Opioid use disorder
Anesthetic relevance

High

Anesthetic management

Suboxone or methadone therapy may be continued

Specialty

Pain

Signs and symptoms

Opioid withdrawal may include increased pain, cramping, diarrhea, anxiety, and insomnia.

Diagnosis

Consider Clinical Opioid Withdrawal Scoring (COWS)

Treatment

Consider reinitiating home therapy if not already started. Use non-opioid pain adjuncts (regional, GABA agonists, NSAIDs) and higher dosing of full mu receptor agonists (e.g. fentanyl, hydromorphone)

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This article focuses primarily on management considerations for patients on Suboxone or methadone therapy.

Epidemiology

According to the 2019 Substance Abuse and Mental Health Administration National Survey on Drug Use and Health, 5.7 million people (2.1 percent of people aged 12 or older) in the US were estimated to have used heroin at some point in their lives while 431,000 (0.2 percent) reported use in the last month[1]. Illicit fentanyl and prescription drug misuse have also contributed to rising rates of opioid overdose deaths from approximately 3,000 in 2010 to over 15,000 in 2016[2]

Anesthetic implications

Patients with opioid use disorder on maintenance therapy with Suboxone (buprenorphine-naloxone) or methadone are at high risk of inadequately controlled pain post-procedure due to low dosing or slow titration. Additionally, patients with poorly managed pain are at risk of prolonged hospital stays, increased cravings, and potential relapse[3].

Pathophysiology

Buprenorphine is a partial mu-opioid receptor agonist and kappa-opioid receptor. It is unique in that its action at the mu-opioid receptor can block binding of other opioids.

Methadone is a synthetic long-acting mu-opioid agonist that similarly binds and occupies receptor. It is multifaceted in that it is an NMDA antagonist (a pathway implicated in the development of opioid tolerance). This explains the perioperative benefits of methadone and ketamine as opioid sensitizers. Methadone also acts as a serotonin and norepinephrine reuptake inhibitor which improves mood in patients (albeit while increasing the risk of serotonin syndrome)[4].

Anesthetic management

Preoperative optimization

Patients can continue to receive adequate pain control peri-operatively while continuing on their home opioid agonist therapy[5]. The dose of buprenorphine has implications for the risk of opioid tolerance and increased post-operative pain. According to UCSF guidelines for perioperative management of buprenorphine, for example, patients on a high dose of buprenorphine (>8 mg/day) should consider gradual dose reduction prior to elective surgery to prevent decreased efficacy of full mu-opioid agonists during the treatment of acute pain[6][7]At doses lower than 8 mg/day of buprenorphine, patients can continue their normal Suboxone dose through procedure day and day of discharge.

Similarly, it is recommended that patients continue their dose of home methadone[1]. One approach is to split a patient's total daily dose into three divided doses. This takes into account methadone's biphasic pharmacokinetics (having both alpha and beta elimination). Alpha elimination corresponds to methadone's analgesic duration which approximates to 8 hours. This is in contrast to its beta elimination (preventing withdrawal in patient's on opioid maintenance therapy) which lasts 30-60 hours[8].

Non-opioid agents include medications such as Tylenol and the gabapentinoids, gabapentin/pregabalin. A shared neuro-inflammatory and central sensitization process akin to that of neuropathic pain may explain the cross-benefit of gabapentin in patients with opioid-induced hyperalgesia[9].

Intraoperative management

Regional anesthesia techniques (including continuous epidural and peripheral nerve catheters) should be strongly considered in a non-opioid driven anesthetic. Providers should consider Toradol and redosing of Tylenol in longer procedures. Ketamine is a useful adjunct due to its useful effect of increasing opioid sensitivity when run at low dose rates (0.2-0.3 mg/kg/hr). Its use may be limited in elderly patients who are at increased risk of experiencing dysphoria/delirium post-operatively or are more sensitive to adverse effects from polypharmacy.

Similarly, IV methadone given as a single dose of 0.1-0.3 mg/kg (based on ideal body weight) has been reported to significantly reduce post-operative opioid requirements and has been studied extensively in patient's receiving spinal fusion procedures[4]. This has not been studied well however amongst patients already on methadone or those with opioid use disorder. If given intraoperatively, it would be prudent to compare this dosing with the patient's home methadone dose (given TID). Generally, 1/2 to 1/3 of a patient's oral methadone dose is thought to be the equivalent IV dose[8].

Concurrent use of both Suboxone and methadone is not recommended both perioperatively and as an outpatient due to the opioid antagonist effects of naloxone and shared cytochrome metabolism[10].

Otherwise, the use of full mu-opioid receptor agonists (fentanyl, hydromorphone) remain important to the management of intraoperative pain. Providers should consider scheduled dosing throughout the procedure balancing the risk of hypotension and respiratory depression (seen in older patients, those with OSA, and patients with end-organ failure).

Postoperative management

Consider continuing patients' Suboxone or methadone while simultaneously implementing a multimodal post-operative pain management plan. Providers should continue typical opioid regimens for mild-severe pain (oxycodone, fentanyl, hydromorphone) acknowledging that higher than normal starting doses of opioids may be required. The typical calculation of milligram morphine equivalents (MME) do not give an accurate sense of equivalent dosing. Regional techniques (neuraxial, peripheral nerve catheters), gabapentinoids, and ketamine can be important supplements to reduce opioid needs. Providers may also consider post-operative stay in the ICU for pain management and consultation of in-house pain service.

References

  1. Rudd, Rose A.; Seth, Puja; David, Felicita; Scholl, Lawrence (2016-12-30). "Increases in Drug and Opioid-Involved Overdose Deaths - United States, 2010-2015". MMWR. Morbidity and mortality weekly report. 65 (50–51): 1445–1452. doi:10.15585/mmwr.mm655051e1. ISSN 1545-861X. PMID 28033313.
  2. US Department of Justice. "2018 National Drug Assessment" (PDF). Drug Enforcement Administration. Retrieved January 21, 2023.
  3. pubs.asahq.org https://pubs.asahq.org/anesthesiology/article/126/6/1180/18722/To-Stop-or-Not-That-Is-the-QuestionAcute-Pain. Retrieved 2022-08-03. Missing or empty |title= (help)
  4. 4.0 4.1 Murphy, Glenn S.; Szokol, Joseph W. (2019-09-01). "Intraoperative Methadone in Surgical Patients". Anesthesiology. 131 (3): 678–692. doi:10.1097/aln.0000000000002755. ISSN 0003-3022.
  5. Alford, Daniel P.; Compton, Peggy; Samet, Jeffrey H. (2006-01-17). "Acute pain management for patients receiving maintenance methadone or buprenorphine therapy". Annals of Internal Medicine. 144 (2): 127–134. doi:10.7326/0003-4819-144-2-200601170-00010. ISSN 1539-3704. PMC 1892816. PMID 16418412.
  6. "UCSF Guideline for the Perioperative Management of Buprenorphine" (PDF).
  7. Quaye, Aurora Naa-Afoley; Zhang, Yi (2018-11-30). "Perioperative Management of Buprenorphine: Solving the Conundrum". Pain Medicine. 20 (7): 1395–1408. doi:10.1093/pm/pny217. ISSN 1526-2375.
  8. 8.0 8.1 Harrison, Thomas Kyle; Kornfeld, Howard; Aggarwal, Anuj Kailash; Lembke, Anna (2018-09-01). "Perioperative Considerations for the Patient with Opioid Use Disorder on Buprenorphine, Methadone, or Naltrexone Maintenance Therapy". Anesthesiology Clinics. 36 (3): 345–359. doi:10.1016/j.anclin.2018.04.002. ISSN 1932-2275. PMID 30092933.
  9. Compton, Peggy; Kehoe, Priscilla; Sinha, Karabi; Torrington, Matt A.; Ling, Walter (2010-06-01). "Gabapentin improves cold-pressor pain responses in methadone-maintained patients". Drug and Alcohol Dependence. 109 (1–3): 213–219. doi:10.1016/j.drugalcdep.2010.01.006. ISSN 1879-0046. PMC 2875370. PMID 20163921.
  10. Drug interactions involving methadone and buprenorphine. World Health Organization. 2009.