Jacques Cotting

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.

Severity of illness and organ dysfunction scoring in children.

Objective: To describe predictive and descriptive general scores that can be used to estimate the severity of illness in critically ill children. Design: Review of the medical literature. Setting: Pediatric intensive care units (PICUs). Patients: Critically ill children. Interventions: None. Measurements and Main Results: Two predictive scores are frequently used in PICUs: the Pediatric Risk of Mortality III score and the Pediatric Index of Mortality 2. The data considered in these scores are collected at baseline. Predictive scores can be used to compare expected and observed mortality in PICUs or to estimate the balance in the baseline severity of illness of patients included in the different arms of a randomized clinical trial. Only one descriptive score is validated to estimate the severity of cases of multiple organ dysfunction syndrome in PICUs, namely, the Pediatric Logistic Organ Dysfunction score. The data required to calculate this score are collected from baseline to discharge from the PICU or up to 2 hrs before death in the PICU. The Pediatric Logistic Organ Dysfunction score can be used to describe the clinical outcome of patients during their stay in a PICU. Conclusion: Pediatric Risk of Mortality III, Pediatric Index of Mortality 2, and Pediatric Logistic Organ Dysfunction scores are the best available tools to estimate the severity of illness in critically ill children.

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.

Albuterol delivery in an in vitro pediatric ventilator lung model: comparison of jet, ultrasonic, and mesh nebulizers.

Objective: To determine the influence of nebulizer types and nebulization modes on bronchodilator delivery in a mechanically ventilated pediatric lung model. Design: In vitro, laboratory study. Setting: Research laboratory of a university hospital. Interventions: Using albuterol as a marker, three nebulizer types (jet nebulizer, ultrasonic nebulizer, and vibrating-mesh nebulizer) were tested in three nebulization modes in a nonhumidified bench model mimicking the ventilatory pattern of a 10-kg infant. The amounts of albuterol deposited on the inspiratory filters (inhaled drug) at the end of the endotracheal tube, on the expiratory filters, and remaining in the nebulizers or in the ventilator circuit were determined. Particle size distribution of the nebulizers was also measured. Measurements and Main Results: The inhaled drug was 2.8% ± 0.5% for the jet nebulizer, 10.5% ± 2.3% for the ultrasonic nebulizer, and 5.4% ± 2.7% for the vibrating-mesh nebulizer in intermittent nebulization during the inspiratory phase (p < 0.01). The most efficient nebulizer was the vibrating-mesh nebulizer in continuous nebulization (13.3% ± 4.6%, p < 0.01). Depending on the nebulizers, a variable but important part of albuterol was observed as remaining in the nebulizers (jet and ultrasonic nebulizers), or being expired or lost in the ventilator circuit (all nebulizers). Only small particles (range 2.39–2.70 µm) reached the end of the endotracheal tube. Conclusions: Important differences between nebulizer types and nebulization modes were seen for albuterol deposition at the end of the endotracheal tube in an in vitro pediatric ventilator–lung model. New aerosol devices, such as ultrasonic and vibrating-mesh nebulizers, were more efficient than the jet nebulizer.

Mycoplasma hominis necrotizing pleuropneumonia in a previously healthy adolescent

BackgroundMycoplasma hominis is a fastidious micro-organism causing systemic infections in the neonate and genital infections in the adult. It can also be the cause of serious extra-genital infections, mainly in immunosuppressed or predisposed subjects.Case PresentationWe describe a case of severe pneumonia and pericarditis due to Mycoplasma hominis in a previously healthy adolescent who did not respond to initial therapy.ConclusionsMycoplasma hominis could be an underestimated cause of severe pneumonia in immunocompetent patients and should be particularly suspected in those not responding to standard therapy.

In vitro evaluation of bronchodilator drug delivery by jet nebulization during pediatric mechanical ventilation.

Objective: To determine the influence of jet nebulizer brands and nebulization mode on albuterol delivery in a mechanically ventilated pediatric lung model. Design: In vitro, laboratory study. Setting: Research laboratory of a university hospital. Interventions: Using albuterol as a marker, six jet nebulizers (Microneb NA420, Sidestream, Acorn II, Cirrus, Upmist, Micro Mist) were tested in four nebulization modes in a bench model mimicking the ventilatory pattern of a 10-kg infant (Galileo ventilator, Hamilton Medical). The amounts of albuterol deposited on the inspiratory filters at the end of the endotracheal tube were determined, as well as the pressure, flow profiles, and particle size distribution of the jet nebulizers. Measurements and Main Results: Pooling the data of the six jet nebulizer brands (n = 30) indicated that intermittent nebulization during the expiratory phase was more efficient (6.5 ± 2.5% of the initial dose, p < .001) than intermittent nebulization during the inspiratory phase (1.9 ± 1.2%) and continuous nebulization with air from the ventilator (4.0 ± 1.5%) or from an external source (4.2 ± 1.4%). The particle size distribution at 6 L· min−1 was between 2.81 and 3.30 &mgr;m. Conclusions: In our in vitro pediatric lung model, the quantity of inhaled drug was low. Jet nebulizer brands and nebulization modes significantly affected drug delivery, and in vitro models designed for adults cannot be extrapolated to infants.

Substitution of exudative trace element losses in burned children

We describe an intravenous copper-selenium-zinc substitution policy in children with major burns using adult doses adapted to total body surface area. Blood levels and clinical course confi rm its safety, with a rapidly favourable clinical evolution. Major burn injuries are associated with trace element defi ciencies, which lead to impaired wound healing and infectious complications. Low plasma levels of zinc (Zn) and copper (Cu) are inadequately compensated for during hospitalization [1], and enteral supplements are unsuccessful in correcting the status [2]. Additionally, there are currently no clear recommendations regarding trace element requirements in children. Th e aim of the present study was to determine if our trace element supplementation policy for adults adapted to total body surface area would achieve normalization of plasma concen trations of trace elements in burned children.

Nitric oxide added to the sweep gas infusion reduces local clotting formation in adult blood oxygenators.

Nitric oxide (NO) is an inhibitor of platelet aggregation. We analyzed the effect of direct infusion of NO into adult blood oxygenators on local clot formation. Nonheparinized calves in a control group (n = 3) and NO group (n = 4) were connected to a jugulocarotid cardiopulmonary bypass (CPB; centrifugal pump) for 6 hours. The venous line and pumphead were heparin coated, whereas the oxygenator, the heat exchanger, and the arterial line were not. A total of 80 ppm of NO was mixed with the sweep gas infusion in the NO group. The pressure gradient through the oxygenator (&dgr;P.Ox.) was monitored, and its evolution was compared between groups. Oxygenators membranes were analyzed and photographed, allowing for calculation of the percentage of surface area covered with clots by using a computer image analysis program. The &dgr;P.Ox. reached a plateau of 193 ± 26% of the basal value in the NO group after 120 minutes, whereas a similar plateau of 202 ± 22% was reached after only 20 minutes in the control group (p < 0.05). The surface area of the oxygenator covered with clots was significantly reduced in the NO group (0.54 ± 0.41%) compared with the control group (5.78 ± 3.80%, p < 0.05). However, general coagulation parameters were not modified by local NO administration. The activated coagulation time remained stable between 110 and 150 seconds in both groups (p = not significant [ns]), and there were no differences in hematocrit, thrombin time, partial thromboplastin time, or fibrinogen between groups during the 6 hours of CPB. Thus, the mixed infusion of a continuous low dose of NO into adult oxygenators during prolonged CPB prevented local clot formation, whereas the general coagulation pattern remained unchanged.

A highly sensitive LC–tandem MS assay for the measurement in plasma and in urine of salbutamol administered by nebulization during mechanical ventilation in healthy volunteers

The new-generation nebulizers are commonly used for the administration of salbutamol in mechanically ventilated patients. The different modes of administration and new devices have not been compared. We developed a liquid chromatography-tandem mass spectrometry method for the determination of concentrations as low as 0.05 ng/mL of salbutamol, corresponding to the desired plasma concentration after inhalation. Salbutamol quantification was performed by reverse-phase HPLC. Analyte quantification was performed by electrospray ionization-triple quadrupole mass spectrometry using selected reaction monitoring detection ESI in the positive mode. The method was validated over concentrations ranging from 0.05 to 100 ng/mL in plasma and from 0.18 to 135 ng/mL in urine. The method is precise, with mean inter-day coefficient of variation (CV%) within 3.1-8.3% in plasma and 1.3-3.9% in urine, as well as accurate. The proposed method was found to reach the required sensitivity for the evaluation of different nebulizers as well as nebulization modes. The present assay was applied to examine whether salbutamol urine levels, normalized with the creatinine levels, correlated with the plasma concentrations. A suitable, convenient and noninvasive method of monitoring patients receiving salbutamol by mechanical ventilation could be implemented.

Placental Immaturity, Endocardial Fibroelastosis and Fetal Hypoxia

We describe a term newborn who, after a normal gestational course, presented at birth with absent cardiac activity and no spontaneous breathing. Death occurred within 30 h. Autopsy revealed placental villous immaturity, multiple acute hypoxic lesions, but also chronic hypoxic lesions like endocardial fibroelastosis. This striking association of endocardial fibroelastosis and placental villous immaturity is reviewed and correlated with 2 other cases of placental villous immaturity that led to in utero death at 39 and 41 weeks of gestation. Placental villous immaturity must be suspected and looked for by both pediatricians and obstetricians in every case of stillbirth or perinatal asphyxia of unclear origin. In order to minimize the risk of recurrence in further pregnancies, elective cesarean section may be considered.