Buprenorphine-precipitated opioid withdrawal is seen in physically opioid-dependent patients who have recently taken full agonist opioids and are subsequently receiving buprenorphine. (J Addict Med. 2021 Nov 16. doi:10.1097/ADM.0000000000000929.) Withdrawal intensity can range from mild to life-threatening. (J Addict Med. 2021 Nov 16. doi:10.1097/ADM.0000000000000929; Cardiovascular toxicol. 2021;21:349.)
Patients with severe withdrawal typically present to the emergency room for acute treatment, and reports indicate this occurs more frequently in fentanyl users. (J Addict Med. 2021 Nov 16. doi:10.1097/ADM.0000000000000929; Familiarization practice. 2021 Jun 26. doi:10.1093/fampra/cmab073.)
The optimal treatment of buprenorphine-precipitated opioid withdrawal is unclear. Supportive care such as clonidine and antiemetics may help in mild cases, but are inadequate in severe cases. (J Addict Med. 2021 Nov 16. doi:10.1097/ADM.0000000000000929; Cardiovascular toxicol. 2021;21:349.) The administration of supplemental buprenorphine may be limited by the ceiling effect resulting from the partial agonism of buprenorphine. The effectiveness of full agonist opioids (eg, hydromorphone) for treating buprenorphine-precipitated opioid withdrawal is limited by high-affinity blockade of buprenorphine at mu-opioid receptors.
Successfully overcoming the opioid activation deficiency causing this withdrawal requires overcoming this block and may require full doses of agonists well outside the range of common clinical practice (eg, 32 mg of hydromorphone IV). (J Addict Med. 2021 Nov 16. doi:10.1097/ADM.0000000000000929; Alcohol addiction. 2014;144:1; https://bit.ly/3niag8h.)
Ketamine has an ideal pharmacological profile for treating buprenorphine-precipitated opioid withdrawal, as it reduces opioid withdrawal symptoms independent of direct binding to mu-opioid receptors, among other properties. A recent case report described the successful use of ketamine (0.6 mg/kg IV over 1 hour) in the emergency department for severe opioid withdrawal precipitated by buprenorphine. (J Addict Med. 2021 Nov 16. doi:10.1097/ADM.0000000000000929.) Ketamine is inexpensive, safe, and familiar to emergency physicians, and should be considered when faced with a case that is severely refractory to other treatment.
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