Higher Versus Lower Protein Delivery in Critically Ill Patients: A Systematic Review and Bayesian Meta-Analysis

Samuel Heuts; Zheng-Yii Lee; Charles Chin Han Lew; Julia L M Bels; Andrea Gabrio; Michal J Kawczynski; Daren K Heyland; Matthew J Summers; Adam M Deane; Dieter Mesotten; Lee-Anne S Chapple; Christian Stoppe; Marcel C G van de Poll

doi:10.1097/CCM.0000000000006562

Higher Versus Lower Protein Delivery in Critically Ill Patients: A Systematic Review and Bayesian Meta-Analysis

Crit Care Med. 2024 Dec 27. doi: 10.1097/CCM.0000000000006562. Online ahead of print.

Authors

Samuel Heuts^{1

2}, Zheng-Yii Lee^{3

4}, Charles Chin Han Lew^{5

6}, Julia L M Bels⁷, Andrea Gabrio⁸, Michal J Kawczynski^{1

2}, Daren K Heyland⁹, Matthew J Summers^{10

11}, Adam M Deane¹², Dieter Mesotten^{13

14}, Lee-Anne S Chapple^{10

11}, Christian Stoppe^{4

15}, Marcel C G van de Poll^{7

16}

Affiliations

¹ Department of Cardiothoracic Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands.
² Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
³ Department of Anaesthesiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
⁴ Department of Cardiac Anaesthesiology and Intensive Care Medicine, Charité, Berlin, Germany.
⁵ Department of Dietetics and Nutrition, Ng Teng Fong General Hospital Singapore, Singapore.
⁶ Faculty of Health and Social Sciences, Singapore Institute of Technology, Singapore.
⁷ Department of Intensive Care Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.
⁸ Department of Statistics and Methodology, Maastricht University, Maastricht, The Netherlands.
⁹ Clinical Evaluation Research Unit, Department of Critical Care Medicine, Queen's University, Kingston, ON, Canada.
¹⁰ Intensive Care Unit, Royal Adelaide Hospital, Adelaide, SA, Australia.
¹¹ Adelaide School of Medicine, University of Adelaide, Adelaide, SA, Australia.
¹² Department of Critical Care, University of Melbourne, Parkville, VIC, Australia.
¹³ Department of Intensive Care Medicine, Ziekenhuis Oost-Limburg, Genk, Belgium.
¹⁴ UHasselt, Faculty of Medicine and Life Sciences, Diepenbeek, Belgium.
¹⁵ Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Würzburg, Würzburg, Germany.
¹⁶ School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.

PMID: 39728669
DOI: 10.1097/CCM.0000000000006562

Abstract

Objectives: Recent multicenter trials suggest that higher protein delivery may result in worse outcomes in critically ill patients, but uncertainty remains. An updated Bayesian meta-analysis of recent evidence was conducted to estimate the probabilities of beneficial and harmful treatment effects.

Data sources: An updated systematic search was performed in three databases until September 4, 2024. The study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and the protocol was preregistered in PROSPERO (CRD42024546387).

Study selection: Randomized controlled trials that studied adult critically ill patients comparing protein doses delivered enterally and/or parenterally with similar energy delivery between groups were included.

Data extraction: Data extraction was performed by two authors independently, using a predefined worksheet. The primary outcome was mortality. Posterior probabilities of any benefit (relative risk [RR] < 1.00) or harm (RR > 1.00) and other important beneficial and harmful effect size thresholds were estimated. Risk of bias assessment was performed using the risk of bias 2.0 tool. All analyses were performed using a Bayesian hierarchical random-effects models, under vague priors.

Data synthesis: Twenty-two randomized trials (n = 4164 patients) were included. The mean protein delivery in the higher and lower protein groups was 1.5 ± 0.6 vs. 0.9 ± 0.4 g/kg/d. The median RR for mortality was 1.01 (95% credible interval, 0.84-1.16). The posterior probability of any mortality benefit from higher protein delivery was 43.6%, while the probability of any harm was 56.4%. The probabilities of a 1% (RR < 0.99) and 5% (RR < 0.95) mortality reduction by higher protein delivery were 38.7% and 22.9%, respectively. Conversely, the probabilities of a 1% (RR > 1.01) and 5% (RR > 1.05) mortality increase were 51.5% and 32.4%, respectively.

Conclusions: There is a considerable probability of an increased mortality risk with higher protein delivery in critically ill patients, although a clinically beneficial effect cannot be completely eliminated based on the current data.