Continuous-infusion granisetron compared to ondansetron for the prevention of nausea and vomiting after high-dose chemotherapy

OBJECTIVES: The main aim was to calculate the prevalence of mental pathology in women between 18 and 70 in a Health District of Pamplona; second, to describe comorbidity and to analyse how mental pathology was recorded in the clinical histories. DESIGN: An observational crossover study with randomised selection. SETTING: A community study in the Txantrea quarter of Pamplona, covering 21,590 inhabitants, with 7605 women between 18 and 70. PATIENTS: Randomised sample, stratified by age, of 237 women between 18 and 70 taken from the 1991 Census. MEASUREMENTS AND RESULTS: In a face-to-face interview at the Health Centre, the DIS Questionnaire, which diagnoses mental illness, was administered to all participants. A check was made to see if mental pathology was recorded in their clinical history. The prevalence of mental illnesses, mainly Phobias and Depression, in the "last year of life" was 33.3% (27.5-39.5), which fell to 24.9% (19.7-30.7) when tobacco abuse was excluded. The most common pathologies were: Depression (17.3%), Tobacco dependency (17.3%), simple Phobia (14.8%), Agoraphobia (13.5%), social Phobia (8.9%) and post-traumatic stress (8.0%). CONCLUSIONS: Understanding the high psychological morbidity in these urban women can contribute to the development of Mental Health Promotion and Prevention Programmes and foment fuller mental health training for Primary Care professionals.     

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 [< or = 5 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.     

A comparison of ranitidine, droperidol or placebo in the prevention of nausea and vomiting after hysterectomy

Surgical procedures including the extent of systematic lymphadenectomy are still under discussion in the treatment of esophageal cancer. In the own patients' population 92 subtotal en bloc-esophagectomies with a standard two field lymphadenectomy were performed. A total of 1483 lymph nodes were resected in the thoracic and abdominal compartments with an incidence of 16.1% being metastatic. Stage pN1 disease occurred in 57.6% of the patients. The median number of lymph nodes resected in each specimen was 16, independent of tumor stage, -site or R-classification. The number of infiltrated nodes increased with tumor stages. R-classification, tumor stage and number of involved lymph nodes could be analyzed as prognostic factors. After R0-resection a median survival rate of 25.4 months could be achieved, following pN0-stage that of 27.4 months. In case of two metastatic lymph nodes the prognosis decreased significantly to 14.4 months (p < 0.01). Therefore, two field lymphadenectomy may show a therapeutic benefit only in a subgroup of patients with a limited number of lymph nodes infiltrated.     

Tropisetron in the prevention of acute and delayed nausea and vomiting over six courses of emetogenic chemotherapy

Tropisetron (Navoban") suppresses nausea and vomiting induced by cancer chemotherapy by antagonizing central and peripheral 5-HT3 receptors. In this open-label study, tropisetron was evaluated in 873 patients who were either refractory to antiemetic treatment during previous chemotherapy or at high risk of emesis as a result of current chemotherapy. The most commonly used agents alone or in combination were cyclophosphamide (35%), fluorouracil (30%), carboplatin (24%) and cisplatin (21%). The primary tumors were breast cancer (27%), lung cancer (16%), gynecological cancers (12%) and lymphoma (9%). Tropisetron was administered as a 15 min infusion prior to chemotherapy and an additional oral 5 mg dose was taken by 80% of the patients on subsequent days. During course 1, complete response to tropisetron was obtained in 64% of patients on day 1, 54% on day 2, 63% on day 3, 71% on day 4 and 77% on day 5. Very similar response rates were found for the six chemotherapy courses. There were few failures after complete and partial response, at maximum 3 and 15%, respectively. Moreover, 24-38% of those with partial response and 7-29% of those with failure could achieve a complete response during the following cycle. The treatment was well tolerated, the most frequently reported adverse events being constipation (3.7%) and headache (2.6%).     

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.     

Ondansetron versus droperidol or placebo to prevent nausea and vomiting after otologic surgery

This study compares the preoperative administration of ondansetron with that of droperidol or saline solution for the prevention of nausea and vomiting in otologic surgery patients. A total of 120 otherwise healthy individuals were randomly assigned to receive either saline solution, ondansetron (4 mg intravenously), or droperidol (25 microg/kg intravenously) before anesthetic induction. Intraoperative and postanesthesia care unit times were recorded along with incidence of nausea, vomiting, pain, nausea and recovery scores, and the administration of rescue antiemetics. Similar assessments were made during the next 24 hours. Demographics were similar, but more males received ondansetron. Anesthetic recovery scores were lower after administration of droperidol than after ondansetron. Incidence of nausea was similar between groups, but severity was greater with placebo and droperidol than with ondansetron. More vomiting occurred with placebo than with ondansetron or droperidol. No intergroup differences in rescue antiemetic administration were noted, however. Twenty-four hours later, more patients receiving placebo had nausea or vomited than patients receiving droperidol or ondansetron. Fewer women in the ondansetron group vomited than in the other two groups. Ondansetron 4 mg intravenously is as effective as droperidol and better than saline solution in preventing nausea and vomiting in patients undergoing otologic surgery. No cost advantage as determined by lower use of rescue antiemetics or shorter postanesthesia care unit times was noted after ondansetron therapy.     

Prevention of postoperative nausea and vomiting with ondansetron: a prospective, randomized, double-blind study in 90 patients

Cortical variation in mammals and other terrestrial vertebrates, re-examined by current comparative methodology (out-group analysis), indicates that separate lateral (olfactory), dorsal and medial (hippocampal) pallial or cortical formations arose with the origin of vertebrates. Although the exact origin of mammalian isocortex (so-called neocortex) is still disputed, it appears that the earliest mammals already had a six-layered isocortex with ten to 20 functional subdivisions. Among placental mammals, at least, isocortex has expanded numerous times, producing additional cortical subdivisions. Because these expansions were independent transformations of a simpler cortex, they produced subdivisions that are not homologous.     

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.     

Control of nausea and vomiting with ondansetron in patients treated with intensive non-cisplatin chemotherapy for acute myeloid leukaemia

18 consecutive patients with acute myeloid leukaemia (AML) treated with 34 cycles of intensive chemotherapy received ondansetron as antiemetic treatment. 14 patients were chemotherapy-naive, while 4 patients were treated for relapsed leukaemia. All patients received at least one cycle of chemotherapy, 11 patients (61%) received two cycles and 5 patients (28%) received three cycles. The remission induction regimen consisted of cytarabine 200 mg/m2 daily from day 1 to day 7, in combination with an anthracycline or amsacrine on 3 days. During the second and third cycle the dose of cytarabine was increased. Ondansetron was administered as follows: 8 mg intravenously before the start of chemotherapy, followed by 8 mg orally three times daily for 10 days. 50% of patients had no episodes of vomiting during the first cycle of chemotherapy and 78% had less than five episodes of vomiting over 10 days. 72% of patients had no or only mild nausea. These high response rates were maintained during the subsequent cycles. No side-effects due to ondansetron were registered. These data indicate that ondansetron is efficacious in preventing nausea and vomiting in patients with AML treated with intensive chemotherapy.     

Ondansetron for prevention of postoperative nausea and vomiting following minor oral surgery: a double-blind randomized study

The efficacy and safety of ondansetron in preventing postoperative nausea and vomiting following minor oral surgery was evaluated in a prospective randomized double-blind study. Of a total of seventy-seven patients, randomly 38 had 4 mg of ondansetron and 39 had normal saline as placebo intravenously immediately prior to induction of anaesthesia. A standard general anaesthetic with thiopentone, suxamethonium, fentanyl, nitrous oxide and isoflurane was employed. Postoperatively nausea was assessed verbally and on a visual analog scale at 1, 4 and 24 hours from the time of awakening. Episodes of vomiting were recorded. Eight patients (21.1%) in the ondansetron group compared to 19 (48.7%) in the placebo group had nausea (P < 0.05) and 1 (2.6%) in the ondansetron group compared with 9 (23.1%) in the placebo group vomited (P < 0.05). Patients who vomited twice or more and the number who required a rescue antiemetic were significantly fewer in the ondansetron group (P < 0.05). Cardiovascular parameters were stable and showed no significant difference in the two groups. There were no significant adverse effects that could be directly attributable to ondansetron.     

Efficacy of ondansetron in radiation-induced nausea and vomiting: review of the literature

Radiotherapy-induced emesis depends on the site of irradiation, the field size and the dose per fraction and is generally less intense than chemotherapy-induced emesis. Established anti-emetic drugs offer only limited symptom control (50%). Ondansetron, a 5HT3 receptors antagonist, had proven a complete or a major control efficacy (0-2 emetic episodes) of 68 to 95% in three pilot studies (fractionated, single-dose and total body irradiations). In controlled studies, ondansetron efficacy was significantly higher than placebo, metoclopramide and prochlorperazine. The treatment was well tolerated in the different studies.     

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.     

Efficacy of ondansetron in prophylaxis of postoperative nausea and vomiting in patients following infratentorial surgery: a placebo-controlled prospective double-blind study

Competitive PCR was used to monitor the survival of a 520-bp DNA target sequence from a recombinant plasmid, pVACMC1, after admixture of the plasmid with freshly sampled human saliva. The fraction of the target remaining amplifiable ranged from 40 to 65% after 10 min of exposure to saliva samples from five subjects and from 6 to 25% after 60 min of exposure. pVACMC1 plasmid DNA that had been exposed to degradation by fresh saliva was capable of transforming naturally competent Streptococcus gordonii DL1 to erythromycin resistance, although transforming activity decreased rapidly, with a half-life of approximately 50 s. S. gordonii DL1 transformants were obtained in the presence of filter-sterilized saliva and a 1-microg/ml final concentration of pVACMC1 DNA. Addition of filter-sterilized saliva instead of heat-inactivated horse serum to S. gordonii DL1 cells induced competence, although with slightly lower efficiency. These findings indicate that DNA released from bacteria or food sources within the mouth has the potential to transform naturally competent oral bacteria. However, further investigations are needed to establish whether transformation of oral bacteria can occur at significant frequencies in vivo.     

Treatment of cisplatin-related nausea and vomiting with a combination of ondansetron and metoclopramide: a pilot study

Forty chemotherapy-naive patients receiving high-dose cisplatin were included in a pilot study of a combination of ondansetron plus metoclopramide as antiemetic therapy. Patients received ondansetron 16 mg plus metoclopramide 0.5 mg/kg in 250 cm3 of normal saline i.v. 15 min before cisplatin administration on day 1; then ondansetron 8 mg was given orally b.i.d. and metoclopramide 0.5 mg/kg was given intramuscularly t.i.d. for 4 days. This combination was given to all patients receiving the first cycle of chemotherapy. At the second cycle of chemotherapy all patients received the same antiemetic treatment as above plus methylprednisolone 125 mg i.v. on day 1 and the intramuscularly once a day for 4 days. There were 20 females and 20 males with a mean performance status of 1 (range 0-2) and a mean age of 58 years (range 36-68). Ten patients had ovarian carcinoma, eight patients had uterine adenocarcinoma and 22 and non-small cell lung carcinoma. The mean cisplatin dose was 96 mg/m2. All patients denied significant alcohol consumption. At cycle 1, complete protection against acute emesis was achieved in 22 patients (55%), major protection in 12 cases (30%), minor protection in four patients (10%) and failure in two cases (5%). On the other hand, the efficacy of this combination on delayed vomiting was not striking. For delayed vomiting, complete protection was observed in nine patients (23%), major protection in 13 cases (33%), minor protection in 10 patients (25%) and failure in eight cases (20%). At cycle 2, patients also received methylprednisolone showing complete protection from vomiting in 19 cases (47%) and major protection on 12 cases (30%). Results achieved with ondansetron plus metoclopramide are in the range reported for ondansetron alone in the medical literature. Although this study was not prospectively carried out in a randomized fashion, the results are not suggestive of a possible positive effect of metoclopramide addition to ondansetron. On the other hand, these results stress the role that corticosteroids may play in the control of delayed emesis. Toxicity was predictable and the frequency of side-effects was in the range reported in other studies with ondansetron.     

Patients' self-reported functional status after granisetron or ondansetron therapy to prevent chemotherapy-induced nausea and vomiting at six cancer centers

Patient functional status after administration of either granisetron or ondansetron to prevent acute chemotherapy-induced nausea and vomiting (CINV) was studied. Pharmacists and nurses from six cancer centers distributed Functional Living Index-Emesis (FLIE) questionnaires to 115 outpatients receiving either granisetron or ondansetron for prevention of CINV. The emetogenic potential of each patient's chemotherapy regimen was high, moderately high, or moderate. Immediately before and 72 hours after chemotherapy, each patient rated his or her reaction to each of 18 items on the questionnaire on a 7-point scale. Possible scores ranged from 18 to 126, with higher scores indicating higher levels of functioning. The occurrence of nausea in the granisetron group was 40.0% compared with 43.2% in the ondansetron group; the occurrence of vomiting was 18.8% in the granisetron group and 11.1% in the ondansetron group. Patients who received highly emetogenic chemotherapy had significantly lower scores on the FLIE after chemotherapy than before. Patients with both nausea and vomiting reported a much higher negative impact on functional status after chemotherapy than those with nausea only. The mean prechemotherapy and postchemotherapy FLIE scores were 124.2 and 110.4 for granisetron and 124.9 and 111.9 for ondansetron. Granisetron and ondansetron did not differ significantly in their effect on functional status reported by patients before and 72 hours after receiving cancer chemotherapy.     

Epidural buprenorphine and epidural droperidol for post-operative nausea or vomiting

For 120 young patients who had undergone reconstruction of anterior cruciate ligament of the knee, we investigated the effect of epidural administration of buprenorphine on the incidence of nausea or vomiting, and the anti-emetic effect of epidural administration of droperidol. In the group who had received bolus injection of buprenorphine 0.1 mg, nausea or vomiting occurred early most often, and the injection was not useful to prolong analgesic effect. In the another group who had received continuous epidural infusion of buprenorphine 0.3 mg, nausea or vomiting occurred late. Bolus injection of droperidol 2.5 mg was not useful to prevent nausea or vomiting caused by continuous epidural infusion of buprenorphine. While, continuous infusion of droperidol 5 mg was effective in decreasing nausea or vomiting caused by continuous epidural infusion of buprenorphine. In conclusion, continuous epidural administration of droperidol is useful to prevent nausea or vomiting.     

Does oral ondansetron reduce the incidence of nausea and vomiting after surgery for strabismus in children?

OBJECTIVE: To compare the efficacy of oral ondansetron with oral metoclopramide for the prevention of postoperative vomiting and nausea in children undergoing strabismus surgery. STUDY DESIGN: Prospective, randomized, double-blind trial. PATIENTS: Thirty children of physical class 1, age 9 +/- 4 years, scheduled for strabismus surgery, were randomized into two groups (ondansetron and metoclopramide). METHODS: In the ondansetron group, the children received the first oral dose of ondansetron (4 mg) 1 hour before induction of anaesthesia and the other doses 8 and 16 hours later. In the metoclopramide group, children received metoclopramide (5 mg) in the same conditions. Anaesthesia was induced with thiopentone, vecuronium and fentanyl and maintained with halothane and N2O/O2. Patients were evaluated by an independent observer for nausea and emesis in recovery room (0-2 h) and on the ward. The adverse effects of oral ondansetron and metoclopramide were assessed. RESULTS: There were non-significant differences between the two groups for incidence of nausea and vomiting (40% and 53% in ondansetron group versus 33 and 60% in metoclopramide group, respectively. CONCLUSION: Unlike intravenous ondansetron, oral ondansetron is not superior to metoclopramide for the prevention of nausea and vomiting caused by strabismus surgery in children.