Perioperative Serum 25-Hydroxyvitamin D Levels as a Predictor of Postoperative Opioid Use and Opioid Use Disorder: a Cohort Study.
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ABSTRACT: Importance
Vitamin D deficiency is associated with chronic pain syndromes and higher opioid use among cancer patients, but its association with opioid use among opioid-naïve subjects following a major surgical procedure with acute pain has not been explored.Objective
To determine the association between serum 25-hydroxyvitamin D (25(OH)D) levels, opioid use, and opioid use disorder.Methods
We identified commercially insured subjects aged 18-64 years with available perioperative serum 25-hydroxyvitamin D (25D) levels who underwent one of nine major surgical procedures in 2000-2014. Primary outcomes were dose and duration of opioid use measured using pharmacy claims. Secondary outcome was opioid use disorder captured using diagnosis codes. Multivariable negative binomial models with generalized estimating equations were performed examining the association between 25D levels and postoperative opioid use measures, adjusting for age, sex, race/ethnicity, Charlson score, education, income, latitude, and season of blood draw. Adjusted Cox regression was used to examine the association with opioid use disorder.Results
Among 5446 subjects, serum 25(OH)D was sufficient (≥ 20 ng/mL) among 4349 (79.9%) subjects, whereas 837 (15.4%) had insufficient (12 to < 20 ng/mL) and 260 (4.8%) had deficient (< 12 ng/mL) levels. On multivariable analysis, as compared with subjects with sufficient 25(OH)D levels, subjects with deficient 25(OH)D levels had 1.7 more days (95% CI 0.76, 2.58) of opioid use per year and had 98.7 higher morphine milligram equivalent dose (95% CI 55.7, 141.8) per year. Among 11,713 study cohort, subjects with deficient 25(OH)D levels were more likely to be diagnosed with opioid use disorders (HR 2.41; 95% CI 1.05, 5.52).Conclusion
Patients undergoing common surgical procedures with deficient 25D levels are more likely to have higher opioid use and an increased risk of opioid use disorder compared to those with sufficient levels. Serum 25D levels may serve as a biomarker to identify subjects at increased risk of opioid misuse.
SUBMITTER: Kim Y
PROVIDER: S-EPMC7459073 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Normal vitamin D homeostasis is critical for optimal health; nevertheless, vitamin D deficiency is a worldwide public health problem. Vitamin D insufficiency is most commonly due to inadequate cutaneous synthesis of cholecalciferol and/or insufficient intake of vitamin D, but can also arise as a consequence of pathological states such as obesity. Serum concentrations of 25(OH)D (calcidiol) are low in obesity, and fail to increase appropriately after vitamin D supplementation. Although sequestration of vitamin D in adipose tissues or dilution of ingested or cutaneously synthesized vitamin D in the large fat mass of obese patients has been proposed to explain these findings, here we investigate the alternative mechanism that reduced capacity to convert parent vitamin D to 25(OH)D due to decreased expression of CYP2R1, the principal hepatic vitamin D 25-hydroxylase. To test this hypothesis, we isolated livers from female mice of 6 to 24 weeks of age, weaned onto either a normal chow diet or a high-fat diet, and determined the abundance of Cyp2r1 mRNA using digital droplet-quantitative PCR. We observed a significant (p < 0.001) decrease in Cyp2r1 mRNA in the liver of high-fat diet-fed mice relative to lean-chow-fed female mice. Moreover, there was a significant (p < 0.01) relationship between levels of Cyp2r1 mRNA and serum 25(OH)D concentrations as well as between Cyp2R1 mRNA and the ratio of circulating 25(OH)D3 to cholecalciferol (p < 0.0001). Using linear regression we determined a curve with 25(OH)D3/cholecalciferol versus normalized Cyp2R1 mRNA abundance with an R2 value of 0.85. Finally, we performed ex vivo activity assays of isolated livers and found that obese mice generated significantly less 25(OH)D3 than lean mice (p < 0.05). Our findings indicate that expression of CYP2R1 is reduced in obesity and accounts in part for the decreased circulating 25(OH)D. © 2019 American Society for Bone and Mineral Research.
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