Thapar P, Zacny J P, Thompson W, Apfelbaum J L
Department of Anesthesia and Critical Care, University of Chicago, Illinois 60637.
Anesthesiology. 1995 Jan;82(1):53-9. doi: 10.1097/00000542-199501000-00008.
There is a need for a standard by which to compare the degree of subjective and behavioral impairment caused by anesthetic drugs, because anesthesiologists may not be able to gauge how extreme or important a statistically significant change in psychomotor functioning is. This study examined the psychomotor and subjective effects of alcohol at blood concentrations equal or greater than 0.10% as a standard with which to compare those effects caused by sedative and analgesic agents commonly used in ambulatory surgery.
Twelve healthy human volunteers (11 men and 1 nonpregnant woman), with an average age of 28 yr (range 24-34 yr) and an average alcohol consumption of four drinks per week, were selected in this institutional review board-approved study. Each subject was exposed to five drug conditions (70 mg/70 kg propofol intravenously, 2 mg/70 kg midazolam intravenously, 50 micrograms/70 kg fentanyl intravenously, 0.8 g/kg alcohol orally, and placebo orally and intravenously) in a double-blind randomized fashion over five weekly sessions. Testing was done at baseline and at different intervals until 240 min after drug administration. Testing included psychomotor performance (Maddox Wing, eye-hand coordination, auditory reaction time test, and digit symbol substitution test), subjective effects (strength of drug effect scale, drug liking scale, and visual analog scale), and short-term memory. Psychomotor performance was used as an index of objective impairment, and mood was used as an index of subjective impairment.
After consumption of the alcoholic beverage, a blood alcohol level of 0.11 +/- 0.003% (mean +/- SE) was obtained at 15 min after injection. The study drugs not only produced statistically significant impairment (i.e., impairment greater than that seen with placebo) but also, at one or more times after injection, produced impairment similar to that observed with alcohol at a blood alcohol concentration of 0.11%. Midazolam produced a similar degree of impairment to that of alcohol for a longer duration than did fentanyl and propofol.
This study provides evidence that degree of impairment caused by sedative and analgesic drugs used in ambulatory surgery is similar to that obtained with a dose of alcohol that produces a blood alcohol concentration of 0.11%. We suggest that anesthesiologists can use alcohol as a standard by which to assess degree of impairment produced by drugs used for sedation/analgesia.
需要一个标准来比较麻醉药物引起的主观和行为损害程度，因为麻醉医生可能无法判断心理运动功能的统计学显著变化有多严重或多重要。本研究检测了血液浓度等于或高于0.10%的酒精的心理运动和主观效应，以此作为比较门诊手术中常用镇静和镇痛药物所引起效应的标准。
在这项经机构审查委员会批准的研究中，选取了12名健康志愿者（11名男性和1名未怀孕女性），平均年龄28岁（范围24 - 34岁），平均每周饮酒量为4杯。在五个每周一次的疗程中，以双盲随机方式让每位受试者暴露于五种药物状态（静脉注射70mg/70kg丙泊酚、静脉注射2mg/70kg咪达唑仑、静脉注射50μg/70kg芬太尼、口服0.8g/kg酒精以及口服和静脉注射安慰剂）。在基线以及给药后不同时间间隔直至240分钟进行测试。测试包括心理运动表现（马多克斯翼试验、眼手协调试验、听觉反应时间测试和数字符号替换测试）、主观效应（药物效应强度量表、药物喜好量表和视觉模拟量表）以及短期记忆。心理运动表现用作客观损害指标，情绪用作主观损害指标。
饮用酒精饮料后，注射后15分钟时血液酒精水平为0.11±0.003%（均值±标准误）。研究药物不仅产生了统计学显著的损害（即比安慰剂引起更严重的损害），而且在注射后某一或多个时间点，产生的损害与血液酒精浓度为0.11%时酒精所引起的损害相似。咪达唑仑产生的损害程度与酒精相似，且持续时间比芬太尼和丙泊酚更长。
本研究提供了证据表明门诊手术中使用的镇静和镇痛药物所引起的损害程度与产生血液酒精浓度为0.11%的酒精剂量所造成的损害程度相似。我们建议麻醉医生可以将酒精作为评估用于镇静/镇痛药物所产生损害程度的标准。
