Current issues of ACP Journal Club are published in Annals of Internal Medicine


Review: Enteral immunonutrition reduces infection risk, days on ventilation, and hospital stay in critically ill patients


ACP J Club. 2000 July-Aug;133:9. doi:10.7326/ACPJC-2000-133-1-009

Source Citation

Beale RJ, Bryg DJ, Bihari DJ. Immunonutrition in the critically ill: a systematic review of clinical outcome. Crit Care Med. 1999 Dec;27:2799-805. [PubMed ID: 10628629]



What is the effectiveness of enteral nutrition with an immune-enhancing feed in patients who are critically ill?

Data sources

Studies were identified by searching MEDLINE (1967 to January 1998) using the terms human, enteral nutrition, arginine, nucleotides, omega-3 fatty acids, immunonutrition, IMPACT, and Immun-Aid. Authors and manufacturers of IMPACT (Novartis Nutrition, Switzerland) and Immun-Aid (McGaw, USA) were contacted.

Study selection

English-language, randomized, controlled trials were selected if they included patients who were critically ill and required enteral nutrition by a nasoenteric or jejunostomy tube; had obtained approval by an institutional review board and informed consent; compared standard enteral feed with an enteral feed enriched with arginine with or without glutamine, nucleotides, and omega-3 fatty acids; and reported on clinically important outcomes.

Data extraction

2 reviewers extracted data on study quality, patient diagnosis, type of feeds, mortality, infection, days on mechanical ventilation, hospital length of stay, intensive care unit length of stay, days of diarrhea, Acute Physiology and Chronic Health Evaluation II score, and calorie and nitrogen intake.

Main results

15 studies were identified, and 12 (1482 participants) were included in the analysis. Immune-enhancing feed reduced the risk for infection (P = 0.005, 8 studies), days on mechanical ventilation (P = 0.04, 5 studies), and hospital length of stay (P = 0.002, 10 studies) more than did standard feed (Table); no difference existed for overall mortality (relative risk 1.05, 95% CI 0.79 to 1.41, P = 0.76, 12 studies), intensive care unit length of stay (P = 0.2, 6 studies), or days of diarrhea (P = 0.78, 3 studies).


Enteral nutrition with an immune-enhancing feed reduces the risk for infection, days on mechanical ventilation, and hospital length of stay in patients who are critically ill.

Source of funding: In part, Novartis Nutrition.

For correspondence: Dr. R.J. Beale, Department of Intensive Care, Guy’s and St. Thomas’ Hospital Trust, St. Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, England, UK. FAX 44-207-960-5842. E-mail: Richard.Beale@gstt.

Table. Immune-enhancing feed vs standard feed for critically ill patients*

Outcomes Cumulative event rates RRR (95% CI) NNT (CI)
Immune-enhancing feed Standard feed
Infection 29% 38% 23% (7 to 37) 11 (7 to 40)
Weighted mean decrease (CI)
Mechanical ventilation, d 2.6 (0.1 to 5.1)
Hospital length of stay, d 2.9 (1.4 to 4.4)

*Abbreviations defined in Glossary. Weighted event rates, RRR, NNT, and CI calculated from data provided by author. Follow-up data not available.


As implied by a previous meta-analysis (1) and individual studies (2, 3), the main concern about immunonutrition is a question of increased mortality. Does the article by Beale and colleagues provide sufficient evidence to alleviate such fears and to warrant clinical recommendations? The authors limited their search to English-language studies, used only MEDLINE, and combined only studies of Impact and Immun-Aid. Interpreting differences in duration of mechanical ventilation and hospital length of stay is difficult when more deaths occur in the experimental group and when those that occur happen earlier in the course of illness (2). Immunonutrition reduces infection rates (consistent signal across studies, including the meta-analyses). However, further work needs to be done to define which subgroups benefit or are harmed and especially whether a different treatment effect exists in elective surgical compared with critically ill patients. Only then can we recommend immunostimulating ingredients to all critically ill patients.

Daren K. Heyland, MD, MSc
Frantisek Novak, MD
Kingston General Hospital
Kingston, Ontario, Canada


1. Heys SD, Walker LG, Smith I, Eremin O. Enteral nutritional supplementation with key nutrients in patients with critical illness and cancer: a meta-analysis of randomized controlled clinical trials. Ann Surg. 1999;229:467-77.

2. Atkinson S, Sieffert E, Bihari D. A prospective, randomized, double-blind, controlled clinical trial of enteral immunonutrition in the critically ill. Guy’s Hospital Intensive Care Group. Crit Care Med. 1998;26:1164-72.

3. Bower RH, Cerra FB, Bershadsky B, et al. Early enteral administration of a formula (Impact) supplemented with arginine, nucleotides, and fish oil in intensive care unit patients: results of a multicenter, prospective, randomized, clinical trial. Crit Care Med. 1995;23:436-49.