The efficacy of the 5-HT3 receptor antagonists combined with droperidol for PONV prophylaxis is similar to their combination with dexamethasone. A meta-analysis of randomized controlled trials

PURPOSE: The aim of this quantitative systematic review is to compare the efficacy and side effects of combining one of the 5-HT(3) receptor antagonists (5-HT) with droperidol or dexamethasone for postoperative nausea and vomiting (PONV) prophylaxis. METHODS: We performed a systematic search (Medline, Embase, and the Cochrane Library) for randomized controlled trials that compared the antiemetic efficacy of combining one of the 5-HT with droperidol or dexamethasone vs 5-HT alone. Relevant endpoints were prevention of early (0 to 6 hr), and overall (0 to 24 hr) PONV, and side effects. The articles that could meet the inclusion criteria were scored for inclusion and methodological validity using the three-item, five-point, Oxford-scale. Relative risk and numbers needed-to-treat with 95% confidence intervals were calculated for each combination vs 5-HT alone. The two combinations were then indirectly compared. A random effects model was used. RESULTS: We considered 41 trials for analysis but subsequently excluded eight. Thirty-three trials with data from 3,447 patients were analyzed. Except for early nausea with the 5-HT plus droperidol, both combinations were significantly more effective than 5-HT in preventing early and overall PONV. There was no difference in antiemetic efficacy between the two combinations. The incidence of commonly reported side effects was also similar in the two combination groups. CONCLUSION: We conclude that there is no statistically significant difference in antiemetic efficacy or side effects profile when one of the 5-HT is combined with either droperidol or dexamethasone and that both combination regimens are significantly more effective than 5-HT alone.     

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.     

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.     

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.     

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.     

Individualized outcome feedback produces voluntary antiemetic prescribing practice changes.

STUDY OBJECTIVE: To determine the impact of individualized outcome feedback on antiemetic prescribing practices and compare outcomes of a cost-effective, standardized antiemetic protocol (PROT) to that of customized antiemetic therapy (NONPROT). DESIGN: Prospective, observational study with randomized component. SETTING: Postanesthesia care unit (PACU) of an academic medical center. PATIENTS: 3027 consecutive ASA physical status I, II, and III patients receiving general anesthesia. INTERVENTIONS: Patients were randomized to receive 0.625 mg droperidol or 4 mg ondansetron for postoperative nausea and/or vomiting (PONV) from a protocol, or received customized antiemetic therapy. MEASUREMENTS AND MAIN RESULTS: Incidence of PACU PONV, selection of PROT versus NONPROT, patient satisfaction, and use of PONV prophylaxis were measured and indexed by an attending anesthesiologist in a monthly report for 4 months. Monthly expenditures for antiemetic therapy prior to, during, and after the study were collected. Literature on PONV outcomes, appropriate timing, and selection of PONV prophylaxis was distributed. The NONPROT group was slightly older than the PROT group; otherwise, demographics were similar between all groups. The incidence of PONV did not differ between the PROT and NONPROT groups (11% vs. 10%), and the incidence of PONV in patients receiving prophylaxis was higher in both groups (17% PROT vs. 15% NONPROT). Patients receiving ondansetron as a first-line drug required rescue therapy less often (5%) than those receiving droperidol (14%); however, patient satisfaction was indistinguishable among all groups. During the study, the use of prophylaxis decreased 47% without an increase in PONV, and PROT selection increased 54%. CONCLUSIONS: Individualized outcome feedback produced a 48% reduction in monthly expenditures for ondansetron and droperidol, which was sustained after the study. Patients satisfaction between ondansetron 4 mg and droperidol 0.625 mg given in the PACU did not differ in spite of a slightly greater efficacy of ondansetron as a first-line drug.     

Combination of droperidol and ondansetron reduces PONV after pediatric strabismus surgery more than single drug therapy

BACKGROUND: Pediatric strabismus surgery is associated with a very high incidence of postoperative nausea and vomiting [(PONV) 44-88%]. Droperidol (10-75 microg kg(-1)) and ondansetron (50-150 microg kg(-1)) have shown variable success in reducing the incidence and severity of PONV. Combination of these two drugs has shown promising results. This randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the efficacy and safety of the combination of these two drugs in reducing the incidence and severity of PONV in pediatric strabismus surgery. METHODS: After institutional approval and parental informed consent, 240 children of ASA physical status I and II of either sex, aged 1-15 years were included in this study. None of the children received any premedication and a standardized anesthesia technique was used for all the children. They were prospectively randomized to one of the four treatment groups. Group PP received normal saline placebo intravenously after induction and at the end of the procedure. Group DP received droperidol 25 microg kg(-1) after induction and normal saline at the end. Group OP received ondansetron 150 microg kg(-1) after induction and saline at the end. Group DO received droperidol 15 microg kg(-1) after induction and ondansetron 100 microg kg(-1) at the end. RESULTS: Combination prophylaxis resulted in a lower incidence of PONV (13%) as compared to placebo (62.5%, P<0.001), ondansetron (37%, P<0.001), or droperidol (32%, P<0.01). CONCLUSION: Droperidol 15 microg kg(-1) in combination with ondansetron 100 microg kg(-1), administered at the induction and end of the operative procedure respectively, is more effective than either drug given individually in reducing the incidence of PONV after strabismus surgery.     

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.     

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.     

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.     

Small-dose droperidol effectively reduces nausea in a general surgical adult patient population

In this prospective, randomized, placebo-controlled study, we (1) determined whether 0.625 mg of IV droperidol given 30 min before emergence from general anesthesia reduces the incidence of immediate and delayed postoperative nausea and vomiting (PONV) in a general surgical adult patient population, and (2) compared the efficacy of droperidol, ondansetron, and promethazine for the rescue treatment of PONV. One hundred fifty adult patients receiving general anesthesia for >2 h received either droperidol (0.625 mg IV) or a placebo before emergence. Patients requiring treatment for PONV in the postanesthesia care unit were randomized to receive either droperidol (0.625 mg IV), ondansetron (4 mg IV), or promethazine (12. 5 mg IV). Droperidol effectively prevented PONV (6.8% in droperidol-treated patients versus 40.8% in placebo-treated patients, P: < 0.001). Droperidol, ondansetron, and promethazine were equally effective in treating established PONV, without significant differences in side effects or time to postanesthesia care unit discharge. Implications: Droperidol 0.625 mg IV before emergence from general anesthesia effectively reduces postoperative nausea and vomiting (PONV) in the general surgical population. Our randomized, double-blinded, placebo-controlled study demonstrated a reduction in PONV from 41% to 7%. Droperidol is a safe and inexpensive alternative to ondansetron. Droperidol, ondansetron, and promethazine are also equally effective in treating PONV in the postanesthesia care unit.     

Prophylaxe von ��belkeit und Erbrechen in der postoperativen Phase

Objective

The aim of the present study was to conduct a meta-analysis of the results from randomized controlled trials investigating the relative efficacy of droperidol versus metoclopramide for the prevention of postoperative nausea and vomiting (PONV).

Methods

A systematic literature search for randomized controlled trials comparing droperidol and metoclopramide for the prevention of PONV was performed according to the PRISMA recommendations. The incidence of PONV within the early (0?C6?h) and cumulative postoperative periods (0?C48?h) was collated and the pooled relative risk (RR) with the corresponding 95% confidence interval (CI) was calculated. Results from a subgroup analysis are presented excluding the data of a Japanese group (Fujii et al.) which are given in parentheses.

Results

A total of 41 (30) trials with a total number of 3,491 (2,721) patients were included and of these 12 (8) trials with 1,403 (1,083) patients reported data of the early period and 32 (21) studies with 2,656 (1,836) patients comprised data of the cumulative period. A total of 1,797 (1,309) patients were treated with droperidol (0.25?C5?mg) and 1,694 (1,412) with metoclopramide (5?C50?mg). In the early period the risk for PONV after metoclopramide was 35% (95%-CI: 17?C57%) higher than after prophylaxis with droperidol (without Fujii data: 46%; 23?C73%). During the cumulative period the risk for PONV after metoclopramide was increased by 20% (95%-CI: 7?C37%) compared to droperidol (without Fujii data: 25%; 4?C50%). Due to heterogenous dosing of both drugs subgroup analyses with distinct dose intervals were performed with increments of 0.75?mg for droperidol and 7?mg for metoclopramide. Droperidol was superior in 17 (12) out of 19 (14) subgroup analyses. Comparing recommended doses of droperidol (0.75?C1.5?mg) with low doses of metoclopramide (7?C14?mg) and medium metoclopramide doses (14?C21?mg) PONV was increased by 12% (95%-CI: ?11% to 42%) and 32% (95%-CI: 4%?C66%), respectively when metoclopramide instead of droperidol was used. When higher doses of metoclopramide (>20?mg) were used the superiority of droperidol was less pronounced and did not reach statistical significance due to the limited numbers of trials included in this analysis (3 studies, 662 patients). The risk for PONV after high-dose metoclopramide was increased by 13% (95%-CI: ?21% to +61%) for the early period and by 19% (95%-CI: ?11% to +57%) for the cumulative observation period.

Conclusion

For the prevention of postoperative nausea and vomiting droperidol is significantly superior to metoclopramide doses below 20?mg. There was no obvious positive dose response with respect to increasing doses of metoclopramide. There was also a trend towards higher efficacy of droperidol compared to higher doses of metoclopramide (??20?mg). However, there were not enough comparative studies to show a statistically significant result in this subgroup analysis. These data support the notion that droperidol in low doses may represent the more effective D₂-antagonist for a pharmacological armamentarium to cope with PONV.     

Prophylaxis of postoperative nausea and vomiting: controversies in the use of serotonin 5-hydroxytryptamine subtype 3 receptor antagonists

Postoperative nausea and vomiting (PONV) continues to be a "big little problem" despite recent advances in anesthesia. Because of an increased interest in, and the abundant publications on this topic, guidelines for the management of PONV were published in 2003. Several key but controversial issues regarding PONV prophylaxis were left unaddressed, however. These included whether clinical differences exist between the 5-hydroxytryptamine subtype 3 (5-HT3) receptor antagonists, concern over optimal dosage and timing of administration, optimal 5-HT3 receptor antagonist combination therapy, and whether rescue therapy is effective after prior administration of the same or a different 5-HT3 receptor antagonist. The application of these antiemetics in clinical practice has raised questions regarding the role of the 5-HT3 receptor antagonists in the treatment of postdischarge nausea and vomiting and opioid-induced nausea and vomiting. A brief overview of the incidence, risk factors and current management recommendations for PONV and current controversies with special emphasis on the 5-HT3 receptor antagonists, is discussed.     

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.      

Klinische Pharmakologie

The rule of three describes three steps which are needed for an optimal control of postoperative nausea and vomiting (PONV). Firstly, patients at high risk of PONV need to be identified. Knowledge about predictive factors may help to identify patients who may best profit from prophylaxis and those where prophylaxis is not worthwhile since the baseline risk is too low. Secondly, for high-risk patients a low emetogenic anaesthesia technique should be chosen, and thirdly, these patients should additionally receive a prophylactic antiemetic cocktail. At present, butyrophenones (e.g. droperidol), 5-HT(3) receptor antagonists ("setrons") and steroids (e.g. dexamethasone) are the most rational choices for the antiemetic cocktail. Although there is strong evidence that there is an additive effect when these antiemetics are combined, economic constraints may influence the number of antiemetics that are eventually chosen. Identification of high-risk patients remains the most difficult part of the rule of three. Risk scores have been proposed and have been widely implemented in clinical practice. The sensitivity and specificity of such scores, however, remain particularly unsatisfactory. Unless more reliable risk scores are developed, aggressive treatment of established PONV symptoms may be more useful and more cost-effective than prophylaxis for many patients.     

A randomized comparison of a multimodal management strategy versus combination antiemetics for the prevention of postoperative nausea and vomiting

A multimodal management strategy for the prevention of postoperative nausea and vomiting (PONV) appears to be superior to single-drug prophylaxis. We tested the hypothesis that a multimodal PONV prophylaxis regimen incorporating total IV anesthesia (TIVA) with propofol and a combination of ondansetron and droperidol is more effective than a combination of these antiemetics in the presence of an inhaled anesthetic. Ninety patients undergoing laparoscopic cholecystectomy were randomized to one of three groups. Group 1 (multimodal group) received TIVA with propofol, droperidol, and ondansetron. Group 2 (combination group) received droperidol and ondansetron with isoflurane and nitrous oxide for the maintenance of anesthesia. Group 3 (TIVA group) received propofol for the induction and maintenance of anesthesia. The complete response rate (no PONV and no rescue antiemetic) at 2 h after surgery was 90%, 63%, and 66% in Groups 1, 2, and 3, respectively (P < 0.05, Group 1 versus Group 2). At 24 h, the complete response rate was 80%, 63%, and 43% in Groups 1, 2, and 3, respectively (P < 0.05, Group 1 versus Group 3). Patient satisfaction was also greater in the multimodal group than in the other two groups in the postanesthesia care unit (P < 0.05). In conclusion, the multimodal management strategy for PONV was associated with a higher complete response rate and greater patient satisfaction when compared with similar antiemetic prophylaxis with inhaled anesthesia or TIVA with propofol.     

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.     

A comparison of ranitidine,droperidol or placebo in the prevention of nausea and vomiting after hysterectomy

Purpose

The effect of ranitidine on postoperative nausea and vomiting (PONV) was assessed when compared with droperidol and with placebo.

Methods

Three groups of sixty patients were studied in a double-blind randomized manner. The first group received ranitidine tablets 300 mg on the night before and on the following morning, one hour before induction of anaesthesia. Thirty minutes before surgery ended they were given isotonic saline 0.3 ml iv. The second group had placebo in place of ranitidine while before the operation ended, droperidol 0.75 mg (0.3 ml) was injected. The third group received placebos rather than the study drugs. The immediate two-hour postoperative recovery room period and that on the ward were evaluated until the next morning. PONV information was gathered from complaints by the patients and from direct questioning by the nursing staff. Droperidol 0.75 mg iv served as the “rescue drug”.

Results

Less PONV occurred in patients who received antiemetics vthan those given placebo: recovery room, P = 0.0109; ward, P = 0.007. Droperidol better suppressed PONV in the recovery room (P = 0.005) with no statistical significance seen between ranitidine and placebo. On the ward, both antiemetics were more effective than placebo (ranitidine, P = 0.01; droperidol, P = 0.003). “Rescue drug” requirements throughout the study periods were not statistically significant.

Conclusion

Although both anti-emetics were associated with a smaller incidence of PONV than was placebo, droperidol was superior to ranitidine in preventing sickness during the immediate postoperative period. The need for the “rescue drug” was similar in all groups.     

A small dose of droperidol decreases postoperative nausea and vomiting in adults but cannot improve an already excellent patient satisfaction

BACKGROUND: We evaluated whether or not 1) a routine prophylaxis with 20 microg x kg(-1) body weight of droperidol would efficiently prevent postoperative nausea and vomiting (PONV) after elective surgery in adults and 2) an efficient prophylaxis would improve patient satisfaction. METHODS: With approval of the local ethics committe and after having obtained informed written consent, 1334 patients in a randomised, single-blinded fashion either received droperidol (group 1, n=665) or saline intravenously (group 2, n=669) 20 min before the end of a standard O2/N2O/fentanyl/isoflurane anaesthesia of at least 30 min duration. End points: incidence of PONV during the first 24 h; individual episodes of nausea or vomiting, overall patient satisfaction with the procedure. RESULTS: Compared to saline, intravenous injection of droperidol substantially and significantly reduced the incidence of PONV from 30% to 20% (P<0.0001). Women suffered three times more frequently from PONV (10.5% vs. 30%, P<0.0001). Droperidol significantly reduced the incidence of PONV from 35.4% to 24.4% in women (relative risk reduction: 31%, P=0.0002), but not in men (13.1% vs. 8.2%, relative risk reduction: 37%, P=0.159)--without impact on overall patient satisfaction (98.8% vs. 97.1%, P=0.439). Distribution of surgical procedures, sex, age, height, weight and anaesthetic duration were not different between groups. To prevent one woman from suffering PONV, nine had to be treated prophylactically at an individual drug cost (German prices) of about Euro0.80 per woman. CONCLUSION: Routine PONV prophylaxis with 20 microg x kg(-1) body weight of droperidol is cost-efficient and appropriate in women but not in men.     

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.