Vitamin D levels in patients admitted to the intensive care unit and the association with organ dysfunction and glutamine levels

Abstract

The prohormone vitamin D is best known for its key role in the metabolism of calcium and phosphate. [1] In critically ill patients, the potential to influence outcome through its pleiotropic effects on bone, muscle, cardiac and immunological function (where it is stimulatory to the innate but immunomodulatory to the adaptive immune system) has created interest in the use of vitamin D in the intensive care unit (ICU) among intensivists. [2,3] Vitamin D deficiency is highly prevalent in ICU patients, with a prevalence of 50-82%, and is associated with increased inflammatory markers, multi-organ dysfunction, immune dysregulation and poorer outcomes. [1,2,4-7] Elevated inflammatory markers, particularly C-reactive protein (CRP) and procalcitonin (PCT), occur with vitamin D deficiency. [8] A Brazilian cohort of critically ill patients with 25-hydroxyvitamin D (25(OH)D) levels <12 ng/mL had increased organ system dysfunction and a greater change in sequential organ failure assessment (SOFA) score. [9,10] Furthermore, observational studies have shown an independent association between vitamin D deficiency and mortality. [9,10] In meta-analyses examining vitamin D deficiency among critically ill patients, increased rates of infection, sepsis and mortality have been noted. [5,7] Randomised controlled trials (RCTs) that have investigated vita min D supplementation in deficient critically ill patients have shown little benefit. The VITdAL-ICU (Effect of High-Dose Vitamin D 3 on Hospital Length of Stay in Critically Ill Patients with Vitamin D Deficiency) RCT that assessed outcomes of critically ill vita min D-deficient patients following vitamin D supplementation did not demonstrate improvement in length of hospital stay, hospital mortality or 6-month mortality, except in severely vitamin D-deficient patients (25(OH)D <12 ng/mL), where mortality was reduced (hazard ratio (HR) 0.56 (95% confidence interval (CI) 0.35-0.90)). [11] Moreover, in patients supplemented with vitamin D, median inflammatory marker levels were reduced on day 28 compared with placebo (CRP 51 v. 32 mg/L (p=0.04); PCT 0.2 v. 0.1 ng/mL (p=0.05)). [11] In contrast, no improved 90-day mortality outcome was noted in the recent VIOLET (Early High-Dose Vitamin D 3 for Critically Ill, Vitamin D-Deficient Patients) double-blind, placebo-controlled RCT of early vitamin D 3 supplementation with a single enteral dose of 540 000 IU vitamin D 3 compared with placebo in vitamin D-deficient (25(OH)D <20 ng/mL) critically ill patients. [12] Recent data have illustrated that vitamin D deficiency (25(OH)D <15 ng/mL) during early critical illness is crucial in the regulation of glutathione and glutamate pathways. Both pathways influence glutamine metabolism and ultimately serum glutamine levels. [13] There is no consensus with regard to the data examining glutamine supplementation in critically ill patients. Some studies have shown reduced infection rates, ICU and hospital stay, and mortality This open-access article is distributed under Creative Commons licence CC-BY-NC 4...