Efficacy of High-Dose Vitamin D Supplementation in the Critically Ill Patients

Abstract

Vitamin D deficiency and its adverse skeletal sequelae are well recognized in the general population. Recent observation of high prevalence of low vitamin D states and their associations with worse clinical outcomes in critically ill populations have sparked interest in the role of supplementation for these patients. High-dose vitamin D efficaciously increases serum levels, but its impact on clinical outcome has not been examined. This article will review results from observational studies on prevalence and outcomes of hypovitaminosis D in critically ill patients, as well as caveats of vitamin D interventional trials. Improved understanding of vitamin D metabolism in critical illness will clarify the therapeutic potential of this pleiotropic hormone and facilitate implementation of cost-effective clinical trials.

Vitamin D and acute myocardial infarction

“…Taking together, these considerations, along with older age, higher incidence of well-known cardiovascular risk factors, and lower rate of reperfusion strategy, might explain the worse outcome of AMI patients presenting with low vitamin D levels (Figure 2). A similar prognostic relevance has also been reported in critically ill patients, in whom a low vitamin D status was significantly associated with disease severity and mortality[50-52]. …”

“…Indeed, in more than 3000 patients undergoing coronary angiography, a significant association between hypovitaminosis D and lower left ventricular function was shown[49]. Of note, in this report, vitamin D deficiency was associated with deaths due to heart failure and with sudden cardiac deaths[50]. This highlights the possible relevance of vitamin D contribution to several aspects of AMI, such as acute ventricular dysfunction, heart failure progression, post-AMI ventricular remodeling, inflammation, thrombotic/bleeding balance and arrhythmias, which should be more deeply investigated through well-designed studies.…”

Vitamin D: Way More Important in Critical Care Than We May Have Recognized

“…In addition to single reports suggesting that higher vitamin D levels confer mortality benefits, [39][40][41]43,47,66,67 a number of randomized controlled trial meta-analyses demonstrate the consistency of the inverse relationship between vitamin D level and mortality from any cause.…”

“…46 Longer-term outcomes support that finding, with the lowest vitamin D levels linked to greater rehospitalizations for acute heart failure (HF) and subsequent acute coronary syndrome, 40 higher 1-year mortality, 39 and deaths from HF and sudden cardiac death. 47 Reduced Exercise Capacity and Higher Mortality in HF One of the definitive manifestations of HF, often considered a prognostic marker, is diminished exercise capacity, measured via peak oxygen consumption (VO 2 ). A recent study found that 87% of HF patients had VDD (<20 ng/mL) and 25% had severe VDD (<10 ng/mL); those with severe VDD had significantly lower VO 2 , peak VO 2 %, and higher brain natriuretic peptide compared with those with higher levels.…”

Vitamin D assessment in perioperative medicine and critical care

“…These alterations in vitamin D status in states of critical illness may contribute to overdiagnosis and potentially overtreatment later on. While supplementation of cholecalciferol during intensive care can be considered standard of care using doses recommended for the overall population (600-4000 IU daily), high bolus doses have been shown to be necessary in critical illness if correction of vitamin D deficiency is the goal [22]. In the only large randomized clinical trial investigating this intervention published to date, no significant benefit was found regarding the primary endpoint (length of stay) or overall mortality [4].…”