A double-blind, parallel-group, placebo-controlled, dose-ranging, multicenter study of intravenous granisetron in the treatment of postoperative nausea and vomiting in patients undergoing surgery with general anesthesia

Study Objective: To compare the effectiveness of granisetron with placebo in the treatment of established postoperative nausea and vomiting (PONV).

Design: Randomized, placebo-controlled study.

Setting: 34 hospitals in Europe, Scandinavia, and South Africa.

Patients: 519 ASA physical status I, II, and III patients who developed PONV within 4 hours of the end of surgery performed with general anesthesia.

Interventions: Patients received a single intravenous dose of granisetron 0.1 mg, 1 mg, or 3 mg, or placebo when symptoms of nausea or vomiting were experienced. Additional rescue medication could be given at the investigator's discretion if nausea and vomiting were not controlled.

Measurements and Main Results: At all doses investigated, granisetron was significantly more effective (p ≤ 0.001) than placebo in controlling vomiting: 38%, 46%, and 49% of patients receiving granisetron, 0.1 mg, 1.0 mg, and 3.0 mg, respectively, experienced no vomiting in the first 24 hours following drug administration, compared with 20% receiving placebo. There was a statistically significant linear relationship between vomiting control and granisetron dose (p < 0.001). Survival distributions of time to resolution of vomiting confirmed the statistically significant difference between patients receiving granisetron and those receiving placebo. Granisetron was well tolerated: the most common adverse experiences were pain, constipation, anemia, and headache, and the incidence of adverse experiences was not statistically significantly higher in any of the granisetron groups than in the placebo group.

Conclusion: Granisetron was significantly more effective than placebo in all groups. Further studies in specific subgroups may be warranted.     

RETRACTED ARTICLE: Prevention of postoperative nausea and vomiting with granisetron: a randomized,double-blind comparison with droperidol

The effects of granisetron for preventing postoperative nausea and vomiting were investigated in a randomized, double-blind comparison with droperidol and placebo in 100 patients undergoing general anaesthesia for major gynaecological surgery. The patients received a single dose of either granisetron (40 μg · kg^{? 1}, n = 25), dropéridol (1.25 mg, n = 25; 2.5 mg n = 25) or placebo (saline, n = 25) iv over two to five minutes immediately before induction of anaesthesia. The antiemetic effects of these drugs were evaluated during the first three and the next 21 hr after recovery from anaesthesia. During 0– 3 hr after anaesthesia, the frequency of nausea and vomiting was 60%, 12%, 16% and 12% after administration of placebo, granisetron, droperidol 1.25 mg or droperidol 2.5 mg, respectively. The corresponding frequencies during 3– 24 hr after anaesthesia were 44%, 8%, 36% and 12%. The efficacy of granisetron in preventing postoperative nausea and vomiting was almost equal to that of droperidol 2.5 mg. The awakening time in the patients who had received droperidol 2.5 mg was prolonged by approximately three minutes compared with the placebo group (P < 0.05), and postoperative drowsiness/sedation was observed in these patients. In conclusion, preoperative prophylactic administration of granisetron is superior to that of droperidol in the prevention of postoperative nausea and vomiting after anaesthesia.     

Single-dose i.v. granisetron in the prevention of postoperative nausea and vomiting

In this randomized, double-blind, parallel group, placebo-controlled, dose-ranging study, we have compared three doses (0.1 mg, 1.0 mg and 3.0 mg) of the 5-HT3 receptor antagonist, granisetron (Kytril), as prophylactic therapy for the prevention of postoperative nausea and vomiting. The aims were to determine the optimal dose of granisetron and to evaluate its safety profile. We studied 527 adult patients, undergoing elective open abdominal surgery or vaginal hysterectomy during general anaesthesia. Antiemetic prophylaxis with a single dose of granisetron 1.0 mg or 3.0 mg resulted in a significant reduction (P < 0.001 compared with placebo) in the numbers of patients experiencing postoperative vomiting, or nausea, or who achieved total control during the postoperative periods 0-6 h and 0-24 h. The two higher doses of granisetron (1.0 mg and 3.0 mg) provided effective prophylaxis against vomiting, with 78% and 77% of patients, respectively, being free from vomiting in the first 6 h after surgery, and 63% and 62% in the first 24 h. This compares with 50% and 34% at 0-6 h and 0-24 h, respectively, in the placebo group. Granisetron was well tolerated and the optimum dose was 1.0 mg.      

Preoperative oral granisetron prevents postoperative nausea and vomiting

Background: Postoperative nausea and vomiting (PONV) is a commonly observed adverse effect of anaesthesia. This study was designed to evaluate the efficacy of granisetron administered orally for preventing PONV in female patients undergoing major gynaecological surgery.
Methods: In a prospective, randomized, placebo-controlled, double-blind study, 120 patients received orally either placebo or granisetron (1 mg, 2 mg or 4 mg) (n=30 for each) 1 h before surgery. The same standard general plus regional anaesthetic technique was employed throughout. Postoperatively, during the first 24 h after anaesthesia, the incidence of PONV and adverse events was recorded by nursing staff.
Results: The incidence of PONV was 47% with placebo, 37% with granisetron 1 mg, 10% with granisetron 2 mg and 10% with granisetron 4 mg (P<0.05; overall Fisher's exact probability test). No difference in the incidence of adverse events was observed among the groups.
Conclusion: Preoperative oral granisetron in a minimum dose of 2 mg is effective for preventing PONV after major gynaecological surgery.     

格拉司琼对腹腔镜胆囊切除术后恶心、呕吐的预防作用--随机双盲对照研究

目的探讨格拉司琼对腹腔镜胆囊切除手术（laparoscopic cholecystectomy，LC）后恶心、呕吐（postoperative nausea and vomiting，PONV）的预防作用。方法选择120例ASAⅠ-Ⅱ级LC，随机分为A、B、C组，双盲法于手术结束后分别静脉注射格拉司琼3mg（A组）、6mg（B组）和生理盐水6ml（C组），观察3组病入手术结束后0～4h、4～8h、8-24h、24～48h恶心、呕吐、头痛、头昏情况。结果A、B组术后各时段恶心、呕吐发生率比C组明显减少（Y=4．021，P=0．045；x^2=4．267，P=0．039），A、B2组之间比较差异无显著性；头痛、头昏发生率B组显著高于A组（x^2=4．021，P=0．045；x^2=4．267，P=0．039），B组头痛发生率与C组比较差异无显著性（x^2=2．813，P=0．094），B组头昏发生率高于C组（x^2=4．267，P=0．039）。结论静注3mg或6mg格拉司琼能明显减少LC术后恶心、呕吐的发生率，但剂量增大会增加副作用。     

Ondansetron, granisetron, and dexamethasone compared for the prevention of postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy

BACKGROUND: Laparoscopic cholecystectomies are associated with an appreciably high rate of postoperative nausea and vomiting (PONV). This study was designed to compare the effectiveness of ondansetron, granisetron, and dexamethasone for the prevention of PONV in patients after laparoscopic cholecystectomy. METHODS: A total of 80 American Society of Anesthesiologists (ASA) physical class I-II patients scheduled for laparoscopic cholecystectomy were included in this randomized, double blind, placebo-controlled study. All patients received a similar standardized anesthesia and operative treatment. Patients were randomly divided into four groups (n = 20 each). Group 1, consisting of control patients, received 0.9% NaCl; group 2 patients received ondansetron 4 mg i.v.; group 3 patients received granisetron 3 mg i.v.; and group 4 patients received dexamethasone 8 mg i.v., all before the induction of anesthesia. Both nausea and vomiting were assessed during the first 24 h after the procedure. RESULTS: The total incidence of PONV was 75% with placebo, 35% with ondansetron, 30% with granisetron, and 25% with dexamethasone. The incidence of PONV was significantly less frequent in groups receiving antiemetics (p < 0.05). The differences between dexamethasone, granisetron, and ondansetron were not significant. CONCLUSIONS: Prophylactic dexamethasone 8 mg i.v. significantly reduced the incidence of PONV in patients undergoing laparoscopic cholecystectomy. Dexamethasone 8 mg was as effective as ondansetron 4 mg and granisetron 3 mg, and it was more effective than placebo.     

Single-dose aprepitant vs ondansetron for the prevention of postoperative nausea and vomiting: a randomized, double-blind phase III trial in patients undergoing open abdominal surgery

Background: The neurokinin₁ antagonist aprepitant is effective for preventionof chemotherapy-induced nausea and vomiting. We compared aprepitantwith ondansetron for prevention of postoperative nausea andvomiting. Methods: Nine hundred and twenty-two patients receiving general anaesthesiafor major abdominal surgery were assigned to receive a singlepreoperative dose of oral aprepitant 40 mg, oral aprepitant125 mg, or i.v. ondansetron 4 mg in a randomized, double-blindtrial. Vomiting episodes, use of rescue therapy, and nauseaseverity (verbal rating scale) were documented for 48 h aftersurgery. Primary efficacy endpoints were complete response (novomiting and no use of rescue therapy) 0–24 h after surgeryand no vomiting 0–24 h after surgery. The secondary endpointwas no vomiting 0–48 h after surgery. Results: Aprepitant at both doses was non-inferior to ondansetron forcomplete response 0–24 h after surgery (64% for aprepitant40 mg, 63% for aprepitant 125 mg, and 55% for ondansetron, lowerbound of 1-sided 95% CI > 0.65), superior to ondansetronfor no vomiting 0–24 h after surgery (84% for aprepitant40 mg, 86% for aprepitant 125 mg, and 71% for ondansetron; P< 0.001), and superior for no vomiting 0–48 h aftersurgery (82% for aprepitant, 40 mg, 85% for aprepitant, 125mg, and 66% for ondansetron; P < 0.001). The distributionof peak nausea scores was lower in both aprepitant groups vsondansetron (P < 0.05). Conclusions: Aprepitant was non-inferior to ondansetron in achieving completeresponse for 24 h after surgery. Aprepitant was significantlymore effective than ondansetron for preventing vomiting at 24and 48 h after surgery, and in reducing nausea severity in thefirst 48 h after surgery. Aprepitant was generally well tolerated.     

Comparison of granisetron and granisetron plus dexamethasone for the prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy

BACKGROUND: Laparoscopic cholecystectomies are associated with an appreciably high rate of postoperative nausea and vomiting (PONV). This study was designed to compare the effectiveness of granisetron plus dexamethasone with granisetron alone for the prevention of postoperative nausea and vomiting in patients after laparoscopic cholecystectomy. METHODS: In a randomized, double-blind study, 120 patients of both sexes received granisetron 40 micro g kg-1 alone or granisetron 40 micro g kg-1 plus dexamethasone 8 mg (n=60 of each) intravenously immediately before induction of anesthesia. Perioperative anesthetic care was standardized in all patients. Patients were then observed for 24 h after administration of the study drug. RESULTS: A complete response (defined as no PONV and no need for another rescue antiemetic) was achieved in 83% of the patients given granisetron and in 95% of the patients given granisetron plus dexamethasone (P<0.05). The overall cumulative incidences (0-24 h) of PONV were 11 (18.3%) in the granisetron and three (5%) in the combination group. No difference in adverse events were observed in any of the groups. CONCLUSION: The combination (granisetron plus dexamethasone) further increases the chance of complete response than granisetron alone. Therefore, the combination might be considered clinically relevant in a high risk setting.     

Tropisetron vs ondansetron for prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy: a randomized double-blind,placebo-controlled study

Background: Postoperative nausea and vomiting are observed in increased frequency after laparoscopic surgery. This study was performed in order to compare the efficacy of two 5-hydroxytryptamine-3 (5-HT3) receptor antagonists, ondansetron and tropisetron, in preventing postoperative nausea and vomiting (PONV) after laparoscopic cholecystectomy. Methods: Using a randomized, double-blind study design, 87 ASA I and II patients scheduled for laparoscopic cholecystectomy were randomly assigned to receive 4 mg ondansetron (Group A, n = 29), 5 mg tropisetron (Group B, n = 31), or placebo (Group C, n = 27) intravenously (IV) before induction of anesthesia. The end points evaluated were frequency of nausea, nausea intensity rated on a scale from 1 (mild) to 5 (most severe), frequency of vomiting, and need for rescue antiemetics. These parameters were measured immediately after surgery (0 h), at 3 h, 6 h, and 12 h postoperatively. Results: The frequency of nausea was significantly higher in group A (31.2%) compared to group B (14%) at 12 h postoperatively (p <0.01). However, patients of group A had significantly lower nausea scores at 3 h postoperatively compared to group B. Postoperative vomiting occurred in 13.8% of patients in group A and 9.6% of patients in group B throughout the whole study period (p = n.s.). The need for rescue antiemetics was similar between groups A and B. Both groups were superior to placebo concerning all studied parameters. Conclusion: Our results show that ondansetron may be more effective in controlling nausea intensity during the first 3 h after laparoscopic cholecystectomy, while tropisetron has a longer-acting activity, with a major impact on nausea frequency at 12 h postoperatively.     

Esomeprazole for the prevention of postoperative nausea and vomiting. A randomized, placebo-controlled trial

BACKGROUND: Postoperative nausea and vomiting still represents a major problem after surgery. Although risk factors for postoperative nausea and vomiting and procedures to reduce postoperative nausea and vomiting have been described, the incidence of postoperative nausea and vomiting remains high. The aim of the present study was to investigate the potential role of the proton pump inhibitor esomeprazole to reduce postoperative nausea and vomiting after elective surgery. METHODS: In a randomized, double-blind trial, ASA I-III patients at high risk for postoperative nausea and vomiting received esomeprazole tablets 3 x 40 mg or matching placebo the evening before surgery, 2 h preoperatively and 24 h postoperatively. Total intravenous anaesthesia with propofol and remifentanil without nitrous oxide (FiO2 0.5) was used. Patients were interviewed using a standardized postoperative nausea and vomiting questionnaire at discharge from the post-anaesthesia care unit, 6 h and 24 h later. The severity of nausea was estimated on a 0-100 point numerical scale (0 = no nausea, 100 = maximum nausea). RESULTS: The incidence of vomiting was similar in the esomeprazole (n = 45) and the placebo (n = 48) groups (64.4% vs. 60.5%, P > 0.05). The average nausea score was 17.8 with esomeprazole and was 18.7 with placebo (P > 0.05). Only 24.7% of all patients (esomeprazole 24.4%, placebo 25.0%) did not experience any nausea or vomiting. CONCLUSION: There is no evidence that prophylactic esomeprazole reduces the incidence of postoperative nausea and vomiting or the degree of postoperative nausea.     

A comparison of cyclizine and granisetron alone and in combination for the prevention of postoperative nausea and vomiting

We conducted a randomised double-blinded study of 960 women undergoing day-case surgery to determine whether combination anti-emetic therapy of granisetron and cyclizine was more effective at decreasing the incidence of postoperative nausea and vomiting than these agents used alone. The women were randomly allocated to three groups to receive intravenous granisetron 1 mg, cyclizine 50 mg or both before induction of general anaesthesia. The incidence of postoperative nausea and vomiting was 77/322 (24%) in the granisetron group, 73/316 (23%) in the cyclizine group and 53/322 (17%) in those women given both drugs (p = 0.04). There was no difference in the requirement for rescue anti-emetic drugs. There were no differences in the anaesthetic techniques used in the three groups. We conclude that the risk of postoperative nausea and vomiting is less with cyclizine and granisetron given together than with either given alone.     

Preoperative oral granisetron for the prevention of postoperative nausea and vomiting after breast surgery.

OBJECTIVE: To evaluate the efficacy and safety of oral granisetron for the prevention of postoperative nausea and vomiting after breast surgery. DESIGN: Prospective, randomised, double-blind, placebo-controlled study. SETTING: University affiliated hospital, Japan. SUBJECTS: 100 women listed for partial or modified radical mastectomy with or without axillary dissection. INTERVENTIONS: Patients were given either placebo or granisetron in three different doses (1 mg, 2 mg, 4 mg) orally 1 hour preoperatively (n = 25 in each group). A standard general anaesthetic technique and postoperative analgesia were used. MAIN OUTCOME MEASURES: All episodes of nausea and vomiting during the first 24 hours after anaesthesia. RESULTS: Complete response, defined as no nausea and vomiting and no need for a "rescue" antiemetic, during the first 24 hours after anaesthesia was recorded in 13 (52%) with placebo, 14 (56%) with granisetron 1 mg, 22 (88%) with 2 mg, and 22 (88%) with 4 mg, respectively (p = 0.006, Fisher's exact test). No clinically serious adverse events were seen in any of the groups. CONCLUSION: Preoperative oral granisetron, in doses of more than 2 mg, is effective for the prevention of postoperative nausea and vomiting in women undergoing general anaesthesia for breast surgery.     

地塞米松和格拉司琼预防腹腔镜胆囊切除术后恶心呕吐比较的研究

目的：研究地塞米松和格拉司琼预防腹腔镜胆囊切除术后恶心呕吐的临床效果及两者有无交互作用。方法：80例ASAⅠ～Ⅱ级择期全身麻醉下行腹腔镜胆囊切除术的患者，随机分为4组：地塞米松组、格拉司琼组、地塞米松＋格拉司琼组和对照组，每组20人。各组患者均于麻醉诱导前经静脉给予止吐药，记录术后24h内恶心呕吐评分及刀口愈合情况。结果：各实验组术后恶心呕吐评分均低于对照组（P〈0．05）；地塞米松组和格拉司琼组相比差异无统计学意义（P〉0．05）；地塞米松＋格拉司琼组与格拉司琼组、地塞米松组相比均矧氏（P〈0．05）；析因分析认为地塞米松和格拉司琼两药联合应用对预防术后恶心呕吐具有协同作用；各组术后刀口愈合均良好。结论：地塞米松和格拉司琼均能较好预防术后恶心呕吐，两者效果无明显差异，两药联合应用具有协同作用。     

Intravenous dolasetron and ondansetron in prevention of postoperative nausea and vomiting: a multicenter, double-blind, placebo-controlled study

Background: Intravenous dolasetron mesilate has shown efficacy in the prevention of postoperative nausea and vomiting (PONV) when administered as a single dose prior to emergence from anesthesia. This trial compared intravenous dolasetron and ondansetron for the prevention of PONV when administered at induction of anesthesia.
Methods: This double-blind, placebo-controlled, multicenter trial randomized patients to one of four single IV treatments: placebo, 25 or 50 mg dolasetron, or 4 mg ondansetron. Efficacy was measured by complete response (0 emetic episodes and no rescue medication), nausea severity and patient satisfaction as measured on a visual analog scale (VAS), investigator's rating of nausea severity, and total response (complete response with no nausea [≤ mm VAS]).
Results: 514 patients at 24 sites were evaluated for efficacy. The 50 mg dolasetron and 4 mg ondansetron doses were statistically equivalent, and superior to placebo, for all efficacy measures. Complete response rates were 49%, 51%, 71% and 64% for placebo, 25 and 50 mg dolasetron, and ondansetron, respectively. Dolasetron 50 mg was statistically superior to 25 mg dolasetron for complete response, total response, VAS maximum nausea, time to first emetic episode, and patient satisfaction. The majority of adverse events were of mild-to-moderate intensity. Headache was the most frequently reported treatment-related adverse event with a 3%-5% incidence across treatments.
Conclusion: When given at induction of anesthesia, 50 mg intravenous dolasetron is equivalent to 4 mg ondansetron and superior to 25 mg dolasetron and placebo for the prevention of PONV. All treatments were safely administered and well tolerated.