Abstract
BackgroundThe state-of-the-art nutrition used for critically ill children is based essentially on expert opinion and extrapolations from adult studies or on studies in non-critically ill children. In critically ill adults, withholding parenteral nutrition (PN) during the first week in ICU improved outcome, as compared with early supplementation of insufficient enteral nutrition (EN) with PN. We hypothesized that withholding PN in children early during critical illness reduces the incidence of new infections and accelerates recovery.Methods/DesignThe Pediatric Early versus Late Parenteral Nutrition in Intensive Care Unit (PEPaNIC) study is an investigator-initiated, international, multicenter, randomized controlled trial (RCT) in three tertiary referral pediatric intensive care units (PICUs) in three countries on two continents. This study compares early versus late initiation of PN when EN fails to reach preset caloric targets in critically ill children. In the early-PN (control, standard of care) group, PN comprising glucose, lipids and amino acids is administered within the first days to reach the caloric target. In the late-PN (intervention) group, PN completing EN is only initiated beyond PICU-day 7, when EN fails. For both study groups, an early EN protocol is applied and micronutrients are administered intravenously. The primary assessor-blinded outcome measures are the incidence of new infections during PICU-stay and the duration of intensive care dependency. The sample size (n = 1,440, 720 per arm) was determined in order to detect a 5% absolute reduction in PICU infections, with at least 80% 1-tailed power (70% 2-tailed) and an alpha error rate of 5%. Based on the actual incidence of new PICU infections in the control group, the required sample size was confirmed at the time of an a priori- planned interim-analysis focusing on the incidence of new infections in the control group only.DiscussionClinical evidence in favor of early administration of PN in critically ill children is currently lacking, despite potential benefit but also known side effects. This large international RCT will help physicians to gain more insight in the clinical effects of omitting PN during the first week of critical illness in children.Trial registrationClinicalTrials.gov: NCT01536275 on 16 February 2012.
Highlights
The state-of-the-art nutrition used for critically ill children is based essentially on expert opinion and extrapolations from adult studies or on studies in non-critically ill children
Sample size calculation and interim analyses In the design phase of the PEPaNIC trial, and based on the previous adult EPaNIC trial results, the sample size (N = 1,440, 720 patients per arm) was determined in order to detect a reduction in the incidence of new infections during pediatric intensive care units (PICU)-stay from 20 to 15% (Absolute Risk Reduction 5%), with at least 80% 1-tailed power and at least 70% 2-tailed power and at an alpha error of 5%
Thousands of children are annually exposed to this non-evidence-based treatment, which is assumed to result in faster recovery
Summary
The clinical evidence for the administration of PN in critically ill children is missing [18]. Thousands of children are annually exposed to this non-evidence-based treatment, which is assumed to result in faster recovery (benefit) This large international RCT will help PICU physicians to obtain more insight into the possibility of the omission of PN during the first week of critical illness. Authors’ contributions TF: participated in the design of the study and analysis plan, helped to draft the manuscript. PJW: participated in the design of the study, revising the manuscript for important intellectual content. KJ: participated in the design of the study, revising the manuscript for important intellectual content.
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