Plasma and urine neutrophil gelatinase-associated lipocalin in the diagnosis of new onset acute kidney injury in critically ill patients

Introduction

Neutrophil gelatinase-associated lipocalin (NGAL) has been demonstrated to be a useful early diagnostic biomarker of acute kidney injury (AKI) where the timing of the insult is certain. However, NGAL is not well validated in adult critical care practice because of indeterminate timing of injury. Therefore, we sought to establish the predictive ability of both urine and plasma NGAL to detect AKI in ICU patients.

Method

This prospective observational study was performed in a busy large district general hospital mixed surgical-medical ICU in Reading, UK. Consecutive adult admissions to the ICU, with absence of chronic kidney disease, renal transplant or AKI as defined by RIFLE criteria were included. Blood and urine specimens were collected at admission and every 24 hours until 72 hours and tested for NGAL. The purpose of the study was to assess whether urinary NGAL (uNGAL) or plasma NGAL (pNGAL) can predict the occurrence of AKI at an earlier point of time than the conventional markers, that is creatinine and urine output as is used in RIFLE criteria.

Results

Over a 12-month period, 194 patients were enrolled. In total, 59 (30.4%) patients developed AKI. The admission pNGAL and uNGAL were significantly higher in the patients who developed AKI compared to the non-AKI patients (436 ng/mL (240, 797) versus 168 ng/mL (121.3, 274.3) P <0.001 and 342 ng/mL (61.5, 1,280) versus 34.5 ng/mL (11.5, 107.75) P <0.001 respectively). Hospital mortality was higher in the AKI group (17% versus 4%). Plasma NGAL performed fairly on admission (AUROC 0.77) and thereafter performance improved at 24 and 48 hours (AUROC 0.88 and 0.87) following ICU admission. Urine NGAL had a fair predictive value on admission (AUROC 0.79) and at 24 hours (AUROC 0.78) and was good at 48 hours (AUROC 0.82).

Conclusions

In critically ill patients without pre-existing kidney disease, both pNGAL and uNGAL measured at admission can predict AKI (defined by RIFLE criteria) occurrence up to 72 hours post-ICU admission and their performance (AUROC) was fair. The accuracy of NGAL appeared to improve slightly as patients progressed through their ICU stay. Serial measurements of NGAL (both pNGAL and uNGAL) may be of added value in an ICU setting to predict the occurrence of AKI.     

NGAL、KIM-1、TIMP-2对脓毒症所致AKI早期诊断价值的前瞻性临床队列研究

目的评估血浆中性粒细胞明胶酶相关载脂蛋白（pNGAL）、尿中性粒细胞明胶酶相关载脂蛋白（uNGAL）、尿肾损伤分子-1（KIM-1）和尿金属蛋白酶抑制物-2（TIMP-2）对脓毒症急性肾损伤（AKI）的早期诊断价值。 方法收集2015年6月至2016年1月期间入住苏北人民医院重症医学科（ICU）的脓毒症患者,连续观察72 h,以是否出现AKI进行分组,即脓毒症AKI组及脓毒症非AKI组,收集各组患者的一般资料,入ICU时（0 h）,入ICU后6、12、24、48、72 h时的外周静脉血及尿液样本,并采用酶联免疫吸附试验（ELISA）测定各时刻pNGAL、uNGAL、尿KIM-1、尿TIMP-2的表达水平,绘制受试者工作特征（ROC）曲线,计算曲线下面积（AUC）,评价pNGAL、uNGAL、尿KIM-1、尿TIMP-2对脓毒症AKI的早期诊断价值。 结果研究期间共有522例患者入住我院ICU,最终纳入符合研究标准的脓毒症患者共90例,其中38例发生AKI,占42.22%。脓毒症AKI组患者pNGAL、uNGAL水平在入住ICU后6 h开始升高（P<0.05）,12 h开始明显升高,24 h达到峰值,在6、12、24、48、72 h时pNGAL浓度明显高于同时刻脓毒症非AKI组患者,差异具有统计学意义（P<0.05）。脓毒症AKI组患者尿KIM-1、尿TIMP-2水平在入住ICU后6 h开始升高（P<0.05）,12 h开始明显升高并达到峰值,在6、12、24、48、72 h时尿KIM-1水平明显高于同时刻脓毒症非AKI组患者,差异具有统计学意义（P<0.05）。ROC曲线显示pNGAL、uNGAL、尿KIM-1、尿TIMP-2的ROC的AUC分别为0.862、0.858、0.788、0.771,其诊断截断值分别为119.30、120.36、90.07、3299.50 ng/L。各时间点绘制ROC曲线显示,在T-12 h时,pNGAL、尿KIM-1及尿TIMP-2的ROC的AUC分别为1.00、0.96、0.92,在T-18 h时,uNGAL的ROC的AUC为0.95。 结论脓毒症AKI患者pNGAL、uNGAL、尿KIM-1、尿TIMP-2表达水平明显早于血肌酐升高,早于AKI临床诊断标准,有望用于脓毒症AKI的早期诊断。     

Accuracy of plasma neutrophil gelatinase-associated lipocalin in the early diagnosis of contrast-induced acute kidney injury in critical illness

Purpose

Neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker for acute kidney injury (AKI). We evaluated the diagnostic and prognostic accuracies of plasma NGAL (pNGAL) for contrast-induced AKI (CI-AKI) in critically ill patients.

Methods

In a prospective observational study in two adult intensive care units in a university hospital, 100 consecutive critically ill patients with stable serum creatinine concentrations up to 48 h before contrast medium (CM) injection were enrolled. Serial blood sampling for pNGAL analysis was performed at enrolment, 2, 6, and 24 h after CM injection. The primary outcome was CI-AKI, defined by AKIN criteria, within the first 72 h following CM injection. Secondary outcomes were the need for renal replacement therapy (RRT) and mortality.

Results

Of the 98 patients analyzed, 30 developed CI-AKI. The pNGAL levels did not differ in patients with or without CI-AKI, and were higher in septic patients compared to nonseptic patients, and in patients with AKI preceding CM injection. The discriminative value of pNGAL to predict CI-AKI and mortality was poor; although, it did predict the need for RRT requirement after CM injection (area under receiver-operating characteristic curve, 0.85, 0.80, 0.83 and 0.86 at H0, H2, H6 and H24, respectively).

Conclusion

CI-AKI was common in critically ill patients. pNGAL levels were higher in patients with sepsis or previous AKI, but did not help to diagnose CI-AKI any earlier than serum creatinine after CM injection. However, pNGAL could be of interest to detect patients at risk of subsequent RRT requirement.     

The nature and discriminatory value of urinary neutrophil gelatinase-associated lipocalin in critically ill patients at risk of acute kidney injury

Background

Different molecular forms of urinary neutrophil gelatinase-associated lipocalin (NGAL) have recently been discovered. We aimed to explore the nature, source and discriminatory value of urinary NGAL in intensive care unit (ICU) patients.

Methods

We simultaneously measured plasma NGAL (pNGAL), urinary NGAL (uNGAL), and estimated monomeric and homodimeric uNGAL contribution using Western blotting-validated enzyme-linked immunosorbent assays [uNGAL_E1 and uNGAL_E2] and their calculated ratio in 102 patients with the systemic inflammatory response syndrome and oliguria, and/or a creatinine rise of >25 μmol/L.

Measurements and main results

Bland–Altman analysis demonstrated that, despite correlating well (r = 0.988), uNGAL and uNGAL_E1 were clinically distinct, lacking both accuracy and precision (bias: 266.23; 95 % CI 82.03–450.44 ng/mg creatinine; limits of agreement: ?1,573.86 to 2,106.32 ng/mg creatinine). At best, urinary forms of NGAL are fair (area under the receiver operating characteristic [AUROC] ≤0.799) predictors of renal or patient outcome; most perform significantly worse. The 44 patients with a primarily monomeric source of uNGAL had higher pNGAL (118.5 ng/ml vs. 72.5 ng/ml; p < 0.001), remaining significant following Bonferroni correction.

Conclusions

uNGAL is not a useful predictor of outcome in this ICU population. uNGAL patterns may predict distinct clinical phenotypes. The nature and source of uNGAL are complex and challenge the utility of NGAL as a uniform biomarker.     

Assessment of biochemical markers in the early post-burn period for predicting acute kidney injury and mortality in patients with major burn injury: comparison of serum creatinine,serum cystatin-C,plasma and urine neutrophil gelatinase-associated lipocalin

Introduction

The reported mortality rates range from 28% to 100% in burn patients who develop acute kidney injury (AKI) and from 50% to 100% among such patients treated with renal replacement therapy. Recently, the serum cystatin C and plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) levels have been introduced as early biomarkers for AKI; the levels of these biomarkers are known to increase 24 to 48 hours before the serum creatinine levels increase. In this study, we aimed to estimate the diagnostic utility of the cystatin C and plasma and urine NGAL levels in the early post-burn period as biomarkers for predicting AKI and mortality in patients with major burn injuries.

Methods

From May 2011 to July 2012, 90 consecutive patients with a burn wound area comprising ≥ 20% of the total body surface area (TBSA) were enrolled in this study. Whole blood and urine samples were obtained for measuring the serum creatinine, serum cystatin C, and urine and plasma NGAL levels at 0, 3, 6, 12, 24, and 48 hours after admission. Receiver operating characteristic curve, area under the curve, and multivariate logistic regression analyses were performed to assess the predictive values of these biomarkers for AKI and mortality.

Results

In the multivariate logistic regression analysis, all variables, including age, percentage TBSA burned, sex, inhalation injury, and serum creatinine levels, serum cystatin C levels, and plasma and urine NGAL levels were independently associated with AKI development. Moreover, age, sex, percentage TBSA burned, and plasma and urine NGAL levels were independently associated with mortality. However, inhalation injury and the serum creatinine and cystatin C levels were not independently associated with mortality.

Conclusions

Massively burned patients who maintained high plasma and urine NGAL levels until 12 hours after admission were at the risk of developing early AKI and early mortality with burn shock. However, the plasma and urine NGAL levels in the early post-burn period failed to predict late AKI and non-burn shock mortality in this study. Nevertheless, the plasma and urine NGAL levels were independently associated with AKI development and mortality within 48 hours after admission.     

Diagnostic and prognostic value of neutrophil gelatinase-associated lipocalin,matrix metalloproteinase-9, and tissue inhibitor of matrix metalloproteinases-1 for sepsis in the Emergency Department: an observational study

Introduction

The aim of this study was to evaluate the early diagnostic, risk stratification and prognostic value of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), compared with procalcitonin (PCT) and the Mortality in Emergency Department Sepsis (MEDS) score in septic patients in the emergency department (ED).

Methods

In total, 480 consecutive adult patients were enrolled in this study. They fulfilled the systemic inflammatory response syndrome (SIRS) criteria and were admitted to the ED of Beijing Chaoyang Hospital from February 2013 to August 2013. A total of 40 healthy controls comprised the control group. The patients were classified into four groups: SIRS, sepsis, severe sepsis, and septic shock. Serum NGAL, MMP-9, TIMP-1 and PCT were measured, and MEDS score was calculated at enrollment. The prognostic values of NGAL, MMP-9 and TIMP-1 were compared with PCT and MEDS score. A 28-day follow-up was performed for all patients.

Results

The median levels of serum NGAL and TIMP-1 increased with sepsis severity. The areas under the receiver operating characteristic (AUC) curves of NGAL or TIMP-1 were greater than those of PCT and MEDS score in diagnosing and predicting 28-day mortality, and the AUC of a combination of NGAL and MEDS score or TIMP-1 and MEDS score was more significant. Serum NGAL, MMP-9 and TIMP-1 levels were significantly higher in non-survivors than survivors at 28 days’ follow-up. In addition, the level of NGAL was much higher in septic patients with acute kidney injury (AKI) than those without AKI. NGAL, TIMP-1, MMP-9 and MEDS score were found to be independent predictors of 28-day mortality in septic patients. The levels of serum NGAL and TIMP-1 were positively correlated with PCT and MEDS score in every septic group.

Conclusions

NGAL and TIMP-1 are valuable for the risk stratification, early diagnosis and prognostication of sepsis in the ED. NGAL is also a valuable biomarker for prognosis of septic patients with AKI in the ED.     

New biomarker panel of plasma neutrophil gelatinase–associated lipocalin and endotoxin activity assay for detecting sepsis in acute kidney injury

Purpose

Septic acute kidney injury (AKI) shows an unacceptably high mortality rate. Detection of sepsis is important for the clinical management of AKI patients. This study was undertaken to evaluate 2 biomarkers of neutrophil gelatinase–associated lipocalin (NGAL) and endotoxin activity (EA) assay and their combination for detecting sepsis in AKI.

Materials and Methods

Adult intensive care unit patients consisting of 40 non-AKI, 65 AKI without sepsis, 10 non-AKI with sepsis, and 24 septic AKI were examined in a cross-sectional manner. Plasma NGAL and EA values in whole blood were measured at recruitment. We evaluated whether combining 2 different biomarkers would improve the performance of each biomarker using receiver operating characteristic analysis.

Results

Plasma NGAL was significantly higher in septic AKI patients than in the other AKI patients and non-AKI patients, whereas EA values were higher in septic patients than nonseptic patients irrespective of AKI complication. Combination of plasma NGAL and EA value increased the area under the curve of the receiver operating characteristic curve and showed better performance compared with a clinical model consisting of clinically available variables.

Conclusion

Combinations of plasma NGAL and EA, which are operating via different pathological pathways, significantly improved their detection performance in complicated conditions of septic AKI.     

Evaluation of urinary tissue inhibitor of metalloproteinase-2 in acute kidney injury: a prospective observational study

Introduction

Tissue inhibitor of metalloproteinase-2 (TIMP-2) is an emerging acute kidney injury (AKI) biomarker. We evaluated the performance of urinary TIMP-2 in an adult mixed ICU by comparison with other biomarkers that reflect several different pathways of AKI.

Methods

In this study, we prospectively enrolled 98 adult critically ill patients who had been admitted to the adult mixed ICU. Urinary TIMP-2 and N-acetyl-β-d-glucosaminidase (NAG) and plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin-6 (IL-6) and erythropoietin (EPO) were measured on ICU admission. We evaluated these biomarkers’ capability of detecting AKI and its severity as determined by using the Kidney Disease Improving Global Outcomes serum creatinine criteria, as well as its capacity to predict in-hospital mortality. The impact of sepsis, the leading cause of AKI in ICUs, was also evaluated.

Results

We found AKI in 42 patients (42.9%). All biomarkers were significantly higher in AKI than in non-AKI. In total, 27 patients (27.6%) developed severe AKI. Urinary TIMP-2 was able to distinguish severe AKI from non-severe AKI with an area under the receiver operating characteristic curve (AUC-ROC) of 0.80 (95% confidence interval, 0.66 to 0.90). A total of 41 cases (41.8%) were complicated with sepsis. Although plasma NGAL and IL-6 were increased by sepsis, urinary TIMP-2 and NAG were increased not by sepsis, but by the presence of severe AKI. Plasma EPO was increased only by septic AKI. In-hospital mortality was 15.3% in this cohort. Urinary TIMP-2 and NAG, and plasma NGAL, were significantly higher in non-survivors than in survivors, although plasma IL-6 and EPO were not. Among the biomarkers, only urinary TIMP-2 was able to predict in-hospital mortality significantly better than serum creatinine.

Conclusion

Urinary TIMP-2 can detect severe AKI with performance equivalent to plasma NGAL and urinary NAG, with an AUC-ROC value higher than 0.80. Furthermore, urinary TIMP-2 was associated with mortality. Sepsis appeared to have only a limited impact on urinary TIMP-2, in contrast to plasma NGAL.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0716-5) contains supplementary material, which is available to authorized users.     

Brazilian Sepsis Epidemiological Study (BASES study)

Introduction

Consistent data about the incidence and outcome of sepsis in Latin American intensive care units (ICUs), including Brazil, are lacking. This study was designed to verify the actual incidence density and outcome of sepsis in Brazilian ICUs. We also assessed the association between the Consensus Conference criteria and outcome

Methods

This is a multicenter observational cohort study performed in five private and public, mixed ICUs from two different regions of Brazil. We prospectively followed 1383 adult patients consecutively admitted to those ICUs from May 2001 to January 2002, until their discharge, 28th day of stay, or death. For all patients we collected the following data at ICU admission: age, gender, hospital and ICU admission diagnosis, APACHE II score, and associated underlying diseases. During the following days, we looked for systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock criteria, as well as recording the sequential organ failure assessment score. Infection was diagnosed according to CDC criteria for nosocomial infection, and for community-acquired infection, clinical, radiological and microbiological parameters were used.

Results

For the whole cohort, median age was 65.2 years (49–76), median length of stay was 2 days (1–6), and the overall 28-day mortality rate was 21.8%. Considering 1383 patients, the incidence density rates for sepsis, severe sepsis and septic shock were 61.4, 35.6 and 30.0 per 1000 patient-days, respectively. The mortality rate of patients with SIRS, sepsis, severe sepsis and septic shock increased progressively from 24.3% to 34.7%, 47.3% and 52.2%, respectively. For patients with SIRS without infection the mortality rate was 11.3%. The main source of infection was lung/respiratory tract.

Conclusion

Our preliminary data suggest that sepsis is a major public health problem in Brazilian ICUs, with an incidence density about 57 per 1000 patient-days. Moreover, there was a close association between ACCP/SCCM categories and mortality rate.     

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.     

Urine biochemistry in septic and non-septic acute kidney injury: a prospective observational study

Purpose

Determine whether there are unique patterns to the urine biochemistry profile in septic compared with non-septic acute kidney injury (AKI) and whether urinary biochemistry predicts worsening AKI, need for renal replacement therapy and mortality.

Materials and Methods

Prospective cohort study of critically ill patients with septic and non-septic AKI, defined by the RIFLE (Risk, Injury, Failure, Loss, End-Stage) criteria. Urine biochemistry parameters were compared between septic and non-septic AKI and were correlated with neutrophil gelatinase-associated lipocalin (NGAL), worsening AKI, renal replacement therapy (RRT), and mortality.

Results

Eighty-three patients were enrolled, 43 (51.8%) with sepsis. RIFLE class was not different between groups (P = .43). Urine sodium (UNa) < 20 mmol/L, fractional excretion of sodium (FeNa) < 1%, and fractional excretion of urea (FeU) < 35% were observed in 25.3%, 57.8%, and 33.7%, respectively. Septic AKI had lower UNa compared with non-septic AKI (P = .04). There were no differences in FeNa or FeU between groups. Urine NGAL was higher for FeNa≥1% compared to FeNa<1% (177.4 ng/mL [31.9-956.5] vs 48.0 ng/mL [21.1-232.4], P = .04). FeNa showed low correlation with urine NGAL (P = .05) and plasma NGAL (P = .14). There was poor correlation between FeU and urine NGAL (P = .70) or plasma NGAL (P = .41). UNa, FeNa, and FeU showed poor discrimination for worsening AKI, RRT and mortality.

Conclusion

Urine biochemical profiles do not discriminate septic and non-septic AKI. UNa, FeNa, and FeU do not reliably predict biomarker release, worsening AKI, RRT or mortality. These data imply limited utility for these measures in clinical practice in critically ill patients with AKI.     

Is plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) determination in donors and recipients predictive of renal function after kidney transplantation?

Objectives

Delayed graft function (DGF) is still a major issue in kidney transplantation. Plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) were evaluated in a population of kidney donors and recipients to investigate their performance to predict early renal function.

Design and methods

Plasma (pNGAL) and urine (uNGAL) samples were obtained from donors before organ procurement, and from recipients before transplantation, and then 6, 24 and 48 h after the procedure. Kidney transplantations were performed from both living donors (LDs, n = 17) and deceased donors (DDs, n = 80). Recovery of renal function was evaluated as the time to reach serum creatinine < 2 mg/l or glomerular filtration rate (GFR) > 40 mL/min. Logistic regression was used to assess the ability of different variables to predict the occurrence of DGF.

Results

Plasma NGAL levels were significantly lower in LDs than in DDs. No episodes of DGF were recorded among LD kidney recipients, but DGF was observed in 25% of patients in the DD group. There was no correlation between donor pNGAL and uNGAL values and the occurrence of post-transplant DGF. Recipient pNGAL performed better than uNGAL in terms of predicting DGF occurrence. Donor pNGAL and uNGAL values did not influence the time needed to reach serum creatinine levels of < 2 mg/dl after transplantation. When time to reach eGFR of > 40 mL/min is considered, only donor uNGAL seems to be a predictor of graft function recovery. However, recipient pNGAL values obtained 24 and 48 h after transplantation, but not uNGAL values, were found to be a significant predictor of graft function recovery.

Conclusions

Plasma NGAL level determination in recipients, but not in donors, proved to be a reliable predictor of DGF occurrence and renal function restoration, but too long for an interval to be able to compete with biomarkers currently used in clinical practice.     

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.     

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.     

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.     

血中性粒细胞明胶酶相关脂质运载蛋白对ICU中急性肾损伤的早期诊断价值

目的研究检测血中性粒细胞明胶酶相关脂质运载蛋白(NGAL)对重症患者急性肾损伤(AKI)的早期诊断价值。方法以2011年1月到2011年9月收入首都医科大学附属复兴医院ICU的重症患者作为研究对象,登记患者284例,最终有268例患者纳入研究,其中AKI组112例,非AKI组156例,并选取40例健康体检者作为健康对照组。研究组留取患者入选时血样和入选后1～4 d血样,用酶联免疫吸附法(ELISA)检测血清NGAL(pNGAL)水平。用受试者工作特征曲线(ROC)评价pNGAL对AKI的早期诊断作用以及预测需肾脏替代治疗(RRT)和AKI严重程度的关系。结果血NGAL可以诊断入ICU后48 h内的AKI发生,ROC曲线下面积为0.82(95%CI 0.68～0.93);预测RRT的使用,ROC曲线下面积为0.84(95%CI 0.73～0.95);与AKI的严重程度密切相关(R=0.554,P<0.001)。结论在成人普通ICU中血NGAL可以成为AKI的早期诊断标记物,能预测RRT的使用,与AKI的严重程度密切相关。     

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.     

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 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.

     

Plasma neutrophil gelatinase-associated lipocalin for the prediction of acute kidney injury in acute heart failure

Introduction

The accurate prediction of acute kidney injury (AKI) in patients with acute heart failure (AHF) is an unmet clinical need. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel sensitive and specific marker of AKI.

Methods

A total of 207 consecutive patients presenting to the emergency department with AHF were enrolled. Plasma NGAL was measured in a blinded fashion at presentation and serially thereafter. The potential of plasma NGAL levels to predict AKI was assessed as the primary endpoint. We defined AKI according to the AKI Network classification.

Results

Overall 60 patients (29%) experienced AKI. These patients were more likely to suffer from pre-existing chronic cardiac or kidney disease. At presentation, creatinine (median 140 (interquartile range (IQR), 91 to 203) umol/L versus 97 (76 to 132) umol/L, P < 0.01) and NGAL (114.5 (IQR, 67.1 to 201.5) ng/ml versus 74.5 (60 to 113.9) ng/ml, P < 0.01) levels were significantly higher in AKI compared to non-AKI patients. The prognostic accuracy for measurements obtained at presentation, as quantified by the area under the receiver operating characteristic curve was mediocre and comparable for the two markers (creatinine 0.69; 95%CI 0.59 to 0.79 versus NGAL 0.67; 95%CI 0.57 to 0.77). Serial measurements of NGAL did not further increase the prognostic accuracy for AKI. Creatinine, but not NGAL, remained an independent predictor of AKI (hazard ratio (HR) 1.12; 95%CI 1.00 to 1.25; P = 0.04) in multivariable regression analysis.

Conclusions

Plasma NGAL levels do not adequately predict AKI in patients with AHF.