Comparison of the performance of two general and three specific scoring systems for meningococcal septic shock in children

OBJECTIVE: To evaluate the performance at admission to the pediatric intensive care unit (PICU) of five severity scores, two general (the Pediatric Risk of Mortality [PRISM] II and III scores) and three specific for meningococcal septic shock (Leclerc, Glasgow Meningococcal Septicemia Prognostic Score [GMSPS], and Gedde-Dahl's MOC score) in children with this condition. DESIGN: Multicenter, retrospective, cohort study. SETTING: The PICUs from four tertiary centers. PATIENTS: Patients were 192 children ranging in age from 1 month to 14 yrs consecutively admitted to the participating PICUs during a period of 12 yrs and 6 months (January 1983 to June 1995), who were diagnosed with presumed or confirmed meningococcal septic shock. Patients with a length of stay <2 hrs were excluded from the study. INTERVENTIONS: Clinical and laboratory data gathered during the first 2 hrs after admission were used to compute the scoring systems tested. MEASUREMENTS AND MAIN RESULTS: There were 66 deaths (34%). Neisseria meningitidis was cultured from 142 (74%) children. GMSPS and PRISM II provided the best discriminative capability, as measured by the area under the receiver operating characteristic curve (SEM): 0.816 (0.036) and 0.803 (0.041), respectively. The other three scores gave lower receiver operating characteristic areas: PRISM III = 0.777 (0.043), MOC = 0.775 (0.037), and Leclerc = 0.661 (0.045). There was a statistically significant difference between the areas under the receiver operating characteristic curve of GMSPS and Leclerc (p < .01) but not between the GMSPS and the remaining three scores. All five scores presented good calibration with no significant differences between observed and predicted mortality (Hosmer-Lemeshow goodness-of-fit test). CONCLUSIONS: The specific GMSPS and the general pediatric severity system PRISM II performed better than the other three scores, being appropriate tools to assess severity of illness at admission to the PICU in children with presumed meningococcal septic shock.     

A new prognostic scoring system for meningococcal septic shock in children. Comparison with three other scoring systems

OBJECTIVE: To develop a quick and sensitive method for identification of children with presumed meningococcal septic shock at risk of death at admission to the pediatric intensive care unit (PICU) and to compare its performance with three other prognostic systems: Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS), Malley score and the Paediatric Index of Mortality (PIM). DESIGN: Multicenter retrospective cohort study. SETTING: PICUs of 14 tertiary hospitals. PATIENTS: The developmental sample included 192 children consecutively admitted to the PICUs with presumed or confirmed meningococcal septic shock from 1983 to 1995. The validation sample included 158 children consecutively admitted from 1996 to 1998. INTERVENTIONS: Clinical and laboratory data gathered during the first 2 h after admission were used to develop the new score and to compute the other scoring systems. Logistic regression was applied to identify the independent predictors of death. MEASUREMENTS AND RESULTS: Overall mortality was 31.5%. The new score included seven variables: cyanosis (2 points), Glasgow coma scale less than 8 (2 points), refractory hypotension (2 points), oliguria (1 point), leukocytes less than 4000/mm(3) (1 point), partial thromboplastin time more than 150% of control value (1 point) and base deficit more than 10 mmol/l (1 point). The new score provided the best discriminative capability, as measured by the area under the ROC curve (SEM) in the validation sample =0.88 (0.03), PIM =0.82 (0.04), Malley I =0.80 (0.04), GMSPS =0.79 (0.04) and Malley II =0.76 (0.04). CONCLUSIONS: A new prognostic score is proposed for therapeutic stratification of children with presumed meningococcal septic shock.     

The outcome of children admitted to intensive care with meningococcal septicaemia

Objective To review our experience of children with meningococcal septicaemia, and to validate, in our group, severity scores used in different populations to predict outcome.Design Retrospective review of case notes and charts.Patients A total of 35 children were admitted to the paediatric intensive care unit (ICU) in the Royal Children's Hospital (RCH) in the 8 years between January 1985 and December 1992 with proven meningococcal septicaemia.Results Ages ranged from 4 months to 16 years, with a median age of 20 months. The median meningococcal score was 4 and the median PRISM score was 20, with scores above these being significantly associated with death (P<0.0001). Thirty-two children (91%) received infusions of colloid for hypovolaemia and twenty-nine (83%) received one or more inotropic drugs. Twenty-one children (60%) required mechanical ventilation for a median of 16.5 h (range 7–574). Seven children (20%) underwent plasmapheresis. Six children (17%) underwent haemofiltration and two (6%), peritoneal dialysis. One patient received extracorporeal membrane oxygenation (ECMO) because of circulatory failure. Twenty-one children (60%) developed disseminated intravascular coagulation, renal failure and/or skin or limb necrosis. The overall survival was 66%, and all survivors are functionally normal.Conclusion The mortality from the disease remains at 34% despite the technological advances in intensive care. The PRISM and meningococcal scores are useful in predicting outcome. Novel methods of treatment (e.g., plasmapheresis or ECMO) may be valuable.     

Admission plasma vasopressin levels in children with meningococcal septic shock

Objective Vasopressin (AVP) response has been reported to be inappropriately low in adult established septic shock. We studied admission AVP levels in children with meningococcal septic shock (MSS).Patients and methods All children with meningococcal infection admitted to our PICU between May 2001 and August 2002 were classified as MSS (persistent hypotension despite fluid therapy, with perfusion abnormalities and the need for vasoactive drug infusion for at least 24 h or until death), or meningococal infection without shock (fever and purpura, with or without meningitis). Blood samples were collected at admission and AVP levels were subsequently determined using Nichols Institute Diagnostics vasopressin assay. Eighteen of 19 children with MSS (7 deaths) and 15 without shock (no death) were included.Results In children with MSS median admission AVP level was 41.6 pg/ml (1.4–498.9) and in those without 3.3 pg/ml (1.6–63.8). In children with MSS the AVP level was not correlated with duration of shock and fluid expansion prior to AVP sampling, or with age-adjusted blood pressure and natremia at the time of blood sampling. AVP levels were higher in nonsurvivors, but not significantly so. Only one nonsurvivor had an admission AVP level below 30 pg/ml.Conclusions In our children with established MSS who died the admission AVP level were not inappropriately low. Further studies including serial AVP level assessments are needed before concluding that AVP administration is of little interest in children with MSS.     

简化急性生理评分Ⅱ与牛津急性疾病严重程度评分对重症监护病房患者短期预后的预测价值比较

目的比较简化急性生理评分（SAPS）Ⅱ与牛津急性疾病严重程度评分（OASIS）对重症监护病房（ICU）患者短期预后预测价值的差异,以期为实际临床工作中疾病严重程度评分系统的选择提供一定的研究证据。 方法从美国重症监护数据库（MIMIC-Ⅲ）（2001年至2012年）提取成年（年龄≥18岁）ICU患者的基本信息、生命体征以及相关实验室检验指标等,按各评分系统的要求分别计算SAPS Ⅱ与OASIS评分,以ICU内病死为首要结局指标,绘制接受者操作特征（ROC）曲线,计算并比较曲线下面积（AUC）的差异。 结果共有38 468例ICU成年患者被纳入最终分析,其中男性患者占56.61%,年龄中位数为65.72岁,ICU病死率为8.28%（3185/38 468）。与存活患者相比,ICU死亡患者具有更高的SAPS Ⅱ（存活者 vs死亡者：32分 vs 51分,H=3473.792,P<0.001）与OASIS评分（存活者 vs死亡者：30分vs 41分,H=3422.382,P<0.001）以及更高的机械通气比例（存活者 vs死亡者：22.76% vs 73.59%,χ²=3831.865,P<0.001）。ROC曲线分析显示,SAPS Ⅱ评分与OASIS评分的AUC分别为0.8147（95%CI：0.8068~0.8226）和0.8123（95%CI：0.8042~0.8204）,Hanley-McNeil检验显示二者AUC差异无统计学意义（Z=0.686,P=0.4928）。 结论SAPS Ⅱ评分与OASIS评分对成年ICU患者短期预后的预测价值并无显著差异,更加简便的OASIS评分有望成为ICU疾病严重程度评分的另一选择。     

Characteristics and immediate outcome of childhood meningitis treated in the pediatric intensive care unit

Objective To describe patient characteristics, use of technology and mortality in children with meningitis admitted to the pediatric intensive care unit (PICU).Design Retrospective cohort study.Setting Fifteen US PICUs.Patients All admissions with a diagnosis of meningitis between 1995 and 2000 in the Pediatric Intensive Care Unit Evaluations (PICUEs) database.Measurements and results Of 559 patients with meningitis, 58% were male. The median age was 19 months and the median length of PICU stay was 2 days. The crude PICU mortality rate was 7%. Three hundred thirty-four (60%) patients had bacterial meningitis. Non-survivors had significantly higher Pediatric Risk of Mortality (PRISM) III scores and also constituted a larger proportion of the patients with bacterial meningitis, coma and shock upon PICU admission. The use of invasive devices was higher among non-survivors, patients with bacterial meningitis or those who were in coma or shock upon PICU admission. There was significant variation in the use of intracranial pressure (ICP) monitors by coma status and by institution. In multivariate analysis, patients had 1.26 higher odds of mortality for each unit increase in PRISM III score (odds ratio 1.26, 95% confidence interval: 1.19–1.34), while adjusting for other variables.Conclusion In a large cohort of children admitted to the PICU with meningitis, severity of illness, particularly the presence of shock or coma, was significantly associated with both the higher use of invasive medical devices and higher mortality. There was significant variation in the use of ICP monitors among the various PICUs without statistical association with survival.Presented, in part, at the 14^th Pediatric Critical Care Colloquium, San Diego, CA, USA, October 2002     

Prognostic performance of disease severity scores in patients with septic shock presenting to the emergency department

BackgroundAn accurate disease severity score that can quickly predict the prognosis of patients with sepsis in the emergency department (ED) can aid clinicians in distributing resources appropriately or making decisions for active resuscitation measures. This study aimed to compare the prognostic performance of quick sequential organ failure assessment (qSOFA) with that of other disease severity scores in patients with septic shock presenting to an ED.MethodsWe performed a prospective, observational, registry-based study. The discriminative ability of each disease severity score to predict 28-day mortality was evaluated in the overall cohort (which included patients who fulfilled previously defined criteria for septic shock), the newly defined sepsis subgroup, and the newly defined septic shock subgroup.ResultsA total of 991 patients were included. All disease severity scores had poor discriminative ability for 28-day mortality. The sequential organ failure assessment and acute physiology and chronic health evaluation II scores had the highest area under the receiver-operating characteristic curve (AUC) values, which were significantly higher than the AUC values of other disease severity scores in the overall cohort and the sepsis and septic shock subgroups. The discriminative ability of each disease severity score decreased as the mortality rate of each subgroup increased.ConclusionsAll disease severity scores, including qSOFA, did not display good discrimination for 28-day mortality in patients with serious infection and refractory hypotension or hypoperfusion; additionally, none of the included scoring tools in this study could consistently predict 28-day mortality in the newly defined sepsis and septic shock subgroups.     

Can generic scores (Pediatric Risk of Mortality and Pediatric Index of Mortality) replace specific scores in predicting the outcome of presumed meningococcal septic shock in children?

OBJECTIVE: To compare, in children with septic shock and purpura, the accuracy in predicting death of two specific scores (the MenOPP bedside clinical [MOC] score of Gedde Dahl and the score of Groupe Francophone de Réanimation Pédiatrique [GFRP]), the C-reactive protein (CRP) level, and the two pediatric generic scores (the Pediatric Risk of Mortality [PRISM] and Pediatric Index of Mortality [PIM] scores). DESIGN: Prospective, population-based study with analysis of previous comparative studies. SETTING: A 14-bed pediatric intensive care unit in a university hospital. PATIENTS: All children admitted consecutively to the pediatric intensive care unit with septic shock and purpura (n = 58, with 16 deaths [27.6%]) from January 1993 to May 2000. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The MOC and GFRP scores and the CRP level were prospectively determined at admission. The PRISM score was prospectively calculated within 24 hrs of admission or at the time of death, and the PIM score was calculated retrospectively between 1993 and 1997 and then prospectively from admission data. The nonparametric estimate of the area under the receiver operating characteristic curves (AUC) was calculated from the raw data using the Wilcoxon-Mann-Whitney two-sample statistic, and the standard error of the AUCs was calculated with DeLong's method. All the scores had an AUC >0.80, the PRISM probability of death having the best one (0.96 +/- 0.02). The PRISM value, which is easier to calculate, had an AUC of 0.95 +/- 0.02. The PRISM score performed significantly better than the PIM score (AUC, 0.83 +/- 0.06; p <.01) and the CRP level (AUC, 0.80 +/- 0.06; p <.01); however, there was no significant difference between the MOC (AUC, 0.91 +/- 0.04) and GFRP scores (AUC, 0.87 +/- 0.05). Analyzing literature and calculating AUCs from original data of previous studies, we observed that the superiority of the PRISM score had never been demonstrated in meningococcal diseases. CONCLUSIONS: The PRISM score performed better than the PIM score, and was not surpassed by specific scores. Thus, we propose its use for outcome prediction in children with septic shock and purpura. However, if the PRISM score is to be used as inclusion criterion for clinical trials, it should be evaluated within a few hours after admission.     

Diagnostic value and prognostic evaluation of Presepsin for sepsis in an emergency department

Introduction

Presepsin levels are known to be increased in sepsis. The aim of this study was to evaluate the early diagnostic and prognostic value of Presepsin compared with procalcitonin (PCT), Mortality in Emergency Department Sepsis (MEDS) score and Acute Physiology and Chronic Health Evaluation II (APACHE II) score in septic patients in an emergency department (ED) and to investigate Presepsin as a new biomarker of sepsis.

Methods

This study enrolled 859 consecutive patients with at least two diagnostic criteria for systemic inflammatory response syndrome (SIRS) who were admitted to Beijing Chao-yang Hospital ED from December 2011 to October 2012, and 100 age-matched healthy controls. Patients were stratified into four groups: SIRS, sepsis, severe sepsis, and septic shock. Plasma Presepsin and serum PCT were measured, and MEDS score and APACHE II score were calculated at enrollment. Comparisons were analyzed using the Kruskal-Wallis and Mann–Whitney U tests.

Results

On admission, the median levels of plasma Presepsin increased with sepsis severity. The areas under the receiver operating characteristic (AUC) curves of Presepsin were greater than those of PCT in diagnosing sepsis, and predicting severe sepsis and septic shock. The AUC of Presepsin for predicting 28-day mortality in septic patients was slightly lower than that of PCT, MEDS score and APACHE II score. The AUC of a combination of Presepsin and MEDS score or APACHE II score was significantly higher than that of MEDS score or APACHE II score alone in predicting severe sepsis, and was markedly higher than that of Presepsin alone in predicting septic shock and 28-day mortality in septic patients, respectively. Plasma Presepsin levels in septic patients were significantly higher in non-survivors than in survivors at 28 days’ follow-up. Presepsin, MEDS score and APACHE II score were found to be independent predictors of severe sepsis, septic shock and 28-day mortality in septic patients. The levels of plasma Presepsin were positively correlated with PCT, MEDS score and APACHE II score in every septic group.

Conclusion

Presepsin is a valuable biomarker for early diagnosis of sepsis, risk stratification, and evaluation of prognosis in septic patients in the ED.     

A new scoring system derived from base excess and platelet count at presentation predicts mortality in paediatric meningococcal sepsis

Introduction

The aim of this study was to derive a novel prognostic score for mortality in paediatric meningococcal sepsis (MS) based on readily available laboratory markers.

Methods

A multicentre retrospective cohort study for the consortium set and a single centre retrospective study for replication set. The consortium set were 1,073 children (age 1 week to 17.9 years) referred over a 15-year period (1996 to 2011), who had an admission diagnosis of MS, referred to paediatric intensive care units (PICUs) in six different European centres. The consortium set was split into a development set and validation set to derive the score. The replication set were 134 children with MS (age 2 weeks to 16 years) referred over a 4-year period (2007 to 2011) to PICUs via the Children''s Acute Transport Service (CATS), London.

Results

A total of 85/1,073 (7.9%) children in the consortium set died. A total of 16/134 (11.9%) children in the replication set died. Children dying in the consortium set had significantly lower base excess, C-reactive protein (CRP), platelet and white cell count, more deranged coagulation and higher lactate than survivors. Paediatric risk of mortality (PRISM) score, Glasgow meningococcal septicaemia prognosis score (GMSPS) and Rotterdam score were also higher. Using the consortium set, a new scoring system using base excess and platelet count at presentation, termed the BEP score, was mathematically developed and validated. BEP predicted mortality with high sensitivity and specificity scores (area under the curve (AUC) in the validation set = 0.86 and in the replication set = 0.96). In the validation set, BEP score performance (AUC = 0.86, confidence interval (CI): 0.80 to 0.91) was better than GMSPS (AUC = 0.77, CI: 0.68, 0.85), similar to Rotterdam (AUC = 0.87, CI: 0.81 to 0.93) and not as good as PRISM (AUC = 0.93, CI: 0.85 to 0.97).

Conclusions

The BEP score, relying on only two variables that are quickly and objectively measurable and readily available at presentation, is highly sensitive and specific in predicting death from MS in childhood.     

Prognostic value of procalcitonin in children with meningococcal sepsis

OBJECTIVE: To compare procalcitonin, lactate, and C-reactive protein as prognostic markers in children with meningococcal septic shock. DESIGN: Prospective observational study. SETTING: Alder Hey Children's Hospital, Liverpool, UK. PATIENTS: Children admitted to our hospital during a 16-month period with a diagnosis of meningococcal sepsis. RESULTS: Plasma procalcitonin at admission was significantly higher in children with septic shock (median, 73.80 vs. 16.44 ng/mL), those requiring ventilation (median, 47.02 vs. 12.00 ng/mL), and those with a duration of hospital stay >10 days (median, 131.35 vs. 19.26 ng/mL). Both procalcitonin and lactate reliably discriminated between those children with septic shock (area under the curve [AUC] = 0.85 and 0.84, respectively) and durations of hospital stay exceeding 10 days (AUC = 0.87 and 0.79, respectively) and those without, but C-reactive protein did not. Procalcitonin alone reliably discriminated between those children requiring ventilation and those who did not (AUC = 0.72). CONCLUSION: Procalcitonin is a reliable prognostic marker of septic shock, requirement for ventilation, and prolonged hospital stay in children with meningococcal sepsis and performs better than lactate and C-reactive protein.     

英国国家早期预警评分对急诊老年严重脓毒症及脓毒症休克患者预后的评估价值

目的探讨英国国家早期预警评分(NEWS)对急诊老年严重脓毒症及脓毒性休克患者病情及预后的评估。方法收集首都医科大学宣武医院急诊老年严重脓毒症和脓毒性休克患者116例,就诊后采集患者的常规生理生化指标,并行NEWS评分,APACHEⅡ评分和SOFA评分,随访28 d,根据患者预后分为死亡组和存活组,分别比较死亡组和存活组NEWS评分,APACHEⅡ评分及SOFA评分区别;比较脓毒性休克和严重脓毒症组的NEWS评分,APACHEⅡ评分及SOFA评分的区别;NEWS评分与APACHEⅡ评分。SOFA评分的相关性分析;通过分析ROC曲线下面积(AUC)确定NEWS评分对老年严重脓毒症和脓毒性休克患者预后的评估价值。结果脓毒性休克组患者NEWS评分;APACHEII评分和SOFA评分大于严重脓毒症组;死亡组NEWS评分;APACHEII评分和SOFA评分均显著大于存活组(P<0.05);NEWS评分水平与APACHEⅡ评分。SOFA评分具有显著相关性(r=0.807、0.883,P<0.05),NEWS评分;APACHEII评分和SOFA评分预测死亡ROC曲线下面积分别为0.870、880、0.865(P>0.05)。结论 NEWS评分对急诊老年严重脓毒症和脓毒性休克患者的病情和预后具有重要的评估价值,评分愈高提示患者预后愈差。     

Persistently low plasma thioredoxin is associated with meningococcal septic shock in children

Objective To compare plasma levels of thioredoxin (Trx), TNF-α and IL-1β in children during the acute phase of meningococcal septic shock (MSS) and in convalescence. Design and setting Retrospective, observational study in the paediatric intensive care unit of a postgraduate teaching hospital. Patients Thirty-five children requiring intensive care for meningococcal sepsis; paired convalescent samples from 30 survivors (median interval between samples 62 days); 25 healthy control children. Measurements and results Plasma Trx levels were significantly lower in the children with MSS, both during the acute illness (5.5 ng/ml, IQR 1.4–11.4) and in convalescence (2.5 ng/ml, IQR 0.4–6.9) than controls (18.8 ng/ml, IQR 7.9–25.0). Levels of IL-1β and TNF-α were higher in patients with acute MSS (30.3 pg/ml, IQR 3.6–63.6, and 145.9 pg/ml, IQR 31.8–278.1 respectively) than controls (3.7 pg/ml, IQR 0–36.9, and 23.8 pg/ml, IQR 0–124.3, respectively). Levels fell in convalescence (3.7 pg/ml, IQR 0–25.5, 3.7 pg/ml, IQR 0–304.8, respectively). Plasma Trx was higher in non-survivors, albeit a small group (n = 5), than in survivors (n = 30). Trx, IL-1β, and TNF-α levels were not correlated with predicted mortality as assessed by the paediatric risk of mortality (PRISM) score. Conclusions Children with MSS exhibit persistently low plasma levels of Trx during acute illness and in convalescence.     

血清冷诱导RNA结合蛋白与脓毒性休克患者病情严重程度及预后的相关性

目的探讨血清冷诱导RNA结合蛋白(CIRP)与脓毒性休克患者病情严重程度及预后的相关性。方法回顾性选取2018年1月至2020年1月海南医学院第二附属医院急诊重症监护室(EICU)收治的脓毒性休克患者107例为研究对象。收集患者一般资料、急性生理和慢性健康状况评估系统Ⅱ(APACHEⅡ)评分、序贯器官衰竭估计(SOFA)评分、CIRP、血乳酸(Lac)、血清肌酐(s Cr)、血白细胞计数(WBC)、中性粒细胞百分比(NeuR)及降钙素原(PCT)。根据患者28 d预后情况将其分为死亡组和存活组。采用Pearson相关分析探讨脓毒性休克患者CIRP与SOFA评分及APACHEⅡ评分的相关性;采用Logistic回归分析探讨脓毒性休克患者28 d死亡的危险因素;绘制受试者工作特征(ROC)曲线并评估各指标对脓毒性休克患者28 d死亡的预测价值。结果随访28 d后,25例(23.4%)患者死亡(死亡组),82例(76.6%)患者存活(存活组)。死亡组APACHEⅡ评分、SOFA评分、CIRP、血Lac、s Cr及PCT水平明显高于存活组(P <0.05)。Pearson相关分析结果显示,脓毒性休克患者CIRP与SOFA评分及APACHEⅡ评分均呈正相关(r=0.337,P=0.005;r=0.249,P=0.039)。多因素Logistic回归分析结果显示,APACHEⅡ评分[OR=1.138,95%CI(1.066,1.214)]、SOFA评分[OR=1.326,95%CI(1.174,1.478)]、CIRP[OR=1.322,95%CI(1.141,1.502)]及PCT[OR=1.055,95%CI(1.003,1.108)]为脓毒性休克患者28 d死亡的危险因素(P <0.05)。CIRP、SOFA评分、APACHEⅡ评分、PCT预测脓毒性休克患者28 d死亡的ROC曲线下面积(AUC)分别为0.915[95%CI(0.823,0.969)]、0.834[95%CI(0.726,0.913)]、0.798[95%CI(0.684,0.885)]、0.685[95%CI(0.562,0.792)]。CIRP预测脓毒性休克患者28 d死亡的AUC大于SOFA评分、APACHEⅡ评分、PCT预测脓毒性休克患者28 d死亡的AUC(Z=2.134,P=0.041;Z=2.348,P=0.026;Z=3.64,P <0.001)。CIRP的最佳临界值为2.6μg/L时,预测脓毒性休克患者28 d死亡的敏感度为96.8%,特异度为73.7%。结论血清CIRP与脓毒性休克患者病情严重程度及预后密切相关,为28 d死亡的独立危险因素,可作为评价脓毒性休克患者预后的较好指标。     

Simple coagulation tests improve survival prediction in patients with septic shock

Summary.  Background:  Classic mortality prediction models in intensive care units (ICUs) are based on clinical scores, which do not contain any coagulation test (SAPS-II or SOFA scores). Objectives:  To determine whether coagulation tests can improve mortality prediction in patients with septic shock. Patients and methods:  One hundred fifty-eight consecutive patients with septic shock entering our institution's ICU were investigated on the first day of admission, and deaths were registered during the first month. Results:  Among all the coagulation tests performed, only the fibrinogen (Fg) plasma level, together with the SAPS-II score and the age, were included in our simplified mortality score [area under the receiver operating curve (AUC) 0.927, standard deviation (SD) 0.030], which was more efficient than SAPS-II and SOFA scores themselves in predicting first-week mortality, its optimized cut-off having a very high negative predictive value (NPV) [0.989; 95% confidence interval (CI) 0.967–1.000)]. A simplified score predicting first-month mortality, containing the prothrombin ratio and the antithrombin activity values in addition to the age, the hemoglobin concentration, and the SAPS-II and SOFA scores (AUC 0.889, SD 0.026), was found to be superior to the SAPS-II and SOFA scores, the optimized cut-off value having a high NPV (0.952; 95% CI 0.888–1.000). Conclusions:  In patients admitted to an ICU with septic shock, some initial coagulation test values can help identify those who will survive in the first week and then in the first month.     

The study on pro-adrenomedullin as a new biomarker in sepsis prognosis and risk stratification

OBJECTIVE: To assess the clinical value of pro-adrenomedullin (pro-ADM) in the prognosis and risk stratification in sepsis. METHODS: Fifty-one critically ill patients admitted to the intensive care unit (ICU) were prospectively stratified into four groups according to internationally recognized criteria: systemic inflammatory response syndrome (SIRS, 25 cases), sepsis (12 cases), severe sepsis (9 cases) and septic shock (5 cases). The levels of plasma pro-ADM was determined in every patient using a new sandwich immunoassay, and compared with procalcitonin (PCT), C-reactive protein (CRP) and interleukin-6 (IL-6), and the acute physiology and chronic health evaluation II (APACHEII) score. RESULTS: (1) Median pro-ADM concentration was 0.34 mug/L for SIRS, 2.23 mug/L for sepsis, 4.57 mug/L for severe sepsis and 8.21 mug/L for septic shock. The plasma concentration of pro-ADM exhibited a gradual increase, and the median pro-ADM value was highest in the septic shock group (all P<0.05). (2) Compared with the other biomarkers, in the sepsis, severe sepsis and septic shock groups, the plasma concentration of pro-ADM and APACHEII score in the non-survivors was significantly higher than in the survivors (pro-ADM: 2.01 mug/L vs. 9.75 mug/L, APACHEII score: 23.44 scores vs. 38.21 scores, both P<0.05). (3) By the receiver operating characteristic (ROC) curve plot analysis of pro-ADM in sepsis, the area under the ROC curve for pro-ADM (0.87) in survivors was similar to the area under the ROC curve for PCT (0.81) and APACHEII score (0.81), and was significantly higher than the area under the ROC curve for CRP (0.53) and IL-6 (0.71). CONCLUSION: The measurement of pro-ADM is a new and useful marker in sepsis prognosis and risk strafification.     

Validation of the Glasgow Meningococcal Septicemia Prognostic Score: a 10-year retrospective survey

OBJECTIVE: To derive performance characteristics for the Glasgow Meningococcal Septicemia Prognostic Score (GMSPS). DESIGN: Retrospective case-note study. SETTING: Two children's hospitals with Regional Intensive Care Unit. PATIENTS: One hundred twenty-three children with proven meningococcal septicemia (some with concurrent meningitis) from January 1, 1977 to December 31, 1986. MEASUREMENTS AND MAIN RESULTS: All 14 children who died after arrival scored greater than or equal to 8 either on admission (n = 8) or afterward (n = 6). Of 109 survivors, five scored greater than or equal to 8 (two were postictal at the time of scoring). A GMSPS of greater than or equal to 10 at or after admission predicted death with sensitivity 100%, specificity 98%, and positive predictive value of 88%; for GMSPS of both greater than or equal to 8 or 9, the values were 100%, 95%, and 74%, respectively. CONCLUSIONS: The GMSPS is a rapid clinical score that performs well in identifying children with poor prognosis who might benefit from early intensive care. It should be studied prospectively and compared with other scoring systems.     

Thrombin activatable fibrinolysis inhibitor is associated with severity and outcome of severe meningococcal infection in children

Summary.  Background and objectives:  In pediatric meningococcal sepsis, an imbalance between coagulation and fibrinolysis and proinflammatory action play major roles. We hypothesized that thrombin activatable fibrinolysis inhibitor (TAFI) and/or TAFI activation markers are involved in the pathogenesis of meningococcal sepsis. Patients and methods:  Children with severe meningococcal sepsis ( n  =   112) previously included in Rotterdam-based trials participated in this study. Clinical and laboratory parameters and severity scores were assessed. TAFI and TAFI activation markers were determined: TAFI activation peptide (TAFI-AP) and (in)activated TAFI [TAFIa(i)]. The –438G/A, Ala147Thr, and Thr325Ile polymorphisms were genotyped. Results:  TAFI levels were significantly decreased in patients with meningococcal disease at admission compared to the convalescence state. TAFI was decreased in patients with septic shock vs. those with no shock. TAFI-AP levels were increased in patients with disseminated intravascular coagulation (DIC) vs. patients without DIC. TAFI-AP and TAFIa(i) were significantly increased in non-survivors vs. survivors. TAFI-AP levels and the TAFI-AP/TAFI ratio were also strongly correlated to severity scores and laboratory parameters. The TAFI 325Ile/Ile genotype was overrepresented in patients with DIC. Conclusions:  Activation markers of TAFI were associated with the occurrence of DIC and mortality in meningococcal sepsis patients. A determination of TAFI, TAFI-AP, and TAFIa(i) is required to enable coherent interpretation of the role of TAFI in disease.     

A predominantly anti-inflammatory cytokine profile is associated with disease severity in meningococcal sepsis

Objective This study aimed to determine whether an anti-inflammatory profile in meningococcal disease is associated with an increased risk of severe disease or septic shock.Design and setting Prospective observational study in a tertiary care childrens hospital.Patients and participants 63 children with confirmed meningococcal disease.Interventions Plasma concentrations of interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor- (TNF) were assayed on admission. Receiver operator characteristic curve analysis was used to determine optimum thresholds for IL-1Ra:TNF, IL-1Ra:IL-6 and IL-1Ra:IL-8 ratios.Measurements and results Median IL-1Ra:TNF and IL-1Ra:IL-6 ratios were significantly higher in severe disease with septic shock than in severe disease without septic shock and in non severe disease (IL-1Ra:TNF 263 vs. 185 vs. 108; IL-1Ra:IL-6 139 vs. 23 vs. 17). Median IL-1Ra:IL-8 ratios were not significantly different in the three groups. A significantly larger proportion of children with high IL-1Ra:TNF- and IL-1Ra:IL-6 ratios developed severe disease with septic shock than those with a low ratios (95.2% vs. 4.8%; 76.2% vs. 23.8%).Conclusions An anti-inflammatory profile appears to be associated with the development of severe disease and septic shock in meningococcal sepsis. This may imply that experimental new therapies of pro-inflammatory cytokine inhibition and anti-inflammatory cytokines in meningococcal disease could be detrimental.