High dose vitamin D administration in ventilated intensive care unit patients: A pilot double blind randomized controlled trial

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 D3 or 100,000 IU vitamin D3 daily for 5 consecutive days enterally (total vitamin D3 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 D3 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 D3 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)

Antimicrobial Activity of Mesenchymal Stem Cells: Current Status and New Perspectives of Antimicrobial Peptide-Based Therapies

“…Indeed, Vitamin D3 has been shown to directly regulate expression of the human antimicrobial peptides LL-37 and hBD-2 (179, 180). However, a recent pilot study in mechanically ventilated ICU patients showed that high dose of vitamin D3 was associated with decreased hospital length of stay, but no statically significant change in plasma LL-37 concentrations or other clinical outcomes (181). While the stimulatory effect of Vitamin D has been described for the osteogenic potential of MSCs (182), future experiments are required to address their effect on the expression of AMPs both in vitro and in vivo .…”

Impact of high-dose vitamin D 3 on plasma free 25-hydroxyvitamin D concentrations and antimicrobial peptides in critically ill mechanically ventilated adults

“…The parent RCT was approved by the Emory University Institutional Review Board (www.clinicaltrials.gov NCT01372995) and published previously (5). Written informed consent was obtained from all subjects or their legally authorized representative.…”

“…those with frank vitamin D deficiency) without improvement in other clinical outcomes; thus, vitamin D therapy in this setting remains controversial and there is a need for further investigations (15, 38). In our recent RCT in mechanically ventilated adults, high-dose vitamin D 3 increased plasma total 25(OH)D levels by 2 to 3-fold, but did not alter plasma LL-37 concentrations (5). …”

“…The potential benefit of vitamin D administration in critically ill patients is being investigated given the high rate of vitamin D deficiency in this patient population (1–5) and its strong association between low blood levels of total 25-hydroxyvitamin D [25(OH)D] and adverse clinical outcomes, such as increased risk of mortality (6–13). Recently, several randomized clinical trials (RCT) have reported clinical effects of administration of vitamin D in adult intensive care unit (ICU) patients (5, 14–16).…”

“…Recently, several randomized clinical trials (RCT) have reported clinical effects of administration of vitamin D in adult intensive care unit (ICU) patients (5, 14–16). Three of the recent RCTs studied various high-dose regimens of vitamin D 3 (cholecalciferol) and reported some beneficial effects on secondary clinical endpoints, including mortality (15) and hospital length of stay (LOS) (5, 16), concomitant with increased total 25(OH)D levels in blood.…”