Bailey P L, Pace N L, Ashburn M A, Moll J W, East K A, Stanley T H
Department of Anesthesiology, University of Utah School of Medicine, Salt Lake City 84132.
Anesthesiology. 1990 Nov;73(5):826-30. doi: 10.1097/00000542-199011000-00005.
More than 80 deaths have occurred after the use of midazolam (Versed), often in combination with opioids, to sedate patients undergoing various medical and surgical procedures. We investigated the respiratory effects of midazolam (0.05 mg.kg-1) and fentanyl (2.0 micrograms.kg-1) in volunteers. The incidence of hypoxemia (oxyhemoglobin saturation less than 90%) and apnea (no spontaneous respiratory effort for 15 s) and the ventilatory response to carbon dioxide were evaluated. Midazolam alone produced no significant respiratory effects. Fentanyl alone produced hypoxemia in half of the subjects and significant depression of the ventilatory response to CO2, but did not produce apnea. Midazolam and fentanyl in combination significantly increased the incidence of hypoxemia (11 of 12 subjects) and apnea (6 of 12 subjects), but did not depress the ventilatory response to CO2 more than did fentanyl alone. Adverse reactions linked to midazolam and reported to the Department of Health and Human Services highlight apnea- and hypoxia-related problems as among the most frequent adverse reactions. Seventy-eight per cent of the deaths associated with midazolam were respiratory in nature, and in 57% an opioid had also been administered. All but three of the deaths associated with the use of midazolam occurred in patients unattended by anesthesia personnel. We conclude that combining midazolam with fentanyl or other opioids produces a potent drug interaction that places patients at a high risk for hypoxemia and apnea. Adequate precautions, including monitoring of patient oxygenation with pulse oximetry, the administration of supplemental oxygen, and the availability of persons skilled in airway management are recommended when benzodiazepines are administered in combination with opioids.
在使用咪达唑仑（速眠安）后已发生80多例死亡，通常是在与阿片类药物联合使用时，用于对接受各种医疗和外科手术的患者进行镇静。我们研究了咪达唑仑（0.05mg/kg）和芬太尼（2.0μg/kg）对志愿者的呼吸影响。评估了低氧血症（氧合血红蛋白饱和度低于90%）和呼吸暂停（15秒内无自主呼吸）的发生率以及对二氧化碳的通气反应。单独使用咪达唑仑未产生明显的呼吸影响。单独使用芬太尼使一半的受试者出现低氧血症，并显著抑制对二氧化碳的通气反应，但未导致呼吸暂停。咪达唑仑和芬太尼联合使用显著增加了低氧血症（12名受试者中的11名）和呼吸暂停（12名受试者中的6名）的发生率，但对二氧化碳通气反应的抑制程度并不比单独使用芬太尼时更严重。与咪达唑仑相关并向卫生与公众服务部报告的不良反应突出显示，与呼吸暂停和缺氧相关的问题是最常见的不良反应之一。与咪达唑仑相关的死亡中有78%是呼吸系统性质的，并且在57%的病例中还使用了阿片类药物。与使用咪达唑仑相关的死亡中，除3例之外均发生在无麻醉人员照料的患者身上。我们得出结论，将咪达唑仑与芬太尼或其他阿片类药物联合使用会产生强效的药物相互作用，使患者处于发生低氧血症和呼吸暂停的高风险中。当苯二氮䓬类药物与阿片类药物联合使用时，建议采取充分的预防措施，包括用脉搏血氧饱和度仪监测患者的氧合情况、给予补充氧气以及配备气道管理技术熟练的人员。
