Perioperative Management for Orthopedic Surgery in the Patient Recovering from Opioid Addiction

Educational Objectives

The goal of this program is to improve perioperative anesthesia and analgesia management in patients receiving medication-assisted treatment (MAT) for opioid addiction. After hearing and assimilating this program, the clinician will be better able to:

1. Differentiate among options available for MAT.

2. Make appropriate recommendations for discontinuation of MAT therapies prior to surgical procedures.

3. Prescribe postoperative analgesia with the lowest risk for contributing to relapse of a patient who has recovered from opioid addiction.

4. Identify signs of withdrawal from buprenorphine.

5. Compare the efficacies and safety of medications used to ease perioperative pain and anxiety in patients who have recovered from opioid addiction.

Summary

Introduction

Dr. Hargrave

Case presentation: the patient is a 55-yr-old man with multiple childhood injuries and surgeries; he had a motor vehicle accident several years ago that necessitated several surgeries and treatment by pain specialists for chronic pain; during that period, the patient developed an opioid addiction after prescribed use of opioids and illegal use of heroin; he recovered from his addiction through medication-assisted treatment (MAT) using buprenorphine (current dose, 8 mg/day); the patient is experiencing knee pain secondary to a recent tear of the anterior cruciate ligament (ACL) sustained while hiking; he is scheduled to undergo ACL repair and was instructed by the orthopedic surgeon to discontinue buprenorphine; physical examination, vital signs, and clinical tests are unremarkable; his Mallampati score is 2

Options for MAT

Dr. Boone

Stages of rehabilitation: some programs combine detoxification and rehabilitation; acute detoxification lasts 3 to 5 days, depending on the addictive substance; in the presented case, 3 days may have been required; initial rehabilitation is inpatient (eg, a 6-wk residential program); patients graduate from inpatient or residential treatment to partial hospitalization (PHP) or intensive outpatient programs (IOP); following IOP, patients are often placed in transitional housing or sober living facilities; treatment focus is placement of patients in the least restrictive environment that allows achievement of their goals

Components offered by rehabilitation programs: oversight by a psychiatrist trained in addiction medicine, with consulting of other services, as needed; therapy focused on addictions, including motivational interviewing, which uses the Transtheoretical Model to assess readiness for change

Medication options for treating substance use disorders

Methadone: for treatment of opioid use disorder; highly regulated (can be prescribed only at specialty clinics); requires daily dosing at the clinic; depending on the dose, patients may be seen by a nurse; often, patients see a therapist every week, in addition to visits with a psychiatrist; random drug screening is performed; patients should engage in group as well as individual therapy; if drug screening reveals use of benzodiazepines, the clinic may consider dose reduction; methadone may be discontinued for those whose testing reveals heroin use on, eg, 2 occasions; patients who are compliant (report daily to the clinic and have multiple negative drug screens) may earn “take-home privileges” (ie, may be given a 1-2 wk supply of medication)

Naltrexone: nonregulated (can be prescribed by any physician); initially given orally and can be transitioned to a monthly, long-acting injectable form; also used in the treatment of alcohol use disorder (administration before drinking to reduce alcohol consumption; use as a challenge to confirm abstinence)

Buprenorphine: case presentation patient — the safest use of buprenorphine would be initiation following detoxification and complete abstinence from heroin for ≈7 days; prescription of buprenorphine — requires an X waiver; clinicians who complete the training can dispense buprenorphine in the office, which patients often prefer over attending methadone treatment clinics; patients receive a sublingual film that combines buprenorphine and naloxone in a 4:1 ratio (Suboxone); it is also available in a long-acting, subcutaneous injectable form

Use of perioperative opioids in patients on MAT: uncontrolled pain and anxiety create risk for relapse; the use of nonopioid medications should be maximized; patients should be discharged with an overdose prevention kit; if opioids are absolutely necessary, use the lowest effective dose; patients should also receive a medication disposal bag for safely discarding unused doses; patients who have been abstinent for long periods may have lost tolerance and are especially vulnerable; ample reassurance and family support are essential

Perioperative Management for Patients Receiving MAT

Dr. Corba

Most-encountered medications for MAT: buprenorphine, buprenorphine-naloxone, and naltrexone

Buprenorphine: a partial µ-opioid receptor agonist; information on the mechanism of action and effects of buprenorphine in the epidural or intravenous space is limited; anecdotal reports have noted prolonged local anesthetic effects when used in a regional anesthetic block; the drug is combined with naloxone in a 4:1 ratio; this low concentration of naloxone has minimal effect on intraoperative delivery of opioids; buprenorphine has an extremely long half-life; therefore, if the drug has not been discontinued prior to surgery (eg, in acute cases), opioid requirements during the procedure may be increased

Naltrexone: administration can cause withdrawal effects in opioid-dependent patients

Buprenorphine-naloxone: more effective than clonidine in the supervised withdrawal setting; pharmacodynamically, buprenorphine-naloxone is a µ-opioid receptor agonist with κ- and δ-antagonist activity; it has a long plasma half-life and strong binding affinity for opioid receptors; because of this binding affinity, the drug prevents analgesic and anesthetic effects of opioids commonly used in clinical doses; implications for perioperative anesthesia — if a patient who is having elective surgery is taking buprenorphine or buprenorphine-naloxone, the drug should be held for ≥3 days prior to surgery to ensure adequate response to intraoperative opioids and postoperative analgesia; options include increasing the dose of buprenorphine and employing it as a single agent for pain relief, or using a multimodal approach

Methadone: a long-acting µ-opioid receptor agonist; in 2009, this long-acting synthetic opioid accounted for 2% of opioid prescriptions and >30% of overdose deaths; methadone was used in the past for treatment of chronic pain (primarily because of its low cost); however, use of methadone should be limited to treatment of opioid use disorder because of associated risks for drug-drug interactions and cardiac effects (ie, prolongation of the QT interval; Takotsubo [“broken heart”] syndrome; Brugada-like syndrome [sudden death associated with right bundle branch block and ST-segment elevation])

Recommended intraoperative anesthesia for the case patient: regional anesthesia — associated with reductions in pain scores, drowsiness, and postoperative nausea, better mobility, and earlier discharge; possible block failure is a disadvantage; complications are rare, particularly with ultrasound guidance; patients should undergo preoperative assessment to rule out contraindications (eg, local infection, coagulopathy) and be fully informed about required procedures

Multimodal pharmacologic therapy: initially included the use of, eg, gabapentin, acetaminophen (eg, Mapap, Pharbetol, Tylenol), other medications used off-label for pain control; currently, preoperative regimens containing an anti-inflammatory medication, acetaminophen, and a gabapentinoid (pregabalin [Lyrica] or gabapentin) are used to help minimize intraoperative need for anesthesia and postoperative opioid requirements

Opioids in perioperative anesthesia: use of opioids in neuraxial techniques (spinal, epidural, or combined spinal-epidural anesthesia) is risky in a patient with a history of addiction; anxiety about perioperative use of opioids is a valid concern in patients who have recovered from addiction and fear that even short-term use will result in relapse

Dependence vs addiction: these are significantly different concepts; dependence — studies show that, in rats, only 4 doses of oxycodone are required to induce dependence (ie, physiological need for a medication in order to maintain normal function); addiction — a learned behavior; individuals with addiction largely use medications to achieve euphoria; neuroadaptation occurs and cravings (which are associated with a loss of control) develop; positron emission tomography (PET) studies of dopamine receptors in individuals addicted to cocaine, methamphetamine, alcohol, or heroin support the view that this loss of control results from loss of frontal inhibition; after 1 yr of abstinence, PET images essentially return to normal; however, there is evidence that these receptors “light up” with the mere discussion of “getting high”

Conclusions: it is unclear whether use of a small intraoperative dose of an opioid causes consequential activation of dopamine receptors; recommendations for multimodal therapy represent current best practices for maintaining a functional pain level and decreasing anxiety about surgery among individuals undergoing outpatient treatment for opioid addiction

Case presentation continued (Dr. Hargrave): the patient becomes febrile, tachycardic, and has dilated pupils in the postanesthesia care unit (PACU)

Postoperative Complications in Patients Receiving MAT

Dr. Goeller

Special needs of patients receiving MAT: typically, anesthesia care for an ACL repair involves preoperative medication, intraoperative pain control using a variety of approaches, and rapidly addressing postoperative escalations of pain; patients on MAT have different baseline needs and therefore require education and setting of expectations before surgery, layering of multiple medications, and use of opioid-minimizing tactics, such as regional anesthesia

Protocols for elective surgery in patients on long-term buprenorphine therapy: algorithm pathways depend on the level of expected pain and whether the patient has remained on buprenorphine; because of variability in the half-life of buprenorphine, some activity may persist in patients who discontinue the drug 2 to 3 days before surgery; the case presentation patient likely was approaching complete clearance of buprenorphine at the time of surgery

Preoperative management: the protocol recommends discontinuation of buprenorphine but cites case reports that describe variable requirements for postoperative analgesia with this approach, as well as for continuing the drug through surgery or increasing the dose by 25%

Postoperative management: demand-only patient-controlled analgesia (to avoid rapid agonism of available opioid receptors and possible respiratory compromise); high level of care to facilitate monitoring; regional anesthesia with continuous catheters (eg, adductor canal block) that can be left in place after discharge; ACL repair with grafting from a lower-extremity tendon decreases pain, further minimizing need for opioids; during hospitalization, an α-2 agonist drip (eg, dexmedetomidine; typically delivered in the intensive care unit) can be a helpful adjunct; round-the-clock acetaminophen provides a good baseline; gabapentin and pregabalin can have a substantial benefit after orthopedic surgery

Overt signs of withdrawal in the PACU: address with slow titration of a short-acting opioid, followed by a protocol to prevent continuation of the withdrawal process; signs of withdrawal include manifestations of excess sympathetic activity (eg, piloerection, salivation, diarrhea, dilated pupils, agitation); occurrence of seizures suggests withdrawal from a substance other than buprenorphine; in a typical patient, goals are optimal pain control and rapid de-escalation after the first 48 hr; however, patients on maintenance MAT should undergo gentle de-escalation of medications given for additional analgesic needs, while being carefully monitored for symptoms of withdrawal; these patients initially require high doses to overcome agonism at the µ-opioid receptors and achieve adequate pain control (layering of multiple medications at low doses is advised)

Questions and Answers (Drs. Boone, Corba, and Goeller)

The psychiatric component of pain: patients in emotional pain are likely to feel physical pain more acutely; such patients require a good support system, in addition to pharmacologic interventions; maximize contact with clinicians; pain should be acknowledged; if patients are anxious about pain that has been adequately addressed, hydroxyzine (eg, 20-50 mg every 6 hr) may be prescribed; provide reassurance; benzodiazepines generally are not recommended; counsel patients that the goal is a “tolerable level” of postoperative pain; the role of pain receptors — upregulation of pain receptors and central and peripheral sensitization may occur in patients with addiction and dependence; PET studies show that counseling alone can significantly effect dopamine receptors; many medications that do not trigger narcotic receptors (eg, clonidine patches, high-dose anti-inflammatory drugs, acetaminophen, gabapentin) are available to ease pain and anxiety

Ketamine and posterior blocks: ketamine — central effects on the N-methyl-D-aspartate (NMDA) receptors have been demonstrated; useful intraoperatively for analgesia (as an intermittent bolus or infusion) in patients with high opioid dose requirements; NMDA receptor antagonism is not known to increase risk for relapse in patients who have recovered from opioid addiction; posterior blocks — eg, sciatic, femoral nerve; useful but associated with risk for nerve injury; with ACL repair, blocks may delay contraction of the quadriceps muscles postoperatively

Multimodal analgesia: pregabalin and gabapentin are equally efficacious; there is more flexibility in dosing with gabapentin than with pregabalin; there is greater risk for side effects of, eg, edema (≤15 lb of fluid gain), excessive drowsiness, with pregabalin than with gabapentin

Abuse potential of gabapentinoids: studies in rats prompted classification of gabapentin and pregabalin as Schedule II drugs; when using these medications to manage chronic pain, the clinician should be vigilant about possible signs of abuse

Intraoperative-only use of opioids in recovered patients: avoids the “reward” of euphoria; patients concerned about relapse may consent to anesthesia that includes opioids if they are assured that only nonopioid analgesia will be used after they have regained awareness (ie, patients are engaged in the treatment plan, which helps to alleviate some of their anxiety)

Dexmedetomidine in orthopedic surgery: dexmedetomidine does not have analgesic properties but can prevent some of the agitation patients experience on emergence from anesthesia, and thereby contribute to opioid sparing; may be used intraoperatively as a drip or in multiple boluses

Readings

Aboujaoude E, Salame WO. Naltrexone. a pan-addiction treatment? CNS Drugs. 2016 Aug;30(8):719-33. doi: 10.1007/s40263-016-0373-0. PMID: 27401883; Alinejad S et al. A systematic review of the cardiotoxicity of methadone. EXCLI J. 2015;14:577–600; Christensen JE et al. Isokinetic strength deficit 6 months after adductor canal blockade for anterior cruciate ligament reconstruction. Orthop J Sports Med. 2017;5(11):2325967117736249; Gajraj NM. Pregabalin. its pharmacology and use in pain Management. Anesth Analg; 2007; 105(6): p 1805-1815; Ford NF. An opioid-benzodiazepine interaction: benzodiazepines as opioids? J Pharmacol Pharmacother. 2018;9:165-6; Trifilieff P and Martinez D. Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity. Neuropharmacology 2014;76:498–509; Zoorob R et al. Buprenorphine therapy for opioid use disorder. Am Fam Physician. 2018 Mar 1;97(5):313-320. PMID: 29671504; Zorumski CF et al. Ketamine: NMDA receptors and beyond. J Neurosci. 2016; 36(44):11158–64.

Disclosures

For this program, members of the faculty and planning committee reported nothing to disclose. In her portion of the lecture, Dr. Boone presents information related to the off-label or investigational use of a therapy, drug, or device.

Acknowledgements

Dr. Hargrave, Dr. Boone, Dr. Corba, and Dr. Goeller were recorded at the 47th Annual American Osteopathic College of Anesthesiologists’ Mid-Year Seminar, held March 13-15, 2020 in Chicago, IL and presented by American Osteopathic College of Anesthesiologists. For information on CME offerings from American Osteopathic College of Anesthesiologists, please visit aocaonline.org. The Audio Digest Foundation thanks the speakers and the American Osteopathic College of Anesthesiologists for their cooperation in the production of this program.

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