Association of Organ Dysfunction Scores and Functional Outcomes Following Pediatric Critical Illness.

OBJECTIVES: Short-term and long-term morbidity and mortality are common following pediatric critical illness. Severe organ dysfunction is associated with significant in-hospital mortality in critically ill children; however, the performance of pediatric organ dysfunction scores as predictors of functional outcomes after critical illness has not been previously assessed. DESIGN: Secondary analysis of a prospective observational cohort. SETTING: A multidisciplinary, tertiary, academic PICU. PATIENTS: Patients less than or equal to 18 years old admitted between June 2012 and August 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The maximum pediatric Sequential Organ Failure Assessment and Pediatric Logistic Organ Dysfunction-2 scores during admission were calculated. The Functional Status Scale score was obtained at baseline, 6 months and 3 years following discharge. New morbidity was defined as a change in Functional Status Scale greater than or equal to 3 points from baseline. The performance of organ dysfunction scores at discriminating new morbidity or mortality at 6 months and 3 years was measured using the area under the curve. Seventy-three patients met inclusion criteria. Fourteen percent had new morbidity or mortality at 6 months and 23% at 3 years. The performance of the maximum pediatric Sequential Organ Failure Assessment and Pediatric Logistic Organ Dysfunction-2 scores at discriminating new morbidity or mortality was excellent at 6 months (areas under the curves 0.9 and 0.88, respectively) and good at 3 years (0.82 and 0.79, respectively). CONCLUSIONS: Severity of organ dysfunction is associated with longitudinal change in functional status and short-term and long-term development of new morbidity and mortality. Maximum pediatric Sequential Organ Failure Assessment and Pediatric Logistic Organ Dysfunction-2 scores during critical illness have good to excellent performance at predicting new morbidity or mortality up to 3 years after critical illness. Use of these pediatric organ dysfunction scores may be helpful for prognostication of longitudinal functional outcomes in critically ill children.

The Fragility of Statistically Significant Findings in Pediatric Critical Care Randomized Controlled Trials.

OBJECTIVES: The Fragility Index measures the number of events on which the statistical significance of a result depends and has been suggested as an adjunct statistical assessment for interpretation of trial results. This study aimed to assess the robustness of statistically significant results from pediatric critical care randomized controlled trials with dichotomous outcomes. DATA SOURCES: A previously published scoping review of pediatric critical care randomized controlled trials (www.PICUtrials.net). STUDY SELECTION: A total of 342 trials were screened for inclusion. After applying inclusion/exclusion criteria, 43 fulfilled eligibility criteria and were included in the analysis. DATA EXTRACTION: Calculation of Fragility Index for trials reporting a statistically significant dichotomous outcome, and analysis of the relationship between trial characteristics and Fragility Index. DATA SYNTHESIS: The median Fragility Index was 2 (interquartile range, 1-6). The median sample size was 98 (interquartile range, 50-148) and sample size demonstrated a strong correlation with the Fragility Index (r = 0.729; n = 43; p < 0.001). The median number of outcome events was 8 (interquartile range, 4-15) and the total number of outcome events also showed a strong correlation with the Fragility Index (r = 0.728; n = 43; p < 0.001). CONCLUSIONS: Results from pediatric critical care randomized controlled trials with dichotomous outcomes reporting statistically significant findings often hinge on a small number of outcome events. Clinicians should exercise caution when interpreting results of trials with a low Fragility Index.

Adaptation and Validation of a Pediatric Sequential Organ Failure Assessment Score and Evaluation of the Sepsis-3 Definitions in Critically Ill Children.

Importance: The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) uses the Sequential Organ Failure Assessment (SOFA) score to grade organ dysfunction in adult patients with suspected infection. However, the SOFA score is not adjusted for age and therefore not suitable for children. Objectives: To adapt and validate a pediatric version of the SOFA score (pSOFA) in critically ill children and to evaluate the Sepsis-3 definitions in patients with confirmed or suspected infection. Design, Setting, and Participants: This retrospective observational cohort study included all critically ill children 21 years or younger admitted to a 20-bed, multidisciplinary, tertiary pediatric intensive care unit between January 1, 2009 and August 1, 2016. Data on these children were obtained from an electronic health record database. The pSOFA score was developed by adapting the original SOFA score with age-adjusted cutoffs for the cardiovascular and renal systems and by expanding the respiratory criteria to include noninvasive surrogates of lung injury. Daily pSOFA scores were calculated from admission until day 28 of hospitalization, discharge, or death (whichever came first). Three additional pediatric organ dysfunction scores were calculated for comparison. Exposures: Organ dysfunction measured by the pSOFA score, and sepsis and septic shock according to the Sepsis-3 definitions. Main Outcomes and Measures: The primary outcome was in-hospital mortality. The daily pSOFA scores and additional pediatric organ dysfunction scores were compared. Performance was evaluated using the area under the curve. The pSOFA score was then used to assess the Sepsis-3 definitions in the subgroup of children with confirmed or suspected infection. Results: In all, 6303 patients with 8711 encounters met inclusion criteria. Each encounter was treated independently. Of the 8482 survivors of hospital encounters, 4644 (54.7%) were male and the median (interquartile range [IQR]) age was 69 (17-156) months. Among the 229 nonsurvivors, 127 (55.4%) were male with a median (IQR) age of 43 (8-144) months. In-hospital mortality was 2.6%. The maximum pSOFA score had excellent discrimination for in-hospital mortality, with an area under the curve of 0.94 (95% CI, 0.92-0.95). The pSOFA score had a similar or better performance than other pediatric organ dysfunction scores. According to the Sepsis-3 definitions, 1231 patients (14.1%) were classified as having sepsis and had a mortality rate of 12.1%, and 347 (4.0%) had septic shock and a mortality rate of 32.3%. Patients with sepsis were more likely to die than patients with confirmed or suspected infection but no sepsis (odds ratio, 18; 95% CI, 11-28). Of the 229 patients who died during their hospitalization, 149 (65.0%) had sepsis or septic shock during their course. Conclusions and Relevance: The pSOFA score was adapted and validated with age-adjusted variables in critically ill children. Using the pSOFA score, the Sepsis-3 definitions were assessed in children with confirmed or suspected infection. This study is the first assessment, to date, of the Sepsis-3 definitions in critically ill children. Use of these definitions in children is feasible and shows promising results.

The Fragility Index in a Cohort of Pediatric Randomized Controlled Trials.

Data suggest inadequacy of common statistical techniques for reporting outcomes in clinical trials. The Fragility Index can measure how many events the statistical significance hinges on, and may facilitate better interpretation of trial results. This study aimed to assess the Fragility Index in pediatric randomized controlled trials (RCTs) with statistically significant findings published in high-quality medical journals. A Fragility Index was calculated on included trials with dichotomous positive outcomes. Analysis of the relationship between trial characteristics and the Fragility Index was performed. Of the 429 abstracts screened, 17 met the inclusion criteria and underwent analysis. The median Fragility Index was 7 with an interquartile range of 2-11. In 41% of the studies, the number of patients lost to follow-up or withdrawn prior to analysis was equal to or greater than the Fragility Index. There was no correlation between the RCT sample size and the Fragility Index (r = 0.249, p = 0.335) nor the event group size and the Fragility Index (r = 0.250, p = 0.334). There was a strong negative correlation between the original p-value and the Fragility Index (r = -0.700, p = 0.002). The Fragility Index is a calculated metric that may assist in applying clinical relevance to statistically significant outcomes in pediatric randomized controlled trials with dichotomous outcomes.