The association of serum vitamin D concentration with serious complications after noncardiac surgery. (Vats)

Turan A, Hesler BD, You J, Saager L, Grady M, Komatsu R, Kurz A, Sessler DI. The association of serum vitamin D concentration with serious complications after noncardiac surgery. Anesth Analg. 2014 Sep;119(3):603-12.

Full-text for Children’s and Emory users.

BACKGROUND: Vitamin D deficiency is a global health problem. Epidemiological studies demonstrate that vitamin D is both cardioprotective and neuroprotective. Vitamin D also plays a substantial role in innate and acquired immunity. Our goal was to evaluate the association of serum vitamin D concentration on serious postoperative complications and death in noncardiac surgical patients.

METHODS: We retrospectively analyzed the data of 3509 patients who had noncardiac surgery at the Cleveland Clinic Main Campus and had a serum vitamin D measurement. The relationship between serum vitamin D concentration and all-cause in-hospital mortality, in-hospital cardiovascular morbidity, and serious in-hospital infections was assessed as a common effect odds ratio (OR) by using a multivariate generalized estimating equation model with adjustment for demographic, medical history variables, and type and duration of surgery.

RESULTS: Higher vitamin D concentrations were associated with decreased odds of in-hospital mortality/morbidity (P = 0.003). There was a linear reduction of the corresponding common effect odds ratio (OR 0.93, 95% confidence interval, 0.88-0.97) for severe in-hospital outcomes for each 5 ng/mL increase in vitamin D concentration over the range from 4 to 44 ng/mL. In addition, we found that the odds versus patients with vitamin D <13 ng/mL (i.e., 1st quintile) were significantly lower in patients with vitamin D 13-20, 20-27, 27-36, and > 36 ng/mL (i.e., 2nd-5th quintiles); the corresponding estimated ORs were 0.65 (99% confidence interval, 0.43-0.98), 0.53 (0.35-0.80), 0.44 (0.28-0.70), and 0.49 (0.31-0.78), respectively. However, there was no statistically significant difference among individual quintiles >13 ng/mL.

CONCLUSIONS: Vitamin D concentrations were associated with a composite of in-hospital death, serious infections, and serious cardiovascular events in patients recovering from noncardiac surgery. While causality cannot be determined from our retrospective analysis, the association suggests that a large randomized trial of preoperative vitamin D supplementation and postoperative outcomes is warranted.

Randomized controlled trial of calcitriol in severe sepsis. (Fortenberry)

Leaf DE, Raed A, Donnino MW, Ginde AA, Waikar SS. Randomized controlled trial of calcitriol in severe sepsis. Am J Respir Crit Care Med. 2014 Sep 1;190(5):533-41.

Full-text for Children’s and Emory users.

RATIONALE: Vitamin D and its metabolites have potent immunomodulatory effects in vitro, including up-regulation of cathelicidin, a critical antimicrobial protein.

OBJECTIVES: We investigated whether administration of 1,25-dihydroxyvitamin D (calcitriol) to critically ill patients with sepsis would have beneficial effects on markers of innate immunity, inflammation, and kidney injury.

METHODS: We performed a double-blind, randomized, placebo-controlled, physiologic study among 67 critically ill patients with severe sepsis or septic shock. Patients were randomized to receive a single dose of calcitriol (2 μg intravenously) versus placebo. The primary outcome was plasma cathelicidin protein levels assessed 24 hours after study drug administration. Secondary outcomes included leukocyte cathelicidin mRNA expression, plasma cytokine levels (IL-10, IL-6, tumor necrosis factor-α, IL-1β, and IL-2), and urinary kidney injury markers.

MEASUREMENTS AND MAIN RESULTS: Patients randomized to calcitriol (n = 36) versus placebo (n = 31) had similar plasma cathelicidin protein levels at 24 hours (P = 0.16). Calcitriol-treated patients had higher cathelicidin (P = 0.04) and IL-10 (P = 0.03) mRNA expression than placebo-treated patients 24 hours after study drug administration. Plasma cytokine levels (IL-10, IL-6, tumor necrosis factor-α, IL-1β, and IL-2) and urinary kidney injury markers were similar in calcitriol- versus placebo-treated patients (P > 0.05 for all comparisons). Calcitriol had no effect on clinical outcomes nor were any adverse effects observed.

CONCLUSIONS: Calcitriol administration did not increase plasma cathelicidin protein levels in critically ill patients with sepsis and had mixed effects on other immunomodulatory markers. Additional phase II trials investigating the dose and timing of calcitriol as a therapeutic agent in specific sepsis phenotypes may be warranted. Clinical trial registered with (NCT 01689441).