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Sample records for clinical septic shock

  1. Septic shock

    MedlinePlus

    Septic shock is a serious condition that occurs when a body-wide infection leads to dangerously low blood ... Septic shock occurs most often in the very old and the very young. It may also occur in ...

  2. Septic shock; current pathogenetic concepts from a clinical perspective.

    PubMed

    Tsiotou, Adelais G; Sakorafas, George H; Anagnostopoulos, George; Bramis, John

    2005-03-01

    Sepsis is an infection-induced syndrome characterized by a generalized inflammatory state and represents a frequent complication in the surgical patient. The normal reaction to infection involves a series of complex immunologic processes. A potent, complex immunologic cascade ensures a prompt protective response to microbial invasion in humans. Although activation of the immune system during microbial invasion is generally protective, septic shock develops in a number of patients as a consequence of excessive or poorly regulated immune response to the offending organism (Gram-negative or Gram-positive bacteria, fungi, viruses, or microbial toxins). This unbalanced reaction may harm the host through a maladaptive release of endogenously generated inflammatory compounds. Many mechanisms are involved in the pathogenesis of septic shock, including the release of cytokines, the activation of neutrophils, monocytes, and microvascular endothelial cells, as well as the activation of neuroendocrine reflexes and plasma protein cascade systems, such as the complement system, the intrinsic (contact system) and extrinsic pathways of coagulation, and the fibrinolytic system. In critically ill patients, the gastrointestinal tract plays a central role in the pathogenesis of septic shock. The potential for complementary and synergistic interaction of the different components in this cascade highlights the difficulty encountered in trying to identify a single means of altering the progression of sepsis and septic shock to multiple organ dysfunction syndrome (MODS) and multiple organ failure (MOF). PMID:15735579

  3. Steroids in the treatment of clinical septic shock.

    PubMed Central

    Schumer, W

    1976-01-01

    A prospective (Part I) and a retrospective (Part II) study were used to determine the safety and efficacy of corticosteroids in the treatment of septic shock. In Part I, 172 consecutive patients in septic shock admitted over an 8-year period were treated with either steroid or saline: 43 received dexamethasone (DMP), 43 received methylprednisolone (MPS), and 86 received saline. The study was double-blind and randomized, and the three groups were compared for age, severity of shock, presence of underlying disease, and year of study. In the 86 saline-treated patients, the mortality rate was 38.4% (33/86); in the steroid-treated patients, it was 10.4% (9/86). With MPS the mortality rate was 11.6% (5/43), and with DMP it was 9.3% (4/43). Thus, overall mortality was significantly less in the steroid-treated group than in the control group. Further, there was no significant difference in mortality rate between the DMP- and the MPS-treated patients. In Part II, 328 patients were studied retrospectively. One-hundred sixty were treated without steroid, and 168 were treated with either DMP or MPS. Again, the two groups of patients were compared for severity of shock, underlying disease, age, and year of study. Mortality among patients treated without steroid was 42.5% (68/160) and among patients treated with steroid was 14% (24/168); there was no significant difference in mortality rate between DMP- and MPS-treated patients. In Parts I and II combined, complications occurred in 6% of steroid-treated patients with no significant difference between DMP- and MPS-treated groups. PMID:786190

  4. 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

  5. Acute Biliary Septic Shock

    PubMed Central

    1990-01-01

    Forty-seven cases of biliary tract infection with septic shock are presented. The sepsis was caused by empyema of the gallbladder in 23 cases and by cholangitis in the remainder. Gallstones were most frequently the cause of the sepsis. An appropriate diagnostic description of the syndrome of biliary tract infection and septic shock should therefore include a description of the underlying biliary disease as well as the term acute biliary shock. In this series, emergency surgical management by removal of gallstones and drainage of suppuration was felt to be the most appropriate treatment. There was a high incidence of gallbladder rupture (10.6%) and intrahepatic stones (53.2%). Of the 13 patients who died, 8 might have survived if early operation had been performed after the diagnosis of acute biliary septic shock was established. PMID:2278914

  6. Rescue treatment with terlipressin in children with refractory septic shock: a clinical study

    PubMed Central

    Rodríguez-Núñez, Antonio; López-Herce, Jesús; Gil-Antón, Javier; Hernández, Arturo; Rey, Corsino

    2006-01-01

    children with refractory vasodilatory septic shock. The addition of TP to high doses of catecholamines, however, can induce excessive vasoconstriction. Additional studies are needed to define the safety profile and the clinical effectiveness of TP in children with septic shock. PMID:16469127

  7. 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

  8. Review of a large clinical series: Predicting death for patients with abdominal septic shock.

    PubMed

    Hanisch, Ernst; Brause, Rüdiger; Paetz, Jürgen; Arlt, Björn

    2011-01-01

    This paper reports the result of the MEDAN project that analyzes a multicenter septic shock patient data collection. The mortality prognosis based on 4 scores that are often used is compared with the prognosis of a trained neural network. We built an alarm system using the network classification results. Method. We analyzed the data of 382 patients with abdominal septic shock who were admitted to the intensive care unit (ICU) from 1998 to 2002. The analysis includes the calculation of daily sepsis-related organ failure assessment (SOFA), Acute Physiological and Chronic Health Evaluation (APACHE) II, simplified acute physiology score (SAPS) II, multiple-organ dysfunction score (MODS) scores for each patient and the training and testing of an appropriate neural network. Results. For our patients with abdominal septic shock, the analysis shows that it is not possible to predict their individual fate correctly on the day of admission to the ICU on the basis of any current score. However, when the trained network computes a score value below the threshold during the ICU stay, there is a high probability that the patient will die within 3 days. The trained neural network obtains the same outcome prediction performance as the best score, the SOFA score, using narrower confidence intervals and considering three variables only: systolic blood pressure, diastolic blood pressure and the number of thrombocytes. We conclude that the currently best available score for abdominal septic shock may be replaced by the output of a trained neural network with only 3 input variables. PMID:21262751

  9. Effects of Safflower Yellow on the Treatment of Severe Sepsis and Septic Shock: A Randomized Controlled Clinical Trial

    PubMed Central

    Li, Xiao-jin; Wang, Ru-rong; Kang, Yan; Liu, Jin; Zuo, Yun-xia; Zeng, Xue-feng; Cheng, Gong

    2016-01-01

    Objective. To evaluate the clinical effect of safflower yellow on the treatment of severe sepsis and septic shock. Methods. 85 patients with severe sepsis and septic shock were randomly selected to receive either therapy according to the international guidelines for management of severe sepsis and septic shock (Surviving Sepsis Campaign 2012) (control group, n = 45) or conventional therapy plus safflower yellow (study group, n = 40). The 28-day mortality and 28-day Kaplan-Meier survival curves were compared as primary outcomes. Results. The 28-day mortality from all causes and in-hospital mortality were significantly lower in the study group (50%, 17.5%) as compared to the control group (78.58%, 54.76%) (P = 0.007, all causes, P < 0.001, in-hospital), and the 28-day Kaplan-Meier survival curve was higher in the study group than in the control group (P = 0.008, all causes, P < 0.001, in-hospital, Log Rank). 72 hours after treatment, secondary outcomes including heart rate, leukocyte counts, lactate levels, and platelet counts of patients in the study group were ameliorated significantly as compared with the control group. Conclusion. This study offers a potential new strategy employing safflower yellow to more effectively treat patients with severe sepsis and septic shock. This trial is registered with identifier ChiCTR-TRC-14005196. PMID:26989426

  10. Effects of Safflower Yellow on the Treatment of Severe Sepsis and Septic Shock: A Randomized Controlled Clinical Trial.

    PubMed

    Li, Xiao-Jin; Wang, Ru-Rong; Kang, Yan; Liu, Jin; Zuo, Yun-Xia; Zeng, Xue-Feng; Cheng, Gong

    2016-01-01

    Objective. To evaluate the clinical effect of safflower yellow on the treatment of severe sepsis and septic shock. Methods. 85 patients with severe sepsis and septic shock were randomly selected to receive either therapy according to the international guidelines for management of severe sepsis and septic shock (Surviving Sepsis Campaign 2012) (control group, n = 45) or conventional therapy plus safflower yellow (study group, n = 40). The 28-day mortality and 28-day Kaplan-Meier survival curves were compared as primary outcomes. Results. The 28-day mortality from all causes and in-hospital mortality were significantly lower in the study group (50%, 17.5%) as compared to the control group (78.58%, 54.76%) (P = 0.007, all causes, P < 0.001, in-hospital), and the 28-day Kaplan-Meier survival curve was higher in the study group than in the control group (P = 0.008, all causes, P < 0.001, in-hospital, Log Rank). 72 hours after treatment, secondary outcomes including heart rate, leukocyte counts, lactate levels, and platelet counts of patients in the study group were ameliorated significantly as compared with the control group. Conclusion. This study offers a potential new strategy employing safflower yellow to more effectively treat patients with severe sepsis and septic shock. This trial is registered with identifier ChiCTR-TRC-14005196. PMID:26989426

  11. Severe sepsis and septic shock

    PubMed Central

    Schorr, Christa A; Zanotti, Sergio; Dellinger, R Phillip

    2014-01-01

    Morbidity and mortality from sepsis remains unacceptably high. Large variability in clinical practice, plus the increasing awareness that certain processes of care associated with improved critical care outcomes, has led to the development of clinical practice guidelines in a variety of areas related to infection and sepsis. The Surviving Sepsis Guidelines for Management of Severe Sepsis and Septic Shock were first published in 2004, revised in 2008, and recently revised again and published in 2013. The first part of this manuscript is a summary of the 2013 guidelines with some editorial comment. The second part of the manuscript characterizes hospital based sepsis performance improvement programs and highlights the sepsis bundles from the Surviving Sepsis Campaign as a key component of such a program. PMID:24335487

  12. Vasoplegia in septic shock (review).

    PubMed

    Gamcrlidze, M M; Intskirveli, N A; Vardosanidze, K D; Chikhladze, Kh E; Goliadze, L Sh; Ratiani, L R

    2015-02-01

    Vasoplegia is considered as a key factor responsible for the death of patients with septic shock, due to persistent and irreversible hypotension. The latter associated with vascular hyporeactivity to vasoconstrictors is a significant independent prognostic factor of mortality in severe sepsis. Loss of control of the vascular tone occurs through the complex, multifactorial mechanism and implicates deeply disrupted balance between vasoconstrictors and vasodilators. The aim of this review is to discuss in detail the recent suggested alternative mechanisms of vasoplegia in severe sepsis: Overproduction of nitric oxide (NO) by activation of inducible form of nitric oxide synthase (iNOS); up-regulation of prostacyclin (PG12); vasopressin deficiency; significantly elevated levels of circulating endothelin; increased concentrations of vasodilator peptides such as adrenomedulin (AM) and calcitonin gene-related peptide (CGRP); oxidative stress inducing endothelial dysfunction and vascular hyporeactivity to vasoconstrictors; inactivation of catecholamines by oxidation; over-activation of ATP-sensitive potassium channels (KATP channels) during septic shock and their involvement in vascular dysfunction. The review also discusses some therapeutic approaches based on pathogenetic mechanisms of severe sepsis and their efficacy in treatment of patients with septic shock. The loss of vascular tone control occurs through the complex, multifactorial mechanism and implicates deeply disrupted balance between vasoconstrictors and vasodilators in the pathogenesis of septic shock. Overproduction of nitric oxide (NO) by the inducible form of nitric oxide synthase (iNOS); up-regulation of prostacyclin (PG12); vasopressin deficiency; elevated levels of circulating endothelin; increased concentrations of vasodilator peptides such as adrenomedulin (AM) and calcitonin gene-related peptide (CGRP); oxidative stress inducing endothelial dysfunction and vascular hyporeactivity to vasoconstrictors

  13. 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. PMID:26473439

  14. 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

    2015-01-01

    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. PMID:26702879

  15. Clinical course of sepsis, severe sepsis, and septic shock in a cohort of infected patients from ten Colombian hospitals

    PubMed Central

    2013-01-01

    Background Sepsis has several clinical stages, and mortality rates are different for each stage. Our goal was to establish the evolution and the determinants of the progression of clinical stages, from infection to septic shock, over the first week, as well as their relationship to 7-day and 28-day mortality. Methods This is a secondary analysis of a multicenter cohort of inpatients hospitalized in general wards or intensive care units (ICUs). The general estimating equations (GEE) model was used to estimate the risk of progression and the determinants of stages of infection over the first week. Cox regression with time-dependent covariates and fixed covariates was used to determine the factors related with 7-day and 28-day mortality, respectively. Results In 2681 patients we show that progression to severe sepsis and septic shock increases with intraabdominal and respiratory sources of infection [OR = 1,32; 95%IC = 1,20-1,46 and OR = 1.21, 95%CI = 1,11-1,33 respectively], as well as according to Acute Physiology and Chronic Health Evaluation II (APACHE II) [OR = 1,03; 95%CI = 1,02-1,03] and Sequential Organ Failure Assessment (SOFA) [OR = 1,16; 95%CI = 1,14-1,17] scores. The variables related with first-week mortality were progression to severe sepsis [HR = 2,13; 95%CI = 1,13-4,03] and septic shock [HR = 3,00; 95%CI = 1,50-5.98], respiratory source of infection [HR = 1,76; 95%IC = 1,12-2,77], APACHE II [HR = 1,07; 95% CI = 1,04-1,10] and SOFA [HR = 1,09; 95%IC = 1,04-1,15] scores. Conclusions Intraabdominal and respiratory sources of infection, independently of SOFA and APACHE II scores, increase the risk of clinical progression to more severe stages of sepsis; and these factors, together with progression of the infection itself, are the main determinants of 7-day and 28-day mortality. PMID:23883312

  16. 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 Central

    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

    2016-01-01

    BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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. PMID:27049857

  17. Antimicrobial therapy in patients with septic shock.

    PubMed

    Pastene, Bruno; Duclos, Gary; Martin, Claude; Leone, Marc

    2016-04-01

    Providing antibiotics is a life-saving intervention in patients with septic shock. Cultures as clinically appropriate before antimicrobial therapy are required. Guidelines recommend providing broad-spectrum antibiotics within the first hour after recognition of shock. The site of infection, the patient's history and clinical status, and the local ecology all affect the choice of empirical treatment. The appropriateness of this choice is an important determinant of patient outcome. At 48-96h, the antimicrobial treatment should be systematically reassessed based on the clinical course and culture results. Cessation, de-escalation, continuation, or escalation are discussed according to these variables. Unnecessary treatment should be avoided to reduce the emergence of multidrug resistant pathogens. PMID:27062114

  18. Lemierre's syndrome presenting with septic shock.

    PubMed

    Marulasiddappa, Vinay; Tejesh, C A

    2013-11-01

    Lemierre's syndrome is a rare condition characterized by septic thrombophlebitis of the internal jugular vein and metastatic abscesses following oropharyngeal infection. Though classically caused by Fusobacterium necrophorum, a number of other causative organisms have been reported in literature. We report a case of Lemierre's syndrome following parapharyngeal abscess due to staphylococcus aureus which progressed to septic shock. PMID:24501493

  19. Lemierre's syndrome presenting with septic shock

    PubMed Central

    Marulasiddappa, Vinay; Tejesh, C. A.

    2013-01-01

    Lemierre's syndrome is a rare condition characterized by septic thrombophlebitis of the internal jugular vein and metastatic abscesses following oropharyngeal infection. Though classically caused by Fusobacterium necrophorum, a number of other causative organisms have been reported in literature. We report a case of Lemierre's syndrome following parapharyngeal abscess due to staphylococcus aureus which progressed to septic shock. PMID:24501493

  20. Pancreatic injury in patients with septic shock: A literature review

    PubMed Central

    Chaari, Anis; Abdel Hakim, Karim; Bousselmi, Kamel; Etman, Mahmoud; El Bahr, Mohamed; El Saka, Ahmed; Hamza, Eman; Ismail, Mohamed; Khalil, Elsayed Mahmoud; Kauts, Vipin; Casey, William Francis

    2016-01-01

    Sepsis and septic shock are life threatening condition associated with high mortality rate in critically-ill patients. This high mortality is mainly related to the inadequacy between oxygen delivery and cellular demand leading to the onset of multiorgan dysfunction. Whether this multiorgan failure affect the pancreas is not fully investigated. In fact, pancreatic injury may occur because of ischemia, overwhelming inflammatory response, oxidative stress, cellular apoptosis and/or metabolic derangement. Increased serum amylase and/or lipase levels are common in patients with septic shock. However, imaging test rarely reveal significant pancreatic damage. Whether pancreatic dysfunction does affect the prognosis of patients with septic shock or not is still a matter of debate. In fact, only few studies with limited sample size assessed the clinical relevance of the pancreatic injury in this group of patients. In this review, we aimed to describe the epidemiology and the physiopathology of pancreatic injury in septic shock patients, to clarify whether it requires specific management and to assess its prognostic value. Our main finding is that pancreatic injury does not significantly affect the outcome in septic shock patients. Hence, increased serum pancreatic enzymes without clinical features of acute pancreatitis do not require further imaging investigations and specific therapeutic intervention. PMID:27559431

  1. Pancreatic injury in patients with septic shock: A literature review.

    PubMed

    Chaari, Anis; Abdel Hakim, Karim; Bousselmi, Kamel; Etman, Mahmoud; El Bahr, Mohamed; El Saka, Ahmed; Hamza, Eman; Ismail, Mohamed; Khalil, Elsayed Mahmoud; Kauts, Vipin; Casey, William Francis

    2016-07-15

    Sepsis and septic shock are life threatening condition associated with high mortality rate in critically-ill patients. This high mortality is mainly related to the inadequacy between oxygen delivery and cellular demand leading to the onset of multiorgan dysfunction. Whether this multiorgan failure affect the pancreas is not fully investigated. In fact, pancreatic injury may occur because of ischemia, overwhelming inflammatory response, oxidative stress, cellular apoptosis and/or metabolic derangement. Increased serum amylase and/or lipase levels are common in patients with septic shock. However, imaging test rarely reveal significant pancreatic damage. Whether pancreatic dysfunction does affect the prognosis of patients with septic shock or not is still a matter of debate. In fact, only few studies with limited sample size assessed the clinical relevance of the pancreatic injury in this group of patients. In this review, we aimed to describe the epidemiology and the physiopathology of pancreatic injury in septic shock patients, to clarify whether it requires specific management and to assess its prognostic value. Our main finding is that pancreatic injury does not significantly affect the outcome in septic shock patients. Hence, increased serum pancreatic enzymes without clinical features of acute pancreatitis do not require further imaging investigations and specific therapeutic intervention. PMID:27559431

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

    PubMed Central

    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. PMID:27227060

  4. Symmetrical peripheral gangrene caused by septic shock

    PubMed Central

    Shimbo, Keisuke; Yokota, Kazunori; Miyamoto, Junpei; Okuhara, Yukako; Ochi, Mitsuo

    2015-01-01

    We report three cases of symmetrical peripheral gangrene (SPG) caused by septic shock. Most of sepsis survivors with SPG require amputation of the affected extremities. To preserve the length of the thumb and fingers, we performed surgical amputation and used flaps to cover the amputated peripheral extremities.

  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. 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

  7. Septic lung and shock lung in man.

    PubMed Central

    Clowes, G H; Hirsch, E; Williams, L; Kwasnik, E; O'Donnell, T F; Cuevas, P; Saini, V K; Moradi, I; Farizan, M; Saravis, C

    1975-01-01

    Two series of patients were studied by serial measurements of blood gas exchange and pulmonarmonary dysfunction and to evaluate the dangers of respiratory failure in post traumatic patients. There were 27 patients who had sustained profound hemorrhagic shock and massive blood replacement averaging 9.7 liters and 38 patients who suffered general peritonitis or other forms of fulminating nonthoracic sepsis. All were supported by endotrachael intubation and volume controlled ventilators. The overall mortality for the post shock patients without sepsis was 12% while in the septic patients it was 35%. The maximal pulmonary arteriovenous shunt encountered in the post hemorrhagic shock patients at 36 hours averaged 20 plus or minus 8% and was accompanied by high cardiac indices (average 5.1 plus or minus 1.3 L/M-2/min) but no significant rise of pulmonary arterial pressure or peak inspiratory pressure (PIP). Severe pulmonary dysfunction subsequently occurred only in those patients who later became septic. The studies on the septic patients were divided according to the magnitude of the cardiac indices (the high indices averaged 4.8 plus or minus 1.6L/M-2/min) and thelow indices averaged 1.9 plus or minus 1.0 L/M-2/min. In the former, the average maximal shunt of 30 plus or minus 6% was sustained for 4 or more days, accompanied by an elevation of PIP to 36 plus or minus 6 cm H2O and by Pa pressure of 28 plus or minus 5 mm Hg. The patients in low output septic shock usually had an associated bronchopneumonia and had an average venous admixture of 34 plus or minus 8% and PIP values of 41 plus or minus 8 cm H2O. The mean Pa pressure in this group was 29 plus or minus 6 mm Hg. PMID:236738

  8. Novel therapies for septic shock over the past 4 decades.

    PubMed

    Suffredini, Anthony F; Munford, Robert S

    2011-07-13

    Infections that result in shock and organ failure are a major public health problem worldwide. Severe sepsis and septic shock affect patients of all ages and often complicate chronic diseases. They are the major causes of death in critical care units and contribute substantially to hospital inpatient costs. Translating the scientific advances of the last 4 decades into clinical practice has been challenging. Despite many attempts to develop new therapies, the basic elements of treatment have not changed since the 1960s. In this Grand Rounds, we summarize the results of the clinical trials conducted during the last 4 decades, discuss some lessons learned, and suggest possible directions for future investigation. PMID:21750297

  9. Alteco endotoxin hemoadsorption in Gram-negative septic shock patients

    PubMed Central

    Shum, Hoi Ping; Leung, Yuk Wah; Lam, Sin Man; Chan, King Chung; Yan, Wing Wa

    2014-01-01

    Background and Aims: Severe sepsis and septic shock are common causes of mortality and morbidity in an intensive care unit setting. Endotoxin, derived from the outer membranes of Gram-negative bacteria, is considered a major factor in the pathogenesis of sepsis. This study investigated the effect of Alteco endotoxin hemoadsorption device on Gram-negative septic shock patients. Materials and Methods: An open, controlled, prospective, randomized, single-center trial was conducted between February 2010 and June 2012. Patients with septic shock due to intra-abdominal sepsis were randomized to either conventional therapy (n = 8) or conventional therapy plus two 2-hourly sessions of Alteco endotoxin hemoadsorption (n = 7). Primary endpoint was the Sequential Organ Failure Assessment (SOFA) score changes from 0 to 72 h. Secondary end points included vasopressor requirement, PaO2/FiO2 ratio (PFR), length of stay (LOS), and 28-day mortality. Results: This study was terminated early as interim analysis showed a low probability of significant findings. No significant difference was noted between the two groups with respect to change in SOFA score, vasopressor score, PFR, LOS, and 28-day mortality. Side-effect was minimal. Conclusions: We could not identify any clinical benefit on the addition of Alteco endotoxin hemoadsorption to conventional therapy in patients who suffered from intra-abdominal sepsis with shock. The side effect profile of this novel device was acceptable. PMID:25538412

  10. 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

  11. [Advances in the research of early goal-directed therapy in severe sepsis and septic shock].

    PubMed

    Sun, W; Yuan, H X; An, Y Z

    2016-05-20

    Nowadays, severe infection has become one of the common problems in clinic. The morbidity of severe sepsis and septic shock is increasing, which becomes a big threat to patients with burn wounds or chronic diseases. It has become a key subject about how to cure severe sepsis and septic shock. In recent years, mortality of patients in such condition has declined slightly, which might be attributed to the application of early goal-directed therapy (EGDT) in certain degree. This article reviews application of EGDT in severe sepsis and septic shock, in order to analyze its effectiveness and boundedness, as well as predict its development. PMID:27188487

  12. Vasopressor and Inotropic Management Of Patients With Septic Shock

    PubMed Central

    Pollard, Sacha; Edwin, Stephanie B.; Alaniz, Cesar

    2015-01-01

    Numerous studies have evaluated the role of vasopressors and inotropes in the management of septic shock. This review assesses available evidence for the use of specific vasopressors in the management of septic shock. Use of adjunctive vasopressor therapy is also evaluated, examining the potential value of individual agents. Lastly, inotropic agents are evaluated for use in patients with myocardial dysfunction. PMID:26185405

  13. Corticosteroids and Pediatric Septic Shock Outcomes: A Risk Stratified Analysis

    PubMed Central

    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

    Background The potential benefits of corticosteroids for septic shock may depend on initial mortality risk. Objective We determined associations between corticosteroids and outcomes in children with septic shock who were stratified by initial mortality risk. Methods 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. Results 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. Conclusions Risk stratified analysis failed to demonstrate any benefit from corticosteroids in this pediatric septic shock cohort. PMID:25386653

  14. Steroids for septic shock: back from the dead? (Pro).

    PubMed

    Balk, Robert A

    2003-05-01

    The use of corticosteroids as adjunctive therapy for severe sepsis and septic shock has been a source of controversy for the past 35 years. Despite a wealth of preclinical data supporting both survival and physiologic benefit for early steroid use, the data in human sepsis have been much less convincing. There have even been reports suggesting the potential for harm associated with the administration of early high-dose corticosteroids in patients with severe sepsis and septic shock. Recent trials have reported hemodynamic and survival benefits associated with the use of more physiologic steroid replacement therapy in patients with vasopressor-dependent septic shock. These results coupled with the observation of "relative adrenal insufficiency" in some patients with severe sepsis and septic shock may once again establish a defined role for corticosteroid therapy in the management of severe sepsis and septic shock. PMID:12740234

  15. [CLINICAL ASPECTS OF SEPTIC ENCEPHALOPATHY].

    PubMed

    Fesenko, O V; Sinopal'nikov, A I; Filatov, V V; Danishevsky, S V; Styrt, E A

    2016-01-01

    Septic encephalopathy is a form of general cerebral dysfunction caused by a systemic inflammatory reaction. Its investigation encounters enormous difficulties for the lack of reliable biological markers of neuronal lesions and methods for the evaluation of consciousness in severely ill patients. Hence, the importance of correct clinical interpretation of the character and magnitude of CNS activity. Examples are presented demonstrating the difficulty of interpreting disorders in CNS activity associated with evere community-acquired pneumonia. PMID:27172727

  16. High doses of corticosteroids in the treatment of septic shock.

    PubMed

    Hellman, A; Alestig, K

    1985-01-01

    High doses of corticosteroids are reported to be beneficial in the treatment of septic shock in many animal species, e.g. dog, rat and rabbit. Recent findings in baboons subjected to E. coli shock indicate that early treatment with a combination of antibiotics and steroids strongly enhance survival rate. In clinical studies the protective effects of steroids are more ambiguous, however. In part this may be explained by variations in the amount of steroids used or by the fact that in some studies the steroid is administered late in shock. The dose recommended, 30 mg/kg bw of methylprednisolone or an equivalent amount of another glucocorticoid given once or twice, is based on animal as well as clinical documentation. PMID:3911703

  17. Activated protein C downregulates p38 mitogen-activated protein kinase and improves clinical parameters in an in-vivo model of septic shock.

    PubMed

    Nold, Marcel F; Nold-Petry, Claudia A; Fischer, Doris; Richter, Bernd; Blaheta, Roman; Pfeilschifter, Josef; Muhl, Heiko; Schranz, Dietmar; Veldman, Alex

    2007-11-01

    Despite the success of the anti-coagulant protease protein C (PC) in treating septic shock in humans, the signaling pathways used are still unclear. To explore the effects of treatment with PC zymogen and its activated form aPC in a setting of sepsis, we employed a piglet model of endotoxic shock. In the aPC group, we observed a 65%-90% reduction in plasma TNF-alpha levels and a concomitant clinical improvement. Unexpectedly, administration of aPC also resulted in stabilization of the plasma pH above 7.2. Moreover, phosphorylated p38 mitogen-activated protein kinase (p38MAPK) was virtually absent in the livers of those piglets receiving aPC. In cultured human umbilical vein endothelial cells, we observed that nanomolar concentrations of PC and aPC inhibited the phosphorylation of p38MAPK. Furthermore, we showed that the regulation of the pro-apoptotic cell cycle regulator p53 by PC and aPC is dependent on the reduction of p38MAPK activation. The transduction of these effects involves all three receptors associated with protein C signaling, namely endothelial protein C receptor, protease-activated receptor 1, and sphingosine 1-phosphate receptor 1. Ultimately, this study elucidates novel signaling pathways regulated by protein C and emphasises the pivotal importance of its multiple modes of action beyond anticoagulation. APC's clinical success may, in part, be due to p38MAPK inhibition. PMID:18000619

  18. Septic Shock Due to Biliary Stones in a Postcholecystectomy Patient.

    PubMed

    Azfar, Mohammad Feroz; Khan, Muhammad Faisal; Khursheed, Moazzum

    2015-10-01

    Septic shock leading to multi-organ failure is not uncommon. Early diagnosis to confirm the source is the distinctive attribute of sepsis management guidelines. Cholangitis as the source of sepsis can become a diagnostic dilemma in patients who have had cholecystectomy in the past. CT abdomen should be the investigation of choice in this group of patients. This report describes two postcholecystectomy patients who presented with septic shock secondary to biliary stones. The source of septic shock in both patients were biliary stones was confirmed with abdominal CT. Ultrasound abdomen failed to report biliary stones in these patients. Both improved on percutaneous transhepatic biliary drainage. PMID:26522207

  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. PMID:20391818

  20. Extracorporeal membrane oxygenation therapy in neonates with septic shock.

    PubMed

    McCune, S; Short, B L; Miller, M K; Lotze, A; Anderson, K D

    1990-05-01

    Neonatal septic shock has significant morbidity and mortality with current therapeutic measures. At Children's National Medical Center, from June 1984 to October 1986, 10 of 100 patients treated with venoarterial extracorporeal membrane oxygenation (ECMO) had a documented diagnosis of septic shock. All of these infants fulfilled criteria consistent with 80% mortality using conventional intensive medical management. However, the survival rate for the septic neonates in this study was 100%. Compared with other groups of infants treated with ECMO, these septic neonates required significantly more ventilatory support after ECMO and had a higher incidence of chronic lung disease (30% v 12%). The septic neonates were also at higher risk for intracranial hemorrhage than the other infants treated with ECMO (40% v 26%). The necessity for prolonged intubation after ECMO for patients with septic shock suggests that this condition may be associated with additional structural damage not seen with meconium aspiration syndrome or respiratory distress syndrome. Nevertheless, for neonatal patients with septic shock unresponsive to conventional medical management, ECMO must be considered a viable alternative treatment. PMID:2352078

  1. An Elevated Percentage of Reticulated Platelet Is Associated With Increased Mortality in Septic Shock Patients

    PubMed Central

    Wu, Qin; Ren, Jianan; Hu, Dong; Jiang, Pengjun; Li, Guanwei; Anjum, Nadeem; Wang, Gefei; Gu, Guosheng; Chen, Jun; Wu, Xiuwen; Liu, Song; Li, Yuan; Zhao, Yunzhao; Li, Jieshou

    2015-01-01

    Abstract Microcirculatory changes and coagulation disturbances are thought to play a key role in sepsis. Some evidence suggests that the percentage of reticulated platelets (RP%) may be a valuable and cost-effective sepsis screening parameter. This was a prospective study in surgical patients to investigate the potential value of RP% as a predictor of mortality in septic shock patients. This was a prospective study conducted in a surgical critical care center of a Chinese tertiary care hospital. Consecutive septic shock patients were enrolled at admission. Age- and sex-matched non-septic patients were recruited as control patients. RP% was determined by flow cytometry in 68 septic shock patients and 68 controls. Compared with survivors, septic patients who died presented with a significantly higher RP% (P < 0.001). The area under the receiver-operating characteristic curve for the RP% association with mortality was 0.867 (95 % CI 0.780–0.953, P < 0.001). Kaplan–Meier survival curves showed that mortality risk was significantly different when patients were stratified based on RP% (P < 0.001). This association was preserved in a multi-logistic regression analysis that included clinical confounders (P < 0.014). This prospective study demonstrates that increased RP% identifies septic shock patients who have a high risk of death. RP% has the potential to act as a marker for patient stratification in future clinical trials. PMID:25984667

  2. Mortality Prediction Model of Septic Shock Patients Based on Routinely Recorded Data

    PubMed Central

    Carrara, Marta; Baselli, Giuseppe; Ferrario, Manuela

    2015-01-01

    We studied the problem of mortality prediction in two datasets, the first composed of 23 septic shock patients and the second composed of 73 septic subjects selected from the public database MIMIC-II. For each patient we derived hemodynamic variables, laboratory results, and clinical information of the first 48 hours after shock onset and we performed univariate and multivariate analyses to predict mortality in the following 7 days. The results show interesting features that individually identify significant differences between survivors and nonsurvivors and features which gain importance only when considered together with the others in a multivariate regression model. This preliminary study on two small septic shock populations represents a novel contribution towards new personalized models for an integration of multiparameter patient information to improve critical care management of shock patients. PMID:26557154

  3. Right ventricular dysfunction in patients with septic shock.

    PubMed

    Dhainaut, J F; Lanore, J J; de Gournay, J M; Huyghebaert, M F; Brunet, F; Villemant, D; Monsallier, J F

    1988-01-01

    Using a rapid computerized thermodilution method, we examined the evolution of right ventricular performance in 23 patients with septic shock. Nine survived the episode of septic shock. The other 14 patients died of refractory circulatory shock. Significant right ventricular systolic dysfunction, defined as decreased ejection fraction (-39%) and right ventricular dilation (+38%) was observed in all patients with septic shock. However, in the survivors, increased right ventricular preload may prevent hemodynamic evidence of right ventricular pump failure by utilizing the Frank-Starling mechanism to maintain stroke volume. Conversely, in the nonsurvivors, right ventricular dysfunction was more prononced two days after the onset of septic shock, leading to a fall in stroke. In the last patients, a decrease in contractility appears to be the major factor accounting for decreased right ventricular performance, as evidenced by the marked increase in end-systolic volume (+27%) without significant change in pulmonary artery pressure, during the later stage of septic shock. The observed right ventricular pump failure then appears associated with an alteration in diastolic mechanical properties of this ventricle, as suggested by a leftward displacement of the individual pressure-volume curves. PMID:3403793

  4. 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 R2 > 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

  5. [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. PMID:26323988

  6. [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. PMID:25152109

  7. 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

  8. Protocolized Care for Early Septic Shock (ProCESS) statistical analysis plan

    PubMed Central

    Pike, Francis; Yealy, Donald M; Kellum, John A; Huang, David T; Barnato, Amber E; Eaton, Tammy L; Angus, Derek C; Weissfeld, Lisa A

    2014-01-01

    Background The Protocolized Care for Early Septic Shock study is a randomised, multicentre, prospective, three-arm, parallel-group trial of alternative resuscitation strategies for early septic shock. Objective To state our analysis plan for trial data. Methods Our plan is to guide data collection and analysis using pre-existing definitions and testing, with local consensus-based efforts where needed. We examine protocolised care (two experimental approaches) and compare this to usual “wild type” care. Results Our plan is to address three aims (clinical efficacy, biology of illness and recovery, and costs and cost-effectiveness) and four hypotheses, and we specify rules for handling data and determining outcomes. Conclusion By using measures to maintain study conduct and analysis rigour, we hope to improve understanding of early septic shock resuscitation and care of patients. PMID:24289512

  9. Panayiotopoulos syndrome in a child masquerading as septic shock.

    PubMed

    Zaki, Syed Ahmed; Verma, Devendra Kumar; Tayde, Pavan

    2016-06-01

    Panayiotopoulos syndrome (PS) is a benign childhood epilepsy with predominant autonomic symptoms. The syndrome can have varied presentations resulting in diagnostic dilemma. We herein describe a 3-year-old boy with PS, who had manifestations similar to septic shock. His investigations were normal and had a complete recovery. Through this case, we wish to highlight the unusual presentation of PS as septic shock. Physicians should be aware of the different ways in which this syndrome can present to ensure its early diagnosis and treatment. PMID:27390462

  10. Panayiotopoulos syndrome in a child masquerading as septic shock

    PubMed Central

    Zaki, Syed Ahmed; Verma, Devendra Kumar; Tayde, Pavan

    2016-01-01

    Panayiotopoulos syndrome (PS) is a benign childhood epilepsy with predominant autonomic symptoms. The syndrome can have varied presentations resulting in diagnostic dilemma. We herein describe a 3-year-old boy with PS, who had manifestations similar to septic shock. His investigations were normal and had a complete recovery. Through this case, we wish to highlight the unusual presentation of PS as septic shock. Physicians should be aware of the different ways in which this syndrome can present to ensure its early diagnosis and treatment. PMID:27390462

  11. Methylmalonic acidemia mimicking diabetic ketoacidosis and septic shock in infants

    PubMed Central

    Saini, Navdeep; Malhotra, Ashwini; Chhabra, Sanjay; Chhabra, Sunny

    2015-01-01

    Methylmalonic acidemia (MMA) is most common inherited type of organic acidemia. It has diverse presentation in older infants without any initial apparent symptoms. MMA sometimes present with sudden metabolic decompensation, which may mimics common emergencies like septic shock and diabetic ketoacidosis (DKA) without early recognition can be fatal. In born error of metabolism especially organic acidemia should be suspected in any infant presented with severe high anion gap metabolic acidosis. We report two cases of MMA in infants presented acutely mimicking DKA and septic shock. PMID:25810618

  12. Cryoprecipitate infusion fails to improve organ function in septic shock.

    PubMed

    Hesselvik, F; Brodin, B; Carlsson, C; Cedergren, B; Jorfeldt, L; Liedén, G

    1987-05-01

    Plasma fibronectin may be of critical importance for the septic patient through its proposed function as the major opsonin for macrophage clearance of circulating, noncellular debris. As a rule, critically ill, septic patients are depleted of fibronectin. In earlier uncontrolled studies, infusion of fibronectin-rich cryoprecipitate had resulted in improved renal and pulmonary functions and changes in peripheral hemodynamics. In this controlled study, 32 septic ICU patients (mean initial fibronectin level = 60% of normal) received cryoprecipitate or control infusions. Although the fibronectin level was significantly elevated to the normal range in the cryoprecipitate group, no effects were seen in hemodynamics, oxygen metabolism, or lung and kidney functions. Our results indicate that this form of fibronectin therapy does not influence the impaired organ function in septic shock. PMID:3552444

  13. 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. PMID:26313437

  14. [SEPTIC SHOCK IN PATIENT WITH SEVERE HEAD TRAUMA].

    PubMed

    Sichev, A A; Tabasaransky, T Φ; Savin, I A; Gorachev, A S; Tenedieva, V D; Abramov, T A; Oshorov, A V; Polupan, A A; Mazkovsky, I V; Gavrilov, A G; Potapov, A A

    2015-01-01

    The clinical observation illustrates the role of screening of inflammatory markers and advanced hemodynamic monitoring in optimization of the treatment of the patient with severe traumatic brain injury (sTBI). The level of consciousness by the Glasgow Coma Scale at admission was 5 points. From the first day of stay the patient suffered hyperthermia to 39,0° C° The diagnosis of the aspiration pneumonia was determined by radiological signs, bronchoscopy and inflammatory blood markers, C-reactive protein, leukocytosis. From the second day the constant infusion of norepinephrine was necessary to maintain mean ABP above 80 mmHg. On the 10th day the patient's condition deteriorated sharply. Developed hyperthermia to 40, 2° and cardiovascular collapse (in spite of the high level of norepinephrine support a sharp decline in ABP up to 49/20 mmHg). Invasive advanced hemodynamic PiCCO monitoring (transpulmonary thermodilution) was started Septic shock was suspected. Standard laboratory tests did not meet the criteria for septic shock. Witnessed a slight increase in CRP and procalcitonin (PCT) was within normal limits. Diagnostic search was supplemented by a study of interleukins (IL-6 and IL-2R) in the blood plasma. The significant increase in their values, was regarded as the initial manifestations of the systemic inflammatory response. Sepsis was confirmed. The extended antibiotic therapy started Continuous Veno-Venous hemofiltration was used as part of treatment of the inflammatory-toxic condition. In two days of the therapy the patient's condition has stabilized, the patient recovered consciousness in the form of opening the eyes, simple instructions. At discharge, the patient's condition according to the Glasgow outcome scale was estimated at 4 points. PMID:26596036

  15. [Role of vasopressin in septic shock : critical evaluation].

    PubMed

    Gradwohl-Matis, I; Brunauer, A; Dankl, D; Dünser, M

    2014-06-01

    Restoration of adequate tissue perfusion is the goal of resuscitation in septic shock. A growing understanding of microcirculatory dysfunction in sepsis led to a change in resuscitation practice away from targeting arterial and central venous pressures and towards tissue perfusion-guided protocols. This change in the approach to resuscitation was accompanied by a change in the role of vasoconstrictors. This review summarizes the pathophysiological and therapeutic mainstays of septic shock resuscitation and attempts to critically evaluate the scientific evidence on the use of vasopressin as a non-adrenergic vasoconstrictor in septic shock. Based on the published study results vasopressin appears to be of potential benefit in adult patients with moderate septic shock (norepinephrine requirements < 15 μg/min) and lacking signs of systemic hypoperfusion (e.g. normal arterial lactate levels). A vasopressin infusion with the sole target to increase arterial blood pressure despite the presence of systemic hypoperfusion is dangerous and can result in a critical deterioration of tissue perfusion. PMID:24838480

  16. Management of sepsis and septic shock in infants and children.

    PubMed

    von Rosenstiel, N; von Rosenstiel, I; Adam, D

    2001-01-01

    Sepsis and septic shock constitute an important cause of morbidity and mortality in critically ill children. Thus, the systemic response to infection and its management remains a major challenge in clinical medicine. Apart from antibiotic administration, the majority of available therapies are limited to supportive strategies, although considerable efforts are being undertaken to devise innovative approaches that modulate host inflammatory responses. In suspected sepsis, 2 or 3 days' empiric antibiotic therapy should begin immediately after cultures have been obtained without awaiting results. Antibiotics should be re-evaluated when the results of the cultures and susceptibility tests are available. The initial antibiotic (combination) is determined by the likely causative agent, susceptibility patterns within a specific institution, CNS penetration, toxicity, and the patient's hepatic and renal function. The likely offending micro-organism in turn depends primarily on the patient's age, coexistence of any premorbid condition leading to impaired immune response, and the presenting signs and symptoms. Close attention to cardiovascular, respiratory, fluid and electrolyte, haematological, renal and metabolic/nutritional support is essential to optimise outcome. Fluid resuscitation is of utmost importance to overcome hypovolaemia on the basis of a diffuse capillary leak. Monitoring and normalisation of the heart rate is essential. In case of nonresponse to fluid resuscitation, inotropic and vasoactive agents are commonly used to increase cardiac output, maintain adequate blood pressure and enhance oxygen delivery to the tissue. Because respiratory distress syndrome is seen in about 40% of critically ill children with septic shock, increased inspired oxygen is essential. To provide optimal relief from respiratory muscle fatigue and facilitate the provision of positive airway pressure, early intubation and mechanical ventilation should be considered. Renal support is

  17. Increased survival of cirrhotic patients with septic shock

    PubMed Central

    2013-01-01

    Introduction 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. Methods 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. Results 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). Conclusions 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. PMID:23601847

  18. 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

  19. Gas-Forming Pyogenic Liver Abscess with Septic Shock

    PubMed Central

    Ishaq, Muhammad K.; Jones, Kellie R.

    2015-01-01

    The pyogenic liver abscess caused by Clostridium perfringens (C. perfringens) is a rare but rapidly fatal infection. The main virulence factor of this pathogen is its α-toxin (lecithinase), which decomposes the phospholipid in cell membranes leading to cell lysis. Once the bacteria are in blood stream, massive intravascular hemolysis occurs. This can present as anemia on admission with evidence of hemolysis as indicated by low serum haptoglobin, high serum lactate dehydrogenase (LDH), elevated indirect bilirubin, and spherocytosis. The clinical course of C. perfringens septicemia is marked by rapidly deteriorating course with a mortality rate ranging from 70 to 100%. The very rapid clinical course makes it difficult to diagnose on time, and most cases are diagnosed at autopsy. Therefore it is important to consider C. perfringens infection in any severely ill patient with fever and evidence of hemolysis. We present a case of seventy-seven-year-old male with septic shock secondary to pyogenic liver abscess with a brief review of existing literature on C. perfringens. PMID:26090240

  20. 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

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

    PubMed

    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

    2015-12-01

    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

  2. Management of Septic Shock in the Remote Prehospital Setting.

    PubMed

    Joynes, Emma Lucy; Martin, Jodie; Ross, Mark

    2016-01-01

    This study aims to assess the management of septic shock by air medical retrieval teams in the remote setting. A retrospective observational study was performed over 36 months. Sixty-seven adult patients who met the criteria for septic shock were included. Respiratory sepsis was the working diagnosis for 53% of patients; this was confirmed on intensive care unit (ICU) discharge in 39% of patients. Intravenous antibiotics and oxygen were delivered in over 90% of patients. Central and arterial line insertions were performed in 48% and 40% of patients, respectively, and 79% of patients were catheterized. Thirty-three percent of patients required intubation, and 80% of patients received an initial crystalloid fluid bolus of 20 mL/kg. Vasopressors were started in 89% of patients. Upon reaching definitive care, 91% of patients were admitted to a high-dependency or ICU setting, with a median length of ICU stay of 4 days and a 30-day mortality of 13%. Of those admitted to the ICU, intubation was required in 48%, new renal support in 20%, and blood pressure support in 84% of patients, respectively. Septic shock was recognized early and managed aggressively by remote retrieval teams, which may have contributed to the low mortality rate observed. PMID:27393760

  3. The potential role of thromboxane and prostacyclin in endotoxic and septic shock.

    PubMed

    Cook, J A; Wise, W C; Butler, R R; Reines, H D; Rambo, W; Halushka, P V

    1984-01-01

    The potential role of thromboxane (TxA2), a platelet aggregator and vasoconstrictor, and prostacyclin (PGI2) a platelet anti-aggregator and vasodilator, in endotoxic and septic shock was investigated. Early endotoxic shock in the rat is associated with marked elevations of plasma TxB2 (the stable metabolite of TxA2) and lesser increases in plasma 6-keto-PGF1 alpha (the stable metabolite of PGI2). Selective inhibition of TxA2 synthesis by several different chemical classes of Tx synthetase inhibitors was beneficial in endotoxic shock. In contrast, shock induced by acute intra-abdominal sepsis in the rat was characterized by high levels of plasma 6-keto-PGF1 alpha, which exceeded plasma TxA2 six- to eight fold at most time intervals studied. Tx synthetase inhibitors were not protective in this model of acute sepsis, but treatment with fatty acid cyclo-oxygenase inhibitors, an antibiotic (gentamicin), or reduction in arachidonic acid metabolism by essential fatty acid (EFA) deficiency significantly prolonged survival time. An important aspect of the latter study is that decreased arachidonic acid metabolism was an effective adjunct to antibiotic therapy. Conjoint administration of gentamicin in EFA-deficient rats or with indomethacin synergistically improved long-term survival, a result that was not evident with single treatment interventions. In addition to experimental studies, plasma TxB2 levels were measured during clinical sepsis. These studies demonstrated that plasma TxB2 levels were elevated tenfold in patients dying of septic shock compared with septic survivors or nonseptic controls. These composite experimental and clinical observations suggest that arachidonic acid metabolites play a role in the pathogenesis of endotoxic and septic shock. PMID:6440569

  4. Current haemodynamic management of septic shock.

    PubMed

    Vincent, Jean-Louis; Orbegozo Cortés, Diego; Acheampong, Angela

    2016-04-01

    Early and adequate resuscitation of patients with acute circulatory failure is important to restore the balance between oxygen needs and delivery. Haemodynamic management can globally be separated into three categories according to the VIP mnemonic - Ventilate, Infuse, Pump - which should be considered simultaneously in the patient with shock. Sufficient oxygen should be given early, and endotracheal intubation and mechanical ventilation performed without hesitation if there is any indication that oxygenation is inadequate. Fluids should be administered using the SOSD mnemonic - Salvage, Optimization, Stabilization, De-escalation. After initial liberal administration, ongoing requirements should be guided by repeated fluid challenges using a combination of balanced crystalloid solutions and colloid. Noradrenaline is the vasopressor of choice and should be started early. Dobutamine may be needed to improve myocardial contractility and cardiac output. Haemodynamic support should be personalized according to individual patient characteristics and global and regional parameters of haemodynamic and oxygenation status. PMID:27079763

  5. 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.

  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. PMID:26825315

  7. Assessment of Neutrophil Function in Patients with Septic Shock: Comparison of Methods

    PubMed Central

    Wenisch, C.; Fladerer, P.; Patruta, S.; Krause, R.; Hörl, W.

    2001-01-01

    Patients with septic shock are shown to have decreased neutrophil phagocytic function by multiple assays, and their assessment by whole-blood assays (fluorescence-activated cell sorter analysis) correlates with assays requiring isolated neutrophils (microscopic and spectrophotometric assays). For patients with similar underlying conditions but without septic shock, this correlation does not occur. PMID:11139215

  8. Venoarterial extracorporeal membrane oxygenation support for neonatal and pediatric refractory septic shock

    PubMed Central

    Rambaud, Jerome; Guellec, Isabelle; Léger, Pierre-Louis; Renolleau, Sylvain; Guilbert, Julia

    2015-01-01

    Objective: To report our institutional experience of veno-arterial extracorporeal membrane oxygenation (VA ECMO) in children with refractory septic shock. Materials and Methods: We retrospectively reviewed our ECMO database to identify patients who received VA ECMO for septic shock from January 2004 to June 2013 at our Pediatric Intensive Care Unit in Armand-Trousseau Hospital. We included all neonates and children up to the age of 18 years who received VA ECMO for septic shock. For each patient, we collected the pre-ECMO inotrope score, clinical circulatory and ventilatory parameters, infecting organism, ECMO duration and complications, and length of hospital stay. Main Results: The study included 14 neonates and 8 older children (the pediatric population, with a mean age of 30 months, range: 1–113 months). Survival was 64% among newborns and 50% among pediatric patients. Multiorgan failure or severity scores did not show any correlation with mortality (Pediatric Logistic Organ Dysfunction score, P = 0.94; the score for neonatal acute physiology-perinatal extension II, P = 0.34). In the pediatric population, the inotrope score was higher in the survivor group (127.5 vs. 332.5, P = 0.07). Blood samples taken shortly before cannulation showed that pH (P = 0.27), lactate level (P = 0.33), PaO2/FiO2 ratio (P = 0.49), or oxygenation index (P = 0.35) showed no correlation to success or failure of ECMO. Conclusion: ECMO can be safely used to resuscitate and support children with refractory septic shock. We recommend that patients with oliguria whose lactate level has not decreased within 6 h of starting maximum drug therapy be transferred to an ECMO referral center. PMID:26628825

  9. Gastric tonometry versus cardiac index as resuscitation goals in septic shock: a multicenter, randomized, controlled trial

    PubMed Central

    Palizas, Fernando; Dubin, Arnaldo; Regueira, Tomas; Bruhn, Alejandro; Knobel, Elias; Lazzeri, Silvio; Baredes, Natalio; Hernández, Glenn

    2009-01-01

    Introduction Resuscitation goals for septic shock remain controversial. Despite the normalization of systemic hemodynamic variables, tissue hypoperfusion can still persist. Indeed, lactate or oxygen venous saturation may be difficult to interpret. Our hypothesis was that a gastric intramucosal pH-guided resuscitation protocol might improve the outcome of septic shock compared with a standard approach aimed at normalizing systemic parameters such as cardiac index (CI). Methods The 130 septic-shock patients were randomized to two different resuscitation goals: CI ≥ 3.0 L/min/m2 (CI group: 66 patients) or intramucosal pH (pHi) ≥ 7.32 (pHi group: 64 patients). After correcting basic physiologic parameters, additional resuscitation consisting of more fluids and dobutamine was started if specific goals for each group had not been reached. Several clinical data were registered at baseline and during evolution. Hemodynamic data and pHi values were registered every 6 hours during the protocol. Primary end point was 28 days' mortality. Results Both groups were comparable at baseline. The most frequent sources of infection were abdominal sepsis and pneumonia. Twenty-eight day mortality (30.3 vs. 28.1%), peak Therapeutic Intervention Scoring System scores (32.6 ± 6.5 vs. 33.2 ± 4.7) and ICU length of stay (12.6 ± 8.2 vs. 16 ± 12.4 days) were comparable. A higher proportion of patients exhibited values below the specific target at baseline in the pHi group compared with the CI group (50% vs. 10.9%; P < 0.001). Of 32 patients with a pHi < 7.32 at baseline, only 7 (22%) normalized this parameter after resuscitation. Areas under the receiver operator characteristic curves to predict mortality at baseline, and at 24 and 48 hours were 0.55, 0.61, and 0.47, and 0.70, 0.90, and 0.75, for CI and pHi, respectively. Conclusions Our study failed to demonstrate any survival benefit of using pHi compared with CI as resuscitation goal in septic-shock patients. Nevertheless, a

  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. Beyond the guidelines of paediatric septic shock: A focused review

    PubMed Central

    Temsah, Mohamad-Hani

    2015-01-01

    Severe sepsis and septic shock continue to cause major morbidity and mortality among children, especially in the resource-limited areas. Guidelines that focus on these entities, such as “Surviving Sepsis” and “Paediatric Advanced Life Support” guidelines, are revised and updated on regular basis to incorporate new evidence based medicine. There is ongoing need to review these updated guidelines, and address potentially best available solutions for adapting them into suitable practical steps for paediatricians worldwide, especially those working in resource-limited areas. The available recommendations may help to improve sepsis management in middle- and low-income countries; however, guidelines must be wisely implemented according to the available resources, with follow up auditing to ensure appropriate implementation.

  12. Survival characteristics during septic shock in 39 baboons.

    PubMed

    Wilson, M F; Brackett, D J; Archer, L T; Beller-Todd, B K; Tompkins, P; Hinshaw, L B

    1982-01-01

    In septic shock nonsurvival is characterized by failure of multiple organ systems. The design of therapeutic measures to increase survival would be enhanced if critical responses could be identified early. Escherichia coli LD100 was given to 39 baboons by IV infusion over two hours followed by different therapy regimens in 31 [2--4]. There were 18 permanent survivors (seven days or more), all receiving antibiotic/steroid combination therapy. Responses of survivors and nonsurvivors were measured and compared during the first 12 hours from onset of infusion. Changes in blood pressure and acid-base parameters were not significantly different between groups. Five responses indicative of permanent survival were lower heart rates, less elevation of blood urea nitrogen, normal blood glucose at eight hours, hyperglycemia with normal insulin at 12 hours, and lower plasma lactate concentrations beginning at four hours. PMID:6753527

  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

    2016-03-01

    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

  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. 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

  16. Ibuprofen, methylprednisolone, and gentamicin as conjoint therapy in septic shock.

    PubMed

    Wise, W C; Halushka, P V; Knapp, R G; Cook, J A

    1985-01-01

    Septic shock is associated with increased metabolism of arachidonic acid to thromboxane A2 (TxA2) and prostacyclin (PGI2). The effects of ibuprofen, methylprednisolone-sodium succinate, and gentamicin alone, or in combination on survival time and, TxA2 and PGI2 production in rats in a LD100 fecal peritonitis shock model were assessed. Plasma levels of TxA2 and PGI2 were measured by radioimmunoassay of their stable metabolites immunoreactive (i) TxB2 and i6-keto-PGF1 alpha, respectively. Drugs were given 30 min before induction of fecal peritonitis. Survival times in hours were as follows: fecal peritonitis = 10.5 +/- 0.4 (n = 50); ibuprofen (15 mg/kg) = 16.1 +/- 0.8 (n = 8); methylprednisolone-sodium succinate (40 mg/kg) = 17.1 +/- 0.7 (n = 22); methylprednisolone-sodium succinate (80 mg/kg) = 46.1 +/- 10.4 (n = 25) with 8% long-term survivors (survival greater than 7 days); gentamicin (4 mg/kg) = 23.8 +/- 4.4 (n = 16); methylprednisolone-sodium succinate (40 mg/kg) + ibuprofen = 20.3 +/- 1.8 (n = 6); gentamicin + methylprednisolone-sodium succinate = 31.0 +/- 1.6 (n = 11); gentamicin + ibuprofen = 28.5 + 2.3 (n = 12); gentamicin + methylprednisolone-sodium succinate (40 mg/kg) + ibuprofen = 46.9 +/- 5.4 (n = 8). Treatment with the combination of gentamicin + ibuprofen + methylprednisolone-sodium succinate (80 mg/kg) resulted in a mean survival time of 116 +/- 13.9 h with 26% long-term survivors. Methylprednisolone-sodium succinate (40 mg/kg) reduced (P less than 0.05) plasma iTxB2 from 995 +/- 78 (n = 16) to 714 +/- 48 (n = 18) pg/ml and i6-keto-PGF1 alpha from 4,090 +/- 334 (n = 12) to 2,009 +/- 119 (n = 17) pg/ml, 4 h post-FP. Methylprednisolone-sodium succinate (80 mg/kg) produced no further decrease in either iTxB2 or i6-keto-PGF1 alpha. Ibuprofen reduced the fecal peritonitis-induced iTxB2 and i6-keto-PGF1 alpha synthesis to nondetectable levels (less than 200 pg/ml). The latter results demonstrate that methylprednisolone-sodium succinate is less effective

  17. Depressed left ventricular performance. Response to volume infusion in patients with sepsis and septic shock

    SciTech Connect

    Ognibene, F.P.; Parker, M.M.; Natanson, C.; Shelhamer, J.H.; Parrillo, J.E.

    1988-05-01

    Volume infusion, to increase preload and to enhance ventricular performance, is accepted as initial management of septic shock. Recent evidence has demonstrated depressed myocardial function in human septic shock. We analyzed left ventricular performance during volume infusion using serial data from simultaneously obtained pulmonary artery catheter hemodynamic measurements and radionuclide cineangiography. Critically ill control subjects (n = 14), patients with sepsis but without shock (n = 21), and patients with septic shock (n = 21) had prevolume infusion hemodynamic measurements determined and received statistically similar volumes of fluid resulting in similar increases in pulmonary capillary wedge pressure. There was a strong trend (p = 0.004) toward less of a change in left ventricular stroke work index (LVSWI) after volume infusion in patients with sepsis and septic shock compared with control subjects. The LVSWI response after volume infusion was significantly less in patients with septic shock when compared with critically ill control subjects (p less than 0.05). These data demonstrate significantly altered ventricular performance, as measured by LVSWI, in response to volume infusion in patients with septic shock.

  18. Effectiveness of anisodamine for the treatment of critically ill patients with septic shock (ACIdoSIS study): study protocol for randomized controlled trial

    PubMed Central

    Zhou, Jiancang; Shang, You; Wang, Xin’an; Yin, Rui; Zhu, Zhenhua; Chen, Wensen; Tian, Xin; Yu, Yuetian; Zuo, Xiangrong; Chen, Kun; Ji, Xuqing; Ni, Hongying

    2015-01-01

    Background Septic shock is an important contributor of mortality in the intensive care unit (ICU). Although strenuous effort has been made to improve its outcome, the mortality rate is only marginally decreased. The present study aimed to investigate the effectiveness of anisodamine in the treatment of septic shock, in the hope that the drug will provide alternatives to the treatment of septic shock. Methods The study is a multi-center randomized controlled clinical trial. Study population will include critically ill patients with septic shock requiring vasopressor use. Blocked randomization was performed where anisodamine and control treatments were allocated at random in a ratio of 1:1 in blocks of sizes 2, 4, 6, 8, and 10 to 354 subjects. Interim analysis will be performed. The primary study end point is the hospital mortality, and other secondary study endpoints include ICU mortality, length of stay in ICU and hospital, organ failure free days. Adverse events including new onset psychosis, urinary retention, significant hypotension and tachycardia will be reported. Discussion The study will provide new insight into the treatment of septic shock and can help to reduce mortality rate of septic shock. Trial registration NCT02442440 (https://register.clinicaltrials.gov/). PMID:26605292

  19. Ascorbate-dependent vasopressor synthesis: a rationale for vitamin C administration in severe sepsis and septic shock?

    PubMed

    Carr, Anitra C; Shaw, Geoffrey M; Fowler, Alpha A; Natarajan, Ramesh

    2015-01-01

    Severe systemic inflammatory response to infection results in severe sepsis and septic shock, which are the leading causes of death in critically ill patients. Septic shock is characterised by refractory hypotension and is typically managed by fluid resuscitation and administration of catecholamine vasopressors such as norepinephrine. Vasopressin can also be administered to raise mean arterial pressure or decrease the norepinephrine dose. Endogenous norepinephrine and vasopressin are synthesised by the copper-containing enzymes dopamine β-hydroxylase and peptidylglycine α-amidating monooxygenase, respectively. Both of these enzymes require ascorbate as a cofactor for optimal activity. Patients with severe sepsis present with hypovitaminosis C, and pre-clinical and clinical studies have indicated that administration of high-dose ascorbate decreases the levels of pro-inflammatory biomarkers, attenuates organ dysfunction and improves haemodynamic parameters. It is conceivable that administration of ascorbate to septic patients with hypovitaminosis C could improve endogenous vasopressor synthesis and thus ameliorate the requirement for exogenously administered vasopressors. Ascorbate-dependent vasopressor synthesis represents a currently underexplored biochemical mechanism by which ascorbate could act as an adjuvant therapy for severe sepsis and septic shock. PMID:26612352

  20. Treatment of LD100 Escherichia coli septic shock with netilmicin and methylprednisolone in baboons.

    PubMed

    Flournoy, D J; Archer, L T; Beller, B K; Passey, R; Hinshaw, L B

    1986-01-01

    Treatment efficacy with netilmicin sulphate/methylprednisolone sodium succinate in a severe septic shock baboon model, using an LD100 of live Escherichia coli, was evaluated. All the animals treated with both netilmicin and methylprednisolone were permanent (greater than or equal to 7 days) survivors, whereas none of the untreated baboons lived more than 24 hours. These results indicate that, in a baboon model, netilmicin is an effective alternative to gentamicin (with methylprednisolone) in the treatment of severe septic shock. PMID:3526104

  1. Beneficial and side effects of arginine vasopressin and terlipressin for septic shock.

    PubMed

    Xiao, Xudong; Zhu, Yu; Zhen, Danyang; Chen, Xiao Ming; Yue, Wu; Liu, Liangming; Li, Tao

    2015-05-15

    Arginine vasopressin (AVP) and its analog, terlipressin (TP), were all demonstrated beneficial for septic shock. What advantages and disadvantages that AVP and TP have for septic shock as well as the mechanism, however, are not completely known. With cecal ligation and puncture-induced septic shock rats and lipopolysaccharide-induced septic shock rabbits, we systematically compared the beneficial and side effects of AVP and TP, in septic shock and the sex difference, and investigated their relationship to Rho kinase and calcium sensitivity. The results indicated that low dose of TP (2.6 μg/kg/h) in combination with norepinephrine (NE) improving vascular reactivity and animal survival were superior to a small dose of AVP (0.03 U/kg/h) in septic shock rats and rabbits. This improving effect of AVP and TP on vascular reactivity was closely related to the activation of Rho-kinase and Rho-kinase-mediating vascular calcium sensitization. A small dose of TP did not result in hyponatremia, did not increase blood bilirubin and decrease platelet count, whereas AVP did. Animal survival and vascular reactivity in female rats after TP or AVP administration were slightly better than male rats, while there were no significant differences. It was suggested that a small dose of TP has better beneficial effect and less side effects on septic shock than AVP. AVP and TP improving vascular reactivity is closely related to Rho-kinase activation and calcium sensitivity improvement. TP or plus NE may be more appropriate for early emergency care for severe septic shock than AVP. PMID:25769491

  2. 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

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

    PubMed

    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

  4. The Role of Mannose-Binding Lectin in Severe Sepsis and Septic Shock

    PubMed Central

    De Pascale, Gennaro; Cutuli, Salvatore Lucio; Pennisi, Mariano Alberto; Antonelli, Massimo

    2013-01-01

    Severe sepsis and septic shock are a primary cause of death in patients in intensive care unit (ICU). Investigations upon genetic susceptibility profile to systemic complications during severe infections are a field of increasing scientific interest. Particularly when adaptive immune system is compromised or immature, innate immunity plays a key role in the immediate defense against invasive pathogens. Mannose-binding lectin (MBL) is a serum protein that recognizes a wide range of pathogenic microorganisms and activates complement cascade via the antibody-independent pathway. More than 30% of humans harbor mutations in MBL gene (MBL2) resulting in reduced plasmatic levels and activity. Increased risk of infection acquisition has been largely documented in MBL-deficient patients, but the real impact of this form of innate immunosuppression upon clinical outcome is not clear. In critically ill patients higher incidence and worse prognosis of severe sepsis/septic shock appear to be associated with low-producers haplotypes. However an excess of MBL activation might be also harmful due to the possibility of an unbalanced proinflammatory response and an additional host injury. Strategies of replacement therapies in critically ill patients with severe infections are under investigation but still far to be applied in clinical practice. PMID:24223476

  5. 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

  6. Hepatic Perfusion Alterations in Septic Shock Patients: Impact of Early Goal-directed Therapy

    PubMed Central

    Zhang, Xi-Wen; Xie, Jian-Feng; Liu, Ai-Ran; Huang, Ying-Zi; Guo, Feng-Mei; Yang, Cong-Shan; Yang, Yi; Qiu, Hai-Bo

    2016-01-01

    Background: Early goal-directed therapy (EGDT) has become an important therapeutic management in early salvage stage of septic shock. However, splenic organs possibly remained hypoperfused and hypoxic despite fluid resuscitation. This study aimed to evaluate the effect of EGDT on hepatic perfusion in septic shock patients. Methods: A prospective observational study was carried out in early septic shock patients who were admitted to Intensive Care Unit within 24 h after onset and who met all four elements of the EGDT criteria after treatment with the standard EGDT procedure within 6 h between December 1, 2012 and November 30, 2013. The hemodynamic data were recorded, and oxygen metabolism and hepatic functions were monitored. An indocyanine green clearance test was applied to detect the hepatic perfusion. The patients’ characteristics were compared before treatment (T0), immediately after EGDT (T1), and 24 h after EGDT (T2). This study is registered at ClinicalTrials.org, NCT02060773. Results: Twenty-one patients were included in the study; however, the hepatic perfusion data were not included in the analysis for two patients; therefore, 19 patients were eligible for the study. Hemodynamics data, as monitored by pulse-indicator continuous cardiac output, were obtained from 16 patients. There were no significant differences in indocyanine green plasma disappearance rate (ICG-PDR) and 15-min retention rate (R15) at T0 (11.9 ± 5.0%/min and 20.0 ± 13.2%), T1 (11.4 ± 5.1%/min and 23.6 ± 14.9%), and T2 (11.0 ± 4.5%/min and 23.7 ± 15.3%) (all P > 0.05). Both of the alterations of ICG-PDR and R15 showed no differences at T0, T1, and T2 in the patients of different subgroups that achieved different resuscitation goal numbers when elected (P > 0.05). Conclusion: There were no hepatic perfusion improvements after EGDT in the early phase of patients with septic shock. Trial Registration: Clinicaltrials.gov NCT02060773 (https://clinicaltrials.gov/ct2/show/NCT02060773

  7. Effect of ozone pre-conditioning on redox activity in a rat model of septic shock.

    PubMed

    Guanche, Dailen; Hernandez, Frank; Zamora, Zullyt; Alonso, Yaima

    2010-10-01

    The confirmed advantageous effects of oxygen/ozone therapy in several clinical conditions stimulated experimental studies on effects of the therapy in induced septic shock. This study researches the influence of Ozone Oxidative Pre-conditioning (OOP) in unbalance between pro-oxidant and antioxidant activity generated in liver and lung during a process of sepsis. The study was conducted on male rats. Sepsis was induced by intraperitoneal injection of fecal material and pre-treatment with ozone/oxygen mixture was administered before fecal material injection. Activities of catalase, glutathione peroxide, and superoxide dismutase were measured, as well as conjugated dienes (CD) and thiobarbituric acid reactive substances (TBARS) were estimated. The results demonstrated that OOP not cause oxidative damage. It reduced levels of pro-oxidant biomarkers in lung and liver, with decreased total pro-oxidant activity and elevated total antioxidant activity from a system for diagnosis of oxidative stress in both tissues. These results suggest that OOP protected liver and lung for oxidative stress in septic shock. PMID:20626256

  8. Current management of the septic shock patient: experimental basis for treatment.

    PubMed

    Hinshaw, L B; Beller-Todd, B K; Archer, L T

    1982-01-01

    Experimental research has shown that following the intravenous infusion of animals with bacteria or endotoxin a myriad of adverse vascular events occur resulting in deficient organ perfusion and cell death. The primary goals of therapy for sepsis and septic shock, therefore, should include elimination of the source of infection and/or infectious agents and prevention or reversal of adverse vascular events. The following review describes the evolution of an effective therapy for shock consisting of steroid in combination with antibiotic and discusses its relevance and application for humans in severe sepsis or septic shock. PMID:6756669

  9. 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. PMID:23542126

  10. 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

  11. Protective effect of pentoxifylline plus thalidomide against septic shock in mice

    PubMed Central

    ARRIETA, OSCAR; ORTIZ-REYES, ARACELI; REMBAO, DANIEL; CALVILLO, MINERVA; RIVERA, ERIKA; SOTELO, JULIO

    1999-01-01

    Mortality caused by septic shock in experimental animals is reduced by thalidomide, an inhibitor of tumour necrosis factor α. Another drug that could act on the pathopysiological mechanisms of septic shock is pentoxifylline, an inhibitor of platelet aggregation that increases the flexibility of the erythrocyte membrane and has fibrinolytic activity. We studied the effect of pentoxifylline alone and combined with thalidomide in septic shock; 97 NIH mice were injected with lipopolysaccharides of Salmonella abortus equi and D galactosamine. Animals were separated in 4 groups; group A (n = 20) was used as control, group B (n = 15) received thalidomide 50 mg/kg, group C (n = 20) received pentoxifylline 40 mg/kg, and group D (n = 15) received thalidomide plus pentoxifylline. Mortality was recorded every hour. Additionally, 5 animals from each group were sacrificed 8 h after the induction of septic shock for histological analysis of heart, lung, brain, kidney, small intestine, adrenal glands and liver. Microscopic findings were rated as absent, mild, moderate and severe damage. In control animals histological analysis showed intense haemorrhage and necrosis in all organs studied. When compared with controls, treatment with pentoxifylline plus thalidomide reduced mortality (P < 0.03). The tissue damage was less severe in animals from the groups that received pentoxifylline or pentoxifylline plus thalidomide (P < 0.05). Pentoxifylline seems to potentiate the beneficial effects of thalidomide, reducing mortality and attenuating the pathological changes produced by septic shock. PMID:10365082

  12. Effects and mechanism analysis of combined infusion by levosimendan and vasopressin on acute lung injury in rats septic shock.

    PubMed

    Wang, Xuebing; Ma, Shaolin; Liu, Yang; Xu, Wei; Li, Zhanxia

    2014-12-01

    This research is aimed to discover the influence and underling mechanism of combined infusion of arginine vasopressin with levosimendan on acute lung injury in rat septic shock with norepinephrine supplemented. The traditional fecal peritonitis-induced septic shock model was undergone in rats for study. It is observed that the combined infusion supplemented with norepinephrine brought about a lower mean pulmonary artery pressure; lower high-mobility group box 1 levels, pulmonary levels of interleukin-6, and arterial total nitrate/nitrite; lower apoptotic cells scores and total histological scores; but higher pulmonary gas exchange when compared with the separate infusion group and norepinephrine group. This therapy shows potential clinical beneficial assistance in sepsis-induced acute lung injury. The results suggest the mechanism of such effect is through abating pulmonary artery pressure, and more importantly suppressing inflammatory responses in lung when compared with norepinephrine infusion group and the separate infusion of levosimendan or vasopressin alone. PMID:25002345

  13. Early initiation of low-dose corticosteroid therapy in the management of septic shock: a retrospective observational study

    PubMed Central

    2012-01-01

    Introduction The use of low-dose steroid therapy in the management of septic shock has been extensively studied. However, the association between the timing of low-dose steroid therapy and the outcome has not been evaluated. Therefore, we evaluated whether early initiation of low-dose steroid therapy is associated with mortality in patients with septic shock. Methods We retrospectively analyzed the clinical data of 178 patients who received low-dose corticosteroid therapy for septic shock between January 2008 and December 2009. Time-dependent Cox regression models were used to adjust for potential confounding factors in the association between the time to initiation of low-dose corticosteroid therapy and in-hospital mortality. Results The study population consisted of 107 men and 71 women with a median age of 66 (interquartile range, 54 to 71) years. The 28-day mortality was 44% and low-dose corticosteroid therapy was initiated within a median of 8.5 (3.8 to 19.1) hours after onset of septic shock-related hypotension. Median time to initiation of low-dose corticosteroid therapy was significantly shorter in survivors than in non-survivors (6.5 hours versus 10.4 hours; P = 0.0135). The mortality rates increased significantly with increasing quintiles of time to initiation of low-dose corticosteroid therapy (P = 0.0107 for trend). Other factors associated with 28-day mortality were higher Simplified Acute Physiology Score (SAPS) 3 (P < 0.0001) and Sequential Organ Failure Assessment (SOFA) scores (P = 0.0007), dose of vasopressor at the time of initiation of low-dose corticosteroid therapy (P < 0.0001), need for mechanical ventilation (P = 0.0001) and renal replacement therapy (P < 0.0001), while the impaired adrenal reserve did not affect 28-day mortality (81% versus 82%; P = 0.8679). After adjusting for potential confounding factors, the time to initiation of low-dose corticosteroid therapy was still significantly associated with 28-day mortality (adjusted odds

  14. Septic Shock in Advanced Age: Transcriptome Analysis Reveals Altered Molecular Signatures in Neutrophil Granulocytes

    PubMed Central

    Vieira da Silva Pellegrina, Diogo; Severino, Patricia; Vieira Barbeiro, Hermes; Maziero Andreghetto, Flávia; Tadeu Velasco, Irineu; Possolo de Souza, Heraldo; Machado, Marcel Cerqueira César; Reis, Eduardo Moraes; Pinheiro da Silva, Fabiano

    2015-01-01

    Sepsis is one of the highest causes of mortality in hospitalized people and a common complication in both surgical and clinical patients admitted to hospital for non-infectious reasons. Sepsis is especially common in older people and its incidence is likely to increase substantially as a population ages. Despite its increased prevalence and mortality in older people, immune responses in the elderly during septic shock appear similar to that in younger patients. The purpose of this study was to conduct a genome-wide gene expression analysis of circulating neutrophils from old and young septic patients to better understand how aged individuals respond to severe infectious insult. We detected several genes whose expression could be used to differentiate immune responses of the elderly from those of young people, including genes related to oxidative phosphorylation, mitochondrial dysfunction and TGF-β signaling, among others. Our results identify major molecular pathways that are particularly affected in the elderly during sepsis, which might have a pivotal role in worsening clinical outcomes compared with young people with sepsis. PMID:26047321

  15. Intraosseous and intravenous administration of antibiotics yields comparable plasma concentrations during experimental septic shock

    PubMed Central

    Strandberg, G; Larsson, A; Lipcsey, M; Michalek, J; Eriksson, M

    2015-01-01

    Background We aimed to investigate whether comparable antibiotic concentrations could be reached with intraosseous and intravenous administration during septic shock. Methods In this randomized, prospective experimental study conducted at an animal research laboratory at the University Hospital of Uppsala, eight anesthetized pigs, weighing 21.2 to 29.1 kg (mean: 25.2 ± 2.3 kg), received endotoxin infusion at 4 μg/kg/h for 6 h. At the onset of clinical shock, alternatively after 3 h of endotoxemia, they received 75 mg/kg of cefotaxime and 7 mg/kg of gentamicin either in a proximal tibial intraosseous catheter or in a peripheral intravenous catheter. Mixed venous samples were taken after 5, 15, 30, 60, 120 and 180 min and analyzed for antibiotic concentrations. Results For both antibiotics, plasma concentrations after intraosseous and intravenous administration followed similar curves throughout the observation period, and peak concentrations were comparable. Mean concentration area under the curve (AUC mg × h/l) for cefotaxime was 108.1 ± 19.5 after intraosseous and 116.5 ± 11.1 after intravenous administration; ratio 0.93, (95% CI 0.71–1.19). Mean AUC for gentamicin was 28.1 ± 6.8 for intraosseous and 32.2 ± 3.5 for intravenous administration; ratio 0.87 (95% CI 0.62–1.19). Conclusions In this porcine septic shock model, intraosseous and intravenous administration of gentamicin and cefotaxime yielded comparable concentrations. In an emergency, intraosseous administration of these antibiotics may be considered in severe infections when venous access is difficult. PMID:25557933

  16. Targeting the ubiquitin proteasome pathway for the treatment of septic shock in patients

    PubMed Central

    2009-01-01

    Endotoxic shock is a serious systemic inflammatory response to an external biological stressor. The responsiveness of NF-κB is built upon rapid protein modification and degradation involving the ubiquitin proteasome pathway. Using transgenic mice, we have obtained in vivo evidence that interference with this pathway can alleviate the symptoms of toxic shock. We posit that administration of proteasome inhibitors may enhance the survival of patients with septic shock. PMID:19691815

  17. 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

  18. Optimal Meropenem Concentrations To Treat Multidrug-Resistant Pseudomonas aeruginosa Septic Shock

    PubMed Central

    Cotton, Frédéric; Roisin, Sandrine; Vincent, Jean-Louis; Jacobs, Frédérique

    2012-01-01

    A patient with septic shock due to extensively drug resistant (XDR) Pseudomonas aeruginosa was cured by optimizing the meropenem (MEM) regimen to obtain at least 40% of the time between two administrations in which drug levels were four times higher than the MIC of the pathogen. As the standard drug dose did not achieve these optimal concentrations, the MEM regimen was progressively increased up to 12 g/day (3 g every 6 h in a 3-h extended infusion), which eventually resulted in sepsis resolution. High MEM dosage may represent a valuable therapeutic option for infection due to multidrug-resistant (MDR) strains, and drug monitoring would allow rapid regimen adjustment in clinical practice. PMID:22290984

  19. Changes in plasma kynurenic acid concentration in septic shock patients undergoing continuous veno-venous haemofiltration.

    PubMed

    Dabrowski, Wojciech; Kocki, Tomasz; Pilat, Jacek; Parada-Turska, Jolanta; Malbrain, Manu L N G

    2014-02-01

    Kynurenic acid (KYNA) is one of the end products of tryptophan metabolism. The aim of this study was to analyse plasma KYNA concentration in septic shock patients (SSP) with acute kidney injury (AKI) undergoing continuous veno-venous haemofiltration (CVVH). Changes in KYNA content were compared to alterations in the levels of procalcitonin (PCT), C-reactive protein and lactate. Adult SSP with AKI were examined. Measurements were conducted at seven time points: before beginning CVVH and at 6, 12, 24, 48, 72 and 96 h after the beginning of CVVH. Based on clinical outcomes, the data were analysed separately for survivors and non-survivors. Twenty-seven patients were studied. CVVH was associated with reduced plasma KYNA concentration only in survivors. Plasma KYNA concentration correlated with the levels of lactate and PCT only in survivors. (1) CVVH reduced plasma KYNA concentration only in survivors; (2) lack of this reduction may predict fatal outcomes in SSP. PMID:24043287

  20. Lincomycin protects mice from septic shock in beta-glucan-indomethacin model.

    PubMed

    Nameda, Sachiko; Miura, Noriko N; Adachi, Yoshiyuki; Ohno, Naohito

    2007-12-01

    We have developed a septic shock model in mice by sequential administration of beta-glucan, a biological response modifier, and indomethacin (IND), a nonsteroidal anti-inflammatory drug. Lethality was significantly related to the translocation of gut flora to various organs and mal-adjustment of the cytokine network. In the present study, we have examined the effect of antibiotics on this model to further clarify meanings of microbial flora. Schizophyllan (SPG), antitumor beta-glucan for clinical use, obtained from the culture filtrate of Schizophyllum commune, was used to induce sepsis. Lincomycin (LCM), imipenem (IPM), cilastatine (CS), and ampicillin (ABPC) were used for antibiotics treatment. The survival rate of SPG/IND-treated mice was significantly increased by administering LCM or ABPC/IPM/CS, and the effect was more significant by LCM. In in vitro spleen cell culture, LCM decreased proinflammatory cytokine production. Moreover, prednisolone, immune suppresser treatment improved survival of SPG/IND-treated mice. These findings suggest that LCM is an effective antibiotic in this endogenous septic model by modulating gut microbial flora and, at least a part, by regulating cytokine production of leukocytes. PMID:18057718

  1. 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. PMID:21817894

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

    PubMed

    Samannodi, Mohammed; Zhao, Andrew; Nemshah, Yaser; Shiley, Kevin

    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

  3. 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

  4. Why activated Protein C was not successful in severe sepsis and septic shock: Are we still tilting at windmills?

    PubMed Central

    Lai, Peggy S.; Thompson, B. Taylor

    2013-01-01

    Drotrecogin alpha activated (DAA), trade name Xigris, is a recombinant human protein C that has been the subject of controversy since 2001 when it became the first biologic agent approved for the treatment of severe sepsis and septic shock. The PROWESS trial showed a 6.1% absolute reduction in 28-day mortality although these findings were not replicated in later trials, ultimately leading to the withdrawal of DAA in 2011. Observational trials, however, have consistently shown a mortality benefit with the use of DAA, leading to the questions, did DAA truly fail and if so, why? While these questions may never be definitively answered based on available evidence, several factors may explain the conflicting results.. In clinical practice, DAA may have been preferentially given to subjects more likely to survive. Contemporary treatments including early antibiotic administration and volume resuscitation may have mitigated the inflammatory processes leading to disordered coagulation and microvascular thrombosis and thus reduced or abolished the therapeutic opportunity for DAA. Later randomized clinical trials of DAA focused on the clinical phenotype of refractory shock largely due to a strong efficacy signal in this subset from PROWESS; however, this clinical phenotype may not be tightly linked, at least after contemporary early resuscitation strategies, to the mechanistic phenotype of dysregulated coagulation that may have been a better target for DAA. Future trials of biologic therapies in severe sepsis and septic shock should use a combination of clinical phenotype and biomarkers to identify responsive populations that may benefit from such therapies. PMID:23925482

  5. Liver gluconeogenic metabolites in young and old rats during septic shock.

    PubMed

    Schumer, W

    1988-07-01

    Aged individuals have diminished resistance to severe sepsis and septic shock. Previous studies in young animals showed that the liver's gluconeogenic capacity was an important determinant of survival in shock states. This study compared hepatic carbohydrate intermediates from young rats and old rats to correlate changes during peritonitis septic shock with known differences in survival times. Old control rats had glucose 6-phosphate (G6P) concentrations two-fold higher than young controls, 354 +/- 49 nanomole/g wet liver vs 180 +/- 41, suggesting a reduced ability to convert hexose monophosphate precursor into blood sugar. There was a 53% increase in G6P levels in the peritonitis livers, to 540 +/- 155 nanomole/g liver while in young septic rats the G6P decreased 33 per cent. These opposite, highly significant changes in shock (P = 0.01) show the reduced ability of old animals to mobilize gluconeogenic precursors. Fructose 1,6-biphosphate (FBP) in old control liver was 14 +/- 3 nanomole/g liver and did not change in shock; in young rats, FBP was 7.0 +/- 3 nanomole and increased 230 per cent in shock, showing a different metabolic response in young and old animals. These data suggest older animals may be more vulnerable to shock because of lower gluconeogenic potential. PMID:3389597

  6. 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. PMID:20523274

  7. 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. PMID:25227191

  8. Intravenous catheter-related septic shock caused by Staphylococcus sciuri and Escherichia vulneris.

    PubMed

    Horii, T; Suzuki, Y; Kimura, T; Kanno, T; Maekawa, M

    2001-01-01

    Staphylococcus sciuri and Escherichia vulneris were isolated concurrently in a blood sample from a patient with septic shock, which was probably associated with an indwelling catheter. Our results also showed that S. sciuri is an important reservoir of genetic determinants of beta-lactam resistance as a human pathogen carrying the mecA and beta-lactamase genes. PMID:11868769

  9. Blood pressure alterations in burn patients with septic shock under hydro-cortisone treatment

    PubMed Central

    Alinejad, Faranak; Momeni, Mahnoush; Fatemi, Mohammad Javad; Saberi, Mohsen; Sattarzade, Mahboobeh; Babajani, Rafat; Rahbar, Hossein

    2015-01-01

    Background and Objectives: Hydrocortisone is widely used in septic shock cases resistant to fluid and vasopressor therapy. It may result in increased blood pressure and survival. However the efficacy is no established among patients with severe burn and septic shock. Accordingly it was assessed in this study. Materials and Methods: The patients older than 14 years of age with resistant septic shock were enrolled during one-year period. The hydrocortisone was prescribed 100 mg three times per day and the alterations in systolic and diastolic blood pressures were recorded. Results: Twenty-nine patients were enrolled including 19 men and 10 women. The mean age was 37 ± 19 years and the mean burn surface area was 60 ± 20. Fourteen patients had positive blood culture. The most common isolated microorganism were Pseudomonas aeuroginosa in 34.6%(10 cases), and then Acinetobacter in 13.8%(4 cases). The infection was from wound in 79% and the remaining 21% had pneumonia. Twenty-one patients had good response to hydrocortisone and the increase in systolic and diastolic blood pressures was significant; but the mortality rate was similar. Conclusion: Treatment with hydrocortisone would result in increase in systolic and diastolic blood pressure in burn patients with resistant septic shock. PMID:26885331

  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. [Septic shock Fusobacterium necrophorum from origin gynecological at complicated an acute respiratory distress syndrome: a variant of Lemierre's syndrome].

    PubMed

    Huynh-Moynot, Sophie; Commandeur, Diane; Danguy des Déserts, Marc; Drouillard, Isabelle; Leguen, Patrick; Ould-Ahmed, Mehdi

    2011-01-01

    We report a case of a female patient of 47 years old who presents in a state of septic shock with acute insufficient respiratory complicated with syndrome of acute respiratory distress, together with a list of abdominal pain and polyarthralgia too. In her case of medical history, it is retained that she has had a intra-uterine device since 6 years without medical follow up. The initial thoraco-abdomino-pelvic scan shows a left ovarian vein thrombosis, as well as the opaqueness alveolus diffused interstitiel bilaterally and an aspect of ileitis. The IUD is taken off because of sudden occuring of purulent leucorrhoea. This results in a clinical and paraclinical improvement, whereas aminopenicillin was administered to the patient since 1 week. The microbiological blood test allows to put in evidence Fusobacterium necrophorum found in a blood culture and is sensitive to the amoxicilline-acide clavulanique and metronidazole. Isolation of this bacteria, classically found in Lemierre's syndrome, allowed to explain the multilfocalization of the symtoms and the list of pain. The whole concerns about a variant of Lemierre's syndrom: a state of septic shock secondary then caused by the anaerobic Gram negative bacilli, which is a commensal bacteria of the female genital tractus, complicated of septic emboli typical. PMID:21464014

  12. Mitochondrial nitric oxide synthase participates in septic shock myocardial depression by nitric oxide overproduction and mitochondrial permeability transition pore opening.

    PubMed

    Xu, Ce; Yi, Chenju; Wang, Huiping; Bruce, Iain C; Xia, Qiang

    2012-01-01

    The aim of this study was to determine whether mitochondrial nitric oxide (NO) synthase (NOS) is involved in septic shock myocardial depression. The cecal ligation and puncture (CLP) method was used to induce septic shock. There was a significant depression of hemodynamic parameters recorded in the septic shock stage. After using nonselective NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME), inducible NOS inhibitor aminoguanidine (AMG), and neuronal NOS inhibitor 7-nitroindazole (7-NI), depression of the parameters was partly attenuated. Nitric oxide production in isolated cardiac mitochondria increased obviously in the CLP-septic shock stage, L-NAME and 7-NI both decreased NO production significantly. Nitrite/nitrate (NOx) production in the septic shock stage was much greater than those in the corresponding sham groups, and NOx production in the cytosol by inducible NOS was greater. Treatment with AMG suppressed NOx production in the cytosol by iNOS, whereas treatment with 7-NI decreased NOx production in the mitochondria. Mitochondrial NOS expression increased significantly in the septic shock stage, and its overexpression was attenuated using 7-NI. There was no significant decrease in the mitochondrial permeability transition pore measurement in the CLP-septic shock group, whereas a significant decrease was observed in those treated with L-NAME or 7-NI. These results indicate that overexpression of mitochondrial NOS is involved in myocardial depression. PMID:21993446

  13. Effect of high dose corticosteroids alone or combined with other drugs on survival in septic shock.

    PubMed

    Almqvist, P M; Ekström, B; Kuenzig, M; Haglund, U; Schwartz, S I

    1985-01-01

    The effect of high dose corticosteroids on survival has been studied in a limited number of canine septic shock models which are reviewed in this presentation. Following injection of live bacteria neither methylprednisolone, nor gentamicin but a combination improved survival. Methylprednisolone increased survival following a slow but not a bolus infusion of endotoxin. In a recent study the effects of short term treatment with methylprednisolone, naloxone and ibuprofen were studied in endotoxin shock. All control animals died within 36 hours. Five of 9 dogs receiving the combination methylprednisolone, naloxone and ibuprofen were permanent survivors. The combined treatment with methylprednisolone and ibuprofen also increased survival. Dogs treated with methylprednisolone alone did not differ significantly from controls. It is concluded that methylprednisolone alone has no significant effect on survival in septic shock, but seems to be an important therapeutic factor to achieve increased survival. PMID:3867205

  14. 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.

  15. The Italian SEPSIS study: preliminary results on the incidence and evolution of SIRS, sepsis, severe sepsis and septic shock.

    PubMed

    Salvo, I; de Cian, W; Musicco, M; Langer, M; Piadena, R; Wolfler, A; Montani, C; Magni, E

    1995-11-01

    This prospective, multicenter, epidemiological study was carried out in 99 Italian ICUs, distributed throughout the country, from April 1993 to March 1994. In the study, we applied the new ACCP/SCCM classification system for sepsis (SIRS, sepsis, severe sepsis and septic shock) and determined the prevalence, incidence, evolution and outcome of these categories in critically ill patients. The preliminary analysis of 1101 patients showed that on admission SIRS accounted for about half of the diagnoses (52%) with sepsis, severe sepsis and septic shock accounting for 4.5%, 2.1% and 3% of patients, respectively. Patients with severe sepsis or septic shock more frequently had high SAPS scores than patients without sepsis. Mortality rates were similar in patients with SIRS (26.5%) and without SIRS or infection (24%), but rose to 36% in patients with sepsis, to 52% in those with severe sepsis and to 81.8% in those with septic shock. Sepsis, severe sepsis and septic shock were more common in patients with medical diagnoses, and neither severe sepsis nor septic shock was observed in trauma patients. With respect to evolution, the incidence of septic shock was progressively higher in patients admitted with more severe "sepsis-related" diagnoses, while only a trivial difference in rates of incidence was observed between SIRS patients and those admitted without SIRS or any septic disorder (nil). The breakdown of the various ACCP/SCCM "sepsis-related" diagnoses at any time during the study was: SIRS in 58% of the population, sepsis in 16.3%, severe sepsis in 5.5% and septic shock in 6.1%. It seems reasonable to expect from the final evaluation of our study answers to the questions raised by the ACCP/SCCM Consensus Conference about the correlations between "sepsis-related" diagnosis, severity score, organ dysfunction score and outcome. PMID:8636531

  16. 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.

  17. A case of Lemierre's syndrome with septic shock and complicated parapneumonic effusions requiring intrapleural fibrinolysis

    PubMed Central

    Croft, Daniel P.; Philippo, Sean M.; Prasad, Paritosh

    2015-01-01

    Lemierre's syndrome is a septic thrombophlebitis of the internal jugular vein, which can lead to severe systemic illness. We report a case of an otherwise healthy 26-year-old man who suffered from pharyngitis followed by septic shock requiring intubation and vasopressor support from Fusobacterium necrophorum bacteremia. The septic emboli to his lungs caused complicated bilateral parapneumonic effusions, which recurred after initial drainage. He required bilateral chest tubes and intrapleural tPA to successfully drain his effusions. His fever curve and overall condition improved with the resolution of his effusions and after a 33-day hospitalization, he recovered without significant disability. The severity of his illness and difficult to manage complicated parapneumonic effusions were the unique facets of this case. Using an evidence-based approach of tPA and DNase for complicated parapneumonic effusions in Lemierre's syndrome can be safe and effective. PMID:26744664

  18. A case of Lemierre's syndrome with septic shock and complicated parapneumonic effusions requiring intrapleural fibrinolysis.

    PubMed

    Croft, Daniel P; Philippo, Sean M; Prasad, Paritosh

    2015-01-01

    Lemierre's syndrome is a septic thrombophlebitis of the internal jugular vein, which can lead to severe systemic illness. We report a case of an otherwise healthy 26-year-old man who suffered from pharyngitis followed by septic shock requiring intubation and vasopressor support from Fusobacterium necrophorum bacteremia. The septic emboli to his lungs caused complicated bilateral parapneumonic effusions, which recurred after initial drainage. He required bilateral chest tubes and intrapleural tPA to successfully drain his effusions. His fever curve and overall condition improved with the resolution of his effusions and after a 33-day hospitalization, he recovered without significant disability. The severity of his illness and difficult to manage complicated parapneumonic effusions were the unique facets of this case. Using an evidence-based approach of tPA and DNase for complicated parapneumonic effusions in Lemierre's syndrome can be safe and effective. PMID:26744664

  19. Population Pharmacokinetics of Piperacillin in the Early Phase of Septic Shock: Does Standard Dosing Result in Therapeutic Plasma Concentrations?

    PubMed Central

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

    2015-01-01

    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.) PMID:26349823

  20. Accuracy of a real-time continuous glucose monitoring system in children with septic shock: A pilot study

    PubMed Central

    Prabhudesai, Sumant; Kanjani, Amruta; Bhagat, Isha; Ravikumar, Karnam G.; Ramachandran, Bala

    2015-01-01

    Aims: The aim of this prospective, observational study was to determine the accuracy of a real-time continuous glucose monitoring system (CGMS) in children with septic shock. Subjects and Methods: Children aged 30 days to 18 years admitted to the Pediatric Intensive Care Unit with septic shock were included. A real-time CGMS sensor was used to obtain interstitial glucose readings. CGMS readings were compared statistically with simultaneous laboratory blood glucose (BG). Results: Nineteen children were included, and 235 pairs of BG-CGMS readings were obtained. BG and CGMS had a correlation coefficient of 0.61 (P < 0.001) and a median relative absolute difference of 17.29%. On Clarke's error grid analysis, 222 (94.5%) readings were in the clinically acceptable zones (A and B). When BG was < 70, 70–180, and > 180 mg/dL, 44%, 100%, and 76.9% readings were in zones A and B, respectively (P < 0.001). The accuracy of CGMS was not affected by the presence of edema, acidosis, vasopressors, steroids, or renal replacement therapy. On receiver operating characteristics curve analysis, a CGMS reading <97 mg/dL predicted hypoglycemia (sensitivity 85.2%, specificity 75%, area under the curve [AUC] =0.85). A reading > 141 mg/dL predicted hyperglycemia (sensitivity 84.6%, specificity 89.6%, AUC = 0.87). Conclusion: CGMS provides a fairly, accurate estimate of BG in children with septic shock. It is unaffected by a variety of clinical variables. The accuracy over extremes of blood sugar may be a concern. We recommend larger studies to evaluate its use for the early detection of hypoglycemia and hyperglycemia. PMID:26730114

  1. "Beat the Shock Clock": An Interprofessional Team Improves Pediatric Septic Shock Care.

    PubMed

    Tuuri, Rachel E; Gehrig, Madeline G; Busch, Carrie E; Ebeling, Myla; Morella, Kristen; Hunt, Lisa; Russell, W Scott

    2016-06-01

    Ideal care for septic shock (SS) is difficult. This interprofessional quality improvement intervention in a mid-volume pediatric emergency department aimed to reduce time to vascular access, fluid resuscitation, and antibiotics for SS. Intensive education, a care pathway, and an order set were applied. Outcome measures for patients with criteria for SS before and after intervention were compared. There were 43 patients pre-intervention (January 2009 to June 2011) and 63 post-intervention (June 2012 to June 2013). Median time to vascular access decreased from 37 minutes pre-intervention to 24 minutes post-intervention (p = 0.05). Median time to first fluid bolus decreased from 35 to 26 minutes (p = 0.08). Percentage of boluses delivered rapidly by pressure method increased from 21% to 74% (p < 0.0001). Median time to antibiotics decreased from 92 to 55 minutes (p = 0.02). In conclusion, a multimodal, interprofessional quality improvement intervention in a mid-sized pediatric emergency department improved the time to critical interventions for SS. PMID:26307185

  2. Early Fluid Resuscitation and High Volume Hemofiltration Decrease Septic Shock Progression in Swine

    PubMed Central

    Zhao, Ping; Zheng, Ruiqiang; Xue, Lu; Zhang, Min; Wu, Xiaoyan

    2015-01-01

    This study aimed to assess the effects of early fluid resuscitation (EFR) combined with high volume hemofiltration (HVHF) on the cardiopulmonary function and removal of inflammatory mediators in a septic shock swine model. Eighteen swine were randomized into three groups: control (n = 6) (extracorporeal circulating blood only), continuous renal replacement therapy (CRRT) (n = 6; ultrafiltration volume = 25 mL/Kg/h), and HVHF (n = 6; ultrafiltration volume = 85 mL/Kg/h). The septic shock model was established by intravenous infusion of lipopolysaccharides (50 µg/kg/h). Hemodynamic parameters (arterial pressure, heart rate, cardiac output, stroke volume variability, left ventricular contractility, systemic vascular resistance, and central venous pressure), vasoactive drug parameters (dose and time of norepinephrine and hourly fluid intake), pulmonary function (partial oxygen pressure and vascular permeability), and cytokines (interleukin-6 and interleukin-10) were observed. Treatment resulted in significant changes at 4–6 h. HVHF was beneficial, as shown by the dose of vasoactive drugs, fluid intake volume, left ventricular contractility index, and partial oxygen pressure. Both CRRT and HVHF groups showed improved removal of inflammatory mediators compared with controls. In conclusion, EFR combined with HVHF improved septic shock in this swine model. The combination decreased shock progression, reduced the need for vasoactive drugs, and alleviated the damage to cardiopulmonary functions. PMID:26543849

  3. Terlipressin as rescue therapy for intractable hypotension due to septic shock in children.

    PubMed

    Matok, Ilan; Vard, Amir; Efrati, Ori; Rubinshtein, Marina; Vishne, Tali; Leibovitch, Leah; Adam, Miriam; Barzilay, Zohar; Paret, Gideon

    2005-04-01

    Intractable hypotension due to septic shock is associated with high mortality rates in critically ill children worldwide. The use of terlipressin (triglycyl-lysine-vasopressin), an analog of vasopressin with a longer duration of action, recently emerged as a treatment of hypotension not responsive to vasopressors and inotropes. This was a retrospective study set in an 18-bed pediatric critical care department in a tertiary care children's hospital. We reviewed the files of all children with septic shock who were treated with terlipressin between January 2003 and February 2004. Fourteen children (mean age, 5.6 years; range, 4 days to 17.7 years) were treated with terlipressin in 16 septic shock episodes. Significant improvements in respiratory and hemodynamic indices were noted shortly after treatment. Mean arterial blood pressure increased significantly from 54 +/- 3 to 72 +/- 5 mmHg 10 min after terlipressin administration (P = 0.001). Heart rate decreased from 153.0 +/- 6.5 beats/min to 138.0 +/- 7.5 beats/min 12 h after treatment onset (P = 0.003). Epinephrine infusion was decreased or stopped in eight patients after terlipressin administration. Urine output increased from 1.6 +/- 0.5 mL/kg/h to 4.3 +/- 1.2 mL/kg/h 1 h after treatment onset (P = 0.011). PaO2 increased from 95.1 +/- 12.3 mmHg to 110.1 +/- 20.5 mmHg, and the oxygenation index decreased from 10.2 +/- 2.2 to 9.2 +/- 1.7. Terlipressin treatment of hypotension due to septic shock was successful in eight out of 16 episodes. Six of the 14 patients with poor prognosis for survival recovered. We conclude that terlipressin improves hemodynamic indices and renal function in critically ill children. Terlipressin should be considered as a rescue therapy in intractable shock not responsive to catecholamines in children. PMID:15803052

  4. 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. PMID:23603767

  5. 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

  6. 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

  7. Septic Shock Secondary to a Urinary Tract Infection with Pediococcus Pentosaceus.

    PubMed

    Han, Amneet; Mehta, Jeet; Pauly, Rebecca R

    2016-01-01

    We present a case of a urinary tract infection secondary to Pediococcus pentosaceus causing septic shock and acute kidney injury in a 70-year-old male. We demonstrate successful treatment with a 10-day course of piperacillin/tazobactam. Recently, Pediococci have been found to be the cause of opportunistic infections in humans. This has posed a challenge to treating infections caused by this species because it has been found to be resistant to multiple antibiotics, including glycopeptides. PMID:27443041

  8. Septic shock, necrotizing pneumonitis, and meningoencephalitis caused by Mycoplasma pneumoniae in a child: a case report.

    PubMed

    Barreira, Eliane R; Souza, Daniela C; Góes, Patricia F; Bousso, Albert

    2009-04-01

    Mycoplasma pneumoniae is an important causative agent of respiratory infection in childhood. Although the infection caused by M. pneumoniae is classically described as benign, severe and life-threatening pulmonary and extrapulmonary complications can occur. This study describes the first case of septic shock related to M. pneumoniae in a child with necrotizing pneumonitis, severe encephalitis, and multiple organs involvement, with a favorable outcome after lobectomy and systemic corticosteroids. PMID:19023109

  9. 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

  10. 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

  11. 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. PMID:24667627

  12. Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock

    PubMed Central

    2011-01-01

    Introduction The present study was designed to determine the effects of continuously infused norepinephrine (NE) plus (1) terlipressin (TP) or (2) arginine vasopressin (AVP) or (3) placebo on sublingual microcirculation in septic shock patients. The primary study end point was a difference of ≥ 20% in the microvascular flow index of small vessels among groups. Methods The design of the study was a prospective, randomized, double-blind clinical trial. NE was titrated to maintain mean arterial pressure (MAP) between 65 and 75 mmHg after establishment of normovolemia in 60 septic shock patients. Thereafter patients (n = 20 per group) were randomized to receive continuous infusions of either TP (1 μg/kg/hour), AVP (0.04 U/minute) or placebo (isotonic saline). In all groups, open-label NE was adjusted to maintain MAP within threshold values if needed. The sublingual microcirculatory blood flow of small vessels was assessed by sidestream dark-field imaging. All measurements, including data from right heart catheterization and norepinephrine requirements, were obtained at baseline and 6 hours after randomization. Results TP and AVP decreased NE requirements at the end of the 6-hour study period. The data are medians (25th and 75th interquartile ranges (IQRs)): 0.57 μg/kg/minute (0.29 to 1.04) vs. 0.16 μg/kg/minute (0.03 to 0.37) for TP and 0.40 μg/kg/minute (0.20 to 1.05) vs. 0.23 μg/kg/minute (0.03 to 0.77) for AVP, with statistical significance of P < 0.05 vs. baseline and vs. placebo. There were no differences in sublingual microcirculatory variables, systemic hemodynamics, oxygen transport and acid-base homeostasis among the three study groups during the entire observation period. The proportions of perfused vessels increased in relation to baseline within all study groups, and there were no significant differences between groups. The specific data were as follows (median (IQR)): 9.7% (2.6 to 19.8) for TP, 8.9% (0.0 to 17.8) for AVP, and 6.9% (3.5 to 10.1) for

  13. Rescue therapy with terlipressin by continuous infusion in a child with catecholamine-resistant septic shock.

    PubMed

    Zeballos, Gonzalo; López-Herce, Jesús; Fernández, Carmen; Brandstrup, Kay B; Rodríguez-Núñez, Antonio

    2006-01-01

    A 2-month-old female infant presented with septic shock, refractory to high doses of catecholamines. Continuous infusion of terlipressin at a rate of 10 mcg/kgh produced a significant increase in the mean arterial pressure that was evident within half and hour, so allowing a reduction in the rate of catecholamine infusion. However, 18 h later, the blood pressure fell again and finally the patient died. This case shows the potential value of terlipressin infusion to restore normal mean arterial pressure in children with vasodilatory shock and hypotension refractory to catecholamines. PMID:16325320

  14. 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

  15. 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

  16. Efficacy of selective mineralocorticoid and glucocorticoid agonists in canine septic shock

    PubMed Central

    Hicks, Caitlin W.; Sweeney, Daniel A.; Danner, Robert L.; Eichacker, Peter Q.; Suffredini, Anthony F.; Feng, Jing; Sun, Junfeng; Behrend, Ellen N.; Solomon, Steven B.; Natanson, Charles

    2011-01-01

    Background Corticosteroid regimens that stimulate both mineralocorticoid and glucocorticoid pathways consistently reverse vasopressor-dependent hypotension in septic shock, but have variable effects on survival. Objective and Methods To determine if exogenous mineralocorticoid and glucocorticoid stimulation have distinct effects, and whether the timing on such stimulation alters their effects, in septic shock. Desoxycorticosterone (DOC), a selective mineralocorticoid agonist; dexamethasone (DEX), a selective glucocorticoid agonist; and placebo were administered either several days before (prophylactic) or immediately after (therapeutic) infectious challenge and continued for 96 h in 74 canines with staphylococcal pneumonia. Measurements and Main Results Effects of DOC and DEX were different and opposite depending on timing of administration for survival (p=0.05); fluid requirements (p=0.05); central venous pressures (p≤0.007); indicators of hemoconcentration [i.e. sodium (p=0.0004), albumin (p=0.05), and platelet counts (p=0.02)]; IL-6 levels (p=0.04); and cardiac dysfunction (p=0.05). Prophylactic DOC treatment significantly improved survival, shock, and all the other outcomes above, but therapeutic DOC did not. Conversely, prophylactic DEX was much less effective for improving these outcomes compared to therapeutic DEX, with the exception of shock reversal. Prophylactic DEX given before sepsis induction also significantly reduced serum aldosterone and cortisol levels and increased body temperature and lactate levels compared to therapeutic DEX (p≤0.05), consistent with adrenal suppression. Conclusions In septic shock, mineralocorticoids are only beneficial if given prophylactically, while glucocorticoids are most beneficial when given close to the onset of infection. Prophylactic mineralocorticoids should be further investigated in patients at high risk to develop sepsis, whereas glucocorticoids should only be administered therapeutically to prevent adrenal

  17. The cathelicidin-derived tritrpticin enhances the efficacy of ertapenem in experimental rat models of septic shock.

    PubMed

    Ghiselli, Roberto; Cirioni, Oscar; Giacometti, Andrea; Mocchegiani, Federico; Orlando, Fiorenza; Silvestri, Carmela; Licci, Alberto; Della Vittoria, Agnese; Scalise, Giorgio; Saba, Vittorio

    2006-08-01

    Sepsis remains a serious clinical problem despite intense efforts to improve survival. In this study, the efficacy of ertapenem combined with the cathelicidin tritrpticin was investigated in two rat models of septic shock. Main outcome measures were bacterial growth in blood, peritoneum, spleen, liver, and mesenteric lymph nodes; endotoxin, interleukin 6, and tumor necrosis factor alpha concentrations in plasma; and lethality. Adult male Wistar rats were given (1) an intraperitoneal injection of 1 mg Escherichia coli serotype 0111:B4 LPS or (2) intra-abdominal sepsis induced via cecal ligation and puncture. For each model, all animals were randomized to receive intraperitoneally isotonic sodium chloride solution, 1 mg/kg tritrpticin, 15 mg/kg ertapenem, and 1 mg/kg tritrpticin combined with 15 mg/kg ertapenem. Each group included 20 animals. All compounds significantly reduced bacterial growth and lethality as compared with saline treatment. Treatment with tritrpticin resulted in significant decrease in plasma endotoxin and cytokine levels, whereas ertapenem exerted opposite effect. The combination between tritrpticin and ertapenem proved to be the most effective treatment in reducing all variables measured. In conclusion, tritrpticin enhances ertapenem efficacy in gram-negative septic shock rat models. PMID:16878029

  18. 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

  19. Shock

    MedlinePlus

    ... problems) Hypovolemic shock (caused by too little blood volume) Anaphylactic shock (caused by allergic reaction) Septic shock ( ... as heart attack or heart failure ) Low blood volume (as with heavy bleeding or dehydration ) Changes in ...

  20. Hitch-hiker taken for a ride: an unusual cause of myocarditis, septic shock and adult respiratory distress syndrome

    PubMed Central

    Kushawaha, Anurag; Brown, Mark; Martin, Ismael; Evenhuis, Walther

    2013-01-01

    Rocky Mountain spotted fever (RMSF) is a serious tick-borne illness caused by Rickettsia rickettsii that is endemic in southeastern USA. Although RMSF has been described as causing the classic clinical triad of fever, headache and a characteristic rash, serious and potentially life-threatening manifestations can occur. Cardiopulmonary involvement, although infrequent, may occur with severe cases of RMSF. Rickettsial myocarditis is an uncommon occurrence. We present a case of a previously healthy 26-year-old man, who was hitch-hiking across the southeastern USA, with serologically proven RMSF causing adult respiratory distress syndrome, septic shock and myocarditis manifested by elevated cardiac enzymes and decrease in myocardial function. After treatment with antibiotics, the myocarditis resolved. Therefore, although unusual, clinicians should be aware of possible myocardial involvement in patients with appropriate tick-exposure histories or other clinical signs of RMSF. PMID:23314875

  1. Pressor Response to Noradrenaline in the Setting of Septic Shock: Anything New under the Sun—Dexmedetomidine, Clonidine? A Minireview

    PubMed Central

    Géloën, A.; Pichot, C.; Leroy, S.; Julien, C.; Ghignone, M.; May, C. N.; Quintin, L.

    2015-01-01

    Progress over the last 50 years has led to a decline in mortality from ≈70% to ≈20% in the best series of patients with septic shock. Nevertheless, refractory septic shock still carries a mortality close to 100%. In the best series, the mortality appears related to multiple organ failure linked to comorbidities and/or an intense inflammatory response: shortening the period that the subject is exposed to circulatory instability may further lower mortality. Treatment aims at reestablishing circulation within a “central” compartment (i.e., brain, heart, and lung) but fails to reestablish a disorganized microcirculation or an adequate response to noradrenaline, the most widely used vasopressor. Indeed, steroids, nitric oxide synthase inhibitors, or donors have not achieved overwhelming acceptance in the setting of septic shock. Counterintuitively, α2-adrenoceptor agonists were shown to reduce noradrenaline requirements in two cases of human septic shock. This has been replicated in rat and sheep models of sepsis. In addition, some data show that α2-adrenoceptor agonists lead to an improvement in the microcirculation. Evidence-based documentation of the effects of alpha-2 agonists is needed in the setting of human septic shock. PMID:26783533

  2. 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. PMID:25403265

  3. 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

  4. 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

  5. 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. PMID:27104016

  6. Levosimendan Versus Dobutamine in Myocardial Injury Patients with Septic Shock: A Randomized Controlled Trial

    PubMed Central

    Meng, Jian-biao; Hu, Ma-hong; Lai, Zhi-zhen; Ji, Chun-lian; Xu, Xiu-juan; Zhang, Geng; Tian, Shuyuan

    2016-01-01

    Background We aimed to investigate the effect of levosimendan on biomarkers of myocardial injury and systemic hemodynamics in patients with septic shock. Material/Methods After achieving normovolemia and a mean arterial pressure of at least 65 mmHg, 38 septic shock patients with low cardiac output (left ventricular ejective fraction), LEVF ≤45%) were randomly divided into two groups: levosimendan dobutamine. Patients in the levosimendan and dobutamine groups were maintained with intravenous infusion of levosimendan (0.2 μg/kg/minute) and dobutamine (5 μg/kg/minute) for 24 hours respectively. During treatment we monitored hemodynamics and LVEF, and measured levels of heart-type fatty acid binding protein (HFABP), troponin I (TNI), and brain natriuretic peptide(BNP). In addition, the length of mechanical ventilation, intensive care unit (ICU) stay, hospital stay, and 28-day mortality were compared between the two groups. Results The levosimendan group and the dobutamine group were well matched with respect to age (years, 55.4±1 7.5 versus 50.2±13.6) and gender (males, 68.4% versus 57.9%). Levosimendan-treated patients had higher stroke volume index (SVI), cardiac index (CI), LVEF, and left ventricular stroke work index (LVSWI), and lower extravascular lung water index (EVLWI) compared to dobutamine-treated patients (p<0.05). HFABP, TNI, and BNP in the levosimendan group were less than in the dobutamine group (p<0.05). There was no difference in the mechanical ventilation time, length of stay in ICU and hospital, and 28-day mortality between the two groups. Conclusions Compared with dobutamine, levosimendan reduces biomarkers of myocardial injury and improves systemic hemodynamics in patients with septic shock. However, it does not reduce the days on mechanical ventilation, length of stay in ICU and hospital, or 28-day mortality. PMID:27138236

  7. Impact of positive fluid balance on mortality and length of stay in septic shock patients

    PubMed Central

    Koonrangsesomboon, Wachiraporn; Khwannimit, Bodin

    2015-01-01

    Background: Fluid management is important in critically patients. The aim of this study was to determine the relationship between fluid balance and adverse outcomes of septic shock. Methods: A retrospective study was conducted in the medical Intensive Care Unit (ICU) of a tertiary university hospital in Thailand, over a 7-year period. Results: A total of 1048 patients with an ICU mortality rate of 47% were enrolled. The median cumulative fluid intake at 24, 48, and 72 h from septic shock onset were 4.2, 7.7, and 10.5 L, respectively. Nonsurvivors had a significantly higher median cumulative fluid intake at 24, 48, and 72 h (4.6 vs. 3.9 L, 8.2 vs. 7.1 L, and 11.4 vs. 9.9 L, respectively, P < 0.001 for all). Nonsurvivors also had a significantly higher cumulative and mean fluid balance within 72 h (5.4 vs. 4.4 L and 2.8 vs. 1.6 L, P < 0.001 for both). In multivariate logistic regression analysis, mean fluid balance quartile within 72 h, was independently associated with an increase in ICU and hospital mortality. Quartile 3 and 4 have statistically significant increases in mortality compared with quartile 1 (odds ratio [95% confidence interval] 3.04 [1.9–4.48] and 4.16 [2.49–6.95] for ICU mortality and 2.75 [1.74–4.36] and 3.16 [1.87–5.35] for hospital mortality, respectively, P < 0.001 for all). In addition, the higher amount of mean fluid balance was associated with prolonged ICU stays. Conclusions: Positive fluid balance over 3 days is associated with increased ICU and hospital mortality along with prolonged ICU stays in septic shock patients. PMID:26813080

  8. Gender Differences in Mortality in Patients with Severe Sepsis and Septic Shock

    PubMed Central

    Pietropaoli, Anthony P.; Glance, Laurent G.; Oakes, David; Fisher, Susan G.

    2012-01-01

    Background Although the incidence of sepsis is higher in men than women, it is controversial whether there are gender differences in sepsis-associated mortality. Objective To test the hypothesis that hospital mortality is higher in men compared to women with severe sepsis or septic shock and requiring intensive care. Methods Retrospective cohort study of 18,757 intensive care unit (ICU) patients, including 8,702 women (46%), with severe sepsis or septic shock in the Cerner Project IMPACT database. Results Hospital mortality was higher in women vs. men (35% vs. 33%, p = 0.006). After adjusting for differences in baseline characteristics and processes of care, women had a higher likelihood of hospital mortality than men (OR = 1.11, 95% CI = 1.04 – 1.19, p = 0.002). Women were less likely than men to receive deep venous thrombosis prophylaxis (OR = 0.90, 95% CI = 0.84 – 0.97), invasive mechanical ventilation (OR = 0.81, 95% CI = 0.76 – 0.86), and hemodialysis catheters (OR = 0.85, 95% CI = 0.78 – 0.93). Women were more likely than men to receive red blood cell transfusions (OR = 1.15, 95% CI = 1.09 – 1.22) and code status limitations (OR = 1.31, 95% CI = 1.18 – 1.47). Conclusions In this large cohort of ICU patients, women with severe sepsis or septic shock had a higher risk of dying in the hospital than men. This difference remained after multivariable adjustment. We also found significant gender disparities in some aspects of care delivery, but these did not explain the higher mortality in women. PMID:21056869

  9. Success of applying early goal-directed therapy for septic shock patients in the emergency department

    PubMed Central

    Worapratya, Panita; Wanjaroenchaisuk, Apisit; Joraluck, Jutharat; Wuthisuthimethawee, Prasit

    2016-01-01

    Background Since early goal-directed therapy (EGDT) became standard care in severe sepsis and septic shock patients in intensive care units many years ago, we suppose that the survival rate of severe sepsis and septic shock patients improves if the resuscitative procedure is quickly implemented and is initiated in the emergency room. Objective We aimed at recording emergency department time to improve our patient care system as well as determine the rate at which EGDT goals can be achieved. The second analysis is to find out how much we can improve the survival rate. Methods This was a prospective observational study in an emergency room setting at a tertiary care facility where EGDT was applied for resuscitation of severe sepsis and septic shock patients. The data recorded were the initial vital signs, APACHE II (Acute Physiology and Chronic Health Evaluation II) score, SAP II (Simplified Acute Physiology II) score, SOFA (Sequential Organ Failure Assessment) score, time at which EGDT goals were achieved (central venous oxygen saturation [ScvO2] >70%), initial and final diagnosis, and outcome of treatment. The t-test and Mann–Whitney U-test were used to compare between the achieved goal and nonachieved goal groups. Results There were 63 cases of severe sepsis in the study period. Only 55 patients submitted a signed consent form and had central line insertion. Twenty-eight (50.9%) cases were male. Thirty-nine (70.9%) patients achieved the goal, and the mean SAP II score was 8. There were no statistically significant differences between the two groups (P-value =0.097). Thirty of the 39 patients (70.9%) survived in the achieved goal group, which was a statistically significant improvement of the survival rate when compared with only one of 16 patients (6.3%) surviving in the nonachieved goal group (P<0.001).

  10. Hypertonic fluid administration in patients with septic shock: a prospective randomized controlled pilot study.

    PubMed

    van Haren, Frank M P; Sleigh, James; Boerma, E Christiaan; La Pine, Mary; Bahr, Mohamed; Pickkers, Peter; van der Hoeven, Johannes G

    2012-03-01

    We assessed the short-term effects of hypertonic fluid versus isotonic fluid administration in patients with septic shock. This was a double-blind, prospective randomized controlled trial in a 15-bed intensive care unit. Twenty-four patients with septic shock were randomized to receive 250 mL 7.2% NaCl/6% hydroxyethyl starch (HT group) or 500 mL 6% hydroxyethyl starch (IT group). Hemodynamic measurements included mean arterial blood pressure (MAP), central venous pressure, stroke volume index, stroke volume variation, intrathoracic blood volume index, gastric tonometry, and sublingual microcirculatory flow as assessed by sidestream dark field imaging. Systolic tissue Doppler imaging velocities of the medial mitral annulus were measured using echocardiography to assess left ventricular contractility. Log transformation of the ratio MAP divided by the norepinephrine infusion rate (log MAP/NE) quantified the combined effect on both parameters. Compared with the IT group, hypertonic solution treatment resulted in an improvement in log MAP/NE (P = 0.008), as well as an increase in systolic tissue Doppler imaging velocities (P = 0.03) and stroke volume index (P = 0.017). No differences between the groups were found for preload parameters (central venous pressure, stroke volume variation, intrathoracic blood volume index) or for afterload parameters (systemic vascular resistance index, MAP). Hypertonic solution treatment decreased the need for ongoing fluid resuscitation (P = 0.046). No differences between groups were observed regarding tonometry or the sublingual microvascular variables. In patients with septic shock, hypertonic fluid administration did not promote gastrointestinal mucosal perfusion or sublingual microcirculatory blood flow in comparison to isotonic fluid. Independent of changes in preload or afterload, hypertonic fluid administration improved the cardiac contractility and vascular tone compared with isotonic fluid. The need for ongoing fluid

  11. 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

  12. Pathophysiology of septic shock: From bench to bedside.

    PubMed

    McConnell, Kevin W; Coopersmith, Craig M

    2016-04-01

    Our understanding of sepsis and its resultant outcomes remains a paradox. On the one hand, we know more about the pathophysiology of sepsis than ever before. However, this knowledge has not been successfully translated to the bedside, as the vast majority of clinical trials for sepsis have been negative. Yet even in the general absence of positive clinical trials, mortality from sepsis has fallen to its lowest point in history, in large part due to educational campaigns that stress timely antibiotics and hemodynamic support. While additional improvements in outcome will assuredly result from further compliance with evidence based practices, a deeper understanding of the science that underlies the host response in sepsis is critical to the development of novel therapeutics. In this review, we outline immunopathologic abnormalities in sepsis, and then look at potential approaches to therapeutically modulate them. Ultimately, an understanding of the science underlying sepsis should allow the critical care community to utilize precision medicine to combat this devastating disease on an individual basis leading to improved outcomes. PMID:27085986

  13. SPG/IND-induced septic shock in a LPS-low responder strain, C3H/HeJ mice.

    PubMed

    Saito, Maki; Nameda, Sachiko; Miura, Noriko N; Adachi, Yoshiyuki; Ohno, Naohito

    2008-05-01

    The administration of beta-glucan (sonifilan; SPG) in combination with a non-steroidal anti-inflammatory drug, indomethacin (IND), induced lethal septic shock in mice. To demonstrate the influence of bacterial lipopolysaccharide (LPS) in this lethal toxicity, LPS non-responder C3H/HeJ mice were used to compare features of sepsis and physicochemical parameters in the present study. The administration of SPG and IND induced the death of C3H/HeJ mice, lowering rectal temperature, reducing body weight, increasing serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels, shortening the gastrointestinal tract, and increasing the GOT/GPT level. Microbial translocation to various organs was also significantly increased. These results strongly suggested that LPS-non-responding strain also induced septic shock in this experimental model, and other pathogen-associated molecular patterns (PAMPs) may significantly contribute to the septic shock. PMID:18093793

  14. Procalcitonin determined at emergency department as an early indicator of progression to septic shock in patient with sepsis associated with ureteral calculi

    PubMed Central

    Ko, Young Hwii; Ji, Yoon Seob; Park, Sin-Youl; Kim, Su Jin; Song, Phil Hyun

    2016-01-01

    ABSTRACT Introduction: 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. Materials and Methods: 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. Results: 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%. Conclusion: Our study demonstrated elevated initial PCT levels as an early independent predictor to progress into septic shock in patients with sepsis associated with ureteral calculi. PMID:27256181

  15. “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

  16. Low-dose hydrocortisone in patients with cirrhosis and septic shock: a randomized controlled trial

    PubMed Central

    Arabi, Yaseen M.; Aljumah, Abdulrahman; Dabbagh, Ousama; Tamim, Hani M.; Rishu, Asgar H.; Al-Abdulkareem, Abdulmajeed; Knawy, Bandar Al; Hajeer, Ali H.; Tamimi, Waleed; Cherfan, Antoine

    2010-01-01

    Background Recent studies have reported a high prevalence of relative adrenal insufficiency in patients with liver cirrhosis. However, the effect of corticosteroid replacement on mortality in this high-risk group remains unclear. We examined the effect of low-dose hydrocortisone in patients with cirrhosis who presented with septic shock. Methods We enrolled patients with cirrhosis and septic shock aged 18 years or older in a randomized double-blind placebo-controlled trial. Relative adrenal insufficiency was defined as a serum cortisol increase of less than 250 nmol/L or 9 μg/dL from baseline after stimulation with 250 μg of intravenous corticotropin. Patients were assigned to receive 50 mg of intravenous hydrocortisone or placebo every six hours until hemodynamic stability was achieved, followed by steroid tapering over eight days. The primary outcome was 28-day all-cause mortality. Results The trial was stopped for futility at interim analysis after 75 patients were enrolled. Relative adrenal insufficiency was diagnosed in 76% of patients. Compared with the placebo group (n = 36), patients in the hydrocortisone group (n = 39) had a significant reduction in vasopressor doses and higher rates of shock reversal (relative risk [RR] 1.58, 95% confidence interval [CI] 0.98–2.55, p = 0.05). Hydrocortisone use was not associated with a reduction in 28-day mortality (RR 1.17, 95% CI 0.92–1.49, p = 0.19) but was associated with an increase in shock relapse (RR 2.58, 95% CI 1.04–6.45, p = 0.03) and gastrointestinal bleeding (RR 3.00, 95% CI 1.08–8.36, p = 0.02). Interpretation Relative adrenal insufficiency was very common in patients with cirrhosis presenting with septic shock. Despite initial favourable effects on hemodynamic parameters, hydrocortisone therapy did not reduce mortality and was associated with an increase in adverse effects. (Current Controlled Trials registry no. ISRCTN99675218.) PMID:21059778

  17. 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

  18. A Selective V1A Receptor Agonist, Selepressin, Is Superior to Arginine Vasopressin and to Norepinephrine in Ovine Septic Shock*

    PubMed Central

    He, Xinrong; Su, Fuhong; Taccone, Fabio Silvio; Laporte, Régent; Kjølbye, Anne Louise; Zhang, Jing; Xie, Keliang; Moussa, Mouhamed Djahoum; Reinheimer, Torsten Michael

    2016-01-01

    interleukin-6 and nitrite/nitrate levels. Selepressin-treated animals survived longer than the other animals. Conclusions: In this clinically relevant model, selepressin, a selective V1A receptor agonist, was superior to arginine vasopressin and to norepinephrine in the treatment of septic shock, especially when administered early. PMID:26496451

  19. Coagulation phenotypes in septic shock as evaluated by calibrated automated thrombography.

    PubMed

    Perrin, Julien; Charron, Cyril; François, Jean-Hugues; Cramer-Bordé, Elisabeth; Lévy, Bruno; Borgel, Delphine; Vieillard-Baron, Antoine

    2015-01-01

    Sepsis induces alterations of coagulation suggesting both hypercoagulable or hypocoagulable features. The result of their combination remains unknown, making it difficult to predict whether one prevails over the other. Thrombin generation tests (TGTs) stand as an interesting tool to establish an integrative phenotype of coagulation. It has been reported that septic patients display a hypocoagulable trait using TGT. However, protein C (PC) system response was not evaluated. We aimed at describing the thrombin generation profile in patients with septic shock under conditions that are sensitive to PC system to evaluate the net results of coagulation abnormalities and to determine whether hypercoagulable or hypocoagulable traits coexist within a given individual. Thrombin generation was studied in plasma from patients presenting with septic shock at diagnosis and 6 h after a conventional therapeutic management using calibrated automated thrombography with or without thrombomodulin (TM) addition. Patients exhibit clear alterations of TGT that present as both consumption-related hypocoagulability (evidenced without TM addition) but also hypercoagulability by decreased sensitivity to the PC system evidenced with TM addition. No difference could be demonstrated between survivors and nonsurvivors at Day 28, but patients who do not respond to therapeutics at 6 h seem to be more hypercoagulable. More importantly, if our results evidence heterogeneity between patients, we show that alterations of coagulation result in an equilibrium in the majority of patients, thus suggesting "normocoagulability"; but, in the presence of a biological imbalance between baseline thrombin generation and sensitivity to TM, the global effect mostly tends toward hypercoagulability. Thus, TGT may help identify distinct biological coagulation phenotypes in the complex alterations induced by sepsis. PMID:25255379

  20. [A case of severe hypotension with catecholamine-resistant septic shock in the perioperative period].

    PubMed

    Hamaguchi, Eisuke; Kawano, Hiroaki

    2012-04-01

    We report general anesthesia of a 79-year-old man complicated with septic shock from abdominal artery graft infection. When he entered the operating room, intravenous dopamine, dobutamine, and noradrenaline had been administered and his bood pressure was 50/32 mmHg. General anesthesia was induced with inhalation of oxygen-sevoflurane and rocuronium, and maintained with sevoflurane-oxygen. During the operation, the patient's blood pressure was 40-50/30-35 mmHg, and heart rate decreased gradually to 50 beats x min(-1). Although various vasopressors (dopamine, dobutamine, noradrenaline, adrenaline, ephedrine, phenylephrine, atropine and vasopressin) were administered, they were not effective to improve severe hypotension. After the operation, we started blood purification (PMX-DHP+CHDF), and in consequence blood pressure increased. It was thought that hemodynamics improved remarkably by reducing humoral mediators. In conclusion, it is considered that patients with septic shock should undergo immediate diagnosis and the source control should be performed in the minimum period, because it is possible that any vasopressor become ineffective when hypercytokinemia developes. PMID:22590945

  1. Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock

    PubMed Central

    Van Amersfoort, Edwin S.; Van Berkel, Theo J. C.; Kuiper, Johan

    2003-01-01

    Bacterial sepsis and septic shock result from the overproduction of inflammatory mediators as a consequence of the interaction of the immune system with bacteria and bacterial wall constituents in the body. Bacterial cell wall constituents such as lipopolysaccharide, peptidoglycans, and lipoteichoic acid are particularly responsible for the deleterious effects of bacteria. These constituents interact in the body with a large number of proteins and receptors, and this interaction determines the eventual inflammatory effect of the compounds. Within the circulation bacterial constituents interact with proteins such as plasma lipoproteins and lipopolysaccharide binding protein. The interaction of the bacterial constituents with receptors on the surface of mononuclear cells is mainly responsible for the induction of proinflammatory mediators by the bacterial constituents. The role of individual receptors such as the toll-like receptors and CD14 in the induction of proinflammatory cytokines and adhesion molecules is discussed in detail. In addition, the roles of a number of other receptors that bind bacterial compounds such as scavenger receptors and their modulating role in inflammation are described. Finally, the therapies for the treatment of bacterial sepsis and septic shock are discussed in relation to the action of the aforementioned receptors and proteins. PMID:12857774

  2. Anthrapyrazolone analogues intercept inflammatory JNK signals to moderate endotoxin induced septic shock

    NASA Astrophysics Data System (ADS)

    Prasad, Karothu Durga; Trinath, Jamma; Biswas, Ansuman; Sekar, Kanagaraj; Balaji, Kithiganahalli N.; Guru Row, Tayur N.

    2014-11-01

    Severe sepsis or septic shock is one of the rising causes for mortality worldwide representing nearly 10% of intensive care unit admissions. Susceptibility to sepsis is identified to be mediated by innate pattern recognition receptors and responsive signaling pathways of the host. The c-Jun N-terminal Kinase (JNK)-mediated signaling events play critical role in bacterial infection triggered multi-organ failure, cardiac dysfunction and mortality. In the context of kinase specificities, an extensive library of anthrapyrazolone analogues has been investigated for the selective inhibition of c-JNK and thereby to gain control over the inflammation associated risks. In our comprehensive biochemical characterization, it is observed that alkyl and halogen substitution on the periphery of anthrapyrazolone increases the binding potency of the inhibitors specifically towards JNK. Further, it is demonstrated that hydrophobic and hydrophilic interactions generated by these small molecules effectively block endotoxin-induced inflammatory genes expression in in vitro and septic shock in vivo, in a mouse model, with remarkable efficacies. Altogether, the obtained results rationalize the significance of the diversity oriented synthesis of small molecules for selective inhibition of JNK and their potential in the treatment of severe sepsis.

  3. Effect of nitric oxide on beta-glucan/indomethacin-induced septic shock.

    PubMed

    Nameda, Sachiko; Saito, Maki; Miura, Noriko N; Adachi, Yoshiyuki; Ohno, Naohito

    2005-07-01

    We have previously shown that repeated administration of nonsteroidal anti-inflammatory drugs (NSAIDs) to mice treated with beta-glucan, a biological response modifier, induced severe lethality. The lethality would be strongly related to the translocation of enterobacterial flora to the peritoneal cavity and disruption of the cytokine network. Reports suggest that nitric oxide (NO) can have an effective or detrimental role in septic shock. In the present study, we examined the effect of NO, an inflammatory mediator, on beta-glucan/indomethacin (IND)- induced septic shock by inhibiting its synthesis with N(G)-nitro-L-arginine methyl ester (L-NAME), a nonselective NO synthase (NOS) inhibitor. Nitrite concentration was used as an indicator of NO generation. Mortality in beta-glucan/IND-treated mice was increased by administering L-NAME. Numbers of bacteria in various organs of mice treated with beta-glucan/IND rose significantly within a couple of days of the administration of L-NAME. Additionally, TNF-alpha, IL-1beta, and IL-6 concentrations were enhanced in peritoneal exuded cells in culture. These results suggest a significant loss of the bactericidal activity of macrophages on the administration of a NOS inhibitor which enhanced the rate of enterobacterial invasion to the peritoneal cavity, resulting in systemic inflammatory response syndrome. The production of NO, therefore, provides a protective effect in beta-glucan/IND-induced sepsis. PMID:15997109

  4. Septic Shock Induced by Bacterial Prostatitis with Morganella morganii subsp. morganii in a Posttransplantation Patient

    PubMed Central

    Li, Xiaofan; Chen, Jianhui

    2015-01-01

    Bacterial infection is a common complication after Hematopoietic Stem Cell Transplantation (HSCT). Morganella morganii is ubiquitous Gram-negative facultative anaerobe, which may cause many kinds of opportunistic infection. Herein we report a case of a 55-year-old man who presented with frequent urination, urgency, and mild pain that comes and goes low in the abdomen and around the anus. The patient had a medical history of chronic prostatitis for 4 years. He received HLA-matched sibling allo-HSCT because of angioimmunoblastic T-cell lymphoma 29 months ago. The routine examination of prostatic fluid showed increased leukocytes and the culture of prostatic fluid showed Morganella morganii subsp. morganii. The patient developed chills and fever 18 hours after examination. Both urine culture and blood culture showed Morganella morganii subsp. morganii. The patient was successfully treated with antibiotic therapy and septic shock management. Taken together, Morganella morganii should be considered a possible pathogen when immunocompromised patients develop prostatitis. Also, prostatic massage could be a possible trigger of septic shock induced by Morganella morganii subsp. morganii in a posttransplantation patient. PMID:26798544

  5. Septic Shock Induced by Bacterial Prostatitis with Morganella morganii subsp. morganii in a Posttransplantation Patient.

    PubMed

    Li, Xiaofan; Chen, Jianhui

    2015-01-01

    Bacterial infection is a common complication after Hematopoietic Stem Cell Transplantation (HSCT). Morganella morganii is ubiquitous Gram-negative facultative anaerobe, which may cause many kinds of opportunistic infection. Herein we report a case of a 55-year-old man who presented with frequent urination, urgency, and mild pain that comes and goes low in the abdomen and around the anus. The patient had a medical history of chronic prostatitis for 4 years. He received HLA-matched sibling allo-HSCT because of angioimmunoblastic T-cell lymphoma 29 months ago. The routine examination of prostatic fluid showed increased leukocytes and the culture of prostatic fluid showed Morganella morganii subsp. morganii. The patient developed chills and fever 18 hours after examination. Both urine culture and blood culture showed Morganella morganii subsp. morganii. The patient was successfully treated with antibiotic therapy and septic shock management. Taken together, Morganella morganii should be considered a possible pathogen when immunocompromised patients develop prostatitis. Also, prostatic massage could be a possible trigger of septic shock induced by Morganella morganii subsp. morganii in a posttransplantation patient. PMID:26798544

  6. Anthrapyrazolone analogues intercept inflammatory JNK signals to moderate endotoxin induced septic shock

    PubMed Central

    Prasad, Karothu Durga; Trinath, Jamma; Biswas, Ansuman; Sekar, Kanagaraj; Balaji, Kithiganahalli N.; Guru Row, Tayur N.

    2014-01-01

    Severe sepsis or septic shock is one of the rising causes for mortality worldwide representing nearly 10% of intensive care unit admissions. Susceptibility to sepsis is identified to be mediated by innate pattern recognition receptors and responsive signaling pathways of the host. The c-Jun N-terminal Kinase (JNK)-mediated signaling events play critical role in bacterial infection triggered multi-organ failure, cardiac dysfunction and mortality. In the context of kinase specificities, an extensive library of anthrapyrazolone analogues has been investigated for the selective inhibition of c-JNK and thereby to gain control over the inflammation associated risks. In our comprehensive biochemical characterization, it is observed that alkyl and halogen substitution on the periphery of anthrapyrazolone increases the binding potency of the inhibitors specifically towards JNK. Further, it is demonstrated that hydrophobic and hydrophilic interactions generated by these small molecules effectively block endotoxin-induced inflammatory genes expression in in vitro and septic shock in vivo, in a mouse model, with remarkable efficacies. Altogether, the obtained results rationalize the significance of the diversity oriented synthesis of small molecules for selective inhibition of JNK and their potential in the treatment of severe sepsis. PMID:25428720

  7. Early goal-directed resuscitation of patients with septic shock: current evidence and future directions.

    PubMed

    Gupta, Ravi G; Hartigan, Sarah M; Kashiouris, Markos G; Sessler, Curtis N; Bearman, Gonzalo M L

    2015-01-01

    Severe sepsis and septic shock are among the leading causes of mortality in the intensive care unit. Over a decade ago, early goal-directed therapy (EGDT) emerged as a novel approach for reducing sepsis mortality and was incorporated into guidelines published by the international Surviving Sepsis Campaign. In addition to requiring early detection of sepsis and prompt initiation of antibiotics, the EGDT protocol requires invasive patient monitoring to guide resuscitation with intravenous fluids, vasopressors, red cell transfusions, and inotropes. The effect of these measures on patient outcomes, however, remains controversial. Recently, three large randomized trials were undertaken to re-examine the effect of EGDT on morbidity and mortality: the ProCESS trial in the United States, the ARISE trial in Australia and New Zealand, and the ProMISe trial in England. These trials showed that EGDT did not significantly decrease mortality in patients with septic shock compared with usual care. In particular, whereas early administration of antibiotics appeared to increase survival, tailoring resuscitation to static measurements of central venous pressure and central venous oxygen saturation did not confer survival benefit to most patients. In the following review, we examine these findings as well as other evidence from recent randomized trials of goal-directed resuscitation. We also discuss future areas of research and emerging paradigms in sepsis trials. PMID:26316210

  8. Septic shock

    MedlinePlus

    ... the body Complete blood count (CBC) and blood chemistry Presence of bacteria or other organisms Low blood oxygen level Disturbances in the body's acid-base balance Poor organ function or organ failure Other ...

  9. A high angiopoietin-2/angiopoietin-1 ratio is associated with a high risk of septic shock in patients with febrile neutropenia

    PubMed Central

    2013-01-01

    Introduction Endothelial barrier breakdown is a hallmark of septic shock, and proteins that physiologically regulate endothelial barrier integrity are emerging as promising biomarkers of septic shock development. Patients with cancer and febrile neutropenia (FN) present a higher risk of sepsis complications, such as septic shock. Nonetheless, these patients are normally excluded or under-represented in sepsis biomarker studies. The aim of our study was to validate the measurement of a panel of microvascular permeability modulators as biomarkers of septic shock development in cancer patients with chemotherapy-associated FN. Methods This was a prospective study of diagnostic accuracy, performed in two distinct in-patient units of a university hospital. Levels of vascular endothelial growth factor A (VEGF-A), soluble fms-like tyrosine kinase-1 (sFlt-1) and angiopoietin (Ang) 1 and 2 were measured after the onset of neutropenic fever, in conditions designed to mimic the real-world use of a sepsis biomarker, based on our local practice. Patients were categorized based on the development of septic shock by 28 days as an outcome. Results A total of 99 consecutive patients were evaluated in the study, of which 20 developed septic shock and 79 were classified as non-complicated FN. VEGF-A and sFlt-1 levels were similar between both outcome groups. In contrast, Ang-2 concentrations were increased in patients with septic shock, whereas an inverse finding was observed for Ang-1, resulting in a higher Ang-2/Ang-1 ratio in patients with septic shock (5.29, range 0.58 to 57.14) compared to non-complicated FN (1.99, range 0.06 to 64.62; P = 0.01). After multivariate analysis, the Ang-2/Ang-1 ratio remained an independent factor for septic shock development and 28-day mortality. Conclusions A high Ang-2/Ang-1 ratio can predict the development of septic shock in cancer patients with febrile neutropenia. PMID:23915833

  10. Skin necrosis after a low-dose vasopressin infusion through a central venous catheter for treating septic shock.

    PubMed

    Kim, Eun Hee; Lee, Sae Hwan; Byun, Seung Woon; Kang, Ho Suk; Koo, Dong Hoe; Park, Hyun-Gu; Hong, Sang Bum

    2006-12-01

    This is a report on a case of severe skin necrosis in a vasodilatory septic shock patient after the infusion of low-dose vasopressin through a central venous catheter. An 84-year-old male was hospitalized for edema on both legs at Asan Medical Center, Seoul, Korea. On hospital day 8, the patient began to complain of dyspnea and he subsequently developed severe septic shock caused by E. coli. After being transferred to the medical intensive care unit, his hypotension, which was refractory to norepinephrine, was controlled by an infusion of low-dose vasopressin (0.02 unit/min) through a central venous catheter into the right subclavian vein. After the infusion of low-dose vasopressin, severe skin necrosis with bullous changes developed, necessitating discontinuation of the low-dose vasopressin infusion. The patient expired from refractory septic shock. Although low-dose vasopressin can control hypotension in septic shock patients, low-dose vasopressin must be used with caution because ischemic complications such as skin necrosis can develop even with administration through a central venous catheter. PMID:17249516

  11. Steroid therapy in septic shock. Survival studies in a laboratory model.

    PubMed

    Fabian, T C; Patterson, R

    1982-12-01

    The efficacy of pharmacologic doses of steroids in the treatment of septic shock was evaluated using a laboratory model. The model produced a septic insult of gradual onset followed by a rapid progression, allowing for the evaluation of postcontamination therapeutic regimens. In Sprague-Dawley rats, the cecum was ligated distal to the ileocecal valve and doubly punctured. Control animals (n = 41) received no postoperative therapy. Mortality was 37 per cent at 24 hours and 90 per cent at 48 hours. Approximately 25 animals were assigned to each of five experimental groups. Pharmacologic doses of methylprednisolone at four and eight hours postoperatively did not alter survival. Short-term gentamicin (STG) at four and eight hours improved early survival, which then declined to control values. Addition of steroid to STG had no effect. Long-term gentamicin (LTG) administered through the third postoperative day produced significant increased survival over controls throughout the study. Pharmacologic doses of steroid at four and eight hours added to LTG resulted in a significant increase (P less than 0.05) in survival rate over the treatment with LTG alone. PMID:6760756

  12. Circulating high sensitivity troponin T in severe sepsis and septic shock: distribution, associated factors, and relation to outcome

    PubMed Central

    Røsjø, Helge; Varpula, Marjut; Hagve, Tor-Arne; Karlsson, Sari; Ruokonen, Esko; Pettilä, Ville

    2010-01-01

    Purpose To assess the clinical utility of a recently developed highly sensitive cardiac troponin T (hs-cTnT) assay for providing prognostic information on patients with sepsis. Methods cTnT levels were measured by the novel hs-cTnT assay at two time points (inclusion and 72 h thereafter) in a subgroup of patients from the FINNSEPSIS study and associations with clinical outcomes were examined. Results for the hs-cTnT assay were compared to those of the established fourth-generation cTnT assay. Results cTnT measured by the fourth-generation and hs-cTnT assay was detectable in 124 (60%) and 207 (100%) patients, respectively, on inclusion in this study. hs-cTnT levels on inclusion correlated with several indices of risk in sepsis, including the simplified acute physiology score (SAPS) II and sequential organ failure assessment (SOFA) scores. The level of hs-cTnT on inclusion was higher in hospital non-survivors (n = 47) than survivors (n = 160) (median 0.054 [Q1–3, 0.022–0.227] versus 0.035 [0.015–0.111] μg/L, P = 0.047), but hs-cTnT level was not an independent predictor of in-hospital mortality. hs-cTnT levels on inclusion were also higher in patients with septic shock during the hospitalization (0.044 [0.024–0.171] versus 0.033 [0.012–0.103] μg/L, P = 0.03), while this was not the case for the fourth-generation cTnT assay or NT-proBNP levels. Conclusions Circulating hs-cTnT is present in patients with severe sepsis and septic shock, associates with disease severity and survival, but does not add to SAPS II score for prediction of mortality. hs-cTnT measurement could still have a role in sepsis as an early marker of shock. Electronic supplementary material The online version of this article (doi:10.1007/s00134-010-2051-x) contains supplementary material, which is available to authorized users. PMID:20938765

  13. Glucose–insulin–potassium infusion in sepsis and septic shock: no hard evidence yet

    PubMed Central

    van der Horst, Iwan CC; Ligtenberg, Jack JM; Bilo, Henk JG; Zijlstra, Felix; Gans, Rijk OB

    2003-01-01

    There is no hard evidence yet for a positive effect of glucose–insulin–potassium infusion in sepsis, septic shock or burn patients. Each individual element of the glucose–insulin–potassium regimen, and eventually euglycaemia, should theoretically be beneficial. At present, evidence exists only for reduced mortality with strict metabolic treatment (i.e. blood glucose levels of 4.4–6.1 mmol/l) in critically ill patients admitted to surgical intensive care units, and for better metabolic regulation (i.e. blood glucose levels of 7.0–10.0 mmol/l) in patients with hyperglycaemia and/or diabetes mellitus, and in patients without signs of heart failure (i.e. Killip class I) during acute myocardial infarction. PMID:12617733

  14. Survival of primates in lethal septic shock following delayed treatment with steroid.

    PubMed

    Hinshaw, L B; Archer, L T; Beller-Todd, B K; Benjamin, B; Flournoy, D J; Passey, R

    1981-01-01

    We recently developed a methylprednisolone sodium succinate (MPSS)/gentamicin sulfate (GS) regimen that prevented death in baboons given a 2-hour infusion of LD100 E coli (J. Surg. Res. 28:151, 1980). Steroid treatment was begun in that study 30 minutes after initiation of E coli. Our current aim was to determine if baboons would survive if MPSs treatment was delayed until all E coli were infused and severe hypotension had ensued. Fourteen lightly anesthetized baboons (P.c. cynocephalus) were administered E. coli and seven were then treated with MPSS and GS for 10 hours. All nontreated baboons died, while six of seven treated animals survived. In the treated group, hypoglycemia and hypoinsulinemia were reversed, tachycardia was reduced and neutrophil recovery was improved. Baboons with delayed MPSS, however, evidenced diminished perfusion and recovered more slowly than those with earlier MPSs treatment. In conclusion, primates in septic shock are clearly protected with delayed steroid/antibiotic therapy. PMID:7018730

  15. Septic shock during platelet transfusion in a patient with acute myeloid leukaemia.

    PubMed

    Haesebaert, Julie; Bénet, Thomas; Michallet, Mauricette; Vanhems, Philippe

    2013-01-01

    Although rare, transfusion-associated bacterial contamination (TABC) is nowadays the main risk associated with platelet concentrate (PC) transfusion. Consequences vary from spontaneously resolving symptoms to severe sepsis and death. In this report we have summarised a case of bacterial contamination and sepsis during PC transfusion in a patient with acute myeloid leukaemia. Fifteen minutes after the PC transfusion began, she developed chills and rapidly worsened to septic shock. The episode was managed appropriately. The patient's blood cultures and PC unit cultures grew Escherichia coli. The microbiological susceptibilities of isolates from the patient and platelet bag were identical. No other source of E coli was found. Donor and blood products issued from the same donation investigations were negative. The causality between sepsis and PC transfusion might be difficult to confirm. As no method is available in daily practice to eliminate TABC risk, physicians should always consider TABC by immediately stopping the transfusion and conducting appropriate investigations. PMID:24172770

  16. Soluble Heparan Sulfate in Serum of Septic Shock Patients Induces Mitochondrial Dysfunction in Murine Cardiomyocytes.

    PubMed

    Martin, Lukas; Peters, Carsten; Schmitz, Susanne; Moellmann, Julia; Martincuks, Antons; Heussen, Nicole; Lehrke, Michael; Müller-Newen, Gerhard; Marx, Gernot; Schuerholz, Tobias

    2015-12-01

    The heart is one of the most frequently affected organs in sepsis. Recent studies focused on lipopolysaccharide-induced mitochondrial dysfunction; however myocardial dysfunction is not restricted to gram-negative bacterial sepsis. The purpose of this study was to investigate circulating heparan sulfate (HS) as an endogenous danger associated molecule causing cardiac mitochondrial dysfunction in sepsis. We used an in vitro model with native sera (SsP) and sera eliminated from HS (HS-free), both of septic shock patients, to stimulate murine cardiomyocytes. As determined by extracellular flux analyzing, SsP increased basal mitochondrial respiration, but reduced maximum mitochondrial respiration, compared with unstimulated cells (P < 0.0001 and P < 0.0001, respectively). Cells stimulated with HS-free serum revealed unaltered basal and maximum mitochondrial respiration, compared with unstimulated cells (P = 0.1174 and P = 0.8992, respectively). Cellular ATP-level were decreased in SsP-stimulated cells but unaltered in cells stimulated with HS-free serum compared with unstimulated cells (P < 0.0001 and P = 0.1593, respectively). Live-cell imaging revealed an increased production of mitochondrial reactive oxygen species in cells stimulated with SsP compared with cells stimulated with HS-free serum (P < 0.0001). Expression of peroxisome proliferator-activated receptors (PPARα and PPARγ) and their co-activators PGC-1α, which regulate mitochondrial function, were studied using PCR. Cells stimulated with SsP showed downregulated PPARs and PGC-1α mRNA-levels compared with HS-free serum (P = 0.0082, P = 0.0128, and P = 0.0185, respectively). Blocking Toll-like receptor 4 revealed an inhibition of HS-dependent downregulation of PPARs and PGC-1α (all P < 0.0001). In conclusion, circulating HS in serum of septic shock patients cause cardiac mitochondrial dysfunction, suggesting that HS may be targets of therapeutics in septic

  17. Multifaceted interventions to decrease mortality in patients with severe sepsis/septic shock-a quality improvement project.

    PubMed

    Siontis, Brittany; Elmer, Jennifer; Dannielson, Richard; Brown, Catherine; Park, John; Surani, Salim; Ramar, Kannan

    2015-01-01

    Despite knowledge that EGDT improves outcomes in septic patients, staff education on EGDT and compliance with the CPOE order set has been variable. Based on results of a resident survey to identify barriers to decrease severe sepsis/septic shock mortality in the medical intensive care unit (MICU), multifaceted interventions such as educational interventions to improve awareness to the importance of early goal-directed therapy (EGDT), and the use of the Computerized Physician Order Entry (CPOE) order set, were implemented in July 2013. CPOE order set was established to improve compliance with the EGDT resuscitation bundle elements. Orders were reviewed and compared for patients admitted to the MICU with severe sepsis/septic shock in July and August 2013 (controls) and 2014 (following the intervention). Similarly, educational slide sets were used as interventions for residents before the start of their ICU rotations in July and August 2013. While CPOE order set compliance did not significantly improve (78% vs. 76%, p = 0.74), overall EGDT adherence improved from 43% to 68% (p = 0.0295). Although there was a trend toward improved mortality, this did not reach statistical significance. This study shows that education interventions can be used to increase awareness of severe sepsis/septic shock and improve overall EGDT adherence. PMID:26500811

  18. Cardiac Troponin Is a Predictor of Septic Shock Mortality in Cancer Patients in an Emergency Department: A Retrospective Cohort Study

    PubMed Central

    Yang, Zhi; Qdaisat, Aiham; Hu, Zhihuang; Wagar, Elizabeth A.; Reyes-Gibby, Cielito; Meng, Qing H.; Yeung, Sai-Ching J.

    2016-01-01

    Background Septic shock may be associated with myocardial damage; however, the prognostic value of cardiac enzymes in cancer patients with septic shock is unknown. In this study, we evaluated the prognostic significance of cardiac enzymes in combination with established prognostic factors in predicting the 7-day mortality rate of patients with septic shock, and we constructed a new scoring system, Septic Oncologic Patients in Emergency Department (SOPED), which includes cardiac enzymes, to predict 7-day mortality rates. Methods and Findings We performed a retrospective cohort study of 375 adult cancer patients with septic shock who visited the emergency department of a comprehensive cancer center between 01/01/2004 and 12/31/2013. The 7-day and 28-day mortality rates were 19.7% and 37.6%, respectively. The creatine kinase myocardial band fraction and troponin-I were significantly higher in patients who died in ≤7 days and ≤28 days than in those who did not. In Cox regression models, troponin-I >0.05 ng/mL plus Predisposition, Infection, Response, and Organ Failure (PIRO2011) or Mortality in Emergency Department Sepsis (MEDS) score was a significant predictor of survival for ≤7 days. With our new SOPED scoring system, the receiver operating characteristic area under the curve was 0.836, higher than those for PIRO2011 and MEDS. Conclusions Troponin-I >0.05 ng/mL was an important predictor of short-term mortality (≤7 days). The SOPED scoring system, which incorporated troponin-I, was more prognostically accurate than were other scores for 7-day mortality. Large multicenter studies are needed to verify our results and prospectively validate the prognostic performance of the SOPED score. PMID:27077648

  19. Neurohypophyseal response to fluid resuscitation with hypertonic saline during septic shock in rats.

    PubMed

    Santiago, Michael Brian; Vieira, Alexandre Antonio; Elias, Lucila L K; Rodrigues, José Antunes; Giusti-Paiva, Alexandre

    2013-02-01

    Septic shock is a serious condition with a consequent drop in blood pressure and inadequate tissue perfusion. Small-volume resuscitation with hypertonic saline (HS) has been proposed to restore physiological haemodynamics during haemorrhagic and endotoxic shock. In the present study, we sought to determine the effects produced by an HS infusion in rats subjected to caecal ligation and perforation (CLP). Male Wistar rats were randomly grouped and submitted to either CLP or sham surgery. Either HS (7.5% NaCl, 4 ml kg(-1) i.v.) or isotonic saline (IS; 0.9% NaCl, 4 ml kg(-1) i.v.) was administered 6 h after CLP. Recordings of mean arterial pressure and heart rate were made during this protocol. Moreover, measurements of electrolyte, vasopressin and oxytocin secretion were analysed after either the HS or the IS treatment. Six hours after CLP, we observed a characteristic decrease in mean arterial pressure that occurs after CLP. The HS infusion in these rats produced a transient elevation of the plasma sodium concentration and osmolality and increased plasma vasopressin and oxytocin levels. Moreover, the HS infusion could restore the mean arterial pressure after CLP, which was completely blunted by the previous injection of the vasopressin but not the oxytocin antagonist. The present study demonstrated that rats subjected to CLP and an infusion of hypertonic saline respond with secretion of neurohypophyseal hormones and a transient increase in blood pressure mediated by the V(1) receptor. PMID:22903979

  20. Clostridium sordellii as a Cause of Fatal Septic Shock in a Child with Hemolytic Uremic Syndrome.

    PubMed

    Beyers, Rebekah; Baldwin, Michael; Dalabih, Sevilay; Dalabih, Abdallah

    2014-01-01

    Clostridium sordellii is a toxin producing ubiquitous gram-positive anaerobe, mainly associated with trauma, soft tissue skin infections, and gynecologic infection. We report a unique case of a new strain of Clostridium sordellii (not present in the Center for Disease Control (CDC) database) infection induced toxic shock syndrome in a previously healthy two-year-old male with colitis-related hemolytic uremic syndrome (HUS). The patient presented with dehydration, vomiting, and bloody diarrhea. He was transferred to the pediatric critical care unit (PICU) for initiation of peritoneal dialysis (PD). Due to increased edema and intolerance of PD, he was transitioned to hemodialysis through a femoral vascular catheter. He subsequently developed severe septic shock with persistent leukocytosis and hypotension, resulting in subsequent death. Stool culture confirmed Shiga toxin producing Escherichia coli 0157:H7. A blood culture was positively identified for Clostridium sordellii. Clostridium sordelli is rarely reported in children; to our knowledge this is the first case described in a pediatric patient with HUS. PMID:24891968

  1. Septic shock caused by Klebsiella oxytoca: An autopsy case and a survival case with driving Extracorporeal Membrane Oxygenation

    PubMed Central

    Hagiwara, S; Murata, M; Aoki, M; Kaneko, M; Oshima, K

    2013-01-01

    We report two cases of Klebsiella oxytoca bacteremia. Case 1 was a 56-year-old man who was transferred to our hospital by ambulance due to diarrhea and general fatigue. On arrival, he was clearly conscious. However he was in septic shock. We injected broad spectrum antibacterial agents and started intensive care. Though intensive care included continuous hemodiafiltration (CHDF), he died 22 hours after admission. Case 2 was a 69-year-old man with a history of gastrectomy for gastric cancer. He had been admitted to a previous hospital due to ileus. His ileus tube was removed on the eighth day, and he then developed a fever of 38 ºC on the following day. He went into shock and became unconscious; he was therefore transferred to our hospital. We diagnosed septic shock and disseminated intravascular coagulation (DIC). We injected broad spectrum antibacterial agents, and recombinant thrombomodulin alpha (rTM). Although he was started in intensive care, his hemodynamics were unstable on the day following admission. Extracorporeal membrane oxygenation (ECMO) and intra-aortic balloon pumping (IABP) were started to maintain his hemodynamics. His condition gradually improved, and he was transferred to the previous hospital for rehabilitation on the 28th day. ECMO for septic shock in adults is unusual; however ECMO can be introduced even in patients with severe sepsis under careful monitoring. The new anti-DIC agent rTM is useful for safe driving of ECMO in patients with DIC. PMID:24376326

  2. Use of venous-to-arterial carbon dioxide tension difference to guide resuscitation therapy in septic shock

    PubMed Central

    Mallat, Jihad; Lemyze, Malcolm; Tronchon, Laurent; Vallet, Benoît; Thevenin, Didier

    2016-01-01

    The mixed venous-to-arterial carbon dioxide (CO2) tension difference [P (v-a) CO2] is the difference between carbon dioxide tension (PCO2) in mixed venous blood (sampled from a pulmonary artery catheter) and the PCO2 in arterial blood. P (v-a) CO2 depends on the cardiac output and the global CO2 production, and on the complex relationship between PCO2 and CO2 content. Experimental and clinical studies support the evidence that P (v-a) CO2 cannot serve as an indicator of tissue hypoxia, and should be regarded as an indicator of the adequacy of venous blood to wash out the total CO2 generated by the peripheral tissues. P (v-a) CO2 can be replaced by the central venous-to-arterial CO2 difference (ΔPCO2), which is calculated from simultaneous sampling of central venous blood from a central vein catheter and arterial blood and, therefore, more easy to obtain at the bedside. Determining the ΔPCO2 during the resuscitation of septic shock patients might be useful when deciding when to continue resuscitation despite a central venous oxygen saturation (ScvO2) > 70% associated with elevated blood lactate levels. Because high blood lactate levels is not a discriminatory factor in determining the source of that stress, an increased ΔPCO2 (> 6 mmHg) could be used to identify patients who still remain inadequately resuscitated. Monitoring the ΔPCO2 from the beginning of the reanimation of septic shock patients might be a valuable means to evaluate the adequacy of cardiac output in tissue perfusion and, thus, guiding the therapy. In this respect, it can aid to titrate inotropes to adjust oxygen delivery to CO2 production, or to choose between hemoglobin correction or fluid/inotrope infusion in patients with a too low ScvO2 related to metabolic demand. The combination of P (v-a) CO2 or ΔPCO2 with oxygen-derived parameters through the calculation of the P (v-a) CO2 or ΔPCO2/arteriovenous oxygen content difference ratio can detect the presence of global anaerobic metabolism

  3. Use of venous-to-arterial carbon dioxide tension difference to guide resuscitation therapy in septic shock.

    PubMed

    Mallat, Jihad; Lemyze, Malcolm; Tronchon, Laurent; Vallet, Benoît; Thevenin, Didier

    2016-02-01

    The mixed venous-to-arterial carbon dioxide (CO2) tension difference [P (v-a) CO2] is the difference between carbon dioxide tension (PCO2) in mixed venous blood (sampled from a pulmonary artery catheter) and the PCO2 in arterial blood. P (v-a) CO2 depends on the cardiac output and the global CO2 production, and on the complex relationship between PCO2 and CO2 content. Experimental and clinical studies support the evidence that P (v-a) CO2 cannot serve as an indicator of tissue hypoxia, and should be regarded as an indicator of the adequacy of venous blood to wash out the total CO2 generated by the peripheral tissues. P (v-a) CO2 can be replaced by the central venous-to-arterial CO2 difference (ΔPCO2), which is calculated from simultaneous sampling of central venous blood from a central vein catheter and arterial blood and, therefore, more easy to obtain at the bedside. Determining the ΔPCO2 during the resuscitation of septic shock patients might be useful when deciding when to continue resuscitation despite a central venous oxygen saturation (ScvO2) > 70% associated with elevated blood lactate levels. Because high blood lactate levels is not a discriminatory factor in determining the source of that stress, an increased ΔPCO2 (> 6 mmHg) could be used to identify patients who still remain inadequately resuscitated. Monitoring the ΔPCO2 from the beginning of the reanimation of septic shock patients might be a valuable means to evaluate the adequacy of cardiac output in tissue perfusion and, thus, guiding the therapy. In this respect, it can aid to titrate inotropes to adjust oxygen delivery to CO2 production, or to choose between hemoglobin correction or fluid/inotrope infusion in patients with a too low ScvO2 related to metabolic demand. The combination of P (v-a) CO2 or ΔPCO2 with oxygen-derived parameters through the calculation of the P (v-a) CO2 or ΔPCO2/arteriovenous oxygen content difference ratio can detect the presence of global anaerobic metabolism

  4. Comparative analysis of survival between elderly and non-elderly severe sepsis and septic shock resuscitated patients

    PubMed Central

    Palomba, Henrique; Corrêa, Thiago Domingos; Silva, Eliézer; Pardini, Andreia; de Assuncao, Murillo Santucci Cesar

    2015-01-01

    Objective To compare outcomes between elderly (≥65 years old) and non-elderly (<65 years old) resuscitated severe sepsis and septic shock patients and determine predictors of death among elderly patients. Methods Retrospective cohort study including 848 severe sepsis and septic shock patients admitted to the intensive care unit between January 2006 and March 2012. Results Elderly patients accounted for 62.6% (531/848) and non-elderly patients for 37.4% (317/848). Elderly patients had a higher APACHE II score [22 (18-28) versus 19 (15-24); p<0.001], compared to non-elderly patients, although the number of organ dysfunctions did not differ between the groups. No significant differences were found in 28-day and in-hospital mortality rates between elderly and non-elderly patients. The length of hospital stay was higher in elderly compared to non-elderly patients admitted with severe sepsis and septic shock [18 (10-41) versus 14 (8-29) days, respectively; p=0.0001]. Predictors of death among elderly patients included age, site of diagnosis, APACHE II score, need for mechanical ventilation and vasopressors. Conclusion In this study population early resuscitation of elderly patients was not associated with increased in-hospital mortality. Prospective studies addressing the long-term impact on functional status and quality of life are necessary. PMID:26313436

  5. Choice of Fluid Therapy in the Initial Management of Sepsis, Severe Sepsis, and Septic Shock.

    PubMed

    Chang, Ronald; Holcomb, John B

    2016-07-01

    Sepsis results in disruption of the endothelial glycocalyx layer and damage to the microvasculature, resulting in interstitial accumulation of fluid and subsequently edema. Fluid resuscitation is a mainstay in the initial treatment of sepsis, but the choice of fluid is unclear. The ideal resuscitative fluid is one that restores intravascular volume while minimizing edema; unfortunately, edema and edema-related complications are common consequences of current resuscitation strategies. Crystalloids are recommended as first-line therapy, but the type of crystalloid is not specified. There is increasing evidence that normal saline is associated with increased mortality and kidney injury; balanced crystalloids may be a safer alternative. Albumin is similar to crystalloids in terms of outcomes in the septic population but is costlier. Hydroxyethyl starches appear to increase mortality and kidney injury in the critically ill and are no longer indicated in these patients. In the trauma population, the shift to plasma-based resuscitation with decreased use of crystalloid and colloid in the treatment of hemorrhagic shock has led to decreased inflammatory and edema-mediated complications. Studies are needed to determine if these benefits also occur with a similar resuscitation strategy in the setting of sepsis. PMID:26844975

  6. Fc gamma receptor IIa (CD32) polymorphism in fulminant meningococcal septic shock in children.

    PubMed

    Bredius, R G; Derkx, B H; Fijen, C A; de Wit, T P; de Haas, M; Weening, R S; van de Winkel, J G; Out, T A

    1994-10-01

    Antibodies are essential in host defense against Neisseria meningitidis. Therefore, interactions among IgG and Fc receptors (Fc gamma R) on phagocytes may be crucial. Genetic polymorphic forms of Fc gamma RIIa (CD32) express different functional activities. In a retrospective study, Fc gamma R polymorphisms were determined in 25 children who survived fulminant meningococcal septic shock: 11 had Fc gamma RIIa-R/R131, the poor IgG2-binding allotype, which is a significantly more frequent rate than found in a healthy white population (44% vs. 23%; P = .028; odds ratio = 2.67; 95% confidence interval, 1.09-6.53). The relevance of this finding was further supported by the fact that neutrophils with the Fc gamma RIIa-R/R131 allotype phagocytized N. meningitidis opsonized with polyclonal IgG2 antibodies less effectively than did IIa-H/H131 neutrophils. Our findings suggest an important role for anti-N. meningitidis IgG2 and the Fc gamma RIIa polymorphism in host defense against systemic meningococcal infections. PMID:7930726

  7. Immature Platelet Fraction in Septic Patients: Clinical Relevance of Immature Platelet Fraction is Limited to the Sensitive and Accurate Discrimination of Septic Patients From Non-Septic Patients, Not to the Discrimination of Sepsis Severity

    PubMed Central

    Park, Sang Hyuk; Ha, Sang Ook; Cho, Young-Uk; Park, Chan-Jeoung

    2016-01-01

    Background The immature platelet fraction (IPF) reflects the degree of reticulated platelets. We evaluated performances of IPF as a biomarker for the discrimination of septic patients from non-septic patients and sepsis severity. Methods Total 312 patients admitted between March and July 2013 were enrolled and samples were obtained at admission. Lactate (LA), procalcitonin (PCT), C-reactive protein (CRP), immature granulocyte fraction (IG), immature reticulocyte fraction (IRF), and IPF were analyzed as sepsis biomarkers and their performances were compared. Results The performance of IPF (area under the curve [AUC]=0.868) in the discrimination of septic patients from non-septic patients was comparable to PCT/CRP/LA/IG (AUC=0.923/0.940/0.781/0.812, P=0.233/0.106/0.186/0.353, respectively), and was significantly better than the IRF (AUC=0.658, P=0.007). Sensitivity (89.8%, 95% confidence interval [CI] 84.9-99.8%) and accuracy (83.2%, 95% CI 78.8-90.0%) of IPF were the best among all biomarkers. The performance of IPF in discriminating septic patients from non-septic patients with local infection showed similar results. However, the IPF could not efficiently discriminate sepsis severity (AUC=0.599), similar to other biomarkers (AUC=0.519-0.752). Conclusions The IPF possessed high sensitivity/accuracy in discriminating septic patients from non-septic patients, regardless of local infection status. However, the IPF did not efficiently discriminate sepsis severity. The clinical relevance of IPF as a sepsis biomarker is, therefore, limited to sensitive and accurate discrimination of septic patients from non-septic patients, not discrimination of sepsis severity. PMID:26522752

  8. Multicountry survey of emergency and critical care medicine physicians’ fluid resuscitation practices for adult patients with early septic shock

    PubMed Central

    McIntyre, Lauralyn; Rowe, Brian H; Walsh, Timothy S; Gray, Alasdair; Arabi, Yaseen; Perner, Anders; Gordon, Anthony; Marshall, John; Cook, Deborah; Fox-Robichaud, Alison; Bagshaw, Sean M; Green, Robert; Schweitzer, Irwin; Turgeon, Alexis; Zarychanski, Ryan; English, Shane; Chassé, Michaël; Stiell, Ian; Fergusson, Dean

    2016-01-01

    Objectives Evidence to guide fluid resuscitation evidence in sepsis continues to evolve. We conducted a multicountry survey of emergency and critical care physicians to describe current stated practice and practice variation related to the quantity, rapidity and type of resuscitation fluid administered in early septic shock to inform the design of future septic shock fluid resuscitation trials. Methods Using a web-based survey tool, we invited critical care and emergency physicians in Canada, the UK, Scandinavia and Saudi Arabia to complete a self-administered electronic survey. Results A total of 1097 physicians’ responses were included. 1 L was the most frequent quantity of resuscitation fluid physicians indicated they would administer at a time (46.9%, n=499). Most (63.0%, n=671) stated that they would administer the fluid challenges as quickly as possible. Overall, normal saline and Ringer's solutions were the preferred crystalloid fluids used ‘often’ or ‘always’ in 53.1% (n=556) and 60.5% (n=632) of instances, respectively. However, emergency physicians indicated that they would use normal saline ‘often’ or ‘always’ in 83.9% (n=376) of instances, while critical care physicians said that they would use saline ‘often’ or ‘always’ in 27.9% (n=150) of instances. Only 1.0% (n=10) of respondents indicated that they would use hydroxyethyl starch ‘often’ or ‘always’; use of 5% (5.6% (n=59)) or 20–25% albumin (1.3% (n=14)) was also infrequent. The majority (88.4%, n=896) of respondents indicated that a large randomised controlled trial comparing 5% albumin to a crystalloid fluid in early septic shock was important to conduct. Conclusions Critical care and emergency physicians stated that they rapidly infuse volumes of 500–1000 mL of resuscitation fluid in early septic shock. Colloid use, specifically the use of albumin, was infrequently reported. Our survey identifies the need to conduct a trial on the efficacy of albumin and

  9. Early goal-directed therapy in severe sepsis and septic shock: insights and comparisons to ProCESS, ProMISe, and ARISE.

    PubMed

    Nguyen, H Bryant; Jaehne, Anja Kathrin; Jayaprakash, Namita; Semler, Matthew W; Hegab, Sara; Yataco, Angel Coz; Tatem, Geneva; Salem, Dhafer; Moore, Steven; Boka, Kamran; Gill, Jasreen Kaur; Gardner-Gray, Jayna; Pflaum, Jacqueline; Domecq, Juan Pablo; Hurst, Gina; Belsky, Justin B; Fowkes, Raymond; Elkin, Ronald B; Simpson, Steven Q; Falk, Jay L; Singer, Daniel J; Rivers, Emanuel P

    2016-01-01

    Prior to 2001 there was no standard for early management of severe sepsis and septic shock in the emergency department. In the presence of standard or usual care, the prevailing mortality was over 40-50 %. In response, a systems-based approach, similar to that in acute myocardial infarction, stroke and trauma, called early goal-directed therapy was compared to standard care and this clinical trial resulted in a significant mortality reduction. Since the publication of that trial, similar outcome benefits have been reported in over 70 observational and randomized controlled studies comprising over 70,000 patients. As a result, early goal-directed therapy was largely incorporated into the first 6 hours of sepsis management (resuscitation bundle) adopted by the Surviving Sepsis Campaign and disseminated internationally as the standard of care for early sepsis management. Recently a trio of trials (ProCESS, ARISE, and ProMISe), while reporting an all-time low sepsis mortality, question the continued need for all of the elements of early goal-directed therapy or the need for protocolized care for patients with severe and septic shock. A review of the early hemodynamic pathogenesis, historical development, and definition of early goal-directed therapy, comparing trial conduction methodology and the changing landscape of sepsis mortality, are essential for an appropriate interpretation of these trials and their conclusions. PMID:27364620

  10. Interaction of antimicrobial peptide temporin L with lipopolysaccharide in vitro and in experimental rat models of septic shock caused by gram-negative bacteria.

    PubMed

    Giacometti, Andrea; Cirioni, Oscar; Ghiselli, Roberto; Mocchegiani, Federico; Orlando, Fiorenza; Silvestri, Carmela; Bozzi, Argante; Di Giulio, Antonio; Luzi, Carla; Mangoni, Maria Luisa; Barra, Donatella; Saba, Vittorio; Scalise, Giorgio; Rinaldi, Andrea C

    2006-07-01

    Sepsis remains a major cause of morbidity and mortality in hospitalized patients, despite intense efforts to improve survival. The primary lead for septic shock results from activation of host effector cells by endotoxin, the lipopolysaccharide (LPS) associated with cell membranes of gram-negative bacteria. For these reasons, the quest for compounds with antiendotoxin properties is actively pursued. We investigated the efficacy of the amphibian skin antimicrobial peptide temporin L in binding Escherichia coli LPS in vitro and counteracting its effects in vivo. Temporin L strongly bound to purified E. coli LPS and lipid A in vitro, as proven by fluorescent displacement assay, and readily penetrated into E. coli LPS monolayers. Furthermore, the killing activity of temporin L against E. coli was progressively inhibited by increasing concentrations of LPS added to the medium, further confirming the peptide's affinity for endotoxin. Antimicrobial assays showed that temporin L interacted synergistically with the clinically used beta-lactam antibiotics piperacillin and imipenem. Therefore, we characterized the activity of temporin L when combined with imipenem and piperacillin in the prevention of lethality in two rat models of septic shock, measuring bacterial growth in blood and intra-abdominal fluid, endotoxin and tumor necrosis factor alpha (TNF-alpha) concentrations in plasma, and lethality. With respect to controls and single-drug treatments, the simultaneous administration of temporin L and beta-lactams produced the highest antimicrobial activities and the strongest reduction in plasma endotoxin and TNF-alpha levels, resulting in the highest survival rates. PMID:16801429

  11. Angiopoietin Balance in Septic Shock Patients With Acute Kidney Injury: Effects of Direct Hemoperfusion With Polymyxin B-Immobilized Fiber.

    PubMed

    Ebihara, Itaru; Hirayama, Kouichi; Nagai, Miho; Shiina, Eri; Koda, Megumi; Gunji, Masanobu; Okubo, Yuki; Sato, Chihiro; Usui, Joichi; Yamagata, Kunihiro; Kobayashi, Masaki

    2016-08-01

    Acute kidney injury (AKI) occurs in approximately 50% of patients in septic shock, and mortality from septic AKI is extremely high. Angiopoietin levels may play a role in the pathogenesis of vascular permeability. It was reported that direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX) therapy ameliorates the angiopoietin balance in patients with sepsis. Although dysregulated angiopoietin balance in sepsis has been demonstrated, mechanisms underlying the development of AKI in sepsis have not been identified. We investigated angiopoietin levels in septic patients with/without AKI treated with DHP-PMX therapy. We used an enzyme-linked immunoassay to measure serum angiopoietin-1 and -2 levels in 38 septic shock patients treated with DHP-PMX. The renal function of all patients was normal for less than 3 months. Twenty-seven of the patients were diagnosed with AKI. The angiopoietin-1 level of the AKI group was significantly lower than that of the non-AKI group at the initiation of DHP-PMX therapy, but there was no significant difference between the two groups at the end of DHP-PMX therapy. In the AKI group with recovery, the mean angiopoietin-1 level at the end of DHP-PMX therapy was significantly elevated compared to the level before DHP-PMX therapy, and the mean angiopoietin-2 level at the end of DHP-PMX therapy was significantly decreased compared to the level before DHP-PMX therapy. These results suggest that angiopoietins may play a role in the pathogenesis of AKI and that DHP-PMX therapy may ameliorate the angiopoietin balance in AKI patients with sepsis. PMID:27523077

  12. Clinical and microbiological outcome in septic patients with extremely low 25-hydroxyvitamin D levels at initiation of critical care.

    PubMed

    De Pascale, G; Vallecoccia, M S; Schiattarella, A; Di Gravio, V; Cutuli, S L; Bello, G; Montini, L; Pennisi, M A; Spanu, T; Zuppi, C; Quraishi, S A; Antonelli, M

    2016-05-01

    A relationship between vitamin D status and mortality in patients in intensive care units (ICU) has been documented. The present study aims to describe the clinical profile and sepsis-related outcome of critically ill septic patients with extremely low (<7 ng/mL) vitamin D levels at ICU admission. We conducted an observational study in the ICU of a teaching hospital including all patients admitted with severe sepsis/septic shock and undergoing 25-hydroxyvitamin D (25(OH)D) testing within the first 24 hours from admission. We studied 107 patients over 12 months. At ICU admission vitamin D deficiency (≤20 ng/mL) was observed in 93.5% of the patients: 57 (53.3%) showed levels <7 ng/mL. As primary outcome, sepsis-related mortality rate was higher in patients with vitamin D levels <7 ng/mL (50.9% versus 26%). Multivariate regression analysis showed that vitamin D concentration <7 ng/mL on ICU admission (p 0.01) and higher mean SAPS II (p <0.01) score were independent predictors of sepsis-related mortality. Patients with very low vitamin D levels suffered higher rate of microbiologically confirmed infections but a lower percentage of microbiological eradication with respect to patients whose values were >7 ng/mL (80.7% versus 58%, p 0.02; 35.3% versus 68%; p 0.03, respectively). Post hoc analysis showed that, in the extremely low vitamin D group, the 52 patients with pneumonia showed a longer duration of mechanical ventilation (9 days (3.75-12.5 days) versus 4 days (2-9 days), p 0.04) and the 66 with septic shock needed vasopressor support for a longer period of time (7 days (4-10 days) versus 4 days (2-7.25 days), p 0.02). Our results suggest that in critical septic patients extremely low vitamin D levels on admission may be a major determinant of clinical outcome. Benefits of vitamin D replacement therapy in this population should be elucidated. PMID:26721785

  13. TNFAIP2 Inhibits Early TNFα-Induced NF-x03BA;B Signaling and Decreases Survival in Septic Shock Patients.

    PubMed

    Thair, Simone A; Topchiy, Elena; Boyd, John H; Cirstea, Mihai; Wang, Catherine; Nakada, Taka-Aki; Fjell, Christopher D; Wurfel, Mark; Russell, James A; Walley, Keith R

    2016-01-01

    During septic shock, tumor necrosis factor alpha (TNFα) is an early response gene and induces a plethora of genes and signaling pathways. To identify robust signals in genes reliably upregulated by TNFα, we first measured microarray gene expression in vitro and searched methodologically comparable, publicly available data sets to identify concordant signals. Using tag single-nucleotide polymorphisms in the genes common to all data sets, we identified a genetic variant of the TNFAIP2 gene, rs8126, associated with decreased 28-day survival and increased organ dysfunction in an adult cohort in the Vasopressin and Septic Shock Trial. Similar to this cohort, we found that an association with rs8126 and increased organ dysfunction is replicated in a second cohort of septic shock patients in the St. Paul's Hospital Intensive Care Unit. We found that TNFAIP2 inhibits NF-x03BA;B activity, impacting the downstream cytokine interleukin (IL)-8. The minor G allele of TNFAIP2 rs8126 resulted in greater TNFAIP2 expression, decreased IL-8 production and was associated with decreased survival in patients experiencing septic shock. These data suggest that TNFAIP2 is a novel inhibitor of NF-x03BA;B that acts as an autoinhibitor of the TNFα response during septic shock. PMID:26347487

  14. Effects of Shenfu Injection in the Treatment of Septic Shock Patients: A Multicenter, Controlled, Randomized, Open-Label Trial

    PubMed Central

    Zhang, Xinchao; Lin, Peihong; Wei, Jie; Cao, Yu; Pan, Shuming; Walline, Joseph; Qian, Chuanyun; Shan, Zhigang

    2016-01-01

    The effect of Shenfu on biochemical parameters and survival during resuscitation in patients with septic shock was examined. This was a multicenter, controlled, randomized, open-label trial carried out in 210 patients with septic shock from seven medical centers in China. They were randomized to Shenfu or saline. The primary outcome was lactate clearance. The secondary outcomes were shock index normalization, dose of vasopressors, ICU stay, hospital stay, and mortality. A total of 199 patients completed the trial. Blood pressure, heart rate, and other routine lab tests showed no difference between the groups. Lactate levels and lactate clearance were similar between the two groups. Hospital and ICU stay were similar between the two groups. When considering all patients, the 7- and 28-day mortality were similar between the two groups, but when considering only patients with lactate levels ≥4.5 mmol/L, the Shenfu group showed a better 7-day survival than the control group (7 days: 83.3% versus 54.5%, P = 0.034; 28 days: 72.7% versus 47.6%, P = 0.092). Shenfu may improve the 7-day survival in patients with impaired lactate clearance (≥4.5 mmol/L), but the mechanism for this effect is unclear. Additional studies are necessary to characterize the hemodynamic changes after Shenfu infusion. This trial is registered with ChiCTR-TRC-11001369. PMID:27446222

  15. Overexpression of GTP Cyclohydrolase 1 Feedback Regulatory Protein Is Protective in a Murine Model of Septic Shock

    PubMed Central

    Starr, Anna; Sand, Claire A.; Heikal, Lamia; Kelly, Peter D.; Spina, Domenico; Crabtree, Mark; Channon, Keith M.; Leiper, James M.; Nandi, Manasi

    2014-01-01

    ABSTRACT Overproduction of nitric oxide (NO) by inducible NO synthase contributes toward refractory hypotension, impaired microvascular perfusion, and end-organ damage in septic shock patients. Tetrahydrobiopterin (BH4) is an essential NOS cofactor. GTP cyclohydrolase 1 (GCH1) is the rate-limiting enzyme for BH4 biosynthesis. Under inflammatory conditions, GCH1 activity and hence BH4 levels are increased, supporting pathological NOS activity. GCH1 activity can be controlled through allosteric interactions with GCH1 feedback regulatory protein (GFRP). We investigated whether overexpression of GFRP can regulate BH4 and NO production and attenuate cardiovascular dysfunction in sepsis. Sepsis was induced in mice conditionally overexpressing GFRP and wild-type littermates by cecal ligation and puncture. Blood pressure was monitored by radiotelemetry, and mesenteric blood flow was quantified by laser speckle contrast imaging. Blood biochemistry data were obtained using an iSTAT analyzer, and BH4 levels were measured in plasma and tissues by high-performance liquid chromatography. Increased BH4 and NO production and hypotension were observed in all mice, but the extents of these pathophysiological changes were attenuated in GFRP OE mice. Perturbations in blood biochemistry were similarly attenuated in GFRP OE compared with wild-type controls. These results suggest that GFRP overexpression regulates GCH1 activity during septic shock, which in turn limits BH4 bioavailability for iNOS. We conclude that the GCH1-GFRP axis is a critical regulator of BH4 and NO production and the cardiovascular derangements that occur in septic shock. PMID:25046538

  16. Overexpression of GTP cyclohydrolase 1 feedback regulatory protein is protective in a murine model of septic shock.

    PubMed

    Starr, Anna; Sand, Claire A; Heikal, Lamia; Kelly, Peter D; Spina, Domenico; Crabtree, Mark; Channon, Keith M; Leiper, James M; Nandi, Manasi

    2014-11-01

    Overproduction of nitric oxide (NO) by inducible NO synthase contributes toward refractory hypotension, impaired microvascular perfusion, and end-organ damage in septic shock patients. Tetrahydrobiopterin (BH4) is an essential NOS cofactor. GTP cyclohydrolase 1 (GCH1) is the rate-limiting enzyme for BH4 biosynthesis. Under inflammatory conditions, GCH1 activity and hence BH4 levels are increased, supporting pathological NOS activity. GCH1 activity can be controlled through allosteric interactions with GCH1 feedback regulatory protein (GFRP). We investigated whether overexpression of GFRP can regulate BH4 and NO production and attenuate cardiovascular dysfunction in sepsis. Sepsis was induced in mice conditionally overexpressing GFRP and wild-type littermates by cecal ligation and puncture. Blood pressure was monitored by radiotelemetry, and mesenteric blood flow was quantified by laser speckle contrast imaging. Blood biochemistry data were obtained using an iSTAT analyzer, and BH4 levels were measured in plasma and tissues by high-performance liquid chromatography. Increased BH4 and NO production and hypotension were observed in all mice, but the extents of these pathophysiological changes were attenuated in GFRP OE mice. Perturbations in blood biochemistry were similarly attenuated in GFRP OE compared with wild-type controls. These results suggest that GFRP overexpression regulates GCH1 activity during septic shock, which in turn limits BH4 bioavailability for iNOS. We conclude that the GCH1-GFRP axis is a critical regulator of BH4 and NO production and the cardiovascular derangements that occur in septic shock. PMID:25046538

  17. Polymyxin B-immobilized fiber hemoperfusion with low priming volume in an elderly septic shock patient with marked endotoxemia.

    PubMed

    Nakamura, Tsukasa; Kawagoe, Yasuhiro; Ueda, Yoshihiko; Koide, Hikaru

    2005-01-01

    An 84-year-old woman with septic shock caused by pyelonephritis is described herein. She was admitted for severe back pain and high fever. Her white blood cell (WBC) count and C-reactive protein (CRP) and endotoxin levels were elevated at 38,000/microl, 40.0 mg/dl, and 8,400 pg/ml, respectively. Her blood pressure was 80/34 mm Hg. Urinalysis revealed occult blood with innumerable WBCs. Plain abdominal radiography showed calcium stones in both kidneys. Septic shock with endotoxemia was diagnosed, and the patient was treated with antibiotics, gamma-globulin, and dopamine. However, her plasma endotoxin level remained high for 3 days. We performed direct hemoperfusion twice using a polymyxin B-immobilized fiber (PMX-F) column with a low priming volume. After PMX-F treatment, the patient's temperature decreased to 36.8 degrees C; her WBC count and CRP level decreased to 9,200/microl and 3.8 mg/dl, respectively. Her plasma endotoxin level decreased to 840 pg/ml after the first treatment and to 188 pg/ml after the second treatment. The next day, her blood endotoxin level further decreased to 32 pg/ml. Her blood pressure increased to 92/60 mm Hg after the first treatment and to 118/76 mm Hg after the second treatment. The patient was discharged on day 26 after admission. Our experience in this case suggests that PMX-F treatment with a low priming volume may be beneficial in elderly patients with septic shock and marked endotoxemia. PMID:16156319

  18. Intravenous ketamine for treatment of super-refractory convulsive status epilepticus with septic shock: A report of two cases

    PubMed Central

    Shrestha, Gentle Sunder; Joshi, Pankaj; Chhetri, Santosh; Karn, Ragesh; Acharya, Subhash Prasad

    2015-01-01

    Refractory and super-refractory status epilepticus is a life-threatening neurological emergency, associated with high morbidity and mortality. Treatment should be aimed to stop seizure and to avoid cerebral damage and another morbidity. Published data about effectiveness, safety and outcome of various therapies and treatment approaches are sparse and are mainly based on small case series and retrospective data. Here we report successful management of two cases of super-refractory status epilepticus refractory to anesthetic therapy with midazolam and complicated by septic shock, managed successfully with ketamine infusion. PMID:25983437

  19. Patterns of central venous oxygen saturation, lactate and veno-arterial CO2 difference in patients with septic shock

    PubMed Central

    Mahajan, Rubina Khullar; Peter, John Victor; John, George; Graham, Petra L.; Rao, Shoma V.; Pinsky, Michael R.

    2015-01-01

    Background and Aims: Tissue hypoperfusion is reflected by metabolic parameters such as lactate, central venous oxygen saturation (ScvO2) and the veno-arterial CO2 (vaCO2) difference. We studied the relation of these parameters over time and with outcome in patients with severe septic shock. Materials and Methods: In this single-center, prospective observational cohort study, adult patients (≥18 years) with circulatory shock were included. Echocardiography and simultaneous arterial and venous blood gases were done on enrolment (0 h) and at 24, 48 and 72 h. The partial pressure of CO2, lactate and ScvO2 were recorded from the central venous blood samples. The vaCO2 was calculated as the difference in CO2 between paired venous and arterial blood gas samples. Results: Of the 104 patients with circulatory shock, 79 patients (44 males) with septic shock aged 49.8 (standard deviation ± 14.6) years and with sequential organ failure assessment (SOFA) score of 11.0 ± 3.4 were included. 71 patients (89.9%) were ventilated (11.4 ± 12.3 ventilator-free days). The duration of hospitalization was 16.6 ± 12.8 days and hospital mortality 50.6%. Lactate significantly decreased over time with a greater decrement in survivors than nonsurvivors (−0.35 vs. −0.10, P < 0.001). For every l/min increase in cardiac output, vaCO2 decreased by 0.34 mmHg (P = 0.006). There was no association between ScvO2 and mortality (P = 0.930). 0 h SOFA and vaCO2 ≤6 mmHg were strongly associated (P = 0.005, P = 0.018, respectively) with higher odds of mortality. However, this association was evident only in those with ScvO2 >70% and not in ScvO2 ≤70%. Conclusion: In septic shock, vaCO2 ≤6 mmHg is independently associated with mortality, particularly in those with normalized ScvO2 consistent with metabolic microcirculatory abnormalities in these patients. PMID:26628822

  20. Prognosis Biomarkers of Severe Sepsis and Septic Shock by 1H NMR Urine Metabolomics in the Intensive Care Unit

    PubMed Central

    Modesto-Alapont, Vicente; Gonzalez-Marrachelli, Vannina; Vento-Rehues, Rosa; Jorda-Miñana, Angela; Blanquer-Olivas, Jose; Monleon, Daniel

    2015-01-01

    Early diagnosis and patient stratification may improve sepsis outcome by a timely start of the proper specific treatment. We aimed to identify metabolomic biomarkers of sepsis in urine by 1H-NMR spectroscopy to assess the severity and to predict outcomes. Urine samples were collected from 64 patients with severe sepsis or septic shock in the ICU for a 1H NMR spectra acquisition. A supervised analysis was performed on the processed spectra, and a predictive model for prognosis (30-days mortality/survival) of sepsis was constructed using partial least-squares discriminant analysis (PLS-DA). In addition, we compared the prediction power of metabolomics data respect the Sequential Organ Failure Assessment (SOFA) score. Supervised multivariate analysis afforded a good predictive model to distinguish the patient groups and detect specific metabolic patterns. Negative prognosis patients presented higher values of ethanol, glucose and hippurate, and on the contrary, lower levels of methionine, glutamine, arginine and phenylalanine. These metabolites could be part of a composite biopattern of the human metabolic response to sepsis shock and its mortality in ICU patients. The internal cross-validation showed robustness of the metabolic predictive model obtained and a better predictive ability in comparison with SOFA values. Our results indicate that NMR metabolic profiling might be helpful for determining the metabolomic phenotype of worst-prognosis septic patients in an early stage. A predictive model for the evolution of septic patients using these metabolites was able to classify cases with more sensitivity and specificity than the well-established organ dysfunction score SOFA. PMID:26565633

  1. Fulminant course of unilateral emphysematous pyelonephritis revealing a renal actinomycosis caused by Actinomyces meyeri, an unknown cause of septic shock.

    PubMed

    Herbland, Alexandre; Leloup, Maxime; Levrat, Quentin; Guillaume, Frédéric; Verrier, Virginie; Bouillard, Philippe; Landois, Thierry; Ouaki, Charlie Frédéric; Lesieur, Olivier

    2014-01-01

    The objective of this case report is to describe the first case of renal actinomycosis caused by Actinomyces meyeri presenting as severe emphysematous pyelonephritis and complicated by septic shock and multi-organ failure. Emphysematous pyelonephritis is a potentially life-threatening infection mostly described in diabetic patients and predominantly caused by uropathogenic bacteria. Actinomycosis is an uncommon chronic infection due to anaerobic gram-positive bacteria that unusually involves the urinary tract. We report the first case of emphysematous pyelonephritis caused by A. meyeri in a 75-year-old non-diabetic woman. The patient presented with an altered status, fever, nausea, and vomiting lasting for 2 days. A computed tomography scan revealed unilateral emphysematous pyelonephritis. She was rapidly admitted to intensive care unit for a septic shock with multiple organ dysfunctions. A conservative management consisting in renal percutaneous drainage, supportive measures, and prolonged adapted antibiotic therapy resulted in complete recovery. This case report illustrates that renal actinomycosis should be considered in case of emphysematous pyelonephritis given the good prognosis of this infection with conservative medical treatment. PMID:25878793

  2. Serum Procalcitonin and Procalcitonin Clearance as a Prognostic Biomarker in Patients with Severe Sepsis and Septic Shock

    PubMed Central

    Huang, Min-Yi; Chen, Chun-Yu; Chien, Ju-Huei; Wu, Kun-Hsi; Chang, Yu-Jun; Wu, Han-Ping

    2016-01-01

    We evaluated the tendency of the plasma concentration and procalcitonin (PCT) clearance (PCTc) to act as biomarkers of prognosis in patients with severe sepsis and septic shock. From 2011 to 2013, we prospectively analyzed patients with sepsis admitted to the intensive care unit (ICU). The serum PCT was evaluated at the time of sepsis diagnosis and again after 48 h (day 3) and 96 h (day 5). PCTc after 48 h (PCTc-day 3) and 96 h (PCTc-day 5) was also calculated to evaluate the prognostic value for survival in patients with sepsis. A total of 48 patients were included. Overall mortality was 16.7% (8 patients). PCTc was higher in survivors than in nonsurvivors, with significant differences on day 3 and day 5 (p = 0.033; p = 0.002, resp.); however, serum PCT levels on day 1, day 3, and day 5 were not significant prognostic factors for survival. The prognosis of patients with severe sepsis and septic shock may be associated with PCTc. Dynamic changes of PCT reflected as PCTc at 48 h (day 3) and 96 h (day 5) after admission to the ICU may serve as a predictor of survival in critically ill patients with severe sepsis. PMID:27088084

  3. Serum Procalcitonin and Procalcitonin Clearance as a Prognostic Biomarker in Patients with Severe Sepsis and Septic Shock.

    PubMed

    Huang, Min-Yi; Chen, Chun-Yu; Chien, Ju-Huei; Wu, Kun-Hsi; Chang, Yu-Jun; Wu, Kang-Hsi; Wu, Han-Ping

    2016-01-01

    We evaluated the tendency of the plasma concentration and procalcitonin (PCT) clearance (PCTc) to act as biomarkers of prognosis in patients with severe sepsis and septic shock. From 2011 to 2013, we prospectively analyzed patients with sepsis admitted to the intensive care unit (ICU). The serum PCT was evaluated at the time of sepsis diagnosis and again after 48 h (day 3) and 96 h (day 5). PCTc after 48 h (PCTc-day 3) and 96 h (PCTc-day 5) was also calculated to evaluate the prognostic value for survival in patients with sepsis. A total of 48 patients were included. Overall mortality was 16.7% (8 patients). PCTc was higher in survivors than in nonsurvivors, with significant differences on day 3 and day 5 (p = 0.033; p = 0.002, resp.); however, serum PCT levels on day 1, day 3, and day 5 were not significant prognostic factors for survival. The prognosis of patients with severe sepsis and septic shock may be associated with PCTc. Dynamic changes of PCT reflected as PCTc at 48 h (day 3) and 96 h (day 5) after admission to the ICU may serve as a predictor of survival in critically ill patients with severe sepsis. PMID:27088084

  4. Cathelicidin peptide sheep myeloid antimicrobial peptide-29 prevents endotoxin-induced mortality in rat models of septic shock.

    PubMed

    Giacometti, Andrea; Cirioni, Oscar; Ghiselli, Roberto; Mocchegiani, Federico; D'Amato, Giuseppina; Circo, Raffaella; Orlando, Fiorenza; Skerlavaj, Barbara; Silvestri, Carmela; Saba, Vittorio; Zanetti, Margherita; Scalise, Giorgio

    2004-01-15

    The present study was designed to investigate the antiendotoxin activity and therapeutic efficacy of sheep myeloid antimicrobial peptide (SMAP)-29, a cathelicidin-derived peptide. The in vitro ability of SMAP-29 to bind LPS from Escherichia coli 0111:B4 was determined using a sensitive limulus chromogenic assay. Two rat models of septic shock were performed: (1) rats were injected intraperitoneally with 1 mg E. coli 0111:B4 LPS and (2) intraabdominal sepsis was induced via cecal ligation and single puncture. All animals were randomized to receive parenterally isotonic sodium chloride solution, 1 mg/kg SMAP-29, 1 mg/kg polymyxin B or 20 mg/kg imipenem. The main outcome measures were: abdominal exudate and plasma bacterial growth, plasma endotoxin and tumor necrosis factor-alpha concentrations, and lethality. The in vitro study showed that SMAP-29 completely inhibited the LPS procoagulant activity at approximately 10 microM peptide concentration. The in vivo experiments showed that all compounds reduced the lethality when compared with control animals. SMAP-29 achieved a substantial decrease in endotoxin and tumor necrosis factor-alpha plasma concentrations when compared with imipenem and saline treatment and exhibited a slightly lower antimicrobial activity than imipenem. No statistically significant differences were noted between SMAP-29 and polymyxin B. SMAP-29, because of its double antiendotoxin and antimicrobial activities, could be an interesting compound for septic shock treatment. PMID:14563656

  5. Creating a pro-survival and anti-inflammatory phenotype by modulation of acetylation in models of hemorrhagic and septic shock.

    PubMed

    Li, Yongqing; Alam, Hasan B

    2012-01-01

    Shock, regardless of etiology, is characterized by decreased tissue perfusion resulting in cell death, organ dysfunction, and poor survival. Current therapies largely focus on restoring tissue perfusion through resuscitation but have failed to address the specific cellular dysfunction caused by shock. Acetylation is rapidly emerging as a key mechanism that regulates the expression of numerous genes (epigenetic modulation through activation of nuclear histone proteins), as well as functions of multiple cytoplasmic proteins involved in key cellular functions such as cell survival, repair/healing, signaling, and proliferation. Cellular acetylation can be increased immediately through the administration of histone deacetylase inhibitors (HDACI). A series of studies have been performed using: (1) cultured cells; (2) single-organ ischemia-reperfusion injury models; (3) rodent models of lethal septic and hemorrhagic shock; (4) swine models of lethal hemorrhagic shock and multi-organ trauma; and (5) tissues from severely injured trauma patients, to fully characterize the changes in acetylation that occur following lethal insults and in response to treatment with HDACI. These data demonstrate that: (1) shock causes a decrease in acetylation of nuclear and cytoplasmic proteins; (2) hypoacetylation can be rapidly reversed through the administration of HDACI; (3) normalization of acetylation prevents cell death, decreases inflammation, attenuates activation of pro-apoptotic pathways, and augments pro-survival pathways; (4) the effect of HDACI significantly improves survival in lethal models of septic shock, hemorrhagic shock, and complex poly-trauma without need for conventional fluid resuscitation or blood transfusion; and (5) improvement in survival is not due to better resuscitation but due to an enhanced ability of cells to tolerate lethal insults.As different models of hemorrhagic or septic shock have specific strengths and limitations, this chapter will summarize our

  6. Creating a Pro-survival and Anti-inflammatory Phenotype by Modulation of Acetylation in Models of Hemorrhagic and Septic Shock

    PubMed Central

    Li, Yongqing

    2016-01-01

    Shock, regardless of etiology, is characterized by decreased tissue perfusion resulting in cell death, organ dysfunction, and poor survival. Current therapies largely focus on restoring tissue perfusion through resuscitation but have failed to address the specific cellular dysfunction caused by shock. Acetylation is rapidly emerging as a key mechanism that regulates the expression of numerous genes (epigenetic modulation through activation of nuclear histone proteins), as well as functions of multiple cytoplasmic proteins involved in key cellular functions such as cell survival, repair/healing, signaling, and proliferation. Cellular acetylation can be increased immediately through the administration of histone deacetylase inhibitors (HDACI). A series of studies have been performed using: (1) cultured cells; (2) single-organ ischemia-reperfusion injury models; (3) rodent models of lethal septic and hemorrhagic shock; (4) swine models of lethal hemorrhagic shock and multi-organ trauma; and (5) tissues from severely injured trauma patients, to fully characterize the changes in acetylation that occur following lethal insults and in response to treatment with HDACI. These data demonstrate that: (1) shock causes a decrease in acetylation of nuclear and cytoplasmic proteins; (2) hypoacetylation can be rapidly reversed through the administration of HDACI; (3) normalization of acetylation prevents cell death, decreases inflammation, attenuates activation of pro-apoptotic pathways, and augments pro-survival pathways; (4) the effect of HDACI significantly improves survival in lethal models of septic shock, hemorrhagic shock, and complex poly-trauma without need for conventional fluid resuscitation or blood transfusion; and (5) improvement in survival is not due to better resuscitation but due to an enhanced ability of cells to tolerate lethal insults. As different models of hemorrhagic or septic shock have specific strengths and limitations, this chapter will summarize our

  7. The Early Expression of HLA-DR and CD64 Myeloid Markers Is Specifically Compartmentalized in the Blood and Lungs of Patients with Septic Shock

    PubMed Central

    Mikaszewska-Sokolewicz, Małgorzata; Hoser, Grażyna; Zielińska-Borkowska, Urszula

    2016-01-01

    Identification of reliable biomarkers is key to guide targeted therapies in septic patients. Expression monitoring of monocyte HLA-DR and neutrophil CD64 could fulfill the above need. However, it is unknown whether their expression on circulating cells reflects the status of tissue resident cells. We compared expressions of HLA-DR and CD64 markers in the circulation and airways of septic shock patients and evaluated their outcome prognostic value. The expression of CD64 on neutrophils and HLA-DR on monocytes was analyzed in the peripheral blood and mini-bronchoalveolar lavage fluid cells by flow cytometry. Twenty-seven patients with septic shock were enrolled into the study. The fluorescence intensity of HLA-DR on circulating monocytes was 3.5-fold lower than on the pulmonary monocytes (p = 0.01). The expression of CD64 on circulating and airway neutrophils was similar (p = 0.47). Only the expression of CD64 on circulating neutrophils was higher in nonsurvivors versus survivors (2.8-fold; p = 0.031). Pulmonary monocytes display a higher level of HLA-DR activation compared to peripheral blood monocytes but the expression of neutrophil CD64 is similar on lung and circulating cells. Death in septic patients was effectively predicted by neutrophil CD64 but not monocytic HLA-DR. Prognostic value of cellular activation markers in septic shock appears to strongly depend on their level of compartmentalization. PMID:27413252

  8. Vagus nerve electrical stimulation inhibits serum levels of S100A8 protein in septic shock rats.

    PubMed

    Lei, Ming; Liu, Xin-Xin

    2016-05-01

    The vagus nerve and the released acetylcholine exert anti-inflammatory effects and inhibit septic shock. However, their detailed mechanisms remain to be elucidated. The present study aimed to investigate the effects of vagus nerve electrical stimulation on serum S100A8 levels in septic shock rats. A total of 36 male Sprague-Dawley rats were randomly divided into six equal groups: i) Sham group, receiving sham operation; ii) CLP group, subjected to cecal ligation and puncture (CLP) to establish a model of polymicrobial sepsis; iii) VGX group, subjected to CLP and bilateral cervical vagotomy; iv) STM group, subjected to CLP, bilateral cervical vagotomy and electrical stimulation on the left vagus nerve trunk; v) α‑bungarotoxin (BGT) group was administered α‑BGT prior to electrical stimulation; vi) Anti‑receptor for advanced glycation end products (RAGE) group, administered intraperitoneal injection of anti‑RAGE antibody prior to electrical stimulation. The right carotid artery was cannulated to monitor mean artery pressure (MAP). The serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured to assess the liver function. Serum S100A8 and advanced glycation end product (AGE) levels were measured using enzyme‑linked immunosorbent assays. The expression of hepatic RAGE was determined by western blotting. The present study revealed that Sprague‑Dawley rats exhibited progressive hypotension and significantly increased serum AST and ALT levels following CLP challenge compared with the sham group. The levels of S100A8 and AGEs, and the protein expression of hepatic RAGE were significantly increased following CLP compared with the sham group. Vagus nerve electrical stimulation significantly prevented the development of CLP‑induced hypotension, alleviated the hepatic damage, reduced serum S100A8 and AGEs production, and reduced the expression of hepatic RAGE. The inhibitory effect of vagus nerve electrical

  9. Inhaled nitric oxide in acute respiratory distress syndrome with and without septic shock requiring norepinephrine administration: a dose–response study

    PubMed Central

    Mourgeon, Eric; Puybasset, Louis; Law-Koune, Jean-Dominique; Lu, Qin; Abdennour, Lamine; Gallart, Lluis; Malassine, Patrick; Rao, GS Umamaheswara; Cluzel, Philippe; Bennani, Abdelhai; Coriat, Pierre; Rouby, Jean-Jacques

    1997-01-01

    Background: The aim of this prospective study was to assess whether the presence of septic shock could influence the dose response to inhaled nitric oxide (NO) in NO-responding patients with adult respiratory distress syndrome (ARDS). Results: Eight patients with ARDS and without septic shock (PaO2 = 95 ± 16 mmHg, PEEP = 0, FiO2 = 1.0), and eight patients with ARDS and septic shock (PaO2 = 88 ± 11 mmHg, PEEP = 0, FiO2 = 1.0) receiving exclusively norepinephrine were studied. All responded to 15 ppm inhaled NO with an increase in PaO2 of at least 40 mmHg, at FiO2 1.0 and PEEP 10 cmH2O. Inspiratory intratracheal NO concentrations were recorded continuously using a fast response time chemiluminescence apparatus. Seven inspiratory NO concentrations were randomly administered: 0.15, 0.45, 1.5, 4.5, 15, 45 and 150 ppm. In both groups, NO induced a dose-dependent decrease in mean pulmonary artery pressure (MPAP), pulmonary vascular resistance index (PVRI), and venous admixture (QVA/QT), and a dose-dependent increase in PaO2/FiO2 (P ≤ 0.012). Dose-response of MPAP and PVRI were similar in both groups with a plateau effect at 4.5 ppm. Dose-response of PaO2/FiO2 was influenced by the presence of septic shock. No plateau effect was observed in patients with septic shock and PaO2/FiO2 increased by 173 ± 37% at 150 ppm. In patients without septic shock, an 82 ± 26% increase in PaO2/FiO2 was observed with a plateau effect obtained at 15 ppm. In both groups, dose-response curves demonstrated a marked interindividual variability and in five patients pulmonary vascular effect and improvement in arterial oxygenation were dissociated. Conclusion: For similar NOinduced decreases in MPAP and PVRI in both groups, the increase in arterial oxygenation was more marked in patients with septic shock. PMID:11056694

  10. Variation in the use of renal replacement therapy in patients with septic shock: a substudy of the prospective multicenter observational FINNAKI study

    PubMed Central

    2014-01-01

    Introduction Indications for renal replacement therapy (RRT) have not been generally standardized and vary among intensive care units (ICUs). We aimed to assess the proportion, indications, and modality of RRT, as well as the association between the proportion of RRT use and 90-day mortality in patients with septic shock in Finnish adult ICUs. Methods We identified patients with septic shock from the prospective observational multicenter FINNAKI study conducted between 1 September 2011 and 1 February 2012. We divided the ICUs into high-RRT and low-RRT ICUs according to the median of the proportion of RRT-treated patients with septic shock. Differences in indications, and modality of RRT between ICU groups were assessed. Finally, we performed an adjusted logistic regression analysis to evaluate the possible association of the ICU group (high vs. low-RRT) with 90-day mortality. Results Of the 726 patients with septic shock, 131 (18.0%, 95% CI 15.2 to 20.9%) were treated with RRT. The proportion of RRT-treated patients varied from 3% up to 36% (median 19%) among ICUs. High-RRT ICUs included nine ICUs (354 patients) and low-RRT ICUs eight ICUs (372 patients). In the high-RRT ICUs patients with septic shock were older (P = 0.04), had more cardiovascular (P <0.001) and renal failures (P = 0.003) on the first day in the ICU, were more often mechanically ventilated, and received higher maximum doses of norepinephrine (0.25 μg/kg/min vs. 0.18 μg/kg/min, P <0.001) than in the low-RRT ICUs. No significant differences in indications for or modality of RRT existed between the ICU groups. The crude 90-day mortality rate for patients with septic shock was 36.2% (95% CI 31.1 to 41.3%) in the high-RRT ICUs compared to 33.9% (95% CI 29.0 to 38.8%) in the low-RRT ICUs, P = 0.5. In an adjusted logistic regression analysis the ICU group (high-RRT or low-RRT ICUs) was not associated with 90-day mortality. Conclusions Patients with septic shock in ICUs with a high

  11. Clinical Features, Short-Term Mortality, and Prognostic Risk Factors of Septic Patients Admitted to Internal Medicine Units: Results of an Italian Multicenter Prospective Study.

    PubMed

    Mazzone, Antonino; Dentali, Francesco; La Regina, Micaela; Foglia, Emanuela; Gambacorta, Maurizia; Garagiola, Elisabetta; Bonardi, Giorgio; Clerici, Pierangelo; Concia, Ercole; Colombo, Fabrizio; Campanini, Mauro

    2016-01-01

    Only a few studies provided data on the clinical history of sepsis within internal Medicine units. The aim of the study was to assess the short-term mortality and to evaluate the prognostic risk factors in a large cohort of septic patients treated in internal medicine units. Thirty-one internal medicine units participated to the study. Within each participating unit, all admitted patients were screened for the presence of sepsis. A total of 533 patients were included; 78 patients (14.6%, 95%CI 11.9, 18.0%) died during hospitalization; mortality rate was 5.5% (95% CI 3.1, 9.6%) in patients with nonsevere sepsis and 20.1% (95%CI 16.2, 28.8%) in patients with severe sepsis or septic shock. Severe sepsis or septic shock (OR 4.41, 95%CI 1.93, 10.05), immune system weakening (OR 2.10, 95%CI 1.12, 3.94), active solid cancer (OR 2.14, 95% CI 1.16, 3.94), and age (OR 1.03 per year, 95% CI 1.01, 1.06) were significantly associated with an increased mortality risk, whereas blood culture positive for Escherichia coli was significantly associated with a reduced mortality risk (OR 0.46, 95%CI 0.24, 0.88). In-hospital mortality of septic patients treated in internal medicine units appeared similar to the mortality rate obtained in recent studies conducted in the ICU setting. PMID:26825876

  12. Preliminary Safety and Efficacy of L-carnitine Infusion for the Treatment of Vasopressor-Dependent Septic Shock: A Randomized Control Trial

    PubMed Central

    Puskarich, Michael A.; Kline, Jeffrey A.; Krabill, Virginia; Claremont, Heather; Jones, Alan E.

    2014-01-01

    Background Sepsis is characterized by metabolic disturbances, and previous data suggest a relative carnitine deficiency may contribute to metabolic dysfunction. Studies regarding safety and patient-centered efficacy of carnitine during septic shock are lacking. Methods This was a double-blind randomized control trial of levocarnitine (L-carnitine) infusion vs normal saline for the treatment of vasopressor-dependent septic shock. Patients meeting consensus definition for septic shock with a cumulative vasopressor index ≥3 and sequential organ failure assessment (SOFA) score ≥5 enrolled within 16 hours of the recognition of septic shock were eligible. The primary safety outcome was difference in serious adverse events (SAEs) per patient between groups. Efficacy outcomes included proportion of patients demonstrating a decrease in SOFA score of 2 or more points at 24 hours and short- and long-term survival. Results Of the 31 patients enrolled, 16 were in the L-carnitine and 15 were in the placebo arm. There was no difference in SAEs between placebo and intervention (2.1 vs 1.8 SAEs per patient, P = .44). There was no difference in the proportion of patients achieving a decrease in SOFA score of 2 or more points at 24 hours between placebo and treatment (53% vs 44%, P = .59). Mortality was significantly lower at 28 days in the L-carnitine group (4/16 vs 9/15, P = .048), with a nonsignificant improved survival at 1 year (P = .06). Conclusion L-carnitine infusion appears safe in vasopressor-dependent septic shock. Preliminary efficacy data suggest potential benefit of L-carnitine treatment, and further testing is indicated. PMID:23851424

  13. Interleukin-1 receptor blockade improves survival and hemodynamic performance in Escherichia coli septic shock, but fails to alter host responses to sublethal endotoxemia.

    PubMed Central

    Fischer, E; Marano, M A; Van Zee, K J; Rock, C S; Hawes, A S; Thompson, W A; DeForge, L; Kenney, J S; Remick, D G; Bloedow, D C

    1992-01-01

    The present study was undertaken to evaluate the extent to which an endogenous interleukin-1 (IL-1) response contributes to the hemodynamic and metabolic consequences of sublethal endotoxemia or lethal Gram-negative septic shock. Young, healthy baboons received either a sublethal dose of lipopolysaccharide (LPS) or an LD100 of live Escherichia coli bacteria, and one half of the animals in each group were continuously infused with IL-1 receptor antagonist (IL-1ra). Plasma IL-1 beta was not detected in this model of endotoxemia. Administration of IL-1ra had only minimal effects on the modest hemodynamic and metabolic responses to sublethal endotoxemia, and did not attenuate the plasma cytokine response. In contrast, high circulating levels of IL-1 beta (range 300-800 pg/ml) were seen during lethal E. coli septic shock. IL-1ra treatment significantly attenuated the decrease in mean arterial blood pressure (MAP) (from -72 +/- 8 to -43 +/- 6 mm Hg; P less than 0.05) and cardiac output (from -0.81 +/- 0.17 to -0.48 +/- 0.15 liter/min; P less than 0.05), and significantly improved survival from 43 to 100% at 24 h (P less than 0.05). The plasma IL-1 beta and IL-6 responses to lethal E. coli septic shock were also significantly diminished by IL-1ra treatment (P less than 0.05), whereas tumor necrosis factor-alpha (TNF alpha) concentrations were unaffected. We conclude that an exaggerated systemic IL-1 beta response is characteristic of lethal E. coli septic shock, and contributes significantly to the hemodynamic and metabolic consequences of E. coli septic shock. IL-1ra can significantly attenuate the cytokine cascade and improve survival. PMID:1533231

  14. Predictors of outcome in ICU patients with septic shock caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae.

    PubMed

    Falcone, M; Russo, A; Iacovelli, A; Restuccia, G; Ceccarelli, G; Giordano, A; Farcomeni, A; Morelli, A; Venditti, M

    2016-05-01

    The aim of this study was to identify factors associated with mortality in intensive care unit patients with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) septic shock. A retrospective analysis of intensive care unit patients with KPC-Kp infection and septic shock observed in a large teaching hospital from November 2010 to December 2014 was performed. A total of 111 patients were included in the study. The most frequent source of infection was unknown-focus bacteraemia in 53 patients (47.7%). The rate of resistance to colistin was 51.3%; 30-day mortality was reported for 44 patients (39.6%). Surviving patients were more frequently treated with an initial therapy (within 24 hours) including two or more antibiotics displaying in vitro activity against the isolated KPC-Kp strain (41.8 vs. 18.1%, p 0.01) and were also more likely to receive a definitive therapy including two or more in vitro active antibiotics (85.1 vs. 15.9%, p <0.001). Cox regression analysis revealed that a colistin-containing antibiotic regimen (hazard ratio (HR) 0.21, confidence interval (CI) 95% 0.05-0.72, p <0.001), use of two or more in vitro active antibiotics as definite therapy (HR 0.08, CI 95% 0.02-0.21, p <0.001) and control of removable source of infection (HR 0.14, CI 95% 0.04-0.25, p <0.001) were associated with favourable outcome; colistin resistance (HR 8.09, CI 95% 3.14-11.23, p 0.001) and intra-abdominal source of infection (HR 2.92, CI 95% 2.11-4.12, p 0.002) were associated with death. In conclusion, use of a definitive therapy with at least two antibiotics displaying in vitro activity against the KPC-Kp isolates was the most important determinant of favourable outcome, whilst isolation of colistin-resistant strains was associated with death in septic patients with KPC-Kp infection. PMID:26850826

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

    PubMed Central

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

    2015-01-01

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

  16. Association of susceptibility to septic shock with platelet endothelial cell adhesion molecule-1 gene Leu125Val polymorphism and serum sPECAM-1 levels in sepsis patients

    PubMed Central

    Sun, Wei; Li, Fang-Shun; Zhang, Yuan-Huai; Wang, Xiao-Ping; Wang, Chao-Rong

    2015-01-01

    Sepsis is a systemic inflammatory response to infection and includes severe sepsis, septic shock and death. Platelet endothelial cell adhesion molecule-1 (PECAM-1) is one cell adhesion molecule expressed on platelets and leukocytes. It regulates platelet activation and mediates transendothelial migration of leukocytes, thus maintaining the integrity of the vasculature. There are some animal experiments associated with the protective role of PECAM-1 against septic shock. However few host genetic risk factors have been identified for sepsis severity and susceptibility to septic shock. A case-control study was conducted, which included 217 patients with sepsis and 90 control subjects recruited from our hospital. One single nucleotide polymorphisms (SNP) of PECAM-1 gene Leu125Val (C373G) was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Serum soluble PECAM-1 (sPECAM-1) levels were determined by enzyme-linked immunosorbent assay (ELISA). Our results showed that the CG and GG genotypes of SNP in Leu125Val of PECAM-1 (rs668: C>G) was significantly associated with increased susceptibility to septic shock compared with CC genotype in sepsis patients (CG genotype, OR: 2.493, 95% CI: 1.175~5.287, P = 0.016; GG genotype: OR: 3.328, 95% CI: 1.445~7.666, P = 0.004). The serum levels of sPECAM-1 in the sepsis patients (47.1 ± 17.5 ng/ml) were significantly higher than those in the healthy controls (61.3 ± 20.9 ng/ml, P<0.01). Among sepsis patients, the serum levels of sPECAM-1 were significantly higher in CG and GG genotype than in CC genotype. In septic shock patients, nonsurvivors (83.7 ± 12.6 ng/ml, n = 69) had a significantly higher serum sPECAM-1 level than the survivors (76.9 ± 12.7 ng/ml, n = 53) (P<0.01). In conclusion, PECAM-1 Leu125Val polymorphism and its sPECAM-1 levels are associated with sepsis severity and susceptibility to septic shock. PMID:26884965

  17. Association of susceptibility to septic shock with platelet endothelial cell adhesion molecule-1 gene Leu125Val polymorphism and serum sPECAM-1 levels in sepsis patients.

    PubMed

    Sun, Wei; Li, Fang-Shun; Zhang, Yuan-Huai; Wang, Xiao-Ping; Wang, Chao-Rong

    2015-01-01

    Sepsis is a systemic inflammatory response to infection and includes severe sepsis, septic shock and death. Platelet endothelial cell adhesion molecule-1 (PECAM-1) is one cell adhesion molecule expressed on platelets and leukocytes. It regulates platelet activation and mediates transendothelial migration of leukocytes, thus maintaining the integrity of the vasculature. There are some animal experiments associated with the protective role of PECAM-1 against septic shock. However few host genetic risk factors have been identified for sepsis severity and susceptibility to septic shock. A case-control study was conducted, which included 217 patients with sepsis and 90 control subjects recruited from our hospital. One single nucleotide polymorphisms (SNP) of PECAM-1 gene Leu125Val (C373G) was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Serum soluble PECAM-1 (sPECAM-1) levels were determined by enzyme-linked immunosorbent assay (ELISA). Our results showed that the CG and GG genotypes of SNP in Leu125Val of PECAM-1 (rs668: C>G) was significantly associated with increased susceptibility to septic shock compared with CC genotype in sepsis patients (CG genotype, OR: 2.493, 95% CI: 1.175~5.287, P = 0.016; GG genotype: OR: 3.328, 95% CI: 1.445~7.666, P = 0.004). The serum levels of sPECAM-1 in the sepsis patients (47.1 ± 17.5 ng/ml) were significantly higher than those in the healthy controls (61.3 ± 20.9 ng/ml, P<0.01). Among sepsis patients, the serum levels of sPECAM-1 were significantly higher in CG and GG genotype than in CC genotype. In septic shock patients, nonsurvivors (83.7 ± 12.6 ng/ml, n = 69) had a significantly higher serum sPECAM-1 level than the survivors (76.9 ± 12.7 ng/ml, n = 53) (P<0.01). In conclusion, PECAM-1 Leu125Val polymorphism and its sPECAM-1 levels are associated with sepsis severity and susceptibility to septic shock. PMID:26884965

  18. Meropenem Population Pharmacokinetics in Critically Ill Patients with Septic Shock and Continuous Renal Replacement Therapy: Influence of Residual Diuresis on Dose Requirements

    PubMed Central

    Llaurado-Serra, Mireia; Vaquer, Sergi; Castro, Pedro; Rodríguez, Alejandro H.; Pontes, Caridad; Calvo, Gonzalo; Torres, Antoni; Martín-Loeches, Ignacio

    2015-01-01

    Meropenem dosing in critically ill patients with septic shock and continuous renal replacement therapy (CRRT) is complex, with the recommended maintenance doses being 500 mg to 1,000 mg every 8 h (q8h) to every 12 h. This multicenter study aimed to describe the pharmacokinetics (PKs) of meropenem in this population to identify the sources of PK variability and to evaluate different dosing regimens to develop recommendations based on clinical parameters. Thirty patients with septic shock and CRRT receiving meropenem were enrolled (153 plasma samples were tested). A population PK model was developed with data from 24 patients and subsequently validated with data from 6 patients using NONMEM software (v.7.3). The final model was characterized by CL = 3.68 + 0.22 · (residual diuresis/100) and V = 33.00 · (weight/73)2.07, where CL is total body clearance (in liters per hour), residual diuresis is the volume of residual diuresis (in milliliters per 24 h), and V is the apparent volume of distribution (in liters). CRRT intensity was not identified to be a CL modifier. Monte Carlo simulations showed that to maintain concentrations of the unbound fraction (fu) of drug above the MIC of the bacteria for 40% of dosing interval T (referred to as 40% of the ƒuT>MIC), a meropenem dose of 500 mg q8h as a bolus over 30 min would be sufficient regardless of the residual diuresis. If 100% of the ƒuT>MIC was chosen as the target, oligoanuric patients would require 500 mg q8h as a bolus over 30 min for the treatment of susceptible bacteria (MIC < 2 mg/liter), while patients with preserved diuresis would require the same dose given as an infusion over 3 h. If bacteria with MICs close to the resistance breakpoint (2 to 4 mg/liter) were to be treated with meropenem, a dose of 500 mg every 6 h would be necessary: a bolus over 30 min for oligoanuric patients and an infusion over 3 h for patients with preserved diuresis. Our results suggest that residual diuresis may be an easy and

  19. Abnormal activation of potassium channels in aortic smooth muscle of rats with peritonitis-induced septic shock.

    PubMed

    Kuo, Jiunn-Horng; Chen, Shiu-Jen; Shih, Chih-Chin; Lue, Wei-Ming; Wu, Chin-Chen

    2009-07-01

    This study was conducted to examine the role of membrane hyperpolarization in mediating vascular hyporeactivity induced by cecal ligation and puncture (CLP) in endothelial-denuded strips of rat thoracic aorta ex vivo. The CLP for 18 h elicited a significant fall of blood pressure and a severe vascular hyporeactivity to norepinephrine as seen in severe sepsis. At the end of the in vivo experiments, thoracic aortas were removed from both CLP-treated and control rats. After removal of the endothelium, aortic segments were mounted in myographs for the recording of isometric tension and smooth muscle membrane potential. The membrane potential recording showed that a hyperpolarization was observed in the CLP-treated rats when compared with the control rats. This hyperpolarization was reversed by iberiotoxin (a large-conductance Ca2+-activated K+ channel blocker), 4-aminopyridine (a voltage-dependent K+ channel blocker), barium (an inward rectifier K+ channels blocker), N-(1-adamantyl)-N'-cyclohexyl-4-morpholinecarboxamidine hydrochloride (a pore-forming blocker of adenosine triphosphate (ATP)-sensitive K+ channels [KATP]), or methylene blue (a nonspecific guanylyl cyclase [GC] inhibitor). However, this hyperpolarization was not significantly affected by apamin (a small-conductance Ca2+-activated K+ channel blocker), glibenclamide (a sulfonylurea blocker of KATP), N(omega)-nitro-L-arginine methyl ester (a NOS inhibitor), or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (an NO-sensitive GC inhibitor). In addition, the basal tension of the tissues obtained from CLP rats was increased simultaneously, whereas membrane potential was reversed. In contrast, none of these inhibitors had significant effects on the membrane potential or the basal tension in control tissues. Thus, we provide electrophysiological and functional evidence demonstrating that an abnormal activation of K+ channels in vascular smooth muscle in animals with septic shock induced by CLP. Our observations

  20. Vitamin D deficiency at admission is not associated with 90-day mortality in patients with severe sepsis or septic shock: Observational FINNAKI cohort study.

    PubMed

    Ala-Kokko, Tero I; Mutt, Shivaprakash J; Nisula, Sara; Koskenkari, Juha; Liisanantti, Janne; Ohtonen, Pasi; Poukkanen, Meri; Laurila, Jouko J; Pettilä, Ville; Herzig, Karl-Heinz

    2016-01-01

    Introduction Low levels of vitamin D have been associated with increased mortality in patients that are critically ill. This study explored whether vitamin D levels were associated with 90-day mortality in severe sepsis or septic shock. Methods Plasma vitamin D levels were measured on admission to the intensive care unit (ICU) in a prospective multicentre observational study. Results 610 patients with severe sepsis were included; of these, 178 (29%) had septic shock. Vitamin D deficiency (<50 nmol/L) was present in 333 (55%) patients. The 90-day mortality did not differ among patients with or without vitamin D deficiency (28.3% vs. 28.5%, p = 0.789). Diabetes was more common among patients deficient compared to those not deficient in vitamin D (30% vs. 18%, p < 0.001). Hospital-acquired infections at admission were more prevalent in patients with a vitamin D deficiency (31% vs. 16%, p < 0.001). A multivariable adjusted Cox regression model showed that low vitamin D levels could not predict 90-day mortality (<50 nmol/L: hazard ratio (HR) 0.99 (95% CI: 0.72-1.36), p > 0.9; and <25 nmol/L: HR 0.44 (95% CI: 0.22-0.87), p = 0.018). Conclusions Vitamin D deficiency detected upon ICU admission was not associated with 90-day mortality in patients with severe sepsis or septic shock. Key messages In severe sepsis and septic shock, a vitamin D deficiency upon ICU admission was not associated with increased mortality. Compared to patients with sufficient vitamin D, patients with deficient vitamin D more frequently exhibited diabetes, elevated C-reactive protein levels, and hospital-acquired infections upon ICU admission, and they more frequently developed acute kidney injury. PMID:26800186

  1. Severe sepsis and septic shock in pre-hospital emergency medicine: survey results of medical directors of emergency medical services concerning antibiotics, blood cultures and algorithms.

    PubMed

    Casu, Sebastian; Häske, David

    2016-06-01

    Delayed antibiotic treatment for patients in severe sepsis and septic shock decreases the probability of survival. In this survey, medical directors of different emergency medical services (EMS) in Germany were asked if they are prepared for pre-hospital sepsis therapy with antibiotics or special algorithms to evaluate the individual preparations of the different rescue areas for the treatment of patients with this infectious disease. The objective of the survey was to obtain a general picture of the current status of the EMS with respect to rapid antibiotic treatment for sepsis. A total of 166 medical directors were invited to complete a short survey on behalf of the different rescue service districts in Germany via an electronic cover letter. Of the rescue districts, 25.6 % (n = 20) stated that they keep antibiotics on EMS vehicles. In addition, 2.6 % carry blood cultures on the vehicles. The most common antibiotic is ceftriaxone (third generation cephalosporin). In total, 8 (10.3 %) rescue districts use an algorithm for patients with sepsis, severe sepsis or septic shock. Although the German EMS is an emergency physician-based rescue system, special opportunities in the form of antibiotics on emergency physician vehicles are missing. Simultaneously, only 10.3 % of the rescue districts use a special algorithm for sepsis therapy. Sepsis, severe sepsis and septic shock do not appear to be prioritized as highly as these deadly diseases should be in the pre-hospital setting. PMID:26719078

  2. Incidence and Predictors of New-Onset Atrial Fibrillation in Septic Shock Patients in a Medical ICU: Data from 7-Day Holter ECG Monitoring

    PubMed Central

    Guenancia, Charles; Binquet, Christine; Laurent, Gabriel; Vinault, Sandrine; Bruyère, Rémi; Prin, Sébastien; Pavon, Arnaud; Charles, Pierre-Emmanuel; Quenot, Jean-Pierre

    2015-01-01

    Purpose We investigated incidence, risk factors for new-onset atrial fibrillation (NAF), and prognostic impact during septic shock in medical Intensive Care Unit (ICU) patients. Methods Prospective, observational study in a university hospital. Consecutive patients from 03/2011 to 05/2013 with septic shock were eligible. Exclusion criteria were age <18 years, history of AF, transfer with prior septic shock. Included patients were equipped with long-duration (7 days) Holter ECG monitoring. NAF was defined as an AF episode lasting >30 seconds. Patient characteristics, infection criteria, cardiovascular parameters, severity of illness, support therapies were recorded. Results Among 66 patients, 29(44%) developed NAF; 10 (34%) would not have been diagnosed without Holter ECG monitoring. NAF patients were older, with more markers of heart failure (troponin and NT-pro-BNP), lower left ventricular ejection fraction (LVEF), longer QRS duration and more nonsustained supra ventricular arrhythmias (<30s) on day 1 than patients who maintained sinus rhythm. By multivariate analysis, age (OR: 1.06; p = 0.01) and LVEF<45% (OR: 13.01, p = 0.03) were associated with NAF. NAF did not predict 28 or 90 day mortality. Conclusions NAF is common, especially in older patients, and is associated with low ejection fraction. We did not find NAF to be independently associated with higher mortality. PMID:25965915

  3. Gram-negative bacteremia produces both severe systolic and diastolic cardiac dysfunction in a canine model that simulates human septic shock.

    PubMed Central

    Natanson, C; Fink, M P; Ballantyne, H K; MacVittie, T J; Conklin, J J; Parrillo, J E

    1986-01-01

    A canine sepsis model that simulates the human cardiovascular response to septic shock was produced in 10 conscious unsedated dogs by implanting an Escherichia coli-infected clot into the peritoneum, resulting in bacteremia. By employing serial, simultaneous measurements of radionuclide scan-determined left ventricular (LV) ejection fraction (EF) and thermodilution cardiac index (CI), the end-diastolic volume index (EDVI) was calculated (EDVI = stroke volume index divided by EF). By using three different methods of quantifying serial ventricular performance (EF, shifts in the Starling ventricular function curve using EDVI vs. stroke work index, and the ventricular function curve response to volume infusion), this study provides evidence (P less than 0.01) that septic shock produces a profound, but reversible, decrease in systolic ventricular performance. This decreased performance was not seen in controls and was associated with ventricular dilatation (P less than 0.01); the latter response was dependent on an adequate volume infusion. Further studies of EDVI and pulmonary capillary wedge pressure during diastole revealed a significant, though reversible, shift (P less than 0.001) in the diastolic volume/pressure (or compliance) relationship during septic shock. PMID:3722379

  4. Ozonotherapy in an induced septic shock. I. Effect of ozonotherapy on rat organs in evaluation of free radical reactions and selected enzymatic systems.

    PubMed

    Madej, Pawel; Plewka, Andrzej; Madej, Janusz A; Nowak, Marcin; Plewka, Danuta; Franik, Grzegorz; Golka, Darek

    2007-04-01

    The confirmed advantageous effects of oxygen/ozone therapy in several clinical conditions stimulated experimental studies on effects of the therapy in rats with an induced septic shock. The studies were conducted on adult male rats of Wistar strain. Four groups of the animals, each of 15 rats, included: I--control group, (C); II--animals intraperitoneally administered with O(2)/O(3) (CO), III--rats given of Escherichia coli endotoxin (lipopolysaccharide-LPS) (CL), IV--rats administered with the lipopolysaccharide plus administered with the oxygen/ozone mixture (OL). Activities of catalase and superoxide dismutase and of free radical reactions were estimated. The exposure to LPS augmented activities of SOD and of catalase in liver, lungs and heart. In all the examined organs LPS induced significant changes in levels of free radicals. Except of the lungs, parallel administration of the rats with LPS and ozone/oxygen revoked development of the alterations. The obtained results point to a strong, stabilizing and regenerative effect of ozonotherapy. PMID:17372841

  5. Fatal Candida septic shock during systemic chemotherapy in lung cancer patient receiving corticosteroid replacement therapy for hypopituitarism: a case report.

    PubMed

    Morichika, Daisuke; Sato-Hisamoto, Akiko; Hotta, Katsuyuki; Takata, Katsuyoshi; Iwaki, Noriko; Uchida, Koji; Minami, Daisuke; Kubo, Toshio; Tanimoto, Mitsune; Kiura, Katsuyuki

    2014-05-01

    Invasive candidiasis has increased as nosocomial infection recently in cancer patients who receive systemic chemotherapy, and the timely risk assessment for developing such specific infection is crucial. Especially in those concomitantly with hypopituitarism, febrile neutropenia with candidiasis can cause severe stress and lead potentially to sudden fatal outcome when the temporal steroid coverage for the adrenal insufficiency is not fully administered. We report a 72-year-old male case diagnosed as non-small-cell lung cancer, Stage IIIA. He had received a steroid replacement therapy for the prior history of hypophysectomy due to pituitary adenoma with hydrocortisone of 3.3 mg/day, equivalent to prednisolone of 0.8 mg/day. This very small dosage of steroid was hardly supposed to weaken his immune system, but rather potentially led to an inappropriate supplementation of his adrenal function, assuming that the serum sodium and chlorine levels decreased. On Day 6 of second cycle of chemotherapy with carboplatin and paclitaxel, he developed sudden febrile neutropenia, septic shock and ileus, leading to death. After his death, the venous blood culture on Day 7 detected Candida albicans. Autopsy findings showed a massive necrotizing enterocolitis with extensive Candida invasion into submucous tissue. In conclusion, this case may suggest that (i) immediate initiation of antifungal therapy soon after the careful risk assessment of Candida infection and (ii) adequate administration of both basal steroid replacement therapy and temporal steroid coverage for febrile neutropenia might have improved his fatal outcome. PMID:24646812

  6. Aetiology of Bacteraemia as a Risk Factor for Septic Shock at the Onset of Febrile Neutropaenia in Adult Cancer Patients

    PubMed Central

    Rosa, Regis Goulart; Goldani, Luciano Zubaran

    2014-01-01

    Septic shock (SS) at the onset of febrile neutropaenia (FN) is an emergency situation that is associated with high morbidity and mortality. The impact of the specific aetiology of bloodstream infections (BSIs) in the development of SS at the time of FN is not well established. The aim of this study was to evaluate the association between the aetiology of BSIs and SS at the time of FN in hospitalised adult cancer patients. This prospective cohort study was performed at a single tertiary hospital from October 2009 to August 2011. All adult cancer patients admitted consecutively to the haematology ward with FN were evaluated. A stepwise logistic regression was conducted to verify the association between the microbiological characteristics of BSIs and SS at the onset of FN. In total, 307 cases of FN in adult cancer patients were evaluated. There were 115 cases with documented BSI. A multivariate analysis showed that polymicrobial bacteraemia (P = 0.01) was associated with SS. The specific blood isolates independently associated with SS were viridans streptococci (P = 0.02) and Escherichia coli (P = 0.01). Neutropaenic cancer patients with polymicrobial bacteraemia or BSI by viridans streptococci or Escherichia coli are at increased risk for SS at the time of FN. PMID:24804223

  7. Effects of ATP-sensitive potassium channel blockers on vascular hyporeactivity, mesenteric blood flow, and survival in lipopolysaccharide-induced septic shock model.

    PubMed

    Boz, Mustafa; Atilla, Pergin; Iskit, Alper B; Ilhan, Mustafa

    2016-08-01

    In this study, the possible therapeutic effects of various ATP-sensitive potassium channel (KATP) blockers (glibenclamide, repaglinide, 5-HD, HMR-1098) have been tested in experimental septic shock model. Rats were given lipopolysaccharide (1 mg·kg(-1)) to create experimental shock model and 4 h later, under 400 mg·kg(-1) chloral hydrate anesthesia, parameters such as blood pressure, mesenteric blood flow, the response of mesenteric circulation to phenylephrine (vasoconstrictor stimulation), and organ and oxidative damage were analyzed. Also 75 mg·kg(-1) lethal dose of lipopolysaccharide was given to mice and effects of KATP blockers on survival have been tested. Non-selective blocker glibenclamide with sulphonylurea structure and sarcolemmal KATP channel blocker HMR-1098, which have the similar chemical structure, have improved the pathological parameters such as decrease in mesenteric blood flow, vascular hyporeactivity, but could not prevent the decrease in blood pressure, and oxidative and organ damage that were observed in the shock model. Also, both blockers have decreased the mortality rate from 80% to 40%-50%. Similar (preventive) therapeutic effects were not observed with non-selective blocker repaglinide and mitochondrial KATP channel blocker 5-HD, which were non-sulphonylurea structure. As a result, only KATP channel blockers that have sulphonylurea structure can be a new therapeutic approach in septic shock. PMID:27239899

  8. Cardiac tamponade and septic shock caused by viral infection in a previously healthy woman.

    PubMed

    Laurila, J J; Ala-Kokko, T I; Tuokko, H; Syrjälä, H

    2005-10-01

    A previously healthy woman was admitted to hospital after 'flu-like' symptoms for 5 days followed by acute intense abdominal and lower back pain. On admission she was found to be in severe shock and was transferred to the ICU. Echocardiography revealed cardiac tamponade, and pericardiocentesis was performed immediately. Thereafter her cardiovascular state improved, but she developed hypotension with low systemic vascular resistance and required vasoactive treatment for 4 days. Nine days after admission the patient was transferred to the ward, after which she recovered rapidly and completely. The cause of her illness was extensively screened. No underlying disease was found, and all bacterial cultures remained negative. Acute virus infection was confirmed by diagnostic elevations of antibody titers to Influenza A and adenovirus. Adenovirus was also isolated from her bronchoalveolar lavage fluid. PMID:16146481

  9. StO₂ guided early resuscitation in subjects with severe sepsis or septic shock: a pilot randomised trial.

    PubMed

    Nardi, Olivier; Polito, Andrea; Aboab, Jérôme; Colin, Gwenhael; Maxime, Virginie; Clair, Bernard; Friedman, Diane; Orlikowski, David; Sharshar, Tarek; Annane, Djillali

    2013-06-01

    The scientific community has agreed upon developing accurate monitoring of tissue perfusion and oxygenation to improve the management of subjects with sepsis. This pilot study aimed to investigate the feasibility of targeting tissue oxygen saturation (StO₂) in addition to the currently recommended resuscitation goals, central venous pressure, mean arterial pressure and central venous oxygen saturation, in patients with severe sepsis or septic shock. A pilot, single-centre, randomised, non-blinded trial recruited 30 subjects with severe sepsis upon intensive care unit admission at an academic medical centre in France. Subjects were randomly assigned to a 6 h resuscitation strategy following the Surviving Sepsis Campaign guidelines with (experimental) or without (control) StO₂. StO₂ was measured over several muscles (masseter, deltoid and pectoral or thenar muscles), and a StO₂ above 80 % over at least 2 muscles was the therapeutic goal. The primary outcome was evaluated as follows: 7-day mortality or worsening of SOFA score between day 7 and study onset, i.e., DSOFA > 0). Thirty subjects were included in the study over a period of 40 weeks. Fifteen subjects were included in each group. Monitoring of StO₂ over three areas was performed in the experimental group. However, measures over the pectoral muscle provided poor results. At study day 7, there were 5/15 (33.3 %) subjects who died or had a DSOFA > 0 in the experimental arm and 4/15 (26.6 %) who died or had a DSOFA > 0 in the control arm (p = 1.00). This pilot study was the first randomised controlled trial using an algorithm derived from the SSC recommendations, which included StO₂ as a treatment goal. However, the protocol showed no clear trend for or against targeting StO₂. PMID:23381608

  10. Transfusion of Red Blood Cells Is Associated With Improved Central Venous Oxygen Saturation But Not Mortality in Septic Shock Patients

    PubMed Central

    Sadaka, Farid; Trottier, Steven; Tannehill, David; Donnelly, Paige L; Griffin, Mia T; Bunaye, Zerihun; O’Brien, Jacklyn; Korobey, Matthew; Lakshmanan, Rekha

    2014-01-01

    Background Although the optimum hemoglobin (H) concentration for patients with septic shock (SS) has not been specifically investigated, current guidelines suggest that H of 7 - 9 g/dL, compared with 10 - 12 g/dL, was not associated with increased mortality in critically ill adults. This contrasts with early goal-directed resuscitation protocols that use a target hematocrit of 30% in patients with low central venous oxygen saturation (ScvO2) during the first 6 hours of resuscitation of SS. Methods Data elements were prospectively collected on all patients with SS patients (lactic acid (LA) > 4 mmol/L, or hypotension). Out of a total of 396 SS patients, 46 patients received red blood cell (RBC) transfusion for ScvO2 < 70% (RBC group). We then matched 71 SS patients that did not receive RBC transfusion (NRBC group) on the following goals (G): LA obtained within 6 hours (G1), antibiotics given within 3 hours (G2), 20 mL/kg fluid bolus followed by vasopressors (VP) if needed to keep mean arterial pressure > 65 mm Hg (G3), central venous pressure > 8 mm Hg within 6 hours (G4) and ScvO2 > 70% within 6 hours (G5). Results In the RBC group, after one unit of RBC transfusion, ScvO2 improved from average of 63% (± 12%) to 68% (± 10%) (P = 0.02). Sixteen patients required another unit of RBC, and this resulted in increase of ScvO2 to 78% (± 11%) (P < 0.01). The RBC and NRBC groups were matched on sequential organ failure assessment (SOFA) scores and all five goals. There was no difference in mortality between the two groups: 41% vs. 39.4% (OR: 0.8, 95% CI: 0.4 - 1.7, P = 0.6). Conclusions In our study, transfusion of RBC was not associated with decreased mortality in SS patients. PMID:25247015

  11. Treatment with Histone Deacetylase Inhibitor Attenuates MAP Kinase Mediated Liver Injury in a Lethal Model of Septic Shock1

    PubMed Central

    Finkelstein, Robert A.; Li, Yongqing; Liu, Baoling; Shuja, Fahad; Fukudome, Eugene; Velmahos, George C.; deMoya, Marc; Alam, Hasan B.

    2016-01-01

    Background Despite global efforts to improve the treatment of sepsis, it remains a leading cause of morbidity and mortality in intensive care units. We have previously shown that suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, markedly improves survival in a murine model of lipopolysaccharide (LPS)-induced shock. SAHA has anti-inflammatory properties that have not been fully characterized. The liver plays an important role in the production of acute phase reactants involved in the inflammatory cascade and is also one of the major organs that can become dysfunctional in septic shock. The purpose of this study was to assess the effect of SAHA treatment on MAP kinases and associated inflammatory markers in murine liver after LPS-induced injury. Methods C57B1/6J mice were randomly divided into three groups: (A) experimental-given intraperitoneal (i.p.) SAHA (50 mg/kg) in dimethyl sulfoxide (DMSO) vehicle solution (n =12); (B) control-given vehicle only (n = 12), and; (C) sham-given no treatment (n = 7). Two hours later, experimental and control mice were injected with LPS (20 mg/kg, i.p.) and experimental mice received a second dose of SAHA. Livers were harvested at 3, 24, and 48 h for analysis of inflammatory markers using Western Blot, Polymerase Chain Reaction (PCR), and Enzyme-Linked Immunosorbent Assay (ELISA) techniques. Results After 3 h, the livers of animals treated with SAHA showed significantly (P < 0.05) decreased expression of the pro-inflammatory MAP kinases phosphorylated p38, phosphorylated ERK, myeloperoxidase and interleukin-6, and increased levels of the anti-inflammatory interleukin-10 compared with controls. Phospho-p38 expression remained low in the SAHA treated groups at 24 and 48 h. Conclusion Administration of SAHA is associated with attenuation of MAPK activation and alteration of inflammatory and anti-inflammatory markers in murine liver after a lethal LPS insult. The suppression of MAPK activity is rapid (within 3 h

  12. Pseudomonas aeruginosa septic shock associated with ecthyma gangrenosum in an infant with agammaglobulinemia.

    PubMed

    Almeida, João Fernando Lourenço de; Sztajnbok, Jaques; Troster, Eduardo Juan; Vaz, Flávio Adolfo Costa

    2002-01-01

    Ecthyma gangrenosum (EG) due to Pseudomonas aeruginosa is a rare and invasive infection that can be associated with agammaglobulinemia. The cornerstone of the treatment is based on prompt recognition with appropriate antibiotic coverage and intravenous immunoglobulin. The authors report a case of EG emphasizing the clinical and therapeutic aspects of this condition. PMID:12163911

  13. Effects of Ringer’s sodium pyruvate solution on serum tumor necrosis factor-α and interleukin-6 upon septic shock

    PubMed Central

    Dong, Wei; Zhang, Guannan; Qu, Feng

    2015-01-01

    Objective: To study the effects of Ringer’s sodium pyruvate solution on tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) upon septic shock. Methods: Ninety emergency patients with septic shock were divided into a treatment group and a control group by random draw. The control group was resuscitated with 50 ml of compound sodium chloride (Ringer’s solution), and the treatment group was given 50 ml of Ringer’s sodium pyruvate solution. Both groups were basically treated. Results: All patients were successfully resuscitated. After treatment, extravascular lung water index, intrathoracic blood volume index, systemic vascular resistance index and cardiac index of the two groups were significantly improved compared with those before treatment (P<0.05). However, there were no significant inter-group differences at different time points (P>0.05). Blood lactic acid level, central venous oxygen saturation index and urine output were also improved after treatment, with significant inter-group differences (P<0.05). Serum TNF-α and IL-6 levels of both groups significantly decreased after treatment (P<0.05), and the levels of the treatment group were significantly lower than those of the control group (P<0.05). During 28 days of follow-up, the mortality rate of the treatment group (4.4%) was significantly lower than that of the control group (20.0%) (P<0.05). Conclusion: Patients with septic shock are complicated with disordered expressions of inflammatory factors. During resuscitation, Ringer’s sodium pyruvate solution can effectively promote blood circulation, mitigate inflammation and maintain acid-base equilibrium, thus decreasing the prognostic mortality rate. PMID:26150866

  14. [A pilot study comparing pulse high volume hemofiltration (pHVHF) and coupled plasma filtration adsorption (CPFA) in septic shock patients].

    PubMed

    Lentini, P; Cruz, D; Nalesso, F; de Cal, M; Bobek, I; Garzotto, F; Zanella, M; Brendolan, A; Piccinni, P; Ronco, C

    2009-01-01

    High-volume hemofiltration (HVHF) and coupled plasma filtration adsorption (CPFA) have shown potential to improve the treatment of sepsis in animals, but there have been no studies comparing these two treatments in humans. Our aim was to compare the hemodynamic effects of HVHF and CPFA in septic shock patients with acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT). We performed a cross-over study enrolling patients with septic shock and AKI who were receiving CRRT. Patients were treated with pulse HVHF and continuous veno-venous hemofiltration (CVV H) on day 1 and CPFA and CVV H on day 2 or vice versa. HVHF was performed for 8-10 hours with a replacement fluid rate of 85 mL/kg/h. CPFA was performed for 8-10 hours with a plasma flow rate of 15%. CVV H was performed for the rest of the day with a replacement fluid rate of 35 mL/kg/h. The primary endpoints were changes in mean arterial pressure, vasopressor requirement (expressed as vasopressor score, VS), and noradrenaline dose after pulse HVHF and CPFA. The two treatments were compared using nonparametric tests. We enrolled 8 patients (median age 70.5 years, SOFA 12.5, SAPS II 69.5). There was a trend towards a reduction in VS with HVHF and CPFA (HVHF p=0.13, CPFA p<0.05). There was no significant difference between the two treatments in terms of percentage change in VS score (p=0.22). The data from this pilot study provide no evidence for a difference in hemodynamic effects between pulse HVHF and CPFA in patients with septic shock already receiving CRRT. A larger sample size is needed to adequately explore this issue. PMID:19918752

  15. Surviving lethal septic shock without fluid resuscitation in a rodent model

    PubMed Central

    Li, Yongqing; Liu, Baoling; Fukudome, Eugene Y.; Kochanek, Ashley R.; Finkelstein, Robert A.; Chong, Wei; Jin, Guang; Lu, Jennifer; deMoya, Marc A.; Velmahos, George C.; Alam, Hasan B.

    2016-01-01

    Background We have recently demonstrated that treatment with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, before a lethal dose of lipopolysaccharide (LPS) improves survival in mice. The purpose of the present study was to determine whether SAHA treatment would attenuate LPS-induced shock and improve survival when given postinsult in a rodent model. Methods C57BL/6J mice were intraperitoneally (IP) injected with LPS (30 mg/kg), and 2 hours later randomized into 2 groups: (1) vehicle animals (n = 10) received dimethyl sulfoxide (DMSO) solution only; and (2) SAHA animals (n = 10) were given SAHA (50 mg/kg, IP) in DMSO solution. Survival was monitored over the next 7 days. In a second study, LPS-injected mice were treated with either DMSO or SAHA as described, and normal (sham) animals served as controls. Lungs were harvested at 4, 6, and 8 hours after LPS injection for analysis of gene expression. In addition, RAW264.7 mouse macrophages were cultured to assess the effects of SAHA post-treatment on LPS-induced inflammation using enzyme-linked immunosorbent assay. Results All LPS-injected mice that received the vehicle agent alone died within 24 hours, whereas the SAHA-treated animals displayed a significant improvement in 1 week survival (80% vs 0%; P < .001). LPS insult significantly enhanced gene expression of MyD88, tumor necrosis factor (TNF)-α and interleukin (IL)-6, and was associated with an increased protein secretion of TNF-α and IL-6 into the cell culture medium. In contrast, SAHA treatment significantly attenuated all of these LPS-related alterations. Conclusion We report for the first time that administration of SAHA (50 mg/kg IP) after a lethal dose of LPS significantly improves long-term survival, and attenuates expression of the proinflammatory mediators TNF-α and IL-6. Furthermore, our data suggest that the anti-inflammatory effects of SAHA may be due to downregulation of the MyD88-dependent pathway, and decreased

  16. Skeletal muscle oxygen saturation does not estimate mixed venous oxygen saturation in patients with severe left heart failure and additional severe sepsis or septic shock

    PubMed Central

    Podbregar, Matej; Možina, Hugon

    2007-01-01

    Introduction Low cardiac output states such as left heart failure are characterized by preserved oxygen extraction ratio, which is in contrast to severe sepsis. Near infrared spectroscopy (NIRS) allows noninvasive estimation of skeletal muscle tissue oxygenation (StO2). The aim of the study was to determine the relationship between StO2 and mixed venous oxygen saturation (SvO2) in patients with severe left heart failure with or without additional severe sepsis or septic shock. Methods Sixty-five patients with severe left heart failure due to primary heart disease were divided into two groups: groups A (n = 24) and B (n = 41) included patients without and with additional severe sepsis/septic shock, respectively. Thenar muscle StO2 was measured using NIRS in the patients and in 15 healthy volunteers. Results StO2 was lower in group A than in group B and in healthy volunteers (58 ± 13%, 90 ± 7% and 84 ± 4%, respectively; P < 0.001). StO2 was higher in group B than in healthy volunteers (P = 0.02). In group A StO2 correlated with SvO2 (r = 0.689, P = 0.002), although StO2 overestimated SvO2 (bias -2.3%, precision 4.6%). In group A changes in StO2 correlated with changes in SvO2 (r = 0.836, P < 0.001; ΔSvO2 = 0.84 × ΔStO2 - 0.67). In group B important differences between these variables were observed. Plasma lactate concentrations correlated negatively with StO2 values only in group A (r = -0.522, P = 0.009; lactate = -0.104 × StO2 + 10.25). Conclusion Skeletal muscle StO2 does not estimate SvO2 in patients with severe left heart failure and additional severe sepsis or septic shock. However, in patients with severe left heart failure without additional severe sepsis or septic shock, StO2 values could be used to provide rapid, noninvasive estimation of SvO2; furthermore, the trend in StO2 may be considered a surrogate for the trend in SvO2. Trial Registration: NCT00384644 PMID:17227587

  17. Peptide inhibition of p22phox and Rubicon interaction as a therapeutic strategy for septic shock.

    PubMed

    Kim, Ye-Ram; Koh, Hyun-Jung; Kim, Jae-Sung; Yun, Jin-Seung; Jang, Kiseok; Lee, Joo-Youn; Jung, Jae U; Yang, Chul-Su

    2016-09-01

    Sepsis is a clinical syndrome that complicates severe infection and is characterized by the systemic inflammatory response syndrome (SIRS), is a life threatening disease characterized by inflammation of the entire body. Upon microbial infection, p22phox-gp91phox NADPH oxidase (NOX) complexes produce reactive oxygen species (ROS) that are critical for the elimination of invading microbes. However, excess production of ROS represents a key element in the cascade of deleterious processes in sepsis. We have previously reported direct crosstalk between autophagy and phagocytosis machineries by demonstrating that the Rubicon protein interacts with p22phox upon microbial infection, facilitating phagosomal trafficking of the p22phox-gp91phox NOX complex to induce a ROS burst, inflammatory cytokine production, and thereby, potent anti-microbial activities. Here, we showed N8 peptide, an N-terminal 8-amino acid peptide derived from p22phox, was sufficient for Rubicon interaction and thus, capable of robustly blocking the Rubicon-p22phox interaction and profoundly suppressing ROS and inflammatory cytokine production. Consequently, treatment with the Tat-N8 peptide or a N8 peptide-mimetic small-molecule dramatically reduced the mortality associated with Cecal-Ligation-and-Puncture-induced polymicrobial sepsis in mice. This study demonstrates a new anti-sepsis therapeutic strategy by blocking the crosstalk between autophagy and phagocytosis innate immunity machineries, representing a potential paradigm shift for urgently needed therapeutic intervention against this life-threatening SIRS. PMID:27267627

  18. The Role of Hepatic Invariant (I)NKT Cells in Systemic/Local Inflammation and Mortality During Polymicrobial Septic Shock1

    PubMed Central

    Hu, Caroline K.; Venet, Fabienne; Heffernan, David S.; Wang, Yvonne L.; Horner, Brian; Huang, Xin; Chung, Chun-Shiang; Gregory, Stephen H.; Ayala, Alfred

    2009-01-01

    Natural killer T (NKT)4 cells have been described as “innate regulatory cells” because of their rapid response to conserved glycolipids presented on CD1d via their invariant TCR. However, little is known about the contribution of the hepatic NKT cell to the development of a local and/or systemic immune response to acute septic challenge (cecal ligation & puncture; CLP). We found not only that mice deficient in invariant [i] NKT cells (Jα18 -/-) had a marked attenuation in CLP induced mortality, but also exhibited an oblation of the systemic inflammatory response (with little effect on splenic/ peritoneal immune responsiveness). Flow cytometric data indicated that following CLP, there was a marked decline in the % of CD3+αGalCer-CD1d-tetramer+ cells in the mouse C57BL/6J and Balb/c liver non-parenchymal cell population. This was associated with the marked activation of these cells (increased expression of CD69 and CD25) as well as a rise in the frequency of NKT cells positive for both Th1 and Th2 intracellular cytokines. In this respect, when mice were pre-treated in vivo with anti-CD1d blocking antibody we observed not only that this inhibited the systemic rise of IL-6 and IL-10 levels in septic mice and improved overall septic survival, but that the CLP induced changes in liver macrophage IL-6 and IL-10 expressions were inversely effected by this treatment. Together, these findings suggest that the activation of hepatic iNKT cells plays a critical role in regulating the innate immune/ systemic inflammatory response and survival in a model of acute septic shock. PMID:19201902

  19. Temperature variability analysis using wavelets and multiscale entropy in patients with systemic inflammatory response syndrome, sepsis, and septic shock

    PubMed Central

    2012-01-01

    Background Even though temperature is a continuous quantitative variable, its measurement has been considered a snapshot of a process, indicating whether a patient is febrile or afebrile. Recently, other diagnostic techniques have been proposed for the association between different properties of the temperature curve with severity of illness in the Intensive Care Unit (ICU), based on complexity analysis of continuously monitored body temperature. In this study, we tried to assess temperature complexity in patients with systemic inflammation during a suspected ICU-acquired infection, by using wavelets transformation and multiscale entropy of temperature signals, in a cohort of mixed critically ill patients. Methods Twenty-two patients were enrolled in the study. In five, systemic inflammatory response syndrome (SIRS, group 1) developed, 10 had sepsis (group 2), and seven had septic shock (group 3). All temperature curves were studied during the first 24 hours of an inflammatory state. A wavelet transformation was applied, decomposing the signal in different frequency components (scales) that have been found to reflect neurogenic and metabolic inputs on temperature oscillations. Wavelet energy and entropy per different scales associated with complexity in specific frequency bands and multiscale entropy of the whole signal were calculated. Moreover, a clustering technique and a linear discriminant analysis (LDA) were applied for permitting pattern recognition in data sets and assessing diagnostic accuracy of different wavelet features among the three classes of patients. Results Statistically significant differences were found in wavelet entropy between patients with SIRS and groups 2 and 3, and in specific ultradian bands between SIRS and group 3, with decreased entropy in sepsis. Cluster analysis using wavelet features in specific bands revealed concrete clusters closely related with the groups in focus. LDA after wrapper-based feature selection was able to classify

  20. Pathology Image Of the Month: Rapidly Progressive Hemorrhagic Cellulitis of Bilateral Lower Extremities with Subsequent Septic Shock and Death.

    PubMed

    Connor, Ellen E; Jackson, Nicole R; McGoey, Robin R

    2016-01-01

    A 51-year-old man presented to a community based emergency department with bilateral lower extremity swelling that began four days prior and that had evolved into recent blister formation on the left lower extremity. Medical history was significant only for hypertension and a recent self-described episode of "food poisoning" five days earlier characterized by diarrhea, nausea, and vomiting that quickly resolved. Physical exam revealed marked bilateral lower extremity edema and an ecchymotic rash below the knee. In addition to the rash, there were large flaccid bullae on the left leg, mostly intact but some notable for draining of scanty serosanguinous fluid. The patient was tachycardic with a rate of 114 bpm and initial labs showed thrombocytopenia (platelets 56 x 103/uL [140-440 x 103/uL]), hypoglycemia (15mg/dl [70-105mg/dl]), an elevated creatinine (2.7mg/dL [0.7- 1.25mg/dL]), and aspartate aminotransferase (AST 156U/L [5- 34U/L]). Two sets of blood cultures were drawn, broad spectrum antibiotics including doxycycline were empirically initiated and then he was subsequently transported to a tertiary care hospital for escalation of care. Within hours of presentation to the tertiary care facility, the rash appeared progressively hemorrhagic and bullous, lactic acidosis and coagulopathy developed and hemodynamic instability and septic shock necessitated endotracheal intubation and vasopressors. He was taken to the operating room for skin debridement but was emergently converted to bilateral above the knee lower extremity amputations due to the extent of the soft tissue necrosis. The patient remained intubated and in critical condition following surgery and the ecchymotic rash reappeared at the amputation sites. A newly developed ecchymotic rash with bullae formation was noted on the right upper extremity forearm. At that time, the clinicians were notified that four out of four blood culture bottles from admission were rapidly growing a microorganism. The family

  1. Impact on mortality of the timing of renal replacement therapy in patients with severe acute kidney injury in septic shock: the IDEAL-ICU study (initiation of dialysis early versus delayed in the intensive care unit): study protocol for a randomized controlled trial

    PubMed Central

    2014-01-01

    Background One of the most dreaded complications of septic shock is acute kidney injury. It occurs in around 50% of patients, with a mortality rate of about 60% at 3 months. There is no consensus on the optimal time to initiate renal replacement therapy. Retrospective and observational studies suggest that early implementation of renal replacement therapy could improve the prognosis for these patients. Methods/design This protocol summarizes the rationale and design of a randomized, controlled, multicenter trial investigating the effect of early versus delayed renal replacement therapy in patients with severe acute kidney injury in early septic shock. In total, 864 critically ill adults with septic shock and evidence of acute kidney injury, defined as the failure stage of the RIFLE classification, will be enrolled. The primary outcome is mortality at 90 days. Secondary outcomes include safety, number of days free of mechanical ventilation, number of days free of renal replacement therapy, intensive care length of stay, in-hospital length of stay, quality of life as evaluated by the EQ-5D and renal replacement therapy dependence at hospital discharge. The primary analysis will be intention to treat. Recruitment started in March 2012 and will be completed by March 2015. Discussion This protocol for a randomized controlled study investigating the impact of the timing of renal replacement therapy initiation should provide an answer to a key question for the management of patients with acute kidney injury in the context of septic shock, for whom the mortality rate remains close to 60% despite improved understanding of physiopathology and recent therapeutic advances. Trial registration ClinicalTrials.gov identifier NCT01682590, registered on 10 September 2012. PMID:24998258

  2. Mass transfer, clearance and plasma concentration of procalcitonin during continuous venovenous hemofiltration in patients with septic shock and acute oliguric renal failure

    PubMed Central

    Level, Claude; Chauveau, Philippe; Guisset, Olivier; Cazin, Marie Cécile; Lasseur, Catherine; Gabinsky, Claude; Winnock, Stéphane; Montaudon, Danièle; Bedry, Régis; Nouts, Caroline; Pillet, Odile; Benissan, Georges Gbikpi; Favarel-Guarrigues, Jean Claude; Castaing, Yves

    2003-01-01

    Objectives To measure the mass transfer and clearance of procalcitonin (PCT) in patients with septic shock during continuous venovenous hemofiltration (CVVH), and to assess the mechanisms of elimination of PCT. Setting The medical department of intensive care. Design A prospective, observational study. Patients Thirteen critically ill patients with septic shock and oliguric acute renal failure requiring continuous venovenous postdilution hemofiltration with a high-flux membrane (AN69 or polyamide) and a 'conventional' substitution volume (< 2.5 l/hour). Measurements and main results PCT was measured with the Lumitest PCT Brahms® in the prefilter and postfilter plasma, in the ultrafiltrate at the beginning of CVVH (T0) and 15 min (T15'), 60 min (T60') and 6 hours (T6h) after setup of CVVH, and in the prefilter every 24 hours during 4 days. Mass transfer was determined and the clearance and the sieving coefficient were calculated according to the mass conservation principle. Plasma and ultrafiltrate clearances, respectively, at T15', T60' and T6h were 37 ± 8.6 ml/min (not significant) and 1.8 ± 1.7 ml/min (P < 0.01), 34.7 ± 4.1 ml/min (not significant) and 2.3 ± 1.8 ml/min (P < 0.01), and 31.5 ± 7 ml/min (not significant) and 5 ± 2.3 ml/min (P < 0.01). The sieving coefficient significantly increased from 0.07 at T15' to 0.19 at T6h, with no difference according to the nature of the membrane. PCT plasma levels were not significantly modified during the course of CCVH. Conclusions We conclude that PCT is removed from the plasma of patients with septic shock during CCVH. Most of the mass is eliminated by convective flow, but adsorption also contributes to elimination during the first hours of CVVH. The effect of PCT removal with a conventional CVVH substitution fluid rate (<2.5 l/hour) on PCT plasma concentration seems to be limited, and PCT remains a useful diagnostic marker in these septic patients. The impact of high-volume hemofiltration on the PCT clearance

  3. Salmonella Typhi–Induced Septic Shock and Acute Respiratory Distress Syndrome in a Previously Healthy Teenage Patient Treated With High-Dose Dexamethasone

    PubMed Central

    Ugas, Melissa Brosset; Carroll, Timothy; Kovar, Lacey; Chavez-Bueno, Susana

    2016-01-01

    Typhoid fever is commonly characterized by fever and abdominal pain. Rare complications include intestinal hemorrhage, bowel perforation, delirium, obtundation, and septic shock. Herein we describe the case of a previously healthy 16-year-old male without history of travel, diagnosed with typhoid fever complicated by septic shock and acute respiratory distress syndrome treated with high-dose dexamethasone. This case details severe complications of typhoid fever that are uncommonly seen in developed countries, and the successful response to high-dose dexamethasone as adjunct therapy. High-dose dexamethasone treatment has reportedly decreased Salmonella Typhi mortality, but controlled studies specifically performed in children are lacking, and most reports of its use are over 30 years old and all have originated in developing countries. Providers should include Salmonella Typhi in the differential diagnosis of the pediatric patient with fever, severe abdominal pain, and enteritis, and be aware of its potentially severe complications and the limited data on safety and efficacy of adjunctive therapies that can be considered in addition to antibiotics. PMID:27294165

  4. Salmonella Typhi-Induced Septic Shock and Acute Respiratory Distress Syndrome in a Previously Healthy Teenage Patient Treated With High-Dose Dexamethasone.

    PubMed

    Ugas, Melissa Brosset; Carroll, Timothy; Kovar, Lacey; Chavez-Bueno, Susana

    2016-01-01

    Typhoid fever is commonly characterized by fever and abdominal pain. Rare complications include intestinal hemorrhage, bowel perforation, delirium, obtundation, and septic shock. Herein we describe the case of a previously healthy 16-year-old male without history of travel, diagnosed with typhoid fever complicated by septic shock and acute respiratory distress syndrome treated with high-dose dexamethasone. This case details severe complications of typhoid fever that are uncommonly seen in developed countries, and the successful response to high-dose dexamethasone as adjunct therapy. High-dose dexamethasone treatment has reportedly decreased Salmonella Typhi mortality, but controlled studies specifically performed in children are lacking, and most reports of its use are over 30 years old and all have originated in developing countries. Providers should include Salmonella Typhi in the differential diagnosis of the pediatric patient with fever, severe abdominal pain, and enteritis, and be aware of its potentially severe complications and the limited data on safety and efficacy of adjunctive therapies that can be considered in addition to antibiotics. PMID:27294165

  5. Role of endotoxemia in cardiovascular dysfunction and mortality. Escherichia coli and Staphylococcus aureus challenges in a canine model of human septic shock.

    PubMed Central

    Natanson, C; Danner, R L; Elin, R J; Hosseini, J M; Peart, K W; Banks, S M; MacVittie, T J; Walker, R I; Parrillo, J E

    1989-01-01

    Using different types of bacteria and a canine model simulating human septic shock, we investigated the role of endotoxin in cardiovascular dysfunction and mortality. Either Escherichia coli (a microorganism with endotoxin) or Staphylococcus aureus (a microorganism without endotoxin) were placed in an intraperitoneal clot in doses of viable or formalin-killed bacteria. Cardiovascular function of conscious animals was studied using simultaneous radionuclide heart scans and thermodilution cardiac outputs. Serial plasma endotoxin levels were measured. S. aureus produced a pattern of reversible cardiovascular dysfunction over 7-10 d that was concordant (P less than 0.01) with that of E. coli. Although this cardiovascular pattern was not altered by formalin killing (S. aureus and E. coli), formalin-killed organisms produced a lower mortality and less myocardial depression (P less than 0.01). S. aureus, compared to E. coli, produced higher postmortem concentrations of microorganisms and higher mortality (P less than 0.025). E. coli produced significant endotoxemia (P less than 0.01), though viable organisms (versus nonviable) resulted in higher endotoxin blood concentrations (P less than 0.05). Significant endotoxemia did not occur with S. aureus. Thus, in the absence of endotoxemia, S. aureus induced the same cardiovascular abnormalities of septic shock as E. coli. These findings indicate that structurally and functionally distinct microorganisms, with or without endotoxin, can activate a common pathway resulting in similar cardiovascular injury and mortality. PMID:2642920

  6. Harmonizing international trials of early goal-directed resuscitation for severe sepsis and septic shock: methodology of ProCESS, ARISE, and ProMISe

    PubMed Central

    2013-01-01

    Purpose To describe and compare the design of three independent but collaborating multicenter trials of early goal-directed resuscitation for severe sepsis and septic shock. Methods We reviewed the three current trials, one each in the USA (ProCESS: protocolized care for early septic shock), Australasia (ARISE: Australasian resuscitation in sepsis evaluation), and the UK (ProMISe: protocolised management in sepsis). We used the 2010 CONSORT (consolidated standards of reporting trials) statement and the 2008 CONSORT extension for trials assessing non-pharmacologic treatments to describe and compare the underlying rationale, commonalities, and differences. Results All three trials conform to CONSORT guidelines, address the same fundamental questions, and share key design elements. Each trial is a patient-level, equal-randomized, parallel-group superiority trial that seeks to enroll emergency department patients with inclusion criteria that are consistent with the original early goal-directed therapy (EGDT) trial (suspected or confirmed infection, two or more systemic inflammatory response syndrome criteria, and refractory hypotension or elevated lactate), is powered to detect a 6–8 % absolute mortality reduction (hospital or 90-day), and uses trained teams to deliver EGDT. Design differences appear to primarily be driven by between-country variation in health care context. The main difference between the trials is the inclusion of a third, alternative resuscitation strategy arm in ProCESS. Conclusions Harmonization of study design and methods between severe sepsis trials is feasible and may facilitate pooling of data on completion of the trials. PMID:23958738

  7. A novel ligand-independent peptide inhibitor of TREM-1 suppresses tumor growth in human lung cancer xenografts and prolongs survival of mice with lipopolysaccharide-induced septic shock

    PubMed Central

    Sigalov, Alexander B.

    2014-01-01

    Triggering receptor expressed on myeloid cells-1 (TREM-1) amplifies the inflammatory response and plays a role in cancer and sepsis. Inhibition of TREM-1 by short hairpin RNA (shRNA) in macrophages suppresses cancer cell invasion in vitro. In the clinical setting, high levels of TREM-1 expression on tumor-associated macrophages are associated with cancer recurrence and poor survival of patients with non-small cell lung cancer (NSCLC). TREM-1 upregulation on peritoneal neutrophils has been found in human sepsis patients and in mice with experimental lipopolysaccharide (LPS)-induced septic shock. However, the precise function of TREM-1 and the nature of its ligand are not yet known. In this study, we used the signaling chain homooligomerization (SCHOOL) model of immune signaling to design a novel, ligand-independent peptide-based TREM-1 inhibitor and demonstrated that this peptide specifically silences TREM-1 signaling in vitro and in vivo. Utilizing two human lung tumor xenograft nude mouse models (H292 and A549) and mice with LPS-induced sepsis, we show for the first time that blockade of TREM-1 function using non-toxic and non-immunogenic SCHOOL peptide inhibitors: 1) delays tumor growth in xenograft models of human NSCLC, 2) prolongs survival of mice with LPS-induced septic shock, and 3) substantially decreases cytokine production in vitro and in vivo. In addition, targeted delivery of SCHOOL peptides to macrophages utilizing lipoprotein-mimicking nanoparticles significantly increased peptide half-life and dosage efficacy. Together, the results suggest that ligand-independent modulation of TREM-1 function using small synthetic peptides might be a suitable treatment for sepsis and NSCLC and possibly other types of inflammation-associated disorders. PMID:24836682

  8. Interleukin-6 Kinetics can be Useful for Early Treatment Monitoring of Severe Bacterial Sepsis and Septic Shock

    PubMed Central

    Cantara, Giulio; Sechtem, Udo; Athanasiadis, Anastasios

    2016-01-01

    Early appropriate anti-microbial therapy is necessary to improve outcomes of septic patients. We describe 20 case histories of patients with severe bacterial sepsis regarding kinetics of several biomarkers. We found that interleukin-6 is able to predict survival and might be able to evaluate appropriateness of anti-microbial therapy. PMID:27103972

  9. Effect of early goal-directed therapy on mortality in patients with severe sepsis or septic shock: a meta-analysis of randomised controlled trials

    PubMed Central

    Yu, Hong; Chi, Dongmei; Wang, Siyang; Liu, Bin

    2016-01-01

    Objective To determine whether patients with severe sepsis or septic shock could benefit from a strict and early goal-directed therapy (EGDT) protocol recommended by Surviving Sepsis Campaign (SSC) Guidelines. Methods MEDLINE/PubMed, EMBASE/OVID and Cochrane Central Register of Controlled Trials (CENTRAL) were searched between March 1983 and March 2015. Eligible studies evaluated the outcomes of EGDT versus usual care or standard therapy in patients with severe sepsis or septic shock. The primary outcomes were mortality within 28 days, 60 days and 90 days. Included studies must report at least one metric of mortality. Results 5 studies that enrolled 4303 patients with 2144 in the EGDT group and 2159 in the control group were included in this meta-analysis. Overall, there were slight decreases of mortality within 28 days, 60 days and 90 days in the random-effect model in patients with severe sepsis or septic shock receiving EGDT resuscitation. However, none of the differences reached statistical significance (RR=0.86; 95% CI 0.69 to 1.06; p=0.16; p for heterogeneity=0.008, I2=71%; RR=0.94; 95% CI 0.81 to 1.10; p=0.46; p for heterogeneity=0.16, I2=43%; RR=0.98; 95% CI 0.88 to 1.10; p=0.75; p for heterogeneity=0.87, I2=0%, respectively). Conclusions The current meta-analysis pooled data from five RCTs and found no survival benefit of EGDT in patients with sepsis. However, the included trials are not sufficiently homogeneous and potential confounding factors in the negative trials (ProCESS, ARISE and ProMISe) might bias the results and diminish the treatment effect of EGDT. Further well-designed studies should eliminate all potential source of bias to determine if EGDT has a mortality benefit. PMID:26932135

  10. [Lateral Approach Tracheal Intubation in a Semi-sitting Position Utilizing a Videolaryngoscope in a Patient with Respiratory Failure due to Septic Shock].

    PubMed

    Fujiwara, Atsushi; Komasawa, Nobuyasu; Nishihara, Isao; Minami, Toshiaki

    2015-05-01

    Here we report our success in performing lateral approach tracheal intubation in a patient with severe respiratory failure due to septic shock caused by shoulder joint abscess. A 71-year-old woman presented with severe respiratory difficulty due to sepsis from a shoulder joint abscess and was scheduled for emergent drainage and irrigation. She could not breathe sufficiently in the supine position and thus maintained a semi-sitting position. She was also unable to move from the ward bed to the operating table due to severe shoulder pain. We induced anesthesia in a semi-sitting position in the ward bed. Mask ventilation was performed using the two-hand technique from the lateral approach. Tracheal intubation was also performed with a left lateral approach utilizing the Pentax-AWS Airwayscope (AWS). Lateral approach for tracheal intubation utilizing AWS may be useful in patients who present with severe respiratory difficulty. PMID:26422963