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.     

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.     

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.     

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.     

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.     

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.     

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.     

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。     

The effect of neuroleptics and neuroleptic/analgesic combinations on the sensitivity to seizures in mice

Combinations of neuroleptic and morphine-like analgesic drugs are used alone for minor surgery or as anesthetic premedication. While morphine-like analgesics given in the therapeutic dose range show anticonvulsant properties, there is evidence indicating that neuroleptics are rather proconvulsant. This study was performed to investigate the influence of the most widely used combinations pethidine/promethazine and fentanyl/droperidol on seizure susceptibility. METHODS: Thresholds for convulsions induced by electroshock and pentetrazole infusion were used as models for seizure susceptibility. The drugs tested were injected s.c. 20-30 min before determination of the seizure threshold. RESULTS: Pethidine/promethazine and fentanyl/droperidol reduced the susceptibility to seizures induced by electroshock. Promethazine and droperidol alone elevated the threshold only at the highest doses used (2 mg/kg and 2.5 mg/kg respectively). Promethazine, whether given alone or in combination with pethidine, showed no effect on the threshold for pentetrazole-induced convulsions. Droperidol alone lowered the threshold for pentetrazole-induced clonic convulsions only at the lowest dose used (0.625 mg/kg), but lowered that for tonic convulsions at all doses studied (0.625, 1.25 and 2.5 mg/kg). The combination of fentanyl and droperidol lowered the threshold for both clonic and tonic convulsions at the two lower doses (12.5 micrograms/kg fentanyl + 0.625 mg/kg droperidol and 25 micrograms/kg fentanyl + 1.25 mg/kg droperidol). Only the highest dose studied (50 micrograms/kg fentanyl + 2.5 mg/kg droperidol) showed no significant effect. CONCLUSION: Pethidine and fentanyl show anticonvulsant properties in mice, but it is evident from our results that there is some interaction between their combinations with neuroleptics and seizure susceptibility. This is more pronounced with the combination fentanyl/droperidol in the model of pentetrazole-induced convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of droperidol and ondansetron on dispersion of myocardial repolarization in children

Objectives: To compare the effects of droperidol and ondansetron on electrocardiographic indices of myocardial repolarization in children. Aim: To refine understanding of the torsadogenic risk to children exposed to anti‐emetic prophylaxis in the perioperative period. Background: QT interval prolongation is associated with torsades des pointes (TdP), but is a poor predictor of drug torsadogenicity. Susceptibility to TdP arises from increased transmural dispersion of repolarization (TDR) across the myocardial wall, rather than QT interval prolongation per se. TDR can be measured on the electrocardiogram as the time interval between the peak and end of the T wave (Tp‐e). Tp‐e may therefore provide a readily available, noninvasive assay of drug torsadogenicity. The perioperative period is one of high risk for TdP in children with or at risk of long QT syndromes. Droperidol and ondansetron are two drugs commonly administered perioperatively, for prophylaxis of nausea and vomiting, which can prolong the QT interval. This study investigated their effects on myocardial repolarization. Methods: One hundred and eight ASA1‐2 children undergoing elective day‐case surgery were randomized to receive droperidol, ondansetron, both or neither. Pre‐ and post‐administration 12‐lead electrocardiogram (ECGs) were recorded. QT and Tp‐e intervals were measured and compared within and between groups, for the primary endpoint of a 25 ms change in Tp‐e. Results: Eighty children completed the study. There were no demographic or baseline ECG differences between groups. QT intervals lengthened by 10–17 ms after allocated treatments, with no between‐group differences. Values remained within normal limits for all groups. Tp‐e intervals increased by 0–7 ms, with no between‐group differences. There were no instances of dysrhythmia. Conclusions: Droperidol and ondansetron, in therapeutic anti‐emetic doses, produce equivalent, clinically insignificant QT prolongation and negligible Tp‐e prolongation, suggesting that neither is torsadogenic in healthy children at these doses.     

Cost-effectiveness of prophylactic antiemetic therapy with ondansetron, droperidol, or placebo

BACKGROUND: In an era of growing economic constraints on healthcare delivery, anesthesiologists are increasingly expected to understand cost analysis and evaluate clinical practices. Postoperative nausea and vomiting (PONV) are distressing for patients and may increase costs in an ambulatory surgical unit. The authors compared the cost-effectiveness of four prophylactic intravenous regimens for PONV: 4 mg ondansetron, 0.625 mg droperidol, 1.25 mg droperidol, and placebo. METHODS: Adult surgical outpatients at high risk for PONV were studied. Study drugs were administered intravenously within 20 min of induction of nitrous oxide-isoflurane or enflurane anesthesia. A decision-tree analysis was used to group patients into 12 mutually exclusive subgroups based on treatment and outcome. Costs were calculated for the prevention and treatment of PONV. Cost-effectiveness analysis was performed for each group. RESULTS: Two thousand sixty-one patients were enrolled. Efficacy data for study drugs have been previously reported, and the database from that study was used for pharmacoeconomic analysis. The mean-median total cost per patient who received prophylactic treatment with 4 mg ondansetron, 0.625 mg droperidol, 1.25 mg droperidol, and placebo were $112 or $16.44, $109 or $0.63, $104 or $0.51, and $164 or $51.20, respectively (P = 0.001, active treatment groups vs. placebo). The use of a prophylactic antiemetic agent significantly increased patient satisfaction (P < 0.05). Personnel costs in managing PONV and unexpected hospital admission constitute major cost components in our analysis. Exclusion of nursing labor costs from the calculation did not alter the overall conclusions regarding the relative costs of antiemetic therapy. CONCLUSION: The use of prophylactic antiemetic therapy in high-risk ambulatory surgical patients was more effective in preventing PONV and achieved greater patient satisfaction at a lower cost compared with placebo. The use of 1.25 mg droperidol intravenously was associated with greater effectiveness, lower costs, and similar patient satisfaction compared with 0.625 mg droperidol intravenously and 4 mg ondansetron intravenously.     

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.     

Cost-effectiveness of Prophylactic Antiemetic Therapy with Ondansetron, Droperidol, or Placebo

Background: In an era of growing economic constraints on healthcare delivery, anesthesiologists are increasingly expected to understand cost analysis and evaluate clinical practices. Postoperative nausea and vomiting (PONV) are distressing for patients and may increase costs in an ambulatory surgical unit. The authors compared the cost-effectiveness of four prophylactic intravenous regimens for PONV:-4 mg ondansetron, 0.625 mg droperidol, 1.25 mg droperidol, and placebo.

Methods: Adult surgical outpatients at high risk for PONV were studied. Study drugs were administered intravenously within 20 min of induction of nitrous oxide-isoflurane or enflurane anesthesia. A decision-tree analysis was used to group patients into 12 mutually exclusive subgroups based on treatment and outcome. Costs were calculated for the prevention and treatment of PONV. Cost-effectiveness analysis was performed for each group.

Results: Two thousand sixty-one patients were enrolled. Efficacy data for study drugs have been previously reported, and the database from that study was used for pharmacoeconomic analysis. The mean-median total cost per patient who received prophylactic treatment with 4 mg ondansetron, 0.625 mg droperidol, 1.25 mg droperidol, and placebo were $112 or $16.44, $109 or $0.63, $104 or $0.51, and $164 or $51.20, respectively (P = 0.001, active treatment groups vs. placebo). The use of a prophylactic antiemetic agent significantly increased patient satisfaction (P < 0.05). Personnel costs in managing PONV and unexpected hospital admission constitute major cost components in our analysis. Exclusion of nursing labor costs from the calculation did not alter the overall conclusions regarding the relative costs of antiemetic therapy.     

Granisetron-droperidol combination for the prevention of postoperative nausea and vomiting in female patients undergoing breast surgery

We have compared the efficacy and safety of the combination granisetron- droperidol with each antiemetic alone in preventing postoperative nausea and vomiting (PONV) after breast surgery. In a randomized, double-blind study, 150 female patients received granisetron 3 mg, droperidol 1.25 mg or granisetron 3 mg with droperidol 1.25 mg (n = 50 each) i.v., immediately before induction of anaesthesia. A standard general anaesthetic technique was used. The incidence of PONV during the first 24 h after anaesthesia was 18% with granisetron, 38% with droperidol and 4% with the granisetron-droperidol combination (P < 0.05; overall Fisher's exact probability test). We conclude that the granisetron-droperidol combination was more effective than each antiemetic alone in the prevention of PONV in female patients undergoing breast surgery.      

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。     

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.     

Treating "rebound" emesis following outpatient gynecologic laparoscopy: the efficacy of a two-dose regimen of droperidol and ondansetron.

STUDY OBJECTIVE: To evaluate the efficacy of a two-dose combination of droperidol and ondansetron as compared with single-dose droperidol alone, single-dose combined droperidol and ondansetron, and two-dose droperidol alone, for management of postoperative nausea and vomiting (PONV) among gynecologic laparoscopy outpatients. DESIGN: Randomized, double-blind comparison trial. SETTING: Tertiary outpatient gynecologic unit. PATIENTS: A total of 120 female patients scheduled for gynecologic laparoscopy were enrolled. Patients who had experienced nausea or vomiting, or who had taken drugs with antiemetic action in the 24-hour period prior to the study, as well as breast-feeding mothers, were excluded from participation. INTERVENTIONS: Patients were assigned to four treatment groups: i) single dose of droperidol 1.25 mg, ii) two doses of droperidol 1.25 mg, iii) single dose of droperidol 1.25 mg and ondansetron 4 mg in combination, and iv) two doses of droperidol 1.25 mg and ondansetron 4 mg in combination. The first dose of antiemetic was administered prior to induction and the second dose was given by infusion 4 hours later, prior to discharge. MEASUREMENTS AND MAIN RESULTS: A visual analogue scale (VAS, 10 cm) was used to obtain patients' experience of nausea, vomiting, and pain at 0.5, 1.5, 2.5, and 3.5 hours after arrival at the postanesthetic care unit (PACU). Following discharge, approximately 24 hours after arrival at the PACU, the same measures were obtained by a follow-up interview using a verbal 10-point scale. No significant differences in incidence of PONV were noted among the four treatment groups (p = 0.419). However, both single- and two-dose droperidol and ondansetron combination therapy demonstrated attenuation of PONV severity in the 3.5- to 24-hour postinduction period (p < 0.05). CONCLUSIONS: The findings of this study suggest that prophylactic two-dose combined ondansetron and droperidol offers no added benefit over single-dose therapy for routine use in the gynecologic outpatient population.     

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.     

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.     

Droperidol prevents and treats nausea and vomiting after enflurane anaesthesia

One hundred and twelve women undergoing elective orthopaedic surgery under enflurane anaesthesia were given, in a double-blind random fashion, 2.5 mg of droperidol i.m. before anaesthesia, or 1.25 mg of droperidol or a saline placebo i.v. at the end of anaesthesia in an attempt to prevent post-operative vomiting. The administration of droperidol 1.25 mg (for those receiving initially 1.25 mg of droperidol) or saline (for those receiving initially 2.5 mg of droperidol or saline) was repeated i.m. during the 24 post-operative hours in a blind manner if the patient complained of nausea, retched or vomited. Significantly fewer patients (P less than 0.05) given i.m. or i.v. droperidol had emetic symptoms than patients given saline. Furthermore, 51% of the patients given saline needed additional doses of saline, whereas only 27% of the patients given i.m. and 36% of the patients given i.v. droperidol required a second dose (P less than 0.05 between groups). More of the patients given saline (23%) than those given droperidol (8% to 9%), as a blind drug (P less than 0.05), needed to be given additional droperidol as a known anti-emetic because of the failure of the blind drug to prevent or treat symptoms. It is concluded that droperidol given either as a single dose of 2.5 mg i.m. or in repeated doses of 1.25 mg i.v. is effective in the prevention and treatment of post-operative nausea and vomiting after enflurane anaesthesia.