Droperidol and 5-HT3-receptor antagonists, alone or in combination, for prophylaxis of postoperative nausea and vomiting. A meta-analysis of randomised controlled trials

BACKGROUND: Droperidol and 5-HT3-receptor antagonists are among the most potent antiemetics to prevent postoperative nausea and vomiting (PONV). Combinations of these drugs have been used to increase the efficacy of antiemetic treatment. However, so far the quantitative effect of this combination has not been evaluated systematically. METHODS: Results from randomised controlled trials investigating the efficacy of 5-HT3-receptor antagonists or droperidol alone versus the combination of both drugs to prevent PONV were included in a meta-analysis. Studies were systematically searched using Medline, EMBASE, the Cochrane-Library, and by manually screening the reference lists of matching review articles and current issues of locally available peer-reviewed anaesthesia journals. Seven papers with data on granisetron published by Fujii and co-workers were not considered. The main end point in each study was defined as occurrence of nausea, retching, or vomiting within 6 h ("early PONV") and within 48 h ("late PONV") after surgery. The relative risks (RR) and the numbers needed to treat (NNT) of the pooled data with their corresponding 95% confidence intervals (given in parentheses) were calculated using a random effects model. RESULTS: Eight studies with 881 patients (adults: n=801; children (mean age: 8 yr): n=80) were included in the analysis. Droperidol was applied to 340 patients, 5-HT3-receptor antagonists to 198, and 343 were treated with a combination of both drugs. Seven out of these eight studies reported increased antiemetic efficacy of the combination group compared with the single drugs (droperidol and 5-HT3-receptor antagonists respectively). However, in none of the trials did this difference reach statistical significance. When a meta-analytic analysis based on these results was performed the combination of droperidol with a 5-HT3-receptor antagonist was not associated with a significantly increased antiemetic efficacy. In 12 to 13 patients a 5-HT3-receptor antagonist has to be added to droperidol prophylaxis to prevent one additional patient from PONV who would have had suffered from PONV when treated with droperidol alone (RR "early PONV": 1.52 (0.95-2.44); RR "late PONV": 1.24 (0.89-1.74)). Similar results were obtained when the antiemetic effect of adding droperidol to a prophylaxis with 5-HT3-receptor antagonists was analysed. In this case 10 to 12 patients have to be treated with the 5-HT3-droperidol combination instead of with a 5-HT3-receptor antagonist alone to prevent one additional patient from PONV (RR "early PONV": 1.55 (0.68-3.52); RR "late PONV": 1.29 (0.77-2.17)). There were no reports of an increased incidence of adverse effects. CONCLUSION: The data on the combination of droperidol with 5-HT3-receptor antagonists suggest that there is a trend towards increased efficacy of the combination therapy compared to the single drugs. However, so far there are insufficient data to recommend this combination treatment for prophylaxis.     

Dexamethasone for the prevention of postoperative nausea and vomiting: a quantitative systematic review

The role of dexamethasone in the prevention of postoperative nausea and vomiting (PONV) is unclear. We reviewed efficacy and safety data of dexamethasone for prevention of PONV. A systematic search (MEDLINE, EMBASE, Cochrane Library, hand searching, bibliographies, all languages, up to April 1999) was done for full reports of randomized comparisons of dexamethasone with other antiemetics or placebo in surgical patients. Relevant end points were prevention of early PONV (0 to 6 h postoperatively), late PONV (0 to 24 h), and adverse effects. Data from 1,946 patients from 17 trials were analyzed: 598 received dexamethasone; 582 received ondansetron, granisetron, droperidol, metoclopramide, or perphenazine; 423 received a placebo; and 343 received a combination of dexamethasone with ondansetron or granisetron. With placebo, the incidence of early and late PONV was 35% and 50%, respectively. Sixteen different regimens of dexamethasone were tested, most frequently, 8 or 10 mg IV in adults, and 1 or 1.5 mg/kg IV in children. With these doses, the number needed to treat to prevent early and late vomiting compared with placebo in adults and children was 7.1 (95% CI 4.5 to 18), and 3.8 (2.9 to 5), respectively. In adults, the number needed to treat to prevent late nausea was 4.3 (2.3 to 26). The combination of dexamethasone with ondansetron or granisetron further decreased the risk of PONV; the number needed to treat to prevent late nausea and vomiting with the combined regimen compared with the 5-HT3 receptor antagonists alone was 7.7 (4.8 to 19) and 7.8 (4.1 to 66), respectively. There was a lack of data from comparisons with other antiemetics for sensible conclusions. There were no reports on dexamethasone-related adverse effects. IMPLICATIONS: When there is a high risk of postoperative nausea and vomiting, a single prophylactic dose of dexamethasone is antiemetic compared with placebo, without evidence of any clinically relevant toxicity in otherwise healthy patients. Late efficacy seems to be most pronounced. It is very likely that the best prophylaxis of postoperative nausea and vomiting currently available is achieved by combining dexamethasone with a 5-HT3 receptor antagonist. Optimal doses of this combination need to be identified.     

Dexamethasone for prophylaxis of postoperative nausea and vomiting. A meta-analysis of randomized controlled studies

OBJECTIVE: Randomised controlled trials investigating the efficacy of dexamethasone alone or in combination with other antiemetics to prevent postoperative nausea and vomiting (PONV) were included in a meta-analysis to estimate the relative efficacy of these treatments. METHODS: Studies were systematically searched using Medline, EMBASE, the Cochrane-Library, and by manual screening the reference lists and current issues of locally available anaesthesia journals. Studies identified were divided into four different groups. For each subgroup an independent analysis was performed: 1. Dexamethasone vs. placebo, 2. Dexamethasone + other antiemetic vs. other antiemetic alone, 3. Dexamethasone + other antiemetic vs. dexamethasone alone, 4. Dexamethasone vs. other antiemetics. The main end point in each study was defined as complete absence of nausea, retching, and vomiting after prophylactic antiemetic treatment. The pooled odds-ratios, the relative risk (RR) and the numbers-needed-to-treat (NNT) with their corresponding 95%-confidence intervals (given in parentheses) were calculated using a random effects model. RESULTS: A total of 26 studies with 2561 patients were analysed. 1. As a sole antiemetic agent dexamethasone is superior to placebo to prevent PONV (RR: 0.49 (0.15-0.42); NNT: 3.4 (2.5-5.3)). 2. When dexamethasone and an other antiemetic (e.g. a 5-HT3-antagonist) are combined this drug combination is significantly more effective than the single antiemetic without dexamethasone (RR: 0.60 (0.46-0.78); NNT: 7.3 (5.7-10.2)). 3. A similar result was obtained when the dexamethasone combination was compared with dexamethasone alone. The combination is statistically superior (RR: 0.16 (0.08-0.32); NNT: 3.2 (2.2-6.3)). 4. Dexamethasone was usually compared with 5-HT3-antagonist and to a less extends also with dopamine antagonists. Summarising these studies, there was no significant difference concerning effectiveness (RR: 1.35 (0.99-1.85); NNT: 10.6 (5.6-92.6)). CONCLUSION: Dexamethasone has antiemetics effects that are superior to placebo treatment and are comparable with conventional antiemetic agents (e.g. 5-HT3-antagonist, dopamine antagonists). The drug is especially useful in combination with other antiemetics and increases the efficacy of the antiemetic partner drug.     

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.     

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.     

5-HT3 receptor antagonistsvs traditional agents for the prophylaxis of postoperative nausea and vomiting

PURPOSE: Numerous antiemetics have been studied for the prevention of postoperative nausea and vomiting (PONV) including traditional agents (metoclopramide, perphenazine, prochlorperazine, cyclizine and droperidol) and the 5-HT3 receptor antagonists (ondansetron, dolasetron, granisetron and tropisetron). The results have been divergent and inconsistent. The purpose of this quantitative systematic review was to evaluate the effectiveness of 5HT3 receptor antagonists compared to traditional antiemetics for the prevention of PONV METHODS: A systematic search of the English language literature using computerized MEDLINE, EMBASE, and Pre-MEDLINE databases from 1966 to October 1999 and a manual search of references from retrieved articles were performed. Individual efficacy and adverse effect data was extracted from each of the studies according to a predefined protocol. The summary odds ratios were calculated using the Dersimonian and Laird method under a random effects model. RESULTS: A total of 41 trials met our pre-defined inclusion criteria and were included in our analysis. Results in the 32 studies examining PONV indicated a 46% reduction in the odds of PONV in the 5-HT3-treated group (0.54 [95% CI 0.42-0.71], P < 0.001). Evaluation of PONV by traditional antiemetic agent demonstrated a 39% reduction compared with droperidol (0.61 [95% CI 0.42-0.89], P < 0.001) and a 56% reduction compared with metoclopramide (0.44 [95% CI 0.31-0.62], P < 0.001). Results in the 34 studies examining vomiting indicated a 38% reduction in the odds of vomiting in the 5-HT3-treated group (0.62 [95% CI 0.48-0.81], P < 0.001). CONCLUSIONS: The 5-HT3 receptor antagonists are superior to traditional antiemetic agents for the prevention of PONV and vomiting. The reduction in the odds of PONV and vomiting is significant in the overall analysis and the subgroup analyses comparing 5-HT3 receptor antagonists with droperidol and metoclopramide.     

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.      

Postoperative nausea and vomiting with special reference to risk factors and prevention in laparoscopic surgery

The current incidence, risk factors and prevention of postoperative nausea and vomiting (PONV) were prospectively evaluated in 1703 inpatients. The objectives of the study were: 1) to create a predictive model based on patient characteristics in order to enable the estimation of the risk for PONV, 2) to ascertain the antiemetic efficacy of prophylactic intravenous ondansetron in comparison with droperidol and placebo against PONV following laparoscopic surgery, and 3) to evaluate the antiemetic effectiveness of combining ondansetron with a low dose of droperidol in high-risk inpatients. The incidence of nausea and vomiting after common surgical procedures was high. In the recovery room, the overall incidence of nausea and vomiting was 18% and 5%, respectively, and over the whole 24-h observation period the respective figures were 52% and 25%. The most significant predictive factors associated with an increased risk for the symptoms were female sex, a previous history of postoperative nausea and vomiting, a history of motion sickness, a longer duration of surgery and non-smoking. Based on these five items, a risk score predicting nausea and vomiting was constructed with a moderately good discriminating power, as judged from the area under the receiver operating characteristic curve. Intravenous ondansetron 4 mg was ineffective in the prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy. A higher dose of prophylactic ondansetron 8 mg effectively reduced the incidence and alleviated the intensity of PONV in women scheduled to have laparoscopy for gynaecological and general surgical procedures, as compared with placebo. The antiemetic efficacy of prophylactic ondansetron 8 mg and droperidol 1.25 mg was similar as for overall nausea during the 24-h observation period, but ondansetron seemed to be slightly more efficacious in preventing vomiting. Both ondansetron and droperidol were well-tolerated with only minor side-effects. In a high-risk, female, inpatient laparoscopic population, with a mean estimated risk of 65% for PONV, prophylactically administered ondansetron 8 mg in combination with either a 0.75 mg or 1.25 mg dose of droperidol reduced the incidence of post-operative nausea to 35% and that of vomiting to 15% during the first 24 h after surgery. Of these drug combinations, the smaller dose of droperidol resulted in less postoperative sedation than the higher dose; both combinations being otherwise equally well-tolerated without serious adverse events. These results indicate that postoperative nausea and vomiting can, to some extent, be predicted by a few patient characteristics, and in laparoscopic surgery - which is associated with an increased risk for PONV - the incidence can be reduced with either a single dose of ondansetron or droperidol or a combination of these drugs.     

Comparison of ondansetron with ondansetron and dexamethasone in prevention of PONV in diagnostic laparoscopy

PURPOSE: To compare the efficacy of ondansetron-dexamethasone combination with ondansetron alone for prevention of postoperative nausea and vomiting (PONV). METHODS: This double blind, randomized study was carried out in 51 female patients, aged 20-40 yr, ASA-1 physical status undergoing gynecological diagnostic laparoscopy. Group 1 (n = 26) received 4 mg ondansetron i.v. and group 2 (n = 25) received a combination of 4 mg ondansetron and 8 mg dexamethasone i.v. soon after induction of anesthesia. Postoperatively patients were assessed hourly for four hours and then at 24 hr for nausea, vomiting, pain and post anesthetic discharge score. Vomiting occurring up to two hours was considered early vomiting and from 2-24 hr as delayed vomiting. RESULTS: The postoperative nausea score was lower in patients receiving a combination of ondansetron and dexamethasone (3.76) than ondansetron alone (4.38) at 0 hr (P < 0.01), 2 hr (P < 0.05) and 24 hr (P < 0.01). In group 1, 38.5% of patients had a nausea score of > or = 5 (major nausea) compared with only 12% of patients in group 2 (P < 0.025). The overall incidence of vomiting was greater in group 1 (35%) than in group 2 (8%) (P < 0.05). The combination group showed better control of delayed vomiting compared with the ondansetron group (4% vs 35%) (P < 0.01). CONCLUSION: The combination of ondansetron and dexamethasone provides adequate control of PONV, with delayed PONV being better controlled than early PONV.     

Prophylaxis of postoperative nausea and vomiting with oral, long-acting dimenhydrinate in gynecologic outpatient laparoscopy

Dimenhydrinate is an inexpensive antiemetic with few side effects available as an oral, long-acting (LA) formulation (Gravol L/A) containing 25 mg of immediate and 50 mg of sustained release drug. We designed this double-blind comparison trial to assess the efficacy of dimenhydrinate LA versus droperidol alone and the combination for prophylaxis of nausea, vomiting, and retching in outpatient gynecologic laparoscopy. One-hundred-forty-one women were randomized into 3 groups: 1) droperidol (placebo capsule preoperatively and IV droperidol 0.625 mg before induction), 2) dimenhydrinate LA preoperatively and IV placebo before induction, or 3) combination. Information regarding nausea, vomiting, retching, pain, and sedation was recorded in the postanesthesia care unit (PACU) and collected by telephone for the presence of symptoms: on arrival home; at bedtime; upon arising, and at lunchtime the following day. The overall incidence of complete treatment failure (rescue medication in PACU or nausea, vomiting, or retching at any time point) was 28 of 46 (61%), 28 of 48 (58%), and 22 of 47 (47%); and for treatment failure vomiting (rescue medication in PACU or vomiting or retching at any time point) was 16 of 46 (35%), 11 of 48 (23%), and 5 of 47 (11%), for the droperidol, dimenhydrinate, and combination groups, respectively (P = 0.007 for droperidol versus combination). There were no differences in sedation or pain. Preoperative administration of an oral dose of LA dimenhydrinate in combination with droperidol when compared with droperidol alone effectively reduced the incidence of vomiting but not nausea in women undergoing elective outpatient gynecologic laparoscopy. IMPLICATIONS: Dimenhydrinate is an inexpensive antiemetic with few side effects available as a long-acting oral formulation. Women undergoing outpatient gynecologic laparoscopy were given droperidol, an effective antiemetic, dimenhydrinate alone, or the combination of the two drugs. Dimenhydrinate plus droperidol significantly reduced the overall incidence of vomiting, but not nausea, when compared with droperidol alone.     

Additive anti-emetic efficacy of prophylactic ondansetron with droperidol in out-patient gynecological laparoscopy

PURPOSE: To determine the efficacy of ondansetron and droperidol, alone and in combination, administered for prophylaxis of postoperative nausea and vomiting (PONV) in women undergoing general anesthesia for outpatient gynecological laparoscopy. METHODS: Following Institutional Ethics Board approval and patient consent, 160 female out- patients scheduled for laparoscopy were randomly allotted in a double-blind fashion to receive: i) saline (placebo), ii) 4 mg ondansetron, iii) 1.25 mg droperidol, or iv) 4 mg ondansetron and 1.25 mg droperidol combination intravenously on induction. Following a standardized general anesthesia, patients were interviewed and assessed for PONV at various times. RESULTS: During the first 24 hr after surgery, the incidence of PONV in the placebo group was 71%. This was reduced to 61% with droperidol alone (P = 0.334), to 46% with ondansetron alone (P = 0.027), and to 23% with the combination group (P<0.001). A statistically significant difference was observed between combination and droperidol (P<0.001) and between combination and ondansetron (P = 0.036). There were fewer requests for rescue medication from the combination group (7.7%) than from the ondansetron and placebo groups. CONCLUSION: The results of this study suggest that the combination of 4 mg ondansetron and 1.25 mg droperidol is more efficacious as a prophylactic anti-emetic than either agent alone during the 24 hr post-surgery. This additive effect may be due to the different mechanisms of action of ondansetron and 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.     

Comparison of ondansetron and droperidol in the prevention of postoperative nausea and vomiting after laparoscopic surgery in women

Background : Women undergoing laparoscopic surgery are susceptible to postoperative nausea and vomiting (PONV). Ondansetron and droperidol are useful antiemetics. This study was designed to ascertain primarily the relative difference in efficacy of ondansetron and droperidol and secondarily between these drugs and placebo in the prevention of PONV after laparoscopic surgery. Methods : The prophylactic antiemetic efficacy of ondansetron and droperidol was compared in a prospective, randomised, double–blind, placebo–controlled trial of 439 female inpatients scheduled for laparoscopic surgery. During induction of standardised general anaesthesia the patients received intravenously either ondansetron 8 mg (n=195), droperidol 1.25 mg (n=193) or placebo (n=51). The occurrence of nausea, vomiting, sideeffects and the need for rescue antiemetic medication were recorded for 24 h postoperatively. Results : The proportion of patients with nausea was 48%, 50% and 67% in the ondansetron, droperidol and placebo groups, respectively; with a significant difference when both ondansetron (P=0.02) and droperidol (P=0.04) were compared with placebo. Vomiting occurred in 18%, 26% and 37% of the patients in the three groups, respectively (P=0.05 between ondansetron and droperidol, P=0.004 between ondansetron and placebo, P=0.16 between droperidol and placebo). The proportion of patients given rescue medication was 34%, 28% and 49%, respectively (P=0.23 for ondansetron and droperidol, P=0.07 for ondansetron and placebo, P=0.007 for droperidol and placebo). During early recovery the patients treated with ondansetron were significantly more alert than after droperidol. Serious side–effects were not observed. Headache was significantly more common after ondansetron than after droperidol treatment. Conclusions : The efficacy of prophylactic ondansetron and droperidol in reducing postoperative nausea associated with laparoscopic surgery in female inpatients was similar, but ondansetron appeared to be slightly more efficient than droperidol in preventing vomiting. Ondansetron and droperidol were both significantly better than placebo in the prophylaxis of PONV.     

Antiemetic prophylaxis for office-based surgery: are the 5-HT3 receptor antagonists beneficial?

BACKGROUND: Office-based surgery has become increasingly popular because of its cost-saving potential. However, the occurrence of postoperative nausea and vomiting (PONV) can delay patient discharge. Prophylaxis using a combination of antiemetic drugs has been suggested as an effective strategy for minimizing PONV. The authors designed this randomized, double-blinded, placebo-controlled study to assess the efficacy of ondansetron and dolasetron when administered in combination with droperidol and dexamethasone for routine antiemetic prophylaxis against PONV in the office-based surgery setting. METHODS: Following institutional review board approval, 135 consenting outpatients with American Society of Anesthesiologists physical status I-III who were undergoing superficial surgical procedures lasting 20-40 min were randomly assigned to one of three antiemetic treatment groups. Propofol was administered for induction of anesthesia, followed by 2-4% desflurane with 67% nitrous oxide in oxygen. Desflurane was subsequently adjusted to maintain a clinically adequate depth of anesthesia with an electroencephalographic Bispectral Index value between 50 and 60. All patients received 0.625 mg intravenous droperidol and 4 mg intravenous dexamethasone after induction of anesthesia. The study medication, containing normal saline (control), 12.5 mg intravenous dolasetron, or 4 mg intravenous ondansetron, was administered prior to the end of surgery. All patients received local anesthetics at the incisional site and 30 mg intravenous ketolorac to minimize postoperative pain. Recovery profiles, incidence of PONV, requirement for rescue antiemetic drugs, complete response rates, and patient satisfaction were assessed. RESULTS: The recovery times to patient orientation, oral intake, ambulation, and actual discharge did not differ among the three groups. The incidence of PONV, nausea scores, and requirement for rescue antiemetics were also similar in all three groups during the 24-h study period. In addition, the complete response rates to the prophylactic antiemetics (96-98%) and percentages of very satisfied patients (93-98%) were equally high in all three groups. However, the antiemetic drug acquisition costs were US $2.50, $15.50, and $18.50 in the control, dolasetron, and ondansetron groups, respectively. CONCLUSION: The addition of dolasetron (12.5 mg) or ondansetron (4 mg) failed to improve the antiemetic efficacy of droperidol (0.625 mg intravenous) and dexamethasone (4 mg intravenous) when they were used for routine prophylaxis in the office-based surgery setting.     

Randomized, double-blind trial of dolasetron versus droperidol for prophylaxis of postoperative nausea and vomiting in patients undergoing TRAM flap breast reconstruction surgery

Clinical observation indicates that patients undergoing transverse rectus abdominus musculocutaneous (TRAM) flap breast reconstruction surgery frequently experience postoperative nausea and/or vomiting (PONV). No controlled trials have evaluated the role of pharmacologic prophylaxis of PONV in this population. A prospective randomized, double-blinded, active-controlled trial comparing intraoperative intravenous droperidol 1 mg with dolasetron 50 mg was conducted. Seventy-one patients were included in the intention-to-treat analysis. The incidence of the primary end point of PONV within 24 hours after surgery was 81.8% versus 78.9% for droperidol and dolasetron, respectively (p = 0.8). No significant differences were detected in the time to onset of PONV, incidence of severe nausea or emesis, or incidence of emesis alone. Time to rescue antiemetic use was longer in the droperidol group (7.1 vs. 1.3 hours, p = 0.002). Adverse effects were similar between the two groups. No PONV-related complications occurred during the trial period. The incidence of PONV in TRAM flap breast reconstruction surgery patients remains high despite prophylactic intraoperative antiemetic administration.     

Efficacy, dose-response, and adverse effects of droperidol for prevention of postoperative nausea and vomiting

PURPOSE: To estimate the efficacy and harm produced by droperidol in the prevention of postoperative nausea and vomiting (PONV). METHODS: Systematic search (MEDLINE, EMBASE, Cochrane library, hand-searching, bibliographies, all languages, up to May 1999) for randomised comparisons of droperidol with placebo in surgical patients. Relevant end points were prevention of early PONV (up to six hours postoperatively), and late PONV (24 hr), and adverse effects. Combined data were analysed using relative risk and NNT. RESULTS: In 76 trials, 5,351 patients received 24 different regimens of droperidol. The average incidence of early and late PONV in controls was 34% and 51%, respectively. Droperidol was more efficacious than placebo in preventing PONV. In adults, the anti-nausea effect was short-lived, and there was no dose-responsiveness; with 0.25 to 0.30 mg the number-needed-to-treat (NNT) to prevent early nausea was 5. For both early and late anti-vomiting efficacy there was dose-responsiveness; best efficacy was with 1.5 mg to 2.5 mg (NNT, 7). In children, there was dose-responsiveness; best efficacy was with 75 microg x kg(-1) (NNT to prevent early and late vomiting, 4). Two children had extrapyramidal symptoms with droperidol (NNT in children, 91; in any patient, 408). There was dose-responsiveness for sedation and drowsiness (with 2.5 mg the NNT was 7.8). Droperidol prevented postoperative headache (NNT, -25). CONCLUSIONS: Droperidol is anti-emetic in the surgical setting. The effect on nausea is short-lived but more pronounced than the effect on vomiting. Sedation and drowsiness are dose-dependent, extrapyramidal symptoms are rare, and there is a protective effect against headache.     

Dexamethasone 8 mg in combination with ondansetron 4 mg appears to be the optimal dose for the prevention of nausea and vomiting after laparoscopic cholecystectomy

PURPOSE: The combination of antiemetic drugs could be a solution to prevent severe postoperative nausea and vomiting (PONV). The aim of this randomized double blind, dose-ranging study was to determine the minimum single effective dose of dexamethasone combined with ondansetron for the prevention of PONV in patients undergoing laparoscopic cholecystectomy. METHODS: One hundred eighty patients were allocated randomly to one of six groups to receive saline (P group), ondansetron 4 mg (O group), or ondansetron 4 mg and dexamethasone at doses of 2 mg (OD2 group), 4 mg (OD4 group), 8 mg (OD8 group), and 16 mg (OD16 group). A standardized general anesthetic was used. All episodes of PONV during the intervals of zero to six hours, 6-12 hr and 12-24 hr after surgery were evaluated using a numeric scoring system. Mean visual analogue scale pain scores at rest and on movement, the time to first demand of analgesia, total analgesic consumption in 12 hr epochs, duration of hospital stay, and side effects were recorded. RESULTS: The incidence of PONV in the OD8 (16%) and OD16 (16%) groups was lower than in the 83% (P < 0.001) and O groups (50%) at the 12-24 hr epoch (P < 0.05). There were no differences in antiemetic effect between the O, OD2 and OD4 groups and between the OD8 and OD16 groups. Pain scores, total analgesic consumption, duration of hospital stay and side effects were similar among groups. CONCLUSION: Our results suggest that 8 mg is the minimum dose of dexamethasone that, combined with ondansetron 4 mg will effectively prevent PONV in patients undergoing laparoscopic cholecystectomy.     

Postoperative nausea and vomiting management in maxillofacial procedures: Dexamethasone combined with metoclopramide

BackgroundEfficient prevention and management of postoperative nausea and vomiting (PONV) continues to be a concern that needs to be addressed. There was a persistently high incidence of PONV despite prophylaxis with, metoclopramide, droperidol, dimenhydrinate or ondansetron when each was used alone in ‘at risk’ patients. Dexamethasone was also used as a stand alone drug in patients undergoing surgery. However, the current opinion questions the role of monotherapy. Drug combinations are deemed to be more useful for balanced anti-emesis. The aim of this study was to evaluate the prophylactic antiemetic effects of the combination dexamethasone–metoclopramide in patients undergoing maxillofacial procedures.Patients and methodsIn this placebo-controlled, double-blind study, 208 outpatients under standardized anesthetic technique were randomized to receive dexamethasone 8 mg before anesthesia induction and metoclopramide, 10 mg at the end of surgery (Group A), dexamethasone 8 mg before anesthesia induction and placebo at the end of surgery (Group B), placebo before anesthesia induction and metoclopramide, 10 mg at the end of surgery (Group C) or placebo before anesthesia induction and at the end of surgery (Group D). Complete response to prophylactic antiemetic medication was defined as no vomiting, no sustained moderate nausea and no requesting of antiemetic drug.ResultsDuring predischarge period, the number of patients with complete response to prophylactic antiemetic medication was significantly higher in Groups B (90.4%) and A (86.5%) in comparison with Groups D (55.8%) and C (75%). At the 24 h follow-up evaluation, complete response was higher in Group A (96.2%) in comparison with Groups C (67.3%) and D (78.8%).ConclusionsDexamethasone–metoclopramide combination is not more effective than administration of dexamethasone alone in the prophylaxis of (PONV).     

Prophylactic antiemetics for laparoscopic cholecystectomy: droperidol, metoclopramide, and droperidol plus metoclopramide

BACKGROUND: Postoperative nausea and vomiting (PONV) is one of the most significant problems in laparoscopic surgery. The antiemetic effects of metoclopramide and droperidol used alone or in combination for prevention of PONV after laparoscopic cholecystectomy (LC) were assessed in this prospective, double blind, placebo controlled randomized study. PATIENTS AND METHODS: A series of 140 patients, ASA physical status I or II, were included in the study. Patients were randomized to one of the following groups: 1, placebo; 2, metoclopramide 10 mg after the induction of anesthesia and placebo at 12 h postoperatively; 3, droperidol 1.25 mg after the induction of anesthesia and droperidol 1.25 mg at 12 h postoperatively; and 4, droperidol 1.25 mg plus metoclopramide 10 mg after the induction of anesthesia and droperidol 1.25 mg at 12 h postoperatively. Patients were observed for 24 hours for PONV, pain, need for rescue analgesics, and adverse events. RESULTS: Data were analyzed using the Student's t-test and chi-square test, with P < 0.05 considered statistically significant. The mean incidence of PONV was 54% with placebo, 42% with metoclopramide, 14% with two doses of droperidol alone, and 11% with a combination of metoclopramide plus droperidol. The patients receiving a combination of metoclopramide and droperidol had a significantly lower rate of PONV than those administered metoclopramide alone (P < 0.05) or placebo (P < 0.001). Those receiving two-dose droperidol alone also had a significantly lower incidence of PONV compared with metoclopramide (P < 0.05) and placebo (P < 0.001). There was no statistically significant difference between the metoclopramide and placebo groups. Sedation was significantly greater in patients administered droperidol 12 h postoperatively. CONCLUSION: The combination of metoclopramide and droperidol, and two-dose droperidol alone, were found to significantly decrease the incidence of PONV after LC, whereas metoclopramide alone proved inefficient.     

Combination of granisetron and droperidol in the prevention of nausea and vomiting after middle ear surgery.

STUDY OBJECTIVES: To evaluate the efficacy and safety of granisetron-droperidol combination for the prevention of postoperative nausea and vomiting (PONV) after middle ear surgery. DESIGN: Prospective, randomized, double-blind study. SETTING: University hospital. PATIENTS: 150 ASA physical status I patients (108 females, 42 males) scheduled for elective middle ear surgery. INTERVENTIONS: Patients received granisetron 40 micrograms/kg (n = 50), droperidol 20 micrograms/kg (n = 50), or granisetron 40 micrograms/kg plus droperidol 20 micrograms/kg (n = 50) intravenously immediately before induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: A standard general anesthetic technique and postoperative analgesia were used throughout the study. A complete response, defined as no PONV and no need for another rescue antiemetic, from 0 to 3 hours after anesthesia occurred in 78%, 56%, and 94% of patients who had received granisetron, droperidol, and granisetron plus droperidol, respectively. The corresponding incidence between 3 and 24 hours after anesthesia was 80%, 52% and 94%. Thus, a complete response within the first 24-hour postanesthetic period was greater in patients receiving granisetron-droperidol combination than in those receiving granisetron alone or droperidol alone (p < 0.05). No clinically adverse events were observed in any of the groups. CONCLUSIONS: A combination of granisetron and droperidol is more effective than droperidol or granisetron alone for the prevention of PONV after middle ear surgery.