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Attitudes, management and consequences of nausea and vomiting of pregnancy in the United States and Canada.

BACKGROUND: Nausea and vomiting of pregnancy (NVP) affects a large proportion of pregnant women. In 1983, Bendectin((R)), the only FDA-approved drug for NVP, was removed from the market by its manufacturer due to legal costs based on claims of teratogenicity, which were subsequently proven to be unsubstantiated. In Canada, a generic form of Bendectin (Diclectin; a doxylamine/pyridoxine combination) has continued to be available, with increasing use over the last few years. OBJECTIVE: To characterize the attitudes, management and consequences of NVP among pregnant women in the USA, where no approved drug for NVP is available, and in Canada, where such a drug is available. DESIGN: Prospective, observational study. RESULTS: Women suffering from NVP (N = 1444) were interviewed, of which 42% were American and 58% were Canadian. The two groups had similar maternal characteristics and a similar distribution of severity of NVP, although among Canadian women the NVP continued for slightly longer. American respondents were treated significantly more often by an obstetrician as their primary caregiver, were more commonly advised by their caregiver to change their diet and/or lifestyle and to use non-pharmacological agents to manage their NVP, and more often perceived anti-emetics as posing an increased risk for malformations (all P < 0.001). Canadian respondents reported a family physician as their primary caregiver significantly more often, were more commonly advised to take anti-emetic medications and perceived their NVP as causing a concern to their unborn (all P < 0.001). American women experienced significantly larger weight loss, more hospitalizations and more time lost from paid work. CONCLUSIONS: Lack of an approved drug for symptoms of NVP may be associated with unwarranted and preventable adverse health effects. Because this is an observational study, these associations do not necessarily prove causation.

Adult↗

Nissen fundoplication may induce gastric myoelectrical disturbance in children.

BACKGROUND: Recurrent vomiting with failure to thrive is a common problem in neurologically impaired children. Many undergo fundoplication to control the underlying gastroesophageal reflux, but the results of surgery are not always satisfactory, and postoperative retching may be a major problem. Retching is part of the emetic reflex and is associated with nausea, which is itself associated with disturbed gastric electrical control activity, resulting in a gastric dysrhythmia. METHODS: By recording gastric electrical control activity before and after Nissen fundoplication using the noninvasive technique of surface electrogastrography, the authors have shown that (1) Neurologically impaired children with gastroesophageal reflux more commonly have a preexisting gastric dysrhythmia (65% neurologically impaired v 20% neurologically normal children with gastroesophageal reflux, P<.05), (2) Children who retch preoperatively are three times more likely to retch postoperatively, and (3) 25% of neurologically impaired children may start to retch postoperatively for the first time. CONCLUSION: The authors propose that in neurologically impaired children, loss of central inhibitory mechanisms may result in inappropriate activation of the emetic reflex, which may be heightened by antireflux surgery.

Child↗

Tachykinin NK1 receptor antagonists act centrally to inhibit emesis induced by the chemotherapeutic agent cisplatin in ferrets.

These studies have compared the pharmacological profile of two non-peptide human type neurokinin1 (hNK1) receptor selective antagonists, L-741,671 and a quaternised compound L-743,310. In radioligand binding studies L-741,671 and L-743,310 had high affinity for ferret and cloned hNK1 receptors [Ki (nM) ferret 0.7 and 0.1; human 0.03 and 0.06, respectively] but low affinity for rodent NK1 receptors [Ki (nM) 64 and 17, respectively] suggesting that ferret receptors have hNK1-like binding pharmacology. Studies in vivo showed that L-741,671 and L-743,310 had equivalent functional activity in the periphery (ID50s of 1.6 and 2 micrograms/kg i.v., respectively) as measured by inhibition of plasma protein extravasation evoked in the oesophagus of guinea pigs by resiniferatoxin (7 nmol/kg i.v.). Using an in situ brain perfusion technique in anaesthetised rats, L-741,671 was shown to be much more brain penetrant than the quaternary compound L-743,310 which had an entry rate similar to the poorly brain penetrant plasma marker inulin. These compounds thus provided an opportunity to compare the anti-emetic effects of equi-active hNK1 receptor antagonists with and without brain penetration to central NK1 receptor sites. When tested against cisplatin-induced emesis in ferrets, L-741,671 (0.3, 1 and 3 mg/kg i.v.) produced marked dose-dependent inhibition of retching and vomiting but L-743,310 was inactive at 3 and 10 micrograms/kg i.v. In contrast, direct central injection of L-741,671 and L-743,310 (30 micrograms) into the vicinity of the nucleus tractus solitarius or L-743,310 (200 micrograms) intracisternally was shown to inhibit retching and vomiting induced by i.v. cisplatin. L-741,671 and L-743,310 had equivalent functional activity, at the same dose, against cisplatin-induced emesis when injected centrally. These observations indicated that had L-743,310 penetrated into the brain after systemic administration it would have been active in the cisplatin-induced emesis assay and so show that brain penetration is essential for the anti-emetic action of systemically administered NK1 receptor antagonists.

Animals↗

Opioid receptor involvement in the adaptation to motion sickness in Suncus murinus.

The aim of the present study was to investigate an opioid receptor involvement in the adaptation response to motion sickness in Suncus murinus. Different groups of animals were treated intraperitoneally with either saline, morphine (0.1 and 1.0 mg/kg), naloxone (1.0, 10.0 and 5.0 mg/kg) or a combination of naloxone plus morphine in the absence or 30 min prior to a horizontal motion stimulus of 1 Hz and 40 mm amplitude. For the study of adaptation, different groups received saline on the first trial, and in subsequent trials (every 2 days) they received either saline, naloxone (1.0 and 10.0 mg/kg, i.p.) or morphine (0.1 mg/kg, i.p.) 30 min prior to the motion stimulus. Pretreatment with morphine caused a dose-related reduction in emesis induced by a single challenge to a motion stimulus. Pretreatment with naloxone alone did not induce emesis in its own right nor did it modify emesis induced by a single challenge to a motion stimulus. However, pretreatment with naloxone (5.0 mg/kg, i.p.) revealed an emetic response to morphine (P<.001) (1.0 mg/kg, i.p.) and antagonised the reduction of motion sickness induced by morphine. In animals that received saline or naloxone (1.0 mg/kg), a motion stimulus inducing emesis decreased the responsiveness of animals to a second and subsequent motion stimulus challenge when applied every 2 days for 11 trials. However, the animals receiving naloxone 10.0 mg/kg prior to the second and subsequent challenges showed no significant reduction in the intensity of emesis compared to the first trial. The data are revealing of an emetic potential of morphine when administered in the presence of a naloxone pretreatment. The administration of naloxone is also revealing of an additional inhibitory opioid system whose activation by endogenous opioid(s) may play a role in the adaptation to motion sickness on repeated challenge in S. murinus.

Adaptation, Psychological↗

The effect of electroacupuncture as an adjunct on cyclophosphamide-induced emesis in ferrets.

The effect of electroacupuncture (EA) on cyclophosphamide-induced emesis in ferrets was studied at acupuncture point Neiguan (P6) with various electrical stimulation parameters (5-100 Hz, 1.5-3 V, 5-20 min, n=6/group). The combination therapy of EA (100 Hz, 1.5 V and 10 min) with the lower doses of ondansetron (0.04 mg/kg), droperidol (0.25 mg/kg) and metoclopramide (2.24 mg/kg) significantly reduced the total number of emetic episodes by 52%, 36% and 73%, respectively, as well as the number of emetic episodes in the first phase as compared to the sham acupuncture control (P<.01). These EA/drug combinations also showed a significant effect in preventing emesis as compared to either EA or drug alone (P<.05). The present study suggests that acupuncture may be useful as an adjunctive therapy in the treatment of chemotherapy-induced emesis.

Animals↗

Conditioned taste aversion induced by self-administered drugs: paradox revisited.

In this paper we have reviewed the literature on Conditioned Taste Aversion (CTA) with specific attention to the "apparent paradox" in this literature. This paradox refers to the fact that drugs which are self-administered (SA) by animals and are therefore presumed to possess positive reinforcing properties are also endowed with the capacity to induce a CTA. We have argued that the CTA literature contains evidence of the existence of two qualitatively distinct types of CTA, one which is mediated by emetic agents and the other induced by SA drugs. We first provided evidence to support the notion that the traditional explanation of CTA as a function of "drug toxicity" and its resultant gastrointestinal distress does not fit the data on the nature of CTA induced by SA drugs. We proposed instead that "drug shyness" or the novelty of the drug state of these psychoactive SA drugs constitutes a better explanation of the CTA of SA drugs. We provided further evidence suggesting a functional relationship between the positive reinforcing and aversive properties of SA drugs. We have based this contention on a review of the behavioral, physiological and neurochemical data concerning the nature of CTA of SA drugs. The examination of these data reveals that the neural mechanisms underlying both the positive and aversive properties of SA drugs are the same and at the same time different from the neural mechanisms underlying the induction of CTA by emetic agents. Finally, we discussed the relevance of this interaction between the positive and aversive properties of SA drugs in the context of their abuse liability and the control they exert on drug-oriented behavior.

Animals↗

Buprenorphine versus domperidone in chemotherapy-induced emesis: a pilot study.

A randomized double-blind cross-over study was performed to evaluate the possible anti-emetic effect of the partial opiate antagonist buprenorphine in comparison to domperidone in chemotherapy-induced nausea and vomiting. Emesis was of significantly shorter duration on domperidone treatment. Most patients preferred domperidone, mainly due to adverse side-effects of buprenorphine. Nevertheless, emesis in buprenorphine treatment was less disabling. Therefore, it might be useful to search for new alternatives in this group of drugs or to use them in a combination regimen of anti-emetic agents.

Adult↗

Prophylactic use of tropisetron or metoclopramide during adjuvant abdominal radiotherapy of seminoma stage I: a randomised, open trial in 23 patients.

BACKGROUND AND PURPOSE: Nausea and vomiting are frequent side effects during adjuvant abdominal radiotherapy in seminoma stage I patients. This study evaluates the efficacy and side effects of prophylactically administered tropisetron in comparison to metoclopramide. MATERIALS AND METHODS: Twenty-three seminoma stage I patients who were to undergo adjuvant abdominal radiotherapy (30 Gy) were included in a prospective, randomised, open study. The patients were allocated to receive adjuvant daily tropisetron 5 mg p.o. (TROP group) (11 patients) or metoclopramide 30 mg p.o. (MET group) (12 patients), allowing an eventual dose increase to 60 mg. Evaluation was based on diary cards filled in by the patients during the treatment period. Nausea, vomiting, abdominal pain and bowel motions were assessed. RESULTS: Nausea was significantly lower in the TROP group as compared with the MET group (median: 0.14 vs. 1.32; P = 0.03). Thirty percent of all patients experienced vomiting. In the TROP group one patient had a mean number of emetic events > 0 as compared with 6 patients in the MET group (P = 0.07). Two patients in the TROP group and one in the MET group discontinued therapy due to lacking control of emesis. In two further patients the doubling of the metoclopramide resulted in acceptable control of nausea/vomiting. Both drugs were generally well tolerated. CONCLUSION: Seminoma stage I patients on tropisetron experienced less nausea and vomiting during abdominal radiotherapy than patients receiving metoclopramide. The costs of the former drug may, however, not justify its use as first choice anti-emetic since few patients in either group experienced severe nausea.

Adult↗

Behavioral conditioning and experimental motion-induced sickness.

Adult male squirrel monkeys were the subjects of experiments conducted to determine whether or not repeated exposures to sickness-inducing horizontal rotation would result in behavioral conditioning of emetic responses. The development of conditioned food aversion and feeding suppression as a consequence of pre- and postrotation eating was quantified. It was concluded that neither instrumental conditioning nor classical conditioning were valid alternative hypotheses for the occurrence of repeated vomiting episodes over a period of ten daily exposures to motion. Conditioned aversion to fresh banana and feeding suppression developed gradually if rotation, which induced multiple bouts of vomiting, was sustained for 1- or 2-hour sessions. If spinning was terminated immediately after the first emetic response, no aversion or suppression emerged. The occurrence of food aversion, by itself, is questioned as a valid index of the presence of subjective concomitants of motion sickness in animals.

Animals↗

Does increasing the steroid dose enhance the efficacy of the antiemetic combination of granisetron and methylprednisolone in gynecologic cancer patients--a randomized study.

OBJECTIVE: The authors administered two doses of oral methylprednisolone in combination with 3mg granisetron intravenously for the prophylaxis of cisplatin-induced emesis in gynecologic cancer patients. MATERIALS AND METHODS: Thirty-nine patients received 100mg (group A) and 25 received 200mg (group B) methylprednisolone in the antiemetic combination in a randomized prospective trial. RESULTS: No vomiting in 90.2 and 96.7%, one emetic episode in 3 and 1.1% and two episodes in 3 and 2.2% were detected in groups A and B, respectively. More than two emetic episodes were considered to be a failure and were observed only in group A (3.8%). There was no significant difference between the two treatment groups (P=0.3160). CONCLUSIONS: There was no evidence for enhanced antiemetic effect of elevated steroidal dose in combination with granisetron.

Adult↗

Improvement of cisplatin-induced emesis and delayed gastric emptying by KB-R6933, a novel 5-HT3 receptor antagonist.

The effects of a novel 5-hydroxytryptamine3 (5-HT3) receptor antagonist, KB-R6933, 6-amino-5-chloro-1-isopropyl-2-(4-methyl-1-piperazinyl)-benzimidazole dimaleate, on emesis and delayed gastric emptying induced by cisplatin were assessed in experimental models. Prophylactic intravenous or oral treatment with KB-R6933 prolonged the latent period until the first emetic episode and decreased the number of emetic episodes induced by cisplatin in ferrets. KB-R6933 immediately inhibited the subsequent emesis when administered to the ferrets which exhibited established vomiting after administration of cisplatin. In rats treated with cisplatin, the gastric emptying rate was significantly reduced. KB-R6933 reversed the reduction of gastric emptying induced by cisplatin. These results suggest that KB-R6933 is an antiemetic agent, and could improve the cisplatin-induced delay of gastric emptying.

Animals↗

Transneuronal tracing of neural pathways controlling activity of diaphragm motoneurons in the ferret.

Previous studies have shown that neurons in addition to those in the medullary respiratory groups are involved in activating phrenic motoneurons during a number of behaviors, including vomiting and reaction to vestibular stimulation. However, the location of premotor inspiratory neurons outside of the main medullary respiratory groups is largely unknown, particularly in emetic species. In the present study, the transneuronal tracer pseudorabies virus was injected into the diaphragm of the ferret, and the locations of retrogradely-labeled motoneurons and transneuronally-labeled pre-motoneurons in the brainstem and cervical and thoracic spinal cord were mapped. Injections of a monosynaptic tracer, cholera toxin, were also made in order to verify the location of motoneurons innervating the diaphragm. Phrenic motoneurons identified with pseudorabies virus and cholera toxin were confined largely to the C5-C7 levels of spinal cord, and often gave rise to prominent polarized dendritic arbors that extended across the midline. At post-inoculation survival times > or = three days, transneuronally-labeled interneurons were located in the cervical and thoracic spinal cord and portions of the brainstem, including the midline pontomedullary reticular formation and the lateral medullary reticular formation. Double-labeling studies revealed that although the infected midline neurons were located in the proximity of serotonergic neurons, only a small number of the virus-containing cells were positive for serotonin. These findings suggest that neurons in the midline of the medulla and pons influence the activity of phrenic motoneurons, perhaps during inspiratory behaviors unique to emetic animals (such as vomiting).

Animals↗

Delta(9)-tetrahydrocannabinol and synthetic cannabinoids prevent emesis produced by the cannabinoid CB(1) receptor antagonist/inverse agonist SR 141716A.

There is substantial clinical evidence that Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and its synthetic analogs (nabilone and levonantradol) can prevent emesis in cancer patients receiving chemotherapy. Limited available animal studies also support the antiemetic potential of these cannabinoids. The present study investigates the mechanism of antiemetic action of cannabinoids in an established animal model of emesis, the least shew (Cryptotis parva). Since cannabinoid agonists prevent emesis, it was hypothesized that blockade of either the cannabinoid CB(1) receptor or the cannabinoid CB(2) receptor would induce vomiting. Thus, the emetic potential of SR 141716A (CB(1) receptor antagonist) or SR 144528 (CB(2) receptor antagonist) was investigated. Both intraperitoneal (0, 1, 2.5, 5, 10 and 20 mg/kg, n = 7-15 per group) and subcutaneous (0, 10, 20 and 40 mg/kg, n = 6-9 per group) administration of SR 141716A caused emesis (ED(50) = 5.52 +/- 1.23 and 20.2 +/- 1.02 mg/kg, respectively) in the least shrew in a dose-dependent manner. Indeed, both the frequency of emesis and the percentage of animals vomiting increased with increasing doses of SR 141716A. Significant effects were seen at the 10- and 20-mg/kg doses for the IP route, while only the 40-mg/kg dose produced significant emesis via the SC route. The CB(2) antagonist failed to produce emesis via either route of administration. SR 141716A at an IP dose of 20 mg/kg was used to induce emesis for drug interaction studies. Thus, varying doses of three different classes of cannabinoid agonists [CP 55, 940 (0, 0.1, 0.5 and 1 mg/kg), WIN 55, 212-2 (0, 1, 5 and 10 mg/kg), and Delta(9)-THC (0, 5, 10 and 20 mg/kg)], were administered IP to different groups of shrews 10 min prior to SR 141716A injection. The frequency of emesis was recorded for 30 min following the administration of SR 141716A. The order of potency for redcing both the frequency of emesis and the percentage of shrews vomiting was CP 55, 940 > WIN 55, 212-2 > Delta(9)-THC which is consistent with an action on the CB(1) receptor. These results suggest that the antiemetic activity of Delta(9)-THC and its synthetic analogs reside in their ability to stimulate the cannabinoid CB(1) receptor. Furthermore, the antiemetic potency of CP 55, 940 is 45 times greater than Delta(9)-THC. On the other hand, blockade of CB(1) receptors can induce vomiting, which implicates an important role for endogenous cannabinoids in emetic circuits.

Analgesics, Non-Narcotic↗

A prospective randomized double-blind trial comparing ondansetron versus prochlorperazine for the prevention of nausea and vomiting in patients undergoing fractionated radiotherapy.

In a multicentre, international double-blind trial, patients undergoing courses of five or more daily radiotherapy treatments to the upper abdomen were randomized to receive either oral ondansetron 8 mg t.d.s. or oral prochlorperazine 10 mg t.d.s. throughout their radiation course in order to try to prevent nausea and vomiting. A total of 192 patients were recruited, 135 of whom were included in the efficacy analysis; of these, 70 received ondansetron and 65 prochlorperazine. Forty-three (61%) of the patients prescribed ondansetron and 23 (35%) of those given prochlorperazine had a complete response, with no emetic episodes throughout their treatment course (P = 0.002). There was, however, no significant difference between the two groups with respect to the incidence and severity of nausea. Seventeen (24%) of the patients on ondansetron and 19 (29%) of those given prochlorperazine were treatment failures, experiencing more than five emetic episodes on their worst day during the study. Both drugs were well tolerated, although constipation was seen more commonly with ondansetron.

Adult↗

The efficacy and safety of ondansetron in the prophylaxis of cancer-chemotherapy induced nausea and vomiting in children.

The management of chemotherapy induced emesis presents a major difficulty in the paediatric population. Ondansetron is a 5-HT3 antagonist and its antiemetic properties have been established in adults receiving chemotherapy. Experience in the treatment of children, however, is limited. There is no standard comparative antiemetic in paediatric practice, so this European, multi-centred study aimed to assess the clinical efficacy and safety of ondansetron in a large cohort of children receiving a range of emetogenic chemotherapy regimens for malignant disease. Two hundred patients were entered into the study, of whom 183 fulfilled entry criteria. Forty per cent (10/25) of patients receiving cisplatin, 68% (27/40) receiving ifosfamide and 70% (83/118) receiving other drugs had less than 3 emetic episodes (vomit or retch) during their worst 24 hours of chemotherapy. The number of days without vomiting or retching during and shortly after receiving chemotherapy was also related to the emetic potential of the agents in the regimen: cisplatin 82/182 (45%), ifosfamide 137/213 (64%) and other agents 430/566 (76%). The control of nausea appeared better than that of emesis in each of the sub-groups analysed. Ondansetron was safe, well tolerated and effective in the prevention of vomiting in children receiving a wide variety of chemotherapy regimens.

Antineoplastic Agents↗

Ondansetron prevents postoperative emesis in male outpatients. S3A-379 Study Group.

STUDY OBJECTIVES: To determine (1) the efficacy and safety of ondansetron in the prevention of postoperative nausea and vomiting (PONV) in male outpatients; (2) prognostic factors for PONV in male outpatients; and (3) patients' perceptions of the debilitating effects of PONV in the ambulatory surgery setting. DESIGN: Prospective, randomized, stratified, double-blind study. SETTING: Multicenter-24 medical centers. PATIENTS: 468 ASA physical status I and II males at least 12 years of age scheduled for general anesthesia. INTERVENTIONS: All patients received intravenous ondansetron 4 mg or placebo prior to undergoing general balanced (opioid) anesthesia. MEASUREMENTS AND MAIN RESULTS: In the postanesthesia care unit (PACU), the number of emetic episodes, vital signs, adverse events, and nausea assessments were recorded by a blinded observer. After discharge, and until the end of the 24-hour study period, patients completed a diary that collected emetic episodes, adverse events, nausea, and pharmacoeconomic data. There were no differences in patient demographics or safety profiles between groups. The number of patients with no emesis and no nausea during the 24-hour study period was significantly greater (p < 0.05) with ondansetron 4 mg compared with placebo. Prognostic factors for an increased likelihood of developing PONV in males included a history of motion sickness or previous PONV, patients undergoing nonorthopedic procedures, and surgeries lasting longer than one hour. Finally, 38% of patients experiencing PONV perceived PONV to be as, or more debilitating than, the aftereffects of surgery itself. CONCLUSIONS: Ondansetron 4 mg was more effective than placebo in preventing PONV in male outpatients. Males at potential risk for developing PONV include: (1) those with a history of motion sickness and/or PONV; (2) patients undergoing nonorthopedic procedures; and (3) procedures lasting longer than one hour. Such patients may benefit from receipt of a prophylactic antiemetic. Postoperative nausea and vomiting has a debilitating effect that can be differentiated by patients from the effects of surgery itself.

Adult↗

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.

Adolescent↗

Oral dolasetron mesylate for prevention of postoperative nausea and vomiting: a multicenter, double-blind, placebo-controlled study. The Oral Dolasetron PONV Prevention Study Group.

STUDY OBJECTIVE: To examine the safety and effectiveness of a range of single oral doses of dolasetron mesylate for the prevention of postoperative nausea and vomiting. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: 32 hospitals. PATIENTS: 789 female ASA physical status I, II, and III patients, ages 18 to 60 years, weighing between 45 and 100 kg, scheduled for major gynecologic surgery (including abdominal hysterectomy, gynecologic laparotomy, or vaginal hysterectomy) with general anesthesia. INTERVENTIONS: 25, 50, 100, or 200 mg oral doses of dolasetron mesylate or placebo were administered 1 to 2 hours before induction of anesthesia. Efficacy was assessed for 24 hours postrecovery by measuring complete response (no emetic episodes, no rescue medication), total response (complete response with no nausea), time to first emetic episode or rescue, and patient visual analog scale evaluations of nausea severity and satisfaction with antiemetic therapy. MEASUREMENTS AND MAIN RESULTS: Complete response rates for the 50, 100, and 200 mg dose groups were statistically greater than placebo (p < or = 0.018). Likewise, total response rates were statistically greater in the 50, 100, and 200 mg dose groups than in the placebo group (p = 0.012). Percentage of patients with no nausea and patient satisfaction scores were significantly higher for each dolasetron dose group than placebo (p < or = 0.047 and p < or = 0.004, respectively). Efficacy peaked at the 50 mg dose. The incidence of adverse events was similar in the placebo (30.1%) and dolasetron groups (29.4%). Headache was the most frequent treatment-related adverse event, with 2% to 5% incidence across groups. Incidence of adverse events did not increase with increasing dolasetron doses. Dose-related decreases in blood pressure at acute time points were not clinically significant. CONCLUSION: Single oral doses of dolasetron, administered 1 to 2 hours before induction of anesthesia, are safe and effective for preventing postoperative nausea and vomiting in this patient sample. Maximal antiemetic response was seen with the 50 mg oral dolasetron dose.

Adolescent↗