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Vitamin D administration may be associated with lower mortality in critical care patients

Vitamin D administration might reduce the risk of death, intensive care stay and mechanical ventilation days among critically ill adult patients, according to the findings of a systematic review

Vitamin D administration to patients within critical care significantly reduces the risk of death compared with placebo, duration of their stay within an intensive care unit and the number of days for which mechanical ventilation is needed, according to the findings of a systematic review and meta-analysis by European and Canadian researchers.

Except for rare circumstances such as the complete absence of UV radiation, the human body can synthesise vitamin D. Whilst the vitamin is known to play a role in the regulation of calcium and phosphate levels in circulation, the active metabolite of vitamin D, calcitriol, has been found in vitro to up-regulate different anti-inflammatory pathways. Furthermore, as dysregulated host immune responses to infection often occur, leading to sepsis, multiple organ failure, and death, vitamin D deficiency appears to be associated with an increased susceptibility of sepsis. In fact, a 2020 meta-analysis suggested that severe vitamin D deficiency may be independently associated with increased mortality in adult patients with sepsis. Despite these findings, correcting vitamin D deficiency, through high-dose vitamin D administration, does not reduce hospital length of stay, hospital mortality, or 6-month mortality compared with placebo, unless patients had severe deficiency of the vitamin. Nevertheless, one small trial in 36 patients with COVID-19, did find that high dose (300,000 IU) vitamin D administration to intensive care patients, decreased the length of stay and duration of mechanical ventilation. 

With some uncertainty over the value of vitamin D administration to critically ill patients, in the present study, researchers undertook a systematic review and meta-analysis of clinical outcomes in critically ill patients given vitamin D. They focused on randomised trials that included adults treated within an intensive care unit and for whom vitamin D administration, or its metabolite, was provided via either an enteral or parenteral route. Studies were also required to have a comparator group who received standard care and which reported on the outcomes of interest, i.e., mortality, length of intensive care unit (ICU) and hospital stay or the duration of mechanical ventilation. The primary outcome of interest was overall mortality, whereas secondary outcomes were hospital and ICU length of stay and the duration of mechanical ventilation.

Vitamin D administration and critical care outcomes

A total of 16 studies with 2449 patients were included in the analysis. Only 12 studies included vitamin D-deficient patients (i.e., < 30ng/ml) whereas the remaining 4 studies did not specify a threshold.

In terms of mortality, vitamin D administration was associated with a 22% reduced risk of death compared with placebo (risk ratio, RR = 0.78, 95% CI 0.62 – 0.97, p = 0.03). With respect to ICU length of stay, vitamin D supplementation lead to a mean difference in length of stay (compared to placebo) of 3.13 days (95% CI -5.36 to – 0.89, p = 0.006). Based on 7 studies, the length of hospital stay was no different to placebo. Finally, vitamin D administration was significantly associated with a reduction in the number days for which patients required mechanical ventilation (mean difference = -5.07 days, 95% CI -7.42 to -2.73, p < 0.0001). There was also an important effect of the route of administration, with parenteral having a more significant effect on mortality compared with the enteral route.

The authors concluded that vitamin D administration may be associated with a lower mortality among critically ill patients. However, they added that since several smaller and inconsistent studies with an inherent risk of bias were included, larger and more definitive trials were needed to support the findings regarding the type of supplementation and specific populations that achieve the greatest benefit.

Menger J et al. Administration of vitamin D and its metabolites in critically ill adult patients: an updated systematic review with meta-analysis of randomized controlled trials Crit Care 2022

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