Stéphane Leteurtre

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)

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.

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.

No resuscitation orders and withdrawal of therapy in French paediatric intensive care units

Objective: To determine the incidence of different modes of death in French paediatric intensive care units and to compare patients’characteristics, including a severity of illness score (Paediatric Risk of Mortality: PRISM score) and prior health status (Paediatric Overall Performance Category scale), according to the mode of death. Design: A 4‐month prospective cohort study. Setting: Nine French multidisciplinary paediatric intensive care units. Patients: All patients who died in PICUs, except premature babies. Main results: Among 712 admissions, 13% patients died. Brain death was declared in 20%, failure of cardiopulmonary resuscitation occurred in 26%, do‐not‐resuscitate status was identified in 27%, and withdrawal of supportive therapy was noted in 27%. The PRISM score and the baseline Paediatric Overall Performance Category were not different between the four groups. Brain‐dead patients were older than those in whom a do‐not‐resuscitate order and withdrawal of therapy were made (median age 81 vs 7 and 4 months). Conclusions: Decisions to limit or to withdraw supportive care were made for a majority of patients dying in French paediatric intensive care units. Chronic health evaluation and severity of illness index are not sufficient to describe dead‐patient populations.

Do new strategies in meningococcemia produce better outcomes

Meningococcal septic shock (MSS) has high mortality and morbidity rates. In addition to the traditional prompt antibiotics and respiratory and circulatory support, new treatment strategies have been proposed. Against the Inflammatory CascadeImmunotherapy, such as antiserum to Escherichia coli J5 and human antilipid A monoclonal antibodies/centoxin (HA-1A), did not significantly alter the mortality rate of MSS; we are awaiting the results of the bactericidal/permeability-increasing protein multicenter trial. Two series reported the effects of hemofiltration and hemodiafiltration in MSS, but the true benefits remain unknown. To Treat Hemostatic AbnormalitiesIn MSS, heparin is still controversial and antithrombin concentrate use has been reported in only one child. Several case reports on protein C and recombinant tissue plasminogen activator have been published; the efficacy (improvement in shock and organ dysfunction and reduction in amputation rate) and safety (intracerebral hemorrhage with recombinant tissue plasminogen activator) of these treatments need further evaluation. Blood and plasma exchange appear to be safe and are supposed to reduce mortality, but it is difficult to draw firm conclusions from published studies. Finally, local application of medicinal leeches has been reported to improve purpuric lesions. To Induce VasodilationProstacyclin, or epoprostenol, infusion, sodium nitroprussiate infusion, sympathetic blockade, and topical nitroglycerin have been reported to improve distal perfusion; however, these reports are all anecdotal. Other StrategiesImprovement in limb perfusion was achieved after hyperbaric oxygenation in patients with purpura fulminans caused by different pathogens. Most authors recommend monitoring of compartment pressures and performing fasciotomy as indicated. Finally, extracorporeal membrane oxygenation was recently proposed to support seven children with intractable MSS. ConclusionsThere is no proof that unconventional treatments have a significant impact on outcome in MSS; prospective multicenter trials are needed. At present, early recognition of meningococcal sepsis and appropriate treatment seem to be the optimal methods of improving outcome. Efforts to find an effective meningococcal vaccine must be continued.

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.

Protein C concentrate and recombinant tissue plasminogen activator in meningococcal septic shock.

Meningococcal septic shock (MSS), with its high mortality (20% to 50%) (1) and morbidity rates (skin necrosis and limb ischemia [SNLI] are observed in up to 72% of survivors) (2), remains a challenging problem. Although it has been reported that protein C (PC) levels are decreased (3) and plasminogen activator inhibitor-1 levels are increased (4) in children with MSS, two recent case reports that suggest a beneficial effect for PC and recombinant tissue plasminogen activator (rt-PA) (5, 6) and other previous reports (7-12) do not produce any proof of efficacy of these costly treatments.

Indications and Effects of Plasma Transfusions in Critically Ill Children

RATIONALE Plasma transfusions are frequently prescribed for critically ill children, although their indications lack a strong evidence base. Plasma transfusions are largely driven by physician conceptions of need, and these are poorly documented in pediatric intensive care patients. OBJECTIVES To identify patient characteristics and to characterize indications leading to plasma transfusions in critically ill children, and to assess the effect of plasma transfusions on coagulation tests. METHODS Point-prevalence study in 101 pediatric intensive care units in 21 countries, on 6 predefined weeks. All critically ill children admitted to a participating unit were included if they received at least one plasma transfusion. MEASUREMENTS AND MAIN RESULTS During the 6 study weeks, 13,192 children were eligible. Among these, 443 (3.4%) received at least one plasma transfusion and were included. The primary indications for plasma transfusion were critical bleeding in 22.3%, minor bleeding in 21.2%, planned surgery or procedure in 11.7%, and high risk of postoperative bleeding in 10.6%. No bleeding or planned procedures were reported in 34.1%. Before plasma transfusion, the median international normalized ratio (INR) and activated partial thromboplastin time (aPTT) values were 1.5 and 48, respectively. After plasma transfusion, the median INR and aPTT changes were -0.2 and -5, respectively. Plasma transfusion significantly improved INR only in patients with a baseline INR greater than 2.5. CONCLUSIONS One-third of transfused patients were not bleeding and had no planned procedure. In addition, in most patients, coagulation tests are not sensitive to increases in coagulation factors resulting from plasma transfusion. Studies assessing appropriate plasma transfusion strategies are urgently needed.