Background: Midazolam and acetaminophen are often co-administered in anesthesia practice. Both are metabolized by CYP 3A4 enzyme in the liver, and hence compete for the enzyme sites. This might lead to reduced metabol...Background: Midazolam and acetaminophen are often co-administered in anesthesia practice. Both are metabolized by CYP 3A4 enzyme in the liver, and hence compete for the enzyme sites. This might lead to reduced metabolic breakdown and enhanced pharmacodynamic effects of midazolam in the presence of acetaminophen. Methods: The present study was undertaken to test this hypothesis. After IRB approval from Mount Sinai Medical Center, 15 healthy volunteers were used for 2 tests. For the first test, they were randomly assigned to receive oral doses of either midazolam 0.3 mg/kg in cherry syrup (Protocol A), or midazolam 0.3 mg/kg plus cherry flavored acetaminophen 15 mg/kg (Protocol B). At set intervals from 0 to 480 min, the blood levels of midazolam and the subjects pulse rate, mean arterial pressure, respiratory rate, BIS index, and OAA/S scores were determined. After 2 weeks, the same subjects underwent the second test;they received the other medication protocol. Results: Acetaminophen slightly, but not significantly, increased the half life of blood midazolam, and the depressive effects of midazolam on the clinical signs of the subjects. Conclusion: These results lead us to conclude that there is no need to reduce the doses of midazolam when used in combination with acetaminophen.展开更多
目的观察帕金森病(Parkinson’s disease,PD)患者与非PD患者丙泊酚诱导意识消失所需的效应室浓度(effect-site concentration,Ce)。方法纳入2022年10月16日至2023年10月14日于首都医科大学附属北京天坛医院就诊的患者,筛选年龄50~80岁,...目的观察帕金森病(Parkinson’s disease,PD)患者与非PD患者丙泊酚诱导意识消失所需的效应室浓度(effect-site concentration,Ce)。方法纳入2022年10月16日至2023年10月14日于首都医科大学附属北京天坛医院就诊的患者,筛选年龄50~80岁,美国麻醉医师协会(American Society of Anesthesiologists,ASA)分级Ⅱ-Ⅲ级,行双侧脑深部电刺激手术的PD患者(PD组),并按照年龄和性别匹配选取同期行非神经外科非心脏手术的非PD患者(Non-PD组)各37例为研究对象。采用Schnider模型靶控泵注丙泊酚,警觉/镇静观察(Observer’s Assessment of Alertness/Sedation,OAA/S)评分达1分后20 s评估意识状态,采集5 min临床试验数据后停药,记录给药后OAA/S评分1分时、停药后OAA/S评分3分时丙泊酚的Ce、患者状态指数(patient state index,PSI)。结果PD患者组诱导至无意识状态所需丙泊酚剂量明显少于Non-PD患者组[(2.2±0.4)mg/L vs(3.1±0.4)mg/L,P<0.05];与Non-PD患者比较,PD患者意识消失和意识恢复时的PSI值更高(P<0.05),意识恢复时间明显延长(P<0.05),意识恢复时丙泊酚Ce更低(P<0.05)。结论PD患者诱导意识消失所需的丙泊酚剂量降低,且需要在更低的Ce下苏醒,苏醒时间明显长于非PD患者,在意识消失和苏醒时的PSI均高于非PD患者,麻醉管理中应予以重视。展开更多
文摘Background: Midazolam and acetaminophen are often co-administered in anesthesia practice. Both are metabolized by CYP 3A4 enzyme in the liver, and hence compete for the enzyme sites. This might lead to reduced metabolic breakdown and enhanced pharmacodynamic effects of midazolam in the presence of acetaminophen. Methods: The present study was undertaken to test this hypothesis. After IRB approval from Mount Sinai Medical Center, 15 healthy volunteers were used for 2 tests. For the first test, they were randomly assigned to receive oral doses of either midazolam 0.3 mg/kg in cherry syrup (Protocol A), or midazolam 0.3 mg/kg plus cherry flavored acetaminophen 15 mg/kg (Protocol B). At set intervals from 0 to 480 min, the blood levels of midazolam and the subjects pulse rate, mean arterial pressure, respiratory rate, BIS index, and OAA/S scores were determined. After 2 weeks, the same subjects underwent the second test;they received the other medication protocol. Results: Acetaminophen slightly, but not significantly, increased the half life of blood midazolam, and the depressive effects of midazolam on the clinical signs of the subjects. Conclusion: These results lead us to conclude that there is no need to reduce the doses of midazolam when used in combination with acetaminophen.
文摘目的观察帕金森病(Parkinson’s disease,PD)患者与非PD患者丙泊酚诱导意识消失所需的效应室浓度(effect-site concentration,Ce)。方法纳入2022年10月16日至2023年10月14日于首都医科大学附属北京天坛医院就诊的患者,筛选年龄50~80岁,美国麻醉医师协会(American Society of Anesthesiologists,ASA)分级Ⅱ-Ⅲ级,行双侧脑深部电刺激手术的PD患者(PD组),并按照年龄和性别匹配选取同期行非神经外科非心脏手术的非PD患者(Non-PD组)各37例为研究对象。采用Schnider模型靶控泵注丙泊酚,警觉/镇静观察(Observer’s Assessment of Alertness/Sedation,OAA/S)评分达1分后20 s评估意识状态,采集5 min临床试验数据后停药,记录给药后OAA/S评分1分时、停药后OAA/S评分3分时丙泊酚的Ce、患者状态指数(patient state index,PSI)。结果PD患者组诱导至无意识状态所需丙泊酚剂量明显少于Non-PD患者组[(2.2±0.4)mg/L vs(3.1±0.4)mg/L,P<0.05];与Non-PD患者比较,PD患者意识消失和意识恢复时的PSI值更高(P<0.05),意识恢复时间明显延长(P<0.05),意识恢复时丙泊酚Ce更低(P<0.05)。结论PD患者诱导意识消失所需的丙泊酚剂量降低,且需要在更低的Ce下苏醒,苏醒时间明显长于非PD患者,在意识消失和苏醒时的PSI均高于非PD患者,麻醉管理中应予以重视。
