• Johannes Menger, Zheng-Yii Lee, Quirin Notz, Julia Wallqvist, HasanM ShahnazMSDepartment of Anesthesiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia., Gunnar Elke, Martin Dworschak, Patrick Meybohm, Daren K Heyland, and Christian Stoppe.
• Department of Anesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Würzburg, Würzburg, Germany.
• Crit Care. 2022 Sep 6; 26 (1): 268.

BackgroundThe clinical significance of vitamin D administration in critically ill patients remains inconclusive. The purpose of this systematic review with meta-analysis was to investigate the effect of vitamin D and its metabolites on major clinical outcomes in critically ill patients, including a subgroup analysis based on vitamin D status and route of vitamin D administration.MethodsMajor databases were searched through February 9, 2022. Randomized controlled trials of adult critically ill patients with an intervention group receiving vitamin D or its metabolites were included. Random-effect meta-analyses were performed to estimate the pooled risk ratio (dichotomized outcomes) or mean difference (continuous outcomes). Risk of bias assessment included the Cochrane tool for assessing risk of bias in randomized trials.ResultsSixteen randomized clinical trials with 2449 patients were included. Vitamin D administration was associated with lower overall mortality (16 studies: risk ratio 0.78, 95% confidence interval 0.62-0.97, p = 0.03; I2 = 30%), reduced intensive care unit length of stay (12 studies: mean difference - 3.13 days, 95% CI - 5.36 to - 0.89, n = 1250, p = 0.006; I2 = 70%), and shorter duration of mechanical ventilation (9 studies: mean difference - 5.07 days, 95% CI - 7.42 to - 2.73, n = 572, p < 0.0001; I2 = 54%). Parenteral administration was associated with a greater effect on overall mortality than enteral administration (test of subgroup differences, p = 0.04), whereas studies of parenteral subgroups had lower quality. There were no subgroup differences based on baseline vitamin D levels.ConclusionsVitamin D supplementation in critically ill patients may reduce mortality. Parenteral administration might be associated with a greater impact on mortality. Heterogeneity and assessed certainty among the studies limits the generalizability of the results.Trial RegistrationPROSPERO international prospective database of systematic reviews (CRD42021256939-05 July 2021).© 2022. The Author(s).

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