Severe Prolonged Sedation Associated with Coadministration of Protease Inhibitors and Intravenous Midazolam During Bronchoscopy
Severe Prolonged Sedation Associated with Coadministration of Protease Inhibitors and Intravenous Midazolam During Bronchoscopy
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DOI：
10.1002/j.1875-9114.2011.01045.x
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发表时间：
2012-06-01
期刊：
影响因子：
4.1
通讯作者：
Pham, Paul A.
中科院分区：
文献类型：
--
作者：
Hsu, Alice Jenh;Carson, Kathryn A.;Pham, Paul A.
研究目的 确定在住院支气管镜检查过程中接受静脉注射咪达唑仑的人类免疫缺陷病毒 (HIV) 阳性患者，如果接受包含蛋白酶抑制剂的抗逆转录病毒治疗，与未接受任何抗逆转录病毒治疗的患者相比，是否更有可能经历严重的长时间镇静。设计回顾性队列研究。设置三级护理学术医疗中心。患者 对 2003 年 1 月 1 日至 2006 年 12 月 31 日期间接受支气管镜检查时接受静脉注射咪达唑仑的 241 名 HIV 阳性成人进行了分析； 51 名患者正在接受包含蛋白酶抑制剂的抗逆转录病毒治疗方案（暴露组），而 190 名患者则未服用任何抗逆转录病毒药物（非暴露组）。测量和主要结果从电子数据库和患者病历中收集患者人口统计数据、用药记录和支气管镜检查数据。暴露组和非暴露组具有相似的人口统计特征，只是暴露组患者的 HIV 病毒载量较低，并且在支气管镜检查前精神状态改变或呼吸窘迫的可能性较小。此外，暴露组中男性和乙型或丙型肝炎病毒合并感染的患者比例较高。暴露组严重长时间镇静的发生率为 9.80%，而非暴露组为 1.58%（相对风险 [RR] 6.21，95% 置信区间 [CI] 1.5325.12）。与严重长时间镇静相关的特异性蛋白酶抑制剂是阿扎那韦-利托那韦和洛匹那韦-利托那韦。与非暴露组相比，暴露组的住院时间长约 3 天。结论 尽管静脉注射咪达唑仑和蛋白酶抑制剂之间的相互作用众所周知，但据我们所知，这项研究是对住院 HIV 阳性患者队列中严重长时间镇静风险的首次系统评估。蛋白酶抑制剂与静脉注射咪达唑仑的共同给药与镇静时间严重延长以及住院时间增加有关。因此，应密切监测这些药物的同时使用，或应考虑使用替代镇静剂进行程序镇静。
Study Objective To determine whether human immunodeficiency virus (HIV)-positive patients who received intravenous midazolam during an inpatient bronchoscopy procedure were more likely to experience severe prolonged sedation if they were taking antiretroviral therapy that included a protease inhibitor versus those who were not taking any antiretroviral therapy. Design Retrospective cohort study. Setting Tertiary care academic medical center. Patients Two hundred forty-one HIV-positive adults who received intravenous midazolam while undergoing bronchoscopy between January 1, 2003, and December 31, 2006, were analyzed; 51 patients were taking an antiretroviral regimen that included a protease inhibitor (exposed group), whereas 190 patients were not taking any antiretroviral agents (nonexposed group). Measurements and Main Results Patient demographics, medication administration records, and bronchoscopy data were collected from electronic databases and patient medical records. The exposed and nonexposed groups had similar demographic characteristics except that patients in the exposed group had lower HIV viral loads and were less likely to have altered mental status or respiratory distress before bronchoscopy. In addition, the exposed group had a higher proportion of males and patients with hepatitis B or C virus coinfection. The incidence of severe prolonged sedation was 9.80% in the exposed group versus 1.58% in the nonexposed group (relative risk [RR] 6.21, 95% confidence interval [CI] 1.5325.12). Specific protease inhibitors associated with severe prolonged sedation were atazanavir-ritonavir and lopinavir-ritonavir. Length of hospital stay was approximately 3 days longer in the exposed group compared with the nonexposed group. Conclusion Although the interaction between intravenous midazolam and protease inhibitors is well known, this study was the first systematic evaluation, to our knowledge, of the risk of severe prolonged sedation in a cohort of hospitalized HIV-positive patients. Coadministration of protease inhibitors with intravenous midazolam was associated with severe prolonged sedation as well as increased length of hospital stay. Therefore, concomitant use of these drugs should be closely monitored, or alternative sedatives for procedural sedation should be considered.