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Comparison of granisetron, ondansetron and tropisetron for control of vomiting and nausea induced by cisplatin.

Severe nausea and vomiting are common and one of the most feared side effects of cisplatin-based chemotherapy. A total of 106 patients were randomized to receive a single dose of 8 mg ondansetron or 3 mg granisetron or 5 mg tropisetron intravenously as prevention of cisplatin-induced acute nausea and vomiting. Antiemetic therapy was done within 30 minutes before initiating chemotherapy. A questionnaire evaluating nausea, vomiting and retches was administered to patients and the responses were categorized as complete, partial or failure. The response determination was repeated in the first 24 hours, and within 24-72 hours following cisplatin administration. The complete response rates for ondansetron, granisetron and tropisetron in the first 24 hours were 51.4%, 65.7% and 61.1% respectively. All three agents were highly effective against cisplatin-induced acute and late vomiting and the results were statistically significant. This study demonstrated no significant difference in effectiveness of these three antiemetics. 5-HT3 (5-hydroxytryptamine 3) receptor antagonists have similar efficacy in the prevention of nausea and vomiting due to cisplatin. Thus, we recommend that drug choice be based on cost-benefit and patient tolerance.

Adult↗

Comparison of buccal and oral prochlorperazine in the treatment of dizziness associated with nausea and/or vomiting.

The dizziness inherent in vertiginous disorders is often accompanied by nausea and/or vomiting. While prochlorperazine is effective in relieving nausea and vomiting, its low bioavailability following first pass metabolism in the liver and metabolism in the intestinal wall, compounded by the likelihood of regurgitation in the nauseous patient, may limit the therapeutic value of the oral preparation. A buccal preparation achieves higher plasma concentrations by direct absorption into the systemic circulation. In this randomised, double-blind, double-dummy trial in patients with vestibular disorders, in keeping with previous pharmacokinetic studies, buccal prochlorperazine achieved a significantly faster onset of effect compared with oral prochlorperazine (p = 0.04), and was significantly better in reducing the frequency of nausea (p = 0.02) and severity of vomiting (p = 0.05) at 24-36 hours. The frequency of vomiting was also reduced by buccal prochlorperazine compared with oral prochlorperazine, but this difference was only of borderline significance (p = 0.07). Buccal prochlorperazine was well tolerated and well rated by both patients and investigators, having no more adverse effects on the buccal mucosa than placebo and causing less drowsiness and sedation compared with the oral preparation. No advantages were reported for the oral preparation over buccal prochlorperazine. Buccal prochlorperazine is therefore safe and effective, and suitable for the treatment of dizziness associated with nausea and/or vomiting in patients suffering from vertiginous disorders.

Administration, Oral↗

Anxiety and drug taste as predictors of anticipatory nausea in cancer chemotherapy.

Interview data from 192 patients receiving cytotoxic chemotherapy for the first time were analyzed to identify factors predictive of the development of anticipatory nausea. Posttreatment nausea and vomiting (particularly vomiting), tastes of drugs during injections, and anxiety before injections were all associated with an increased probability of anticipatory nausea. An index consisting of those three variables, plus age, was found to have good predictive power, even when the predictor variables were assessed only at the first chemotherapy administration and the index was used to predict the development of anticipatory nausea at any time during the first six chemotherapy cycles.

Adolescent↗

Comparison of domperidone, droperidol, and metoclopramide in the prevention and treatment of nausea and vomiting after balanced general anesthesia.

Women (185) undergoing elective orthopedic surgery under balanced general anesthesia were given 5 or 10 mg of domperidone, 1.25 mg of droperidol, 10 mg of metoclopramide, or a saline placebo intravenously in a double-blind random fashion 5 minutes before the end of anesthesia to prevent postoperative vomiting. Administration of the same antiemetic was repeated intramuscularly during the first 24 hours postoperatively if the patient complained of nausea or retched or vomited. Sigificantly (p less than 0.05 to p less than 0.001), fewer of the patients given droperidol were nauseated (25%) or vomited (17%) in comparison with patients given saline (incidence of nausea was 55% and vomiting 40%). Incidences of nausea and vomiting were similar in patients given domperidone, metoclopramide, or saline. Furthermore, 39 to 45% of the patients given domperidone, metoclopramide, or saline needed additional doses of the same drug, whereas only 22% of the patient given droperidol required a second dose. It is concluded that droperidol is effective in the prevention and treatment of postoperative nausea and vomiting after balanced general anesthesia but that domperidone or metoclopramide are not.

Adult↗

A dose ranging study of dexamethasone for preventing patient-controlled analgesia-related nausea and vomiting: a comparison of droperidol with saline.

UNLABELLED: We designed this study to determine the minimum dose of dexamethasone for preventing nausea and vomiting associated with the use of morphine by patient-controlled analgesia (PCA). Two hundred forty female patients were randomly assigned to receive dexamethasone 2, 4, 8, or 12 mg IV immediately before induction of anesthesia. Droperidol (0.1 mg/mL with morphine 1 mg/mL in PCA pump) and saline were used as controls. The complete response (no postoperative nausea and vomiting and no need for rescue antiemetic for a 24-h postoperative period) rates for dexamethasone 8 mg (72.2%) and 12 mg (78.9%) were significantly more than for saline (42.9%) (P < 0.05). Patients who received dexamethasone 12 or 8 mg also reported higher patient satisfaction than those who received saline (P < 0.05). These results were as effective as adding droperidol 0.1 mg/mL to the morphine PCA without causing drowsiness, restlessness, or arrhythmias. Smaller doses of dexamethasone (4 or 2 mg) were not effective for this propose. The results suggest that dexamethasone 8 mg IV is the minimum effective dose for the reduction of PCA morphine-related nausea and vomiting. IMPLICATIONS: Morphine administration by patient-controlled analgesia (PCA) is often associated nausea and vomiting. In this double-blind study, the minimum effective dose of dexamethasone for reducing this complication was 8 mg. This was as effective as adding droperidol 0.1 mg/mL to the morphine PCA without causing drowsiness, restlessness or arrhythmias.

Aged↗

Ondansetron, orally disintegrating tablets versus intravenous injection for prevention of intrathecal morphine-induced nausea, vomiting, and pruritus in young males.

In this study we compared the efficacy of orally disintegrating tablets (ODT) and IV ondansetron for preventing spinal morphine-induced pruritus and postoperative nausea and vomiting (PONV) in healthy young male patients. Patients who received bupivacaine with 0.20 mg morphine for spinal anesthesia were randomly assigned to the ODT group (ODT ondansetron 8 mg, n = 50), the IV group (4 mg ondansetron IV, n = 50), or the placebo group (n = 50). Each individual was assessed for pruritus, postoperative nausea and vomiting, and pain at 0, 2, 6, 12, 18, and 24 h after surgery using three distinct visual analog scales. The frequencies of postoperative nausea and vomiting and frequencies of requirement for rescue antiemetic and antipruritic were recorded. There were no significant differences among the three groups with respect to incidence or severity of PONV or postoperative pain visual analog scale scores. The incidences of pruritus in the ODT (56%) and IV (66%) groups were significantly different from that in the placebo group (86%) (P < 0.02 for both). Only the ODT group had significantly lower mean pruritus visual analog scale scores at 0, 2, 6, and 12 h postsurgery than the placebo group (P < 0.023 for all). The frequency of requirement for rescue antipruritic was significantly less in the ODT group than the placebo group (P = 0.013). Both ODT ondansetron 8 mg and IV ondansetron 4 mg are more effective than placebo for preventing spinal morphine-induced pruritus, but neither form of this agent reduces spinal morphine-induced postoperative nausea and vomiting in this patient group.

Administration, Oral↗

Acupressure for nausea and vomiting in cancer patients receiving chemotherapy.

Practitioners working with patients undergoing chemotherapy regularly encourage them to use acupressure in the form of Sea Bands for the relief of treatment-related nausea and vomiting. This mini-review sets out to uncover and examine the evidence base for this recommendation. A mini systematic review was carried out to identify randomized controlled trials comparing the use of acupressure plus usual care with usual care alone. The population was adult patients receiving cancer chemotherapy. The outcome was nausea or vomiting duration or intensity. Searches on Medline, Embase, AMED, the Cochrane Library, Cancerlit and Cinahl identified two randomized controlled trials involving 482 patients with compared acupressure to no intervention control. The results suggest that acupressure may decrease nausea among patients undergoing chemotherapy but further work is required before conclusively advising patients on the efficacy of acupressure in preventing and treating chemotherapy-induced nausea.

Acupressure↗

The management of nausea and vomiting in advanced cancer.

Nausea and vomiting represent a significant problem in patients with advanced cancer, which not only affects their quality of life but also the lives of informal carers. The application of nursing assessment tools, underpinned by a thorough knowledge regarding the physiology and aetiology of nausea and vomiting in this group of patients enables nurses to plan and provide effective interventions, in collaboration with other members of the multidisciplinary team. This article describes the physiological basis of nausea and vomiting. Epidemiological data informs the subsequent discussion, which focuses on assessment in terms of identifying the problem and its cause(s), setting goals with the patient and his/her carers, planning appropriate nursing intervention to support medical interventions and evaluating clinical outcomes. Pharmacological and non-pharmacological interventions for nausea and vomiting are discussed.

Antiemetics↗

Effects of granisetron with droperidol or dexamethasone on prevention of postoperative nausea and vomiting after general anesthesia for cesarean section.

This prospective, placebo-controlled, double-blinded, and randomized study was undertaken to compare the efficacy of granisetron, droperidol, and combinations of granisetron with droperidol or dexamethasone on postoperative nausea and vomiting in patients undergoing general anesthesia for cesarean section. Patients (n = 150) who were scheduled for cesarean section under general anesthesia were randomly assigned to one of the five groups: physiological saline 5 ml in Group A, granisetron 40 microg/kg + dexamethasone 8 mg in Group B, granisetron 40 microg/kg + droperidol 1.25 mg in Group C, droperidol 1.25 mg in Group D, and granisetron 40 microg/kg in Group E were administered intravenously after clamping of the fetal umbilical cord. Postoperative nausea and vomiting was observed for 024 h after the anesthesia. Cesarean sections were all performed under general anesthesia. Postoperative nausea and vomiting was more common in placebo group (56.7%) than the others during the 0-24 h after the anesthesia (p < 0.05). All granisetron groups were more effective than placebo and droperidol groups during the postoperative 3-24 h (p < 0.01). Although this trial lacks statistical power, granisetron alone and combinations with droperidol or dexamethasone were effective similarly. All treatment groups, except droperidol during the postoperative 3-24 h, were effective for prevention of postoperative nausea and vomiting during the postoperative 0-24 h.

Adult↗

Risk-benefit of antiemetics in prevention and treatment of chemotherapy-induced nausea and vomiting.

The development of effective antiemetic prophylaxis is one of the most significant steps forward in the area of supportive care. Fifteen years ago, patients receiving chemotherapy had to face the fact that nausea and vomiting were inevitable adverse effects, which could only be partially prevented by treatment with antiemetics such as dopamine (DA) D2 receptor antagonists and corticosteroids. The first group of drugs specifically developed as antiemetics was the serotonin (5-hydroxytryptamine [5-HT](3)) receptor antagonists. These drugs have dramatically improved prophylaxis of chemotherapy-induced emesis, particularly when used in combination with a corticosteroid. This combination has resulted in a significant decrease in the number of patients vomiting, whereas the improvement in the prophylaxis of nausea has been less successful. Another group of antiemetics, the neurokinin (NK) 1 receptor antagonists, has recently been developed, and the first drug in this class, aprepitant, has been approved by the FDA and the EU authorities. Studies have showed that patients benefit from the use of this drug in combination with standard antiemetic therapy (5-HT 3 receptor antagonist plus a corticosteroid), both in the acute and delayed phase of nausea and vomiting induced by cisplatin-based chemotherapy. This development has not only led to improved efficacy but also to a decreased risk associated with the use of antiemetics. One of the problems with traditional antiemetics, for example, the DA D2 receptor antagonists, is the risk of unpleasant adverse effects including restlessness and dystonic reactions. To avoid these adverse effects, combination with benzodiazepines or antihistamines was necessary, often resulting in sedation. Modern research also includes pharmacogenomic investigations. This has led to speculation about the importance of drug-drug interactions involving antiemetics through competition for metabolism by the cytochrome P450 isoenzymes. The worst possible interaction would be a decrease in the effect of different cytotoxins but there is no evidence that such interactions are of importance in daily clinical practice. Guidelines are useful tools in the optimisation of antiemetic prophylaxis but, unfortunately, implementation of the evidence-based recommendations is far from successful. A prerequisite for further optimisation of antiemetic prophylaxis is updating of the guidelines, including recommendations for the use of NK 1 receptor antagonists (aprepitant), followed by implementation of these recommendations in the clinic. Future research must include 'the difficult trials' focusing on the remaining groups of patients with severe chemotherapy-induced nausea and vomiting, including patients with refractory and breakthrough emesis.

Antiemetics↗

Granisetron: an update on its clinical use in the management of nausea and vomiting.

Nausea and vomiting are typical side effects of cytotoxic therapy and some surgical procedures. These symptoms can represent a major therapeutic challenge and, if inadequately controlled by antiemetic treatment, will result in increased mortality, morbidity, and health care costs. However, the management of nausea and vomiting has improved greatly in recent years following the introduction of the 5-HT3-receptor antagonists, known as 'setrons.' In light of recent developments in antiemetic care, including the approval of the first neurokinin-1-receptor antagonist aprepitant (Emend; Merck and Company, Inc.; West Point, PA) and a new 5-HT3 receptor antagonist palonosetron (Aloxi; MGI Pharma; Minneapolis, MN), this article provides an update on the clinical experience gained with the 5-HT3-receptor antagonist granisetron (Kytril; Roche Laboratories, Inc.; Nutley, NJ) for the management of chemotherapy-induced, radiation-induced, and postoperative nausea and vomiting, and also reviews its use in special patient populations. Granisetron is a potent and highly selective 5-HT3-receptor antagonist that has little or no affinity for other receptors, a characteristic that is thought to underlie the favorable side-effect and safety profiles of this agent. Extensive clinical trial data have shown granisetron to be an effective and well-tolerated agent for the treatment of nausea and vomiting in the oncology and surgical settings. Granisetron has also been shown to be effective and well tolerated in special populations, such as patients refractory to antiemetic treatment, patients with hepatic or renal impairment, and children. Data also suggest that its safety profile and minimal potential for drug-drug interactions would make it an antiemetic agent of choice for elderly cancer patients.

Antiemetics↗

Optimum management of nausea and vomiting in cancer chemotherapy.

Nausea and vomiting continue to be critical problems in cancer chemotherapy, although considerable progress has been made toward understanding the neuropharmacological mechanisms of vomiting and how chemotherapeutic agents and antiemetics affect these mechanisms. The principles of behavioural psychology have also been applied in an effort to understand and effectively manage these complications which have potentially serious consequences. For example, there is now some degree of rationality to our use of metoclopramide for cisplatin-induced nausea and vomiting, the use of combination antiemetic regimens, and use of lorazepam for the prevention (albeit unproven) of anticipatory nausea and vomiting. It must be admitted, however, that our approach is for the most part still empirical. Selecting an antiemetic programme is not a simple task. The emetogenic potential of the chemotherapy being used, the presence of coexisting diseases, the potential toxicity of the antiemetic drug and whether antiemetic therapy is to take place in the hospital or in an outpatient setting, the familiarity of the clinician with the various antiemetic therapies, and cost are all factors which need to be considered. Although phenothiazines remain the standard treatment, they are of little value against chemotherapy programmes that produce moderate or severe problems. Newer pharmacological approaches including butyrophenones, cannabinoids, metoclopramide, high-dose corticosteroids, and benzodiazepines have shown increased antiemetic efficacy, as have combinations of these agents which are directed against multiple sites of emetogenic activity. The role of behavioural therapies, which have been shown to be effective particularly in children and in anticipatory nausea and vomiting, needs to be more firmly established. Rather than recommending a given antiemetic programme for any particular chemotherapy, it is preferable to think in terms of initial approaches and how they can be modified. No one antiemetic programme is effective or safe in all situations.

Antineoplastic Agents↗

Three years' experience with tropisetron in the control of nausea and vomiting in cisplatin-treated patients.

The efficacy and tolerability of tropisetron in preventing cisplatin-induced nausea and vomiting was studied in 2 open trials and compared with the efficacy and tolerability of metoclopramide plus lorazepam in a randomised crossover trial. In the first study, tropisetron 10mg was administered intravenously over 15 minutes before the cisplatin infusion and a second 10mg dose was given after the 60-minute infusion of cisplatin (greater than 50 mg/m2) in 54 patients with advanced cancers, for a total of 165 courses. Good responses for nausea and vomiting were recorded in 83.0% and 87.9% of courses, respectively, with complete protection from nausea and vomiting in 44.8% and 66.1% of courses, respectively. In the second study in 25 patients whose characteristics and cisplatin schedule were comparable with those of the first study, very similar results were achieved in 104 courses of chemotherapy, despite a reduction in tropisetron dose to a single 5mg intravenous infusion 15 minutes before cisplatin. The efficacies of intravenous tropisetron 5mg and metoclopramide 2 mg/kg plus lorazepam administered 15 minutes before cisplatin in preventing acute and delayed nausea and vomiting were compared in a randomised crossover study involving 20 patients. Tropisetron was significantly superior (p less than 0.001) in controlling both acute and delayed (day 1) symptoms. In all studies, the tolerability of tropisetron was excellent. The most frequent side effect was mild to moderate headache, occurring in 5 to 7% of patients. In conclusion, our experience suggests that tropisetron is an effective and well tolerated antiemetic drug that improves the quality of life of cancer patients administered highly emetogenic chemotherapy regimens.

Adult↗

Prevention of chemotherapy-induced nausea and emesis in patients responding poorly to previous antiemetic therapy. Comparing tropisetron with optimised standard antiemetic therapy.

In a multicentre trial, 78 patients with a variety of malignancies, who had experienced insufficient control of emesis (greater than or equal to 3 episodes within 24 hours) while receiving standard antiemetics during previous chemotherapy, were randomly assigned to receive tropisetron 5mg once daily for 5 days or conventional antiemetic drugs. No attempt was made to standardise the conventional antiemetic treatment, which was given according to the usual practice of the participating institutions. Emesis was evaluated by counting emetic episodes and nausea by asking the patients to record on a diary chart the duration and severity of the nausea. Emesis was much better controlled with tropisetron than with standard drugs, complete control during the first 24 hours being achieved in 42% and 8% of patients, respectively, (p less than 0.001). Nausea was of significantly shorter duration (6.9 vs 10.3 hours; p less than 0.01) and was less severe (p less than 0.005) in the tropisetron group. The patients' overall assessment of treatment outcome was markedly better for tropisetron than for the standard antiemetic therapy. The superior efficacy of tropisetron was especially marked during the first 24 hours. For delayed nausea, no significant difference between treatments was seen. No serious adverse effects were observed.

Adult↗

Prevention of postoperative nausea and vomiting after thyroidectomy: combined antiemetic treatment with dexamethasone and ginger versus dexamethasone alone.

BACKGROUND: The aim of this study was to compare the prophylactic effects of dexamethasone plus ginger and dexamethasone alone on postoperative nausea and vomiting (PONV) in patients undergoing thyroidectomy. METHODS: One hundred and twenty patients undergoing general anaesthesia for thyroidectomy were enrolled in this randomised, double-blind study. Patients received oral diazepam 10mg with either oral placebo (group I) or 0.5g of ginger (group II) as premedication 1 hour prior to surgery. Standard general anaesthetic techniques and postoperative analgesia were employed. Both group I and group II received intravenous dexamethasone 150 microg/kg immediately before the induction of anaesthesia. Data were recorded over a 24-hour observation period after surgery. RESULTS: In the dexamethasone-treated group, 14 patients experienced nausea, two patients retched, three patients vomited once, two patients vomited repeatedly, and 14 patients required a rescue antiemetic. In the dexamethasone-plus-ginger-treated group, 12 patients experienced nausea, one patient retched, four patients vomited once, no patients vomited repeatedly, and 13 patients required a rescue antiemetic. Dexamethasone plus ginger did not significantly reduce nausea and vomiting compared with dexamethasone alone during the observation period. CONCLUSION: In conclusion, the prophylactic combination of antiemetic treatment with dexamethasone and ginger was not clinically or statistically superior to dexamethasone alone in preventing PONV in patients undergoing thyroidectomy.

Administration, Oral↗

[Principles of managing chemotherapy-induced nausea and vomiting].

Chemotherapy-induced nausea and vomiting (emesis) can significantly affect a patient's quality of life, leading to poor compliance with further chemotherapy treatment. For patients treated with emetogenic chemotherapy, it is very important to prevent nausea and vomiting completely. The incidence and severity of nausea and/or vomiting in patients receiving chemotherapy are affected by numerous factors, including: 1) the specific chemotherapeutic agents used; 2) their dosage; 3) the schedule and route of administration; and 4) individual patient variability. Approximately 70 to 80% of all cancer patients receiving chemotherapy experience emesis, whereas 10% to 44% experience anticipatory emesis. The following general principles are recommended. 1) A 5-HT3 receptor antagonist should be administered prior to each day's 1st dose of moderately or highly emetogenic chemotherapy. 2) Dexamethasone should be administered once daily either orally or intravenously for every day of moderately or highly-emetogenic chemotherapy and for 2-3 days after chemotherapy for regimens that are likely to cause significant delayed-emesis. 3) The most effective way to treat anticipatory nausea and/or vomiting is to prevent it by using optimal antiemetic therapy during every cycle of treatment.

Antiemetics↗

Prevention of nausea and vomiting after middle ear surgery: combination of ondansetron and dexamethasone is the right choice.

OBJECTIVE: To determine the efficacy of a combination of ondansetron and dexamethasone in preventing postoperative nausea and vomiting after middle ear surgery compared with ondansetron alone. DESIGN: A prospective, randomized, double-blind study with prestudy power analysis performed to determine the sample size. SETTING: A tertiary teaching hospital. METHOD: One hundred patients undergoing tympanomastoidectomy under general anesthesia were included in the study. Patients in group O (n = 50) received ondansetron 4 mg and those in group OD (n = 50) received ondansetron 4 mg with dexamethasone 8 mg 30 minutes before the end of surgery. All patients were monitored for nausea score, episodes of vomiting, and rescue antiemetic requirement in 48 hours after surgery. The total number of complete responders was calculated. Patients' satisfaction at the end of the study period was also estimated. RESULTS: In patients receiving combination antiemetic (group OD), the nausea score was significantly less (p < .01) at 6, 12, and 24 hours after surgery. The total incidence of vomiting was reduced from 28% in group O to 6% in group OD. Rescue antiemetic requirement was significantly less (p < .01) in group OD. The number of complete responders significantly improved in the combination group (92% vs 62%). The patients were also found to be more satisfied in this group. CONCLUSION: Prophylaxis with a combination of ondansetron and dexamethasone decreased the incidence of nausea and vomiting after middle ear surgery to a minimum and improved patients' satisfaction significantly in the postoperative period.

Adult↗

Transdermally administered scopolamine vs. dimenhydrinate. I. Effect on nausea and vertigo in experimentally induced motion sickness.

The effect of transdermally administered scopolamine (TTS-scopolamine) (2.5 cm2 surface area, one and two patches) and dimenhydrinate (100 mg) on experimental motion sickness was examined in 16 healthy volunteers in a randomized double-blind study. Nausea was induced by Coriolis manoeuvre and vertigo by calorization of the ear. In all subjects, scopolamine was found in urine in concentrations indicating adequate absorption of the drug. One TTS-scopolamine, two TTS-scopolamine and dimenhydrinate caused a statistically significant reduction in nausea when compared with placebo. Dimenhydrinate was somewhat more effective against nausea than one TTS-scopolamine. Vertigo was significantly reduced after dimenhydrinate and two TTS-scopolamine. Side effects of both drugs were negligible, though gait disturbances and vertigo could occur occasionally after two TTS-scopolamine. No dose-response relationship was found between the urinary excretion of scopolamine and alleviation of nausea. Dimenhydrinate and TTS-scopolamine are both effective against motion sickness, the latter provided it is applied 6 to 8 hours before exposure to the stimulus causing the motion sickness.

Adult↗