The epidemiology of the systemic inflammatory response

Objective: To examine the incidence, risk factors, aetiologies and outcome of the various forms of the septic syndromes (the systemic inflammatory response syndrome [SIRS] sepsis, severe sepsis, and septic shock) and their relationships with infection.¶Design: Review of published cohort studies examining the epidemiology of the septic syndromes, with emphasis on intensive care unit (ICU) patients.¶Results: The prevalence of SIRS is very high, affecting one-third of all in-hospital patients, and > 50 % of all ICU patients; in surgical ICU patients, SIRS occurs in > 80 % patients. Trauma patients are at particularly high risk of SIRS, and most these patients do not have infection documented. The prevalence of infection and bacteraemia increases with the number of SIRS criteria met, and with increasing severity of the septic syndromes. About one-third of patients with SIRS have or evolve to sepsis. Sepsis may occur in approximately 25 % of ICU patients, and bacteraemic sepsis in 10 %. In such patients, sepsis evolves to severe sepsis in > 50 % of cases, whereas evolution to severe sepsis in non-ICU patients is about 25 %. Severe sepsis and septic shock occur in 2 %–3 % of ward patients and 10 %–15 % or more ICU patients, depending on the case-mix; 25 % of patients with severe sepsis have shock. There is a graded severity from SIRS to sepsis, severe sepsis and septic shock, with an associated 28-d mortality of approximately 10 %, 20 %, 20 %–40 %, and 40 %–60 %, respectively. Mortality rates are similar within each stage, whether infection is documented or not, and microbiological characteristics of infection do not substantially influence outcome, although the source of infection does. While about three of four deaths occur during the first months after sepsis, the septic syndromes significantly impact on long-term outcome, with an estimated 50 % reduction of life expectancy over the following five years. The major determinants of outcome, both short-term and long-term, of patients with sepsis are the severity of underlying diseases and comorbidities, the presence of shock and organ failures at onset of sepsis or evolving thereafter. It has been estimated that two-thirds of the overall mortality can be attributed to sepsis.¶Conclusions: The prevalence of sepsis in ICU patients is very high, and most patients have clinically or microbiologically documented infection, except in specific subset of patients. The prognosis of septic syndromes is related to underlying diseases and the severity of the inflammatory response and its sequelae, reflected in shock and organ dysfunction/failures.     

Circulating endothelin-1 and tumor necrosis factor-α: early predictors of mortality in patients with septic shock

Objectives: To determine the predictive value of early determination of tumor necrosis factor (TNF)-α, TNF-α 1 and 2 soluble receptors (sTNFR1 and sTNFR2) and endothelin-1 (ET-1) for mortality in patients with septic shock.¶Design: Prospective study.¶Setting: Intensive care unit of a university hospital.¶Patients: Twenty-one patients with septic shock.¶Interventions: None.¶Measurements and Results: Patients with septic shock had a pulmonary artery catheter inserted and blood samples drawn at time zero, 6, 12 and 24 h, simultaneously with hemodynamic assessments. Plasma levels of all markers were measured by ELISA. All patients were followed up to hospital discharge or death. Age and APACHE II scores were significantly higher in nonsurvivors (n = 11) than in survivors (n = 10). Hemodynamic assessments did not aid in the discrimination between the two groups of patients (P > 0.05). Levels of TNF-α were higher in nonsurvivors than in survivors at all time-points. sTNFR1 and sTNFR2 were also significantly elevated in nonsurvivors, but not in all measurements. Endothelin-1, however, was significantly higher in nonsurvivors than in survivors only at 6 h (P = 0.02). When both TNF-α and ET-1 were increased at early time-points, the best predictive values for mortality were obtained [positive and negative predictive values of 72 and 100 % at 6 h, odds ratio 3.0, 95 % CI (1.2–7.6)].¶Conclusions: Increased levels of TNF-α were consistently higher at all time-points in nonsurvivors with septic shock. ET-1 levels, however, appeared also to be an early and sensitive predictor of mortality. Very early determination of TNF-α and ET-1 in septic shock may help to identify patients at higher risk for adverse outcome.     

Hypothermia and cytokines in septic shock

Background: Hypothermic patients with sepsis have been reported to have a higher mortality than febrile septic patients. The failure to mount a febrile response in sepsis is poorly understood. Since the proinflammatory cytokines play a crucial role in the genesis of fever, we postulated that hypothermic patients with sepsis would have lower circulating levels of these cytokines than febrile patients¶Methods: Patients with septic shock who were enrolled into the placebo limb of the North American study of the safety and efficacy of murine monoclonal antibody to tumor necrosis factor for the treatment of septic shock (NORASEPT II) were analyzed. Body temperature, interleukin-6, tumor necrosis factor α, soluble tumor necrosis factor receptor-55, and soluble tumor necrosis factor receptor-75 concentrations were measured at enrollment. The study population was divided into a hypothermic (temperature ≤ 35.6 °C) and a febrile group (temperature ≥ 38.3 °C) according to the core temperature at enrollment (normothermia was an exclusion criteria). Clinical, demographic, and cytokine data were extracted, allowing for comparisons between these two groups of patients. In addition, the correlation between the core body temperature and cytokine levels at enrollment was determined¶Results: A complete data set was available for 930 patients; 195 patients (21 %) were hypothermic at enrollment. The 28-day survival of these patients was significantly lower than that of the febrile patients (34 % vs. 59 %, p < 0.001). Hypothermia (and enrollment temperature) were independent predictors of mortality. The hypothermic patients had a higher incidence of organ dysfunction at enrollment than the febrile patients. There was no significant difference in the cytokine profile between the two groups of patients. In addition, there was no correlation between the core body temperature at enrollment and the circulating levels of cytokines measured¶Conclusion: Hypothermic patients with septic shock have a significantly higher mortality with a higher incidence of organ dysfunction than febrile septic shock patients. The hypothermia in these patients cannot be explained by lower levels of circulating proinflammatory cytokines.     

Incidence and mortality of severe sepsis in surgical intensive care patients: the influence of patient gender on disease process and outcome

Objective: Laboratory studies demonstrated significant detrimental effects of male sex-steroids (testosterone) on immune functions following hemorrhagic shock and soft-tissue trauma. Moreover, better survival of female mice subjected to severe sepsis was observed when compared to male animals. The aims of the present study were to evaluate whether or not gender differences regarding incidence and mortality of severe sepsis do exist in surgical intensive care patients and to elucidate the influence of patient age on incidence and mortality of severe sepsis/septic shock.¶Design: Data base review of prospectively collected data from surgical intensive care patients.¶Setting: Surgical intensive care unit of the department of surgery of a university hospital.¶Patients: Prospectively collected data of 4218 intensive care patients (2709 male, 1509 female).¶Results: Significantly fewer female patients were referred to the intensive care unit (6.6 % vs 10.8 % of all patients; P < 0.05) leading to a significantly smaller proportion of female intensive care patients (35.8 % vs 64.2 %). No gender differences regarding number of failing organs or surgical procedure (exception vascular surgery) were observed in patients with and without severe sepsis/septic shock, indicating that the patients studied are comparable regarding general health prior to admission to SICU. Among all female patients referred to SICU only 7.6 % developed severe sepsis/septic shock, while 10.4 % of all male patients suffered from severe sepsis or septic shock (P < 0.05). This gender difference results from a significantly lower incidence of severe sepsis/septic shock in female patients between 60 and 79 years. No gender difference regarding mortality rates of severe sepsis/septic shock was observed (men 64.9 %, women 65.5 %).¶Conclusions: Our results indicate a significantly smaller number of female patients requiring intensive care as well as a significantly lower incidence of severe sepsis/septic shock in female intensive care patients. Mortality from severe sepsis/septic shock, however, is not affected by gender.     

Procalcitonin (PCT) is useful in predicting the bacterial origin of an acute circulatory failure in critically ill patients

Objective: To evaluate the accuracy of procalcitonin (PCT) in predicting bacterial infection in ICU medical and surgical patients.¶Setting: A 10-bed medical surgical unit.¶Design: PCT, C-reactive protein (CRP), interleukin 6 (IL-6) dosages were sampled in four groups of patients: septic shock patients (SS group), shock without infection (NSS group), patients with systemic inflammatory response syndrome related to a proven bacterial infection (infect. group) and ICU patients without shock and without bacterial infection (control group).¶Results: Sixty patients were studied (SS group: n = 16, NSS group, n = 18, infect. group, n = 16, control group, n = 10). The PCT level was higher in patients with proven bacterial infection (72 - 153 ng/ml vs 2.9 - 10 ng/ml, p = 0.0003). In patients with shock, PCT was higher when bacterial infection was diagnosed (89 ng/ml - 154 vs 4.6 ng/ml - 12, p = 0.0004). Moreover, PCT was correlated with severity (SAPS: p = 0.00005, appearance of shock: p = 0.0006) and outcome (dead: 71.3 g/ml, alive: 24.0 g/ml, p = 0.006). CRP was correlated with bacterial infection (p < 10^-5) but neither with SAPS nor with day 28 mortality. IL-6 was correlated with neither infection nor day 28 mortality but was correlated with SAPS. Temperature and white blood cell count were unable to distinguish shocked patients with or without infection. Finally, when CRP and PCT levels were introduced simultaneously in a stepwise logistic regression model, PCT remained the unique marker of infection in patients with shock (PCT S 5 ng/ml, OR: 6.2, 95 %CI: 1.1-37, p = 0.04).¶Conclusion: The increase of PCT is related to the appearance and severity of bacterial infection in ICU patients. Thus, PCT might be an interesting parameter for the diagnosis of bacterial infections in ICU patients.     

Endotoxaemia in patients with severe sepsis or septic shock

Objective: To examine the incidence and the bacteriological and clinical significance of endotoxaemia in ICU patients with severe sepsis or septic shock. Design: Prospective review. Setting: A 15-bed general ICU in a university hospital. Patients: One hundred sixteen patients hospitalised in our ICU fulfilling Bone's criteria for severe sepsis or septic shock and with an available early endotoxin assay (chromogenic limulus assay). Interventions: None. Measurements and results: The clinical characteristics of the population were: age 63.6 ± 11.4 years; SAPS II: 45.4 ± 15.6; mechanical ventilation: 72.4 %; septic shock: 51.7 % (n = 60); bacteraemia: 28.4 % (n = 33); gram-negative bacteria (GNB) infection 47.4 % (n = 55); ICU mortality: 39.6 % (n = 46). Detectable endotoxin occurred in 61 patients (51.2 %; mean level: 310 ± 810 pg/ml). There was no relationship between detectable endotoxin and severity of infection at the moment of the assay. Endotoxaemia was associated with a higher incidence of bacteraemia (39.3 % vs 16.3 %; p = 0.01). There was a trend (p = 0.09) towards an association between positive endotoxin and gram-negative bacteraemia or GNB infection but this was non-significant. This relationship became significant only in the case of bacteraemia associated with GNB infection irrespective of the site of infection. Conclusion: Early detection of endotoxaemia appeared to be associated with GNB infection only in cases of bacteraemic GNB infection. Early endotoxaemia correlated neither to occurrence of organ dysfunction nor mortality in patients with severe sepsis or septic shock. This study suggests that the use of endotoxaemia as a diagnostic or a prognostic marker in daily practice remains difficult. Received: 28 September 1999 Final revision received: 31 January 2000 Accepted: 1 February 2000     

TISS and mortality after discharge from intensive care

Objective: To examine the effect of high levels of pre-intensive care unit (ICU) discharge care, as assessed by the Therapeutic Intervention Scoring System (TISS), on subsequent hospital mortality.¶Design: A 1-year prospective, observational study.¶Setting: The ICU and wards of a university teaching hospital with no high dependency facility (HDU).¶Patients: A total of 283 patients were discharged to hospital wards between July 1997 and June 1998.¶Results: 11 % of all ICU discharges subsequently died in hospital. Patients discharged with a TISS of 20 or greater had a 21.4 % mortality compared to 3.7 % for those with a TISS of less than 10. Increasing age, Acute Physiology Score (APS) on admission and male sex were also significantly associated with post-discharge death.¶Conclusions: In a hospital without HDU facilities, patients who are receiving HDU levels of care on discharge from the ICU have a high in-hospital mortality.     

Lack of significant treatment effect of plasma exchange in the treatment of drug-induced toxic epidermal necrolysis?

Objective: Comparison of outcome in patients with toxic epidermal necrolysis (TEN) in patients who received plasma exchange (PE) compared with the results in two other centres that used almost identical treatment protocols but without PE.¶Design: Retrospective comparative case series with two recently published case series serving as controls.¶Setting: National burns intensive care unit (ICU) and Department of Transfusion Medicine at Linköping University Hospital, Sweden.¶Patients: 8 consecutive patients admitted with TEN who received PE during 1987–1997.¶Interventions: Neither prophylactic antibiotics nor cortisone were used. The patients were given a median of 5.5 PE treatments (range 1–8).¶Results: Eight patients with a median (range) age of 45 years (5–89) and with a median skin involvement total body surface area (TBSA) of 38 % (12–100) were treated. The length of stay in the burns ICU was 15 (13–25) days and the time from onset of the cutaneous signs until complete re-epithelialisation was 24 days (13–55) for the seven survivors. Five patients fulfilled the diagnostic criteria of sepsis. One patient with extensive ischaemic cardiac disease developed septic shock and died (mortality 12.5 %). Two patients developed side effects from PE.¶Conclusions: To our knowledge, this is the largest series yet presented using PE in the treatment of TEN. Our results, in patients with less cutaneous involvement, similar causative agents, and similar demographic data as in the other two studies (controls), were no different as far as mortality, length of stay, or time to re-epithelialisation were concerned. This finding does not support the use of PE in the treatment of TEN.     

Septic shock in patients with the acquired immunodeficiency syndrome

Objective: To evaluate the prognosis of patients with septic shock admitted to an intensive care unit (ICU), according to their HIV serostatus. Design: Retrospective study. Setting: Medical ICU of a university hospital. Patients: 76 patients with septic shock admitted to the same ICU, of whom 28 were HIV positive and 48 were HIV negative. Measurements and results: Severity scores, number and type of organ failures, and survival rates were assessed in the two groups of patients. Glasgow Coma Scale and general severity scores [Acute Physiology and Chronic Health Evaluation II and Simplified Acute Physiology Score (SAPS)] were significantly worse in HIV-infected patients. The total number of organ failures was also higher in the HIV-positive group: 3.7 ± 0.2 vs 3.1 ± 0.2 in the HIV-negative group (p < 0.001). On day 28, 21 (46 %) HIV-negative patients were dead compared to 26 (93 %) patients in the HIV-positive group (p < 0.001). In the multivariate analysis, HIV infection was an independent risk factor for mortality, as were the SAPS score, use of mechanical ventilation, and the McCabe score. Conclusions: This study reports a considerable excess mortality in HIV-infected patients with septic shock. Although severity of illness was clearly much more pronounced in HIV-positive patients, retroviral infection was independently associated with death. Improving survival in HIV-positive patients with septic shock may require earlier diagnosis and treatment of the causative infection. Received: 30 September 1996 Accepted: 8 July 1997     

Tumor necrosis factor gene polymorphism and septic shock in surgical infection

OBJECTIVES: To evaluate the relationship of the genotype distribution of the tumor necrosis factor (TNF)-alpha polymorphism with regard to the plasma TNF-alpha concentration and the development of septic shock as well as mortality of infected patients in a surgical intensive care unit (SICU). DESIGN: A total of 112 postoperative critically ill infected patients were prospectively enrolled. SETTING: SICU of a tertiary university-affiliated medical center. PATIENTS: Patients who were consecutively admitted to the SICU because of surgical infection with sepsis. INTERVENTION: Blood sampling. MEASUREMENTS AND MAIN RESULTS: Blood sample was obtained 24 hrs after intensive care unit (ICU) admission or within 2 hrs after the onset of septic shock to determine the plasma TNF-alpha level and to analyze the genotype of the biallelic polymorphism of the TNF-alpha. RESULTS: The allele frequency of the TNF2 in our infected ICU patients was 12%. Forty-two (37.5%) patients admitted fulfilled the criteria of septic shock during their ICU stay. Patients carrying the TNF2 allele were not more likely to develop septic shock, nor did they have a higher mortality rate. In the patients with septic shock, those carrying the TNF2 allele had a significantly higher mortality rate than those with the homozygous TNF1 genotype (92% vs. 62%, p < .05). In those who developed septic shock, the TNF2 allele was significantly associated with higher TNF levels. CONCLUSION: In patients admitted to SICU with surgical infection, the frequency of TNF2 allele was higher than in the general population. SICU patients with TNF2 allele did not show a higher incidence of developing septic shock, nor was there a higher baseline TNF-alpha level after infection. However, once septic shock had developed, the mortality rate was higher in those patients carrying the TNF2 allele.     

Skin lesions in the ICU

Objective: The objective of this study is to identify the dermatological disorders (DDs) responsible for the most common skin lesions in the ICU, their incidence and their impact on mortality, degree of severity and length of stay in the ICU.¶Design and setting: We performed a 2-year prospective study in a general medical and surgical ICU including, exceptionally, paediatric cases.¶Patients: We included all patients who presented skin lesions upon admission or developed them during their ICU stay.¶Results: Forty-six patients (10 % of all admissions) were enrolled, with 51 DDs. SAPS II score (43) and mean length of stay (19 days) were significantly higher than in the general group of ICU admissions. Differences in mortality rates (26 % versus 29 %) were not statistically significant.¶Conclusions: DDs are entities that should be borne in mind in the critically ill patient; their incidence is by no means negligible and makes careful examination of the skin mandatory both on admission and during a patient's ICU stay.     

Procalcitonin for early diagnosis and differentiation of SIRS, sepsis, severe sepsis, and septic shock

Objective: To determine the value of procalcitonin (PCT) in the early diagnosis (and differentiation) of patients with SIRS, sepsis, severe sepsis, and septic shock in comparison to C-reactive protein (CRP), white blood cell and thrombocyte count, and APACHE-II score (AP-II).¶Design: Prospective cohort study including all consecutive patients admitted to the ICU with the suspected diagnosis of infection over a 7-month period.¶Patients and methods: A total of 185 patients were included: 17 patients with SIRS, 61 with sepsis, 68 with severe sepsis, and 39 patients with septic shock. CRP, cell counts, AP-II and PCT were evaluated on the first day after onset of inflammatory symptoms.¶Results: PCT values were highest in patients with septic shock (12.89 - 4.39 ng/ml; P < 0.05 vs patients with severe sepsis). Patients with severe sepsis had significantly higher PCT levels than patients with sepsis or SIRS (6.91 - 3.87 ng/ml vs 0.53 - 2.9 ng/ml; P < 0.001, and 0.41 - 3.04 ng/ml; P < 0.001, respectively). AP-II scores did not differ significantly between sepsis, severe sepsis and SIRS (19.26 - 1.62, 16.09 - 2.06, and 17.42 - 1.72 points, respectively), but was significantly higher in patients with septic shock (29.27 - 1.35, P < 0.001 vs patients with severe sepsis). Neither CRP, cell counts, nor the degree of fever showed significant differences between sepsis and severe sepsis, whereas white blood cell count and platelet count differed significantly between severe sepsis and septic shock.¶Conclusions: In contrast to AP-II, PCT appears to be a useful early marker to discriminate between sepsis and severe sepsis.     

Incidence of severe sepsis and septic shock in German intensive care units: the prospective,multicentre INSEP study

Purpose

To estimate the incidence density, point prevalence and outcome of severe sepsis and septic shock in German intensive care units (ICUs).

Methods

In a prospective, multicentre, longitudinal observational study, all patients already on the ICU at 0:00 on 4 November 2013 and all patients admitted to a participating ICU between 0:00 on 4 November 2013 and 2359 hours on 1 December 2013 were included. The patients were followed up for the occurrence of severe sepsis or septic shock (SEPSIS-1 definitions) during their ICU stay.

Results

A total of 11,883 patients from 133 ICUs at 95 German hospitals were included in the study, of whom 1503 (12.6 %) were diagnosed with severe sepsis or septic shock. In 860 cases (57.2 %) the infections were of nosocomial origin. The point prevalence was 17.9 % (95 % CI 16.3–19.7).The calculated incidence rate of severe sepsis or septic shock was 11.64 (95 % CI 10.51–12.86) per 1000 ICU days. ICU mortality in patients with severe sepsis/septic shock was 34.3 %, compared with 6 % in those without sepsis. Total hospital mortality of patients with severe sepsis or septic shock was 40.4 %. Classification of the septic shock patients using the new SEPSIS-3 definitions showed higher ICU and hospital mortality (44.3 and 50.9 %).

Conclusions

Severe sepsis and septic shock continue to be a frequent syndrome associated with high hospital mortality. Nosocomial infections play a major role in the development of sepsis. This study presents a pragmatic, affordable and feasible method for the surveillance of sepsis epidemiology. Implementation of the new SEPSIS-3 definitions may have a major effect on future epidemiological data.

     

Adequate antibiotic therapy prior to ICU admission in patients with severe sepsis and septic shock reduces hospital mortality

IntroductionIn patients with severe sepsis and septic shock as cause of Intensive Care Unit (ICU) admission, we analyze the impact on mortality of adequate antimicrobial therapy initiated before ICU admission.MethodsWe conducted a prospective observational study enrolling patients admitted to the ICU with severe sepsis or septic shock from January 2008 to September 2013. The primary end-point was in-hospital mortality. We considered two groups for comparisons: patients who received adequate antibiotic treatment before or after the admission to the ICU.ResultsA total of 926 septic patients were admitted to ICU, and 638 (68.8%) had available microbiological isolation: 444 (69.6%) received adequate empirical antimicrobial treatment prior to ICU and 194 (30.4%) after admission. Global hospital mortality in patients that received treatment before ICU admission, between 0-6h ICU, 6–12h ICU, 12–24h ICU and after 24 hours since ICU admission were 31.3, 53.2, 57.1, 50 and 50.8% (p<0.001). The multivariate analysis showed that urinary focus (odds ratio (OR) 0.20; 0.09–0.42; p<0.001) and adequate treatment prior to ICU admission (OR 0.37; 0.24–0.56; p<0.001) were protective factors whereas APACHE II score (OR 1.10; 1.07–1.14; p<0.001), septic shock (OR 2.47; 1.57–3.87; p<0.001), respiratory source (OR 1.91; 1.12–3.21; p=0.016), cirrhosis (OR 3.74; 1.60–8.76; p=0.002) and malignancy (OR 1.65; 1.02–2.70; p=0.042) were variables independently associated with in-hospital mortality. Adequate treatment prior to ICU was a protective factor for mortality in patients with severe sepsis (n=236) or in septic shock (n=402).ConclusionsThe administration of adequate antimicrobial therapy before ICU admission is decisive for the survival of patients with severe sepsis and septic shock. Our efforts should be directed to assure the correct administration antibiotics before ICU admission in patients with sepsis.     

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

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 proportion of RRT had more severe organ dysfunctions and received more organ-supportive treatments. Importantly, the ICU group (high-RRT or low-RRT group) was not associated with 90-day mortality.     

Protein C zymogen in severe sepsis: a double-blinded,placebo-controlled,randomized study

Purpose

To determine whether protein C zymogen (protein C concentrates or human protein C) improves clinically relevant outcomes in adult patients with severe sepsis and septic shock.

Methods

This is a randomized, double-blind, placebo-controlled, parallel-group trial that from September 2012 to June 2014 enrolled adult patients with severe sepsis or septic shock and high risk of death and of bleeding (e.g., APACHE II greater than 25, extracorporeal membrane oxygenation or disseminated intravascular coagulopathy). All patients completed their follow-up 90 days after randomization and data were analyzed according to the intention-to-treat principle. Follow-up was performed at 30 and 90 days after randomization. The primary endpoint was a composite outcome of prolonged intensive care unit (ICU) stay and/or 30-day mortality. Secondary endpoints included mortality.

Results

The study was stopped early in a situation of futility for the composite outcome of prolonged ICU stay and/or 30-day mortality that was 79 % (15 patients) in the protein C zymogen group and 67 % (12 patients) in the placebo group (p = 0.40) and for a concomitant safety issue: ICU mortality was 79 % (15 patients) in the protein C zymogen group vs 39 % (7 patients) in the placebo group (p = 0.020), and 30-day mortality was 68 vs 39 % (p = 0.072).

Conclusion

Protein C zymogen did not improve clinically relevant outcomes in severe sepsis and septic shock adult patients. Given its high cost and the potential increase in mortality, the use of this drug in adult patients should be discouraged.

     

Markers of tissue hypoperfusion in pediatric septic shock

Objective: To describe measurements of global oxygenation parameters, markers of splanchnic hypoperfusion and those of metabolic activity related to cellular energy production among critically ill children with septic shock.¶Design: Clinical study of a series of cases.¶Patients and participants: 11 previously healthy children with septic shock admitted to the pediatric intensive care unit (ICU) of a university hospital.¶Interventions: None.¶Measurements and results: Oxygen consumption, oxygen delivery (DO₂), serum bicarbonate, arterial pH, gastric intramucosal pH (pHi), gastroarterial carbon dioxide tension gradient, serum lactate, pyruvate, lactate to pyruvate ratio (L/P), ketone body ratio, and the esterified to free carnitine ratio were measured serially at 0, 6, 12, 24, 36, and 48 h after admission to the pediatric ICU. All children survived. One patient failed to show supranormal DO₂ ( > 570 ml/min per m²). Normalization of serum bicarbonate and lactate were associated with patient recovery. One patient presented an increasingly abnormal L/P ratio with normal lactate levels, suggesting an increased utilization of pyruvate rather than an increased cytosolic redox potential. Although values of gastric pHi < 7.30 were observed in 43 % of samples, serial measurements in individuals showed significant variability and unpredictable trends. Free fatty acid concentrations, ketone body production, and carnitine levels remained within the normal range.¶Conclusions: In this study, trends in serum bicarbonate and lactate somewhat characterized the recovery of children with septic shock. Based on our data, it is unclear how other markers may have been used to modify therapy.     

Predictors of short-term mortality in critically ill patients with solid malignancies

Admission of cancer patients with serious medical complications to the ICU remains controversial primarily because of the high short-term mortality rates in these patients. However, the cancer patient population is heterogeneous regarding age, underlying conditions, and curability of their disease, suggesting that large variations may occur in the effectiveness of intensive care within this subgroup of critically ill patients.¶Objectives: To identify factors predicting 30-day mortality in patients with solid tumors admitted to a medical ICU.¶Patients and methods: We conducted a retrospective study in 120 consecutive cancer patients (excluding patients with hematological malignancies) admitted to the medical ICU of a 650-bed university hospital between January 1990 and July 1997. Medical history, physical and laboratory test findings at admission, and therapeutic interventions within the first 24 h in the ICU were recorded. The study endpoint was vital status 30 days after ICU admission. Stepwise logistic regression was used to identify independent prognostic factors.¶Results: The observed 30-day mortality rate was 58.7 % (n = 68), with most deaths (92 %) occurring in the ICU. Univariate predictors of 30-day mortality were either protective [prior surgery for the cancer (p = 0.01) and complete remission (p = 0.01)] or associated with higher mortality [Knaus scale C or D (p = 0.02), shock (p = 0.04), need for vasopressors (p = 0.0006) or for mechanical ventilation (p = 0.0001), SAPS II score greater than 36 (p = 0.0001), LOD score greater than 6 (p = 0.0001), and ODIN score > 2 (p = 0.0001)]. Three variables were independent predictors: previous surgery for the cancer (OR 0.20, 95 % CI 0.07–0.58), LOD score > 6 (OR 1.26, 95 % CI 1.09–1.44), and need for mechanical ventilation (OR 3.55, 95 % CI; 1.26–6.7). Variables previously thought to be indicative of a poor prognosis (i. e., advanced age, metastatic or progressive disease, neutropenia or bone marrow transplantation) were not predictive of outcome.¶Conclusion: When transfer to an ICU is considered an option by patients and physicians, 30-day mortality is better estimated by an evaluation of acute organ dysfunction than by the characteristics of the underlying malignancy.     

Comparison of a specialist retrieval team with current United Kingdom practice for the transport of critically ill patients

Objective: The inter-hospital transfer of critically ill patients in the United Kingdom is commonly undertaken using standard ambulance under junior doctor escort, despite recommendations for the use of specialist retrieval teams. Patients are transferred into University College London Hospitals (UCLH) intensive care unit (ICU) by both methods. We undertook to evaluate the effect of transfer method on acute physiology (within 2 h of ICU admission) and early mortality ( < 12 h after ICU admission).¶Design: Retrospective review of all transfers over 1 year.¶Setting: UCLH ICU.¶Subjects: 259 transfers; 168 by specialist retrieval team (group A) and 91 by standard ambulance with doctor provided by referring hospital (group B).¶Interventions: None¶Main outcome measures: Acute physiology (pH, PaO₂, PaCO₂, heart rate (HR), mean arterial blood pressure (MAP), 24 h severity of illness scores (APACHE II, SAPS II), length of stay and mortality.¶Results: There were no differences in demographic characteristics or severity of illness between the two groups; nevertheless significantly more patients in group B than in group A were severely acidotic (pH < 7.1: 11 % vs. 3 %, p < 0.008) and hypotensive (MAP < 60: 18 % vs. 9 %, p < 0.03) upon arrival. In addition, there were more deaths within the first 12 h after admission with 7.7 % deaths (7/91) in group B transfers vs. 3 % (5/168) in group A.¶Conclusions: The use of a specialist transfer team may significantly improve the acute physiology of critically ill patients and may reduce early mortality in ICU.     

Acute neuromuscular respiratory failure after ICU discharge

Objective: To describe a syndrome of acute neuromuscular respiratory failure (NM-ARF) caused by ICU-acquired acute myopathy and neuropathy.¶Design: Case series.¶Setting: General Regional University Hospital in Brescia, Italy.¶Patients: Five adult patients with NM-ARF after prolonged ICU stay and successful weaning from the ventilator and ICU discharge.¶Interventions: None.¶Measurements: Clinical signs of NM-ARF, electroneurography and electromyography (ENMG) of peripheral nerves and muscles, and functional assessment of respiratory muscles.¶Results: NM-ARF was diagnosed at the time of (one case), or 1–3 days after, ICU discharge. Limb weakness alarmed the physicians, while the signs of the NM-ARF were initially undetected. In the first observed case the acute respiratory failure was near fatal, and necessitated ICU readmission, while in the other cases 2 weeks of aggressive chest physiotherapy permitted resolution of the respiratory failure. History, clinical course and ENMG indicated the diagnosis of critical illness myopathy and neuropathy (CRIMYNE). Three patients recovered fully, while two had persisting evidence of axonal polyneuropathy several months after the onset.¶Conclusions: Critically ill patients with prolonged ICU stay, sepsis and MOF are at great risk of developing CRIMYNE, which in turn may be responsible for NM-ARF. This latter complication may arise after resolution of the respiratory and cardiac dysfunctions and successful weaning from the ventilator. As NM-ARF may cause unplanned ICU readmission or even unexpected death, strict clinical surveillance and monitoring of respiratory muscle function is recommended after discharge to the general ward of patients with proven NM-ARF. Early intensive chest physiotherapy can resolve the condition.