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Intensive Care Medicine

, Volume 29, Issue 5, pp 834–840 | Cite as

Early enteral immunonutrition in patients with severe sepsis

Results of an interim analysis of a randomized multicentre clinical trial
  • Guido Bertolini
  • Gaetano Iapichino
  • Danilo Radrizzani
  • Rebecca Facchini
  • Bruno Simini
  • Paola Bruzzone
  • Giancarlo Zanforlin
  • Gianni Tognoni
Brief Report
First Online:
Received:
Accepted:

Abstract

Objective

To compare the mortality of critically ill patients given either enteral feeding with an immune-enhancing formula or parenteral nutrition (PN). We report the results of a planned interim analysis on patients with severe sepsis which was undertaken earlier than planned once a meta-analysis suggested excess mortality in patients with severe sepsis given enteral immunonutrition.

Design

Randomised multicentre unblinded controlled clinical trial.

Setting

Thirty-three General Intensive Care Units in Italy.

Patients and participants

Among the 237 recruited patients, 39 had severe sepsis or septic shock; 21 of them received PN.

Interventions

Eligible patients received either total PN or enteral nutrition, the latter containing extra L-arginine, omega-3 fatty acids, vitamin E, beta carotene, zinc, and selenium.

Measurements and results

The primary endpoint for the subgroup analysis on patients with severe sepsis was mortality on Intensive Care Unit (ICU). The ICU mortality of patients with severe sepsis given enteral nutrition (EN) was higher than for those given PN (44.4% vs 14.3%; p=0.039). More patients given EN than patients given PN still had severe sepsis when they died (38.9% vs 9.5%, p=0.055). Recruitment of patients with severe sepsis was subsequently stopped.

Conclusions

Our results show that enteral immunonutrition, compared to PN, may be associated with excess mortality in patients with severe sepsis.

Keywords

Critically ill patients Enteral nutrition Parenteral nutrition Immunonutrition Severe sepsis 
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References

  1. 1.
    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 25:95–101CrossRefPubMedGoogle Scholar
  2. 2.
    National Advisory Group on Standards and Practice Guidelines for Parenteral Nutrition (A.S.P.E.N.) (1998) Safe practices for parenteral nutrition formulations. JPEN J Parenter Enteral Nutr 22:49–66PubMedGoogle Scholar
  3. 3.
    Buchman AL, Moukarzel AA, Bhuta S, Belle M, Ament ME, Eckhert CD, Hollander D, Gornbein J, Kopple JD, Vijayaroghavan SR (1995) Parenteral nutrition is associated with intestinal morphologic and functional changes in humans. JPEN J Parenter Enteral Nutr 19:453–460PubMedGoogle Scholar
  4. 4.
    Border JR, Hassett J, LaLuca J, Seibel R, Steinberg S, Mills B, Losi P, Border D (1987) The gut origin septic states in multiple trauma (TSS=40) in the ICU. Ann Surg 206:427–448PubMedGoogle Scholar
  5. 5.
    Deitch EA, Winterton J, Li M, Berg R (1987) The gut as a portal of for bacteremia: role of protein malnutrition. Ann Surg 205:681–690PubMedGoogle Scholar
  6. 6.
    Cerra FB, Benitez MR, Blackburn GL, Irwin RS, Jeejeebhoy K, Katz DP, Pingleton SK, Pomposelli J, Rombeau JL, Shronts E, Wolfe RR, Zaloga GP (1997) Applied nutrition in ICU patients. A consensus statement of the American College of Chest Physicians. Chest 111:769–778PubMedGoogle Scholar
  7. 7.
    Jolliet P, Pichard C, Biolo G (1998) Enteral nutrition in intensive care patients: a practical approach (ESICM statement). Intensive Care Med 24:848–859Google Scholar
  8. 8.
    Moore FA, Feliciano DV, Andrassy RJ, McArdle AH, Booth FV, Morgenstain-Wagner TB, Kellum JM, Welling RE, Moore EE (1992) Early enteral feeding, compared with parenteral, reduces postoperative septic complications. The results of a meta-analysis. Ann Surg 216:172–183PubMedGoogle Scholar
  9. 9.
    Heyland DK, Cook DJ, Guyatt GH (1993) Enteral nutrition in the critically ill patient: a critical review of the evidence. Intensive Care Med 19:435–442PubMedGoogle Scholar
  10. 10.
    Heyland DK (2000) Enteral and parenteral nutrition in the seriously ill, hospitalized patient: a critical review of the evidence. J Nutr Health Aging 1:31–41Google Scholar
  11. 11.
    Lipman TO (1998) Grains or veins: is enteral nutrition really better than parenteral nutrition? A look at the evidence. JPEN J Parenter Enteral Nutr 22:167–182PubMedGoogle Scholar
  12. 12.
    Heys SD, Walker LG, Smith I, Remin O (1999) Enteral nutritional supplementation with key nutrients in patients with critical illness and cancer. A meta-analysis of randomized controlled clinical trial. Ann Surg 229:467–477CrossRefPubMedGoogle Scholar
  13. 13.
    Beale RJ, Bryg DJ, Bihari DJ (1999) Immunonutrition in the critically ill: a systematic review of clinical outcome. Crit Care Med 27:2799–2805Google Scholar
  14. 14.
    Heyland DK, Novak F (2001) Immunonutrition in the critically ill patients: more harm than good? JPEN J Parenter Enteral Nutr 25:51–55Google Scholar
  15. 15.
    Le Gall JR, Lemeshow S, Saulnier F (1993) A New Simplified Acute Physiology Score (SAPS II) Based on a European/North American Multicenter Study. JAMA 270:2957–2963PubMedGoogle Scholar
  16. 16.
    Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 101:1644–1655PubMedGoogle Scholar
  17. 17.
    Vincent JL, Moreno R, Takala J, Willatts S, De Mendoca A, Bruining H, Reinhart CK, Suter PM, Thijs LG (1996) The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Medi 22:707–710CrossRefGoogle Scholar
  18. 18.
    Miranda RD, Moreno R, Iapichino G (1997) Nine equivalents of nursing manpower use score (NEMS). Intensive Care Med 23:760–765PubMedGoogle Scholar
  19. 19.
    Iapichino G, Radrizzani D, Bertolini G, Ferla L, Pasetti G, Pezzi A, Porta F, Miranda DR (2001) Daily classification of the level of care. A method to describe clinical course of illness, use of resources and quality of intensive care assistance. Intensive Care Med 27:131–136PubMedGoogle Scholar
  20. 20.
    Human Medicines Evaluation Unit (1996) ICH topic E6: guideline for good clinical practice. European Agency for the Evaluation of Medical Products, London, pp 17–20Google Scholar
  21. 21.
    Pocock SJ, Hughes MD (1989) Practical problems in interim analyses, with particular regard to estimation. Control Clin Trials 10:209–221CrossRefGoogle Scholar
  22. 22.
    Mantel N (1963) Chi-square tests with one degree of freedom: extensions of the Mantel-Haenszel procedure. J Am Stat Assoc J 58:690–700Google Scholar
  23. 23.
    Kleinbaum DG, Kupper LL, Morgenstern H (1982) Epidemiologic research. Principles and quantitative methods. Van Nostrand Reinhold, New York, pp 296–297Google Scholar
  24. 24.
    Hosmer DW, Lemeshow S (1989) Applied logistic regression. Wiley, New York, pp 68–71Google Scholar
  25. 25.
    Iapichino G, Gattinoni L, Solca M, Radrizzani D, Zucchetti M, Langer M, Vesconi S (1982) Protein sparing and protein replacement in acutely injured patients during TPN with and without aminoacid supply. Intensive Care Med 8:25–31PubMedGoogle Scholar
  26. 26.
    Cerra FB, McPherson JP, Kostantinidis FN, Kostantinidis NN, Teasley KM (1988) Enteral nutrition does not prevent multiple organ failure syndrome (MOFS) after sepsis. Surgery 104:727–733PubMedGoogle Scholar
  27. 27.
    Barton RG (1997) Immune-enhancing enteral formulas: are they beneficial in critically ill patients? Nutr Clin Pract 12:51–62PubMedGoogle Scholar
  28. 28.
    Cohen J, Guyatt G, Bernard GR, Calandra T, Cook D, Elbourne D, Marshall J, Nunn A, Opal S (2001) New strategies for clinical trials in patients with sepsis and septic shock. Crit Care Med 29:880–885PubMedGoogle Scholar
  29. 29.
    Moore FA (2001) Effects of immune-enhancing diets on infectious morbidity and multiple organ failure. JPEN J Parenter Enteral Nutr 25:36–43PubMedGoogle Scholar
  30. 30.
    Suchner U, Heyland DK, Peter K (2002) Immune-modulatory actions of arginine in the critically ill. Br J Nutr 87[Suppl 1]:121–132Google Scholar
  31. 31.
    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 286:944–953PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Guido Bertolini
    • 1
  • Gaetano Iapichino
    • 3
  • Danilo Radrizzani
    • 5
  • Rebecca Facchini
    • 1
  • Bruno Simini
  • Paola Bruzzone
    • 4
  • Giancarlo Zanforlin
    • 3
  • Gianni Tognoni
    • 2
  1. 1.GiViTI Coordinating Center, Istituto di Ricerche Farmacologiche "Mario Negri"Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele DaccòRanica, BergamoItaly
  2. 2.Consorzio "Mario Negri Sud"ChietiItaly
  3. 3.Polo Universitario S. PaoloIstituto di Anestesia e Rianimazione dell'Università di MilanoMilanItaly
  4. 4.Ospedale Maggiore IRCCS, Polo Universitario S. PaoloIstituto di Anestesia e Rianimazione dell'Università di MilanoMilanItaly
  5. 5.Servizio Anestesia e RianimazioneAzienda Ospedaliera LegnanoMilanItaly

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