Residency · Residency · Anesthesiology

The Opioid Crisis: Perioperative Stewardship and the Opioid-Tolerant Patient

Introduction

The opioid epidemic has fundamentally changed how anesthesiologists approach perioperative pain management. Over 100,000 Americans die annually from drug overdoses, with opioids implicated in over 75% of these deaths. Surgical prescriptions have been identified as a significant gateway to chronic opioid use, and anesthesiologists are uniquely positioned to implement responsible prescribing practices and optimize care for the growing population of opioid-tolerant patients.

The Opioid Crisis: Scope and Context

Epidemiology

The first wave of the crisis began in the 1990s with increased prescribing of opioids following campaigns emphasizing "pain as the fifth vital sign." The second wave around 2010 saw a rise in heroin use as prescription opioid access tightened. The third wave from 2013 to the present is dominated by synthetic opioids, primarily illicit fentanyl and its analogs, which account for the majority of overdose deaths. Surgical opioid prescriptions contribute to the problem, with 5 to 8% of opioid-naive patients continuing opioid use beyond 90 days after surgery. Risk factors for persistent postoperative opioid use include preoperative anxiety and depression, tobacco use, alcohol use disorder, and higher initial opioid prescription quantity.

The Anesthesiologist's Role

Perioperative physicians are among the highest-volume opioid prescribers. They are responsible for intraoperative opioid administration, postoperative pain management, and discharge prescribing. This creates an opportunity to implement multimodal opioid-sparing strategies that reduce both acute pain and the risk of chronic opioid use.

Perioperative Opioid Stewardship

Preoperative Planning

All patients should be screened for current and prior opioid use, substance use disorders, and risk factors for persistent opioid use. The Prescription Drug Monitoring Program (PDMP) should be reviewed before surgery. Realistic pain expectations are set by discussing the difference between pain control and pain elimination. Preoperative education about pain management and opioid risks helps patients report lower pain scores and use fewer opioids postoperatively. Preemptive multimodal analgesia with acetaminophen 1 g PO, gabapentin 300 to 600 mg PO, and celecoxib 200 to 400 mg PO (when not contraindicated) can be started before surgery.

Intraoperative Opioid-Sparing Strategies

Multimodal analgesia (MMA) includes IV acetaminophen 1 g (most effective when given before surgical stimulus), ketorolac 15 to 30 mg IV (after surgical hemostasis is achieved), and sub-anesthetic ketamine infusion at 0.1 to 0.5 mg/kg/hr, which reduces postoperative opioid consumption by 30 to 40% and is particularly effective in opioid-tolerant patients. Dexmedetomidine at 0.2 to 0.7 mcg/kg/hr provides analgesic, opioid-sparing, anti-shivering, and emergence delirium-reducing effects. IV lidocaine infusion at 1 to 2 mg/kg/hr has anti-hyperalgesic properties and is most studied for abdominal surgery. Magnesium sulfate at 30 to 50 mg/kg bolus followed by 15 mg/kg/hr acts as an NMDA antagonist with a modest opioid-sparing effect. Dexamethasone at 4 to 8 mg IV provides anti-inflammatory and antiemetic effects and prolongs nerve block duration.

Regional anesthesia includes neuraxial techniques (epidural, spinal) as the gold standard for major abdominal and lower extremity surgery, peripheral nerve blocks as single-shot or continuous catheter techniques, fascial plane blocks (TAP, quadratus lumborum, erector spinae, pectoralis blocks), and local infiltration analgesia with surgeon-administered wound infiltration using long-acting local anesthetic such as liposomal bupivacaine.

Postoperative Prescribing

The minimum effective quantity of opioid analgesics should be prescribed at discharge. Evidence-based guidelines indicate that most procedures require 0 to 15 opioid tablets (5 mg oxycodone equivalents). Prescriptions should be tailored to the specific surgery using procedure-specific opioid prescribing guidelines. Clear instructions should provide scheduled non-opioid analgesics with opioids reserved for breakthrough pain only. Opioids should not be prescribed "just in case" because overprescribing leads to diversion and misuse. A plan for unused medication disposal through pharmacy take-back programs or FDA-approved home disposal should be included.

The Opioid-Tolerant Patient

Definition

Opioid-tolerant patients are those receiving 60 mg or more of oral morphine equivalents per day, 25 mcg/hr or more of transdermal fentanyl, or equivalent doses of other opioids for one week or more. This category also includes patients on medication-assisted treatment (MAT) for opioid use disorder: methadone, buprenorphine (Suboxone), and naltrexone (Vivitrol).

Pathophysiology of Tolerance

Pharmacodynamic tolerance involves receptor downregulation, desensitization, and altered intracellular signaling. Opioid-induced hyperalgesia (OIH) is a paradoxical increase in pain sensitivity caused by chronic opioid exposure, mediated by NMDA receptor activation, glial cell activation, and central sensitization. It clinically presents as diffuse, poorly localized pain that worsens with opioid dose escalation. OIH is distinguished from tolerance (which improves with dose increase) by its worsening with higher doses. Both phenomena increase perioperative opioid requirements and complicate pain management.

Preoperative Management of Chronic Opioid Therapy

The patient's baseline opioid regimen should be continued through the morning of surgery, including long-acting formulations. Intraoperatively, the regimen is converted to IV equivalents, ensuring baseline requirements are met before layering on surgical pain management. Planning for 30 to 50% higher opioid requirements compared to opioid-naive patients is necessary. The patient's pain management physician or addiction medicine specialist should be engaged in perioperative planning.

Buprenorphine Perioperative Management

Current evidence favors continuing buprenorphine throughout the perioperative period, though dose reduction to 8 to 16 mg/day may be considered for major surgery. Buprenorphine is a partial mu-agonist with high receptor affinity, but it does not prevent supplemental full mu-agonist opioids from providing additional analgesia. Discontinuing buprenorphine risks withdrawal, relapse, and untreated pain. If full agonist opioids are needed for breakthrough pain, higher doses should be used (for example, hydromorphone 0.5 to 1 mg IV) and titrated to effect. Discontinuation more than 72 hours before surgery should be avoided unless directed by an addiction specialist.

Methadone Perioperative Management

Methadone should be continued at the patient's usual dose throughout the perioperative period. It provides baseline analgesia but is not sufficient for acute surgical pain, so supplementation with short-acting opioids for surgical pain is needed. QTc monitoring is important because methadone prolongs the QT interval, and a baseline ECG should be obtained. Coordination with the patient's methadone clinic verifies the dose and ensures continuity.

Naltrexone Perioperative Management

Oral naltrexone should be discontinued 72 hours before surgery (half-life approximately 4 hours, but the active metabolite 6-beta-naltrexol has a longer duration). For IM naltrexone (Vivitrol), if within 30 days of the last injection, mu-opioid receptors are significantly blocked. Regional anesthesia and multimodal non-opioid analgesia become essential. If opioids are required, very high doses with close monitoring in a step-up care setting are needed, and addiction medicine should be consulted.

Intraoperative Strategies for the Opioid-Tolerant Patient

Ketamine is the single most important adjunct because NMDA antagonism counteracts both tolerance and OIH. A bolus of 0.25 to 0.5 mg/kg at induction followed by an infusion of 0.1 to 0.3 mg/kg/hr intraoperatively and continued at 0.05 to 0.15 mg/kg/hr postoperatively for 24 to 72 hours is recommended. Aggressive regional anesthesia should be used whenever feasible. The full multimodal regimen (acetaminophen, NSAIDs, dexmedetomidine, lidocaine infusion, magnesium) is employed. Patient-controlled analgesia (PCA) postoperatively with demand doses typically 50 to 100% higher than standard is used. Methadone as an intraoperative analgesic at 0.1 to 0.2 mg/kg IV provides long-acting analgesia and has NMDA antagonist properties.

Identifying and Managing Substance Use Disorder Perioperatively

Red Flags for Opioid Use Disorder

Red flags include requests for specific opioids by name and dose, "lost" prescriptions, frequent emergency department visits for pain, PDMP showing multiple prescribers or pharmacies, positive urine drug screen for non-prescribed substances, and escalating doses without functional improvement.

Perioperative Principles

Pain must be treated adequately because undertreating pain in patients with substance use disorder is harmful and increases relapse risk. A non-judgmental, compassionate approach is essential. Addiction medicine or pain management specialists should be involved early. Multimodal analgesia is even more critical in this population. A clear discharge plan with limited opioid supply, close follow-up, and PDMP review should be developed. Naloxone education and prescription should be provided or referred for before discharge.

Key Clinical Pearls

Perioperative opioid prescriptions are a modifiable risk factor for chronic opioid use; the minimum effective quantity should be prescribed with opioids always paired with scheduled non-opioid analgesics. Buprenorphine and methadone should be continued through the perioperative period because discontinuation creates risk without benefit and is no longer recommended by current guidelines. Ketamine is the most valuable pharmacologic tool for the opioid-tolerant patient, reducing opioid requirements, counteracting opioid-induced hyperalgesia, and providing antidepressant properties. Regional anesthesia is not just preferred in opioid-tolerant patients; it is often the difference between manageable and unmanageable postoperative pain.

References

1. Goel A, Azargive S, Weissman JS, et al. Perioperative Pain and Addiction Interdisciplinary Network (PAIN) clinical practice advisory for perioperative management of buprenorphine. Can J Anaesth. 2019;66(11):1335-1348.
2. Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC Clinical Practice Guideline for Prescribing Opioids for Pain. MMWR Recomm Rep. 2022;71(3):1-95.
3. Lembke A, Ottestad E, Schmiesing C. Patients maintained on buprenorphine for opioid use disorder should continue buprenorphine through the perioperative period. Pain Med. 2019;20(3):425-428.
4. Wick EC, Grant MC, Wu CL. Postoperative multimodal analgesia pain management with nonopioid analgesics and techniques: a review. JAMA Surg. 2017;152(7):691-697.

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