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

0 Key w o r d s ANAESTHESIA:laparoscopic cholecystectomy; PHARMACOLOGY:ondansetron , tropisetron, granisetron, metoclopramide; COMPLICATIONS:nausea, vomiting; VOMITING"antiemetics, postoperative Purpose: Postoperative nausea and vomiting (PONV) is a distressing adverse effect of general anaesthesia. The aim o f the current study was to compare the antiemetic activity of different 5-hydroxytryptamine 3 receptor antagonists with that of metoclopramide and placebo. Methods: In a prospective, randomized, double-blind study we have compared the antiemetic activity o f the prophylactic administration o f ondansetron 4 rag, tropisetron 5 mg and granisetron 3 mg with that o f 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) o f 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 o f PONV than metoclopramide and placebo. Metoclopramide was ineffective. Objeetif: Les nausdes et vomissements postopdratoires (NVP) sont des effets secondaires pdnibles de l'anesthdsie gdndrale. L'objectif de cette dtude dtait de comparer l'activitd antidmdtique de diffdrents antagonistes des rdcepteurs de la 5-hydroxytryptamine avec celle de la mdtoclopramide et d' un placebo. Mdthode: Au cours d'une dtude randomisde, prospective et en double aveugle, les auteurs ont compard l'effet antidmdtique procurd par l'administration prdventive d'ondanestron 4 rag, de tropisetron 5 mg et de granisetron 3 mg avec ceUe de la mdtoclopramide 10 mg et d'un placebo chez 132 patients op#rds pour une choldcystectomie par laparoscopie. Tousles m~dicaments ?t l'~tude de m~me que le placebo ont ~td administrds par perfusion iv 10 rain avant l'induction. La prise en charge anesth~sique p~riop~ratoire a ~td standardis~e chez tousles sujets. Les naus#es et vomissements ont 6t~ #valuds par l'interrogatoire personnel du patient ?t 1, 4, 9, 12, 18 et 24 h apr~s le r#veil. Lorsque les patients avaient des nausdes et/ou des vomissements, un antidm~tique de sauvetage (m~toclopramide 10 mg iv) ~tait administrd. R~sultats: Pour une p~riode de 24 h apr~s l'intervention, le pourcentage de patients sans complication dmdtique a #td respectivement de 65,5%, 52%, 48~ 29,2% et 27,6% pour le groupe ondansetron, granisetron, tropisetron, m~toclopramide et placebo. L'ondansetron administr~ pr~ventivement a produit une incidence plus faible (P = 0,02) de NVP que la m~toclopramide et le placebo. Le ddlai prdcddant l'administration de l'anti#mdtique de sauvetage a dt~ plus long (P < 0,01) dans le groupe ondansetron que dans les groupes mdtoclopramide et placebo. II n'y a eu aune diffdrence entre les groupes ondanestron, tropisetron et granisetron. Conclusion: L'ondanestron administr~ pr~ventivement a produit une incidence plus faible de NVP que la m~toclopramide et le placebo. La mdtoclopramide n 'a pas dt~ efficace. Postoperative nausea and vomiting (PONV) are among the most common and distressing symptoms occurring after surgery. ! Postoperative patients are willing to be more sedated and to experience more pain, if only they are spared the psychological and physical distress of nausea and vomiting.2 It is believed that the frequency of the emetic symptoms (nausea and vomiting) has changed little in the past 30 yr) Laparoscopic cholecystectomy has.emerged as a popular alternative to traditional laparotomy and cholecystectomy in the management of cholelithiasis.4 Taylor et al. reported that postoperative antiemetic therapy was needed in 53% of patients after laparoscopic cholecystectomy.5 Ondansetron, tropisetron and granisetron are selective 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists that have been used for the treatment of PONV. 6-8 However, no direct comparison has been published on the efficacy of the aforementioned serotonin antagonists. We have conducted this prospective, randomized, double-blind study to compare the antiemetic activity of the prophylactic administration of ondansetron, tropisetron and granisetron with that of metoclopramide and placebo in patients undergoing laparoscopic cholecystectomy. local Ethics Committee, we studied 132 ASA group I or II patients of both sexes, aged 21-68 (mean 37.4 [10.6 SD]) yr and weighing 40-101 (mean 72.5 [12.9]) kg. All patients were undergoing elective laparoscopic cholecystectomy. We excluded patients who were receiving drugs known to have antiemetic effects (such as tricyclic antidepressants, scopolamine, phenothiazines, lorazepam, corticosteroids and trimethobenzamides). We also excluded patients who had experienced nausea or vomiting or who had taken antiemetic treatment in the 48 hr before surgery. No premedication was given and patients were fasted from midnight before surgery. In the operating room, the ECG, haemoglobin oxygen saturation by pulse oximetry, and arterial blood pressure were monitored. Temperature was monitored by a nasopharyngeal thermistor a n d maintained at 36.5 _+ 0.5~ Neuromuscular function was monitored by a peripheral nerve stimulator. Before induction of anaesthesia and after the establishment of venous access, patients were randomized to receive either, ondansetron 4 mg, tropisetron 5 mg, granisetron 3 mg, metoclopramide 10 mg or placebo (normal saline). All study drugs and placebo were diluted by a pharmacist to a fixed volume of 50 ml and marked only with a coded label to maintain the doubleblind nature of the study arid were administered intravenously over ten minutes. Thereafter, anaesthesia was induced in all patients with fentanyl 2 lag. kg-j, thiopentone 5 mg. kg-l and atracurium 0.5 mg. kg-1. After tracheal intubation, anaesthesia was maintained with 70% nitrous oxide in oxygen and isoflurane (0.5-1.2%). Additional fentanyl was administered as needed to maintain haemodynamic stability. After intubation the concentrations of the nitrous oxide, oxygen, carbon dioxide and isoflurane were determined continuously by a multiple-gas a (...truncated)