Alain Martinot

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)

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.

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.

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.

Decline in pneumococcal meningitis after the introduction of the heptavalent-pneumococcal conjugate vaccine in northern France

Background: The impact of the heptavalent-pneumococcal conjugate vaccine on the incidence of pneumococcal meningitis in Europe has not yet been assessed. Objective: To determine whether heptavalent-pneumococcal conjugate vaccine implementation in northern France has resulted in a decrease in the incidence of pneumococcal meningitis in children. Design: Multicentre retrospective cohort study from 2000 through 2005. Settings: All paediatric departments of the 18 hospitals in northern France. Patients: Patients <18 years of age, admitted for laboratory-confirmed pneumococcal meningitis during the study period, were included. Interventions: Data were collected from medical files and the microbiological laboratories of each hospital and compared with the regional hospital discharge codes, using a capture–recapture method. Main outcome measures: The study assessed and compared global and age-related incidence rates of pneumococcal meningitis in 2001 (pre-vaccine era) and 2005. Results: 77 cases were found through the capture–recapture method. The incidence rate of pneumococcal meningitis varied from 1.65/100 000 children <18 years in 2001 to 0.80/100 000 children in 2005 (53% reduction, 95% CI 31 to 74; p = 0.08). This has so far been significant only for children <2 years of age (8.9/100 000 in 2001 to 1.8/100 000 in 2005; 82% reduction, 95% CI 52 to 95; p = 0.03). Conclusion: A decline in pneumococcal meningitis has been observed in infants since heptavalent-pneumococcal conjugate vaccination began in our area.

Suboptimal care in the initial management of children who died from severe bacterial infection: a population-based confidential inquiry.

Objectives: To study the frequency and types of suboptimal care and medical errors in children who died of severe bacterial infection as the first-stage procedure intended to improve quality of care. Design: Population-based confidential inquiry. Setting: Two adjoining administrative districts in France. Patients: Children older than 3 months dead from severe bacterial infection from 2000 through 2006. Interventions: The medical files were summarized on standardized forms and then evaluated independently by two experts, who determined whether the initial management before the patients’ arrival in intensive care was or was not optimal, in comparison with current guidelines. Measurements and Main Results: Of 23 deaths from severe bacterial infection, 21 could be analyzed; management was considered suboptimal in 76%. The coefficient of agreement between the experts was high, with a weighted &kgr; of 0.73. The types of errors identified included parental delay in seeking medical care (33%; 95% confidence interval, [12–54]), physicians’ delay in administering appropriate treatment (antibiotic therapy in the case of purpura; 38%; 95% confidence interval, 16–60), insufficient doses of or failure to repeat fluid resuscitation (24%; 95% confidence interval, [9 –35]), and overall underestimation of disease severity (38%; 95% confidence interval, [16–60]). Conclusion: This study found a high frequency of suboptimal care in the initial management of children who died of severe bacterial infection, with four separate types of errors. Other studies are needed to assess the potential avoidability of this type of death.

Daily estimation of the severity of multiple organ dysfunction syndrome in critically ill children

Background: Daily evaluation of multiple organ dysfunction syndrome has been performed in critically ill adults. We evaluated the clinical course of multiple organ dysfunction over time in critically ill children using the Pediatric Logistic Organ Dysfunction (PELOD) score and determined the optimal days for measuring scores. Methods: We prospectively measured daily PELOD scores and calculated the change in scores over time for 1806 consecutive patients admitted to seven pediatric intensive care units (PICUs) between September 1998 and February 2000. To study the relationship between daily scores and mortality in the PICU, we evaluated changes in daily scores during the first four days; the mean rate of change in scores during the entire PICU stay between survivors and nonsurvivors; and Cox survival analyses using a change in PELOD score as a time-dependent covariate to determine the optimal days for measuring daily scores. Results: The overall mortality among the 1806 patients was 6.4%. A high PELOD score (≥ 20 points) on day 1 was associated with an odds ratio (OR) for death of 40.7 (95% confidence interval [CI] 20.3–81.4); a medium score (10–19 points) on day 1 was associated with an OR for death of 4.2 (95% CI 2.0–8.7). Mortality was 50% when a high score on day 1 increased on day 2. The course of daily PELOD scores differed between survivors and nonsurvivors. A set of seven days (days 1, 2, 5, 8, 12, 16 and 18) was identified as the optimal period for measurement of daily PELOD scores. Interpretation: PELOD scores indicating a worsening condition or no improvement over time were indicators of a poor prognosis in the PICU. A set of seven days for measurement of the PELOD score during the PICU stay provided optimal information on the progression of multiple-organ dysfunction syndrome in critically ill children.

Clinical decision rules for evaluating meningitis in children.

Purpose of reviewDistinguishing between bacterial and aseptic meningitis in children is sometimes difficult. Guidelines recommend that patients with acute meningitis be systematically hospitalized and treated with antibiotics until the cerebrospinal fluid culture results are available. This strategy ensures rapid treatment for bacterial meningitis, but also involves unnecessary admissions and antibiotics for aseptic meningitis. Some authors have, therefore, proposed different combinations of predictors in clinical decision rules to distinguish as early as possible between bacterial and aseptic meningitis. To be useful, these rules must have near-100% sensitivity for bacterial meningitis, good specificity (to reduce unnecessary antibiotics and admissions), and easy bedside application. Recent findingsThe present review examines the performance and level of validation of decision rules proposed after the Haemophilus influenzae vaccination entered widespread use. Most of these rules have been validated incompletely, if at all. Only one rule incorporates the best single validated predictive marker for distinguishing between bacterial and aseptic meningitis in children: serum procalcitonin level. SummaryTwo rules are highly promising, meeting the three major conditions after a retrospective validation process in large samples. These rules can be applied cautiously to patients with the same inclusion and exclusion criteria as those in the derivation sets, while awaiting prospective multicenter validation studies.

Spondylodiscitis and mediastinitis after esophageal perforation owing to a swallowed radiolucent foreign body

A 6-year-old boy with aphagia presented with a radiolucent foreign body, esophageal perforation, mediastinitis, and a C6-C7 spondylodiscitis. A rigid plastic gear wheel was removed via thoracotomy, and the mediastinal abscess was drained through the esophagomediastinal fistula. Treatment included antibiotics as well as nonsurgical orthopedic management of the spondylodiscitis. The recovery period was uneventful, and the patient has remained asymptomatic for 2 years. Physicians must be aware of radiolucent foreign bodies. Computed tomography is very helpful in establishing the diagnosis of radiolucent foreign body, mediastinal abscess, and spondylodiscitis.