Perioperative opioid prescribing and iatrogenic opioid use disorder and overdose: a state-of-the-art narrative review.

BACKGROUND/IMPORTANCE: Considerable attention has been paid to identifying and mitigating perioperative opioid-related harms. However, rates of postsurgical opioid use disorder (OUD) and overdose, along with associated risk factors, have not been clearly defined. OBJECTIVE: Evaluate the evidence connecting perioperative opioid prescribing with postoperative OUD and overdose, compare these data with evidence from the addiction literature, discuss the clinical impact of these conditions, and make recommendations for further study. EVIDENCE REVIEW: State-of-the-art narrative review. FINDINGS: Nearly all evidence is from large retrospective studies of insurance claims and Veterans Health Administration (VHA) data. Incidence rates of new OUD within the first year after surgery ranged from 0.1% to 0.8%, while rates of overdose events ranged from 0.01% to 0.8%. Higher rates were seen among VHA patients, which may reflect differences in data completeness and/or risk factors. Identified risk factors included those related to substance use (preoperative opioid use; non-opioid substance use disorders; preoperative sedative, anxiolytic, antidepressant, and gabapentinoid use; and postoperative new persistent opioid use (NPOU)); demographic attributes (chiefly male sex, younger age, white race, and Medicaid or no insurance coverage); psychiatric comorbidities such as depression, bipolar disorder, and PTSD; and certain medical and surgical factors. Several challenges related to the use of administrative claims data were identified; there is a need for more granular retrospective studies and, ideally, prospective cohorts to assess postoperative OUD and overdose incidence with greater accuracy. CONCLUSIONS: Retrospective data suggest an incidence of new postoperative OUD and overdose of up to 0.8% during the first year after surgery, but prospective studies are lacking.

Genetic predisposition may not improve prediction of cardiac surgery-associated acute kidney injury.

Background: The recent integration of genomic data with electronic health records has enabled large scale genomic studies on a variety of perioperative complications, yet genome-wide association studies on acute kidney injury have been limited in size or confounded by composite outcomes. Genome-wide association studies can be leveraged to create a polygenic risk score which can then be integrated with traditional clinical risk factors to better predict postoperative complications, like acute kidney injury. Methods: Using integrated genetic data from two academic biorepositories, we conduct a genome-wide association study on cardiac surgery-associated acute kidney injury. Next, we develop a polygenic risk score and test the predictive utility within regressions controlling for age, gender, principal components, preoperative serum creatinine, and a range of patient, clinical, and procedural risk factors. Finally, we estimate additive variant heritability using genetic mixed models. Results: Among 1,014 qualifying procedures at Vanderbilt University Medical Center and 478 at Michigan Medicine, 348 (34.3%) and 121 (25.3%) developed AKI, respectively. No variants exceeded genome-wide significance (p < 5 × 10-8) threshold, however, six previously unreported variants exceeded the suggestive threshold (p < 1 × 10-6). Notable variants detected include: 1) rs74637005, located in the exonic region of NFU1 and 2) rs17438465, located between EVX1 and HIBADH. We failed to replicate variants from prior unbiased studies of post-surgical acute kidney injury. Polygenic risk was not significantly associated with post-surgical acute kidney injury in any of the models, however, case duration (aOR = 1.002, 95% CI 1.000-1.003, p = 0.013), diabetes mellitus (aOR = 2.025, 95% CI 1.320-3.103, p = 0.001), and valvular disease (aOR = 0.558, 95% CI 0.372-0.835, p = 0.005) were significant in the full model. Conclusion: Polygenic risk score was not significantly associated with cardiac surgery-associated acute kidney injury and acute kidney injury may have a low heritability in this population. These results suggest that susceptibility is only minimally influenced by baseline genetic predisposition and that clinical risk factors, some of which are modifiable, may play a more influential role in predicting this complication. The overall impact of genetics in overall risk for cardiac surgery-associated acute kidney injury may be small compared to clinical risk factors.

Limited clinical utility for GWAS or polygenic risk score for postoperative acute kidney injury in non-cardiac surgery in European-ancestry patients.

BACKGROUND: Prior studies support a genetic basis for postoperative acute kidney injury (AKI). We conducted a genome-wide association study (GWAS), assessed the clinical utility of a polygenic risk score (PRS), and estimated the heritable component of AKI in patients who underwent noncardiac surgery. METHODS: We performed a retrospective large-scale genome-wide association study followed by a meta-analysis of patients who underwent noncardiac surgery at the Vanderbilt University Medical Center ("Vanderbilt" cohort) or Michigan Medicine, the academic medical center of the University of Michigan ("Michigan" cohort). In the Vanderbilt cohort, the relationship between polygenic risk score for estimated glomerular filtration rate and postoperative AKI was also tested to explore the predictive power of aggregating multiple common genetic variants associated with AKI risk. Similarly, in the Vanderbilt cohort genome-wide complex trait analysis was used to estimate the heritable component of AKI due to common genetic variants. RESULTS: The study population included 8248 adults in the Vanderbilt cohort (mean [SD] 58.05 [15.23] years, 50.2% men) and 5998 adults in Michigan cohort (56.24 [14.76] years, 49% men). Incident postoperative AKI events occurred in 959 patients (11.6%) and in 277 patients (4.6%), respectively. No loci met genome-wide significance in the GWAS and meta-analysis. PRS for estimated glomerular filtration rate explained a very small percentage of variance in rates of postoperative AKI and was not significantly associated with AKI (odds ratio 1.050 per 1 SD increase in polygenic risk score [95% CI, 0.971-1.134]). The estimated heritability among common variants for AKI was 4.5% (SE = 4.5%) suggesting low heritability. CONCLUSION: The findings of this study indicate that common genetic variation minimally contributes to postoperative AKI after noncardiac surgery, and likely has little clinical utility for identifying high-risk patients.

Patient Factors Associated With Opioid Consumption in the Month Following Major Surgery.

OBJECTIVE: The aim of this study was to determine preoperative patient characteristics associated with postoperative outpatient opioid use and assess the frequency of postoperative opioid overprescribing. SUMMARY BACKGROUND DATA: Although characteristics associated with inpatient opioid use have been described, data regarding patient factors associated with opioid use after discharge are lacking. This hampers the development of individualized approaches to postoperative prescribing. METHODS: We included opioid-naïve patients undergoing hysterectomy, thoracic surgery, and total knee and hip arthroplasty in a single-center prospective observational cohort study. Preoperative phenotyping included self-report measures to assess pain severity, fibromyalgia survey criteria score, pain catastrophizing, depression, anxiety, functional status, fatigue, and sleep disturbance. Our primary outcome measure was self-reported total opioid use in oral morphine equivalents. We constructed multivariable linear-regression models predicting opioids consumed in the first month following surgery. RESULTS: We enrolled 1181 patients; 1001 had complete primary outcome data and 913 had complete phenotype data. Younger age, non-white race, lack of a college degree, higher anxiety, greater sleep disturbance, heavy alcohol use, current tobacco use, and larger initial opioid prescription size were significantly associated with increased opioid consumption. Median total oral morphine equivalents prescribed was 600 mg (equivalent to one hundred twenty 5-mg hydrocodone pills), whereas median opioid consumption was 188 mg (38 pills). CONCLUSIONS: In this prospective cohort of opioid-naïve patients undergoing major surgery, we found a number of characteristics associated with greater opioid use in the first month after surgery. Future studies should address the use of non-opioid medications and behavioral therapies in the perioperative period for these higher risk patients.

Patterns of Initial Opioid Prescribing to Opioid-Naive Patients.

OBJECTIVE: To determine the proportion of initial opioid prescriptions for opioid-naive patients prescribed by surgeons, dentists, and emergency physicians. We hypothesized that the percentage of such prescriptions grew as scrutiny of primary care and pain medicine opioid prescribing increased and guidelines were developed. SUMMARY OF BACKGROUND DATA: Data regarding the types of care for which opioid-naive patients are provided initial opioid prescriptions are limited. METHODS: A retrospective cross-sectional study using a nationwide insurance claims dataset to study US adults aged 18 to 64 years. Our primary outcome was a change in opioid prescription share for opioid-naive patients undergoing surgical, emergency, and dental care from 2010 to 2016; we also examined the type and amounts of opioid filled. RESULTS: From 87,941,718 analyzed lives, we identified 16,292,018 opioid prescriptions filled by opioid-naive patients. The proportion of prescriptions for patients receiving surgery, emergency, and dental care increased by 15.8% from 2010 to 2016 (P < 0.001), with the greatest increases related to surgical (18.1%) and dental (67.8%) prescribing. In 2016, surgery patients filled 22.0% of initial prescriptions, emergency medicine patients 13.0%, and dental patients 4.2%. Surgical patients' mean total oral morphine equivalents per prescription increased from 240 mg (SD 509) in 2010 to 403 mg (SD 1369) in 2016 (P < 0.001). Over the study period, surgical patients received the highest proportion of potent opioids (90.2% received hydrocodone or oxycodone). CONCLUSIONS: Initial opioid prescribing attributable to surgical and dental care is increasing relative to primary and chronic pain care. Evidence-based guideline development for surgical and dental prescribing is warranted in order to curb iatrogenic opioid morbidity and mortality.

The gender authorship gap in gynecologic oncology research.

Female first authorship and senior authorship in academic obstetrics and gynecology has increased over time but gender-specific publishing data are lacking within gynecologic oncology. We examined contribution by gender to the subspecialty's flagship journal, Gynecologic Oncology, over five decades, from 1972 to 2014, to identify trends in gender representation. Chi-square tests were used to compare gender distributions within and between the first and last years studied (1972-73 and 2014) as well as linear regression to model trends over time. Female first and senior authorship increased significantly from 1972 to 2014 (first: χ2 = 20.9, p < .01; senior: χ2 = 9.9, p < .01). The number of female first authors increased markedly after 2000. Male senior authors still outnumber female senior authors. Papers with senior female authors were more likely to have female first authors, suggesting a mentorship role. Subspecialty-wide gender equity initiatives should encourage continued mentorship of women by female colleagues.

Medial branch radiofrequency ablation outcomes in patients with centralized pain.

BACKGROUND AND OBJECTIVES: We hypothesized that patients with characteristics of centralized pain (fibromyalgia (FM)-like phenotype) would be less likely to respond to radiofrequency ablation (RFA), which may explain some of the failures of this peripherally directed therapy. METHODS: We conducted a prospective, observational study of patients undergoing RFA using a number of validated self-report measures of pain, mood and function. The 2011 Fibromyalgia Survey Criteria were used to assess for symptoms of centralized pain and was the primary predictor of interest. We constructed multivariable linear regression models to evaluate covariates independently associated with change in pain 3 months after RFA. RESULTS: 141 patients scheduled for medial branch blocks were enrolled in the study; 55 underwent RFA (51 with complete 3 months' follow-up). Patients with higher FM scores had less improvement in overall body pain; however, this was not statistically significant (adjusted mean change in pain FM+0.41, FM-1.11, p=0.396). In a secondary analysis, the FM score was not associated with change in back pain (p=0.720), with both groups improving equally. This cohort also reported significant improvement in anxiety, physical function, catastrophizing, and sleep disturbance at 3 months after RFA. CONCLUSIONS: Although patients with high baseline centralized pain exhibited less improvement in overall pain, this trend was not statistically significant, possibly due to insufficient power. The same trend was not seen with change in spine pain with both groups improving equally. Centralized pain patients may have less improvement in overall pain but may have equal improvement in their site-specific pain levels after localized interventions.