Effect of low-dose droperidol on the QT interval during and after general anesthesia: a placebo-controlled study

BACKGROUND: Since the effects of antiemetic doses of droperidol on the QT interval have not been previously studied, the authors designed a randomized, double-blind, placebo-controlled study to evaluate the intraoperative and postoperative effects of small-dose droperidol (0.625 and 1.25 mg intravenous) on the QT interval when used for antiemetic prophylaxis during general anesthesia. METHODS: One hundred twenty outpatients undergoing otolaryngologic procedures with a standardized general anesthetic technique were enrolled in this study. After anesthetic induction and before the surgical incision, 60 patients were given either saline or 0.625 or 1.25 mg intravenous droperidol in a total volume of 2 ml. A standard electrocardiographic lead II was recorded immediately before and every minute after the injection of the study medication during a 10-min observation period. The QTc (QT interval corrected for heart rate) was evaluated from the recorded electrocardiographic strips. In 60 additional patients, a 12-lead electrocardiogram was obtained before and at specific intervals up to 2 h after surgery to assess the effects of droperidol and general anesthesia on the QTc. Any abnormal heartbeats or arrhythmias during the operation or the subsequent 2-h monitoring interval were also noted. RESULTS: Intravenous droperidol, 0.625 and 1.25 mg, prolonged the QT interval by an average of 15 +/- 40 and 22 +/- 41 ms, respectively, at 3-6 min after administration during general anesthesia, but these changes did not differ significantly from that seen with saline (12 +/- 35 ms) (all values mean +/- SD). There were no statistically significant differences among the three study groups in the number of patients with greater than 10% prolongation in QTc (vs. baseline). Although general anesthesia was associated with a 14- to 16-ms prolongation of the QTc interval in the early postoperative period, there was no evidence of droperidol-induced QTc prolongation after surgery. Finally, there were no ectopic heartbeats observed on any of the electrocardiographic rhythm strips or 12-lead recordings during the perioperative period. CONCLUSION: Use of a small dose of droperidol (0.625-1.25 mg intravenous) for antiemetic prophylaxis during general anesthesia was not associated with a statistically significant increase in the QTc interval compared with saline. More importantly, there was no evidence of any droperidol-induced QTc prolongation immediately after surgery.     

Prolongation of QTc Interval after Postoperative Nausea and Vomiting Treatment by Droperidol or Ondansetron

Background: At dosages above 0.1 mg/kg, droperidol inducesa 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.

Methods: 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.

Results: 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.     

七氟烷对QT间期延长的影响在老年人中更明显

背景七氟炕和氟哌利多能延长QT间期。高龄不仅与QT问期延长有关,它也是一种}j起药物诱导的QT间期延长的危险因素。本研究中,我们比较了七氟炕和氧哌利多对于矫正的QT（QYc）间期和心室复极化的传播（T波波峰至T波结束的时间间隔[Tp-e]）在老年患者和年轻患者中的差别。方法在七氟烷（1．5％-2．5％）麻醉和给予止吐剂量的氟哌利多（1．25rag）的30例老年患者（≥70岁）和30例年轻患者（20—69岁）中,测量2小时QT间期和代表心肌壁复极化传播的Tp—e间期。通过3种不同的公式使心率的QT间期标准化：Bazen公式、Matsunaga公式和Vandewa船公式。数据以均数±标准差表示。结果老年组的平均年龄比年轻组大24．4岁（P〈0．05）。两组的QTc间期在麻醉前没有明显的差异。通过3种公式计算发现七氟烷明显延长老年组患者的QTc间期（用Bazecc公式得出在麻醉前、使用七氟烷60分钟、75分钟、90分钟和120分钟时的QTc间期分别是0．434±0．028秒、0．450±0．037秒、0．463±0．037秒、0．461±0．037秒和0．461±O．038秒）。在老年组患者中七氟炕引起QTc间期延长的程度明显高于年轻组（用Bazecc公式计算吸入七氟烷60分钟时：0．450±0．037秒VS0．432±0．034秒;75分钟时：0．463±0．037秒vs0．441±0．037秒;120分钟时：0．461±0．038秒vs0．436±0．030秒）。但是七氟炕引起的QTc间期的延长既不随着时间的延长而延长也不被氟哌利多加重。两组中的Tp—e间期都没有受到影响。结论与年轻组相比,七氟烷引起老年组患者QTc间期的延长更加明显。尽管七氟烷不影响复极化的透壁传播,其引起的QTc闻期延长也不随着时间和给予氧哌利多而加重,但是老年患者在使用七氖烷麻醉期间仍要严密监测QT间期及其相关的心律失常。     

Prolongation of QTc interval after postoperative nausea and vomiting treatment by droperidol or ondansetron

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

The additive interactions between ondansetron and droperidol for preventing postoperative nausea and vomiting

Prophylactic ondansetron or droperidol reduces the incidence of postoperative nausea and vomiting (PONV). Previous studies showed that the combination of these two drugs produced better antiemetic effect than either drug alone. We present a nonparametric method to determine the pharmacologic interaction between ondansetron and droperidol and compared the observed response of the drug combination with that predicted from additivity. This is calculated as the product of the individual drug response, normalized to that of the controls. Five minutes before induction of anesthesia, 400 patients scheduled for laparoscopic gynecologic surgery were randomly assigned to receive 1) saline IV; 2) ondansetron 4 mg IV; 3) droperidol 1.25 mg IV; or 4) a combination of droperiodol 1.25 mg and ondansetron 4 mg IV. A standardized anesthetic technique and postoperative analgesic regimen were used. Patients were reviewed regularly for 48 h. Changes in the heart rate adjusted QT (QTc) interval were measured from electrocardiograms recorded before and 5 min after study drug administration. In a subgroup of 160 patients, QTc intervals were measured again at 2-3 h after surgery. During the first 48 h after the surgery, the proportion of patients experiencing PONV was 68% (95% CI 58-77) in the control group. A single dose of ondansetron or droperidol decreased the incidence of PONV to 30% (95% CI 21-40) and 28% (95% CI 20-38), respectively. The predicted incidence of PONV after drug combination, 11.8% (7.1-11.9), was similar to that observed, 12.1% (6.4-20.2), P = 0.94. The corresponding predicted and observed treatment responses in the combination group were 88.2% and 87.9%, respectively. There was a modest and transient increase in QTc interval after administration of ondansetron, droperidol, or their combination. The changes were however similar among groups. We conclude that the interaction between ondansetron and droperiodol was additive. Both drugs acted independently of each other through their specific mechanisms of action. The incidence of QTc prolongation did not increase with the drug combination.     

Prolongation of the QT interval by enflurane, isoflurane, and halothane in humans

Previous investigations in laboratory animals have documented the ability of the volatile anesthetics to prolong the QT interval and the QT interval corrected for level of heart rate, QTc. The purpose of the present investigation was to evaluate the direct electrocardiographic and hemodynamic effects of enflurane, isoflurane, and halothane in healthy, unpremedicated patients using an inhalation induction to avoid the confounding effects of other anesthetic agents. Experiments were conducted in 22 adult male patients, (ASA physical status I or II) divided into three groups given either enflurane (n = 6), isoflurane (n = 8), or halothane (n = 8) anesthesia. Twenty-four-hour preoperative, preinduction, and postinduction hemodynamic and electrocardiographic measurements were obtained. Anesthetic blood concentrations, levels of plasma electrolytes, and arterial blood gas tensions were also quantitated. Halothane administration (0.81 +/- 0.06 mM) did not significantly alter the PR interval or QRS duration but significantly increased the QT (0.38 +/- 0.01 to 0.45 +/- 0.01 s) and QTc intervals (0.39 +/- 0.01 to 0.44 +/- 0.02 s). Isoflurane anesthesia (1.04 +/- 0.11 mM) did not significantly change QRS duration or PR and QT intervals but significantly prolonged the QTc interval (0.42 +/- 0.01 to 0.47 +/- 0.14 s). Similarly, enflurane anesthesia (2.16 +/- 0.13 mM) significantly prolonged the QTc (0.40 +/- 0.01 to 0.46 +/- 0.14 s) without change in QRS duration or PR and QT intervals. Plasma electrolyte levels and arterial gas tensions remained within normal limits in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Haloperidol is as effective as ondansetron for preventing postoperative nausea and vomiting

PURPOSE: Recent warnings regarding the safety of droperidol have limited use of this drug as an antiemetic. Haloperidol, a butyrophenone derivative similar to droperidol, has not been rigorously evaluated as an antiemetic. The aim of this study was to compare the prophylactic antiemetic efficacy of haloperidol vs ondansetron for the prevention of postoperative nausea and vomiting (PONV) after general anesthesia. METHODS: Ninety non-smoking female patients were eligible to participate in this randomized double-blinded study. Approximately 30 min before the end of surgery, patients were randomly assigned to receive either haloperidol 2 mg iv, or ondansetron 4 mg iv, respectively. The incidence of PONV, average pain and sedation scores, recovery times, and changes of the rate-corrected QT (QTc) interval were observed postoperatively. RESULTS: The proportion of patients who experienced PONV in the first 24 hr was similar in the two groups (28% and 26% for haloperidol and ondansetron groups, respectively). The incidence of PONV was significantly less in both groups than predicted according to the patients' underlying risks (53% for the haloperidol group, P=0.016; 51% for the ondansetron group, P=0.015). Pain scores, sedation scores, and recovery times were similar in the two groups, and no prolongation of the QTc interval was observed in either group. CONCLUSIONS: Haloperidol 2 mg iv given 30 min before the end of surgery is effective in preventing PONV, with efficacy comparable to ondansetron 4 mg iv for the first 24 hr after general anesthesia.     

Prolongation of the QT interval by volatile anesthetics in chronically instrumented dogs

The influence of volatile anesthetics on ventricular repolarization in vivo (QT interval) has not been studied in a systematic fashion. The purpose of this investigation was to characterize the electrocardiographic and hemodynamic actions of the volatile anesthetics halothane, isoflurane, and enflurane in chronically instrumented dogs. Because autonomic nervous system tone may influence ECG findings, experiments were completed with and without concomitant pharmacologic autonomic nervous system blockade. In six groups comprising 50 experiments with 21 instrumented dogs, anesthesia was mask-induced with nitrous oxide, oxygen, and one of the volatile anesthetics and maintained with the volatile anesthetic in 100% oxygen for 2 hours. Changes in the ECG and in hemodynamics were compared to the conscious state. In the absence of autonomic nervous system blockade, halothane and isoflurane significantly prolonged the QT interval (0.24 +/- 0.01 to 0.30 +/- 0.01 second and 0.22 +/- 0.01 to 0.28 +/- 0.01 second, respectively), whereas enflurane produced no change in ventricular repolarization (0.24 +/- 0.01 to 0.26 +/- 0.01 second). All of the volatile anesthetics increased the QT interval corrected for changes in basal heart rate (QTc), and all agents decreased intravascular pressure and dP/dt. Following autonomic nervous system blockade, halothane, isoflurane, and enflurane significantly increased the QT interval and QTc. The results demonstrate that ventricular repolarization is directly altered by the volatile anesthetics independent of changes in autonomic nervous tone. Whether or not such effects are additive with other congenital or acquired forms of QTc prolongation has yet to be examined. The present results indicate that caution should be used during the administration of volatile anesthetics to patients with abnormalities of the QT interval.     

Sustained prolongation of the QTc interval after anesthesia with sevoflurane in infants during the first 6 months of life

BACKGROUND: Sevoflurane, an inhalational anesthetic frequently administered to infants, prolongs the QT interval of the electrocardiogram in adults. A long QT interval resulting in fatal arrhythmia may also be responsible for some cases of sudden death in infants. As the QT interval increases during the second month of life and returns to the values recorded at birth by the sixth month, we evaluated the effect of sevoflurane on the QT interval during and after anesthesia in this particular population. METHODS: In this prospective two-group trial we examined pre-, peri-, and postoperative electrocardiograms of 36 infants aged 1 to 6 months scheduled for elective inguinal or umbilical hernia repair. Anesthesia was induced and maintained with either sevoflurane, or the well-established pediatric anesthetic halothane. Heart rate corrected (c) QTc and JTc interval (indicator of intraventricular conduction delays) were recorded from electrocardiograms before and during anesthesia, and at 60 min after emergence from anesthesia. RESULTS: Prolonged QTc was observed during sevoflurane anesthesia (mean [+/-SD], 473 +/- 19 ms, P< 0.01). Sixty minutes after emergence from anesthesia, QTc was still prolonged (433 +/- 15 ms) in infants treated with sevoflurane compared with those treated with halothane (407 +/- 33 ms, P< 0.01). Analogous differences were found for the JTc interval. CONCLUSIONS: Despite a shorter elimination time than better known inhalational anesthetics, sevoflurane induction and anesthesia results in sustained prolongations of QTc and JTc interval in infants in the first 6 months of life. Electrocardiogram monitoring until the QTc interval has returned to preanesthetic values may increase safety after sevoflurane anesthesia.     

The interaction of antiemetic dose of droperidol with propofol on QT interval during anesthetic induction

Purpose

We investigated the effect of low-dose droperidol on heart rate-corrected QT (QTc) interval and interaction with propofol.

Methods

Seventy-two patients undergoing upper limb surgery were included in this study. Patients were randomly allocated to one of three groups: group S (n = 24), which received 1 ml saline; group D1 (n = 24), which received 1.25 mg droperidol; or group D2 (n = 24), which received 2.5 mg droperidol. One minute later, fentanyl (3 μg/kg) was administered. Two minutes after fentanyl administration, anesthesia was induced using propofol (1.5 mg/kg) and vecronium. Tracheal intubation was performed 3 min after the administration of propofol. Heart rate, mean arterial pressure, bispectral index, and QTc interval were recorded at the following time points: immediately before the droperidol injection (baseline); 3 min after the saline or droperidol injection; 3 min after the propofol injection; and 2 min after tracheal intubation.

Results

Compared to baseline, the QTc interval in group S and group D1 was significantly shorter after propofol injection, but recovered after tracheal intubation. In group D2, the QTc interval was significantly prolonged after droperidol injection, but recovered after propofol injection, and was significantly prolonged after tracheal intubation.

Conclusions

We found that saline or 1.25 mg droperidol did not prolong QTc interval, whereas 2.5 mg droperidol prolonged the QTc interval significantly, and that propofol injection counteracted the prolongation of the QTc interval induced by 2.5 mg droperidol.     

The effectiveness of rescue antiemetics after failure of prophylaxis with ondansetron or droperidol: a preliminary report

STUDY OBJECTIVES: To compare the effectiveness of treating established postoperative nausea and vomiting (PONV) with an antiemetic acting at a different receptor with that of treating PONV with the antiemetic used for prophylaxis. DESIGN: Analysis of data collected in a previously published randomized, double-blind, placebo-controlled study. SETTING: Outpatient surgical procedures from 50 institutions in North America. PATIENTS: Patients (N = 2061) undergoing outpatient surgical procedures planned to last no more than 2 hours. INTERVENTIONS: Patients were randomized to receive ondansetron 4 mg, droperidol 1.25, droperidol 0.625 mg, or placebo. In the postoperative anesthesia care unit, patients who developed PONV received rescue antiemetics at the discretion of the attending anesthesiologist. The following antiemetics were used for rescue: ondansetron 4 mg, droperidol 0.625 to 1.25 mg, metoclopramide 10 mg, promethazine 6.25 to 25 mg, and dimenhydrinate 25 to 50 mg. MEASUREMENTS: The complete response rate (no nausea, no emesis, and no need for further rescue) after administration of the rescue antiemetic in patients with established PONV was calculated. The complete response rate after administration of each of the different rescue antiemetics was compared with that after administration of the same antiemetic used for PONV prophylaxis. MAIN RESULTS: In patients who failed prophylaxis with ondansetron 4 mg, the complete response rate was significantly higher (P = .02) after rescue with promethazine 6.25 to 25 mg (78%) than after rescue with ondansetron 4 mg (46%). In patients who failed prophylaxis with droperidol 0.625 and 1.25 mg, the complete response rate was significantly higher after rescue with promethazine 6.25 to 25 mg (77%; P = .02) and dimenhydrinate 25 to 50 mg (78%; P = .04) than after rescue with droperidol 0.625 to 1.25 mg (56%). CONCLUSION: In patients who failed prophylaxis with ondansetron or droperidol, promethazine was significantly more effective than the agent used for prophylaxis for the treatment of PONV. In patients who failed prophylaxis with droperidol, dimenhydrinate was also more effective than droperidol for the treatment of established PONV in the postoperative anesthesia care unit.     

Sustained Prolongation of the QTc Interval after Anesthesia with Sevoflurane in Infants during the First 6 Months of Life

Background: Sevoflurane, an inhalational anesthetic frequently administered to infants, prolongs the QT interval of the electrocardiogram in adults. A long QT interval resulting in fatal arrhythmia may also be responsible for some cases of sudden death in infants. As the QT interval increases during the second month of life and returns to the values recorded at birth by the sixth month, we evaluated the effect of sevoflurane on the QT interval during and after anesthesia in this particular population.

Methods: In this prospective two-group trial we examined pre-, peri-, and postoperative electrocardiograms of 36 infants aged 1 to 6 months scheduled for elective inguinal or umbilical hernia repair. Anesthesia was induced and maintained with either sevoflurane, or the well-established pediatric anesthetic halothane. Heart rate corrected (c) QTc and JTc interval (indicator of intraventricular conduction delays) were recorded from electrocardiograms before and during anesthesia, and at 60 min after emergence from anesthesia.

Results: Prolonged QTc was observed during sevoflurane anesthesia (mean [+/-SD], 473 +/- 19 ms, P < 0.01). Sixty minutes after emergence from anesthesia, QTc was still prolonged (433 +/- 15 ms) in infants treated with sevoflurane compared with those treated with halothane (407 +/- 33 ms, P < 0.01). Analogous differences were found for the JTc interval.     

Droperidol for perioperative sedation causes a transient prolongation of the QTc time in children under volatile anesthesia

BACKGROUND: Droperidol is useful for postoperative sedation in infants and children after cardiac surgery because it provides sedation and akinesia with minimal respiratory depression. However, droperidol has been associated with QT prolongation and ventricular arrhythmias. We investigated, if neuroleptanalgesic doses of droperidol led to QT prolongation and cardiac arrhythmias in children undergoing cardiac surgery. METHODS: We retrospectively analysed electrocardiogram rhythm strips that were obtained before and in time increments after a 100 microg x kg(-1) intravenous bolus of droperidol in 20 children undergoing cardiac surgery. The longest QT interval was determined in each ECG and corrected for heart rate (QTc). All arrhythmias were recorded. RESULTS: Droperidol led to a significant increase in QTc time that was still present at 15 min but had resolved within 30 min after the bolus. No associated arrhythmias were observed. CONCLUSIONS: The statistically significant prolongation of QTc time after a sedative dose of droperidol is of concern because it may increase the risk for malignant cardiac arrhythmias. A large, prospective study is necessary to identify the true risk for arrhythmias after droperidol in this patient population, but our study suggests that any arrhythmogenic risk, if present, will be very transient, since the increase in QTc time was limited to a period of less than 30 min after the bolus.     

Prevention of postoperative nausea and vomiting after intrathecal morphine for Cesarean section: a randomized comparison of dexamethasone, droperidol, and a combination

BACKGROUND: Intrathecal morphine provides good analgesia after cesarean delivery but the side effects include nausea and vomiting. Low-dose droperidol (0.625 mg) combined with dexamethasone 4 mg is postulated to have an additive antiemetic effect with less side effects. We therefore compared single doses of dexamethasone and droperidol alone with a low-dose combination of the two, to prevent spinal morphine-induced nausea and vomiting after cesarean section. METHODS: In a double-blind study, 120 women undergoing elective cesarean section under spinal anesthesia (using 0.5% bupivacaine 10 mg and morphine 0.2 mg) were allocated randomly to receive dexamethasone 8 mg, droperidol 1.25 mg, dexamethasone 4 mg and droperidol 0.625 mg, or placebo, before the end of surgery. The incidences of nausea and vomiting, sedative score, pain score, and side effects were recorded. RESULTS: The incidence of nausea and vomiting within 6 h postoperatively was lower and incidence of no nausea and vomiting for 24 h postoperatively was significantly higher for the combination group compared to the placebo group and the dexamethasone only group. Sedation scores within 3 h postoperatively and incidence of restlessness for the combination group were significantly lower than in the droperidol only group. CONCLUSION: An additive antiemetic effect and no significant side effects were shown for the combination of dexamethasone 4 mg and droperidol 0.625 mg. This combination was more effective than either dexamethasone 8 mg or droperidol 1.25 mg alone in preventing nausea and vomiting after spinal anesthesia using 0.5% bupivacaine and morphine 0.2 mg.     

Droperidol causes multifocal ventricular dysrhythmias

We report a case of ventricular chaotic arrhythmia after droperidol administration. A 49-year-old woman with chronic renal failure receiving hemodialysis, was scheduled for total hysterectomy under general anesthesia. General anesthesia was induced with thiopental 200 mg, fentanyl 0.1 mg and vecuronium 5 mg for endotracheal intubation. Anesthesia was maintained with 1% isoflurane and 60% nitrous oxide in oxygen. Droperidol 10 mg was injected for neuroleptanalgesia. After two minutes, ventricular chaotic arrhythmia occurred. Lidocaine 80 mg was injected. General anesthesia was stopped. After two minutes, arrhythmia disappeared. Several reports suggest that patients with preexisting conduction defects or prolonged QTc interval may be at risk to develop ventricular arrhythmias after droperidol administration. Administration of droperidol may have exaggerated prolongation of QTc interval.     

Droperidol and Ondansetron-induced QT Interval Prolongation: A Clinical Drug Interaction Study

Background: Droperidol and ondansetron have previously been found to prolong the QT interval in the treatment of postoperative nausea and vomiting. However, this adverse effect has never been confirmed and compared with both drugs under controlled conditions. The objective was to study the effects of droperidol and ondansetron alone or in combination on QT interval duration in healthy subjects.

Methods: Sixteen healthy volunteers, eight males and eight females, were enrolled in this prospective, double-blind, randomized, placebo-controlled study. Subjects received 1 mg droperidol, 4 mg ondansetron, 1 mg droperidol plus 4 mg ondansetron, or a placebo, intravenously in a crossover design. Fridericia-corrected QT interval (QTcF) and plasma concentrations were measured repeatedly during 10 h at each study period. The primary endpoint was the maximal placebo time-matched and baseline-subtracted QTcF prolongation ([DELTA][DELTA]QTcF).

Results: Compared with placebo, both droperidol and ondansetron significantly prolonged the QTcF interval. [DELTA][DELTA]QTcF prolongation was 25 +/- 8 ms after droperidol, significantly greater than the 17 +/- 10-ms prolongation with ondansetron (P = 0.014). The combination of droperidol and ondansetron significantly increased the mean maximal [DELTA][DELTA]QTcF by 28 +/- 10 ms. The combination induced greater QTcF prolongation compared with ondansetron alone (P = 0.001), but not with droperidol alone (P = 0.33). There was no significant pharmacokinetic interaction between droperidol and ondansetron.     

A comparison of three antiemetic combinations for the prevention of postoperative nausea and vomiting

In this study we compared the efficacy and safety of three antiemetic combinations in the prevention of postoperative nausea and vomiting (PONV). Ninety ASA status I-II women, aged 18-65 yr, undergoing general anesthesia for major gynecological surgery, were included in a prospective, randomized, double-blinded study. A standardized anesthetic technique and postoperative analgesia (intrathecal morphine plus IV patient-controlled analgesia (PCA) with morphine) were used in all patients. Patients were randomly assigned to receive ondansetron 4 mg plus droperidol 1.25 mg after the induction of anesthesia and droperidol 1.25 mg 12 h later (Group 1, n = 30), dexamethasone 8 mg plus droperidol 1.25 mg after the induction of anesthesia and droperidol 1.25 mg 12 h later (Group 2, n = 30), or ondansetron 4 mg plus dexamethasone 8 mg after the induction of anesthesia and placebo 12 h later (Group 3, n = 30). A complete response, defined as no PONV in 48 h, occurred in 80% of patients in Group 1, 70% in Group 3, and 40% in Group 2 (P = 0.004 versus Groups 1 and 3). The incidences of side effects and other variables that could modify the incidence of PONV were similar among groups. In conclusion, ondansetron, in combination with droperidol or dexamethasone, is more effective than dexamethasone in combination with droperidol in women undergoing general anesthesia for major gynecological surgery with intrathecal morphine plus IV PCA with morphine for postoperative analgesia. IMPLICATIONS: The combination of ondansetron plus dexamethasone or droperidol was significantly better than the combination of dexamethasone plus droperidol in the prophylaxis of postoperative nausea and vomiting in women undergoing general anesthesia for major gynecological surgery, with intrathecal and IV morphine (patient-controlled analgesia) for management of postoperative pain.     

Ventricular tachycardia after ondansetron administration in a child with undiagnosed long QT syndrome

Purpose

To describe a case of ventricular tachycardia after co-administration of ondansetron and dimenhydrinate to a child with occult congenital QT prolongation.

Clinical features

A previously healthy 11-yr-old girl presented for surgical excision of a thyroglossal duct cyst under general anesthesia. Induction and maintenance of anesthesia were unremarkable, and the surgery was carried out without incident. Prior to emergence, ondansetron 0.1 mg·kg^?1 and dimenhydrinate 0.4 mg·kg^?1 were administered. Within approximately two minutes, polymorphic premature ventricular contractions developed and, subsequently, polymorphic ventricular tachycardia ensued. A 12-lead electrocardiogram revealed a profoundly prolonged QT interval that decreased but failed to normalize completely postoperatively. Our patient was diagnosed subsequently with congenital QT prolongation.

Conclusion

The QT interval is prolonged by the administration of ondansetron in a manner similar to that seen with droperidol, whereas dimenhydrinate is not considered to exert significant effects on the QT interval. Individuals with occult QT prolongation are at risk of experiencing malignant dysrhythmias when ondansetron is administered, especially in conjunction with anesthetic agents that also prolong the QT. The incidence of congenital QT prolongation in the general population has been estimated to be 1:2,500, and it may be undiagnosed preoperatively, especially in pediatric patients.     

氟哌利多、阿扎司琼和格拉司琼对患者校正QT间期影响的比较

目的比较氟哌利多、阿扎司琼、格拉司琼对患者校正QT(QTc)间期的影响。方法择期手术患者80例,随机均分为四组,于麻醉前30min分别静注氟哌利多2.5mg(A组)、阿扎司琼10mg(B组)、格拉司琼3mg(C组)和生理盐水5ml(D组)。记录用药前后ECG,分析QTc间期的变化。结果与用药前比较,A组患者用药后5、10minQTc间期明显延长(P<0.05),且明显长于D组(P<0.05)。其它三组用药后QTc间期无显著变化。结论预防性应用止吐剂量的氟哌利多可引起QTc间期显著延长。