Vitamin D Supplementation in Critically Ill-Narrative Review

Abstract

Background: Studies have shown a high prevalence of vitamin D deficiency in critically ill patients, and these patients are at higher risk for pneumonia and have increased incidence of sepsis and mortality. In this study, we reviewed available literature from randomized controlled trials (RCTs) on vitamin D supplementation in critically ill patients and summarized the evidence in this narrative review.

Methods: Randomized controlled trials that included vitamin D supplementation as an intervention were eligible for inclusion. No limits were set regarding vitamin D dosage or route of administration, as well as for primary and secondary outcomes. A search was conducted in MEDLINE via PubMed for eligible RCTs. References from systematic reviews (SRs) and meta-analyses (MAs) were screened, and Clinicaltrials.gov was searched for ongoing studies.

Results: A total of 21 RCTs involving 3166 patients were analyzed. There was a large heterogeneity in terms of patients' characteristics and inclusion criteria. Only six studies included patients with vitamin D levels < 50 nmol/L. Regarding clinically important outcomes, most of the studies did not show differences between the intervention and control group in terms of mortality, intensive care unit (ICU) or hospital length of stay (LoS).

Conclusions: There is great variability in trial designs regarding the selection of patients, dosage, dosing intervals and routes of administration of vitamin D supplements. Better study designs are mandatory for future clinical research, with measuring and reporting basal vitamin D levels before randomization. Since variability in supplementation regimes limits the possibility of data synthesis, standardized protocols for vitamin D supplementation should be used in clinical trial settings.

Keywords: ICU; critically ill; supplementation; vitamin D.

Figure 1

Flow diagram of the literature search. MEDLINE was searched for interventional trials and systematic reviews, and Clinical.trials.gov was searched for ongoing studies.

Figure 2

Dose-response curve for vitamin D supplementation. Supplementation in patients on the left side of the curve will lead to a steep increase in plasma concentration, while supplementation in patients on the right side of the curve will have little effect on increasing plasma concentration.