Vitamin D Supplementation during Intensive Care Unit Stay Is Associated with Improved Outcomes in Critically Ill Patients with Sepsis: A Cohort Study

Abstract

Background: Vitamin D, as a common micronutrient, has been widely used in critically ill patients. However, whether supplementation of vitamin D in adult patients with sepsis can improve their prognosis remains controversial.

Methods: Data from the Mart for Intensive Care IV database was used in this retrospective cohort study, and adult patients with sepsis were enrolled. Critically ill patients, admitted to intensive care units (ICUs) between 2008 and 2019 at the Beth Israel Deaconess Medical Center (BIDMC), were divided into the vitamin D supplementation group and non-vitamin D supplementation group. The primary outcomes were defined as all-cause in-hospital, 28-day, and 90-day mortality rates after admission to the ICU. A 1:1 propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and overlap weighting (OW) analyses were used to minimize selection bias and balance the baseline demographic characteristics. Regression and survival analyses were performed to assess the association between vitamin D supplementation and clinical outcomes in patients with sepsis.

Results: In total, 3539 patients with sepsis were enrolled as study participants; of these, 315 were supplemented with vitamin D during their ICU stay. In-hospital, 28-day, and 90-day mortality rates were significantly lower in patients with sepsis supplemented with vitamin D. Multivariate regression analysis showed vitamin D supplementation as a potential protective factor for in-hospital mortality with an odds ratio (OR) = 0.70 (0.51-0.96) after adjusting for all confounders. The hazard ratios (HRs) for 28-day and 90-day mortality were 0.65 (0.50-0.85) and 0.70 (0.55-0.90), respectively. The survival analysis showed that the vitamin D supplementation group had a higher survival probability within 28 and 90 days (p-value < 0.05). These results remained relatively stable post PSM, IPTW, and OW. However, we found no evidence that vitamin D supplementation could shorten the length of stay in the ICU or hospital.

Conclusions: Vitamin D supplementation during an ICU stay was associated with improved prognosis in patients with sepsis, as evidenced by lower in-hospital, 28-day, and 90-day mortality rates and lower disease severity-related scores, but showed no influence on the length of stay in the hospital or ICU.

Keywords: intensive care units; mortality risk; prognosis; sepsis; vitamin D.

Figure 1

Study flowchart. MIMIC-IV database, the Mart for Intensive Care IV database; PSM, propensity score matching. ICU, intensive care unit. PSM, propensity score matching; IPTW, inverse probability of treatment weighting; OW, overlap weighting.

Figure 2

Survival analysis between vitamin D users and non-vitamin D users. (A) Kaplan–Meier survival curve of the two groups within 28 days and table of number at risk. (B) Kaplan–Meier survival curve of the two groups within 90 days and table of number at risk. The y axis shows the survival probability of patients over time, and the table of numbers at risk shows the number of survivors at each time point.

Figure 3

Regression analysis to explore the impact of vitamin D supplementation on the clinical outcomes of patients with sepsis post PSM, IPTW, and OW. (A) Association between vitamin D supplementation and in-hospital mortality. (B) Association between vitamin D supplementation and 28-day mortality. (C) Association between vitamin D supplementation and 90-day mortality. PSM, propensity score matching; IPTW, inverse probability of treatment weighting; OW, overlap weighting. The data are presented as the median (25 to 75 percentiles).

Figure 4

Survival analysis between vitamin D users and non-vitamin D users post PSM, IPTW, and OW. (A1,A2) Kaplan–Meier survival curves of the two groups within 28 days and 90 days post PSM. (B1,B2) Kaplan–Meier survival curves of the two groups within 28 days and 90 days post IPTW. (C1,C2) Kaplan–Meier survival curves of the two groups within 28 days and 90 days post OW. The y axis shows the survival probability of patients over time, and the table of numbers at risk shows the number of survivors at each time point. PSM, propensity score matching; IPTW, inverse probability of treatment weighting; OW, overlap weighting.

Figure 5

Multivariate regression analysis to explore the impact of vitamin D supplementation dosage on the clinical outcomes of patients with sepsis. (A) Association between vitamin D dosage and in-hospital mortality. (B) Association between vitamin D dosage and 28-day mortality. (C) Association between vitamin D dosage and 90-day mortality. The data are presented as the median (25 to 75 percentiles).