Francis Leclerc

Validation of the paediatric logistic organ dysfunction (PELOD) score: prospective, observational, multicentre study

BACKGROUND Multiple organ dysfunction syndrome is more frequent than death in paediatric intensive care units. Estimation of the severity of this syndrome could be a useful additional outcome measure in clinical trials in such units. We aimed to validate the paediatric logistic organ dysfunction (PELOD) score and estimate its validity when recorded daily (dPELOD). METHODS We did a prospective, observational, multicentre cohort study in seven multidisciplinary, tertiary-care paediatric intensive care units of university-affiliated hospitals (two French, three Canadian, and two Swiss). We included 1806 consecutive patients (median age 24 months; IQR 5-90). PELOD score includes six organ dysfunctions and 12 variables and was recorded daily. For each variable, the most abnormal value each day and during the whole stay were used in calculating the dPELOD and PELOD scores, respectively. Outcome was vital status at discharge. We used Hosmer-Lemeshow goodness-of-fit tests to evaluate calibration and areas under receiver operating characteristic curve (AUC) to estimate discrimination. FINDINGS 370 (21%) patients had no organ dysfunction, 471 (26%) had one, 457 (25%) had two, and 508 (28%) had three or more. Case fatality rate was 6.4% (115 deaths). PELOD score was significantly higher in non-survivors (mean 31.0 [SE 1.2]) than survivors (9.4 [0.2]; p<0.0001). Calibration (p=0.54) and discrimination (AUC=0.91, SE=0.01) of PELOD and dPELOD (p> or =0.39; AUC> or =0.79) scores were good. INTERPRETATION PELOD and dPELOD scores are valid outcome measures of the severity of multiple organ dysfunction syndrome in paediatric intensive care units; their use should significantly reduce the sample size required to complete clinical trials in critically ill children.

DEVELOPMENT OF A PEDIATRIC MULTIPLE ORGAN DYSFUNCTION SCORE : USE OF TWO STRATEGIES

Background. An organ dysfunction (OD) scoring system for critically ill children is not yet available, and the method for developing such a system is not well defined. The aim of this study was to compare two developmental methods for assessing OD in critically ill children. Methods. Consecutive admissions between January and May 1997 in three French and Canadian pediatric intensive care units (PICUs) were studied prospectively. Physiologic data were selected using a Delphi method; the most ab normal values during PICU stay were recorded. The outcome measure was the vital status at PICU discharge. Six organ systems were studied: hepatic, cardiovascular, renal, hematologic, respiratory, and neurologic. For each of the six organ systems, the PEdiatric Multiple OD (PEMOD) system included one variable and the PEdiatric Lo gistic OD (PELOD) system included several variables. Severity levels and relative weights of ODs were determined according to the mortality rate (PEMOD) or by logistic regression (PELOD). Results. There were 594 admissions, including 51 deaths (9%). Severity levels and relative weights of ODs were: four levels graded from 1 to 4 for the PEMOD system and three levels with scores of 1, 10, and 20 for PELOD system. For both systems, calibrations were good (p = 0.23 and p = 0.44 respectively). The PELOD system was more discriminant than the PEMOD system (areas under the ROC curves 0.98 and 0.92, respectively, p < 10 -5). Moreover, with the PEMOD system, four ODs did not contribute significantly to the prediction of PICU outcome. Conclusions. The PELOD system was more discriminant and had the advantage of taking into ac count both the relative severities among ODs and the degree of severity of each OD. Key words: intensive care unit; multiple organ failure; outcome measure; patient out come assessment; pediatric severity of illness index. (Med Decis Making 1999;19: 399-410)

Role of viruses and atypical bacteria in exacerbations of asthma in hospitalized children: a prospective study in the Nord-Pas de Calais region (France).

We studied the role of viruses and atypical bacteria in children hospitalized with exacerbated asthma by a prospective study of children with acute asthma admitted to the Department of Pediatrics in Lille, and to 15 hospitals in the Nord‐Pas de Calais region, from October 1, 1998–June 30, 1999. We included children aged 2–16 years with active asthma, defined as three or more recurrent episodes of reversible wheezing. The severity of asthma and of asthmatic exacerbations was recorded. Immunofluorescence assays (IFA) on nasopharyngeal secretions (NPS), serological tests, or both, were used for detection of influenza virus, respiratory syncytial virus (RSV), adenovirus, parainfluenza virus, and coronavirus. Polymerase chain reaction (PCR) assays on NPS were used for rhinovirus and enterovirus. Serological tests for Chlamydia pneumoniae and Mycoplasma pneumoniae were performed. A control group of asymptomatic asthmatic outpatients was examined for respiratory viruses (using IFA and PCR). Eighty‐two symptomatic children (mean age, 7.9 years) were examined. Viruses were detected in 38% (enterovirus, 15.8%; rhinovirus, 12%; RSV, 7.3%). Serological tests for atypical bacteria were positive in 10% of patients (C. pneumoniae, 5%; M. pneumoniae, 5%). Among the 27 control subjects (mean age, 7.9 years), one PCR was positive for enterovirus. There was no correlation between severity of chronic asthma or asthmatic exacerbations and the diagnosis of infection. Atypical bacterial pathogen infections were linked with prolonged asthmatic symptoms. In conclusion, we confirmed the high incidence of viral infection in acute exacerbations of asthma, especially enteroviruses or rhinoviruses. Persistent clinical features were more frequently associated with atypical bacterial infections, suggesting that these infections should be investigated and treated in cases of persistent asthmatic symptoms. Pediatr Pulmonol. 2003; 35:75–82.

Serum Procalcitonin Level and Other Biological Markers to Distinguish Between Bacterial and Aseptic Meningitis in Children: A European Multicenter Case Cohort Study

OBJECTIVE To validate procalcitonin (PCT) level as the best biological marker to distinguish between bacterial and aseptic meningitis in children in the emergency department. DESIGN Secondary analysis of retrospective multicenter hospital-based cohort studies. SETTING Six pediatric emergency or intensive care units of tertiary care centers in 5 European countries. PARTICIPANTS Consecutive children aged 29 days to 18 years with acute meningitis. MAIN OUTCOME MEASURES Univariate analysis and meta-analysis to compare the performance of blood parameters (PCT level, C-reactive protein level, white blood cell count, and neutrophil count) and cerebrospinal fluid parameters (protein level, glucose level, white blood cell count, and neutrophil count) quickly available in the emergency department to distinguish early on between bacterial and aseptic meningitis. RESULTS Of 198 patients analyzed, 96 had bacterial meningitis. Sensitivity of cerebrospinal fluid Gram staining was 75%. The PCT level had significantly better results than the other markers for area under the receiver operating characteristic curve (0.98; 95% confidence interval, 0.95-0.99; P = .001). At a 0.5-ng/mL threshold, PCT level had 99% sensitivity (95% confidence interval, 97%-100%) and 83% specificity (95% confidence interval, 76%-90%) for distinguishing between bacterial and aseptic meningitis. The diagnostic odds ratio between high PCT level and bacterial meningitis was 139 (95% confidence interval, 39-498), without significant heterogeneity between centers. CONCLUSIONS The PCT level is a strong predictor for distinguishing between bacterial and aseptic meningitis in children in the emergency department. Its combination with other parameters in an effective clinical decision rule could be helpful.

Parental involvement in treatment decisions regarding their critically ill child: a comparative study of France and Quebec.

Objective: To examine whether physicians or parents assume responsibility for treatment decisions for critically ill children and how this relates to subsequent parental experience. A significant controversy has emerged regarding the role of parents, relative to physicians, in relation to treatment decisions for critically ill children. Anglo-American settings have adopted decision-making models where parents are regarded as responsible for such life-support decisions, while in France physicians are commonly considered the decision makers. Design: Grounded theory qualitative methodology. Setting: Four pediatric intensive care units (two in France and two in Quebec, Canada). Patients: Thirty-one parents of critically ill children; nine physicians and 13 nurses who cared for their children. Interventions: None. Measurements and Main Results: Semistructured interviews were conducted. In France, physicians were predominantly the decision makers for treatment decisions. In Quebec, decisional authority practices were more varied; parents were the most common decision maker, but sometimes it was physicians, while for some decisional responsibility depended on the type of decision to be made. French parents appeared more satisfied with their communication and relationship experiences than Quebec parents. French parents referred primarily to the importance of the quality of communication rather than decisional authority. There was no relationship between parents’ actual responsibility for decisions and their subsequent guilt experience. Conclusions: It was remarkable that a certain degree of medical paternalism was unavoidable, regardless of the legal and ethical norms that were in place. This may not necessarily harm parents’ moral experiences. Further research is required to examine parental decisional experience in other pediatric settings.

PELOD-2: an update of the PEdiatric logistic organ dysfunction score.

Objective:Multiple organ dysfunction syndrome is the main cause of death in adult ICUs and in PICUs. The PEdiatric Logistic Organ Dysfunction score developed in 1999 was primarily designed to describe the severity of organ dysfunction. This study was undertaken to update and improve the PEdiatric Logistic Organ Dysfunction score, using a larger and more recent dataset. Design:Prospective multicenter cohort study. Setting:Nine multidisciplinary, tertiary-care PICUs of university-affiliated hospitals in France and Belgium. Patients:All consecutive children admitted to these PICUs (June 2006–October 2007). Intervention:None. Measurements and Main Results:We collected data on variables considered for the PEdiatric Logistic Organ Dysfunction-2 score during PICU stay up to eight time points: days 1, 2, 5, 8, 12, 16, and 18, plus PICU discharge. For each variable considered for the PEdiatric Logistic Organ Dysfunction-2 score, the most abnormal value observed during time points was collected. The outcome was vital status at PICU discharge. Identification of the best variable cutoffs was performed using bivariate analyses. The PEdiatric Logistic Organ Dysfunction-2 score was developed by multivariable logistic regressions and bootstrap process. We used areas under the receiver-operating characteristic curve to evaluate discrimination and Hosmer-Lemeshow goodness-of-fit tests to evaluate calibration. We enrolled 3,671 consecutive patients (median age, 15.5 mo; interquartile range, 2.2–70.7). Mortality rate was 6.0% (222 deaths). The PEdiatric Logistic Organ Dysfunction-2 score includes ten variables corresponding to five organ dysfunctions. Discrimination (areas under the receiver-operating characteristic curve = 0.934) and calibration (chi-square test for goodness-of-fit = 9.31, p = 0.317) of the PEdiatric Logistic Organ Dysfunction-2 score were good. Conclusion:We developed and validated the PEdiatric Logistic Organ Dysfunction-2 score, which allows assessment of the severity of cases of multiple organ dysfunction syndrome in the PICU with a continuous scale. The PEdiatric Logistic Organ Dysfunction-2 score now includes mean arterial pressure and lactatemia in the cardiovascular dysfunction and does not include hepatic dysfunction. The score will be in the public domain, which means that it can be freely used in clinical trials.

The pediatric multiple organ dysfunction syndrome

Objectives: To review the epidemiology of pediatric multiple organ dysfunction syndrome (MODS) and summarize current concepts regarding the pathophysiology of shock, organ dysfunction, and nosocomial infections in this population. Data Source: A MEDLINE-based literature search using the keywords MODS and child, without any restriction to the idiom. Main Results: Critically ill children may frequently develop multisystemic manifestations during the course of severe infections, multiple trauma, surgery for congenital heart defects, or transplantations. Descriptive scores to estimate the severity of pediatric MODS have been validated. Young age and chronic health conditions have also been recognized as important contributors to the development of MODS. Unbalanced inflammatory processes and activation of coagulation may lead to the development of capillary leak and acute respiratory distress syndrome. Neuroendocrine and metabolic responses may result in insufficient adaptive immune response and the development of nosocomial infections, which may further threaten host homeostasis. Conclusions: Over the last 20 yrs, there has been an increasing knowledge on the epidemiology of pediatric MODS and on the physiologic mechanisms involved in the genesis of organ dysfunction. Nevertheless, further studies are needed to more clearly evaluate what is the long-term outcome of pediatric MODS.

Distinguishing between bacterial and aseptic meningitis in children: European comparison of two clinical decision rules

Background Clinical decision rules (CDRs) could be helpful to safely distinguish between bacterial and aseptic meningitis (AM). Objective To compare the performance of two of these CDRs for children: the Bacterial Meningitis Score (BMS) and the Meningitest. Design Secondary analysis of retrospective multicentre hospital-based cohort study. Setting Six paediatric emergency or intensive care units of tertiary care centres in five European countries. Patients Consecutive children aged 29 days to 18 years presenting with acute meningitis and procalcitonin (PCT) measurement. Intervention None. Main outcome measures The sensitivity and specificity of the BMS (start antibiotics in case of seizure, positive cerebrospinal fluid (CSF) Gram staining, blood neutrophil count ≥10 ×109/l, CSF protein level ≥80 mg/dl or CSF neutrophil count ≥1000 ×106/l) and the Meningitest (start antibiotics in case of seizure, purpura, toxic appearance, PCT level ≥0.5 ng/ml, positive CSF Gram staining or CSF protein level ≥50 mg/dl) were compared using a McNemar test. Results 198 patients (mean age 4.8 years) from six centres in five European countries were included; 96 had bacterial meningitis. The BMS and Meningitest both showed 100% sensitivity (95% CI 96% to 100%). The BMS had a significantly higher specificity (52%, 95% CI 42% to 62% vs 36%, 95% CI 27% to 46%; p<10−8). Conclusion The Meningitest and the BMS were both 100% sensitive. This result provides level II evidence for the sensitivity of both rules, which can be used cautiously. However, use of the BMS could safely avoid significantly more unnecessary antibiotic treatments for children with AM than can the Meningitest in this population.

The moral experience of parents regarding life-support decisions for their critically-ill children: a preliminary study in France

The common paediatric critical care practice in France is for physicians (rather than parents) to maintain the ultimate responsibility for lifesupport decisions in children. Some French literature asserts that it is inappropriate for parents to bear such responsibilities because they do not have the required knowledge and should be protected from feeling culpable for such decisions. The aim of this grounded theory preliminary study was to examine the moral experience of parents of critically-ill children that required life-support decisions in France. A convenience purposive sample of seven parents was recruited in Paris. Five principal themes emerged as significant from these interviews: (1) a need for more information; (2) physicians should be responsible for life-support decisions; (3) the childs concerns and wishes need to be better heard; (4) maternal guilt; and (5) physicians require better training in parent communication. These findings raise important issues for clinical practice and further research in France.

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.