The goal of this program is to improve the management of pain with buprenorphine. After hearing and assimilating this program, the clinician will be better able to:
Buprenorphine: is a mixed opioid agonist antagonist and a partial agonist with slow dissociation; its action depends on the receptor it binds to; for opioid use disorder (OUD), it alleviates withdrawal symptoms and blocks the effects of other opioids; it has a ceiling effect at certain receptors; initially, it was believed to be superior to other treatments because patients maintained some opioid tolerance, reducing the risk for fatal overdose during relapse compared with complete abstinence; buprenorphine lacks the cardiac adverse effects associated with methadone; it is easier to administer, ie, patients can take it at home rather than requiring daily clinic visits
Ceiling effect: primarily applies to respiratory depression, though it may also influence gastrointestinal (GI) adverse effects; buprenorphine does not cause the same sedation and respiratory depression as traditional opioids; however, its pain efficacy matches other synthetic opioids; this discrepancy is linked to the complex nature of 5 opioid receptors and a G protein independent signalling pathway called biased agonism; studies on arrest in 3 knockout mice, where a part of a signaling pathway is altered, show that these mice do not experience the typical respiratory depression or adverse effects when given morphine
Action on other receptors: binding to the κ receptor may explain its potential use in treating refractory depression, and anxiety; this may be because of its impact on dopamine levels and the ability to alleviate the emotional component of pain; similar to ketamine, buprenorphine may be addressing the psychoactive aspect of pain, reducing the emotional distress associated with it; binding to the δ receptor may reduce the reward benefit typically associated with opioid use
Administration: buprenorphine has poor oral bioavailability because of first pass metabolism; it is primarily used sublingually; a subcutaneous injectable depot form exists; buprenorphine can cross the blood brain barrier, and hepatically metabolized by CYP3A4 enzymes into norbuprenorphine (active metabolite), which can be detected in urine drug screens; its half life is 38 hr and is mainly excreted via the feces
Dosing and contraindications: varies depending on whether it is for OUD or pain; for OUD, guidelines recommend starting low dose and titrating to ≤24 mg daily, usually in once or twice daily doses; for pain management, more frequent dosing (every 6-8 hr) may be more effective because of its μ receptor binding properties; no renal dose adjustment is needed; in patients categorized as Child Pugh class C, the dose should be reduced by ≈50%, and transdermal or subcutaneous depot forms are not recommended; evidence on pediatric and elderly populations is limited; it is categorized as pregnancy category C drug; buprenorphine readily crosses the placental barrier, and fetal abnormalities have been reported in some pregnancies where it was used; it is considered relatively safe for breastfeeding; methadone is often preferred for pregnant patients with OUD, with a switch back to buprenorphine after delivery and during breastfeeding; contraindications for buprenorphine use are primarily allergy to the medication and intestinal obstruction
Adverse effects: buprenorphine not ideal for elderly patients because of its potential anticholinergic adverse effects and central nervous system depression; it carries a theoretical risk for hypertension, QT prolongation, and lowering the seizure threshold; these events are rarely observed; despite maintaining some tolerance, patients starting buprenorphine for OUD still face an overdose risk if they relapse, as their tolerance will have decreased; a significant concern recently highlighted by the US Food and Drug Administration is increased tooth and potentially bone decay with long-term sublingual use; for patients with pain, the stigma associated with an “addiction drug” can be a barrier
Availability and use: the availability of buprenorphine has improved significantly in recent years (especially with the removal of the special US Drug Enforcement Agency waiver requirement in some areas)
Use: historically, for minor procedures, patients on buprenorphine were often maintained on their medication with additional pain management; recommendations now suggest tapering opioid use before major surgery (eg, spine surgery) for better postoperative pain control; for patients on buprenorphine for OUD, the approach is mixed; evidence suggests that reducing μ receptor binding 2 wk prior to surgery improves postoperative pain management, regardless of the binding agent; tapering buprenorphine raises concerns about relapse and potential overdose; for managing pain, a discussion about tapering is warranted; aggressive multimodal analgesia during and after surgery is recommended; the rationale is to block as many pain receptors as possible, regardless of the specific opioid or agonist antagonist involved; emerging case reports and meta-analyses suggest that maintaining buprenorphine may be preferable; the clinician must assess the patient’s baseline chronic pain and communicate with the surgical team; importantly, one must consider the smoking status, because nicotine sensitizes pain receptors, potentially exacerbating pain; the clinician may consult acute or chronic pain management teams for guidance on managing potentially higher opioid doses
Dahan A, Yassen A, Romberg R, et al. Buprenorphine induces ceiling in respiratory depression but not in analgesia. Br J Anaesth. 2006;96(5):627-632. doi:10.1093/bja/ael051; Grande LA, Cundiff D, Greenwald MK, et al. Evidence on buprenorphine dose limits: a review. J Addict Med. 2023;17(5):509-516. doi:10.1097/ADM.0000000000001189; He L, Gooding SW, Lewis E, et al. Pharmacological and genetic manipulations at the μ-opioid receptor reveal arrestin-3 engagement limits analgesic tolerance and does not exacerbate respiratory depression in mice. Neuropsychopharmacology. 2021;46(13):2241-2249. doi:10.1038/s41386-021-01054-x; Togioka BM, Patel P. Buprenorphine and Naloxone. In: StatPearls. Treasure Island (FL): StatPearls Publishing; February 24, 2024; Quaye AN, Zhang Y. Perioperative management of buprenorphine: solving the conundrum. Pain Med. 2019;20(7):1395-1408. doi:10.1093/pm/pny217; White LD, Hodge A, Vlok R, et al. Efficacy and adverse effects of buprenorphine in acute pain management: systematic review and meta-analysis of randomised controlled trials. Br J Anaesth. 2018;120(4):668-678. doi:10.1016/j.bja.2017.11.086.
For this program, members of the faculty and planning committee reported nothing relevant to disclose. Dr. Bailey-Classen's lecture contains information related to the off-label or investigational use of a therapy, product, or device.
Dr. Bailey-Classen was recorded at the 2024 Annual Convention and Conclave of the American Osteopathic College of Anesthesiologists, held September 7-10, 2024, in Palm Springs, CA, and presented by the American Osteopathic College of Anesthesiologists. For information on upcoming CME activities from this presenter, please visit aocaonline.org. Audio Digest thanks the speakers and American Osteopathic College of Anesthesiologists for their cooperation in the production of this program.
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AN671302
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