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PubMed1992

Oral transmucosal fentanyl citrate for preanesthetic medication of pediatric day surgery patients with and without droperidol as a prophylactic anti-emetic.

he safety and efficacy of oral transmucosal fentanyl citrate (OTFC) as a preanesthetic medication and the efficacy of droperidol as a prophylactic anti-emetic were evaluated in 100 children aged 2-8 yr undergoing general anesthesia for outpatient surgery. Patients were randomly assigned to one of four groups and managed in a double-blinded manner: 1) placebo lozenge 45 min preoperatively and placebo (normal saline) injected intravenously after induction of anesthesia; 2) placebo lozenge 45 min preoperatively and 50 micrograms/kg droperidol intravenously after induction; 3) 15-20 micrograms/kg OTFC lozenge 45 min preoperatively and placebo intravenously after induction; and 4) 15-20 micrograms/kg OTFC lozenge 45 min preoperatively and droperidol 50 micrograms/kg intravenously after induction. Anesthesia was induced and maintained with halothane and nitrous oxide in oxygen. Heart rate, respiratory rate, blood pressure, and hemoglobin oxygen saturation (SpO2) were monitored throughout the study. Scoring systems were used to evaluate sedation, anxiety, cooperation, and ease and quality of anesthetic induction. Emergence, recovery, and discharge times were recorded. Nausea, vomiting, and adverse effects were noted. Preoperatively, children receiving OTFC had significantly greater sedation, slower respiratory rates, lower SpO2, and less excitement during induction. Postoperative nausea and vomiting occurred significantly more frequently after OTFC than after placebo. Prophylactic droperidol did not significantly reduce the incidence of nausea and vomiting. The authors conclude that, in pediatric surgical outpatients, OTFC reliably induces preoperative sedation and facilitates inhalation induction of anesthesia, but it is associated with significant decreases in respiratory rate and SpO2 and a high incidence of postoperative nausea and vomiting that is not significantly reduced by prophylactic droperidol.

Administration, Oral↗

PubMed1998

Increased risk of venous thrombosis in carriers of natural anticoagulant deficiencies. Results of the family studies of the Spanish Multicenter Study on Thrombophilia (EMET study).

Several studies have demonstrated a higher risk of thrombosis in carriers of anticoagulant deficiencies than in non-deficient individuals from families with thrombophilia. The prevalences in Spain were established in a multicenter study (the EMET study) and all the deficient individuals were invited to recruit all available family members to be screened for the same deficiency in order to establish the risk of thrombosis in deficient individuals. Five-hundred-and-eighty-three individuals from 114 families with natural anticoagulant deficiencies were analysed. Propositi and relatives with a history of thrombosis were asked about the localization and the age at the first episode and whether or not it was spontaneous. Three families with antithrombin deficiency, 35 with protein C, 60 with protein S, four with plasminogen, four with heparin cofactor II, seven with combined deficiencies and one family with dysfibrinogenemia were included in the analysis. The risk of thrombosis was increased for individuals deficient in antithrombin (adjusted odds ratio 21.23; 95% confidence interval 5.71-78.94), protein C (adjusted odds ratio 12.62; 95% confidence interval 4.75-33.51), protein S type I (adjusted odds ratio 19.95; 95% confidence interval 7.40-53.82), protein S type III (adjusted odds ratio 8.11; 95% confidence interval 2.66-21.99) or in protein C plus protein S (adjusted odds ratio 8.99; 95% confidence interval 2.79-28.93), but not for those deficient in plasminogen or heparin cofactor II. The thrombosis-free survival was shortened for deficient individuals in antithrombin (median 30 years), protein C (median 46 years), protein S type-I (median 48 years), protein S type III (median 61 years) and combined protein C and S (median 40 years). In conclusion, individuals carrying anticoagulant deficiencies have an increased risk of thrombosis, especially those with antithrombin, protein C or type I protein S deficiencies.

Adult↗

PubMed1992

Interaction of epirubicin with other cytotoxics and anti-emetic drugs.

Epirubicin is usually administered in combination with other cytotoxics. Few pharmacological studies address whether relevant clinical interactions occur in vitro between these drugs. This study investigated whether epirubicin interacted with other cytotoxics or anti-emetics. The following drugs were prepared at pharmacological concentrations, etoposide (200 micrograms/ml), 5-fluorouracil (120 micrograms/ml), cisplatin (100 micrograms/ml), vincristine (100 micrograms/ml) and cyclophosphamide (1 micrograms/ml) respectively were admixed with epirubicin (1 micrograms/ml). Epirubicin was analysed by high performance liquid chromatography using in-line UV and fluorescence detectors. Experiments were performed in quadruplicate. No significant interactions were noted. The experiments were repeated for stemetil and maxolon. Maxolon did not interact with epirubicin but stemetil produced an interfering peak in the assay. We conclude that interaction studies are an important step in the workup of chemotherapy regimens.

Antiemetics↗

PubMed1993

Assessing the benefits of anti-emetic innovation.

This paper reviews recent anti-emetic developments, with particular reference to the 5-HT3 receptor antagonists. These drugs are at least as effective as conventional regimens for controlling acute nausea and vomiting in patients receiving highly or moderately emetogenic chemotherapy and abdominal radiotherapy. They have less side effects than do alternative drugs. Improved control of acute nausea and vomiting by 5-HT3 receptor antagonists seems to reduce anticipatory symptoms in subsequent cycles. Dexamethasone enhances activity of 5-HT3 receptor antagonists in highly emetogenic chemotherapy. Improved control of acute nausea and vomiting by 5-HT3 receptor antagonists may remove one obstacle to offering palliative chemotherapy.

Antiemetics↗

PubMed1995

The pattern of emesis following high-dose cyclophosphamide and the anti-emetic efficacy of ondansetron.

Two randomized, double-blind placebo-controlled ondansetron dose ranging studies in patients receiving high-dose cyclophosphamide (with or without doxorubicin) were completed in the US. These studies enable the pattern of emesis and nausea for 3 days following high-dose cyclophosphamide to be described and give some insight into the mechanisms of emesis which may be operating. Nausea and vomiting induced by cyclophosphamide-based chemotherapy has a long latency of onset (8-13 h) and continues for at least 3 days. These findings are of particular importance as many of these patients receive chemotherapy as outpatients and emphasize the need for appropriate anti-emetic prophylaxis for patients at home. Ondansetron was extremely effective over this time in the control of emesis and nausea. These results suggest that high-dose cyclophosphamide-induced emesis over days 1-3 is largely mediated via 5-hydroxytryptamine (5-HT) and 5-HT3 receptors.

Antiemetics↗

PubMed1997

The anti-emetic efficacy of a combination of ondansetron and droperidol.

The anti-emetic efficacy of a combination of ondansetron 8 mg with either droperidol 0.75 mg or 1.25 mg given prophylactically was studied in a randomised blinded trial of 94 female inpatients with a previous history of postoperative nausea and vomiting and scheduled to have laparoscopic surgery. A standardised general anaesthetic technique was used for all patients. The mean estimated risk of postoperative sickness according to predictive patient characteristics was 65% for both treatment groups. During the 24 h study period, the proportion of patients with nausea was similar (35%) in both groups, and vomiting occurred in 16% and 14% of the patients in the droperidol 0.75 mg and 1.25 mg groups, respectively. No serious adverse events were observed. Ondansetron in combination with droperidol 0.75 mg resulted in less drowsiness than in combination with 1.25 mg (p = 0.03). In conclusion, a prophylactic combination treatment of ondansetron 8 mg with a small dose of droperidol was clinically effective and well tolerated for the prevention of postoperative nausea and vomiting after laparoscopic surgery in patients with a high probability of nausea and vomiting.

Adult↗

PubMed1989

The effect on motion sickness and oculomotor function of GR 38032F, a 5-HT3-receptor antagonist with anti-emetic properties.

1. The 5-hydroxytryptamine (5-HT3) receptor antagonist, GR 38032F, which possesses potent anti-emetic properties in vomiting induced by cancer chemotherapeutic drugs, has been tested to determine its value in the prophylaxis of motion sickness induced by cross-coupled stimulation. The double-blind trial compared GR 38032F with both a placebo (lactose) and with hyoscine. In addition, studies of ocular pursuit and saccadic eye movements were carried out following the administration of each drug. 2. The prophylactic effect of GR 38032F on motion-induced nausea was indistinguishable from that of placebo, whereas following hyoscine subjects showed a highly significant (P less than 0.001) increase in tolerance to cross-coupled stimulation. Tests of oculomotor function showed no effect on saccadic eye movement from either drug. However, both drugs produced a significant (P less than 0.05) though small reduction in eye velocity gain during pursuit eye movement. 3. These findings suggest that the 5-HT3 receptor is not involved in the neural pathways that bring about motion sickness, but that it may have a role in the control of ocular pursuit. The absence of an anti-motion sickness effect from a drug that is effective in the treatment of vomiting induced by cancer chemotherapy serves to emphasize that different neural mechanisms are involved in the generation of motion sickness.

Adolescent↗

PubMed1982

Droperidol (Dehydrobenzperidol): postoperative anti-emetic effect when given intravenously to gynaecological patients.

In a double-blind investigation, comprising 300 gynaecological patients, the prophylactic use of droperidol i.v. at the start of the anaesthesia produced significant reduction in the frequency of nausea and vomiting postoperatively in the first 24 h from 34.4% to 10.3% (P=0.0001). There was no significant difference between the effect of droperidol 2.5 mg and 5 mg (P=0.45). Increased postoperative sedation was the only side-effect of any importance observed; however, this did not result in any increased period of observation in the recovery room, and the majority of patients considered it advantageous. Droperidol is recommended as a prophylactic anti-emetic for selected groups of patients, given as 2.5 mg i.v. at the start of the anaesthesia.

Adult↗

PubMed1998

Surgeon's experience as a factor for emetic sequelae after middle ear surgery.

PURPOSE: To test the hypothesis that an experienced surgeon is associated with less postoperative nausea and vomiting (PONV). METHODS: A post hoc analysis was done on the data of 167 patients from 3 randomized studies on the prevention of PONV, with transdermal scopolamine, ondansetron and propofol, in middle ear surgery under general anaesthesia. RESULTS: The patients in the residents' group suffered more from PONV (69% vs. 42%, P < 0.01) and from retching or vomiting (52% vs. 23%, P < 0.001) than those in the specialists' group. The proportion of patients needing droperidol was also higher in the residents' group (66% vs. 27%, P < 0.001). The durations of anaesthesia and surgery seemed to correlate positively with PONV. In matched-pair analysis, residentship was confirmed as a risk factor for emetic symptoms. In the residents' group, prophylaxis of PONV resulted in a decrease in retching and vomiting from 71% to 29% (P < 0.01), and in patients needing droperidol from 87% to 46% (P < 0.01). CONCLUSION: The patients operated by residents need more aggressive prophylaxis for PONV than those operated by specialists in middle ear surgery.

Adult↗

PubMed1994

Effects of anti-emetics on water excretion in humans.

1. The anti-emetic drug metoclopramide has been shown to stimulate secretion of the antidiuretic hormone arginine vasopressin. Since metoclopramide is used to treat nausea, which is another potent stimulus to vasopressin secretion, the aim of this study was to determine whether metoclopramide might limit free water excretion and so cause hyponatraemia. 2. Metoclopramide 20 mg (0.2-0.3 mg/kg), prochlorperazine 12.5 mg (0.1-0.2 mg/kg) and placebo were administered intravenously in a double blind randomized crossover way at 2 week intervals and the effects on urine flow rate, plasma osmolality, thirst ratings and plasma sodium and atrial natriuretic peptide concentrations determined in water-loaded (10 mL/kg) healthy young men. 3. There were no differential effects on any variable of either drug versus placebo. 4. These results indicate that metoclopramide is unlikely to cause any significant water retention in a clinical setting or precipitate hyponatraemia.

Adult↗

PubMed2000

Gastric fundus relaxation and emetic sequences induced by apomorphine and intragastric lipid infusion in healthy humans.

OBJECTIVES: Experimental animal studies have suggested that gastric relaxation precedes emesis, whether induced by peripheral or central stimuli. We aimed to quantify the gastric relaxatory and symptomatic responses to a standardized emetic inductor. METHODS: In healthy volunteers, we measured the gastric and symptomatic response to two different proemetic stimuli: a peripheral stimulus (intragastric infusion at 5 ml/min of 50% fat emulsion in water) and a central stimulus (s.c. apomorphine at 0.01 mg/kg). Proximal gastric tone was continuously recorded by an electronic barostat. Symptoms were simultaneously quantified by a graded questionnaire. RESULTS: Lipid-induced gastric relaxation occurred in 17/17 subjects and was followed by nausea in 12/17. The total amount of intragastric fat required to trigger gastric relaxation was 139 +/- 34 ml and to induce nausea, 258 +/- 32 ml. Gastric relaxation after subcutaneous apomorphine occurred in 13/14, and nausea/emesis, in the same 13/14. As expected, timing of events after stimulation was much shorter in response to the central than to the peripheral stimulus. Thus, gastric relaxation began 4.0 +/- 0.6 min after subcutaneous apomorphine and 28 +/- 7 min after the onset of lipid infusion (p < 0.05); likewise, the symptomatic response to central stimulation with apomorphine was 8.5 +/- 1.8 min versus 52 +/- 6 min for lipid infusion, p < 0.05. However, the magnitude of gastric relaxation was quite similar for both stimuli (apomorphine: 208 +/- 35 ml; intragastric lipid: 235 +/- 23 ml). No correlation was observed between the symptomatic response and the magnitude of the gastric relaxation, whether elicited by intragastric infusion of lipids or by subcutaneous apomorphine. Specifically, when symptomatic and gastric motor responses were compared in each of the 14 subjects who received both stimuli, no significant correlation between individual responses was detected. CONCLUSIONS: Gastric relaxation invariably precedes nausea and emesis and is of the same magnitude whether induced by apomorphine (central stimulus) or intragastric lipid infusion (peripheral stimulus). Nevertheless, in some instances and depending on the nature of the stimulus, fundic relaxation is a physiological event unassociated with nausea.

Adult↗

PubMed1999

Pathological effect of synthetic cereulide, an emetic toxin of Bacillus cereus, is reversible in mice.

Cereulide is the causative toxin of the emetic type of food-borne illness caused by Bacillus cereus. This toxin was previously shown to be associated with fulminant liver failure in a human case. Mice were injected i.p. with synthetic cereulide and the development of histopathological changes was examined. Hepatocytes showed mitochondrial swelling with loss of cristae, and dose-dependent increase of small fatty droplets. These microsteatotic hepatocytes were distributed mainly in the pericentral area. At higher cereulide doses, massive degeneration of hepatocytes occurred. The serum values of hepatic enzymes were highest on days 2-3 after the inoculation of cereulide, and rapidly decreased thereafter. General recovery from the pathological changes and regeneration of hepatocytes was observed after 4 weeks.

Animals↗

PubMed1977

Emetic and refusal activity of deoxynivalenol to swine.

The minimum emetic dose of deoxynivalenol to swine weighing 9 to 10 kg was 0.05 mg/kg of body weight intraperitoneally and 0.1 to 0.2 mg/kg orally. There was no emesis by undosed pigs consuming vomitus from pigs orally dosed with deoxynivalenol or penned with such pigs without access to vomitus. Analysis by gas-liquid chromatography of a sample of Gibberella zeae-infected corn containing about 25% visually damaged kernels indicated 12 ppm of deoxynivalenol. Deoxynivalenol added to feed reduced feed consumption of 20- to 45-kg pigs, ranging from a 20% decrease with 3.6 ppm to 90% reduction with 40 ppm. Loss in weight was associated with feed refusal. Feed refusal, however, was much greater for naturally infected corn samples than for feeds with equal concentrations of the pure compound added, indicating the involvement of an additional factor(s) in the swine refusal response.

Animals↗

PubMed1964

Relation of pyrogenic and emetic properties of enterobacteriaceal endotoxin and of staphylococcal enterotoxin.

Martin, William J. (College of Medicine, University of Utah, Salt Lake City), and Stanley Marcus. Relation of pyrogenic and emetic properties of enterobacteriaceal endotoxin and of staphylococcal enterotoxin. J. Bacteriol. 87:1019-1026. 1964.-The pyrogenic, endotoxic fraction of enterobacteriaceal organisms, isolated in a relatively impure or purified state, is both pyrogenic in rabbits and cats as well as emeticogenic in cats in microgram amounts. Employing classical methods for preparation of enterobacteriaceal endotoxin from known enterotoxic strains of Staphylococcus aureus yielded preparations with less than one-hundredth the activity of the enterobacteriaceal material. However, a purified enterotoxin material from an S. aureus strain, with protein-like rather than polysaccharidelike properties, was found to be both pyrogenic and emeticogenic in microgram amounts. These results suggest the probability that the enterobacteriaceal pyrogenemetic substance(s) is a significant part of the whole cell, whereas the staphylococcal enterotoxin is elaborated as a metabolic product which apparently does not accumulate in the whole cell.

Animals↗

PubMed1992

Mechanism of the anti-emetic activity of 5-HT3 receptor antagonists.

Ondansetron, a potent and highly selective 5-HT3 receptor antagonist, prevents emesis following chemotherapy by antagonising the action of 5-hydroxytryptamine (5-HT) at 5-HT3 receptors on vagal afferent neurons that innervate the gastrointestinal tract and 5-HT3 receptors in the central vomiting system. Evidence suggests that chemotherapy induces the release of 5-HT from enterochromaffin cells in the small intestine. This stimulates vagal afferent nerves via 5-HT3 receptors. Information is then relayed, via the vagus nerve, to the central vomiting system. 5-HT3 receptors are also found in the hind-brain vomiting system including the area postrema (the site of the chemoreceptor trigger zone for emesis). Therefore, following chemotherapy, 5-HT activates 5-HT3 receptors at 2 sites to induce emesis. Clinical data showing that a single dose of ondansetron prevents acute emesis suggest that it is important to block the initiation of the emetic reflex. This may prevent the recruitment of central mechanisms involving 5-HT3 receptors.

Antiemetics↗

PubMed1986

Serum bile acids, gamma-glutamyltransferase and routine liver function tests in emetic and nonemetic pregnancies.

The etiology of nausea and vomiting in pregnancy is still unknown. One possibility is that ovarian and placental hormones may play some part. The liver is the major site of metabolic inactivation of steroid hormones. In this study, 102 healthy pregnant women, of whom 62 complained of nausea, were followed throughout pregnancy. Liver function tests were performed to ascertain whether emesis gravidarum is related to impaired hepatic function. In this series, all values were within the normal ranges. Serum levels of total bilirubin and gamma-glutamyl-transferase were significantly decreased and those of total serum bile acids significantly increased in emetic women compared to nonemetic subjects. Furthermore, the metabolic load on the liver seems to follow a biphasic course as there is an apparent minimum in liver function variables in the second trimester. It is concluded that a slow adaptation to the increased hormonal load on the liver might be responsible for the condition of emesis gravidarum.

Adult↗

PubMed2001

Anti-emetics.

Nausea and vomiting are common symptoms of migraine, which can be controlled with a variety of anti-emetics including phenothiazines and antihistamines. Metoclopramide and domperidone have an additional prokinetic effect which may be important in migraine to overcome gastric stasis and enhance absorption of oral medication.

Antiemetics↗

PubMed2007

Transdermal scopolamine: an alternative to ondansetron and droperidol for the prevention of postoperative and postdischarge emetic symptoms.

BACKGROUND: Given the controversy regarding the use of droperidol and the high cost of the 5-HT3 antagonists, a cost-effective alternative for routine use as a prophylactic antiemetic would be desirable. We designed two parallel, randomized, double-blind sham and placebo-controlled studies to compare the early and late antiemetic efficacy and adverse event profile of transdermal scopolamine (TDS) 1.5 mg, to ondansetron 4 mg IV, and droperidol 1.25 mg IV for antiemetic prophylaxis as part of a multimodal regimen in "at risk" surgical populations. METHODS: A total of 150 patients undergoing major laparoscopic (n = 80) or plastic (n = 70) surgery procedures received either an active TDS patch (containing scopolamine 1.5 mg) or a similar appearing sham patch 60 min before entering the operating room. All patients received a standardized general anesthetic technique. A second study medication was administered in a 2-mL numbered syringe containing either saline (for the two active TDS groups), droperidol, 1.25 mg, or ondansetron, 4 mg (for the sham patch groups), and was administered IV near the end of the procedure. The occurrence of postoperative nausea and vomiting/retching, need for rescue antiemetics, and the complete response rates (i.e., absence of protracted nausea or repeated episodes of emesis requiring antiemetic rescue medication) was reported. In addition, complaints of visual disturbances, dry mouth, drowsiness, and restlessness were noted up to 72 h after surgery. RESULTS: There were no significant differences in any of the emetic outcomes or need for rescue antiemetics among the TDS, droperidol, and ondansetron groups in the first 72 h after surgery. The complete response rates varied from 41% to 51%, and did not significantly differ among the treatment groups. The overall incidence of dry mouth was significantly more frequent in the TDS groups than in the droperidol and ondansetron groups (21% vs 3%). CONCLUSIONS: Premedication with TDS was as effective as droperidol (1.25 mg) or ondansetron (4 mg) in preventing nausea and vomiting in the early and late postoperative periods. However, the use of a TDS patch is more likely to produce a dry mouth.

Adjuvants, Anesthesia↗