Eosinopenia is a reliable marker of sepsis on admission to medical intensive care units

Introduction

Eosinopenia is a cheap and forgotten marker of acute infection that has not been evaluated previously in intensive care units (ICUs). The aim of the present study was to test the value of eosinopenia in the diagnosis of sepsis in patients admitted to ICUs.

Methods

A prospective study of consecutive adult patients admitted to a 12-bed medical ICU was performed. Eosinophils were measured at ICU admission. Two intensivists blinded to the eosinophils classified patients as negative or with systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, or septic shock.

Results

A total of 177 patients were enrolled. In discriminating noninfected (negative + SIRS) and infected (sepsis + severe sepsis + septic shock) groups, the area under the receiver operating characteristic curve was 0.89 (95% confidence interval (CI), 0.83 to 0.94). Eosinophils at <50 cells/mm³ yielded a sensitivity of 80% (95% CI, 71% to 86%), a specificity of 91% (95% CI, 79% to 96%), a positive likelihood ratio of 9.12 (95% CI, 3.9 to 21), and a negative likelihood ratio of 0.21(95% CI, 0.15 to 0.31). In discriminating SIRS and infected groups, the area under the receiver operating characteristic curve was 0.84 (95% CI, 0.74 to 0.94). Eosinophils at <40 cells/mm³ yielded a sensitivity of 80% (95% CI, 71% to 86%), a specificity of 80% (95% CI, 55% to 93%), a positive likelihood ratio of 4 (95% CI, 1.65 to 9.65), and a negative likelihood ratio of 0.25 (95% CI, 0.17 to 0.36).

Conclusion

Eosinopenia is a good diagnostic marker in distinguishing between noninfection and infection, but is a moderate marker in discriminating between SIRS and infection in newly admitted critically ill patients. Eosinopenia may become a helpful clinical tool in ICU practices.     

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.

     

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.     

Neutrophil gelatinase-associated lipocalin in adult septic patients with and without acute kidney injury

Purpose

To study the impact of inflammation/sepsis on the concentrations of neutrophil gelatinase-associated lipocalin (NGAL) in plasma and urine in adult intensive care unit (ICU) patients and to estimate the predictive properties of NGAL in plasma and urine for early detection of acute kidney injury (AKI) in patients with septic shock.

Methods

Sixty-five patients admitted to the general ICU at the Karolinska University Hospital Solna, Sweden, with normal plasma creatinine were assessed for eligibility. Twenty-seven patients with systemic inflammatory response syndrome (SIRS), severe sepsis, or septic shock without AKI and 18 patients with septic shock and concomitant AKI were included in the final analysis. Plasma and urine were analyzed twice daily for plasma NGAL (pNGAL), C-reactive protein (CRP), procalcitonin, myeloperoxidase, plasma cystatin C, plasma creatinine, urine NGAL (uNGAL), urine cystatin C, and urine α1-microglobulin.

Results

Of the 45 patients, 40 had elevated peak levels of pNGAL. Peak levels of pNGAL were not significantly different between septic shock patients with and without AKI. Peak levels of uNGAL were below the upper reference limit in all but four patients without AKI. uNGAL was a good predictor (area under ROC 0.86) whereas pNGAL was a poor predictor (area under ROC 0.67) for AKI within the next 12 h in patients with septic shock.

Conclusions

pNGAL is raised in patients with SIRS, severe sepsis, and septic shock and should be used with caution as a marker of AKI in ICU patients with septic shock. uNGAL is more useful in predicting AKI as the levels are not elevated in septic patients without AKI.     

Incidence,treatment, and outcome of severe sepsis in ICU-treated adults in Finland: the Finnsepsis study

Objective

To determine the incidence and outcome of severe sepsis in the adult Finnish population and to evaluate how treatment guidelines in severe sepsis are applied in clinical practice.

Study design

A prospective study in 24 closed multidisciplinary ICUs in 21 hospitals (4 university and 17 tertiary hospitals) in Finland.

Patients

All 4,500 consecutive ICU admission episodes were screened for severe sepsis during a 4-month period (1 November 2004 – 28 February 2005). The referral population was 3,743,225.

Results

The severe sepsis criteria were fulfilled in 470 patients, who had472 septic episodes. The incidence of severe sepsis in the ICUs in Finland was 0.38/1000 in the adult population (95% confidence interval 0.34–0.41). The mean ICU length of stay was 8.2?±?8.1?days. ICU, hospital, and 1-year mortality rates were 15.5%, 28.3%, and 40.9%, respectively. Respiratory failure requiring ventilation support was the most common organ failure (86.2%); septic shock was present in 77% and acute renal failure in 20.6% of cases. Activated protein C was given to only 15 of the 55 patients with indication (27%) and low-dose corticosteroids to 150 of 366 (41%) patients with septic shock.

Conclusions

This prospective study found the incidence of ICU-treated severe sepsis in Finland to be 0.38 per 1,000 of the population. The ICU and hospital mortalities were also lower than earlier reported in United States or Australia. Evidence-based sepsis therapies were not used as often as recommended.

     

De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock

Purposes

We set out to assess the safety and the impact on in-hospital and 90-day mortality of antibiotic de-escalation in patients admitted to the ICU with severe sepsis or septic shock.

Methods

We carried out a prospective observational study enrolling patients admitted to the ICU with severe sepsis or septic shock. De-escalation was defined as discontinuation of an antimicrobial agent or change of antibiotic to one with a narrower spectrum once culture results were available. To control for confounding variables, we performed a conventional regression analysis and a propensity score (PS) adjusted-multivariable analysis.

Results

A total of 712 patients with severe sepsis or septic shock at ICU admission were treated empirically with broad-spectrum antibiotics. Of these, 628 were evaluated (84 died before cultures were available). De-escalation was applied in 219 patients (34.9 %). By multivariate analysis, factors independently associated with in-hospital mortality were septic shock, SOFA score the day of culture results, and inadequate empirical antimicrobial therapy, whereas de-escalation therapy was a protective factor [Odds-Ratio (OR) 0.58; 95 % confidence interval (CI) 0.36–0.93). Analysis of the 403 patients with adequate empirical therapy revealed that the factor associated with mortality was SOFA score on the day of culture results, whereas de-escalation therapy was a protective factor (OR 0.54; 95 % CI 0.33–0.89). The PS-adjusted logistic regression models confirmed that de-escalation therapy was a protective factor in both analyses. De-escalation therapy was also a protective factor for 90-day mortality.

Conclusions

De-escalation therapy for severe sepsis and septic shock is a safe strategy associated with a lower mortality. Efforts to increase the frequency of this strategy are fully justified.     

Diagnostic and prognostic value of presepsin in the management of sepsis in the emergency department: a multicenter prospective study

Introduction

Sepsis, severe sepsis and septic shock are common conditions with high mortality. Their early diagnosis in the Emergency Department (ED) is one of the keys to improving survival. Procalcitonin (PCT) has been used as a biomarker in septic patients but has limited specificity and can be elevated in other scenarios of systemic inflammatory response syndrome (SIRS). Soluble CD14 (sCD14) or presepsin is the free fragment of a glycoprotein expressed on monocytes and macrophages. Preliminary reports suggest that levels of presepsin are significantly higher in septic patients than in healthy individuals. The aim of this study is to investigate the diagnostic and prognostic value of presepsin compared to PCT in people presenting at the ED with SIRS and suspected sepsis or septic shock.

Methods

This study was conducted in two major hospitals in Turin, Italy. One hundred six patients presenting to the EDs with suspected sepsis or septic shock were included, and another eighty-three patients affected by SIRS, but with no clinical evidence of infection, were recruited as controls. Blood samples were collected at first medical evaluation and for some patients after 24 and 72 h. The samples were analyzed using the PATHFAST Presepsin assay for sCD14, and commercial kits were used for other determinations (for example, PCT). Definitive diagnosis and survival rates were obtained afterward by analysis of digital medical records.

Results

Elevated concentrations of presepsin at presentation were observed in septic patients compared to control patients. The same trend was observed for mean values of PCT. Higher values of presepsin were observed in septic patients at presentation (time 0). The diagnostic accuracy of PCT was generally higher, and areas under the curve (AUCs) were 0.875 for PCT and 0.701 for presepsin. Mean presepsin values were significantly higher in nonsurvivor septic patients (60-day mortality) than in survivors. No significant correlation was noted between PCT and survival.

Conclusions

In our experience, presepsin was useful in the early diagnosis of infection in a complex population of patients with SIRS, sepsis, severe sepsis and septic shock who presented to the ED. Presepsin showed a significant prognostic value, and initial values were significantly correlated with in-hospital mortality of patients affected by sepsis, severe sepsis or septic shock.     

Prediction of pediatric sepsis mortality within 1 h of intensive care admission

Purpose

The definitions of sepsis and septic shock have recently been revised in adults, but contemporary data are needed to inform similar approaches in children.

Methods

Multicenter cohort study including children <16 years admitted with sepsis or septic shock to ICUs in Australia and New Zealand in the period 2012–2015. We assessed septic shock criteria at ICU admission to define sepsis severity, using 30-day mortality as outcome. Through multivariable logistic regression, a pediatric sepsis score was derived using variables available within 60 min of ICU admission.

Results

Of 42,523 pediatric admissions, 4403 children were admitted with invasive infection, including 1697 diagnosed as having sepsis/septic shock on admission. Mortality was 8.5% (144/1697) and 50.7% of deaths occurred within 48 h of admission. The presence of septic shock as defined by the 2005 consensus was sensitive but not specific in predicting mortality (AUC = 0.69; 95% CI 0.65–0.72). Combinations of hypotension, vasopressor therapy, and lactate >2 mmol/l discriminated poorly (AUC <0.60). Multivariate models showed that oxygenation markers, ventilatory support, hypotension, cardiac arrest, serum lactate, pupil responsiveness, and immunosuppression were the best-performing predictors (0.843; 0.811–0.875). We derived a pediatric sepsis score (0.817; 0.779–0.855), and every one-point increase was associated with a 28.5% (23.8–33.2%) increase in the odds of death. Children with a score ≥6 had 19.8% mortality and accounted for 74.3% of deaths. The sepsis score performed comparably when applied to all children admitted with invasive infection (0.810; 0.781–0.840).

Conclusions

We observed mortality patterns specific to pediatric sepsis that support the need for specialized definitions of sepsis severity in children. We demonstrated the importance of lactate, cardiovascular, and respiratory derangements at ICU admission for the identification of children with substantially higher risk of sepsis mortality.

     

Incidence and risk factors for mortality in paediatric severe sepsis: results from the national paediatric intensive care registry in Japan

Purpose

To assess the incidence, background, outcome and risk factors for death of severe sepsis in Japanese paediatric intensive care units (PICUs).

Methods

A data analysis of a prospective, multicentre, 3-year case registry from nine medical-surgical Japanese PICUs. Children with severe sepsis, aged 0–15?years, who were consecutively admitted to the participating PICUs from 1 January 2007 to 31 December 2009 were enrolled. The incidence, background, causative pathogens or infective foci, outcome and risk factors for death caused by severe sepsis were analysed.

Results

One hundred forty-one cases were registered. After the exclusion of 14 patients because of incomplete data or inappropriate entry, 127 patients were eligible for the analysis. There were 60 boys and 67 girls, aged 23 [5–68] (median [IQR]) months and weighed 10 [5.5–16.5]?kg. The incidence was 1.4?% of total PICU admissions. Sepsis was community-acquired in 35?%, PICU-acquired in 37?% and acquired in hospital general wards in 28?%. Methicillin-resistant Staphylococcus aureus was the most frequent pathogen. The crude 28-day mortality was 18.9?%, comparable to the mean PIM-2 predicted mortality (17.7?%). The mortality rate in patients with shock was significantly increased to 28?% compared to those without shock (5?%). The presences of existing haematological disorders (OR 8.97, 95?% CI, 1.56–51.60) and shock (OR 5.35, 1.04–27.44) were significant factors associated with mortality by multivariate analysis.

Conclusions

The mortality from severe sepsis/septic shock in Japanese PICUs was?~19?%. Haematological disorders and presence of shock were associated with death.     

The impact of the severity of sepsis on the risk of hypoglycaemia and glycaemic variability

Introduction

The purpose of this study was to assess the relation between glycaemic control and the severity of sepsis in a cohort of patients treated with intensive insulin therapy (IIT).

Methods

In a prospective, observational study, all patients in the intensive care unit (ICU) (n = 191) with sepsis, severe sepsis or septic shock were treated with IIT (target blood glucose (BG) level 80 to 140 mg/dl instead of strict normoglycaemia). BG values were analysed by calculating mean values, rate of BG values within different ranges, rate of patients experiencing BG values within different levels and standard deviation (SD) of BG values as an index of glycaemic variability.

Results

The number of patients with hypoglycaemia and hyperglycaemia was highly dependent on the severity of sepsis (critical hypoglycaemia ≤ 40 mg/dl: sepsis: 2.1%, severe sepsis: 6.0%, septic shock: 11.5%, p = 0.1497; hyperglycaemia: >140 mg/dl: sepsis: 76.6%, severe sepsis: 88.0%, septic shock: 100%, p = 0.0006; >179 mg/dl: sepsis: 55.3%, severe sepsis: 73.5%, septic shock: 88.5%, p = 0.0005; >240 mg/dl: sepsis: 17.0%, severe sepsis: 48.2%, septic shock: 45.9%, p = 0.0011). Multivariate analyses showed a significant association of SD levels with critical hypoglycaemia especially for patients in septic shock (p = 0.0197). In addition, SD levels above 20 mg/dl were associated with a significantly higher mortality rate relative to those with SD levels below 20 mg/dl (24% versus 2.5%, p = 0.0195).

Conclusions

Patients with severe sepsis and septic shock who were given IIT had a high risk of hypoglycaemia and hyperglycaemia. Among these patients even with a higher target BG level, IIT mandates an increased awareness of the occurrence of critical hypoglycaemia, which is related to the severity of the septic episode.     

Incidence, organ dysfunction and mortality in severe sepsis: a Spanish multicentre study

Introduction

Sepsis is a leading cause of admission to non-cardiological intensive care units (ICUs) and the second leading cause of death among ICU patients. We present the first extensive dataset on the epidemiology of severe sepsis treated in ICUs in Spain.

Methods

We conducted a prospective, observational, multicentre cohort study, carried out over two 3-month periods in 2002. Our aims were to determine the incidence of severe sepsis among adults in ICUs in a specific area in Spain, to determine the early (48 h) ICU and hospital mortality rates, as well as factors associated with the risk of death.

Results

A total of 4,317 patients were admitted and 2,619 patients were eligible for the study; 311 (11.9%) of these presented at least 1 episode of severe sepsis, and 324 (12.4%) episodes of severe sepsis were recorded. The estimated accumulated incidence for the population was 25 cases of severe sepsis attended in ICUs per 100,000 inhabitants per year. The mean logistic organ dysfunction system (LODS) upon admission was 6.3; the mean sepsis-related organ failure assessment (SOFA) score on the first day was 9.6. Two or more organ failures were present at diagnosis in 78.1% of the patients. A microbiological diagnosis of the infection was reached in 209 episodes of sepsis (64.5%) and the most common clinical diagnosis was pneumonia (42.8%). A total of 169 patients (54.3%) died in hospital, 150 (48.2%) of these in the ICU. The mortality in the first 48 h was 14.8%. Factors associated with early death were haematological failure and liver failure at diagnosis, acquisition of the infection prior to ICU admission, and total LODS score on admission. Factors associated with death in the hospital were age, chronic alcohol abuse, increased McCabe score, higher LODS on admission, ΔSOFA 3-1 (defined as the difference in the total SOFA scores on day 3 and on day 1), and the difference of the area under the curve of the SOFA score throughout the first 15 days.

Conclusions

We found a high incidence of severe sepsis attended in the ICU and high ICU and hospital mortality rates. The high prevalence of multiple organ failure at diagnosis and the high mortality in the first 48 h suggests delays in diagnosis, in initial resuscitation, and/or in initiating appropriate antibiotic treatment.     

Prohormones for prediction of adverse medical outcome in community-acquired pneumonia and lower respiratory tract infections

Introduction

The benefits and use of low-dose corticosteroids (LDCs) in severe sepsis and septic shock remain controversial. Surviving sepsis campaign guidelines suggest LDC use for septic shock patients poorly responsive to fluid resuscitation and vasopressor therapy. Their use is suspected to be wide-spread, but paucity of data regarding global practice exists. The purpose of this study was to compare baseline characteristics and clinical outcomes of patients treated or not treated with LDC from the international PROGRESS (PROmoting Global Research Excellence in Severe Sepsis) cohort study of severe sepsis.

Methods

Patients enrolled in the PROGRESS registry were evaluated for use of vasopressor and LDC (equivalent or lesser potency to hydrocortisone 50 mg six-hourly plus 50 μg 9-alpha-fludrocortisone) for treatment of severe sepsis at any time in intensive care units (ICUs). Baseline characteristics and hospital mortality were analyzed, and logistic regression techniques used to develop propensity score and outcome models adjusted for baseline imbalances between groups.

Results

A total of 8,968 patients with severe sepsis and sufficient data for analysis were studied. A total of 79.8% (7,160/8,968) of patients received vasopressors, and 34.0% (3,051/8,968) of patients received LDC. Regional use of LDC was highest in Europe (51.1%) and lowest in Asia (21.6%). Country use was highest in Brazil (62.9%) and lowest in Malaysia (9.0%). A total of 14.2% of patients on LDC were not receiving any vasopressor therapy. LDC patients were older, had more co-morbidities and higher disease severity scores. Patients receiving LDC spent longer in ICU than patients who did not (median of 12 versus 8 days; P <0.001). Overall hospital mortality rates were greater in the LDC than in the non-LDC group (58.0% versus 43.0%; P <0.001). After adjusting for baseline imbalances, in all mortality models (with vasopressor use), a consistent association remained between LDC and hospital mortality (odds ratios varying from 1.30 to 1.47).

Conclusions

Widespread use of LDC for the treatment of severe sepsis with significant regional and country variation exists. In this study, 14.2% of patients received LDC despite the absence of evidence of shock. Hospital mortality was higher in the LDC group and remained higher after adjustment for key determinates of mortality.     

Changes in peroxisome proliferator-activated receptor-gamma activity in children with septic shock

Purpose

To assess changes in peroxisome proliferator-activated receptor-γ (PPARγ) in peripheral blood mononuclear cells (PBMC) from critically ill children with sepsis. Additionally, to investigate the effects of sepsis on the endogenous activator of PPARγ, 15-deoxy-?^12,14-PGJ₂ (15d-PGJ₂), and the downstream targets of PPARγ activity, adiponectin and resistin.

Methods

Single-center, prospective case–control study in critically ill children with systemic inflammatory response syndrome, sepsis or septic shock.

Results

PPARγ nuclear protein expression was decreased but PPARγ activity was increased in PBMC from children with septic shock compared with controls. PPARγ activity on day 1 was significantly higher in patients with higher pediatric risk of mortality (PRISM) score compared with controls [mean 0.22 optical density (OD) ± standard error of the mean (SEM) 0.03 versus 0.12 OD ± 0.02; p < 0.001]. Patients with resolved sepsis had increased levels of the endogenous PPARγ ligand, 15d-PGJ₂, compared with patients with systemic inflammatory response syndrome (SIRS) and septic shock (77.7 ± 21.7 versus 58 ± 16.5 pg/ml; p = 0.03). Plasma high-molecular-weight adiponectin (HMWA) and resistin levels were increased in patients with septic shock on day 1 and were significantly higher in patients with higher PRISM scores. Nonsurvivors from sepsis had higher resistin levels on the first day of hospitalization compared with survivors from septic shock [660 ng/ml, interquartile range (IQR) 585–833 ng/ml versus 143 ng/ml, IQR 66–342 ng/ml; p < 0.05].

Conclusions

Sepsis is associated with altered PPARγ expression and activity in PBMC. Plasma adipokines correlate with risk of mortality scores in sepsis and may be useful biomarkers. Further studies are needed to understand the mechanisms underlying changes in PPARγ in sepsis.     

Challenges in assessing the burden of sepsis and understanding the inequalities of sepsis outcomes between National Health Systems: secular trends in sepsis and infection incidence and mortality in Germany

Purpose

Sepsis contributes considerably to global morbidity and mortality, while reasons for its increasing incidence remain unclear. We assessed risk adjusted secular trends in sepsis and infection epidemiology in Germany.

Methods

Retrospective cohort study using nationwide German hospital discharge data. We assessed incidence, outcomes and trends of hospital-treated sepsis and infections between 2010 and 2015. Sepsis was identified by explicit ICD-10 sepsis codes. As sensitivity analysis, results were compared with sepsis cases identified by implicit sepsis coding (combined infection and organ dysfunction codes).

Results

Among 18 664 877 hospital admissions in 2015, 4 213 116 (22.6%) patients had at least one infection code. There were 320 198 patients that had explicit sepsis codes including 136 542 patients with severe sepsis and septic shock; 183 656 patients were coded as sepsis without organ dysfunction. For patients with explicitly coded sepsis (including severe sepsis), or with severe sepsis alone, mortality rates over the period 2010–2015 decreased from 26.6 to 23.5%, and from 47.8 to 41.7%, respectively.

Conclusions

Sepsis and infection remain significant causes of hospital admission and death in Germany. Sepsis-related mortality is higher and has declined to a lesser degree than in other high-income countries. Although infection rates steadily increased, the observed annual increase of sepsis cases seems to result, to a considerable degree, from improved coding of sepsis.

     

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.     

Beneficial effects of the heme oxygenase-1/carbon monoxide system in patients with severe sepsis/septic shock

Purpose

We evaluated the relations among the arterial carbon monoxide (CO) concentration, heme oxygenase (HO)-1 expression by monocytes, oxidative stress, plasma levels of cytokines and bilirubin, and the outcome of patients with severe sepsis or septic shock.

Methods

Thirty-six patients who fulfilled the criteria for severe sepsis or septic shock and 21 other patients without sepsis during their stay in the intensive care unit were studied. HO-1 protein expression by monocytes, arterial CO, oxidative stress, bilirubin, and cytokines were measured.

Results

Arterial blood CO, cytokine, and bilirubin levels, and monocyte HO-1 protein expression were higher in patients with severe sepsis/septic shock than in non-septic patients. Increased HO-1 expression was related to the arterial CO concentration and oxidative stress. There was a positive correlation between survival and increased HO-1 protein expression or a higher CO level.

Conclusions

Arterial CO and monocyte HO-1 protein expression were increased in critically ill patients, particularly those with severe sepsis or septic shock, suggesting that oxidative stress is closely related to HO-1 expression. The HO-1/CO system may play an important role in sepsis.     

Fluid management and risk factors for renal dysfunction in patients with severe sepsis and/or septic shock

Introduction

The causative role of new hydroxyethyl starch (HES 130/0.4) in renal dysfunction frequency (a > 50% increase in serum creatinine or need for renal replacement therapy (RRT)) remains debated. Using the database of a multicenter study focusing on patients with severe sepsis and septic shock, the present study aimed at identifying factors associated with the occurrence of renal dysfunction.

Methods

Among the 435 patients in a multicenter study of patients with severe sepsis and septic shock in 15 Southern French ICUs, 388 patients surviving after 24 hour, without a history of renal failure were included. Factors associated with renal dysfunction and RRT were isolated using a multivariate analysis with logistic regression.

Results

Renal dysfunction was reported in 117 (33%) patients. Ninety patients required RRT. Among study participants, 379 (98%) were administered fluids in the first 24 hours of management: HES 130/0.4 only (n = 39), crystalloids only (n = 63), or both HES 130/0.4 and crystalloids (n = 276). RRT was independently associated with the need for vasopressors and the baseline value of serum creatinine in the first 24 hours. Multivariate analysis indicated that male gender, SAPS II score, being a surgical patient, lack of decrease in SOFA score during the first 24 hours, and the interventional period of the study were independently associated with renal dysfunction. Mortality increased in the presence of renal dysfunction (48% versus 24%, P < 0.01).

Conclusions

Despite being used in more than 80% of patients with severe sepsis and/or septic shock, the administration of HES 130/0.4 in the first 24 hours of management was not associated with the occurrence of renal dysfunction.     

Heat stress is associated with decreased lactic acidemia in rat sepsis

Background

Elevated plasma lactate has been shown to correlate with mortality in patients with septic shock. Heat stress prior to sepsis has resulted in reduction in acute lung injury and mortality. We investigated whether heat stress resulted in decreased plasma lactate concentration and protected the lung by decreasing the inflammatory response to sepsis.

Results

Plasma lactate concentration was elevated in septic rats without prior heat stress. Lactic acid levels were significantly lower in heat-treated septic rats (P < 0.05) and were not significantly different when compared with control rats. Septic rats with or without heat pretreatment had significantly higher myeloperoxidase activity in the lung than did control groups. Heat pretreatment did not prevent neutrophil infiltration or inflammatory mediator production in the lung.

Conclusion

Prior heat stress ameliorates lactic acidemia in rat sepsis. Heat stress did not attenuate the pulmonary inflammatory process. The mechanism of heat-induced protection from lactic acidemia in sepsis needs to be further explored.     

Quality of life of survivors from severe sepsis and septic shock may be similar to that of others who survive critical illness

Introduction

The objective of the present study was to compare the health-related quality of life (HR-QoL) of survivors from severe sepsis and septic shock with HR-QoL in others who survived critical illness not involving sepsis.

Methods

From March 1997 to March 2001, adult patients in an eight-bed medical/surgical intensive care unit (ICU) of a tertiary care hospital admitted with severe sepsis or septic shock (sepsis group; n = 305) were enrolled and compared with patients admitted without sepsis (control group; n = 392). Patients younger than 18 years (n = 48) and those whose ICU stay was 1 day or less (n = 453) were excluded. In addition, patients exhibiting nonsevere sepsis on admission were excluded (n = 87). Finally, patients who developed nonsevere sepsis or severe sepsis/septic shock after admission were also excluded (n = 88).

Results

In-hospital mortality rates were 34% in the sepsis group and 26% in the control group. There were no differences in sex, age, main activity (work status), and previous health state between groups. Survivors in the sepsis group had a significantly higher Acute Physiology and Chronic Health Evaluation II score on admission (17 versus 12) and stayed significantly longer in the ICU. A follow-up appointment was held 6 months after ICU discharge, and an EQ-5D (EuroQol five-dimension) questionnaire was administered. A total of 104 sepsis survivors and 133 survivors in the control group answered the EQ-5D questionnaire. Sepsis survivors reported significantly fewer problems only in the anxiety/depression dimension. Although there were no significant differences in the other dimensions of the EQ-5D, there was a trend towards fewer problems being reported by sepsis survivors.

Conclusion

Evaluation using the EQ-5D at 6 months after ICU discharge indicated that survivors from severe sepsis and septic shock have a similar HR-QoL to that of survivors from critical illness admitted without sepsis.