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Early enteral immunonutrition in patients with severe sepsis

Results of an interim analysis of a randomized multicentre clinical trial

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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.

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Author information

Authors and Affiliations

  1. GiViTI Coordinating Center, Istituto di Ricerche Farmacologiche "Mario Negri", Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò, Ranica, Bergamo, Italy

    Guido Bertolini & Rebecca Facchini

  2. Consorzio "Mario Negri Sud", S. Maria Imbaro, Chieti, Italy

    Gianni Tognoni

  3. Polo Universitario S. Paolo, Istituto di Anestesia e Rianimazione dell'Università di Milano, Milan, Italy

    Gaetano Iapichino & Giancarlo Zanforlin

  4. Ospedale Maggiore IRCCS, Polo Universitario S. Paolo, Istituto di Anestesia e Rianimazione dell'Università di Milano, Milan, Italy

    Paola Bruzzone

  5. Servizio Anestesia e Rianimazione, Azienda Ospedaliera Legnano, Milan, Italy

    Danilo Radrizzani

Authors
  1. Guido Bertolini
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  2. Gaetano Iapichino
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  3. Danilo Radrizzani
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  4. Rebecca Facchini
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  5. Bruno Simini
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  6. Paola Bruzzone
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  7. Giancarlo Zanforlin
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  8. Gianni Tognoni
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Corresponding author

Correspondence to Guido Bertolini.

Additional information

An editorial regarding this article can be found in the same issue (http://dx.doi.org/10.1007/s00134-003-1710-6).

GiViTI stands for Gruppo Italiano per la Valutazione degli Interventi in Terapia Intensiva (Italian Group for the Evaluation of Interventions in Intensive Care Medicine). G. Bertolini, G. Iapichino, D. Radrizzani, and B. Simini are members of the GiViTI steering committee. The study was supported by Abbott Italia, Roma, Italy. A complete list of study participants appears in the appendix.

Appendix: Participating clinicians (with their hospitals in capitals) and advisory board members

Appendix: Participating clinicians (with their hospitals in capitals) and advisory board members

Participating clinicians

ANCONA Pennacchioni S; AOSTA Vernero S; BENEVENTO Pezza B; BIELLA Giachello S; BOLOGNA BELLARIA Mingarelli M; BOLOGNA MAGGIORE Marri I; BORGOMANERO (NO) Musso T; BRESCIA Antonini B; CAGLIARI Murru S; CASTELLANA GROTTE (BA) Di Masi P; CITTADELLA (PD) Todesco L; DESIO (MI) Ostaldo M; DOLO (VE) Altafini L; FAENZA (RA) Casalini P; FERRARA Marchi M, Tonini P; FIRENZE Oggioni R; GENOVA Garavini L; LANCIANO (CH) Genovesi N, Carinci P; LANUSEI (NU) Lerede D; LECCO CIVILE Holzer G; LECCO MANZONI Tavola M; MACERATA Paternesi N, Brunori M; MANTOVA Sgarioto V; MILANO MAGGIORE Sicignano A; MILANO S. CARLO Raffaeli M, Cibin C; MILANO S. PAOLO Zanforlin G; MILANO S. RAFFAELE Colombo S; NAPOLI De Cristofaro M; OLBIA Messina M; PALERMO Tetamo R; PAVIA Negri G; PERUGIA Gorietti A; PESARO Breschi C; PESCIA (PT) Dal Poggetto L; PISA Malacarne P; RAVENNA Garelli A; ROMA Morrone L; TORINO S. G. BOSCO Livigni S; TORINO UMBERTO I Segala V; TORINO LE MOLINETTE Cavallo R; VICENZA S. BORTOLO Lieta E, Digito A, Marcante S

Advisory board members

M. Braga (Ospedale S. Raffaele, Milano), F.B. Pallavicini (Ospedale San Martino, Genova), M.G. Gentile (Ospedale Niguarda, Milano); M. Zanello (Ospedale Bellaria, Bologna)

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Bertolini, G., Iapichino, G., Radrizzani, D. et al. Early enteral immunonutrition in patients with severe sepsis. Intensive Care Med 29, 834–840 (2003). https://doi.org/10.1007/s00134-003-1711-5

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  • DOI: https://doi.org/10.1007/s00134-003-1711-5

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