Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Intensive Care Medicine
Published in: Intensive Care Medicine 1/2005

01-01-2005 | Systematic Review

Parenteral vs. enteral nutrition in the critically ill patient: a meta-analysis of trials using the intention to treat principle

Authors: Fiona Simpson, Gordon Stuart Doig

Published in: Intensive Care Medicine | Issue 1/2005

Login to get access

Abstract

Objective

Controversy surrounds the use of parenteral nutrition in critical illness. Previous overviews used composite scales to identify high-quality trials, which may mask important differences in true methodological quality. Using a component-based approach this meta-analysis investigated the effect of trial quality on overall conclusions reached when standard enteral nutrition is compared to standard parenteral nutrition in critically ill patients.

Methods

An extensive literature search was undertaken to identify all eligible trials. We retrieved 465 publications, and 11 qualified for inclusion. Nine trials presented complete follow-up, allowing the conduct of an intention to treat analysis.

Results

Aggregation revealed a mortality benefit in favour of parenteral nutrition, with no heterogeneity. A priori specified subgroup analysis demonstrated the presence of a potentially important treatment-subgroup interaction between studies of parenteral vs. early enteral nutrition compared to parenteral vs. late enteral. Six trials with complete follow-up reported infectious complications. Infectious complications were increased with parenteral use. The I 2 measure of heterogeneity was 37.7%.

Conclusions

Intention to treat trials demonstrated reduced mortality associated with parenteral nutrition use. A priori subgroup analysis attributed this reduction to trials comparing parenteral to delayed enteral nutrition. Despite an association with increased infectious complications, a grade B+ evidence-based recommendation (level II trials, no heterogeneity) can be generated for parenteral nutrition use in patients in whom enteral nutrition cannot be initiated within 24 h of ICU admission or injury.
Literature
1.
Dudrick SJ, Wilmore DW, Vars HM, Rhoads JE (1968) Long-term total parenteral nutrition with growth, development, and positive nitrogen balance. Surgery 64:134–142PubMed
2.
Dudrick SJ (2003) Early developments and clinical applications of total parenteral nutrition. JPEN J Parenter Enteral Nutr 27:291–299PubMed
3.
Spencer CTCC (2001) The development of TPN: an interview with pioneer surgical nutritionist Jonathan E. Rhoads, MD. J Am Diet Assoc 101:747–750CrossRefPubMed
4.
Varga P, Griffiths R, Chiolero R, Nitenberg G, Leverve X, Pertkiewicz M, Roth E, Wernerman J, Pichard C, Preiser JC (2003) Is parenteral nutrition guilty? Intensive Care Med 29:1861–1864CrossRefPubMed
5.
Marik PE, Pinsky M (2003) Death by parenteral nutrition. Intensive Care Med 29:2104CrossRef
6.
Preiser JC, Berre J, Carpentier Y, Jolliet P, Pichard C, Van Gossum A, Vincent JL (1999) Management of nutrition in European intensive care units: results of a questionnaire. Working Group on Metabolism and Nutrition of the European Society of Intensive Care Medicine. Intensive Care Med 25:95–101CrossRefPubMed
7.
Martin CM, Doig GS, Heyland DK, Morrison T, Sibbald WJ (2004) Multicentre, cluster-randomized clinical trial of algorithms for critical-care enteral and parenteral therapy (ACCEPT). Can Med Assoc J 170:197–204
8.
LeLorier J, Gregoire G, Benhaddad A, Lapierre J, Derderian F (1997) Discrepancies between meta-analyses and subsequent large randomized, controlled trials. N Engl J Med 337:536–542CrossRefPubMed
9.
Smith R, Chalmers I (2001) Britain’s gift: a “Medline” of synthesised evidence. BMJ 323:1437–1438PubMed
10.
Juni P, Altman DG, Egger M (2001) Systematic reviews in health care: assessing the quality of controlled clinical trials. BMJ 323:42–46CrossRefPubMed
11.
Cochrane Injuries Group Albumin Reviewers (1998) Human albumin administration in critically ill patients: systematic review of randomised controlled trials. BMJ 317:235–240PubMed
12.
Schulz KF, Grimes DA (2002) Allocation concealment in randomised trials: defending against deciphering. Lancet 359:614–618CrossRefPubMed
13.
Wilkes MM, Navickis RJ (2001) Patient survival after human albumin administration. A meta-analysis of randomized, controlled trials. Ann Intern Med 135:149–164PubMed
14.
Egger M, Juni P, Bartlett C, Holenstein F, Sterne J (2003) How important are comprehensive literature searches and the assessment of trial quality in systematic reviews? Empirical study. Health Technol Assess 7:1–76
15.
Heyland DK, Dhaliwal R, Drover JW, Gramlich L, Dodek P (2003) Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. JPEN J Parenter Enteral Nutr 27:355–373PubMed
16.
Heyland DK, Novak F, Drover JW, Jain M, Su X, Suchner U (2001) Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. JAMA 286:944–953CrossRefPubMed
17.
Heyland DK (2000) Enteral and parenteral nutrition in the seriously ill, hospitalized patient: a critical review of the evidence. J Nutr Health Aging 4:31–41PubMed
18.
Heyland DK, MacDonald S, Keefe L, Drover JW (1998) Total parenteral nutrition in the critically ill patient: a meta-analysis. JAMA 280:2013–2019CrossRefPubMed
19.
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12
20.
Moher D, Jadad AR, Nichol G, Penman M, Tugwell P, Walsh S (1995) Assessing the quality of randomized controlled trials: an annotated bibliography of scales and checklists. Control Clin Trials 16:62–73CrossRefPubMed
21.
Juni P, Witschi A, Bloch R, Egger M (1999) The hazards of scoring the quality of clinical trials for meta-analysis. JAMA 282:1054–1060CrossRefPubMed
22.
Huwiler-Muntener K, Juni P, Junker C, Egger M (2002) Quality of reporting of randomized trials as a measure of methodologic quality. JAMA 287:2801–2804CrossRefPubMed
23.
Haynes R, Wilczynski N, McKibbon A, Walker C, Sinclair J (1994) Developing Optimal Search Strategies for Detecting Clinically Sound Studies in MEDLINE. J Am Med Inform Assoc 1:447–458PubMed
24.
Juni P, Holenstein F, Sterne J, Bartlett C, Egger M (2002) Direction and impact of language bias in meta-analyses of controlled trials: empirical study. Int J Epidemiol 31:115–123CrossRefPubMed
25.
Doig GS, Simpson F, Delaney A (2004) A review of the true methodological quality of nutritional support trials conducted in the critically ill: time for improvement. Anesth Analg (in press)
26.
Graf J, Doig GS, Cook DJ, Vincent JL, Sibbald WJ (2002) Randomized, controlled clinical trials in sepsis: has methodological quality improved over time? Crit Care Med 30:461–472CrossRefPubMed
27.
Lachin JM (2000) Statistical considerations in the intent-to-treat principle. Control Clin Trials 21:167–189CrossRefPubMed
28.
Flather MD, Farkouth ME, Pogue JM, Yusuf S (1997) Strengths and limitations of meta-analysis: larger studies may be more reliable. Control Clin Trials 18:568–579CrossRefPubMed
29.
Prentice RL (1989) Surrogate endpoints in clinical trials: definition and operational criteria. Stat Med 8:431–440PubMed
30.
Novak F, Heyland DK, Avenell A, Drover JW, Su X (2002) Glutamine supplementation in serious illness: a systematic review of the evidence. Crit Care Med 30:2022–2029CrossRefPubMed
31.
Kleinbaum DG, Kupper LL, Morgenstern H (1982) Measures of disease frequency: incidence. In: Kleinbaum DG, Kupper LL, Morgenstern H (eds) Epidemiological research: principles and quantitative methods. Van Nostrand Reinhold, New York, pp 96–115
32.
Villar J, Mackey ME, Carroli G, Donner A (2001) Meta-analyses in systematic reviews of randomized controlled trials in perinatal medicine: comparison of fixed and random effects models. Stat Med 20:3635–3647CrossRefPubMed
33.
Deeks JJ (2002) Issues in the selection of a summary statistic for meta-analysis of clinical trials with binary outcomes. Stat Med 21:1575–1600CrossRefPubMed
34.
Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558CrossRefPubMed
35.
Brookes ST, Whitley E, Peters TJ, Mulheran PA, Egger M, Davey SG (2001) Subgroup analyses in randomised controlled trials: quantifying the risks of false-positives and false-negatives. Health Technol Assess 5:1–56
36.
Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF (1999) Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses. Lancet 354:1896–1900CrossRefPubMed
37.
Braga M, Vignali A, Gianotti L, Cestari A, Profili M, Di C, V (1995) Benefits of early postoperative enteral feeding in cancer patients. Infusionsther Transfusionsmed 22:280–284PubMed
38.
Gianotti L, Braga M, Gentilini O, Balzano G, Zerbi A, Di Carlo V (2000) Artificial nutrition after pancreaticoduodenectomy. Pancreas 21:344–351CrossRefPubMed
39.
Di Carlo, V, Gianotti L, Balzano G, Zerbi A, Braga M (1999) Complications of pancreatic surgery and the role of perioperative nutrition. Dig Surgery 16:320–326CrossRef
40.
Braga M, Gianotti L, Vignali A, Cestari A, Bisagni P, Di C, V (1998) Artificial nutrition after major abdominal surgery: impact of route of administration and composition of the diet. Crit Care Med 26:24–30CrossRefPubMed
41.
Braga M, Vignali A, Gianotti L, Cestari A, Profili M, Di C, V (1996) Immune and nutritional effects of early enteral nutrition after major abdominal operations. Eur J Surgery 162:105–112
42.
Bertolini G, Iapichino G, Radrizzani D, Facchini R, Simini B, Bruzzone P, Zanforlin G, Tognoni G (2003) Early enteral immunonutrition in patients with severe sepsis: results of an interim analysis of a randomized multicentre clinical trial. Intensive Care Med 29:834–840CrossRefPubMed
43.
Hadfield RJ, Sinclair DG, Houldsworth PE, Evans TW (1995) Effects of enteral and parenteral nutrition on gut mucosal permeability in the critically ill. Am J Respir Crit Care Med 152:1545–1548PubMed
44.
Wischmeyer PE, Lynch J, Liedel J, Wolfson R, Riehm J, Gottlieb L, Kahana M (2001) Glutamine administration reduces Gram-negative bacteremia in severely burned patients: a prospective, randomized, double-blind trial versus isonitrogenous control. Crit Care Med 29:2075–2080CrossRefPubMed
45.
Hadley MN, Grahm TW, Harrington T, Schiller WR, McDermott MK, Posillico DB (1986) Nutritional support and neurotrauma: a critical review of early nutrition in forty-five acute head injury patients. Neurosurgery 19:367–373PubMed
46.
Moore FA, Moore EE, Jones TN, McCroskey BL, Peterson VM (1989) TEN versus TPN following major abdominal trauma-reduced septic morbidity. J Trauma 29:916–922PubMed
47.
Young B, Ott L, Twyman D, Norton J, Rapp R, Tibbs P, Haack D, Brivins B, Dempsey R (1987) The effect of nutritional support on outcome from severe head injury. J Neurosurg 67:668–676PubMed
48.
Rayes N, Hansen S, Seehofer D, ller AR, Serke S, Bengmark S, Neuhaus P (2002) Early enteral supply of fiber and Lactobacilli versus conventional nutrition: a controlled trial in patients with major abdominal surgery. Nutrition 18:609–615CrossRefPubMed
49.
Reynolds JV, Kanwar S, Welsh FKS, Windsor ACJ, Murchan P, Barclay GR, Guillou PJ (1997) Does the route of feeding modify gut barrier function and clinical outcome in patients after major upper gastrointestinal surgery? JPEN J Parenter Enteral Nutr 21:196–201PubMed
50.
Kudsk KA, Minard G, Wojtysiak SL, Croce M, Fabian T, Brown RO (1994) Visceral protein response to enteral versus parenteral nutrition and sepsis in patients with trauma. Surgery 116:516–523PubMed
51.
Dunham CM, Frankenfield D, Belzberg H, Wiles C, Cushing B, Grant Z (1994) Gut failure-predictor of or contributor to mortality in mechanically ventilated blunt trauma patients? J Trauma 37:30–34PubMed
52.
Woodcock NP, Zeigler D, Palmer MD, Buckley P, Mitchell CJ, MacFie J (2001) Enteral versus parenteral nutrition: a pragmatic study. Nutrition 17:1–12
53.
Gianotti L, Braga M, Vignali A, Balzano G, Zerbi A, Bisagni P, Di C, V, Fischer JE, Rombeau J, Harrington D (1997) Effect of route of delivery and formulation of postoperative nutritional support in patients undergoing major operations for malignant neoplasms. Arch Surg 132:1222–1230PubMed
54.
Rapp RP, Young B, Twyman D, Bivins BA, Haack D, Tibbs PA, Bean JR (1983) The favorable effect of early parenteral feeding on survival in head-injured patients. J Neurosurg 58:906–912PubMed
55.
Adams S, Dellinger EP, Wertz MJ, Oreskovich MR, Simonowitz D, Johansen K (1986) Enteral versus parenteral nutritional support following laparotomy for trauma: a randomized prospective trial. J Trauma 26:882–891PubMed
56.
Kalfarentzos F, Kehagias J, Mead N, Kokkinis K, Gogos CA (1997) Enteral nutrition is superior to parenteral nutrition in severe acute pancreatitis: results of a randomized prospective trial. Br J Surg 84:1665–1669CrossRefPubMed
57.
Cerra FB, McPherson JP, Konstantinides FN, Konstantinides NN, Teasley KM (1988) Enteral nutrition does not prevent multiple organ failure syndrome (MOFS) after sepsis. Surgery 104:727–733PubMed
58.
Borzotta AP, Pennings J, Papasadero B, Paxton J, Mardesic S, Borzotta R, Parrott A, Bledsoe F (1994) Enteral versus parenteral nutrition after severe closed head injury. J Trauma 37:459–468PubMed
59.
Hollis S, Campbell F (1999) What is meant by intention to treat analysis? Survey of published randomised controlled trials. BMJ 319:670–674PubMed
60.
Heyland DK (2000) Parenteral nutrition in the critically-ill patient: more harm than good? Proc Nutr Soc 59:457–466PubMed
61.
van Nieuwenhoven CA, Buskens E, van Tiel FH, Bonten MJ (2001) Relationship between methodological trial quality and the effects of selective digestive decontamination on pneumonia and mortality in critically ill patients. JAMA 286:335–340CrossRefPubMed
62.
Cohen J, Cristofaro P, Carlet J, Opal S (2004) A new method of classifying infections in critically ill patients. Crit Care Med 32:1510–1534CrossRefPubMed
63.
Hardy RJ, Thompson SG (1998) Detecting and describing heterogeneity in meta-analysis. Stat Med 17:841–856CrossRefPubMed
64.
Preiser JC, Chiolero R, Wernerman J (2003) Nutritional papers in ICU patients: what lies between the lines? Intensive Care Med 29:156–166PubMed
65.
Finfer S, Bellomo R, Myburgh J, Norton R (2003) Efficacy of albumin in critically ill patients. BMJ 326:559–560CrossRefPubMed
66.
Dellinger RP, Zimmerman JL, Taylor RW, Straube RC, Hauser DL, Criner GJ, Davis K Jr, Hyers TM, Papadakos P (1998) Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Inhaled Nitric Oxide in ARDS Study Group. Crit Care Med 26:15–23CrossRefPubMed
67.
Schulz KF, Chalmers I, Altman DG (2002) The landscape and lexicon of blinding in randomized trials. Ann Intern Med 136:254–259PubMed
68.
Cook DJ (1995) Clinical trials in the treatment of sepsis: an evidence-based approach. In: Sibbald WJ, Vincent JL (eds) Clinical trials for the treatment of sepsis. Springer, Berlin Heidelberg New York, pp XIX–XXXI
69.
Drummond MF, Stoddart GL, Torrance GW (1995) Cost-effectiveness analysis In: Drummond MF, Stoddart GL, Torrance GW (eds) Methods for the economic evaluation of health care programmes. Oxford University Press, New York, pp 74–112
Metadata
Title
Parenteral vs. enteral nutrition in the critically ill patient: a meta-analysis of trials using the intention to treat principle
Authors
Fiona Simpson
Gordon Stuart Doig
Publication date
01-01-2005
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 1/2005
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-004-2511-2

Other articles of this Issue 1/2005

Intensive Care Medicine 1/2005 Go to the issue

Correspondence

Authors’ reply

Review

Efficacy of heat and moisture exchangers in preventing ventilator-associated pneumonia: meta-analysis of randomized controlled trials

Technical Note

Analysis of blood glucose measurements using capillary and arterial blood samples in intensive care patients

Neonatal and Pediatric Intensive Care

Characteristics and immediate outcome of childhood meningitis treated in the pediatric intensive care unit

Editorial

D-dimer for the diagnosis of pulmonary embolism: a call for sticking to evidence

Original

Prediction of responses to various stimuli during sedation: a comparison of three EEG variables