High Dose Vitamin D Administration in Ventilated Intensive Care Unit Patients: A Pilot Double Blind Randomized Controlled Trial.

Jenny E Han, Jennifer L Jones, Vin Tangpricha, Mona A Brown, Lou Ann S Brown, Li Hao, Gautam Hebbar, Moon Jeong Lee, Shuling Liu, Thomas R Ziegler, Greg S Martin

Journal: Journal of clinical & translational endocrinology 2016;4():59-65

PMID: 27419080

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Plain Language Summary

Patients in intensive care (ICU) have a high prevalence of Vitamin D deficiency. (Measured by plasma concentration of 25 hydroxy Vitamin D (25(OH)D)). Several studies have shown associations between Vitamin D deficiency and increased hospital length of stay (LOS), readmission rates, sepsis, mortality and other respiratory complications. There are studies to show improvements in clinical outcomes with high dose vitamin D therapy in critically ill patients but the literature is limited. The aim of this small pilot study was to test the safety and efficacy of high levels of Vitamin D supplementation, in divided doses over several days, on mechanically ventilated adult ICU patients. The levels of 25(OH)D increased in both supplemented groups (group 1: 250,000 IU over 5 days and group 2: 500,000 IU over 5 days), and not in the placebo. These groups both had reduced LOS compared with the placebo. The other measured outcomes were not statistically affected. High dose Vitamin D was well tolerated in these critically ill patients but further testing is required to clarify the benefits.

Abstract

BACKGROUND

There is a high prevalence of vitamin D deficiency in the critically ill patient population. Several intensive care unit studies have demonstrated an association between vitamin D deficiency [25-hydroxyvitamin D (25(OH)D) < 20 ng/mL] and increased hospital length of stay (LOS), readmission rate, sepsis and mortality.

MATERIAL AND METHODS

Pilot, double blind randomized control trial conducted on mechanically ventilated adult ICU patients. Subjects were administered either placebo, 50,000 IU vitamin D or 100,000 IU vitamin D daily for 5 consecutive days enterally (total vitamin D dose = 250,000 IU or 500,000 IU, respectively). The primary outcome was plasma 25(OH)D concentration 7 days after oral administration of study drug. Secondary outcomes were plasma levels of the antimicrobial peptide cathelicidin (LL37), hospital LOS, SOFA score, duration of mechanical ventilation, hospital mortality, mortality at 12 weeks, and hospital acquired infection.

RESULTS

A total of 31 subjects were enrolled with 13 (43%) being vitamin D deficient at entry (25(OH)D levels < 20 ng/mL). The 250,000 IU and 500,000 IU vitamin D regimens each resulted in a significant increase in mean plasma 25(OH)D concentrations from baseline to day 7; values rose to 45.7±19.6 ng/mL and 55.2 ± 14.4 ng/mL, respectively, compared to essentially no change in the placebo group (21±11.2 ng/mL), p<0.001. There was a significant decrease in hospital length of stay over time in the 250,000 IU and the 500,000 IU vitamin D group, compared to the placebo group (25 ± 14 and 18 ± 11 days compared to 36 ± 19 days, respectively; p=0.03). There was no statically significant change in plasma LL-37 concentrations or other clinical outcomes by group over time.

CONCLUSIONS

In this pilot study, high-dose vitamin D3 safely increased plasma 25(OH)D concentrations into the sufficient range and was associated with decreased hospital length of stay without altering other clinical outcomes.

CLINICAL TRIAL REGISTRATION

www.clinicaltrials.gov (NCT01372995).

Address: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University, Atlanta, GA.; Emory Critical Care Center, Emory University, Atlanta, GA.; Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, GA.; Atlanta VA Medical Center, Decatur, GA.; Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Emory University, Atlanta, GA.; Rollins School of Public Health, Emory University, Atlanta, GA.

DOI: 10.1016/j.jcte.2016.04.004