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.
