Use of long-acting opioids is a key risk factor in the development of androgen deficiency. Dose was significantly associated with androgen deficiency, but more so for men on short-acting than on long-acting opioids.
Strategies are needed to identify at-risk patients for adverse events associated with prescription opioids. This study identified prescription opioid misuse in an integrated health system using electronic health record (EHR) data, and examined predictors of misuse and overdose. The sample included patients from an EHR-based registry of adults who used prescription opioids in 2011 in Kaiser Permanente Northern California, a large integrated health care system. We characterized time-at-risk for opioid misuse and overdose, and used Cox proportional hazard models to model predictors of these events from 2011 to 2014. Among 396,452 patients, 2.7% were identified with opioid misuse and 1044 had an overdose event. Older patients were less likely to meet misuse criteria or have an overdose. Whites were more likely to be identified with misuse, but not to have an overdose. Alcohol and drug disorders were related to higher risk of misuse and overdose, with the exception that marijuana disorder was not related to opioid misuse. Higher daily opioid dosages and benzodiazepine use increased the risk of both opioid misuse and overdose. We characterized several risk factors associated with misuse and overdose using EHR-based data, which can be leveraged relatively quickly to inform preventive strategies to address the opioid crisis.
Among a contemporary sample of men receiving chronic daily opioids, we found a high prevalence of hypogonadism associated with duration of action, but not with total daily dose of the opioid.
Objective. Androgen deficiency is common among men who use opioids daily for chronic pain. In previous studies, we found that long-acting opioids are associated with greater odds of androgen suppression than equipotent doses of short-acting opioids. Here we examined whether specific commonly prescribed opioids were associated with greater odds of androgen deficiency compared to hydrocodone. Design. Retrospective cohort study. Setting and Patients. Within a large, integrated health care delivery system, this study was comprised of men ages 18–80 on a stable regimen of a single opioid for chronic non-cancer pain. Methods. Morning serum total testosterone levels were measured in subjects prescribed one opioid for at least 90 days. The association between individual opioids and androgen deficiency was assessed with logistic regression, controlling for dose, obesity, age, hypertension, hyperlipidemia, and diabetes, using hydrocodone as a referent. Results. This study included 1,159 men. Men on fentanyl (odds ratio [OR] 25.7, 95% CI 2.82–234.97), methadone (OR 7.33, 95% CI 3.29–16.33), or oxycodone (OR 3.15, 95% CI 1.87–5.33) were more likely to be androgen deficient than men on hydrocodone. Increases in dose affected the odds of androgen deficiency differently for different opioids. Increased doses of hydrocodone (OR 1.18 per 10-mg increase in drug, 95% CI 1.09–1.28) and oxycodone (OR 1.01, 95% CI 1.00–1.02) were associated with increased odds of androgen deficiency. Conclusions. Our results suggest that certain opioids are associated with increased odds of androgen deficiency compared with hydrocodone. Transdermal fentanyl, methadone and oxycodone were associated with higher odds of androgen deficiency than hydrocodone.
Buprenorphine, a semisynthetic thebaine derivative, is a unique opioid, as it has activity at multiple receptors, including mu (partial agonist), kappa (antagonist), OLR-1 (agonist), and delta (antagonist). Because buprenorphine's pharmacology is relatively complex, misconceptions about its actions are common. Most other opioids act solely or predominately as full mu receptor agonists. Common practice at many institutions calls for the cessation of regular buprenorphine use 48-72 hours prior to surgery. This practice is based on three foundational theories that have come from scant data about the properties of buprenorphine: (1) that buprenorphine is only a partial mu agonist and therefore is not a potent analgesic; (2) because buprenorphine has a ceiling effect on respiratory depression, it also has a ceiling effect on analgesia; and (3) that buprenorphine acts as a "blockade" to the analgesic effects of other opiates when coadministered due to its strong binding affinity. However, several recent studies have called this practice into question. At our institution, we continue buprenorphine perioperatively, whenever possible, in order to provide superior pain control, discourage potentially problematic use and the more dangerous side effects of full mu agonist opiates, and avoid putting recovery at risk for those with opiate dependency issues. We present a unique case comparing two different outcomes for the same surgical course performed at two different times on the same chronic pain patient. These differences may be attributable to the variable of buprenorphine being present for one perioperative course and not the other. Pain control was easier to achieve, and functional recovery was greater when buprenorphine was maintained throughout the perioperative period when compared with using a full mu agonist opioid for chronic pain preoperatively. This is an outcome that much of the literature heretofore suggests would be unlikely. We review some aspects of buprenorphine's unique pharmacology that may explain why remaining on buprenorphine perioperatively may be preferable, which contradicts many practice guidelines.
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