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Delta-9-tetrahydrocannabinol interferes with the establishment and the expression of conditioned rejection reactions produced by cyclophosphamide: a rat model of nausea.

Reliable animal models of nausea are necessary to better understand the neurobiology of nausea and to assess treatment effectiveness. We present such a model based on conditioned rejection reactions in rats. Our results demonstrate that delta-9-tetrahydrocannabinol (THC), a treatment reported to reduce chemotherapy-induced nausea in humans, also reduces conditioned rejection reactions in rats. Rats were administered THC or vehicle prior to a pairing of saccharin solution with cyclophosphamide or saline during conditioning and/or prior to test. THC interfered with the establishment of cyclophosphamide-induced conditioned rejection during conditioning and with the expression of conditioned rejection during testing. Our results confirm that the conditioned rejection reaction in the rat is a useful animal model of nausea.

Animals↗

Cannabidiol, a non-psychoactive component of cannabis and its synthetic dimethylheptyl homolog suppress nausea in an experimental model with rats.

Rats display conditioned rejection reactions during an oral infusion of a flavor previously paired with an emetic drug; considerable evidence indicates that these rejection reactions reflect nausea. Here we report that cannabidiol, a major non-psychoactive cannabinoid found in marijuana and its synthetic dimethylheptyl homolog interfere with nausea elicited by lithium chloride and with conditioned nausea elicited by a flavor paired with lithium chloride. These results suggest that cannabinoids without psychoactive side-effects may have therapeutic value in the treatment of chemotherapy-induced nausea.

Animals↗

Ondansetron in the treatment of nausea and vomiting induced by chemotherapy. Portuguese Ondansetron Study Group.

One-hundred and forty-five chemotherapy patients receiving cisplatin- and non-cisplatin-containing regimens participated in an open evaluation of ondansetron, a 5-HT3 receptor antagonist, in the prophylaxis of acute and delayed nausea and vomiting. The study had two groups of patients, one receiving cisplatin-containing regimens (Group A) and the other, non-cisplatin-containing regimens (Group B). There were 51 patients recruited to Group A. Ondansetron was given to these patients at a dose of 8 mg intravenously 15 min before chemotherapy, followed by an intravenous infusion for 24 h (1 mg/h), or 8 mg intravenously 4 and 8 h after the start of cisplatin, followed by 8 mg orally three times/day for 5 days. Ninety-four patients were recruited to Group B: these patients received ondansetron at a dose of 8 mg intravenously immediately before chemotherapy or 8 mg orally 1-2 h prior to it, and 8 mg orally three times/day for 3-5 days. For acute emesis (first 24 h), complete control was achieved in 79.5% of Group A patients and in 78.1% of Group B. For delayed emesis (days 2-5), 79.7% of Group A patients and 84.6% of Group B were completely protected during the entire study period. Nausea was also well controlled with ondansetron; 83.2% (Group A) and 86.5% (Group B) reported only mild nausea or no nausea at all. Ondansetron was effective in the control of both cisplatin- and non-cisplatin-induced emesis and well tolerated without any serious drug-related adverse events.

Adolescent↗

Control of nausea and vomiting by Navoban (tropisetron) in 131 children receiving cytotoxic chemotherapy.

One hundred and thirty-one children with a median age of 5 years were administered Navoban (tropisetron), a selective antagonist of the serotonin receptor (5-HT3), dosed once daily at 0.2 mg/kg (with a maximum of 5 mg daily) in a study aimed at evaluating the prevention of nausea and vomiting induced by anti-cancer chemotherapy. The most common malignancy (in 49% of patients) was acute lymphocytic leukaemia. Patients received Navoban during one or more courses of emetogenic chemotherapy for a total of 455 courses administered intravenously or intravenously and intrathecally (IV + IT). Most patients (89%) had already received cytotoxic chemotherapy before enrollment for the trial. On Day 1, Navoban was administered slowly and intravenously as a single dose before the start of chemotherapy, or by mouth as a single daily dose on subsequent days (median treatment duration = 5 days). On the first 5 days of each course of chemotherapy, response to Navoban per 24-hour period was graded as: complete (absence of both nausea and vomiting), partial (1-4 vomits and/or less than 5 hours of nausea), or failure (more than 4 vomits and/or at least 5 hours of nausea). Ninety-six per cent of the intravenous chemotherapy group and 97% of the IV + IT chemotherapy group had a complete (70% and 55% respectively) or partial (26% and 42% respectively) response during the first 24-hour period of the first course in which Navoban was used. The second and subsequent courses yielded similar percentages. Delayed emesis was observed mainly during those courses employing the most emetogenic chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Isopropyl alcohol inhalation: alternative treatment of postoperative nausea and vomiting.

BACKGROUND: The mechanisms for postoperative nausea and vomiting are numerous and pathways not well elucidated. Although many medications have been developed to help prevent postoperative nausea and vomiting, the search for better approaches to recovery treatment continues. OBJECTIVE: The purpose of this study was to evaluate the effectiveness of isopropyl alcohol (IPA) inhalation for treatment of postoperative nausea and vomiting for patients who have general anesthesia for a surgical procedure. METHOD: Participants were recruited from an urban hospital on the East Coast of the United States. Participants were assigned to an experimental or control group and IPA inhalation was compared to the standard anti-emetic treatment for rescue treatment in the immediate postoperative period. Postoperative nausea and vomiting was rated using a descriptive ordinal scale. RESULTS: The results of this study show IPA to be effective and that there was no significant difference between the standard treatment protocol and treatment with IPA. Treatment with IPA was significantly more cost effective than standard drug treatment. DISCUSSION: Further research is recommended to evaluate the length of effectiveness, standard dose needed, most effective mode of inhalation, and factors blocking IPA effectiveness.

2-Propanol↗

The role of psychological variables in post-chemotherapy nausea: anxiety and expectation.

Post-treatment nausea (PN) is a common side effect following cancer chemotherapy. Wide variability in PN is often evidenced among patients even within a specific drug regimen and dosage combination. Such variability might reflect the influence of psychological factors, such as anxiety and expectations for nausea, on the experience of PN. Sixty-five chemotherapy patients were studied across their initial two to four infusions. Ratings of state anxiety and PN were obtained for each infusion. Expectations for chemotherapy-related nausea were assessed prior to the initial infusion. Hierarchical regression analyses indicated that state anxiety was significantly related to the experience of PN while expectations for nausea were unrelated to PN. Subanalyses indicated that the strength of the anxiety-PN relationship was inversely related to the emetic potential of the chemotherapy regimen a patient received. It was concluded that understanding of the factors that contribute to the experience of PN necessitates consideration of not only pharmacological, but psychological and physiological, factors as well.

Antineoplastic Agents↗

Effect of prophylactic ondansetron on postoperative nausea and vomiting after elective craniotomy.

This prospective, randomized, placebo-controlled, double-blind study was designed to evaluate the efficacy of ondansetron, a 5-HT3 antagonist, in preventing postoperative nausea and vomiting (PONV) after elective craniotomy in adult patients. The authors also tried to discover certain predictors for postcraniotomy nausea and vomiting. We studied 170 ASA physical status I and II patients, aged 15 to 70 years, undergoing elective craniotomy for resecting various intracranial tumors and vascular lesions. A standardized anesthesia technique and postoperative analgesia were used for all patients. Patients were divided into two groups and received either saline placebo (Group 1) or ondansetron 4 mg (Group 2) intravenously at the time of dural closure. Patients were extubated at the end of surgery and episodes of nausea and vomiting were noted for 24 hours postoperatively in the neurosurgical intensive care unit. Demographic data, duration of surgery, and anesthesia and analgesic requirements were comparable in both groups. Overall, a 24-hour incidence of postoperative emesis was significantly reduced in patients who received ondansetron compared with those who received a saline placebo (39% in Group 1 and 11% in Group 2, P = .001). There was a significant reduction in the frequency of emetic episodes and rescue antiemetic requirement in patients treated with ondansetron; however, ondansetron did not significantly reduce the incidence of nausea alone (14% in Group 2 vs 5% in Group 1, P = .065). Prophylactic ondansetron had a favorable influence on PONV outcome measures such as patient satisfaction and number needed to prevent emesis (3.5). Side effects were similar in both groups. We conclude that ondansetron 4 mg given at the time of dural closure is safe and effective in preventing emetic episodes after elective craniotomy in adult patients.

Adolescent↗

Randomized, double-blinded comparison of tropisetron and placebo for prevention of postoperative nausea and vomiting after supratentorial craniotomy.

This prospective, randomized, placebo-controlled, double-blinded study was designed to evaluate the efficacy of tropisetron in preventing postoperative nausea and vomiting after elective supratentorial craniotomy in adult patients. We studied 65 ASA physical status I-III patients aged 18 to 76 years who were undergoing elective craniotomy for resection of various supratentorial tumors. Patients were divided into two groups and received either 2 mg of tropisetron (group T) or saline placebo (group P) intravenously at the time of dural closure. A standard general anesthetic technique was used. Episodes of nausea and vomiting and the need for rescue antiemetic medication were recorded during 24 hours postoperatively. Demographic data, duration of surgery and anesthesia, and sedation scores were comparable in both groups. Nausea occurred in 30% of group T patients and in 46.7% of group P patients (P >.05). The incidence of emetic episodes was 26.7% and 56.7% in the two groups (P <.05). Rescue antiemetic medication was needed in 26.7% and 60% of the patients (P <.05). Administration of a single dose of tropisetron (2 mg intravenously) given at the time of dural closure was effective in reducing postoperative nausea and vomiting after elective craniotomy for supratentorial tumor resection in adult patients.

Adolescent↗

Increased nausea and vomiting induced by naloxone in patients receiving cancer chemotherapy.

To evaluate the role of endogenous opiates in chemo-therapy-induced nausea and vomiting, the narcotic-antagonist naloxone was administered to six pediatric patients receiving cancer chemotherapy. Naloxone was administered by continuous intravenous (i.v.) infusion after randomized, double-blind controlled assignment at a dose of 0, 10 or 40 micrograms/kg/h for 12 h. Each patient was studied for four consecutive and identical courses of chemotherapy (eight courses for each naloxone dose or 24 courses in all). A dose-related increase in nausea (nausea score 2.5 +/- 2.24, 3.83 +/- 2.73, and 5.75 +/- 2.86/12 h, p = 0.003), vomiting (emetic events 6.0 +/- 7.50, 8.08 +/- 6.71, and 10.3 +/- 8.91/12 h, p = 0.035), and patient aversion (course preference rank 1.5 +/- 0.45, 2.83 +/- 1.17, and 3.25 +/- 0.42/4 courses, p = 0.014) was observed. The infusion of naloxone in the absence of chemotherapy was without effect. These results support a role for endogenous opiates in regulating chemotherapy-induced nausea and vomiting, and further suggest that narcotic agents may be effective antiemetics in this setting.

Adolescent↗

Marijuana use and its association with adherence to antiretroviral therapy among HIV-infected persons with moderate to severe nausea.

BACKGROUND: Adherence to antiretroviral therapy (ART) is essential to successful treatment of HIV infection. Two recent studies reported a negative correlation between marijuana use and adherence to ART. Some patients, however, report that smoking marijuana improves adherence to ART. This study therefore sought to identify which subgroups of patients may have differential adherence to ART in association with recent marijuana use. METHODS: Cross-sectional survey design within a public health care system for HIV/AIDS. RESULTS: With a 5% refusal rate, 252 patients completed the interview, 175 (69%) were on ART, and 168 (67%) provided ART adherence data. Forty-one subjects (24%), predominantly whites, used marijuana. In bivariate analysis, no association between ART adherence and marijuana use was found (odds ratio [OR] = 0.92, 95% CI = 0.4-1.9). Adherence was positively associated with undetectable plasma virus and negatively associated with alcohol and other illicit drug use. Examining subgroups of patients, among those with nausea, marijuana users were more likely to show an association with adherence than nonusers (OR = 3.3), while among those without nausea, marijuana use was lower associated with adherence (OR = 0.52, P for homogeneity 0.02). This relationship was confirmed in multivariate analyses controlling for the interactions between nausea and marijuana use, in which other illicit drug use remained a factor related to nonadherence. DISCUSSION: These data suggest that medicinal use of marijuana may facilitate, rather than impede, ART adherence for patients with nausea, in contrast to the use of other illicit substances, which were associated with lower rates of ART adherence. To demonstrate any causal relationship between marijuana and adherence would require a longitudinal or controlled study.

Adult↗

Pharmacology, pharmacogenetics, and clinical efficacy of 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting.

PURPOSE OF REVIEW: The use of selective 5-hydroxytryptamine type 3 receptor antagonists has improved the management of postoperative nausea and vomiting, but has not completely eliminated it. In this article, we discuss the pharmacology of 5-hydroxytryptamine type 3 receptor antagonists and the impact of pharmacogenetics on postoperative nausea and vomiting. RECENT FINDINGS: Dolasetron, granisetron, ondansetron, palonosetron, and tropisetron have similar mechanisms of action but different pharmacokinetic and pharmacodynamic properties. Genetic polymorphism in the cytochrome P450 mono-oxygenase system, drug efflux transporter adenosine triphosphate-binding cassette subfamily B member 1 and 5-hydroxytryptamine type 3 receptor subunits also contribute to the interindividual variation in response to different 5-hydroxytryptamine type 3 receptor antagonists. These differences account for differences in the duration of action and clinical efficacy of these agents. SUMMARY: Pharmacogenetics testing in patients may help differentiate responders to 5-hydroxytryptamine type 3 receptor antagonists from non-responders and allow the anesthesiologist to individualize antiemetic therapy. The cost-effectiveness of such screening in postoperative nausea and vomiting management has, however, not been evaluated. Given the multifactorial nature of postoperative nausea and vomiting, a multimodal approach to reduce or eliminate risk factors will be most successful in its management.

ATP Binding Cassette Transporter, Subfamily B↗

The efficacy of 5-HT3 receptor antagonists for the prevention of postoperative nausea and vomiting after craniotomy: a meta-analysis.

The purpose of this meta-analysis was to assess the efficacy of prophylactic administration of 5-HT3 receptor antagonists for postoperative nausea and vomiting in neurosurgical patients at 24 and 48+ hours. After a systematic search, 7 published randomized placebo controlled trials involving 448 craniotomy patients (222 treatment, 226 control) were included in the meta-analysis. Study drugs included ondansetron, granisetron, and tropisetron. The cumulative incidence of emesis was significantly reduced in the treatment group at 24 hours [relative risk (RR)=0.50, 95% confidence interval (CI): 0.38-0.66] and 48+ hours (RR=0.52, 95% CI: 0.36-0.75). There were no differences between the treatment and control groups in the cumulative incidence of nausea at 24 hours (RR=0.76, 95% CI: 0.54-1.06) and 48+ hours (RR=0.81, 95% CI: 0.62-1.06). The cumulative incidence of both nausea and vomiting continued to increase after 24 hours in both groups. Despite the ability of 5-HT3 receptor antagonists to reduce emetic episodes, future investigations should seek to address the control of postoperative nausea and to reduce further postoperative emesis in this population.

Antiemetics↗

A randomized controlled trial of ginger to treat nausea and vomiting in pregnancy.

OBJECTIVES: To estimate whether the use of ginger to treat nausea or vomiting in pregnancy is equivalent to pyridoxine hydrochloride (vitamin B6). METHODS: A randomized, controlled equivalence trial involving 291 women less than 16 weeks pregnant was undertaken at a teaching hospital in Australia. Women took 1.05 g of ginger or 75 mg of vitamin B6 daily for 3 weeks. Differences from baseline in nausea and vomiting scores were estimated for both groups at days 7, 14, and 21. RESULTS: Ginger was equivalent to vitamin B6 in reducing nausea (mean difference 0.2, 90% confidence interval [CI] -0.3, 0.8), retching (mean difference 0.3; 90% CI -0.0, 0.6) and vomiting (mean difference 0.5; 90% CI 0.0, 0.9), averaged over time, with no evidence of different effects at the 3 time points. CONCLUSION: For women looking for relief from their nausea, dry retching, and vomiting, the use of ginger in early pregnancy will reduce their symptoms to an equivalent extent as vitamin B6. LEVEL OF EVIDENCE: I

Adult↗

Addition of droperidol to patient-controlled analgesia: effect on nausea and vomiting.

A double-blind trial of the effect of droperidol on the incidence of nausea and vomiting in patients using patient-controlled analgesia was carried out in 60 healthy women undergoing abdominal hysterectomy. After a standard anaesthetic including droperidol 2.5 mg as a prophylactic antiemetic, patients were randomly allocated to receive postoperative patient-controlled analgesia with either morphine alone (2 mg.ml-1) or morphine (2 mg.ml-1) with droperidol (0.2 mg.ml-1) added to the syringe. Verbal scores and visual analogue scores for nausea, vomiting, pain and sedation were made at 4, 12 and 24 h postoperatively, and any requirement for intramuscular prochlorperazine noted. There was no difference between the groups at any time in the amount of morphine consumed or in pain scores. At 12 h, patients receiving droperidol experienced significantly less nausea, and over the first 24 h, 31% required prochlorperazine compared with 59.3% of patients not receiving droperidol. The number of patients with sedation at 24 h was significantly greater in the droperidol group. We conclude that the addition of droperidol to morphine both reduces nausea and the need for further antiemetic treatment.

Adult↗

Impact of postoperative nausea and vomiting in the surgical setting.

Postoperative nausea and vomiting is one of the most common complications of inpatient and day case surgical procedures. In a climate where total cost of an illness is becoming increasingly important, postoperative nausea and vomiting is a major contributor to direct and indirect costs for both the hospital and patient. In patient terms, the impact of increased recovery room stays and extra nursing time required by PONV patients has been estimated to range from 96-576 more surgical procedures which may be performed in an 'average' day case surgery centre. Postoperative nausea and vomiting is perceived by patients to account for equal or more debilitation than surgery itself and may cause them to lose wages due to absence from work. Reducing the incidence of nausea and vomiting and its associated problems may therefore provide opportunities to improve patient care, decrease the size of waiting lists and improve utilisation of scarce healthcare resources.

Activities of Daily Living↗

Comparison of ondansetron and droperidol in reducing postoperative nausea and vomiting associated with patient-controlled analgesia.

In a randomised, placebo-controlled trial we have compared the efficacy of ondansetron and droperidol in reducing postoperative nausea and vomiting associated with patient-controlled analgesia after orthopaedic surgery. One hundred and forty five patients, ASA 1 and 2, undergoing major orthopaedic surgery were anaesthetised using a standardised technique. They were randomly allocated to receive patient-controlled analgesia as morphine 1 mg.ml-1 alone; morphine as before plus a single dose of 1.25 mg droperidol together with 0.083 mg.ml-1 in the infusion syringe; or morphine as before plus 4 mg ondansetron and 0.13 mg.ml-1 in the syringe. The patient-controlled analgesia bolus dose was set at 1 ml with a 5 min lockout and a 4 h maximum dose of 30 mg morphine. There was no background infusion. The occurrence of nausea, vomiting and sedation was assessed every 4 h. The incidence of vomiting decreased from 59% in the morphine-only group to 35% and 14% in the droperidol (p < 0.05) and ondansetron groups (p < 0.001) respectively. The number of patients suffering from nausea alone was not significantly different between the three groups, although those in the ondansetron group experienced less severe nausea (p < 0.05) when using a two point scale. The droperidol group had significantly higher sedation scores than the other two groups (p < 0.005). We conclude that ondansetron is superior to droperidol when used with patient-controlled analgesia and causes less sedation.

Adolescent↗

Comparison of ondansetron, metoclopramide and placebo as premedicants to reduce nausea and vomiting after major surgery.

In a randomised, double-blind study, we have compared the incidence of postoperative nausea and vomitting in 124 patients undergoing major lower limb orthopaedic surgery following oral premedication with temazapam and ondansetron 8 mg, metoclopramide 10 mg or placebo. They received a standardised epidural and general anaesthetic. An epidural mixture containing bupivacaine 0.1% and fentanyl 10 mg.ml-1 was infused postoperatively. The occurrence of nausea and vomiting was assessed every 4 h for 24 h. The incidence of vomiting significantly decreased from 55% and 43% in the placebo and metoclopramide groups, respectively, to 26% in the ondansetron group (p = 0.03). The incidence of nausea and vomiting in patients who had previously suffered was also significantly reduced from 67% and 68% in the placebo and metoclopramide groups, respectively, to 29% in the ondansetron group (p = 0.035). We conclude that oral premedication with ondansetron 8 mg was superior to metoclopramide 10 mg and placebo in preventing postoperative nausea and vomiting following major orthopaedic surgery in patients given epidural opioid analgesia.

Adolescent↗

Effectiveness of pre-emptive metoclopramide infusion in alleviating pain, discomfort and nausea associated with nasogastric tube insertion: a randomised, double-blind, placebo-controlled trial.

Aim of this study was to demonstrate that intravenous metoclopramide can reduce pain, nausea and discomfort during nasogastric tube (NGT) insertion in ED. This prospective, randomised, double-blind, placebo-controlled trial was conducted in the university-based ED. One-hundred patients were enrolled. Before NGT insertion, each eligible patient was randomised to one of the two treatment arms: one group received 2 cc of 10 mg IV metoclopramide, whereas others received 2 cc of normal saline. Before and after the procedure, pain, nausea and discomfort were evaluated using 100-mm visual analogue scale (VAS). This study was analysed using the paired sample test, the independent sample test and the chi(2) test. Forty-nine patients received metoclopramide, and 51 received normal saline. Although initial VAS levels elicited for pain, nausea and discomfort were similar, consequent VAS levels of those in the metoclopramide group were significantly lower as compared with those in the normal saline group. The mean differences of VAS levels were statistically significant for three symptoms (p < 0.001). Mean VAS levels of nausea, discomfort and pain during NGT insertion were significantly lower following administration of IV metoclopramide as compared with normal saline.

Adolescent↗