Anesthesia Implications

Affinity – High μ-receptor affinity (1000x morphine and 10x naloxone) means other perioperative opioids will not compete well for μ-receptors. Primary point is that intraoperative opioids may be less effective or ineffective. Picture a dose response curve with a steeper slope but a lower maximal efficacy.

Potency – Roughly 30x the potency of morphine.

Reversal – Narcan reversal of buprenorphine is difficult. Doses up to 10 mg may be needed to reverse the clinical effects. Additionally, the half-life of buprenorphine is much longer than Narcan, so a Narcan maintenance infusion would likely be needed to suppress buprenorphine’s effects over the long term (which isn’t realistic in most anesthetic plans).

Minor procedures – recommended to continue buprenorphine, supplement with adjuncts but not opioids without agreement from patient and prescriber.

Planned surgeries of moderate/severe pain – consult with buprenorphine provider for short-acting opioid to stop buprenorphine for 24hrs for 4mg dose, 48hrs for 8mg dose, 72hrs for 12mg dose. Consult with buprenorphine provider for doses greater than 12mg (hold up to 5 days) and anticipate opioid tolerance if permission for other opioids is attained. Ensure outpatient follow-up with prescribing physician.

Emergency surgeries (or buprenorphine not held) – anticipate tolerance and plan to maximize multimodal analgesia. Depending on the level of tolerance, using an opioid-focused analgesia can have consequences that may outweigh the benefits (uncontrolled post-operative pain management, respiratory depression, an increase in hospital stay and healthcare costs, hyperalgesia, and an increase chance for relapse). Consider PCA to be managed by Acute Pain Services (APS). Ensure outpatient follow-up with the prescribing physician.

The Parturient – Methadone and buprenorphine maintenance therapy prevents maternal withdrawal from opioids, but may still cause withdrawal if on a high enough dose of a full-agonist opioid.

Dosing considerations – High doses (up to 32mg/day PO) are seen for opioid use disorder. Lower doses divided to BID or TID (4-24mg/day PO, median dose 16mg/day PO) for chronic pain. Sublingual (Subutex): 16mg binds to 79-95% of μ-receptors, and greater than 24-32mg does not produce any greater opioid effect.

Suboxone (sublingual) – see “Buprenorphine/Naloxone”. This is buprenorphine + Narcan. This is designed to give the patient the effects of buprenorphine, but to disallow patient abuse by IV injection. The Narcan component has extensive first-pass hepatic metabolism with only 0-2% bioavailability orally, and less than 10% bioavailability sublingual. In other words, if suboxone is taken as prescribed, it will have its therapeutic affects. If the patient attempts to abuse this drug by injecting it, the Narcan component will reverse the buprenorphine effects. Therefore, Suboxone has a lower abuse rate than buprenorphine alone.

Classification: mu partial agonist, weak kappa receptor antagonist, and delta receptor agonist

Time to Onset: Sublingual: 30-60 mins; IV: 15-30 mins

Time to Peak: Sublingual: 2-4 hours; IV: 60 mins

Duration: Sublingual half-life: ~ 24-60h (highly variable); IV: half-life 2-7 hrs (highly variable); SQ: Extended-release injection (Sublocade) can last 28 days, terminal half-life 43 to 60 days; Transdermal patch: half-life: ~26 hours.

Method of Action: mu partial-agonist, weak kappa and delta antagonist. Antagonism is greater for kappa than delta receptors. Buprenorphine is a highly lipophilic semi-synthetic thebaine derivative. Partial agonists never achieve the same intensity as a full agonist, so there is less risk of respiratory depression, but they have a ceiling effect beyond which additional opioid analgesia is not possible and antagonist properties as well as other adverse effects will predominate.

Metabolism: Liver (CYP450 3A4) and intestinal mucosa. Active metabolite is norbuprenorphine.

Elimination: Buprenorphine and metabolites are excreted 30% in the urine and 70% through the feces. Renal impairment (including administration pre or post-hemodialysis) was NOT associated with increased buprenorphine plasma concentrations.

Additional Notes:
Buprenorphine is approved by the FDA for opioid use disorder, off-label use for heroin withdrawal and perineural anesthesia.

Contraindications, Precautions, Side Effects:
GI obstruction, paralytic ileus
Long QT syndrome, class IA or III antiarrythmics, hypokalemia, hypomagnesemia
Respiratory Depression
Patient taking any agent that blocks CYP3A4 (erythromycin, diltiazem, ketoconazole, ritonavir, verapamil, ciprofloxacin, etc.) will have reduced metabolism in the liver and increased risk of overdose.
Preexisting hepatic impairment increases risk of hepatitis