Eisenhauer M D, Eliasson A H, Taylor A J, Coyne P E, Wortham D C
Department of Medicine, Walter Reed Army Medical Center, Washington, DC.
Chest. 1994 Feb;105(2):389-95. doi: 10.1378/chest.105.2.389.
There have been 15 published cases of probable pentamidine-induced torsade de pointes (TdP). A prospective analysis of this complication of therapy is valuable considering the high frequency of Pneumocystis carinii pneumonia in the AIDS population, and the role of pentamidine in its therapy.
Open, nonrandomized, prospective study of HIV-infected patients receiving intravenous pentamidine in a 12-month period.
Walter Reed Army Medical Center, a tertiary care, referral-based facility in Washington, DC.
Eighteen HIV-infected patients were enrolled with informed consent; four were withdrawn from statistical analysis after receiving only one or two doses of empiric intravenously administered pentamidine.
Daily 12-lead electrocardiography, echocardiography, weekly signal-averaged electrocardiography, and weekly 24-h ambulatory electrocardiography were performed on each patient. Of the 14 subjects, 3 developed TdP. These 3 patients and 2 others developed a prolonged rate corrected, QT interval (QTc) to greater than 0.48 s (max QTc mean, 0.55 s, mean increase, 0.12 s). The QTc prolongation was noted in all five patients by the fourth daily dose (4 mg/kg/d) of pentamidine. The other 9 patients developed minimal change in QTc intervals throughout therapy (max QTc mean, 0.45 s; mean increase, 0.03 s). The maximum QTc increase was significantly different between these two cohorts (p < 0.03). The occurrence of TdP in the subgroup of patients developing prolonged QTc intervals to greater than 0.48 s (3 of 5 patients), or a change in QTc of greater than 0.08 s (3 of 4 patients) over individual baseline also was significant (p = 0.03 and p = 0.01, respectively). No baseline clinical variables associated with TdP or QTc prolongation were identified.
Intravenously administered pentamidine frequently results in QTc prolongation with a subsequent risk of TdP in HIV-infected patients. All patients treated with intravenously administered pentamidine should be evaluated with baseline and daily ECGs, at least during the first week of therapy, and should be closely monitored for a change in the QT interval. An increase in QTc to above 0.48 s or greater than 0.08 s above baseline carries a significant risk for proarrhythmia, and in this instance, continuous electrocardiographic monitoring or an alternative antibiotic regimen should be considered.
已有15例已发表的可能由喷他脒诱发的尖端扭转型室速（TdP）病例。鉴于艾滋病患者中卡氏肺孢子虫肺炎的高发病率以及喷他脒在其治疗中的作用，对这种治疗并发症进行前瞻性分析很有价值。
对在12个月期间接受静脉注射喷他脒的HIV感染患者进行开放、非随机、前瞻性研究。
华盛顿特区的沃尔特·里德陆军医疗中心，一家三级医疗、以转诊为基础的机构。
18名HIV感染患者在获得知情同意后入组；4名患者在仅接受一或两剂经验性静脉注射喷他脒后退出统计分析。
对每位患者进行每日12导联心电图、超声心动图、每周信号平均心电图以及每周24小时动态心电图检查。在14名受试者中，3人发生了TdP。这3名患者和另外2人出现了校正心率后的QT间期（QTc）延长至大于0.48秒（最大QTc平均值为0.55秒，平均增加0.12秒）。在喷他脒每日第四剂（4毫克/千克/天）时，所有5名患者均出现了QTc延长。其他9名患者在整个治疗过程中QTc间期变化极小（最大QTc平均值为0.45秒；平均增加0.03秒）。这两个队列的最大QTc增加量有显著差异（p<0.03）。在QTc间期延长至大于0.48秒的患者亚组中（5名患者中的3名），或个体基线QTc变化大于0.08秒的患者亚组中（4名患者中的3名），TdP的发生也具有显著性（分别为p = 0.03和p = 0.01）。未发现与TdP或QTc延长相关的基线临床变量。
静脉注射喷他脒在HIV感染患者中常导致QTc延长，随后有发生TdP的风险。所有接受静脉注射喷他脒治疗的患者应在基线时以及每日进行心电图评估，至少在治疗的第一周内如此，并且应密切监测QT间期的变化。QTc增加至高于0.48秒或高于基线0.08秒以上有发生心律失常的显著风险，在这种情况下，应考虑持续心电图监测或更换抗生素治疗方案。
