Opioid Prescribing and Monitoring - (Second Edition)
Primary Care Models for Pain Management

Buprenorphine and Surgery: What’s the Protocol?

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Surgery presents a plethora of inherent risks for patients receiving long-term opioid therapy. Patients may require higher-than-usual postoperative opioid doses for acute pain due to an underlying physical tolerance, and may transition to another opioid shortly after a major surgical procedure requiring conscious sedation with sedative hypnotics and/or general anesthesia. Converting to or adding another opioid is generally manageable in the majority of cases. Many opioids are easily titratable, and conversion, although sometimes tedious, is achievable with careful monitoring.

Because of their pharmacological and pharmacokinetic characteristics, however, unique opioids such as tapentadol, tramadol, levorphanol, methadone, and buprenorphine require special consideration when preparing for either elective or same-day emergency surgery. This chapter introduces buprenorphine’s unique characteristics and elucidates important considerations that are paramount to appropriately and safely managing pain in each of these surgical situations.

FDA-Approved Indications for Buprenorphine

Buprenorphine is US Food and Drug Administration (FDA) approved in various dosage formulations for treating opioid abuse disorder, acute pain (injectable), and chronic pain severe enough to require daily around-the-clock dosing (transdermal and buccal film). Formulations that are approved specifically for opioid abuse disorder but lack the FDA indication for analgesia are available as single entity buprenorphine (Subutex) and also co-formulated with naloxone; the combination products, available generically or as brand-name products, are summarized in Table 1, page 74.1 Single entity buprenorphine products specifically indicated for pain appear in Table 2, page 74.

Table 1: Available Dosages of Buprenorphine/Naloxone Combination Products

Pharmacological and Pharmacokinetic Characteristics of Buprenorphine

Buprenorphine is a dehydroxylated phenanthrene and is chemically similar to other opioids such as hydrocodone, oxycodone, levorphanol, hydromorphone, oxymorphone, and others.2 Unlike its chemical cousins, however, buprenorphine is a partial agonist at the m-opioid receptor (MOR) and an antagonist at k receptors.3 As a partial agonist, buprenorphine is able to activate MORs; at low to moderate doses, it can achieve the same or superior analgesia compared to a full m opioid agonist.3 However, because it’s a partial agonist, it exhibits a plateaued dose-response curve. As the dose of buprenorphine increases, the response increases to a certain point before plateauing. This is also known as buprenorphine’s ceiling effect, since doses beyond this ceiling will not yield increased analgesia or euphoria.3 A similar plateauing occurs in the retention of carbon dioxide (CO2) concentrations. In the absence of concomitant sedative-hypnotics, CO2 accumulation remains constant as the buprenorphine dose escalates, theoretically lowering the risk of overdose.4,5

Although buprenorphine has a lower intrinsic activity than full opioid agonists at higher doses, it has the highest affinity of any opioid toward the MOR.6 Due to this incredibly strong binding of the MOR, buprenorphine can actually displace full opioid agonists, such as morphine and methadone, from the receptor. Buprenorphine, however, will not be easily displaced by those same opioids.3,7,8 Compared to many other opioids, it also has an extremely slow dissociation rate, which is a measure of disengagement from the target receptor.3 Buprenorphine’s dissociation rate of about 166 minutes, along with its half-life of approximately 25 to 45 hours and high lipophilicity, causes it to be eliminated from the body relatively slowly over a 2- to 3-day period.3

Dilemmas for the Surgical Patient Receiving Buprenorphine

These pharmacological and pharmacokinetic characteristics could be problematic for surgical patients who are chronically using buprenorphine. A new full opioid agonist given postoperatively to control a patient’s acute pain will not displace buprenorphine from the MOR, leaving the patient susceptible to increased pain and agitation. Starting an opioid agonist while the patient still has buprenorphine in his or her systemic circulation can create other problems as well. As soon as the patient’s body eliminates all of the buprenorphine, the new opioid will be able to occupy all available MORs. This abrupt transition could greatly increase the frequency of side effects and risk of opioid-induced respiratory depression. Consequently, providers should have proper procedures in place for surgical patients currently receiving buprenorphine.

Procedure for Elective Surgery

The primary difference between elective surgery and same-day emergency surgery is that elective surgery allows ample time prior to the surgery for preparation and appropriately planning for patient management. Hence, elective surgery provides a clear advantage to patients on chronic buprenorphine therapy, since it generally allows sufficient time for a team of clinicians to ensure that a plan, such as completely tapering a patient off of buprenorphine, can be successfully completed. However, this is still a difficult process with specific dilemmas that must be addressed.

Due to buprenorphine’s relatively long half-life and slow dissociation rate from the MOR, the Substance Abuse and Mental Health Services Administration (SAMHSA) recommends that patients should be tapered off from buprenorphine gradually over 2 to 4 weeks (depending on the dose) prior to surgery.9 This period allows buprenorphine to be fully cleared from the body well before the need to initiate full opioid agonists for postsurgical pain management. Buprenorphine would otherwise block the MORs and prevent the opioid agonists from eliciting analgesia.

If the patient has been using buprenorphine to treat a pain disorder, short-
acting opioid agonists, such as hydrocodone, oxycodone, or morphine, should be prescribed on an as-needed basis so the patient has adequate pain relief prior to the surgery. Once the patient is admitted for surgery, the hospital or clinic would then be able to begin its pre-, intra-, and postoperative patient pain management plan according to its institutional policies. After the surgery, when the patient no longer requires the use of additional opioids for postsurgical pain management, buprenorphine may be reintroduced and titrated until an adequate dose is achieved.

This scenario assumes that the patient had not been illegally obtaining buprenorphine from non-medical sources to self-treat an opioid abuse disorder prior to surgery. A patient who had done so but not disclosed it to his or her providers would most likely require incredibly high doses of opioid agonists during and after the surgery to overcome buprenorphine’s low intrinsic activity and high binding affinity. When the buprenorphine cleared out of the patient’s body after 2 to 3 days, the patient would then be at significant risk for respiratory depression. Given this possibility, providers may want to universally screen patients for buprenorphine use prior to surgery.

Last updated on: September 13, 2017