title: A Randomized Study of a Single Dose of Intramuscular Cholecalciferol in Critically Ill Adults.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Prospective randomized interventional study.
  
  
  METHODS
  Tertiary, academic adult ICU.
  
  
  METHODS
  Fifty critically ill adults with the systemic inflammatory response syndrome.
  
  
  METHODS
  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.
  
  
  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.affiliation: 1Intensive Care Unit, St. Vincent's Hospital, Sydney, NSW, Australia. 2Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia. 3Bone Biology Division, Garvan Institute for Medical Research, Sydney, NSW, Australia. 4Critical Care and Trauma Division, George Institute for Global Health, Sydney, NSW, Australia. 5Intensive Care Unit, Princess Alexandra Hospital, Brisbane, QLD, Australia. 6Intensive Care Unit, Wesley Hospital, Brisbane, QLD, Australia. 7University of Queensland, Brisbane, QLD, Australia. 8Departement of Anesthesiology, LMU, Munich, Germany. 9Intensive Care Unit, St. George Hospital, Sydney, NSW, Australia.
authors.forename: Priya
authors.initials: P
authors.lastname: Nair
authors.forename: Bala
authors.initials: B
authors.lastname: Venkatesh
authors.forename: Paul
authors.initials: P
authors.lastname: Lee
authors.forename: Stephen
authors.initials: S
authors.lastname: Kerr
authors.forename: Dominik J
authors.initials: DJ
authors.lastname: Hoechter
authors.forename: Goce
authors.initials: G
authors.lastname: Dimeski
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Grice
authors.forename: John
authors.initials: J
authors.lastname: Myburgh
authors.forename: Jacqueline R
authors.initials: JR
authors.lastname: Center
mesh_terms: D000046:Academic Medical Centers; D000328:Adult; D000368:Aged; D001315:Australia; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003422:Critical Care / Q000379:methods; D016638:Critical Illness / Q000401:mortality; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D007273:Injections, Intramuscular; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018570:Risk Assessment; D018746:Systemic Inflammatory Response Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D014808:Vitamin D Deficiency / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D018836:Inflammation Mediators; D002762:Cholecalciferol