The effectiveness of high versus lower enteral protein intake, considering energy intake, on clinical outcomes in critically ill children: A systematic review and meta-analysis

Abstract

Background & aims

The optimal protein intake for critically ill children remains uncertain. This systematic review aimed to evaluate the effectiveness of high versus lower enteral protein intake, accounting for energy intake, on clinical and nutritional outcomes in children hospitalized in pediatric intensive care units (PICU).

Methods

Following the JBI methodology, a comprehensive search was conducted across Medline, CINAHL Ultimate, Embase, and Cochrane Library from inception to March 18, 2024. Randomized controlled trials (RCTs) involving critically ill children admitted to PICU for ≥48 h and receiving enteral nutrition were eligible. Studies comparing protein intake of <1.1 g/kg/day or >2 g/kg/day to internationally recommended intakes were included. Two independent reviewers screened, selected, extracted the data, and assessed the risk of bias using the JBI critical appraisal checklist for RCTs; a third reviewer resolved any disagreements. Meta-analyses were performed for nitrogen balance, PICU length of stay, prealbumin and blood urea levels using a random-effects model to account for between-study heterogeneity.

Results

Eight RCTs were included, assessing high (n = 6) and low (n = 2) enteral protein intake versus the recommended intake, mostly in infants aged 2–4 months, with bronchiolitis or after cardiac surgery. Four studies presented an unclear risk of bias and four a high risk. High protein intake (∼3 g/kg/day) was associated with significantly higher nitrogen balance values (effect size: 0.59; 95 % CI: 0.18–1.01; p = 0.0055) compared to the recommended intake (∼1.6 g/kg/day) but had no impact on PICU length of stay and was associated with increased blood urea levels. Among four RCTs assessing gastrointestinal tolerance, two reported increased diarrhea or gastric retention. Data on low versus recommended intake were limited to two studies.

Conclusions

High enteral protein intake may increase nitrogen balance in this PICU population, but potential adverse effects and the lack of evidence for clinical benefit raise concerns about its safety. Further well-powered RCTs are needed to evaluate the effects of protein doses within the 1–2.2 g/kg/day ranges in more diverse PICU populations.

Registration and publication of the protocol

This study protocol was registered in PROSPERO (number: CRD42022315325) and subsequently published in JBI Evidence Synthesis (DOI: 10.11124/JBIES-22-00133).