Agin-Liebes Gabrielle, Huhn Andrew S, Strain Eric C, Bigelow George E, Smith Michael T, Edwards Robert R, Gruber Valerie A, Tompkins D Andrew
University of California, San Francisco, Department of Psychiatry and Behavioral Sciences, 401 Parnassus Ave, San Francisco, CA, 94143, USA; Zuckerberg San Francisco General Hospital, 1001 Potrero Ave, Ward 95, San Francisco, CA, 94110, USA.
Johns Hopkins University School of Medicine, Department of Psychiatry and Behavioral Sciences, 4940 Eastern Avenue, Baltimore, MD, 21224, USA.
Drug Alcohol Depend. 2021 Sep 1;226:108869. doi: 10.1016/j.drugalcdep.2021.108869. Epub 2021 Jun 25.
Acute pain management in patients with opioid use disorder who are maintained on methadone presents unique challenges due to high levels of opioid tolerance in this population. This randomized controlled study assessed the analgesic and abuse liability effects of escalating doses of acute intravenous (IV) hydromorphone versus placebo utilizing a validated experimental pain paradigm, quantitative sensory testing (QST).
Individuals (N = 8) without chronic pain were maintained on 80-100 mg/day of oral methadone. Participants received four IV, escalating/incremental doses of hydromorphone over 270 min (32 mg total) or four placebo doses within a session test day. Test sessions were scheduled at least one week apart. QST and abuse liability measures were administered at baseline and after each injection.
No significant differences between the hydromorphone and placebo control conditions on analgesic indices for any QST outcomes were detected. Similarly, no differences on safety or abuse liability indices were detected despite the high doses of hydromorphone utilized. Few adverse events were detected, and those reported were mild in severity.
The findings demonstrate that methadone-maintained individuals are highly insensitive to the analgesic effects of high-dose IV hydromorphone and may require very high doses of opioids, more efficacious opioids, or combined non-opioid analgesic strategies to achieve adequate analgesia.
对于使用美沙酮维持治疗的阿片类药物使用障碍患者，急性疼痛管理面临独特挑战，因为该人群阿片类药物耐受性水平较高。这项随机对照研究利用经过验证的实验性疼痛范式——定量感觉测试（QST），评估了递增剂量的急性静脉注射氢吗啡酮与安慰剂的镇痛效果及滥用倾向影响。
8名无慢性疼痛的个体口服美沙酮，剂量为每天80 - 100毫克。在一个测试日内，参与者接受4次静脉注射，氢吗啡酮剂量递增/逐次增加，共270分钟（总量32毫克），或4次安慰剂注射。测试 sessions 至少间隔一周安排。在基线和每次注射后进行QST和滥用倾向测量。
在任何QST结果的镇痛指标上，未检测到氢吗啡酮与安慰剂对照条件之间的显著差异。同样，尽管使用了高剂量的氢吗啡酮，但在安全性或滥用倾向指标上也未检测到差异。检测到的不良事件很少，且报告的不良事件严重程度较轻。
研究结果表明，美沙酮维持治疗的个体对高剂量静脉注射氢吗啡酮的镇痛效果高度不敏感，可能需要非常高剂量的阿片类药物、更有效的阿片类药物或联合非阿片类镇痛策略才能实现充分镇痛。
