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16th September 2022
Vitamin D administration to critical care patients leads to a significant reduction in mortality, the length of stay in critical care and the need for mechanical ventilation 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. Nevertheless, based on the currently available evidence, it seems that correction of a deficiency, through high dose vitamin D administration to critically ill patients does not reduce hospital length of stay, hospital mortality, or 6-month mortality compared to placebo, unless patients had severe deficiency of the vitamin. Despite this, 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.
Given this uncertainty, for 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., < 30 ng/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 to 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 to 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