Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients

BMJ : British Medical Journal

Mar 2011

DOI: 10.1136/bmj.d1542

Citations:352

Influential Citations:6

Interventional (Human) Studies

Enhanced Details

Methods

Randomised, double-blind, factorial trial conducted in 10 Scottish critical care units; 502 adults (mean age 63.8 years; 39% women) in intensive care or high dependency units with gastrointestinal failure requiring parenteral nutrition for ≥48 hours; 89% level 3 care; 25% medical; median APACHE II score 20.

Intervention

Parenteral nutrition regimens delivered intravenously for up to seven days: four formulations: standard PN (12.5 g nitrogen, 2000 kcal); glutamine PN (12.5 g nitrogen including 20.2 g glutamine, 2000 kcal); standard PN plus selenium (500 μg/day); glutamine PN plus selenium (500 μg/day). Glutamine 20.2 g/day; selenium 500 μg/day; all formulations are isonitrogenous and isocaloric. Delivered via parenteral nutrition bags of 1500 mL; started as soon as practicable; body weight–based adjustments allowed; no additional parenteral nitrogen or energy beyond bag contents; maximum duration seven days.

Results

Primary outcomes were new infections within 14 days and mortality. In the intention-to-treat population, selenium did not significantly reduce new infections overall (126/251 vs 139/251; OR 0.81, 95% CI 0.57–1.15; P=0.24); glutamine did not reduce infections (134/250 vs 131/252; OR 1.07, 95% CI 0.75–1.53; P=0.71). No interaction between treatments. Six-month mortality showed no significant benefit for selenium (107/251 vs 114/251; OR 0.89, 95% CI 0.62–1.29) or for glutamine (115/250 vs 106/252; OR 1.18, 95% CI 0.82–1.70). In analyses restricted to those who received ≥5 days of trial PN, selenium reduced new infections (OR 0.53, 95% CI 0.30–0.93; P=0.03); glutamine did not. No impact on length of stay, antibiotic use, or modified SOFA. Conclusion: No overall benefit of glutamine or selenium with parenteral nutrition on new infections or mortality; selenium for ≥5 days may reduce new infections—confirmation needed.

Limitations

Limitations include: prespecified ITT analysis showed no overall benefit; observed infection reduction with selenium occurred only in a ≥5 days subgroup (risk of type I error in subgroup analyses); ventilator use data were not collected; start time for parenteral nutrition was not prespecified; center-to-center variation in PN dosing; pragmatic design may limit precision and generalizability to non-Scottish or different PN practices.

Abstract

Objective To determine whether inclusion of glutamine, selenium, or both in a standard isonitrogenous, isocaloric preparation of parenteral nutrition influenced new infections and mortality among critically ill patients. Design Randomised, double blinded, factorial, controlled trial. Setting Level 2 and 3 (or combined) critical care units in Scotland. All 22 units were invited, and 10 participated. Participants 502 adults in intensive care units and high dependency units for ≥48 hours, with gastrointestinal failure and requiring parenteral nutrition. Interventions Parenteral glutamine (20.2 g/day) or selenium (500 μg/day), or both, for up to seven days. Main outcome measures Primary outcomes were participants with new infections in the first 14 days and mortality. An intention to treat analysis and a prespecified analysis of patients who received ≥5 days of the trial intervention are presented. Secondary outcomes included critical care unit and acute hospital lengths of stay, days of antibiotic use, and modified SOFA (Sepsis-related Organ Failure Assessment) score. Results Selenium supplementation did not significantly affect patients developing a new infection (126/251 v 139/251, odds ratio 0.81 (95% CI 0.57 to 1.15)), except for those who had received ≥5 days of supplementation (odds ratio 0.53 (0.30 to 0.93)). There was no overall effect of glutamine on new infections (134/250 v 131/252, odds ratio 1.07 (0.75 to 1.53)), even if patients received ≥5 days of supplementation (odds ratio 0.99 (0.56 to 1.75)). Six month mortality was not significantly different for selenium (107/251 v 114/251, odds ratio 0.89 (0.62 to 1.29)) or glutamine (115/250 v 106/252, 1.18 (0.82 to 1.70)). Length of stay, days of antibiotic use, and modified SOFA score were not significantly affected by selenium or glutamine supplementation. Conclusions The primary (intention to treat) analysis showed no effect on new infections or on mortality when parenteral nutrition was supplemented with glutamine or selenium. Patients who received parenteral nutrition supplemented with selenium for ≥5 days did show a reduction in new infections. This finding requires confirmation. Trial registration Current Controlled Trials ISRCTN87144826 show less