Granisetron reduces the incidence of nausea and vomiting after middle ear surgery

We studied the efficacy of granisetron, a selective 5-hydroxytryptamine type-3 receptor antagonist, in preventing postoperative nausea and vomiting (PONV) after middle ear surgery. In a randomized, double-blind, placebo-controlled study, 60 ASA I patients received placebo (saline) or granisetron 40 micrograms kg-1 i.v. immediately before induction of anaesthesia (n = 30 in each group). A standard general anaesthetic technique was used. During the first 24 h after anaesthesia, the incidence of PONV in patients who had received granisetron was lower than in those who had received placebo (17% vs 63%; P < 0.05). There were no clinically important adverse effects in either group. We conclude that granisetron, given before anaesthesia, reduced the incidence of PONV after middle ear surgery.     

The effects of dexamethasone on antiemetics in female patients undergoing gynecologic surgery

This randomized, double-blind study compared the effects of dexamethasone plus either droperidol, metoclopramide, or granisetron with each antiemetic alone for preventing postoperative nausea and vomiting (PONV) in 270 female patients undergoing general anesthesia for major gynecological surgery. Patients were randomly assigned to receive either droperidol 1.25 mg (Group D1, n = 45), droperidol 1.25 mg plus dexamethasone 8 mg (Group D2, n = 45), metoclopramide 10 mg (Group M1, n = 45), metoclopramide 10 mg plus dexamethasone 8 mg (Group M2, n = 45), granisetron 40 micrograms/kg (Group G1, n = 45), or granisetron 40 micrograms/kg plus dexamethasone 8 mg (Group G2, n = 45) immediately before the induction of anesthesia. A standard general anesthetic technique and postoperative analgesia were used throughout the study. Complete response, defined as no PONV and no administration of rescue antiemetic medication during the first 24 h after anesthesia, was 49% in Group D1, 60% in Group D2 (P = 0.199 versus Group D1), 51% in Group M1, 62% in Group M2 (P = 0.198 versus Group M1), 80% in Group G1, and 96% in Group G2 (P = 0.025 versus Group G1). Our results suggest that dexamethasone enhances the antiemetic efficacy of granisetron but does not potentiate the other antiemetics-droperidol and metoclopramide-in female patients undergoing major gynecological surgery. Implications: We compared the efficacy of dexamethasone plus three different antiemetics-droperidol, metoclopramide, and granisetron-for the prevention of nausea and vomiting after gynecologic surgery. The granisetron-dexamethasone combination was the most effective for preventing post-operative emetic symptoms.     

Prophylactic oral antiemetics for preventing postoperative nausea and vomiting: granisetron versus domperidone

In this prospective, randomized, double-blinded study, we evaluated the efficacy of the oral antiemetics, granisetron and domperidone, for the prevention of postoperative nausea and vomiting (PONV) in 100 women undergoing major gynecologic surgery. Patients received either granisetron 2 mg or domperidone 20 mg (n = 50 in each group) orally 1 h before surgery. Standardized anesthetic techniques and postoperative analgesia regimens were used. Complete response (defined as no PONV and no administration of rescue antiemetic medication) for 0-3 h after anesthesia was 88% with granisetron and 52% with domperidone; the corresponding incidence for 3-24 h after anesthesia was 86% and 48% (P < 0.05). No clinically important adverse events due to the drugs were observed in any of the groups. In conclusion, the efficacy of preoperative oral granisetron is superior to that of domperidone for the prevention of PONV after major gynecologic surgery. IMPLICATIONS: We compared the efficacy of granisetron and domperidone administered orally for the prevention of postoperative nausea and vomiting in women undergoing gynecologic surgery. Preoperative oral granisetron was more effective than domperidone.     

In vitro effect of ketones and hyperglycemia on feline hemoglobin oxidation and D- and L-lactate production

Postoperative nausea and vomiting (PONV) are unpleasant, often underestimated side effects of anaesthesia and surgery, not devoid of medical complications. Prevention with antiemetics is only partially effective. Propofol has been shown recently to possess antiemetic properties in several situations. In this prospective, randomized, controlled trial, we have compared the antiemetic efficacy of subhypnotic doses of propofol, with Intralipid as placebo, after thyroidectomy. We studied 64 patients of both sexes, aged 22-71 yr, ASA I or II, undergoing thyroidectomy. After premedication with a benzodiazepine, balanced anaesthesia was produced with isoflurane and nitrous oxide in oxygen, and supplementary analgesia with fentanyl i.v. as required. Postoperative analgesia was provided with non-opioids, and piritramide 0.25 mg kg-1 i.m. on demand. Patients were allocated randomly and blindly to receive a 20-h infusion of either propofol or 10% Intralipid 0.1 ml kg-1 h-1. Intralipid, the excipient of propofol, was chosen as placebo as it is devoid of antiemetic effects. Sedation scores, respiratory and cardiovascular variables, and incidence of PONV were assessed every 4 h for 24 h. Pulse oximetry and ECG were monitored continuously. Both groups were comparable in characteristics, surgical and anaesthesia procedures, amount of opioids given during and after operation, and total amount of the study drug infused after operation. Occurrence of PONV was similar before the start (propofol 41%, Intralipid 50%) and after completion (propofol 0.64%, Intralipid 1.6%) of infusion and decreased with time in both groups during the infusion. However, symptoms were reduced to nil with propofol but persisted and were more severe with Intralipid during infusion (P < or = 0.01). The overall incidence of PONV during infusion was 10% (three of 32 patients) in the propofol group and 65% (21 of 32 patients) in the Intralipid group. Cardiovascular and respiratory variables, and SpO2 were unaltered, and sedation decreased similarly with time in both groups. We conclude that propofol, given at subhypnotic doses, effectively reduced the incidence of PONV without untoward sedative or cardiovascular effects.     

Calcium antagonists--clinical considerations

BACKGROUND: Postoperative nausea and vomiting (PONV) following major arthroplasty with spinal anaesthesia and intrathecal morphine is reported in 45-74% of patients. This randomised, double-blind, placebo-controlled trial was undertaken to determine whether a subhypnotic infusion of propofol has a prophylactic antiemetic effect in this patient population. METHODS: 82 patients undergoing hip or knee replacement under subarachnoid bupivacaine anaesthesia plus morphine 0.25 mg were randomised at the end of surgery to receive either propofol 30 mg x h(-1) or fat emulsion (Intralipid) 3 ml x h(-1) for 20 h postoperatively. Blinded observers recorded episodes of nausea, vomiting and pruritus. RESULTS: PONV in the intervention group was 40% vs 59% in the controls (P=0.1, not significant). Pruritus occurred in 34%, with a similar rate in both groups. CONCLUSION: These results suggest that routine use of postoperative, subhypnotic propofol infusion as PONV prophylaxis is not justified in this patient population.     

Prophylactic oral dolasetron mesylate reduces nausea and vomiting after abdominal hysterectomy. The Canadian Dolasetron Study Group

PURPOSE: The incidence of postoperative nausea and vomiting (PONV) varies from 50% to 75% after gynaecological surgery under general anaesthesia. This study evaluates the dose-response relationships, safety, and efficacy of the new 5-HT3 antagonist, dolasetron mesylate, in the prevention of PONV in women undergoing total abdominal hysterectomy (TAH). METHODS: Three hundred and seventy four women scheduled for TAH under general anaesthesia were studied at 13 Canadian centres. Patients received in a randomized, double-blind manner 25, 50, 100, or 200 mg dolasetron or placebo po one to two hours before induction of anaesthesia. The anesthetic protocol was standardized. Efficacy was evaluated for 24 hr after surgery by comparing the number of emetic episodes, administration of rescue medication, severity of nausea, and patient satisfaction. RESULTS: Analysis of complete response (no emetic episodes and no rescue for 24 hr) revealed a linear dose-response relationship across dolasetron groups (P < 0.002). Dolasetron 100 mg (P < 0.003) and 200 mg (P < 0.01) were superior to placebo. The percentage of patients with no emetic episodes increased from 29.3% (placebo) to 54.1 % (100 mg). Subgroup analysis revealed ASA status (I > II), previous history of PONV, previous history of motion sickness, and total morphine dose (> 55 mg associated with less PONV than < 55 mg) influenced the incidence of emetic symptoms, but did not alter the results of the primary analysis. CONCLUSION: Prophylactic dolasetron (100 mg and 200 mg) reduces the incidence of PONV in patients having total abdominal hysterectomy.     

Destruction of the auditory thalamus disrupts the production of fear but not the inhibition of fear conditioned to an auditory stimulus

Although ondansetron (4 mg I.V.) is effective in the prevention and treatment of postoperative nausea and vomiting (PONV) after ambulatory surgery, the optimal timing of its administration, the cost-effectiveness, the cost-benefits, and the effect on the patient's quality of life after discharge have not been established. In this placebo-controlled, double-blind study, 164 healthy women undergoing outpatient gynecological laparoscopic procedures with a standardized anesthetic were randomized to receive placebo (Group A), ondansetron 2 mg at the start of and 2 mg after surgery (Group B), ondansetron 4 mg before induction (Group C), or ondansetron 4 mg after surgery (Group D). The effects of these regimens on the incidence, severity, and costs associated with PONV and discharge characteristics were determined, along with the patient's willingness to pay for antiemetics. Compared with ondansetron given before induction of anesthesia, the administration of ondansetron after surgery was associated with lower nausea scores, earlier intake of normal food, decreased incidence of frequent emesis (more than two episodes), and increased times until 25% of patients failed prophylactic antiemetic therapy (i.e., had an emetic episode or received rescue antiemetics for severe nausea) during the first 24 h postoperatively. This prophylactic regimen was also associated with the highest patient satisfaction and lowest cost-effectiveness ratios. Compared with the placebo group, ondansetron administered after surgery significantly reduced the incidence of PONV in the postanesthesia care unit and during the 24-h follow-up period and facilitated the recovery process by reducing the time to oral intake, ambulation, discharge readiness, resuming regular fluid intake and a normal diet. When ondansetron was given as a "split dose," its prophylactic antiemetic efficacy was not significantly different from that of the placebo group. In conclusion, the prophylactic administration of ondansetron after surgery, rather than before induction, may be associated with increased patient benefits. Implications: Ondansetron 4 mg I.V. administered immediately before the end of surgery was the most efficacious in preventing postoperative nausea and vomiting, facilitating both early and late recovery, and improving patient satisfaction after outpatient laparoscopy.     

Antiemetic prophylaxis after laparoscopic cholecystectomy: comparative study of dehydrobenzperidol, metoclopramide, ondansetron and placebo

OBJECTIVES: To compare the efficacy of ondansetron to that of metoclopramide, dehydrobenzperidol and placebo for the prevention of postoperative nausea and vomiting (PONV) after laparoscopic cholecystectomy in a double-blind random study. PATIENTS AND METHOD: A total of 100 ASA I, II and III patients undergoing scheduled laparoscopic cholecystectomy were divided into 4 groups according to whether they received one of the following intravenously just prior to anesthetic induction: 1.25 mg dehydrobenzperidol (group D), 10 mg metoclopramide (group M), 4 mg ondansetron (group O) or 2 ml of saline (group P). All received general anesthesia with induction by thiopental, analgesia with fentanyl, muscle relaxation with atracurium and maintenance with oxygen-air and isoflurane. Episodes of nausea and/or vomiting during the first 24 h after surgery were recorded. Treatment was considered effective if no episodes occurred during this period. RESULTS: Nine of the 100 patients were excluded from the study. There were no significant differences in demographic variables among the 4 groups. The incidence of PONV was significantly greater in group P than in any of the other groups. There were no significant differences in PONV among groups D, M and O. CONCLUSIONS: Ondansetron provides safe, effective prophylaxis for PONV after laparoscopic cholecystectomy, but it is not superior to the antiemetic drugs usually used. Its use may be justified in patients in whom dehydrobenzperidol or metoclopramide are contraindicated.     

Familial inv(X) (p22q22): ovarian dysgenesis in two sisters with del Xq and fertility in one male carrier

PURPOSE: To evaluate the antiemetic efficacy and safety of adding the dopamine antagonist prochlorperazine to the combination of granisetron and dexamethasone in the prevention of acute nausea and vomiting following high-dose cisplatin. PATIENTS AND METHODS: Sixty patients receiving cisplatin (> or = 75 mg/m2) (median dose = 100 mg/m2) were enrolled at three sites. Patients received prochlorperazine spansule 15 mg orally, 60 minutes prior to and 12 hours after cisplatin; dexamethasone 20 mg intravenously, 45 minutes prior to cisplatin, and 10 mg intravenously or orally, 12 hours after cisplatin; and granisetron 10 micrograms/kg intravenously, 30 minutes prior to cisplatin. Efficacy was assessed during the 24-hour period after cisplatin using complete antiemetic response (no emetic episodes and no rescue antiemetics) and patient assessment of nausea and satisfaction using 100-mm visual analog scales (nausea: 0 = none, 100 = nausea as bad as it can be; satisfaction: 0 = not at all satisfied, 100 = satisfied as can be). RESULTS: Complete response (0 emetic episodes) was noted in 84% (49/58) of patients. Forty-two patients (72%) experienced no nausea. The mean change in posttreatment nausea visual analog scales from baseline was 8.9 mm. Forty-eight patients (83%) were completely satisfied with their antiemetic treatment. The mean posttreatment patient satisfaction score was 92 mm. Treatment was well tolerated, with infrequent and minor adverse events. CONCLUSIONS: This three-drug antiemetic regimen is well tolerated and highly effective in the prevention of acute nausea and vomiting arising from high-dose cisplatin. Further studies evaluating this regimen are warranted.     

Efficacy, dose-response, and safety of ondansetron in prevention of postoperative nausea and vomiting: a quantitative systematic review of randomized placebo-controlled trials

OBJECTIVE: The authors reviewed efficacy and safety data for ondansetron for preventing postoperative nausea and vomiting (PONV). METHODS: Systematically searched, randomized, controlled trials (obtained through MEDLINE, EMBASE, Biological Abstracts, manufacturer's database, manual searching of journals, and article reference lists) were analyzed. Relevant end points were prevention of early PONV (within 6 h after surgery) and late PONV (within 48 h) and adverse effects. Relative benefit and number-needed-to-treat were calculated. The number-needed-to-treat indicated how many patients had to be exposed to ondansetron to prevent PONV in one of them who would have vomited or been nauseated had he or she received placebo. RESULTS: Fifty-three trials were found that had data from 7,177 patients receiving 24 different ondansetron regimens and from 5,712 controls receiving placebo or no treatment. Average early and late PONV incidences without ondansetron were 40% and 60%, respectively. There was a dose response for oral and intravenous ondansetron. Best number-needed-to-treat to prevent PONV with the best documented regimens was between 5 and 6. This was achieved with an intravenous dose of 8 mg and an oral dose of 16 mg. Antivomiting efficacy was consistently better than antinausea efficacy. Efficacy in children was poorly documented. Ondansetron significantly increased the risk for elevated liver enzymes (number-needed-to-harm was 31) and headache (number-needed-to-harm was 36). CONCLUSIONS: If the risk of PONV is very high, for every 100 patients receiving an adequate dose of ondansetron 20 patients will not vomit who would have vomited had they received placebo. The antinausea effect is less pronounced. Of these 100, three will have elevated liver enzymes and three will have a headache who would not have had these adverse effects without the drug.     

Evaluation of the results of cleft lip and palate surgical treatment: preliminary report

We have analysed randomized controlled studies which reported the incidence of postoperative nausea and vomiting (PONV) after propofol anaesthesia compared with other anaesthetics (control). Cumulative data of early (0-6 h) and late (0-48 h) PONV were recorded as occurrence or non-occurrence of nausea or vomiting. Combined odds ratio and number-needed-to-treat were calculated for propofol as an induction or maintenance regimen, early or late outcomes, and different emetic events. This was performed for all control event rates and within a range of 20-60% control event rates. We analysed 84 studies involving 6069 patients. The effect of propofol on PONV was dependent mainly on the method of administration, time of measurement and range of control event rates. When all studies were included the number-needed-to-treat to prevent PONV with propofol was more than 9 when used for induction of anaesthesia and at best 6 when used for maintenance. Within the 20-60% control event rate range, best results were achieved with propofol maintenance to prevent early PONV: the number-needed-to-treat to prevent early nausea was 4.7 (95% confidence interval 3.8-6.3), vomiting 4.9 (4-6.1) and any emetic event 4.9 (3.7-7.1). Within the 20-60% control event rate, of five patients treated with propofol for maintenance of anaesthesia, one will not vomit or be nauseated in the immediate postoperative period who would otherwise have vomited or been nauseated. This may be clinically relevant. In all other situations the difference between propofol and control may have reached statistical significance but was of doubtful clinical relevance. Treatment efficacy should be established within a defined range of control event rates for meaningful estimates of efficacy and for comparisons.     

Intravenous dolasetron mesilate in the prevention of postoperative nausea and vomiting in females undergoing gynecological surgery

STUDY OBJECTIVE: To evaluate a range of doses of intravenous (i.v.) dolasetron mesilate, in preventing postoperative nausea and vomiting (PONV). DESIGN: Double-blind, placebo-controlled, randomized, multicenter trial. SETTING: Ten hospitals and/or surgical centers. PATIENTS: 281 women undergoing gynecologic surgery with general anesthesia. INTERVENTIONS: Patients received one of four single, i.v. doses of dolasetron mesilate (12.5 mg, 25 mg, 50 mg, and 100 mg) or placebo administered following cessation of anesthesia. MEASUREMENTS AND MAIN RESULTS: Patients were monitored for 24 hours following study drug administration. The antiemetic efficacy of each dolasetron mesilate dose was evaluated by recording the number and timing of emetic episodes, and the effects on nausea were assessed by use of visual analog scales (VAS). Safety was assessed by adverse event reports, clinical laboratory tests, electrocardiographic (ECG) measurements, and monitoring vital signs. Complete responses (patients with no emetic episodes and no escape antiemetic medication requirements in 24 hours) were achieved by 54% in the 12.5-mg, 67% in the 25-mg, and 59% in both the 50-mg and 100-mg dolasetron mesilate dose groups, and by 43% in the placebo group. Nausea VAS assessments demonstrated that dolasetron-treated patients were significantly (p = 0.048) more likely to report no nausea (VAS score < 5 mm) than those in the placebo group. Adverse events reported generally were mild in intensity, and there were no clinically significant changes in laboratory tests, vital signs, or ECG parameters. CONCLUSIONS: Dolasetron was effective and well tolerated for the prevention of PONV in female patients undergoing gynecologic surgery with general anesthesia.     

Treatment of postoperative nausea and vomiting with single intravenous doses of dolasetron mesylate: a multicenter trial. Dolasetron Mesylate PONV Treatment Study Group

This study was conducted to determine the efficacy and safety of four intravenous (I.V.) doses of dolasetron, an investigational 5-HT3 receptor antagonist, for the treatment of postoperative nausea and/or vomiting (PONV) after outpatient surgery under general anesthesia. This multicenter, randomized, double-blind trial compared the antiemetic efficacy of 12.5, 25, 50, or 100 mg I.V. dolasetron with placebo over 24 h using complete response (no emetic episodes and no rescue medication), time to first emetic episode or rescue medication, and patient nausea and satisfaction with antiemetic therapy as rated by visual analog scale (VAS). Of 1557 patients enrolled, 620 patients were eligible for treatment. Complete response rates for all dolasetron doses--12.5 mg (35%), 25 mg (28%), 50 mg (29%), and 100 mg (29%)--were significantly more effective than placebo (11%, P < 0.05). There was a significant gender interaction for complete response (P < 0.01). Of the patients in the 25-mg and 100-mg dose groups, 12% and 13%, respectively, experienced no nausea (VAS score < 5 mm) versus 5% in the placebo group (P < 0.05). There were no clinically relevant changes in vital signs or laboratory values and no trends with dose for adverse events. Dolasetron is effective for treating PONV and has an adverse event profile similar to that of placebo. The 12.5-mg dose was as effective as larger doses for complete response. IMPLICATIONS: Nausea and vomiting are common problems for postsurgical patients. In this study of 620 patients undergoing surgery, a 12.5-mg dose of intravenous dolasetron, a new serotonin-receptor blocker, was significantly more effective than placebo in treating established postoperative nausea and vomiting. Dolasetron 12.5 mg was as safe as placebo.     

Efficacy of ondansetron and prochlorperazine for the prevention of postoperative nausea and vomiting after total hip replacement or total knee replacement procedures: a randomized, double-blind, comparative trial

BACKGROUND: Limited data are available on the efficacy of ondansetron hydrochloride compared with prochlorperazine maleate for the treatment of postoperative nausea and vomiting (PONV). OBJECTIVE: To evaluate the comparative efficacy of ondansetron and prochlorperazine for the prophylaxis of PONV in patients undergoing total hip replacement or total knee replacement procedures. METHODS: A randomized, double-blind, comparative trial was conducted at a tertiary care, university hospital. Seventy-eight patients undergoing elective total hip or total knee replacement procedures received a single dose of ondansetron hydrochloride (n = 37), 4 mg intravenously, or prochlorperazine maleate (n = 41), 10 mg intramuscularly, at the end of the surgical procedure. Rescue therapy was administered every 4 hours as needed during the initial 48 hours. Primary outcome measures were the incidences and severity of PONV. Secondary outcome measures included the number of rescue antiemetic doses required, number of physical therapy cancellations because of PONV, length of hospital stay, and cost of antiemetic agents administered. RESULTS: The incidence of nausea was significantly greater in the ondansetron group compared with the prochlorperazine group (81% vs 56%; odds ratio, 3.4; 95% confidence interval, 1.2-9.4) as was the severity of nausea (P = .04). Multivariate analysis identified administration of ondansetron, history of PONV, obesity, and female sex as risk factors for a nausea event. The incidence of vomiting tended to be greater in the ondansetron group (49% vs 32%; odds ratio, 2.0; 95% confidence interval, 0.8-5.0). The need for rescue antiemetic therapy was also greater in the ondansetron group (46% vs 27%; odds ratio, 2.3; 95% confidence interval, 0.9-6.0). The mean antiemetic drug cost per patient was significantly greater for the ondansetron group ($47.56 vs $2.47; P<.001). However, the proportion of patients who were unable to participate in physical therapy because of PONV and the median length of hospital stay were similar in both groups. CONCLUSION: Prochlorperazine is associated with superior efficacy and significant cost savings compared with ondansetron for the prevention of PONV in patients undergoing total hip and total knee replacement procedures.     

Results of a survey of anesthetists on postoperative nausea and vomiting

OBJECTIVE: Although an increasing number of studies concerning postoperative nausea and vomiting (PONV) have been performed, we do not know, what anaesthesiologists think about this problem and how they handle it in their daily routine. METHODS: A survey was performed involving anesthesiologists at 30 institutions of different size. 474 out of 1000 questionnaires were returned. RESULTS: When asked what kind of general anaesthesia they prefere in a woman at a very high risk to suffer PONV, the following answers were obtained: anaesthesia induction with propofol (78%), thiopentone (17%), etomidate (5%). Maintenance of anaesthesia with an inhalation anesthetic (44%) or with propofol (44%). The remaining 14% would use a combination of these techniques (6%) or neuroleptanaesthesia with droperidol (5%) or midazolam (1%). Only 10% of the respondants would omit nitrous oxide. There is no consensus about the optimal amount of intraoperative opioids. Fentanyl, alfentanil, and sufentanil are rated to contribute equally to the occurence of PONV, whereas opioids used for postoperative analgesia are thought to have substantial differences: piritramid is rated to be much less emetogenic than tramadol and morphine. 70% advocate routine antiemetic prophylaxis for high-risk patients (most often mentioned risk factors were: female sex: 85%, obesity: 81%, high doses of intraoperative opioids: 72%) and 23% administrate antiemetics even for all patients. Ondansetron and droperidol are suggested to be superior to metoclopramide, triflupromazine, dimenhydrinate, and transdermal scopolamine. However, metoclopramide is the drug of first choice for more than 50% of the respondants followed by droperidol, whereas only 29% use ondansetron as a first line drug. An unexpected high number of anaesthesiologists (13%) have experience with non-pharmacological methods for prophylaxis and treatment of PONV. Acupuncture/acupressure (10%) was most often mentioned. CONCLUSION: A great majority (93%) stated, that PONV is a relevant problem, that still remains unsolved. This proofs the need for further controlled studies.     

Oral clonidine premedication reduces vomiting in children after strabismus surgery

This is a prospective randomized double-blind trial conducted to determine whether preoperative orally administered clonidine causes or potentiates postoperative vomiting in 140 children (3-12 yr) undergoing strabismus surgery. They were all inpatients and classified randomly into four groups (n = 35 each); placebo (control), diazepam 0.4 mg.kg-1, clonidine 2 micrograms.kg-1, and clonidine 4 micrograms.kg-1. These agents were administered 93-112 min (mean; 100 min) before the anticipated time of induction of anaesthesia. All children received inhalational anaesthesia with halothane and nitrous oxide in oxygen. Muscle relaxation in all patients was obtained with vecuronium and residual neuromuscular blockade was antagonized with neostigmine and atropine before tracheal extubation. Diclofenac suppository was prescribed to prevent postoperative pain. No opioids or postoperative antiemetics were administered. All children remained in hospital for two days postoperatively. The incidence and frequency of vomiting were compared in the groups with Kruskall-Wallis Rank test. Clonidine 4 micrograms.kg-1 caused a lower incidence and frequency of vomiting than did placebo and diazepam (incidence and frequency: 11% and 1.37% and 3, and 34% and 2 in clonidine 4 micrograms.kg-1, placebo, and diazepam, respectively; P < 0.05 for clonidine 4 micrograms.kg-1 vs placebo and diazepam). However, low-dose clonidine was ineffective. These data suggest that preanaesthetic medication with clonidine 4 micrograms.kg-1 may be useful for preventing emesis following strabismus surgery. This property of clonidine indicates that it may be superior to other sedative premedicants such as diazepam and midazolam.     

The effect of blockade of the AMPA/kainate receptors of the nucleus accumbens on synaptic dopamine release during an emotional conditioned response

We studied the effect of combining prophylactic ondansetron (4 mg intravenously [IV]) to desflurane-based anesthesia in 90 ASA grade I or 11 women undergoing outpatient gynecological laparoscopy. Recovery after anesthesia, with special focus on postoperative nausea and vomiting (PONV), was assessed. Control groups received a similar desflurane anesthetic (placebo) or a propofol-infusion-based (active control) anesthetic. The study design was randomized, controlled, and double-blind (regarding ondansetron) and single-blind (regarding the anesthetic technique). Early recovery (eye opening, orientation, following commands, sitting) was similar in the three groups. However, overall home readiness (toleration of oral fluids, walking, pain tolerable by oral analgesics, no or only mild nausea) was achieved faster in the desflurane group receiving ondansetron (109 [21-937] min, P < 0.01) and in the propofol group (110 [33-642] min, P < 0.001) when compared to the desflurane only group (372 [45-723] min) (median [range]). The total incidence of PONV in the desflurane-only group was 80% (P < 0.01), compared to 40% and 20% in the desflurane group receiving ondansetron and the propofol group, respectively. The postoperative antiemetic requirements were consistently and significantly (P < 0.01) higher in the desflurane-only group compared to the other two groups. Postoperative sedation, analgesic requirements, and psychomotor recovery (assessed by the Maddox Wing and the Digit Symbol Substitution Tests) were similar in the three groups. Our results suggest that in order to achieve a propofol-like recovery profile in patients with a high likelihood of PONV, desflurane should be combined with a potent antiemetic (e.g., ondansetron).     

JC virus detection in the cerebrospinal fluid of AIDS patients with progressive multifocal leucoencephalopathy and monitoring of the antiviral treatment by a PCR method

Data from two published and one new meta-analysis were reviewed to compare the antiemetic efficacy of three different anaesthetic regimens: (i) propofol anaesthesia compared with another anaesthetic (control); (ii) anaesthesia without nitrous oxide compared with the same anaesthetic with nitrous oxide (control); (iii) propofol anaesthesia without nitrous oxide (TIVA) compared with another anaesthetic with nitrous oxide (control). Efficacy (prevention of postoperative nausea and vomiting compared with control) was estimated using odds ratio and number-needed-to-treat methods, and compared within a range of 20-60% control event rates for early efficacy (0-6 h) and 40-80% for late efficacy (0-48 h). Propofol anaesthesia or omitting nitrous oxide had similar effects on vomiting, both early and late. Propofol (but not omitting nitrous oxide) decreased the incidence of nausea. TIVA studies were documented poorly; appropriate comparison with other interventions were not possible. Efficacy of treatments should be compared within a setting-specific range of control event rates. There is insufficient evidence that TIVA with propofol is an anaesthetic technique with a low emetogenic potency.     

A lymphoma cell line resistant to 4-piperidinopiperidine was less sensitive to CPT-11

The purpose of the study was to assess the toxicity and efficacy of an oral, combination antiemetic regimen including granisetron (Kytril; SmithKline Beecham Pharmaceuticals, Philadelphia, PA, USA) in the setting of highly emetogenic conditioning chemotherapy for stem cell transplantation. Antiemetic prophylaxis consisted of oral granisetron 2 mg once daily, oral prochlorperazine 10 mg q 6 h and oral dexamethasone 4 mg q 6 h, beginning 1 h prior to chemotherapy on each of the 4 days of chemotherapy and continuing until 24 h after the completion of high-dose chemotherapy (HDC). Patients received either CVP (cyclophosphamide 6 g/m2, VP-16 1800 mg/m2 and carboplatin 1200 mg/m2) or CTP (thiotepa 500 mg/m2 in place of VP-16) in four daily doses given over 4 h from days -4 to -1. Previously mobilized and cryopreserved peripheral blood stem cells (PBSC) were reinfused on day +1. Evaluation of nausea, emetic episodes (EE), adverse events, and rescue medications were recorded on a daily patient diary. Thirty-six patients were entered. Fifty-three percent (95% CI = 37-75%) of patients achieved complete response for emesis (CR = 0 EE/24 h) and 75% (95% CI = 58-90%) had combined complete and major response (CR+MR = 0-3 EE/24 h) during all 5 of the treatment days. During the 5 study days, the average number of patient-days with no emesis was 3.7 (74%) and with 1-3 EE was 4.3 (86%). On days -4, -3, -2, -1 and 0, the combined CR+MR rate for emesis was 97, 92, 86, 78 and 75%, respectively. Nausea was absent or mild on all 5 study days in 57% (95% CI = 37-75%). Eight patients had severe late-onset emesis occurring on days +1 to +3 after reinfusion of stem cells. No clinically significant toxicities attributable to the antiemetic regimen were observed. An all oral antiemetic regimen of granisetron, prochlorperazine and dexamethasone appears to be safe and highly effective in patients receiving multiple, daily, high-dose chemotherapy regimens. This regimen offers the advantage of cost-savings, a low side-effect profile and ease of administration in the predominately outpatient setting of HDC with peripheral blood stem cell transplant (PBSCT).     

The efficacy of RS-25259, a long-acting selective 5-HT3 receptor antagonist, for preventing postoperative nausea and vomiting after hysterectomy procedures

We evaluated the safety and efficacy of RS-25259, a potent and long-acting selective 5-HT3 receptor antagonist, for the prevention of postoperative nausea and vomiting (PONV) in women undergoing hysterectomy procedures. In this randomized, double-blind, placebo controlled, dose-ranging study, 218 healthy, consenting women were assigned to one of the six treatment groups: placebo or RS-25259 0.1, 0.3, 1.0, 3.0, or 30 microg/kg. All patients underwent a standardized general anesthetic technique. The study medication was administered i.v. 20-30 min before the end of surgery. During the initial 24-h period after surgery, the incidence of vomiting, the need for rescue antiemetics, the time to the first episode of emesis, and administration of rescue antiemetic medication, as well as a nausea visual analog scale and verbal categorical scale scores were recorded. In addition, recovery times from the end of anesthesia and the incidences of perioperative side effects were noted. Only 30 microg/kg RS-25259 significantly decreased the incidence of vomiting and the requirement for rescue antiemetics. The largest dose of RS-25259 also delayed the time to the first emetic episode and reduced the number of treatment failures. However, no differences were found in the severity of postoperative nausea (versus saline), and postoperative headaches were more common after the administration of RS-25259 0.3-30 microg/kg i.v. In conclusion, RS-25259 30 microg/kg i.v. was effective in reducing the incidence of PONV after major gynecologic surgery, but the occurrence of headaches with the larger doses of RS-25259 is a concern. Implications: RS-25259, a long-acting 5-HT3 antagonist, was effective in reducing postoperative vomiting only at the largest dose studied (30 microg/kg). However, RS-25259 had no antinausea activity, and the larger doses were associated with an increased incidence of headaches in the postoperative period.