Indian Journal of Critical Care Medicine

Register      Login



Volume / Issue

Online First

Related articles

VOLUME 25 , ISSUE 10 ( October, 2021 ) > List of Articles

Original Article

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

Amrita Bhattacharyya, Rajeshwari Subramaniam

Keywords : Intensive care unit outcomes, Sepsis, Vitamin D

Citation Information : Bhattacharyya A, Subramaniam R. 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.

DOI: 10.5005/jp-journals-10071-23993

License: CC BY-NC 4.0

Published Online: 21-06-2022

Copyright Statement:  Copyright © 2021; Jaypee Brothers Medical Publishers (P) Ltd.


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.

  1. Bikle D. Nonclassic actions of vitamin D. J Clin Endocrinol Metab 2009;94(1):26–34. DOI: 10.1210/jc.2008-1454.
  2. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357(3):266–281. DOI: 10.1056/NEJMra070553.
  3. Bartley J. Vitamin D: emerging roles in infection and immunity. Expert Rev Anti Infect Ther 2010;8(12):1359–1369. DOI: 10.1586/eri.10.102.
  4. Zhang Y-P, Wan Y-D, Sun T-W, Kan Q-C, Wang L-X. Association between vitamin D deficiency and mortality in critically ill adult patients: a meta-analysis of cohort studies. Crit Care 2014;18(6):684. DOI: 10.1186/s13054-014-0684-9.
  5. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016;315(8):801–810. DOI: 10.1001/jama.2016.0287.
  6. Sinha H, Maitra S, Anand RK, Aggarwal R, Rewari V, Subramaniam R, et al. Epidemiology and Prognostic Utility of Cellular Components of Hematological System in Sepsis. Indian J Crit Care Med 2021;25(6):660–667. DOI: 10.5005/jp-journals-10071-23874.
  7. Amrein K, Schnedl C, Holl A, Riedl R, Christopher KB, Pachler C, et al. Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized clinical trial. JAMA 2014;312(15):1520–1530. DOI: 10.1001/jama.2014.13204.
  8. Ginde AA, Brower RG, Caterino JM, Finck L, Banner-Goodspeed VM, Grissom CK, et al. Early high-dose vitamin D3 for critically ill, vitamin D-deficient patients. N Engl J Med 2019;381(26):2529–2540. DOI: 10.1056/NEJMoa1911124.
  9. Leaf DE, Raed A, Donnino MW, Ginde AA, Waikar SS. Randomized controlled trial of calcitriol in severe sepsis. Am J Respir Crit Care Med 2014;190(5):533–541. DOI: 10.1164/rccm.201405-0988OC.
  10. Yadav S, Joshi P, Dahiya U, Baidya DK, Goswami R, Guleria R, et al. Admission vitamin D status does not predict outcome of critically ill patients on mechanical ventilation: an observational pilot study. Indian J Anaesth 2018;62(1):47–52. DOI: 10.4103/ija.IJA_531_17.
  11. Venkatesh B, Davidson B, Robinson K, Pascoe R, Appleton C, Jones M. Do random estimations of vitamin D3 and parathyroid hormone reflect the 24-h profile in the critically ill? Intensive Care Med 2012;38(1):177–179. DOI: 10.1007/s00134-011-2415-x.
  12. Nair P, Venkatesh B, Center JR. Vitamin D deficiency and supplementation in critical illness-the known knowns and known unknowns. Crit Care 2018;22(1):276. DOI: 10.1186/s13054-018-2185-8.
  13. Malihi Z, Wu Z, Lawes CMM, Scragg R. Adverse events from large dose vitamin D supplementation taken for one year or longer. J Steroid Biochem Mol Biol 2019;188:29–37. DOI: 10.1016/j.jsbmb.2018.12.002.
  14. Amrein K, Sourij H, Wagner G, Holl A, Pieber TR, Smolle KH, et al. Short-term effects of high-dose oral vitamin D3 in critically ill vitamin D deficient patients: a randomized, double-blind, placebo-controlled pilot study. Crit Care 2011;15(2):R104. DOI: 10.1186/cc10120.
  15. de Haan K, Groeneveld ABJ, de Geus HRH, Egal M, Struijs A. Vitamin D deficiency as a risk factor for infection, sepsis and mortality in the critically ill: systematic review and meta-analysis. Crit Care 2014;18(6):660. DOI: 10.1186/s13054-014-0660-4.
  16. Martucci G, McNally D, Parekh D, Zajic P, Tuzzolino F, Arcadipane A, et al. Trying to identify who may benefit most from future vitamin D intervention trials: a post hoc analysis from the VITDAL-ICU study excluding the early deaths. Crit Care 2019;23(1):200. DOI: 10.1186/s13054-019-2472-z.
  17. Amrein K, Parekh D, Westphal S, Preiser J-C, Berghold A, Riedl R, et al. Effect of high-dose vitamin D3 on 28-day mortality in adult critically ill patients with severe vitamin D deficiency: a study protocol of a multicentre, placebo-controlled double-blind phase III RCT (the VITDALIZE study). BMJ Open 2019;9(11):e031083. DOI: 10.1136/bmjopen-2019-031083.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.