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[Is ginger a relevant antiemetic for postoperative nausea and vomiting?].

OBJECTIVE: Ginger (Zingiber officinale) has traditionally been used in China for gastrointestinal symptoms, including nausea and vomiting. A recent systematic review on the possible antiemetic effect of ginger for various indications, including PONV, morning sickness, and motion sickness, concluded that ginger was a promising antiemetic herbal remedy, but the clinical data were insufficient to draw firm conclusions. Since that publication, additional data has accumulated and thus an updated meta-analysis was performed. METHODS: A systematic search of the literature was performed using different search strategies in MEDLINE, EMBASE, and the Cochrane Library. Six randomized controlled trials including 538 patients were identified investigating ginger to prevent postoperative nausea and vomiting (PONV). Data on the incidences of PONV, nausea, vomiting, and the need for rescue antiemetics within the first 24 postoperative hours were extracted and the pooled relative risk and the numbers needed to treat (NNT) were calculated using a random effects model. RESULTS: The pooled relative risk to suffer from PONV after pre-treatment with ginger was 0.84 (95 %-confidence interval 0.69 - 1.03). About 11 patients must be treated with ginger for one additional patient remaining free from PONV (NNT: 11; 95 %-CI: 6 - 250). Results for nausea, vomiting, and need for antiemetic rescue treatment are similar. CONCLUSION: Ginger is not a clinically relevant antiemetic in the PONV setting.

Antiemetics↗

Antiemetics in patients receiving chemotherapy for cancer: a randomized comparison of delta-9-tetrahydrocannabinol and prochlorperazine.

Delta-9-tetrahydrocannabinol (THC) is an effective antiemetic as compared with placebos in patients receiving chemotherapy for cancer. In this study we compared THC with prochlorperazine (compazine) in a randomized, double-blind, crossover trial with patients who had failed to benefit from standard antiemetic therapy. Regardless of the emetic activity of the chemotherapeutic agents, there were more complete responses to THC courses (in 36 of 79 courses) than to prochlorperazine (in 16 of 78 courses). Of 25 patients who were treated with both drugs and who expressed a preference, 20 preferred THC (P = 0.005). Among patients under 20 years of age there was a higher proportion of complete responses to THC courses (15 of 20) than among older patients (21 of 59 courses; P = 0.004). Increased food intake occurred more frequently with THC (P = 0.008) and was associated with the presence of a "high." Of 36 THC courses resulting in complete antiemetic responses, 32 were associated with a high. We conclude that THC is an effective antiemetic in many patients who receive chemotherapy for cancer and for whom other antiemetics are ineffective. (N Engl J Med 302:135--138, 1980).

Adolescent↗

Peripheral nerve injection injury with antiemetic agents.

Antiemetics are widely used drugs, frequently administered to alleviate postoperative and postchemotherapeutic nausea and vomiting. While antiemetics do not induce peripheral neurotoxicity when administered systemically, it is not known whether peripheral nerve injury can occur as a result of inadvertent intraneural injection during intramuscular administration. The purpose of this study was to characterize the neurotoxic effect of three commonly used antiemetic agents (promethazine, dimenhydrinate, and prochlorperazine) as compared to saline in the rat sciatic nerve model. Intrafascicular and extrafascicular injection as well as direct application of the antiemetic drugs were performed. Nerves were harvested at 2 weeks postoperatively for histology and morphometry, with an additional sacrifice point at 8 weeks for the intrafascicular injection group. Injection injuries caused by antiemetic drugs differed depending on the agent injected and the location of injection. Extrafascicular injection and direct application caused no damage. Intrafascicular injection caused diffuse axonal injury in the promethazine and dimenhydrinate groups, while prochlorperazine caused only focal injury. Regeneration was prominent at 8 weeks in all intrafascicular injection groups in this rat model. Prochlorperazine thus appears to be less neurotoxic when injected intraneurally and should preferentially be used for intramuscular injections.

Animals↗

Methodology of antiemetic trials: a review.

Chemotherapy-related nausea and vomiting can be controlled with available antiemetics in a high percentage of patients, while emesis remains a critical problem in some subgroups and with certain drugs. In the ceaseless attempt to find newer drugs and better treatment modalities, a sound methodology in antiemetic research is essential. Several factors should always be considered when planning an antiemetic trial: first, the different emetic power of various chemotherapy agents, their dosages and route and schedule of administration and second, the type of antiemetic used, its dosage and timing, and its possible combination with other antiemetics. Important factors which influence outcome but which are often under-evaluated are those related to patient population such as age, gender, and previous experience with chemotherapy. Considering the relevance of subjective phenomena in nausea and vomiting, it is essential that any study be randomized and double blinded. The parallel type of study design is preferable to the cross-over and a large number of patients is usually required to achieve meaningful results. Efficacy and toxicity should be properly evaluated by trained personnel in a standardized way, using a validated, relatively simple methodology.

Adult↗

The effects of dexamethasone on antiemetics in female patients undergoing gynecologic surgery.

UNLABELLED: This randomized, double-blind study compared the effects of dexamethasone plus either droperidol, metoclopramide, or granisetron with each antiemetic alone for preventing postoperative nausea and vomiting (PONV) in 270 female patients undergoing general anesthesia for major gynecological surgery. Patients were randomly assigned to receive either droperidol 1.25 mg (Group D1, n = 45), droperidol 1.25 mg plus dexamethasone 8 mg (Group D2, n = 45), metoclopramide 10 mg (Group M1, n = 45), metoclopramide 10 mg plus dexamethasone 8 mg (Group M2, n = 45), granisetron 40 micrograms/kg (Group G1, n = 45), or granisetron 40 micrograms/kg plus dexamethasone 8 mg (Group G2, n = 45) immediately before the induction of anesthesia. A standard general anesthetic technique and postoperative analgesia were used throughout the study. Complete response, defined as no PONV and no administration of rescue antiemetic medication during the first 24 h after anesthesia, was 49% in Group D1, 60% in Group D2 (P = 0.199 versus Group D1), 51% in Group M1, 62% in Group M2 (P = 0.198 versus Group M1), 80% in Group G1, and 96% in Group G2 (P = 0.025 versus Group G1). Our results suggest that dexamethasone enhances the antiemetic efficacy of granisetron but does not potentiate the other antiemetics-droperidol and metoclopramide-in female patients undergoing major gynecological surgery. IMPLICATIONS: We compared the efficacy of dexamethasone plus three different antiemetics-droperidol, metoclopramide, and granisetron-for the prevention of nausea and vomiting after gynecologic surgery. The granisetron-dexamethasone combination was the most effective for preventing post-operative emetic symptoms.

Adult↗

High-dose metoclopramide and dexamethasone as an antiemetic in outpatients receiving chemotherapy for breast cancer. Second study.

Forty-six outpatients with breast cancer who had experienced severe emesis as a result of chemotherapy were evaluated for the antiemetic efficacy of high-dose metoclopramide (HD-MCP) and dexamethasone (DXM). Chemotherapy consisted of: cyclophosphamide 600, methotrexate 40 and 5-fluorouracil 600 mg/m2 (CMF) given intravenously every 3 weeks. The dosage of antiemetic drugs was MCP 2 mg/kg and DXM 0.2 mg/kg given by slow intravenous drip 0.5 h before the administration of chemotherapy. 138 courses of combined chemotherapy--HD-MCP and DXM--were administered, with a mean of 3 courses and a range of 1-10 courses per patient. Complete protection--no nausea and no vomiting--was achieved in 17.7% of the courses. Partial protection--no vomiting with mild nausea or 1-3 episodes of vomiting--in 45.3% of the courses. The total antiemetic efficacy was 63%. The most common side effects were: drowsiness, dry mouth, restlessness and diarrhea. Sixteen patients (35%) refused to continue the antiemetic regimen because of the side effects. HD-MCP and DXM have antiemetic efficacy, but because of these side effects, further studies are required to determine the optimal dose of each of these drugs.

Adult↗

Methylprednisolone as an antiemetic in patients on cis-platinum chemotherapy. Results of a controlled randomized study.

In cytostatic drug treatment, nausea and vomiting are very frequent, unpleasant and undesirable side effects that cause considerable discomfort to the patient. However, many established antiemetics (Torecan, haloperidol, Valium, Largactil etc.) have not shown significant antiemetic activity in the patients to whom cytostatics were applied. In our controlled randomized clinical trial, the antiemetic activity of methylprednisolone was investigated and compared with placebo (10 ml saline) and Torecan. All the compounds were injected before cis-platinum administration, knowing that this agent induces vomiting in almost 100% of patients. Ninety patients entered the study and have been evaluated. The results of the trial have shown that methylprednisolone in the single dose of 250 mg applied i.v. 2 h before injection of a cytostatic agent experienced pronounced antiemetic activity in 48% of the patients (15/31), as compared to Torecan 21% (6/29) and placebo 13% (4/30). This difference was statistically significant (P less than 0.01). No side effects were recorded after methylprednisolone application. The results of the study showed that methylprednisolone possesses a pronounced antiemetic activity in almost half of the patients treated with cis-platinum.

Adult↗

Integrating aprepitant and palonosetron into clinical practice: a role for the new antiemetics.

Chemotherapy-induced nausea and vomiting (CINV) are among the most feared side effects of cancer treatment. With increasingly more complex chemotherapy treatments, CINV plays an important role in determining patients' quality of life, as well as when to halt potentially lifesaving therapy. Although significant progress has been made in the treatment of CINV, patients undergoing chemotherapy continue to report that this side effect is persistent and distressing. In 2003, two new agents were added to the armamentarium of antiemetic therapy. The U.S. Food and Drug Administration approved palonosetron, a longer-acting serotonin antagonist, and aprepitant, a neurokinin-1 antagonist and the first in a new class of antiemetics, for the treatment of CINV. Although the indications for both agents are similar, they have distinct differences. Decisions regarding placement of these agents into existing antiemetic protocols can be based on national guidelines, review of the literature, and clinical experience. This article will review current antiemetic therapy with an emphasis on the new additions to the treatment of CINV. Aprepitant and palonosetron represent significant changes in the treatment of CINV. Oncology nurses need to know current approaches to maximize effective antiemetic therapy.

Antiemetics↗

Pharmacokinetic optimisation of antiemetic therapy.

Antiemetic drugs are used to treat nausea and vomiting due to a variety of causes and have a wide range of pharmacological properties. The choice of drug will, therefore, depend in part on the condition being treated. The drugs can be classified as dopamine antagonists (including phenothiazines and nonphenothiazines), corticosteroids, cannabinoids, benzodiazepines, serotonin antagonists, antihistamines and anticholinergics. There is very little evidence of a relationship between plasma drug concentrations and either their efficacy or the incidence of adverse effects with most antiemetic drugs. With drugs for which concentration-effect studies have been performed, e.g. the benzodiazepines and antihistamines, the effects monitored have not been directly relevant to their use as antiemetics. Antiemetics are used widely, for example, in cancer chemotherapy. Nonetheless, apart from metoclopramide, little work has been done on the influence of indicators of systemic disease on the pharmacokinetics of antiemetic drugs.

Adrenal Cortex Hormones↗

Metoclopramide. A review of antiemetic trials.

Early clinical trials of metoclopramide at traditional doses failed to demonstrate protection against antineoplastic drug-induced vomiting, and its antiemetic potential for oncology patients was not re-examined until the unacceptable nausea and vomiting of the newly introduced cisplatin emphasised the need for improved supportive care. Repetition of the early studies with metoclopramide at usual doses (0.15 to 0.30 mg/kg) in cisplatin-induced emesis confirmed the lack of benefit for low dose therapy. However, on the basis of known pharmacodynamic data, metoclopramide was evaluated as an antiemetic in animal models, and a dose-related response was observed for cisplatin-induced emesis. After establishing safety in a phase I trial, rigorously controlled studies were conducted to assess the antiemetic potential of high dose metoclopramide in preventing cisplatin-induced emesis. Metoclopramide (2 mg/kg) was administered intravenously for a total of 5 doses during a 9-hour period beginning 30 minutes before administration of high-dose cisplatin (120 mg/m2). The results of 3 sequential trials established the superiority of metoclopramide over placebo, prochlorperazine, and tetrahydrocannabinol. Toxicity consisted of mild sedation, diarrhoea, and reversible extrapyramidal reactions. In no case was it necessary to discontinue metoclopramide because of adverse drug reactions. These encouraging results were rapidly followed by a series of pilot studies designed to extend the use of metoclopramide to other clinical situations. Intermediate dose metoclopramide (1 mg/kg for 6 doses) appeared effective particularly for emesis associated with lower doses of cisplatin (50 mg/m2 or less). The results of studies of short course metoclopramide (2 mg/kg for 3 doses) provided a promising alternative regimen for the outpatient setting. As with high dose metoclopramide, the toxicity of these two protocols was acceptable, manifesting as sedation, diarrhoea, and extrapyramidal reactions. Uncontrolled observations of continued metoclopramide treatment during subsequent courses of cisplatin suggest preservation of antiemetic efficacy, and preliminary results of studies of metoclopramide in non-cisplatin-containing regimens also suggest benefit. The combination of metoclopramide with other effective antiemetic agents may provide improved protection. These studies show how a rational approach based on preclinical observations can expand the usefulness of a drug at first thought ineffective in chemotherapy-induced emesis.

Antiemetics↗

Rationale for combination antiemetic therapy and strategies for the use of ondansetron in combinations.

The identification of several safe and effective agents for the control of chemotherapy-induced nausea and vomiting has prompted an intensive effort to develop combination antiemetic regimens. The principal rationale for development of drug combinations is the potential for blocking different types of neurotransmittor receptors controlling the emetic process. Studies have shown that the combination of a neurotransmitter receptor blocker, a corticosteroid, and a benzodiazepine improves antiemetic efficacy, lessens side effects, and decreases the length of treatment and the number of drug administrations. Ondansetron appears to be an excellent antiemetic for use in combination programs because of its highly selective, 5-hydroxytryptamine (5-HT3)-blocking properties and its proven single-agent effectiveness and safety. Preliminary data show that ondansetron can be combined with dexamethasone safely with enhanced antiemetic results. Ondansetron merits further study in combination antiemetic programs.

Antiemetics↗

[Antiemetics and its clinical evaluations].

Nausea and vomiting induced by anticancer agents are common problems associated with chemotherapy for cancer. Recent trials have examined a variety of antiemetics, representing several different classes of drugs. High dose metoclopramide provided the impetus for many of the current studies because of its effect against cisplatin induced vomiting. However, current regimens are not yet entirely effective in many patients receiving cisplatin or other highly emetogenic anticancer agents. A promising new class of antiemetics, 5-hydroxytryptamine receptor antagonists are undergoing clinical evaluations. Members of this class are easily and safely administered to patients receiving cisplatin or other emetogenic anticancer agents. These are highly active antiemetics, both prophylactic and interventional treatment. Lack of extrapyramidal reaction and other adverse effects associated with its use makes the drug a very attractive one. However, studies of antiemetics require consideration of methodologic issues that may not be of concern in trials of anticancer agents. The results of these studies can be affected by the patient population, the sample size, pharmacologic variables, the trial design, the method of analysis, etc. Recently, developments both in new-antiemetics and better ways of using the existing ones, lead us to cautious thought that nausea and vomiting due to cancer chemotherapy can be controlled substantially with benefit to the patients.

Antiemetics↗

[Methylprednisolone as an antiemetic in the chemotherapy of ovarian cancer].

The authors examined the antiemetic effect of methylprednisolone (Lemod Solu) of the firm "Upjoh" in 35 patients with ovarian cancer in the course of the cisplatinum therapy. The control group comprised 15 patients with the same degree of ovarian cancer spreading in whom metoclopramide was used as the antiemetic. The antiemetic effect of methylprednisolone was found in the three fifths of patients having received the preparation from the first cisplatinum therapy cycle and in more than half of those in whom methylprednisolone was included in the second or third cisplatinum therapy cycle. The antiemetic effect of methylprednisolone proved to be significantly better than that of metoclopramide whose antiemetic effect was recorded in one fifth of the patients.

Antiemetics↗

Antiemetic efficacy of high-dose intravenous metoclopramide and dexamethasone in patients receiving cisplatin-based chemotherapy: a randomized controlled trial.

High-dose intravenous (IV) metoclopramide has shown efficacy with few side effects for the treatment of nausea and vomiting on the day of cisplatin administration. From November 1984 to January 1986, two randomized trials in an antiemetic study were conducted. In trial I, the antiemetic effect of a short course of high-dose dexamethasone was compared with that of high-dose metoclopramide in 29 patients with lung cancer receiving chemotherapy containing cisplatin (80 mg/m2 IV) in a randomized controlled trial. Dexamethasone was given IV at a dose of 16 mg 1/2 hr before and 8 mg, 1 1/2, 3 1/2 and 5 1/2 hr after cisplatin. Metoclopramide was given IV at a dose of 2 mg/kg, 1/2 hr before and 1 1/2, 3 1/2 and 5 1/2 hr after cisplatin. Major emetic control (0-2 episodes of vomiting) during the 24 hr after cisplatin administration was achieved in 55% (6/11) and 67% (12/18) of the patients receiving dexamethasone and metoclopramide, respectively, without serious toxicity. The duration of nausea or anorexia was similar for the two treatment groups. In trial II, the combination of metoclopramide and dexamethasone was compared with metoclopramide alone to assess the additive antiemetic effect of the two drugs in 23 patients with lung cancer receiving cisplatin at a dose of 120 mg/m2 IV in a randomized cross-over study. A major antiemetic response was observed in 27% (3/11) and 92% (11/12) of the patients receiving metoclopramide alone and metoclopramide plus dexamethasone, respectively (p less than 0.005). The duration of nausea and anorexia was similar for the two treatment groups. Patients tended to prefer the combination of metoclopramide and dexamethasone; however, the difference was not statistically significant (p = 0.14) in the small number of patients entered in this study. Despite excellent control of acute chemotherapy-induced emesis, 45% of 52 patients experienced delayed nausea and vomiting more than 24 hr after cisplatin administration even among those who had had an excellent short-term response to the antiemetic agents.

Adult↗

Antiemetics for patients treated with antitumor chemotherapy.

The clinical efficacy of antiemetic drugs was tested in cancer patients who were given a placebo and two antiemetic drugs alone and in combination according to random sequences. The method of investigation allowed assessment of the antiemetic effect and side effects of each drug or combination of drugs using a minimum number of patients. The trial design takes into account carry-over effects and biased selection and is potentially useful in the study of drug side effects. Fifteen patients received cyclizine, metoclopramide, cyclizine and metoclopramide, or placebo in a random sequence without evidence that the drugs tested were better than the placebo. A combination of Nabilone and metoclopramide was used in an unrandomized pilot study (prior to the withdrawal of Nabilone from clinical use); these patients recorded better scores for nausea and vomiting and patient acceptability than those in the randomized study. Present antiemetics remain inadequate and although cannabinol derivatives show an improved antiemetic effect, they cause moderate side effects themselves.

Adolescent↗

Which antiemetic?

The choice of antiemetic should not be arbitrary, but should be based on knowledge of the different pathways of the various stimuli that lead to nausea and vomiting and the neuroreceptors involved. The steps to be taken in choosing an appropriate antiemetic are described. They are (a) to establish the probable cause of the nausea and vomiting, (b) to consider the afferent pathways involved, (c) to define the neuroreceptors activated at each of these sites, (d) to select the group of antiemetics that antagonizes these neuroreceptors, and (e) to choose the most potent antiemetic with the fewest side effects in that group. Causes for failure to respond to a chosen antiemetic are considered and the action to be taken is described.

Antiemetics↗

[Comparison of clinical effects between granisetron alone and combination of granisetron and methylprednisolone against the nausea and vomiting induced by CDDP chemotherapy--comparative study by the cross-over trial. University of Tsukuba Antiemetics Study Group].

A cross-over clinical trial was carried out to compare the antiemetic effect and safety between granisetron alone (40 micrograms/kg) and the combination of granisetron and methylprednisolone (MP: 10 mg/kg) in urological cancer patients treated with cisplatin. Forty-eight courses were given with granisetron alone and 47 courses with both granisetron and MP. The antiemetic effect of nausea and vomiting was evaluated in the acute emetic phase. during the 24 hours following the CDDP administration, and in the delayed emetic phase, 2 to 7 days after the administration. Combination therapy of granisetron and MP demonstrated a greater antiemetic effect during the 72 hours following the CDDP administration than by granisetron alone. But there was no significant difference in antiemetic effect between combination therapy and granisetron alone after the 3rd day. Combination therapy also demonstrated more efficacy in complete antiemetic effect, with no emesis and less than moderate nausea, than by granisetron alone. Both treatments showed no side effects and were safe.

Aged↗

Risk factors and antiemetic management of chemotherapy-induced nausea and vomiting.

PURPOSE/OBJECTIVES: To review the emetic potential of chemotherapeutic agents and the specific factors that may help to identify patients who are most vulnerable to nausea and vomiting following chemotherapy. To review the classes of antiemetic drugs that effectively control nausea and vomiting associated with chemotherapeutic regimens. DATA SOURCES: Journal articles, abstracts, and clinical experience. DATA SYNTHESIS: The trend toward outpatient care requires aggressive antiemetic therapy from the outset, with clear recognition of the risk factors for chemotherapy-induced nausea and vomiting. The basic categories of antiemetics include 5-hydroxytryptamine, (5-HT3)-receptor antagonists, phenothiazines, butyrophenones, substituted benzamides, and cannabinoids. Additional agents often used in combination with these antiemetics include corticosteroids and benzodiazepines. CONCLUSIONS: The 5-HT3-receptor antagonists offer enhanced control of emesis while causing few side effects. For highly emetogenic chemotherapy regimens, the combination of 5-HT3-receptor antagonists and dexamethasone appears superior to other single agents or combinations in preventing nausea and vomiting. IMPLICATIONS FOR NURSING PRACTICE: Nursing care involves educating patients about self-care initiatives for effective management of chemotherapeutic side effects, including compliance with prescribed antiemetic regimens to prevent nausea and vomiting.

Adult↗