Charbit Beny, Albaladejo Pierre, Funck-Brentano Christian, Legrand Mathieu, Samain Emmanuel, Marty Jean
Department of Anesthesiology and Intensive Care, Beaujon University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
Anesthesiology. 2005 Jun;102(6):1094-100. doi: 10.1097/00000542-200506000-00006.
At dosages above 0.1 mg/kg, droperidol induces a dose-dependent QTc interval prolongation. Although subject to controversy, low-dose droperidol has recently been suspected to induce cardiac arrhythmias. Hence, 5-hydroxytryptamine type 3 antagonists have become the first-line drug for management of postoperative nausea and vomiting. These drugs are also known to prolong the QTc interval at high dosages. This study describes QTc interval changes associated with postoperative nausea and vomiting treatment by droperidol or ondansetron at low doses.
Eighty-five patients with postoperative nausea and vomiting were included in this prospective, single-blind study. Patients received either 0.75 mg intravenous droperidol (n = 43) or 4 mg intravenous ondansetron (n = 42). Electrocardiographic recordings were obtained before administration of antiemetic drug and then 1, 2, 3, 5, 10, and 15 min after. Electrocardiographic monitoring was maintained for 3 h in eight patients in each group.
The QTc interval was prolonged (> 450 ms in men, > 470 ms in women) in 21% of the patients before antiemetic drug administration. This was significantly correlated with lower body temperature and longer duration of anesthesia. Compared with predrug QTc measurement, both antiemetics were associated with a significant QTc interval prolongation (P < 0.0001). The mean maximal QTc interval prolongation was 17 +/- 9 ms after droperidol occurring at the second minute and 20 +/- 13 ms after ondansetron at the third minute (both P < 0.0001). Compared with predrug measurement, the QTc interval was significantly lower after the 90th minute in both groups.
Droperidol and ondansetron induced similar clinically relevant QTc interval prolongations. When used in treatment of postoperative nausea and vomiting, a situation where prolongation of the QTc interval seems to occur, the safety of 5-hydroxytryptamine type 3 antagonists may not be superior to that of low-dose droperidol.
当剂量高于0.1mg/kg时,氟哌利多可引起剂量依赖性的QTc间期延长。尽管存在争议,但最近有怀疑低剂量氟哌利多可诱发心律失常。因此,5-羟色胺3型拮抗剂已成为治疗术后恶心和呕吐的一线药物。这些药物在高剂量时也会延长QTc间期。本研究描述了低剂量氟哌利多或昂丹司琼治疗术后恶心和呕吐时QTc间期的变化。
85例术后恶心和呕吐患者纳入这项前瞻性单盲研究。患者分别接受0.75mg静脉注射氟哌利多(n = 43)或4mg静脉注射昂丹司琼(n = 42)。在给予止吐药前以及给药后1、2、3、5、10和15分钟记录心电图。每组8例患者进行3小时的心电图监测。
在给予止吐药前,21%的患者QTc间期延长(男性>450ms,女性>470ms)。这与较低的体温和较长的麻醉持续时间显著相关。与给药前QTc测量相比,两种止吐药均与QTc间期显著延长相关(P<0.0001)。氟哌利多给药后第2分钟QTc间期平均最大延长为17±9ms,昂丹司琼给药后第3分钟为20±13ms(均P<0.0001)。与给药前测量相比,两组在第90分钟后QTc间期显著降低。
氟哌利多和昂丹司琼引起相似的具有临床意义的QTc间期延长。当用于治疗术后恶心和呕吐(似乎会出现QTc间期延长的情况)时,5-羟色胺3型拮抗剂的安全性可能并不优于低剂量氟哌利多。