A Randomized Study of a Single Dose of Intramuscular Cholecalciferol in Critically Ill Adults.

Abstract

OBJECTIVES:

To determine the effect of two doses of intramuscular cholecalciferol on serial serum 25-hydroxy-vitamin-D levels and on pharmacodynamics endpoints: calcium, phosphate, parathyroid hormone, C-reactive protein, interleukin-6, and cathelicidin in critically ill adults.

DESIGN:

Prospective randomized interventional study.

SETTING:

Tertiary, academic adult ICU.

PATIENTS:

Fifty critically ill adults with the systemic inflammatory response syndrome.

INTERVENTION:

Patients were randomly allocated to receive a single intramuscular dose of either 150,000 IU (0.15 mU) or 300,000 IU (0.3 mU) cholecalciferol.

MEASUREMENTS AND MAIN RESULTS:

Pharmacokinetic, pharmacodynamic parameters, and outcome measures were collected over a 14-day period or until ICU discharge, whichever was earlier. Prior to randomization, 28 of 50 patients (56%) were classified as vitamin D deficient. By day 7 after randomization, 15 of 23 (65%) and 14 of 21 patients (67%) normalized vitamin D levels with 0.15 and 0.3 mU, respectively (p=0.01) and by day 14, 8 of 10 (80%) and 10 of 12 patients (83%) (p=0.004), respectively. Secondary hyperparathyroidism was manifested in 28% of patients at baseline. Parathyroid hormone levels decreased over the study period with patients achieving vitamin D sufficiency at day 7 having significantly lower parathyroid hormone levels (p<0.01). Inflammatory markers (C-reactive protein and interleukin-6) fell significantly over the study period. Greater increments in 25-hydroxy-vitamin-D were significantly associated with greater increments in cathelicidin at days 1 and 3 (p=0.04 and 0.004, respectively). Although in-hospital mortality rate did not differ between the groups, patients who did not mount a parathyroid hormone response to vitamin D deficiency had a higher mortality (35% vs 12%; p=0.05). No significant adverse effects were observed.

CONCLUSIONS:

A single dose of either dose of intramuscular cholecalciferol corrected vitamin D deficiency in the majority of critically ill patients. Greater vitamin D increments were associated with early greater cathelicidin increases, suggesting a possible mechanism of vitamin D supplementation in inducing bactericidal pleiotropic effects.

• Authors: Priya Nair, Bala Venkatesh, Paul Lee, Stephen Kerr, Dominik J Hoechter, Goce Dimeski, Jeffrey Grice, John Myburgh, Jacqueline R Center
• Journal: Critical care medicine (Crit Care Med) Vol. 43 Issue 11 Pg. 2313-20 (Nov 2015) ISSN: 1530-0293 [Electronic] United States
• PMID: 26186566 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Inflammation Mediators
• Cholecalciferol

Topics

• Academic Medical Centers
• Adult
• Aged
• Australia
• Cholecalciferol (administration & dosage, pharmacokinetics)
• Critical Care (methods)
• Critical Illness (mortality)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Hospital Mortality
• Humans
• Inflammation Mediators (analysis)
• Injections, Intramuscular
• Intensive Care Units
• Male
• Middle Aged
• Prospective Studies
• Risk Assessment
• Systemic Inflammatory Response Syndrome (diagnosis, drug therapy, mortality)
• Vitamin D Deficiency (diagnosis, drug therapy)