Buprenorphine as a Post-operative Analgesic in Opioid-Naive Patients After Ankle Fracture Surgery

Addictive full-agonist opioids, like oxycodone, remain a staple of post-operative analgesia after many types of surgery. However, perioperative exposure to opioid analgesics risks addiction in up to 7% of cases. Moreover, opioid overdoses kill over 80,000 in the United States (US) annually. Buprenorphine, a partial-agonist of the μ-opioid receptor and an antagonist of the κ-opioid receptor, may be able to safely function as a post-operative analgesic, reducing our reliance on full-agonist opioids post-operatively. Compared to full-agonist opioids, buprenorphine has a favorable safety profile. It has been hypothesized that buprenorphine's unique pharmacodynamics give it a lower addictive potential compared to full-agonist opioids. Moreover, it endows a ceiling on respiratory depression, has reduced dysphoric and psychotomimetic effects, and does not result in immunosuppression at therapeutic analgesic doses. International studies have suggested that transdermal buprenorphine is noninferior to tramadol, transdermal fentanyl, and oral celecoxib in the management of acute post-operative pain in opioid-naïve patients following orthopaedic surgery. However, the efficacy of buprenorphine for postoperative analgesia has never been studied in the United States, whose population has different beliefs and expectations surrounding pain control when compared to international populations. The major goal of this project is to determine the safety and efficacy of transdermal buprenorphine for postoperative analgesia, as a first step toward exploring the ability of buprenorphine to mitigate the incidence of opioid dependence in the postoperative setting.

This study will assess whether buprenorphine can reduce the use of full-agonist opioids following ankle fracture surgery. Approximately one in five opioid-naïve patients undergoing ankle fracture surgery continue to use opioids 3 to 6 months out from surgery, suggesting that this population is relatively susceptible to developing post-operative opioid dependence. The investigators will divide patients into two groups. One group will be treated with a 7-day transdermal buprenorphine patch. The other will be treated with a placebo patch. Both groups will otherwise receive a post-operative pain management regimen that is in accordance with the standard of care. The investigators hypothesize that participants treated with the buprenorphine patch will experience improved analgesia with the use fewer full-agonist opioids following ankle fracture surgery than those treated with the placebo patch. This hypothesis will be tested with the following aims.

Specific Aim 1: To measure the analgesic effect of buprenorphine on post-operative analgesia. In this Aim, the investigators will test the hypothesis that use of buprenorphine patches will reduce the average pain scores and consumption of full-agonist opioids after ankle fracture surgery. In sub-Aim 1.1, the investigators will quantify postoperative pain by monitoring participants' visual analog scale pain scores and full-agonist opioid consumption over the first post-operative week. In sub-Aim 1.2, the investigators will track the number of episodes of breakthrough pain in the hospital, the number of calls to the clinic with a chief complaint of uncontrolled pain, and the number of presentations to an emergency department for uncontrolled surgery-related pain.

Specific Aim 2: To examine the safety of buprenorphine as a post-operative analgesic following ankle fracture surgery. In this Aim, the investigators will test the hypothesis that participants treated with buprenorphine patches will experience fewer adverse events related to opioid exposure compared to those treated with placebo patches. The investigators will monitor for adverse effects of buprenorphine and full-agonist opioids, including respiratory depression, constipation, nausea, and vomiting. The investigators will track the number of presentations to an emergency department with a diagnosis of opioid toxicity. For pilot data, the investigators will also monitor use of opioids for analgesia at the 3-month postoperative time point as a secondary outcome.

This study assesses whether buprenorphine safely reduces full-agonist opioid use after orthopaedic surgery. Completion of the Aims of this study will permit future studies assessing whether buprenorphine comprises a less-addictive alternative for postoperative analgesia compared to full-agonist opioids. Annually, there are 40-50 million major surgeries performed in the US. As 6-7% of opioid-naïve patients develop long-term opioid use after major surgery, exploring avenues to decrease the impact of post-operative analgesia on the opioid epidemic is critical.

Inclusion criteria

• Patient is 18 years of age or older
• Patient is undergoing single stage ORIF of an ankle fracture
• Patient is English-speaking

Exclusion criteria

• Patient is under 18 years of age
• Patient's ankle fracture is treated with external fixation
• Patient has a concomitant osseous or visceral injury
• Patient has a history of opioid use disorder or a current diagnosis of opioid use disorder
• Patient has a history of alcohol use disorder or a current diagnosis of alcohol use disorder
• Patient was taking opioid medication or narcotic drugs prior to their injury
• Patient has a current active malignancy
• Patient is taking a medication that carries a prohibitively high risk of drug-drug interaction with buprenorphine, hydrocodone, or oxycodone in the view of their treating physician or nurse anesthetist
• Patient has an anaphylactic allergy to buprenorphine, hydrocodone, or oxycodone
• Patient is not English-speaking
• Patient is pregnant
• Patient is unable to complete pain diary or communicate pain scores
• Patient is incarcerated
• Patient has a Gustilo-Anderson Type III open fracture