How I Do It: Buprenorphine Conversions/Inductions in the Pain Clinic and Postoperative Settings
May 1, 2021
Treating pain in the setting of opioid use disorder (OUD) presents a unique clinical challenge for both the perioperative clinician providing anesthesia care and clinicians treating chronic pain in the outpatient setting. Buprenorphine is a partial mu-opioid-receptor agonist with applications for the treatment of chronic pain and OUD.1 Buprenorphine has an improved side effect profile compared with several other full-opioid agonists.2
Multiple formulations of buprenorphine are approved for clinical use. The transdermal patch and buccal film are dosed in micrograms and indicated for the treatment of chronic pain alone. The sublingual formulation is dosed in milligrams and is indicated for either physiologic opioid dependence or OUD.
The Drug Addiction Treatment Act (DATA) 2000 mandates specialized training and an X-waiver to prescribe the sublingual (PL1)
for OUD, but the same formulation can be prescribed for chronic pain without the X-waiver.3 The Trump administration, through the Department of Health and Human Services, attempted to eliminate the X-waiver requirement for buprenorphine
for OUD. However, this directly went against the aforementioned DATA 2000 and was repealed by the Biden administration two weeks later, to the dismay of many organizations, including the American Society of Regional Anesthesia and Pain Medicine.4
We present our own experience and protocols in the initiation and conversion of buprenorphine in the hospital and pain clinic settings.
We are frequently faced with patients with OUD who require surgical intervention. Many of these individuals present to the emergency department with acute illness, active opioid use, or opioid withdrawal. These individuals are usually stabilized on standard opioids (ie, full opioid agonists) or methadone prior to surgery and may continue to receive standard opioid therapy during the intraoperative and immediate postoperative periods. At this point, anesthesiologists have a potentially lifesaving opportunity to initiate buprenorphine prior to discharge.
If OUD patients do not initiate treatment prior to discharge, they are unlikely to seek help once outside of the medical environment. These patients must be willing to attempt treatment, which is more likely to occur if an organized effort is made during their hospitalization. Based on our experience, the direct approach is best. We treat them with respect and openly acknowledge their challenges with pain, withdrawal, and cravings, and offer to assist in any way possible. To manage postoperative pain, we typically employ a multimodal analgesic approach with a ketamine infusion, regional anesthesia when possible, and multimodal non-opioid agents while minimizing opioid withdrawal. We carefully monitor and record opioid withdrawal symptoms using the Clinical Opioid Withdrawal Scale (COWS). We offer our treatment program daily. If the patient expresses interest, we consult our opioid aftercare program to arrange for outpatient treatment.
Initiating buprenorphine can be lifesaving for the patient with OUD who has had surgery and is facing hospital discharge. If sent home without treatment of their OUD, these individuals face high mortality rates in the first 28 days following discharge. Approximately 32 per 1000 patients will die during this time frame.5
Perioperative buprenorphine is not inferior to other opioid analgesics.6 A transition to buprenorphine can be accomplished quickly and safely while maintaining pain relief and avoiding opioid withdrawal.7 The secret is to create a brief window between standard opioid dosing and buprenorphine dosing by administering microdoses of the latter. This is done similarly to how naloxone is titrated to antagonize opioid side effects. If done gradually, the transition can be accomplished without inducing pain or withdrawal in the patient.
Our approach is to withhold opioids until the end of their dosing schedule. For parenteral opioids, this may last 2–3 hours after the last dose or until there is a request for pain medication. For oral opioids, we recommend waiting 3–4 hours after the last dose, but this is flexible depending on the needs of the patient. We initially offer 2 mg of sublingual buprenorphine and observe for withdrawal symptoms or discomfort. In our experience, opioid withdrawal at this point is uncommon. We offer 2-mg increments every two hours as needed for pain management and up to 16 mg in the first 24 hours. Our experience is that patients rarely request more than 12 mg in the first 24 hours. Patients also report equal or better analgesia and no symptoms of opioid withdrawal.
On the second day of buprenorphine initiation, we ask for feedback from the patients regarding their level of satisfaction with the process. Most of the patients express that they are very satisfied with the transition. On the second day of treatment, in conjunction with the recommendation from our addiction specialist colleagues, we also advance to 8 mg of buprenorphine given twice daily. A “warm hand-off” is provided to our addiction specialist colleagues for follow up after-care.
We have successfully initiated buprenorphine treatment in many patients who would have otherwise left the hospital without clear treatment plans. With this approach, we have found that patients who accept treatment are likely to continue it during the critical first month and for an extended period thereafter. Every month of continued retention is potentially a life saved and an opportunity for further therapy.
Anesthesiologists can make a huge impact on the opioid crisis by continuing maintenance OUD treatment for patients in recovery or by initiating treatment in the postoperative period prior to hospital discharge. Any physician can prescribe buprenorphine in the hospital setting. Once you become familiar and comfortable with the process, it is neither time consuming nor burdensome and certainly saves lives.
There is evidence that buprenorphine can provide similar analgesia to morphine, but it is unclear whether a full or partial mu-agonist is more effective.8,9 We do not advocate utilizing buprenorphine as first-line pain therapy or as a replacement for patients on full agonist therapy. That said, we have found buprenorphine useful in elderly patients and those with underlying renal or hepatic issues, because it typically causes less constipation and nausea than morphine.2
The weekly transdermal buprenorphine patch can be initiated at 5 µg per hour for opioid-naive patients, whereas an initial dose of 10 µg per hour is likely necessary for opioid-tolerant patients. Comparatively, the buccal formulation can be prescribed at a twice-daily dose of 75 g or 300 mcg for opioid-naïve and opioid-tolerant patients, respectively. The recommended dose for opioid-tolerant patients is equivalent to 90–160 oral doses of morphine 10.
While manufacturers of the microgram formulation recommend at least a partial opioid taper prior to initiating therapy, the reality is that the risk of iatrogenic opioid withdrawal with the microgram formulation is likely to be low. This is because the 20 µg per hour buprenorphine patch provides the patient with a maximum dose of 480 µg within a 24-hour period; the highest recommended starting dose of the buccal formulation is 600 µg.8 A positron emission tomography scan demonstrated that four hours after a 1000- µg dose of buprenorphine, 71–85% of mu receptors were available for occupancy.11
The possibility of precipitated withdrawal is more likely when converting to milligram formulations of buprenorphine; however, the risk remains fairly low if the patient follows instructions appropriately.8
Several techniques for converting buprenorphine dosage have been described in the literature for both pain and addiction. The first method involves the classical induction approach, where withdrawal is induced by intentionally withholding opioids, and patients are monitored based on their COWS scores. The second methods involves micro-induction dosing of buprenorphine (Figure 1), in which low-milligram doses of buprenorphine (0.5–1 mg) are initiated alongside full opioid agonists. The buprenorphine is subsequently and slowly up-titrated while the full opioid agonist dose is down-titrated and eventually discontinued.12 We have found success with both methods.
Daily schedule of buprenorphine up-titration and down-titration and discontinuation of full-agonist opioid therapy in a patient receiving 80 mg of controlled-release oxycodone 80 mg three times per day.
Day 1: 0.5 mg twice daily* 80 mg, 3 times daily
Day 2: 1 mg twice daily† 80 mg, 3 times daily
Day 3: 1 mg 3 times daily† 80 mg, 3 times daily
Day 4: 2 mg 3 times daily 80 mg, twice daily
Day 5: 4 mg 3 times daily, None
Day ≥ 6: Adjust dose to symptoms, None
* One-quarter 2-mg tablet
† One-half 2-mg tablet
Figure 1. Example of micro-induction dosing
The dose received by one patient was tapered from approximately 270 morphine milligram equivalents (MME) down to 90 MME and was micro-induced to 12 mg of buprenorphine/naloxone daily. There was noted improvement in the patient’s side effect profile, and no describable change in his chronic pain symptoms. Another patient with a history of coronary artery disease who was receiving 400 MME of oxycodone for back pain presented with chronic constipation. The patient requested for inpatient hospitalization for buprenorphine conversion, because he was concerned about the effects that withdrawal may have on his cardiac status. He was induced 16 hours after his last dose of oxycodone. His COWS was > 20 but improved 30 minutes after the first dose of buprenorphine. He is currently maintained on 18 mg of once-daily buprenorphine therapy. His visual analog scale scores increased slightly by 10%, but his constipation and mood improved significantly.
Sudheer Potru, DO, FASAM, is the medical director of the Complex Pain and High-Risk Opioid Clinic, staff physician in the department of anesthesiology and pain medicine at Atlanta VA Medical Center, and assistant professor in the department of anesthesiology at Emory University School of Medicine in Atlanta, GA.
Eugene Viscusi, MD, is a professor of anesthesiology, chief of pain medicine, and director of acute pain management at Sidney Kimmel Medical College of Thomas Jefferson University in Philadelphia, PA.
- Coe MA, Lofwall MR, Walsh SL. Buprenorphine Pharmacology review: Update on transmucosal and long-acting formulations. J Addiction Med. 2019;13(2):93-103. https://doi.org/10.1097/ADM.0000000000000457.
- Khanna I, Pillarisetti S. Buprenorphine – an attractive opioid with underutilized potential in treatment of chronic pain. J Pain Res. 2015;8:859-870; https://doi.org/10.2147/JPR.S85951.
- Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2014;(2):CD002207. https://doi.org/10.1002/14651858.CD002207.pub4.
- Diamond D. Biden kills Trump plan on opioid-treatment prescriptions. The Washington Post. 2021, Jan. 27. Accessed March 28, 2021. https://www.washingtonpost.com/health/2021/01/27/biden-kills-buprenorphine-waiver/.
- White SR, Bird SM, Merrall ELC, Hutchinson SJ. Drugs-related death soon after hospital-discharge among drug treatment clients in Scotland: Record linkage, validation, and investigation of risk-Factors. PLoS One. 2015;10(11):e0141073. https://doi.org/10.1371/journal.pone.0141073.
- Macintyre PE, Russell RA, Usher KAN, Gaughwin M, Huxtable CA. Pain relief and opioid requirements in the first 24 hours after surgery in patients taking buprenorphine and methadone opioid substitution therapy. Anaesth Intensive Care. 2013;41(2):222-230. https://doi.org/10.1177/0310057X1304100212.
- Patel N, Schwenk ES, Ferd P, Torjman MC, Baratta JL, Viscusi ER. An anesthesiologist-led inpatient buprenorphine initiative. Pain Pract. 2021, Jan. 23; Online ahead of print. https://doi.org/10.1111/papr.12996.
- Webster L, Gudin J, Raffa RB, et al. Understanding buprenorphine for use in chronic pain: Expert opinion. Pain Med. 2020;21(4):714-723. https://doi.org/10.1093/pm/pnz356.
- American Geriatrics Society Panel on Pharmacological Management of Persistent Pain in Older Persons. Pharmacological management of persistent pain in older persons. J Am Geriatr Soc. 2009;57(8):1331-1346. https://doi.org/10.1111/j.1532-5415.2009.02376.x.
- Aiyer R, Gulati A, Gungor S, Bhatia A, Mehta N. Treatment of chronic pain with various buprenorphine formulations: A systematic review of clinical studies. Anesth Analg. 2018;127(2):529-538. https://doi.org/10.1213/ANE.0000000000002718.
- Greenwald MK, Johanson C-E, Moody DE, et al. Effects of buprenorphine maintenance dose on μ-opioid receptor availability, plasma concentrations, and antagonist blockade in heroin-dependent volunteers. Neuropsychopharmacol. 2003;28(11):2000-2009. https://doi.org/10.1038/sj.npp.1300251.
- Ahmed S, Bhivandkar S, Lonergan BB, Suzuki J. Microinduction of buprenorphine/naloxone: A review of the literature. Am J Addict. 2020, December 30. Online ahead of print. https://doi.org/10.1111/ajad.13135.