From the Department of Emergency Medicine, Highland Hospital-Alameda Health System, Oakland, CA (CH, JL, AL, MO, ESA, AAH); Department of Emergency Medicine, University of California, San Francisco, San Francisco, CA (ESA, AAH); Department of Medicine, Highland Hospital- Alameda Health System, Oakland, CA (MU, AAH); University of California, Los Angeles, Los Angeles, CA (SS); Department of Psychiatry and Behavioral Neurosciences, School of Medicine, and Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI (MKG).
J Addict Med. 2022;16(4):483-487. doi: 10.1097/ADM.0000000000000929. Epub 2021 Nov 16.
Optimal treatment of buprenorphine precipitated opioid withdrawal (BPOW) is unclear. Full agonist treatment of BPOW is limited by buprenorphine's high-affinity blockade at mu-opioid receptors (μORs). Buprenorphine's partial agonism (low intrinsic efficacy) at μORs can limit the effectiveness of even massive doses once BPOW has begun. Adjunct medications, such as clonidine, are rarely effective in severe BPOW. Ketamine is an N -methyl-D-aspartate receptor antagonist with a potentially ideal pharmacologic profile for treatment of BPOW. Ketamine reduces opioid withdrawal symptoms independently of direct μOR binding, synergistically potentiates the effectiveness of buprenorphine μOR signaling, reverses (resensitizes) fentanyl induced μOR receptor desensitization, and inhibits descending pathways of hyperalgesia and central sensitization. Ketamine's rapid antidepressant effects potentially address depressive symptoms and subjective distress that often accompanies BPOW. Ketamine is inexpensive, safe, and available in emergency departments. To date, neither ketamine as treatment for BPOW nor to support uncomplicated buprenorphine induction has been described.
We report a case of an illicit fentanyl-using OUD patient who experienced severe BPOW during an outpatient low-dose cross taper buprenorphine induction (ie, "microdose"). The BPOW was successfully treated in the emergency department with a combination of ketamine (0.6 mg/kg intravenous over 1 hour) combined with high-dose buprenorphine (16 mg sublingual single dose); 3 days later he was administered a month-long dose of extended-release subcutaneous buprenorphine which was repeated monthly (300 mg). At 90 days the patient remained in treatment and reported continuous abstinence from fentanyl use.
This single case observation raises important questions about the potential therapeutic role of ketamine as a treatment for BPOW. BPOW is an important clinical problem for which there is currently only limited guidance and no universally accepted approach. Prospective study comparing the effectiveness of differing pharmacologic approaches to treat BPOW is urgently needed.
布比卡因诱发的阿片类药物戒断（BPOW）的最佳治疗方法尚不清楚。BPOW 的完全激动剂治疗受到布比卡因对 μ 阿片受体（μOR）高亲和力阻断的限制。布比卡因在 μOR 上的部分激动作用（低内在效能），即使在 BPOW 开始后，即使使用大剂量也可能限制其疗效。辅助药物，如可乐定，在严重 BPOW 中很少有效。氯胺酮是一种 N-甲基-D-天冬氨酸受体拮抗剂，具有治疗 BPOW 的潜在理想药理学特征。氯胺酮可独立于直接 μOR 结合减轻阿片类药物戒断症状，协同增强布比卡因 μOR 信号的有效性，逆转（重新敏化）芬太尼诱导的 μOR 受体脱敏，并抑制痛觉过敏和中枢敏化的下行通路。氯胺酮的快速抗抑郁作用可能解决 BPOW 常伴随的抑郁症状和主观痛苦。氯胺酮便宜、安全，并且在急诊科都有。迄今为止，既没有描述氯胺酮作为 BPOW 的治疗方法，也没有描述其作为支持简单布比卡因诱导的方法。
我们报告了一例使用非法芬太尼的 OUD 患者，他在门诊低剂量交叉滴注布比卡因诱导（即“微剂量”）过程中经历了严重的 BPOW。BPOW 在急诊科成功治疗，方法是静脉注射 0.6mg/kg 氯胺酮 1 小时，同时给予高剂量布比卡因（16mg 舌下单次剂量）；3 天后，他接受了一个月的皮下缓释布比卡因治疗，每月重复一次（300mg）。90 天后，患者仍在接受治疗，并报告持续戒断芬太尼。
这一单一病例观察提出了关于氯胺酮作为 BPOW 治疗方法的潜在治疗作用的重要问题。BPOW 是一个重要的临床问题，目前只有有限的指导意见，也没有普遍接受的方法。迫切需要进行比较不同药物治疗 BPOW 效果的前瞻性研究。
