Impact of protein intervention timings on critically ill patients: A systematic review and meta- analysis

Sharma, Pranav Kumar; Arora, Sanjiya; Bhavsar, Tirth; Kamboj, Mamta; Kamboj, Rahul; Gupta, Varnika; Ramamurthi, Anitha Sigamani; Uthayakumar, Kumari; Singh, Ajay; Chaudhary, Sachin Mahendrakumar; Das, Arghadip; Bajrami, Arianisa; Singh, Sumesh; Tripathi, Devendra

Impact of protein intervention timings on critically ill patients: A systematic review and meta- analysis

Volume 11 (2025): Issue 4 (October 2025)

By: Pranav Kumar Sharma, Sanjiya Arora, Tirth Bhavsar, Mamta Kamboj, Rahul Kamboj, Varnika Gupta, Anitha Sigamani Ramamurthi, Kumari Uthayakumar, Ajay Singh, Sachin Mahendrakumar Chaudhary, Arghadip Das, Arianisa Bajrami, Sumesh Singh and Devendra Tripathi

Open Access

|Oct 2025

Figures & Tables

PRISMA flow diagram of search strategy and selection of studies.

Risk of bias summary: review authors’ judgements about each risk of bias item for each included study

Forest plot for infectious complications

Forest plot for number of days on mechanical ventilation

Basic characteristics of the selected studies

Study/Year/Country	Study Type	Patient	Early Protein (EP)	Late Protein (LP)	Outcome measures
Casaer/ 2011/Belgium	Prospective randomized, control, parallel group, multicenter trial.	Critically ill adults in ICU. Total n=4640 EP=2312 LP=2328	Within 48 hours of ICU	≥8 days of ICU admission	Mortality, length of ICU stay, length of hospital stay, any new infection, metabolic complications, organ failure.
Doig/2013/Australia	Randomized, single blind, multicenter clinical trial	Critically ill (medical, trauma, and surgical) adults in ICU Total n= 1372 EP= 686 Standard care=686	Within 24 hours of admission	Standard care	Mortality (>60 days), ICU length of stay, hospital length of stay, infection, organ failure
Vicic/2013/Croatia	Prospective multicenter cohort study	Burns patients in ICU Total n=102 EP= 52 LP=50	Within 4 hours of admission in ICU	After first wound dressing	Mortality, pneumonia, sepsis, renal failure, wound infection, multi-organ failure, bacterial and fungal infections.
Sun/2013/China	Randomized controlled single center trial	Severe acute pancreatitis patients Total n=60 EP=30 LP=30	Within 48 hours after admission	From the 8^th day after admission	Mortality, length of ICU stay, pancreatic infection, multiple organ dysfunction, systemic inflammatory response syndrome (SIPS), surgery
Bakkar/2014/Netherlands	Randomized controlled multicenter trial	Acute pancreatitis patients Total patients n=205 EP=101 LP=104	Within 24 hours after randomization	Standard care 72 hours after presentation	Mortality, infected pancreatic necrosis, pneumonia, bacteremia, mechanical ventilation, organ failure, ICU length of stay.
Li/2014/China	Randomized controlled single center trial	Cancer patients undergoing gastric cancer surgery Total n=300 EP=150 LP=150	Post-operative day 2	Standard care	Wound infection, urinary tract infection, post-operative fever, vomiting, nausea, bloating
Mehmoodzadeh/2014/Iran	Randomized controlled single center trial	Patients with esophageal or upper gastrointestinal malignancies undergoing surgical resection Total n= 109 EP= 54 LP=55	First post-operative day (oral)	No oral nutrition until the first bowel sounds returned and there was resolution of ileus.	Pneumonia, ICU length of stay, hospital length of stay, Rehospitalization, peritonitis, esophageal fistula, paralysis of the recurrent laryngeal nerve.
Song/2017/Korea	Prospective single center cohort study	Critically ill mechanically ventilated ICU patients Total n=210 EP=34 Standard care=176	Within the first 24 hours of ICU admission	Standard care	ICU Mortality, 28 day mortality, hospital mortality, hospital length of stay.
Bendavid/2019/Israel	Retrospective single center cohort study	Critically ill ICU patients Total n=2253 EP=1040 LP=1213	Within first 3 days of ICU admission	After first 3 days of ICU admission	Mortality (60 days)
Koekkoek/2019/Netherlands	Retrospective multicenter cohort study	Critically ill patients on mechanical ventilation Total n=455 EP=337 LP=117	<3 days of ICU admission	After 3 days of ICU admission	ICU mortality, hospital mortality, mortality (6 months), days on mechanical ventilation, ICU length of stay, hospital length of stay.
Sim/2021/Korea	Retrospective cohort study	Emergency abdominal surgery for intra-abdominal infection Total n= 111 EP= 66 LP= 45	Within 48 hours of ICU admission	After 48 hours	Mortality (30 days), in-hospital mortality, infectious complications, pneumonia, ICU length of stay, hospital length of stay.
Ortiz-Reyes/2022/USA	Randomized controlled multi-national trial	ICU patients with circulatory shock Total n=626 EP=526 LP=100	<48 hours from ICU admission	>48 hours from ICU admission	Mortality (60 days), multiple organ dysfunction syndrome (MODS), sepsis, days on mechanical ventilation, gut ischemia.
Gao/2022/China	Randomized controlled multicenter trial	Abdominal surgery for gastrointestinal cancers Total n=230 EP=115 LP=115	From day 3 after surgery	From day 8 after surgery	Nasocomial infections, infectious complications, non-infectious complications, adverse events, days on mechanical ventilation, ICU length of stay, hospital length of stay.

Quality assessment of selected studies using Newcastle-Ottawa Scale (NoS)

Study	Selection				Comparability	Outcome of interest			Overall Quality of study
					Comparability
	Representativeness of the exposed cohort	Selection of non-exposed cohort	Ascertainment of exposure	Outcome present at start of study	Comparability of cohorts	Assessment of outcome	Length of follow-up	Adequacy of follow-up
Vicic [2013]	*	*	*	*		*	*	*	Poor
Song [2017]	*	*	*	*	*	*	*	*	Good
Bendavid [2019]	*	*	*	*	**	*	*	*	Good
Koekkoek [2019]	*	*	*	*	**	*	*	*	Good
Sim [2021]	*	*	*	*	**	*	*	*	Good

DOI: https://doi.org/10.2478/jccm-2025-0047 | Journal eISSN: 2393-1817 | Journal ISSN: 2393-1809

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Language: English

Page range: 323 - 336

Submitted on: Jan 1, 2025

Accepted on: Oct 8, 2025

Published on: Oct 31, 2025

Published by: University of Medicine, Pharmacy, Science and Technology of Targu Mures

In partnership with: Paradigm Publishing Services

Publication frequency: 4 issues per year

Keywords:

protein supplementation,

critical care nutrition,

timing of nutritional support,

Related subjects:

Internal medicine, other,

Surgery,

Surgery, other,

Anaesthesiology,

Emergency medicine and intensive-care medicine

© 2025 Pranav Kumar Sharma, Sanjiya Arora, Tirth Bhavsar, Mamta Kamboj, Rahul Kamboj, Varnika Gupta, Anitha Sigamani Ramamurthi, Kumari Uthayakumar, Ajay Singh, Sachin Mahendrakumar Chaudhary, Arghadip Das, Arianisa Bajrami, Sumesh Singh, Devendra Tripathi, published by University of Medicine, Pharmacy, Science and Technology of Targu Mures
This work is licensed under the Creative Commons Attribution 4.0 License.

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Impact of protein intervention timings on critically ill patients: A systematic review and meta- analysis

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Basic characteristics of the selected studies

Quality assessment of selected studies using Newcastle-Ottawa Scale (NoS)

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