Vitamin D supplementation and the outcomes of critically ill adult patients: a systematic review and meta-analysis of randomized controlled trials

Abstract

this meta-analysis assessed the association between vitamin D supplementation and the outcomes of critically ill adult patients. A literature search was conducted using the PubMed, Web of Science, EBSCO, Cochrane Library, Ovid MEDLINE, and Embase databases until March 21, 2020. We only included randomized controlled trials (RCTs) comparing the efficacy of vitamin D supplementation with placebo in critically ill adult patients. The primary outcome was their 28-day mortality. Overall, 9 RCTs with 1867 patients were included. In the pooled analysis of the 9 RCTs, no significant difference was observed in 28-day mortality between the vitamin D supplementation and placebo groups (20.4% vs 21.7%, OR, 0.73; 95% CI, 0.46-1.15; I 2 = 51%). This result did not change as per the method of vitamin D supplementation (enteral route only: 19.9% vs 18.2%, OR, 1.19; 95% CI, 0.88-1.57; I 2 = 10%; intramuscular or intravenous injection route: 25.6% vs 40.8%, OR, 0.48; 95% CI, 0.21-1.06; I 2 = 19%) or daily dose (high dose: 20.9% vs 19.8%, OR, 0.83; 95% CI, 0.51-1.36; I 2 = 53%; low dose: 15.6% vs 21.3%, OR, 0.74; 95% CI, 0.32-1.68; I 2 = 0%). No significant difference was observed between the vitamin D supplementation and placebo groups regarding the length of ICU stay (standard mean difference [SMD], − 0.30; 95% CI, − 0.61 to 0.01; I 2 = 60%), length of hospital stay (SMD, − 0.17; 95% CI, − 041 to 0.08; I 2 = 65%), and duration of mechanical ventilation (SMD, − 0.41; 95% CI, − 081 to 0.00; I 2 = 72%). In conclusion, this meta-analysis suggested that the administration of vitamin D did not provide additional advantages over placebo for critically ill patients. However, additional studies are needed to confirm our findings. Vitamin D, a fat-soluble vitamin, is an essential nutrient in bone metabolism and calcium and phosphorus homeostasis. However, the system of vitamin D is complex, in which some novel pathways have been found for host response to vitamin D treatment including non-canonical pathways of vitamin D activation 1,2 leading to production of non-or low-calcemic analogs 3 and of lumisterol activation 4. In clinical practice, vitamin D is used for the treatment of hyperproliferative skin diseases, hyperparathyroidism, and osteoporosis. Vitamin D also exhibits other non-skeletal pleiotropic properties, such as immunomodulatory, antimicrobial, cardiovascular, and muscular effects. Therefore, vitamin D deficiency is associated with many diseases including tuberculosis, nonalcoholic fatty liver disease, cardiovascular disease, and metabolic syndrome 5-7. In the United States, adults aged 20-39 years are at the highest risk of vitamin D deficiency

The Effect of Vitamin D Supplementation on Clinical Outcomes for Critically Ill Patients: A Systemic Review and Meta-Analysis of Randomized Clinical Trials

“…To our knowledge, this is the most updated and comprehensive meta-analysis to evaluate the effect of vitamin D supplementation in critically ill patients. Our results are generally consistent with the latest meta-analysis by Lan et al ( 16 ), in which they analyzed nine RCTs with 1,867 patients. They indicated that vitamin D supplementation did not reduce the mortality, length of ICU and hospital stay, as well as duration of MV.…”

Vitamin therapy in sepsis

“… 94 – 96 However, a recent meta-analysis in adults showed no association with length of stay, duration of mechanical ventilation, or mortality. 97 In contrast, an RCT of 109 children with sepsis demonstrated that a single dose of vitamin D reduced inflammatory markers, reduced cardiovascular organ failure scores, and decreased progression to septic shock. 98 Factors such as variability in study design, small sample size, and heterogeneous populations have made it difficult to ascertain the effect of vitamin D supplementation on outcomes in critical illness and whether vitamin D deficiency is a modifiable risk factor (Table 4 ).…”

“… 98 Factors such as variability in study design, small sample size, and heterogeneous populations have made it difficult to ascertain the effect of vitamin D supplementation on outcomes in critical illness and whether vitamin D deficiency is a modifiable risk factor (Table 4 ). 89 , 97 , 99 …”

Vitamin D and acute and severe illness – a mechanistic and pharmacokinetic perspective

“…Jointly, meta-analyses of these trials showed no effect on length of hospital or ICU stay and/or requirement for mechanical ventilation (127)(128)(129)(130). No effect on mortality (total 28-day or split by mortality in hospital or ICU; mortality after 7, 28-30, 84 days and 6 months) was reported in 3 of the meta-analyses (128)(129)(130), while Putzu (127) reported a lower odds ratio (0.70 CI: 0.50-0.98) for total mortality (as recorded at the last day of data collection of an individual study) with vitamin D supplementation. The largest, recent multi-centre RCT (n= 1360) (123) was only included in the meta-analyses conducted by Lan (128).…”