Effect of Early Administration of Vitamin D on Clinical Outcome in Critically Ill Sepsis Patients: A Randomized Placebo-controlled Trial

Abstract

A bstract Background Administration of vitamin D to unselected heterogeneous critically ill patients did not demonstrate outcome benefit. The current study was undertaken to identify if early administration of vitamin D can reduce intensive care unit (ICU) length of stay and improve clinical outcomes in critically ill patients with sepsis. Methods This single-center randomized double-blind placebo-controlled trial was done in the ICU and emergency inpatient ward of a tertiary care teaching institute in New Delhi, India. A total of 126 adult patients aged 18 to 80 years of either sex diagnosed to have sepsis were included within 24 hours of admission to the hospital and randomized into vitamin D or placebo groups. The patients in the intervention group received vitamin D3 540,000 units dissolved in 45 mL of milk. The placebo group received 45 mL of milk. Results The median length of ICU stay (8 vs 9 days; p = 0.32), median length of hospital stay (12 vs 12 days; p = 0.33), median duration of vasopressors requirement (4 vs 3 days; p = 0.84), median duration of mechanical ventilation (5 vs 7 days; p = 0.23), requirement of tracheostomy (34 vs 39%; p = 0.71), and 90-day mortality [35 vs 46%; p = 0.29; HR 0.72 (0.42–1.24)] were similar in vitamin D and placebo arm. A subgroup analysis in patients with severe vitamin D deficiency (vitamin D <12 ng/mL) revealed a significantly decreased incidence of tracheostomy (28 vs 57%; p = 0.04), a trend toward decreased 90-day mortality [34 vs 66%; p = 0.08; HR 0.44 (0.19–1.01)], and duration of mechanical ventilation (6 vs 11 days; p = 0.05) in patients receiving vitamin D. Conclusion Administration of large-dose vitamin D within 24 hours of admission does not reduce the length of ICU stay in critically ill sepsis patients. How to cite this article Bhattacharyya A, Subramaniam R, Baidya DK, Aggarwal P, Wig N. Effect of Early Administration of Vitamin D on Clinical Outcome in Critically Ill Sepsis Patients: A Randomized Placebo-controlled Trial. Indian J Crit Care Med 2021;25(10):1147–1154.

Administration of vitamin D and its metabolites in critically ill adult patients: an updated systematic review with meta-analysis of randomized controlled trials

“…We identified two active studies from ClinicalTrials.gov (see Additional file 1 ). We obtained additional data upon request from the corresponding authors: ICU LOS [ 28 , 29 ], hospital LOS [ 28 ], duration of mechanical ventilation [ 28 , 29 ].

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“…A total of 2449 patients were enrolled in 16 RCTs (sample size range 24–1059) [ 7 – 9 , 19 – 21 , 28 – 37 ] Twelve studies included only vitamin D deficient patients (< 30 ng/mL) [ 7 – 9 , 20 , 30 , 32 – 37 ] Four studies did not have a threshold vitamin D level for inclusion [ 19 , 21 , 28 , 31 ]. Across all studies, vitamin D was administered through PO, EN, IV or IM route.…”

“…3 ). Seven studies [ 7 , 8 , 19 , 28 , 30 , 31 , 36 ] reported hospital LOS with vitamin D supplementation having no significant effect (Additional file 5 ).

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“…Nine studies [ 7 , 9 , 19 , 20 , 28 – 30 , 35 , 37 ] reported duration of mechanical ventilation. In comparison to placebo, vitamin D supplementation was associated with a significant reduction in mechanical ventilation duration (mean difference − 5.07 days, 95% CI − 7.42 to − 2.73; p < 0.0001, I 2 = 54%, Fig.…”

“…The included studies showed different time windows in which the interventional strategy was started after ICU admission. While the VIOLET trial [ 8 ] and the study by Bhattacharyya et al [ 28 ] required supplementation within the first 14 h after ICU admission, the VITdal-ICU [ 7 ] as well as the RECTIFY study allowed cholecalciferol intake within the first two days after ICU admission. In the smaller studies (< 100 patients in total), the timeframe varied up to 72 h after ICU admission [ 20 ] or was not reported at all.…”