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Managing acute pain in patients with Opioid Use Disorder and �perioperative recommendations

February 10, 2025

Dr. Julia Eidelman, DO

Anesthesiology and Pain Medicine

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Opioids

Side Effects

Tolerance & Dependence

Nausea

Constipation

Delirium

Opioid-induced hyperalgesia

Stimulate mesolimbic reward system

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Opioid Epidemic

  • Top public concern
  • Since 1999 : 1 million deaths
  • Worsened during COVID pandemic
  • 2021 : > 80,000 deaths related to illicit opioid related overdoses, fentanyl
  • 2022: 100,000 people died from opioid related overdose
  • Currently
    • 2.1 million Americans have Opioid Use Disorder
    • Tens of millions on opioid for chronic pain

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OUD (Opioid Use Disorder) = pattern of compulsive use of opioids despite negative consequences

  • There is a connection between perioperative opioid use, postoperative opioid use, and the development of opioid use disorder

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  • Risk factors for developing OUD after surgery
    • Preoperative use of opioids
    • Substance use disorders
    • Preoperative sedatives, anxiolytic
    • Antidepressant use
    • Male sex, younger age, white race, Medicaid, no insurance
    • Psychiatric: Depression, Bipolar, PTSD

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ERAS Protocols

Enhanced Recovery After Surgery

  • Established in 2021, Emphasis on Multimodal Analgesia
  • Reduce risk of OUD after surgery
  • Retrospective study of patients with underwent sleeve gastrectomy or Roux-en-Y gastric bypass following ERAS protocol
    • Decreased length of stay
    • Decreased opioid requirement at discharge
    • 36% reduction in total inpatient opioid use
    • 57% total outpatient opioid use
  • Surgical specialists write highest number of postoperative opioid prescriptions

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ERAS protocols

MMA (Multimodal Analgesia)

Opioid sparing techniques

ERAS = a more systematic approach to Multimodal Analgesia with a goal to minimize perioperative opioid usage Maximize Non-opioid pharmacology

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  • Multimodal Analgesia in Perioperative Setting
    • Neuraxial, Peripheral nerve blocks, IV Lidocaine, acetaminophen, NSAIDs, Ketamine, Membrane stabilizers (gabapentin, pregabalin), magnesium, dexmedetomidine, clonidine
    • Muscle spasms: cyclobenzaprine, tizanidine, methocarbamol

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  • FDA Approved OUD treatment
    • Opioid agonists approved in USA: buprenorphine, methadone
    • Opioid antagonist: naltrexone (prevent recurrence & tx alcohol use disorder)

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Buprenorphine – long acting partial MOR agonist

  • MOA: high affinity partial agonist at mu-opioid receptors + antagonist at kappa and delta opioid receptors + partial agonist at nociceptin receptor
    • Binds very tight to opioid receptor
    • Can theoretically displace full agonists (heroin, oxycodone, morphine) = withdrawal and block euphoric effects
  • Lower risk of respiratory depression and accidental overdose when compared to methadone and other full agonists
    • Favorable safety profile, Ceiling Effect
  • Buprenorphine prescribed for OUD has increased significantly compared to methadone
  • Buprenorphine use during perioperative period
    • Should not be discontinued or tapered perioperatively ( vs prior 2017 ASA rec.)
    • Preop: discuss pain expectations, MMA, regional, early mobilization
    • In presence of buprenorphine, you will need higher than normal doses of any full mu agonist

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Recommendations – American Society of Anesthesiologists

  • Buprenorphine use during perioperative period
    • Should not be discontinued or tapered perioperatively ( vs prior 2017 ASA rec.)
    • Preop: discuss pain expectations, MMA, regional, early mobilization
    • In presence of buprenorphine, you will need higher than normal doses of any full mu agonist

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Buprenorphine

  • Long acting
  • High receptor affinity
  • Slow dissociation rate
  • Increasing evidence in use for
    • Acute Pain
    • Post operative period

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  • Forms
    • Suboxone - SL
    • Subutex - SL
    • Zubsolv - SL
    • Belbuca – buccal
    • Buprenex – Short acting injectable
    • Sublocade – Long acting injectable
    • Butrans – Transdermal patch

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Forms of Buprenorphine

  • Sublingual (Addiction Treatment) - milligram dosing
    • Tablets
      • buprenorphine (used for pregnancy and patients with naloxone allergy)
      • Buprenorphine + naloxone (4:1 ratio)
    • Films - buprenorphine + naloxone (to discourage injection use)
  • Transdermal (Pain) - Butrans - microgram dosing
    • 5 mcg/hr, 7.5 mcg/hr, 10 mcg/hr, 15 mcg/hr, 20 mcg/hr
  • Buccal (Pain) - Belbuca - microgram dosing
    • 75 mcg q12hr, 150, 300, 450, 600, 750, 900 mcg
  • Pain dosing is lower than OUD dosing

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Butrans (buprenorphine transdermal film)

  • Long acting opioid, changed every 7 days, for severe and persistent pain

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Belbuca

buprenorphine buccal film

  • Long acting opioid, taken every 12 hours for severe and persistent pain
  • The buccal film technology allows for 46% to 65% bioavailability of buprenorphine
  • Onset 30-60 minutes, Peak plasma concentration at 3 hours, duration 6-12 hrs

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Patients taking buprenorphine + Acute Pain

  • Duration of action for analgesia - 6-12 hours
  • Hospitalized for 3+ days → change from once daily to every 8 hrs to take full analgesic effect

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  • Increase buprenorphine dose and/or add short acting full mu receptor agonists (fentanyl, hydromorphone, morphine)
  • Maximum dosage: 32 mg/day
  • Reasonable to consider tapering from higher doses to 12-16 mg/day in patients who are expected to have severely painful surgery
  • Oral short acting - 10-20mg oxycodone q3-4 hrs

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  • Orthopedic surgeons are encountering patients:
    • Older patients > 65 years old
    • Chronic Pain
    • Opioid Use Disorder
  • Conversion of opioid naïve 🡪 chronic use is 8-20% with use of SA opioids after total joint arthroplasty, spinal decompression, spinal fusion
    • Short acting opioids may not be good if post operative use is expected to be > 2 weeks and have opioid tolerance, geriatric, or undergoing major surgery (spinal fusion, total joint)

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Buprenorphine in Opiate Naïve Geriatric Patient

  • Movement towards opioid sparing protocols
  • Not tolerated by all geriatric patients
    • Kidney and Liver disease / NSAIDs and Acetaminophen
    • Emerging evidence to use Gabapentin sparingly in patients over 65 years old
  • Buprenorphine
    • Not dialyzed
    • No dose adjustment for renal or hepatic impairment
    • Lower rates of nausea, constipation, cognitive impairment
    • Continue through perioperative period
  • Perioperative Transdermal Buprenorphine (Butrans) in Opiate Naïve
    • Place prior to surgery, up to 7 day relief, remove, 12-18hr gradual tapering of medication
    • Safe and efficacious to add oxycodone/SA opioids for acute pain exacerbations

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Methadone

  • MOA: long-acting opioid agonist, N-methyl-D-aspartate (NMDA) receptor antagonism.
  • Drug interactions
    • Ex: Pt takes methadone + carbamazepine (induces CYP4503A) = accelerate metabolism and may cause acute opioid withdrawal
  • Methadone Maintenance Treatment patient with acute pain
    • Continue baseline opioid
    • Multimodal nonopioid analgesic strategies + supplement incremental opioid
      • Will require higher doses compared to opioid naive
    • Taper once acute pain subsides
  • Retrospective study: Patient on Methadone or Buprenorphine Maintenance + TKA → 7x opioids in perioperative period
  • Postpartum patient on MMT → 70% higher opioid required post Cesarean delivery vs opioid naive patients

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Methadone dosing

  • Long elimination half-life: 24 hours
  • Routes: Oral, IV, subcutaneous
  • Conversion from PO to parenteral
    • ½ oral maintenance dose
    • Divide into BID, TID, or QID dosing
    • 30mg PO methadone daily → 15mg given at 5mg every 8 hours IV
    • May still be undertreated due to significant variability in oral bioavailability
  • IV : more rapid and higher peak serum concentration than oral
    • IV methadone dosing: 0.1-0.2 mg/kg IBW, max 20mg during induction
  • Analgesic effect (6-8 hour) vs Anticraving ( > 24 hours)
  • Acute pain dosing - q8hr
  • OUD - once daily

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Patient taking Methadone + Acute Pain

  • Patient hospitalized for 3+ days on Methadone
  • Divide daily dose to be given every 8 hours
  • Increase 10-20% per day
  • Return to baseline prior to discharge
  • Obtain EKG if methadone is increased > 100mg per day
    • QT prolongation, threatening arrhythmias, torsades de pointes
    • Dose dependent QTc prolongation
  • Better to increase methadone than add an additional ER morphine or oxycodone
  • Oral short acting - 10-20mg oxycodone q2-4 hrs
  • PCA - smaller doses, more continuous levels without large plasma peaks

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Naltrexone

  • XR naltrexone (monthly injection)
  • Oral naltrexone (50mg)
  • MOA: blocks activation of mu opioid receptors, blocks analgesic effect of opioids for acute pain
  • Reduce cravings for alcohol
  • Chronic blockade of opioids = increase opioid receptors = more sensitive to opioid agonists = risk of side effects may be increased (resp. depression)
  • Prior to surgery discontinuation guidelines
    • Oral naltrexone - 3 days prior
    • XR naltrexone - 1 month prior
  • Acute Pain treatment
    • Maximize nonopioid - ketamine, lidocaine infusion, regional
    • Higher doses required if given while naltrexone is in effect

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Naltrexone

  • Low dose
  • Low doses: 4.5mg daily
    • Found to upregulate endogenous opioid production
    • Reduce central pain in patients
  • Studied in:
    • post-COVID syndrome
    • POTS
    • Crohn’s disease
    • Chronic Pain
    • Multiple Sclerosis
    • Fibromyalgia ***most evidence for off-label use
    • Inflammatory Skin Disorders
  • Side Effects: vivid dreams, GI upset, headache, diarrhea

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OUD patient in remission

  • Patients in remission from OUD without medication
    • Giving them opioids for acute pain can cause relapse
    • Avoid opioids if possible
    • Regional anesthesia
  • Opioid tolerance is lost within weeks - months
    • Treat as opioid naive
  • May be preferable to use buprenorphine rather then other opioids

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References

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