Vitamin D in the ICU: More sun for critically ill adult patients?

Critical illness in patients is characterized by systemic inflammation and oxidative stress. Vitamin D has a myriad of biological functions relevant to this population, including immunomodulation by the alteration of cytokine production and nuclear factor loop amplification. Low serum levels have consistently been found in observational studies conducted on critically ill patients, but the causality with mortality and worse outcomes has not been confirmed. The current focus is on interventional trials, whereas the pharmacokinetic profile of vitamin D administration remains sparse and the optimal strategy has not been confirmed. So far, high-dose oral or enteral supplementation is the most studied strategy. The largest randomized controlled trial published so far, the VITdAL-ICU (Effect of High-dose Vitamin D3 on Hospital Length of Stay in Critically Ill Patients with Vitamin D Deficiency) trial, showed no benefits on mortality in its primary analysis. However, secondary analysis suggested improvement in those patients with severe deficiency (i.e., 25-dihydroxyvitaminD <12 ng/mL). Smaller trials investigated intramuscular and intravenous administration and found interesting intermediate biochemical findings, including increased cathelicidins, but were not powered to investigate relevant clinical outcomes in the critically ill. The latest meta-analysis, which was recently published, does not support benefits of vitamin D supplementation in the heterogeneous population of critically ill patients. The European guidelines, published in the last year, suggest supplementing severely deficient patients with levels <12.5 ng/mL within the first week after ICU admission. However, other societies do not support such supplementation in their older recommendations. Large trials are currently recruiting ICU patients and could elucidate potential clinical benefits of vitamin D therapy in the critically ill.