Antioxidant micronutrient supplements for adult critically ill patients: A bayesian multiple treatment comparisons meta-analysis

Abstract

Background & aims: Antioxidant micronutrients (AxMs) have been administered to critically ill adults attempting to counteract the oxidative stress imposed during critical illness. However, results are conflicting and relative effectiveness of AxMs regimens is unknown. We conducted a Bayesian multi-treatment comparison (MTC) meta-analysis to identify the best AxM treatment regimen that will improve clinical outcomes.

Methods: PubMed, EMBASE, Web of Science and Cochrane databases were searched from the inception of databases through August 2020. Randomized controlled trials (RCT) comparing AxMs supplementations with placebo among critically ill adults were included. Two authors assessed trial quality using Cochrane risk of bias tool and assessed certainty of evidence (CoE). A random effect model, non-informative priors Bayesian MTC meta-analysis using gemtc package in R version 3.6.2 was performed. AxMs treatment effect on clinical outcomes (mortality, infection rates, intensive care unit (ICU) and hospital stays and ventilator days) were represented by absolute risk differences (ARD) for dichotomous outcomes and mean differences (MD) for continuous outcomes. Prior to final analysis, we repeated the search through January 2021.

Results: 37 RCT (4905 patients) were included with 16 direct comparisons. With respect to mortality, the ARD for "vitamin E" compared with placebo was centred at -0.19 [95%CrI: -0.54,0.16; very low CoE] and was ranked the best treatment for mortality reduction as per surface under the cumulative ranking curve (SUCRA 0.71, 95%CrI: 0.07,1.00). A combination of "selenium, zinc and copper" was ranked the best for lowest ICU stay [-9.40, 95% CrI: -20.0,1.50; low CoE]. A combination of "selenium, zinc, copper and vitamin E" was ranked the best treatment for infection risk reduction [-0.22, 95% CrI: -0.61,0.17; very low CoE]. Ventilator days were least with a combination of "selenium, zinc and manganese" [2.80, 95% CrI: -6.30,0.89; low CoE]. Hospital stay was the lowest using a combination of "selenium, zinc and copper" [-13.00, 95% CrI: -38.00,13.00; very low CoE]. There is substantial uncertainty present in the rankings due to wide and overlapping 95% CrIs of SUCRA scores for the treatments.

Conclusions: Studies on critically ill adult patients have suggested a possible beneficial effects of certain AxM supplementations over and above the recommended dietary allowance. However, evidence does not support their use in clinical practice due to the low confidence in the estimates. Current studies evaluating specific AxMs or their combinations are limited with small sample sizes.

Registration: PROSPERO, CRD42020210199.

Take-home message: Evidence suggesting a potential benefit of AxMs use more than recommended doses in critically ill adults is weak, indicating that there is no justification for this practice.

Keywords: Antioxidant micronutrient; Bayesian multiple treatment comparison; Critical illness; Network meta-analysis.