Kienbaum P, Thürauf N, Michel M C, Scherbaum N, Gastpar M, Peters J
Abteilung für Anästhesiologie und Intensivmedizin, Universität GH Essen, Germany.
Anesthesiology. 1998 May;88(5):1154-61. doi: 10.1097/00000542-199805000-00004.
Acute displacement of opioids from their receptors by administration of large doses of opioid antagonists during general anesthesia is a new approach for detoxification of patients addicted to opioids. The authors tested the hypothesis that mu-opioid receptor blockade by naloxone induces cardiovascular stimulation mediated by the sympathoadrenal system.
Heart rate, cardiac index, and intravascular pressures were measured in 10 patients addicted to opioids (drug history; mean +/- SD, 71 +/- 51 months) during a program of methadone substitution (96 +/- 57 mg/day). Cardiovascular variables and concentrations of catecholamine in plasma were measured in the awake state, during methohexital-induced anesthesia (dose, 74 +/- 44 microg x kg(-1) x min(-1)) before administration of naloxone, and repeatedly during the first 3 h of mu-opioid receptor blockade. Naloxone was administered initially in an intravenous dose of 0.4 mg, followed by incremental bolus doses (0.8, 1.6, 3.2, and 6.4 mg) at 15-min intervals until a total dose of 12.4 mg had been administered within 60 min; administration was then continued by infusion (0.8 mg/h).
Concentration of epinephrine in plasma increased 30-fold (15 +/- 9 to 458 +/- 304 pg/ml), whereas concentration of norepinephrine in plasma only increased to a minor extent (76 +/- 44 to 226 +/- 58 pg/ml, P < 0.05). Cardiac index increased by 74% (2.7 +/- 0.41 to 4.7 +/- 1.7 min(-1) x m(-2)), because of increases in heart rate (89 +/- 16 to 108 +/- 17 beats/min) and stroke volume (+44%), reaching maximum 45 min after the initial injection of naloxone. In parallel, systemic vascular resistance index decreased (-40%). Systolic arterial pressure significantly increased (113 +/- 16 to 138 +/- 16 mmHg), whereas diastolic arterial pressure did not change.
Despite barbiturate-induced anesthesia, acute mu-opioid receptor blockade in patients addicted to opioids induces profound epinephrine release and cardiovascular stimulation. These data suggest that long-term opioid receptor stimulation changes sympathoadrenal and cardiovascular function, which is acutely unmasked by mu-opioid receptor blockade. Because of the attendant cardiovascular stimulation, acute detoxification using naloxone should be performed by trained anesthesiologists or intensivists.
在全身麻醉期间通过给予大剂量阿片类拮抗剂使阿片类药物从其受体上急性解离，是一种用于阿片类药物成瘾患者脱毒的新方法。作者检验了纳洛酮阻断μ-阿片受体可诱导由交感肾上腺系统介导的心血管刺激这一假说。
在10名阿片类药物成瘾患者（用药史；平均±标准差，71±51个月）进行美沙酮替代治疗（96±57毫克/天）期间，测量其心率、心脏指数和血管内压力。在清醒状态下、在给予纳洛酮前的甲己炔巴比妥诱导麻醉期间（剂量，74±44微克·千克⁻¹·分钟⁻¹）以及在μ-阿片受体阻断的最初3小时内反复测量心血管变量和血浆中儿茶酚胺浓度。纳洛酮最初静脉注射剂量为0.4毫克，随后每隔15分钟递增推注剂量（0.8、1.6、3.2和6.4毫克），直至在60分钟内给予总量12.4毫克；然后持续输注（0.8毫克/小时）。
血浆肾上腺素浓度增加了30倍（15±9至458±304皮克/毫升），而血浆去甲肾上腺素浓度仅略有增加（76±44至226±58皮克/毫升，P<0.05）。心脏指数增加了74%（2.7±0.41至±1.7分钟⁻¹·米⁻²），这是由于心率增加（89±16至108±17次/分钟）和每搏输出量增加（+44%），在最初注射纳洛酮后45分钟达到最大值。同时，全身血管阻力指数下降（-40%）。收缩动脉压显著升高（113±16至138±16毫米汞柱），而舒张动脉压未改变。
尽管有巴比妥类药物诱导的麻醉，但阿片类药物成瘾患者急性μ-阿片受体阻断仍会引起大量肾上腺素释放和心血管刺激。这些数据表明，长期的阿片受体刺激会改变交感肾上腺和心血管功能，而μ-阿片受体阻断会使其急性暴露。由于伴随的心血管刺激，使用纳洛酮进行急性脱毒应由训练有素的麻醉医生或重症监护医生进行。
