Neither vitamin D levels nor supplementation are associated with persistent critical illness: A retrospective cohort analysis

Background: Low levels of vitamin D are associated with poor outcomes among critically ill patients, thought to be mediated via vitamin D's pleiotropic effects on the immune system. The relationship between vitamin D and the development of persistent critical illness (ICU stay >10 days) is unknown. The purpose of this study was to develop hypotheses about whether lower levels of vitamin D are associated with increased rates of persistent critical illness, and whether repletion of vitamin D among those with low levels leads to decreased persistent critical illness. Methods: We conducted a secondary analysis of (a) a cohort of patients admitted to the University Medical Center Graz, Austria, who were admitted to seven medical and surgical ICUs from July 2008 ‐ April 2010, to evaluate the association between vitamin D and the development of persistent critical illness; and (b) the cohort from the VITdAL‐ICU randomized clinical trial, to understand the impact of vitamin D3 supplementation on the development of persistent critical illness in patients with vitamin D deficiency. Results: In the retrospective cohort of 655 people, 628 were included in the analysis of whom 28.8% (n = 181) developed persistent critical illness. The mean 25‐hydroxyvitamin D level was 17.4 ng/mL (IQR 11.2, 25.2). Among patients admitted to the ICU, vitamin D3 level on admission was not significantly associated with the development of persistent critical illness compared to those discharged alive earlier (RRR: 1.02, 95% CI: 1.00 ‐1.04) or who died (RRR: 1.02, 95% CI: 0.99 ‐1.05). In the VITdAL‐ICU randomized trial, the mean 25‐hydroxyvitamin D level was 13.1ng/mL (SD: 4.3) and 13.0 ng/mL (SD: 4.0) in the placebo and treatment groups respectively. In the 475 patients, 46.7% (n = 222) developed persistent critical illness. Supplementation with vitamin D3 did not lead to less persistent illness relative to those discharged alive before the onset of persistent critical illness (RRR: 1.19, 95% CI 0.76 ‐ 1.80) or those who died before the onset of persistent critical illness (RRR: 1.34, 95% CI 0.72 ‐ 2.52). Conclusion: Vitamin D3 deficiency was not associated with persistent critical illness, nor did supplementation with vitamin D3 mitigate the development of persistent critical illness.