Demographics and Baseline Medical Conditions for 3509 Noncardiac Surgical Patients by Quintiles of Serum Vitamin

September 2014 • Volume 119 • Number 3 www.anesthesia-analgesia.org 603 Copyright © 2014 International Anesthesia Research Society DOI: 10.1213/ANE.0000000000000096 Vitamin D (25-hydroxyvitamin D) deficiency (<25 nmol/L or <10 ng/mL) or insufficiency (25–75 nmol/L or 10–30 ng/mL)1 affects >1 billion people worldwide, spanning age groups, ethnicities, and gender.2 In the United States, more than one-third of adults,3,4 more than half of all hospitalized patients,5 and >95% of critically ill patients have a vitamin D deficiency.6 The multifaceted implications of vitamin D deficiency have long been recognized. For example, in a discussion on rickets at the Annual Meeting of the British Medical Association in 1888, WB Cheadle stated, “...the first point upon which I would venture to insist is that rickets is not to be regarded as a mere affection of the bones .... but it is something far more than this; the disease affects not only bones but muscles and ligaments, mucous membrane and skin, the blood and the nervous system.”7 There is now better understanding of the ways vitamin D contributes to vital processes aside from its “traditional” role in skeletal maintenance. Vitamin D receptors are found in most of the immune system cells, including macrophages, B and T lymphocytes, and neutrophils.8 Vitamin D also regulates antimicrobial peptide gene expression, thus improving innate immunity.6,9,10 As might therefore be expected, vitamin D deficiency is associated with infections, particularly respiratory infections.9,11,12 Low vitamin D concentrations are also associated with inflammation, especially in patients with cardiac disease.13 Inflammation increases the risk of cardiovascular disease and accompanies about 80% of all sudden cardiac deaths.14,15 It is thus not surprising that multiple investigations support a link between vitamin D deficiency and cardiovascular risk.16–18 The summative effects of vitamin D were evaluated in a prospective cohort from the Third National Health and Nutrition Examination Survey (NHANES III), a program designed to assess the health and nutritional status in the United States by combining interviews and physical examinations. NHANES III demonstrated an association between vitamin D deficiency and all-cause mortality.4,19 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. (Anesth Analg 2014;119:603–12) The Association of Serum Vitamin D Concentration with Serious Complications After Noncardiac Surgery