In this meta-analysis, a nonsignificant trend toward reduction in the longest all-cause mortality in patients resuscitated with EGDT was noted. However, EGDT significantly reduced intensive care unit mortality in severe sepsis and septic shock patients. TSA indicated a lack of firm evidence for the results. More powered, randomized controlled trials are needed to determine the effects.

  2. Understanding hypovolaemic, cardiogenic and septic shock.

    PubMed

    Garretson, Sharon; Malberti, Shelly

    Shock is a complex physiological syndrome. If it is not detected and treated promptly, it can lead to death. This article reviews and summarises the latest findings, treatment and nursing and medical interventions for three of the most common forms of shock, namely, hypovolaemic, cardiogenic and septic shock.

  3. [Glycemic control in sepsis and septic shock: friend or foe?].

    PubMed

    Ellger, B; Westphal, M; Stubbe, H D; Van den Heuvel, I; Van Aken, H; Van den Berghe, G

    2008-01-01

    Intensive care patients commonly suffer from hyperglycemia. Evidence is growing that strictly maintaining normoglycemia by intensive insulin therapy (IIT) ameliorates outcome in these patients. Whether or not this also holds true for patients with sepsis and septic shock is the issue of this post-hoc analysis of the database (2,748 patients) of 2 recent prospective clinical trials. A total of 950 patients suffering from sepsis were identified and of these 462 fulfilled the diagnostic criteria of septic shock upon admission to the intensive care unit (ICU). Patients were treated by either IIT [mean glycemia 5.88 mmol/l (106 mg/dl)] or conventional glucose management [mean glycemia 8.44 mmol/l (152 mg/dl)]. Under IIT the mortality of patients treated for more than 3 days in the ICU was lowered by 7.6% (p=0.03) in septic patients and by 8.7% (p=0.08) in septic shock patients. Polyneuropathy occurred less frequently under IIT compared to conventional glucose management (sepsis -9.8%, septic shock -14%; p<0.001). The incidence of acute renal failure was not affected by either treatment regimen (sepsis -3.3%, septic shock -3.1%; p<0.25). Intensive insulin therapy was associated with an increased risk of hypoglycemia (sepsis +16.7%, septic shock +18.8; p<0.0001) which did not, however, directly affect morbidity nor mortality. These data suggest that IIT improves outcome of patients with sepsis or septic shock. Hypoglycemia is a frequent complication, but its clinical relevance remains to be defined.

  4. Estimating Ten-Year Trends in Septic Shock Incidence and Mortality in United States Academic Medical Centers Using Clinical Data.

    PubMed

    Kadri, Sameer S; Rhee, Chanu; Strich, Jeffrey R; Morales, Megan K; Hohmann, Samuel; Menchaca, Jonathan; Suffredini, Anthony F; Danner, Robert L; Klompas, Michael

    2017-02-01

    Reports that septic shock incidence is rising and mortality rates declining may be confounded by improving recognition of sepsis and changing coding practices. We compared trends in septic shock incidence and mortality in academic hospitals using clinical vs claims data. We identified all patients with concurrent blood cultures, antibiotics, and vasopressors for ≥ two consecutive days, and all patients with International Classification of Diseases, 9th edition (ICD-9) codes for septic shock, at 27 academic hospitals from 2005 to 2014. We compared annual incidence and mortality trends. We reviewed 967 records from three hospitals to estimate the accuracy of each method. Of 6.5 million adult hospitalizations, 99,312 (1.5%) were flagged by clinical criteria, 82,350 (1.3%) by ICD-9 codes, and 44,651 (0.7%) by both. Sensitivity for clinical criteria was higher than claims (74.8% vs 48.3%; P < .01), whereas positive predictive value was comparable (83% vs 89%; P = .23). Septic shock incidence, based on clinical criteria, rose from 12.8 to 18.6 cases per 1,000 hospitalizations (average, 4.9% increase/y; 95% CI, 4.0%-5.9%), while mortality declined from 54.9% to 50.7% (average, 0.6% decline/y; 95% CI, 0.4%-0.8%). In contrast, septic shock incidence, based on ICD-9 codes, increased from 6.7 to 19.3 per 1,000 hospitalizations (19.8% increase/y; 95% CI, 16.6%-20.9%), while mortality decreased from 48.3% to 39.3% (1.2% decline/y; 95% CI, 0.9%-1.6%). A clinical surveillance definition based on concurrent vasopressors, blood cultures, and antibiotics accurately identifies septic shock hospitalizations and suggests that the incidence of patients receiving treatment for septic shock has risen and mortality rates have fallen, but less dramatically than estimated on the basis of ICD-9 codes. Copyright © 2016 American College of Chest Physicians. All rights reserved.

  5. Acute bag-valve breathing maneuvers plus manual chest compression is safe during stable septic shock: a randomized clinical trial

    PubMed Central

    Blattner, Clarissa Netto; dos Santos, Rafael Saldanha; Dias, Fernando Suparregui; Dias, Alexandre Simões; Mestriner, Régis Gemerasca; Vieira, Silvia Regina Rios

    2017-01-01

    Objective To evaluate the effects of bag-valve breathing maneuvers combined with standard manual chest compression techniques on safety, hemodynamics and oxygenation in stable septic shock patients. Design A parallel, assessor-blinded, randomized trial of two groups. A computer-generated list of random numbers was prepared by an independent researcher to allocate treatments. Setting The Intensive Care Unit at Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul. Participants Fifty-two subjects were assessed for eligibility, and 32 were included. All included subjects (n = 32) received the allocated intervention (n = 19 for the Experimental Group and n = 13 for the Control Group). Intervention Twenty minutes of bag-valve breathing maneuvers combined with manual chest compression techniques (Experimental Group) or chest compression, as routinely used at our intensive care unit (Control Group). Follow-up was performed immediately after and at 30 minutes after the intervention. Main outcome measure Mean artery pressure. Results All included subjects completed the trial (N = 32). We found no relevant effects on mean artery pressure (p = 0.17), heart rate (p = 0.50) or mean pulmonary artery pressure (p = 0.89) after adjusting for subject age and weight. Both groups were identical regarding oxygen consumption after the data adjustment (p = 0.84). Peripheral oxygen saturation tended to increase over time in both groups (p = 0.05), and there was no significant association between cardiac output and venous oxygen saturation (p = 0.813). No clinical deterioration was observed. Conclusion A single session of bag-valve breathing maneuvers combined with manual chest compression is hemodynamically safe for stable septic-shocked subjects over the short-term. PMID:28444068

  6. Acute bag-valve breathing maneuvers plus manual chest compression is safe during stable septic shock: a randomized clinical trial.

    PubMed

    Blattner, Clarissa Netto; Santos, Rafael Saldanha Dos; Dias, Fernando Suparregui; Dias, Alexandre Simões; Mestriner, Régis Gemerasca; Vieira, Silvia Regina Rios

    2017-01-01

    To evaluate the effects of bag-valve breathing maneuvers combined with standard manual chest compression techniques on safety, hemodynamics and oxygenation in stable septic shock patients. A parallel, assessor-blinded, randomized trial of two groups. A computer-generated list of random numbers was prepared by an independent researcher to allocate treatments. The Intensive Care Unit at Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul. Fifty-two subjects were assessed for eligibility, and 32 were included. All included subjects (n = 32) received the allocated intervention (n = 19 for the Experimental Group and n = 13 for the Control Group). Twenty minutes of bag-valve breathing maneuvers combined with manual chest compression techniques (Experimental Group) or chest compression, as routinely used at our intensive care unit (Control Group). Follow-up was performed immediately after and at 30 minutes after the intervention. Mean artery pressure. All included subjects completed the trial (N = 32). We found no relevant effects on mean artery pressure (p = 0.17), heart rate (p = 0.50) or mean pulmonary artery pressure (p = 0.89) after adjusting for subject age and weight. Both groups were identical regarding oxygen consumption after the data adjustment (p = 0.84). Peripheral oxygen saturation tended to increase over time in both groups (p = 0.05), and there was no significant association between cardiac output and venous oxygen saturation (p = 0.813). No clinical deterioration was observed. A single session of bag-valve breathing maneuvers combined with manual chest compression is hemodynamically safe for stable septic-shocked subjects over the short-term.

  7. Hemodynamic Analysis of Pediatric Septic Shock and Cardiogenic Shock Using Transpulmonary Thermodilution

    PubMed Central

    Lee, En-Pei; Hsia, Shao-Hsuan; Lin, Jainn-Jim; Chan, Oi-Wa; Lee, Jung; Lin, Chia-Ying

    2017-01-01

    Septic shock and cardiogenic shock are the two most common types of shock in children admitted to pediatric intensive care units (PICUs). The aim of the study was to investigate which hemodynamic variables were associated with mortality in children with shock. We retrospectively analyzed 50 children with shock (37 septic shock cases and 13 cardiogenic shock cases) in the PICU and monitored their hemodynamics using transpulmonary thermodilution from 2003 to 2016. Clinical factors were analyzed between the patients with septic and cardiogenic shock. In addition, hemodynamic parameters associated with mortality were analyzed. The 28-day mortality was significantly higher in the septic group than in the cardiogenic group (p = 0.016). Initially, the parameters of cardiac output and cardiac contractility were higher in the septic group (p < 0.05) while the parameters of preload and afterload were all higher in the cardiogenic group (p < 0.05). Cardiac index was significantly lower in the nonsurvivors of cardiogenic shock at the time of initial admission and after the first 24 hours (both p < 0.05), while systemic vascular resistance index (SVRI) was significantly lower in the nonsurvivors of septic shock (p < 0.001). Therefore, during the first 24 hours after intensive care, SVRI and cardiac index are the most important hemodynamic parameters associated with mortality. PMID:28401152

  8. [Primary management and treatment of paediatric septic shock].

    PubMed

    Kneyber, Martin C J; van Heerde, Marc; Henneveld, Hetty Th

    2010-01-01

    Paediatric shock is common. Hypovolaemic and septic shock are the main forms. Early and rapid results-oriented therapy of paediatric septic shock has a favourable effect on survival. There is an international guideline for the primary management of paediatric shock during the first hour after presentation of the patient. The goal of treatment is to prevent oxygen debt and consequently organ failure. The main symptoms of paediatric shock are tachycardia and reduced consciousness. In a child in shock, the clinical picture should be recognized within 15 minutes and an attempt should be made to reverse the situation by rapid fluid infusion. If the shock persists after 15 minutes, vasoactive medication should be given and the child should be transferred to a local paediatric intensive care unit. Intubation and mechanical ventilation are then also required.

  9. Balanced crystalloids for septic shock resuscitation

    PubMed Central

    Corrêa, Thiago Domingos; Cavalcanti, Alexandre Biasi; de Assunção, Murillo Santucci Cesar

    2016-01-01

    Timely fluid administration is crucial to maintain tissue perfusion in septic shock patients. However, the question concerning which fluid should be used for septic shock resuscitation remains a matter of debate. A growing body of evidence suggests that the type, amount and timing of fluid administration during the course of sepsis may affect patient outcomes. Crystalloids have been recommended as the first-line fluids for septic shock resuscitation. Nevertheless, given the inconclusive nature of the available literature, no definitive recommendations about the most appropriate crystalloid solution can be made. Resuscitation of septic and non-septic critically ill patients with unbalanced crystalloids, mainly 0.9% saline, has been associated with a higher incidence of acid-base balance and electrolyte disorders and might be associated with a higher incidence of acute kidney injury. This can result in greater demand for renal replacement therapy and increased mortality. Balanced crystalloids have been proposed as an alternative to unbalanced solutions in order to mitigate their detrimental effects. Nevertheless, the safety and effectiveness of balanced crystalloids for septic shock resuscitation need to be further addressed in a well-designed, multicenter, pragmatic, randomized controlled trial. PMID:28099643

  10. Clinical characteristics, sepsis interventions and outcomes in the obese patients with septic shock: an international multicenter cohort study

    PubMed Central

    2013-01-01

    Introduction Data are sparse as to whether obesity influences the risk of death in critically ill patients with septic shock. We sought to examine the possible impact of obesity, as assessed by body mass index (BMI), on hospital mortality in septic shock patients. Methods We performed a nested cohort study within a retrospective database of patients with septic shock conducted in 28 medical centers in Canada, United States and Saudi Arabia between 1996 and 2008. Patients were classified according to the World Health Organization criteria for BMI. Multivariate logistic regression analysis was performed to evaluate the association between obesity and hospital mortality. Results Of the 8,670 patients with septic shock, 2,882 (33.2%) had height and weight data recorded at ICU admission and constituted the study group. Obese patients were more likely to have skin and soft tissue infections and less likely to have pneumonia with predominantly Gram-positive microorganisms. Crystalloid and colloid resuscitation fluids in the first six hours were given at significantly lower volumes per kg in the obese and very obese patients compared to underweight and normal weight patients (for crystalloids: 55.0 ± 40.1 ml/kg for underweight, 43.2 ± 33.4 for normal BMI, 37.1 ± 30.8 for obese and 27.7 ± 22.0 for very obese). Antimicrobial doses per kg were also different among BMI groups. Crude analysis showed that obese and very obese patients had lower hospital mortality compared to normal weight patients (odds ratio (OR) 0.80, 95% confidence interval (CI) 0.66 to 0.97 for obese and OR 0.61, 95% CI 0.44 to 0.85 for very obese patients). After adjusting for baseline characteristics and sepsis interventions, the association became non-significant (OR 0.80, 95% CI 0.62 to 1.02 for obese and OR 0.69, 95% CI 0.45 to 1.04 for very obese). Conclusions The obesity paradox (lower mortality in the obese) documented in other populations is also observed in septic shock. This may be related in

  11. Marked elevation of procalcitonin level can lead to a misdiagnosis of anaphylactic shock as septic shock.

    PubMed

    Kim, Young Jun; Kang, Sang Woo; Lee, Jae Hoon; Cho, Ji Hyun

    2015-08-01

    The case of a 74-year-old woman who presented with hyperthermia and hypotension is reported. Laboratory test results revealed marked elevation of C-reactive protein (CRP) and procalcitonin (PCT) levels. The clinical presentation and laboratory test results were suggestive of septic shock. No infectious focus was identified. The shock recurred after what was subsequently understood to be an unintended re-challenge with risedronate sodium. Drug-induced anaphylactic shock was finally diagnosed. Anaphylactic shock may be misdiagnosed as septic shock in patients who present with markedly elevated PCT levels. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Relationship of systemic, hepatosplanchnic, and microcirculatory perfusion parameters with 6-hour lactate clearance in hyperdynamic septic shock patients: an acute, clinical-physiological, pilot study

    PubMed Central

    2012-01-01

    Background Recent clinical studies have confirmed the strong prognostic value of persistent hyperlactatemia and delayed lactate clearance in septic shock. Several potential hypoxic and nonhypoxic mechanisms have been associated with persistent hyperlactatemia, but the relative contribution of these factors has not been specifically addressed in comprehensive clinical physiological studies. Our goal was to determine potential hemodynamic and perfusion-related parameters associated with 6-hour lactate clearance in a cohort of hyperdynamic, hyperlactatemic, septic shock patients. Methods We conducted an acute clinical physiological pilot study that included 15 hyperdynamic, septic shock patients undergoing aggressive early resuscitation. Several hemodynamic and perfusion-related parameters were measured immediately after preload optimization and 6 hours thereafter, with 6-hour lactate clearance as the main outcome criterion. Evaluated parameters included cardiac index, mixed venous oxygen saturation, capillary refill time and central-to-peripheral temperature difference, thenar tissue oxygen saturation (StO2) and its recovery slope after a vascular occlusion test, sublingual microcirculatory assessment, gastric tonometry (pCO2 gap), and plasma disappearance rate of indocyanine green (ICG-PDR). Statistical analysis included Wilcoxon and Mann–Whitney tests. Results Five patients presented a 6-hour lactate clearance <10%. Compared with 10 patients with a 6-hour lactate clearance ≥10%, they presented a worse hepatosplanchnic perfusion as represented by significantly more severe derangements of ICG-PDR (9.7 (8–19) vs. 19.6 (9–32)%/min, p < 0.05) and pCO2 gap (33 (9.1-62) vs. 7.7 (3–58) mmHg, p < 0.05) at 6 hours. No other systemic, hemodynamic, metabolic, peripheral, or microcirculatory parameters differentiated these subgroups. We also found a significant correlation between ICG-PDR and pCO2 gap (p = 0.02). Conclusions Impaired 6-hour lactate clearance could be

  13. A synopsis of 2007 ACCM clinical practice parameters for hemodynamic support of term newborn and infant septic shock.

    PubMed

    Carcillo, Joseph A

    2014-03-01

    This is a synopsis of the term newborn and infant portion of the 2007 document (Brierley et al., Crit Care Med 2009;37(2):666-88) which examined and graded new studies performed to test the utility and efficacy of the 2002 recommendations. This 2007 document examined and graded relevant new treatment and outcome studies to determine to what degree, if any, the 2002 guidelines should be modified. More than 30 clinical investigators and clinicians affiliated with the Society of Critical Care Medicine who had special interest in hemodynamic support of pediatric patients with sepsis volunteered to be members of the "update" task force. Subcommittees were formed to review and grade the literature using the evidence-based scoring system of the American College of Critical Care Medicine. The literature was accrued in part by searching PUBMED/MEDLINE using the following keywords: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, and ECMO. The search was narrowed to identify studies specifically relevant to term newborns, infants, and children. "Best Practice Outcomes" were identified and described clinical practice in these centers was used as a model. The new taskforce is presently working on updating new guidelines evaluating the literature of the past 6 years. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Severe sepsis and septic shock in pregnancy.

    PubMed

    Barton, John R; Sibai, Baha M

    2012-09-01

    Pregnancies complicated by severe sepsis and septic shock are associated with increased rates of preterm labor, fetal infection, and preterm delivery. Sepsis onset in pregnancy can be insidious, and patients may appear deceptively well before rapidly deteriorating with the development of septic shock, multiple organ dysfunction syndrome, or death. The outcome and survivability in severe sepsis and septic shock in pregnancy are improved with early detection, prompt recognition of the source of infection, and targeted therapy. This improvement can be achieved by formulating a stepwise approach that consists of early provision of time-sensitive interventions such as: aggressive hydration (20 mL/kg of normal saline over the first hour), initiation of appropriate empiric intravenous antibiotics (gentamicin, clindamycin, and penicillin) within 1 hour of diagnosis, central hemodynamic monitoring, and the involvement of infectious disease specialists and critical care specialists familiar with the physiologic changes in pregnancy. Thorough physical examination and imaging techniques or empiric exploratory laparotomy are suggested to identify the septic source. Even with appropriate antibiotic therapy, patients may continue to deteriorate unless septic foci (ie, abscess, necrotic tissue) are surgically excised. The decision for delivery in the setting of antepartum severe sepsis or septic shock can be challenging but must be based on gestational age, maternal status, and fetal status. The natural inclination is to proceed with emergent delivery for a concerning fetal status, but it is imperative to stabilize the mother first, because in doing so the fetal status will likewise improve. Aggressive [corrected] treatment of sepsis can be expected to reduce the progression to severe sepsis and septic shock and prevention strategies can include preoperative skin preparations and prophylactic antibiotic therapy as well as appropriate immunizations.

  15. Epidemiological and clinical characteristics of community-acquired severe sepsis and septic shock: a prospective observational study in 12 university hospitals in Korea.

    PubMed

    Park, Dae Won; Chun, Byung Chul; Kim, June Myung; Sohn, Jang Wook; Peck, Kyong Ran; Kim, Yang Soo; Choi, Young Hwa; Choi, Jun Yong; Kim, Sang Il; Eom, Joong Sik; Kim, Hyo Youl; Song, Joon Young; Song, Young Goo; Choi, Hee Jung; Kim, Min Ja

    2012-11-01

    A prospective multicenter observational study was performed to investigate the epidemiology and outcomes of community-acquired severe sepsis and septic shock. Subjects included 1,192 adult patients admitted to the 22 participating intensive care units (ICUs) of 12 university hospitals in the Korean Sepsis Registry System from April, 2005 through February, 2009. Male accounted for 656 (55%) patients. Mean age was 65.0 ± 14.2 yr. Septic shock developed in 740 (62.1%) patients. Bacteremia was present in 422 (35.4%) patients. The 28-day and in-hospital mortality rates were 23.0% and 28.0%, respectively. Men were more likely to have comorbid illnesses and acute organ dysfunctions, and had higher mortality and clinical severity compared to women. While respiratory sources of sepsis were common in men, urinary sources were predominant in women. In the multivariate logistic regression analysis, cancer (odds ratio 1.89; 95% confidence interval 1.13-3.17), urinary tract infection (0.25; 0.13-0.46), APACHE II score (1.05; 1.02-1.09), SOFA score on day 1 (1.13; 1.06-1.21) and metabolic dysfunction (2.24, 1.45-3.45) were independent clinical factors for gender-related in-hospital mortality. This study provided epidemiological and clinical characteristics of community-acquired severe sepsis and septic shock in ICUs in Korea, and demonstrated the impact of clinical factors on gender difference in mortality.

  16. The Septic Shock 3.0 Definition and Trials: A Vasopressin and Septic Shock Trial Experience.

    PubMed

    Russell, James A; Lee, Terry; Singer, Joel; Boyd, John H; Walley, Keith R

    2017-06-01

    The Septic Shock 3.0 definition could alter treatment comparisons in randomized controlled trials in septic shock. Our first hypothesis was that the vasopressin versus norepinephrine comparison and 28-day mortality of patients with Septic Shock 3.0 definition (lactate > 2 mmol/L) differ from vasopressin versus norepinephrine and mortality in Vasopressin and Septic Shock Trial. Our second hypothesis was that there are differences in plasma cytokine levels in Vasopressin and Septic Shock Trial for lactate less than or equal to 2 versus greater than 2 mmol/L. Retrospective analysis of randomized controlled trial. Multicenter ICUs. We compared vasopressin-to-norepinephrine group 28- and 90-day mortality in Vasopressin and Septic Shock Trial in lactate subgroups. We measured 39 cytokines to compare patients with lactate less than or equal to 2 versus greater than 2 mmol/L. Patients with septic shock with lactate greater than 2 mmol/L or less than or equal to 2 mmol/L, randomized to vasopressin or norepinephrine. Concealed vasopressin (0.03 U/min.) or norepinephrine infusions. The Septic Shock 3.0 definition would have decreased sample size by about half. The 28- and 90-day mortality rates were 10-12 % higher than the original Vasopressin and Septic Shock Trial mortality. There was a significantly (p = 0.028) lower mortality with vasopressin versus norepinephrine in lactate less than or equal to 2 mmol/L but no difference between treatment groups in lactate greater than 2 mmol/L. Nearly all cytokine levels were significantly higher in patients with lactate greater than 2 versus less than or equal to 2 mmol/L. The Septic Shock 3.0 definition decreased sample size by half and increased 28-day mortality rates by about 10%. Vasopressin lowered mortality versus norepinephrine if lactate was less than or equal to 2 mmol/L. Patients had higher plasma cytokines in lactate greater than 2 versus less than or equal to 2 mmol/L, a brisker cytokine response to infection. The Septic

  17. Diabetes insipidus after discontinuation of vasopressin infusion for septic shock.

    PubMed

    Rana, H; Ferguson, N; Dicpinigaitis, P V

    2017-09-11

    Despite widespread use of vasopressin for the treatment of septic shock, few cases of diabetes insipidus (DI) following its discontinuation have been reported. A 54-year-old man presented with pneumonia progressing to septic shock, requiring norepinephrine and vasopressin for refractory hypotension. After clinical improvement, the patient on 3 separate occasions developed polyuria and severe hypernatremia upon discontinuation of vasopressin, with prompt recovery upon its resumption. Occurrence of DI upon discontinuation of vasopressin infusion appears to be rare, but incidence may be underestimated due to a paucity of published reports. Actual incidence and underlying mechanism of this phenomenon remain to be elucidated. © 2017 John Wiley & Sons Ltd.

  18. Empiric antimicrobial therapy in severe sepsis and septic shock: optimizing pathogen clearance.

    PubMed

    Liang, Stephen Y; Kumar, Anand

    2015-07-01

    Mortality and morbidity in severe sepsis and septic shock remain high despite significant advances in critical care. Efforts to improve outcome in septic conditions have focused on targeted, quantitative resuscitation strategies utilizing intravenous fluids, vasopressors, inotropes, and blood transfusions to correct disease-associated circulatory dysfunction driven by immune-mediated systemic inflammation. This review explores an alternate paradigm of septic shock in which microbial burden is identified as the key driver of mortality and progression to irreversible shock. We propose that clinical outcomes in severe sepsis and septic shock hinge upon the optimized selection, dosing, and delivery of highly potent antimicrobial therapy.

  19. Empiric Antimicrobial Therapy in Severe Sepsis and Septic Shock: Optimizing Pathogen Clearance

    PubMed Central

    Liang, Stephen Y.

    2015-01-01

    Mortality and morbidity in severe sepsis and septic shock remain high despite significant advances in critical care. Efforts to improve outcome in septic conditions have focused on targeted, quantitative resuscitation strategies utilizing intravenous fluids, vasopressors, inotropes, and blood transfusions to correct disease-associated circulatory dysfunction driven by immune-mediated systemic inflammation. This review explores an alternate paradigm of septic shock in which microbial burden is identified as the key driver of mortality and progression to irreversible shock. We propose that clinical outcomes in severe sepsis and septic shock hinge upon the optimized selection, dosing, and delivery of highly potent antimicrobial therapy. PMID:26031965

  20. Reduced oxygen utilization in septic shock: disorder or adaptation?

    PubMed

    Steiner, Alexandre A

    2015-01-01

    A fall in oxygen utilization during septic or endotoxic shock is thought to reflect circulatory hypoxia or mitochondrial dysfunction, but these pathology-oriented hypotheses do not explain all clinical observations. Here we discuss an alternative hypothesis of how oxygen utilization could fall as the result of a physiological thermometabolic adaptation.

  1. Control groups in recent septic shock trials: a systematic review.

    PubMed

    Pettilä, Ville; Hjortrup, Peter Buhl; Jakob, Stephan M; Wilkman, Erika; Perner, Anders; Takala, Jukka

    2016-12-01

    The interpretation of septic shock trial data is profoundly affected by patients, control intervention, co-interventions and selected outcome measures. We evaluated the reporting of control groups in recent septic shock trials. We searched for original articles presenting randomized clinical trials (RCTs) in adult septic shock patients from 2006 to 2016. We included RCTs focusing on septic shock patients with at least two parallel groups and at least 50 patients in the control group. We selected and evaluated data items regarding patients, control group characteristics, and mortality outcomes, and calculated a data completeness score to provide an overall view of quality of reporting. A total of 24 RCTs were included (mean n = 287 patients and 71 % of eligible patients were randomized). Of the 24 studies, 14 (58 %) presented baseline data on vasopressors and 58 % the proportion of patients with elevated lactate values. Five studies (21 %) provided data to estimate the proportion of septic shock patients fulfilling the Sepsis-3 definition. The mean data completeness score was 19 out of 36 (range 8-32). Of 18 predefined control group characteristics, a mean of 8 (range 2-17) were reported. Only 2 (8 %) trials provided adequate data to confirm that their control group treatment represented usual care. Recent trials in septic shock provide inadequate data on the control group treatment and hemodynamic values. We propose a standardized trial dataset to be created and validated, comprising characteristics of patient population, interventions administered, hemodynamic values achieved, surrogate organ dysfunction, and mortality outcomes, to allow better analysis and interpretation of future trial results.

  2. The clinical impact of multidrug-resistant gram-negative bacilli in the management of septic shock

    PubMed Central

    Pop-Vicas, Aurora; Opal, Steven M

    2014-01-01

    Multi-antibiotic drug-resistant (MDR) gram-negative bacilli are becoming a major threat to the standard care of septic patients. Empiric antimicrobial drug regimens to cover likely bacterial pathogens have to be altered in keeping with the spread of MDR pathogens in the health care setting and in the community. Reliable antibiotics for broad spectrum coverage for sepsis such as extended spectrum β-lactam antibiotics, carbapenems, and fluoroquinolones can no longer be counted upon to provide activity against a range of common, virulent pathogens that cause sepsis. In some regions of Asia, South America, and Eastern Europe in particular, MDR pathogens have become a major concern, necessitating the use of potentially toxic and costly antibiotic combinations as initial antibiotic therapy for septic shock. In this brief review, we will focus on the emergence of MDR gram-negative pathogens, resistance mechanisms, and suggest some management and prevention strategies against MDR pathogens. PMID:24200870

  3. The clinical impact of multidrug-resistant gram-negative bacilli in the management of septic shock.

    PubMed

    Pop-Vicas, Aurora; Opal, Steven M

    2014-01-01

    Multi-antibiotic drug-resistant (MDR) gram-negative bacilli are becoming a major threat to the standard care of septic patients. Empiric antimicrobial drug regimens to cover likely bacterial pathogens have to be altered in keeping with the spread of MDR pathogens in the health care setting and in the community. Reliable antibiotics for broad spectrum coverage for sepsis such as extended spectrum β-lactam antibiotics, carbapenems, and fluoroquinolones can no longer be counted upon to provide activity against a range of common, virulent pathogens that cause sepsis. In some regions of Asia, South America, and Eastern Europe in particular, MDR pathogens have become a major concern, necessitating the use of potentially toxic and costly antibiotic combinations as initial antibiotic therapy for septic shock. In this brief review, we will focus on the emergence of MDR gram-negative pathogens, resistance mechanisms, and suggest some management and prevention strategies against MDR pathogens.

  4. Evaluating the management of septic shock using patient simulation.

    PubMed

    Ottestad, Einar; Boulet, John R; Lighthall, Geoffrey K

    2007-03-01

    Develop a scoring system that can assess the management of septic shock by individuals and teams. Retrospective review of videotapes of critical care house staff managing a standardized simulation of septic shock. Academic medical center; videotapes were made in a recreated intensive care unit environment using a high-fidelity patient simulator. Residents in medicine, surgery, and anesthesiology who had participated in the intensive care unit rotation. The septic patient was managed by the intensive care unit team in a graded manner with interns present for the first 10 mins and more senior-level help arriving after 10 mins. The intern was graded separately for the first 10 mins, and the team was graded for the entire 35-min performance. Both technical and nontechnical scoring systems were developed to rate the management of septic shock. Technical scores are based on guidelines and principles of managing septic shock. Team leadership, communication, contingency planning, and resource utilization were addressed by the nontechnical rating. Technical scores were calculated for both interns and teams; nontechnical scores applied only to the team. Of 16 technical checklist items, interns completed a mean of 7 with a range of 1.5-11. Team technical ratings had a mean of 9.3 with a range of 3.3-13. Nontechnical scores showed similar intergroup variability with a mean of 26 and a range of 10-35. Technical and nontechnical scores showed a modest correlation (r = .40, p = .05). Interrater reliabilities for intern and team technical scores were both r = .96 and for nontechnical scores r = .88. Objective measures of both knowledge-based and behavioral skills pertinent to the management of septic shock were made. Scores identified both adequate and poor levels of performance. Such assessments can be used to benchmark clinical skills of individuals and groups over time and may allow the identification of interventions that improve clinical effectiveness in sepsis management.

  5. The current management of septic shock.

    PubMed

    Russel, J A

    2008-10-01

    This is a review of the management of septic shock that suggests an approach to treatment (ABCDEF: Airway, Breathing, Circulation, Drugs, Evaluate the source of sepsis, Fix the source of sepsis) for clinicians. The incidence of septic shock is increasing and mortality ranges from 30% to 70%. The commonest sources of infection are lung (25%), abdomen (25%), and other sources. Septic shock occurs because of highly complex interactions between the infecting microorganism(s) and the responses of the human host. The innate immune response is rapidly followed by the more specific adaptive immune response. Septic shock is characterized by alterations in the coagulant/anticoagulant balance such that there is a more pro-coagulant phenotype. Lung protective ventilation (which means the use of relatively low tidal volumes of 4 -6 mL/kg ideal body weight) is recommended for treatment of patients who have septic shock. Rivers early goal-directed therapy is recommended because it showed a significant increase in survival. Surviving Sepsis guidelines recommend resuscitation of septic shock with either crystalloid or colloid. Patients who have septic shock should be treated with intravenous broad-spectrum antibiotics as rapidly as possible and certainly within one hour. Activated protein C (APC) is a vitamin K dependent serine protease that is an anticoagulant and is also cytoprotective and anti-inflammatory. APC (24 mg/kg/hour infusion for 96 hours) decreased mortality (APC 25% vs placebo 31%, relative risk 0.81P=0.005) and improved organ dysfunction in patients at high risk of death (e.g. APACHE II >25 [APC 31% vs placebo 44%]). APC is not recommended to treat surgical patients who have one organ system dysfunction. In 2006, the European regulatory authority indicated that there must be another randomized placebo-controlled trial of APC to further establish efficacy as assessed by mortality reduction. Vasopressin is a key stress hormone in response to hypotension. The VASST

  6. Development and validation of a clinical prediction rule for candidemia in hospitalized patients with severe sepsis and septic shock.

    PubMed

    Guillamet, Cristina Vazquez; Vazquez, Rodrigo; Micek, Scott T; Ursu, Oleg; Kollef, Marin

    2015-08-01

    To develop and internally validate a prediction rule for the presence of candidemia in patients with severe sepsis and septic shock (candidemia rule) that will fill the gap left by previous rules. To compare the accuracy of the available Candida prediction models. Retrospective cohort study. Barnes-Jewish Hospital, St. Louis, Missouri. Two thousand five hundred ninety-seven consecutive patients with a positive blood culture and severe sepsis or septic shock. Logistic regression and a bootstrap resampling procedure were employed for model development and internal validation. Two hundred sixty-six (10.2%) had blood cultures positive for Candida spp. Mortality was significantly higher in patients with candidemia than in patients with bacteremia (47.0% versus 28.4%; P<.001). Administration of total parenteral nutrition, prior antibiotic exposure, transfer from an outside hospital or admission from a nursing home, mechanical ventilation and presence of a central vein catheter were independent predictors of candidemia while the lung as a source for infection was protective. The prediction rule had an area under the receiver operating characteristic curve of 0.798 (95% CI 0.77-0.82). Internal validation using bootstrapping technique with 1000 repetitions produced a similar area under the receiver operating characteristic curve of 0.797 (bias, -0.037; root mean square error 0.039). Our prediction rule outperformed previous rules with a better calibration slope of 0.96 and Brier score of 0.08. We developed and internally validated a prediction rule for candidemia in hospitalized patients with severe sepsis and septic shock that outperformed previous prediction rules. Our study suggests that locally derived prediction models may be superior by accounting for local case mix and risk factor distribution. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Role of echocardiography in reducing shock reversal time in pediatric septic shock: a randomized controlled trial.

    PubMed

    El-Nawawy, Ahmed A; Abdelmohsen, Aly M; Hassouna, Hadir M

    2017-09-03

    To evaluate the role of echocardiography in reducing shock reversal time in pediatric septic shock. A prospective study conducted in the pediatric intensive care unit of a tertiary care teaching hospital from September 2013 to May 2016. Ninety septic shock patients were randomized in a 1:1 ratio for comparing the serial echocardiography-guided therapy in the study group with the standard therapy in the control group regarding clinical course, timely treatment, and outcomes. Shock reversal was significantly higher in the study group (89% vs. 67%), with significantly reduced shock reversal time (3.3 vs. 4.5 days). Pediatric intensive care unit stay in the study group was significantly shorter (8±3 vs. 14±10 days). Mortality due to unresolved shock was significantly lower in the study group. Fluid overload was significantly lower in the study group (11% vs. 44%). In the study group, inotropes were used more frequently (89% vs. 67%) and initiated earlier (12[0.5-24] vs. 24[6-72]h) with lower maximum vasopressor inotrope score (120[30-325] vs. 170[80-395]), revealing predominant use of milrinone (62% vs. 22%). Serial echocardiography provided crucial data for early recognition of septic myocardial dysfunction and hypovolemia that was not apparent on clinical assessment, allowing a timely management and resulting in shock reversal time reduction among children with septic shock. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  8. Predictive factors of septic shock and mortality in neutropenic patients.

    PubMed

    Ramzi, Jeddi; Mohamed, Zarrouk; Yosr, Benabdennebi; Karima, Kacem; Raihane, Benlakhal; Lamia, Aissaoui; Hela, Ben Abid; Zaher, Belhadjali; Balkis, Meddeb

    2007-12-01

    Neutropenia is a major risk factor for developing a serious infection. Bacteremia still causes significant mortality among neutropenic patients with cancer. The purpose of this study was to identify risk factors for septic shock and for mortality in neutropenic patients with leukemia and bacteremia. Consecutive samples from 20 patients with acute myeloid leukemia and bacteremia were studied during a 1 year period (January-December 2003). All patients received empirical antibiotic therapies for febrile episodes using ceftazidime plus amikacin. About 110 neutropenic febrile episodes were noted: clinically documented 14.54%, microbiologically documented 16.36% and fever of unknown origin 69.09%. Gram-negative organism caused eight febrile episodes: Pseudomonas (5), Klebsiella (3). Gram-positive organism caused 10 episodes: Staphylococcus (6), Streptococci (2), Enterococci (2). Pulmonary infection accounted for 25% of clinically documented infections. About 14 of the 110 febrile episodes were associated with septic shock causing mortality in 7 patients. In a univariate analysis variables associated with septic shock were: pulmonary infection (OR = 17, p = 0.001), serum bicarbonate < 17 mmol/l (OR = 68, p < 0.001) and serum lactate >3 mmol/l (OR = 62, p < 0.001). Variables associated with mortality were: pulmonary infection (OR = 83, p < 0.001) and serum bicarbonate < 17 mmol/l (OR = 61, p < 0.001). In a multivariate analysis two variables were associated with septic shock: pulmonary infection (OR = 5, p = 0.043) and serum lactate >3 mmol/l (OR = 10, p = 0.003). An elevated serum lactate (>3 mmol/l) and low serum bicarbonate ( < 17 mmol/l) at the onset of bacteremia are useful biomarkers in predicting septic shock and mortality in neutropenic patients.

  9. Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial.

    PubMed

    Morelli, Andrea; Ertmer, Christian; Westphal, Martin; Rehberg, Sebastian; Kampmeier, Tim; Ligges, Sandra; Orecchioni, Alessandra; D'Egidio, Annalia; D'Ippoliti, Fiorella; Raffone, Cristina; Venditti, Mario; Guarracino, Fabio; Girardis, Massimo; Tritapepe, Luigi; Pietropaoli, Paolo; Mebazaa, Alexander; Singer, Mervyn

    2013-10-23

    /L for the control group (IQR, -0.3 for 0.6; P = .007); for norepinephrine, -0.11 μg/kg/min (IQR, -0.46 to 0.02) for the esmolol group vs -0.01 μg/kg/min (IQR, -0.2 to 0.44) for the control group (P = .003). Fluid requirements were reduced in the esmolol group: median AUC was 3975 mL/24 h (IQR, 3663 to 4200) vs 4425 mL/24 h(IQR, 4038 to 4775) for the control group (P < .001). We found no clinically relevant differences between groups in other cardiopulmonary variables nor in rescue therapy requirements. Twenty-eight day mortality was 49.4% in the esmolol group vs 80.5% in the control group (adjusted hazard ratio, 0.39; 95% CI, 0.26 to 0.59; P < .001). For patients in septic shock, open-label use of esmolol vs standard care was associated with reductions in heart rates to achieve target levels, without increased adverse events. The observed improvement in mortality and other secondary clinical outcomes warrants further investigation. clinicaltrials.gov Identifier: NCT01231698.

  10. CE: Assessing Patients During Septic Shock Resuscitation.

    PubMed

    Bridges, Elizabeth

    2017-10-01

    : In 2015, the Surviving Sepsis Campaign six-hour bundle was updated. The revised version now recommends documenting the reassessment of volume status and tissue perfusion after initial fluid resuscitation through a repeated focused examination. This article addresses the practice and interpretation of two components of this examination in adults: capillary refill time and skin mottling score. It further discusses how to best integrate these noninvasive parameters into the care of patients undergoing resuscitation for septic shock.

  11. Multiple cerebral infarcts following septic shock.

    PubMed

    Nagaratnam, Nages; Brakoulias, Vlasios; Ng, Kevin

    2002-07-01

    A 60-year-old female in septic shock developed neurological signs and symptoms. She had left-sided hemiparesis, left homonymous hemianopia, bimanual coordination disorder, a language dysfunction of anomic aphasic type and a non-aphasic right hemispheric communication disorder. Computer tomography demonstrated bilateral anterior and posterior watershed as well as territorial infarctions. Risk factors included chronic airways limitation, cardiac failure and heavy smoking. Carotid duplex studies were normal. The mechanisms can be explained by flow changes and thrombus formation.

  12. Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine

    PubMed Central

    Brierley, Joe; Carcillo, Joseph A.; Choong, Karen; Cornell, Tim; DeCaen, Allan; Deymann, Andreas; Doctor, Allan; Davis, Alan; Duff, John; Dugas, Marc-Andre; Duncan, Alan; Evans, Barry; Feldman, Jonathan; Felmet, Kathryn; Fisher, Gene; Frankel, Lorry; Jeffries, Howard; Greenwald, Bruce; Gutierrez, Juan; Hall, Mark; Han, Yong Y.; Hanson, James; Hazelzet, Jan; Hernan, Lynn; Kiff, Jane; Kissoon, Niranjan; Kon, Alexander; Irazusta, Jose; Lin, John; Lorts, Angie; Mariscalco, Michelle; Mehta, Renuka; Nadel, Simon; Nguyen, Trung; Nicholson, Carol; Peters, Mark; Okhuysen-Cawley, Regina; Poulton, Tom; Relves, Monica; Rodriguez, Agustin; Rozenfeld, Ranna; Schnitzler, Eduardo; Shanley, Tom; Skache, Sara; Skippen, Peter; Torres, Adalberto; von Dessauer, Bettina; Weingarten, Jacki; Yeh, Timothy; Zaritsky, Arno; Stojadinovic, Bonnie; Zimmerman, Jerry; Zuckerberg, Aaron

    2013-01-01

    Background The Institute of Medicine calls for the use of clinical guidelines and practice parameters to promote “best practices” and to improve patient outcomes. Objective 2007 update of the 2002 American College of Critical Care Medicine Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock. Participants Society of Critical Care Medicine members with special interest in neonatal and pediatric septic shock were identified from general solicitation at the Society of Critical Care Medicine Educational and Scientific Symposia (2001–2006). Methods The Pubmed/MEDLINE literature database (1966–2006) was searched using the keywords and phrases: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, extracorporeal membrane oxygenation (ECMO), and American College of Critical Care Medicine guidelines. Best practice centers that reported best outcomes were identified and their practices examined as models of care. Using a modified Delphi method, 30 experts graded new literature. Over 30 additional experts then reviewed the updated recommendations. The document was subsequently modified until there was greater than 90% expert consensus. Results The 2002 guidelines were widely disseminated, translated into Spanish and Portuguese, and incorporated into Society of Critical Care Medicine and AHA sanctioned recommendations. Centers that implemented the 2002 guidelines reported best practice outcomes (hospital mortality 1%–3% in previously healthy, and 7%– 10% in chronically ill children). Early use of 2002 guidelines was associated with improved outcome in the community hospital emergency department (number needed to treat = 3.3) and tertiary pediatric intensive care setting (number needed to treat = 3.6); every hour that went by without guideline adherence was associated with a 1.4-fold increased mortality risk. The updated 2007 guidelines continue to recognize an increased likelihood that

  13. Mortality in Patients With Septic Shock by Multidrug Resistant Bacteria.

    PubMed

    Busani, Stefano; Serafini, Giulia; Mantovani, Elena; Venturelli, Claudia; Giannella, Maddalena; Viale, Pierluigi; Mussini, Cristina; Cossarizza, Andrea; Girardis, Massimo

    2017-01-01

    Patients with septic shock by multidrug resistant (MDR) microorganism maybe considered a specific population of critical patients at very high risk of death in whom the effects of standard sepsis treatment has never been assessed. The objective of this retrospective analysis was to evaluate the risk factors for 30-day mortality and the impact of sepsis management in patients with septic shock caused by MDR bacteria. Patients with septic shock by MDR bacteria admitted to the mixed intensive care unit (ICU) of Modena University Hospital during a 6-year period were studied. The clinical and microbiological characteristics and sepsis treatments provided were analyzed and compared between survivors (S) and nonsurvivors (NS) at 30 days after septic shock appearance. Ninety-four patients were studied. All therapeutic interventions applied to patients during their ICU stay did not show statistical significance between S and NS groups, except for administration of immunoglobulin M (IgM) preparation which were provided more frequently in S group ( P < .05). At the multivariate adjusted analysis, preexisting cancer (odds ratio [OR] = 2.965) and Acinetobacter baumannii infections (OR = 3.197) were independently correlated with an increased risk of 30-day mortality, whereas treatment with IgM preparation was protective (OR = 0.283). This retrospective study showed that in patients with septic shock caused by MDR bacteria, history of cancer and infection sustained by A baumannii increase the risk of mortality and that standard sepsis treatments do not seem to provide any protective effect. Adjunctive therapy with IgM preparation seems to be beneficial, but further appropriate studies are needed to confirm the results observed.

  14. [Suprahepatic vein catheterization in 4 cases of severe septic shock].

    PubMed

    Inzunza, C; Cornu, M; Bruhn, A; Castillo, L; Bugedo, G; Acuña, D; Medeiros, S; Hernández, G

    2001-05-01

    Splanchnic hypoperfusion, with pathogenic implications for multiple organ failure, can occur during septic shock. We report four patients with septic shock in whom regional hepatosplenic splanchnic perfusion was monitored through suprahepatic vein catheterization and gastric tonometry. Suprahepatic lactate and oxygen saturation showed splanchnic hypoperfusion in all patients. These parameters improved only in the patient that survived. Gastric tonometry was more inconsistent. We conclude that suprahepatic vein catheterization could have a role in the management of septic shock.

  15. Predictors of septic shock in obstructive acute pyelonephritis.

    PubMed

    Tambo, Mitsuhiro; Okegawa, Takatsugu; Shishido, Toshihide; Higashihara, Eiji; Nutahara, Kikuo

    2014-06-01

    Acute pyelonephritis (APN) with obstructive uropathy is not uncommon and often causes serious conditions including sepsis and septic shock. We assessed the risk factors for septic shock in patients with obstructive APN associated with upper urinary tract calculi. We retrospectively studied 69 patients with obstructive APN associated with upper urinary tract calculi who were admitted to our hospital. Emergency drainage for decompression of the renal collecting system was performed for empirical treatment in cases of failure of initial treatment and for severe cases. We assessed the risk factors for septic shock by multivariate logistic regression analysis. Overall, 45 patients (65.2 %) underwent emergency drainage and 23 (33.3 %) patients showed septic shock. Poor performance status and the presence of diabetes mellitus (DM) in the septic shock group were more common than in the non-septic shock group (p = 0.012 and p = 0.011, respectively). The platelet count and serum albumin level in the septic shock group were significantly lower than in the non-septic shock group (p = 0.002 and p = 0.003, respectively). Positive rates of midstream urine culture and blood culture in the septic shock group were significantly higher than in the non-septic shock group (p = 0.022 and p = 0.001, respectively). Multivariate analysis showed that decreases in the platelet count (OR 5.43, p = 0.014) and serum albumin level (OR 5.88, p = 0.023) were independent risk factors for septic shock. Patients with obstructive APN associated with upper urinary tract calculi who have decreases in platelet count and serum albumin level should be treated with caution against the development of septic shock.

  16. Glucose-insulin and potassium infusions in septic shock.

    PubMed

    Hamdulay, Shahir S; Al-Khafaji, Ali; Montgomery, Hugh

    2006-03-01

    Glucose-insulin and potassium (GIK) infusions are beneficial in treating ischemic myocardial depression. Myocardial depression is also an important feature in septic shock. We describe two cases of pressor-resistant hypodynamic septic shock that responded to high-dose GIK infusions. In each case, hemodynamic profiles improved sufficiently to allow withdrawal of vasopressor agents. Further assessment of GIK in patients with hypodynamic septic shock is necessary to confirm efficacy and prognostic significance.

  17. Chlorhexidine Anaphylaxis Masquerading as Septic Shock.

    PubMed

    Hong, Choon Chiet; Wang, Siew May; Nather, Aziz; Tan, Jiong Hao; Tay, Sen Hee; Poon, Keah How

    2015-01-01

    Chlorhexidine is a commonly used antiseptic and disinfectant in the health-care setting. Its usage has increased in recent years with intensive campaigns and infection control guidelines to combat hospital-acquired infections. As a result, patients and health-care workers (HCW) are exposed to increasing chlorhexidine usage. In recent years, adverse reactions to chlorhexidine ranging from allergic contact dermatitis, photosensitivity, fixed drug eruptions, urticaria and anaphylactic shock have been reported. Most have been isolated case reports on adverse reactions occurring in healthy individuals or HCW. We report a case of anaphylactic shock caused by applying chlorhexidine cleansing solution and masquerading as septic shock from left-leg necrotising fasciitis. © 2015 S. Karger AG, Basel.

  18. Initial resuscitation and management of pediatric septic shock

    PubMed Central

    Martin, Kelly; Weiss, Scott L.

    2015-01-01

    The pediatric sepsis syndrome remains a common cause of morbidity, mortality, and health care utilization costs worldwide. The initial resuscitation and management of pediatric sepsis is focused on 1) rapid recognition of abnormal tissue perfusion and restoration of adequate cardiovascular function, 2) eradication of the inciting invasive infection, including prompt administration of empiric broad-spectrum antimicrobial medications, and 3) supportive care of organ system dysfunction. Efforts to improve early and aggressive initial resuscitation and ongoing management strategies have improved outcomes in pediatric severe sepsis and septic shock, though many questions still remain as to the optimal therapeutic strategies for many patients. In this article, we will briefly review the definitions, epidemiology, clinical manifestations, and pathophysiology of sepsis and provide an extensive overview of both current and novel therapeutic strategies used to resuscitate and manage pediatric patients with severe sepsis and septic shock. PMID:25604591

  19. Sepsis and septic shock: a review.

    PubMed

    Chong, Josebelo; Dumont, Tiffany; Francis-Frank, Lyndave; Balaan, Marvin

    2015-01-01

    Sepsis and septic shock are a continuum of disease resulting from a complex host response to infection. They are major health issues in the United States, causing significant financial burden to the health care system in addition to multisystem morbidity and high rates of mortality. In recent decades, landmark trials in sepsis management have demonstrated improved mortality. Although the value of protocol-driven care is currently under question, it is clear that early recognition, prompt resuscitation, and timely use of antibiotics are of utmost importance.

  20. The impact of serial lactate monitoring on emergency department resuscitation interventions and clinical outcomes in severe sepsis and septic shock: an observational cohort study.

    PubMed

    Dettmer, Matthew; Holthaus, Christopher V; Fuller, Brian M

    2015-01-01

    Monitoring in the setting of critical illness must be linked to beneficial therapy to affect clinical outcome. Elevated serum lactate is associated with an increase in mortality in emergency department (ED) patients with severe sepsis and septic shock. The reduction of lactate levels toward normal during acute resuscitation is associated with improved clinical outcomes. The majority of data demonstrating the interventions used to achieve a reduction in lactate levels and the associated clinical outcomes have been obtained during protocolized randomized trials. We therefore conducted a retrospective observational cohort study of 243 adult patients with severe sepsis and septic shock to assess the interventions associated with nonprotocolized serial lactate monitoring and to assess clinical outcomes. A multivariable model was used to assess outcome differences between the serial lactate (SL) and no serial lactate (NL) cohorts. The SL group received more crystalloid resuscitation (3.6 L vs. 2.5 L; P < 0.01), central venous oxygen saturation monitoring (30% vs. 12%; P < 0.01), and central venous pressure monitoring (23.5% vs. 11.8%; P = 0.02). By day 28, a total of 31 patients in the SL group (23.5%) and 44 in the NL group (39.6%) had died. Multivariable logistic regression analysis demonstrated that the lack of serial lactate monitoring was independently associated with mortality (adjusted odds ratio, 2.09; 95% confidence interval [CI], 1.12 - 3.89; P = 0.02). The SL group also showed greater improvement in 24-h Sequential Organ Failure Assessment scores (1.16 vs. 0.19; P = 0.03), decreased intensive care unit length of stay in days (4.6 vs. 6.0; P = 0.04), and more ventilator-free (19.9 vs. 16; P = 0.05) and vasopressor-free (21.6 vs. 17.9; P = 0.02) days. In the setting of routine clinical care, serial lactate monitoring is associated with an increase in crystalloid administration, resuscitation interventions, and improved clinical outcomes in ED patients with

  1. Bench-to-bedside review: Vasopressin in the management of septic shock

    PubMed Central

    2011-01-01

    This review of vasopressin in septic shock differs from previous reviews by providing more information on the physiology and pathophysiology of vasopressin and vasopressin receptors, particularly because of recent interest in more specific AVPR1a agonists and new information from the Vasopressin and Septic Shock Trial (VASST), a randomized trial of vasopressin versus norepinephrine in septic shock. Relevant literature regarding vasopressin and other AVPR1a agonists was reviewed and synthesized. Vasopressin, a key stress hormone in response to hypotension, stimulates a family of receptors: AVPR1a, AVPR1b, AVPR2, oxytocin receptors and purinergic receptors. Rationales for use of vasopressin in septic shock are as follows: first, a deficiency of vasopressin in septic shock; second, low-dose vasopressin infusion improves blood pressure, decreases requirements for norepinephrine and improves renal function; and third, a recent randomized, controlled, concealed trial of vasopressin versus norepinephrine (VASST) suggests low-dose vasopressin may decrease mortality of less severe septic shock. Previous clinical studies of vasopressin in septic shock were small or not controlled. There was no difference in 28-day mortality between vasopressin-treated versus norepinephrine-treated patients (35% versus 39%, respectively) in VASST. There was potential benefit in the prospectively defined stratum of patients with less severe septic shock (5 to 14 μg/minute norepinephrine at randomization): vasopressin may have lowered mortality compared with norepinephrine (26% versus 36%, respectively, P = 0.04 within stratum). The result was robust: vasopressin also decreased mortality (compared with norepinephrine) if less severe septic shock was defined by the lowest quartile of arterial lactate or by use of one (versus more than one) vasopressor at baseline. Other investigators found greater hemodynamic effects of higher dose of vasopressin (0.06 units/minute) but also unique adverse

  2. [Myocardial function analysis with echocardiography-Doppler in septic shock].

    PubMed

    Fayssoil, A; Checinski, A

    2012-02-01

    Septic shock is a severe sepsis associated with cardio-circulatory failure and tissular hypoperfusion. Echocardiography-Doppler remains essential for the assessment of myocardial function in septic shock. This ultrasound procedure helps clinicians for the analysis of left ventricular systolic function, left ventricular diastolic function, right ventricular function and cardiac filling.

  3. Insulin in sepsis and septic shock.

    PubMed

    Das, Undurti N

    2003-07-01

    NF-kappaB activation, and elevated concentrations of macrophage migration inhibitory factor (MIF), tumor necrosis factor-alpha (TNF-alpha), interleukin-1(IL-1), IL-6, free radicals, inducible nitric oxide (iNO), and stress hyperglycemia occurs in sepsis and this leads to systemic inflammatory response and myocardial depression seen in sepsis and septic shock. Conversely, insulin suppresses production of MIF, TNF-alpha, IL-1, IL-6, and free radicals, enhances endothelial NO generation, and enhances the production of anti-inflammatory cytokines IL-4, and IL-10, corrects stress hyperglycemia and improves myocardial function. This supports my earlier proposal that insulin (with or without glucose and potassium) therapy to maintain euglycemia suppresses the inflammatory response, improves myocardial function, and thus, is of benefit in acute myocardial infarction, sepsis andseptic shock.

  4. [A prospective clinical study of pleth variability index in prediction of volume responsiveness in patients with septic shock].

    PubMed

    Lu, Nianfang; Zheng, Ruiqiang; Lin, Hua; Yu, Jiangquan; Shao, Jun; Wu, Xiaoyan; Wang, Haixia

    2015-01-01

    To evaluate the role of pleth variability index ( PVI ) by passive leg raising ( PLR ) test in volume responsiveness and volume status prediction in patients with septic shock. A prospective randomized controlled trial ( RCT ) was conducted. Eighty-seven patients suffering from septic shock undergoing mechanical ventilation in Department of Critical Care Medicine of Subei People's Hospital from June 2012 to September 2014 were enrolled. The hemodynamic changes before and after PLR were monitored by pulse indicated continuous cardiac output ( PiCCO ) and PVI monitoring. Responsive group: positive fluid response was defined as an increase in cardiac index ( CI )≥10% after PLR. Unresponsive group: negative fluid response was defined as an increase in CI<10% after PLR. The hemodynamic parameters, including heart rate ( HR ), mean arterial pressure ( MAP ), central venous pressure ( CVP ), stroke volume variation ( SVV ), CI and PVI, and the changes in cardiac parameters (ΔHR, ΔMAP, ΔCVP, ΔSVV, ΔCI, and ΔPVI ) before and after PLR were determined. The relations between hemodynamic parameters and their changes with ΔCI were analyzed by the Pearson analysis. The role of the parameters for volume responsiveness prediction was evaluated by receiver operating characteristic ( ROC ) curves. 145 PLRs in 87 patients with septic shock were conducted, with 67 in responsive group and 78 in unresponsive group. There were no statistically significant differences in HR, MAP, CVP and CI before PLR between the responsive and unresponsive groups. SVV and PVI in responsive group were significantly higher than those in the unresponsive group [ SVV: ( 16.9±3.1 )% vs. ( 8.4±2.2 ) %, t = 9.078, P = 0.031; PVI: ( 20.6±4.3 )% vs. ( 11.1±3.2 )%, t = 19.189, P = 0.022 ]. There were no statistically significant differences in HR, MAP, CVP, SVV, and PVI after PLR between the responsive group and unresponsive group. CI in the responsive group was significantly higher than that in the

  5. Corticosteroids and pediatric septic shock outcomes: a risk stratified analysis.

    PubMed

    Atkinson, Sarah J; Cvijanovich, Natalie Z; Thomas, Neal J; Allen, Geoffrey L; Anas, Nick; Bigham, Michael T; Hall, Mark; Freishtat, Robert J; Sen, Anita; Meyer, Keith; Checchia, Paul A; Shanley, Thomas P; Nowak, Jeffrey; Quasney, Michael; Weiss, Scott L; Banschbach, Sharon; Beckman, Eileen; Howard, Kelli; Frank, Erin; Harmon, Kelli; Lahni, Patrick; Lindsell, Christopher J; Wong, Hector R

    2014-01-01

    The potential benefits of corticosteroids for septic shock may depend on initial mortality risk. We determined associations between corticosteroids and outcomes in children with septic shock who were stratified by initial mortality risk. We conducted a retrospective analysis of an ongoing, multi-center pediatric septic shock clinical and biological database. Using a validated biomarker-based stratification tool (PERSEVERE), 496 subjects were stratified into three initial mortality risk strata (low, intermediate, and high). Subjects receiving corticosteroids during the initial 7 days of admission (n = 252) were compared to subjects who did not receive corticosteroids (n = 244). Logistic regression was used to model the effects of corticosteroids on 28-day mortality and complicated course, defined as death within 28 days or persistence of two or more organ failures at 7 days. Subjects who received corticosteroids had greater organ failure burden, higher illness severity, higher mortality, and a greater requirement for vasoactive medications, compared to subjects who did not receive corticosteroids. PERSEVERE-based mortality risk did not differ between the two groups. For the entire cohort, corticosteroids were associated with increased risk of mortality (OR 2.3, 95% CI 1.3-4.0, p = 0.004) and a complicated course (OR 1.7, 95% CI 1.1-2.5, p = 0.012). Within each PERSEVERE-based stratum, corticosteroid administration was not associated with improved outcomes. Similarly, corticosteroid administration was not associated with improved outcomes among patients with no comorbidities, nor in groups of patients stratified by PRISM. Risk stratified analysis failed to demonstrate any benefit from corticosteroids in this pediatric septic shock cohort.

  6. Effect of norepinephrine on the outcome of septic shock.

    PubMed

    Martin, C; Viviand, X; Leone, M; Thirion, X

    2000-08-01

    Despite increasingly sophisticated critical care, the mortality of septic shock remains elevated. Accordingly, care remains supportive. Volume resuscitation combined with vasopressor support remains the standard of care as adjuvant therapy, and many consider dopamine to be the pressor of choice. Because of fear of excessive vasoconstriction, norepinephrine is considered to be deleterious. The present study was designed to identify factors associated with outcome in a cohort of septic shock patients. Special attention was paid to hemodynamic management and to the choice of vasopressor used, to determine whether the use of norepinephrine was associated with increased mortality. Prospective, observational, cohort study. Intensive care unit of a university hospital. Ninety-seven adult patients with septic shock. Data from these patients were examined to select variables independently and significantly associated with outcome during the hospital stay. Nineteen clinical, biological, and hemodynamic variables were collected at study entry or during the first 48-72 hrs and analyzed for each patient. A stepwise logistic regression analysis and a model building strategy were used to identify variables independently and significantly associated with outcome. The overall hospital mortality was 73% (71 patients). Five variables were significantly associated with outcome. One factor was strongly associated with a favorable outcome: the use of norepinephrine as part of the hemodynamic support of the patients. The 57 patients who were treated with norepinephrine had significantly lower hospital mortality (62% vs. 82%, p < .001; relative risk = 0.68; 95% confidence interval = 0.54-0.87) than the 40 patients treated with vasopressors other than norepinephrine (high-dose dopamine and/or epinephrine). Four variables were associated with a poor outcome and significantly higher hospital mortality: pneumonia as a cause of septic shock (82% vs. 61%, p < .03; relative risk = 1.47; 95

  7. Antimicrobial therapeutic determinants of outcomes from septic shock among patients with cirrhosis

    PubMed Central

    Arabi, Yaseen M; Dara, Saqib I; Memish, Ziad; Al Abdulkareem, Abdulmajeed; Tamim, Hani M; Al-Shirawi, Nehad; Parrillo, Joseph E; Dodek, Peter; Lapinsky, Stephen; Feinstein, Daniel; Wood, Gordon; Dial, Sandra; Zanotti, Sergio; Kumar, Anand

    2012-01-01

    It is unclear whether practice-related aspects of antimicrobial therapy contribute to the high mortality from septic shock among patients with cirrhosis. We examined the relationship between aspects of initial empiric antimicrobial therapy and mortality in patients with cirrhosis and septic shock. This was a nested cohort study within a large retrospective database of septic shock from 28 medical centers in Canada, the United States, and Saudi Arabia by the Cooperative Antimicrobial Therapy of Septic Shock Database Research Group between 1996 and 2008. We examined the impact of initial empiric antimicrobial therapeutic variables on the hospital mortality of patients with cirrhosis and septic shock. Among 635 patients with cirrhosis and septic shock, the hospital mortality was 75.6%. Inappropriate initial empiric antimicrobial therapy was administered in 155 (24.4%) patients. The median time to appropriate antimicrobial administration was 7.3 hours (interquartile range, 3.2-18.3 hours). The use of inappropriate initial antimicrobials was associated with increased mortality (adjusted odds ratio [aOR], 9.5; 95% confidence interval [CI], 4.3-20.7], as was the delay in appropriate antimicrobials (aOR for each 1 hour increase, 1.1; 95% CI, 1.1-1.2). Among patients with eligible bacterial septic shock, a single rather than two or more appropriate antimicrobials was used in 226 (72.9%) patients and was also associated with higher mortality (aOR, 1.8; 95% CI, 1.0-3.3). These findings were consistent across various clinically relevant subgroups. Conclusion: In patients with cirrhosis and septic shock, inappropriate and delayed appropriate initial empiric antimicrobial therapy is associated with increased mortality. Monotherapy of bacterial septic shock is also associated with increased mortality. The process of selection and implementation of empiric antimicrobial therapy in this high-risk group should be restructured. (Hepatology 2012;56:2305–2315) PMID:22753144

  8. Early hemodynamic resuscitation in septic shock: understanding and modifying oxygen delivery

    PubMed Central

    2014-01-01

    In a previous issue of Critical Care, researchers have focused on the venous-to-arterial carbon dioxide difference (Pv-aCO2) as a surrogate marker for systemic perfusion in patients with septic shock. Although the complex mechanisms responsible for an increased Pv-aCO2 in septic shock need to be further unraveled, the potential prognostic value of Pv-aCO2 seems clinically relevant and useful in daily practice in view of its easy availability. PMID:24602317

  9. Early hemodynamic resuscitation in septic shock: understanding and modifying oxygen delivery.

    PubMed

    van Beest, Paul A; Spronk, Peter E

    2014-02-18

    In a previous issue of Critical Care, researchers have focused on the venous-to-arterial carbon dioxide difference (Pv-aCO2) as a surrogate marker for systemic perfusion in patients with septic shock. Although the complex mechanisms responsible for an increased Pv-aCO2 in septic shock need to be further unraveled, the potential prognostic value of Pv-aCO2 seems clinically relevant and useful in daily practice in view of its easy availability.

  10. Vasopressin compared with norepinephrine augments the decline of plasma cytokine levels in septic shock.

    PubMed

    Russell, James A; Fjell, Chris; Hsu, Joseph L; Lee, Terry; Boyd, John; Thair, Simone; Singer, Joel; Patterson, Andrew J; Walley, Keith R

    2013-08-01

    Changes in plasma cytokine levels may predict mortality, and therapies (vasopressin versus norepinephrine) could change plasma cytokine levels in early septic shock. Our hypotheses were that changes in plasma cytokine levels over 24 hours differ between survivors and nonsurvivors, and that there are different effects of vasopressin and norepinephrine on plasma cytokine levels in septic shock. We studied 394 patients in a randomized, controlled trial of vasopressin versus norepinephrine in septic shock. We used hierarchical clustering and principal components analysis of the baseline cytokine concentrations to subgroup cytokines; we then compared survivors to nonsurvivors (28 d) and compared vasopressin- versus norepinephrine-induced changes in cytokine levels over 24 hours. A total of 39 plasma cytokines were measured at baseline and at 24 hours. Hierarchical clustering and principal components analysis grouped cytokines similarly. Survivors (versus nonsurvivors) had greater decreases of overall cytokine levels (P < 0.001). Vasopressin decreased overall 24-hour cytokine concentration compared with norepinephrine (P = 0.037). In less severe septic shock, the difference in plasma cytokine reduction over 24 hours between survivors and nonsurvivors was less pronounced than that seen in more severe septic shock. Furthermore, vasopressin decreased interferon-inducible protein 10 and granulocyte colony-stimulating factor more than did norepinephrine in less severe septic shock, whereas vasopressin decreased granulocyte-macrophage colony-stimulating factor in patients who had more severe shock. Survivors of septic shock had greater decreases of cytokines, chemokines and growth factors in early septic shock. Vasopressin decreased 24-hour plasma cytokine levels more than did norepinephrine. The vasopressin-associated decrease of cytokines differed according to severity of shock. Clinical trial registered with www.controlled-trials.com (ISRCTN94845869).

  11. Role of circulating soluble chemokines in septic shock.

    PubMed

    de Pablo, R; Monserrat, J; Prieto, A; Alvarez-Mon, M

    2013-11-01

    Chemokines are a large superfamily of small proteins that function not only in leukocyte trafficking, but are also necessary for linkage between innate and adaptive immunity. Little is known about their role in septic shock. We hypothesized that serum levels of the most important chemokines are related to organ failure, disease severity and outcome. A prospective observational study was carried out. Surgical-clinical Intensive Care Unit. Ninety-two patients diagnosed with septic shock using international criteria. Forty patients were excluded due to acquired immunity disturbances. Samples from 36 healthy controls were also analyzed. None. In 46% of the patients who suffered acute respiratory distress syndrome (ARDS), IL-8 levels were higher than in patients without ARDS (499.9±194.1 vs. 190.8±91.7 pg/ml; P=.039). This molecule was also higher in 36% of the patients with sepsis-induced acute renal failure (ARF) (453.3±181.6 vs. 201.3±95.9 pg/ml; P=.049). Coagulopathy was found in 19% of the septic shock patients with elevated serum IL-8 levels (635.8±292.3 vs. 218.7±87.0 pg/ml; P=.010), elevated MIP-1α (91.4±27.3 vs. 58.8±11.1 pg/ml; P=.044), and low circulating RANTES levels (8162.2±6321.0 vs. 18781.8±11.1 pg/ml; P=.027). No significant differences were found between survivors and non-survivors at any time of follow-up. Upon admission to the ICU, IL-8 is a reliable biomarker of sepsis-induced AFR, ARDS and coagulopathy. Altered circulating MIP-1α and RANTES levels are also found in patients with septic shock and coagulopathy. However, chemokines do not appear to be good biomarkers of mortality in septic shock. Copyright © 2012 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  12. Clinical Effects of a Longer Duration of Polymyxin B-Immobilized Fiber Column Direct Hemoperfusion Therapy for Severe Sepsis and Septic Shock.

    PubMed

    Yamashita, Chizuru; Hara, Yoshitaka; Kuriyama, Naohide; Nakamura, Tomoyuki; Nishida, Osamu

    2015-08-01

    Polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) therapy is widely used for the treatment of severe sepsis and septic shock, and is generally performed for 2 h. Although previous studies demonstrated the efficacy of PMX-DHP therapy, it currently remains unclear whether its optimal duration is 2 h. This retrospective study analyzed 37 patients with septic shock who showed a poor clinical response to 2 h of PMX-DHP, and underwent a longer duration of this therapy. The mean duration of PMX-DHP therapy was 15.8 ± 7.9 h, and none of the patients developed adverse events, which enabled the therapy to be performed safely. The pressure catecholamine index [CAIP = catecholamine index/mean arterial pressure; catecholamine index = dopamine + dobutamine + (adrenaline + noradrenaline) × 100 μg/kg per min], as an indicator of hemodynamics, improved significantly in the survival group in the period between the start and 24 h after the end of PMX-DHP therapy (P < 0.01), and between 2 h after the start of and the end of this therapy (P < 0.05). In addition, the P/F ratio improved significantly in the group of surviving patients with acute respiratory distress syndrome (ARDS) in the period between the start and 24 h after the end of PMX-DHP therapy (P < 0.01), and between 2 h after the start of and the end of this therapy (P < 0.01). These results suggest that a longer duration of PMX-DHP therapy can be expected to improve the hemodynamics and pulmonary oxygenation capacity of patients with severe sepsis/septic shock. Strict prospective studies are needed in the future. © 2015 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

  13. Optimizing antimicrobial therapy of sepsis and septic shock: focus on antibiotic combination therapy.

    PubMed

    Vazquez-Grande, Gloria; Kumar, Anand

    2015-02-01

    There has been little improvement in septic shock mortality in the past 70 years, despite ever more broad-spectrum and potent antimicrobials. In the past, resuscitative elements have been the primary area of clinical septic shock management and research. The question of the optimal use of antimicrobial therapy was relatively ignored in recent decades. This review explores the pathophysiology of sepsis in an attempt to produce a better understanding and define key determinants of antimicrobial therapy response in septic shock. Optimizing existing antimicrobials delivery can drive significant improvements in the outcome of sepsis and septic shock. Inappropriate antimicrobial selection and dosing or delays in the administration substantially increase mortality and morbidity in life-threatening infections. Definitive combination therapy (where a pathogen known to be susceptible to a given agent is additionally covered by another agent) remains controversial. Although some in vitro studies, animal models, and clinical studies of infection including endocarditis, gram-negative bacteremia, and neutropenic infections have supported combination therapy, the potential clinical benefit in other severe infections has been questioned. Several meta-analyses have failed to demonstrate improvement of outcome with combination therapy in immunocompetent patients with sepsis and/or gram-negative bacteremia. These meta-analyses did not undertake subgroup analyses of the septic shock population. This article reviews the existing evidence supporting combination therapy for severe infections, sepsis, and septic shock.

  14. [Importance of the forensic autopsy in the diagnosis of septic shock: a case report].

    PubMed

    Sibón-Olano, A; Sánchez-Rodríguez, E; Payá, M; Barrera-Pérez, E; Salguero-Villadiego, M; Fernández-Rodríguez, A

    2017-08-25

    Septic shock sometimes starts with unspecific symptoms that hamper the clinical diagnosis and, therefore an appropriate treatment. When the septic shock follows a fulminating course with a fatal outcome, the etiological diagnosis has to be conducted post-mortem. Sudden unexpected deaths in children and young adults are frequently the object of medico-legal autopsies. Some sudden unexpected deaths have an infectious origin, which requires further analyses, including microbiology, to establish the cause of death. Here, the case of a fatal septic shock in a 19-month old male infant is presented. After a mild foot injury, an infection by Streptococcus pyogenes progressed to septic shock with a fatal outcome as post-mortem studies demonstrated.

  15. Understanding sepsis: from SIRS to septic shock.

    PubMed

    Hynes-Gay, Patricia; Lalla, Patti; Leo, Maria; Merrill-Bell, Audrey; Nicholson, Marjorie; Villaruel, Elizabeth

    2002-01-01

    Sepsis remains the leading cause of death in non-coronary ICU patients, despite improvements in supportive treatment modalities such as antimicrobial drugs and ventilation therapy. Further, the incidence of sepsis is projected to increase in years to come, related to factors including a rise in immunosuppressed patient populations and more widespread use of invasive lines and procedures. In this article, the authors seek to advance nurses' understanding of sepsis by reviewing the SIRS to septic shock paradigm and using a case study to illustrate how a patient progressed along the continuum. The role of the critical care nurse is an important aspect of the care of these patients. Early identification of patients at risk for, or who are developing, sepsis is crucial in order to improve patient outcomes.

  16. Evaluating the Impact of Classroom Education on the Management of Septic Shock Using Human Patient Simulation.

    PubMed

    Lighthall, Geoffrey K; Bahmani, Dona; Gaba, David

    2016-02-01

    Classroom lectures are the mainstay of imparting knowledge in a structured manner and have the additional goals of stimulating critical thinking, lifelong learning, and improvements in patient care. The impact of lectures on patient care is difficult to examine in critical care because of the heterogeneity in patient conditions and personnel as well as confounders such as time pressure, interruptions, fatigue, and nonstandardized observation methods. The critical care environment was recreated in a simulation laboratory using a high-fidelity mannequin simulator, where a mannequin simulator with a standardized script for septic shock was presented to trainees. The reproducibility of this patient and associated conditions allowed the evaluation of "clinical performance" in the management of septic shock. In a previous study, we developed and validated tools for the quantitative analysis of house staff managing septic shock simulations. In the present analysis, we examined whether measures of clinical performance were improved in those cases where a lecture on the management of shock preceded a simulated exercise on the management of septic shock. The administration of the septic shock simulations allowed for performance measurements to be calculated for both medical interns and for subsequent management by a larger resident-led team. The analysis revealed that receiving a lecture on shock before managing a simulated patient with septic shock did not produce scores higher than for those who did not receive the previous lecture. This result was similar for both interns managing the patient and for subsequent management by a resident-led team. We failed to find an immediate impact on clinical performance in simulations of septic shock after a lecture on the management of this syndrome. Lectures are likely not a reliable sole method for improving clinical performance in the management of complex disease processes.

  17. Clinical effects of direct hemoperfusion using a polymyxin-B immobilized column in solid organ transplanted patients with signs of severe sepsis and septic shock. A pilot study.

    PubMed

    Ruberto, F; Pugliese, F; D'Alio, A; Martelli, S; Bruno, K; Marcellino, V; Summonti, D; Celli, P; Perrella, S; Cappannoli, A; Pietropaoli, C; Tosi, A; Diana, B; Novelli, G; Rossi, M; Ginanni-Corradini, S; Ferretti, G; Berloco, P B; Pietropaoli, P

    2007-10-01

    Polymyxin B (PMX-B) is a polycationic antibiotic, known to bind the lipid A portion of endotoxin, a cell wall component found exclusively in gram negative bacteria (GNB). An extracorporeal hemoperfusion device (TORAYMYXIN) has been developed: PMX is covalently bound on the surface of an insoluble carrier material so that the endotoxin can be inactivated in the blood without exerting its toxicity on the brain and kidney. The aim of this study was to clarify the efficacy, safety and clinical effects of direct hemoperfusion with an immobilized polymyxin-B fiber column (DHP-PMX) in solid organ transplanted patients with severe sepsis or septic shock. From June 2004 to May 2005, 15 patients (10 men and 5 women), mean age 55 years old (46-65 range), underwent kidney or liver transplantation and developed severe sepsis or septic shock, as defined by the Consensus Conference of American College Physicians/Society of Critical Care Medicine (ACCP/SCCM) criteria. GNB were detected in all the patients receiving conventional treatments including antibiotic therapy, vasopressive or inotropic agents, and ventilation support. The DHP-PMX treatment was performed three times in each patient. Hemodynamic and respiratory parameters, dosage of vasopressor/inotropic drugs were assessed at baseline and after each treatment. No adverse events occurred. From baseline to 3rd treatment, mean arterial pressure (MAP) was increased (from 63+/-5 to 83+/-4 mmHg), while the dosage of dobutamine (from 7.5+/-3 to 3+/-2 mcg/kg/min) and noradrenaline (from 1.3+/-0.45 to 0.05+/-0.02 mcg/kg/min) were reduced. The PaO2/FiO2 ratio increased (from 234+/-38.47 to 290+/-107.48 mmHg). The use of DHP-PMX in association with conventional therapy may be an important aid in patients with sepsis.

  18. Asymmetric dimethylarginine and L-arginine levels in neonatal sepsis and septic shock.

    PubMed

    Aydemir, Ozge; Ozcan, Beyza; Yucel, Husniye; Bas, Ahmet Yagmur; Demirel, Nihal

    2015-05-01

    Nitric oxide (NO) formed by the enzyme NO synthase (NOS) from L-arginine, is an important mediator for pathogen elimination. Being a potent vasodilator NO is implicated in hypotension and decreased organ perfusion in sepsis. Asymmetric dimethylarginine (ADMA) is an endogenous NOS inhibitor. We investigated ADMA and L-arginine levels in neonatal sepsis and their relation to disease severity. A prospective controlled study was conducted including 31 neonates with sepsis and 20 controls. Serum ADMA and L-arginine levels were measured within 24 h of sepsis diagnosis. Clinical and laboratory data including clinical risk index for babies (CRIB) score, presence of septic shock, organ dysfunction and death were recorded. L-arginine and ADMA levels were higher in neonates with sepsis compared to controls (p = 0.029 and p = 0.001, respectively). Neonates with septic shock had higher ADMA levels compared to septic neonates without shock (p = 0.026) and controls (p < 0.001). L-arginine levels were higher in neonates with septic shock compared to septic neonates without shock (p = 0.012) and controls (p < 0.001). Survivors and non-survivors had similar L-arginine and ADMA levels. ADMA levels were correlated with CRIB score (rho = 0.320, p = 0.025). L-arginine and ADMA levels are elevated in neonatal sepsis and even higher levels are observed in septic shock.

  19. An unusual case of septic shock in a geriatric patient.

    PubMed

    Kourelis, Taxiarchis; Kannan, Subramanian; Foley, Raymond J

    2010-03-01

    Capnocytophaga canimorsus is a gram-negative rod that is a normal inhabitant of the oral flora of most dogs, cats and other animals. Clinically significant infections of humans by this common organism are extremely rare. We present a case of an 87-year-old woman who presented with septic shock and multiorgan system failure. Blood cultures were positive for a gram-negative rod that five days after admission was identified as C. canimorsus. She was treated aggressively with intravenous fluid resuscitation, vasopressors and parenteral antibiotics and recovered. The epidemiology, virulence factors, and treatment options for C. canimorsus are discussed.

  20. Advanced Hemodynamic Management in Patients with Septic Shock.

    PubMed

    Saugel, Bernd; Huber, Wolfgang; Nierhaus, Axel; Kluge, Stefan; Reuter, Daniel A; Wagner, Julia Y

    2016-01-01

    In patients with sepsis and septic shock, the hemodynamic management in both early and later phases of these "organ dysfunction syndromes" is a key therapeutic component. It needs, however, to be differentiated between "early goal-directed therapy" (EGDT) as proposed for the first 6 hours of emergency department treatment by Rivers et al. in 2001 and "hemodynamic management" using advanced hemodynamic monitoring in the intensive care unit (ICU). Recent large trials demonstrated that nowadays protocolized EGDT does not seem to be superior to "usual care" in terms of a reduction in mortality in emergency department patients with early identified septic shock who promptly receive antibiotic therapy and fluid resuscitation. "Hemodynamic management" comprises (a) making the diagnosis of septic shock as one differential diagnosis of circulatory shock, (b) assessing the hemodynamic status including the identification of therapeutic conflicts, and (c) guiding therapeutic interventions. We propose two algorithms for hemodynamic management using transpulmonary thermodilution-derived variables aiming to optimize the cardiocirculatory and pulmonary status in adult ICU patients with septic shock. The complexity and heterogeneity of patients with septic shock implies that individualized approaches for hemodynamic management are mandatory. Defining individual hemodynamic target values for patients with septic shock in different phases of the disease must be the focus of future studies.

  1. Advanced Hemodynamic Management in Patients with Septic Shock

    PubMed Central

    Huber, Wolfgang; Nierhaus, Axel; Kluge, Stefan; Reuter, Daniel A.; Wagner, Julia Y.

    2016-01-01

    In patients with sepsis and septic shock, the hemodynamic management in both early and later phases of these “organ dysfunction syndromes” is a key therapeutic component. It needs, however, to be differentiated between “early goal-directed therapy” (EGDT) as proposed for the first 6 hours of emergency department treatment by Rivers et al. in 2001 and “hemodynamic management” using advanced hemodynamic monitoring in the intensive care unit (ICU). Recent large trials demonstrated that nowadays protocolized EGDT does not seem to be superior to “usual care” in terms of a reduction in mortality in emergency department patients with early identified septic shock who promptly receive antibiotic therapy and fluid resuscitation. “Hemodynamic management” comprises (a) making the diagnosis of septic shock as one differential diagnosis of circulatory shock, (b) assessing the hemodynamic status including the identification of therapeutic conflicts, and (c) guiding therapeutic interventions. We propose two algorithms for hemodynamic management using transpulmonary thermodilution-derived variables aiming to optimize the cardiocirculatory and pulmonary status in adult ICU patients with septic shock. The complexity and heterogeneity of patients with septic shock implies that individualized approaches for hemodynamic management are mandatory. Defining individual hemodynamic target values for patients with septic shock in different phases of the disease must be the focus of future studies. PMID:27703980

  2. Intravenous immunoglobulin for severe sepsis and septic shock: clinical effectiveness, cost-effectiveness and value of a further randomised controlled trial.

    PubMed

    Soares, Marta O; Welton, Nicky J; Harrison, David A; Peura, Piia; Shankar-Hari, Manu; Harvey, Sheila E; Madan, Jason; Ades, Anthony E; Rowan, Kathryn M; Palmer, Stephen J

    2014-12-01

    Prior to investing in a large, multicentre randomised controlled trial (RCT), the National Institute for Health Research in the UK called for an evaluation of the feasibility and value for money of undertaking a trial on intravenous immunoglobulin (IVIG) as an adjuvant therapy for severe sepsis/septic shock. In response to this call, this study assessed the clinical and cost-effectiveness of IVIG (using a decision model), and evaluated the value of conducting an RCT (using expected value of information (EVI) analysis). The evidence informing such assessments was obtained through a series of systematic reviews and meta-analyses. Further primary data analyses were also undertaken using the Intensive Care National Audit & Research Centre Case Mix Programme Database, and a Scottish Intensive Care Society research study. We found a large degree of statistical heterogeneity in the clinical evidence on treatment effect, and the source of such heterogeneity was unclear. The incremental cost-effectiveness ratio of IVIG is within the borderline region of estimates considered to represent value for money, but results appear highly sensitive to the choice of model used for clinical effectiveness. This was also the case with EVI estimates, with maximum payoffs from conducting a further clinical trial between £ 137 and £ 1,011 million. Our analyses suggest that there is a need for a further RCT. Results on the value of conducting such research, however, were sensitive to the clinical effectiveness model used, reflecting the high level of heterogeneity in the evidence base.

  3. The Impact of Various Platelet Indices as Prognostic Markers of Septic Shock

    PubMed Central

    Yu, Xuezhong; Guo, Shigong; Ji, Xu; Sun, Tongwen; Lan, Chao; Lavergne, Valery; Ghannoum, Marc; Li, Li

    2014-01-01

    Introduction Platelet indices, including mean platelet volume (MPV), are readily available blood tests, although their prognostic value in patients with septic shock has not been fully explored. Current evidence has found contradictory results. This study aims to explore the behavior of platelet indices in septic shock and their clinical prognostic value. Methods Charts of septic shock patients from January to December 2012 in a tertiary medical center in Northern China were reviewed retrospectively. Platelet indices were recorded during the first five consecutive days after admission, as well as the penultimate and the last day of hospital stay. The data were compared between surviving and non-surviving patients. Results A total of 124 septic shock patients were enrolled. Thirty-six of the patients survived and 88 of them expired. MPV in the non-survivor group was higher than that of the survivor group, especially on the last day. PDW and PLCR showed increased trends, while PCT and PLT decreased in the non-survivor group. Among the PLT indices, MPV had the highest area under the receiver operating characteristic curve (0.81) with a precision rate of 75.6% at a cut-off of 10.5.Compared with other more usual septic shock prognostic markers, MPV is second only to lactate for the highest area under the curve. Conclusion A statistically significant difference was seen between survivors and non-survivors for platelet indices which make them easily available and useful prognostic markers for patients in septic shock. PMID:25118886

  4. Goal-directed resuscitation for patients with early septic shock.

    PubMed

    Peake, Sandra L; Delaney, Anthony; Bailey, Michael; Bellomo, Rinaldo; Cameron, Peter A; Cooper, D James; Higgins, Alisa M; Holdgate, Anna; Howe, Belinda D; Webb, Steven A R; Williams, Patricia

    2014-10-16

    Early goal-directed therapy (EGDT) has been endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients presenting to the emergency department with septic shock. However, its effectiveness is uncertain. In this trial conducted at 51 centers (mostly in Australia or New Zealand), we randomly assigned patients presenting to the emergency department with early septic shock to receive either EGDT or usual care. The primary outcome was all-cause mortality within 90 days after randomization. Of the 1600 enrolled patients, 796 were assigned to the EGDT group and 804 to the usual-care group. Primary outcome data were available for more than 99% of the patients. Patients in the EGDT group received a larger mean (±SD) volume of intravenous fluids in the first 6 hours after randomization than did those in the usual-care group (1964±1415 ml vs. 1713±1401 ml) and were more likely to receive vasopressor infusions (66.6% vs. 57.8%), red-cell transfusions (13.6% vs. 7.0%), and dobutamine (15.4% vs. 2.6%) (P<0.001 for all comparisons). At 90 days after randomization, 147 deaths had occurred in the EGDT group and 150 had occurred in the usual-care group, for rates of death of 18.6% and 18.8%, respectively (absolute risk difference with EGDT vs. usual care, -0.3 percentage points; 95% confidence interval, -4.1 to 3.6; P=0.90). There was no significant difference in survival time, in-hospital mortality, duration of organ support, or length of hospital stay. In critically ill patients presenting to the emergency department with early septic shock, EGDT did not reduce all-cause mortality at 90 days. (Funded by the National Health and Medical Research Council of Australia and the Alfred Foundation; ARISE ClinicalTrials.gov number, NCT00975793.).

  5. Euglycemic hyperinsulinemia in severe sepsis and septic shock.

    PubMed

    Su, Fuhong; Wang, Zhen; Bruhn, Alejandro; Verdant, Colin; Cai, Ying; Vincent, Jean-Louis

    2006-01-01

    Recent studies have suggested that strict glucose control with intensive insulin therapy in critically ill patients may result in better outcomes. Whether this is also true in septic shock has not been determined. In addition, whether it is the insulin administration per se or the glucose control that contributes to the beneficial effects is unclear. We raised the hypothesis that euglycemic hyperinsulinemia (EH) might improve the outcome from septic shock due to peritonitis. Fourteen anesthetized, mechanically ventilated, and hemodynamically monitored sheep received 1.5 g/kg body weight i.p. feces to induce sepsis. Ringer's lactate and 6% hydroxyethyl starch solutions were infused throughout the experiment to prevent hypovolemia. Two hours after feces injection, the animals were randomized to either an EH group (n = 7) receiving insulin 0.25 U/ kg/h, 20% glucose (to maintain blood glucose at 40-90 mg/dl), and potassium (to maintain the potassium level at 4.0- 5.5 mmol/l) or a control group (n = 7) with no intervention. All animals were studied until their spontaneous death or for 30 h. The EH group received a greater volume of 20% glucose, but blood glucose and potassium concentrations were similar in the two groups. No significant differences were found in hemodynamic variables. The circulating interleukin-6 levels increased in both groups after feces injection, but tended to be lower in the EH group (p < 0.05). The survival times were similar in the two groups (median 20.0 h in the EH group vs. 17.0 h in the control group; p = 0.73). In this clinically relevant sheep septic shock model, EH decreased blood interleukin-6 concentrations but did not change hemodynamics or improve the outcome. Copyright 2006 S. Karger AG, Basel.

  6. Comparison of the effects of albumin and crystalloid on mortality in adult patients with severe sepsis and septic shock: a meta-analysis of randomized clinical trials.

    PubMed

    Xu, Jing-Yuan; Chen, Qi-Hong; Xie, Jian-Feng; Pan, Chun; Liu, Song-Qiao; Huang, Li-Wei; Yang, Cong-Shan; Liu, Ling; Huang, Ying-Zi; Guo, Feng-Mei; Yang, Yi; Qiu, Hai-Bo

    2014-12-15

    The aim of this study was to examine whether albumin reduced mortality when employed for the resuscitation of adult patients with severe sepsis and septic shock compared with crystalloid by meta-analysis. We searched for and gathered data from MEDLINE, Elsevier, Cochrane Central Register of Controlled Trials and Web of Science databases. Studies were eligible if they compared the effects of albumin versus crystalloid therapy on mortality in adult patients with severe sepsis and septic shock. Two reviewers extracted data independently. Disagreements were resolved by discussion with other two reviewers until a consensus was achieved. Data including mortality, sample size of the patients with severe sepsis, sample size of the patients with septic shock and resuscitation endpoints were extracted. Data were analyzed by the methods recommended by the Cochrane Collaboration Review Manager 4.2 software. A total of 5,534 records were identified through the initial search. Five studies compared albumin with crystalloid. In total, 3,658 severe sepsis and 2,180 septic shock patients were included in the meta-analysis. The heterogeneity was determined to be non-significant (P = 0.86, I(2) = 0%). Compared with crystalloid, a trend toward reduced 90-day mortality was observed in severe sepsis patients resuscitated with albumin (odds ratio (OR) 0.88; 95% CI, 0.76 to 1.01; P = 0.08). However, the use of albumin for resuscitation significantly decreased 90-day mortality in septic shock patients (OR 0.81; 95% CI, 0.67 to 0.97; P = 0.03). Compared with saline, the use of albumin for resuscitation slightly improved outcome in severe sepsis patients (OR 0.81; 95% CI, 0.64 to 1.08; P = 0.09). In this meta-analysis, a trend toward reduced 90-day mortality was observed in severe sepsis patients resuscitated with albumin compared with crystalloid and saline. Moreover, the 90-day mortality of patients with septic shock decreased significantly.

  7. Kawasaki Shock Syndrome in a 12-Year-Old Girl Mimicking Septic Shock.

    PubMed

    Sinhabahu, Vindika Prasad; Suntharesan, Janani; Wijesekara, Dimuthu Saraji

    2016-01-01

    Kawasaki disease is diagnosed when fever lasts for more than 5 days with the presence of four out of five of the following clinical features: bilateral conjunctival congestion, changes in the lips and oral cavity, polymorphous exanthem, changes in peripheral extremities, and acute nonpurulent cervical lymphadenopathy (Nakamura et al., 2012). The average age of onset is 2 years and 90% of patients are below 5 years of age. Boys are more affected than girls (Cox and Sallis, 2009). This case report describes an adolescent female who was initially managed as having septic shock and subsequently found to have Kawasaki shock syndrome.

  8. Kawasaki Shock Syndrome in a 12-Year-Old Girl Mimicking Septic Shock

    PubMed Central

    Suntharesan, Janani; Wijesekara, Dimuthu Saraji

    2016-01-01

    Kawasaki disease is diagnosed when fever lasts for more than 5 days with the presence of four out of five of the following clinical features: bilateral conjunctival congestion, changes in the lips and oral cavity, polymorphous exanthem, changes in peripheral extremities, and acute nonpurulent cervical lymphadenopathy (Nakamura et al., 2012). The average age of onset is 2 years and 90% of patients are below 5 years of age. Boys are more affected than girls (Cox and Sallis, 2009). This case report describes an adolescent female who was initially managed as having septic shock and subsequently found to have Kawasaki shock syndrome. PMID:28101385

  9. Sepsis and septic shock-is a microcirculation a main player?

    PubMed

    Lipinska-Gediga, Małgorzata

    2016-01-01

    Shock, defined at a cellular level, is a condition in which oxygen delivery to the cells is not sufficient to sustain cellular activity and support organ function. The central role of microcirculation in providing oxygen to the cells makes it of prime importance in determining organ function. In sepsis and septic shock, macrocirculatory alterations and microcirculatory dysfunction participate concurrently in the pathophysiology of organ failure. Haemodynamic coherence in shock is a condition in which normalization of systemic haemodynamic variables results in simultaneous amelioration in the perfusion of the microcirculation and restoration of tissue oxygenation as a final result. Septic shock is most frequently characterized by a lack of microcirculatory recruitment despite of macrocirculatory successful resuscitation. The lack of haemodynamic coherence between macrocirculation and microcirculation in septic patients results in treatment failure and increased mortality. The monitoring of microcirculation and the effects of its changes are an important area of future clinical research and treatment modification.

  10. Arginine-vasopressin in catecholamine-refractory septic versus non-septic shock in extremely low birth weight infants with acute renal injury

    PubMed Central

    Meyer, Sascha; Gottschling, Sven; Baghai, Ali; Wurm, Donald; Gortner, Ludwig

    2006-01-01

    Introduction The aim of this study was to assess the efficacy of arginine-vasopressin (AVP) as a rescue therapy in catecholamine-refractory septic and non-septic shock in extremely low birth weight (ELBW) infants with acute renal injury. Methods Prospective assessment of AVP therapy in three ELBW infants with catecholamine-refractory septic shock and acute renal injury (mean birth weight 600 ± 30 g) and three ELBW infants with non-septic shock and acute renal injury (mean birth weight 770 ± 110 g) at a University hospital. The main outcome measures were restoration of blood pressure with adequate organ perfusion and survival at discharge. Results In all three ELBW infants with catecholamine-resistant septic shock, systemic arterial blood pressure increased substantively with restoration of urine output after AVP administration (dosage, 0.035 to 0.36 U/kg/h; length, 70 ± 21 hours). In the three ELBW infants with non-septic shock, only a transient stabilization in mean arterial pressure with restoration of urine output was observed after AVP therapy (dosage, 0.01 to 0.36 U/kg/h; length, 30 ± 16 hours). The mortality rate was 1/3 in the sepsis group versus 3/3 in the non-septic group. Conclusion AVP may be a promising rescue therapy in catecholamine-resistant shock in ELBW infants with acute renal injury. Larger prospective clinical trials are warranted to assess the efficacy and safety of AVP as a pressor adjunct in septic versus non-septic shock in ELBW infants. PMID:16677425

  11. Evaluation of a Model-Based Hemodynamic Monitoring Method in a Porcine Study of Septic Shock

    PubMed Central

    Revie, James A.; Stevenson, David; Chase, J. Geoffrey; Pretty, Chris J.; Lambermont, Bernard C.; Ghuysen, Alexandre; Kolh, Philippe; Shaw, Geoffrey M.; Desaive, Thomas

    2013-01-01

    Introduction. The accuracy and clinical applicability of an improved model-based system for tracking hemodynamic changes is assessed in an animal study on septic shock. Methods. This study used cardiovascular measurements recorded during a porcine trial studying the efficacy of large-pore hemofiltration for treating septic shock. Four Pietrain pigs were instrumented and induced with septic shock. A subset of the measured data, representing clinically available measurements, was used to identify subject-specific cardiovascular models. These models were then validated against the remaining measurements. Results. The system accurately matched independent measures of left and right ventricle end diastolic volumes and maximum left and right ventricular pressures to percentage errors less than 20% (except for the 95th percentile error in maximum right ventricular pressure) and all R 2 > 0.76. An average decrease of 42% in systemic resistance, a main cardiovascular consequence of septic shock, was observed 120 minutes after the infusion of the endotoxin, consistent with experimentally measured trends. Moreover, modelled temporal trends in right ventricular end systolic elastance and afterload tracked changes in corresponding experimentally derived metrics. Conclusions. These results demonstrate that this model-based method can monitor disease-dependent changes in preload, afterload, and contractility in porcine study of septic shock. PMID:23585774

  12. Right heart in septic shock: prospective observational study.

    PubMed

    Singh, Ratender Kumar; Kumar, Sudeep; Nadig, Sreevatsa; Baronia, Arvind Kumar; Poddar, Banani; Azim, Afzal; Gurjar, Mohan

    2016-01-01

    The right heart often receives less attention during echocardiography. The situation is no different in septic shock. We prospectively investigated the echocardiographic indices of the right heart in septic shock adult patients. Septic shock ICU patients within 24 h of admission were subjected to transthoracic echocardiography (TTE) as per the 2005 guidelines from the American Society of Echocardiography. Eighty-eight septic shock patients (M:F = 52:36) underwent TTE. Thirty-six patients survived. Significant differences in demographic and biochemical (laboratory and metabolic) parameters, severity scores, life-support therapies (vasopressors, ventilation), and length of ICU stay were observed between survivors and non-survivors. Right heart abnormalities of chamber dimension and systolic and diastolic function existed in 79, 25, and 86 % of patients, respectively. Right ventricle subcostal wall thickness (91 %), pulse Doppler myocardial performance index (73 %), and E/E' (63 %) were the predominant abnormalities in chamber dimension, systolic function, and diastolic function of the right heart, respectively. However, the presence of these abnormalities did not signify poor survival in our study. Right heart dimensional and functional abnormalities exist in high proportions in septic shock. However, their predictability of poor outcomes remains questionable.

  13. [Septic shock in intensive care units. Current focus on treatment].

    PubMed

    Arriagada S, Daniela; Donoso F, Alejandro; Cruces R, Pablo; Díaz R, Franco

    2015-01-01

    Essential therapeutic principles in children with septic shock persist over time, although some new concepts have been recently incorporated, and fully awareness of pediatricians and intensivists is essential. Fluid resuscitation is a fundamental intervention, but the kind of ideal fluid has not been established yet, as each of these interventions has specific limitations and there is no evidence supportive of the superiority of one type of fluid. Should septic shock persists despite adequate fluid resuscitation, the use of inotropic medication and/or vasopressors is indicated. New vasoactive drugs can be used in refractory septic shock caused by vasopressors, and the use of hydrocortisone should be considered in children with suspected adrenal insufficiency, as it reduces the need for vasopressors. The indications for red blood cells transfusion or the optimal level of glycemia are still controversial, with no consensus on the threshold value for the use of these blood products or the initiation of insulin administration, respectively. Likewise, the use of high-volume hemofiltration is a controversial issue and further study is needed on the routine recommendation in the course of septic shock. Nutritional support is crucial, as malnutrition is a serious complication that should be properly prevented and treated. The aim of this paper is to provide update on the most recent advances as concerns the treatment of septic shock in the pediatric population. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Streptococcus pneumoniae causing septic arthritis with shock and revealing multiple myeloma

    PubMed Central

    Riachy, Moussa Albert

    2011-01-01

    The authors present the case of a 43-year-old male who presented at the emergency department, with a mean arterial pressure of 48 mm of Hg, a sinus tachycardia of 142/min and shallow breathing at 30/min. Two days previously, he started a high-grade fever with a concomitant reddish and painful left knee and right elbow, without any treatment. Septic shock was diagnosed and the patient was started on empiric antibiotics combining ceftriaxone and vancomycin and vasopressors (norepinephrine). The painful knee and elbow joints were aspirated and cultures grew Streptococcus pneumoniae. The patient’s clinical condition improved progressively and after investigation, the diagnosis of multiple myeloma was concluded. Pneumococcal septic arthritis, an extraordinary cause of septic arthritis, is a manifestation of an underlying disease and can be responsible for septic shock. Its diagnosis should direct further investigations. It can occur in patients with joint disease but should emphasise the search of systemic immunosuppression. PMID:22694889

  15. [Acute kidney injury and septic shock: experiences in treatment].

    PubMed

    Pozzato, Marco; Ferrari, Fiorenza; Livigni, Sergio; Quarello, Francesco

    2012-01-01

    Acute kidney injury (AKI) occurs in 5-45% of critically ill patients, and renal replacement therapy (RRT) is required in 4-10% of patients with AKI. AKI has long been considered to be hemodynamic damage from low blood flow resulting in shock, and efforts have been made to prevent and cure it by increasing the renal blood flow and improving the cardiac output and perfusion pressure. In recent years, new experimental studies on patients with septic AKI have shown that the renal blood flow remains unaltered or even increases in septic shock. An important mechanism in the pathophysiology of sepsis and septic shock appears to be apoptosis rather than ischemic necrosis. The type of treatment as well as the dose and timing of initiation of RRT seem to have strategic importance in the recovery of AKI in patients admitted to the ICU. In critically ill (often postsurgical and septic) patients with acute renal failure the use of new anticoagulation strategies has permitted to perform treatments for a sufficient number of hours to achieve the correct level of purification by minimizing the downtime and the bleeding risk. In our center the use of protocols for different methods and different types of anticoagulants has simplified the treatment of all patients with AKI and septic shock admitted to the ICU.

  16. Time to initiation of treatment with polymyxin B cartridge hemoperfusion in septic shock patients.

    PubMed

    Takeyama, Naoshi; Noguchi, Hiroshi; Hirakawa, Akihiko; Kano, Hideki; Morino, Kazuma; Obata, Toru; Sakamoto, Tetsuya; Tamai, Fumihiro; Ishikura, Hiroyasu; Kase, Youichi; Kobayashi, Makoto; Naka, Toshio; Takahashi, Yoshiki

    2012-01-01

    We investigated whether early initiation of hemoperfusion with a polymyxin B cartridge (PMX) after the diagnosis of septic shock could improve the clinical outcome. A prospective, open-labeled, multicenter cohort study was performed at intensive care units in Japan. 41 patients received PMX within 6 h after the diagnosis of septic shock (early group) and 51 patients were treated after 6 h (late group). The early group had a significantly shorter duration of ventilator support and also had a lower catecholamine requirement. PMX was effective for improvement of hypotension, hypoperfusion, the sequential organ failure assessment score, and pulmonary oxygenation regardless of the timing of its initiation. The 28-day mortality rate did not differ between the two groups. Early initiation of PMX shortened the duration of ventilator support and also reduced the catecholamine requirement, so early treatment of septic shock should achieve a better outcome. Copyright © 2012 S. Karger AG, Basel.

  17. Enterococcus hirae Bacteremia Associated with Acute Pancreatitis and Septic Shock

    PubMed Central

    Dicpinigaitis, Peter V.; De Aguirre, Manuel; Divito, Joseph

    2015-01-01

    Infection with Enterococcus hirae has rarely been reported in humans but is not uncommon in mammals and birds. We describe a case of Enterococcus hirae bacteremia associated with acute pancreatitis, acute cholecystitis, and septic shock responsive to antibiotic therapy and supportive critical care management. Unique aspects of this case of Enterococcus hirae bacteremia are its association with acute pancreatitis and its geographical origin. To our knowledge, this is the first report of Enterococcus hirae bacteremia occurring in a patient in the United States. Although human infection with this organism appears to be rare, all cases reported to date describe bacteremia associated with severe and life-threatening illness. Thus, physicians need to be cognizant of the clinical significance of this heretofore little recognized pathogen. PMID:26417465

  18. [Beta-blockers in septic shock: a review].

    PubMed

    Vela-Vásquez, R S; Grigorov-Tzenkov, I; Aguilar, J L

    2015-02-01

    In septic shock, high adrenergic stress is associated with cardiovascular and systemic adverse effects, which can negatively affect the results. Beta-adrenergic receptor block has been shown to be effective in controlling the disproportionate increase in heart rate, maintaining a favorable hemodynamic profile and apparently improving the efficiency of the cardiovascular system in order to maintain tissue perfusion. They have also been shown to modulate favorably catecholamine-induced immunosuppression and to decrease insulin resistance, protein catabolism, and proinflammatory cytokine expression associated with cardiovascular dysfunction. Selective beta-1 blockers appear to provide better results than non-selective blockers, even suggesting a positive impact on mortality. Future clinical trials are still needed to confirm these findings and define the scope of their benefits.

  19. A targeted real-time early warning score (TREWScore) for septic shock.

    PubMed

    Henry, Katharine E; Hager, David N; Pronovost, Peter J; Saria, Suchi

    2015-08-05

    Sepsis is a leading cause of death in the United States, with mortality highest among patients who develop septic shock. Early aggressive treatment decreases morbidity and mortality. Although automated screening tools can detect patients currently experiencing severe sepsis and septic shock, none predict those at greatest risk of developing shock. We analyzed routinely available physiological and laboratory data from intensive care unit patients and developed "TREWScore," a targeted real-time early warning score that predicts which patients will develop septic shock. TREWScore identified patients before the onset of septic shock with an area under the ROC (receiver operating characteristic) curve (AUC) of 0.83 [95% confidence interval (CI), 0.81 to 0.85]. At a specificity of 0.67, TREWScore achieved a sensitivity of 0.85 and identified patients a median of 28.2 [interquartile range (IQR), 10.6 to 94.2] hours before onset. Of those identified, two-thirds were identified before any sepsis-related organ dysfunction. In comparison, the Modified Early Warning Score, which has been used clinically for septic shock prediction, achieved a lower AUC of 0.73 (95% CI, 0.71 to 0.76). A routine screening protocol based on the presence of two of the systemic inflammatory response syndrome criteria, suspicion of infection, and either hypotension or hyperlactatemia achieved a lower sensitivity of 0.74 at a comparable specificity of 0.64. Continuous sampling of data from the electronic health records and calculation of TREWScore may allow clinicians to identify patients at risk for septic shock and provide earlier interventions that would prevent or mitigate the associated morbidity and mortality. Copyright © 2015, American Association for the Advancement of Science.

  20. Fluid therapy for septic shock resuscitation: which fluid should be used?

    PubMed

    Corrêa, Thiago Domingos; Rocha, Leonardo Lima; Pessoa, Camila Menezes Souza; Silva, Eliézer; de Assuncao, Murillo Santucci Cesar

    2015-01-01

    Early resuscitation of septic shock patients reduces the sepsis-related morbidity and mortality. The main goals of septic shock resuscitation include volemic expansion, maintenance of adequate tissue perfusion and oxygen delivery, guided by central venous pressure, mean arterial pressure, mixed or central venous oxygen saturation and arterial lactate levels. An aggressive fluid resuscitation, possibly in association with vasopressors, inotropes and red blood cell concentrate transfusion may be necessary to achieve those hemodynamic goals. Nonetheless, even though fluid administration is one of the most common interventions offered to critically ill patients, the most appropriate type of fluid to be used remains controversial. According to recently published clinical trials, crystalloid solutions seem to be the most appropriate type of fluids for initial resuscitation of septic shock patients. Balanced crystalloids have theoretical advantages over the classic solutions, but there is not enough evidence to indicate it as first-line treatment. Additionally, when large amounts of fluids are necessary to restore the hemodynamic stability, albumin solutions may be a safe and effective alternative. Hydroxyethyl starches solutions must be avoided in septic patients due to the increased risk of acute renal failure, increased need for renal replacement therapy and increased mortality. Our objective was to present a narrative review of the literature regarding the major types of fluids and their main drawbacks in the initial resuscitation of the septic shock patients.

  1. Fluid therapy for septic shock resuscitation: which fluid should be used?

    PubMed Central

    Corrêa, Thiago Domingos; Rocha, Leonardo Lima; Pessoa, Camila Menezes Souza; Silva, Eliézer; de Assuncao, Murillo Santucci Cesar

    2015-01-01

    Early resuscitation of septic shock patients reduces the sepsis-related morbidity and mortality. The main goals of septic shock resuscitation include volemic expansion, maintenance of adequate tissue perfusion and oxygen delivery, guided by central venous pressure, mean arterial pressure, mixed or central venous oxygen saturation and arterial lactate levels. An aggressive fluid resuscitation, possibly in association with vasopressors, inotropes and red blood cell concentrate transfusion may be necessary to achieve those hemodynamic goals. Nonetheless, even though fluid administration is one of the most common interventions offered to critically ill patients, the most appropriate type of fluid to be used remains controversial. According to recently published clinical trials, crystalloid solutions seem to be the most appropriate type of fluids for initial resuscitation of septic shock patients. Balanced crystalloids have theoretical advantages over the classic solutions, but there is not enough evidence to indicate it as first-line treatment. Additionally, when large amounts of fluids are necessary to restore the hemodynamic stability, albumin solutions may be a safe and effective alternative. Hydroxyethyl starches solutions must be avoided in septic patients due to the increased risk of acute renal failure, increased need for renal replacement therapy and increased mortality. Our objective was to present a narrative review of the literature regarding the major types of fluids and their main drawbacks in the initial resuscitation of the septic shock patients. PMID:26313437

  2. Risk factors and pathogenic significance of severe sepsis and septic shock in 2286 patients with gram-negative bacteremia.

    PubMed

    Kang, Cheol-In; Song, Jae-Hoon; Chung, Doo Ryeon; Peck, Kyong Ran; Ko, Kwan Soo; Yeom, Joon-Sup; Ki, Hyun Kyun; Son, Jun Seong; Lee, Seung Soon; Kim, Yeon-Sook; Jung, Sook-In; Kim, Shin-Woo; Chang, Hyun-Ha; Ryu, Seong Yeol; Kwon, Ki Tae; Lee, Hyuck; Moon, Chisook

    2011-01-01

    The aim of this study was to identify risk factors for development of severe sepsis or septic shock and to evaluate the clinical impact of severe sepsis on outcome in patients with gram-negative bacteremia (GNB). From the database of a nationwide surveillance for bacteremia, patients with GNB were analyzed. Data of patients with severe sepsis or septic shock were compared with those of patient with sepsis. Of 2286 patients with GNB, 506 (22.1%) fulfilled the criteria of severe sepsis or septic shock. Factors associated with severe sepsis or septic shock in the multivariate analysis included renal disease, indwelling urinary catheter, hematologic malignancy, and neutropenia. The 30-day mortality of patients with severe sepsis or septic shock was significantly higher than that of patients with sepsis (39.5% [172/435] vs. 7.4% [86/1170]; P < 0.001). Multivariable analysis revealed that solid tumor, liver disease, pulmonary disease, pneumonia, and pathogens other than Escherichia coli, which were risk factors of development of severe sepsis or septic shock, were also found to be strong predictors of mortality. Severe sepsis or septic shock was a significant factor associated with mortality (OR, 3.34; 95% CI, 2.35-4.74), after adjustment for other variables predicting poor prognosis. Severe sepsis or septic shock was a common finding in patients with GNB, predicting a higher mortality rate. Renal disease and indwelling urinary catheter were the most important risk factors significantly associated with severe sepsis or septic shock among patients with GNB. Copyright © 2010 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  3. Disulfiram ethanol reaction mimicking anaphylactic, cardiogenic, and septic shock.

    PubMed

    Bourcier, Simon; Mongardon, Nicolas; Daviaud, Fabrice; Moachon, Laurence; Arnould, Marc-Antoine; Perruche, Franck; Pène, Frédéric; Cariou, Alain

    2013-01-01

    Shock is a common reason for medical intensive care unit admission, with septic and cardiogenic accounting for most of the etiologies. However, the potential severity of adverse side effects of drugs indicates that any medication should be carefully scrutinized for potential pharmacokinetic and pharmacodynamic interactions that may result. We herein report the case of a life-threatening shock mimicking successively anaphylactic, cardiogenic, and septic shock, which was finally related to disulfiram ethanol reaction. Indeed, disulfiram ethanol reaction is known to provoke unpleasant symptoms through vasodilatation in various organs. However, extreme manifestations of vasodilatory shock may lead to circulatory failure and lactic acidosis. Because of large prevalence of alcoholism and disulfiram medication, emergency physicians and medical specialists should be aware of this life-threatening condition, with its misleading presentation.

  4. Trial of early, goal-directed resuscitation for septic shock.

    PubMed

    Mouncey, Paul R; Osborn, Tiffany M; Power, G Sarah; Harrison, David A; Sadique, M Zia; Grieve, Richard D; Jahan, Rahi; Harvey, Sheila E; Bell, Derek; Bion, Julian F; Coats, Timothy J; Singer, Mervyn; Young, J Duncan; Rowan, Kathryn M

    2015-04-02

    Early, goal-directed therapy (EGDT) is recommended in international guidelines for the resuscitation of patients presenting with early septic shock. However, adoption has been limited, and uncertainty about its effectiveness remains. We conducted a pragmatic randomized trial with an integrated cost-effectiveness analysis in 56 hospitals in England. Patients were randomly assigned to receive either EGDT (a 6-hour resuscitation protocol) or usual care. The primary clinical outcome was all-cause mortality at 90 days. We enrolled 1260 patients, with 630 assigned to EGDT and 630 to usual care. By 90 days, 184 of 623 patients (29.5%) in the EGDT group and 181 of 620 patients (29.2%) in the usual-care group had died (relative risk in the EGDT group, 1.01; 95% confidence interval [CI], 0.85 to 1.20; P=0.90), for an absolute risk reduction in the EGDT group of -0.3 percentage points (95% CI, -5.4 to 4.7). Increased treatment intensity in the EGDT group was indicated by increased use of intravenous fluids, vasoactive drugs, and red-cell transfusions and reflected by significantly worse organ-failure scores, more days receiving advanced cardiovascular support, and longer stays in the intensive care unit. There were no significant differences in any other secondary outcomes, including health-related quality of life, or in rates of serious adverse events. On average, EGDT increased costs, and the probability that it was cost-effective was below 20%. In patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation, hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment Programme; ProMISe Current Controlled Trials number, ISRCTN36307479.).

  5. Arginine vasopressin for the treatment of septic shock in adults.

    PubMed

    Bauer, Seth R; Lam, Simon W

    2010-10-01

    Sepsis remains one of the leading causes of mortality in the United States. Cardiovascular compromise is one of the major contributors to the high mortality associated with sepsis. Current cardiovascular support in patients with septic shock involves fluid administration, use of catecholamines, and potentially the use of inotropes, corticosteroids, or arginine vasopressin. Vasopressin is an endogenous hormone essential for both osmotic and cardiovascular homeostasis. Various studies have suggested that exogenous administration of arginine vasopressin may be an effective adjunctive therapy to traditional catecholamines for the management of hypotension during septic shock. Of particular interest is the Vasopressin and Septic Shock Trial (VASST), which found no mortality benefit when comparing the addition of arginine vasopressin to norepinephrine versus continuous dose increases in norepinephrine alone. However, results of the a priori subgroup and post hoc analyses of this trial suggest that patients may benefit if arginine vasopressin is used in patients with less severe shock, defined as those receiving a relatively low norepinephrine-equivalent dose of 5-14 μg/minute, or in those at risk for renal failure. Current guidelines from the Surviving Sepsis Campaign recommend arginine vasopressin 0.03 unit/minute may be added to norepinephrine with the anticipation of an effect equal to higher doses of norepinephrine alone. Many practitioners continue to utilize arginine vasopressin for patients with septic shock due to its mechanisms of benefit on pathophysiologic derangements in this disease. Clinicians must be knowledgeable about the use of arginine vasopressin in septic shock, including controversial areas where guidelines do not always provide concrete recommendations.

  6. Empiric Antibiotic Therapy for Severe Sepsis and Septic Shock.

    PubMed

    Oshima, Taku; Kodama, Yoshiyuki; Takahashi, Waka; Hayashi, Yosuke; Iwase, Shinya; Kurita, Takeo; Saito, Daiki; Yamaji, Yoshihiro; Oda, Shigeto

    2016-04-01

    A retrospective study was conducted to investigate the validity and the effectiveness of early empiric antibiotic and de-escalation therapy for the treatment of severe sepsis and septic shock patients in the intensive care unit (ICU). Patients admitted to the ICU at Chiba University Hospital from January 1, 2010, to December 31, 2012, for the treatment of severe sepsis or septic shock were selected for analysis. One-hundred and ten patients were enrolled for the analysis. Carbapenems were selected most frequently (57.3%), followed by cephalosporins (22.7%), and penicillins (21.8%). Empiric antibiotic therapy was appropriate for 85 (77.3%) patients. Mortality rates for patients with inappropriate empiric therapy was 36.8%, whereas mortality rates for patients with appropriate empiric therapy was 17.5%. Among the patients with appropriate empiric antibiotic administration, de-escalation was associated with lower mortality rates of 5.0% for severe sepsis and 9.7% for septic shock patients. The mortality rates for the no de-escalation group were 19.0% and 35.7%, respectively. Empiric antibiotic therapy was acceptable for severe sepsis and septic shock patients treated in the ICU. The appropriate selection of empiric antibiotics was related to a greater rate of de-escalation and better survival. The risk of multi-drug-resistant bacterial infections was not as high as expected, but will need further attention in the future.

  7. Pseudomonas aeruginosa septic shock secondary to "gripe water" ingestion.

    PubMed

    Sas, David; Enrione, Maria A; Schwartz, Richard H

    2004-02-01

    We report the case of a 9-month-old girl who presented in septic shock after ingestion of a contaminated herbal supplement commonly used to treat colic. Herbal supplements are widely used by well-meaning parents for many common conditions. Pediatricians should be aware that the variable manufacturing and packaging conditions of herbal supplements can lead to contamination with infectious agents.

  8. Effects of Xuebijing injection on microcirculation in septic shock.

    PubMed

    Wang, Liang; Liu, Zhiyong; Dong, Zhe; Pan, Jieyi; Ma, Xiaochun

    2016-05-01

    This study was conducted to investigate whether Xuebijing injection can rectify the dysfunction of microcirculation in septic shock and assessed the microcirculatory parameters directly via orthogonal polarization spectral and software AVA 3.0. Anesthetized and mechanically ventilated beagle dogs were modeled for septic shock via lipopolysaccharide (LPS) intravenous injection. They were divided randomly into four groups, control group accepted operation only for jejunostomy and cystostomy; LPS group accepted operation and LPS intravenous injection; saline group accepted operation, LPS intravenous injection, and saline resuscitation; XBJ group accepted operation, LPS intravenous injection, saline resuscitation, and Xuebijing injection infusion. The MAP was recorded via right femoral artery catheterization, at the same time, the blood gas analysis was taken via that pathway at the set time points. ScvO2 was obtained via right jugular vein catheterization at the related time points. Microcirculatory parameters were recorded by orthogonal polarization spectral via the jejunum stoma, and the microcirculation image was analyzed via the software AVA 3.0 later. Xuebijing injection improved microcirculation of the jejunum villus in canine model of septic shock induced by endotoxin, especially for the proportion of perfused vessels. Based on the adequate fluid resuscitation, Xuebijing injection plays a helpful role of improving microcirculation in septic shock. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Pathogens and outcomes in pediatric septic shock patients supported by extracorporeal membrane oxygenation.

    PubMed

    Chang, Tu-Hsuan; Wu, En-Ting; Lu, Chun-Yi; Huang, Shu-Chien; Yang, Tzu-I; Wang, Ching-Chia; Chen, Jong-Min; Lee, Ping-Ing; Huang, Li-Min; Chang, Luan-Yin

    2017-08-04

    Refractory septic shock is the leading cause of mortality in children. There is limited evidence to support extracorporeal membrane oxygenation (ECMO) use in pediatric septic shock. We described the etiology and outcomes of septic patients in our institution and attempted to find predictive factors. We retrospectively reviewed 55 pediatric patients with septic shock who required ECMO support in a tertiary medical center from 2008 to 2015. Septic shock was defined as culture proved or clinical suspected sepsis with hypotension or end-organ hypoperfusion. ECMO would be applied when pediatric advanced life support steps were performed thoroughly without clinical response. Patient's demographics, laboratory parameters before and after ECMO, and outcomes were analyzed. Among 55 children with ECMO support, 31% of them survived on discharge. For 25 immunocompromised patients, causal pathogens were found in 17 patients: 7 due to bacteremia, 9 with preexisting virus infections and one with invasive fungal infection. Among 30 previously healthy patients, causal pathogens were found in 18 patients: 10 due to bacteremia (the most common was pneumococcus), 7 with preexisting virus infections including influenza (n = 4), adenovirus (n = 2), RSV, and 1 patient had mixed virus and bacterial infections. Predictive factors associated with death were arterial blood gas pH, CO2 and Glasgow Coma Scale (p < 0.05). SOFA score was a valuable predictive scoring system for outcome prediction (p < 0.05). Pediatric patients with refractory septic shock had high mortality rate and ECMO could be used as a rescue modality, and SOFA score could be applied to predict outcomes. Copyright © 2017. Published by Elsevier B.V.

  10. Racial differences in vasopressor requirements for septic shock.

    PubMed

    Bauman, Zachary M; Killu, Keith F; Rech, Megan A; Bernabei-Combs, Jenna L; Gassner, Marika Y; Coba, Victor E; Tovbin, Alina; Kunkel, Patti L; Mlynarek, Mark E

    2014-03-01

    The objective of this study was to compare vasopressor requirements between African American (AA) patients and white patients in septic shock. This was a retrospective cohort review conducted over a 2-year period measuring total and mean dosage of various vasopressors used between two racial groups during the treatment of patients admitted with septic shock. The study included patients admitted to the intensive care unit with septic shock at an 805-bed tertiary, academic center. All septic shock patients were managed with vasopressors. Vasopressor selection, dosage, and duration were at the discretion of the treating physician. Total, mean, and duration of vasopressor dosing requirements were obtained for study participants. Comorbidities, prehospitalization antihypertensive medication requirements, intravenous fluids given during the septic shock phase, and source of infection were analyzed. One hundred fifty-nine patients with septic shock were analyzed, of which 96 (60.4%) were AAs (P < 0.059). African Americans had higher rates of end-stage renal disease and hypertension compared with whites, 85.7% vs. 14.3% (P < 0.011; odds ratio [OR], 15.684) and 68.3% vs. 31.7% (P < 0.007; OR, 3.357), respectively. Norepinephrine (NE) was administered to 150 patients, 57.2% of which were AAs (P < 0.509). Thirteen patients received dopamine (5% AAs, P < 0.588), 40 patients received phenylephrine (15.7% AAs, P < 0.451), and five patients received epinephrine (1.9% AAs, P < 0.660). Comparing vasopressors between races, only NE showed statistical significance via logistic regression modeling for the AA race in terms of total dosage (AAs 736.8 [SD, 897.3] μg vs. whites 370 [SD, 554.2] μg, P < 0.003), duration of vasopressor used (AAs 38.38 [SD, 34.75] h vs. whites 29.09 [SD, 27.11] h, P < 0.037), and mean dosage (AAs 21.08 [SD, 22.23] μg/h vs. whites 12.37 [SD, 13.86] μg/h, P < 0.01). Mortality between groups was not significant. Logistic regression identified discrepancy of

  11. Antimicrobial resistance patterns, clinical features, and risk factors for septic shock and death of nosocomial E coli bacteremia in adult patients with hematological disease: A monocenter retrospective study in China.

    PubMed

    Ma, Jie; Li, Ning; Liu, Yajie; Wang, Chong; Liu, Xiaoyan; Chen, Shengmei; Xie, Xinsheng; Gan, Silin; Wang, Meng; Cao, Weijie; Wang, Fang; Liu, Yanfan; Wan, Dingming; Sun, Ling; Sun, Hui

    2017-05-01

    The aim of this retrospective analysis was to evaluate the antimicrobial resistance, clinical features, and risk factors for septic shock and death of nosocomial E coli bacteremia in adult patients in a single hematological center in China. A retrospective case-control study of 157 adult hematological patients with 168 episodes of E coli bacteremia was initiated from April 2012 to July 2015. Antimicrobial susceptibility as well as antimicrobial co-resistance rates were analyzed. Clinical features and outcomes were also studied. In addition, risk factors for septic shock and death were investigated. Among the 553 positive blood isolates during the study period, the prevalence of E coli was 33.3% and ESBL production strains represented 61.9% of those examined. In all the E coli strains isolated, 85.6% were multidrug-resistance (MDR), 2.4% were extensive drug resistance (XDR), and 6.0% were resistant to carbapenems. More MDR phenotype was noted in ESBL-EC strains (98.6% vs 62.8%, P<.001) and isolates from neutropenic patients (98.6% vs 62.8%, P < .001). In the antimicrobial susceptibility test, carbapenems and amikacin exhibited not only higher in vitro activity against E coli (94.0% and 92.0%, respectively), but lower co-resistance rates to other antibiotics. Carbapenem resistant strains retained full sensitivity to tigecycline and 60% to amikacin. Piperacillin/tazobatam was the third sensitive drug to both ESBL-EC (77.1%) and non-ESBL-EC (86.0%). In our series, 81.6% episodes received appropriate initial antibiotic treatment and no significant decrease in it was found in bacteremia due to ESBL E coli and patients with neutropenia, septic shock. Septic shock was noted in 15.5% patients and the overall 30-day mortality rate was 21.7%. Multivariate analysis revealed that induction chemotherapy (OR 2.126; 95% CI 1.624-11.332; P = .003) and polymicrobial infection (OR 3.628; 95% CI 1.065-21.219; P = .041) were risk factors for septic shock, whereas male (OR 2

  12. Drotrecogin alfa (activated) in adults with septic shock.

    PubMed

    Ranieri, V Marco; Thompson, B Taylor; Barie, Philip S; Dhainaut, Jean-François; Douglas, Ivor S; Finfer, Simon; Gårdlund, Bengt; Marshall, John C; Rhodes, Andrew; Artigas, Antonio; Payen, Didier; Tenhunen, Jyrki; Al-Khalidi, Hussein R; Thompson, Vivian; Janes, Jonathan; Macias, William L; Vangerow, Burkhard; Williams, Mark D

    2012-05-31

    There have been conflicting reports on the efficacy of recombinant human activated protein C, or drotrecogin alfa (activated) (DrotAA), for the treatment of patients with septic shock. In this randomized, double-blind, placebo-controlled, multicenter trial, we assigned 1697 patients with infection, systemic inflammation, and shock who were receiving fluids and vasopressors above a threshold dose for 4 hours to receive either DrotAA (at a dose of 24 μg per kilogram of body weight per hour) or placebo for 96 hours. The primary outcome was death from any cause 28 days after randomization. At 28 days, 223 of 846 patients (26.4%) in the DrotAA group and 202 of 834 (24.2%) in the placebo group had died (relative risk in the DrotAA group, 1.09; 95% confidence interval [CI], 0.92 to 1.28; P=0.31). At 90 days, 287 of 842 patients (34.1%) in the DrotAA group and 269 of 822 (32.7%) in the placebo group had died (relative risk, 1.04; 95% CI, 0.90 to 1.19; P=0.56). Among patients with severe protein C deficiency at baseline, 98 of 342 (28.7%) in the DrotAA group had died at 28 days, as compared with 102 of 331 (30.8%) in the placebo group (risk ratio, 0.93; 95% CI, 0.74 to 1.17; P=0.54). Similarly, rates of death at 28 and 90 days were not significantly different in other predefined subgroups, including patients at increased risk for death. Serious bleeding during the treatment period occurred in 10 patients in the DrotAA group and 8 in the placebo group (P=0.81). DrotAA did not significantly reduce mortality at 28 or 90 days, as compared with placebo, in patients with septic shock. (Funded by Eli Lilly; PROWESS-SHOCK ClinicalTrials.gov number, NCT00604214.).

  13. Early alterations of B cells in patients with septic shock

    PubMed Central

    2013-01-01

    Introduction It has recently been proposed that B lymphocytes are involved in sepsis pathogenesis. The goal of this study is to investigate potential abnormalities in a subset distribution and activation of circulating B lymphocytes in patients with septic shock. Methods This observational prospective study was conducted in a medical-surgical ICU. All patients with septic shock were eligible for inclusion. B-cell phenotypes (CD19+CD69+, CD19+CD23+, CD19+CD5+, CD19+CD80, CD19+CD86+, CD19+CD40 and CD19+CD95+) were assessed by quantitative flow cytometry upon admission to the ICU and 3, 7, 14 and 28 d later. Results Fifty-two patients were included. Thirty-six healthy volunteers matched for age and sex were used as controls. The patients had lymphopenia that was maintained during 28 d of follow-up. In patients with septic shock who died, the percentage of CD19+CD23+ was lower during the 7 d of follow-up than it was in survival patients. Moreover, the percentage of CD80+ and CD95+ expression on B cells was higher in patients who died than in survivors. Receiver operating characteristic curve analysis showed that a CD19+CD23+ value of 64.6% at ICU admission enabled discrimination between survivors and nonsurvivors with a sensitivity of 90.9% and a specificity of 80.0% (P = 0.0001). Conclusions Patients with septic shock who survive and those who don't have different patterns of abnormalities in circulating B lymphocytes. At ICU admission, a low percentage of CD23+ and a high of CD80+ and CD95+ on B cells were associated with increased mortality of patients with septic shock. Moreover, a drop in circulating B cells persisted during 28 d of ICU follow-up. PMID:23721745

  14. Increased survival of cirrhotic patients with septic shock.

    PubMed

    Sauneuf, Bertrand; Champigneulle, Benoit; Soummer, Alexis; Mongardon, Nicolas; Charpentier, Julien; Cariou, Alain; Chiche, Jean-Daniel; Mallet, Vincent; Mira, Jean-Paul; Pène, Frédéric

    2013-04-19

    The overall outcome of septic shock has been recently improved. We sought to determine whether this survival gain extends to the high-risk subgroup of patients with cirrhosis. Cirrhotic patients with septic shock admitted to a medical intensive care unit (ICU) during two consecutive periods (1997-2004 and 2005-2010) were retrospectively studied. Forty-seven and 42 cirrhotic patients presented with septic shock in 1997-2004 and 2005-2010, respectively. The recent period differed from the previous one by implementation of adjuvant treatments of septic shock including albumin infusion as fluid volume therapy, low-dose glucocorticoids, and intensive insulin therapy. ICU and hospital survival markedly improved over time (40% in 2005-2010 vs. 17% in 1997-2004, P = 0.02 and 29% in 2005-2010 vs. 6% in 1997-2004, P = 0.009, respectively). Furthermore, this survival gain in the latter period was sustained for 6 months (survival rate 24% in 2005-2010 vs. 6% in 1997-2004, P = 0.06). After adjustment with age, the liver disease stage (Child-Pugh score), and the critical illness severity score (SOFA score), ICU admission between 2005 and 2010 remained an independent favorable prognostic factor (odds ratio (OR) 0.09, 95% confidence interval (CI) 0.02-0.4, P = 0.004). The stage of the underlying liver disease was also independently associated with hospital mortality (Child-Pugh score: OR 1.42 per point, 95% CI 1.06-1.9, P = 0.018). In the light of advances in management of both cirrhosis and septic shock, survival of such patients substantially increased over recent years. The stage of the underlying liver disease and the related therapeutic options should be included in the decision-making process for ICU admission.

  15. Septic shock attributed to Candida infection: importance of empiric therapy and source control.

    PubMed

    Kollef, Marin; Micek, Scott; Hampton, Nicholas; Doherty, Joshua A; Kumar, Anand

    2012-06-01

    Delayed treatment of candidemia has previously been shown to be an important determinant of patient outcome. However, septic shock attributed to Candida infection and its determinants of outcome have not been previously evaluated in a large patient population. A retrospective cohort study of hospitalized patients with septic shock and blood cultures positive for Candida species was conducted at Barnes-Jewish Hospital, a 1250-bed urban teaching hospital (January 2002-December 2010). Two hundred twenty-four consecutive patients with septic shock and a positive blood culture for Candida species were identified. Death during hospitalization occurred among 155 (63.5%) patients. The hospital mortality rate for patients having adequate source control and antifungal therapy administered within 24 hours of the onset of shock was 52.8% (n = 142), compared to a mortality rate of 97.6% (n = 82) in patients who did not have these goals attained (P < .001). Multivariate logistic regression analysis demonstrated that delayed antifungal treatment (adjusted odds ratio [AOR], 33.75; 95% confidence interval [CI], 9.65-118.04; P = .005) and failure to achieve timely source control (AOR, 77.40; 95% CI, 21.52-278.38; P = .001) were independently associated with a greater risk of hospital mortality. The risk of death is exceptionally high among patients with septic shock attributed to Candida infection. Efforts aimed at timely source control and antifungal treatment are likely to be associated with improved clinical outcomes.

  16. Interleukin-10 rs2227307 and CXCR2 rs1126579 polymorphisms modulate the predisposition to septic shock

    PubMed Central

    Cardoso, Cristina Padre; de Oliveira, Argenil José de Assis; Botoni, Fernando Antônio; Rezende, Isabela Cristina Porto; Alves-Filho, Jose Carlos; Cunha, Fernando de Queiroz; Estanislau, Juliana de Assis Silva Gomes; Magno, Luiz Alexandre Viana; Rios-Santos, Fabricio

    2015-01-01

    Despite major improvements in its treatment and diagnosis, sepsis is still a leading cause of death and admittance to the intensive care unit (ICU). Failure to identify patients at high risk of developing septic shock contributes to an increase in the sepsis burden and rapid molecular tests are currently the most promising avenue to aid in patient risk determination and therapeutic anticipation. The primary goal of this study was to evaluate the genetic susceptibility that affects sepsis outcome in 72 sepsis patients admitted to the ICU. Seven polymorphisms were genotyped in key inflammatory response genes in sepsis, including tumour necrosis factor-α, interlelukin (IL)-1β, IL-10, IL-8, Toll-like receptor 4, CXCR1 and CXCR2. The primary finding showed that patients who were homozygous for the major A allele in IL-10 rs1800896 had almost five times higher chance to develop septic shock compared to heterozygotes. Similarly, selected clinical features and CXCR2 rs1126579 single nucleotide polymorphisms modulated septic shock susceptibility without affecting survival. These data support the hypothesis that molecular testing has clinical usefulness to improve sepsis prognostic models. Therefore, enrichment of the ICU portfolio by including these biomarkers will aid in the early identification of sepsis patients who may develop septic shock. PMID:26038959

  17. Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

    PubMed

    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

    2016-02-23

    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. To evaluate the validity of clinical criteria to identify patients with suspected infection who are at risk of sepsis. 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. 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). 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). 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 infection, of whom 1289 [16%] died), the predictive validity for in-hospital mortality was

  18. Long-term outcomes in patients with septic shock transfused at a lower versus a higher haemoglobin threshold: the TRISS randomised, multicentre clinical trial.

    PubMed

    Rygård, Sofie L; Holst, Lars B; Wetterslev, Jørn; Winkel, Per; Johansson, Pär I; Wernerman, Jan; Guttormsen, Anne B; Karlsson, Sari; Perner, Anders

    2016-11-01

    We assessed the predefined long-term outcomes in patients randomised in the Transfusion Requirements in Septic Shock (TRISS) trial. In 32 Scandinavian ICUs, we randomised 1005 patients with septic shock and haemoglobin of 9 g/dl or less to receive single units of leuko-reduced red cells when haemoglobin level was 7 g/dl or less (lower threshold) or 9 g/dl or less (higher threshold) during ICU stay. We assessed mortality rates 1 year after randomisation and again in all patients at time of longest follow-up in the intention-to-treat population (n = 998) and health-related quality of life (HRQoL) 1 year after randomisation in the Danish patients only (n = 777). Mortality rates in the lower- versus higher-threshold group at 1 year were 53.5 % (268/501 patients) versus 54.6 % (271/496) [relative risk 0.97; 95 % confidence interval (CI) 0.85-1.09; P = 0.62]; at longest follow-up (median 21 months), they were 56.7 % (284/501) versus 61.0 % (302/495) (hazard ratio 0.88; 95 % CI 0.75-1.03; P = 0.12). We obtained HRQoL data at 1 year in 629 of the 777 (81 %) Danish patients, and mean differences between the lower- and higher-threshold group in scores of physical HRQoL were 0.4 (95 % CI -2.4 to 3.1; P = 0.79) and in mental HRQoL 0.5 (95 % CI -3.1 to 4.0; P = 0.79). Long-term mortality rates and HRQoL did not differ in patients with septic shock and anaemia who were transfused at a haemoglobin threshold of 7 g/dl versus a threshold of 9 g/dl. We may reject a more than 3 % increased hazard of death in the lower- versus higher-threshold group at the time of longest follow-up.

  19. Effect of Sodium Selenite Administration and Procalcitonin-Guided Therapy on Mortality in Patients With Severe Sepsis or Septic Shock: A Randomized Clinical Trial.

    PubMed

    Bloos, Frank; Trips, Evelyn; Nierhaus, Axel; Briegel, Josef; Heyland, Daren K; Jaschinski, Ulrich; Moerer, Onnen; Weyland, Andreas; Marx, Gernot; Gründling, Matthias; Kluge, Stefan; Kaufmann, Ines; Ott, Klaus; Quintel, Michael; Jelschen, Florian; Meybohm, Patrick; Rademacher, Sibylle; Meier-Hellmann, Andreas; Utzolino, Stefan; Kaisers, Udo X; Putensen, Christian; Elke, Gunnar; Ragaller, Maximilian; Gerlach, Herwig; Ludewig, Katrin; Kiehntopf, Michael; Bogatsch, Holger; Engel, Christoph; Brunkhorst, Frank M; Loeffler, Markus; Reinhart, Konrad

    2016-09-01

    High-dose intravenous administration of sodium selenite has been proposed to improve outcome in sepsis by attenuating oxidative stress. Procalcitonin-guided antimicrobial therapy may hasten the diagnosis of sepsis, but effect on outcome is unclear. To determine whether high-dose intravenous sodium selenite treatment and procalcitonin-guided anti-infectious therapy in patients with severe sepsis affect mortality. The Placebo-Controlled Trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT), a multicenter, randomized, clinical, 2 × 2 factorial trial performed in 33 intensive care units in Germany, was conducted from November 6, 2009, to June 6, 2013, including a 90-day follow-up period. Patients were randomly assigned to receive an initial intravenous loading dose of sodium selenite, 1000 µg, followed by a continuous intravenous infusion of sodium selenite, 1000 µg, daily until discharge from the intensive care unit, but not longer than 21 days, or placebo. Patients also were randomized to receive anti-infectious therapy guided by a procalcitonin algorithm or without procalcitonin guidance. The primary end point was 28-day mortality. Secondary outcomes included 90-day all-cause mortality, intervention-free days, antimicrobial costs, antimicrobial-free days, and secondary infections. Of 8174 eligible patients, 1089 patients (13.3%) with severe sepsis or septic shock were included in an intention-to-treat analysis comparing sodium selenite (543 patients [49.9%]) with placebo (546 [50.1%]) and procalcitonin guidance (552 [50.7%]) vs no procalcitonin guidance (537 [49.3%]). The 28-day mortality rate was 28.3% (95% CI, 24.5%-32.3%) in the sodium selenite group and 25.5% (95% CI, 21.8%-29.4%) (P = .30) in the placebo group. There was no significant difference in 28-day mortality between patients assigned to procalcitonin guidance (25.6% [95% CI, 22.0%-29.5%]) vs no procalcitonin guidance (28.2% [95% CI, 24

  20. Mannose-binding lectin serum levels in neonatal sepsis and septic shock.

    PubMed

    Wahab Mohamed, Walid Abdel; Saeed, Mohamed Abdullatif

    2012-04-01

    To evaluate mannose-binding lectin (MBL) serum levels as a marker for predicting sepsis, septic shock, and their outcomes in neonates. A prospective study was conducted on 62 neonates (27 preterm and 35 full term) with culture-proven sepsis and 35 controls. Serum levels of MBL were measured by immunoassay. Of 62 infants with positive blood cultures (Gram-negative = 44 and Gram-positive = 18), 11 infants had severe sepsis and 6 neonates developed septic shock. MBL levels were significantly lower in infants with sepsis than in control group (0.39 ± 0.07 vs. 1.34 ± 0.03 μg/ml; p < 0.001). The lowest MBL levels were detected in those infants with septic shock, particularly those who died (p < 0.05). MBL had high sensitivity (96.7), specificity (97.1), positive (98.3), and negative (94.4) predictive values to detect sepsis. Low MBL serum levels could be considered as sensitive and specific marker for predicting sepsis, septic shock, and their clinical outcomes in newborn infants.

  1. Controversies regarding choice of vasopressor therapy for management of septic shock in animals.

    PubMed

    Silverstein, Deborah C; Beer, Kari A Santoro

    2015-01-01

    To review and appraise common vasopressor drugs used to treat septic shock-induced hypotension in volume replete animals. Human and animal publications were searched using PubMed without time limits and the following keywords were used: "vasopressor," "septic shock," "norepinephrine," "dopamine," "epinephrine," and "vasopressin." The choice of vasopressor drug is unlikely to have a marked impact on outcome, but the incidence of adverse events (eg, tachycardia) varies greatly between the various treatment options. In agreement with the 2012 Cochrane Database consensus, norepinephrine is the first-choice vasopressor to maintain a mean arterial pressure ≥65 mm Hg. If an additional agent is required, epinephrine should be administered. Low-dose vasopressin can be added to norepinephrine to either increase the arterial blood pressure to the target goal value or decrease the norepinephrine dose, but should not be used as the initial vasopressor. Dopamine is not recommended except in highly selected circumstances. There is insufficient evidence to make definitive conclusions regarding the treatment of naturally occurring septic shock, but clinical studies are underway to provide further data. The treatment of hypotension in people or animals with septic shock is challenging and vasopressor therapy is associated with a variety of adverse effects. Further research is warranted in dogs and cats to establish evidence-based guidelines. © Veterinary Emergency and Critical Care Society 2015.

  2. 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.

  3. Experimental Septic Shock: Models and Mechanisms

    DTIC Science & Technology

    1976-06-14

    E . coli endotoxin or live E . coli organisms were evaluated during a 24-hour period or until death. Results suggest significant differences between the two shock models: large dosages of endotoxin on contrast to those used in the canine species were required to elicit lethality characteristics. Hypoglycemia and hypoinsulinemia were regularly observed in live E . coli organism induced shock; however, hyperglycemia was a consistent hallmark in the endotoxin infused model. Renal fibrin thrombi were presented only after E .

  4. Clinical characteristics and outcomes of septic bursitis.

    PubMed

    Lieber, Sarah B; Fowler, Mary Louise; Zhu, Clara; Moore, Andrew; Shmerling, Robert H; Paz, Ziv

    2017-05-29

    Limited data guide practice in evaluation and treatment of septic bursitis. We aimed to characterize clinical characteristics, microbiology, and outcomes of patients with septic bursitis stratified by bursal involvement, presence of trauma, and management type. We conducted a retrospective cohort study of adult patients admitted to a single center from 1998 to 2015 with culture-proven olecranon and patellar septic bursitis. Baseline characteristics, clinical features, microbial profiles, operative interventions, hospitalization lengths, and 60-day readmission rates were determined. Patients were stratified by bursitis site, presence or absence of trauma, and operative or non-operative management. Of 44 cases of septic bursitis, patients with olecranon and patellar bursitis were similar with respect to age, male predominance, and frequency of bursal trauma; patients managed operatively were younger (p = 0.05). Clinical features at presentation and comorbidities were similar despite bursitis site, history of trauma, or management. The most common organism isolated from bursal fluid was Staphylococcus aureus. Patients managed operatively were discharged to rehabilitation less frequently (p = 0.04). This study of septic bursitis is among the largest reported. We were unable to identify presenting clinical features that differentiated patients treated surgically from those treated conservatively. There was no clear relationship between preceding trauma or bursitis site and clinical course, management, or outcomes. Patients with bursitis treated surgically were younger. Additional study is needed to identify patients who would benefit from early surgical intervention for septic bursitis.

  5. The epidemiology of septic shock in French intensive care units: the prospective multicenter cohort EPISS study

    PubMed Central

    2013-01-01

    Introduction To provide up-to-date information on the prognostic factors associated with 28-day mortality in a cohort of septic shock patients in intensive care units (ICUs). Methods Prospective, multicenter, observational cohort study in ICUs from 14 French general (non-academic) and university teaching hospitals. All consecutive patients with septic shock admitted between November 2009 and March 2011 were eligible for inclusion. We prospectively recorded data regarding patient characteristics, infection, severity of illness, life support therapy, and discharge. Results Among 10,941 patients admitted to participating ICUs between October 2009 and September 2011, 1,495 (13.7%) patients presented inclusion criteria for septic shock and were included. Invasive mechanical ventilation was needed in 83.9% (n = 1248), inotropes in 27.7% (n = 412), continuous renal replacement therapy in 32.5% (n = 484), and hemodialysis in 19.6% (n = 291). Mortality at 28 days was 42% (n = 625). Variables associated with time to mortality, right-censored at day 28: age (for each additional 10 years) (hazard ratio (HR) = 1.29; 95% confidence interval (CI): 1.20-1.38), immunosuppression (HR = 1.63; 95%CI: 1.37-1.96), Knaus class C/D score versus class A/B score (HR = 1.36; 95%CI:1.14-1.62) and Sepsis-related Organ Failure Assessment (SOFA) score (HR = 1.24 for each additional point; 95%CI: 1.21-1.27). Patients with septic shock and renal/urinary tract infection had a significantly longer time to mortality (HR = 0.56; 95%CI: 0.42-0.75). Conclusion Our observational data of consecutive patients from real-life practice confirm that septic shock is common and carries high mortality in general ICU populations. Our results are in contrast with the clinical trial setting, and could be useful for healthcare planning and clinical study design. PMID:23561510

  6. [Recent data on the physiopathology of septic shock].

    PubMed

    Lissac, J; Kayal, S

    1995-11-01

    This review is going on to emphasize recent advances of the pathophysiology of septic shock (SS) which goes-between the systemic inflammatory response syndrome (SIRS) and the multisystem organ failure (MOF). By several recent studies, our knowledge of the cellular and molecular pathophysiology of the SS has dramatically increased. Bacterial products, immunocompetent cells, soluble mediators, and cell-cell interactions between blood cells and endothelium have been reviewed. The metabolic disorders following SS can also be observed during SIRS. Still further, these abnormalities do not accurately predict prognosis, except some of them. A wealth of pre-clinical data suggests the efficacy and potentially useful therapeutic strategies like specific immunotherapy (anti-endotoxin, antimediators). Discrepancies between animals models and unexpected and disappointing clinical trial results during SS are discussed. Blocking simultaneously the hole metabolic patterns of SS which is a complex, multisystem, and multifactorial pathologic process seems to be a utopian situation. Furthermore SS occuring more frequently as a complication of nosocomial infection, the high cost of such a novel therapeutic strategy has to be taken into account.

  7. Clinical management of septic arthritis in cattle.

    PubMed

    Desrochers, André; Francoz, David

    2014-03-01

    Synovial fluid, ultrasound, and radiographic imaging are common diagnostic tools for septic arthritis. Mycoplasma septic arthritis is suspected in calves with clinical signs of otitis and pneumonia. Commonly affected joints are carpus, stifle, and tarsus. Treatment strategy must include long-term antibiotics, anti-inflammatories, and joint lavage. Knowledge of communication and boundaries for commonly affected joints is essential to perform joint lavage and arthrotomy.

  8. Prospective Testing and Redesign of a Temporal Biomarker Based Risk Model for Patients With Septic Shock: Implications for Septic Shock Biology

    PubMed Central

    Wong, Hector R.; Cvijanovich, Natalie Z.; Anas, Nick; Allen, Geoffrey L.; Thomas, Neal J.; Bigham, Michael T.; Weiss, Scott L.; Fitzgerald, Julie; Checchia, Paul A.; Meyer, Keith; Quasney, Michael; Hall, Mark; Gedeit, Rainer; Freishtat, Robert J.; Nowak, Jeffrey; Raj, Shekhar S.; Gertz, Shira; Howard, Kelli; Harmon, Kelli; Lahni, Patrick; Frank, Erin; Hart, Kimberly W.; Lindsell, Christopher J.

    2015-01-01

    The temporal version of the pediatric sepsis biomarker risk model (tPERSEVERE) estimates the risk of a complicated course in children with septic shock based on biomarker changes from days 1 to 3 of septic shock. We validated tPERSEVERE performance in a prospective cohort, with an a priori plan to redesign tPERSEVERE if it did not perform well. Biomarkers were measured in the validation cohort (n = 168) and study subjects were classified according to tPERSEVERE. To redesign tPERSEVERE, the validation cohort and the original derivation cohort (n = 299) were combined and randomly allocated to training (n = 374) and test (n = 93) sets. tPERSEVERE was redesigned using the training set and CART methodology. tPERSEVERE performed poorly in the validation cohort, with an area under the curve (AUC) of 0.67 (95% CI: 0.58–0.75). Failure analysis revealed potential confounders related to clinical characteristics. The redesigned tPERSEVERE model had an AUC of 0.83 (0.79–0.87) and a sensitivity of 93% (68–97) for estimating the risk of a complicated course. Similar performance was seen in the test set. The classification tree segregated patients into two broad endotypes of septic shock characterized by either excessive inflammation or immune suppression. PMID:26844289

  9. The innate immune response in HIV/AIDS septic shock patients: a comparative study.

    PubMed

    Amancio, Rodrigo T; Japiassu, Andre M; Gomes, Rachel N; Mesquita, Emersom C; Assis, Edson F; Medeiros, Denise M; Grinsztejn, Beatriz; Bozza, Patrícia T; Castro-Faria Neto, Hugo C; Bozza, Fernando A

    2013-01-01

    In recent years, the incidence of sepsis has increased in critically ill HIV/AIDS patients, and the presence of severe sepsis emerged as a major determinant of outcomes in this population. The inflammatory response and deregulated cytokine production play key roles in the pathophysiology of sepsis; however, these mechanisms have not been fully characterized in HIV/AIDS septic patients. We conducted a prospective cohort study that included HIV/AIDS and non-HIV patients with septic shock. We measured clinical parameters and biomarkers (C-reactive protein and cytokine levels) on the first day of septic shock and compared these parameters between HIV/AIDS and non-HIV patients. We included 30 HIV/AIDS septic shock patients and 30 non-HIV septic shock patients. The HIV/AIDS patients presented low CD4 cell counts (72 [7-268] cells/mm(3)), and 17 (57%) patients were on HAART before hospital admission. Both groups were similar according to the acute severity scores and hospital mortality. The IL-6, IL-10 and G-CSF levels were associated with hospital mortality in the HIV/AIDS septic group; however, the CRP levels and the surrogates of innate immune activation (cytokines) were similar among HIV/AIDS and non-HIV septic patients. Age (odds ratio 1.05, CI 95% 1.02-1.09, p=0.002) and the IL-6 levels (odds ratio 1.00, CI 95% 1.00-1.01, p=0.05) were independent risk factors for hospital mortality. IL-6, IL-10 and G-CSF are biomarkers that can be used to predict prognosis and outcomes in HIV/AIDS septic patients. Although HIV/AIDS patients are immunocompromised, an innate immune response can be activated in these patients, which is similar to that in the non-HIV septic population. In addition, age and the IL-6 levels are independent risk factors for hospital mortality irrespective of HIV/AIDS disease.

  10. Naloxone in Septic Shock: Report of Two Cases

    PubMed Central

    Siram, S.; Park, Soon-young

    1984-01-01

    Two cases are reported describing the use of intravenous naloxone in surgical patients with prolonged hypotension unresponsive to conventional intensive care, including dopamine, intravenous fluids, diuretics, and steroids. The findings were in agreement with those of previous reports suggesting that endorphins may contribute to the hypotension of sepsis and that naloxone's antagonistic effect on endorphin may have therapeutic value in the treatment of septic shock. PMID:6471112

  11. [A case of septic shock following incarceration of the penis].

    PubMed

    Horiguchi, A; Hatakeyama, N; Oyama, M; Ikeuchi, K

    1998-03-01

    An 84-year-old male presented to the emergency room with the chief complaint of painful, swollen penis following the use of a constriction ring to maintain penile erection. A high fever, chills and hypotension were recognized. Septic shock was presumed, and administration of antibiotics was started. Microbiologic cultures revealed Escherichia coli in blood. We herein report a rare but serious complication accompanying incarceration of the penis.

  12. Treatment of septic shock with continuous HDF using 2 PMMA hemofilters for enhanced intensity.

    PubMed

    Matsumura, Yosuke; Oda, Shigeto; Sadahiro, Tomohito; Nakamura, Masataka; Hirayama, Yo; Watanabe, Eizo; Abe, Ryuzo; Nakada, Taka-Aki; Tateishi, Yoshihisa; Oshima, Taku; Shinozaki, Koichiro; Hirasawa, Hiroyuki

    2012-01-01

    Cytokines play pivotal roles in the pathophysiology of severe sepsis/septic shock, and continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA-CHDF) removes cytokines efficiently and continuously, mainly through adsorption to a hemofilter membrane. The aim of this study was to investigate the clinical efficacy of enhanced intensity PMMA-CHDF in treating refractory septic shock. Seventy-two septic shock patients admitted to the intensive care unit (ICU) underwent critical care including PMMA-CHDF. We employed enhanced intensity PMMA-CHDF to improve the cytokine removal rate by increasing the hemofilter membrane area in 10 refractory septic shock patients (enhanced intensity group, EI group; 2 extracorporeal CHDF circuits using the hemofilter with a larger membrane area of 2.1 m2). Other patients undergoing conventional PMMA-CHDF and matched for severity with the EI group, comprised a matched conventional group (MC group; using a PMMA membrane hemofilter with a membrane area of 1.0 m2; n=15). The case-control comparison was performed between the 2 groups. Enhanced intensity PMMA-CHDF significantly increased mean arterial pressure by 23.8% in 1 hour (p=0.037), decreased the blood lactate level by 28.6% in 12 hours (p=0.006), and reduced blood IL-6 level in 24 hours (p=0.005). The ICU survival rate in the EI group was significantly better than that in the MC group (60% vs. 13.3%, p=0.028). Enhanced intensity PMMA-CHDF may improve hemodynamics and survival rate in patients with refractory septic shock.

  13. The determinants of hospital mortality among patients with septic shock receiving appropriate initial antibiotic treatment*.

    PubMed

    Labelle, Andrew; Juang, Paul; Reichley, Richard; Micek, Scott; Hoffmann, Justin; Hoban, Alex; Hampton, Nicholas; Kollef, Marin

    2012-07-01

    To identify the determinants of hospital mortality among patients with septic shock receiving appropriate initial antibiotic treatment. A retrospective cohort study of hospitalized patients with blood culture positive septic shock (January 2002-December 2007). Barnes-Jewish Hospital, a 1,250-bed urban teaching hospital. Four hundred thirty-six consecutive patients with septic shock and a positive blood culture. Data abstraction from computerized medical records. Septic shock was associated with bloodstream infection due to Gram-negative bacteria (59.2%) and Gram-positive bacteria (40.8%). Two hundred twenty-four patients (51.4%) died during their hospitalization. The presence of infection attributed to antibiotic-resistant bacteria was similar for patients who survived and expired (22.6% vs. 20.1%; p = .516). Multivariate logistic regression analysis demonstrated that infection acquired in the intensive care unit (adjusted odds ratio 1.99; 95% confidence interval 1.52-2.60; p = .011) and increasing Acute Physiology and Chronic Health Evaluation II scores (one-point increments) (adjusted odds ratio 1.11; 95% confidence interval 1.09-1.14; p < .001) were independently associated with a greater risk of hospital mortality, whereas infection with methicillin-susceptible Staphylococcus aureus (adjusted odds ratio 0.32; 95% confidence interval 0.20-0.52; p = .017) was independently associated with a lower risk of hospital mortality. Patients infected with methicillin-susceptible Staphylococcus aureus infections were statistically younger and had lower Charlson comorbidity and Acute Physiology and Chronic Health Evaluation II scores compared to patients with non-methicillin-susceptible Staphylococcus aureus infections. Among patients with septic shock who receive appropriate initial antibiotic treatment, acquisition of infection in the intensive care unit and severity of illness appear to be the most important determinants of clinical outcome.

  14. [Septic shock. Update of treatment using hypertonic saline and antidiuretic hormone-vasopressin].

    PubMed

    Pascual-Ramírez, J; Aguirre Sánchez-Covisa, M; Araujo, F; Gil Trujillo, S; Collar, L G; Bocharán, S

    2012-01-01

    Safety in the use of small volumes of hypertonic saline solution for hypovolaemic shock and in the treatment of intracranial hypertension has been demonstrated in studies in the field of resuscitation. There is little experience of this for septic shock in humans. Beneficial immunomodulatory effects have been detected in pre-clinical studies. Interactions with the pituitary-adrenal axis and with the secretion of anti-diuretic hormone are varied and suggestive, but are not sufficiently understood. On the other hand, vasopressin has cardiovascular, osmoregulatory, and coagulation effects, and also acts on the hypothalamic-pituitary-adrenal axis. There is a relative deficit of vasopressin in septic shock. Its use in these patients does not seem to have any advantages as regards mortality, but may be beneficial in patients at risk from acute renal failure, or those who receive corticosteroids. Terlipressin is a vasopressin analogue that has also been studied. The synergy between vasopressin and hypertonic saline is a hypothesis that is mainly supported in pre-clinical studies. The use of hypertonic saline solution in septic shock, although promising, is still experimental, and must be restricted to the field of controlled clinical trials.

  15. Effects of High Volume Haemodiafiltration on Inflammatory Response Profile and Microcirculation in Patients with Septic Shock

    PubMed Central

    Tamme, Kadri; Kruusat, Rein; Ehrlich, Hans-Erik; Viirelaid, Mirjam

    2015-01-01

    Background. High volumes of haemofiltration are used in septic patients to control systemic inflammation and improve patient outcomes. We aimed to clarify if extended intermittent high volume online haemodiafiltration (HVHDF) influences patient haemodynamics and cytokines profile and/or has effect upon sublingual microcirculation in critically ill septic shock patients. Methods. Main haemodynamic and clinical variables and concentrations of cytokines were evaluated before and after HVHDF in 19 patients with septic shock requiring renal replacement therapy due to acute kidney injury. Sublingual microcirculation was assessed in 9 patients. Results. The mean (SD) time of HVHDF was 9.4 (1.8) hours. The median convective volume was 123 mL/kg/h. The mean (SD) dose of norepinephrine required to maintain mean arterial pressure at the target range of 70–80 mmHg decreased from 0.40 (0.43) μg/kg/min to 0.28 (0.33) μg/kg/min (p = 0.009). No significant changes in the measured cytokines or microcirculatory parameters were observed before and after HVHDF. Conclusions. The single-centre study suggests that extended HVHDF results in decrease of norepinephrine requirement in patients with septic shock. Haemodynamic improvement was not associated with decrease in circulating cytokine levels, and sublingual microcirculation was well preserved. PMID:26064875

  16. Comparison of Hydroxocobalamin Versus Norepinephrine Versus Saline in a Swine Model of Servere Septic Shock

    DTIC Science & Technology

    2016-05-20

    Versus Saline in a Swine Model of Severe Septic Shock presented at/published to SURF Conference, San Antonio, TX 20 May 2016 with MDWJ 41-108, and has...PRESENTED: Comparison of hydroxocobalamin versus norepinephrine versus saline in a Swine model of severe septic shock 7. FUNDING RECEIVED FOR THIS...Comparison of hydroxocbalamin versus norepinephrine versus saline in a swine model of severe septic shock. Background: Sepsis is associated with a mortality

  17. 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

    Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. To evaluate and, as needed, update definitions for sepsis and septic shock. A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock

  18. Septic arthritis and subsequent fatal septic shock caused by Vibrio vulnificus infection.

    PubMed

    Emamifar, Amir; Asmussen Andreasen, Rikke; Skaarup Andersen, Nanna; Jensen Hansen, Inger Marie

    2015-11-24

    Vibrio vulnificus is a rare but potential fatal bacterium that can cause severe infections. Wound infections, primary sepsis and gastroenteritis are the most common clinical features. Septic arthritis caused by V. vulnificus is an atypical presentation that has been reported in only two case reports; however, it has not been previously noted in Denmark. The authors report a case of septic arthritis caused by V. vulnificus in an immunocompromised patient. The disease progressed to severe sepsis and subsequent death within 10 h of admission.

  19. Prognostic value of the reactive oxygen species in severe sepsis and septic shock patients: a pilot study.

    PubMed

    Montini, Luca; DE Sole, Pasquale; Pennisi, Mariano A; Rossi, Cristina; Scatena, Roberto; DE Pascale, Gennaro; Bello, Giuseppe; Cutuli, Salvatore L; Antonelli, Massimo

    2016-12-01

    Reactive oxygen species (ROS) have been shown to play a role in the pathophysiology of sepsis. The aim of this study was to investigate ROS production over time in critically ill with sepsis patients and its correlation with outcome. This was a pilot single-centre prospective, observational study of patients consecutively admitted to our 18-general ICU. Over a period of 6 months all the consecutive patients with recent-onset of severe sepsis or septic shock were enrolled. Clinical and demographic characteristics of all patients were recorded. ROMs (ROS metabolites), reduced sulfhydryl groups (SH) and plasmatic lactate levels were collected at enrollment in the study and then every 5-7 days over 28 days or until sepsis resolution or death during sepsis. ROMs were analysed spectrophotometrically by the d-ROMs test (Diacron-Italia). SH were assayed in plasma by Ellman's reaction by spectrophotometric method. Septic shock-related mortality was defined as death that occurred during the follow up period, when the signs of shock remained, and death could not be attributed to causes other than septic shock by the attending physician. Twenty-five patients were studied. The SOFA score and the plasmatic lactate levels significantly correlated with the ROMs plasmatic levels. The mortality rate was higher in patients whose ROMs plasmatic levels decreased during septic shock evolution. Serial measurements of the ROMs plasmatic levels together with the SOFA score and lactate levels could help to identify septic shock patients with a very high probability of death.

  20. Blood histamine concentrations are not elevated in humans with septic shock

    SciTech Connect

    Jacobs, R.; Kaliner, M.; Shelhamer, J.H.; Parrillo, J.E.

    1989-01-01

    Histamine has been suggested as an important mediator of the cardiovascular abnormalities during septic shock. To determine if blood histamine levels were increased during human sepsis and septic shock, plasma histamine was measured using a very sensitive radioenzyme assay employing histamine N-methyltransferase (HNMT) in the following patient groups: normal controls (n = 76), nonseptic critically ill (n = 12), nonseptic shock (n = 2), sepsis without shock (n = 28), and septic shock (n = 41). Using this enzyme binding assay, all these groups had similar, normal plasma histamine concentrations, except those patients with septic shock whose mean histamine measurements were significantly reduced (p less than .002). This decrease was found to be due to an artifact of the assay: plasma contained a circulating inhibitor that falsely lowered the measured histamine level. Fractionation of septic shock plasma using molecular exclusion membranes and gel filtration revealed a 5000 MW inhibitory factor. After removal of this inhibitor from plasma, septic shock plasma histamine levels were normal. Thus, septic shock patients may have a circulating inhibitor of the HNMT enzyme, but plasma histamine concentrations are normal. Histaminemia is unlikely to play an important role in the pathogenesis of septic shock in humans.

  1. Hemophagocytic lymphohistiocytosis: a potentially underrecognized association with systemic inflammatory response syndrome, severe sepsis, and septic shock in adults.

    PubMed

    Raschke, Robert A; Garcia-Orr, Roxanne

    2011-10-01

    Hemophagocytic lymphohistiocytosis (HLH) was originally described as a genetic disorder of immune regulation, presenting in neonates with protracted fever, hepatosplenomegaly, and cytopenia. A secondary form of HLH, triggered by serious infections, was subsequently described in adults. We report three adult patients who presented with systemic inflammatory response syndrome and features consistent with severe sepsis and septic shock, who subsequently received a diagnosis of secondary HLH. We reviewed the relationship between infection-triggered HLH and septic shock from the perspective of the adult intensivist. The hyperinflammatory pathophysiologic characteristics of HLH and septic shock are closely intertwined. Clinical and laboratory features of HLH and septic shock overlap in some patients, making the syndromes difficult to distinguish. In our experience and review, progressive pancytopenia was the feature most likely to suggest secondary HLH in the adult patient with presumed (or definite) septic shock. Use of other HLH-2004 diagnostic criteria is hindered by the poor operating characteristics of these tests in critically ill adults. Bone marrow aspiration is the most useful diagnostic test, but may yield an initial false-negative result. The HLH-2004 treatment protocol is not of proven benefit in critically ill adults, but observational data suggest that aggressive immunosuppressive therapy should not be delayed. Further study of HLH in the critical care setting might provide important insights into the pathogenesis and clinical treatment of sepsis.

  2. Resuscitation bundle compliance in severe sepsis and septic shock: improves survival, is better late than never.

    PubMed

    Coba, Victor; Whitmill, Melissa; Mooney, Roberta; Horst, H Mathilda; Brandt, Mary-Margaret; Digiovine, Bruno; Mlynarek, Mark; McLellan, Beth; Boleski, Gail; Yang, James; Conway, William; Jordan, Jack

    2011-01-01

    While clinicians' management of severe sepsis and septic shock has been positively influenced by a number of clinical research studies in the last decade, challenges remain regarding early hemodynamic optimization as envisioned in the Surviving Sepsis Campaign's (SSC) resuscitation bundle (RB). We examined the impact of a hospital-wide continuous quality improvement (CQI) initiative on patients presenting with severe sepsis and septic shock, and the impact of the sepsis RB on patient outcomes when completed beyond the 6-hour recommendation period. The study was an 18-month, prospective cohort study enrolling patients who met the definition of severe sepsis or septic shock. Compliance with the hemodynamic components of the sepsis RB was defined as achieving goal mean arterial pressure (MAP) ≥ 65 mm Hg, central venous pressure (CVP) ≥ 8 mm Hg, and central venous oxygen saturation (ScvO₂) ≥ 70%. Compliance was assessed at 6 hours and 18 hours after diagnosis of severe sepsis or septic shock. In all, 498 patients with severe sepsis and/or septic shock were evaluated to determine the upper limit of the range of hours that compliance with the RB would still improve outcomes. Using 18 hours as a marker, Compliers at 18 hrs and Non-Compliers at 18 hrs were compared. There were 202 patients who had the RB completed in less than or equal to 18 hours. There were 296 patients who did not complete the RB at 18 hours. The Compliers at 18 hrs had a significant 10.2% lower hospital mortality 37.1% (22% relative reduction) compared to the Non-Compliers at 18 hrs hospital mortality of 47.3% (P < .03). When the two groups were adjusted for differences in baseline illness severity, the Compliers at 18 hrs had a greater reduction in predicted mortality of 26.8% versus 9.4%, P < 0.01. Initiating the sepsis RB for patients with severe sepsis and/or septic shock decreased mortality. A CQI initiative that monitored the implementation in real-time allowed for improvement in

  3. Antimicrobial pharmacokinetic and pharmacodynamic issues in the critically ill with severe sepsis and septic shock.

    PubMed

    Varghese, Julie M; Roberts, Jason A; Lipman, Jeffrey

    2011-01-01

    Antimicrobial pharmacokinetics (PK) and pharmacodynamics (PD) are important considerations, particularly in critically ill patients with severe sepsis and septic shock. The pathophysiologic changes that occur in these conditions can have a major effect on pharmacokinetic parameters, which in turn could result in failure to achieve pharmacodynamic targets for antimicrobials thus adversely affecting clinical outcome. This paper discusses the pathophysiologic changes that occur during severe sepsis and septic shock and the consequent effects on antimicrobial PK and PD. The effect of PK/PD on specific antimicrobial classes is discussed and a rational framework for antimicrobial dosing is provided. Knowledge of PK/PD properties of antimicrobials can be used to personalize dosing regimens not only to maximize antimicrobial activity but also to minimize toxicity and reduce the development of antimicrobial resistance.

  4. Plasma cytokine levels predict response to corticosteroids in septic shock.

    PubMed

    Bentzer, Peter; Fjell, Chris; Walley, Keith R; Boyd, John; Russell, James A

    2016-12-01

    To investigate if plasma cytokine concentrations predict a beneficial response to corticosteroid treatment in septic shock patients. A cohort of septic shock patients in whom a panel of 39 cytokines had been measured at baseline (n = 363) was included. Patients who received corticosteroids were propensity score matched to non-corticosteroid-treated patients. An optimal threshold to identify responders to corticosteroid treatment for each cytokine was defined as the concentration above which the odds ratio for 28-day survival between corticosteroid- and non-corticosteroid-treated patients was highest. Propensity score matching partitioned 165 patients into 61 sets; each set contained matched corticosteroid- and non-corticosteroid-treated patients. For 13 plasma cytokines threshold concentrations were found where the odds ratio for survival between corticosteroid- and non-corticosteroid-treated patients was significant (P < 0.05). CD40 ligand was associated with the highest odds ratio and identified 21 % of the patients in the propensity score matched cohort as responders to corticosteroid treatment. Combinations of triplets of cytokines with a significant odds ratio, using the thresholds identified above, were tested to find a higher proportion of responders. IL3, IL6, and CCL4 identified 50 % of the patients in the propensity score matched cohort as responders to corticosteroid treatment. The odds ratio for 28-day survival was 19 (95 % CI 3.5-140, P = 0.02) with a concentration above threshold for a least one of these cytokines. Plasma concentration of selected cytokines is a potential predictive biomarker to identify septic shock patients that may benefit from treatment with corticosteroids.

  5. [Fluid resuscitation strategy in septic shock following urinary infection with severe pulmonary capillary leakage].

    PubMed

    Chang, Ping; Peng, Sheng; Zhou, Jian; Xie, Hai-ting; Liu, Zhan-guo; Wang, Hua

    2013-01-01

    To characterize septic shock following urinary infection with severe pulmonary capillary leakage, and to evaluate the fluid therapy on treatment of hypovolemic shock and the role of transpulmonary thermodilution technique with pulse induced continuous cardiac output (PiCCO) monitoring. A retrospective study was conducted. Eight patients surviving septic shock following urinary infection with severe pulmonary capillary leakage were enrolled, and all of them underwent PiCCO monitoring in the intensive care unit (ICU) when the diagnosis was established. The monitoring started at admission, and ended when shock was corrected or transferred from ICU. The clinical data including general end diastolic volume index (GEDVI), extravascular lung water index (EVLWI), input and output volume of fluid, net fluid balance, oxygenation index (PaO2/FiO2), the level of arterial blood lactic acid, and chest X ray were collected and analyzed retrospectively the characteristics of septic shock following urinary infection, and the role of PiCCO monitoring in fluid resuscitation. Septic shock following urinary infection occurred in a median of 4.5 days in 8 patients after renal and ureteric calculi lithotripsy, accompanied with severe pulmonary vessel effusion and hypoxemia in different degrees. The mean value of EVLWI was (22±7) ml/kg, and the PaO2/FiO2 (164±82) mm Hg at the time of admission to ICU. Conservative fluid resuscitation strategy was adopted in management of septic shock with severe pulmonary capillary leakage, the mean fluid input in 8 patients was (2412±1121) ml/d, and the net fluid balance -553 ml/d, and the central venous pressure (CVP) and GEDVI were maintained at levels of (9±3) mm Hg and (749±236) ml/m(2) respectively. Diuretics were administered to 6 patients and the mean dosage of fursemide was (264±133) mg. Norepinephrine and dobutamine infusion were given to 7 patients to maintain blood pressure at normal range for (4±1) days. Seven patients were

  6. Management of septic shock and severe infections in migrants and returning travelers requiring critical care.

    PubMed

    Alp, E; Erdem, H; Rello, J

    2016-04-01

    During the past decade, global human movement created a virtually "borderless world". Consequently, the developed world is facing "forgotten" and now imported infectious diseases. Many infections are observed upon travel and migration, and the clinical spectrum is diverse, ranging from asymptomatic infection to severe septic shock. The severity of infection depends on the etiology and timeliness of diagnosis. While assessing the etiology of severe infection in travelers and migrants, it is important to acquire a detailed clinical history; geography, dates of travel, places visited, type of transportation, lay-overs and intermediate stops, potential exposure to exotic diseases, and activities that were undertaken during travelling and prophylaxis and vaccines either taken or not before travel are all important parameters. Tuberculosis, malaria, pneumonia, visceral leishmaniasis, enteric fever and hemorrhagic fever are the most common etiologies in severely infected travelers and migrants. The management of severe sepsis and septic shock in migrants and returning travelers requires a systematic approach in the evaluation of these patients based on travel history. Early and broad-spectrum therapy is recommended for the management of septic shock comprising broad spectrum antibiotics, source control, fluid therapy and hemodynamic support, corticosteroids, tight glycemic control, and organ support and monitoring. We here review the diagnostic and therapeutic routing of severely ill travelers and migrants, stratified by the nature of the infectious agents most often encountered among them.

  7. [The MEDAN database: patients with abdominal septic shock].

    PubMed

    Paetz, J; Erz, K; Arlt, B; Hanisch, E

    2003-04-01

    Septic shock still has an unacceptable high mortality rate. To lowering this high mortality rate in the long run, we built a database that is unique in its data amount. Until now we have transferred 282 handwritten patient records into our database. Data were collected retrospectively from 1997 to 2001, based on voluntary cooperation of 62 hospitals. With the preprocessed data of our database we give mainly an epidemiologic overview and make first statistical evaluations. Thereby we noticed that some diagnoses and operations appear significantly higher for deceased patients than for survivors. At the end we discuss the future potential of the database.

  8. Refractory septic shock in children: a European Society of Paediatric and Neonatal Intensive Care definition.

    PubMed

    Morin, Luc; Ray, Samiran; Wilson, Clare; Remy, Solenn; Benissa, Mohamed Rida; Jansen, Nicolaas J G; Javouhey, Etienne; Peters, Mark J; Kneyber, Martin; De Luca, Daniele; Nadel, Simon; Schlapbach, Luregn Jan; Maclaren, Graeme; Tissieres, Pierre

    2016-12-01

    Although overall paediatric septic shock mortality is decreasing, refractory septic shock (RSS) is still associated with high mortality. A definition for RSS is urgently needed to facilitate earlier identification and treatment. We aim to establish a European society of paediatric and neonatal intensive care (ESPNIC) experts' definition of paediatric RSS. We conducted a two-round Delphi study followed by an observational multicentre retrospective study. One hundred and fourteen paediatric intensivists answered a clinical case-based, two-round Delphi survey, identifying clinical items consistent with RSS. Multivariate analysis of these items in a development single-centre cohort (70 patients, 30 % mortality) facilitated development of RSS definitions based on either a bedside or computed severity score. Both scores were subsequently tested in a validation cohort (six centres, 424 patients, 11.6 % mortality). From the Delphi process, the draft definition included evidence of myocardial dysfunction and high blood lactate levels despite high vasopressor treatment. When assessed in the development population, each item was independently associated with the need for extracorporeal life support (ECLS) or death. Resultant bedside and computed septic shock scores had high discriminative power against the need for ECLS or death, with areas under the receiver operating characteristics curve of 0.920 (95 % CI 0.89-0.94), and 0.956 (95 % CI 0.93-0.97), respectively. RSS defined by a bedside score equal to or higher than 2 and a computed score equal to or higher than 3.5 was associated with a significant increase in mortality. This ESPNIC definition of RSS accurately identifies children with the most severe form of septic shock.

  9. A new mass spectrometry-based method for the quantification of histones in plasma from septic shock patients.

    PubMed

    García-Giménez, J L; Romá-Mateo, C; Carbonell, N; Palacios, L; Peiró-Chova, L; García-López, E; García-Simón, M; Lahuerta, R; Gimenez-Garzó, C; Berenguer-Pascual, E; Mora, M I; Valero, M L; Alpízar, A; Corrales, F J; Blanquer, J; Pallardó, F V

    2017-09-06

    The aim of this study was to develop a novel method to detect circulating histones H3 and H2B in plasma based on multiple reaction monitoring targeted mass spectrometry and a multiple reaction monitoring approach (MRM-MS) for its clinical application in critical bacteriaemic septic shock patients. Plasma samples from 17 septic shock patients with confirmed bacteraemia and 10 healthy controls were analysed by an MRM-MS method, which specifically detects presence of histones H3 and H2B. By an internal standard, it was possible to quantify the concentration of circulating histones in plasma, which were significantly higher in patients, and thus confirmed their potential as biomarkers for diagnosing septic shock. After comparing surviving patients and non-survivors, a correlation was found between higher levels of circulating histones and unfavourable outcome. Indeed, histone H3 proved a more efficient and sensitive biomarker for septic shock prognosis. In conclusion, these findings suggest the accuracy of the MRM-MS technique and stable isotope labelled peptides to detect and quantify circulating plasma histones H2B and H3. This method may be used for early septic shock diagnoses and for the prognosis of fatal outcomes.

  10. Continuous cardiac output measurement by un-calibrated pulse wave analysis and pulmonary artery catheter in patients with septic shock.

    PubMed

    Ganter, Michael T; Alhashemi, Jamal A; Al-Shabasy, Adel M; Schmid, Ursina M; Schott, Peter; Shalabi, Sanaa A; Badri, Ahmed M; Hartnack, Sonja; Hofer, Christoph K

    2016-02-01

    Septic shock is a serious medical condition. With increased concerns about invasive techniques, a number of non-invasive and semi-invasive devices measuring cardiac output (CO) have become commercially available. The aim of the present study was to determine the accuracy, precision and trending abilities of the FloTrac and the continuous pulmonary artery catheter thermodilution technique determining CO in septic shock patients. Consecutive septic shock patients were included in two centres and CO was measured every 4 h up to 48 h by FloTrac (APCO) and by pulmonary artery catheter (PAC) using the continuous (CCO) and intermittent (ICO) technique. Forty-seven septic shock patients with 326 matched sets of APCO, CCO and ICO data were available for analysis. Bland and Altman analysis revealed a mean bias ±2 SD of 0.0 ± 2.14 L min(-1) for APCO-ICO (%error = 34.5 %) and 0.23 ± 2.55 L min(-1) for CCO-ICO (%error = 40.4 %). Trend analysis showed a concordance of 85 and 81 % for APCO and CCO, respectively. In contrast to CCO, APCO was influenced by systemic vascular resistance and by mean arterial pressure. In septic shock patients, APCO measurements assessed by FloTrac but also the established CCO measurements using the PAC did not meet the currently accepted statistical criteria indicating acceptable clinical performance.

  11. The role of contact system in septic shock: the next target? An overview of the current evidence.

    PubMed

    Nicola, Henrique

    2017-01-01

    Septic shock remains challenging to intensive care units worldwide, despite recent documented improvement in mortality over the years. Multiple new therapies have been attempted without success in large clinical trials. Evidence concerning the role of the contact system and bradykinin on septic shock physiological manifestations is shown by this article. The objective of the study is to review the current evidence linking contact system activation and septic shock, as well as efficacy of available therapies targeting this pathophysiological pathway and to evaluate the potential of further researching the matter. Multiple animal studies are already available and suggestive of a meaningful role of contact system activation on septic shock. However, human trials are still scarce, and the ones available are not enough to establish such a strong connection. Furthermore, attempted therapies have been successful across multiple species, but not as much in humans. Therefore, contact system and septic shock relationship remains plentiful in questions to be answered in the coming years or decades. Whether the contact system is not as relevant in humans as it is in animals or there is only lack of evidence remains to be explained. The subject is an attractive open field for further research aiming to aid in tackling such a burdensome condition.

  12. Effect of early fluid resuscitation on the lung in a rat model of lipopolysaccharide-induced septic shock.

    PubMed

    Liu, W; Shan, L P; Dong, X S; Liu, X W; Ma, T; Liu, Z

    2013-01-01

    Many clinical trials have showed that early fluid resuscitation can improve the prognosis and reduce the mortality rate of patients with septic shock. However, some experiments suggest that abundant fluid may injure the lung and other tissues. To evaluate the protective effect of early fluid resuscitation and simultaneous norepinephrine treatment on lung function by using the rat model of lipopolysaccharide (LPS)-induced septic shock. Male Wistar rats were randomly divided into four groups: normal control group, septic shock control group, early fluid resuscitation treatment group, early fluid resuscitation and simultaneous norepinephrine treatment group. Blood gas, lactate, fluid volume, and dose of norepinephrine were recorded. Pathological change was observed by hematoxylin and eosin staining and transmission electron microscopy. The activities of hydroxyl radicals, MDA, SOD and MPO were detected by spectrophotometry. The expression of IL-6, IL-8, and TNF-alpha were determined with ELISA kits. LPS could induce rats to suffer from acute lung injury in early stage of septic shock. Early fluid resuscitation could guarantee effective circulating blood volume and tissue perfusion pressure, improve microcirculatory derangements, increase oxygen partial pressure and oxygenation index, but have the tendency to aggravate pulmonary edema. Simultaneous norepinephrine treatment in early stage could decrease the fluid volume, alleviate the degree of pulmonary edema, reduce the expression level of pro-inflammatory mediators in the serum and BALF, and increase the oxygenation index. Early fluid resuscitation and simultaneous norepinephrine treatment may be a superior alternative to protect lung injury secondary to septic shock.

  13. Polymyxin B-immobilized fiber hemoperfusion with the PMX-05R column in elderly patients suffering from septic shock.

    PubMed

    Nakamura, Tsukasa; Kawagoe, Yasuhiro; Suzuki, Tsukasa; Shoji, Hisataka; Ueda, Yoshihiko; Koide, Hikaru

    2007-10-01

    Direct hemoperfusion with the polymyxin B-immobilized fiber (PMX-20R) column has a positive effect on outcome in patients with sepsis or septic shock. The PMX-05R column has a low priming volume and has been used in pediatric patients with septic shock. The aim of the present study was to determine whether PMX-F treatment with the PMX-05R column is effective in elderly patients with septic shock. We performed direct hemoperfusion twice with the PMX-05R column in 8 septic shock patients who were over 80 years of age. Five of the 8 patients survived. The 3 patients who died were undergoing hemodialysis for chronic renal failure, and methicillin-resistant Staphylococcus aureus was detected in all 3. PMX-F treatment significantly increased systolic and diastolic blood pressures (P = 0.0004 for both) and significantly reduced heart rate (P < 0.0001), the blood endotoxin level (P = 0.0011), blood IL-6 level (P = 0.039), C-reactive protein level (P < 0.0001), and white blood cell count (P < 0.0001). Direct hemoperfusion with the PMX-05R column is effective in ameliorating clinical and laboratory abnormalities in elderly septic shock patients.

  14. Early identification and management of patients with severe sepsis and septic shock in the emergency department.

    PubMed

    Keegan, Joshua; Wira, Charles R

    2014-11-01

    Severe sepsis and septic shock have great relevance to Emergency Medicine physicians because of their high prevalence, morbidity, and mortality. Treatment is time-sensitive, depends on early identification risk stratification, and has the potential to significantly improve patient outcomes. In this article, we review the pathophysiology of, and evidence basis for, the emergency department management of severe sepsis and septic shock.

  15. Beta-lactam dosing in critically ill patients with septic shock and continuous renal replacement therapy.

    PubMed

    Ulldemolins, Marta; Vaquer, Sergi; Llauradó-Serra, Mireia; Pontes, Caridad; Calvo, Gonzalo; Soy, Dolors; Martín-Loeches, Ignacio

    2014-06-23

    Although early and appropriate antibiotic therapy remains the most important intervention for successful treatment of septic shock, data guiding optimization of beta-lactam prescription in critically ill patients prescribed with continuous renal replacement therapy (CRRT) are still limited. Being small hydrophilic molecules, beta-lactams are likely to be cleared by CRRT to a significant extent. As a result, additional variability may be introduced to the per se variable antibiotic concentrations in critically ill patients. This article aims to describe the current clinical scenario for beta-lactam dosing in critically ill patients with septic shock and CRRT, to highlight the sources of variability among the different studies that reduce extrapolation to clinical practice, and to identify the opportunities for future research and improvement in this field. Three frequently prescribed beta-lactams (meropenem, piperacillin and ceftriaxone) were chosen for review. Our findings showed that present dosing recommendations are based on studies with drawbacks limiting their applicability in the clinical setting. In general, current antibiotic dosing regimens for CRRT follow a one-size-fits-all fashion despite emerging clinical data suggesting that drug clearance is partially dependent on CRRT modality and intensity. Moreover, some studies pool data from heterogeneous populations with CRRT that may exhibit different pharmacokinetics (for example, admission diagnoses different to septic shock, such as trauma), which also limit their extrapolation to critically ill patients with septic shock. Finally, there is still no consensus regarding the %T>MIC (percentage of dosing interval when concentration of the antibiotic is above the minimum inhibitory concentration of the pathogen) value that should be chosen as the pharmacodynamic target for antibiotic therapy in patients with septic shock and CRRT. For empirically optimized dosing, during the first day a loading dose is required

  16. Beta-lactam dosing in critically ill patients with septic shock and continuous renal replacement therapy

    PubMed Central

    2014-01-01

    Although early and appropriate antibiotic therapy remains the most important intervention for successful treatment of septic shock, data guiding optimization of beta-lactam prescription in critically ill patients prescribed with continuous renal replacement therapy (CRRT) are still limited. Being small hydrophilic molecules, beta-lactams are likely to be cleared by CRRT to a significant extent. As a result, additional variability may be introduced to the per se variable antibiotic concentrations in critically ill patients. This article aims to describe the current clinical scenario for beta-lactam dosing in critically ill patients with septic shock and CRRT, to highlight the sources of variability among the different studies that reduce extrapolation to clinical practice, and to identify the opportunities for future research and improvement in this field. Three frequently prescribed beta-lactams (meropenem, piperacillin and ceftriaxone) were chosen for review. Our findings showed that present dosing recommendations are based on studies with drawbacks limiting their applicability in the clinical setting. In general, current antibiotic dosing regimens for CRRT follow a one-size-fits-all fashion despite emerging clinical data suggesting that drug clearance is partially dependent on CRRT modality and intensity. Moreover, some studies pool data from heterogeneous populations with CRRT that may exhibit different pharmacokinetics (for example, admission diagnoses different to septic shock, such as trauma), which also limit their extrapolation to critically ill patients with septic shock. Finally, there is still no consensus regarding the %T>MIC (percentage of dosing interval when concentration of the antibiotic is above the minimum inhibitory concentration of the pathogen) value that should be chosen as the pharmacodynamic target for antibiotic therapy in patients with septic shock and CRRT. For empirically optimized dosing, during the first day a loading dose is required

  17. [Early goal-directed therapy (EDGT) using continuous central venous oxygen saturation monitoring in a patient with septic shock].

    PubMed

    Oyama, Yoshimasa; Goto, Koji; Yamamoto, Shunsuke; Kusaka, Jyunya; Hidaka, Seigo; Shingu, Chihiro; Noguchi, Takayuki

    2008-04-01

    Septic shock is an adverse clinical condition resulting in multiple organ failure from global tissue hypoxia. The importance of initial treatment is widely recognized. Thus, guidelines for septic shock recommend early goal-directed therapy (EGDT) during the first six hours of treatment. Central venous oxygen saturation monitoring is useful to maintain adequate tissue oxygen delivery. A newly developed central venous oximetry catheter (PreSep Oximetery Catheter, Edwards Lifesciences) allows continuous and easy monitoring of central venous oxygen saturation. This report shows the usefulness of this catheter in a patient who developed septic shock during an emergency operation for perforated bowel. By using EGDT perioperatively with continuous central venous oximetry, multiple organ failure might be successfully avoided.

  18. Reclassifying the spectrum of septic patients using lactate: severe sepsis, cryptic shock, vasoplegic shock and dysoxic shock.

    PubMed

    Ranzani, Otavio Tavares; Monteiro, Mariana Barbosa; Ferreira, Elaine Maria; Santos, Sergio Ricardo; Machado, Flavia Ribeiro; Noritomi, Danilo Teixeira

    2013-01-01

    The current definition of severe sepsis and septic shock includes a heterogeneous profile of patients. Although the prognostic value of hyperlactatemia is well established, hyperlactatemia is observed in patients with and without shock. The present study aimed to compare the prognosis of septic patients by stratifying them according to two factors: hyperlactatemia and persistent hypotension. The present study is a secondary analysis of an observational study conducted in ten hospitals in Brazil (Rede Amil - SP). Septic patients with initial lactate measurements in the first 6 hours of diagnosis were included and divided into 4 groups according to hyperlactatemia (lactate >4mmol/L) and persistent hypotension: (1) severe sepsis (without both criteria); (2) cryptic shock (hyperlactatemia without persistent hypotension); (3) vasoplegic shock (persistent hypotension without hyperlactatemia); and (4) dysoxic shock (both criteria). In total, 1,948 patients were analyzed, and the sepsis group represented 52% of the patients, followed by 28% with vasoplegic shock, 12% with dysoxic shock and 8% with cryptic shock. Survival at 28 days differed among the groups (p<0.001). Survival was highest among the severe sepsis group (69%, p<0.001 versus others), similar in the cryptic and vasoplegic shock groups (53%, p=0.39), and lowest in the dysoxic shock group (38%, p<0.001 versus others). In the adjusted analysis, the survival at 28 days remained different among the groups (p<0.001) and the dysoxic shock group exhibited the highest hazard ratio (HR=2.99, 95%CI 2.21-4.05). The definition of sepsis includes four different profiles if we consider the presence of hyperlactatemia. Further studies are needed to better characterize septic patients, to understand the etiology and to design adequate targeted treatments.

  19. Reclassifying the spectrum of septic patients using lactate: severe sepsis, cryptic shock, vasoplegic shock and dysoxic shock

    PubMed Central

    Ranzani, Otavio Tavares; Monteiro, Mariana Barbosa; Ferreira, Elaine Maria; Santos, Sergio Ricardo; Machado, Flavia Ribeiro; Noritomi, Danilo Teixeira

    2013-01-01

    Objective The current definition of severe sepsis and septic shock includes a heterogeneous profile of patients. Although the prognostic value of hyperlactatemia is well established, hyperlactatemia is observed in patients with and without shock. The present study aimed to compare the prognosis of septic patients by stratifying them according to two factors: hyperlactatemia and persistent hypotension. Methods The present study is a secondary analysis of an observational study conducted in ten hospitals in Brazil (Rede Amil - SP). Septic patients with initial lactate measurements in the first 6 hours of diagnosis were included and divided into 4 groups according to hyperlactatemia (lactate >4mmol/L) and persistent hypotension: (1) severe sepsis (without both criteria); (2) cryptic shock (hyperlactatemia without persistent hypotension); (3) vasoplegic shock (persistent hypotension without hyperlactatemia); and (4) dysoxic shock (both criteria). Results In total, 1,948 patients were analyzed, and the sepsis group represented 52% of the patients, followed by 28% with vasoplegic shock, 12% with dysoxic shock and 8% with cryptic shock. Survival at 28 days differed among the groups (p<0.001). Survival was highest among the severe sepsis group (69%, p<0.001 versus others), similar in the cryptic and vasoplegic shock groups (53%, p=0.39), and lowest in the dysoxic shock group (38%, p<0.001 versus others). In the adjusted analysis, the survival at 28 days remained different among the groups (p<0.001) and the dysoxic shock group exhibited the highest hazard ratio (HR=2.99, 95%CI 2.21-4.05). Conclusion The definition of sepsis includes four different profiles if we consider the presence of hyperlactatemia. Further studies are needed to better characterize septic patients, to understand the etiology and to design adequate targeted treatments. PMID:24553507

  20. Phenylephrine versus norepinephrine for initial hemodynamic support of patients with septic shock: a randomized, controlled trial

    PubMed Central

    Morelli, Andrea; Ertmer, Christian; Rehberg, Sebastian; Lange, Matthias; Orecchioni, Alessandra; Laderchi, Amalia; Bachetoni, Alessandra; D'Alessandro, Mariadomenica; Van Aken, Hugo; Pietropaoli, Paolo; Westphal, Martin

    2008-01-01

    Introduction Previous findings suggest that a delayed administration of phenylephrine replacing norepinephrine in septic shock patients causes a more pronounced hepatosplanchnic vasoconstriction as compared with norepinephrine. Nevertheless, a direct comparison between the two study drugs has not yet been performed. The aim of the present study was, therefore, to investigate the effects of a first-line therapy with either phenylephrine or norepinephrine on systemic and regional hemodynamics in patients with septic shock. Methods We performed a prospective, randomized, controlled trial in a multidisciplinary intensive care unit in a university hospital. We enrolled septic shock patients (n = 32) with a mean arterial pressure below 65 mmHg despite adequate volume resuscitation. Patients were randomly allocated to treatment with either norepinephrine or phenylephrine infusion (n = 16 each) titrated to achieve a mean arterial pressure between 65 and 75 mmHg. Data from right heart catheterization, a thermodye dilution catheter, gastric tonometry, acid-base homeostasis, as well as creatinine clearance and cardiac troponin were obtained at baseline and after 12 hours. Differences within and between groups were analyzed using a two-way analysis of variance for repeated measurements with group and time as factors. Time-independent variables were compared with one-way analysis of variance. Results No differences were found in any of the investigated parameters. Conclusions The present study suggests there are no differences in terms of cardiopulmonary performance, global oxygen transport, and regional hemodynamics when phenylephrine was administered instead of norepinephrine in the initial hemodynamic support of septic shock. Trial registration ClinicalTrial.gov NCT00639015 PMID:19017409

  1. Septic shock and adequacy of early empiric antibiotics in the emergency department.

    PubMed

    Flaherty, Sarah K; Weber, Rachel L; Chase, Maureen; Dugas, Andrea F; Graver, Amanda M; Salciccioli, Justin D; Cocchi, Michael N; Donnino, Michael W

    2014-11-01

    Antibiotic resistance is an increasing concern for Emergency Physicians. To examine whether empiric antibiotic therapy achieved appropriate antimicrobial coverage in emergency department (ED) septic shock patients and evaluate reasons for inadequate coverage. Retrospective review was performed of all adult septic shock patients presenting to the ED of a tertiary care center from December 2007 to September 2008. Inclusion criteria were: 1) Suspected or confirmed infection; 2) ≥ 2 Systemic Inflammatory Response Syndrome criteria; 3) Treatment with one antimicrobial agent; 4) Hypotension requiring vasopressors. Patients were dichotomized by presentation from a community or health care setting. Eighty-five patients with septic shock were identified. The average age was 68 ± 15.8 years. Forty-seven (55.3%) patients presented from a health care setting. Pneumonia was the predominant clinically suspected infection (n = 38, 45%), followed by urinary tract (n = 16, 19%), intra-abdominal (n = 13, 15%), and other infections (n = 18, 21%). Thirty-nine patients (46%) had an organism identified by positive culture, of which initial empiric antibiotic therapy administered in the ED adequately covered the infectious organism in 35 (90%). The 4 patients who received inadequate therapy all had urinary tract infections (UTI) and were from a health care setting. In this population of ED patients with septic shock, empiric antibiotic coverage was inadequate in a small group of uroseptic patients with recent health care exposure. Current guidelines for UTI treatment do not consider health care setting exposure. A larger, prospective study is needed to further define this risk category and determine optimal empiric antibiotic therapy for patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. [Cardiac index, oxygen and serum lactate consumption in infants with hypovolemic and septic shock].

    PubMed

    Gaytán Becerril, A; Olvera Hidalgo, C; Vieto Rodríguez, E E; Chávez Angeles, D S; Elena Salas, M

    1980-01-01

    Determination was made of cardiac output (using the stain dilution technique), gases in blood and serum lactate levels in eight infants with hypovolemic shock and sixteen with septic shock. The data were carried to indexes (values per square meter of body surface). In children with hypovolemic shock the cardiac index was 1.88 +/- 0.031/min/m,2 while in septic patients it was 4.02 +/- 1.011/min/m2. The peripheral resistances were 3,079 din/min/cm.5 in hypovolemic cases and 907 din/min in the septic. In both groups serum lactante levels rised close to 4 mM 61. Oxigen consumption was found low in hypovolemic patients and slightly high in the septic. It is concluded that our data are similar to those reported in similar studies in adults and hypodynamic shock is shown in hypovolemic patients, while hyperdynamic shock appears in septic cases.

  3. Prognostic impact of isolated right ventricular dysfunction in sepsis and septic shock: an 8-year historical cohort study.

    PubMed

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

    2017-09-07

    Echocardiographic myocardial dysfunction is reported commonly in sepsis and septic shock, but there are limited data on sepsis-related right ventricular dysfunction. This study sought to evaluate the association of right ventricular dysfunction with clinical outcomes in patients with severe sepsis and septic shock. Historical cohort study of adult patients admitted to all intensive care units at the Mayo Clinic from January 1, 2007 through December 31, 2014 for severe sepsis and septic shock, who had an echocardiogram performed within 72 h of admission. Patients with prior heart failure, cor-pulmonale, pulmonary hypertension and valvular disease were excluded. Right ventricular dysfunction was defined by the American Society of Echocardiography criteria. Outcomes included 1-year survival, in-hospital mortality and length of stay. Right ventricular dysfunction was present in 214 (55%) of 388 patients who met the inclusion criteria-isolated right ventricular dysfunction was seen in 100 (47%) and combined right and left ventricular dysfunction in 114 (53%). The baseline characteristics were similar between cohorts except for the higher mechanical ventilation use in patients with isolated right ventricular dysfunction. Echocardiographic findings demonstrated lower right ventricular and tricuspid valve velocities in patients with right ventricular dysfunction and lower left ventricular ejection fraction and increased mitral E/e' ratios in patients with combined right and left ventricular dysfunction. After adjustment for age, comorbidity, illness severity, septic shock and use of mechanical ventilation, isolated right ventricular dysfunction was independently associated with worse 1-year survival-hazard ratio 1.6 [95% confidence interval 1.2-2.1; p = 0.002) in patients with sepsis and septic shock. Isolated right ventricular dysfunction is seen commonly in sepsis and septic shock and is associated with worse long-term survival.

  4. Effective use of polymyxin B hemoperfusion in septic shock complicated by urosepsis.

    PubMed

    Malleshappa, P; Ranganath, R; Chaudhari, A P; Singhai, P; Aghariya, M; Shah, A B

    2011-01-01

    Direct hemoperfusion using polymyxin B-immobilized fiber (PMX-DHP) is an established treatment method for septic shock caused by Gram-negative infections. Here we report one instance in which PMX-DHP therapy has been used successfully in a patient with septic shock from urosepsis. After antibiotic therapy, direct hemoperfusion using polymyxin B helped in cardiovascular stability. The patient recovered from the shock within a few days after treatment with polymyxin-B hemoperfusion. As far as we are aware, this is the first reported case of effective treatment of urosepsis complicated by septic shock using PMX-DHP therapy in India.

  5. Incidence, risk factors and impact on outcomes of secondary infection in patients with septic shock: an 8-year retrospective study

    PubMed Central

    Zhao, Guang-ju; Li, Dong; Zhao, Qian; Song, Jia-xing; Chen, Xiao-rong; Hong, Guang-liang; Li, Meng-fang; Wu, Bing; Lu, Zhong-qiu

    2016-01-01

    Secondary infection in septic patients has received widespread attention, although clinical data are still lacking. The present study was performed on 476 patients with septic shock. Time trends for mortality were analyzed using Spearman’s rank correlation test. Risk factors for secondary infection were investigated by binary logistic regression. The extended Cox model with time-varying covariates and hazard ratios (HR) was performed to determine the impact of secondary infection on mortality. Differences in hospital length of stay (LOS) between patients with and without secondary infection were calculated using a multistate model. Thirty-nine percent of septic shock patients who survived the early phase of the disease developed secondary infection. There was a statistically significant increased odds ratio for secondary infection in older patients and patients with a longer LOS in the intensive care unit (ICU), a higher Sequential Organ Failure Assessment (SOFA) score, and endotracheal intubation. Secondary infection significantly reduced the rate of discharge (HR 5.607; CI95 3.612–8.704; P < 0.001) and was associated with an increased hospital LOS of 5.46 days. The present findings represent a direct description of secondary infection in septic shock patients and highlight the influence of this condition on septic shock outcomes. PMID:27924831

  6. Characteristics and outcomes of patients with vasoplegic versus tissue dysoxic septic shock.

    PubMed

    Sterling, Sarah A; Puskarich, Michael A; Shapiro, Nathan I; Trzeciak, Stephen; Kline, Jeffrey A; Summers, Richard L; Jones, Alan E

    2013-07-01

    The current consensus definition of septic shock requires hypotension after adequate fluid challenge or vasopressor requirement. Some patients with septic shock present with hypotension and hyperlactatemia greater than 2 mmol/L (tissue dysoxic shock), whereas others have hypotension alone with normal lactate (vasoplegic shock). The objective of this study was to determine differences in outcomes of patients with tissue dysoxic versus vasoplegic septic shock. This was a secondary analysis of a large, multicenter randomized controlled trial. Inclusion criteria were suspected infection, two or more systemic inflammatory response criteria, and systolic blood pressure less than 90 mmHg after a fluid bolus. Patients were categorized by presence of vasoplegic or tissue dysoxic shock. Demographics and Sequential Organ Failure Assessment scores were evaluated between the groups. The primary outcome was in-hospital mortality. A total of 247 patients were included, 90 patients with vasoplegic shock and 157 with tissue dysoxic shock. There were no significant differences in age, race, or sex between the vasoplegic and tissue dysoxic shock groups. The group with vasoplegic shock had a lower initial Sequential Organ Failure Assessment score than did the group with tissue dysoxic shock (5.5 vs. 7.0 points; P = 0.0002). The primary outcome of in-hospital mortality occurred in 8 (9%) of 90 patients with vasoplegic shock compared with 41 (26%) of 157 in the group with tissue dysoxic shock (proportion difference, 17%; 95% confidence interval, 7%-26%; P < 0.0001; log-rank test P = 0.02). After adjusting for confounders, tissue dysoxic shock remained an independent predictor of in-hospital mortality. In this analysis of patients with septic shock, we found a significant difference in in-hospital mortality between patients with vasoplegic versus tissue dysoxic septic shock. These findings suggest a need to consider these differences when designing future studies of septic shock

  7. [Protective effect of ethyl pyruvate on barrier function of intestinal mucosa in dogs with septic shock].

    PubMed

    Kou, Qiu-Ye; Guan, Xiang-Dong

    2008-03-01

    To investigate the effect of ethyl pyruvate on barrier function of intestinal mucosa in dogs with septic shock. Twenty dogs with septic shock induced by lipopolysaccharides(LPS) were randomly divided into two groups. Dogs randomly received placebo (Ringer's solution, control group, n=8) or ethyl pyruvate in lactated Ringer's solution (0.05 g/kg loading dose over 10 mins, thereafter 0.05 g.kg(-1).h(-1) for 12 hours, EP treatment group, n=12). The diamine oxidase(DAO) activity and D-lactate content were detected at the 0, 8 th, 12 th and 24 th hour of septic shock. Animals were sacrificed at the 24 th hour after septic shock and the jejunal tissue was taken for histopathological examination. The levels of plasma DAO and D-lactate were significantly elevated in both groups after septic shock than those before septic shock. The changes in intestinal parameters of hemoperfusion and permeability in EP treatment group were significantly lowered than those in control group. Inflammation of small intestinal mucosa was more severe in control group than that in EP group, and the pathologic score was significantly lower in EP group(2.33+/-0.25) than that in control group(3.39+/-0.38)(P<0.05). Ethyl pyruvate can lessen intestinal permeability and protect intestinal barrier function in dogs with septic shock.

  8. Similar Microcirculatory Alterations in Patients with Normodynamic and Hyperdynamic Septic Shock.

    PubMed

    Edul, Vanina S Kanoore; Ince, Can; Vazquez, Alejandro Risso; Rubatto, Paolo N; Espinoza, Emilio D Valenzuela; Welsh, Sebastián; Enrico, Carolina; Dubin, Arnaldo

    2016-02-01

    In normodynamic septic shock, the quantitative assessment of sublingual microcirculation has shown decreases in perfused vascular density and red blood cell velocity. However, no studies have been performed in hyperdynamic septic shock. To characterize the microcirculatory patterns and rule out the presence of fast red blood cell velocity in patients with hyperdynamic septic shock. We prospectively evaluated the sublingual microcirculation in healthy volunteers (n = 20) and in patients with hyperdynamic (n = 20) and normodynamic (n = 20) septic shock. Hyperdynamic septic shock was defined by a cardiac index >4.0 L/min/m(2). The microcirculation was assessed with sidestream dark field imaging and AVA 3.0 software. There were no differences in perfused vascular density, proportion of perfused vessels, or microvascular flow index between patients with hyperdynamic and normodynamic septic shock, but these variables were reduced compared with those of healthy volunteers, A similar pattern was observed in red blood cell velocity (912 ± 291, 968 ± 204, and 1303 ± 120 μm/s, respectively; P < 0.0001) and its coefficient of variation. In both types of septic shock, no microvessel had a red blood cell velocity higher than the 100th percentile value for healthy volunteers. Patients with hyperdynamic septic shock showed microcirculatory alterations similar to those of patients with normal cardiac output. Both groups of patients had reduced perfused vascular density and red blood cell velocity and increased flow heterogeneity compared with that of healthy subjects. Fast red blood cell velocity was not found, even in patients with high cardiac output. These results support the conclusion that microcirculatory function is frequently dissociated from systemic hemodynamic derangements in septic shock.

  9. Type of fluid in severe sepsis and septic shock.

    PubMed

    Vincent, J-L; Gottin, L

    2011-12-01

    Fluid resuscitation is an essential aspect of the management of patients with severe sepsis and septic shock, especially in the early stages of disease. Which fluid should be used for this purpose has been a topic of ongoing and sometimes heated debate for many years, yet this is still little evidence to support one fluid over another. Each fluid type has specific adverse effects, and all fluids when given in excess can be detrimental. In this article, we will review the advantages and limitations of the key fluid types currently used for the resuscitation of critically ill patients with sepsis, including the crystalloids (saline solutions and Ringer's lactate), and the colloids (albumin, gelatins, dextrans, and hydroxyethyl starches). We will then briefly summarize the limited evidence to support use of one fluid type over another, and provide general suggestions for fluid use in these patients.

  10. How to choose the therapeutic goals to improve tissue perfusion in septic shock

    PubMed Central

    de Assuncao, Murillo Santucci Cesar; Corrêa, Thiago Domingos; Bravim, Bruno de Arruda; Silva, Eliézer

    2015-01-01

    The early recognition and treatment of severe sepsis and septic shock is the key to a successful outcome. The longer the delay in starting treatment, the worse the prognosis due to persistent tissue hypoperfusion and consequent development and worsening of organ dysfunction. One of the main mechanisms responsible for the development of cellular dysfunction is tissue hypoxia. The adjustments necessary for adequate tissue blood flow and therefore of oxygen supply to metabolic demand according to the assessment of the cardiac index and oxygen extraction rate should be performed during resuscitation period, especially in high complexity patients. New technologies, easily handled at the bedside, and new studies that directly assess the impact of macro-hemodynamic parameter optimization on microcirculation and in the clinical outcome of septic patients, are needed. PMID:26313438

  11. Clinical Characteristics and Outcomes in Polyarticular Septic Arthritis.

    PubMed

    Lieber, Sarah B; Fowler, Mary Louise; Zhu, Clara; Moore, Andrew; Shmerling, Robert H; Paz, Ziv

    2017-09-13

    Septic polyarthritis is rarer than septic monoarthritis, but associated with higher mortality. Septic polyarthritis may be difficult to distinguish clinically from noninfectious inflammatory arthritis. We describe one of the largest samples of septic polyarthritis with the aim of distinguishing septic monoarthritis from polyarthritis. We conducted a retrospective study of adults admitted to tertiary care with septic monoarthritis and polyarthritis. Baseline characteristics, microbial profiles, joint involvement, length of stay, and 60-day readmission rates were determined. We identified 464 and 42 cases of septic monoarthritis and polyarthritis, respectively, including 7 cases of septic polyarthritis with comorbid rheumatoid arthritis. Compared to those with septic monoarthritis, patients with septic polyarthritis were more likely to have rheumatoid arthritis (p < 0.01), sepsis (p < 0.01), and higher peripheral (p < 0.001) and synovial (p < 0.001) white blood cell counts. Operative intervention rates were similar, but mean length of stay was longer in polyarticular septic arthritis (p < 0.001). Patients with septic polyarthritis with/without underlying rheumatoid arthritis were similar in terms of presenting features and outcomes, except for more frequent immunosuppressive therapy in rheumatoid arthritis (p < 0.01). In this sample of patients with septic arthritis, patients with septic polyarthritis were more likely to have systemic infection at presentation than those with septic monoarthritis. Despite this difference, patients with septic monoarthritis and polyarthritis tended to have similar outcomes. While rheumatoid arthritis was observed more frequently among patients with septic polyarthritis, those with/without underlying rheumatoid arthritis had similar presenting features and outcomes.Bottom of Form. Copyright © 2017. Published by Elsevier SAS.

  12. Endotoxin Elimination in Patients with Septic Shock: An Observation Study.

    PubMed

    Adamik, Barbara; Zielinski, Stanislaw; Smiechowicz, Jakub; Kübler, Andrzej

    2015-12-01

    To evaluate the effectiveness of endotoxin elimination with an adsorption column in patients with septic shock and endotoxemia. The elimination therapy was guided by a new bedside method of measuring endotoxin activity (EA). Intensive care unit (ICU) patients with septic shock and suspected Gram-negative infection were consecutively added to the study group within the first 24 h. Endotoxin elimination was performed using hemoperfusion with the Alteco LPS Adsorber. The primary endpoint was improvement in organ function within the first 24 h of treatment. A secondary objective was to assess the usefulness of a new method of measuring EA to help guide endotoxin elimination therapy. Out of 64 patients 18 had a high baseline EA [0.70 EA units (0.66-0.77)]. Those patients had endotoxin elimination treatment in addition to conventional medical therapy. At 24 h after endotoxin elimination, the EA had decreased to 0.56 EA units (0.43-0.77), (p = 0.005); MAP increased from 69 (62-80) to 80 mm Hg (68-88), (p = 0.002), and noradrenaline use decreased from 0.28 (0.15-0.80) to 0.1 μg/kg/min (0.00-0.70) at the same time (p = 0.04). The SOFA score had decreased from 11 (9-15) to 9 (7-14) points 24 h after endotoxin elimination (p = 0.01) with a median delta SOFA -2 points. Endotoxin elimination did not have a significant effect on the ICU length of stay or ICU mortality. Effective endotoxin elimination resulted in a significant improvement in hemodynamic parameters and of organ function. The application of the EA assay was useful for the bedside monitoring of endotoxemia in critically ill ICU patients.

  13. Klebsiella pneumoniae invasive liver abscess syndrome with purulent meningitis and septic shock: A case from mainland China.

    PubMed

    Qian, Yun; Wong, Chi-Chun; Lai, San-Chuan; Lin, Zheng-Hua; Zheng, Wei-Liang; Zhao, Hui; Pan, Kong-Han; Chen, Shu-Jie; Si, Jian-Min

    2016-03-07

    We present a rare case of invasive liver abscess syndrome due to Klebsiella pneumoniae (K. pneumoniae) with metastatic meningitis and septic shock. A previously healthy, 55-year-old female patient developed fever, liver abscess, septic shock, purulent meningitis and metastatic hydrocephalus. Upon admission, the clinical manifestations, laboratory and imaging examinations were compatible with a diagnosis of K. pneumoniae primary liver abscess. Her distal metastasis infection involved meningitis and hydrocephalus, which could flare abruptly and be life threatening. Even with early adequate drainage and antibiotic therapy, the patient's condition deteriorated and she ultimately died. To the best of our knowledge, this is the first case of K. pneumoniae invasive liver abscess syndrome with septic meningitis reported in mainland China. Our findings reflect the need for a better understanding of the epidemiology, risk factors, complications, comorbid medical conditions and treatment of this disease.

  14. Klebsiella pneumoniae invasive liver abscess syndrome with purulent meningitis and septic shock: A case from mainland China

    PubMed Central

    Qian, Yun; Wong, Chi-Chun; Lai, San-Chuan; Lin, Zheng-Hua; Zheng, Wei-Liang; Zhao, Hui; Pan, Kong-Han; Chen, Shu-Jie; Si, Jian-Min

    2016-01-01

    We present a rare case of invasive liver abscess syndrome due to Klebsiella pneumoniae (K. pneumoniae) with metastatic meningitis and septic shock. A previously healthy, 55-year-old female patient developed fever, liver abscess, septic shock, purulent meningitis and metastatic hydrocephalus. Upon admission, the clinical manifestations, laboratory and imaging examinations were compatible with a diagnosis of K. pneumoniae primary liver abscess. Her distal metastasis infection involved meningitis and hydrocephalus, which could flare abruptly and be life threatening. Even with early adequate drainage and antibiotic therapy, the patient’s condition deteriorated and she ultimately died. To the best of our knowledge, this is the first case of K. pneumoniae invasive liver abscess syndrome with septic meningitis reported in mainland China. Our findings reflect the need for a better understanding of the epidemiology, risk factors, complications, comorbid medical conditions and treatment of this disease. PMID:26973425

  15. Arterial bicarbonate may be a useful indicator of inadequate cortisol response in children with catecholamine resistant septic shock.

    PubMed

    Maralihalli, M B; Deshmukh, C T

    2013-01-01

    To study the clinical and biochemical parameters that can predict cortisol insufficiency in children with septic shock. prospective, observational study. Tertiary health-care center. Fifty children admitted with the catecholamine resistant septic shock to a tertiary health-care center. At the time of hospitalization all patients underwent detailed clinical evaluation including, history and physical examination, evaluation with the complete blood count, serum cortisol, renal function tests, liver function tests, prothrombin time activated partial thromboplastin time, arterial blood gas analysis, urine analysis, chest roentgenogram, ultrasonography of the abdomen and chest, urine, and blood culture for bacteria and fungi. Out of 50 children with the catecholamine resistant septic shock, seven had adrenal insufficiency (serum cortisol <18 μg/dl). Of all parameters studied, only arterial bicarbonate at the time of admission to intensive care predicted adrenal insufficiency. On Receptor operative characteristic curve analysis, a bicarbonate level of 10.9 mEq/L had the best accuracy to predict adrenal insufficiency. Arterial bicarbonate may be used as a rapid test for provisional identification of adrenal insufficiency among children with the catecholamine resistant septic shock.

  16. [Septic shock following platelet transfusion contaminated with Citrobacter koseri in a child with postchemotherapy febrile neutropenia].

    PubMed

    Tichit, R; Saumet, L; Marchandin, H; Haouy, S; Latry, P; Sirvent, N

    2016-01-01

    The bacterial transfusion risk is currently the greatest infectious risk of blood transfusion. We report the case of a child with postchemotherapy febrile neutropenia who presented septic shock following platelet transfusion contaminated with Citrobacter koseri. The life-threatening development could have been avoided by strict compliance with good clinical practice. The stability of mortality rates due to adverse effects of bacterial proliferation during platelet transfusions in France since 1994 calls for optimization of all preventive measures throughout the transfusion chain and perfect knowledge of transfusion rules by medical staff and care givers.

  17. Rational fluid therapy for sepsis and septic shock; what do recent studies tell us?

    PubMed

    Rastegar, Asghar

    2015-05-01

    Sepsis and septic shock persist as major healthcare challenge, with high morbidity and mortality. Fluid management is a large part of the treatment in patients with these disorders. Fluid therapy has been an important component of the care of patients for the past century. However, recently well-designed studies have been published focusing on the impact of the type and amount of fluids on important clinical outcomes. This review summarizes all the relevant recent studies and attempts to develop a rational approach to the initial fluid management of patients with suspected sepsis.

  18. 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

    IMPORTANCE Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. OBJECTIVE To evaluate and, as needed, update definitions for sepsis and septic shock. PROCESS A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). KEY FINDINGS FROMEVIDENCE SYNTHESIS Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. RECOMMENDATIONS Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a

  19. Efficacy of postoperative polymyxin B hemoperfusion in secondary peritonitis patients with septic shock: a propensity-matched analysis.

    PubMed

    Yuan, Kuo-Ching; Wang, Shang-Yu; Yu, Ming-Chin; Hsu, Yu-Pao; Pan, Heng-Chih; Chen, Yung-Chang

    2017-02-10

    Severe sepsis and septic shock is still a challenge. Polymyxin B hemoperfusion (PMX) is a device designed to remove circulating endotoxin by adsorption, which is reported to improve treatment outcomes. This study aimed to further verify the efficacy of PMX on postoperative, peritonitis, septic shock patients. This study prospectively analyzed 20 of 155 patients who presented with postoperative septic shock and were treated with PMX in a single institute during the period March 2013 to September 2014 (Clinical Trial Protocol number: ChiCTR-ONC-16008160). A control group (53 patients) was recruited from our own 2012 database using the propensity-matching score method. The data collection includes demographic data, postoperative organ dysfunction status, disease severity and treatment result. The 2 groups (treatment vs. control) were similar in demographic data, organ dysfunction status and disease severity. PMX use provides benefits for recovery of hemodynamic status and many other aspects, including better survival, but is not statistically significant. For survival factor analysis, PMX use is also not significant for patient survival in our study. PMX provided some benefits to patients in the treatment for peritonitis septic shock. An improvement in hemodynamic status was mostly observed. Our study also supports the finding that PMX used as an auxiliary treatment provides improved survival but is not statistically significant, possibly due to the small sample size with multiple comorbidities.

  20. Immediate effects of chest physiotherapy on hemodynamic, metabolic, and oxidative stress parameters in subjects with septic shock.

    PubMed

    dos Santos, Rafael S; Donadio, Márcio V F; da Silva, Gabriela V; Blattner, Clarissa N; Melo, Denizar A S; Nunes, Fernanda B; Dias, Fernando S; Squizani, Eamim D; Pedrazza, Leonardo; Gadegast, Isabella; de Oliveira, Jarbas R

    2014-09-01

    Septic shock presents as a continuum of infectious events, generating tissue hypoxia and hypovolemia, and increased oxidative stress. Chest physiotherapy helps reduce secretion, improving dynamic and static compliance, as well as improving secretion clearance and preventing pulmonary complications. The purpose of this study was to evaluate the immediate effect of chest physiotherapy on hemodynamic, metabolic, inflammatory, and oxidative stress parameters in subjects in septic shock. We conducted a quasi-experimental study in 30 subjects in septic shock, who underwent chest physiotherapy, without associated heart diseases and with vasopressors < 0.5 μg/kg/min. Venous and arterial blood gases, clinical and hemodynamic data, inflammatory data, lactate, and oxidative stress were evaluated before and 15 min after physiotherapy. Thirty subjects with a mean age of 61.8 ± 15.9 y and Sequential Organ Failure Assessment of 8 (range 6-10) were included. Chest physiotherapy caused a normalization of pH (P = .046) and P(aCO2) (P = .008); reduction of lactate (P = .001); and an increase in P(aO2) (P = .03), arterial oxygen saturation (P = .02), and P(aO2)/F(IO2) (P = .034), 15 min after it was applied. The results indicate that chest physiotherapy has immediate effects, improving oxygenation and reducing lactate and oxidative damage in subjects in septic shock. However, it does not cause alterations in the inflammatory and hemodynamic parameters. Copyright © 2014 by Daedalus Enterprises.

  1. Lethal endotoxic shock using alpha-galactosylceramide sensitization as a new experimental model of septic shock.

    PubMed

    Ito, Hiroyasu; Koide, Naoki; Hassan, Ferdaus; Islam, Shamima; Tumurkhuu, Gantsetseg; Mori, Isamu; Yoshida, Tomoaki; Kakumu, Shinichi; Moriwaki, Hisataka; Yokochi, Takashi

    2006-03-01

    The effect of alpha-galactosylceramide (alpha-GalCer) on lipopolysaccharide (LPS)-mediated lethality was examined. Administration of LPS killed all mice pretreated with alpha-GalCer, but not untreated control mice. The lethal shock in alpha-GalCer-sensitized mice was accompanied by severe pulmonary lesions with marked infiltration of inflammatory cells and massive cell death. On the other hand, hepatic lesions were focal and mild. A number of cells in pulmonary and hepatic lesions underwent apoptotic cell death. alpha-GalCer sensitization was ineffective for the development of the systemic lethal shock in Valpha14-positive natural killer T cell-deficient mice. Sensitization with alpha-GalCer led to the circulation of a high level of interferon (IFN)-gamma and further augmented the production of tumor necrosis factor (TNF)-alpha in response to LPS. The lethal shock was abolished by the administration of anti-IFN-gamma or TNF-alpha antibody. Further, the lethal shock did not occur in TNF-alpha-deficient mice. Taken together, alpha-GalCer sensitization rendered mice very susceptible to LPS-mediated lethal shock, and IFN-gamma and TNF-alpha were found to play a critical role in the preparation and execution of the systemic lethal shock, respectively. The LPS-mediated lethal shock using alpha-GalCer sensitization might be useful for researchers employing experimental models of sepsis and septic shock.

  2. Septic shock: recognizing and managing this life-threatening condition in pediatric patients.

    PubMed

    Silverman, Adam M

    2015-04-01

    Septic shock is a relatively rare but life-threatening condition in pediatric patients that can often be difficult to recognize in the emergency department. Once recognized, the emphasis of therapy is to reverse deficits in cellular respiration by increasing oxygen and other substrate delivery to tissue beds. Providing oxygen, improving tissue perfusion through augmentation of cardiac output, and administering antibiotics in a timely manner have all been shown to significantly improve outcomes in children with septic shock. Goal-directed therapy is relatively straightforward, emphasizes the need for effective surveillance and timely recognition of this disease process, and has the potential to significantly reduce morbidity and mortality. This review discusses how to identify specific populations at the greatest risk for septic shock, lays out the essential components of goal-directed therapy, examines potential pitfalls in management, and distinguishes additional ways that emergency clinicians can avoid the devastating consequences of septic shock in pediatric patients.

  3. Feasibility, Utility, and Safety of Midodrine During Recovery Phase From Septic Shock.

    PubMed

    Whitson, Micah R; Mo, Edwin; Nabi, Tasnima; Healy, Lauren; Koenig, Seth; Narasimhan, Mangala; Mayo, Paul H

    2016-06-01

    We describe the feasibility, utility, and safety of oral midodrine to replace IV vasopressors during recovery from septic shock. This was a retrospective study performed in a medical ICU. All study subjects had a diagnosis of septic shock requiring at least 24 hours of IV vasopressors and demonstrated clinical stability with stable or decreasing doses of IV vasopressors. The two groups compared were those who received IV vasopressors only and those who received IV vasopressors with adjunctive midodrine. Of the 275 study patients, 140 received an IV vasopressor only and 135 received midodrine in addition to an IV vasopressor. There was no difference between the groups' demographics (age, sex, Acute Physiology and Chronic Health Evaluation 4 score). Mean IV vasopressor duration was 3.8 days in the IV vasopressor only group and 2.9 days in the IV vasopressor with midodrine group (P < .001). An IV vasopressor was reinstituted after discontinuation in 21 of 140 (15%) patients in the IV vasopressor only group and in 7 of 135 (5.2%) patients in the IV vasopressor with midodrine group (P = .007). ICU length of stay was 9.4 days in the IV vasopressor only group and 7.5 days in the IV vasopressor with midodrine group (P = .017). There were no complications associated with midodrine use except transient bradycardia in one patient, which resolved upon discontinuation of midodrine. Midodrine may reduce the duration of IV vasopressors during recovery phase from septic shock and may be associated with a reduction in length of stay in the ICU. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  4. Vancomycin pharmacodynamics and survival in patients with methicillin-resistant Staphylococcus aureus-associated septic shock.

    PubMed

    Zelenitsky, Sheryl; Rubinstein, Ethan; Ariano, Robert; Iacovides, Harris; Dodek, Peter; Mirzanejad, Yazdan; Kumar, Anand

    2013-03-01

    Given the lack of clinical data to guide optimal dosing of vancomycin in critically ill patients with life-threatening infections, the objective was to characterise vancomycin pharmacodynamics in MRSA-associated septic shock. Cases were extracted from an observational, multicentre study in Canadian Intensive Care Units and included 35 adult patients with MRSA-associated septic shock who received vancomycin and had a measured serum concentration within the first 72 h of therapy. Univariate and multivariate analyses were used to assess variables predictive of in-hospital mortality. Patients who survived were significantly younger and had better renal function, lower probability of chronic obstructive pulmonary disease, higher probability of intravenous drug use, lower probability of healthcare-associated infection and lower APACHE II score. Survivors also received higher vancomycin doses and had higher serum troughs and AUC₂₄/MIC values. The survival rate was 2.5-fold greater in patients who had vancomycin troughs ≥15 mg/L [70.6% (12/17) vs. 27.8% (5/18); P=0.001]. Two significant AUC₂₄/MIC thresholds for survival, ≥451 (P=0.006) and ≥578 (P=0.012), were identified by CART analysis. Only younger age (P=0.028) and higher vancomycin AUC₂₄/MIC (P=0.045) were significant in multivariate analyses of survival. This study of vancomycin in critically ill patients supports the current recommendation for serum troughs of at least 15 mg/L and, in patients with septic shock, an AUC₂₄/MIC threshold higher than the conventional 400. Improved survival was observed with the attainment of these pharmacodynamic targets.

  5. Protocolised Management In Sepsis (ProMISe): a multicentre randomised controlled trial of the clinical effectiveness and cost-effectiveness of early, goal-directed, protocolised resuscitation for emerging septic shock.

    PubMed

    Mouncey, Paul R; Osborn, Tiffany M; Power, G Sarah; Harrison, David A; Sadique, M Zia; Grieve, Richard D; Jahan, Rahi; Tan, Jermaine C K; Harvey, Sheila E; Bell, Derek; Bion, Julian F; Coats, Timothy J; Singer, Mervyn; Young, J Duncan; Rowan, Kathryn M

    2015-11-01

    Early goal-directed therapy (EGDT) is recommended in international guidance for the resuscitation of patients presenting with early septic shock. However, adoption has been limited and uncertainty remains over its clinical effectiveness and cost-effectiveness. The primary objective was to estimate the effect of EGDT compared with usual resuscitation on mortality at 90 days following randomisation and on incremental cost-effectiveness at 1 year. The secondary objectives were to compare EGDT with usual resuscitation for requirement for, and duration of, critical care unit organ support; length of stay in the emergency department (ED), critical care unit and acute hospital; health-related quality of life, resource use and costs at 90 days and at 1 year; all-cause mortality at 28 days, at acute hospital discharge and at 1 year; and estimated lifetime incremental cost-effectiveness. A pragmatic, open, multicentre, parallel-group randomised controlled trial with an integrated economic evaluation. Fifty-six NHS hospitals in England. A total of 1260 patients who presented at EDs with septic shock. EGDT (n = 630) or usual resuscitation (n = 630). Patients were randomly allocated 1 : 1. All-cause mortality at 90 days after randomisation and incremental net benefit (at £20,000 per quality-adjusted life-year) at 1 year. Following withdrawals, data on 1243 (EGDT, n = 623; usual resuscitation, n = 620) patients were included in the analysis. By 90 days, 184 (29.5%) in the EGDT and 181 (29.2%) patients in the usual-resuscitation group had died [p = 0.90; absolute risk reduction -0.3%, 95% confidence interval (CI) -5.4 to 4.7; relative risk 1.01, 95% CI 0.85 to 1.20]. Treatment intensity was greater for the EGDT group, indicated by the increased use of intravenous fluids, vasoactive drugs and red blood cell transfusions. Increased treatment intensity was reflected by significantly higher Sequential Organ Failure Assessment scores and more advanced

  6. Impact of appropriate antimicrobial therapy for patients with severe sepsis and septic shock--a quality improvement study.

    PubMed

    Yokota, Paula K O; Marra, Alexandre R; Martino, Marines D V; Victor, Elivane S; Durão, Marcelino S; Edmond, Michael B; dos Santos, Oscar F P

    2014-01-01

    There is ample literature available on the association between both time to antibiotics and appropriateness of antibiotics and clinical outcomes from sepsis. In fact, the current state of debate surrounds the balance to be struck between prompt empirical therapy and care in the choice of appropriate antibiotics (both in terms of the susceptibility of infecting organism and minimizing resistance arising from use of broad-spectrum agents). The objective of this study is to determine sepsis bundle compliance and the appropriateness of antimicrobial therapy in patients with severe sepsis and septic shock and its impact on outcomes. This study was conducted in the ICU of a tertiary care, private hospital in São Paulo, Brazil. A retrospective cohort study was conducted from July 2005 to December 2012 in patients with severe sepsis and septic shock. A total of 1,279 patients were identified with severe sepsis and septic shock, of which 358 (32.1%) had bloodstream infection (BSI). The inpatient mortality rate was 29%. In evaluation of the sepsis bundle, over time there was a progressive increase in serum arterial lactate collection, obtaining blood cultures prior to antibiotic administration, administration of broad-spectrum antibiotics within 1 hour, and administration of appropriate antimicrobials, with statistically significant differences in the later years of the study. We also observed a significant decrease in mortality. In patients with bloodstream infection, after adjustment for other covariates the administration of appropriate antimicrobial therapy was associated with a decrease in mortality in patients with severe sepsis and septic shock (p = 0.023). The administration of appropriate antimicrobial therapy was independently associated with a decline in mortality in patients with severe sepsis and septic shock due to bloodstream infection. As protocol adherence increased over time, the crude mortality rate decreased, which reinforces the need to implement

  7. Early diastolic dysfunction is associated with intensive care unit mortality in cancer patients presenting with septic shock.

    PubMed

    Mourad, M; Chow-Chine, L; Faucher, M; Sannini, A; Brun, J P; de Guibert, J M; Fouche, L; Lambert, J; Blache, J L; Mokart, D

    2014-01-01

    Cancer patients present a high risk of sepsis and are exposed to cardiotoxic drugs during chemotherapy. Myocardial dysfunction is common during septic shock and can be evaluated at bedside using echocardiography. The aim of this study was to identify early cardiac dysfunctions associated with intensive care unit (ICU) mortality in cancer patients presenting with septic shock. Seventy-two cancer patients admitted to the ICU underwent echocardiography within 48 h of developing septic shock. History of malignancies, anticancer treatments, and clinical characteristics were prospectively collected. ICU mortality was 48%. Diastolic dysfunction (e' ≤8 cm s(-1)) was an independent echocardiographic parameter associated with ICU mortality {odds ratio (OR) 7.7 [95% confidence interval (CI), 2.58-23.38]; P<0.001}. Overall, three factors were independently associated with ICU mortality: sepsis-related organ failure assessment score at admission [OR 1.35 ( 95% CI, 1.05-1.74); P=0.017], occurrence of diastolic dysfunction [OR 16.6 (95% CI, 3.28-84.6); P=0.001], and need for conventional mechanical ventilation [OR 16.6 (95% CI, 3.6-77.15); P<0.001]. Diastolic dysfunction was not associated with exposure to cardiotoxic drugs. Early diastolic dysfunction is a strong and independent predictor of mortality in cancer patients presenting with septic shock. It is not associated with exposure to cardiotoxic drugs. Further studies incorporating monitoring of diastolic function and therapeutic interventions improving cardiac relaxation need to be evaluated in cancer patients presenting with septic shock.

  8. High-fidelity medical simulation training improves medical students' knowledge and confidence levels in septic shock resuscitation.

    PubMed

    Vattanavanit, Veerapong; Kawla-Ied, Jarernporn; Bhurayanontachai, Rungsun

    2017-01-01

    Septic shock resuscitation bundles have poor compliance worldwide partly due to a lack of knowledge and clinical skills. High-fidelity simulation-based training is a new teaching technology in our faculty which may improve the performance of medical students in the resuscitation process. However, since the efficacy of this training method in our institute is limited, we organized an extra class for this evaluation. The aim was to evaluate the effect on medical students' knowledge and confidence levels after the high-fidelity medical simulation training in septic shock management. A retrospective study was performed in sixth year medical students during an internal medicine rotation between November 2015 and March 2016. The simulation class was a 2-hour session of a septic shock management scenario and post-training debriefing. Knowledge assessment was determined by a five-question pre-test and post-test examination. At the end of the class, the students completed their confidence evaluation questionnaire. Of the 79 medical students, the mean percentage score ± standard deviation (SD) of the post-test examination was statistically significantly higher than the pre-test (66.83%±19.7% vs 47.59%±19.7%, p<0.001). In addition, the student mean percentage confidence level ± SD in management of septic shock was significantly better after the simulation class (68.10%±12.2% vs 51.64%±13.1%, p<0.001). They also strongly suggested applying this simulation class to the current curriculum. High-fidelity medical simulation improved the students' knowledge and confidence in septic shock resuscitation. This simulation class should be included in the curriculum of the sixth year medical students in our institute.

  9. High-fidelity medical simulation training improves medical students’ knowledge and confidence levels in septic shock resuscitation

    PubMed Central

    Vattanavanit, Veerapong; Kawla-ied, Jarernporn; Bhurayanontachai, Rungsun

    2017-01-01

    Background Septic shock resuscitation bundles have poor compliance worldwide partly due to a lack of knowledge and clinical skills. High-fidelity simulation-based training is a new teaching technology in our faculty which may improve the performance of medical students in the resuscitation process. However, since the efficacy of this training method in our institute is limited, we organized an extra class for this evaluation. Purpose The aim was to evaluate the effect on medical students’ knowledge and confidence levels after the high-fidelity medical simulation training in septic shock management. Methods A retrospective study was performed in sixth year medical students during an internal medicine rotation between November 2015 and March 2016. The simulation class was a 2-hour session of a septic shock management scenario and post-training debriefing. Knowledge assessment was determined by a five-question pre-test and post-test examination. At the end of the class, the students completed their confidence evaluation questionnaire. Results Of the 79 medical students, the mean percentage score ± standard deviation (SD) of the post-test examination was statistically significantly higher than the pre-test (66.83%±19.7% vs 47.59%±19.7%, p<0.001). In addition, the student mean percentage confidence level ± SD in management of septic shock was significantly better after the simulation class (68.10%±12.2% vs 51.64%±13.1%, p<0.001). They also strongly suggested applying this simulation class to the current curriculum. Conclusion High-fidelity medical simulation improved the students’ knowledge and confidence in septic shock resuscitation. This simulation class should be included in the curriculum of the sixth year medical students in our institute. PMID:28053558

  10. Mortality prediction in patients with severe septic shock: a pilot study using a target metabolomics approach

    PubMed Central

    Ferrario, Manuela; Cambiaghi, Alice; Brunelli, Laura; Giordano, Silvia; Caironi, Pietro; Guatteri, Luca; Raimondi, Ferdinando; Gattinoni, Luciano; Latini, Roberto; Masson, Serge; Ristagno, Giuseppe; Pastorelli, Roberta

    2016-01-01

    Septic shock remains a major problem in Intensive Care Unit, with high lethality and high-risk second lines treatments. In this preliminary retrospective investigation we examined plasma metabolome and clinical features in a subset of 20 patients with severe septic shock (SOFA score >8), enrolled in the multicenter Albumin Italian Outcome Sepsis study (ALBIOS, NCT00707122). Our purpose was to evaluate the changes of circulating metabolites in relation to mortality as a pilot study to be extended in a larger cohort. Patients were analyzed according to their 28-days and 90-days mortality. Metabolites were measured using a targeted mass spectrometry-based quantitative metabolomic approach that included acylcarnitines, aminoacids, biogenic amines, glycerophospholipids, sphingolipids, and sugars. Data-mining techniques were applied to evaluate the association of metabolites with mortality. Low unsaturated long-chain phosphatidylcholines and lysophosphatidylcholines species were associated with long-term survival (90-days) together with circulating kynurenine. Moreover, a decrease of these glycerophospholipids was associated to the event at 28-days and 90-days in combination with clinical variables such as cardiovascular SOFA score (28-day mortality model) or renal replacement therapy (90-day mortality model). Early changes in the plasma levels of both lipid species and kynurenine associated with mortality have potential implications for early intervention and discovering new target therapy. PMID:26847922

  11. When to stop septic shock resuscitation: clues from a dynamic perfusion monitoring

    PubMed Central

    2014-01-01

    Background The decision of when to stop septic shock resuscitation is a critical but yet a relatively unexplored aspect of care. This is especially relevant since the risks of over-resuscitation with fluid overload or inotropes have been highlighted in recent years. A recent guideline has proposed normalization of central venous oxygen saturation and/or lactate as therapeutic end-points, assuming that these variables are equivalent or interchangeable. However, since the physiological determinants of both are totally different, it is legitimate to challenge the rationale of this proposal. We designed this study to gain more insights into the most appropriate resuscitation goal from a dynamic point of view. Our objective was to compare the normalization rates of these and other potential perfusion-related targets in a cohort of septic shock survivors. Methods We designed a prospective, observational clinical study. One hundred and four septic shock patients with hyperlactatemia were included and followed until hospital discharge. The 84 hospital-survivors were kept for final analysis. A multimodal perfusion assessment was performed at baseline, 2, 6, and 24 h of ICU treatment. Results Some variables such as central venous oxygen saturation, central venous-arterial pCO2 gradient, and capillary refill time were already normal in more than 70% of survivors at 6 h. Lactate presented a much slower normalization rate decreasing significantly at 6 h compared to that of baseline (4.0 [3.0 to 4.9] vs. 2.7 [2.2 to 3.9] mmol/L; p < 0.01) but with only 52% of patients achieving normality at 24 h. Sublingual microcirculatory variables exhibited the slowest recovery rate with persistent derangements still present in almost 80% of patients at 24 h. Conclusions Perfusion-related variables exhibit very different normalization rates in septic shock survivors, most of them exhibiting a biphasic response with an initial rapid improvement, followed by a much slower trend

  12. Cardiovascular and metabolic effects of high-dose insulin in a porcine septic shock model.

    PubMed

    Holger, Joel S; Dries, David J; Barringer, Kelly W; Peake, Benjamin J; Flottemesch, Thomas J; Marini, John J

    2010-04-01

    High-dose insulin (HDI) has inotropic and vasodilatory properties in various clinical conditions associated with myocardial depression. The authors hypothesized that HDI will improve the myocardial depression produced by severe septic shock and have beneficial effects on metabolic parameters. In an animal model of severe septic shock, this study compared the effects of HDI treatment to normal saline (NS) resuscitation alone. Ten pigs were randomized to an insulin (HDI) or NS group. All were anesthetized and instrumented to monitor cardiovascular function. In both arms, Escherichia coli endotoxin lipopolysaccharide (LPS) and NS infusions were begun. LPS was titrated to 20 mug/kg/hour over 30 minutes and continued for 5 hours, and saline was infused at 20 mL/kg/hour throughout the protocol. Dextrose (50%) was infused to maintain glucose in the 60-150 mg/dL range, and potassium was infused to maintain a level greater than 2.8 mmol/L. At 60 minutes, the HDI group received an insulin infusion titrated from 2 to 10 units/kg/hour over 40 minutes and continued at that rate throughout the protocol. Survival, heart rate (HR), mean arterial pressure (MAP), pulmonary artery and central venous pressure, cardiac output, central venous oxygen saturation (SVO(2)), and lactate were monitored for 5 hours (three pigs each arm) or 7 hours (two pigs each arm) or until death. Cardiac index, systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), O(2) delivery, and O(2) consumption were derived from measured data. Outcomes from the repeated-measures analysis were modeled using a mixed-effects linear model that assumed normally distributed errors and a random effect at the subject level. No significant baseline differences existed between arms at time 0 or 60 minutes. Survival was 100% in the HDI arm and 60% in the NS arm. Cardiovascular variables were significantly better in the HDI arm: cardiac index (p < 0.001), SVR (p < 0.003), and PVR (p < 0.01). The metabolic

  13. An adaptive, phase II, dose-finding clinical trial design to evaluate L-carnitine in the treatment of septic shock based on efficacy and predictive probability of subsequent phase III success.

    PubMed

    Lewis, Roger J; Viele, Kert; Broglio, Kristine; Berry, Scott M; Jones, Alan E

    2013-07-01

    Sepsis is the tenth leading cause of death in the United States. Despite extensive research, mortality rates for sepsis have not substantially improved in the last several decades. We describe an innovative phase II clinical trial design for evaluating the addition of L-carnitine to the treatment of vasopressor-dependent septic shock. The design incorporates a variety of features to increase efficiency, including a normal dynamic linear dose-response model, adaptive randomization, and early stopping for futility or success based on the probability that a future phase III trial using a 28-day mortality outcome would be successful. Trial design and computer simulation of a trial to be conducted in the emergency department and ICU. Proposed to study intravenous L-carnitine. The proposed trial uses an early endpoint, the 48-hour change in Sequential Organ Failure Assessment score, to drive adaptive randomization and dose selection. We use existing data to model the expected relationship between the Sequential Organ Failure Assessment change and the 28-day mortality to determine the trial's operating characteristics using Monte Carlo simulation. The resulting trial efficiently identifies the best dose of L-carnitine and provides clear guidance regarding whether to continue development into phase III.

  14. An Adaptive, Phase II, Dose-Finding Clinical Trial Design to Evaluate l-Carnitine in the Treatment of Septic Shock Based on Efficacy and Predictive Probability of Subsequent Phase III Success

    PubMed Central

    Lewis, Roger J.; Viele, Kert; Broglio, Kristine; Berry, Scott M.; Jones, Alan E.

    2015-01-01

    Objectives Sepsis is the tenth leading cause of death in the United States. Despite extensive research, mortality rates for sepsis have not substantially improved in the last several decades. We describe an innovative phase II clinical trial design for evaluating the addition of l-carnitine to the treatment of vasopressor-dependent septic shock. Design The design incorporates a variety of features to increase efficiency, including a normal dynamic linear dose–response model, adaptive randomization, and early stopping for futility or success based on the probability that a future phase III trial using a 28-day mortality outcome would be successful. Setting Trial design and computer simulation of a trial to be conducted in the emergency department and ICU. Interventions Proposed to study intravenous l-carnitine. Measurements The proposed trial uses an early endpoint, the 48-hour change in Sequential Organ Failure Assessment score, to drive adaptive randomization and dose selection. Main Results We use existing data to model the expected relationship between the Sequential Organ Failure Assessment change and the 28-day mortality to determine the trial's operating characteristics using Monte Carlo simulation. Conclusions The resulting trial efficiently identifies the best dose of l-carnitine and provides clear guidance regarding whether to continue development into phase III. PMID:23514753

  15. The effects of carnosine in an experimental rat model of septic shock

    PubMed Central

    Sahin, Sabiha; Oter, Serdar; Burukoglu, Dilek; Sutken, Emine

    2013-01-01

    Background To examine the effect of carnosine on liver function and histological findings in experimental septic shock model, 24 Sprague-Dawley rats were used. Material/Methods Rats were divided into control, septic shock, and carnosine-treated septic shock groups. Femoral vein and artery catheterization were performed on all rats. Rats in the control group underwent laparotomy and catheterization; in the test groups, cecal ligation-perforation and bladder cannulation were added. Rats in the treatment group received a single intraperitoneal (IP) injection of 250 mg/kg carnosine 60 minutes after cecal ligation-perforation. Rats were monitored for blood pressure, heart rate, and body temperature to assess the postoperative septic response, and body fluids were replaced as necessary. At the end of 24 hours, rats were sacrificed and liver samples were collected. Results Statistically significant improvements were observed in liver function, tissue and serum MDA levels, and histological findings in rats treated with carnosine, compared to rats with untreated sepsis. HB and HCT values did not change significantly during the course of the experiment. Rats exposed to septic shock and treated with carnosine exhibited decreased sinusoidal dilatation and cellular inflammation into the portal region, compared to the sepsis group; the livers of rats in this group had near-normal histological structure. Conclusions We conclude that carnosine may be an effective treatment for oxidative damage due to liver tissue perfusion defects in cases of septic shock. PMID:23396325

  16. Oxidative status in ICU patients with septic shock.

    PubMed

    Karapetsa, Maria; Pitsika, Marina; Goutzourelas, Nikos; Stagos, Dimitrios; Tousia Becker, Aphrodite; Zakynthinos, Epaminondas

    2013-11-01

    The aim of this pilot study was to investigate variability of oxidative stress during sepsis evolution. ICU patients with the diagnosis of septic shock were included. Thiobarbituric-acid reactive substances, total antioxidant capacity, protein carbonyls in plasma, reduced, oxidized glutathione and catalase activity in erythrocyte lysate were assessed in the 1st, 3rd, 5th and 8th day after sepsis appearance. A total of 17 patients were divided in two groups: survivors (n=7) and non-survivors (n=10). APACHE II was 11.5 ± 5.4 and 19.9 ± 4.97 in survivors and non-survivors respectively (p=0.005), while mean age and SOFA score at sepsis diagnosis, were similar between the two groups. GSH levels, catalase activity and protein carbonyls presented significant different course in time between survivors and non-survivors (p<0.05). Catalase activity was significantly higher in survivors (238.8 ± 51.5) than non-survivors (166.4 ± 40.2; p=0.005), while protein carbonyls levels were significantly lower in survivors (0.32 ± 0.09) than non-survivors (0.48 ± 0.16; p=0.036) on the 1st day. Yet, non-survivors exhibited a declining course in GSH levels during time, while GSH levels were maintained in survivors. Conclusively, a longstanding antioxidant deficiency in non-surviving patients was noted. This phenomenon was clearly prominent in patients' erythrocytes.

  17. Propensity-Based Study of Aminoglycoside Nephrotoxicity in Patients with Severe Sepsis or Septic Shock

    PubMed Central

    Picard, W.; Bazin, F.; Clouzeau, B.; Bui, H.-N.; Soulat, M.; Guilhon, E.; Vargas, F.; Hilbert, G.; Bouchet, S.; Gruson, D.; Moore, N.

    2014-01-01

    To assess the risk of acute kidney injury (AKI) attributable to aminoglycosides (AGs) in patients with severe sepsis or septic shock, we performed a retrospective cohort study in one medical intensive care unit (ICU) in France. Patients admitted for severe sepsis/septic shock between November 2008 and January 2010 were eligible. A propensity score for AG administration was built using day 1 demographic and clinical characteristics. Patients still on the ICU on day 3 were included. Patients with renal failure before day 3 or endocarditis were excluded. The time window for assessment of renal risk was day 3 to day 15, defined according to the RIFLE (risk, injury, failure, loss, and end-stage renal disease) classification. The AKI risk was assessed by means of a propensity-adjusted Cox proportional hazards regression analysis. Of 317 consecutive patients, 198 received AGs. The SAPS II (simplified acute physiology score II) score and nosocomial origin of infection favored the use of AGs, whereas a preexisting renal insufficiency and the neurological site of infection decreased the propensity for AG treatment. One hundred three patients with renal failure before day 3 were excluded. AGs were given once daily over 2.6 ± 1.1 days. AKI occurred in 16.3% of patients in a median time of 6 (interquartile range, 5 to 10) days. After adjustment to the clinical course and exposure to other nephrotoxic agents between day 1 and day 3, a propensity-adjusted Cox proportional hazards regression analysis showed no increased risk of AKI in patients receiving AGs (adjusted relative risk = 0.75 [0.32 to 1.76]). In conclusion, in critically septic patients presenting without early renal failure, aminoglycoside therapy for less than 3 days was not associated with an increased risk of AKI. PMID:25288085

  18. Cost analysis of real-time polymerase chain reaction microbiological diagnosis in patients with septic shock.

    PubMed

    Alvarez, J; Mar, J; Varela-Ledo, E; Garea, M; Matinez-Lamas, L; Rodriguez, J; Regueiro, B

    2012-11-01

    Antibiotic treatment for septic shock is generally prescribed on an empirical basis using broad-spectrum antibiotics. Molecular diagnostic techniques can detect the presence of microbial DNA in blood within a few hours and facilitate early, targeted treatment. The aim of this study was to evaluate the economic impact of a real-time polymerase chain reaction technique, LightCycler SeptiFast (LSC), in patients with sepsis. A cost-minimisation study was carried out in patients admitted with a diagnosis of severe sepsis or septic shock to the intensive care unit of a university hospital. The stay in the intensive care unit, hospital admission, 28-day and six-month mortality, and the economic cost of the clinical process were also evaluated. The study involved 48 patients in the LSC group and 54 patients in the control group. The total cost was €42,198 in the control group versus €32,228 in the LCS group with statistically significant differences (P <0.05), giving rise to an average net saving of €9970 per patient. The mortality rate was similar in both groups. The main finding of this study was the significant economic saving afforded by the use of the LCS technique, due to the shortening of intensive care unit stay and the use of fewer antibiotics.

  19. ACTIVATION OF COMMON ANTIVIRAL PATHWAYS CAN POTENTIATE INFLAMMATORY RESPONSES TO SEPTIC SHOCK

    PubMed Central

    Doughty, Lesley A.; Carlton, Stacey; Galen, Benjamin; Cooma-Ramberan, Indranie; Chung, Chung-Shiang; Ayala, Alfred

    2006-01-01

    Induction of the antiviral cytokine interferon α/β (IFN-α/β) is common in many viral infections. The impact of ongoing antiviral responses on subsequent bacterial infection is not well understood. In human disease, bacterial superinfection complicating a viral infection can result in significant morbidity and mortality. We injected mice with polyinosinic-polycytidylic (PIC) acid, a TLR3 ligand and known IFN-α/β inducer as well as nuclear factor κB (NF-κB) activator to simulate very early antiviral pathways. We then challenged mice with an in vivo septic shock model characterized by slowly evolving bacterial infection to simulate bacterial superinfection early during a viral infection. Our data demonstrated robust induction of IFN-α in serum within 24 h of PIC injection with IFN-α/β–dependent major histocompatibility antigen class II up-regulation on peritoneal macrophages. PIC pretreatment before septic shock resulted in augmented tumor necrosis factor alpha and interleukins 6 and 10 and heightened lethality compared with septic shock alone. Intact IFN-α/β signaling was necessary for augmentation of the inflammatory response to in vivo septic shock and to both TLR2 and TLR4 agonists in vitro. To assess the NF-κB contribution to PIC-modulated inflammatory responses to septic shock, we treated with parthenolide an NF-κB inhibitor before PIC and septic shock. Parthenolide did not inhibit IFN-α induction by PIC. Inhibition of NF-κB by parthenolide did reduce IFN-α–mediated potentiation of the cytokine response and lethality from septic shock. Our data demonstrate that pathways activated early during many viral infections can have a detrimental impact on the outcome of subsequent bacterial infection. These pathways may be critical to understanding the heightened morbidity and mortality from bacterial superinfection after viral infection in human disease. PMID:16878028

  20. Decreased HLA-DR antigen-associated invariant chain (CD74) mRNA expression predicts mortality after septic shock

    PubMed Central

    2013-01-01

    Introduction Septic syndromes remain the leading cause of mortality in intensive care units (ICU). Septic patients rapidly develop immune dysfunctions, the intensity and duration of which have been linked with deleterious outcomes. Decreased mRNA expressions of major histocompatibility complex (MHC) class II-related genes have been reported after sepsis. We investigated whether their mRNA levels in whole blood could predict mortality in septic shock patients. Methods A total of 93 septic shock patients were included. On the third day after shock, the mRNA expressions of five MHC class II-related genes (CD74, HLA-DRA, HLA-DMB, HLA-DMA, CIITA) were measured by qRT-PCR and monocyte human leukocyte antigen-DR (mHLA-DR) by flow cytometry. Results A significant correlation was found among MHC class II related gene expressions. Among mRNA markers, the best prognostic value was obtained for CD74 (HLA-DR antigen-associated invariant chain). For this parameter, the area under the receiver operating characteristic curve (AUC) was calculated (AUC = 0.67, 95% confidence interval (CI) = 0.55 to 0.79; P = 0.01) as well as the optimal cut-off value. After stratification based on this threshold, survival curves showed that a decreased CD74 mRNA level was associated with increased mortality after septic shock (Log rank test, P = 0.0043, Hazard Ratio = 3.0, 95% CI: 1.4 to 6.5). Importantly, this association remained significant after multivariate logistic regression analysis including usual clinical confounders (that is, severity scores, P = 0.026, Odds Ratio = 3.4, 95% CI: 1.2 to 9.8). Conclusion Decreased CD74 mRNA expression significantly predicts 28-day mortality after septic shock. After validation in a larger multicentric study, this biomarker could become a robust predictor of death in septic patients. PMID:24321376

  1. Immune-Response Patterns and Next Generation Sequencing Diagnostics for the Detection of Mycoses in Patients with Septic Shock-Results of a Combined Clinical and Experimental Investigation.

    PubMed

    Decker, Sebastian O; Sigl, Annette; Grumaz, Christian; Stevens, Philip; Vainshtein, Yevhen; Zimmermann, Stefan; Weigand, Markus A; Hofer, Stefan; Sohn, Kai; Brenner, Thorsten

    2017-08-18

    Fungi are of increasing importance in sepsis. However, culture-based diagnostic procedures are associated with relevant weaknesses. Therefore, culture- and next-generation sequencing (NGS)-based fungal findings as well as corresponding plasma levels of β-d-glucan, interferon gamma (INF-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-2, -4, -6, -10, -17A, and mid-regional proadrenomedullin (MR-proADM) were evaluated in 50 septic patients at six consecutive time points within 28 days after sepsis onset. Furthermore, immune-response patterns during infections with Candida spp. were studied in a reconstituted human epithelium model. In total, 22% (n = 11) of patients suffered from a fungal infection. An NGS-based diagnostic approach appeared to be suitable for the identification of fungal pathogens in patients suffering from fungemia as well as in patients with negative blood cultures. Moreover, MR-proADM and IL-17A in plasma proved suitable for the identification of patients with a fungal infection. Using RNA-seq., adrenomedullin (ADM) was shown to be a target gene which is upregulated early after an epithelial infection with Candida spp. In summary, an NGS-based diagnostic approach was able to close the diagnostic gap of routinely used culture-based diagnostic procedures, which can be further facilitated by plasmatic measurements of MR-proADM and IL-17A. In addition, ADM was identified as an early target gene in response to epithelial infections with Candida spp.

  2. Midkine, a multifunctional cytokine, in patients with severe sepsis and septic shock: a pilot study.

    PubMed

    Krzystek-Korpacka, Malgorzata; Mierzchala, Magdalena; Neubauer, Katarzyna; Durek, Grazyna; Gamian, Andrzej

    2011-05-01

    The objective of the study was to evaluate whether severe sepsis and septic shock are related to alterations in midkine concentrations, to identify disease-related factors associated with these alterations, and to initially appraise whether midkine might serve as a biomarker in sepsis. Prospective observational cross-sectional study with 5-day follow-up. Circulating midkine was measured (enzyme-linked immunosorbent assay) in 38 septic (13 with severe sepsis, 25 with septic shock), 82 active inflammatory bowel disease (IBD) (26 with systemic inflammatory response syndrome [SIRS]) patients, and 87 healthy subjects. Midkine significantly increased along with a sequence: health-inflammation (IBD)-systemic inflammation (IBD-SIRS)-severe sepsis/septic shock. High midkine levels (>1,000 ng/L) were found in 63% of septic and in 19% of IBD-SIRS patients, whereas extremely high concentrations (>5,000 ng/L) were found in 16% vs. 4%. Although not different at admission, midkine gradually decreased in severe sepsis and remained high in shock. Similarly, persistently high midkine was observed in patients with cardiovascular insufficiency (CVI) and in mechanically ventilated as compared with normalizing levels in patients without CVI and not requiring ventilation. The differences in devised simple rates (Δ5th-1st) were significant in all these cases. Accordingly, admission midkine was higher in patients with metabolic acidosis. Concerning pathogen, gram-positive infections were associated with the highest midkine levels. In conclusion, sepsis and septic shock are associated with midkine elevation, substantially more pronounced than in inflammation, even systemic, revealing a new potential mediator of deregulation of neutrophil migration. Sepsis-related global hypoxia seems to contribute to midkine elevation. Our results substantiate further research on possible midkine application as a sepsis biomarker: in differentiating SIRS from sepsis and identifying gram-positive sepsis and

  3. Comparison of noninvasive blood pressure monitoring with invasive arterial pressure monitoring in medical ICU patients with septic shock.

    PubMed

    Riley, Leonard E; Chen, Guoqing John; Latham, Heath E

    2017-08-01

    In the critically ill, the insertion of peripheral arterial catheters to monitor hemodynamics is a low-risk procedure, but carries the potential for complications. This study was designed to compare invasive and noninvasive blood pressure measurements in patients with septic shock in a medical ICU. We carried out a prospective observational study of patients admitted with septic shock and a radially inserted peripheral arterial catheter in the medical ICU with 31 adult patients who underwent four pairs of simultaneous noninvasive and invasive blood pressure measurements (124 comparisons), with the invasive blood pressure taken as the gold standard. Agreements between invasive and noninvasive blood pressure methods were assessed using Bland-Altman analysis, and clinical significance was determined by the European Society of Hypertension criteria. In all patients, noninvasive systolic (P=0.0385), diastolic (P<0.0001), and mean arterial pressures (P<0.0001) did correlate statistically with invasive measurements; however, all noninvasive pressure measurements did not correlate clinically according to the European Society of Hypertension criteria. In our patients admitted to the medical ICU with septic shock, noninvasive blood pressure monitoring did not clinically correlate with invasive blood pressure measurements.

  4. 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.

  5. The risk factors for mortality and septic shock in liver transplant recipients with ESKAPE bacteremia.

    PubMed

    Ouyang, Wen; Li, Xiaoxiao; Wan, Qiquan; Ye, Qifa

    2015-01-01

    Although bacteremias due to the six ESKAPE pathogens have recently been identified as a serious emerging problems in solid organ transplant (SOT), no information in liver transplant recipients is available. We sought to investigate the risk factors for mortality and septic shock in liver transplant recipients with ESKAPE bacteremia. A retrospective analysis of bacteremia after liver transplantation was reviewed. Risk factors for mortality and septic shock caused by ESKAPE bacteremia were identified. Forty-nine episodes ofbacteremia in 37 liver transplant recipients were due to ESKAPE strains. The only factor for bacteremia-related mortality independently associated with ESKAPE was septic shock (odds ratio [OR] = 67.500, 95% confidence interval [CI] = 8.464-538.300, P < .001). The factors for septic shock independently associated with ESKAPE were white blood cells count > 15,000/mm3 (OR = 15.205, 95% CI = 2.271-101.799, P = .005) and temperature of 39 °C or greater (OR = 10.959, 95% CI = 1.592-75.450, P = .015). To improve the results of liver transplantation, more effectively therapeutic treatments are of paramount importance when liver transplant recipients with ESKAPE bacteremia present with septic shock, elevated white blood cells count and high body temperature.

  6. [Effects of small volume resuscitation on the hemodynamics and extravascular lung water of septic shock dogs].

    PubMed

    Liang, Lu; Wang, Zhong; Xu, Jun; Yu, Xue-Zhong; Ma, Sui

    2008-04-01

    To observe the effect of small volume resuscitation by hypertonic-hyperoncotic solution on the hemodynamics and extravascular lung water of septic shock dogs. Lipopolysaccharide of E. coli was injected to 24 healthy dogs via femoral vein to induce septic shock. These septic shock dogs were resuscitated with hypertonic salt solutions (HS, 6 ml/kg, n = 6), 6% hydroxyethyl starch in combination with HS (HSS, 6 ml/kg, n=6), normal saline (NS, 100 ml/kg, n=6), and 6% hydroxyethyl starch solutions (HES, 33 ml/kg, n=6), respectively. The changes of hemodynamics and extravascular lung water were observed. After resuscitation, all the solutions improved the hemodynamics of septic shock dogs with significant differences (P<0.05). The effects were superior in HS group and HSS group when compared with in NS group. The extravascular lung water increased in NS group, while no obvious changes were found in the other three groups. All these four solutions can improve the hemodynamics of septic shock dogs. Small volume hypertonic-hyperoncotic solution has a similar effect in hemodynamics as NS, HS, and HES. Meanwhile, it does not increase the extravascular lung water.

  7. Transfusion requirements in septic shock (TRISS) trial - comparing the effects and safety of liberal versus restrictive red blood cell transfusion in septic shock patients in the ICU: protocol for a randomised controlled trial

    PubMed Central

    2013-01-01

    Background Transfusion of red blood cells (RBC) is recommended in septic shock and the majority of these patients receive RBC transfusion in the intensive care unit (ICU). However, benefit and harm of RBCs have not been established in this group of high-risk patients. Methods/Design The Transfusion Requirements in Septic Shock (TRISS) trial is a multicenter trial with assessor-blinded outcome assessment, randomising 1,000 patients with septic shock in 30 Scandinavian ICUs to receive transfusion with pre-storage leuko-depleted RBC suspended in saline-adenine-glucose and mannitol (SAGM) at haemoglobin level (Hb) of 7 g/dl or 9 g/dl, stratified by the presence of haematological malignancy and centre. The primary outcome measure is 90-day mortality. Secondary outcome measures are organ failure, ischaemic events, severe adverse reactions (SARs: anaphylactic reaction, acute haemolytic reaction and transfusion-related circulatory overload, and acute lung injury) and mortality at 28 days, 6 months and 1 year. The sample size will enable us to detect a 9% absolute difference in 90-day mortality assuming a 45% event rate with a type 1 error rate of 5% and power of 80%. An interim analysis will be performed after 500 patients, and the Data Monitoring and Safety Committee will recommend the trial be stopped if a group difference in 90-day mortality with P ≤0.001 is present at this point. Discussion The TRISS trial may bridge the gap between clinical practice and the lack of efficacy and safety data on RBC transfusion in septic shock patients. The effect of restrictive versus liberal RBC transfusion strategy on mortality, organ failure, ischaemic events and SARs will be evaluated. Trial registration ClinicalTrials.gov: NCT01485315. Registration date 30 November 2011. First patient was randomised 3 December 2011. PMID:23702006

  8. Septic versus non-septic acute kidney injury in critically ill patients: characteristics and clinical outcomes

    PubMed Central

    Cruz, Marília Galvão; Dantas, João Gabriel Athayde de Oliveira; Levi, Talita Machado; Rocha, Mário de Seixas; de Souza, Sérgio Pinto; Boa-Sorte, Ney; de Moura, Carlos Geraldo Guerreiro; Cruz, Constança Margarida Sampaio

    2014-01-01

    Objective This study aimed to describe and compare the characteristics and clinical outcomes of patients with septic and non-septic acute kidney injury. Methods This study evaluated an open cohort of 117 critically ill patients with acute kidney injury who were consecutively admitted to an intensive care unit, excluding patients with a history of advanced-stage chronic kidney disease, kidney transplantation, hospitalization or death in a period shorter than 24 hours. The presence of sepsis and in-hospital death were the exposure and primary variables in this study, respectively. A confounding analysis was performed using logistic regression. Results No significant differences were found between the mean ages of the groups with septic and non-septic acute kidney injury [65.30±21.27 years versus 66.35±12.82 years, respectively; p=0.75]. In the septic and non-septic acute kidney injury groups, a predominance of females (57.4% versus 52.4%, respectively; p=0.49) and Afro-descendants (81.5% versus 76.2%, respectively; p=0.49) was observed. Compared with the non-septic patients, the patients with sepsis had a higher mean Acute Physiology and Chronic Health Evaluation II score [21.73±7.26 versus 15.75±5.98; p<0.001)] and a higher mean water balance (p=0.001). Arterial hypertension (p=0.01) and heart failure (p<0.001) were more common in the non-septic patients. Septic acute kidney injury was associated with a greater number of patients who required dialysis (p=0.001) and a greater number of deaths (p<0.001); however, renal function recovery was more common in this group (p=0.01). Sepsis (OR: 3.88; 95%CI: 1.51-10.00) and an Acute Physiology and Chronic Health Evaluation II score >18.5 (OR: 9.77; 95%CI: 3.73-25.58) were associated with death in the multivariate analysis. Conclusion Sepsis was an independent predictor of death. Significant differences were found between the characteristics and clinical outcomes of patients with septic versus non-septic acute kidney

  9. [The significance of lactic acid in early diagnosis and goal-directed therapy of septic shock patients].

    PubMed

    Wang, Tao; Xia, Yongfu; Hao, Dong; Sun, Jianrong; Li, Zhi; Han, Shasha; Tian, Huanhuan; Zhang, Xiaorong; Qi, Zhijiang; Sun, Ting; Gao, Fuquan; Wang, Xiaozhi

    2014-01-01

    To investigate the application of lactic acid in early diagnosis and goal-directed therapy of septic shock, and to provide reference for the early clinical diagnosis and treatment of septic shock. A prospective observational study was conducted, in which patients satisfied with the criteria of septic shock diagnosis were enrolled. The patients were randomly divided into two groups. The lactic group was defined using blood lactic acid concentration < 2 mmol/L as treatment guide target. Control group was defined according to the traditional diagnostic criteria of shock which systolic blood pressure was less than 90 mmHg (1 mmHg= 0.133 kPa) or systolic blood pressure value fell > 40 mmHg baseline or oliguria ( < 0.5 ml. kg-1.h-1) et al traditional septic shock diagnosis criteria and bundle treatment was performed. Organ dysfunction index, the sequential organ failure score (SOFA), acute physiology and chronic health evaluation score II ( APACHE II) score, the time of mechanical ventilation, the time of stay in the intensive care unit ( ICU), and the 7-and 28-day mortality were recorded. There were 26 and 31 septic shock patients in lactic group and control group respectively. Organ dysfunction index had been improved in different degrees after treatment compared with that before treatment. Creatinine ( Cr) at 48 hours after treatment in lactic group was significantly lower than that in control group (μmol/L: 94.48 ± 6.68 vs. 107.44 ± 10.35, P < 0.05), and there was no statistical difference in other indexes. The SOFA score of lactic group at 24 hours and 48 hours after treatment was lower than that of control group (9.27 ± 4.62 vs. 9.79 ± 3.80, t=2.103, P=0.040; 8.54 ± 5.53 vs. 9.70 ± 4.30, t=2.302, P=0.023). APACHE II score of two group after treatment were lower than that before treatment, and lactic group decreased more obviously compared with control group ( 14.25 ± 5.29 vs. 20.00 ± 9.74, t=2.298, P=0.026; 13.60 ± 6.18 vs 18.15 ± 6.62, t=2.653, P=0

  10. The safety and efficacy of the use of vasopressin in sepsis and septic shock.

    PubMed

    Wilson, Stephen J; Mehta, Saurabh S; Bellamy, Mark C

    2005-11-01

    Sepsis remains a significant problem and cause of morbidity and mortality in intensive care. Vasopressin infusions are currently used as rescue therapy for the treatment of vasodilatory, catecholamine-resistant septic shock. At present, there are no large randomised, controlled trials in the literature investigating vasopressin in this role, although two such studies are currently ongoing in Canada. This review outlines the pathophysiology of sepsis and that of vasopressin in sepsis and reviews the available evidence for the use of vasopressin in sepsis and septic shock. A review of the safety data for vasopressin in this indication is included. Recommendations for the use of vasopressin in septic shock, along with suggestions for the direction of further work in the field are presented.

  11. Septic shock due to Klebsiella pneumoniae after medical abortion with misoprostol-only regimen.

    PubMed

    Kaponis, Apostolos; Papatheodorou, Stefania; Makrydimas, George

    2010-09-01

    To report a case of a healthy woman who was admitted to the hospital with septic shock caused by a common uropathogen after self-administration of misoprostol for pregnancy termination. Case report. Tertiary hospital. A 38-year-old woman, gravida 5, para 3, who developed septic shock after medical termination of pregnancy. Suction curettage, antibiotic treatment, plasma and platelet transfusions. Klebsiella pneumoniae was isolated from blood samples. Ten days after her admission she was discharged home in good condition on oral antibiotics. Severe infections leading to septic shock from common pathogen bacteria can occur after medical termination of pregnancy, independently of the regimen used. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  12. Transfusion requirements in septic shock (TRISS) trial - comparing the effects and safety of liberal versus restrictive red blood cell transfusion in septic shock patients in the ICU: protocol for a randomised controlled trial.

    PubMed

    Holst, Lars B; Haase, Nicolai; Wetterslev, Jørn; Wernerman, Jan; Aneman, Anders; Guttormsen, Anne B; Johansson, Pär I; Karlsson, Sari; Klemenzson, Gudmundur; Winding, Robert; Nebrich, Lars; Albeck, Carsten; Vang, Marianne L; Bülow, Hans-Henrik; Elkjær, Jeanie M; Nielsen, Jane S; Kirkegaard, Peter; Nibro, Helle; Lindhardt, Anne; Strange, Ditte; Thormar, Katrin; Poulsen, Lone M; Berezowicz, Pawel; Bådstøløkken, Per M; Strand, Kristian; Cronhjort, Maria; Haunstrup, Elsebeth; Rian, Omar; Oldner, Anders; Bendtsen, Asger; Iversen, Susanne; Langva, Jørn-Åge; Johansen, Rasmus B; Nielsen, Niklas; Pettilä, Ville; Reinikainen, Matti; Keld, Dorte; Leivdal, Siv; Breider, Jan-Michael; Tjäder, Inga; Reiter, Nanna; Gøttrup, Ulf; White, Jonathan; Wiis, Jørgen; Andersen, Lasse Høgh; Steensen, Morten; Perner, Anders

    2013-05-23

    Transfusion of red blood cells (RBC) is recommended in septic shock and the majority of these patients receive RBC transfusion in the intensive care unit (ICU). However, benefit and harm of RBCs have not been established in this group of high-risk patients. The Transfusion Requirements in Septic Shock (TRISS) trial is a multicenter trial with assessor-blinded outcome assessment, randomising 1,000 patients with septic shock in 30 Scandinavian ICUs to receive transfusion with pre-storage leuko-depleted RBC suspended in saline-adenine-glucose and mannitol (SAGM) at haemoglobin level (Hb) of 7 g/dl or 9 g/dl, stratified by the presence of haematological malignancy and centre. The primary outcome measure is 90-day mortality. Secondary outcome measures are organ failure, ischaemic events, severe adverse reactions (SARs: anaphylactic reaction, acute haemolytic reaction and transfusion-related circulatory overload, and acute lung injury) and mortality at 28 days, 6 months and 1 year.The sample size will enable us to detect a 9% absolute difference in 90-day mortality assuming a 45% event rate with a type 1 error rate of 5% and power of 80%. An interim analysis will be performed after 500 patients, and the Data Monitoring and Safety Committee will recommend the trial be stopped if a group difference in 90-day mortality with P ≤0.001 is present at this point. The TRISS trial may bridge the gap between clinical practice and the lack of efficacy and safety data on RBC transfusion in septic shock patients. The effect of restrictive versus liberal RBC transfusion strategy on mortality, organ failure, ischaemic events and SARs will be evaluated.

  13. Efficacy and Safety of Esmolol in Treatment of Patients with Septic Shock

    PubMed Central

    Du, Wei; Wang, Xiao-Ting; Long, Yun; Liu, Da-Wei

    2016-01-01

    Background: Previous studies have suggested that β1-receptor blockers benefit septic shock patients. This study aimed to determine whether β1-receptor blockers benefit tissue perfusion in sepsis and to identify parameters to reduce the risk of this drug in sepsis. Methods: Consecutive septic shock patients were recruited from the Intensive Care Unit of Peking Union Medical College Hospital within 48 h of diagnosis. All patients were hemodynamically stable and satisfactorily sedated with a heart rate (HR) ≥100 beats/min. Esmolol therapy achieved the target HR of 10–15% lower than the baseline HR. Clinical and physiological data of patients were collected prospectively within 1 h prior to esmolol therapy and 2 h after achieving the targeted HR. Results: Sixty-three patients were recruited. After esmolol therapy, blood pressure was unaltered, whereas stroke volume (SV) was increased compared with before esmolol therapy (43.6 ± 22.7 vs. 49.9 ± 23.7 ml, t = −2.3, P = 0.047). Tissue perfusion, including lactate levels (1.4 ± 0.8 vs. 1.1 ± 0.6 mmol/L, t = 2.6, P = 0.015) and the central venous-to-arterial carbon dioxide difference (5.6 ± 3.3 vs. 4.3 ± 2.2 mmHg, t = 2.6 P = 0.016), was also significantly decreased after esmolol therapy. For patients with increased SV (n = 42), cardiac efficiency improved, and esmolol therapy had a lower risk for a decrease in cardiac output (CO). Therefore, pretreatment cardiac systolic and diastolic parameters with (n = 42)/without (n = 21) an increase in SV were compared. Mitral lateral annular plane systolic excursion (MAPSElat) in patients with increased SV was significantly higher than that in those without increased SV (1.3 ± 0.3 vs. 1.1 ± 0.2 cm, t = 2.4, P = 0.034). Conclusions: SV of septic shock patients is increased following esmolol therapy. Although CO is also decreased with HR, tissue perfusion is not worse. MAPSElat can be used to predict an increase in SV before esmolol use. Trial Registration: Clinical

  14. Sustained low-efficiency dialysis in septic shock: Hemodynamic tolerability and efficacy

    PubMed Central

    Mishra, Shakti Bedanta; Singh, Ratender Kumar; Baronia, Arvind Kumar; Poddar, Banani; Azim, Afzal; Gurjar, Mohan

    2016-01-01

    Aim of the Study: Acute kidney injury (AKI) in septic shock has poor outcomes. Sustained low-efficiency dialysis (SLED) is increasingly replacing continuous renal replacement therapy as the preferred modality in Intensive Care Units (ICUs). However, the essential aspects of hemodynamic tolerability and efficacy of SLED in septic shock AKI has been minimally studied. Patients and Methods: We describe hemodynamic tolerability using modified vasopressor index (VI) and vasopressor dependency (VD) and efficacy using a combination of Kt/v, correction of acidosis, electrolyte, and fluid overload. Adult ICU patients of septic shock in AKI requiring SLED were included in this study. Results: One hundred and twenty-four patients of septic shock AKI requiring SLED were enrolled in the study. There were 74 nonsurvivors (NSs). Approximately, 56% (278/498) of the sessions in which vasopressors were required were studied. Metabolic acidosis (49%) was the predominant indication for the initiation of SLED in these patients. Baseline characteristics between survivors and NSs were comparable, except for age, severity scores, AKI stage, and coexisting illness. VI and VD prior to the initiation of SLED and delta VI and VD during SLED were significantly higher in NSs. Hemodynamic tolerability and efficacy of SLED was achievable only at lower vasopressor doses. Conclusion: VI, VD, and combination of Kt/v together with correction of acidosis, electrolyte, and fluid overload can be used to describe hemodynamic tolerability and efficacy of SLED in septic shock AKI. However, at higher vasopressor doses in septic shock, hemodynamic tolerability and efficacy of SLED requires further evidence. PMID:28149027

  15. The pharmacokinetics of vancomycin during the initial loading dose in patients with septic shock

    PubMed Central

    Katip, Wasan; Jaruratanasirikul, Sutep; Pattharachayakul, Sutthiporn; Wongpoowarak, Wibul; Jitsurong, Arnurai; Lucksiri, Aroonrut

    2016-01-01

    Objective To characterize the pharmacokinetics (PK) of vancomycin in patients in the initial phase of septic shock. Methods Twelve patients with septic shock received an intravenous infusion of vancomycin 30 mg/kg over 2 h. The vancomycin PK study was conducted during the first 12 h of the regimen. Serum vancomycin concentration–time data were analyzed using the standard model-independent analysis and the compartment model. Results For the noncompartment analysis the mean values ± standard deviation (SD) of the estimated clearance and volume of distribution of vancomycin at steady state were 6.05±1.06 L/h and 78.73±21.78 L, respectively. For the compartmental analysis, the majority of vancomycin concentration–time profiles were best described by a two-compartment PK model. Thus, the two-compartmental first-order elimination model was used for the analysis. The mean ± SD of the total clearance (3.70±1.25 L/h) of vancomycin was higher than that obtained from patients without septic shock. In contrast, the volume of the central compartment (8.34±4.36 L) and volume of peripheral compartment (30.99±7.84 L) did not increase when compared with patients without septic shock. Conclusion The total clearance of vancomycin was increased in septic shock patients. However, the volume of the central compartment and peripheral compartment did not increase. Consequently, a loading dose of vancomycin should be considered in all patients with septic shock. PMID:27920562

  16. Volume Overload: Prevalence, Risk Factors, and Functional Outcome in Survivors of Septic Shock

    PubMed Central

    Carlbom, David; Caldwell, Ellen; Himmelfarb, Jonathan; Hough, Catherine L.

    2015-01-01

    Rationale: Survivors of septic shock have impaired functional status. Volume overload is associated with poor outcomes in patients with septic shock, but the impact of volume overload on functional outcome and discharge destination of survivors is unknown. Objectives: This study describes patterns of fluid management both during and after septic shock. We examined factors associated with volume overload upon intensive care unit (ICU) discharge. We then examined associations between volume overload upon ICU discharge, mobility limitation, and discharge to a healthcare facility in septic shock survivors, with the hypothesis that volume overload is associated with increased odds of these outcomes. Methods: We retrospectively reviewed the medical records of 247 patients admitted with septic shock to an academic county hospital between June 2009 and April 2012 who survived to ICU discharge. We defined volume overload as a fluid balance expected to increase the subject’s admission weight by 10%. Statistical methods included unadjusted analyses and multivariable logistic regression. Measurements and Main Results: Eighty-six percent of patients had a positive fluid balance, and 35% had volume overload upon ICU discharge. Factors associated with volume overload in unadjusted analyses included more severe illness, cirrhosis, blood transfusion during shock, and higher volumes of fluid administration both during and after shock. Blood transfusion during shock was independently associated with increased odds of volume overload (odds ratio [OR], 2.65; 95% confidence interval [CI], 1.33–5.27; P = 0.01) after adjusting for preexisting conditions and severity of illness. Only 42% of patients received at least one dose of a diuretic during their hospitalization. Volume overload upon ICU discharge was independently associated with inability to ambulate upon hospital discharge (OR, 2.29; 95% CI, 1.24–4.25; P = 0.01) and, in patients admitted from home, upon discharge to

  17. Plesiomonas shigelloides Septic Shock Leading to Death of Postsplenectomy Patient with Pyruvate Kinase Deficiency and Hemochromatosis

    PubMed Central

    2016-01-01

    Although Plesiomonas shigelloides, a water-borne bacterium of the Enterobacteriaceae family, usually causes self-limiting gastroenteritis with diarrhea, several cases of sepsis have been reported. We report the case of a 43-year-old male patient with hemochromatosis, pyruvate kinase deficiency, and asplenia via splenectomy who developed septic shock caused by P. shigelloides complicated by respiratory failure, renal failure, liver failure, and disseminated intravascular coagulation. Early aggressive antimicrobial therapy and resuscitation measures were unsuccessful and the patient passed away. We kindly suggest clinicians to implement early diagnosis of septic shock, empirical coverage with antibiotics, and prompt volume resuscitation based on the high mortality rate of P. shigelloides bacteremia. PMID:27610253

  18. Strongyloidiasis: an unusual cause of septic shock with pneumonia and enteropathy in western countries

    PubMed Central

    Montini, Florent; Grenouillet, Frederic; Capellier, Gilles; Piton, Gaël

    2015-01-01

    We report a case of invasive strongyloidiasis in a patient from the French Antilles who had been living in France for many years, with no history of immunosuppression, and who was hospitalised in the intensive care unit for septic shock with multimicrobial hypoxaemia pneumonia and exudative enteropathy. Initiation of systemic corticosteroid therapy for septic shock seems to have precipitated onset of the parasitic infection, with recurrence of hypoxaemic pneumonia complicated by hypoxic cardiac arrest. The diagnosis was confirmed after roundworm larvae were found on bronchoalveolar lavage. Treatment with ivermectin was initiated, but the patient died in a context of postanoxic encephalopathy. PMID:25819827

  19. Structural changes of the heart during severe sepsis or septic shock.

    PubMed

    Smeding, Lonneke; Plötz, Frans B; Groeneveld, A B Johan; Kneyber, Martin C J

    2012-05-01

    Cardiovascular dysfunction is common in severe sepsis or septic shock. Although functional alterations are often described, the elevated serum levels of cardiac proteins and autopsy findings of myocardial immune cell infiltration, edema, and damaged mitochondria suggest that structural changes to the heart during severe sepsis and septic shock may occur and may contribute to cardiac dysfunction. We explored the available literature on structural (versus functional) cardiac alterations during experimental and human endotoxemia and/or sepsis. Limited data suggest that the structural changes could be prevented, and myocardial function improved by (pre-)treatment with platelet-activating factor, cyclosporin A, glutamine, caffeine, simvastatin, or caspase inhibitors.

  20. [Plasma exchange in treatment refractory septic shock : Presentation of a therapeutic add-on strategy].

    PubMed

    David, S; Hoeper, M M; Kielstein, J T

    2017-02-01

    Sepsis is defined as a systemic inflammatory response of the body to an infection. Besides anti-infective drugs and removal of the site of infection, no specific therapeutics that target the overwhelming host response are available. Clinical researchers are currently evaluating the extracorporeal elimination of circulating cytokines. Modern adsorbing techniques have increasingly been used for this purpose allowing an unselective but highly effective removal of the vast majority of circulating cytokines but also fail to replace used protective factors in patients' plasma. Therapeutic plasma exchange (TPE) however might represent a novel method to remove pathologically elevated cytokines and simultaneously to replace protective plasmatic factors. Here we report the case of a septic shock patient treated with TPE and review the available literature with respect to TPE as an adjunctive therapy in sepsis.

  1. The Role of Adjunctive Therapies in Septic Shock by Gram Negative MDR/XDR Infections

    PubMed Central

    Roat, Erika; Serafini, Giulia; Mantovani, Elena; Biagioni, Emanuela

    2017-01-01

    Patients with septic shock by multidrug resistant microorganisms (MDR) are a specific sepsis population with a high mortality risk. The exposure to an initial inappropriate empiric antibiotic therapy has been considered responsible for the increased mortality, although other factors such as immune-paralysis seem to play a pivotal role. Therefore, beyond conventional early antibiotic therapy and fluid resuscitation, this population may benefit from the use of alternative strategies aimed at supporting the immune system. In this review we present an overview of the relationship between MDR infections and immune response and focus on the rationale and the clinical data available on the possible adjunctive immunotherapies, including blood purification techniques and different pharmacological approaches. PMID:28775744

  2. Similar change in platelets and leucocytes 24 h after injury is associated with septic shock a week later.

    PubMed

    Jol, Saskia; Hietbrink, Falco; Leenen, Luke P H; Koenderman, Leo; van Wessem, Karlijn J P

    2017-03-01

    Septic shock is a severe complication in polytrauma patients. Early identification of patients at risk can guide future prevention strategies. Platelets (PLTs) and leucocytes presumably play an important role in the post-injury inflammatory response. The role of early changes in PLT and leucocyte counts was investigated in search for the aetiology of the development of septic complications. Polytrauma patients (aged 16-80 years) admitted to the intensive care unit with an expected stay of at least 3 days were included. PLT and leucocyte counts were measured on a daily basis for 14 days. A total of 41 patients were included, of whom nine (22%) developed septic shock. There was no difference in (New) Injury Severity Score or Acute Physiology and Chronic Health Evaluation II scores between patients who developed septic shock and patients who did not. Three patients died, one of them in septic shock. Patients who developed septic shock during hospital stay had lower PLTs and a slower recovery to normal PLT counts than patients without septic shock. Patients who developed either a decrease in both PLTs and leucocytes or an increase in PLTs and leucocytes in the first 24 h after trauma were more likely to develop septic shock. This correlation was not found in patients who did not develop septic shock. A similar change in PLT and leucocyte counts in the first 24 h after trauma is associated with the development of septic shock after a week. This indicates an early interaction between PLTs and leucocytes, which needs further investigation to gain more insight in the aetiology of post-injury septic complications. © 2017 Royal Australasian College of Surgeons.

  3. Evolution of Blood Lactate and 90-Day Mortality in Septic Shock. A Post Hoc Analysis of the FINNAKI Study.

    PubMed

    Varis, Elina; Pettilä, Ville; Poukkanen, Meri; Jakob, Stephan M; Karlsson, Sari; Perner, Anders; Takala, Jukka; Wilkman, Erika

    2017-05-01

    Hyperlactatemia predicts mortality in patients with sepsis and septic shock, and its normalization is a potential treatment goal. We investigated the association of blood lactate and its changes over time with 90-day mortality in septic shock. We performed a post hoc analysis of 513 septic shock patients with admission blood lactate measurements in the prospective, observational, multicenter FINNAKI study. Repetitive lactate measurements were available in 496 patients for analyses of change in lactate values during intensive care unit stay.The 90-day mortality for all patients was 33.3%. Patients with admission lactate >2 mmol/L had higher 90-day mortality than those with admission lactate ≤2 mmol/L (43.4% vs. 22.6%, P < 0.001). Patients with persistent hyperlactatemia (>2 mmol/L) at ≥72 h had higher 90-day mortality compared with those with a lactate value of ≤2.0 mmol/L (52.0% vs. 24.3%, P < 0.001). Time-weighted mean lactate values were higher in non-survivors than in survivors, (median [IQR] 2.05 [1.38-4.22] mmol/L vs. 1.29 [0.98-1.77] mmol/L, P < 0.001). Time to normalization of lactate was comparable for 90-day non-survivors and survivors (median [IQR] 17.0 [3.5-43.5] vs. 15.0 [5.0-35.0] h, P = 0.67). In separate models, time-weighted mean lactate, lactate value at ≥72 h, and hyperlactatemia at ≥72 h were independently associated with 90-day mortality, but admission lactate and time to normalization of lactate were not. These findings may inform future clinical trials using combined surrogate endpoints for mortality in septic shock patients.

  4. Polymyxin B-immobilized fiber hemoperfusion in a high school football player with septic shock caused by osteitis pubis.

    PubMed

    Nakamura, Tsukasa; Sato, Eiichi; Fujiwara, Nobuharu; Kawagoe, Yasuhiro; Egawa, Yoshinaga; Ueda, Yoshihiko; Koide, Hikaru

    2011-01-01

    A 17-year-old male high school football player treated by polymyxin B-immobilized fiber (PMX-F) hemoperfusion for mild-moderate septic shock caused by osteitis pubis is described in this study. He was admitted for inguinal pain, gait disturbance, and high fever (40.6°C). His white blood cell (WBC) count and C-reactive protein (CRP), endotoxin, and procalcitonin (PCT) levels were significantly elevated. His blood pressure was 76/46 mm Hg. Magnetic resonance imaging showed bone and muscle injury at the pubic symphysis. Septic shock with high blood endotoxin and PCT concentrations was diagnosed, and the patient was treated with antibiotics, γ-globulin, and dopamine on the admission day. However, the septic shock did not improve. On day 3, we performed direct hemoperfusion twice using a PMX-F column. After the second PMX-F treatment, the patient's temperature decreased to 37.0°C, and his WBC count, CRP levels, blood endotoxin, and PCT levels decreased. The inguinal pain diminished, and the patient's blood pressure increased to 112/76 mm Hg. He was discharged on day 10 after admission. This case reflects association of PMX-F with decreased endotoxin, PCT, and CRP, suggesting the association of PMX-F with clinical improvement in mild-moderate sepsis in a young athlete.

  5. Recent advances in perioperative anesthetic management update in the perioperative support of patients with septic shock and the effect on outcomes.

    PubMed

    Douglas, Aaron; Wurm, Ellen; Pickett, Patrick; Hata, J Steven

    2012-01-01

    Septic shock during the perioperative period imparts significant challenges for anesthetic management. There is increasing support for standardization of care using evidence-based, international consensus guidelines, such as the Surviving Sepsis Campaign. This review will highlight practices in the supportive management relevant to the perioperative care of patients with severe sepsis or septic shock and their effect on clinical outcomes. It will address the epidemiological data of sepsis, the diagnostic criteria, and the role of routine, goal-directed hemodynamic resuscitation. Furthermore, it will review other options for support, including antibiotics, intensive insulin therapy, and intensive care sedation in this high risk patient population.

  6. Septic shock secondary to infection of a left ventricular thrombus.

    PubMed

    Ruiz-Bailén, Manuel; Ramos-Cuadra, Jose Angel; Aragón-Extremera, Victor Manuel; Rucabado-Aguilar, Luis

    2009-10-01

    We report the case of a 45-year-old woman who developed severe shock with multiorgan failure requiring admission to intensive care. Endomyocardial biopsy was performed and she was diagnosed with sepsis secondary to left ventricular thrombus abscess. Surgery was contraindicated and the patient received exclusively medical treatment; the clinical course was satisfactory and the patient is alive one year later. An apical thrombus may rarely be complicated by infection. Although management normally requires surgical excision, medical management may be effective in situations in which surgery is contraindicated.

  7. Analysis and modelling of septic shock microarray data using Singular Value Decomposition.

    PubMed

    Allanki, Srinivas; Dixit, Madhulika; Thangaraj, Paul; Sinha, Nandan Kumar

    2017-06-01

    Being a high throughput technique, enormous amounts of microarray data has been generated and there arises a need for more efficient techniques of analysis, in terms of speed and accuracy. Finding the differentially expressed genes based on just fold change and p-value might not extract all the vital biological signals that occur at a lower gene expression level. Besides this, numerous mathematical models have been generated to predict the clinical outcome from microarray data, while very few, if not none, aim at predicting the vital genes that are important in a disease progression. Such models help a basic researcher narrow down and concentrate on a promising set of genes which leads to the discovery of gene-based therapies. In this article, as a first objective, we have used the lesser known and used Singular Value Decomposition (SVD) technique to build a microarray data analysis tool that works with gene expression patterns and intrinsic structure of the data in an unsupervised manner. We have re-analysed a microarray data over the clinical course of Septic shock from Cazalis et al. (2014) and have shown that our proposed analysis provides additional information compared to the conventional method. As a second objective, we developed a novel mathematical model that predicts a set of vital genes in the disease progression that works by generating samples in the continuum between health and disease, using a simple normal-distribution-based random number generator. We also verify that most of the predicted genes are indeed related to septic shock. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Salivary Cortisol Can Replace Free Serum Cortisol Measurements in Patients With Septic Shock

    PubMed Central

    Orlander, Philip R.

    2011-01-01

    Background: There is a renewed interest in adrenal function during severe sepsis. Most studies have used total serum cortisol levels; however, only free serum cortisol is biologically active. The aim of this study was to determine the validity of salivary cortisol levels as a surrogate for free serum cortisol levels during septic shock. Methods: Fifty-seven patients with septic shock were studied to determine the correlation between total serum cortisol and salivary cortisol to free serum cortisol levels. Thirty-eight patients were included in the salivary to free serum cortisol correlation. Salivary cortisol level was tested by enzyme immunoassay. Serum total cortisol, free cortisol, and cortisol-binding globulin (CBG) levels were determined by liquid chromatography-mass spectrometry, equilibrium analysis, and radioimmunoassay, respectively. Results: The mean ± SD age was 56.6 ± 18.5 years. Fifty-seven percent were women. APACHE (Acute Physiology and Chronic Health Evaluation) II score median was 26, Simplified Acute Physiology Score II median was 61, and Sequential Organ Failure Assessment median was 13. The correlation between salivary and free serum cortisol levels was 0.79 (95% CI, 0.63-0.89; P < .0001). The correlation between free serum cortisol and total serum cortisol levels was 0.86 (95% CI, 0.78-0.92; P < .0001). The mean ± SD free serum cortisol level was 2.27 ± 1.64 μg/dL. The mean ± SD salivary cortisol level was 2.60 ± 2.69 μg/dL. The mean ± SD total serum cortisol level was 21.56 ± 8.71 μg/dL. The mean ± SD CBG level was 23.54 ± 8.33 mg/dL. Conclusions: Salivary cortisol level can be used as a surrogate of free serum cortisol level in patients with septic shock with very good correlation. Salivary cortisol testing is noninvasive, easy to perform, and can be conducted daily. Trial registry: ClinicalTrials.gov; No.: NCT00523198; URL: www.clinicaltrials.gov PMID:21816912

  9. A randomized trial of protocol-based care for early septic shock.

    PubMed

    Yealy, Donald M; Kellum, John A; Huang, David T; Barnato, Amber E; Weissfeld, Lisa A; Pike, Francis; Terndrup, Thomas; Wang, Henry E; Hou, Peter C; LoVecchio, Frank; Filbin, Michael R; Shapiro, Nathan I; Angus, Derek C

    2014-05-01

    .51; P=0.31). There were no significant differences in 90-day mortality, 1-year mortality, or the need for organ support. In a multicenter trial conducted in the tertiary care setting, protocol-based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes. (Funded by the National Institute of General Medical Sciences; ProCESS ClinicalTrials.gov number, NCT00510835.).

  10. Role of alpha-2-macroglobulin and bacterial elastase in guinea-pig pseudomonal septic shock.

    PubMed Central

    Khan, M. M.; Shibuya, Y.; Kambara, T.; Yamamoto, T.

    1995-01-01

    An essential role of alpha-2-macroglobulin (alpha 2M) was revealed in the prevention of septic shock induced in guinea-pigs by an elastase producing strain (IFO-3455) of Pseudomonas aeruginosa. When bacterial peritonitis was induced by inoculating fibrin-thrombin clot containing viable bacteria at a dose of 10(9) c.f.u./kg body weight, the guinea-pigs (n = 6) died within 7-8 hours due to septic shock. Prior to the shock, consumption of two-thirds of the circulating alpha 2M was observed. When circulating alpha 2M was depleted 4 hours after the bacterial inoculation, the guinea-pigs immediately developed shock and died within one hour. This shock was prevented either with a specific elastase inhibitor, HONHCOCH(CH2C6H5)CO-Ala-Gly-NH2, zincov (6 microM), or with human alpha 2M. Simultaneous depletion of circulating Hageman factor also prevented shock in the alpha 2M-depleted animals. These results indicate that septic shock was induced through activation of the Hageman factor dependent system by the bacteria-produced elastase which survived alpha 2M in the circulation. PMID:7537522

  11. Urinary liver-type fatty acid-binding protein in septic shock: effect of polymyxin B-immobilized fiber hemoperfusion.

    PubMed

    Nakamura, Tsukasa; Sugaya, Takeshi; Koide, Hikaru

    2009-05-01

    We aimed to determine retrospectively whether urinary liver-type fatty acid-binding protein (L-FABP) levels are altered in patients with septic shock or severe sepsis without shock and whether polymyxin B-immobilized fiber (PMX-F) hemoperfusion affects these levels. Forty patients with septic shock, 20 patients with severe sepsis without shock, 20 acute renal failure (ARF) patients without septic shock (mean serum creatinine, 2.8 mg/dL), and 30 healthy volunteers were included in this study. Polymyxin B-immobilized fiber hemoperfusion was performed twice in 40 patients. In addition, 10 patients with septic shock without PMX-F treatment (conventional treatment) were also enrolled in this study. Their families did not choose PMX-F treatment. Thus, their informed consents to perform PMX-F treatment were not obtained. Septic shock or severe sepsis was defined by the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee. Patients with septic shock were eligible for inclusion in the study if they had a definable source of infection and/or positive blood cultures. Patients with cardiogenic or hemorrhagic shock were excluded from the study. The patients were not randomly allocated to receive PMX-F treatment. Urinary and serum L-FABP levels were measured by enzyme-linked immunosorbent assay method. Plasma endotoxin levels in patients with septic shock were significantly higher than those in patients with severe sepsis (P < 0.05), patients with ARF (P < 0.001), and healthy subjects (P < 0.001). Urinary L-FABP levels in patients with septic shock were significantly higher than those in patients with severe sepsis without shock (P < 0.001), patients with ARF (P < 0.001), and healthy subjects (P < 0.001), whereas serum L-FABP levels showed no significant differences between patients with septic shock, patients with severe sepsis, patients with ARF, and healthy subjects. Urinary L-FABP was not correlated with serum L-FABP. Twenty

  12. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.

    PubMed

    Dellinger, R Phillip; 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

    2008-01-01

    To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," published in 2004. Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. We used the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation (1) indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost) or clearly do not. Weak recommendations (2) indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. Key recommendations, listed by category, include early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7-10 days

  13. The peroxynitrite catalyst WW-85 improves pulmonary function in ovine septic shock.

    PubMed

    Maybauer, Dirk M; Maybauer, Marc O; Szabó, Csaba; Cox, Robert A; Westphal, Martin; Kiss, Levente; Horvath, Eszter M; Traber, Lillian D; Hawkins, Hal K; Salzman, Andrew L; Southan, Garry J; Herndon, David N; Traber, Daniel L

    2011-02-01

    Systemic inflammatory response syndrome is associated with excessive production of nitric oxide (NO·) and superoxide (O2), forming peroxynitrite, which in turn, acts as a terminal mediator of cellular injury by producing cell necrosis and apoptosis. We examined the effect of the peroxynitrite decomposition catalyst, WW-85, in a sheep model of acute lung injury and septic shock. Eighteen sheep were operatively prepared and randomly allocated to the sham, control, or WW-85 group (n = 6 each). After a tracheotomy, acute lung injury was produced in the control and WW-85 groups by insufflation of four sets of 12 breaths of cotton smoke. Then, a 30-mL suspension of live Pseudomonas aeruginosa bacteria (containing 2 - 5 × 10¹¹ colony-forming units) was instilled into the lungs according to an established protocol. The sham group received only the vehicle (30 mL saline). The sheep were studied in awake state for 24 h and ventilated with 100% oxygen. WW-85 was administered 1 h after injury as bolus infusion (0.1 mg/kg), followed by a continuous infusion of 0.02 mg·kg⁻¹·h⁻¹ until the end of the 24-h experimental period. Compared with injured but untreated controls, WW-85-treated animals had significantly improved gas exchange, reductions in airway obstruction, shunt formation, lung myeloperoxidase concentrations, lung malondialdehyde concentrations, lung 3-nitrotyrosine concentrations, and plasma nitrate-to-nitrite levels. Animals treated with WW-85 exhibited less microvascular leakage and improvements in pulmonary function. These results provide evidence that blockade of the nitric oxide-peroxynitrite pathway improves disturbances from septic shock, as demonstrated in a clinically relevant ovine experimental model.

  14. THE PEROXYNITRITE CATALYST WW-85 IMPROVES PULMONARY FUNCTION IN OVINE SEPTIC SHOCK

    PubMed Central

    Maybauer, Dirk M.; Maybauer, Marc O.; Szabó, Csaba; Cox, Robert A.; Westphal, Martin; Kiss, Levente; Horvath, Eszter M.; Traber, Lillian D.; Hawkins, Hal K.; Salzman, Andrew L.; Southan, Garry J.; Herndon, David N.; Traber, Daniel L.

    2013-01-01

    Systemic inflammatory response syndrome (SIRS) is associated with excessive production of nitric oxide (NO•) and superoxide (O2−), forming peroxynitrite (ONOO−), which in turn, acts as a terminal mediator of cellular injury by producing cell necrosis and apoptosis. We examined the effect of the ONOO− decomposition catalyst WW-85 in a sheep model of acute lung injury (ALI) and septic shock. Eighteen sheep were operatively prepared and randomly allocated, either to the sham, control, or WW-85 group (n=6 each). Following a tracheotomy, ALI was produced in the control and WW-85 group by insufflation of four sets of 12 breaths of cotton smoke. Then, a 30 mL suspension of live Pseudomonas aeruginosa bacteria (containing 2–5×1011 cfu) was instilled into the lungs according to an established protocol. The sham group received only the vehicle (30 mL saline). The sheep were studied in awake state for 24 hrs and ventilated with 100% oxygen. WW-85 was administered 1 h post injury as bolus infusion (0.1 mg/kg), followed by a continuous infusion of 0.02 mg•kg−1•h−1 until the end of the 24-h experimental period. Compared to injured but untreated controls, WW-85-treated animals had significantly improved gas exchange, reductions in airway obstruction, shunt formation, lung myeloperoxidase-, lung malondialdehyde-, lung 3-nitrotyrosine concentrations, and plasma nitrate-to-nitrite (NOx) levels. Animals treated with WW-85 exhibited less microvascular leakage and improvements in pulmonary function. These results provide evidence that blockade of the nitric oxide - peroxynitrite pathway improves disturbances from septic shock, as demonstrated in a clinically relevant ovine experimental model. PMID:20577150

  15. Correlation between different Chinese medicine syndromes and changes in microcirculation in septic shock patients.

    PubMed

    Liu, Jing-feng; Zhao, Meng-ya; Zhuang, Hai-zhou; Liu, Chong; Weng, Yi-bing; Li, Ang; Zhang, Shu-wen; Duan, Mei-li

    2013-10-01

    To investigate the correlation between different Chinese medicine (CM) syndromes and variations in microcirculation in septic shock patients. seventy Septic shock patients were divided into four groups: heat damaging qi-yin group (HDQY, 23 cases); yin exhaustion and yang collapse group (YEYC, 26 cases); excessive heat in Fu organ group (EHFO, 10 cases); and heat damaging nutrient-blood group (HDNB, 11 cases). Sublingual microcirculation parameters were observed by sidestream dark-field (SDF) imaging and scored by Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA), and parameters of microcirculation perfusion variations and prognoses were analyzed. Compared with those with qi-yin heat damage, perfused vessel density (PVD) in other groups decreased dramatically (P<0.05), and APACHE II scores increased significantly (P<0.05). In addition, the recovery time was prolonged substantially (P<0.05), and the mixed venous oxygen saturation (SVO2) decreased (P<0.05). Blood lactic acid increased significantly (P<0.05), and the mixed SVO decreased (P<0.05), in the YEYC group. Compared with the thermal injury camp blood group, sublingual microcirculation parameter variations showed no obvious difference in the YEYC and EHFO groups (P>0.05). There were significant positive correlations between CM syndromes and APACHE II scoring in different groups (r=0.512, P<0.05). There were negative correlations between PVD and APACHE II scoring (r=-0.378, P=0.043), the proportion of perfused vessels (PPV) and APACHE II scoring (r=-0.472, P=0.008), as well as between the microvascular flow index (MFI) and APACHE II scoring (r=-0.424, P=0.023) in different patients. Sublingual microcirculation may serve as a clinical diagnostic parameter of the patient condition, as well as being a prognostic indicator.

  16. Septic shock: a major cause of hospital death after intensive care unit discharge

    PubMed Central

    Giacomini, Matheus Gomes; Lopes, Márcia Valéria Caldeira Angelucci; Gandolfi, Joelma Villafanha; Lobo, Suzana Margareth Ajeje

    2015-01-01

    Objective To assess the causes and factors associated with the death of patients between intensive care unit discharge and hospital discharge. Methods The present is a pilot, retrospective, observational cohort study. The records of all patients admitted to two units of a public/private university hospital from February 1, 2013 to April 30, 2013 were assessed. Demographic and clinical data, risk scores and outcomes were obtained from the Epimed monitoring system and confirmed in the electronic record system of the hospital. The relative risk and respective confidence intervals were calculated. Results A total of 581 patients were evaluated. The mortality rate in the intensive care unit was 20.8% and in the hospital was 24.9%. Septic shock was the cause of death in 58.3% of patients who died after being discharged from the intensive care unit. Of the patients from the public health system, 73 (77.6%) died in the intensive care unit and 21 (22.4%) died in the hospital after being discharged from the unit. Of the patients from the Supplementary Health System, 48 (94.1%) died in the intensive care unit and 3 (5.9%) died in the hospital after being discharged from the unit (relative risk, 3.87%; 95% confidence interval, 1.21 - 12.36; p < 0.05). The post-discharge mortality rate was significantly higher in patients with intensive care unit hospitalization time longer than 6 days. Conclusion The main cause of death of patients who were discharged from the intensive care unit and died in the ward before hospital discharge was septic shock. Coverage by the public healthcare system and longer hospitalization time in the intensive care unit were factors associated with death after discharge from the intensive care unit. PMID:25909313

  17. [Septic shock in ICU: advanced therapeutics, immunoparalysis and genomics. State of the art].

    PubMed

    Arriagada S, Daniela; Donoso F, Alejandro; Cruces R, Pablo; Díaz R, Franco

    2014-08-01

    New and important concepts have emerged for the advanced management of the child with septic shock in the recent decades. Attending physicians in the Pediatric intensive care unit must be fully aware of them to improve patient care in the critical care unit. It should be considered the use of immune therapy only in selected groups of patients. Continuous renal replacement therapies are well tolerated and their early use prevents deleterious fluid overload. Removal of inflammatory mediators by using high volume hemofiltration may play a role in hyperdynamic septic patients. The use of plasmapheresis is recommended in patients with thrombocytopenia-associated multiple organ failure. Extracorporeal support use should be considered in those with refractory septic shock despite goals directed therapy. The immunoparalysis has been associated with nosocomial infections and late mortality. The information from genetic markers may allow early intervention and preventive genomics-based medicine.

  18. Effect of unfractionated heparin on endothelial glycocalyx in a septic shock model.

    PubMed

    Yini, S; Heng, Z; Xin, A; Xiaochun, M

    2015-02-01

    The constituents of vascular endothelial glycocalyx, such as syndecan-1 and heparan sulphate (HS), can be detected in the plasma of patients and animals with septic shock. However, the dynamics of glycocalyx degradation and its association with inflammation remains largely unknown. In this study, we investigated the association between the biomarkers of acute endothelial glycocalyx degradation and inflammatory factors. We also evaluated the effect of unfractionated heparin (UFH) on glycocalyx shedding in a canine septic shock model. Twenty adult beagle dogs were randomly allocated to one of the following four groups (n = 5): (1) a sham group; (2) a shock group [3.5 × 10(8) colony-forming unit (cfu) Escherichia coli (E. coli)/kg]; (3) a basic therapy group (sensitive antibiotics and 0.9% saline, 10 ml/kg/h); and (4) a heparin group (40 units/kg/h UFH plus basic therapy). After the onset of septic shock, systemic haemodynamic indices were measured. Endothelial glycocalyx degradation markers (i.e., syndecan-1, HS) and inflammatory factors [i.e., interleukin 6 (IL-6), tumour necrosis factor (TNF)-α], platelet count and activated partial thromboplastin time were measured at various time points. A lethal dose of E. coli induced a progressive septic shock model. We observed increased syndecan-1 and HS levels, which correlated with IL-6 and TNF-α in the septic shock model. The glycocalyx shedding was reduced by UFH, which might be regulated by the inhibition of inflammatory factors. A therapeutic dose of UFH can protect glycocalyx from shedding by inhibiting inflammation. Additional studies with larger sample sizes are needed to confirm our conclusions. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  19. Impact of methylene blue in addition to norepinephrine on the intestinal microcirculation in experimental septic shock.

    PubMed

    Nantais, Jordan; Dumbarton, Tristan C; Farah, Nizam; Maxan, Alexander; Zhou, Juan; Minor, Samuel; Lehmann, Christian

    2014-01-01

    Methylene blue (MB) has been used with some success as a treatment for the vasoplegia of vasopressor-refractory septic shock. The putative mechanism of action of MB is the inhibition of endothelial nitric oxide within the microvasculature and improved responsiveness to endogenous catecholamines (norepinephrine (NE)). However, to date, no study has demonstrated the microcirculatory effect of methylene blue in septic shock. The objective of this randomized, controlled, animal study was to show, in an experimentally-induced, septic shock model in rats, the effects of MB and NE on global hemodynamics and the microcirculation. Mean arterial pressure (MAP) was drastically reduced following bacterial endotoxin (lipopolysaccharide, LPS) administration in animals not receiving vasopressors. Only the combination of NE + MB restored MAP to control levels by the end of the three hour experiment. Intravital microscopy of the microcirculation was performed in the terminal ileum in order to examine functional capillary density in intestinal muscle layers and the mucosa, as well as leukocyte activation in venules (rolling, adhesion to the endothelium). Untreated LPS animals showed a significant increase in leukocyte adhesion and a decrease in capillary perfusion in the intestinal microcirculation. In groups receiving NE or NE+MB, we observed a significant decrease in leukocyte adhesion and improved functional capillary density, indicating that microvasculature function was improved. This study suggests that methylene blue may be able to improve hemodynamics while preserving microvascular function in septic shock.

  20. Effects of antibiotic administration delay and inadequacy upon the survival of septic shock patients.

    PubMed

    Suberviola Cañas, B; Jáuregui, R; Ballesteros, M Á; Leizaola, O; González-Castro, A; Castellanos-Ortega, Á

    2015-11-01

    To assess how antibiotic administration delay and inadequacy influence survival in septic shock patients. A prospective, observational cohort study was carried out between September 2005 and September 2010. Patients admitted to the ICU of a third level hospital. A total of 342 septic shock patients None The time to antibiotic administration (difference between septic shock presentation and first administered dose of antibiotic) and its adequacy (in vitro susceptibility testing of isolated pathogens) were determined. ICU and hospital mortality were 26.4% and 33.5%, respectively. The median delay to administration of the first antibiotic dose was 1.7h. Deceased patients received antibiotics significantly later than survivors (1.3±14.5h vs. 5.8±18.02h; P=.001). Percentage drug inadequacy was 12%. Those patients who received inadequate antibiotics had significantly higher mortality rates (33.8% vs. 51.2%; P=.03). The coexistence of treatment delay and inadequacy was associated to lower survival rates. Both antibiotic administration delay and inadequacy exert deleterious effects upon the survival of septic shock patients, independently of their characteristics or severity. Copyright © 2015 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

  1. Brain Tissue Oxygenation in Patients with Septic Shock: a Feasibility Study.

    PubMed

    Wood, Michael; Song, Andy; Maslove, David; Ferri, Cathy; Howes, Daniel; Muscedere, John; Boyd, J Gordon

    2016-01-01

    Delirium is common in critically ill patients and its presence is associated with increased mortality and increased likelihood of poor cognitive function among survivors. However, the cause of delirium is unknown. The purpose of this study was to demonstrate the feasibility of using near-infrared spectroscopy (NIRS) to assess brain tissue oxygenation in patients with septic shock, who are at high risk of developing delirium. This prospective observational study was conducted in a 33-bed general medical surgical intensive care unit (ICU). Patients with severe sepsis or septic shock were eligible for recruitment. The FORESIGHT NIRS monitor was used to assess brain tissue oxygenation in the frontal lobes for the first 72 hours of ICU admission. Physiological data was also recorded. We used the Confusion Assessment Method-ICU to screen for delirium. From March 1st 2014-September 30th 2014, 10 patients with septic shock were recruited. The NIRS monitor captured 81% of the available data. No adverse events were recorded. Brain tissue oxygenation demonstrated significant intra- and inter-individual variability in the way it correlated with physiological parameters, such as mean arterial pressure, heart rate, and peripheral oxygen saturation. Mean brain tissue oxygen levels were significantly lower in patients who were delirious for the majority of their ICU stay. It is feasible to record brain tissue oxygenation with NIRS in patients with septic shock. This study provides the infrastructure necessary for a larger prospective observational study to further examine the relationship between brain tissue oxygenation, physiological parameters, and acute neurological dysfunction.

  2. Mortality Risk Factors for Patients with Septic Shock after Implementation of the Surviving Sepsis Campaign Bundles

    PubMed Central

    Kim, Moo Hyun; Jeong, Woo Yong; Jung, In Young; Oh, Dong Hyun; Kim, Yong Chan; Kim, Eun Jin; Jeong, Su Jin; Ku, Nam Su; Kim, June Myung

    2016-01-01

    Background Septic shock remains a leading cause of death, despite advances in critical care management. The Surviving Sepsis Campaign (SSC) has reduced morbidity and mortality. This study evaluated risk factors for mortality in patients with septic shock who received treatment following the SSC bundles. Materials and Methods This retrospective cohort study included patients with septic shock who received treatments following SSC bundles in an urban emergency department between November 2007 and November 2011. Primary and secondary endpoints were all-cause 7- and 28-day mortality. Results Among 436 patients, 7- and 28-day mortality rates were 7.11% (31/436) and 14% (61/436), respectively. In multivariate analysis, high lactate level (odds ratio [OR], 1.286; 95% confidence interval [CI], 1.016–1.627; P=0.036) and low estimated glomerular filtration rate (OR, 0.953; 95% CI, 0.913–0.996; P=0.032) were independent risk factors for 7-day mortality. Risk factors for 28-day mortality were high lactate level (OR, 1.346; 95% CI, 1.083–1.673; P=0.008) and high Acute Physiology and Chronic Health Evaluation II score (OR, 1.153; 95% CI, 1.029–1.293; P=0.014). Conclusion The risk of mortality of septic shock patients remains high in patients with high lactate levels and acute kidney injury. PMID:27659434

  3. Corticosteroid/Antibiotic Treatment of Septic Shock: An Evaluation of Mechanisms.

    DTIC Science & Technology

    1984-06-29

    We have succeeded in developing the first effective therapy to prevent death from septic shock induced by a 100% lethal dose of live E . coli organisms...sodium succinate, and the aminoglycoside antibiotic, gentamicin sulfate. Application of the therapy soon after initiation of E . coli administration

  4. [Nursing management of ventilation and sedation in patients suffering from septic shock].

    PubMed

    Bridey, Céline; Mathieu, Soulène; Steiger, Magali; Trari, Vanessa; Lavoivre, Christine; Ducrocq, Nicolas; Levy, Bruno; Gérard, Alain; Augros, Johann

    2012-06-01

    A significant number of intubated, ventilated and sedated patients suffering from septic shock develop acute respiratory distress syndrome (ARDS). The supervision by a multidisciplinary team optimises both the management of ventilation and the sedation analgesia of the patient. The nursing supervision and care related to this pathology are specific.

  5. Survival of Primates in Lethal Septic Shock Following Delayed Treatment with Steroid.

    DTIC Science & Technology

    1981-02-26

    TECHNICAL REPORT NO. 142 SURVIVAL OF PRIMATES IN LETHAL SEPTIC SHOCK FOLLOWING DELAYED TREAMENT WIn STEROID L. B. Hinshaw, L. T. Archer, B. K. Belier...controlled-temperature heating pads positioned abovd and beneath the body and a temperature probe placed in the rectum. A tracheal cannula was orally

  6. Studies of components of the coagulation systems in normal individuals and septic shock patients.

    PubMed

    Smith-Erichsen, N; Aasen, A O; Gallimore, M J; Amundsen, E

    1982-01-01

    Components of the coagulation system were determined in plasma samples from normal individuals and septic shock patients. The parameters measured included Hageman factor (HF), prekallikrein (PKK), high molecular weight kininogen (HMwK), antithrombin III (AT III), fibrinogen (Fg) and fibrin(ogen) degradation products (FDP's). The combined effects of factors II, VII & X were estimated using Normotest (NT). Plasma levels of HF, PKK, and HMwK and both immunochemical levels and functional activities of AT III were significantly lower in the septic shock patients. NT values were also significantly reduced. Fibrinogen levels varied from very low to very high indicating both Fg consumption and acute-phase synthesis. Elevated FDP levels were seen during septic shock, but no difference between survivors and fatal cases was found. Prekallikrein levels and functional AT III activities were significantly higher in the samples from patients who recovered following septic shock than in the samples from subjects who died. During treatment all the parameters gradually returned toward normal in the survivors, whereas continuous low values for HF, AT III, PKK, and NT were observed in the fatal cases.

  7. [Septic shock associated with pyogenic liver abscess rescued with percutaneous transhepatic abscess drainage].

    PubMed

    Mizuno, Ju; Tsujikawa, Tetsuya; Wakuta, Akiko; Matsuki, Michiko; Morita, Tsubasa; Gouda, Yoshinori

    2003-01-01

    We report a case of septic shock associated with pyogenic liver abscess rescued with percutaneous transhepatic abscess drainage (PTAD). A 70-year-old male patient was admitted to our outpatient department of internal medicine with general fatigue, dullness of bilateral shoulders and extremities, appetite loss, weight loss, headache, and vertigo. Laboratory tests showed severe inflammatory indications, anemia, and high values of hepatobiliary enzymes and blood sugar. Abdominal ultrasonography and enhanced CT showed a pyogenic liver abscess of 10 cm in diameter at S 6-7 in the right hepatic lobe. The patient's condition deteriorated suddenly that night. From the results of abdominal ultrasonography and enhanced CT, we made diagnosis of septic shock associated with pyogenic liver abscess. Emergency abdominal ultrasound-guided PTAD was performed under local anesthetic. Postoperatively, the antibiotic was infused daily through a PTAD tube into the liver abscess space. He recovered and his laboratory tests improved gradually. On abdominal ultrasonography and enhanced CT, the liver abscess disappeared by 19th postoperative day, and PTAD tube was removed. There was no complication during PTAD treatment. We conclude that patients in septic shock should undergo further examinations immediately and treatment of the infected tissue should be started as soon as possible. PTAD may be an additional effective procedure for pyogenic liver abscess in septic shock. Furthermore, local antibiotic lavage through a PTAD tube into the liver abscess space may be an important supplementary method in the management of the illness.

  8. Severe Sepsis and Septic Shock Associated with Chikungunya Virus Infection, Guadeloupe, 2014.

    PubMed

    Rollé, Amélie; Schepers, Kinda; Cassadou, Sylvie; Curlier, Elodie; Madeux, Benjamin; Hermann-Storck, Cécile; Fabre, Isabelle; Lamaury, Isabelle; Tressières, Benoit; Thiery, Guillaume; Hoen, Bruno

    2016-05-01

    During a 2014 outbreak, 450 patients with confirmed chikungunya virus infection were admitted to the University Hospital of Pointe-à-Pitre, Guadeloupe. Of these, 110 were nonpregnant adults; 42 had severe disease, and of those, 25 had severe sepsis or septic shock and 12 died. Severe sepsis may be a rare complication of chikungunya virus infection.

  9. Early goal-directed therapy in treatment of pediatric septic shock.

    PubMed

    de Oliveira, Cláudio Flauzino

    2010-09-01

    In the whole world, around 29,000 children younger than 5 years die every day, and sepsis is the most common cause of death. Whereas in adult patients vasomotor paralysis represents the predominant cause of mortality, death in pediatric sepsis is associated with severe hypovolemia and low cardiac output. The purpose of this article was to review the recent evidence on early treatment of pediatric severe sepsis and septic shock. Although current American College of Critical Care Medicine-Pediatric Advanced Life Support guidelines represent best practice, stronger evidences are lacking to confirm the components of these recommendations. Retrospective studies showed, at the same time, the positive effects arising from the utilization of American College of Critical Care Medicine-Pediatric Advanced Life Support guidelines and the existing barriers to its implementation. And one randomized control trial paralleled the results observed in adult patients and revealed that early goal-directed therapy in children is one of the few therapeutic interventions that proved to be beneficial in septic shock treatment. Early goal-directed therapy in pediatric septic shock is a successful method to optimize and parameterize treatment, but there is still a long way to turn septic shock resuscitation simpler and more widely spread.

  10. Severe Sepsis and Septic Shock Associated with Chikungunya Virus Infection, Guadeloupe, 2014

    PubMed Central

    Rollé, Amélie; Schepers, Kinda; Cassadou, Sylvie; Curlier, Elodie; Madeux, Benjamin; Hermann-Storck, Cécile; Fabre, Isabelle; Lamaury, Isabelle; Tressières, Benoit; Thiery, Guillaume

    2016-01-01

    During a 2014 outbreak, 450 patients with confirmed chikungunya virus infection were admitted to the University Hospital of Pointe-à-Pitre, Guadeloupe. Of these, 110 were nonpregnant adults; 42 had severe disease, and of those, 25 had severe sepsis or septic shock and 12 died. Severe sepsis may be a rare complication of chikungunya virus infection. PMID:27088710

  11. [CPFA (coupled plasma filtration absorption) treatment of septic shock. A retrospective study of nine patients].

    PubMed

    Maruccio, Gianfranco; Montanaro, Alessio; Schiavone, Palmira; Fumarola, Martino; Flores, Antonio; Strippoli, Paolo; Caretto, Vincenzo; Paladini, Daniele; Ramunni, Alfonso

    2012-01-01

    Coupled plasma filtration absorption (CPFA) can increase blood pressure in septic shock and reduce fever during and after treatment. It is not able to stop the activation of intravascular coagulation and does not reduce the need for dialysis or the overall mortality.

  12. [Adherence to international guidelines on early management in severe sepsis and septic shock].

    PubMed

    Quintero, Ricardo Andrés; Martínez, Carlos Arturo; Gamba, Juan Diego; Ortiz, Isadora; Jaimes, Fabián

    2012-09-01

    Complete adherence to early goal-directed therapy has shown a significant reduction in 28-day mortality rate, whereas partial adherence has not shown beneficial effect. The effect of adherence to 6 hour sepsis bundle treatment was evaluated on patients with severe sepsis and septic shock. A prospective cohort study was conducted during a six-month period. The patients were limited to those 16 years or older and included admissions to intensive care units, special care units or emergency departments with severe sepsis or septic shock. The adherence to the 6-hour sepsis bundle was evaluated through 8 interventions as follows: (1) serum lactate measure,( 2) early antibiotic administration, (3) blood culture samples, (4) infusion of intravenous fluids, (5) vasopressor use, (6) central venous catheter, (7) central venous pressure >8 mm Hg, and (8) central venous oxygen saturation >70%. Seven hundred and twenty three patients were screened; 16% (n=116) met the inclusion criteria; 92.2% (n=107) met the criteria for severe sepsis and 37.9% (44) for septic shock; 62.9% (n=73) were subdiagnosed. Complete adherence to the 8 interventions of 6-hour sepsis bundle was 0%; 6 to 7 (19%, n=22), 3 to 5 (67.2%, n=78), and 0 to 2 (98.3%, n=114). Adherence to 6-hour sepsis bundle treatment for severe sepsis and septic shock was not done for the full 8 interventions and only partial accomplishment of the first 4 interventions.

  13. Electrocardiographic Changes in a Patient With Pulmonary Embolism and Septic Shock

    PubMed Central

    Poulimenos, Leonidas E; Giannakopoulos, Antreas K; Tsoukas, Athanasios; Kallistratos, Manolis S; Manolis, Athanasios J

    2011-01-01

    Various electrocardiography (ECG) abnormalities have been reported in patients who present with pulmonary embolism (PE). Severe sepsis is also associated with ECG changes that may mimic ST elevation myocardial infarction. We report a case of an elderly patient with PE and septic shock associated with striking ECG changes. PMID:22194769

  14. Current advances in sepsis and septic shock with particular emphasis on the role of insulin.

    PubMed

    Das, Undurti N

    2003-08-01

    Sepsis and septic shock account for substantial morbidity and mortality in the intensive care units. NF-kappaB activation, and elevated concentrations of macrophage migration inhibitory factor (MIF), tumor necrosis factor-a (TNF-alpha), interleukin-1 (IL-1), IL-6, free radicals, inducible nitric oxide (iNO), and stress hyperglycemia are some of the factors that induce systemic inflammatory response and myocardial depression seen in sepsis. Conversely, adenosine, activated protein C, oxidized phospholipids, w-3 fatty acids, and insulin have beneficial effects in sepsis and septic shock. These molecules and in particular insulin have the ability to suppress synthesis of MIF, TNF-alpha, IL-1, IL-6, and free radicals, enhance endothelial NO production, and enhance the production of anti-inflammatory cytokines IL-10, and IL-4. In addition, insulin corrects stress hyperglycemia and improves myocardial function. Thus insulin, adenosine, activated protein C, oxidized phospholipids, and w-fatty acids show anti-inflammatory actions and explain why and how they are useful in sepsis and septic shock and possibly, other inflammatory conditions. Hence, their combined use may be of significant benefit in sepsis and septic shock.

  15. Immunostimulation using granulocyte- and granulocyte-macrophage colony stimulating factor in patients with severe sepsis and septic shock.

    PubMed

    Schefold, Joerg C

    2011-01-01

    Sepsis is associated with failure of multiple organs, including failure of the immune system. The resulting 'sepsis-associated immunosuppression' resembles a state of immunological anergy that is characterized by repeated 'infectious hits', prolonged multiple-organ failure, and death. As a consequence, adjunctive treatment approaches using measures of immunostimulation with colony-stimulating factors (CSFs) were tested in animal experiments and clinical trials. Herein, data from randomized clinical trials will be discussed in the context of a recently published meta-analysis investigating the effects of granulocyte- and granulocyte-macrophage colony-stimulating factor therapy in patients with severe sepsis and septic shock.

  16. MCPIP1 Negatively Regulates Toll-like Receptor 4 Signaling and Protects Mice from LPS-induced Septic Shock

    PubMed Central

    Huang, Shengping; Miao, Ruidong; Zhou, Zhou; Wang, Tianyi; Liu, Jianguo; Liu, Gang; Chen, Y. Eugene; Xin, Hong-Bo; Zhang, Jifeng; Fu, Mingui

    2013-01-01

    Septic shock is one of leading causes of morbidity and mortality in hospital patients. However, genetic factors predisposing to septic shock are not fully understood. Our previous work showed that MCP-induced protein 1 (MCPIP1) was induced by lipopolysaccharides (LPS), which then negatively regulates LPS-induced inflammatory signaling in vitro. Here we report that although MCPIP1 was induced by various toll-like receptor (TLR) ligands in macrophages, MCPIP1-deficient mice are extremely susceptible to TLR4 ligand (LPS)-induced septic shock and death, but not to the TLR2, 3, 5 and 9 ligands-induced septic shock. Consistently, LPS induced tumor necrosis factor α (TNFα) production in MCPIP1-deficient mice was 20-fold greater than that in their wild-type littermates. Further analysis revealed that MCPIP1-deficient mice developed severe acute lung injury after LPS injection and JNK signaling was highly activated in MCPIP1-deificient lungs after LPS stimulation. Finally, macrophage-specific MCPIP1 transgenic mice were partially protected from LPS-induced septic shock, suggesting that inflammatory cytokines from sources other than macrophages may significantly contribute to the pathogenesis of LPS-induced septic shock. Taken together, these results suggest that MCPIP1 selectively suppresses TLR4 signaling pathway and protects mice from LPS-induced septic shock. PMID:23422584

  17. Risk factors for septic shock in acute obstructive pyelonephritis requiring emergency drainage of the upper urinary tract.

    PubMed

    Kamei, Jun; Nishimatsu, Hiroaki; Nakagawa, Tohru; Suzuki, Motofumi; Fujimura, Tetsuya; Fukuhara, Hiroshi; Igawa, Yasuhiko; Kume, Haruki; Homma, Yukio

    2014-03-01

    To assess the risk factors for septic shock in patients with acute obstructive pyelonephritis requiring emergency drainage of the upper urinary tract. We retrospectively reviewed the records of 48 patients who underwent emergency drainage of the upper urinary tract for sepsis associated with acute obstructive pyelonephritis at our institute. Univariate and multivariate analyses were performed to identify the risk factors. Among 54 events of sepsis, we identified 20 events of septic shock requiring vasopressor therapy. Cases with shock were more likely than those without shock to have ureteral stone (70 vs 38%, p = 0.024) and positive blood culture results (81 vs 28%, p = 0.006). They received drainage significantly earlier than those without shock (1.0 vs 3.5 days, p < 0.001). Univariate analysis demonstrated that acute obstructive pyelonephritis by ureteral stone, rapid progression (the occurrence of symptoms to drainage ≤ 1 day), positive blood culture, leukocytopenia (<4,000/mm(3)), thrombocytopenia (<120,000/mm(3)), and prothrombin time international normalized ratio ≥ 1.20 were correlated with septic shock. Multivariate logistic regression analysis identified thrombocytopenia (p = 0.005) and positive blood culture (p = 0.040) as independent risk factors for septic shock. Thrombocytopenia and positive blood culture were independent risk factors for septic shock in acute obstructive pyelonephritis requiring emergency drainage. Thrombocytopenia would be practically useful as a predictor of septic shock.

  18. Association of Kidney Tissue Barrier Disrupture and Renal Dysfunction in Resuscitated Murine Septic Shock.

    PubMed

    Stenzel, Tatjana; Weidgang, Clair; Wagner, Katja; Wagner, Florian; Gröger, Michael; Weber, Sandra; Stahl, Bettina; Wachter, Ulrich; Vogt, Josef; Calzia, Enrico; Denk, Stephanie; Georgieff, Michael; Huber-Lang, Markus; Radermacher, Peter; McCook, Oscar

    2016-10-01

    Septic shock-related kidney failure is characterized by almost normal morphological appearance upon pathological examination. Endothelial barrier disrupture has been suggested to be of crucial importance for septic shock-induced organ dysfunction. Therefore, in murine resuscitated cecal ligation and puncture (CLP)-induced septic shock, we tested the hypothesis whether there is a direct relationship between the kidney endothelial barrier injury and renal dysfunction. Anesthetized mice underwent CLP, and 15 h later, were anesthetized again and surgically instrumented for a 5-h period of intensive care comprising lung-protective mechanical ventilation, fluid resuscitation, continuous i.v. norepinephrine to maintain target hemodynamics, and measurement of creatinine clearance (CrCl). Animals were stratified according to low or high CrCl. Nitrotyrosine formation, expression of the inducible isoform of the nitric oxide synthase, and blood cytokine (tumor necrosis factor, interleukin-6, interleukin-10) and chemokine (monocyte chemoattractant protein-1, keratinocyte-derived chemokine) levels were significantly higher in animals with low CrCl. When plotted against CrCl and neutrophil gelatinase-associated lipocalin levels, extravascular albumin accumulation, and tissue expression of the vascular endothelial growth factor and angiopoietin-1 showed significant mathematical relationships related to kidney (dys)function. Preservation of the constitutive expression of the hydrogen sulfide producing enzyme cystathione-γ-lyase was associated with maintenance of organ function. The direct quantitative relation between microvascular leakage and kidney (dys)function may provide a missing link between near-normal tissue morphology and septic shock-related renal failure, thus further highlighting the important role of vascular integrity in septic shock-related renal failure.

  19. Serum concentrations of vitamin D and organ dysfunction in patients with severe sepsis and septic shock

    PubMed Central

    Alves, Fernanda Sampaio; Freitas, Flavio Geraldo Resende; Bafi, Antonio Tonete; Azevedo, Luciano Cesar Pontes; Machado, Flavia Ribeiro

    2015-01-01

    Objectives To evaluate the serum concentrations of vitamin D and their variations in patients with severe sepsis or septic shock and in control subjects upon admission and after 7 days of hospitalization in the intensive care unit and to correlate these concentrations with the severity of organ dysfunction. Methods This case-control, prospective, observational study involved patients aged > 18 years with severe sepsis or septic shock paired with a control group. Serum vitamin D concentrations were measured at inclusion (D0) and on the seventh day after inclusion (D7). Severe deficiency was defined as vitamin D levels < 10ng/ml, deficiency as levels between 10 and 20ng/ml, insufficiency as levels between 20 and 30ng/ml, and sufficiency as levels ≥ 30ng/mL. We considered a change to a higher ranking, together with a 50% increase in the absolute concentration, to represent an improvement. Results We included 51 patients (26 with septic shock and 25 controls). The prevalence of vitamin D concentration ≤ 30ng/ml was 98%. There was no correlation between the serum concentration of vitamin D at D0 and the SOFA score at D0 or D7 either in the general population or in the group with septic shock. Patients with improvement in vitamin D deficiency had an improved SOFA score at D7 (p = 0.013). Conclusion In the population studied, patients with septic shock showed improvement in the serum concentrations of vitamin D on the seventh day compared with the controls. We also found a correlation between higher vitamin D concentrations and a greater decrease in the severity of organ dysfunction. PMID:26761476

  20. Polymyxin B-immobilized fiber column hemoperfusion therapy for septic shock.

    PubMed

    Mitaka, Chieko; Tomita, Makoto

    2011-10-01

    Endotoxin, an outer membrane component of gram-negative bacteria, plays an important role in the pathogenesis of septic shock. Endotoxin adsorption therapy by polymyxin B-immobilized fiber column hemoperfusion (PMX) has been used for the treatment of septic shock patients in Japan since 1994. The covalent binding of polymyxin B onto the surface of the polystyrene-based carrier fiber in PMX inactivates the endotoxin in the blood without exerting toxicity. This study was performed as a systematic review to evaluate the efficacy and mechanism of PMX treatment in patients with septic shock. The PubMed database and references from identified articles were used to search and review the literature relating to the efficacy and mechanism of PMX treatment in patients with septic shock. Polymyxin B-immobilized fiber column hemoperfusion adsorbed monocytes, activated neutrophils, and anandamide, as well as endotoxin through direct covalent bond, hydrophobic and ionic interactions, and hydrodynamics, and reduced the blood concentrations of inflammatory cytokines, plasminogen activator inhibitor 1 and adhesion molecules. Polymyxin B-immobilized fiber column hemoperfusion increased blood pressure and reduced the dosage requirements for vasopressive/inotropic agents. The meta-analysis showed that PMX treatment had beneficial effects on the hemodynamics, pulmonary oxygenation, and mortality. These beneficial effects may be attributable to the direct adsorption of endotoxin, monocytes, activated neutrophils, and anandamide, as well as indirect decrease in inflammatory cytokines and other mediators. Polymyxin B-immobilized fiber column hemoperfusion treatment has additional effects on reducing endothelial damage, proapoptotic activity, and immunosuppression. Further studies will be needed to confirm the efficacy and mechanism of PMX treatment in septic shock.

  1. The role of CXCL10 in the pathogenesis of experimental septic shock

    PubMed Central

    2014-01-01

    Introduction The chemokine CXCL10 is produced during infection and inflammation to activate the chemokine receptor CXCR3, an important regulator of lymphocyte trafficking and activation. The goal of this study was to assess the contributions of CXCL10 to the pathogenesis of experimental septic shock in mice. Methods Septic shock was induced by cecal ligation and puncture (CLP) in mice resuscitated with lactated Ringer’s solution and, in some cases, the broad spectrum antibiotic Primaxin. Studies were performed in CXCL10 knockout mice and mice treated with anti-CXCL10 immunoglobulin G (IgG). Endpoints included leukocyte trafficking and activation, core body temperature, plasma cytokine concentrations, bacterial clearance and survival. Results CXCL10 was present at high concentrations in plasma and peritoneal cavity during CLP-induced septic shock. Survival was significantly improved in CXCL10 knockout (CXCL10KO) mice and mice treated with anti-CXCL10 IgG compared to controls. CXCL10KO mice and mice treated with anti-CXCL10 IgG showed attenuated hypothermia, lower concentrations of interleukin-6 (IL-6) and macrophage inhibitory protein-2 (MIP-2) in plasma and lessened natural killer (NK) cell activation compared to control mice. Compared to control mice, bacterial burden in blood and lungs was lower in CXCL10-deficient mice but not in mice treated with anti-CXCL10 IgG. Treatment of mice with anti-CXCL10 IgG plus fluids and Primaxin at 2 or 6 hours after CLP significantly improved survival compared to mice treated with non-specific IgG under the same conditions. Conclusions CXCL10 plays a role in the pathogenesis of CLP-induced septic shock and could serve as a therapeutic target during the acute phase of septic shock. PMID:24890566

  2. CT-proAVP IS NOT A GOOD PREDICTOR OF VASOPRESSOR NEED IN SEPTIC SHOCK.

    PubMed

    Laribi, Said; Lienart, Daphné; Castanares-Zapatero, Diego; Collienne, Christine; Wittebole, Xavier; Laterre, Pierre-François

    2015-10-01

    Septic shock features a high hospital mortality. Improving our ability to risk stratify these patients at admission may help better define management strategies and design studies. The primary objective of this study was to determine if patients dead or with sustained vasopressor need at day 7 had a relative arginine vasopressin (AVP) deficiency as compared with vasopressor-free patients at day 7. Another objective was to explore if plasma CT-proAVP (C terminal part of preprovasopressin) measured within 24 h of sepsis onset could predict patient severity. This was a prospective observational study in a medical and surgical intensive care unit. One hundred thirteen patients were included in this analysis: 102 patients with severe sepsis or septic shock and 11 nonseptic controls. The CT-proAVP was measured at three time points within the first week after sepsis onset. The CT-proAVP measured within 24 h of sepsis onset failed to predict vasopressor need. More importantly, CT-proAVP plasma levels in patients with a sustained need of vasopressors did not differ from vasopressor-free patients at days 1 and 2. The CT-proAVP was more elevated in septic shock as compared with severe sepsis or nonseptic patients. When analyzing 28-day mortality, nonsurvivors featured higher levels of the CT-proAVP compared with survivors. Patients with septic shock and sustained need of vasopressors do not seem to present a relative AVP deficiency. In sepsis, the subgroup of patients that may benefit from AVP supplementation still needs to be identified. Our study further confirms previous data on the ability of the CT-proAVP to predict patient severity in severe sepsis and septic shock.

  3. Prediction of hospital outcome in septic shock: a prospective comparison of tissue Doppler and cardiac biomarkers

    PubMed Central

    2010-01-01

    Introduction Diastolic dysfunction as demonstrated by tissue Doppler imaging (TDI), particularly E/e' (peak early diastolic transmitral/peak early diastolic mitral annular velocity) is common in critical illness. In septic shock, the prognostic value of TDI is undefined. This study sought to evaluate and compare the prognostic significance of TDI and cardiac biomarkers (B-type natriuretic peptide (BNP); N-terminal proBNP (NTproBNP); troponin T (TnT)) in septic shock. The contribution of fluid management and diastolic dysfunction to elevation of BNP was also evaluated. Methods Twenty-one consecutive adult patients from a multidisciplinary intensive care unit underwent transthoracic echocardiography and blood collection within 72 hours of developing septic shock. Results Mean ± SD APACHE III score was 80.1 ± 23.8. Hospital mortality was 29%. E/e' was significantly higher in hospital non-survivors (15.32 ± 2.74, survivors 9.05 ± 2.75; P = 0.0002). Area under ROC curves were E/e' 0.94, TnT 0.86, BNP 0.78 and NTproBNP 0.67. An E/e' threshold of 14.5 offered 100% sensitivity and 83% specificity. Adjustment for APACHE III, cardiac disease, fluid balance and grade of diastolic function, demonstrated E/e' as an independent predictor of hospital mortality (P = 0.019). Multiple linear regression incorporating APACHE III, gender, cardiac disease, fluid balance, noradrenaline dose, C reactive protein, ejection fraction and diastolic dysfunction yielded APACHE III (P = 0.033), fluid balance (P = 0.001) and diastolic dysfunction (P = 0.009) as independent predictors of BNP concentration. Conclusions E/e' is an independent predictor of hospital survival in septic shock. It offers better discrimination between survivors and non-survivors than cardiac biomarkers. Fluid balance and diastolic dysfunction were independent predictors of BNP concentration in septic shock. PMID:20331902

  4. Metabolic profiling of serum samples by 1H nuclear magnetic resonance spectroscopy as a potential diagnostic approach for septic shock.

    PubMed

    Mickiewicz, Beata; Duggan, Gavin E; Winston, Brent W; Doig, Christopher; Kubes, Paul; Vogel, Hans J

    2014-05-01

    To determine whether a nuclear magnetic resonance-based metabolomics approach can be useful for the early diagnosis and prognosis of septic shock in ICUs. Laboratory-based study. University research laboratory. Serum samples from septic shock patients and ICU controls (ICU patients with systemic inflammatory response syndrome but not suspected of having an infection) were collected within 24 hours of admittance to the ICU. None. H nuclear magnetic resonance spectra of septic shock and ICU control samples were analyzed and quantified using a targeted profiling approach. By applying multivariate statistical analysis (e.g., orthogonal partial least squares discriminant analysis), we were able to distinguish the patient groups and detect specific metabolic patterns. Some of the metabolites were found to have a significant impact on the separation between septic shock and control samples. These metabolites could be interpreted in terms of a biological human response to septic shock and they might serve as a biomarker pattern for septic shock in ICUs. Additionally, nuclear magnetic resonance-based metabolomics was evaluated in order to detect metabolic variation between septic shock survivors and nonsurvivors and to predict patient outcome. The area under the receiver operating characteristic curve indicated an excellent predictive ability for the constructed orthogonal partial least squares discriminant analysis models (septic shock vs ICU controls: area under the receiver operating characteristic curve = 0.98; nonsurvivors vs survivors: area under the receiver operating characteristic curve = 1). Our results indicate that nuclear magnetic resonance-based metabolic profiling could be used for diagnosis and mortality prediction of septic shock in the ICU.

  5. Speckle tracking echocardiography in patients with septic shock: a case control study (SPECKSS).

    PubMed

    Ng, Pauline Yeung; Sin, Wai Ching; Ng, Andrew Kei-Yan; Chan, Wai Ming

    2016-05-14

    Sepsis-induced myocardial dysfunction is a well-recognized condition and confers worse outcomes in septic patients. Echocardiographic assessment by conventional parameters such as left ventricular ejection fraction (LVEF) is often affected by ongoing changes in preload and afterload conditions. Novel echocardiographic technologies such as speckle tracking echocardiography (STE) have evolved for direct assessment of the myocardial function. We investigate the measurement of myocardial strain by speckle tracking echocardiography for the diagnosis of sepsis-induced myocardial dysfunction. This is a case-control study at a university-affiliated medical intensive care unit. Consecutive adult medical patients admitted with a diagnosis of septic shock were included. Patients with other causes of myocardial dysfunction were excluded. They were compared to age-matched, gender-matched, and cardiovascular risk-factor-matched controls, who were admitted to hospital for sepsis but did not develop septic shock. Transthoracic echocardiography was performed on all patients within 24 hours of diagnosis, and a reassessment echocardiogram was performed in the study group of patients upon recovery. Patients with septic shock (n = 33) (study group) and 29 matched patients with sepsis but no septic shock (control group) were recruited. The mean sequential organ failure assessment (SOFA) score for the study and control groups were 10.2 and 1.6, respectively (P < 0.001). In patients with septic shock, the mean arterial pressure was lower (76 mmHg vs 82 mmHg, P = 0.032), and the heart rate was higher (99 bpm vs 86 bpm, P = 0.008). The cardiac output (5.9 L/min vs 5.5 L/min, P = 0.401) and systemic vascular resistance (1090 dynes•sec/cm(5) vs 1194 dynes•sec/cm(5), P = 0.303) were similar. The study group had a greater degree of myocardial dysfunction measured by global longitudinal strain (GLS) (-14.5 % vs -18.3 %, P <0.001), and the myocardial strain differed upon diagnosis and

  6. An updated meta-analysis to understand the variable efficacy of drotrecogin alfa (activated) in severe sepsis and septic shock.

    PubMed

    Lai, P S; Matteau, A; Iddriss, A; Hawes, J C L; Ranieri, V; Thompson, B T

    2013-01-01

    Significant debate continues over the efficacy of drotrecogin alpha activated (DAA) in sepsis. This updated meta-analysis provides an updated summary effect estimate and explores the reasons for outcome heterogeneity in placebo-controlled randomized clinical trials of DAA on 28-day all-cause mortality in patients with severe sepsis or septic shock. Computer searches of MEDLINE, EMBASE, the Cochrane Library, ClinicalTrials.gov, published abstracts from major intensive care meetings and examination of reference lists were used to identify five placebo-controlled randomized clinical trials with 7260 patients. The primary endpoint was 28-day all-cause mortality. Secondary outcomes were 28-day incidence of severe bleeding and intracranial hemorrhage. DAA was not associated with improved 28-day all-cause mortality in patients with severe sepsis or septic shock (pooled relative risk (RR) of 0.97 [95% CI 0.83-1.14]), and is associated with an increase in serious bleeding. The significant heterogeneity in the pooled RR for 28-day mortality (I2 value of 59.4%, χ2 P-value 0.043) is no longer present with exclusion of the post-study amendment portion of PROWESS (I2 value of 0%, χ2 P-value 0.44 without PROWESS post-amendment). Using meta-regression, the best ranked predictor of outcome heterogeneity was baseline mortality in the placebo arm, which was among the highest in PROWESS. DAA is not associated with improved survival in patients with severe sepsis or septic shock. Further studies should be done to determine whether changes in supportive therapy for sepsis explain the variable efficacy of DAA in randomized controlled clinical trials observed over time.

  7. Caspase-8 inhibition represses initial human monocyte activation in septic shock model

    PubMed Central

    Oliva-Martin, Maria Jose; Sanchez-Abarca, Luis Ignacio; Rodhe, Johanna; Carrillo-Jimenez, Alejandro; Vlachos, Pinelopi; Herrera, Antonio Jose; Garcia-Quintanilla, Albert; Caballero-Velazquez, Teresa; Perez-Simon, Jose Antonio; Joseph, Bertrand; Venero, Jose Luis

    2016-01-01

    In septic patients, the onset of septic shock occurs due to the over-activation of monocytes. We tested the therapeutic potential of directly targeting innate immune cell activation to limit the cytokine storm and downstream phases. We initially investigated whether caspase-8 could be an appropriate target given it has recently been shown to be involved in microglial activation. We found that LPS caused a mild increase in caspase-8 activity and that the caspase-8 inhibitor IETD-fmk partially decreased monocyte activation. Furthermore, caspase-8 inhibition induced necroptotic cell death of activated monocytes. Despite inducing necroptosis, caspase-8 inhibition reduced LPS-induced expression and release of IL-1β and IL-10. Thus, blocking monocyte activation has positive effects on both the pro and anti-inflammatory phases of septic shock. We also found that in primary mouse monocytes, caspase-8 inhibition did not reduce LPS-induced activation or induce necroptosis. On the other hand, broad caspase inhibitors, which have already been shown to improve survival in mouse models of sepsis, achieved both. Thus, given that monocyte activation can be regulated in humans via the inhibition of a single caspase, we propose that the therapeutic use of caspase-8 inhibitors could represent a more selective alternative that blocks both phases of septic shock at the source. PMID:27250033

  8. Early and adequate antibiotic therapy in the treatment of severe sepsis and septic shock.

    PubMed

    Dickinson, John D; Kollef, Marin H

    2011-10-01

    Severe sepsis and septic shock are conditions that pose difficult challenges to physicians and the health care system. In the past 10 years, a number of retrospective and prospective observational studies have shed light on the importance of a rapid and systematic approach to treatment of these conditions. A key component is early and appropriate use of antibiotics. Delay of even 6 h can dramatically increase hospital mortality. In addition, multivariate analyses have demonstrated that inappropriate initial antibiotics lead to worse outcomes. The treating physician can rapidly identify risk factors for initial inappropriate antibiotics at the bedside, such as recent antibiotic therapy or recent hospitalization. Organized antibiotic order sets have been shown to significantly improve timely appropriate antibiotic administration in septic patients. Finally, emerging laboratory data suggest that early in the course of septic shock, the pharmacokinetics of common broad spectrum antibiotics may be significantly altered due to increased volumes of distribution having dosing implications for antibiotics in septic shock.

  9. Protein C zymogen in adults with severe sepsis or septic shock.

    PubMed

    Crivellari, M; Silvetti, S; Gerli, C; Landoni, G; Franco, A; Bove, T; Pappalardo, F; Zangrillo, A

    2014-01-01

    Activated protein C is associated with a risk of bleeding and its effects on survival in septic shock patients are questionable. Protein C zymogen has no risk of bleeding and improves the outcome of patients with septic shock. We hereby describe the largest published case series of adult patients receiving protein C zymogen. A prospective study on 23 adult patients with severe sepsis or septic shock, two or more organ failures and at high risk for bleeding, treated with protein C zymogen (50IU/kg bolus followed by continuous infusion of 3IU/kg/h for 72h). The Z-test evidenced a significant reduction between the expected mortality (53%) and the observed mortality 30% (Z value=1.99, p=0.046) in our sample population. Protein C levels increased from 34±18% to 66±22% at 6h after PC bolus (p<0.001), and kept on increasing during 72h of administration (p<0.001 to baseline). Sequential Organ Failure Assessment (SOFA), score of organ dysfunction, decreased from baseline to 7 days after administration of protein C from 14±2 to 7±4 (p<0.001). No adverse event drug related was noted. Protein C zymogen administration is safe and its use in septic patients should be investigated through a randomized controlled trial. Copyright © 2012 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  10. Ion transport in circulatory and/or septic shock

    SciTech Connect

    Sayeed, M.M.

    1987-05-01

    This review surveys investigations of membrane ion transport in animals in hemorrhagic, endotoxic, or bacteremic shock. The focus of the review is on ion transport studies in the skeletal muscle and liver. Skeletal muscle Na/sup +/-K/sup +/ transport alterations have been shown during the induction of shock via hemorrhage, endotoxin, or live Gram-negative bacteria in the rodent, canine, and primate species. These alterations include impairment of active cellular K/sup +/ accumulation, increased permeability to /sup 24/Na/sup +/ and Cl/sup -/, and membrane depolarization. The ion transport alterations in the skeletal muscle are compatible with movement of extracellular fluid into the intracellular compartment. Such fluid movements can potentially lead to decreases in circulating plasma volume and thus to circulatory deficits in shock. Studies in the liver of rats subjected to hemorrhagic or endotoxic shock indicated the failure of electrogenic Na/sup +/ pump. Although the hepatic cellular membrane permeability to Na/sup +/ relative to permeability to K/sup +/ appeared unaltered in hemorrhagic shock, endotoxic shock caused an increase in permeability to Na/sup +/. Hepatic cellular /sup 45/Ca/sup +/ regulation also appeared to be adversely affected during endotoxic shock. Alterations in hepatic Na/sup +/-K/sup +/ transport and Ca/sup +/ regulation could contribute to impairment in hepatic glucose production during shock. Although mechanisms of altered membrane ion transport during shock states remain unknown, such changes could occur prior to any substantial loss of cellular metabolic energy.

  11. Genetic variation in heat shock protein 70 is associated with septic shock: narrowing the association to a specific haplotype.

    PubMed

    Kee, C; Cheong, K Y; Pham, K; Waterer, G W; Temple, S E L

    2008-12-01

    Heat shock protein 70 (HSP70) plays a major role in immune responses. Polymorphisms within the gene have been associated with development of septic shock. This study refines the region of the HSP70 gene associated with development of septic shock and confirms its functionality. Subjects (n = 31) were grouped into one of three haplotypes based on their HSPA1B-179C>T and HSPA1B1267A>G genotypes. Mononuclear cells from these subjects were stimulated with heat-killed bacteria (10(7 )colony-forming units/mL Escherichia coli or Streptococcus pneumoniae) for 8 and 21 h. HSP70 and tumour necrosis factor (TNF) mRNA and protein levels were measured by reverse transcriptase-polymerase chain reaction and ELISA, respectively. The HSPA1B-179*C:1267*A haplotype was associated with significantly lower levels of HSPA1B mRNA and protein and higher production of TNF mRNA and protein compared to the other haplotypes. Induction of HSP70 was TNF independent. These results suggest that the HSPA1B-179C>T:1267A>G haplotype is functional and may explain the association of the HSP70 gene with development of septic shock.

  12. The Hyperferritinemic Syndrome: macrophage activation syndrome, Still’s disease, septic shock and catastrophic antiphospholipid syndrome

    PubMed Central

    2013-01-01

    Background Over the last few years, accumulating data have implicated a role for ferritin as a signaling molecule and direct mediator of the immune system. Hyperferritinemia is associated with a multitude of clinical conditions and with worse prognosis in critically ill patients. Discussion There are four uncommon medical conditions characterized by high levels of ferritin, namely the macrophage activation syndrome (MAS), adult onset Still’s disease (AOSD), catastrophic antiphospholipid syndrome (cAPS) and septic shock, that share a similar clinical and laboratory features, and also respond to similar treatments, suggesting a common pathogenic mechanism. Ferritin is known to be a pro-inflammatory mediator inducing expression of pro-inflammatory molecules, yet it has opposing actions as a pro-inflammatory and as an immunosuppressant. We propose that the exceptionally high ferritin levels observed in these uncommon clinical conditions are not just the product of the inflammation but rather may contribute to the development of a cytokine storm. Summary Here we review and compare four clinical conditions and the role of ferritin as an immunomodulator. We would like to propose including these four conditions under a common syndrome entity termed “Hyperferritinemic Syndrome”. PMID:23968282

  13. Colloids for the Initial Management of Severe Sepsis and Septic Shock in Pediatric Patients: A Systematic Review.

    PubMed

    Medeiros, Daniela Nasu Monteiro; Ferranti, Juliana Ferreira; Delgado, Artur Figueiredo; de Carvalho, Werther Brunow

    2015-11-01

    The goal of this study was to perform a systematic review of the literature assessing the use of colloids for the initial treatment of severe sepsis and septic shock in pediatric patients. The PICO [Patient, Intervention, Comparison, Outcome] method was used for the selection of studies, and the Cochrane Bias Tool was used to analyze the quality of the selected studies. Relevant studies were sought using the following databases: EMBASE (1980 to March 2014), PubMed (1970 to March 2014), Cochrane (1980 to March 2014), Web of Science, and Scopus. Searches used the following key words: isotonic solution, crystalloid, saline solution, colloid, resuscitation, fluid therapy, sepsis and septic shock, starch, and gelatin. The filters children and clinical trial were used when possible. Study selection was performed by 1 examiner. The selected articles were analyzed by 2 examiners who validated the articles according to the Cochrane Bias Tool. Discrepancies were resolved by consensus or by a third examiner. A total of 110 articles were selected based on the key words. Of these, 99 were excluded because they assessed postoperative follow-up, burn cases, cardiac surgery, or nutritional therapy or were review articles, guidelines, or editorials. One study was included after an analysis of previous reviews. A total of 12 articles were selected for analysis because they were reports of clinical trials conducted with prospective cohorts and they analyzed the use of crystalloids and colloids or colloids only in the initial treatment of severe sepsis or septic shock in children and adolescents. The total number of patients was 4375, and they ranged in age from 2 months to 15 years, with most patients between 5 and 15 years. Five studies assessed patients diagnosed with malaria, 5 assessed patients with dengue shock syndrome, 1 studied febrile diseases, and 1 examined the progression of patients with septic shock caused by various causes. The studies analyzed did not find evidence to

  14. Pulmonary extraction of biogenic amines during septic shock

    SciTech Connect

    Kerstein, M.D.; Kohler, J.; Gould, S.; Moseley, P.

    1982-10-01

    The effect of live Escherichia coli on the pulmonary extraction of the biogenic amines /sup 14/C 5-hydroxytryptamine, (5-HT) and /sup 3/H-epinephrine was investigated. The labeled isotopes were injected into a central venous catheter and collected from an aortic catheter. One hundred per cent of the labeled epinephrine was recovered in the control and septic state. Only 32.8 +/- 3.6% SEM of the 5-hydroxytryptamine was recovered before sepsis and 42.5 +/- 4.9% SEM after sepsis. During sepsis, mean arterial pressure fell to 58 mm Hg from 121 mm Hg. Pulmonary shunt increased from .7 +/- .05 SEM to .33 +/- .09 SEM.

  15. Population pharmacokinetics of piperacillin in the early phase of septic shock: does standard dosing result in therapeutic plasma concentrations?

    PubMed

    Öbrink-Hansen, Kristina; Juul, Rasmus Vestergaard; Storgaard, Merete; Thomsen, Marianne Kragh; Hardlei, Tore Forsingdal; Brock, Birgitte; Kreilgaard, Mads; Gjedsted, Jakob

    2015-11-01

    Antibiotic dosing in septic shock patients poses a challenge for clinicians due to the pharmacokinetic (PK) variability seen in this patient population. Piperacillin-tazobactam is often used for empirical treatment, and initial appropriate dosing is crucial for reducing mortality. Accordingly, we determined the pharmacokinetic profile of piperacillin (4 g) every 8 h, during the third consecutive dosing interval, in 15 patients treated empirically for septic shock. We developed a population pharmacokinetic model to assess empirical dosing and to simulate alternative dosing regimens and modes of administration. Time above the MIC (T>MIC) predicted for each patient was evaluated against clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/liter). Pharmacokinetic-pharmacodynamic (PK/PD) targets evaluated were 50% fT>4×MIC and 100% fT>MIC. A population PK model was developed using NONMEM, and data were best described by a two-compartment model. Central and intercompartmental clearances were 3.6 liters/h (relative standard error [RSE], 15.7%) and 6.58 liters/h (RSE, 16.4%), respectively, and central and peripheral volumes were 7.3 liters (RSE, 11.8%) and 3.9 liters (RSE, 9.7%), respectively. Piperacillin plasma concentrations varied considerably between patients and were associated with levels of plasma creatinine. Patients with impaired renal function were more likely to achieve predefined PK/PD targets than were patients with preserved or augmented renal function. Simulations of alternative dosing regimens showed that frequent intermittent bolus dosing as well as dosing by extended and continuous infusion increases the probability of attaining therapeutic plasma concentrations. For septic shock patients with preserved or augmented renal function, dose increment or prolonged infusion of the drug needs to be considered. (This study has been registered at ClinicalTrials.gov under registration no. NCT02306928.).

  16. The clinical and hemodynamic presentation of the shock patient.

    PubMed

    Summers, G

    1990-06-01

    It is the nurse's responsibility to assess the critically ill patient and to interpret data so that therapy can be directed to optimally treat that individual. Shock is a complex progressive syndrome that includes specific types, such as cardiogenic, septic, anaphylactic, and hypovolemic. Clinical and hemodynamic parameters provide clues to the specific type of shock and its clinical progress. The progression of the shock state must be monitored by critical care nurses who are knowledgeable of and proficient in clinical assessment skills and the acquisition and interpretation of significant hemodynamic data.

  17. Hemodynamic management of septic shock: is it time for "individualized goal-directed hemodynamic therapy" and for specifically targeting the microcirculation?

    PubMed

    Saugel, Bernd; Trepte, Constantin J; Heckel, Kai; Wagner, Julia Y; Reuter, Daniel A

    2015-06-01

    Septic shock is a life-threatening condition in both critically ill medical patients and surgical patients during the perioperative phase. In septic shock, specific alterations in global cardiovascular dynamics (i.e., the macrocirculation) and in the microcirculatory blood flow (i.e., the microcirculation) have been described. However, the presence and degree of microcirculatory failure are in part independent from systemic macrohemodynamic variables. Macrocirculatory and microcirculatory failure can independently induce organ dysfunction. We review current diagnostic and therapeutic approaches for the assessment and optimization of both the macrocirculation and the microcirculation in septic shock. There are various technologies for the determination of macrocirculatory hemodynamic variables. We discuss the data on early goal-directed therapy for the resuscitation of the macrocirculation. In addition, we describe the concept of "individualized goal-directed hemodynamic therapy." Technologies to assess the local microcirculation are also available. However, adequate resuscitation goals for the optimization of the microcirculation still need to be defined. At present, we are not ready to specifically monitor and target the microcirculation in clinical routine outside studies. In the future, concepts for an integrative approach for individualized hemodynamic management of the macrocirculation and in parallel the microcirculation might constitute a huge opportunity to define additional resuscitation end points in septic shock.

  18. Vasopressin use in critically ill cirrhosis patients with catecholamine-resistant septic shock: The CVICU cohort

    PubMed Central

    Myc, Lukasz A; Stine, Jonathan G; Chakrapani, Rinita; Kadl, Alexandra; Argo, Curtis K

    2017-01-01

    AIM To examine patient-centered outcomes with vasopressin (AVP) use in patients with cirrhosis with catecholamine-refractory septic shock. METHODS We conducted a single center, retrospective cohort study enrolling adult patients with cirrhosis treated for catecholamine-resistant septic shock in the intensive care unit (ICU) from March 2011 through December 2013. Other etiologies of shock were excluded. Multivariable regression models were constructed for seven and 28-d mortality comparing AVP as a second-line therapy to a group of all other vasoactive agents. RESULTS Forty-five consecutive patients with cirrhosis were treated for catecholamine-resistant septic shock; 21 received AVP while the remaining 24 received another agent [phenylephrine (10), dopamine (6), norepinephrine (4), dobutamine (2), milrinone (2)]. In general, no significant differences in baseline demographics, etiology of cirrhosis, laboratory values, vital signs or ICU mortality/severity of illness scores were observed with the exception of higher MELD scores in the AVP group (32.4, 95%CI: 28.6-36.2 vs 27.1, 95%CI: 23.6-30.6, P = 0.041). No statistically significant difference was observed in unadjusted 7-d (52.4% AVP vs 58.3% and P = 0.408) or 28-d mortality (81.0% AVP vs 87.5% non-AVP, P = 0.371). Corticosteroid administration was associated with lower 28-d mortality (HR = 0.37, 95%CI: 0.16-0.86, P = 0.021) independent of AVP use. CONCLUSION AVP is similar in terms of patient centered outcomes of seven and 28-d mortality, in comparison to all other vasopressors when used as a second line vasoactive agent in catecholamine resistant septic shock. Large-scale prospective study would help to refine current consensus standards and provide further support to our findings. PMID:28144392

  19. Serum lactate levels as the predictor of outcome in pediatric septic shock

    PubMed Central

    Jat, Kana Ram; Jhamb, Urmila; Gupta, Vinod K.

    2011-01-01

    Background and Aims: An association of high lactate levels with mortality has been found in adult patients with septic shock. However, there is controversial literature regarding the same in children. The aim of this study was to find the correlation of serum lactate levels in pediatric septic shock with survival. Settings and Design: This was a prospective observational study at PICU of a tertiary care center of North India. Materials and Methods: A total of 30 children admitted to PICU with diagnosis of septic shock were included in the study. PRISM III score and demographic characteristics of all children were recorded. Serum lactate levels were measured in arterial blood at 0-3, 12, and 24 h of PICU admission. The outcome (survival or death) was correlated with serum lactate levels. Results: Septic shock was the most common (79.3%) type of shock and had 50% mortality. Initial as well as subsequent lactate levels were significantly higher in nonsurvivors. A lactate value of more than 45 mg/dl (5 mmol/l) at 0–3, 12, and 24 h of PICU admission had an odds ratio for death of 6.7, 12.5, and 8.6 (95% CI: 1.044–42.431, 1.850–84.442, 1.241–61.683) with a positive predictive value (PPV) of 38%, 71%, 64% and a negative predictive value (NPV) of 80%, 83%, and 83%, respectively. Conclusions: Nonsurvivors had higher blood lactate levels at admission as well as at 12 and 24 h. A lactate value of more than 45 mg/dl (5 mmol/l) was a good predictor of death. PMID:21814374

  20. Transcriptomic meta-analysis reveals up-regulation of gene expression functional in osteoclast differentiation in human septic shock

    PubMed Central

    Mukhopadhyay, Samanwoy; Thatoi, Pravat K.; Pandey, Abhay D.; Das, Bidyut K.; Ravindran, Balachandran; Bhattacharjee, Samsiddhi; Mohapatra, Saroj K.

    2017-01-01

    Septic shock is a major medical problem with high morbidity and mortality and incompletely understood biology. Integration of multiple data sets into a single analysis framework empowers discovery of new knowledge about the condition that may have been missed by individual analysis of each of these datasets. Electronic search was performed on medical literature and gene expression databases for selection of transcriptomic studies done in circulating leukocytes from human subjects suffering from septic shock. Gene-level meta-analysis was conducted on the six selected studies to identify the genes consistently differentially expressed in septic shock. This was followed by pathway-level analysis using three different algorithms (ORA, GSEA, SPIA). The identified up-regulated pathway, Osteoclast differentiation pathway (hsa04380) was validated in two independent cohorts. Of the pathway, 25 key genes were selected that serve as an expression signature of Septic Shock. PMID:28199355

  1. Transcriptomic meta-analysis reveals up-regulation of gene expression functional in osteoclast differentiation in human septic shock.

    PubMed

    Mukhopadhyay, Samanwoy; Thatoi, Pravat K; Pandey, Abhay D; Das, Bidyut K; Ravindran, Balachandran; Bhattacharjee, Samsiddhi; Mohapatra, Saroj K

    2017-01-01

    Septic shock is a major medical problem with high morbidity and mortality and incompletely understood biology. Integration of multiple data sets into a single analysis framework empowers discovery of new knowledge about the condition that may have been missed by individual analysis of each of these datasets. Electronic search was performed on medical literature and gene expression databases for selection of transcriptomic studies done in circulating leukocytes from human subjects suffering from septic shock. Gene-level meta-analysis was conducted on the six selected studies to identify the genes consistently differentially expressed in septic shock. This was followed by pathway-level analysis using three different algorithms (ORA, GSEA, SPIA). The identified up-regulated pathway, Osteoclast differentiation pathway (hsa04380) was validated in two independent cohorts. Of the pathway, 25 key genes were selected that serve as an expression signature of Septic Shock.

  2. Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial.

    PubMed

    Cruz, Dinna N; Antonelli, Massimo; Fumagalli, Roberto; Foltran, Francesca; Brienza, Nicola; Donati, Abele; Malcangi, Vincenzo; Petrini, Flavia; Volta, Giada; Bobbio Pallavicini, Franco M; Rottoli, Federica; Giunta, Francesco; Ronco, Claudio

    2009-06-17

    Polymyxin B fiber column is a medical device designed to reduce blood endotoxin levels in sepsis. Gram-negative-induced abdominal sepsis is likely associated with high circulating endotoxin. Reducing circulating endotoxin levels with polymyxin B hemoperfusion could potentially improve patient clinical outcomes. To determine whether polymyxin B hemoperfusion added to conventional medical therapy improves clinical outcomes (mean arterial pressure [MAP], vasopressor requirement, oxygenation, organ dysfunction) and mortality compared with conventional therapy alone. A prospective, multicenter, randomized controlled trial (Early Use of Polymyxin B Hemoperfusion in Abdominal Sepsis [EUPHAS]) conducted at 10 Italian tertiary care intensive care units between December 2004 and December 2007. Sixty-four patients were enrolled with severe sepsis or septic shock who underwent emergency surgery for intra-abdominal infection. Patients were randomized to either conventional therapy (n=30) or conventional therapy plus 2 sessions of polymyxin B hemoperfusion (n=34). Primary outcome was change in MAP and vasopressor requirement, and secondary outcomes were PaO(2)/FIO(2) (fraction of inspired oxygen) ratio, change in organ dysfunction measured using Sequential Organ Failure Assessment (SOFA) scores, and 28-day mortality. MAP increased (76 to 84 mm Hg; P = .001) and vasopressor requirement decreased (inotropic score, 29.9 to 6.8; P < .001) at 72 hours in the polymyxin B group but not in the conventional therapy group (MAP, 74 to 77 mm Hg; P = .37; inotropic score, 28.6 to 22.4; P = .14). The PaO(2)/FIO(2) ratio increased slightly (235 to 264; P = .049) in the polymyxin B group but not in the conventional therapy group (217 to 228; P = .79). SOFA scores improved in the polymyxin B group but not in the conventional therapy group (change in SOFA, -3.4 vs -0.1; P < .001), and 28-day mortality was 32% (11/34 patients) in the polymyxin B group and 53% (16/30 patients) in the conventional

  3. Septic Participation in Cardiogenic Shock: Exposure to Bacterial Endotoxin.

    PubMed

    Ramirez, Paula; Villarreal, Esther; Gordon, Monica; Gómez, María Dolores; de Hevia, Luis; Vacacela, Karla; Gisbert, Teresa; Quinzá, Adrian; Ruiz, Jesús; Alonso, Ricardo; Bonastre, Juan; Vila, Jordi

    2017-05-01

    In cardiogenic shock (CS), presence of fever, leukocytosis, relatively low systemic vascular resistances, and high serum procalcitonin levels are quite frequent and recurrently involve the search for an infectious complication. We hypothesized that endotoxin exposure in CS could explain this sepsis-like syndrome. Prospective observational study of consecutive CS patients admitted to our intensive care unit (ICU). Patients were followed during the first 3 days after CS onset. All clinical, hemodynamic, and microbiological data were collected. Inflammatory biomarkers and anti-endotoxin antibodies (IgM EndoCAb) were daily measured. We included 37 consecutive CS patients. Twenty-two patients (60%) had body temperature >38.3°C or <35°C; and 23 patients (62%) had a leucocyte count >14,000/mm or <4,000/mm. Microbiological study was performed in 30 patients (81%). No infection was diagnosed in the studied patients. All the patients had serum inflammatory biomarkers levels above normal values including procalcitonin (19 patients [51%] had serum procalcitonin above 2 ng/mL). All the patients had IgM EndoCAb below the normal median value; 22 patients (59.5%) had IgM anti-endotoxin value below 10th percentile range for healthy people. Hemodynamic and respiratory stabilization was achieved in 23 patients (62%) and the ICU mortality rate was 38%, only procalcitonin and interleuquin-6 were associated with higher mortality rate. We have detected extremely low titers of IgM EndoCAb in CS suggesting endotoxin exposure. However, only inflammatory biomarkers were related to ICU mortality.

  4. Incidence and mortality of sepsis, severe sepsis, and septic shock in intensive care unit patients with candidemia.

    PubMed

    Ng, Kevin; Schorr, Christa; Reboli, Annette C; Zanotti, Sergio; Tsigrelis, Constantine

    2015-08-01

    In this incidence study, of 16 074 patients admitted to the intensive care unit (ICU) from 1/1/2003 to 7/31/2011, 161 cases of candidemia were identified. The incidence of sepsis (27%), severe sepsis (31%), and septic shock (40%) was remarkably high in these cases of candidemia, as was the all-cause in-hospital mortality for sepsis (30%), severe sepsis (44%), and septic shock (65%).

  5. Histocompatibility leukocyte antigen-D related expression is specifically altered and predicts mortality in septic shock but not in other causes of shock.

    PubMed

    Caille, Vincent; Chiche, Jean-Daniel; Nciri, Noureddine; Berton, Christine; Gibot, Sébastien; Boval, Bernadette; Payen, Didier; Mira, Jean-Paul; Mebazaa, Alexandre

    2004-12-01

    Although the expression of monocyte histocompatibility leukocyte antigen (HLA)-DR has been shown to be decreased during human sepsis, its level of expression in other nonseptic critical conditions is unclear. The aim of this study was to compare the level of HLA-DR expression on circulating monocytes among patients with septic, hemorrhagic, and cardiogenic shocks and severe sepsis without shock. At admission, HLA-DR expression was exclusively decreased in patients with septic shock (n = 30; P < 0.001), whereas the expression was similar between the other studied groups: cardiogenic shock (n = 16), hemorrhagic shock (n = 11), severe sepsis without shock (n = 18), and healthy volunteers (n = 8). HLA-DR expression was not predictive for overall mortality, but at day 1, an HLA-DR expression of less than 14 of mean fluorescence intensity (that corresponds to 40% labeled monocytes) was predictive of mortality exclusively in patients with septic shock (odds ratio, 11.4 and 95% confidence interval, 1.7; 78.4; P < 0.008). Catecholamine infusion, mechanical ventilation, positive blood culture, and number of units of blood or plasma transfused did not correlate with decreased HLA-DR expression. Thus, the decrease in HLA-DR expression is specific to septic shock and is associated, in septic shock patients, with increased mortality risk.

  6. Ensuring animal welfare while meeting scientific aims using a murine pneumonia model of septic shock.

    PubMed

    Huet, Olivier; Ramsey, Debbie; Miljavec, Sandra; Jenney, Adam; Aubron, Cecile; Aprico, Andrea; Stefanovic, Nada; Balkau, Beverley; Head, Geoff A; de Haan, Judy B; Chin-Dusting, Jaye P F

    2013-06-01

    With animal models, death as an intentional end point is ethically unacceptable. However, in the study of septic shock, death is still considered the only relevant end point. We defined eight humane end points into four stages of severity (from healthy to moribund) and used to design a clinically relevant scoring tool, termed "the mouse clinical assessment score for sepsis" (M-CASS). The M-CASS was used to enable a consistent approach to the assessment of disease severity. This allowed an ethical and objective assessment of disease after which euthanasia was performed, instead of worsening suffering. The M-CASS displayed a high internal consistency (Cronbach α = 0.97) with a high level of agreement and an intraclass correlation coefficient equal to 0.91. The plasma levels of cytokines and markers of oxidative stress were all associated with the M-CASS score (Kruskal-Wallis test, P < 0.05). The M-CASS allows tracking of disease progression and animal welfare requirements.

  7. Data quality aspects of a database for abdominal septic shock patients.

    PubMed

    Paetz, Jürgen; Arlt, Björn; Erz, Kerstin; Holzer, Katharina; Brause, Rüdiger; Hanisch, Ernst

    2004-07-01

    Since many years, medical researchers have investigated the mechanisms that may cause a septic shock. Despite many approaches that analyzed smaller parts of the relevant data or single variables, respectively, no larger database with all the possible relevant data existed. Our work was to bridge this gap. We built a large database for abdominal septic shock patients. While building it, we were confronted with many problems concerning the database realization and the data quality. Thus, we will demonstrate how we built our database and how we assured data quality. This is of interest for all medical or computer scientists who are concerned with building medical databases with retrospective data, e.g. for data mining purposes.

  8. Glucocorticoid administration in sepsis and septic shock: time for a paradigm change?

    PubMed

    Antonucci, E; Fiaccadori, E; Taccone, F S; Vincent, J L

    2014-09-01

    The use of corticosteroids in patients with septic shock remains controversial. Questions remain regarding the more appropriate dose, the optimal timing to initiate therapy, the selection of patients who will benefit most from the treatment and the exact mechanisms involved in their effectiveness. Recent studies have highlighted that, in critically ill patients, corticosteroid metabolism was reduced and associated with high circulating cortisol levels. Hence the required doses of hydrocortisone may be lower than the currently recommended doses in septic shock (i.e. 200 mg/day). However, altered expression and/or function of corticosteroid receptors may still suggest that higher hydrocortisone doses are necessary to overcome this so-called "steroid-resistance". In this article, we summarized these recent concepts and discussed how they could influence the administration of corticosteroids in such patients.

  9. [Polymyxin B hemoperfusion (PMX-F) for severe sepsis and septic shock].

    PubMed

    Hayashi, Yoshiro

    2012-02-01

    PMX-F, which was developed in Japan, is a potential therapeutic option for severe sepsis and septic shock. Despite positive effects on surrogate outcomes, demonstrated in methodologically suboptimal preliminary studies, its benefit on mortality remains unclear. Surprisingly, this expensive investigational therapy has been reimbursed by the Japanese National Health Insurance program since 1994 and 75,000 cartridges have been consumed, sometimes without expert intensive care supervision. Current evidence in intensive care medicine does not justify utilizing PMX-F for severe sepsis and septic shock, considering its unproven benefit, significant cost and potential risks. Even if reduced mortality is shown in future studies, that benefit could easily be cancelled out in settings, such as many Japanese institutions, where intensive care expertise is unavailable.

  10. Septic shock from Pasturella multocida following a cat bite: case report and review of literature.

    PubMed

    Adler, Adam C; Cestero, Cesar; Brown, Robert B

    2011-01-01

    Pasteurella multocida is a gram-negative organism categorized morphologically as a coccobacillus. P. multocida is a natural inhabitant found in the nasopharynx and oropharynx of numerous animal hosts, but serves as an opportunistic pathogen in humans. Pasturella multocida has multiple subspecies; when identified as the cause of infection they are broadly termed pasturelloses. Infections involving P. multocida are typically reported to occur in immune-compromised patients. Few cases in the literature identify pasturellosis as the causative agent of septic shock, especially in cirrhotic patients. Our patient's underlying cirrhosis and past splenectomy place her in the higher risk category for developing invasive Pasturella infection. We report a patient who presented with septic shock that was initially thought to be related to a urinary tract infection. It was later revealed that the patient's condition was caused by a recent cat bite leading to Pasturella bacteremia compounded by hepatic cirrhosis and previous splenectomy.

  11. Exchange Transfusion in the Treatment of Neonatal Septic Shock: A Ten-Year Experience in a Neonatal Intensive Care Unit.

    PubMed

    Pugni, Lorenza; Ronchi, Andrea; Bizzarri, Bianca; Consonni, Dario; Pietrasanta, Carlo; Ghirardi, Beatrice; Fumagalli, Monica; Ghirardello, Stefano; Mosca, Fabio

    2016-05-09

    Septic shock, occurring in about 1% of neonates hospitalized in neonatal intensive care unit (NICU), is a major cause of death in the neonatal period. In the 1980s and 90s, exchange transfusion (ET) was reported by some authors to be effective in the treatment of neonatal sepsis and septic shock. The main aim of this retrospective study was to compare the mortality rate of neonates with septic shock treated only with standard care therapy (ScT group) with the mortality rate of those treated with ScT and ET (ET group). All neonates with septic shock admitted to our NICU from 2005 to 2015 were included in the study. Overall, 101/9030 (1.1%) neonates had septic shock. Fifty neonates out of 101 (49.5%) received one or more ETs. The mortality rate was 36% in the ET group and 51% in the ScT group (p = 0.16). At multivariate logistic regression analysis, controlling for potentially confounding factors significantly associated with death (gestational age, serum lactate, inotropic drugs, oligoanuria), ET showed a marked protective effect (Odds Ratio 0.21, 95% Confidence Interval: 0.06-0.71; p = 0.01). The lack of observed adverse events should encourage the use of this procedure in the treatment of neonates with septic shock.

  12. Exchange Transfusion in the Treatment of Neonatal Septic Shock: A Ten-Year Experience in a Neonatal Intensive Care Unit

    PubMed Central

    Pugni, Lorenza; Ronchi, Andrea; Bizzarri, Bianca; Consonni, Dario; Pietrasanta, Carlo; Ghirardi, Beatrice; Fumagalli, Monica; Ghirardello, Stefano; Mosca, Fabio

    2016-01-01

    Septic shock, occurring in about 1% of neonates hospitalized in neonatal intensive care unit (NICU), is a major cause of death in the neonatal period. In the 1980s and 90s, exchange transfusion (ET) was reported by some authors to be effective in the treatment of neonatal sepsis and septic shock. The main aim of this retrospective study was to compare the mortality rate of neonates with septic shock treated only with standard care therapy (ScT group) with the mortality rate of those treated with ScT and ET (ET group). All neonates with septic shock admitted to our NICU from 2005 to 2015 were included in the study. Overall, 101/9030 (1.1%) neonates had septic shock. Fifty neonates out of 101 (49.5%) received one or more ETs. The mortality rate was 36% in the ET group and 51% in the ScT group (p = 0.16). At multivariate logistic regression analysis, controlling for potentially confounding factors significantly associated with death (gestational age, serum lactate, inotropic drugs, oligoanuria), ET showed a marked protective effect (Odds Ratio 0.21, 95% Confidence Interval: 0.06–0.71; p = 0.01). The lack of observed adverse events should encourage the use of this procedure in the treatment of neonates with septic shock. PMID:27171076

  13. Improved Risk Stratification in Pediatric Septic Shock Using Both Protein and mRNA Biomarkers. PERSEVERE-XP.

    PubMed

    Wong, Hector R; Cvijanovich, Natalie Z; Anas, Nick; Allen, Geoffrey L; Thomas, Neal J; Bigham, Michael T; Weiss, Scott L; Fitzgerald, Julie C; Checchia, Paul A; Meyer, Keith; Quasney, Michael; Hall, Mark; Gedeit, Rainer; Freishtat, Robert J; Nowak, Jeffrey; Raj, Shekhar S; Gertz, Shira; Grunwell, Jocelyn R; Lindsell, Christopher J

    2017-08-15

    We previously derived and validated the Pediatric Sepsis Biomarker Risk Model (PERSEVERE) to estimate baseline mortality risk in children with septic shock. The PERSEVERE biomarkers are serum proteins selected from among the proteins directly related to 80 mortality risk assessment genes. The initial approach to selecting the PERSEVERE biomarkers left 68 genes unconsidered. To determine if the 68 previously unconsidered genes can improve upon the performance of PERSEVERE and to provide biological information regarding the pathophysiology of septic shock. We reduced the number of variables by determining the biological linkage of the 68 previously unconsidered genes. The genes identified through variable reduction were combined with the PERSEVERE-based mortality probability to derive a risk stratification model for 28-day mortality using classification and regression tree methodology (n = 307). The derived tree, PERSEVERE-XP, was then tested in a separate cohort (n = 77). Variable reduction revealed a network consisting of 18 mortality risk assessment genes related to tumor protein 53 (TP53). In the derivation cohort, PERSEVERE-XP had an area under the receiver operating characteristic curve (AUC) of 0.90 (95% confidence interval, 0.85-0.95) for differentiating between survivors and nonsurvivors. In the test cohort, the AUC was 0.96 (95% confidence interval, 0.91-1.0). The AUC of PERSEVERE-XP was superior to that of PERSEVERE. PERSEVERE-XP combines protein and mRNA biomarkers to provide mortality risk stratification with possible clinical utility. PERSEVERE-XP significantly improves on PERSEVERE and suggests a role for TP53-related cellular division, repair, and metabolism in the pathophysiology of septic shock.

  14. Thirst Perception and Osmoregulation of Vasopressin Secretion Are Altered During Recovery From Septic Shock

    PubMed Central

    Siami, Shidasp; Polito, Andrea; Porcher, Raphael; Hissem, Tarik; Blanchard, Anne; Boucly, Catherine; Carlier, Robert; Annane, Djillali; Haymann, Jean-Philippe; Sharshar, Tarek

    2013-01-01

    Objective Vasopressin (AVP) secretion during an osmotic challenge is frequently altered in the immediate post-acute phase of septic shock. We sought to determine if this response is still altered in patients recovering from septic shock. Design Prospective interventional study Setting Intensive care unit (ICU) at Raymond Poincaré and Etampes Hospitals. Patients Normonatremic patients at least 5 days post discontinuation of catecholamines given for a septic shock. Intervention Osmotic challenge involved infusing 500 mL of hypertonic saline solution (with cumulative amount of sodium not exceeding 24 g) over 120 minutes. Measurements and main results Plasma AVP levels were measured 15 minutes before the infusion and then every 30 minutes for two hours. Non-responders were defined as those with a slope of the relation between AVP and plasma sodium levels less than < 0.5 ng/mEq. Among the 30 included patients, 18 (60%) were non-responders. Blood pressure and plasma sodium and brain natriuretic peptide levels were similar in both responders and non-responders during the course of the test. Critical illness severity, hemodynamic alteration, electrolyte disturbances, treatment and outcome did not differ between the two groups. Responders had more severe gas exchange abnormality. Thirst perception was significantly diminished in non-responders. The osmotic challenge was repeated in 4 non-responders several months after discharge and the abnormal response persisted. Conclusion More than half of patients recovering from septic shock have an alteration of osmoregulation characterised by a dramatic decrease in vasopressin secretion and thirst perception during osmotic challenge. The mechanisms of this alteration but also of the relationship between haematosis and normal response remain to be elucidated. PMID:24223220

  15. Effect of high-dose Ascorbic acid on vasopressor's requirement in septic shock

    PubMed Central

    Zabet, Mohadeseh Hosseini; Mohammadi, Mostafa; Ramezani, Masoud; Khalili, Hossein

    2016-01-01

    Objective: Effects of ascorbic acid on hemodynamic parameters of septic shock were evaluated in nonsurgical critically ill patients in limited previous studies. In this study, the effect of high-dose ascorbic acid on vasopressor drug requirement was evaluated in surgical critically ill patients with septic shock. Methods: Patients with septic shock who required a vasopressor drug to maintain mean arterial pressure >65 mmHg were assigned to receive either 25 mg/kg intravenous ascorbic acid every 6 h or matching placebo for 72 h. Vasopressor dose and duration were considered as the primary outcomes. Duration of Intensive Care Unit (ICU) stay and 28-day mortality has been defined as secondary outcomes. Findings: During the study period, 28 patients (14 in each group) completed the trial. Mean dose of norepinephrine during the study period (7.44 ± 3.65 vs. 13.79 ± 6.48 mcg/min, P = 0.004) and duration of norepinephrine administration (49.64 ± 25.67 vs. 71.57 ± 1.60 h, P = 0.007) were significantly lower in the ascorbic acid than the placebo group. No statistically significant difference was detected between the groups regarding the length of ICU stay. However, 28-day mortality was significantly lower in the ascorbic acid than the placebo group (14.28% vs. 64.28%, respectively; P = 0.009). Conclusion: High-dose ascorbic acid may be considered as an effective and safe adjuvant therapy in surgical critically ill patients with septic shock. The most effective dose of ascorbic acid and the best time for its administration should be determined in future studies. PMID:27162802

  16. The Effects of Alternative Resuscitation Strategies on Acute Kidney Injury in Patients with Septic Shock.

    PubMed

    Kellum, John A; Chawla, Lakhmir S; Keener, Christopher; Singbartl, Kai; Palevsky, Paul M; Pike, Francis L; Yealy, Donald M; Huang, David T; Angus, Derek C

    2016-02-01

    Septic shock is a common cause of acute kidney injury (AKI), and fluid resuscitation is a major part of therapy. To determine if structured resuscitation designed to alter fluid, blood, and vasopressor use affects the development or severity of AKI or outcomes. Ancillary study to the ProCESS (Protocolized Care for Early Septic Shock) trial of alternative resuscitation strategies (two protocols vs. usual care) for septic shock. We studied 1,243 patients and classified AKI using serum creatinine and urine output. We determined recovery status at hospital discharge, examined rates of renal replacement therapy and fluid overload, and measured biomarkers of kidney damage. Among patients without evidence of AKI at enrollment, 37.6% of protocolized care and 38.1% of usual care patients developed kidney injury (P = 0.90). AKI duration (P = 0.59) and rates of renal replacement therapy did not differ between study arms (6.9% for protocolized care and 4.3% for usual care; P = 0.08). Fluid overload occurred in 8.3% of protocolized care and 6.3% of usual care patients (P = 0.26). Among patients with severe AKI, complete and partial recovery was 50.7 and 13.2% for protocolized patients and 49.1 and 13.4% for usual care patients (P = 0.93). Sixty-day hospital mortality was 6.2% for patients without AKI, 16.8% for those with stage 1, and 27.7% for stages 2 to 3. In patients with septic shock, AKI is common and associated with adverse outcomes, but it is not influenced by protocolized resuscitation compared with usual care.

  17. Association of serum tumor necrosis factor levels with decrease of cholesterol during septic shock.

    PubMed

    Fraunberger, P; Pilz, G; Cremer, P; Werdan, K; Walli, A K

    1998-11-01

    Recent studies suggest that release of cytokines during inflammatory states such as septic shock leads to hypocholesterolemia. To examine whether tumor necrosis factor alpha (TNF), which is the major cytokine in inflammatory disease, causes hypocholesterolemia, we measured serum levels of total (bioactive and receptor-bound) TNF, cholesterol, Apo B, and Apo A1 in seven patients with septic shock over a period of 8 days. Since elevated serum TNF levels are accompanied by the release of soluble TNF receptors, levels of TNF receptors p55 and p75 were also measured. Patients with septic shock had significantly higher serum TNF and TNF receptor levels compared with healthy controls. Increased cytokine levels were accompanied by a significant decline in total serum cholesterol apolipoprotein A1 and B. In vitro studies with cultured human skin fibroblasts, human umbilical vein endothelial cells, and HepG2 hepatoma cells showed that TNF increased the degradation of 125I-labeled low-density lipoprotein in all the cell lines tested. Recombinant soluble TNF receptors inhibited the TNF-induced stimulation of low-density lipoprotein receptor in a concentration-dependent manner. However, the calculated ratio of TNF receptors to total TNF measured in serum of these patients was not able to counteract the stimulatory effect of TNF, possibly due to the higher molar excess of TNF receptors required to achieve this effect in vitro. Our data strengthen the hypothesis that serum values of total TNF determine the extent of hypocholesterolemia during sepsis and septic shock despite the presence of a high concentration of TNF receptors. Studies with recombinant TNF also confirm the role of TNF in hypocholesterolemia in inflammation.

  18. Does body weight impact the efficacy of vasopressin therapy in the management of septic shock?

    PubMed

    Miller, James T; Welage, Lynda S; Kraft, Michael D; Alaniz, Cesar

    2012-06-01

    Vasopressors used for the management of septic shock are often dosed according to body weight. Use of vasopressin for physiologic replacement in patients with septic shock is usually administered as a standard non-weight-based dose. We hypothesized that the efficacy of vasopressin may be influenced by body weight. The primary objective was to determine if the effects of vasopressin on other vasopressor dosing requirements is related to body weight. Secondary objectives included evaluation of blood pressure and heart rate after the start of vasopressin infusion. A retrospective, cohort study in a large academic health center was conducted. Sixty-four adult inpatients with septic shock (26 medical intensive care unit and 38 surgical intensive care unit) who required vasopressor administration including vasopressin therapy were included. Dosing requirements of vasopressors were captured 1 hour before and during the hour of vasopressin initiation and 2 and 4 hours later. Other information collected during the study period included blood pressure, mean arterial pressure, and heart rate. Most of the patients (n = 61) received vasopressin at a dose of 0.04 U/min. Changes in vasopressor dosing were significantly correlated with weight-adjusted vasopressin at 2 hours (correlation coefficient = -0.36, P = .03) and 4 hours (correlation coefficient = -0.46, P < .001). Use of vasopressin was associated with significant increases in systolic blood pressure, diastolic blood pressure, and mean arterial pressure at each time point compared with baseline. Effects of vasopressin on catecholamine dosing requirements in the setting of septic shock may be influenced by body weight. Prospective studies are needed to examine weight-based dosing of vasopressin in this setting. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Cardiopulmonary Arrest and Resuscitation in Severe Sepsis and Septic Shock: A Research Model.

    PubMed

    Chalkias, Athanasios; Spyropoulos, Vaios; Koutsovasilis, Anastasios; Papalois, Apostolos; Kouskouni, Evaggelia; Xanthos, Theodoros

    2015-03-01

    Cardiopulmonary resuscitation in patients with severe sepsis and septic shock is challenging and usually unsuccessful. The aim of the present study is to describe our swine model of cardiac arrest and resuscitation in severe sepsis and septic shock. In this prospective randomized animal study, 10 healthy female Landrace-Large White pigs with an average weight of 20 ± 1 kg (aged 19 - 21 weeks) were the study subjects. Septicemia was induced by an intravenous infusion of a bolus of 20-mL bacterial suspension in 2 min, followed by a continuous infusion during the rest of the experiment. After septic shock was confirmed, the animals were left untreated until cardiac arrest occurred. All animals developed pulseless electrical activity between the fifth and sixth hours of septicemia, whereas five (50%) of 10 animals were successfully resuscitated. Coronary perfusion pressure was statistically significantly different between surviving and nonsurviving animals. We found a statistically significant correlation between mean arterial pressure and unsuccessful resuscitation (P = 0.046), whereas there was no difference in end-tidal carbon dioxide (23.05 ± 1.73 vs. 23.56 ± 1.70; P = 0.735) between animals with return of spontaneous circulation and nonsurviving animals. During the 45-min postresuscitation monitoring, we noted a significant decrease in hemodynamic parameters, although oxygenation indices and lactate clearance were constantly increased (P = 0.001). This successful basic swine model was for the first time developed and may prove extremely useful in future studies on the periarrest period in severe sepsis and septic shock.

  20. Decreased organ failure in patients with severe SIRS and septic shock treated with the platelet-activating factor antagonist TCV-309: a prospective, multicenter, double-blind, randomized phase II trial. TCV-309 Septic Shock Study Group.

    PubMed

    Poeze, M; Froon, A H; Ramsay, G; Buurman, W A; Greve, J W

    2000-10-01

    Sepsis and organ failure remain the main cause of death on the ICU. Sepsis is characterized by a severe inflammatory response, in which platelet-activating factor (PAF) is considered to play an important role. This study investigated whether treatment with the PAF-antagonist TCV-309 reduces morbidity and mortality in patients with septic shock. The study was conducted as a double-blind, randomized, placebo controlled multicenter study. The included patients had to fulfill the SIRS criteria with a clinical suspicion of infection, an admission APACHE II score greater than 15, and shock, defined as a mean arterial pressure <70 mmHg and/or a decrease > or =40 mmHg despite adequate fluid resuscitation. Patients received 1.0 mg/kg TCV-309 or placebo, twice daily, intravenously during 14 days. The prospectively set goals were MOF score, recovery from shock, mortality, and assessment of the safety of the medication. A total of 98 patients were included of which 97 were analyzed on an intention-to-treat basis. The overall survival at day 56 of TCV-309 treated patients was similar compared to placebo treated patients (51.0% vs. 41.7%, P = 0.47). In contrast, the mean percentage of failed organs per patient present after 14 days in the TCV-309 treated patients was significantly lower compared to the placebo treated patients (11.9% vs. 25.1%, P = 0.04), leading to a reduced need for vasopressors, dialysis, and ventilatory support. Furthermore, the mean APACHE-II score during treatment with TCV-309 was significantly lower and the number of patients recovered from shock after day 14 was significantly higher in the TCV-309 treated patient group (2/32 vs. 9/29, P = 0.01). The number of adverse events was not significantly different between the TCV-309 and placebo treated patients. TCV-309 did not change overall mortality of septic shock, however a substantial reduction in organ dysfunction and morbidity, frequently associated with septic shock was achieved, without significant

  1. Dynamic arterial elastance predicts mean arterial pressure decrease associated with decreasing norepinephrine dosage in septic shock.

    PubMed

    Guinot, Pierre-Grégoire; Bernard, Eugénie; Levrard, Mélanie; Dupont, Hervé; Lorne, Emmanuel

    2015-01-19

    Gradual reduction of the dosage of norepinephrine (NE) in patients with septic shock is usually left to the physician's discretion. No hemodynamic indicator predictive of the possibility of decreasing the NE dosage is currently available at the bedside. The respiratory pulse pressure variation/respiratory stroke volume variation (dynamic arterial elastance (Eadyn)) ratio has been proposed as an indicator of vascular tone. The purpose of this study was to determine whether Eadyn can be used to predict the decrease in arterial pressure when decreasing the NE dosage in resuscitated sepsis patients. A prospective study was carried out in a university hospital intensive care unit. All consecutive patients with septic shock monitored by PICCO2 for whom the intensive care physician planned to decrease the NE dosage were enrolled. Measurements of hemodynamic and PICCO2 variables were obtained before/after decreasing the NE dosage. Responders were defined by a >15% decrease in mean arterial pressure (MAP). In total, 35 patients were included. MAP decreased by >15% after decreasing the NE dosage in 37% of patients (n = 13). Clinical characteristics appeared to be similar between responders and nonresponders. Eadyn was lower in responders than in nonresponders (0.75 (0.69 to 0.85) versus 1 (0. 83 to 1.22), P <0.05). Baseline Eadyn was correlated with NE-induced MAP variations (r = 0.47, P = 0.005). An Eadyn less than 0.94 predicted a decrease in arterial pressure, with an area under the receiver-operating characteristic curve of 0.87 (95% confidence interval (95% CI): 0.72 to 0.96; P <0.0001), 100% sensitivity, and 68% specificity. In sepsis patients treated with NE, Eadyn may predict the decrease in arterial pressure in response to NE dose reduction. Eadyn may constitute an easy-to-use functional approach to arterial-tone assessment, which may be helpful to identify patients likely to benefit from NE dose reduction.

  2. Endothelial Permeability and Hemostasis in Septic Shock: Results From the ProCESS Trial.

    PubMed

    Hou, Peter C; Filbin, Michael R; Wang, Henry; Ngo, Long; Huang, David T; Aird, William C; Yealy, Donald M; Angus, Derek C; Kellum, John A; Shapiro, Nathan I

    2017-07-01

    We studied patients from the Protocolized Care in Early Septic Shock (ProCESS) trial to determine the effects of alternative resuscitation strategies on circulating markers of endothelial cell permeability and hemostasis and the association between biomarkers and mortality. This was a prospective study of biomarkers of endothelial cell permeability (vascular endothelial growth factor [VEGF], soluble fms-like tyrosine kinase 1 [sFLT-1], angiopoietin 2 [Ang-2]) and biomarkers of hemostasis (von Willebrand factor [vWF], thrombomodulin [TM], tissue plasminogen activator [tPA] in 605 of the 1,341 ProCESS participants in a derivation cohort and 305 participants in a validation cohort. Analyses assessed (1) the impact of varying resuscitation strategies on biomarker profiles and (2) the association of endothelial biomarkers with 60-day in-hospital mortality. The study was conducted in 31 US EDs in adult patients with septic shock. Patients were randomly assigned to one of three resuscitation strategies. Blood samples were collected at enrollment, at 6 h, and at 24 h. There were 116 (19.2%) and 52 (17.0%) deaths in the derivation and validation cohorts, respectively. There was no significant association between treatment strategy and any biomarker levels. Permeability (Ang-2 and sFLT-1) and hemostasis (vWF, TM, tPA) biomarkers were higher and VEGF levels were lower in nonsurvivors (P < .05 for all). At baseline, sFLT-1 had the highest point estimate for mortality discrimination (derivation area under the curve [AUC], 0.74; validation, 0.70), similar to lactate (AUC, 0.74) and Sequential Organ Failure Assessment score (AUC, 0.73). In an analysis including all time points and adjusted for age, presence of cancer, and Charlson comorbidity score, the adjusted AUC for sFLT-1 was 0.80. We found no relationship between different resuscitation strategies and biomarker profiles in sepsis, but we did find that elevated levels of endothelial cell biomarkers of permeability and

  3. Prognostic Value of Venoarterial Carbon Dioxide Gradient in Patients with Severe Sepsis and Septic Shock

    PubMed Central

    Troskot, Rosana; Šimurina, Tatjana; Žižak, Mirza; Majstorović, Karolina; Marinac, Ivana; Šutić, Ines Mrakovčić

    2010-01-01

    Aim To investigate the changes in the venoarterial carbon-dioxide gradient (V-a Pco2) and its prognostic value for survival of patients with severe sepsis and septic shock. Methods The study was conducted in General Hospital Holy Spirit from January 2004 to December 2007 and included 71 conveniently sampled adult patients (25 women and 46 men), who fulfilled the severe sepsis and septic shock criteria and were followed for a median of 8 days (interquartile range, 12 days). The patients were divided in two groups depending on whether or not they had been mechanically ventilated. Both groups of patients underwent interventions with an aim to achieve hemodynamic stability. Mechanical ventilation was applied in respiratory failure. Venoarterial carbon dioxide gradient was calculated from the difference between the partial pressure of arterial CO2 and the partial pressure of mixed venous CO2, which was measured with a pulmonary arterial Swan-Ganz catheter. The data were analyzed using Kaplan-Meier survival analysis, along with a calculation of the hazard ratios. Results There was a significant difference between non-ventilated and ventilated patients, with almost 4-fold greater hazard ratio for lethal outcome in ventilated patients (3.85; 95% confidence interval, 1.64-9.03). Furthermore, the pattern of changes of many other variables was also different in these two groups (carbon dioxide-related variables, variables related to acid-base status, mean arterial pressure, systemic vascular resistance, lactate, body mass index, Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology II Score, and Sepsis-related Organ Failure Assessment score). Pco2 values (with a cut-off of 0.8 kPa) were a significant predictor of lethal outcome in non-ventilated patients (P = 0.015) but not in ventilated ones (P = 0.270). Conclusion V-a Pco2 was a significant predictor of fatal outcome only in the non-ventilated group of patients. Ventilated patients are more

  4. Plasma granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor levels in critical illness including sepsis and septic shock: relation to disease severity, multiple organ dysfunction, and mortality.

    PubMed

    Presneill, J J; Waring, P M; Layton, J E; Maher, D W; Cebon, J; Harley, N S; Wilson, J W; Cade, J F

    2000-07-01

    To define the circulating levels of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) during critical illness and to determine their relationship to the severity of illness as measured by the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the development of multiple organ dysfunction, or mortality. Prospective cohort study. University hospital intensive care unit. A total of 82 critically ill adult patients in four clinically defined groups, namely septic shock (n = 29), sepsis without shock (n = 17), shock without sepsis (n = 22), and nonseptic, nonshock controls (n = 14). None. During day 1 of septic shock, peak plasma levels of G-CSF, interleukin (IL)-6, and leukemia inhibitory factor (LIF), but not GM-CSF, were greater than in sepsis or shock alone (p < .001), and were correlated among themselves (rs = 0.44-0.77; p < .02) and with the APACHE II score (rs = 0.25-0.40; p = .03 to .18). G-CSF, IL-6, and UF, and sepsis, shock, septic shock, and APACHE II scores were strongly associated with organ dysfunction or 5-day mortality by univariate analysis. However, multiple logistic regression analysis showed that only septic shock remained significantly associated with organ dysfunction and only APACHE II scores and shock with 5-day mortality. Similarly, peak G-CSF, IL-6, and LIF were poorly predictive of 30-day mortality. Plasma levels of G-CSF, IL-6, and LIF are greatly elevated in critical illness, including septic shock, and are correlated with one another and with the severity of illness. However, they are not independently predictive of mortality, or the development of multiple organ dysfunction. GM-CSF was rarely elevated, suggesting different roles for G-CSF and GM-CSF in human septic shock.

  5. Oxygen challenge test in septic shock patients: prognostic value and influence of respiratory status.

    PubMed

    Mari, Arnaud; Vallée, Fabrice; Bedel, Jérome; Riu, Béatrice; Ruiz, Jean; Sanchez-Verlaan, Pascale; Geeraerts, Thomas; Génestal, Michèle; Silva, Stein; Fourcade, Olivier

    2014-06-01

    Transcutaneous oxygen pressure (PtcO2) value in response to an increase of FiO2 or oxygen challenge test (OCT) in ventilated patients has been reported to be related to peripheral perfusion and outcome during septic shock. However, patients with sepsis-related acute respiratory distress syndrome could demonstrate compromised arterial oxygenation with OCT impairment decoupled to circulatory failure. The aims of this study were to confirm the prognostic value of OCT and to explore the influence of respiratory status on OCT results. This was a prospective study set in an intensive care unit of a tertiary teaching hospital. Fifty-six mechanically ventilated patients with septic shock criteria were studied. Transcutaneous oxygen pressure was measured at baseline and after OCT, at intensive care unit admittance (T0), and 24 h later (T24). Survival at day 28 and hemodynamic and respiratory parameters were analyzed and compared according to outcome and respiratory status. Central hemodynamic parameters or static transcutaneous data did not differ between survivors and nonsurvivors at enrollment. The OCT was statistically different at T24 according to outcome (P < 0.001), but sensitivity was low (53%). Moreover, patients with low OCT results at T24 exhibited more severe respiratory failure (P < 0.01). The OCT at T24 is related to outcome but is influenced by the severity of respiratory failure. Our results suggest considering with caution hemodynamic management based on OCT in septic shock patients with altered pulmonary function.

  6. The PRECISE RCT: evolution of an early septic shock fluid resuscitation trial.

    PubMed

    McIntyre, Lauralyn; Fergusson, Dean A; Rowe, Brian; Cook, Deborah J; Arabi, Yaseen; Bagshaw, Sean M; Emond, Marcel; Finfer, Simon; Fox-Robichaud, Alison; Gray, Alasdair; Green, Robert; Hebert, Paul; Lang, Eddy; Marshall, John; Stiell, Ian; Tinmouth, Alan; Pagliarello, Joe; Turgeon, Alexis; Walsh, Timothy; Worster, Andrew; Zarychanski, Ryan

    2012-10-01

    Severe sepsis and septic shock are the most common reasons for admission to an intensive care unit; and the risk of death is substantial, estimated at approximately 40%. Evidence suggests that early resuscitation strategies that include the use of resuscitation fluids, antibiotics, blood, and inotropes reduce death. Although fluid resuscitation is an immediate life-saving intervention, a fundamental question that remains unanswered is whether the type of resuscitation fluid impacts survival when it is initiated very early in the course of septic shock. A randomized controlled trial published in 2008 confirmed that hydroxyethyl starch fluids cause acute renal failure defined by the requirement for renal replacement therapy. In contrast, a subgroup analysis from a randomized controlled trial suggests that 4% albumin fluid may reduce death from severe sepsis; however, these findings require confirmation in a large randomized trial. Our team is planning a pragmatic early septic shock fluid resuscitation trial that will compare the effectiveness of 5% albumin vs normal saline on 90-day mortality (PRECISE). In this article, we summarize the scientific rationale and inherent challenges associated with the conduct of PRECISE, the background work and planning elements that have been undertaken, and the PRECISE RCT protocol with rationale and justifications provided for the chosen population, the interventions, and the outcome measures. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Thiamine in septic shock patients with alcohol use disorders: An observational pilot study.

    PubMed

    Holmberg, Mathias Johan; Moskowitz, Ari; Patel, Parth Vijay; Grossestreuer, Anne Victoria; Uber, Amy; Stankovic, Nikola; Andersen, Lars Wiuff; Donnino, Michael William

    2017-08-16

    Alcohol-use disorders (AUDs) have been associated with increased sepsis-related mortality. As patients with AUDs are often thiamine deficient, we investigated practice patterns relating to thiamine administration in patients with AUDs presenting with septic shock and explored the association between receipt of thiamine and mortality. We performed a retrospective cohort study of patients presenting with septic shock between 2008 and 2014 at a single tertiary care center. We identified patients with an AUD diagnosis, orders for microbial cultures and use of antibiotics, vasopressor dependency, and lactate levels≥4mmol/L. We excluded those who received thiamine later than 48h of sepsis onset. We included 53 patients. Thirty-four (64%) patients received thiamine. Five patients (15%) received their first thiamine dose in the emergency department. The median time to thiamine administration was 9 (quartiles: 4, 18) hours. The first thiamine dose was most often given parenterally (68%) and for 100mg (88%). In those receiving thiamine, 15/34 (44%) died, compared to 15/19 (79%) of those not receiving thiamine, p=0.02. A considerable proportion of patients with AUDs admitted for septic shock do not receive thiamine. Thiamine administration in this patient population was associated with decreased mortality. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Shoulder Pain after Fall, Septic Shock, and Pyomyositis Associated with Breast Cancer Chemotherapy and Lymphedema

    PubMed Central

    Kitayama, Hiromitsu; Sugiyama, Junko; Hirayama, Michiaki; Onada, Yosihiro; Tsuji, Yasushi

    2016-01-01

    Background As a symptom of pyomyositis, sepsis usually follows local inflammation signs. Here, we report pyomyositis with lymphedema of upper extremity in which septic shock and poor local findings initially presented during chemotherapy for breast cancer. Case Report An 80-year-old woman presented with chronic right shoulder pain during chemotherapy for the recurrent disease. She had a history of postmastectomy lymphedema, diabetes mellitus, and repeated hyaluronic acid injections to the shoulder joint. The pain suddenly worsened with septic shock and no apparent local signs. Magnetic resonance imaging revealed myonecrosis, and no pus was yielded by ultrasound-guided needle aspiration. After 2 weeks of recovery by conservative medical management, surgical drainage was performed. Late formulated massive intramuscular pus showed severe neutrophil infiltration and myonecrosis. Conclusion Pyomyositis can develop into septic shock with poor local signs. Myelosuppression after chemotherapy can cause myonecrosis without macroabscess, and magnetic resonance imaging was useful for the diagnosis of this condition. When unspecified local pain appears during cancer chemotherapy we should consider this disease, too. PMID:27920709

  9. A multicenter study of septic shock due to candidemia: outcomes and predictors of mortality.

    PubMed

    Bassetti, Matteo; Righi, Elda; Ansaldi, Filippo; Merelli, Maria; Trucchi, Cecilia; Cecilia, Trucchi; De Pascale, Gennaro; Diaz-Martin, Ana; Luzzati, Roberto; Rosin, Chiara; Lagunes, Leonel; Trecarichi, Enrico Maria; Sanguinetti, Maurizio; Posteraro, Brunella; Garnacho-Montero, Jose; Sartor, Assunta; Rello, Jordi; Rocca, Giorgio Della; Antonelli, Massimo; Tumbarello, Mario

    2014-06-01

    Candida is the most common cause of severe yeast infections worldwide, especially in critically ill patients. In this setting, septic shock attributable to Candida is characterized by high mortality rates. The aim of this multicenter study was to investigate the determinants of outcome in critically ill patients with septic shock due to candidemia. This was a retrospective study in which patients with septic shock attributable to Candida who were treated during the 3-year study period at one or more of the five participating teaching hospitals in Italy and Spain were eligible for enrolment. Patient characteristics, infection-related variables, and therapy-related features were reviewed. Multiple logistic regression analysis was performed to identify the risk factors significantly associated with 30-day mortality. A total of 216 patients (mean age 63.4 ± 18.5 years; 58.3 % males) were included in the study. Of these, 163 (75 %) were admitted to the intensive care unit. Overall 30-day mortality was 54 %. Significantly higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores, dysfunctional organs, and inadequate antifungal therapy were compared in nonsurvivors and survivors. No differences in survivors versus nonsurvivors were found in terms of the time from positive blood culture to initiation of adequate antifungal therapy. Multivariate logistic regression identified inadequate source control, inadequate antifungal therapy, and 1-point increments in the APACHE II score as independent variables associated with a higher 30-day mortality rate.

  10. Impact of endotracheal intubation on septic shock outcome: A post hoc analysis of the SEPSISPAM trial.

    PubMed

    Delbove, Agathe; Darreau, Cédric; Hamel, Jean François; Asfar, Pierre; Lerolle, Nicolas

    2015-12-01

    The objective of the study to is to determine the characteristics associated with endotracheal intubation in septic shock patients. This is a post hoc analysis of the database of the SEPSISPAM study, including patients with septic shock. Among the 776 patients, 633 (82%) were intubated within 12 hours of study inclusion (early intubation), 113 (15%) were never intubated, and 30 (4%) had delayed intubation. Intensive care units (ICUs) were classified according to frequency of early intubation: early intubation less than 80% of patients (lowest frequency: 7 ICUs, 254 patients), 80% to 90% (middle frequency: 5 ICUs, 170 patients), and greater than 90% (highest frequency: 6 ICUs, 297 patients). Type of ICU, pulmonary infection, lactate greater than 2 mmol/L, lower Pao2/fraction of inspired oxygen ratio, lower Glasgow score, and absence of immunosuppression were independently associated with early intubation. Patients never intubated had a lower initial severity and a low mortality rate. In comparison to patients intubated early, patients with delayed intubation had had fewer days alive without organ support by day 28. Intensive care units with the highest frequency of early intubation had a higher mortality rate in comparison to ICUs with middle frequency of early intubation. A nonsignificant increased mortality was observed in ICU with lowest frequency of early intubation. Practices regarding the place of endotracheal intubation in septic shock may impact outcome. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Pattern of Brain Injury in the Acute Setting of Human Septic Shock

    PubMed Central

    2013-01-01

    Background Sepsis-associated brain dysfunction has been linked to white matter lesions (leukoencephalopathy) and ischemic stroke. Our objective was to assess the prevalence of brain lesions in septic shock patients requiring magnetic resonance imaging (MRI) for an acute neurologic change. Method Seventy-one septic shock patients were included in a prospective observational study. Patients underwent daily neurological examination. Brain MRI was obtained in patients who developed focal neurological deficit, seizure, coma, or delirium. Electroencephalogy was performed in case of coma, delirium, or seizure. Leukoencephalopathy was graded and considered present when white matter lesions were either confluent or diffuse. Patient outcome was evaluated at 6 months with the Glasgow Outcome Scale (GOS). Results We included 71 patients with median age of 65 years (56 to 76) and SAPS II at admission of 49 (38 to 60). MRI was indicated on focal neurological sign in 13 (18%), seizure in 7 (10%), coma in 33 (46%), and delirium in 35 (49%). MRI was normal in 37 patients (52%) and showed cerebral infarcts in 21 (29%), leukoencephalopathy in 15 (21%), and mixed lesions in 6 (8%). EEG malignant pattern was more frequent in patients with ischemic stroke or leukoencephalopathy. Ischemic stroke was independently associated with disseminated intravascular coagulation (DIC), focal neurologic signs, increased mortality, and worse GOS at 6 months. Conclusions Brain MRI in septic shock patients who developed acute brain dysfunction can reveal leukoencephalopathy and ischemic stroke, which is associated with DIC and increased mortality. PMID:24047502

  12. Use of insulin to decrease septic shock-induced myocardial depression in a porcine model.

    PubMed

    Levenbrown, Yosef; Penfil, Scott; Rodriguez, Elena; Zhu, Yan; Hossain, Jobayer; Bhat, A Majeed; Hesek, Anne; O'Neil, Karen B; Tobin, Kelly; Shaffer, Thomas H

    2013-12-01

    Insulin is known to attenuate septic shock-induced myocardial depression. Possible mechanisms include an anti-inflammatory or inotropic effect of insulin. The objective of this study was to determine whether the mechanism of action of insulin in attenuating septic shock-induced myocardial depression is through an immunomodulatory effect. Fourteen pigs were assigned to one of two groups. Both groups received a 4-h infusion of lipopolysaccharide endotoxin from Escherichia coli 0111:B4. Group 2 additionally received insulin at 1.5 U/kg/h with infusions of D50 normal saline and KCl to maintain normal serum glucose and potassium levels. Cardiac function was measured with shortening fraction using transthoracic echocardiogram. Plasma TNF-α, IL-1β, and IL-6 levels were obtained every 30 min. Postmortem cytokine analysis and histomorphology were performed on the heart tissue. Although insulin attenuated septic shock-induced myocardial depression, this was not due to an anti-inflammatory effect and, therefore, likely resulted from an inotropic effect of insulin.

  13. Using quality improvement principles to improve the care of patients with severe sepsis and septic shock.

    PubMed

    Seoane, Leonardo; Winterbottom, Fiona; Nash, Teresa; Behrhorst, Jessica; Chacko, Elen; Shum, Lucas; Pavlov, Andrey; Briski, David; Thibeau, Shelley; Bergeron, Dominique; Rafael, Tiffany; Sundell, Erik

    2013-01-01

    Sepsis, an inflammatory response to an infection that may lead to severe organ dysfunction and death, is the leading cause of death in medical intensive care units. The Society of Critical Care Medicine has issued guidelines and promoted protocols to improve the management of patients with severe sepsis and septic shock. Generally, the medical community has been slow to adopt these guidelines because of the system challenges associated with protocol implementation. We describe an interdisciplinary team approach to the development and implementation of management protocols for treating patients with severe sepsis and septic shock. To determine the effectiveness of the bundled emergency department and critical care order sets developed by the Sepsis Steering Committee, we performed a case review of 1,105 sequential patients admitted to a large academic tertiary referral hospital with a diagnosis of severe sepsis or septic shock between July 2008 and January 2012. Implementation of the protocol led to improved order set use over time, a significant decrease in the median time to antibiotics of 140 (range 1-820) minutes in 2008 to 72 (range 1-1,020) minutes in 2011 (P≤0.001), and a decrease in median length of stay from 8 days (range 1-54) in 2008 to 7 days (range 1-33) in 2011 (P=0.036). A multidisciplinary team approach to sepsis management using protocols and early goal-directed therapy is feasible in a large academic medical center to improve the process of care and outcomes.

  14. [Predictive value of early lactate area for mortality in elderly patients with septic shock].

    PubMed

    Zhang, J X; Yin, M; Chen, X M; Li, C; Wu, D W; Ding, S F; Du, B F; Guo, H P; Qin, W D; Yang, H N; Wang, H

    2016-09-06

    Objective: To investigate the predictive value of early lactate area for mortality in elderly patients with septic shock. Methods: From January 2012 to December 2013, a prospective study was conducted in the Department of Critical Care Medicine, Qilu Hospital of Shandong University. A total of 115 septic shock patients with age ≥65 years were included in the study. Serum lactate was measured every 6 hours, the lactate indicators, including early lactate area, APACHE Ⅱ score etc were recorded. Results: The overall 28-day mortality rate was 67.0%. The top three primary infection sources were lung, abdominal cavity and bloodstream. When compared to survivors, non-survivors had significantly elevated early lactate area and APACHE Ⅱ score and lowered lactate clearance[(27.4±7.6) vs ( 20.3±6.5)], they were significantly more likely to have undergone mechanical ventilation, renal replacement therapy and inotropic or vasopressor support for ≥3 d, and more frequently displayed signs of cardiovascular, respiratory, and renal and hepatic dysfunction (all P<0.05) .Receiver Operating Characteristic curves indicated the lactate area score displayed a strong predictive power for 28 day mortality as indicated by an AUC of 0.758 (P<0.01) and had significantly greater predictive power when compared to the initial lactate or lactate clearance (all P<0.05). Conclusions: In geriatric patients with septic shock, the early lactate area is a useful predictor for early death and showed better predictive value than other lactate indicators.

  15. What happens to the fluid balance during and after recovering from septic shock?

    PubMed Central

    Cunha, Andrea Regina Lopes; Lobo, Suzana Margareth Ajeje

    2015-01-01

    Objective We aimed to evaluate the cumulative fluid balance during the period of shock and determine what happens to fluid balance in the 7 days following recovery from shock. Methods A prospective and observational study in septic shock patients. Patients with a mean arterial pressure ≥ 65mmHg and lactate < 2.0mEq/L were included < 12 hours after weaning from vasopressor, and this day was considered day 1. The daily fluid balance was registered during and for seven days after recovery from shock. Patients were divided into two groups according to the full cohort’s median cumulative fluid balance during the period of shock: Group 1 ≤ 4.4L (n = 20) and Group 2 > 4.4L (n = 20). Results We enrolled 40 patients in the study. On study day 1, the cumulative fluid balance was 1.1 [0.6 - 3.4] L in Group 1 and 9.0 [6.7 - 13.8] L in Group 2. On study day 7, the cumulative fluid balance was 8.0 [4.5 - 12.4] L in Group 1 and 14.7 [12.7 - 20.6] L in Group 2 (p < 0.001 for both). Afterwards, recovery of shock fluid balance continued to increase in both groups. Group 2 had a more prolonged length of stay in the intensive care unit and hospital compared to Group 1. Conclusion In conclusion, positive fluid balances are frequently seen in patients with septic shock and may be related to worse outcomes. During the shock period, even though the fluid balance was previously positive, it becomes more positive. After recovery from shock, the fluid balance continues to increase. The group with a more positive fluid balance group spent more time in the intensive care unit and hospital. PMID:25909308

  16. What happens to the fluid balance during and after recovering from septic shock?

    PubMed

    Cunha, Andrea Regina Lopes; Lobo, Suzana Margareth Ajeje

    2015-01-01

    We aimed to evaluate the cumulative fluid balance during the period of shock and determine what happens to fluid balance in the 7 days following recovery from shock. A prospective and observational study in septic shock patients. Patients with a mean arterial pressure ≥ 65 mmHg and lactate < 2.0 mEq/L were included < 12 hours after weaning from vasopressor, and this day was considered day 1. The daily fluid balance was registered during and for seven days after recovery from shock. Patients were divided into two groups according to the full cohort's median cumulative fluid balance during the period of shock: Group 1 ≤ 4.4 L (n = 20) and Group 2 > 4.4 L (n = 20). We enrolled 40 patients in the study. On study day 1, the cumulative fluid balance was 1.1 [0.6 - 3.4] L in Group 1 and 9.0 [6.7 - 13.8] L in Group 2. On study day 7, the cumulative fluid balance was 8.0 [4.5 - 12.4] L in Group 1 and 14.7 [12.7 - 20.6] L in Group 2 (p < 0.001 for both). Afterwards, recovery of shock fluid balance continued to increase in both groups. Group 2 had a more prolonged length of stay in the intensive care unit and hospital compared to Group 1. In conclusion, positive fluid balances are frequently seen in patients with septic shock and may be related to worse outcomes. During the shock period, even though the fluid balance was previously positive, it becomes more positive. After recovery from shock, the fluid balance continues to increase. The group with a more positive fluid balance group spent more time in the intensive care unit and hospital.

  17. Imbalances in serum angiopoietin concentrations are early predictors of septic shock development in patients with post chemotherapy febrile neutropenia

    PubMed Central

    2010-01-01

    Background Febrile neutropenia carries a high risk of sepsis complications, and the identification of biomarkers capable to identify high risk patients is a great challenge. Angiopoietins (Ang -) are cytokines involved in the control microvascular permeability. It is accepted that Ang-1 expression maintains endothelial barrier integrity, and that Ang-2 acts as an antagonizing cytokine with barrier-disrupting functions in inflammatory situations. Ang-2 levels have been recently correlated with sepsis mortality in intensive care units. Methods We prospectively evaluated concentrations of Ang-1 and Ang-2 at different time-points during febrile neutropenia, and explored the diagnostic accuracy of these mediators as potential predictors of poor outcome in this clinical setting before the development of sepsis complications. Results Patients that evolved with septic shock (n = 10) presented higher levels of Ang-2 measured 48 hours after fever onset, and of the Ang-2/Ang-1 ratio at the time of fever onset compared to patients with non-complicated sepsis (n = 31). These levels correlated with sepsis severity scores. Conclusions Our data suggest that imbalances in the concentrations of Ang-1 and Ang-2 are independent and early markers of the risk of developing septic shock and of sepsis mortality in febrile neutropenia, and larger studies are warranted to validate their clinical usefulness. Therapeutic strategies that manipulate this Ang-2/Ang-1 imbalance can potentially offer new and promising treatments for sepsis in febrile neutropenia. PMID:20509945

  18. Impact of prothrombin time-International Normalized Ratio on outcome of patients with septic shock receiving polymyxin B cartridge hemoperfusion.

    PubMed

    Ishizuka, Mitsuru; Tago, Kazuma; Kubota, Keiichi

    2014-07-01

    Although most patients with septic shock have a poor outcome, some may survive after blood purification treatment such as polymyxin B cartridge hemoperfusion (PMX). To explore the most significant characteristic associated with 28-day mortality in patients with septic shock receiving PMX. Between April 2006 and March 2008, 116 patients with septic shock who had received PMX in a prospectively collected multicenter collaborative study were enrolled. Uni- and multivariate analyses using the Cox proportional hazard model were performed to assess the most significant clinical characteristic that was associated with 28-day mortality. Among 33 clinicolaboratory characteristics, receiver operating characteristic (ROC) curve analyses selected 12 characteristics with recommended cutoff values such as HCO(3)(-) (≤19.8/>19.8; mEq/L), base excess (≤-5.35/>-5.35; mEq/L), diastolic blood pressure (≤48/>48 mmHg), mean arterial pressure (≤73/>73 mmHg), pH (≤7.29/>7.29), interleukin-6 (≤19,150/>19,150 pg/dL), prothrombin time-International Normalized Ratio (PT-INR; ≤2.05/>2.05), predictive value of Acute Physiology and Chronic Health Evaluation II (APACHE II; ≤0.4/>0.4), pyruvate (≤1.82/>1.82 mg/dL), APACHE II score (≤21/>21), acetate/pyruvate ratio (≤19/>19), and acetate (≤44.8/>44.8 mg/dL) on the basis of large area under the ROC curves for 28-day mortality. The results of uni- and multivariate analyses using these selected characteristics revealed that only PT-INR (≤2.05/>2.05; hazard ratio, 2.823; 95% CI, 1.243-6.412; P = .013) was associated with 28-day mortality. Survival curve analysis demonstrated a significant difference in 28-day mortality between patients with lower (≤2.05) and higher (>2.05) PT-INR (P < .001). Prolonged PT-INR is an independent risk factor for 28-day mortality in patients receiving PMX for septic shock. Copyright © 2014 Mosby, Inc. All rights reserved.

  19. Levosimendan increases portal blood flow and attenuates intestinal intramucosal acidosis in experimental septic shock.

    PubMed

    García-Septien, Javier; Lorente, José A; Delgado, Miguel A; de Paula, Marta; Nin, Nicolás; Moscoso, Amelia; Sánchez-Ferrer, Alberto; Perez-Vizcaino, Francisco; Esteban, Andrés

    2010-09-01

    It has been proposed that vasodilatory therapy may increase microcirculatory blood flow and improve tissue oxygenation in septic shock. The authors aimed to evaluate the effects of levosimendan in systemic and splanchnic hemodynamics in a porcine model of septic shock in a randomized animal controlled study. This study was performed in an animal research facility in a university hospital. Anesthetized pigs were monitored with a pulmonary artery catheter and an ultrasonic blood flow probe in the portal vein for measurement of systemic and portal blood flows and with a tonometer placed in the small intestine for measurement of the intramucosal-arterial PCO2 gap. Three groups of pigs were studied: nonseptic (n = 7), septic (n = 7), and septic treated with levosimendan (n = 7). Levosimendan was administered i.v. at t = -10 min (200 microg/kg in i.v. bolus followed by 200 microg/kg per h). Sepsis was induced at t = 0 min by the administration of live Escherichia coli. Vascular reactivity was tested by the hemodynamic response to noradrenaline. Levosimendan markedly attenuated the sepsis-induced increase in pulmonary vascular resistance, decrease in portal/systemic blood flow, oliguria, impairment in oxygenation, hyperkalemia, and the widened intramucosal-arterial PCO2 gap. Systemic blood pressure and vascular resistance did not differ as compared with the septic untreated group. Responses to noradrenaline significantly improved in animals treated with levosimendan. Treatment with levosimendan in this animal model of sepsis attenuated pulmonary vasoconstriction and improved portal blood flow, intestinal mucosal oxygenation, pulmonary function, and vascular reactivity.

  20. The impairment of small nerve fibers in severe sepsis and septic shock.

    PubMed

    Axer, Hubertus; Grimm, Alexander; Pausch, Christine; Teschner, Ulrike; Zinke, Jan; Eisenach, Sven; Beck, Sindy; Guntinas-Lichius, Orlando; Brunkhorst, Frank M; Witte, Otto W

    2016-03-15

    A decrease of small nerve fibers in skin biopsies during the course of critical illness has been demonstrated recently. However, the diagnostic use of skin biopsies in sepsis and its time course is not known. Patients (n=32) with severe sepsis or septic shock were examined using skin biopsies, neurological examination, nerve conduction studies, and sympathetic skin response in the first week after onset of sepsis, 2 weeks and 4 months later and compared to gender- and age-matched healthy controls. Skin biopsies at the ankle and thigh revealed a significant decrease of intraepidermal nerve fiber density (IENFD) during the first week of sepsis and 2 weeks later. All patients developed critical illness polyneuropathy (CIP) according to electrophysiological criteria and 11 showed IENFD values lower than the 0.05 quantile. Four patients were biopsied after 4 months and still showed decreased IENFD. Results of nerve conduction studies and IENFD did considerably change over time. No differences for survival time between patients with IEFND lower and larger than 3.5 fibers/mm were found. Skin biopsy is able to detect an impairment of small sensory nerve fibers early in the course of sepsis. However, it may not be suited as a prognostic parameter for survival. German Clinical Trials Register, DRKS-ID: DRKS00000642, 12/17/2010.

  1. Slowed peak resting frequency and MEG overactivation in survivors of severe sepsis and septic shock.

    PubMed

    Götz, Theresa; Baumbach, Philipp; Huonker, Ralph; Kranczioch, Cornelia; Witte, Otto W; Debener, Stefan; Klingner, Carsten; Brunkhorst, Frank M; Günther, Albrecht

    2016-02-01

    Survivors of severe sepsis and septic shock suffer from residual severe cognitive impairments, which persist even years after intensive care unit (ICU) discharge. As the awareness of long-term consequences gradually grows, research has focused on cognitive impairments via questionnaires, but only few have focused on structural or electrophysiological features, such as the peak resting frequency, which is commonly seen as a hallmark of brain function. We aimed to analyze the long-term progression of the peak resting activity in terms of frequency and power in sepsis survivors. Healthy individuals with no history of ICU stay served as controls. Data were collected three times (shortly, 6 and 12 months after ICU discharge) in sepsis survivors and three times in controls. Participants also underwent behavioral neuropsychological assessment. Sepsis survivors exhibited significantly higher spectral power of the dominant peak, which was shifted towards lower frequencies. Within one year, resting frequency increased to the level of controls, but power did not decrease. We observed a close correlation between resting frequency and mental status. Results support the assumption of a causal relationship between brain oscillations and behavioral performance. We suggest that the postseptic frequency shift is due to abnormal thalamocortical dynamics. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  2. [Role of the kallikrein-kininogen-kinin system in the inflammatory reaction and septic shock].

    PubMed

    Hulot, M; Ers, P; Damas, J; Adam, A

    1984-01-01

    Kinins, which are vasodilatory, permeability-increasing, pain-producing polypeptides, are formed from inactive precursors: kininogens. Their actions make kinins a particularly powerful potential pro-inflammatory factor. However the absence of specific antagonists has so far made it impossible to ascribe them a definite role in inflammation. Two studies of experimental endotoxemia in burns patients, septicemia and septic shock have demonstrated the following facts: activation occurs of specific ( pKK ) and non-specific (plasminogen-plasmin system) kininogenases , K-HMW and K-LMW levels are significantly decreased. Kininogen consumption corresponds to increased BDK production. This would therefore appear to be one of the humoral factors responsible for haemodynamic changes. Though measurement of kininogen levels is still a painstaking process, the development of chromogenic substrates has made pKK and KK measurement simple and fast. Once they have been validated physico-pathologically in a large number of patients, such assays should take their place among the diagnostic weapons of clinical biology at the disposal of clinicians.

  3. Plasma levels of F-actin and F:G-actin ratio as potential new biomarkers in patients with septic shock.

    PubMed

    Belsky, Justin B; Morris, Daniel C; Bouchebl, Ralph; Filbin, Michael R; Bobbitt, Kevin R; Jaehne, Anja K; Rivers, Emanuel P

    2016-01-01

    To compare plasma levels of F-actin, G-actin and thymosin beta 4 (TB4) in humans with septic shock, noninfectious systemic inflammatory response syndrome (SIRS) and healthy controls. F-actin was significantly elevated in septic shock as compared with noninfectious SIRS and healthy controls. G-actin levels were greatest in the noninfectious SIRS group but significantly elevated in septic shock as compared with healthy controls. TB4 was not detectable in the septic shock or noninfectious SIRS group above the assay's lowest detection range (78 ng/ml). F-actin is significantly elevated in patients with septic shock as compared with noninfectious SIRS. F-actin and the F:G-actin ratio are potential biomarkers for the diagnosis of septic shock.

  4. Elevated Serum PCT in Septic Shock With Endotoxemia Is Associated With a Higher Mortality Rate.

    PubMed

    Adamik, Barbara; Smiechowicz, Jakub; Jakubczyk, Dominika; Kübler, Andrzej

    2015-07-01

    To examine the effect of endotoxemia on the procalcitonin (PCT) serum levels and mortality rates of adult patients with septic shock diagnosed on the day of admission to the intensive care unit (ICU).A retrospective observational study was performed over a 2-year period. Levels of PCT were compared for septic shock patients with and without endotoxemia on admission to the ICU. Endotoxemia was identified with an Endotoxin Activity Assay.One hundred fifty-seven patients with septic shock were enrolled into the study. Group 1 consisted of patients with elevated endotoxin activity (EA) (n = 95, EA = 0.57 endotoxin activity unit [EAU] [0.46-0.67]) and Group 2 consisted of patients with low EA (n = 62, EA = 0.27 EAU [0.17-0.36]). Acute Physiology And Chronic Health Evaluation II (APACHE II) score and SOFA score were similar in both groups (APACHE II = 23 [16-29] and 19 [16-25]; Sequential Organ Failure Assessment [SOFA] = 10 [7-13] and 11 [8-12] in Groups 1 and 2, respectively) (nonsignificant). The PCT level was 6 times higher in Group 1 than in Group 2 (19.6 ng/mL vs. 3.1 ng/mL, P < 0.001). There was a strong correlation between EA and serum PCT (P < 0.001, R = 0.5). The presence of endotoxemia on admission to the ICU was associated with an increased mortality rate: 52% in the group of patients with endotoxemia and 25% in the group without endotoxemia. EA in survivors was 0.39 EAU (0.26-0.57) and 0.53 EAU (0.4-0.61) in nonsurvivors (P = 0.004). The median PCT level in survivors was 6.7 ng/mL (2.3-28.0), compared with 16.7 ng/mL (5.3-31.0) in nonsurvivors (P = 0.04).This observational study revealed that endotoxemia in patients with septic shock on admission to the ICU was frequently found and was associated with an elevated PCT level and a high mortality rate. Endotoxemia was a common occurrence in patients with septic shock, regardless of the infecting microorganism.

  5. Prognostic value of brachioradialis muscle oxygen saturation index and vascular occlusion test in septic shock patients.

    PubMed

    Marín-Corral, J; Claverias, L; Bodí, M; Pascual, S; Dubin, A; Gea, J; Rodriguez, A

    2016-05-01

    To compare rSO2 (muscle oxygen saturation index) static and dynamic variables obtained by NIRS (Near Infrared Spectroscopy) in brachioradialis muscle of septic shock patients and its prognostic implications. Prospective and observational study. Intensive care unit. Septic shock patients and healthy volunteers. The probe of a NIRS device (INVOS 5100) was placed on the brachioradialis muscle during a vascular occlusion test (VOT). Baseline, minimum and maximum rSO2 values, deoxygenation rate (DeOx), reoxygenation slope (ReOx) and delta value. Septic shock patients (n=35) had lower baseline rSO2 (63.8±12.2 vs. 69.3±3.3%, p<0.05), slower DeOx (-0.54±0.31 vs. -0.91±0.35%/s, p=0.001), slower ReOx (2.67±2.17 vs. 9.46±3.5%/s, p<0.001) and lower delta (3.25±5.71 vs. 15.1±3.9%, p<0.001) when compared to healthy subjects (n=20). Among septic shock patients, non-survivors showed lower baseline rSO2 (57.0±9.6 vs. 69.8±11.3%, p=0.001), lower minimum rSO2 (36.0±12.8 vs. 51.3±14.8%, p<0.01) and lower maximum rSO2 values (60.6±10.6 vs. 73.3±11.2%, p<0.01). Baseline rSO2 was a good mortality predictor (AUC 0.79; 95%CI: 0.63-0.94, p<0.01). Dynamic parameters obtained with VOT did not improve the results. Septic shock patients present an important alteration of microcirculation that can be evaluated by NIRS with prognostic implications. Monitoring microvascular reactivity in the brachioradialis muscle using VOT with our device does not seem to improve the prognostic value of baseline rSO2. Copyright © 2015 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

  6. Timing of vasopressor initiation and mortality in septic shock: a cohort study

    PubMed Central

    2014-01-01

    Introduction Despite recent advances in the management of septic shock, mortality remains unacceptably high. Earlier initiation of key therapies including appropriate antimicrobials and fluid resuscitation appears to reduce the mortality in this condition. This study examined whether early initiation of vasopressor therapy is associated with improved survival in fluid therapy-refractory septic shock. Methods Utilizing a well-established database, relevant information including duration of time to vasopressor administration following the initial documentation of recurrent/persistent hypotension associated with septic shock was assessed in 8,670 adult patients from 28 ICUs in Canada, the United States of America, and Saudi Arabia. The primary endpoint was survival to hospital discharge. Secondary endpoints were length of ICU and hospital stay as well as duration of ventilator support and vasopressor dependence. Analysis involved multivariate linear and logistic regression analysis. Results In total, 8,640 patients met the definition of septic shock with time of vasopressor/inotropic initiation documented. Of these, 6,514 were suitable for analysis. The overall unadjusted hospital mortality rate was 53%. Independent mortality correlates included liver failure (odds ratio (OR) 3.46, 95% confidence interval (CI), 2.67 to 4.48), metastatic cancer (OR 1.63, CI, 1.32 to 2.01), AIDS (OR 1.91, CI, 1.29 to 2.49), hematologic malignancy (OR 1.88, CI, 1.46 to 2.41), neutropenia (OR 1.78, CI, 1.27 to 2.49) and chronic hypertension (OR 0.62 CI, 0.52 to 0.73). Delay of initiation of appropriate antimicrobial therapy (OR 1.07/hr, CI, 1.06 to 1.08), age (OR 1.03/yr, CI, 1.02 to 1.03), and Acute Physiology and Chronic Health Evaluation (APACHE) II Score (OR 1.11/point, CI, 1.10 to 1.12) were also found to be significant independent correlates of mortality. After adjustment, only a weak correlation between vasopressor delay and hospital mortality was found (adjusted OR 1.02/hr, 95% CI

  7. The Role of ACTH and Corticosteroids for Sepsis and Septic Shock: An Update

    PubMed Central

    Annane, Djillali

    2016-01-01

    Sepsis is a common disorder associated with high morbidity and mortality. It is now defined as an abnormal host response to infection, resulting in life-threatening dysfunction of organs. There is evidence from in vitro and in vivo experiments in various animal models and in patients that endotoxin or sepsis may directly and indirectly alter the hypothalamic–pituitary–adrenal response to severe infection. These alterations may include necrosis or hemorrhage or inflammatory mediator-mediated decreased ACTH synthesis, steroidogenesis, cortisol delivery to tissues, clearance from plasma, and decreased sensitivity of tissues to cortisol. Disruption of the hypothalamic–pituitary–adrenal axis may translate in patients with sepsis into cardiovascular and other organ dysfunction, and eventually an increase in the risk of death. Exogenous administration of corticosteroids at moderate dose, i.e., <400 mg of hydrocortisone or equivalent for >96 h, may help reversing sepsis-associated shock and organ dysfunction. Corticosteroids may also shorten the duration of stay in the ICU. Except for increased blood glucose and sodium levels, treatment with corticosteroids was rather well tolerated in the context of clinical trials. The benefit of treatment on survival remains controversial. Based on available randomized controlled trials, the likelihood of survival benefit is greater in septic shock versus sepsis patients, in sepsis with acute respiratory distress syndrome or with community-acquired pneumonia versus patients without these conditions, and in patients with a blunted cortisol response to 250 μg of ACTH test versus those with normal response. PMID:27379022

  8. Rescue therapy with polymyxin B hemoperfusion in high-dose vasopressor therapy refractory septic shock.

    PubMed

    Monti, G; Terzi, V; Calini, A; Di Marco, F; Cruz, D; Pulici, M; Brioschi, P; Vesconi, S; Fumagalli, R; Casella, G

    2015-05-01

    Refractory septic shock (RSS) requiring major vasopressor support is associated with high mortality, especially in Gram-negative infections. The study aim was to describe hemodynamics, organ failure, and clinical outcomes in high-dose vasopressor therapy (HDVT) RSS patients treated with Polymyxin B hemoperfusion (PMX-HP) as rescue therapy. We retrospectively analyzed 52 patients, unresponsive to conventional therapy, treated with two sessions of PMX-HP requiring HDVT (norepinephrine and/or epinephrine requirement (NEP+EP) ≥ 0.5 µg/kg/min), ≥ 2 organ failures, and suspected/confirmed Gram-negative infection from any source. At baseline, mean arterial pressure (MAP) was 80 ± 13 mmHg and NEP + EP requirement was 1.11 ± 0.56 µg/kg/min. After two PMX-HP sessions, at 72 h, MAP significantly increased and NEP + EP requirement decreased respectively by 12% and 76%. Pulmonary and renal function also improved significantly. Thirty patients (58%) showed a ≥ 50% reduction in NEP + EP dose within only 24 h after the first PMX-HP session (early responders), and 22 did not or died from irreversible shock in the same time frame (early non-responders). The 30-day hospital mortality was 29%; it was 16% in early responders and 45% in early non-responders. On multivariate analysis, SAPS II score, vasopressin, and central venous pressure significantly affected 30-day hospital mortality. This is the first study describing the use of PMX-HP as a rescue therapy in RSS patients with HDVT and MOF. Our results suggest a possible role for PMX-HP in improving hemodynamics, organ function, and mortality in RSS, with a 30-day survival of up to 70%.

  9. Functional modification of vascular endothelial cells by cytokines during septic shock.

    PubMed

    Endo, S; Inada, K; Yamada, Y; Takakuwa, T; Nakae, H; Kasai, T; Koike, S; Inoue, Y; Niimi, M; Wakabayashi, G; Taniguchi, S

    1996-10-01

    The function of vascular endothelial cells is to adjust blood vessel tonus, which contributes to maintaining homeostasis within blood vessels. However, inflammatory cytokines are produced in response to invasion by stimulating vascular endothelial cells and sometimes lead to shock or multiple organ failure. In the present study, we assessed cytokines in sepsis and septic shock, and various factors that are said to have a damaging effect on vascular endothelium. Endotoxin was measured by endotoxin-specific methods. Tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and interleukin 8 (IL-8) were measured by enzyme-linked immunosorbent assay (ELISA). Endothelin-I was measured by radioimmunoassay (RIA). Nitric oxide was measured as metabolites of nitrite and nitrate oxides (NOx) by a method based on the Griess method. Thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (PGF 1 alpha) were both measured by RIA. All of the factors except endotoxin were significantly higher in the septic shock group than in the non-shock group and significantly higher in the non-survivor group than in the survivor group. Significant correlations were also found between endothelin-1 and NOx and between TXB2 and PG1 alpha. Significant correlations were also found between TNF-alpha and IL-6, endothelin-1, NOx and TXB2, but no significant correlations were detected between any of them and endotoxin. In serious diseases such as septic shock, the vascular endothelial constricting factors, endothelin and TXB2, and the blood vessel relaxing factors NOx and PGF1 alpha increase almost simultaneously. This suggests that the body's regulating mechanisms are disrupted in these serious conditions. The results of this study also suggest that inflammatory cytokines may be involved in stimulating the production of these factors.

  10. Erythrocyte selenium concentration predicts intensive care unit and hospital mortality in patients with septic shock: a prospective observational study

    PubMed Central

    2014-01-01

    Introduction Selenoenzymes can modulate the extent of oxidative stress, which is recognized as a key feature of septic shock. The pathophysiologic role of erythrocyte selenium concentration in patients with septic shock remains unknown. Therefore, the objective of this study was to evaluate the association of erythrocyte selenium concentration with glutathione peroxidase (GPx1) activity, GPx1 polymorphisms and with ICU and hospital mortality in septic shock patients. Methods This prospective study included all patients older than 18 years with septic shock on admission or during their ICU stay, admitted to one of the three ICUs of our institution, from January to August 2012. At the time of the patients’ enrollment, demographic information was recorded. Blood samples were taken within the first 72 hours of the patients’ admission or within 72 hours of the septic shock diagnosis for determination of selenium status, protein carbonyl concentration, GPx1 activity and GPx1 Pro198Leu polymorphism (rs 1050450) genotyping. Results A total of 110 consecutive patients were evaluated. The mean age was 57.6 ± 15.9 years, 63.6% were male. Regarding selenium status, only erythrocyte selenium concentration was lower in patients who died in the ICU. The frequencies for GPx1 Pro198Leu polymorphism were 55%, 38% and 7% for Pro/Pro, Pro/Leu and Leu/Leu, respectively. In the logistic regression models, erythrocyte selenium concentration was associated with ICU and hospital mortality in patients with septic shock even after adjustment for protein carbonyl concentration and acute physiology and chronic health evaluation II score (APACHE II) or sequential organ failure assessment (SOFA). Conclusions Erythrocyte selenium concentration was a predictor of ICU and hospital mortality in patients with septic shock. However, this effect was not due to GPx1 activity or Pro198Leu polymorphism. PMID:24887198

  11. Presence of hypogammaglobulinemia - a risk factor of mortality in patients with severe sepsis, septic shock, and SIRS.

    PubMed

    Průcha, M; Zazula, R; Herold, I; Dostál, M; Hyánek, T; Bellingan, G

    2013-01-01

    In this retrospective study we assessed the frequency of hypogammaglobulinemia in 708 patients with SIRS, severe sepsis and septic shock. We evaluated the relationship between hypogammaglobulinemia IgG, IgM and 28 day mortality. Total of 708 patients and 1,513 samples were analyzed. In the three subgroups we investigated, patients met the criteria of SIRS, severe sepsis and septic shock. IgG hypogammaglobulinemia was demonstrated in 114 patients with severe sepsis (25.2%), 11 septic shock patients (24.4%), and in 29 SIRS patients (13.9%). IgM hypogammaglobulinemia was documented in 55 patients with severe sepsis (12.2%), 6 septic shock patients (13.3%), and in 17 SIRS patients (8.1%). Mortality of patients with severe sepsis and normal IgG levels was significantly lower (111 patients; 32.8%) compared with those with IgG hypogammaglobulinemia (49 patients; 43.0%; p=0.001). Mortality of patients with septic shock and IgG hypogammaglobulinemia (n=5) was significantly higher compared with those with normal IgG levels (45.5% vs. 38.2%; p=0.001). Mortality of patients with severe sepsis and IgM hypogammaglobulinemia did not differ from that of patients with normal IgM levels (37.0 vs. 41.8%). Mortality of patients with septic shock and IgM hypogammaglobulinemia was significantly higher compared with those with normal IgM levels (50% vs. 38.5%; p=0.0001). This study documented relatively high incidence of hypogammaglobulinemia IgG and IgM in patients with severe sepsis, septic shock and SIRS respectively. The presence of IgG hypogammaglobulinemia in patients with severe sepsis is independent factor of mortality.

  12. Comparison of Automated Methods Versus the American Burn Association Sepsis Definition to Identify Sepsis and Sepsis With Organ Dysfunction/Septic Shock in Burn-Injured Adults.

    PubMed

    Rech, Megan A; Mosier, Michael J; Zelisko, Susan; Netzer, Giora; Kovacs, Elizabeth J; Afshar, Majid

    To develop an algorithm to identify sepsis and sepsis with organ dysfunction/septic shock in burn-injured patients incorporating criteria from the American Burn Association sepsis definition that possesses good test characteristics compared with International Classification of Diseases, Ninth Revision-Clinical Modification (ICD-9) codes and an algorithm previously validated in nonburn-injured septic patients (Martin et al method). This was a retrospective cohort study of consecutive patients admitted to the burn intensive care unit between January 2008 and March 2015. Of the 4761 admitted, 8.6% (n = 407) met inclusion criteria, of which the case rate for sepsis was 34.2% (n = 139; n = 48 sepsis; n = 91 sepsis with organ dysfunction/septic shock). For sepsis identification, the novel algorithm had an accuracy of 86.0% (95% CI: 82.2-89.2%), sensitivity of 66.9% (95% CI: 59.1-74.7%), and specificity of 95.9% (95% CI: 93.5-98.3%). The novel algorithm had better discrimination (0.81, 95% CI: 0.77-0.86) than the ICD-9 method (0.77, 95% CI: 0.73-0.81), although this was not significant (P = .08). For sepsis with organ dysfunction/septic shock, the novel algorithm plus vasopressors (0.67, 95% CI: 0.63-0.72) and the ICD-9 method (0.63, 95% CI: 0.58-0.68) performed equivocal (P = 0.15) but the Martin method (0.76, 95% CI: 0.71-0.81) had superior discrimination than other methods (P < .01). The novel algorithm is an accurate and simple tool to identify sepsis in the burn cohort with good sensitivity and specificity and equivocal discriminative ability to ICD-9 coding. The Martin method had superior discriminative ability for identifying sepsis with organ dysfunction/septic shock in burn-injured patients than either the novel algorithm plus vasopressors or ICD-9 coding.

  13. Effects of sodium nitroprusside on splanchnic microcirculation in a resuscitated porcine model of septic shock.

    PubMed

    Assadi, A; Desebbe, O; Kaminski, C; Rimmelé, T; Bénatir, F; Goudable, J; Chassard, D; Allaouchiche, B

    2008-01-01

    We tested the hypothesis that sodium nitroprusside (SNP) might improve the impairment of hepatosplanchnic microcirculatory blood flow (MBF) in septic shock. Fourteen pigs were anaesthetized and their lungs mechanically ventilated. Sepsis was induced with i.v. infusion of live Pseudomonas aeruginosa [1x10(8) colony forming units (CFU) ml(-1) kg(-1)] for 1 h. Sixty minutes later, the animals received in a random succession either SNP or normal saline for 30 min. Mean arterial pressure (MAP), cardiac index (CI), mean pulmonary artery pressure (MPAP), carbon dioxide tension of the ileal mucosa (PCO2; by gas tonometry), ileal mucosal and hepatic MBF by laser Doppler flowmetry, blood gases, and lactates were assessed before, during administration, and 30 min after discontinuing the test drug. Bacterial infusion promoted hypodynamic shock (MAP -18%, CI -33%, ileal MBF -19%, and hepatic MBF -27%), which was converted to normodynamic shock by resuscitation. During SNP infusion, ileal mucosal MBF significantly increased (+19%) compared with control (P = 0.033). Although hepatic MBF increased (+42% from baseline), this did not differ from control. In order to maintain a constant central venous pressure and MAP, fluid loading and norepinephrine (P < 0.01) were increased. Acid-base status was not altered by SNP. In a resuscitated porcine model of the early phase of septic shock, SNP improved ileal mucosal MBF but required a concomitant increase in fluid and norepinephrine supplements to maintain constant systemic haemodynamic parameters.

  14. De-escalation of antimicrobial treatment for adults with sepsis, severe sepsis or septic shock.

    PubMed

    Silva, Brenda N G; Andriolo, Régis B; Atallah, Alvaro N; Salomão, Reinaldo

    2013-03-28

    Mortality rates among patients with sepsis, severe sepsis or septic shock are highly variable throughout different regions or services and can be upwards of 50%. Empirical broad-spectrum antimicrobial treatment is aimed at achieving adequate antimicrobial therapy, thus reducing mortality; however, there is a risk that empirical broad-spectrum antimicrobial treatment can expose patients to overuse of antimicrobials. De-escalation has been proposed as a strategy to replace empirical broad-spectrum antimicrobial treatment by using a narrower antimicrobial therapy. This is done by reviewing the patient's microbial culture results and then making changes to the pharmacological agent or discontinuing a pharmacological combination. To evaluate the effectiveness and safety of de-escalation antimicrobial treatment for adult patients diagnosed with sepsis, severe sepsis or septic shock caused by any micro-organism. In this updated version, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 10); MEDLINE via PubMed (from inception to October 2012); EMBASE (from inception to October 2012); LILACS (from inception to October 2012); Current Controlled Trials; bibliographic references of relevant studies; and specialists in the area. We applied no language restriction. We had previously searched the databases to August 2010. We planned to include randomized controlled trials (RCTs) comparing de-escalation (based on culture results) versus standard therapy for adults with sepsis, severe sepsis or septic shock. The primary outcome was mortality (at 28 days, hospital discharge or at the end of the follow-up period). Studies including patients initially treated with an empirical but not adequate antimicrobial therapy were not considered for inclusion. Two authors planned to independently select and extract data and to evaluate methodological quality of all studies. We planned to use relative risk (risk ratio) for dichotomous data

  15. Synergistic effects of glutamine and ciprofloxacin in reduction of Pseudomonas aeruginosa-induced septic shock severity.

    PubMed

    Mazloomi, Ebrahim; Jazani, Nima Hosseini; Sohrabpour, Mohammad; Ilkhanizadeh, Behrouz; Shahabi, Shahram

    2011-12-01

    Systemic inflammatory response induced by over expressing inflammatory mediators is the main pathogenic mechanism of septic shock. Glutamine (Gln) has been demonstrated to inhibit pro-inflammatory cytokine release through enhanced heat shock protein (HSP) expression. To assess the effect of co-administration of Gln and antibiotic ciprofloxacin in reduction of septic shock severity caused by Pseudomonas aeruginosa in mice. Six- to eight-week old male BALB/c mice were used. At first, P. aeruginosa susceptibility to ciprofloxacin was determined. Then, 75% lethal dose (LD 75) of P. aeruginosa in a 10-day period was assessed. For determining survival rate, fifty mice were divided into 5 groups which included control (+), control (-), Gln, ciprofloxacin, and "glutamine+ciprofloxacin" group. All mice, except for control (-), were given an LD75 dose of P. aeruginosa and after 30 min each group received its special treatment: control (-) and control (+) groups received only 500λ phosphate buffer saline (PBS). Gln group received 500λ Ala-Gln, Cip group received 500λ ciprofloxacin. The Cip+Gln group received 500λ Gln and ciprofloxacin. Finally serum TNF-α, IL-10 and HSP-70 concentrations were measured and the severity of liver necrosis was examined. Glutamine in combination with ciprofloxacin significantly increased survival rate and serum HSP-70 and IL-10 concentration and significantly decreased serum TNF-α concentration and the liver necrosis severity in comparison to control (+) group. Gln has synergistic effects with ciprofloxacin in reduction of P. aeruginosa-induced septic shock. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Incidence and prognostic impact of new-onset atrial fibrillation in patients with septic shock: a prospective observational study

    PubMed Central

    2010-01-01

    Introduction Since data regarding new-onset atrial fibrillation (AF) in septic shock patients are scarce, the purpose of the present study was to evaluate the incidence and prognostic impact of new-onset AF in this patient group. Methods We prospectively studied all patients with new-onset AF and all patients suffering from septic shock in a non-cardiac surgical intensive care unit (ICU) during a 13 month period. Results During the study period, 687 patients were admitted to the ICU, of which 58 patients were excluded from further analysis due to pre-existing chronic or intermittent AF. In 49 out of the remaining 629 patients (7.8%) new-onset AF occurred and 50 out of the 629 patients suffered from septic shock. 23 out of the 50 patients with septic shock (46%) developed new-onset AF. There was a steady, significant increase in C-reactive protein (CRP) levels before onset of AF in septic shock patients. ICU mortality in septic shock patients with new-onset AF was 10/23 (44%) compared with 6/27 (22%) in septic shock patients with maintained sinus rhythm (SR) (P = 0.14). During a 2-year follow-up there was a trend towards an increased mortality in septic shock patients with new-onset AF, but the difference did not reach statistical significance (P = 0.075). The median length of ICU stay among surviving patients was longer in patients with new-onset AF compared to those with maintained SR (30 versus 17 days, P = 0.017). The success rate to restore SR was 86%. Failure to restore SR was associated with increased ICU mortality (71.4% versus 21.4%, P = 0.015). Conclusions AF is a common complication in septic shock patients and is associated with an increased length of ICU stay among surviving patients. The increase in CRP levels before onset of AF may support the hypothesis that systemic inflammation is an important trigger for AF. PMID:20537138

  17. Effect of early goal directed therapy on tissue perfusion in patients with septic shock.

    PubMed

    Lu, Yuan-Hua; Liu, Ling; Qiu, Xiao-Hua; Yu, Qin; Yang, Yi; Qiu, Hai-Bo

    2013-01-01

    This study aimed to observe the effect of early goal directed therapy (EGDT) on tissue perfusion, microcirculation and tissue oxygenation in patients with septic shock. Patients with early septic shock (<24 hours) who had been admitted to the ICU of Zhongda Hospital Affiliated to Southeast University from September 2009 through May 2011 were enrolled (research time: 12 months), and they didn't meet the criteria of EGDT. Patients who had one of the following were excluded: stroke, brain injury, other types of shock, severe heart failure, acute myocardial infarction, age below 18 years, pregnancy, end-stage disease, cardiac arrest, extensive burns, oral bleeding, difficulty in opening the mouth, and the onset of septic shock beyond 24 hours. Patients treated with the standard protocol of EGDT were included. Transcutaneous pressure of oxygen and carbon dioxide (PtcO2, PtcCO2) were monitored and hemodynamic measurements were obtained. Side-stream dark field (SDF) imaging device was applied to obtain sublingual microcirculation. Hemodynamics, tissue oxygen, and sublingual microcirculation were compared before and after EGDT. If the variable meets the normal distribution, Student's t test was applied. Otherwise, Wilcoxon's rank-sum test was used. Correlation between variables was analyzed with Pearson's product-moment correlation coefficient method. Twenty patients were involved, but one patient wasn't analyzed because he didn't meet the EGDT criteria. PtcO2 and PtcCO2 were monitored in 19 patients, of whom sublingual microcirculation was obtained. After EGDT, PtcO2 increased from 62.7±24.0 mmHg to 78.0±30.9 mmHg (P<0.05) and tissue oxygenation index (PtcO2/FiO2) was 110.7±60.4 mmHg before EGDT and 141.6±78.2 mmHg after EGDT (P<0.05). The difference between PtcCO2 and PCO2 decreased significantly after EGDT (P<0.05). The density of perfused small vessels (PPV) and microcirculatory flow index of small vessels (MFI) tended to increase, but there were no significant

  18. A Case of Septic Shock caused by Achromobacter xylosoxidans in an Immunocompetent Female Patient after Extracorporeal Shock Wave Lithotripsy for a Ureteral Stone

    PubMed Central

    Lee, So Yon; Park, In Young; Park, So Yeon; Lee, Jin Seo; Kang, Goeun; Kim, Jae Seok

    2016-01-01

    Achromobacter xylosoxidans can cause various types of infections, but its infection in humans is rare. A. xylosoxidans has been reported as a rare etiological agent of infections including primary bacteremia, catheter-related bloodstream infection, endocarditis, otitis, and pneumonia, particularly in immunocompromised hosts. We encountered a case of septic shock caused by A. xylosoxidans in a 52-year-old, immunocompetent woman with no underlying disease, who received extracorporeal shock wave lithotripsy to remove a left upper ureteral stone. She was treated with antibiotics to which the organism was susceptible but died as a result of septic shock. PMID:27104016

  19. A Case of Septic Shock caused by Achromobacter xylosoxidans in an Immunocompetent Female Patient after Extracorporeal Shock Wave Lithotripsy for a Ureteral Stone.

    PubMed

    Lee, Jae Hyuk; Lee, So Yon; Park, In Young; Park, So Yeon; Lee, Jin Seo; Kang, Goeun; Kim, Jae Seok; Eom, Joong Sik

    2016-03-01

    Achromobacter xylosoxidans can cause various types of infections, but its infection in humans is rare. A. xylosoxidans has been reported as a rare etiological agent of infections including primary bacteremia, catheter-related bloodstream infection, endocarditis, otitis, and pneumonia, particularly in immunocompromised hosts. We encountered a case of septic shock caused by A. xylosoxidans in a 52-year-old, immunocompetent woman with no underlying disease, who received extracorporeal shock wave lithotripsy to remove a left upper ureteral stone. She was treated with antibiotics to which the organism was susceptible but died as a result of septic shock.

  20. A comparison of the peritoneal cell population of pregnant rabbits after LPS or TNF-alpha induced septic shock.

    PubMed

    Terlikowski, S; Sulkowska, M; Południewski, G; Dziecioł, J; Sobaniec-Lotowska, M; Musiatowicz, B; Kulikowski, M

    1997-01-01

    Septic shock is a catastrophic consequence of invasive infection. Unfortunately, recent advances in surgical and medical sciences have not significantly reduced the overall mortality from septic shock. Bacterial antigens stimulate a cascade of cytokine release; each cytokine helps the host to overcome infection, but their excessive production causes them to trigger events that lead to septic syndrome and shock. Tumour necrosis factor (TNF-alpha) has a pivotal role in orchestrating the events leading to septic shock. Intraperitoneal administration of certain substances can increase the number and phagocytic activity of cells, which reach naturally the site of infection. Activation of the immunity cells in the peritoneal cavity and their immunocompetence are found to be responsible for the organism protection against abdominal cavity infections. Macrophages, lymphocytes and granulocytes of low activity in the non-stimulated peritoneal cavity become significant due to the influence of numerous biologically active substances. This study was designed to determine the peritoneal response to local administration of LPS or TNF-alpha in the course of experimental septic shock.

  1. Alterations of T helper lymphocyte subpopulations in sepsis, severe sepsis, and septic shock: a prospective observational study.

    PubMed

    Li, Jia; Li, Ming; Su, Longxiang; Wang, Huijuan; Xiao, Kun; Deng, Jie; Jia, Yanhong; Han, Gencheng; Xie, Lixin

    2015-01-01

    Circulating lymphocyte number was significantly decreased in patients with sepsis. However, it remains unknown which severity phase (sepsis, severe sepsis, and septic shock) does it develop and what happen on each subpopulation. Eight patients with differing severities of sepsis (31 sepses, 33 severe sepses, and 16 septic shocks) were enrolled. Quantitative real-time polymerase chain reaction (RT-PCR) of Th1, Th2, and Th17; regulatory T (Treg) cell-specific transcription factor T-bet; GATA-3; RORgammat (RORγt); forkhead box P3 (FOXP3); and IL-17 mRNA were performed, and the enzyme-linked immunosorbent assay (ELISA) was used to detect serum interferon (IFN)-γ, IL-4, and IL-10. In this study, the Th1, Th2, Treg transcription factors, and related cytokines IFN-γ, IL-4, and IL-10 levels of sepsis and severe sepsis patients in peripheral blood were significantly higher than those of the normal controls. Except for IL-17, the T-bet, GATA-3, and IFN-γ levels of septic shock patients were lower than those of sepsis patients. We also observed that the proportions of Th17/Treg in the sepsis and septic shock groups were inversed. From the above, the inflammatory response especially the adaptive immune response is still activated in sepsis and severe sepsis, but significant immunosuppression was developed in septic shock. In addition, the proportion of Th17/Treg inversed may be associated with the illness aggravation of patients with sepsis.

  2. Effect of methylguanidine in a model of septic shock induced by LPS.

    PubMed

    Marzocco, Stefania; Di Paola, Rosanna; Ribecco, Maria Teresa; Sorrentino, Raffaella; Domenico, Britti; Genesio, Massimini; Pinto, Aldo; Autore, Giuseppina; Cuzzocrea, Salvatore

    2004-11-01

    Septic shock, a severe form of sepsis, is characterized by cardiovascular collapse following microbial invasion of the body. The progressive hypotension, hyporeactivity to vasopressor agents and vascular leak leads to circulatory failure with multiple organ dysfunction and death. Many inflammatory mediators (e.g. TNF-alpha, IL-1 and IL-6) are involved in the pathogenesis of shock and, among them, nitric oxide (NO). The overproduction of NO during septic shock has been demonstrated to contribute to circulatory failure, myocardial dysfunction, organ injury and multiple organ failure. We have previously demonstrated with in vitro and in vivo studies that methylguanidine (MG), a guanidine compound deriving from protein catabolism, significantly inhibits iNOS activity, TNF-alpha release and carrageenan-induced acute inflammation in rats. The aim of the present study was to evaluate the possible anti-inflammatory activity of MG in a model of septic shock induced by lipopolysaccharide (LPS) in mice. MG was administered intraperitoneally (i.p.) at the dose of 30 mg/kg 1 h before and at 1 and 6 h after LPS-induced shock. LPS injection (10 mg/kg in 0.9% NaCl; 0.1 ml/mouse; i.p.) in mouse developed a shock syndrome with enhanced NO release and liver, kidney and pancreatic damage 18 h later. NOx levels, evaluated as nitrite/nitrate serum levels, was significantly reduced in MG-treated rats (78.6%, p < 0.0001; n = 10). Immunohistochemistry revealed, in the lung tissue of LPS-treated group, a positive staining for nitrotyrosine and poly(adenosine diphosphate [ADP] ribose) synthase, both of which were reduced in MG-treated mice. Furthermore, enzymatic evaluation revealed a significant reduction in liver, renal and pancreatic tissue damage and MG treatment also improved significantly the survival rate. This study provides evidence that MG attenuates the degree of inflammation and tissue damage associated with endotoxic shock in mice. The mechanisms of the anti-inflammatory effect

  3. Mortality rate among patients with septic shock after implementation of 6-hour sepsis protocol in the emergency department of Thammasat University Hospital.

    PubMed

    Apibunyopas, Yajai

    2014-08-01

    Septic shock is a major healthcare problem effecting people worldwide with high mortality rate. Administering early and appropriate interventions can help improve the outcome. The 6-hour bundle, launched by the Surviving Sepsis Campaign committee was part of efforts to incorporate evidence-based guideline to clinical practice. There were many reports on outcome improvement of septic shock patients after implementation of the 6-hour bundle at the emergency department. To compare mortality rate of septic shockpatients before and after implementing the 6-hour sepsis protocol at the emergency department of Thammasat University Hospital. Study was conducted at the emergency department of Thammasat University Hospital. This is an interrupted time, before and after study, comparing between the prospective cohort period after (Oct 2012 to Nov 2013) and the historical control period before (Feb 2011 to July 2012) implementation of 6-hour sepsis protocol. Primary outcome was hospital mortality of septic shock patients. Secondary outcomes included length of hospital stay and predictive factors for mortality ofseptic shock patients. There were 80patients included in the pre-intervention group and 75patients in the post-intervention group. There was significant improvement in management of septic shock patients. Totalfluid given in 2 hours in the post-intervention group was significantly higher[2,000 (500-3,000) vs. 1,600 (100-3,600);p = 0.038)] when compared with thepre-intervention group. The entire resuscitation bundles compliance rate was significantly increased in the post-intervention group (37.3% vs. 0%; p

  4. Clinical presentation and treatment of septic arthritis in children.

    PubMed

    Moro-Lago, I; Talavera, G; Moraleda, L; González-Morán, G

    The aim of this study is to determine the epidemiological features, clinical presentation, and treatment of children with septic arthritis. A retrospective review was conducted on a total of 141 children with septic arthritis treated in Hospital Universitario La Paz (Madrid) between the years 2000 to 2013. The patient data collected included, the joint affected, the clinical presentation, the laboratory results, the appearance, Gram stain result, and the joint fluid culture, as well as the imaging tests and the treatment. Most (94%) of the patients were less than 2 years-old. The most common location was the knee (52%), followed by the hip (21%). The septic arthritis was confirmed in 53%. No type of fever was initially observed in 49% of them, and 18% had an ESR (mm/h) or CRP (mg/l) less than 30 in the initial laboratory analysis. The joint fluid was purulent in 45% and turbid in 12%. The Gram stain showed bacteria in 4%. The fluid culture was positive in 17%. Staphylococcus aureus was the most common pathogen found, followed by Streptococcus agalactiae, Streptococcus pneumoniae, and Kingella kingae. Antibiotic treatment was intravenous administration for 7 days, followed by 21 days orally. Surgery was performed in 18% of cases. The diagnosis was only confirmed in 53% of the patients. Some of the confirmed septic arthritis did not present with the classical clinical/analytical signs, demonstrating that the traumatologist or paediatrician requires a high initial level of clinical suspicion of the disease. Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Potential Impact of the 2016 Consensus Definitions of Sepsis and Septic Shock on Future Sepsis Research.

    PubMed

    Peake, Sandra L; Delaney, Anthony; Bailey, Michael; Bellomo, Rinaldo

    2017-10-01

    The influence of the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) on the conduct of future sepsis research is unknown. We seek to examine the potential effect of the new definitions on the identification and outcomes of patients enrolled in a sepsis trial. This was a post hoc analysis of the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial of early goal-directed therapy that recruited 1,591 adult patients presenting to the emergency department (ED) with early septic shock diagnosed by greater than or equal to 2 systemic inflammatory response syndrome criteria and either refractory hypotension or hyperlactatemia. The proportion of participants who would have met the Sepsis-3 criteria for quick Sequential Organ Failure Assessment (qSOFA) score, sepsis (an increased Sequential Organ Failure Assessment score ≥2 because of infection) and septic shock before randomization, their baseline characteristics, interventions delivered, and mortality were determined. There were 1,139 participants who had a qSOFA score of greater than or equal to 2 at baseline (71.6% [95% confidence interval {CI} 69.4% to 73.8%]). In contrast, 1,347 participants (84.7% [95% CI 82.9% to 86.4%]) met the Sepsis-3 criteria for sepsis. Only 1,010 participants were both qSOFA positive and met the Sepsis-3 criteria for sepsis (63.5% [95% CI 61.1% to 65.8%]). The Sepsis-3 definition for septic shock was met at baseline by 203 participants (12.8% [95% CI 11.2% to 14.5%]), of whom 175 (86.2% [95% CI 81.5% to 91.0%]) were also qSOFA positive. Ninety-day mortality for participants fulfilling the Sepsis-3 criteria for sepsis and septic shock was 20.4% (95% CI 18.2% to 22.5%) (274/1,344) and 29.6% (95% CI 23.3% to 35.8% [60/203]) versus 9.4% (95% CI 5.8% to 13.1%) (23/244) and 17.1% (95% CI 15.1% to 19.1% [237/1,388]), respectively, for participants not meeting the criteria (risk differences 11.0% [95% CI 6.2% to 14.8%] and 12.5% [95% CI 6.3% to 19

  6. Protein C preserves microcirculation in a model of neonatal septic shock

    PubMed Central

    Fischer, Doris; Nold, Marcel F; Nold-Petry, Claudia A; Furlan, Antonio; Veldman, Alex

    2009-01-01

    Objectives Sepsis remains a disease with a high mortality in neonates. Microcirculatory impairment plays a pivotal role in the development of multiorgan failure in septic newborns. The hemodynamic effects of recombinant activated protein C (rhAPC) were tested in an animal model of neonatal septic shock focusing on intestinal microcirculation. Materials and methods Endotoxic shock was triggered by intravenous application of Escherichia coli lipopolysaccarides in newborn piglets. Thereafter, five animals received a continuous infusion of 24 μg/kg/h rhAPC, and five received vehicle for control. Over the course of three hours, intestinal microcirculation was assessed by intravital microscopy every 30 min. Macrocirculation and blood counts were monitored simultaneously. Results After a short hypotensive period in all animals, the arterial blood pressure returned to baseline in the rhAPC-treated piglets, whereas the hypotension became increasingly severe in the controls. By 90 min, mean blood pressure in the controls was significantly lower than in the treatment group. Similar observations were made regaring microcirculation. After an early impairment in all study animals, functional capillary density and intestinal microcirculatory red blood cell velocity and red blood cell flow recovered in the rhAPC group, but deteriorated further in the control piglets. Conclusion Recombinant activated protein C protects macro- and microcirculation from endotoxic shock. PMID:19774219

  7. [Dopamine and noradrenaline effects in the blood flux regional on therapeutic in the septic shock].

    PubMed

    Miranda, Milena Penteado Ferraro; Soriano, Francisco Garcia; Secoli, Silvia Regina

    2008-03-01

    Norepinephrine and dopamine are used, in the state of shock, with the intention of offering hemodynamic support and to reestablish tissue perfusion. The pharmacological effects of these vasopressors can be diverse, for this reason, their use requires, through the clinician, an interpretation of the hemodynamic effects with observation of the systemic variations and region. With this in mind, the objective of this study was to analyze the publications regarding the effects of norepinephrine and low-dose dopamine in hepatosplenic perfusion and renal in treatment of septic shock. Articles were selected (n = 27) concerning the use of norepinephrine and dopamine in septic shock, published during the period of 1997 to September 2007, revised in PubMed, data base of the National Library of Medicine (NLM). The MESH method was utilized with the descriptors norepinephrine, dopamine and sepsis. The effects of dopamine and norepinephrine in kidney perfusion are similar; there is an increase in diuresis and no change in creatinine clearance. Norepinephrine did not affect kidney tissue perfusion in spite of the increase of vascular tone. Regarding the splancnic effects, these drugs showed an increase in blood flow, though redistributing the blood in this compartment. The best agent for the hemodynamic reestablishment that keeps the adequate regional perfusion remains inconclusive.

  8. Cardiac ischemia in patients with septic shock randomized to vasopressin or norepinephrine

    PubMed Central

    2013-01-01

    Introduction Cardiac troponins are sensitive and specific biomarkers of myocardial necrosis. We evaluated troponin, CK, and ECG abnormalities in patients with septic shock and compared the effect of vasopressin (VP) versus norepinephrine (NE) on troponin, CK, and ECGs. Methods This was a prospective substudy of a randomized trial. Adults with septic shock randomly received, blinded, a low-dose infusion of VP (0.01 to 0.03 U/min) or NE (5 to 15 μg/min) in addition to open-label vasopressors, titrated to maintain a mean blood pressure of 65 to 75 mm Hg. Troponin I/T, CK, and CK-MB were measured, and 12-lead ECGs were recorded before study drug, and 6 hours, 2 days, and 4 days after study-drug initiation. Two physician readers, blinded to patient data and drug, independently interpreted ECGs. Results We enrolled 121 patients (median age, 63.9 years (interquartile range (IQR), 51.1 to 75.3), mean APACHE II 28.6 (SD 7.7)): 65 in the VP group and 56 in the NE group. At the four time points, 26%, 36%, 32%, and 21% of patients had troponin elevations, respectively. Baseline characteristics and outcomes were similar between patients with positive versus negative troponin levels. Troponin and CK levels and rates of ischemic ECG changes were similar in the VP and the NE groups. In multivariable analysis, only APACHE II was associated with 28-day mortality (OR, 1.07; 95% CI, 1.01 to 1.14; P = 0.033). Conclusions Troponin elevation is common in adults with septic shock. We observed no significant differences in troponin, CK, and ECGs in patients treated with vasopressin and norepinephrine. Troponin elevation was not an independent predictor of mortality. Trial registration Controlled-trials.com ISRCTN94845869 PMID:23786655

  9. 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.

  10. Defining metabolic acidosis in patients with septic shock using Stewart approach.

    PubMed

    Mallat, Jihad; Michel, Damien; Salaun, Pascale; Thevenin, Didier; Tronchon, Laurent

    2012-03-01

    The aim of this study was to define the nature of metabolic acidosis in patients with septic shock on admission to intensive care unit (ICU) using Stewart method. We also aimed to compare the ability of standard base excess (SBE), anion gap (AG), and corrected AG for albumin and lactate (AGcorr) to accurately predict the presence of unmeasured anions (UA). Thirty consecutive patients with septic shock were prospectively included on ICU admission. Stewart equations modified by Figge were used to calculate the strong ion difference and the strong ion gap (SIG). Most patients had multiple underlying mechanisms explaining the metabolic acidosis. Unmeasured anions and hyperchloremia were present in 70% of the patients. Increased UA were present in 23% of patients with normal values of SBE and [HCO3-]. In these patients, plasma [Cl-] was significantly lower compared with patients with low SBE and increased UA (103 [102-106.6] vs 108 [106-111] mmol/L; P=.01, respectively). Corrected AG for albumin and lactate had the best correlation with SIG (r²=0.94; P<.0001) with good agreement (bias, 0, and precision, 1.22) and highest area under the receiver operating characteristic curve (0.995; 95% confidence interval, 0.87-1) to discriminate SIG acidosis. Patients with septic shock exhibit a complex metabolic acidosis at ICU admission. High UA may be present with normal values of SBE and [HCO3-] as a result of associated "relative" hypochloremic alkalosis. Corrected AG for albumin and lactate offers the most accurate bedside alternative to Stewart calculation of UA. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Thenar oxygen saturation and invasive oxygen delivery measurements in critically ill patients in early septic shock.

    PubMed

    Mesquida, Jaume; Gruartmoner, Guillem; Martínez, Maria Luisa; Masip, Jordi; Sabatier, Caroline; Espinal, Cristina; Artigas, Antonio; Baigorri, Francisco

    2011-05-01

    This prospective study was aimed to test the hypothesis that tissue hemoglobin oxygen saturation (StO₂) measured noninvasively using near-infrared spectroscopy is a reliable indicator of global oxygen delivery (DO₂) measured invasively using a pulmonary artery catheter (PAC) in patients with septic shock. The study setting was a 26-bed medical-surgical intensive care unit at a university hospital. Subjects were adult patients in septic shock who required PAC hemodynamic monitoring for resuscitation. Interventions included transient ischemic challenge on the forearm. After blood pressure normalization, hemodynamic and oximetric PAC variables and, simultaneously, steady-state StO₂ and its changes from ischemic challenge (deoxygenation and reoxygenation rates) were measured. Fifteen patients were studied. All the patients had a mean arterial pressure above 65 mmHg. The DO₂ index (iDO₂) range in the studied population was 215 to 674 mL O₂/min per m. The mean mixed venous oxygen saturation value was 61% ± 10%, mean cardiac index was 3.4 ± 0.9 L/min per m, and blood lactate level was 4.6 ± 2.7 mmol/L. Steady-state StO₂ significantly correlated with iDO₂, arterial and venous O₂ content, and O₂ extraction ratio. A StO₂ cutoff value of 75% predicted iDO₂ below 450, with a sensitivity of 0.9 and a specificity of 0.9. In patients in septic shock and normalized MAP, low StO₂ reflects extremely low iDO₂. Steady-state StO₂ does not correlate with moderately low iDO₂, indicating poor sensitivity of StO₂ to rule out hypoperfusion.

  12. Impact of Source Control in Patients With Severe Sepsis and Septic Shock.

    PubMed

    Martínez, María Luisa; Ferrer, Ricard; Torrents, Eva; Guillamat-Prats, Raquel; Gomà, Gemma; Suárez, David; Álvarez-Rocha, Luis; Pozo Laderas, Juan Carlos; Martín-Loeches, Ignacio; Levy, Mitchell M; Artigas, Antonio

    2017-01-01

    Time to clearance of pathogens is probably critical to outcome in septic shock. Current guidelines recommend intervention for source control within 12 hours after diagnosis. We aimed to determine the epidemiology of source control in the management of sepsis and to analyze the impact of timing to source control on mortality. Prospective observational analysis of the Antibiotic Intervention in Severe Sepsis study, a Spanish national multicenter educational intervention to improve antibiotherapy in sepsis. Ninety-nine medical-surgical ICUs in Spain. We enrolled 3,663 patients with severe sepsis or septic shock during three 4-month periods between 2011 and 2013. Source control and hospital mortality. A total of 1,173 patients (32%) underwent source control, predominantly for abdominal, urinary, and soft-tissue infections. Compared with patients who did not require source control, patients who underwent source control were older, with a greater prevalence of shock, major organ dysfunction, bacteremia, inflammatory markers, and lactic acidemia. In addition, compliance with the resuscitation bundle was worse in those undergoing source control. In patients who underwent source control, crude ICU mortality was lower (21.2% vs 25.1%; p = 0.010); after adjustment for confounding factors, hospital mortality was also lower (odds ratio, 0.809 [95% CI, 0.658-0.994]; p = 0.044). In this observational database analysis, source control after 12 hours was not associated with higher mortality (27.6% vs 26.8%; p = 0.789). Despite greater severity and worse compliance with resuscitation bundles, mortality was lower in septic patients who underwent source control than in those who did not. The time to source control could not be linked to survival in this observational database.

  13. [Effect of hydroxyethyl starch and Ringer's solution on splanchnic perfusion in dogs with septic shock].

    PubMed

    Yang, Yi; Qiu, Hai-bo; Liu, Song-qiao; Chen, Yong-ming; Li, Na; Shen, Ju-fang; Li, Jia-qiong

    2005-12-01

    To investigate the effect of 6% hydroxyethyl starch (HES) and Ringer's solution (RS) on splanchnic perfusion in dogs with septic shock. Twenty-four mongrel dogs with septic shock induced by lipopolysaccharides (LPS) were randomly divided into two groups: HES group and RS group. Dogs of each group received an intravenous infusion of HES or RS (1 mlxkg(-1)xmin(-1)) for 60 minutes, followed by normal saline for 180 minutes with same infusion speed. Parameters of hemodynamics, oxygen dynamic, and splanchnic perfusion were monitored at 0, 30, 60, 120, 180, 240 minutes after basic measurements (pre-LPS). (1) After LPS infusion, mean arterial pressure (MAP) and cardiac index (CI) lowered significantly (P<0.05). Compared to that of 0 minutes, MAP and CI were elevated by fluid therapy in both groups, but there was no difference between HES and RS group. (2) Compared with pre-LPS, oxygen delivery (DO(2)) was reduced, arterial blood pH lowered and arterial lactate level increased markedly at 0 minutes (P<0.05). DO(2) increased by fluid therapy in both groups, but DO(2) was higher in HES group at the same time points (P<0.05). Compared to 0 minutes, arterial lactate levels were lowered at 180 minutes in both groups. (3) Mesenteric blood flow decreased after LPS infusion in all animals (P<0.05). Mesenteric blood flow increased after HES infusion, at the same time intramucosal pH (pHi) was elevated and Pg-aCO(2) decreased significantly (all P<0.05), but they showed no difference in RS group. At the same time, mesenteric blood flow and pHi was higher in HES group than that in RS group. Both HES and RS could improve MAP and DO(2) in dogs with septic shock, but the effect of HES was better than RS on splanchnic perfusion.

  14. Norepinephrine weaning in septic shock patients by closed loop control based on fuzzy logic

    PubMed Central

    Merouani, Mehdi; Guignard, Bruno; Vincent, François; Borron, Stephen W; Karoubi, Philippe; Fosse, Jean-Philippe; Cohen, Yves; Clec'h, Christophe; Vicaut, Eric; Marbeuf-Gueye, Carole; Lapostolle, Frederic; Adnet, Frederic

    2008-01-01

    Introduction The rate of weaning of vasopressors drugs is usually an empirical choice made by the treating in critically ill patients. We applied fuzzy logic principles to modify intravenous norepinephrine (noradrenaline) infusion rates during norepinephrine infusion in septic patients in order to reduce the duration of shock. Methods Septic patients were randomly assigned to norepinephrine infused either at the clinician's discretion (control group) or under closed-loop control based on fuzzy logic (fuzzy group). The infusion rate changed automatically after analysis of mean arterial pressure in the fuzzy group. The primary end-point was time to cessation of norepinephrine. The secondary end-points were 28-day survival, total amount of norepinephine infused and duration of mechanical ventilation. Results Nineteen patients were randomly assigned to fuzzy group and 20 to control group. Weaning of norepinephrine was achieved in 18 of the 20 control patients and in all 19 fuzzy group patients. Median (interquartile range) duration of shock was significantly shorter in the fuzzy group than in the control group (28.5 [20.5 to 42] hours versus 57.5 [43.7 to 117.5] hours; P < 0.0001). There was no significant difference in duration of mechanical ventilation or survival at 28 days between the two groups. The median (interquartile range) total amount of norepinephrine infused during shock was significantly lower in the fuzzy group than in the control group (0.6 [0.2 to 1.0] μg/kg versus 1.4 [0.6 to 2.7] μg/kg; P < 0.01). Conclusions Our study has shown a reduction in norepinephrine weaning duration in septic patients enrolled in the fuzzy group. We attribute this reduction to fuzzy control of norepinephrine infusion. Trial registration Trial registration: Clinicaltrials.gov NCT00763906. PMID:19068113

  15. Bicarbonate therapy in the treatment of septic shock: a second look.

    PubMed

    El-Solh, Ali A; Abou Jaoude, Philippe; Porhomayon, Jahan

    2010-08-01

    The use of supplemental sodium bicarbonate for the treatment of patients with septic shock and elevated blood lactate levels remains a controversial therapy. We conducted a retrospective study between March 2004 and February 2009 of 36 consecutive patients diagnosed with septic shock who received continuous infusion of bicarbonate therapy. A control group was matched 1:1 for age, site of infection, and predicted mortality by APACHE II. All patients were managed according to standard protocols. The median time until reversal of shock did not achieve statistical significance between the bicarbonate group (44.5 h [95% confidence interval [CI] 34-54] and the control group (55.0 h [95% CI 39-60] (p = 0.09). The median time to liberation of mechanical ventilation was significantly reduced in the bicarbonate group (10 days [95% CI 5.0-13.0] compared to the control group (14 days [95% CI 9.0-19.0], p = 0.02). The length of intensive care unit (ICU) stay was also shorter in the surviving patients who received bicarbonate compared to controls (median 11.5 days (95% CI 6.0-16.0) vs. 16.0 days (95% CI 13.5-19.0), respectively; p = 0.01). However, there was no difference in 28-day mortality between the two study groups (28%; 95% CI 14-45% vs. 33%; 95% CI 19-51%, respectively; p = 0.79). Infusion of sodium bicarbonate in septic patients with arterial hyperlactatemia may facilitate weaning from mechanical ventilation and reduce length of ICU stay.

  16. Impact of Metformin Use on Lactate Kinetics in Patients with Severe Sepsis and Septic Shock.

    PubMed

    Park, Joongmin; Hwang, Sung Yeon; Jo, Ik Joon; Jeon, Kyeongman; Suh, Gee Young; Lee, Tae Rim; Yoon, Hee; Cha, Won Chul; Sim, Min Seob; Carriere, Keumhee Chough; Yeon, Seungmin; Shin, Tae Gun

    2017-05-01

    We aimed to evaluate the impact of metformin use on lactate kinetics in patients with severe sepsis and septic shock. We analyzed data from a registry that included patients who presented to the emergency department and met criteria for severe sepsis or septic shock. Patients were divided into two groups based on metformin use. We compared lactate concentrations, lactate clearance (LC), and normalization at 6 h (H6) and 24 h (H24) after the initial (H0) measurement. Propensity score matching, multiple logistic, and linear regression analysis via a generalized estimating equations method were used. Of 1,318 patients, 71 patients were in the metformin use group and all 71 were selected in a one to two propensity matching. Metformin users showed significantly higher lactate levels at H0 (5.3 vs. 4.4 mmol/L) and H6 (3.8 vs. 2.9 mmol/L) in all patients, although in the matched subset, the effect was marginal (H0, 5.3 vs. 4.9 mmol/L; H6, 3.8 vs. 3.2 mmol/L; H24, 2.7 vs. 2.4 mmol/L). Mean LC (H6, 29% vs. 34%; H24, 43% vs. 49%) and normalization rate (H6, 27% vs. 28%; H24, 49% vs. 52%) were also not significantly different. Although metformin use appeared to be associated with higher lactate levels before using the propensity score method, no significant association was found between metformin use and lactate kinetics variables in the balanced matched subset data. Lactate levels in metformin users were initially elevated in the early phase of resuscitation from severe sepsis and septic shock. However, there was no significant difference in lactate levels, LC, and normalization over the initial 24 h period based on metformin use.

  17. [The influence of intensive insulin therapy on hemodynamics in patients with septic shock].

    PubMed

    Dong, Shi-min; Qin, Yan-jun; Gao, Yu-fang

    2009-05-01

    To elucidate effects of intensive insulin therapy and target glucose control on hemodynamics and cardiac function in patients with septic shock. Twenty-seven patients of septic shock with myocardial depression were divided into routine group (14 cases, level of blood glucose was 4.1 to 6.1 mmol/L) and target group (13 cases, level of blood glucose was 6.2 to 8.3 mmol/L). Hemodynamics and cardiac function parameters were obtained via pulmonary artery catheter after 48 hours. Mean blood glucose level in target group was lower than that in routine group [(6.0+/-1.5) mmol/L vs. (8.2+/-1.9) mmol/L, P<0.05], with dosage of insulin infusion in target group increased as compared with that of routine group [(10.3+/-3.7) U/h vs. (7.5+/-3.0) U/h, P<0.05]. Furthermore, oxygenation index (PaO(2)/FiO(2)), stroke volume index (SVI), cardiac index (CI) and oxygen delivery index (DO(2)I) were increased 20.2%, 23.3%, 15.1% and 11.7%, respectively (all P<0.05). On the other hands, there was no significant difference between target and routine group in mean artery pressure, acute physiology and chronic health evaluation II (APACHEII) score, blood lactic acid (all P>0.05), although the incidence of severe hypoglycemia was higher in target group than the routine group (38.5% vs. 28.6%, P>0.05). Intensive insulin therapy and blood glucose control may improve hemodynamic status and enhance cardiac function in patients with septic shock and myocardial depression.

  18. Diagnostic potential of endotoxin scattering photometry for sepsis and septic shock.

    PubMed

    Shimizu, Tomoharu; Obata, Toru; Sonoda, Hiromichi; Akabori, Hiroya; Miyake, Tohru; Yamamoto, Hiroshi; Tabata, Takahisa; Eguchi, Yutaka; Tani, Tohru

    2013-12-01

    Endotoxin scattering photometry (ESP) is a novel Limulus amebocyte lysate (LAL) assay that uses a laser light-scattering particle-counting method. In the present study, we compared ESP, standard turbidimetric LAL assay, and procalcitonin assay for the evaluation of sepsis after emergency gastrointestinal surgery. A total of 174 samples were collected from 40 adult patients undergoing emergency gastrointestinal surgery and 10 patients with colorectal cancer undergoing elective surgery as nonseptic controls. Plasma endotoxin levels were measured with ESP and turbidimetric LAL assay, and plasma procalcitonin levels were assessed with a standard procalcitonin assay. Plasma endotoxin and procalcitonin levels increased corresponding to the degree of sepsis. Endotoxin scattering photometry significantly discriminated between patients with or without septic shock: sensitivity, 81.1%; specificity, 76.6%; positive predictive value, 48.4%; negative predictive value, 93.8%; and accuracy, 77.6%. The area under the receiver operating characteristic curve for septic shock with the ESP assay (endotoxin cutoff value, 23.8 pg/mL) was 0.8532 ± 0.0301 (95% confidence interval, 0.7841-0.9030; P < 0.0001). The predictive power of ESP was superior to that of turbidimetric assay (difference, 0.1965 ± 0.0588; 95% confidence interval, 0.0812-0.3117; P = 0.0008). There was no significant difference in predictive power between ESP and procalcitonin assay. Endotoxin scattering photometry also discriminated between patients with and without sepsis. Area under the receiver operating characteristic curve analysis showed that ESP had the best predictive power for diagnosing sepsis. In conclusion, compared with turbidimetric LAL assay, ESP more sensitively detected plasma endotoxin and significantly discriminated between sepsis and septic shock in patients undergoing gastrointestinal emergency surgery.

  19. Simultaneous use of traditional Chinese medicine (si-ni-tang) to treat septic shock patients: study protocol for a randomized controlled trial.

    PubMed

    Chen, Huang-Chi; Chen, Wen-Chi; Lin, Kai-Huang; Chen, Yung-Hsiang; Lo, Lun-Chien; Lee, Tsung-Chieh; Hsia, Te-Chun; Wang, Chu-Hsien; Wu, Shin-Hwar; Hsu, Hsin-Whae; Chang, Yu-Jun; Huang, Yu-Chuen; Ku, Tien-Hsiung; Horng, Ming-Hwarng

    2011-08-24

    Even though there are continually upgraded recommendations for managing sepsis, such as "Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock", mortality is still high. Si-ni-tang, a remedy documented in Shanghan Lun, a medical collection from ancient China, is used for treating patients with sepsis and septic shock. Using a well-designed clinical trial, we are eager to survey the effectiveness of the concurrent use of this remedy in restoring these patients' hemodynamic status, or "Yang Qi". Patients admitted to our medical intensive care units with the diagnosis of septic shock, defined as persistent hypotension induced by sepsis despite adequate fluid resuscitation, are eligible for participation. The inclusion criteria include: age from 20 to 85 years, conditions meeting the definition of septic shock, use of vasopressors within 24 hours of entering the study, and use of a nasogastric tube for feeding. The enrolled patients are randomly allocated either to the si-ni-tang group or the placebo group. The prescription of the trial drugs (si-ni-tang/placebo) is 2.25 grams 4 times a day for 7 days or till shock reversal (if shock reversal occurs in less than 7 days). Data, including duration of vasopressor infusion, gender, age, co-morbidities, APACHE II score, predicted mortality, ICU mortality, ICU length of stay, hospital mortality, hospital length of stay, source of sepsis, and culture results, are collected for the following analysis. Si-ni-tang is composed of processed Zingiber officinale, Glycyrrhiza uralensis, and Aconitum carmichaeli. Zingiber officinale and Glycyrrhiza uralensis are found to have the ability to reduce pro-inflammatory cytokine production, to inhibit lipopolisaccharide-induced macrophage activation and function, and to lessen the bacterial load and suppress acute and chronic inflammation. Aconitum carmichaeli is known to have vasopressor activity, and positive chronotropic and inotropic

  20. A Rare Case of Septic Shock Secondary to Emphysematous Hepatitis.

    PubMed

    Nada, Khaled M; El Husseini, Ibrahim; Abu Hishmeh, Mohammad E; Shah, Neerav S; Ibragimova, Nadezhda; Basir, Riyad

    2017-01-01

    To describe a case of emphysematous hepatitis which is a rare clinical entity, characterized by a fatal, rapidly progressive infection of the liver with a radiological appearance simulating emphysematous pyelonephritis and to help provide more data about the causative organisms and precipitating factors of this pathology. Relevant literature was reviewed and, to the best of our knowledge, there is limited data regarding the pathogenesis, causative organisms, and management of this condition. Emphysematous hepatitis is a rapidly progressive infection that can be fatal in the absence of appropriate therapeutic intervention. Initial clinical manifestations are usually subtle and thus high clinical suspicion is required for early diagnosis and management of this condition to help decrease the mortality rates.

  1. A Rare Case of Septic Shock Secondary to Emphysematous Hepatitis

    PubMed Central

    El Husseini, Ibrahim; Shah, Neerav S.; Ibragimova, Nadezhda; Basir, Riyad

    2017-01-01

    Objective To describe a case of emphysematous hepatitis which is a rare clinical entity, characterized by a fatal, rapidly progressive infection of the liver with a radiological appearance simulating emphysematous pyelonephritis and to help provide more data about the causative organisms and precipitating factors of this pathology. Data Sources and Synthesis Relevant literature was reviewed and, to the best of our knowledge, there is limited data regarding the pathogenesis, causative organisms, and management of this condition. Conclusion Emphysematous hepatitis is a rapidly progressive infection that can be fatal in the absence of appropriate therapeutic intervention. Initial clinical manifestations are usually subtle and thus high clinical suspicion is required for early diagnosis and management of this condition to help decrease the mortality rates. PMID:28638665

  2. [The hemodynamic characteristics of septic shock and relationship with syndrome types of traditional Chinese medicine].

    PubMed

    He, Jianzhuo; Wang, Lei; Yin, Xin; Guo, Liheng; Zhang, Minzhou

    2016-02-01

    To observe hemodynamic characteristics and the correlation with syndrome types of traditional Chinese medicine (TCM) in patients with septic shock, so as to direct the treatment based on syndrome differentiation. A prospective observation was conducted. Sixty-eight patients with septic shock admitted to the Department of Critical Care Medicine of Dade Road General Hospital of Guangdong Hospital of TCM from January 2013 to July 2015 were enrolled. Pulse indicating continuous cardiac output (PiCCO) was used to monitor the hemodynamic changes, including heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), cardiac index (CI), global end diastolic volume index (GEDVI), extravascular lung water index (EVLWI), maximum rate of the increase in pressure (dPmax) and systemic vascular resistance index (SVRI), for assessment of hemodynamics. According to the CI, the patients were divided into two groups , i.e. high CI group (CI ≥ 50.0 mL×s(-1)×m(-2), n = 34) and low CI group (CI < 50.0 mL×s(-1)×m(-2), n = 34), and the clinical and hemodynamic characteristics of two groups were investigated. The TCM differentiation was conducted with "four syndromes and four methods", and the hemodynamic characteristics of different syndrome types were investigated, the correlation between the TCM syndrome factors and hemodynamic parameters was analyzed. The patients were divided into survival group and death group, and clinical parameters and hemodynamic characteristics were compared between two groups. The acute physiology and chronic health evaluation II (APACHEII) score and blood glucose of low CI group were higher than those of high CI group [APACHEII score: 24.4±7.2 vs. 19.8±7.4, t = -2.279, P = 0.023; blood glucose (mmol/L): 9.7 (7.7, 14.6) vs. 6.7 (5.6, 10.0), Z = -2.257, P = 0.024], CI and GEDVI were lowered [CI (mL×s(-1)×m(-2)): 36.7±8.3 vs. 68.4±16.7, t = 10.285, P = 0.000; GEDVI (mL/m(2)): 689.0 (566.0, 883.8) vs. 838.5 (692.8, 1?247.3), Z = -2

  3. Global end-diastolic volume index vs CVP goal-directed fluid resuscitation for COPD patients with septic shock: a randomized controlled trial.

    PubMed

    Yu, Jiangquan; Zheng, Ruiqiang; Lin, Hua; Chen, Qihong; Shao, Jun; Wang, Daxin

    2017-01-01

    This study aimed to investigate the clinical effects of early goal-directed therapy according to the global end-diastolic volume index (GEDI) on chronic obstructive pulmonary disease (COPD) patients with septic shock. A total of 71 COPD patients with septic shock were randomly assigned to 2 groups. In the control group (n = 37), fluid resuscitation was performed based on the central venous pressure. In the study group (n = 34), fluid resuscitation was performed until GEDI reached 800 mL/m(2). The following indices were observed for the 2 groups: 6- and 24-hour fluid volumes, norepinephrine dosage, 24-hour blood lactate clearance rate, duration of mechanical ventilation, intensive care unit (ICU) length of stay, ICU mortality, and 90-day survival rate. At both 6- and 24-hour measurements, the fluid volume was lower and norepinephrine dosage was higher in the control group than in the study group (P < .05). The blood lactate clearance rate was lower, the duration of mechanical ventilation was longer, and the length of stay in the ICU was longer in the control group than in the study group (P < .05). No significant difference in mortality or 90-day survival rate was found between the 2 groups. The GEDI goal-directed fluid resuscitation shows better clinical effects than that shown by central venous pressure for COPD patients with septic shock; however, it cannot reduce the mortality rate. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Multifocal necrotising fasciitis and septic shock complicating varicella infection in an adult

    PubMed Central

    Mifsud, Simon; Schembri, Emma Louise; Mallia Azzopardi, Charles; Zammit, Maria Alessandra

    2013-01-01

    A 35-year-old woman with a 3-day history of chickenpox, presented to the hospital in septic shock and with multifocal, non-adjacent lesions of necrotising fasciitis. Necrotising fasciitis is a rare yet life-threatening complication of chickenpox. Blood cultures and wound swabs confirmed the presence of Streptococcus pyogenes. The initial emergency management included oxygen, aggressive fluid resuscitation and antimicrobial therapy. Once the patient was stabilised, surgical management ensued. This included debridement and eventual grafting of the necrotic skin lesions. Intensive management and follow-up for 8 weeks were required before the patient was deemed fit for discharge. PMID:24130210

  5. Septic shock in pregnancy due to pyogenic sacroiliitis: a case report

    PubMed Central

    2009-01-01

    Introduction Lower back pain due to sacroiliac joint dysfunction is a common symptom during pregnancy. However, infection of the sacroiliac joint is rare, even more so if no predisposing factors are present. Case presentation After the onset of unspecific acute pain in the left buttock region, a 31-year-old pregnant woman developed septic shock due to pyogenic sacroiliitis. The medical and obstetric management, treatment applied and patient's experience are described. Conclusion The correct diagnosis and treatment of pyogenic sacroiliitis during pregnancy may avoid joint and bone destruction in addition to maternal and fetal complications. PMID:19830110

  6. Lactate clearance as the predictor of outcome in pediatric septic shock

    PubMed Central

    Choudhary, Richa; Sitaraman, Sadasivan; Choudhary, Anita

    2017-01-01

    Context: Septic shock can rapidly evolve into multiple system organ failure and death. In the recent years, hyperlactatemia has been found to be a risk factor for mortality in critically ill adults. Aims: To evaluate the predictive value of lactate clearance and to determine the optimal cut-off value for predicting outcome in children with septic shock. Settings and Design: A prospective observational study was performed on children with septic shock admitted to pediatric Intensive Care Unit (PICU). Subjects and Methods: Serial lactate levels were measured at PICU admission, 24 and 48 h later. Lactate clearance, percent decrease in lactate level in 24 h, was calculated. The primary outcome measure was survival or nonsurvival at the end of hospital stay. We performed receiver operating characteristic analyses to calculate optimal cut-off values. Results: The mean lactate levels at admission were significantly higher in the nonsurvivors than survivors, 5.12 ± 3.51 versus 3.13 ± 1.71 mmol/L (P = 0.0001). The cut-off for lactate level at admission for the best prediction of mortality was determined as ≥4 mmol/L (odds ratio 5.4; 95% confidence interval [CI] =2.45–12.09). Mean lactate clearance was significantly higher in survivors than nonsurvivors (17.9 ± 39.9 vs. −23.2 ± 62.7; P < 0.0001). A lactate clearance rate of <10% at 24 h had a sensitivity and specificity of 78.7% and 72.2%, respectively and a positive predictive value of 83.1% for death. Failure to achieve a lactate clearance of more than 10% was associated with greater risk of mortality (likelihood ratio + 2.83; 95% CI = 1.82–4.41). Conclusions: Serial lactate levels can be used to predict outcome in pediatric septic shock. A 24 h lactate clearance cut-off of <10% is a predictor of in-hospital mortality in such patients. PMID:28367008

  7. Brain damage complicating septic shock: acute haemorrhagic leucoencephalitis as a complication of the generalised Shwartzman reaction.

    PubMed Central

    Graham, D I; Behan, P O; More, I A

    1979-01-01

    The neuropathological findings in six patients who developed neurological signs after the onset of "septic shock" caused by Gram-negative septicaemia are described. The changes in the brains were characteristic of acute haemorrhagic leucoencephalitis, and there was evidence, particularly in the kidneys, of disseminated intravascular coagulation with tubular necrosis and, in some, appearances indistinguishable from membrano-proliferative glomerulonephritis. It is agreed that acute haemorrhagic leucoencephalitis is another manifestation of a generalised Shwartzman reaction, and it is suggested that activation of complement is the final common pathway that produces tissue damage in the brain and kidney. Images PMID:762582

  8. Effects of dopamine, norepinephrine and dobutamine on gastric mucosal pH of septic shock patients

    PubMed Central

    Wu, Yifen; Zhang, Ning; Wu, Yifu; Zheng, Yanping; You, Xiaoen; Cao, Zhuo; Xu, Yaqi

    2016-01-01

    The effect of different vasoactive drugs on the pH [intracellular pH (pHi)] of gastric mucosa in patients with septic shock was evaluated in the present study. According to the vasoactive drugs applied, 48 patients with septic shock were divided into 3 groups: A, B and C, with 16 cases each. Cases of group A were treated with dopamine, those of group B with norepinephrine while those of group C were treated with norepinephrine plus dobutamine. The changes of pH of gastric mucosa were observed before treatment (baseline) and 6, 12, 24 and 48 h after treatment, and the hemodynamic indicators were observed before treatment (baseline) and 6 h after administration. The gastric mucosal pH was not significantly different between two of the three groups before treatment (each at P>0.05). The gastric mucosal pH of group A did not change 6, 12, 24 and 48 h after treatment with drugs compared with the baseline (all at P>0.05), while the gastric mucosal pH in groups B and C were each statistically higher at the time points of 6, 12, 24 and 48 h after treatment with drugs compared with the respective baselines (all at P<0.05). Following treatment with drugs, the gastric mucosal pH of group C at all the time points of 6, 12, 24 and 48 h after treatment were significantly higher than those of groups A and B at the same time points after treatment, while there were some statistical differences between groups A and B at these time points (6, 12, 24 and 48 h after treatment; P<0.05). The hemodynamic indicators of the patients before treatment were not significantly different between two of the three groups (all at P>0.05). Compared with the baseline values, the mean arterial pressure and the cardiac index of each group after treatment were significantly increased, the pulmonary capillary wedge pressure and the central venous pressure of groups B and C significantly increased (all at P<0.05) and the heart rate of group A was significantly increased (P<0.05). In conclusion, the

  9. Improved prognosis of septic shock in patients with cirrhosis: a multicenter study*.

    PubMed

    Galbois, Arnaud; Aegerter, Philippe; Martel-Samb, Patricia; Housset, Chantal; Thabut, Dominique; Offenstadt, Georges; Ait-Oufella, Hafid; Maury, Eric; Guidet, Bertrand

    2014-07-01

    To determine the evolution of the outcome of patients with cirrhosis and septic shock. A 13-year (1998-2010) multicenter retrospective cohort study of prospectively collected data. The Collège des Utilisateurs des Bases des données en Réanimation (CUB-Réa) database recording data related to admissions in 32 ICUs in Paris area. Thirty-one thousand two hundred fifty-one patients with septic shock were analyzed; 2,383 (7.6%) had cirrhosis. None. Compared with noncirrhotic patients, patients with cirrhosis had higher Simplified Acute Physiology Score II (63.1 ± 22.7 vs 58.5 ± 22.8, p < 0.0001) and higher prevalence of renal (71.5% vs 54.8%, p < 0.0001) and neurological (26.1% vs 19.5%, p < 0.0001) dysfunctions. Over the study period, in-ICU and in-hospital mortality was higher in patients with cirrhosis (70.1% and 74.5%) compared with noncirrhotic patients (48.3% and 51.7%, p < 0.0001 for both comparisons). Cirrhosis was independently associated with an increased risk of death in ICU (adjusted odds ratio = 2.524 [2.279-2.795]). In patients with cirrhosis, factors independently associated with in-ICU mortality were as follows: admission for a medical reason, Simplified Acute Physiology Score II, mechanical ventilation, renal replacement therapy, spontaneous bacterial peritonitis, positive blood culture, and infection by fungus, whereas direct admission and admission during the most recent midterm period (2004-2010) were associated with a decreased risk of death. From 1998 to 2010, prevalence of septic shock in patients with cirrhosis increased from 8.64 to 15.67 per 1,000 admissions to ICU (p < 0.0001) and their in-ICU mortality decreased from 73.8% to 65.5% (p = 0.01) despite increasing Simplified Acute Physiology Score II. In-ICU mortality decreased from 84.7% to 68.5% for those patients placed under mechanical ventilation (p = 0.004) and from 91.2% to 78.4% for those who received renal replacement therapy (p = 0.04). The outcome of patients with cirrhosis and

  10. [Effects of mild hypothemia on hemodynamics of systemic and renal of dog with septic shock].

    PubMed

    Liu, Sibo; Liu, Jinjie; Gao, Kai; Cui, Song; Zhou, Hengjie; Liu, Guoliang; Zhang, Yichao; Yang, Rongli

    2015-11-17

    To explore the effects of mild hypothemia on hemodynamics of systemic and renal of dog with septic shock. 40 healthy dogs were randomly and evenly divided into the normal temperature non-infected group (NTNS), normal temperature infected group (NTS), hypothermia non-infected group (MHNS) and hypothermia infected group (MHS). NTS and MHS were pumped through the femoral vein of Escherichia coli (E.coli 1 × 10⁹ cfu/ml) by 0.5 ml·kg⁻¹·h⁻¹, producting septic shock model with high-power cycle. Combining with blood pump devices and low temperature thermostat bath, the MHNS and MHS implemented extracorporeal blood cooling method to maintain the blood in temperature (33 ± 1) °C. 0, 24, 48, 72 h point, tested specimens from femoral vein for renal function. In the 0-72 h. Pulse indicates the continuous cardiac output monitor (PiCCO) monitored systemic hemodynamics on each time point. In the 0-72 h, color Doppler ultrasound (CDFI) measured renal hemodynamic on each time point. There was an increase of SBP (P<0.05), SVR [(2 415 ± 651) dyn·s·cm⁻⁵ vs (1 613 ± 223) dyn·s·cm⁻⁵, P=0.01] and RI (P=0.04) in the MHS group comparing with the NTS group from 24 to 72 h. CO [(3.58 ± 0.44) L/min vs (4.18 ± 0.60) L/min, P=0.04], HR and PSV was decreased in the MHS group. BUN [(8.6 ± 1.6) mmol/L vs (21.2 ± 4.8) mmol/L, P<0.01] and Scr [(167.6 ± 31.2) µmol/L vs (383.8 ± 35.2) µmol/L, P<0.01] was decreased in MHS group comparing with the NTS group. There was a positively correlation between CO and PSV in the canine model of septic shock (P<0.01); and CO was negatively correlated with RI (P<0.01). In this canine model of septic shock, hypothermia can stable systemic and renal hemodynamics, and improve kidney function.

  11. [Effect of ethyl pyruvate on indices of tissue oxygenation and perfusion in dogs with septic shock].

    PubMed

    Kou, Qiu-ye; Guan, Xiang-dong

    2008-01-01

    To investigate the effect of ethyl pyruvate (EP) on indices of tissue oxygenation and perfusion in dogs with septic shock. Twenty dogs with septic shock induced by lipopolysaccharides (LPS) were randomly divided into two groups. Dog randomly received placebo (Ringer's solution; control group, n =8) or EP in lactated Ringer's solution (0.05 g/kg loading dose over 10 minutes, thereafter 0.05 g.kg(-1).h(-1) for 12 hours; EP treatment group, n =12). Indices of tissue oxygenation and perfusion were monitored every 2 hours after basic measurements (pre-LPS), including oxygen delivery (DO2), oxygen consumption (VO2), serum levels of lactate (Lac), mixed venous oxygen saturation (SvO2), urine output, intramucosal pH (pHi), gastric-to-arteria partial pressure of carbon dioxide gap (Pg-a CO2). DO2, VO2, SvO2 and urine output dropped significantly after septic shock (all P<0.05), but serum levels of Lac and P g-a CO2 elevated markedly (both P<0.05). DO2 increased gradually in EP group and there were significantly differences compared with control group after 8 hours (P<0.05). VO2 showed such a tendency, but there was no statistically significant intergroup difference (P>0.05). SvO2 elevated gradually in EP group, even higher than those of pre-LPS after 10 hours and there were significantly differences compared with control group (P<0.05). Serum levels of Lac decreased gradually and there was significant difference compared with control group after 8 hours (P<0.05). Urine output increased in EP group after 8 hours, and such phenomenon did not happen in control group after 10 hours (P<0.05). pHi elevated to a higher level after 6 hours, and Pg-a CO2 elevated in the treatment group, and there were significantly differences compared with control group (both P<0.05). EP infusion resulted in improved tissue oxygenation and perfusion in dogs with septic shock.

  12. Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial.

    PubMed

    Annane, Djillali; Cariou, Alain; Maxime, Virginie; Azoulay, Elie; D'honneur, Gilles; Timsit, Jean François; Cohen, Yves; Wolf, Michel; Fartoukh, Muriel; Adrie, Christophe; Santré, Charles; Bollaert, Pierre Edouard; Mathonet, Armelle; Amathieu, Roland; Tabah, Alexis; Clec'h, Christophe; Mayaux, Julien; Lejeune, Julie; Chevret, Sylvie

    2010-01-27

    Corticosteroid therapy induces potentially detrimental hyperglycemia in septic shock. In addition, the benefit of adding fludrocortisone in this setting is unclear. To test the efficacy of intensive insulin therapy in patients whose septic shock was treated with hydrocortisone and to assess, as a secondary objective, the benefit of fludrocortisone. A multicenter, 2 x 2 factorial, randomized trial, involving 509 adults with septic shock who presented with multiple organ dysfunction, as defined by a Sequential Organ Failure Assessment score of 8 or more, and who had received hydrocortisone treatment was conducted from January 2006 to January 2009 in 11 intensive care units in France. Patients were randomly assigned to 1 of 4 groups: continuous intravenous insulin infusion with hydrocortisone alone, continuous intravenous insulin infusion with hydrocortisone plus fludrocortisone, conventional insulin therapy with hydrocortisone alone, or conventional insulin therapy with intravenous hydrocortisone plus fludrocortisone. Hydrocortisone was administered in a 50-mg bolus every 6 hours, and fludrocortisone was administered orally in 50-microg tablets once a day, each for 7 days. In-hospital mortality. Of the 255 patients treated with intensive insulin, 117 (45.9%), and 109 of 254 (42.9%) treated with conventional insulin therapy died (relative risk [RR], 1.07; 95% confidence interval [CI], 0.88-1.30; P = .50). Patients treated with intensive insulin experienced significantly more episodes of severe hypoglycemia (<40 mg/dL) than those in the conventional-treatment group, with a difference in mean number of episodes per patient of 0.15 (95% CI, 0.02-0.28; P = .003). At hospital discharge, 105 of 245 patients treated with fludrocortisone (42.9%) died and 121 of 264 (45.8%) in the control group died (RR, 0.94; 95% CI, 0.77-1.14; P = .50). Compared with conventional insulin therapy, intensive insulin therapy did not improve in-hospital mortality among patients who were treated

  13. Acute Neonatal Parotitis with Late-Onset Septic Shock due to Streptococcus agalactiae

    PubMed Central

    Boulyana, M.

    2014-01-01

    Acute neonatal parotitis (ANP) is a very rare disease. Most cases are managed conservatively; early antibiotics and adequate hydration may reduce the need for surgery. The most common cause of ANP is Staphylococcus aureus. We report a rare case of acute neonatal parotitis with late-onset septic shock due to Streptococcus agalactiae. The diagnosis was confirmed with ultrasound and isolation of Streptococcus agalactiae from blood culture. The patient was treated successfully with 10 days of intravenous antibiotics and supportive measures. Despite being rare, streptococcal ANP should be considered in the etiological diagnosis of neonatal sepsis. Early diagnosis and appropriate antibiotic might prevent serious complications. PMID:24653847

  14. New Consensus Definitions for Sepsis and Septic Shock: Implications for Treatment Strategies and Drug Development?

    PubMed

    Berry, Michael; Patel, Brijesh V; Brett, Stephen J

    2017-03-01

    Sepsis continues to escape a precise diagnostic definition. The most recent consensus definition, termed Sepsis-3, highlights the importance of the maladaptive and potentially life-threatening host response to infection. After briefly reviewing the history and epidemiology of sepsis, we go on to describe some of the challenges encountered when classifying such a heterogenous disease state. In the context of these new definitions for sepsis and septic shock, we explore current and potentially novel therapies, and conclude by mentioning some of the controversies of this most recent framework.

  15. Timing, method and discontinuation of hydrocortisone administration for septic shock patients

    PubMed Central

    Ibarra-Estrada, Miguel A; Chávez-Peña, Quetzalcóatl; Reynoso-Estrella, Claudia I; Rios-Zermeño, Jorge; Aguilera-González, Pável E; García-Soto, Miguel A; Aguirre-Avalos, Guadalupe

    2017-01-01

    AIM To characterize the prescribing patterns for hydrocortisone for patients with septic shock and perform an exploratory analysis in order to identify the variables associated with better outcomes. METHODS This prospective cohort study included 59 patients with septic shock who received stress-dose hydrocortisone. It was performed at 2 critical care units in academic hospitals from June 1st, 2015, to July 31st, 2016. Demographic data, comorbidities, medical management details, adverse effects related to corticosteroids, and outcomes were collected after the critical care physician indicated initiation of hydrocortisone. Univariate comparison between continuous and bolus administration of hydrocortisone was performed, including multivariate analysis, as well as Kaplan-Meier analysis to compare the proportion of shock reversal at 7 d after presentation. Receiver operating characteristic (ROC) curves determined the best cut-off criteria for initiation of hydrocortisone associated with the highest probability of shock reversal. We addressed the effects of the taper strategy for discontinuation of hydrocortisone, noting risk of shock relapse and adverse effects. RESULTS All-cause 30-d mortality was 42%. Hydrocortisone was administered as a continuous infusion in 54.2% of patients; time to reversal of shock was 49 h longer in patients who were given a bolus administration [59 h (range, 47.5-90.5) vs 108 h (range, 63.2-189); P = 0.001]. The maximal dose of norepinephrine after initiation of hydrocortisone was lower in patients on continuous infusion [0.19 μg/kg per minute (range, 0.11-0.28 μg)] compared with patients who were given bolus [0.34 μg/kg per minute (range, 0.16-0.49); P = 0.004]. Kaplan-Meier analysis revealed a higher proportion of shock reversal at 7 d in patients with continuous infusion compared to those given bolus (83% vs 63%; P = 0.004). There was a good correlation between time to initiation of hydrocortisone and time to reversal of shock (r = 0

  16. Population pharmacokinetics and dosing simulations of cefepime in septic shock patients receiving continuous renal replacement therapy.

    PubMed

    Carlier, Mieke; Taccone, Fabio S; Beumier, Majorie; Seyler, Lucie; Cotton, Frédéric; Jacobs, Frédérique; Roberts, Jason A

    2015-10-01

    The aim of this study was to describe the population pharmacokinetics of cefepime in septic shock patients requiring continuous renal replacement therapy and to determine whether current or alternative dosing regimens can achieve PK/PD targets. In this observational PK study, 62 samples from 13 patients were analysed using non-linear mixed-effects modelling. Different dosing regimens were evaluated using Monte Carlo simulations with ultrafiltration flow rates (UFRs) of 1000, 1500 and 2000 mL/h. The probability of target attainment was calculated against a conservative (60% T(>MIC)) and a higher PK/PD target (100% T(>MIC)) against an MIC of 8 mg/L, the clinical susceptibility breakpoint for Pseudomonas aeruginosa. A one-compartment model with between-subject variability (BSV) on clearance and volume of distribution (V(d)) described the data adequately. UFR was supported as a covariate on both parameters. Typical values for clearance and V(d) were 4.4L/h (BSV 37%) and 40.9L (BSV 20%), respectively. Dosing simulations showed failure to achieve both a conservative and a higher PK/PD target using a dose of 1g q12h for patients treated with a high UFR (≥1500 mL/h). The dose of 2g q8h or 1g q6h leads to optimal target attainment for high UFR. One gram q8h is optimal for low UFR (≤1000 mL/h). We found important variability in PK parameters. Dosing simulations show that a dose of 2g q8h or 1g q6h is needed to ensure rapid achievement of adequate levels if the UFR is ≥1500 mL/h and 1g q8h for low UFR (≤1000 mL/h).

  17. [Systematic medical record review in Skåne. Diagnostic codes were often wrong in severe sepsis and septic shock].

    PubMed

    Johansson, Daniel; Ekström, Helena; Beronius, Ellen; Rasmussen, Magnus

    2015-09-14

    The reliability of official registers of diagnosis depends on proper adherence to guidelines for diagnosis and diagnosis coding. Such guidelines for severe sepsis and septic shock have changed over the years, reflecting improved knowledge of these serious conditions. In order to investigate the compliance to current Swedish guidelines for diagnosis and coding of severe sepsis and septic shock, we studied the medical records from 300 patients with Escherichia coli bacteremia and 300 patients with Staphylococcus aureus bacteremia. Our study showed that out of 161 patients who fulfilled the criteria for either severe sepsis or septic shock, only 29 (18%) received an accurate diagnosis code. Thus, severe sepsis appears to be underappreciated in official registers of diagnosis in Sweden. It is important to improve the adherence to the present diagnosis guidelines in order for the registers to be reliable.

  18. Effect of mode of hydrocortisone administration on glycemic control in patients with septic shock: a prospective randomized trial.

    PubMed

    Loisa, Pekka; Parviainen, Ilkka; Tenhunen, Jyrki; Hovilehto, Seppo; Ruokonen, Esko

    2007-01-01

    Low-dose hydrocortisone treatment is widely accepted therapy for the treatment of vasopressor-dependent septic shock. The question of whether corticosteroids should be given to septic shock patients by continuous or by bolus infusion is still unanswered. Hydrocortisone induces hyperglycemia and it is possible that continuous hydrocortisone infusion would reduce the fluctuations in blood glucose levels and that tight blood glucose control could be better achieved with this approach. In this prospective randomized study, we compared the blood glucose profiles, insulin requirements, amount of nursing workload needed, and shock reversal in 48 septic shock patients who received hydrocortisone treatment either by bolus or by continuous infusion with equivalent dose (200 mg/day). Duration of hydrocortisone treatment was five days. The mean blood glucose levels were similar in the two groups, but the number of hyperglycemic episodes was significantly higher in those patients who received bolus therapy (15.7 +/- 8.5 versus 10.5 +/- 8.6 episodes per patient, p = 0.039). Also, more changes in insulin infusion rate were needed to maintain strict normoglycemia in the bolus group (4.7 +/- 2.2 versus 3.4 +/- 1.9 adjustments per patient per day, p = 0.038). Hypoglycemic episodes were rare in both groups. No difference was seen in shock reversal. Strict normoglycemia is more easily achieved if the hydrocortisone therapy is given to septic shock patients by continuous infusion. This approach also reduces nursing workload needed to maintain tight blood glucose control.

  19. Efficacy of polymyxin B-immobilized fiber hemoperfusion for patients with septic shock caused by Gram-negative bacillus infection

    PubMed Central

    Saito, Nobuyuki; Sugiyama, Kazuhiro; Ohnuma, Testu; Kanemura, Takashi; Nasu, Michitaka; Yoshidomi, Yuya; Tsujimoto, Yuta; Adachi, Hiroshi; Koami, Hiroyuki; Tochiki, Aito; Hori, Kota; Wagatsuma, Yukiko; Matsumoto, Hisashi

    2017-01-01

    Septic shock-associated mortality in intensive care units (ICUs) remains high, with reported rates ranging 30–50%. In particular, Gram-negative bacilli (GNB), which induce significant inflammation and consequent multiple organ failure, are the etiological bacterial agent in 40% of severe sepsis cases. Hemoperfusion using polymyxin B-immobilized fiber (PMX), which adsorbs endotoxin, is expected to reduce the inflammatory sepsis cascade due to GNB. However, the clinical efficacy of this treatment has not yet been demonstrated. Here, we aimed to verify the efficacy of endotoxin adsorption therapy using PMX through a retrospective analysis of 413 patients who received broad spectrum antimicrobial treatment for GNB-related septic shock between January 2009 and December 2012 in 11 ICUs of Japanese tertiary hospitals. After aligning the patients' treatment time phases, we classified patients in two groups depending on whether PMX hemoperfusion (PMXHP) therapy was administered or not within 24 hours after ICU admission (PMXHP group: n = 134, conventional group: n = 279). The primary study endpoint was the mortality rate at 28 days after ICU admission. The mean age was 72.4 (standard deviation: 12.6) years, and the mean Sequential Organ Failure Assessment score at ICU admission was 9.9 (3.4). The infection sites included intra-abdominal (38.0%), pulmonary (18.9%), and urinary tract (32.2%), and two thirds of all patients had GNB-related bacteremia. Notably, the mortality at 28 days after ICU admission did not differ between the groups (PMXHP: 29.1% vs. conventional: 29.0%, P = 0.98), and PMXHP therapy was not found to improve this outcome in a Cox regression analysis (hazard ratio = 1.16; 95% confidence interval, 0.81–1.64, P = 0.407). We conclude that PMX-based endotoxin adsorption within 24 hours from ICU admission was not associated with mortality among patients with septic shock due to GNB. Trial registration: University Hospital Medical Information Network Clinical

  20. Efficacy of polymyxin B-immobilized fiber hemoperfusion for patients with septic shock caused by Gram-negative bacillus infection.

    PubMed

    Saito, Nobuyuki; Sugiyama, Kazuhiro; Ohnuma, Testu; Kanemura, Takashi; Nasu, Michitaka; Yoshidomi, Yuya; Tsujimoto, Yuta; Adachi, Hiroshi; Koami, Hiroyuki; Tochiki, Aito; Hori, Kota; Wagatsuma, Yukiko; Matsumoto, Hisashi

    2017-01-01

    Septic shock-associated mortality in intensive care units (ICUs) remains high, with reported rates ranging 30-50%. In particular, Gram-negative bacilli (GNB), which induce significant inflammation and consequent multiple organ failure, are the etiological bacterial agent in 40% of severe sepsis cases. Hemoperfusion using polymyxin B-immobilized fiber (PMX), which adsorbs endotoxin, is expected to reduce the inflammatory sepsis cascade due to GNB. However, the clinical efficacy of this treatment has not yet been demonstrated. Here, we aimed to verify the efficacy of endotoxin adsorption therapy using PMX through a retrospective analysis of 413 patients who received broad spectrum antimicrobial treatment for GNB-related septic shock between January 2009 and December 2012 in 11 ICUs of Japanese tertiary hospitals. After aligning the patients' treatment time phases, we classified patients in two groups depending on whether PMX hemoperfusion (PMXHP) therapy was administered or not within 24 hours after ICU admission (PMXHP group: n = 134, conventional group: n = 279). The primary study endpoint was the mortality rate at 28 days after ICU admission. The mean age was 72.4 (standard deviation: 12.6) years, and the mean Sequential Organ Failure Assessment score at ICU admission was 9.9 (3.4). The infection sites included intra-abdominal (38.0%), pulmonary (18.9%), and urinary tract (32.2%), and two thirds of all patients had GNB-related bacteremia. Notably, the mortality at 28 days after ICU admission did not differ between the groups (PMXHP: 29.1% vs. conventional: 29.0%, P = 0.98), and PMXHP therapy was not found to improve this outcome in a Cox regression analysis (hazard ratio = 1.16; 95% confidence interval, 0.81-1.64, P = 0.407). We conclude that PMX-based endotoxin adsorption within 24 hours from ICU admission was not associated with mortality among patients with septic shock due to GNB. University Hospital Medical Information Network Clinical Trial Registry (UMIN

  1. Spontaneous intrahepatic gas gangrene and fatal septic shock.

    PubMed

    Meyns, E; Vermeersch, N; Ilsen, B; Hoste, W; Delooz, H; Hubloue, I

    2009-01-01

    Gas gangrene of the liver is a rare clinical syndrome associated with a high rate of mortality. It is mostly associated with malignancy and immunosuppression. We report on a male patient who presented at the department of emergency medicine with high fever but no localised complaints. CT scan revealed a cavitary lesion filled with air in the liver. Clostridium perfringens was proved to be present in the hepatic lesion and the blood, and clostridium perfringens sepsis with gas gangrene of the liver was diagnosed. Despite early diagnosis and treatment the patient died. The importance of "an aggressive treatment policy" in this kind of life-threatening disease is emphasised.

  2. [Osteomyelitis after septic trochanteric bursitis - clinical case].

    PubMed

    Miguel, C; Gonçalves, I; Matos, Maria L; Coelho, Paulo Clemente

    2010-01-01

    We report the clinical case of a 76 years-old woman with a subacute trochanteric inflammatory pain with low-grade fever and laboratory markers of acute inflammation, associated with the ultrasonographic evidence of bursitis and radiologic evidence of femoral erosions, that resolved after intravenous antibiotherapy. Although rare, the infectious etiology should be considered in patients with clinical manifestations of bursitis and signs of systemic involvement.

  3. Early Trophic Enteral Nutrition Is Associated With Improved Outcomes in Mechanically Ventilated Patients With Septic Shock: A Retrospective Review.

    PubMed

    Patel, Jayshil J; Kozeniecki, Michelle; Biesboer, Annie; Peppard, William; Ray, Ananda S; Thomas, Seth; Jacobs, Elizabeth R; Nanchal, Rahul; Kumar, Gagan

    2016-08-01

    Current guidelines provide weak recommendations for starting enteral nutrition (EN) in patients with septic shock (on vasopressor support). Outcomes of patients receiving EN in septic shock on vasopressor support have not been well studied. We hypothesize that early trophic EN in mechanically ventilated patients with septic shock is associated with improved outcomes. Single-center retrospective study of mechanically ventilated patients admitted with septic shock to identify patients receiving (1) no EN, (2) <600 kcal/d within 48 hours, and (3) ≥600 kcal/d within 48 hours. Outcomes studied included in-hospital mortality, length of intensive care unit stay (LOS), duration of mechanical ventilation (DOMV), and complications of feeding intolerance. Sixty-six patients were identified. In all, 15 received no EN, 37 received <600 kcal/d, and 14 received ≥600 kcal/d EN daily. Median LOS was 12, 5, and 13 days, respectively. The LOS was lower in patients receiving <600 kcal/d when compared to either no EN (P < .001) or those receiving ≥600 kcal/d (P < .001). Median DOMV was lower in patients receiving <600 kcal/d (median 3, P < .001) as compared to no EN (median 7, P < .001) or those receiving ≥600 kcal/d (median 7.5, P < .001). Mortality was not different. There were no significant complications among groups. In patients with septic shock, those receiving <600 kcal/d EN within 48 hours had lower DOMV and LOS when compared to those who did not receive EN or those who received ≥600 kcal/d. These observations provide strong justification for prospective evaluation of the effect of early trophic EN in patients with septic shock. © The Author(s) 2014.

  4. Removal of 2-arachidonylglycerol by direct hemoperfusion therapy with polymyxin B immobilized fibers benefits patients with septic shock.

    PubMed

    Kase, Yoichi; Obata, Toru; Okamoto, Yasuhisa; Iwai, Kenichi; Saito, Keita; Yokoyama, Keitaro; Takinami, Masanori; Tanifuji, Yasumasa

    2008-10-01

    Arachidonylethanolamide (AEA) and 2-arachidonylglycerol (2-AG) are endocannabinoids involved in septic shock, and 8-epi prostaglandin F2alpha (F2-isoprostane) is a biomarker of oxidative stress in biological systems. Because the antibiotic polymyxin B absorbs endocannabinoids as well as endotoxins, direct hemoperfusion therapy with polymyxin B-immobilized fibers (PMX-DHP) decreases serum levels of endocannabinoids. To investigate the features of sepsis and determine the proper use of PMX-DHP, we measured the changes in levels of endocannabinoids and F2-isoprostane in patients with septic shock. Twenty-six patients with septic shock, including those with septic shock induced by peritonitis, underwent laparotomy for drainage. Endocannabinoids absorption with PMX-DHP was examined in two groups of patients: patients whose mean arterial blood pressure (mABP) had increased more than 20 mm Hg (responder group; N = 13); and patients iwhose mABP did not increase or had increased no more than 20 mm Hg (non-responder group; N = 13). Levels of AEA did not change after PMX-DHP in either the non-responder or responder groups, whereas levels of 2-AG decreased significantly after PMX-DHP in the responder group, but not in the non-responder group. F2-isoprostane gradually increased after PMX-DHP treatment; on the other hand, levels of F2-isoprostane remained constant in the responder group. Patients with septic shock are under considerable oxidative stress, and 2-AG plays an important role in the cardiovascular status of these patients. The removal of 2-AG by PMX-DHP benefits patients with septic shock by stabilizing cardiovascular status and decreasing long-term oxidative stress.

  5. Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis.

    PubMed

    Rowan, Kathryn M; Angus, Derek C; Bailey, Michael; Barnato, Amber E; Bellomo, Rinaldo; Canter, Ruth R; Coats, Timothy J; Delaney, Anthony; Gimbel, Elizabeth; Grieve, Richard D; Harrison, David A; Higgins, Alisa M; Howe, Belinda; Huang, David T; Kellum, John A; Mouncey, Paul R; Music, Edvin; Peake, Sandra L; Pike, Francis; Reade, Michael C; Sadique, M Zia; Singer, Mervyn; Yealy, Donald M

    2017-06-08

    After a single-center trial and observational studies suggesting that early, goal-directed therapy (EGDT) reduced mortality from septic shock, three multicenter trials (ProCESS, ARISE, and ProMISe) showed no benefit. This meta-analysis of individual patient data from the three recent trials was designed prospectively to improve statistical power and explore heterogeneity of treatment effect of EGDT. We harmonized entry criteria, intervention protocols, outcomes, resource-use measures, and data collection across the trials and specified all analyses before unblinding. After completion of the trials, we pooled data, excluding the protocol-based standard-therapy group from the ProCESS trial, and resolved residual differences. The primary outcome was 90-day mortality. Secondary outcomes included 1-year survival, organ support, and hospitalization costs. We tested for treatment-by-subgroup interactions for 16 patient characteristics and 6 care-delivery characteristics. We studied 3723 patients at 138 hospitals in seven countries. Mortality at 90 days was similar for EGDT (462 of 1852 patients [24.9%]) and usual care (475 of 1871 patients [25.4%]); the adjusted odds ratio was 0.97 (95% confidence interval, 0.82 to 1.14; P=0.68). EGDT was associated with greater mean (±SD) use of intensive care (5.3±7.1 vs. 4.9±7.0 days, P=0.04) and cardiovascular support (1.9±3.7 vs. 1.6±2.9 days, P=0.01) than was usual care; other outcomes did not differ significantly, although average costs were higher with EGDT. Subgroup analyses showed no benefit from EGDT for patients with worse shock (higher serum lactate level, combined hypotension and hyperlactatemia, or higher predicted risk of death) or for hospitals with a lower propensity to use vasopressors or fluids during usual resuscitation. In this meta-analysis of individual patient data, EGDT did not result in better outcomes than usual care and was associated with higher hospitalization costs across a broad range of patient and

  6. Can sTREM-1 predict septic shock & death in late-onset neonatal sepsis? A pilot study.

    PubMed

    Arízaga-Ballesteros, Víctor; Alcorta-García, Mario René; Lázaro-Martínez, Lizzeth Carolina; Amézquita-Gómez, Jesús Manuel; Alanís-Cajero, José Manuel; Villela, Luis; Castorena-Torres, Fabiola; Lara-Díaz, Víctor Javier

    2015-01-01

    The transmembrane glycoprotein TREM-1 triggers an inflammatory response. Its soluble fraction (sTREM-1) has been shown to have diagnostic accuracy for late-onset neonatal sepsis (LONS). Until now, the potential of sTREM-1 to predict septic shock and/or death in septic neonates has not been explored. This study obtained estimates of the incidence and prevalence of septic shock and/or death in septic neonates for future sample size calculations for confirmatory studies and evaluated the feasibility of using sTREM-1 as a predictor of septic shock and/or death in neonates with LONS criteria. A pilot study with a cross-sectional design was performed from May 1(st) to October 31(st), 2012. The participants were hospitalized neonates who, after three days of life, were diagnosed as having LONS. Plasma sTREM-1 was quantified by ELISA. The main outcome measurement was the development of septic shock and/or death. Of 71 eligible subjects, nine (12.7%) progressed to septic shock and/or death. In the LONS-Non-Shock group, the sTREM-1 median and interquartile range (IQR) plasma value were 10 (10 to 70) pg/mL. In the LONS & Shock/Death group, the values were 567 (260 to 649) pg/mL. These values were significantly different (Mann-Whitney's U test, p=0.001). A ROC curve for a proposed sTREM-1 cut-off value of 300 pg/mL exhibited an area under the curve of 0.884 (95% CI=0.73 to 1.0; p<0.0001), with a sensitivity of 0.78 (95% CI=0.46 to 0.94) and specificity of 0.97 (95% CI=0.92 to 0.99); PPV would be 0.78 (95% CI=0.46 to 0.94) and NPV 0.97 (95% CI=0.92 to 0.99). In neonates with LONS, sTREM-1 has the potential to provide an excellent predictive value for septic shock/death. Larger sample sizes are needed to identify the optimal cut-off value of plasma sTREM-1 for this diagnosis and to provide diagnostic accuracy measures. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Severe Sepsis and Septic Shock Trials (ProCESS, ARISE, ProMISe): What is Optimal Resuscitation?

    PubMed

    Osborn, Tiffany M

    2017-04-01

    Between 2014 and 2015, 3 independent, multicenter, randomized controlled trials evaluated early goal-directed therapy (EGDT) in severe sepsis and septic shock: Protocolized Care for Early Septic Shock (ProCESS) from the United States; Australasian Resuscitation in Sepsis Evaluation (ARISE), and Protocolised Management in Sepsis (ProMISe) in the United Kingdom. All 3 trials confirmed that there was no survival benefit of EGDT compared to usual resuscitation. How should we define usual care for sepsis given these study findings? Furthermore, the definition of sepsis has now been updated. This article reviews key findings of these 3 trials and discusses these important issues in sepsis management.

  8. Inflammatory markers in SIRS, sepsis and septic shock.

    PubMed

    Herzum, I; Renz, H

    2008-01-01

    Despite great advancement in the understanding of the pathophysiology and in the development of novel therapeutic approaches, mortality of sepsis still remains unacceptably high. Adequate laboratory diagnostics represents a major requirement for the improvement of this situation. For a better understanding of the immunological dysregulation in this disease, several markers are now available for routine diagnostics in the clinical laboratory. They include the cytokines interleukin (IL) -6, IL-8, procalcitonin and the LPS-binding protein (LBP). These novel markers will be compared to the conventional procedure of diagnosing inflammatory and infectious disease, such as measurements of C-reactive protein (CRP) as a major acute phase protein and differential blood counting. Important questions addressed in this review are the usefulness of these markers for early diagnosis, their role as prognostic markers and in the risk assessment of patients. Furthermore, we will discuss whether these parameters are to differentiate between systemic inflammatory response syndrome (SIRS) and sepsis at its different degrees. In the case of an infectious nature of the disease, it is important to differentiate between viral or bacterial origin and to monitor the responsiveness of antibiotic therapies. The literature was analysed with focus on the evidence for diagnostic and analytical performance. For this purpose international definition and staging criteria were used in context of criteria for assay performance including sensitivity, specificity, negative and positive predictive values, ROC analysis and other analytical criteria.

  9. Predicting treatment failure in severe sepsis and septic shock: looking for the Holy Grail

    PubMed Central

    2013-01-01

    Procalcitonin has been proposed as a specific biomarker of bacterial infections and has been related to the severity of sepsis. The prognostic ability of the initial concentrations of procalcitonin in sepsis is controversial. Some studies find higher initial concentrations in non-survivors but others find no differences. Prognostic assessment based on follow-up of procalcitonin levels may be better than evaluation of the initial levels of procalcitonin. The persistence of elevated procalcitonin levels is indicative of poor prognosis and is associated with mortality. Procalcitonin kinetics could be a tool for assessing the evolution of severe sepsis and sepsis shock. Procalcitonin should find its place as a biomarker for predicting treatment failure of severe sepsis and septic shock. PMID:24004571

  10. Copeptin, a stable peptide of the arginine vasopressin precursor, is elevated in hemorrhagic and septic shock.

    PubMed

    Morgenthaler, Nils G; Müller, Beat; Struck, Joachim; Bergmann, Andreas; Redl, Heinz; Christ-Crain, Mirjam

    2007-08-01

    Arginine vasopressin (AVP) levels are increased in hemorrhagic and septic shock. Measurement of AVP levels has limitations due to its short half-life and cumbersome detection method. Copeptin is a more stable peptide derived from the same precursor molecule. We evaluated the plasma copeptin concentration in two independent studies: first, in an experimental baboon model of hemorrhagic shock, and second, in a prospective observational study of 101 consecutive critically ill patients at a university hospital. Copeptin was measured with a newly developed sandwich immunoassay using two polyclonal antibodies to the C-terminal region (amino acid sequence 132-164) of pre-pro-AVP. Copeptin concentrations in hemorrhagic shock increased markedly from median (range) of 7.5 [2.7-13) to 269 pM (241-456 pM). After reperfusion, copeptin levels dropped within hours to a plateau of 27 pM (15-78 pM). In the critically ill patient cohort, copeptin values increased significantly with the severity of the disease and were in patients without sepsis [27.6 pM [2.3-297 pM]), in sepsis [50.0 pM [8.5-268 pM]), in severe sepsis [73.6 pM [15.3-317 pM]), and in septic shock [171.5 pM (35.1-504 pM] compared with 4.1 pM (1.0-13.8 pM) in healthy controls (P for all vs. controls <0.001). On admission, circulating copeptin levels were higher in nonsurvivors (171.5 pM, 46.5-504.0 pM) as compared with survivors (86.8 pM, 8.5-386.0 pM; P = 0.01). Copeptin levels correlated with basal cortisol levels (r = 0.42; P < 0.001) and osmolality (r = 0.42; P < 0.001). In a logistic regression model including other covariates besides copeptin (e.g., determinants of fluid status) on survival, serum copeptin levels were the only independent significant predictor of outcome (P = 0.03). Copeptin concentrations are elevated in hemorrhagic and septic shock. Copeptin was higher on admission in nonsurvivors as compared with survivors, suggesting copeptin as a prognostic marker in sepsis. The availability of a reliable

  11. Septic Shock of Unknown Origin: A Case Report of a Pseudoaneurysm of the Mitral-Aortic Intervalvular Fibrosa

    PubMed Central

    Gil, Julio; Antunes, Hugo; Marmelo, Bruno; Abreu, Luis; Goncalves, Maria Luisa; dos Santos, Luis Ferreira; Cabral, Jose Costa

    2017-01-01

    Pseudoaneurysm of the mitral-aortic intervalvular fibrosa (P-MAIVF) is a rare complication of infective endocarditis and trauma, particularly of aortic valve surgery. Clinical symptoms are usually unspecific and generally due to complications. Transesophageal echocardiography (TEE) is the most commonly used exam to diagnose P-MAIVF. The main echocardiographic feature is the presence of a cavity communicating with the left ventricular outflow tract that expands during systole and collapses during diastole. Most frequent complications are formation of a fistulous tract and compression of adjacent structures. Surgical correction is usually the treatment of choice. The authors describe a case of a female patient with a septic shock of unclear origin. After antibiotic therapy and organ-supporting measures without apparent improvements, a TEE revealed infective endocarditis, complicated with P-MAIVF. Despite adequate treatment, the patient did not survive for long enough to be submitted to surgical repair. PMID:28179972

  12. “Immunonutrition” Has Failed to Improve Peritonitis-Induced Septic Shock in Rodents

    PubMed Central

    Boisramé-Helms, Julie; Meyer, Grégory; Degirmenci, Su Emmanuelle; Burban, Mélanie; Schini-Kerth, Valérie; Cynober, Luc; De Bandt, Jean-Pascal; Hasselmann, Michel; Meziani, Ferhat

    2016-01-01

    Background Immunonutrition in sepsis, including n-3 poly-unsaturated fatty acids (PUFAs) or L-arginine supplementation, is a controversial issue that has yielded a great number of studies for the last thirty-five years, and the conclusions regarding the quantity and quality of this support in patients are deceiving. The aim of the present experimental study is to investigate the effects of a pretreatment with enteral nutrition enriched with n-3 PUFAs or L-arginine on vascular dysfunctions, inflammation and oxidative stress during septic shock in rats. Design Rats were fed with enteral Peptamen® HN (HN group), Peptamen® AF containing n-3 PUFAs (AF group) or Peptamen® AF enriched with L-arginine (AFA group). On day 4, peritonitis by cecal ligation and puncture (CLP) was performed. Rats were resuscitated (H18) once septic shock was established. After a 4-hour resuscitation, vessels and organs were harvested to assess inflammation, superoxide anion, nitric oxide and prostacyclin levels. Ex-vivo vascular reactivity was also performed. Results Compared to CLP-AF or CLP-HN groups, 47.6% of CLP-AFA rats died before the beginning of hemodynamic measurements (vs. 8.0% and 20.0% respectively, p<0.05). AF and AFA rats required significantly increased norepinephrine infusion rates to reach the mean arterial pressure objective, compared to CLP-HN rats. Both CLP-AF and CLP-AFA reduced mesenteric resistance arterial contractility, decreased vascular oxidative stress, but increased NF-κB (0.40±0.15 in CLP-AF and 0.69±0.06 in CLP-AFA vs. 0.09±0.03 in SHAM rats and 0.30±0.06 in CLP-HN, ß-actin ratio, p<0.05) and pIκB expression (0.60±0.03 in CLP-AF and 0.94±0.15 in CLP-AFA vs. 0.04±0.01 in SHAM rats and 0.56±0.07 in CLP-HN, ß-actin ratio, p<0.05), nitric oxide and prostacyclin production in septic rats. Conclusions Although n-3 PUFAs or L-arginine supplementation exhibited an antioxidant effect, it worsened the septic shock-induced vascular dysfunction. Furthermore

  13. Albumin replacement in patients with severe sepsis or septic shock.

    PubMed

    Caironi, Pietro; Tognoni, Gianni; Masson, Serge; Fumagalli, Roberto; Pesenti, Antonio; Romero, Marilena; Fanizza, Caterina; Caspani, Luisa; Faenza, Stefano; Grasselli, Giacomo; Iapichino, Gaetano; Antonelli, Massimo; Parrini, Vieri; Fiore, Gilberto; Latini, Roberto; Gattinoni, Luciano

    2014-04-10

    Although previous studies have suggested the potential advantages of albumin administration in patients with severe sepsis, its efficacy has not been fully established. In this multicenter, open-label trial, we randomly assigned 1818 patients with severe sepsis, in 100 intensive care units (ICUs), to receive either 20% albumin and crystalloid solution or crystalloid solution alone. In the albumin group, the target serum albumin concentration was 30 g per liter or more until discharge from the ICU or 28 days after randomization. The primary outcome was death from any cause at 28 days. Secondary outcomes were death from any cause at 90 days, the number of patients with organ dysfunction and the degree of dysfunction, and length of stay in the ICU and the hospital. During the first 7 days, patients in the albumin group, as compared with those in the crystalloid group, had a higher mean arterial pressure (P=0.03) and lower net fluid balance (P<0.001). The total daily amount of administered fluid did not differ significantly between the two groups (P=0.10). At 28 days, 285 of 895 patients (31.8%) in the albumin group and 288 of 900 (32.0%) in the crystalloid group had died (relative risk in the albumin group, 1.00; 95% confidence interval [CI], 0.87 to 1.14; P=0.94). At 90 days, 365 of 888 patients (41.1%) in the albumin group and 389 of 893 (43.6%) in the crystalloid group had died (relative risk, 0.94; 95% CI, 0.85 to 1.05; P=0.29). No significant differences in other secondary outcomes were observed between the two groups. In patients with severe sepsis, albumin replacement in addition to crystalloids, as compared with crystalloids alone, did not improve the rate of survival at 28 and 90 days. (Funded by the Italian Medicines Agency; ALBIOS ClinicalTrials.gov number, NCT00707122.).

  14. Procalcitonin determined at emergency department as na early indicator of progression to septic shock in patient with sepsis associated with ureteral calculi.

    PubMed

    Ko, Young Hwii; Ji, Yoon Seob; Park, Sin-Youl; Kim, Su Jin; Song, Phil Hyun

    2016-01-01

    To investigate the role of initial procalcitonin (PCT) level as an early predictor of septic shock for the patient with sepsis induced by acute pyelonephritis (APN) secondary to ureteral calculi. The data from 49 consecutive patients who met criteria of sepsis due to APN following ureteral stone were collected and divided into two groups: with (n=15) or without (n=34) septic shock. The clinical variables including PCT level for this outcome were retrospectively compared by univariate analysis, followed by multivariable logistic regression model. All subjects had hydronephrosis, and were hospitalized with the mean of 11.8 days (3-42 days). The mean size of the ureteral stones was 7.5mm (3-30mm), and 57% were located in upper ureter. At univariate analysis, patients with septic shock were significantly older, a higher proportion had hypertension, lower platelet count and serum albumin level, higher CRP and PCT level, and higher positive blood culture rate. Multivariate models indicated that lower platelet count and higher PCT level are independent risk factors (p=0.043 and 0.046, respectively). In ROC curve, the AUC was significantly wider in PCT (0.929), compared with the platelet count (0.822, p=0.004). At the cut-off of 0.52ng/mL, the sensitivity and specificity were 86.7% and 85.3%. Our study demonstrated elevated initial PCT levels as an early independente predictor to progress into septic shock in patients with sepsis associated with ureteral calculi.

  15. Polymyxin B-immobilised haemoperfusion and mortality in critically ill patients with sepsis/septic shock: a protocol for a systematic review and meta-analysis

    PubMed Central

    Fujii, Tomoko; Ganeko, Riki; Kataoka, Yuki; Featherstone, Robin; Bagshaw, Sean M

    2016-01-01

    Introduction Polymyxin-B immobilised haemoperfusion (PMX-HP) is a promising adjuvant strategy for the treatment of sepsis and septic shock. PMX-HP therapy works by clearing circulating endotoxin through binding to polymyxin-immobilised fibres during haemoperfusion. Small clinical trials have shown that PMX-HP therapy is associated with improved haemodynamic profile, oxygenation and survival. However, clear inferences have been largely inconclusive due to limitations in study design (eg, small, unblinded) and generalisability. We therefore propose to perform an up-to-date systematic review and evidence synthesis to describe the efficacy, safety and effectiveness of PMX-HP for adult patients with sepsis or septic shock. Methods and analysis We will search the following databases from 1946 to 2016 MEDLINE (Ovid), EMBASE (Ovid), Cochrane Library, Health Technology Assessment Database (HTA), Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed and ‘Igaku Chuo Zasshi’ (ICHUSHI) for randomised controlled trials of PMX-HP in critically ill patients with sepsis or septic shock. There will be no language restrictions in the electronic search for studies. Two reviewers will extract data and appraise the quality of each study independently. The primary outcome will be the pooled risk ratio of 28-day all-cause mortality. Serious adverse events and changes in organ dysfunction scores will also be evaluated. The secondary outcomes will be 90-day all-cause mortality, changes in haemodynamic profile and endotoxin levels, and health services use. Ethics and dissemination Our systematic review will synthesise the evidence on use of the PMX-HP as an adjuvant therapy in sepsis/septic shock to improve patient-centred, physiological and health services outcomes. Research ethics is not required for this review. The study will be disseminated by peer-reviewed publication and conference presentation. Trial registration number CRD42016038356. PMID:27872122

  16. Polymyxin B-immobilised haemoperfusion and mortality in critically ill patients with sepsis/