Continuous Versus Intermittent Nutrition in Pediatric Intensive Care Patients: Protocol for a Randomized Controlled Trial

Abstract

Background Intermittent fasting is a time-restricted feeding strategy with proven health benefits, which is based on multiple metabolic and endocrine changes, in several patient populations and healthy participants. In the pediatric intensive care unit (PICU), artificial feeding is usually administered 24 hours a day, although solid evidence supporting this practice is lacking. This discards the potential benefits of fasting in this population. We hypothesize that intermittent nutrition with a focus on an overnight feeding interruption (intermittent fasting), as compared with 24-hour continuous nutrition, is a feasible and safe strategy, with potential benefits, for critically ill children. Objective The aim of the Continuous versus Intermittent Nutrition in Pediatric Intensive Care randomized controlled trial (RCT) is to investigate a strategy of intermittent nutrition with a focus on an overnight feeding interruption period versus 24-hour nutrition during the first 14 days in the PICU. Methods The Continuous versus Intermittent Nutrition in Pediatric Intensive Care study is an investigator-initiated RCT in a tertiary referral PICU. Critically ill children (term newborn to 18 years), expected to stay in the PICU for ≥48 hours, and dependent on artificial nutrition, are eligible for inclusion. This study will randomize critically ill children (n=140) to a continuous versus intermittent nutrition strategy. In both groups, similar daily caloric targets will be prescribed. In the continuous group (control), nutrition will be administered 24 hours a day, with a maximum interruption period of 2 hours. In the intermittent group (intervention), nutrition will be interrupted during an age-dependent overnight fasting period. The study intervention will last until admission day 14, initiation of oral intake, or discharge from the PICU, whichever comes first. The primary outcome is the difference in ketosis between the groups under the condition of noninferiority regarding caloric intake. Secondary outcomes are feeding intolerance; the proportion of severe and resistant hypoglycemic events and severe gastrointestinal complications; and additional observed effects on nutritional intake, circadian rhythm, and clinically relevant outcome measures of the intermittent feeding strategy compared with continuous nutrition. Results The study was approved by the Dutch national ethical review board in February 2020. The first patient was enrolled on May 19, 2020. By May 2022, a total of 132 patients had been included in the study. Recruitment of the last patient is expected in Q3 2022. Conclusions Although intermittent fasting has been proven to have many health benefits in both animal and human studies, the feasibility and safety of this strategy in a PICU setting must be investigated. This RCT will help physicians gain more insight into the feasibility, safety, and potential clinical effects of intermittent feeding with overnight fasting in critically ill children. Trial Registration Netherlands Trial Register NL7877; https://trialsearch.who.int/Trial2.aspx?TrialID=NL7877 International Registered Report Identifier (IRRID) DERR1-10.2196/36229

Continuous versus Intermittent Enteral Feeding in Critically Ill Children: A Systematic Review

“…For this systematic review, we performed a search in a clinical trial registry ( , 28 December 2022), and to complement this strategy, we also hand-searched the literature to facilitate and retrieve ongoing trials on this topic. Currently, there are two ongoing protocols involving only pediatric patients admitted in the PICU (NCT02973347 and [ 43 ]), categorized as unknown status and ongoing trial, respectively. Additionally, a larger number of registered, active protocols have been identified in adult patients for the comparison of continuous versus bolus-enteral feeding on clinically relevant outcomes.…”

“…The following supporting information can be downloaded at: , Table S1: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA); Table S2: Search strategy for identifying randomized controlled trials on Pubmed; Table S3: Excluded studies with reasons [ 43 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ].…”