Therapy
Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients
This review may be edited
Summary
Posted By: Elizabeth Sweetman
E-Mail: esweetman@med.usyd.edu.au
Posted Date: 15.09.11
Title: Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients
Authors: Andrews PJ, Avenell A, Noble DW, Campbell MK, Croal BL, Simpson WG, Vale LD, Battison CG, Jenkinson DJ, Cook JA; Scottish Intensive care Glutamine or seleNium Evaluative Trial Trials Group.
Reference: BMJ. 2011 Mar 17;342:d1542
Link: Click here for a direct link to the paper. A password may be required for access to fulltext.
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 g/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.
 
Are the Results Valid?
1. Was the assignment of patients to treatments randomized? ( Was allocation concealment maintained?)
Yes, allocation concealment was maintained. A remote telephone computer system was used to generate random allocation to one of four possible study groups including; Group 1: Standard Formulation (12.5 nitrogen, 2000 kcals), Group 2: Glutamine Formulation (12.5 nitrogen including 20.2 g glutamine), Group 3: Standard Formulation with an addition of 500 ug Selenium, Group 4: Glutamine Formulation with an addition of 500 ug Selenium.
2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?
2a. Was followup complete?
Yes there was complete follow-up on the Primary Outcome (Mortality). See Figure 1.
2b. Were patients analyzed in the groups to which they were randomized?
Yes patients were analysed in the groups to which they were randomised.
3. Were patients, health workers, and study personnel blind to treatment?
Yes patients, clinicians and investigators were blinded to treatment allocation.
4. Were the groups similar at the start of the trial?
Yes trial groups were similar at baseline. See Table 1.
5. Aside from the experimental intervention, were the groups treated equally?
Unable to establish this as this information was not provided in the text or in a table format.
What are the Results?
1. How large was the treatment effect?
As this is a 2x2 factorial trial with no evidence of significant interaction (P=0.96) existed between Glutamine and Selenium, the analysis can be resolved into a simple comparison of Glu vs control and SE vs Control.
GLUTAMINE TRIAL (Supplemental Glutamine vs No Glutamine Control)
Primary Outcomes
New Infections(%)134 (54) vs 131 (52) / OR 1.07; CI 0.75- 1.53; P = 0.96
New Confirmed Infections 118 (47) vs 107 (42) / OR 1.23; CI 0.86-1.76; P = 0.27
Mortality (ICU/HDU) 88 (35) vs 80 (32) / OR 1.17; CI 0.80-1.70; P = 0.42
Mortality (Hospital)115 (46) vs 106 (42) / OR 1.18; CI 0.82-1.70; P = 0.38
SELENIUM TRIAL (Supplemental Selenium vs No Selenium)
Primary Outcomes
New Infections (%) 126 (50) vs 139 (55); OR 0.81; 95% CI 0.57-1.15); P = 0.24
New Confirmed Infections (%) 104 (41) vs 121(48); OR 0.75; 95% CI 0.52-1.08; P = 0.12
Mortality- ICU/HDU(%) 84 (33) vs 84 (33); OR 1.004; 95% CI 0.69-1.47; P = 0.98
Mortality - Hospital (%) 107(43) vs 114 (45); OR 0.89; 95% CI 0.62-1.29; P = 0.54
We report only the primary analyses here. The Authors report a number of hypothesis generating sub-group analyses however these are not adjusted for multiple comparisons and should be interpreted with caution.
2. How precise was the estimate of the treatment effect?
See above for 95% Confidence Intervals around the absolute risk differences.
Will the Results Help Me In Caring For My Patients?
1. Can the results be applied to my patient care?
The primary analysis of this trial failed to document any patient benefits for glutamine or selenium use.
The Authors do present hypothesis generating analyses of Glu and SE use in sub-groups of patients who required PN for longer than 5 days. Applying a Bonferroni correction to the p-values of these sub-group analysis reveals them to be non-significant.
2. Were all clinically important outcomes considered?
Costs need to be considered.
Glutamine is Expensive - $59.40 per 500 ml Glamin (Registered TGA product containing Glutamine and AAs). - $135 to $150 for a compounded PN bag containing Glutamine (20 42 g Glutamine).
Selenium is Cheaper - $17.60 (per 120 ug per bag) / $8.80 per 2ml of Selenium & each PN bag requires 4 ml.
3. Are the likely treatment benefits worth the potential harms and costs?
No, this paper does not document treatment benefits that could offset the costs using Glutamine and/or Selenium. See above for costs.

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

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