Intensive Care Medicine

, Volume 36, Issue 9, pp 1540–1547 | Cite as

Probiotics in the critically ill patient: a double blind, randomized, placebo-controlled trial

  • Damien Barraud
  • Claire Blard
  • François Hein
  • Olivier Marçon
  • Aurélie Cravoisy
  • Lionel Nace
  • François Alla
  • Pierre-Edouard Bollaert
  • Sébastien GibotEmail author



Probiotics have been shown to be able to restore a non-pathogenic digestive flora, to prevent digestive colonization by pathogenic bacteria, and to modulate immunity. The aim of this study was to assess the effects of prophylactic probiotic administration in patients ventilated for up to 2 days.


This study was performed as a double-blind, concealed randomized, placebo-controlled trial in a French medical intensive care unit (ICU). Adult patients mechanically ventilated for a period of more than 48 h received enterally administered probiotics (Ergyphilus ®, 2 × 1010 lactic acid bacteria, mostly Lactobacillus rhamnosus GG, once a day) or placebo until successful weaning.


A total of 167 patients were included. The two groups were comparable at baseline. The 28-day mortality rates were not different in the probiotic (25.3%) and placebo groups (23.7%). Mortality rates in ICU and at 90 days were also unaffected by the treatment. The incidence of ICU-acquired infections did not differ significantly except for that of catheter-related bloodstream infections that was lowered by probiotics. On a prespecified subgroup analysis, we found a reduction of the 28-day mortality among severe sepsis patients (total n = 101) treated with probiotics (n = 52) with an odds ratio (OR) for death at 0.38 (95% CI 0.16–0.93, p = 0.035). By contrast, probiotics were associated with a higher mortality rate in non-severe sepsis patients (OR 3.09, 95% CI 0.87–11.01, p = 0.08).


Although numerous uncertainties remain (type and the number of strains to use, delay and length of administration), and despite an acceptable safety profile, the daily prophylactic administration of probiotics cannot be encouraged in the critically ill patient.


Mechanical ventilation ICU-acquired infections Probiotics 



This work was financially funded by CHU Nancy.

Conflict of interest

None of the authors declare any conflict of interest in relation to this study.

Supplementary material

134_2010_1927_MOESM1_ESM.docx (27 kb)
Supplementary material (DOCX 26 kb)


  1. 1.
    Isakow W, Morrow LE, Kollef MH (2007) Probiotics for preventing and treating nosocomial infections: review of current evidence and recommendations. Chest 132:286–294CrossRefPubMedGoogle Scholar
  2. 2.
    McNabb B, Isakow W (2008) Probiotics for the prevention of nosocomial pneumonia: current evidence and opinions. Curr Opin Pulm Med 14:168–175CrossRefPubMedGoogle Scholar
  3. 3.
    Watkinson PJ, Barber VS, Dark P, Young JD (2007) The use of pre- pro- and synbiotics in adult intensive care unit patients: systematic review. Clin Nutr 26:182–192CrossRefPubMedGoogle Scholar
  4. 4.
    Saavedra JM (2001) Clinical applications of probiotic agents. Am J Clin Nutr 73:1147S–1151SPubMedGoogle Scholar
  5. 5.
    Lilly DM, Stillwell RH (1965) Probiotics: growth-promoting factors produced by microorganisms. Science 147:747–748CrossRefPubMedGoogle Scholar
  6. 6.
    Guidelines for the evaluation of probiotics in food: report of a joint FAO/WHO working group on drafting guidelines for the evaluation of probiotics in food (2002) London, ON, CanadaGoogle Scholar
  7. 7.
    Walker WA (2002) Mechanisms of action of probiotics. Clin Infect Dis 46(Suppl 2):S87–S91Google Scholar
  8. 8.
    Siempos II, Ntaidou TK, Falagas ME (2010) Impact of the administration of probiotics on the incidence of ventilator-associated pneumonia: a meta-analysis of randomized controlled trials. Crit Care Med 38:954–962CrossRefPubMedGoogle Scholar
  9. 9.
    Calandra T, Cohen J, International Sepsis Forum Definition of Infection in the ICU Consensus Conference (2005) The international sepsis forum consensus conference on definitions of infection in the intensive care unit. Crit Care Med 33:1538–1548CrossRefPubMedGoogle Scholar
  10. 10.
    Whelan K, Judd PA, Taylor MA (2003) Defining and reporting diarrhoea during enteral tube feeding: do health professionals agree? J Hum Nutr Diet 16:21–26CrossRefPubMedGoogle Scholar
  11. 11.
    Besselink MG, van Santvoort HC, Buskens E, Boermeester MA, van Goor H, Timmerman HM, Nieuwenhuijs VB, Bollen TL, van Ramshorst B, Witteman BJ, Rosman C, Ploeg RJ, Brink MA, Schaapherder AF, Dejong CH, Wahab PJ, van Laarhoven CJ, van der Harst E, van Eijck CH, Cuesta MA, Akkermans LM, Gooszen HG, Dutch Acute Pancreatitis Study Group (2008) Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet 371:651–659CrossRefPubMedGoogle Scholar
  12. 12.
    Lan KKG, DeMets DL (1983) Discrete sequential boundaries for clinical trials. Biometrika 70:659–663CrossRefGoogle Scholar
  13. 13.
    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 101:1644–1655CrossRefPubMedGoogle Scholar
  14. 14.
    McCabe WR, Jackson GG (1962) Gram negative bacteremia: I. Etiology and ecology. Arch Intern Med 110:845–847Google Scholar
  15. 15.
    Jain PK, McNaught CE, Anderson AD, MacFie J, Mitchell CJ (2004) Influence of synbiotic containing Lactobacillus acidophilus La5, Bifidobacterium lactis Bb 12, Streptococcus thermophilus, Lactobacillus bulgaricus and oligofructose on gut barrier function and sepsis in critically ill patients: a randomised controlled trial. Clin Nutr 23:467–475CrossRefPubMedGoogle Scholar
  16. 16.
    McNaught CE, Woodcock NP, Anderson AD, MacFie J (2005) A prospective randomised trial of probiotics in critically ill patients. Clin Nutr 24:211–219CrossRefPubMedGoogle Scholar
  17. 17.
    Kotzampassi K, Giamarellos-Bourboulis EJ, Voudouris A, Kazamias P, Eleftheriadis E (2006) Benefits of a synbiotic formula (Synbiotic 2000Forte) in critically Ill trauma patients: early results of a randomized controlled trial. World J Surg 30:1848–1855CrossRefPubMedGoogle Scholar
  18. 18.
    Besselink MG, van Santvoort HC, Renooij W, de Smet MB, Boermeester MA, Fischer K, Timmerman HM, Ahmed Ali U, Cirkel GA, Bollen TL, van Ramshorst B, Schaapherder AF, Witteman BJ, Ploeg RJ, van Goor H, van Laarhoven CJ, Tan AC, Brink MA, van der Harst E, Wahab PJ, van Eijck CH, Dejong CH, van Erpecum KJ, Akkermans LM, Gooszen HG, Dutch Acute Pancreatitis Study Group (2009) Intestinal barrier dysfunction in a randomized trial of a specific probiotic composition in acute pancreatitis. Ann Surg 250:712–719CrossRefPubMedGoogle Scholar
  19. 19.
    Spindler-Vesel A, Bengmark S, Vovk I, Cerovic O, Kompan L (2007) Synbiotics, prebiotics, glutamine, or peptide in early enteral nutrition: a randomized study in trauma patients. J Parenter Enteral Nutr 31:119–126CrossRefGoogle Scholar
  20. 20.
    Forestier C, Guelon D, Cluytens V, Guillart T, Sirot J, De champs C (2008) Oral probiotic and prevention of Pseudomonas aeruginosa infections: a randomized, double-blind, placebo-controlled pilot study in intensive care unit patients. Crit Care 12:R69CrossRefPubMedGoogle Scholar

Copyright information

© Copyright jointly held by Springer and ESICM 2010

Authors and Affiliations

  • Damien Barraud
    • 1
    • 2
  • Claire Blard
    • 3
  • François Hein
    • 1
    • 2
  • Olivier Marçon
    • 1
    • 2
  • Aurélie Cravoisy
    • 1
    • 2
  • Lionel Nace
    • 1
    • 2
  • François Alla
    • 4
  • Pierre-Edouard Bollaert
    • 1
    • 2
  • Sébastien Gibot
    • 1
    • 2
    Email author
  1. 1.Service de Réanimation Médicale, Hôpital CentralCHU NancyNancy CedexFrance
  2. 2.Centre d’Investigations Cliniques-INSERM 9501, CHU de NancyNancyFrance
  3. 3.Service de Réanimation polyvalenteCHG MâconMâconFrance
  4. 4.Service d’épidémiologie et d’évaluation cliniquesCHU NancyNancyFrance

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