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PubMed2000

Intravenous immunoglobulin for treating sepsis and septic shock.

OBJECTIVES: Death from severe sepsis and septic shock is common, and researchers have explored whether antibodies to the endotoxins in some bacteria reduces mortality. This review summarises the effects of intravenous immunoglobulin (IVIG) in patients with bacterial sepsis or septic shock on mortality, bacteriological failure rates, and duration of stay in hospital. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, Medline 1966 to April 1999, EMBASE 1988 to February 1999; we contacted investigators active in the field for unpublished data. SELECTION CRITERIA: Randomised trials comparing intravenous immunoglobulin (monoclonal or polyclonal) with placebo or no intervention, in patients with bacterial sepsis or septic shock. DATA COLLECTION AND ANALYSIS: Inclusion criteria, trial quality assessment, and data abstraction were done in duplicate. We conducted pre-specified subgroup analyses by type of immunoglobulin preparation. MAIN RESULTS: Twenty-three out of 49 studies met our inclusion criteria. Overall mortality was reduced in patients who received polyclonal IVIG (n=413; RR=0.60; 95% CI 0.47 to 0.76). Mortality was not reduced among patients who received monoclonal antibodies such as anti-endotoxins (n=1,736 in 4 good-quality studies; RR=0.98; 95% CI 0.86 to 1.12) or anti-cytokines (n=4,318; RR=0.93; 95% CI 0.86 to 1.01). A few studies measured secondary outcomes (deaths from sepsis or length of hospitalisation) but no differences in the intervention and control groups were identified except among those who received polyclonal IVIG, where sepsis-related mortality was significantly reduced (n=161; RR=0.35; 95% CI 0.18 to 0.69). REVIEWER'S CONCLUSIONS: In our opinion, polyclonal IVIG significantly reduces mortality and can be used as an adjuvant treatment for sepsis and septic shock. Adjunctive therapy with monoclonal IVIGs remains experimental.

Humans↗
PubMed1995

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

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.

Hospital Mortality↗
PubMed2001

Toward the early diagnosis of neonatal sepsis and sepsis-like illness using novel heart rate analysis.

BACKGROUND AND OBJECTIVE: Abrupt clinical deterioration because of sepsis is a major cause of morbidity and mortality in neonates, and earlier diagnosis should improve therapy of this potentially catastrophic illness. In practice, clinical signs and laboratory data have not been perceived as sensitive or specific for early stages of sepsis. Because heart rate characteristics (HRC) are abnormal during fetal distress and neonatal illness, we hypothesized that abnormal HRC might precede the clinical diagnosis of neonatal sepsis, adding independent information to standard clinical parameters. METHODS: In the neonatal intensive care unit at the University of Virginia, we prospectively studied infants admitted from August 1995 to April 1999 who were at risk for developing sepsis. Infants in the sepsis (culture-positive) and sepsis-like illness (culture-negative) groups had an abrupt clinical deterioration that raised clinical suspicion of infection and prompted physicians to obtain blood cultures and start antibiotic therapy. Infants without sepsis raised no clinical suspicion of illness and had no cultures obtained. We measured novel characteristics-moments and percentiles-of normalized heart rate (HR) time series for 5 days before and 3 days after sepsis, sepsis-like illness, or a random time in controls. We also calculated the Score for Neonatal Acute Physiology (SNAP) and the Neonatal Therapeutic Intervention Scoring System (NTISS) as clinical scores of the severity of illness. RESULTS: There were 46 episodes of culture-positive sepsis in 40 patients and 27 episodes of culture-negative sepsis-like illness in 23 patients. We analyzed 29 control periods in 26 patients. Infants with sepsis and sepsis-like illness had lower birth weights and gestational ages and higher SNAP and NTISS scores than did infants without sepsis. The most important new finding was that the infants in the sepsis and sepsis-like illness groups had increasingly abnormal HRC for up to 24 hours preceding their abrupt clinical deterioration. The abnormal HRC were reduced baseline variability and short-lived decelerations in HR. These abnormalities led to significant changes in HRC measures, for example, the third moment (skewness:.59 +/-.10 for sepsis and.51 +/-. 12 for sepsis-like illness, compared with -.10 +/-.13 for control over the 6 hours before abrupt deterioration). Culture-positive and culture-negative patients had similar HRC and clinical scores, including a significant rise in SNAP in the 24 hours before the event. Multivariable logistic regression analysis showed that HRC and clinical scores independently added information in distinguishing infants with sepsis and sepsis-like illness from control patients in the 24 hours before abrupt deterioration. CONCLUSIONS: Newborn infants who had abrupt clinical deterioration as a result of sepsis and sepsis-like illness had abnormal HRC and SNAP that worsened over 24 hours before the clinical suspicion of sepsis. A strategy for monitoring these parameters in infants at risk for sepsis and sepsis-like illness might lead to earlier diagnosis and more effective therapy.heart rate variability, neonatal sepsis, Score for Neonatal Acute Physiology, Neonatal Therapeutic Intervention Scoring System, newborn.

Analysis of Variance↗
PubMed2005

Sodium/hydrogen exchange activity in sepsis and in sepsis complicated by previous injury: 31P and 23Na NMR study.

OBJECTIVE: Sepsis or septic shock occurs frequently in sick and injured patients and is associated with a significant mortality. Myocardial contractile dysfunction has been proposed to be a major determinant of sepsis-related mortality. This study was directed to examine the role of Na/H exchange activity in myocardial defects after sepsis or after sepsis complicated by a previous burn injury. DESIGN: Laboratory study. SETTING: University research laboratory. SUBJECTS: Sprague-Dawley rats (300-350 g, males). INTERVENTIONS: Cardiac function, cellular Na and Ca, myocardial pH, and high-energy phosphates were examined in perfused hearts harvested after sepsis alone (intratracheal Streptococcus pneumoniae, 0.4 mL of 1 x 10 CFU/mL), after sepsis complicated by previous burn injury (40% total body surface area), and after amiloride (a selective inhibitor of Na/H exchange) treatment of either sepsis alone or sepsis plus burn. MEASUREMENTS AND RESULTS: The ratio of Na signal from the intracellular compartment (Nai) compared with an external standard (monitored by Na-NMR spectroscopy, TmDOTP shift reagent) increased by 70% in sepsis alone and by 41% in sepsis complicated by previous burn injury compared with shams. Cardiac adenosine triphosphate and intracellular pH (P nuclear magnetic resonance spectroscopy) were unchanged by sepsis or sepsis plus burn. Left ventricular pressure and maximal change in pressure over time were reduced after sepsis or after sepsis plus burn injury. Amiloride treatment in either sepsis or sepsis complicated by a previous burn injury prevented myocardial Na and Ca accumulation, attenuated sepsis-related lactic acidosis, and improved left ventricular function. CONCLUSION: Our results suggest that sepsis-related cardiac dysfunction is mediated, in part, by Na/H exchange activity, and inhibition of Na/H exchange activity improves cardiac function after sepsis alone or sepsis complicated by a previous injury.

Amiloride↗
PubMed1993

Oxygen consumption and resting metabolic rate in sepsis, sepsis syndrome, and septic shock.

OBJECTIVE: To test the hypothesis that variations in oxygen consumption (VO2) and resting metabolic rate reflect the severity of bacterial infections and reflect the development of sepsis syndrome and septic shock. DESIGN: Observational study with sequential measurements of VO2 and resting metabolic rate by expiratory gas analysis. SETTING: Medical intensive care unit. PATIENTS: Thirty patients, treated primarily for presumed bacterial infection, were examined on 118 treatment days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: VO2 and resting metabolic rate were measured by expiratory gas analysis. For mechanically ventilated patients, a measurement system was developed, based on a paramagnetic oxygen sensor, an infrared CO2 sensor, and digital signal averaging. Measurements in spontaneously breathing patients were performed with a metabolic monitor. Patients were assigned by clinical criteria to the following groups: sepsis, sepsis syndrome, and septic shock. The lowest VO2 value of each patient in each stage was evaluated. Mean VO2 in 15 patients with sepsis was 180 +/- 19 (SD) mL/min/m2, in 11 patients with sepsis syndrome 156 +/- 22 mL/min/m2, and in eight patients with septic shock 120 +/- 27 mL/min/m2 (p < .001). Mean resting metabolic rate in sepsis was +55 +/- 14%, in sepsis syndrome +24 +/- 12%, and in septic shock +2 +/- 24% (p < .001). Mean oxygen delivery (DO2) was 501 +/- 116 mL/min/m2 in sepsis, 515 +/- 186 mL/min/m2 in sepsis syndrome, and 404 +/- 96 mL/min/m2 in septic shock. Oxygen extraction (VO2/DO2) was highest in sepsis (0.39 vs. 0.33 in sepsis syndrome and 0.29 in septic shock). During recovery from sepsis syndrome or septic shock, a significant increase in resting metabolic rate to +61 +/- 22% was measured in nine patients. CONCLUSIONS: In sepsis syndrome, VO2 and resting metabolic rate are enhanced by 30% compared with normal basal metabolism, but they are markedly reduced compared with uncomplicated sepsis. The higher VO2 in uncomplicated sepsis is flow independent. The noninvasive measurement of VO2 and resting metabolic rate by expiratory gas analysis therefore can be used as a quantitative staging and monitoring parameter for the development of sepsis syndrome and septic shock.

Adult↗
PubMed2001

Activation of the fibrinolytic system and utilization of the coagulation inhibitors in sepsis: comparison with severe sepsis and septic shock.

OBJECTIVES: To determine whether the fibrinolytic system is activated and coagulation inhibitors are utilized in sepsis, to compare the findings detected in sepsis with those found in severe sepsis and septic shock, and to compare the role played by different infectious pathogens on fibrinolysis and coagulation inhibitors. DESIGN AND SETTING: Prospective study comparing patients with sepsis, severe sepsis, and septic shock and healthy volunteers in the general intensive care unit of a tertiary university hospital. PATIENTS: Eighty-two consecutive septic patients (47 with sepsis, 18 with severe sepsis, and 17 with septic shock), and 14 healthy volunteers (controls). MEASUREMENTS AND RESULTS: After blood sampling we measured activation markers of fibrinolysis [plasmin/alpha(2)-antiplasmin complexes (PAP), complexes of tissue plasminogen activator/plasminogen activator inhibitor (tPA/PAI), fibrin(ogen) degradation products (FDPs), D-dimmers fibrin degradation products (D-d)], the utilization marker of antithrombin III (ATIII) thrombin/antithrombin complexes (TAT), several factors of fibrinolysis [plasminogen, tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1), alpha(2)-antiplasmin], and the natural coagulation inhibitors [ATIII, protein C (PrC), protein S (PrS)]. In sepsis, PAP, FDPs, D-d, and TAT were increased to 439.8+/-32.35 microg/l, 57% positive, 49% positive, and 3.46+/-0.27 microg/l, respectively, compared with control subjects (205.57+/-28.58 microg/l, 0% positive, 7% positive, and 1.61+/-0.1 microg/l, respectively). These markers further increased in severe sepsis and septic shock. With the exception of a decrease in ATIII and an increase in tPA and PAI-1, coagulation inhibitors and factors of fibrinolysis were not changed in sepsis. In severe sepsis and mainly in septic shock, coagulation inhibitors (ATIII, PrC) and plasminogen were markedly decreased, whereas tPA and PAI-1 were further increased. All changes were independent of the causative infectious pathogen. CONCLUSIONS: Fibrinolysis is strongly activated and ATIII is utilized in sepsis. These findings are further enhanced in severe sepsis and septic shock. In sepsis only ATIII is decreased. In contrast, in severe sepsis and mainly in septic shock plasminogen and the main coagulation inhibitors (i.e., ATIII, PrC) are depleted, indicating exhaustion of fibrinolysis and coagulation inhibitors. Finally, Gram-positive, Gram-negative and other micro-organisms produce identical impairment.

Adolescent↗
PubMed2006

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

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

Adult↗
PubMed2005

International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics.

OBJECTIVE: Although general definitions of the sepsis continuum have been published for adults, no such work has been done for the pediatric population. Physiologic and laboratory variables used to define the systemic inflammatory response syndrome (SIRS) and organ dysfunction require modification for the developmental stages of children. An international panel of 20 experts in sepsis and clinical research from five countries (Canada, France, Netherlands, United Kingdom, and United States) was convened to modify the published adult consensus definitions of infection, sepsis, severe sepsis, septic shock, and organ dysfunction for children. DESIGN: Consensus conference. METHODS: This document describes the issues surrounding consensus on four major questions addressed at the meeting: a) How should the pediatric age groups affected by sepsis be delineated? b) What are the specific definitions of pediatric SIRS, infection, sepsis, severe sepsis, and septic shock? c) What are the specific definitions of pediatric organ failure and the validity of pediatric organ failure scores? d) What are the appropriate study populations and study end points required to successfully conduct clinical trials in pediatric sepsis? Five subgroups first met separately and then together to evaluate the following areas: signs and symptoms of sepsis, cell markers, cytokines, microbiological data, and coagulation variables. All conference participants approved the final draft of the proceedings of the meeting. RESULTS: Conference attendees modified the current criteria used to define SIRS and sepsis in adults to incorporate pediatric physiologic variables appropriate for the following subcategories of children: newborn, neonate, infant, child, and adolescent. In addition, the SIRS definition was modified so that either criteria for fever or white blood count had to be met. We also defined various organ dysfunction categories, severe sepsis, and septic shock specifically for children. Although no firm conclusion was made regarding a single appropriate study end point, a novel nonmortality end point, organ failure-free days, was considered optimal for pediatric clinical trials given the relatively low incidence of mortality in pediatric sepsis compared with adult populations. CONCLUSION: We modified the adult SIRS criteria for children. In addition, we revised definitions of severe sepsis and septic shock for the pediatric population. Our goal is for these first-generation pediatric definitions and criteria to facilitate the performance of successful clinical studies in children with sepsis.

Adolescent↗
PubMed1995

Systemic inflammatory response syndrome, sepsis, severe sepsis and septic shock: incidence, morbidities and outcomes in surgical ICU patients.

OBJECTIVES: To determine the incidence of systemic inflammatory response syndrome (SIRS), sepsis and severe sepsis in surgical ICU patients and define patient characteristics associated with their acquisition and outcome. DESIGN: One-month prospective study of critically ill patients with a 28 day in-hospital follow up. SETTING: Surgical intensive care unit (SICU) at a tertiary care institution. METHODS: All patients (n = 170) admitted to the SICU between April 1 and April 30, 1992 were prospectively followed for 28 days. Daily surveillance was performed by two dedicated, specifically-trained research nurses. Medical and nursing chart reviews were performed, and follow up information at six and twelve months was obtained. RESULTS: The in-hospital surveillance represented 2246 patient-days, including 658 ICU patient-days. Overall, 158 patients (93%) had SIRS for an incidence of 542 episodes/1000 patients-days. The incidence of SIRS in the ICU was even higher (840 episodes/1000 patients-days). A total of 83 patients (49%) had sepsis; among them 28 developed severe sepsis. Importantly, 13 patients had severe sepsis after discharge from the ICU. Patient groups were comparable with respect to age, sex ratio, and type of surgery performed. Apache II score on admission to the ICU and ASA score at time of surgery were significantly higher (p < 0.05) only for patients who subsequently developed severe sepsis. The crude mortality at 28 days was 8.2% (14/170); it markedly differed among patient groups: 6% for those with SIRS vs. 35% for patients with severe sepsis. Patients with sepsis and severe sepsis had a longer mean length of ICU stay (2.1 +/- 0.2 and 7.5 +/- 1.5, respectively) than those with SIRS (1.45 +/- 0.1) or control patients (1.16 +/- 0.1). Total length of hospital stay also markedly differed among groups (35 +/- 9 (severe sepsis), 24 +/- 2 (sepsis), 11 +/- 0.8 (SIRS), and 9 +/- 0.1 (controls, respectively). CONCLUSIONS: Almost everyone in the SICU had SIRS. Therefore, because of its poor specificity, SIRS was not helpful predicting severe sepsis and septic shock. Patients who developed sepsis or severe sepsis had higher crude mortality and length of stay than those who did not. Studies designed to identify those who develop complications of SIRS would be very useful.

Critical Care↗
PubMed2006

Evaluation of serum C-reactive protein, procalcitonin, tumor necrosis factor alpha, and interleukin-10 levels as diagnostic and prognostic parameters in patients with community-acquired sepsis, severe sepsis, and septic shock.

The diagnostic value of procalcitonin, C-reactive protein, tumor necrosis factor-alpha, and interleukin-10 levels in differentiating sepsis from severe sepsis and the prognostic value of these levels in predicting outcome were evaluated and compared in patients with community-acquired sepsis, severe sepsis, and septic shock in the first 72 h of admission to the hospital. Thirty-nine patients were included in the study. The severe sepsis and septic shock cases were combined in a single "severe sepsis" group, and all comparisons were made between the sepsis (n=21 patients) and the severe sepsis (n=18 patients) groups. Procalcitonin levels in the severe sepsis group were found to be significantly higher at all times of measurements within the first 72 h and were significantly higher at the 72nd hour in patients who died. Procalcitonin levels that remain elevated at the 72nd hour indicated a poor prognosis. C-reactive protein levels were not significantly different between the groups, nor were they indicative of prognosis. No significant differences in the levels of tumor necrosis factor-alpha were found between the sepsis and severe sepsis groups; however, levels were higher at the early stages (at admission and the 24th hour) in patients who died. Interleukin-10 levels were also higher in the severe sepsis group and significantly higher at all times of measurement in patients who died. When the diagnostic and prognostic values at admission were evaluated, procalcitonin and interleukin-10 levels were useful in discriminating between sepsis and severe sepsis, whereas tumor necrosis factor-alpha and interleukin-10 levels were useful in predicting which cases were likely to have a fatal outcome.

Biomarkers↗
PubMed2006

Sepsis and burn complicated by sepsis alter cardiac transporter expression.

UNLABELLED: Sepsis alone and burn complicated by sepsis produce significant cardiac dysfunction. Since calcium handling by the cardiomyocyte is essential for cardiac function, one mechanism for cardiac abnormalities may be calcium dyshomeostasis. We hypothesized that sepsis and burn plus sepsis alter cardiac calcium transporter expression. Sprague-Dawley rats were divided into: (1) control, (2) sepsis (intratracheal S. Pneumoniae, 4x10(6) CFU), and (3) burn (40% TBSA) plus sepsis. Myocyte [Ca(2+)](i) and [Na(+)](i) were quantified with Fura-2 AM and SBFI, respectively. Western blot analysis of rat hearts used antibodies against the sarcoplasmic reticular Ca(2+) ATPase (SERCA), the L-type calcium channel, the Na(+)/Ca(2+) exchanger or the Na(+)/K(+) ATPase. RESULTS: Sepsis in the presence and absence of burn trauma increased [Ca(2+)](i) and [Na(+)](i). SERCA expression was decreased in the sepsis and burn plus sepsis groups while calcium channel expression was transiently increased in these sepsis groups. Na(+)/Ca(2+) exchanger expression exhibited a biphasic pattern of altered expression. Sepsis and burn plus sepsis reduced Na(+)/K(+) ATPase protein levels. These data suggest that altered transporter expression produce cardiomyocyte calcium and sodium loading and may contribute to sepsis-mediated cardiac contractile dysfunction.

Animals↗
PubMed2005

Cytokine elaboration in critically ill infants with bacterial sepsis, necrotizing entercolitis, or sepsis syndrome: correlation with clinical parameters of inflammation and mortality.

OBJECTIVE: To test the hypothesis that cytokines might distinguish critically ill infants with bacterial sepsis or necrotizing enterocolitis (NEC) from those with sepsis syndrome and that these elevations would be correlated with clinical variables of inflammation and mortality. STUDY DESIGN: We measured plasma and tracheal aspirate (TA) levels of interleukin-8 (IL-8), epithelial neutrophil activating peptide (ENA-78), IL-10, and IL-18 in 84 neonates with suspected sepsis or NEC. Thirty-one infants had bacterial sepsis, 19 had NEC, and 34 infants with negative results on cultures had sepsis syndrome. RESULTS: Plasma IL-8 and IL-10 levels were significantly increased in infants with bacterial sepsis compared with those in infants with sepsis syndrome. Plasma IL-8, ENA-78, and IL-10 levels were elevated in infants with NEC compared with those in infants with sepsis syndrome. TA IL-8 and IL-10 levels were also increased in infants with bacterial sepsis; TA ENA-78, and IL-18 were not elevated in infants with sepsis or NEC when compared with infants with sepsis syndrome. Plasma and TA cytokine levels correlated with hematologic parameters. Plasma cytokine levels were higher in infants who did not survive than in infants who did survive. CONCLUSIONS: Plasma and TA cytokine levels are elevated in critically ill infants with bacterial sepsis or NEC compared with those in infants with sepsis syndrome. Our results suggest distinct patterns of cytokine elaboration in different disease states.

Bacterial Infections↗
PubMed2000

Epidemiological differences between sepsis syndrome with bacteremia and culture-negative sepsis.

OBJECTIVE: To explore the association of putative disease markers and potential risk factors with the nosocomial sepsis syndrome. DESIGN: Prospective case-control study matched for gender, age, and length of preinfection hospital stay. SETTING: 1,200-bed tertiary-care center in Spain. PATIENTS: Cases were selected using the sepsis syndrome criteria of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference and were divided into three groups: sepsis with bacteremia (109 cases), sepsis with positive culture other than blood (122 cases), and sepsis with negative culture (115 cases without documented infection but with sepsis syndrome, clinically suspected infection, and empirical antibiotic treatment). Controls were randomly selected from the daily list of inpatients. Data were collected prospectively. Crude and multiple-risk-factor-adjusted odds ratios and their 95% confidence intervals were computed using conditional logistic regression analysis. RESULTS: Presence of coma in the 48 hours before sepsis, intensive care unit (ICU) stay, and decreased serum albumin levels at admission were common epidemiological markers identified for the three groups of cases. Having a central venous catheter was the main healthcare-related risk factor for bacteremia. ICU stay and nasogastric tube were the main risk factors for sepsis with positive culture other than blood. Coma within 48 hours before sepsis and the need of intensive care were the only two markers identified for culture-negative sepsis. CONCLUSION: Culture-negative sepsis does not behave like culture-positive sepsis, and this may imply that implementation of preventive measures to decrease the risk of bacteremia may not decrease the risk of sepsis syndrome.

Bacteremia↗
PubMed2003

Abnormal heart rate characteristics preceding neonatal sepsis and sepsis-like illness.

Late-onset neonatal sepsis is a significant cause of morbidity and mortality, and early detection could prove beneficial. Previously, we found that abnormal heart rate characteristics (HRC) of reduced variability and transient decelerations occurred early in the course of neonatal sepsis and sepsis-like illness in infants in a single neonatal intensive care unit (NICU). We hypothesized that this finding can be generalized to other NICUs. We prospectively collected clinical data and continuously measured RR intervals in all infants in two NICUs who stayed for >7 d. We defined episodes of sepsis and sepsis-like illness as acute clinical deteriorations that prompted physicians to obtain blood cultures and start antibiotics. A predictive statistical model yielding an HRC index was developed on a derivation cohort of 316 neonates in the University of Virginia NICU and then applied to the validation cohort of 317 neonates in the Wake Forest University NICU. In the derivation cohort, there were 155 episodes of sepsis and sepsis-like illness in 101 infants, and in the validation cohort, there were 118 episodes in 93 infants. In the validation cohort, the HRC index 1) showed highly significant association with impending sepsis and sepsis-like illness (receiver operator characteristic area 0.75, p < 0.001) and 2) added significantly to the demographic information of birth weight, gestational age, and days of postnatal age in predicting sepsis and sepsis-like illness (p < 0.001). Continuous HRC monitoring is a generally valid and potentially useful noninvasive tool in the early diagnosis of neonatal sepsis and sepsis-like illness.

Heart Rate↗
PubMed1999

Cytokines in sepsis due to Candida albicans and in bacterial sepsis.

Cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and tumor necrosis factor-soluble receptor (TNF-sR), and adhesion molecules, e.g. vascular adhesion molecule-1 (VCAM-1) and E-selectin, play an important role in the pathogenesis of bacterial sepsis. Experimental data on cytokine expression during candidaemia are controversial. In this study, plasma concentrations of cytokines and adhesion molecules were compared between patients with sepsis due to Candida albicans and bacterial sepsis. Plasma levels of TNF-alpha, TNF-sR, IL-6, VCAM-1 and E-selectin, were determined in 20 patients with sepsis due to C. albicans, in 20 patients with bacterial sepsis, and in 20 controls on days 1, 7 and 14. On day 1, elevated plasma levels of TNF-alpha, TNF-sR and IL-6 were detected in both sepsis groups compared to controls. On day 1, VCAM-1 levels were higher, and E-selectin levels were lower in patients with Candida sepsis than in patients with bacterial sepsis (p < 0.05). At any time, VCAM-1 levels were significantly greater in patients with Candida sepsis than in patients with bacterial sepsis (p < 0.05). Non-survivors, regardless of the etiology of sepsis, had higher blood levels of IL-6, TNF-sR and E-selectin than survivors. The cytokines, TNF-alpha, IL-6 and TNF-sR, and the adhesion molecules, VCAM-1 and E-selectin, are involved in sepsis due to C. albicans as in bacterial sepsis.

Adolescent↗
PubMed2005

The impact of compliance with 6-hour and 24-hour sepsis bundles on hospital mortality in patients with severe sepsis: a prospective observational study.

INTRODUCTION: Compliance with the ventilator care bundle affects the rate of ventilator-associated pneumonia. It was not known, however, whether compliance with sepsis care bundles has an impact on outcome. The aims of the present study were to determine the rate of compliance with 6-hour and 24-hour sepsis bundles and to determine the impact of the compliance on hospital mortality in patients with severe sepsis or septic shock. METHODS: We conducted a prospective observational study on 101 consecutive adult patients with severe sepsis or septic shock on medical or surgical wards, or in accident and emergency areas at two acute National Health Service Trust Teaching hospitals in England. The main outcome measures were: the rate of compliance with 6-hour and 24-hour sepsis care bundles adapted from the Surviving Sepsis Campaign guidelines on patients' clinical care; and the difference in hospital mortality between the compliant and the non-compliant groups. RESULTS: The median age of the patients was 69 years (interquartile range 51 to 78), and 53% were male. The sources of infection were sought and confirmed in 87 of 101 patients. The chest was the most common source (50%), followed by the abdomen (22%). The rate of compliance with the 6-hour sepsis bundle was 52%. Compared with the compliant group, the non-compliant group had a more than twofold increase in hospital mortality (49% versus 23%, relative risk (RR) 2.12 (95% confidence interval (CI) 1.20 to 3.76), P = 0.01) despite similar age and severity of sepsis. Compliance with the 24-hour sepsis bundle was achieved in only 30% of eligible candidates (21/69). Hospital mortality was increased in the non-compliant group from 29% to 50%, with a 76% increase in risk for death, although the difference did not reach statistical significance (RR 1.76 (95% CI 0.84 to 3.64), P = 0.16). CONCLUSION: Non-compliance with the 6-hour sepsis bundle was associated with a more than twofold increase in hospital mortality. Non-compliance with the 24-hour sepsis bundle resulted in a 76% increase in risk for hospital death. All medical staff should practise these relatively simple, easy and cheap bundles within a strict timeframe to improve survival rates in patients with severe sepsis and septic shock.

Aged↗
PubMed1995

Incidence, risk factors, and outcome of severe sepsis and septic shock in adults. A multicenter prospective study in intensive care units. French ICU Group for Severe Sepsis.

OBJECTIVE: To examine the incidence, risk factors, and outcome of severe sepsis in intensive care unit (ICU) patients. DESIGN AND SETTING: Inception cohort study from a 2-month prospective survey of 11,828 consecutive admissions to 170 adult ICUs of public hospitals in France. PATIENTS: Patients meeting clinical criteria for severe sepsis were included and classified as having documented infection (ie, documented severe sepsis, n = 742), or a clinical diagnosis of infection without microbiological documentation (ie, culture-negative severe sepsis, n = 310). MAIN OUTCOME MEASURES: Hospital and 28-day mortality after severe sepsis. RESULTS: Clinically suspected sepsis and confirmed severe sepsis occurred in 9.0 (95% confidence interval [CI], 8.5 to 9.5) and 6.3 (95% CI, 5.8 to 6.7) of 100 ICU admissions, respectively. The 28-day mortality was 56% (95% CI, 52% to 60%) in patients with severe sepsis, and 60% (95% CI, 55% to 66%) in those with culture-negative severe sepsis. Major determinants of both early (< 3 days) and secondary deaths in the whole cohort were the Simplified Acute Physiology Score (SAPS) II and the number of acute organ system failures. Other risk factors for early death included a low arterial blood pH (< 7.33) (P < .001) and shock (P = .03), whereas secondary deaths were associated with the admission category (P < .001), a rapidly or ultimately fatal underlying disease (P < .001), a preexisting liver (P = .01) or cardiovascular (P = .002) insufficiency, hypothermia (P = .02), thrombocytopenia (P = .01), and multiple sources of infection (P = .02). In patients with documented sepsis, bacteremia was associated with early mortality (P = .03). CONCLUSIONS: Only three of four patients presenting with clinically suspected severe sepsis have documented infection. However, patients with clinically suspected sepsis but without microbiological documentation and patients with documented infection share common risk factors and are at similarly high risk of death. In addition to the severity of illness score, acute organ failures and the characteristics of underlying diseases should be accounted for in stratification of patients and outcome analyses.

Adult↗
PubMed2004

An international sepsis survey: a study of doctors' knowledge and perception about sepsis.

BACKGROUND: To be able to diagnose and treat sepsis better it is important not only to improve the knowledge about definitions and pathophysiology, but also to gain more insight into specialists' perception of, and attitude towards, the current diagnosis and treatment of sepsis. METHODS: The study was conducted as a prospective, international survey by structured telephone interview. The subjects were intensive care physicians and other specialist physicians caring for intensive care unit (ICU) patients. RESULTS: The 1058 physicians who were interviewed (including 529 intensivists) agreed that sepsis is a leading cause of death on the ICU and that the incidence of sepsis is increasing, but that the symptoms of sepsis can easily be misattributed to other conditions. Physicians were concerned that this could lead to under-reporting of sepsis. Two-thirds (67%) were concerned that a common definition is lacking and 83% said it is likely that sepsis is frequently missed. Not more than 17% agreed on any one definition. CONCLUSION: There is a general awareness about the inadequacy of the current definitions of sepsis. Physicians caring for patients with sepsis recognise the difficulty of defining and diagnosing sepsis and are aware that they miss the diagnosis frequently.

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