Buprenorphine Micro-Induction in Pregnancy

Background:

Buprenorphine is a highly effective treatment for opioid use disorder, but generally requires a period of opioid abstinence prior to induction. This presents a significant barrier to treatment in cases of acute pain, severe dependence, and critical care. Instead, small and steadily escalating doses of buprenorphine can be given over several days, known as microinduction. This can occur in conjunction with full opioid agonist treatment. In critically ill, opioid-dependent patients, this approach can allow tapering of other opioids and sedatives, facilitating extubation. Additionally, the transition can occur alongside other clinical priorities rather than being delayed until near discharge. Microinduction has been described in multiple settings before, but not during pregnancy.

Case report:

A 33-year-old pregnant patient at 31 1/7 weeks gestation with opioid, sedative-hypnotic, and other substance use disorders and history of endocarditis, neurosyphilis, and hepatitis C presented after being found down with altered mental status. She was intubated in the emergency department for respiratory failure and admitted to the medical intensive care unit on fentanyl and midazolam infusions. Several attempts to wean opioids were unsuccessful, preventing traditional buprenorphine induction.

She required escalating doses of opioids and sedatives for agitation and severe dependence, peaking at midazolam 6 mg/h, fentanyl 175 μg/h, methadone 30 mg/d, and phenobarbital 390 mg/d. Norepinephrine was given for hypotension from this regimen. Subsequently, she was started on a buprenorphine microinduction of 150 μg → 300 μg → 1 mg → 2 mg → 4mg, each given buccally every 6 hours for 4 doses. Microgram doses were given as isolated buprenorphine (Belbuca®), milligram doses were given as buprenorphine-naloxone (Suboxone®). Induction proceeded smoothly.

The day after completing microinduction, both methadone and fentanyl were stopped. She was transitioned onto dexmedetomidine and midazolam was also stopped. She was extubated the next day. Buprenorphine 8mg buccally every 8 hours was continued for maintenance therapy. Her altered mental status resolved shortly after. Coordination of care was arranged with an outpatient substance use disorder treatment program but she left against medical advice. She returned at 38 0/7 weeks and delivered a viable male infant via an uncomplicated spontaneous vaginal delivery. His neonatal course was complicated by neonatal abstinence syndrome, mild laryngomalacia, and poor feeding requiring gastrostomy.

Discussion:

This case demonstrates successful buprenorphine microinduction in a critically ill pregnant patient with severe opioid dependence. Microinduction directly contributed to her recovery, allowing better control of her opioid dependence and withdrawal and reduction of her high opioid and sedative needs. This allowed for earlier extubation and reduced time in intensive care. There is no evidence that microinduction is harmful in pregnancy, and in our case a standard microinduction approach was successful. This is the first such case reported during pregnancy.

Conclusion:

Buprenorphine microinduction should be considered for patients who cannot tolerate standard buprenorphine induction. Pregnancy is not a barrier to microinduction. Theoretic downstream risks from neonatal abstinence syndrome have not been demonstrated in recent studies, and opioid replacement therapy should not be withheld in pregnancy.

References:

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2. Minozzi S, Amato L, Bellisario C, Ferri M, Davoli M. Maintenance agonist treatments for opiate-dependent pregnant women. Cochrane Database Syst Rev. 2013; (12):CD006318. doi: 10.1002/14651858.CD006318.pub3.
   
   
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