Sept2010e-journalclub.html

 

University of Virginia Health System

Nutrition Support E-Journal Club

September 2010

 

Greetings,

We had a great September traineeship week, with trainees that hailed from Maryland, California, Pennsylvania and Hawaii.  Our trainees were treated to some of the last summer-like Virginia Fall weather.  The trees are just starting to get their fall colors on in the local Blue Ridge Mountain tops and it is the season for apple festivals, fresh cider and glorious warm days and cool nights here.   Brampton Civic Hospital/William Osler Health System in Brampton Ontario Canada also hosted an "On the Road" Weekend-Warrior session in September. It was wonderful to meet and interact with RD's from Canada, and we look forward to more programs there in the future.

September Citation: 

Barraud D, Blard C, Hein F, et al.  Probiotics in the critically ill patient: a double blind, randomized, placebo-controlled trial.  Intensive Care Med. 2010;36(9):1540-7.

Summary: 

This was a randomized, double-blind, placebo-controlled trial of a multi-species probiotic administered to 167 mechanically ventilated medical ICU patients.  Patients received either a placebo or probiotic (Ergyphilus- 2X1010 revivable bacteria; Lactobacillus rhamnosus GG, Lactobacillus casei, Lactobacillus acidophilus, and Bifidobacterium bifidum) administered 1 X daily via the enteral feeding tube while intubated (but not exceeding 28 days). Treatment was continued for 2 additional days after ventilator weaning, and then stopped.  If a patient was reintubated within 2 days treatment was continued.  All patients received enteral nutrition through an NG tube with a goal of 30-35 kcal/kg.

The primary endpoint of the study was 28-day mortality. Secondary

endpoints were 90-day mortality, reversal of organ failure, occurrence of ICU-acquired infections and colonization by day 28, and ICU length of stay.

Inclusion and Exclusion Criteria were:

Inclusion criteria:  All intubated adult patients predicted to require mechanical ventilation for at least 2 days were eligible.

Exclusion criteria: Patients that were:

  • < 18 years of age.
  • Predicted duration of mechanical ventilation less than 2 days
  • Immunosuppression (AIDS, malignant hemopathy, neutrophil count < 500, chemotherapy during past 3 months)
  • Pregnancy
  • Short bowel disease
  • Inclusion in another trial
  • Previously enrolled in the study and then readmitted to the ICU.

Major Results reported by authors:

The authors reported that the 28-day mortality rates were not significantly different between the probiotic (25.3%) and placebo groups (23.7%).  Mortality rates in the intensive care unit at 90 days, the overall incidence of ICU-acquired infections, antibiotic consumption and organ failure resolution did not differ significantly different between groups.  However, catheter-related bloodstream infections was significantly less in the group that received probiotics (1.84%) compared to the placebo group (1.84% vs. 6.78% respectively, p = 0.005).

There was a significant reduction in 28-day mortality in the patients with severe sepsis treated with probiotics (n = 52) compared to placebo (n = 49) with an odds ratio (OR) for death at 0.38 (95% CI 0.16-0.93, p = 0.035). However, probiotics were associated with a numerically higher (not statistically significant) mortality rate in the 67 non-severe sepsis patients (OR 3.09, 95% CI 0.87-11.01, p = 0.08).

Author's Conclusions:

"We were unable to observe protective effects of the use of probiotics in critically ill patients ventilated for up to 2 days. Although numerous uncertainties remain (type and number of strains to be used, delay and length of administration), and despite an acceptable safety profile, especially the absence of associated bowel ischemia, the daily prophylactic administration of probiotics cannot be encouraged in the critically ill patient, notably in nonsevere septic patients."

Evaluation:

This was a study where the key to understanding the limitations was simply to read the entire paper.  In the methods section the authors indicate that a power analysis demonstrated that 740 patients would need to be enrolled to be able to detect a 5% decrease in 28-day mortality.  However, an unplanned interim analysis was completed with only 167 patients enrolled after the Besselink study (1) was published and revealed increased mortality with a multi-species probiotic in patients with acute pancreatitis.  Enrollment in the current study was halted for futility after the interim analysis calculated that it would require more than 4,000 patients per group to clearly establish a treatment effect on 28-day mortality. 

Considering the numbers from the power equation, the relatively small numbers of patients used for the subgroup calculations and knowing that small studies are more likely to suggest a treatment effect that is really not there, suggests that the differences in outcome may be related more to chance than the intervention.

Additionally the discussion section revealed that the incidence of catheter related bloodstream infections (CR-BSI) in the control group was unexpectedly high for the patient population.  Considering that there was no difference in antibiotic use or any other infectious complication between groups it is possible that the probiotics did not really lower the incidence of CR-BSI, but that there was merely a chance increase in CR-BSI in the control group.

Our Take Home messages:

  • There was no overall benefit to probiotic supplements in mechanically ventilated medical ICU patients, and the study population was too small to make any firm conclusions regarding the subgroup analysis.
  • Further much larger studies will be needed to know if probiotics have benefits or risks in critically ill patients.
  • Until further/adequate safety and effectiveness data are available probiotics should remain a focus for research, and not an agent to be routinely used in critically ill patients.

"There is no risk that is acceptable if there is no benefit"

References:

  1. Besselink MG, van Santvoort HC, Buskens E, et al.; Dutch Acute Pancreatitis Study Group.  Probiotic prophylaxis in predicted severe acute pancreatitis: a randomized, double-blind, placebo-controlled trial.  Lancet. 2008;23;371(9613):651-9.

Other News:

Check out the full schedule of webinar programs at: www.ginutrition.virginia.edu

  • October 12: Nutritional Care of the Patient with Gastroparesis--Carol Parrish, MS, RD
  • November 16: Calorie and Protein Determination--Joe Krenitsky, MS, RD
  • December 7: Dermatologic Symptoms of Nutrient Deficiency--Maggie Noland, MD

See the latest Practical Gastroenterology article available at: www.ginutrition.virginia.edu

  • Willcutts K. The Art of Fistuloclysis: Nutritional Management of Enterocutaneous Fistulas.  Practical Gastroenterology 2010;XXXIV(9):47.
  • Schiavone PA, Stoner NE, Compher CW, Kinosian BP, Boullata JI.  Management of Catheter-Related Infection in Patients Receiving Home Parenteral Nutrition.  Practical Gastroenterology 2010;XXXIV(10):22.

Joe Krenitsky MS, RD

Carol Rees Parrish MS, RD

PS - Please feel free to forward this on to friends and colleagues.