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.     

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.     

Management of postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy

The common and distressing complications of postoperative nausea and vomiting (PONV) are the main concern of 40–70% of patients undergoing laparoscopic cholecystectomy (LC). The first step in preventing PONV after LC is to reduce the risk factors involving patient characteristics, surgical procedure, anesthetic technique, and postoperative care. Particularly, the use of propofol-based anesthesia can reduce the incidence of PONV after LC. Second, prophylactic antiemetics including antihistamines (dimenhydrinate), phenothiazines (perphenazine), butyrophenones (droperidol), benzamides (metoclopramide), dexamethasone, and serotonin receptor antagonists (ondansetron, granisetron, tropisetron, dolasetron, and ramosetron) are available for preventing PONV after LC. Third, antiemetic therapy combined with a serotonin receptor antagonist (ondansetron, granisetron) and droperidol or dexamethasone is highly effective in the prevention of PONV after LC. Fourth, acupressure at the P6 point is a nonpharmacologic technique that is as effective as ondansetron for preventing PONV after LC. Knowledge regarding the risk factors for PONV and antiemetics is needed for the management of PONV after LC.     

Nondepolarizing neuromuscular blockers inhibit the serotonin-type 3A receptor expressed in Xenopus oocytes

Molecular cloning and sequence comparison indicates a high degree of structural homology between muscle nicotinic acetylcholine (nACh) and serotonin-type 3 (5-HT(3A)) receptors, both members of the direct ligand-gated family of ion channels. Because of the structural similarities and common evolutionary origin of these receptors, neuromuscular blockers (competitive nACh antagonists) may demonstrate pharmacologic cross talk and exhibit attributes of 5-HT(3A) receptor antagonists. We examined six clinically-used neuromuscular blockers for their ability to antagonize currents flowing through the 5-HT(3A) receptors in voltage clamped Xenopus oocytes. The neuromuscular blockers reversibly inhibited the 5-HT(3A) receptor-gated current in the rank order potency of (IC50 mean +/- SEM): d-tubocurarine (0.046 +/- 0.003 microM), atracurium (0.40 +/- 0.03 microM), mivacurium (15.1 +/- 2.93 microM), vecuronium (16.3 +/- 2.24 microM), and rocuronium (19.5 +/- 2.31 microM). Gallamine was essentially inactive as a 5-HT(3A) receptor antagonist with an extrapolated IC50 of 1170 microM. We demonstrate that drugs classically known as competitive nACh receptor antagonists also block 5-HT(3A) receptors. It is likely that certain neuromuscular blockers share pharmacological properties with 5-HT(3A) receptor antagonists, such as a reduction in postoperative nausea and vomiting. With careful drug selection, pharmacological cross talk could potentially be used to minimize polypharmacy and optimize patient management. IMPLICATIONS: Muscle nicotinic acetylcholine and serotonin-type 3A (5-HT(3A)) receptors are similar. Therefore neuromuscular relaxants may block 5-HT(3A) receptors. Our pharmacological study demonstrates that neuromuscular relaxants, as with ondansetron, are 5-HT(3A) receptor antagonists. It is likely that certain neuromuscular relaxants exhibit ondansetron-like clinical properties, such as reduction in postoperative nausea and vomiting.     

Nausea and vomiting after laparoscopic gynecologic surgery: a study of the incidence and the effects of tropisetron prophylaxis

We have studied the incidence of postoperative nausea and vomiting (PONV) and the effect of prophylactic tropisetron, a 5-HT3 antagonist, during the first 24 hr after elective gynecologic laparoscopic surgery. Thirty-two of 68 patients (47%) experienced nausea or vomiting some time during the observation period. Sixteen of these patients (50%) had their first emetic symptoms after discharge from the recovery room. We could see no difference in the frequency of PONV in the patients who were given prophylactic tropisetron 5 mg orally before anesthesia.     

Nausea and vomiting after laparoscopic gynecological surgery: a study of the incidence and the effects of tropisetron prophylaxis

The authors studied the incidence of postoperative nausea and vomiting (PONV) and the effect of prophylactic tropisetron, a 5-HT3 antagonist, during the first 24 h following elective gynecologic laparoscopic surgery. Thirty-two of 68 (47%) of the patients experienced nausea or vomiting some time during the observation period. Sixteen of the 32 PONV patients (50%) had their first emetic symptoms after discharge from the recovery room. We could see no difference in the frequency of PONV in the patients who were given prophylactic tropisetron 5 mg orally before anesthesia.     

The efficacy and cost-effectiveness of prophylactic 5-hydroxytryptamine3 receptor antagonists: tropisetron,ondansetron and dolasetron

There are currently three 5-hydroxytryptamine3 (5-HT3) receptor antagonists available in Australia. In this randomized, double-blind, parallel group study the prophylactic antiemetic effect of a single dose of tropisetron 2 mg, ondansetron 4 mg or dolasetron 12.5 mg was compared after major gynaecological surgery. One hundred and eighteen patients (group T n = 42; group O n = 36; group D n = 40) were evaluated for nausea, vomiting, recovery characteristics and satisfaction for 24 hours postoperatively. A cost-effectiveness analysis was performed. Rescue antiemetic, prochlorperazine 12.5 mg i.m., was given if vomiting occurred more than 10 minutes after arrival in the recovery room. If prochlorperazine was ineffective one hour after administration, droperidol 1 mg i.v. was given. There were no significant differences between groups for the incidence of vomiting during consecutive epochs until 24 hours postoperatively or overall (57%, 75% and 72.5% for groups T, O and D respectively, P = 0.18). The incidence and number of rescue antiementic treatments for nausea or vomiting were similar. The incidence of nausea and the overall and interval nausea scores were similar except for lower "worst nausea" score in group T between 12 and 18 hours (P = 0.02). Recovery times, satisfaction and cost per patient did not differ between groups. We conclude that the risk of postoperative nausea and vomiting remained high in this setting despite 5-HT3 receptor antagonist prophylaxis and that the choice between these agents should be based on the lowest available acquisition cost.     

Effect of prophylactic 5-HT3 receptor antagonists on pruritus induced by neuraxial opioids: a quantitative systematic review

Pruritus is a frequent adverse event observed after neuraxial administration of opioids. Central 5-hydroxytryptamine subtype 3 (5-HT3) receptors may be activated in this process. This systematic review aimed to evaluate the efficacy of prophylactic 5-HT3 receptor antagonists on neuraxial opioid-induced pruritus. We searched Medline, Embase, and Cochrane Collaboration Library databases. Studies were evaluated with the Oxford Validity Scale. Studies with a score of 3 or more and reporting prophylactic administration of 5-HT3 receptor antagonists vs placebo were included. Fifteen randomized double-blind controlled trials (n=1337) were selected. 5-HT3 antagonists (n=775) significantly reduced pruritus [odds ratio (OR) 0.44 (95% confidence interval, 95% CI, 0.29-0.68), P=0.0002, number-needed-to-treat (NNT) 6 (95% CI, 4-14)], the treatment request for pruritus [OR 0.58 (95% CI, 0.43-0.78), P=0.0003, NNT 10 (95% CI, 7-20)], the intensity of pruritus [weighted mean difference (WMD) -0.35 (95% CI, -0.59 to -0.10), P=0.007], the incidence and the intensity of postoperative nausea and vomiting (PONV), and the need of rescue treatment [respectively, Peto odds ratio (Peto OR) 0.43 (95% CI, 0.31-0.58), P<0.00001, NNT 7 (95% CI, 6-10); WMD -0.12 (95% CI, -0.24 to 0.00), P=0.05 and OR 0.42 (95% CI, 0.20-0.86), P=0.02, NNT 8 (95% CI, 5-35)]. However, the funnel plot was asymmetric, suggesting a risk of publication bias. 5-HT3 receptor antagonists may be an effective strategy in preventing neuraxial opioid-induced pruritus and PONV. Further large randomized controlled trials are required to confirm these findings.     

Current therapy for management of postoperative nausea and vomiting: the 5-HT3 receptor antagonists

The control of postoperative nausea and vomiting (PONV) remains a problem in spite of the improvements achieved with newer anesthetic agents, such as propofol, and newer antiemetics. Management of PONV is difficult, this is most likely due to the multiple receptors and neurotransmitters in the central nervous system that mediate the emetic response, and to the multifactorial etiology of PONV. Studies of the four major 5-hydroxytryptamine (serotonin) subtype-3 (5-HT₃) receptor antagonists suggest that they have similar safety and efficacy for prevention and treatment of PONV. These drugs lack the significant side effects observed with traditional antiemetics. Combination regimens of 5-HT₃ receptor antagonists and traditional antiemetics can improve antiemetic efficacy. Areas of future study include comparing the cost effectiveness of these agents and determining optimal combinations of antiemetics to further reduce the incidence of PONV.     

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.     

Inhibitory effect of glucocorticoids on human-cloned 5-hydroxytryptamine3A receptor expressed in xenopus oocytes

BACKGROUND: Methylprednisolone, dexamethasone, and other glucocorticoids have been found effective against nausea and vomiting induced by chemotherapy and surgery. Although the specific 5-hydroxytriptamine3 (5-HT3) receptor antagonists such as ondansetron and ramosetron are used as antiemetics, reports show that the use of 5-HT3 receptor antagonists with some glucocorticoids brings additional effects. Glucocorticoids are reported to be antiemetic. The effect of glucocorticoids on 5-HT3 receptor, however, has not been well characterized. This study was designed to examine whether dexamethasone and methylprednisolone had direct effects on human-cloned 5-HT3A receptor expressed in Xenopus oocytes. METHODS: Homomeric human-cloned 5-HT3A receptor was expressed in Xenopus oocytes. The authors used the two-electrode voltage-clamping technique to study the effect of methylprednisolone and dexamethasone on 5-HT-induced current. RESULTS: Both dexamethasone and methylprednisolone concentration-dependently attenuated 5-HT-induced current. Dexamethasone inhibited 2 microm 5-HT-induced current, which was equivalent to EC30 concentration for 5-HT3A receptor, with an inhibitory concentration 50% of 5.29 +/- 1.02 microm. Methylprednisolone inhibited 2 microm 5-HT-induced current with an inhibitory concentration 50% of 1.07 +/- 0.15 mm. The mode of inhibition with either dexamethasone or methylprednisolone was noncompetitive and voltage-independent. When administered together with the 5-HT3 receptor antagonists, ramosetron or metoclopramide, both glucocorticoids showed an additive effect on 5-HT3 receptor. CONCLUSION: The glucocorticoids had a direct inhibitory effect on 5-HT3 receptors. The combined effect of glucocorticoids and the 5-HT3 receptor antagonists seems additive.     

A comparison of the costs and efficacy of ondansetron versus dolasetron for antiemetic prophylaxis

The optimal dose and timing of 5-HT(3) antagonist administration for prophylaxis against postoperative nausea and vomiting (PONV) remains controversial. Although 5-HT(3) antagonists seem to be most effective when administered near the end of surgery, there are no data on the comparative efficacy or costs associated with the 5-HT(3) antagonists dolasetron and ondansetron when administered at the end of the operation. In this double-blinded study, 200 outpatients undergoing otolaryngologic procedures with a standardized general anesthetic received 4 (O4) or 8 mg (O8) of ondansetron or 12.5 (D12.5) or 25 mg (D25) of dolasetron IV within 30 min before the end of surgery. A blinded observer recorded the emetic episodes, maximum nausea score, recovery room resource and drug use, nursing time spent managing PONV, times to achieve discharge criteria from the Phase 1 and 2 recovery units, postdischarge emesis, and patient satisfaction. Total costs were calculated by using the perspective of a free-standing surgicenter. There were no differences in patient demographics, incidence of PONV, need for rescue medications, time spent in the recovery areas, unanticipated hospital admissions, or patient satisfaction among the four treatment groups. The mean total costs (95% confidence intervals) to prevent PONV in one patient were lowest in the D12.5 group: $23.89 (17.18-28.79) vs $37.81 (30.29-45.32), $33.91 (28.92-39.35), and $75.18 (61.13-89.24) for D25, O4, and O8, respectively. Excluding nursing labor costs did not alter this finding: $18.51 (14.18-22.85), $34.77 (28.03-41.49), $31.77 (28. 92-39.35), and $71.76 (58.17-85.35) for D12.5, D25, O4, and O8, respectively. We conclude that 12.5 mg of dolasetron IV is more cost effective than 4 mg of ondansetron IV for preventing PONV after otolaryngologic surgery and is associated with similar patient satisfaction. Implications: When administered at the end of surgery, 12.5 mg of dolasetron IV is as effective as 25 mg of dolasetron IV, 4 mg of ondansetron IV, and 8 mg of ondansetron IV in preventing emetic symptoms after otolaryngologic surgery and was associated with similar patient satisfaction at a reduced cost. There were no differences in the antiemetic efficacy of the 4 and 8 mg doses of ondansetron.     

Inhibitory Effect of Glucocorticoids on Human-cloned 5-hydroxytryptamine3A Receptor Expressed in Xenopus Oocytes

Background: Methylprednisolone, dexamethasone, and other glucocorticoids have been found effective against nausea and vomiting induced by chemotherapy and surgery. Although the specific 5-hydroxytriptamine3 (5-HT3) receptor antagonists such as ondansetron and ramosetron are used as antiemetics, reports show that the use of 5-HT3 receptor antagonists with some glucocorticoids brings additional effects. Glucocorticoids are reported to be antiemetic. The effect of glucocorticoids on 5-HT3 receptor, however, has not been well characterized. This study was designed to examine whether dexamethasone and methylprednisolone had direct effects on human-cloned 5-HT3A receptor expressed in Xenopus oocytes.

Methods: Homomeric human-cloned 5-HT3A receptor was expressed in Xenopus oocytes. The authors used the two-electrode voltage-clamping technique to study the effect of methylprednisolone and dexamethasone on 5-HT-induced current.

Results: Both dexamethasone and methylprednisolone concentration-dependently attenuated 5-HT-induced current. Dexamethasone inhibited 2 [mu]m 5-HT-induced current, which was equivalent to EC30 concentration for 5-HT3A receptor, with an inhibitory concentration 50% of 5.29 +/- 1.02 [mu]m. Methylprednisolone inhibited 2 [mu]m 5-HT-induced current with an inhibitory concentration 50% of 1.07 +/- 0.15 mm. The mode of inhibition with either dexamethasone or methylprednisolone was noncompetitive and voltage-independent. When administered together with the 5-HT3 receptor antagonists, ramosetron or metoclopramide, both glucocorticoids showed an additive effect on 5-HT3 receptor.     

Antiemetic activity of the NK1 receptor antagonist GR205171 in the treatment of established postoperative nausea and vomiting after major gynaecological surgery

In this double-blind, randomized, parallel group study, we have investigated the antiemetic activity of the potent and selective NK1 receptor antagonist GR205171 25 mg i.v. compared with placebo in the treatment of established postoperative nausea and vomiting (PONV) in patients after major gynaecological surgery performed under general anaesthesia. The incidence of PONV in the study population was 65%. Thirty-six patients were treated with placebo or GR205171 (18 patients per group). GR205171 produced greater control of PONV than placebo over the 24-h assessment period. The stimuli for emesis after PONV are multifactorial and the efficacy of GR205171 in this study supports the broad spectrum potential for NK1 receptor antagonists in the management of postoperative emesis. GR205171 was well tolerated and no adverse events were reported that would preclude the further development of this agent.      

Tropisetron in the prevention of postoperative nausea and vomiting

STUDY OBJECTIVES: To evaluate the efficacy of tropisetron, a selective 5-HT(3) receptor antagonist, in preventing nausea and vomiting in high-risk inpatients undergoing various surgical procedures. DESIGN: Prospective, open, nonrandomized, observational, interventional study. SETTING: Postanesthesia care unit, and surgical wards of the University Hospital Center, Charleroi. PATIENTS: A total of 1,132 elective surgical inpatients (>15 years of age) in two separate surveys. The first prospective survey covered all surgical adult inpatients (n = 671) after various surgical procedures over a 3-month period. A new 3-month survey was performed to assess the effectiveness of the preventive measure and included another 461 patients. INTERVENTIONS: Risk factors associated with nausea and vomiting were recorded in the first survey and used to establish an antiemetic policy. This consisted in the administration of tropisetron 2 mg intravenously after anesthesia induction, if two patient-related risk factors associated with high-risk surgery and general anesthesia were present. MEASUREMENTS AND MAIN RESULTS: Nausea frequency and intensity, assessed every 4 hours using a visual analog scale (VAS), frequency and times of vomiting episodes and the need for rescue medication were recorded for 72 hours postoperatively. Nausea was experienced by 18.8% and vomiting by 9.8% of the patients in the first survey (211 high risk-patients of 671). In the second survey, 137 patients of 461, considered at high-risk received prophylactic tropisetron. The proportion of patients having nausea decreased to 11.1% (p,178 0.01) and vomiting episodes to 2.8% (p < 0.001). Twenty-six of the tropisetron-treated patients (19%) suffered subsequent postoperative nausea and vomiting (PONV). Patient satisfaction with tropisetron was high. CONCLUSION: Prophylactic tropisetron can reduce the incidence of PONV in selected high-risk inpatients undergoing various types of surgical procedures.     

The prophylactic effect of tropisetron on epidural morphine-related nausea and vomiting: a comparison of dexamethasone with saline

Tropisetron is a 5-hydroxytryptamine subtype 3 receptor antagonist that is primarily used in the prevention of chemotherapy-induced nausea and vomiting. We evaluated the prophylactic effect of tropisetron on postoperative nausea and vomiting associated with epidural morphine. Dexamethasone and saline served as controls. One-hundred twenty women (n = 40 in each of three groups) undergoing abdominal total hysterectomy under epidural anesthesia were enrolled in this randomized, double-blinded, and placebo-controlled study. At the end of surgery, Group 1 received IV tropisetron 5 mg, whereas Groups 2 and 3 received dexamethasone 5 mg and saline, respectively. We found that tropisetron did not significantly reduce the occurrence of nausea and vomiting associated with epidural morphine. Dexamethasone, however, reduced the total incidence of nausea and vomiting from 59% to 21% (P < 0.01) and the percentage of patients requiring rescue antiemetic from 38% to 13% (P < 0.05). We conclude that IV tropisetron 5 mg did not prevent the occurrence of postoperative nausea and vomiting associated with epidural morphine. IV dexamethasone 5 mg was effective for this purpose. IMPLICATIONS: We compared the prophylactic IV administration of tropisetron 5 mg to prevent postoperative nausea and vomiting (PONV) associated with epidural morphine with dexamethasone 5 mg and saline in women undergoing hysterectomy. We found that tropisetron 5 mg did not significantly reduce the occurrence of PONV associated with epidural morphine. Dexamethasone 5 mg was effective for this purpose.     

Early vs late intraoperative administration of tropisetron for the prevention of nausea and vomiting in children undergoing tonsillectomy and/or adenoidectomy

BACKGROUND: Tropisetron is a long-acting 5HT3 receptor antagonist and was shown to be effective in the prevention of postoperative nausea and vomiting (PONV) after tonsillectomy. The aim of the study was to compare the effects of early vs late intraoperative administration of tropisetron with regard to prevention of PONV during the first 48 h after extubation. METHODS: In a randomized double-blind study, we investigated 120 children aged 1-12 years undergoing general anesthesia for tonsillectomy or adenotonsillectomy. Patients received 0.1 mg x kg(-1) tropisetron (maximum 2 mg) immediately after inhalational induction (early) and establishment of intravenous access or after the end of surgery before extubation (late). PONV and the need for antiemetic rescue medications were recorded within the following 48 h. Patient data were analyzed using t-test, chi-squared test (significance level of alpha = 0.05) and Spearman rank correlation test. RESULTS: The overall incidence of vomiting was 55.3%, with 60% (36/60) in the early treatment and 51.6% (31/60) in the late treatment group (P = 0.46). The observed time course 48 h postoperatively showed no difference regarding the number of vomiting episodes between the two groups and the need for antiemetic rescue medication. The incidence of nausea was higher in the late application group in the first 6 h after extubation (P = 0.001) and higher in the early application group between 24 and 48 h after extubation (P = 0.02). Morphine and the age over 3 years had a strong influence on the incidence of vomiting. CONCLUSION: The intraoperative time point (early vs late) of intravenous administration of a single prophylactic dose of tropisetron has no impact on the incidence of PONV during the first 48 h after tonsillectomy and/or adenoidectomy in children.     

Prophylactic antiemetic therapy with ondansetron,tropisetron, granisetron and metoclopramide in patients undergoing laparoscopic cholecystectomy: a randomized,double-blind comparison with placebo

Purpose

Postoperative nausea and vomiting (PONV) is a distressing adverse effect of general anaesthesia. The aim of the current study was to compare the antiemetic activity of different 5-hydroxytryptamine₃ receptor antagonists with that of metoclopramide and placebo.

Methods

In a prospective, randomized, double-blind study we have compared the antiemetic activity of the prophylactic administration of ondansetron 4 mg, tropisetron 5 mg and granisetron 3 mg with that of metoclopramide 10 mg and placebo in 132 patients undergoing laparoscopic cholecystectomy. All study drugs and placebo were given as a short iv infusion ten minutes before the induction of anaesthesia. Perioperative anaesthetic care was standardized in all patients. Nausea and vomiting were assessed by direct questioning of the patient at 1, 4, 9, 12, 18 and 24 hr after recovery from anaesthesia. If patients experienced nausea and/or vomiting, rescue antiemetic treatment (metoclopramide 10 mg iv) was administered.

Results

For the 24-hr recovery period after surgery, the percentages of emesis-free patients were 65.5%, 52%, 48%, 29.2% and 27.6% in the ondansetron, granisetron, tropisetron, metoclopramide and placebo groups, respectively. Prophylactic antiemetic treatment with ondansetron resulted in a lower incidence (P = 0.02) of PONV than with metoclopramide or placebo. The times at which rescue antiemetic was first received were longer (P < 0.01) in ondansetron group than in the placebo and metoclopramide groups. There were no statistical differences between ondansetron, tropisetron and granisetron groups.

Conclusions

Ondansetron, when given prophylactically resulted in a significantly lower incidence of PONV than metoclopramide and placebo. Metoclopramide was ineffective.     

Erbrechen nach gynäkologischen Laparoskopien in Allgemeinanästhesie ist assoziiert mit Veränderungen der Serotoninmetabolitenausscheidung

INTRODUCTION: The efficacy of 5-HT(3)-receptor antagonists suggests a role of serotonin in the pathogenesis of postoperative nausea and vomiting (PONV). However, studies investigating the relationship between the turnover of serotonin and PONV were contradictory. Therefore we carried out a pilot study in order to find out whether results can be obtained that would justify further studies on a larger scale. METHODS: A total of 22 patients scheduled for elective gynaecological laparoscopy were enrolled. A balanced anaesthesia using sufentanil, etomidate, cisatracurium, isoflurane and nitrous oxide was administered and 5-hydroxyindoleaceticacid (5-HIAA) concentrations in the urine were measured within the 24 h after surgery. RESULTS: Only the patients that vomited postoperatively had a significant change in the concentrations of 5-HIAA over the time course investigated. However, comparison of urinary 5-HIAA concentrations of the group comprising patients that vomited with those that had no PONV did not reveal a significant difference. CONCLUSIONS: Results of this study support further investigation of the relationship between serotonin and PONV and suggest that there may in fact be an association between PONV and increased serotonin turnover.