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

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 (Sepsisrelated 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 ISRCTN87144826INTRODUCTION Infection and sepsis are major causes of increased mortality, morbidity, and resource use in intensive care units. They are associated with both illness and drug related impairment of the immune system, compounded by malnutrition often observed in patients admitted to critical care. 1The enteral feeding route is preferred for critically ill patients because of its reduced costs and risk of infective complications.2 Parenteral nutrition, however, has an important role because many intensive care patients have gastrointestinal dysfunction. 3Recent systematic reviews have suggested that parenteral administration of glutamine to critically ill patients reduces mortality (risk ratio 0.71 (95% confidence interval 0.55 to 0.92)) and new infections (risk ratio 0.76 (0.62 to 0.93)). 4 Selenium supplementati...

A Randomized Trial of Glutamine and Antioxidants in Critically Ill Patients

“…6,7 However, recent large studies have not confirmed such an effect. 8,9 The objective of the present trial was to evaluate the effect of early glutamine and antioxidant supplementation in critically ill patients. Our a priori hypothesis was that supplementation with these nutrients would reduce 28-day mortality.…”

Antioxidant Strategies in Neurocritical Care

“…Supplementation of critically ill patients with antioxidant nutrients, alone or in combination, is often referred to as "immune nutrition"; and has been studied in various, double-blind, randomized, placebo-controlled trials [83][84][85]. Although results from some of these trials were encouraging, the benefit of this therapy has not been clearly established.…”

Immunonutrition: a South African perspective

“…However, they did find that the evidence was more suggestive of a benefit on mortality in the first month for general ICU patients when compared with those with severe pancreatitis (p-value = 0.02). The more recent SIGNET trial 58 found that 500 μg selenium daily as part of PN in critically ill patients significantly decreased new infections in a subset of patients who received the supplement for ≥ 5 days, but it did not affect mortality. When the SIGNET trial data 58 for selenium supplementation were entered into the current Cochrane systematic review, 111 the random effects risk ratio for mortality changed from 0.75 (0.59-0.96, I 2 = 0%) to 0.86 (0.74-1, I 2 = 0%), and the risk ratio for new infections changed from 1.22 (0.67-2.23, I 2 = 0%) to 0.93 (0.79-1.09, I 2 = 0%).…”

“…The more recent SIGNET trial 58 found that 500 μg selenium daily as part of PN in critically ill patients significantly decreased new infections in a subset of patients who received the supplement for ≥ 5 days, but it did not affect mortality. When the SIGNET trial data 58 for selenium supplementation were entered into the current Cochrane systematic review, 111 the random effects risk ratio for mortality changed from 0.75 (0.59-0.96, I 2 = 0%) to 0.86 (0.74-1, I 2 = 0%), and the risk ratio for new infections changed from 1.22 (0.67-2.23, I 2 = 0%) to 0.93 (0.79-1.09, I 2 = 0%). 111 In one older study, high-dose vitamin C administration during resuscitation (66 mg/kg/hour) was shown to attenuate lipid peroxidation and reduce resuscitation fluid requirements, as well as post-burn oedema.…”

“…57 However, the Scottish Intensive care Glutamine or seleNium Evaluative Trial (SIGNET) in 10 centres in Scotland (n = 5 02) showed no significant effect of glutamine supplementation of TPN on mortality or infectious complications. 58 The lack of effect of glutamine in the Scottish trial has been attributed to various factors, including the low dose of glutamine used (20 g/day), the short period of administration (four to five days) and late implementation. Trials with > 0.3g/kg have been shown to have better outcomes.…”