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PubMedDate not supplied

[Research on antiemetics: an Italian model of success].

At the beginning of the 80's the Italian Group for Clinical Research (G.O.I.R.C.) identified chemotherapy-induced nausea and vomiting as one of the most distressing adverse events, and decided to plan and execute clinical trials on antiemetics in order to reduce this negative impact on patients. Therefore, some consecutive double-blind randomized trials were conducted on cisplatin-treated patients. The first was a dose-finding study on four different high-doses of domperidone, followed by a study comparing two different high-doses of metoclopramide, and a study comparing the addition of a corticosteroid to high-dose metoclopramide with respect to metoclopramide alone. Finally, a study demonstrating that a combination of a higher dose of metoclopramide (3 mg/kg x 2) plus dexamethasone and diphenhydramine was significantly superior with respect to a lower dose of metoclopramide (1 mg/kg x 4) combined with methylprednisolone was carried out. With the introduction of the 5-HT3 receptor antagonists the interest for antiemetic therapy increased and other Italian gynecological and medical oncology centres became involved in the antiemetic research. The Italian Group for Antiemetic Research was formed in 90's and its first study demonstrated the superiority of a combination of a 5-HT3 receptor antagonist plus dexamethasone with respect to the standard three drug combination of high doses of metoclopramide in the prevention of cisplatin-induced acute emesis. In the following years, the Group contributed to the identification of the best antiemetic prophylaxis for acute emesis induced by moderately emetogenic chemotherapy, and for delayed emesis induced by cisplatin. Also a drug utilization review on antiemetics in clinical practice has recently been carried out. Today, the interest of the Group is concentrated in studying the optimal antiemetic prophylaxis for delayed emesis induced by moderately emetogenic chemotherapy. The rules always followed by the Italian Group for Antiemetic Research are: --complete independence of judgement on the efficacy and the tolerability of antiemetic drugs from the pharmaceutical companies; --priority of ethical problems in designing clinical trials; --strict adherence to the methodological problems of antiemetic research and--complete autonomy concerning the study planned, the data computerization and the data elaboration. In the last twelve years approximately 70 Italian centres have enrolled their patients into the studies of the Italian Group for Antiemetic Research.

Antiemetics↗
PubMed2003

Antiemetic use for acute gastroenteritis in children.

OBJECTIVES: To describe patterns of and factors associated with antiemetic use among a population-based sample of children with acute gastroenteritis; to determine if filling a prescription for an antiemetic is associated with a significant risk of adverse events; and to determine if filling a prescription for an antiemetic is associated with an increased risk of subsequent health care use. METHOD AND DESIGN: Retrospective cohort study of 20,222 children aged 1 month to 18 years, receiving Medicaid, who had a first diagnosis of gastroenteritis, diarrhea, or vomiting between January 1, 1998, and December 31, 1998. MAIN OUTCOME MEASURES: Presence of a claim for an antiemetic in the 3 days after the initial diagnosis of acute gastroenteritis, subsequent health care usage, and an adverse event within 14 days of the initial diagnosis. RESULTS: Parents of 1802 children (8.9%) with acute gastroenteritis had a prescription for an antiemetic filled within 3 days of the index visit. Factors associated with antiemetic prescription filling for children include older age, provider type (emergency physician, family physician, or general practitioner vs pediatrician), Spanish as the primary language, and rural residency. There was no difference in adverse events between children for whom an antiemetic prescription was filled and for those who did not have an antiemetic prescription filled (odds ratio, 0.68; 95% confidence interval, 0.31-1.46). No difference in risk of subsequent health care use was seen in children who had an antiemetic prescription filled and those who did not (incidence rate ratio, 1.04; 95% confidence interval, 0.94-1.16). CONCLUSION: Antiemetic use among children with acute gastroenteritis is common and adverse effects seem to be rare.

Acute Disease↗
PubMed1994

Concomitant administration of antiemetics is not necessary with intramuscular dihydroergotamine.

The influence of concomitant administration of an antiemetic agent on the course of nausea was assessed in a field trial of intramuscular dihydroergotamine for the treatment of acute migraine. Of 311 migraine patients enrolled onto the study, 62% (191 of 311) experienced nausea at the outset; 38% (119 of 311) did not. Of those with nausea at the outset, 54% (103 of 191) received an antiemetic. Of those without nausea at the outset, 25% (30 of 119) received an antiemetic. Thus, a total of 43% (133 of 311) of patients received a concomitant antiemetic, whereas 57% (177 of 311) received dihydroergotamine alone. When changes in the incidence of nausea were compared at 30 and 60 minutes after dihydroergotamine, an antiemetic effect was discerned in patients treated with or without a concomitant antiemetic. Antiemetic treatment yielded no significant difference in the percentage of patients experiencing nausea during the study. At baseline, 50% (88 of 177) of patients who received dihydroergotamine alone experienced nausea compared with 77% (103 of 133) of those who received an antiemetic. At the 30-minute point, 35% (61 of 173) of patients who received dihydroergotamine alone still experienced nausea versus 47% (62 of 133) of patients who received an antiemetic. At the 60-minute point, only 24% (42 of 174) of those given dihydroergotamine alone had nausea, compared with 38% (50 of 132) given concomitant antiemetic. Ongoing nausea seems to be a manifestation of the migraine process rather than an adverse effect associated with intramuscular dihydroergotamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed2005

Employment of substandard antiemetic prophylaxis in recent trials of chemotherapy-induced nausea and vomiting.

OBJECTIVE: To determine the prevalence of substandard antiemetic therapy among recently published trials conducted in patients with cancer who received emetogenic chemotherapy. DATA SOURCES: A MEDLINE search was conducted (2000-July 2004) using the key words 5-HT(3) antagonists, ondansetron, granisetron, dolasetron, tropisetron, ramosetron, palonosetron, NK-1 antagonists, and aprepitant. STUDY SELECTION AND DATA EXTRACTION: All antiemetic trials in patients receiving chemotherapy that were published from January 2000 to July 2004 were evaluated. Standard prophylactic antiemetic therapy was derived from contemporary antiemetic guidelines published by oncology professional organizations and expert panels. The number of patients and studies in which patients received standard and substandard antiemetic therapy was determined for both the acute and delayed phases of chemotherapy-induced nausea and vomiting (CINV). Separate determinations were made for severely and moderately emetogenic chemotherapy. The annual percentage of studies in which substandard antiemetic prophylaxis was given and the percentage of patients who received substandard prophylaxis also were determined. DATA SYNTHESIS: Fifty-six studies were reviewed, which included a total of 10 274 patients and 125 study arms. The percentage of patients who received substandard antiemetic prophylaxis was 30% (n = 3063) for acute CINV and 33% (n = 3413) for delayed CINV. The average annual percentage of studies that employed substandard prophylaxis during this time period was 54%. CONCLUSIONS: In recent antiemetic trials for CINV, the employment of substandard antiemetic therapy is common. These results raise important ethical questions regarding contemporary antiemetic trial design.

Antiemetics↗
PubMed2004

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↗
PubMed2005

The utility of antiemetics in the prevention and treatment of postoperative nausea and vomiting in patients scheduled for laparoscopic cholecystectomy.

Postoperative nausea and vomiting (PONV) are distressing and frequent adverse events of anesthesia and surgery, with a relatively high incidence after laparoscopic cholecystectomy. Numerous antiemetics have been studied for the prevention and treatment of PONV in patients scheduled for laparoscopic cholecystectomy. Traditional antiemetics, including anticholinergics (e.g., scopolamine), antihistamines (e.g., dimenhydrinate), phenothiazines (e.g., promethazine), butyrophenones (e.g., droperidol), and benzamide (e.g., metoclopramide), are used for the control of PONV. The available nontraditional antiemetics for the prophylaxis against PONV are dexamethasone and propofol. Serotonin receptor antagonists (ondansetron, granisetron, tropisetron, dolasetron, and ramosetron), compared with traditional antiemetics, are highly efficacious for PONV. The prophylactic ondansetron, granisetron, tropisetron, and dolasetron in antiemetic efficacy are comparable. Ramosetron is effective for the long-term prevention of PONV. None of the available antiemetics is entirely effective, perhaps because most of them act through the blockade on one type of receptor. There is a possibility that combined antiemetics with different sites of activity would be more effective than one drug alone for the prophylaxis against PONV. Combination antiemetic therapy is often effective for the prevention of PONV following laparoscopic cholecystectomy. The efficacy of a combination of serotonin receptor antagonists (ondansetron and granisetron) and droperidol is superior to monotherapy with a serotonin receptor antagonist or droperidol. Similarly, adding dexamethasone to ondansetron or granisetron improves antiemetic efficacy in PONV. Knowledge regarding antiemetics is necessary to completely prevent and treatment of PONV in patients scheduled for laparoscopic cholecystectomy.

Antiemetics↗
PubMed1994

Antiemetic drugs attenuate food aversions in sheep.

Ruminants learn to avoid many foods that contain toxins by associating the flavor of the foods with aversive postingestive feedback. We hypothesized the emetic system is a cause of aversive feedback, and three experiments were conducted to determine whether antiemetic drugs (diphenhydramine, metoclopramide, dexamethasone) would attenuate food aversions caused by the toxicant lithium chloride (LiCl). Lambs were assigned to one of four treatments: antiemetics plus LiCl (A + L), antiemetics alone (A), LiCl alone (L), or neither antiemetics nor LiCl (C). The LiCl was administered immediately after sheep ate oats, wheat, and milo in Exp. 1, 2, and 3, respectively. The antiemetics were given 1 h before and at the time LiCl was administered to sheep. Lambs that received antiemetics (A and A + L) consistently ate more grain than lambs that did not receive the drugs (C and L) (Exp. 1, P < .08; Exp. 2, P < .05; Exp. 3, P < .08), and there was no interaction between antiemetics and LiCl. Thus, the results of all three experiments were consistent with the hypothesis that antiemetic drugs attenuate food aversions caused by the toxicant LiCl because sheep receiving antiemetic drugs (Group A + L) ate more grain than sheep not receiving the drugs (Group L). In addition, we suggest aversive postingestive feedback limited intake of grain because sheep receiving antiemetic drugs (Group A) ate somewhat more grain than sheep not receiving the drugs (Group C).

Animal Feed↗
PubMed1998

Use of ondansetron and other antiemetics in the management of toxic acetaminophen ingestions.

BACKGROUND: Patients presenting with acetaminophen toxicity and vomiting are often treated with antiemetics so that orally administered N-acetylcysteine can be retained. The policy at the West Virginia Poison Center is to reserve ondansetron, an antiemetic with a higher cost than other antiemetics, as a second line agent for patients presenting within 8 hours of an acetaminophen ingestion. METHODS: A retrospective study of cases between January 1993 and December 1995, in which the primary or secondary drug ingested was an adult-strength, acetaminophen-only formulation and the ingestion resulted in vomiting. Seventy-eight patients with laboratory-verified acetaminophen toxicity and vomiting were evaluated for the type of antiemetics used and the antiemetic's effectiveness. RESULTS: Of the 78 acetaminophen toxic patients with vomiting, 17/51 patients (33.3%) who received a nonondansetron antiemetic failed therapy and required IV ondansetron. Of the 24 patients who received ondansetron, 4 patients (16.7%) failed therapy. All four patients who failed ondansetron therapy had previously failed other antiemetic therapy. DISCUSSION: Although ondansetron had a lower failure rate than nonondansetron antiemetics, almost two-thirds of acetaminophen toxic patients with vomiting did not require ondansetron to control their vomiting. Health care costs would have been higher had these patients received ondansetron as their initial therapy. Antiemetics were found to be highly effective as only 3/78 patients (4%) required IV N-acetylcysteine secondary to antiemetic failure. CONCLUSIONS: Ondansetron should be utilized as a second-line agent in the management of acetaminophen toxic patients with vomiting. Because of its lower failure rate, ondansetron should be administered as a first-line agent in patients with a delay in N-acetylcysteine administration approaching 8 or more hours.

Acetaminophen↗
PubMed1995

Nurses' perceptions of antiemetic effectiveness.

PURPOSES: To determine which antiemetics are being used with ondansetron (Zofran, Cerenex Pharmaceuticals, Research Triangle Park, NC) for patients receiving emetogenic chemotherapy, identify the more frequently administered antiemetic regimens, and ascertain nurses' perceptions of the effectiveness of these regimens. DESIGN: Descriptive survey. SETTING: Continental United States. SAMPLE: A random sample (N = 962) of Oncology Nursing Society members who designate themselves as practicing in the area of chemotherapy. METHODS: The Antiemetic Drug(s)/Drug Combination(s) Inventory, an open-ended questionnaire soliciting information on first- and second-line antiemetic regimens for emetogenic chemotherapy protocols, was mailed to 5,950 oncology nurses. Descriptive statistics and nondistributive analysis were used to analyze the data. FINDINGS: Ondansetron was used in 7 of 10 antiemetic regimens, which accounted for 50% of the most frequently used regimens. Nurses rated first-line antiemetic combinations as highly effective. Ondansetron alone was ranked as the seventh most effective first-line antiemetic for cisplatin protocols and fifth for noncisplatin protocols. Nurses noted limitations of ondansetron use, which included delayed nausea and vomiting and the drug's high cost. CONCLUSIONS: Study participants indicated that a variety of drugs were used in antiemetic regimens. Ondansetron use has improved the control of post-chemotherapy nausea, vomiting, and retching. IMPLICATIONS FOR NURSING PRACTICE: Antiemetics are administered regularly in the hospital and home to decrease chemotherapy-related nausea, vomiting, and retching. Managing these side-effects requires superior assessment skills and extensive knowledge of pharmacologic actions. Patient and family education on antiemetics is essential in light of increased administration of outpatient chemotherapy.

Antiemetics↗
PubMed2003

Antiemetic prescription in Italian breast cancer patients submitted to adjuvant chemotherapy.

GOAL: The aim of this study was to investigate if the Multinational Association of Supportive Care in Cancer (MASCC) antiemetic guidelines for the prevention of both acute and delayed emesis induced by highly-moderately emetogenic chemotherapy were transferred in daily clinical practice in Italy 2 years after their publication. PATIENTS AND METHODS: From 16 to 23 March 2000, all consecutive breast cancer patients referred to 87 Italian oncological centers to receive any cycle of adjuvant chemotherapy were monitored. MAIN RESULTS: Of 715 evaluable patients submitted to chemotherapy, 533 received cyclophosphamide, methotrexate, 5-fluorouracil (CMF) and 151 anthracyclines. Patients receiving taxanes or other experimental therapies (31) were not considered. The MASCC-recommended antiemetic prophylaxis against acute/delayed emesis was prescribed in 56.3/45.9% patients. Antiemetic prophylaxis against delayed emesis was not prescribed to 30.6% of patients. The MASCC-recommended prescription against acute emesis was more frequently followed in research centers, in Northern Italy, and in centers with experience on antiemetic research. CONCLUSIONS: Two years after the publication of the MASCC antiemetic guidelines, strong discrepancies between these and antiemetic prescriptions in daily clinical practice in Italy were observed. The similarity of these results with those obtained in our previous drug utilization study on antiemetics, carried out before the publication of the MASCC guidelines, leads us to conclude that the transferability of antiemetic guidelines to daily clinical practice in Italy has been modest. A great effort should be made in Italy by the National Health Service to accelerate the process of implementation of antiemetic guidelines.

Antiemetics↗
PubMed1999

Antiemetic therapy for high-dose chemotherapy with transplantation: report of a retrospective analysis of a 5-HT(3) regimen and literature review.

The goal of this work was to evaluate the efficacy of 5-HT(3) receptor antagonist regimens in the transplant setting through a retrospective analysis of clinic patients and a review of the literature. A retrospective study was performed to evaluate the efficacy of an antiemetic regimen in 24 patients receiving high-dose chemotherapy with bone marrow transplantation. The antiemetic agent used in 96% of the patients was single-agent ondansetron 0.15 mg/kg as a continuous infusion every 12 h starting on the first day of chemotherapy. Efficacy or failure was defined by the need for administration of rescue antiemetics, as documented by nurses' notes and pharmacy records. Overall, 23 (96%) patients experienced antiemetic failure within the first 3 days. Rescue antiemetics yielded improved control of nausea and vomiting in 16 of 23 (70%) patients. These data demonstrate poor antiemetic efficacy of single-agent, continuous-infusion ondansetron in a small group of patients receiving high-dose chemotherapy with bone marrow transplantation. These data are considered in the context of a thorough literature review that shows the limitations of previously reported antiemetic studies in this setting, potential pharmacokinetic interactions, and also highlights the utilization of combination therapy, administered orally or intravenously, to improve efficacy and tolerability of antiemetic therapy. A number of recent investigations suggest that appropriate doses of 5-HT(3) receptor antagonists with phenothiazine and corticosteroids can improve the safety and efficacy of antiemetic regimens in patients undergoing transplantation.

Administration, Oral↗
PubMed2003

An international multicenter protocol to assess the single and combined benefits of antiemetic interventions in a controlled clinical trial of a 2x2x2x2x2x2 factorial design (IMPACT).

For various diseases clinicians have to combine different drugs or interventions when a single drug or intervention does not lead to satisfactory results. However, quantifying the relative benefit of certain drugs or interventions when given alone and in combination under controlled conditions requires a complex factorial design. This paper describes such a method applied to a large multicenter trial for the prevention of postoperative nausea and vomiting (PONV), which may be of great interest for other specialties. Approximately 28 million operations are performed annually in the United States, mainly under general anesthesia with volatile anesthetics. Unfortunately, one-third of these patients suffer from PONV. This prompted extensive research of antiemetic and anesthetic drugs, but none of the interventions appeared to satisfactorily prevent PONV. Scuderi et al. were the first to almost eliminate PONV by combining various antiemetic interventions; however, the relative benefit of each intervention remained unclear. Accordingly, we have designed a large randomized controlled trial studying six different antiemetic interventions-three involving use of various antiemetic drugs and three involving choice of anesthetic drugs-to answer the following main questions: (1) What is the relative benefit of each of the antiemetic intervention? (2) Are certain combinations of antiemetic interventions more effective than others? Using a complete factorial design this leads to 2(3)=8 antiemetic combinations, which multiply with the 2(3)=8 combinations of anesthetic drugs, leading to a total of 2(6)=64 possible combinations. The six factors are the antiemetics ondansetron (versus control), dexamethasone (versus control), droperidol (versus control), and the intravenous anesthetic propofol (versus volatile anesthetics), air (versus nitrous oxide), and remifentanil (versus fentanyl). The primary outcome is freedom from PONV within the first 24 hours after anesthesia. Eligible patients are adults scheduled for elective surgery under general anesthesia with an increased risk for PONV so that the expected incidence in the control group (with none of the six antiemetic interventions) is approximately 60%. In order to allow analyses for up to three factor interactions, a sample size was estimated to be in the range of approximately 5000 patients. To the best of our knowledge this is the first randomized controlled trial of a six-way factorial design that may serve as an example for numerous other medical specialties.

Anesthesia, Inhalation↗
PubMed1984

Paradoxical effects of prophylactic phenothiazine antiemetics in children receiving chemotherapy.

The effectiveness of prophylactic phenothiazine antiemetics on reduction of nausea and vomiting was assessed for 23 children (age, 9-17 years) who had intermittently received antiemetics (ie, for one course but not for another). Each patient was his own control and the courses with antiemetics were compared to the matched courses without antiemetics (Wilcoxon matched-pairs, signed-ranks test). In each case, the matched courses with and without antiemetics were temporally consecutive and equivalent for chemotherapeutic agents and dosages. Significantly higher ratings for severity of nausea (P less than .004), vomiting (P less than .02), and the extent to which these symptoms bothered patients (P less than .001) were found during courses with prophylactic antiemetics. Duration (in hours) of nausea and vomiting was analyzed for the last eight consecutive study patients; in eight of eight patients, a significantly longer duration of nausea (P less than .05) and vomiting (P less than .02) was found for the courses in which antiemetics were given prophylactically. This study suggests that prophylactic phenothiazine antiemetics do not predictably reduce children's nausea and vomiting and may even be associated with an increase in symptoms. Further studies in children are needed to determine which patients might benefit most from antiemetic intervention.

Adolescent↗
PubMed2003

Antiemetic prophylaxis for office-based surgery: are the 5-HT3 receptor antagonists beneficial?

BACKGROUND: Office-based surgery has become increasingly popular because of its cost-saving potential. However, the occurrence of postoperative nausea and vomiting (PONV) can delay patient discharge. Prophylaxis using a combination of antiemetic drugs has been suggested as an effective strategy for minimizing PONV. The authors designed this randomized, double-blinded, placebo-controlled study to assess the efficacy of ondansetron and dolasetron when administered in combination with droperidol and dexamethasone for routine antiemetic prophylaxis against PONV in the office-based surgery setting. METHODS: Following institutional review board approval, 135 consenting outpatients with American Society of Anesthesiologists physical status I-III who were undergoing superficial surgical procedures lasting 20-40 min were randomly assigned to one of three antiemetic treatment groups. Propofol was administered for induction of anesthesia, followed by 2-4% desflurane with 67% nitrous oxide in oxygen. Desflurane was subsequently adjusted to maintain a clinically adequate depth of anesthesia with an electroencephalographic Bispectral Index value between 50 and 60. All patients received 0.625 mg intravenous droperidol and 4 mg intravenous dexamethasone after induction of anesthesia. The study medication, containing normal saline (control), 12.5 mg intravenous dolasetron, or 4 mg intravenous ondansetron, was administered prior to the end of surgery. All patients received local anesthetics at the incisional site and 30 mg intravenous ketolorac to minimize postoperative pain. Recovery profiles, incidence of PONV, requirement for rescue antiemetic drugs, complete response rates, and patient satisfaction were assessed. RESULTS: The recovery times to patient orientation, oral intake, ambulation, and actual discharge did not differ among the three groups. The incidence of PONV, nausea scores, and requirement for rescue antiemetics were also similar in all three groups during the 24-h study period. In addition, the complete response rates to the prophylactic antiemetics (96-98%) and percentages of very satisfied patients (93-98%) were equally high in all three groups. However, the antiemetic drug acquisition costs were US $2.50, $15.50, and $18.50 in the control, dolasetron, and ondansetron groups, respectively. CONCLUSION: The addition of dolasetron (12.5 mg) or ondansetron (4 mg) failed to improve the antiemetic efficacy of droperidol (0.625 mg intravenous) and dexamethasone (4 mg intravenous) when they were used for routine prophylaxis in the office-based surgery setting.

Aged↗
PubMed2000

The use of propofol for its antiemetic effect: a survey of clinical practice in the United States.

STUDY OBJECTIVES: To investigate the use of propofol by anesthesiologists for its antiemetic effect and to compare our findings with published evidence. DESIGN: Anonymous survey of U.S. anesthesiologists. SETTING: American Society of Anesthesiologists' annual meeting. MEASUREMENTS AND MAIN RESULTS: One hundred fifty anesthesiologists were surveyed on how they use propofol to achieve an antiemetic effect. A large majority (84%) of the anesthesiologists surveyed stated they used propofol for its antiemetic effect: 63% of those used propofol for induction only for cases lasting <1 h to achieve an antiemetic effect. In addition 37% used a "sandwich" technique, using propofol at the beginning and end of a case for a similar purpose. There is evidence that the antiemetic effect of propofol is associated with a defined plasma concentration range; mean, 343 ng/mL (10-90% confidence intervals [CI] 200-600 ng/mL). Simulation data demonstrated that after propofol 2 mg/kg, its concentration will drop below 350 ng/mL at 32 min. After 2 mg/kg and 20 mg within 10 min of the end of surgery, its concentration will drop below 350 ng/mL by 7 min after the 20 mg bolus dose. This finding suggests that the plasma concentrations of propofol, when used in these cases, will be below the effective range of antiemetic effect. CONCLUSIONS: Many anesthesiologists used propofol for its antiemetic effect. There is strong evidence for its antiemetic efficacy after anesthesia maintained by a propofol infusion and also for its use in the postanesthesia care unit (PACU). However, there is little evidence to support its use purely at induction of anesthesia or as part of a "sandwich" technique in an attempt to reduce postoperative nausea and vomiting. This is especially true in cases lasting longer than a few minutes.

Anesthesia, Intravenous↗
PubMed2005

Use of antiemetic drugs during pregnancy in Sweden.

BACKGROUND: More than one-half of all pregnant women suffer from nausea and vomiting during pregnancy (NVP), primarily during the first trimester. METHODS: Prospectively ascertained information on drug use during pregnancy was obtained from the Swedish Medical Birth Register during the period July 1, 1995 to 2002. Antiemetics (antiemetic antihistamines, dopamine modulators, and ondansetron) primarily used for NVP were studied, and women reporting the use of these drugs were compared with all women who gave birth during the study period. RESULTS: Use of these antiemetics was reported in 4.5% of the pregnant women--86% of whom reported their use before the first antenatal visit (usually weeks 10-12). Meclozine, followed by other antihistamines, accounted for 68% of the drugs reported. Young maternal age, multiparity, non-smoking, and a period of unwanted childlessness increased the probability of using any of the antiemetics during pregnancy. Women with a low education used these drugs more often than women with a relatively higher education. Neonates born to women who used any of the antiemetics had a reduced risk for low birthweight, prematurity, being small-for-gestational age, and having a malformation. No specific differences were observed with respect to the outcome following a comparison of different antiemetic drugs. CONCLUSIONS: Women using antiemetics as a rule have a better delivery outcome than other women, probably due to an effect of a well-functioning placenta, which is associated with NVP. There were no signs of any significant teratogenicity of the drugs studied, but for some drugs the number of exposures was low.

Adult↗
PubMed1993

Comparison of four antiemetic regimens for the treatment of cisplatin-induced vomiting.

OBJECTIVE: To improve the treatment of cisplatin-induced acute emesis and vomiting, the adjuvant effect of two different doses of metoclopramide and metoclopramide plus droperidol was compared to a defined standard antiemetic regiment. METHOD: One-hundred and twenty-one consecutive cisplatin-based chemotherapy treatments for ovarian carcinoma were randomly assigned to receive standard plus no adjuvant (control, n = 24), high-dose metoclopramide (HDM, n = 33), very high dose metoclopramide (VHDM, n = 50) and very high dose metoclopramide plus droperidol (VHDM+DP, n = 14) antiemetic treatment. The number of vomiting episodes up to 4 h after the treatment were recorded and compared in the four different antiemetic groups. The effect of the number of previous chemotherapy cycles, the strength of previous antiemetic treatments, age and stage of disease on the number of vomiting episodes was also assessed. RESULT: The mean number of vomiting episodes during the first 4 h after the chemotherapy was 9, 6.4, 6.2 and 2.7 among patients receiving the standard HDM, VHDM and VHDM+DP antiemetic regimens, respectively. Analysis of variance of vomiting episodes confirmed significant differences between the groups (P < 0.001, F = 406.5, df = 120). The number of previous chemotherapy cycles and, to a lesser extent, the stage of disease, the strength of previous antiemetic regimens and the age showed significant correlation with the number of vomiting episodes (r = 0.443, -0.159, -0.14 and -0.009 respectively). CONCLUSION: Substantial improvement in the control of cisplating-induced vomiting can be achieved by adding high-dose metoclopramide and droperidol to a basic antiemetic regimen consisting prochlorperazine, dexamethasone and thiethylperazine.

Antiemetics↗
PubMed2005

The effectiveness of rescue antiemetics after failure of prophylaxis with ondansetron or droperidol: a preliminary report.

STUDY OBJECTIVES: To compare the effectiveness of treating established postoperative nausea and vomiting (PONV) with an antiemetic acting at a different receptor with that of treating PONV with the antiemetic used for prophylaxis. DESIGN: Analysis of data collected in a previously published randomized, double-blind, placebo-controlled study. SETTING: Outpatient surgical procedures from 50 institutions in North America. PATIENTS: Patients (N = 2061) undergoing outpatient surgical procedures planned to last no more than 2 hours. INTERVENTIONS: Patients were randomized to receive ondansetron 4 mg, droperidol 1.25, droperidol 0.625 mg, or placebo. In the postoperative anesthesia care unit, patients who developed PONV received rescue antiemetics at the discretion of the attending anesthesiologist. The following antiemetics were used for rescue: ondansetron 4 mg, droperidol 0.625 to 1.25 mg, metoclopramide 10 mg, promethazine 6.25 to 25 mg, and dimenhydrinate 25 to 50 mg. MEASUREMENTS: The complete response rate (no nausea, no emesis, and no need for further rescue) after administration of the rescue antiemetic in patients with established PONV was calculated. The complete response rate after administration of each of the different rescue antiemetics was compared with that after administration of the same antiemetic used for PONV prophylaxis. MAIN RESULTS: In patients who failed prophylaxis with ondansetron 4 mg, the complete response rate was significantly higher (P = .02) after rescue with promethazine 6.25 to 25 mg (78%) than after rescue with ondansetron 4 mg (46%). In patients who failed prophylaxis with droperidol 0.625 and 1.25 mg, the complete response rate was significantly higher after rescue with promethazine 6.25 to 25 mg (77%; P = .02) and dimenhydrinate 25 to 50 mg (78%; P = .04) than after rescue with droperidol 0.625 to 1.25 mg (56%). CONCLUSION: In patients who failed prophylaxis with ondansetron or droperidol, promethazine was significantly more effective than the agent used for prophylaxis for the treatment of PONV. In patients who failed prophylaxis with droperidol, dimenhydrinate was also more effective than droperidol for the treatment of established PONV in the postoperative anesthesia care unit.

Adult↗