Advertisement

Intensive Care Medicine

, Volume 35, Issue 12, pp 2018–2027 | Cite as

Early enteral nutrition, provided within 24 h of injury or intensive care unit admission, significantly reduces mortality in critically ill patients: a meta-analysis of randomised controlled trials

  • Gordon S. Doig
  • Philippa T. Heighes
  • Fiona Simpson
  • Elizabeth A. Sweetman
  • Andrew R. Davies
Systematic Review

Abstract

Purpose

To determine whether the provision of early standard enteral nutrition (EN) confers treatment benefits to critically ill patients.

Methods

Medline and EMBASE were searched. Hand citation review of retrieved guidelines and systematic reviews were undertaken, and academic and industry experts were contacted.

Methodologically sound randomised controlled trials (RCTs) conducted in critically ill patient populations that compared the delivery of standard EN, provided within 24 h of intensive care unit (ICU) admission or injury, to standard care were included.

The primary analysis was conducted on clinically meaningful patient-oriented outcomes. Secondary analyses considered vomiting/regurgitation, pneumonia, bacteraemia, sepsis and multiple organ dysfunction syndrome. Meta-analyses were conducted using the odds ratio (OR) metric and a fixed effects model. The impact of heterogeneity was assessed using the I 2 metric.

Results

Six RCTs with 234 participants were analysed. The provision of early EN was associated with a significant reduction in mortality [OR = 0.34, 95% confidence interval (CI) 0.14–0.85] and pneumonia (OR = 0.31, 95% CI 0.12–0.78). There were no other significant differences in outcomes. A sensitivity analysis and a simulation exercise confirmed the presence of a mortality reduction.

Conclusion

Although the detection of a statistically significant reduction in mortality is promising, overall trial quality was low, trial size was small, and the findings may be restricted to the patient groups enrolled into included trials. The results of this meta-analysis should be confirmed by the conduct of a large multi-centre trial enrolling diverse critically ill patient groups.

Keywords

Early enteral nutrition Critical illness Intensive care unit Meta-analysis Systematic review 

Notes

Acknowledgments

The conduct of this study was not funded. Ethics approval was not required to conduct this integrative meta-epidemiological study.

Conflict of interest statement

GSD has received academic research grants from Fresenius Kabi Deutschland GmbH and Baxter Healthcare Pty Ltd., and speaker's honoraria from Baxter Healthcare Pty Ltd. FS has received academic research grants from Fresenius Kabi Deutschland GmbH and Baxter Healthcare Pty Ltd., and speakers honoraria from Pharmatel-Fesenius Kabi Pty Ltd. EAS has received an academic research grant from Baxter Healthcare Pty Ltd. ARD has received an academic research grant from Cook Medical. PTH declares no competing interests.

References

  1. 1.
    Kreymann KG, Berger MM, Deutz NE, Hiesmayr M, Jolliet P, Kazandjiev G, Nitenberg G, van den Berghe G, Wernerman J, DGEM (German Society for Nutritional Medicine), Ebner C, Hartl W, Heymann C, Spies C, ESPEN (European Society for Parenteral, Enteral Nutrition) (2006) ESPEN guidelines on enteral nutrition: intensive care. Clin Nutr 25:210–223CrossRefPubMedGoogle Scholar
  2. 2.
    Martin CM, Doig GS, Heyland DK, Morrison T, Sibbald WJ (2004) Cluster randomized clinical trial of algorithms for critical care enteral and parenteral therapy (ACCEPT). CMAJ 170:197–204PubMedGoogle Scholar
  3. 3.
    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. J Parenter Enteral Nutr 27:355–373CrossRefGoogle Scholar
  4. 4.
    Doig GS, Simpson F, Finfer S, Delaney A, Davies AR, Mitchell I, Dobb G, Nutrition Guidelines Investigators of the ANZICS Clinical Trials Group (2008) Effect of evidence-based feeding guidelines on mortality of critically ill adults: a cluster randomized controlled trial. JAMA 300:2731–2741CrossRefPubMedGoogle Scholar
  5. 5.
    Heyland DK, Schroter-Noppe D, Drover JW, Jain M, Keefe L, Dhaliwal R, Day A (2003) Nutrition support in the critical care setting: current practice in Canadian ICUs–opportunities for improvement? J Parenter Enteral Nutr 27:74–83CrossRefGoogle Scholar
  6. 6.
    Lewis SJ, Andersen HK, Thomas S (2009) Early enteral nutrition within 24 h of intestinal surgery versus later commencement of feeding: a systematic review and meta-analysis. J Gastrointest Surg 13:569–575CrossRefPubMedGoogle Scholar
  7. 7.
    Marik PE, Zaloga GP (2001) Early enteral nutrition in acutely ill patients: a systematic review. Crit Care Med 29:2264–2270CrossRefPubMedGoogle Scholar
  8. 8.
    Haynes RB, McKibbon KA, Wilczynski NL, Walter SD, Werre SR (2005) Optimal search strategies for retrieving scientifically strong studies of treatment from Medline: analytical survey. BMJ 330:1179CrossRefPubMedGoogle Scholar
  9. 9.
    Wong SS, Wilczynski NL, Haynes RB (2006) Developing optimal search strategies for detecting clinically sound treatment studies in EMBASE. J Med Libr Assoc 94:41–47PubMedGoogle Scholar
  10. 10.
    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 7:1–76PubMedGoogle Scholar
  11. 11.
    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 31:115–123CrossRefPubMedGoogle Scholar
  12. 12.
    Prentice RL (1989) Surrogate endpoints in clinical trials: definition and operational criteria. Stat Med 8:431–440CrossRefPubMedGoogle Scholar
  13. 13.
    Doig GS, Simpson F, Delaney A (2005) A review of the true methodological quality of nutritional support trials conducted in the critically ill: time for improvement. Anesth Analg 100:527–533CrossRefPubMedGoogle Scholar
  14. 14.
    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 30:461–472CrossRefPubMedGoogle Scholar
  15. 15.
    Juni P, Altman DG, Egger M (2001) Systematic reviews in health care: assessing the quality of controlled clinical trials. BMJ 323:42–46CrossRefPubMedGoogle Scholar
  16. 16.
    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 20:3635–3647CrossRefPubMedGoogle Scholar
  17. 17.
    Deeks JJ (2002) Issues in the selection of a summary statistic for meta-analysis of clinical trials with binary outcomes. Stat Med 21:1575–1600CrossRefPubMedGoogle Scholar
  18. 18.
    Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558CrossRefPubMedGoogle Scholar
  19. 19.
    Hatala R, Keitz S, Wyer P, Guyatt G (2005) Tips for learners of evidence-based medicine: 4 assessing heterogeneity of primary studies in systematic reviews and whether to combine their results. CMAJ 172:661–665PubMedGoogle Scholar
  20. 20.
    Glasziou PP, Sanders SL (2002) Investigating causes of heterogeneity in systematic reviews. Stat Med 21:1503–1511CrossRefPubMedGoogle Scholar
  21. 21.
    Minard G, Kudsk KA, Melton S, Patton JH, Tolley EA (2000) Early versus delayed feeding with an immune-enhancing diet in patients with severe head injuries. J Parenter Enteral Nutr 24:145–149CrossRefGoogle Scholar
  22. 22.
    Eyer SD, Micon LT, Konstantinides FN, Edlund DA, Rooney KA, Luxenberg MG, Cerra FB (1993) Early enteral feeding does not attenuate metabolic response after blunt trauma. J Trauma 34:639–643CrossRefPubMedGoogle Scholar
  23. 23.
    Singh G, Ram RP, Khanna SK (1998) Early postoperative enteral feeding in patients with nontraumatic intestinal perforation and peritonitis. J Am Coll Surg 187:142–146CrossRefPubMedGoogle Scholar
  24. 24.
    Grahm TW, Zadrozny DB, Harrington T (1989) The benefits of early jejunal hyperalimentation in the head-injured patient. Neurosurgery 25:729–735CrossRefPubMedGoogle Scholar
  25. 25.
    Cabre E, Rodriguez-Iglesias P, Caballeria J, Quer JC, Sanchez-Lombrana JL, Pares A, Papo M, Planas R, Gassull MA (2000) Short- and long-term outcome of severe alcohol-induced hepatitis treated with steroids or enteral nutrition: a multicenter randomized trial. Hepatology 32:36–42CrossRefPubMedGoogle Scholar
  26. 26.
    Dvorak MF, Noonan VK, Belanger L, Bruun B, Wing PC, Boyd MC, Fisher C (2004) Early versus late enteral feeding in patients with acute cervical spinal cord injury: a pilot study. Spine 29:E175–E180CrossRefPubMedGoogle Scholar
  27. 27.
    Malhotra A, Mathur AK, Gupta S (2004) Early enteral nutrition after surgical treatment of gut perforations: a prospective randomised study. J Postgrad Med 50:102–106PubMedGoogle Scholar
  28. 28.
    Page RD, Oo AY, Russell GN, Pennefather SH (2002) Intravenous hydration versus naso-jejunal enteral feeding after esophagectomy: a randomised study. Eur J Cardiothorac Surg 22:666–672CrossRefPubMedGoogle Scholar
  29. 29.
    De Ledinghen V, Beau P, Mannant P-R, Borderie C, Ripault M-P, Silvain C, Beauchant M (1997) Early feeding or enteral nutrition in patients with cirrhosis after bleeding from esophageal varices? A randomized controlled study. Dig Dis Sci 42:536–541CrossRefPubMedGoogle Scholar
  30. 30.
    Seri S, Aquilio E (1984) Effects of early nutritional support in patients with abdominal trauma. Ital J Surg Sci 14:223–227PubMedGoogle Scholar
  31. 31.
    Carr CS, Ling KDE, Boulos P, Singer M (1996) Randomised trial of safety and efficacy of immediate postoperative enteral feeding in patients undergoing gastrointestinal resection. BMJ 312:869–871PubMedGoogle Scholar
  32. 32.
    Kaur N, Gupta MK, Minocha VR (2005) Early enteral feeding by nasoenteric tubes in patients with perforation peritonitis. World J Surg 29:1023–1027CrossRefPubMedGoogle Scholar
  33. 33.
    Schroeder D, Gillanders L, Mahr K, Hill GL (1991) Effects of immediate postoperative enteral nutrition on body composition, muscle function, and wound healing. J Parenter Enteral Nutr 15:376–383CrossRefGoogle Scholar
  34. 34.
    Hasse JM, Blue LS, Liepa GU, Goldstein RM, Jennings LW, Mor E, Hyusberg BS, Levy MF, Gonwa TA, Klintmalm GB (1995) Early enteral nutrition support in patients undergoing liver transplantation. J Parenter Enteral Nutr 19:437–443CrossRefGoogle Scholar
  35. 35.
    Watters JM, Kirkpatrick SM, Norris SB, Shamji FM, Wells GA (1997) Immediate postoperative enteral feeding results in impaired respiratory mechanics and decreased mobility. Ann Surg 226:369–380CrossRefPubMedGoogle Scholar
  36. 36.
    Sagar S, Harland P, Shields R (1979) Early postoperative feeding with elemental diet. Br Med J 1:293–295CrossRefPubMedGoogle Scholar
  37. 37.
    Beier-Holgersen R, Brandstrup B (1999) Influence of early postoperative enteral nutrition versus placebo on cell-mediated immunity, as measured with the Multitest CMI. Scand J Gastroenterol 34:98–102CrossRefPubMedGoogle Scholar
  38. 38.
    Schilder JM, Hurteau JA, Look KY, Moore DH, Raff G, Stehman FB, Sutton GP (1997) A prospective controlled trial of early postoperative oral intake following major abdominal gynecologic surgery. Gynecol Oncol 67:235–240CrossRefPubMedGoogle Scholar
  39. 39.
    Ibrahim EH, Mehringer L, Prentice D, Sherman G, Schaiff R, Fraser V, Kolleff MH (2002) Early versus late enteral feeding of mechanically ventilated patients: results of a clinical trial. J Parenter Enteral Nutr 26:174–181CrossRefGoogle Scholar
  40. 40.
    Taylor SJ, Fettes SB, Jewkes C, Nelson RJ (1999) Prospective, randomized, controlled trial to determine the effect of early enhanced enteral nutrition on clinical outcome in mechanically ventilated patients suffering head injury. Crit Care Med 27:2525–2531CrossRefPubMedGoogle Scholar
  41. 41.
    Heslin MJ, Latkany L, Leung D, Brooks AD, Hochwald SN, Pisters PW, Shike M, Brennan MF (1997) A prospective, randomized trial of early enteral feeding after resection of upper gastrointestinal malignancy. Ann Surg 226:567–577CrossRefPubMedGoogle Scholar
  42. 42.
    Pupelis G, Austrums E, Jansone A, Sprucs R, Wehbi H (2000) Randomised trial of safety and efficacy of postoperative enteral feeding in patients with severe pancreatitis: preliminary report. Eur J Surg 166:383–387CrossRefPubMedGoogle Scholar
  43. 43.
    Moore EE, Jones TN (1986) Benefits of immediate jejunostomy feeding after major abdominal trauma—a prospective, randomized study. J Trauma 26:874–881CrossRefPubMedGoogle Scholar
  44. 44.
    Peck MD, Kessler M, Cairns BA, Chang YH, Ivanova A, Schooler W (2004) Early enteral nutrition does not decrease hypermetabolism associated with burn injury. J Trauma 57:1143–1148CrossRefPubMedGoogle Scholar
  45. 45.
    Nguyen NQ, Fraser RJ, Bryant LK, Burgstad C, Chapman MJ, Bellon M, Wishart J, Holloway RH, Horowitz M (2008) The impact of delaying enteral feeding on gastric emptying, plasma cholecystokinin, and peptide YY concentrations in critically ill patients. Crit Care Med 36:1469–1474CrossRefPubMedGoogle Scholar
  46. 46.
    Chiarelli A, Enzi G, Casadei A, Baggio B, Valerio A, Mazzoleni F (1990) Very early nutrition supplementation in burned patients. Am J Clin Nutr 51:1035–1039PubMedGoogle Scholar
  47. 47.
    Pupelis G, Selga G, Austrums E, Kaminski A (2001) Jejunal feeding, even when instituted late, improves outcomes in patients with severe pancreatitis and peritonitis. Nutrition 17:91–94CrossRefPubMedGoogle Scholar
  48. 48.
    Kompan L, Kremzar B, Gadzijev E, Prosek M (1999) Effects of early enteral nutrition on intestinal permeability and the development of multiple organ failure after multiple injury. Intensive Care Med 25:157–161CrossRefPubMedGoogle Scholar
  49. 49.
    Kompan L, Vidmar G, Spindler-Vesel A, Pecar J (2004) Is early enteral nutrition a risk factor for gastric intolerance and pneumonia? Clin Nutr 23:527–532CrossRefPubMedGoogle Scholar
  50. 50.
    Chuntrasakul C, Siltharm S, Chinswangwatanakul V, Pongprasobchai T, Chockvivatanavanit S, Bunnak A (1996) Early nutritional support in severe traumatic patients. J Med Assoc Thai 79:21–26PubMedGoogle Scholar
  51. 51.
    Marshall JC (2001) Inflammation, coagulopathy, and the pathogenesis of multiple organ dysfunction syndrome. Crit Care Med 29:S99–S106CrossRefPubMedGoogle Scholar
  52. 52.
    Vincent JL, Zambon M (2006) Why do patients who have acute lung injury/acute respiratory distress syndrome die from multiple organ dysfunction syndrome? Implications for management. Clin Chest Med 27:725–731CrossRefPubMedGoogle Scholar
  53. 53.
    Carrico CJ, Meakins JL, Marshall JC, Fry D, Maier RV (1986) Multiple-organ-failure syndrome. Arch Surg 121:196–208PubMedGoogle Scholar
  54. 54.
    Clark JA, Coopersmith CM (2007) Intestinal crosstalk: a new paradigm for understanding the gut as the “motor” of critical illness. Shock 28:384–393CrossRefPubMedGoogle Scholar
  55. 55.
    Kudsk KA (1998) Early enteral nutrition in surgical patients. Nutrition 14:541–544CrossRefPubMedGoogle Scholar
  56. 56.
    Magnotti LJ, Deitch EA (2005) Burns, bacterial translocation, gut barrier function, and failure. J Burn Care Rehabil 26:383–391CrossRefPubMedGoogle Scholar
  57. 57.
    Tuin A, Poelstra K, Jager-Krikken A, Bok L, Raaben W, Velders MP, Dijkstra G (2009) Role of alkaline phosphatase in colitis in man and rats. Gut 58:379–387CrossRefPubMedGoogle Scholar
  58. 58.
    Goldberg RF, Austen WG Jr, Zhang X, Munene G, Mostafa G, Biswas S, McCormack M, Eberlin KR, Nguyen JT, Tatlidede HS, Warren HS, Narisawa S, Millán JL, Hodin RA (2008) Intestinal alkaline phosphatase is a gut mucosal defense factor maintained by enteral nutrition. Proc Natl Acad Sci USA 105:3551–3556CrossRefPubMedGoogle Scholar
  59. 59.
    Doig GS, Simpson F, Sweetman EA (2009) Evidence-based nutrition support in the intensive care unit: an update on reported trial quality. Curr Opin Clin Nutr Metab Care 12:201–206CrossRefPubMedGoogle Scholar

Copyright information

© Copyright jointly hold by Springer and ESICM 2009

Authors and Affiliations

  • Gordon S. Doig
    • 1
    • 2
  • Philippa T. Heighes
    • 2
  • Fiona Simpson
    • 2
  • Elizabeth A. Sweetman
    • 2
  • Andrew R. Davies
    • 3
  1. 1.Northern Clinical SchoolUniversity of SydneySydneyAustralia
  2. 2.Royal North Shore Hospital, Intensive Care UnitSt. LeonardsAustralia
  3. 3.The Alfred Hospital, Intensive Care UnitMelbourneAustralia

Personalised recommendations