Scenario

You’re working in the ICU when the attending approaches you with a familiar question:

“We just admitted a patient with severe acute pain, but they’re taking buprenorphine for opioid use disorder. Should we stop the buprenorphine so we can treat their pain? Doesn’t buprenorphine block all the opioid receptors anyway?”

Discussion

For years, many clinicians have believed that buprenorphine needed to be discontinued whenever a patient had acute pain. This concern is valid due to the complex nature of buprenorphine being a high-affinity partial mu-agonist molecule that binds tightly to the receptor. If the receptors are occupied, clinicians might ask, how can additional full mu-agonist opioids provide analgesia?

Our understanding of buprenorphine’s multi-mechanistic pharmacology has evolved over the years, with multiple publications, consensus guidelines, and expert opinions discussing how to effectively manage acute pain in this scenario.1,2,3

Greenwald et al conducted a landmark study diving into the mu-opioid receptor availability following daily sublingual buprenorphine maintenance doses in heroin-dependent volunteers.4 Table I maps out the maintenance dose and the corresponding percentage of mu-opioid receptors that are available for binding.

Table I: Mu-Opioid Receptor Maintenance Dose and Binding.
Daily Dose Percent (%) of mu-opioid receptor availability
1 mg 71–85%
2 mg 27–53%
4 mg 36–55%
8 mg 20–35%
12 mg 13–24%
16 mg 9–20%
24 mg 4–15%
32 mg 2–12%
Table adapted from Greenwald et al.

As the Greenwald study shows, even though mechanistically buprenorphine has high binding affinity to the receptor, utilizing PET imaging with the mu-opioid receptor-selective radiotracer [¹¹C] carfentanil, a significant percentage of receptors are available depending on the dose. Buprenorphine can therefore be continued during episodes of acute pain, and as some protocols discuss, the maintenance dose can be divided to utilize the drug’s analgesic duration frequency (eg, 6 to 8 hours) vs withdrawal suppression (eg, 24 hours).3

When managing acute pain in a patient receiving buprenorphine for opioid use disorder (OUD), it’s important to utilize a multimodal approach with the use of various agents, including non-opioids, regional anesthesia, and nonpharmacologic interventions when needed.

Stopping buprenorphine in these clinical scenarios can place the patient at increased risk for opioid withdrawal, worsening pain, difficulty re-initiating treatment, and potentially relapsing to nonmedical opioid use.

Vadeghani et al conducted a systematic review examining perioperative pain management in patients with OUD on buprenorphine. The researchers found that patients whose buprenorphine was interrupted had greater risks for withdrawal, relapse, illicit opioid use, and worsening pain.5

Approach

So, the next time a clinician asks, “Should we stop the buprenorphine so we can treat this patient’s pain?” the answer should be no. Despite its high affinity for the mu-opioid receptor, buprenorphine does not prevent effective acute pain management when evidence-based strategies are utilized. Continuing buprenorphine, utilizing multimodal analgesia, dividing the dose, and adding a full agonist opioid when appropriate allows clinicians to address both pain and OUD.

Our goal is not simply to control pain, but rather to deliver comprehensive care that supports recovery while ensuring that patients receive adequate analgesia during some of their most vulnerable moments.

Sources 

Kohan L, Potru S, Barreveld AM*,* et al. Buprenorphine management in the perioperative period: educational review and recommendations from a multisociety expert panel. Reg Anesth Pain Med. 2021;46(10):840-859. doi: 10.1136/rapm-2021-103007.

  1. Buresh M, Ratner J, Zgierska A, Gordin V, Alvanzo A. Treating perioperative and acute pain in patients on buprenorphine: narrative literature review and practice recommendations. J Gen Intern Med. 2020 Dec;35(12):3635-3643. doi: 10.1007/s11606-020-06115-3.
  2. Sandhu S, Calcaterra SL. How do I manage acute pain for patients prescribed buprenorphine for opioid use disorder? NEJM Evid. 2024 May;3(5):EVIDccon2300275. doi: 10.1056/EVIDccon2300275.
  3. Greenwald MK, Johanson CE, Moody DE, et al. Effects of buprenorphine maintenance dose on mu-opioid receptor availability, plasma concentrations, and antagonist blockade in heroin-dependent volunteers. Neuropsychopharmacology. 2003 Nov;28(11):2000-2009. doi: 10.1038/sj.npp.1300251.
  4. Vadeghani AT, Grant M, Forget P. Perioperative pain management interventions in opioid user patients: an overview of reviews. BMC Anesthesiol. 2024 Sep 5;24(1):310. doi: 10.1186/s12871-024-02703-6.