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Joachim Boldt - One of the best experts on this subject based on the ideXlab platform.

  • Postoperative nausea and vomiting after surgery for prognathism: not only a question of patients' comfort. A placebo-controlled comparison of Dolasetron and droperidol.
    Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery, 2008
    Co-Authors: Swen N. Piper, K. D. Röhm, Peter Kranke, Joachim Boldt, Wolfgang H. Maleck, Rudolf Seifert, Stefan W. Suttner
    Abstract:

    Summary Introduction The aim of this study was to evaluate the efficacy of Dolasetron and droperidol (DHB) for preventing postoperative nausea and vomiting (PONV) in patients undergoing surgery for prognathism. Material and methods In a randomised, placebo-controlled, double-blind trial, the efficacy of 12.5mg Dolasetron i.v. and 1.25mg DHB was evaluated in preventing PONV in 83 patients undergoing surgery for prognathism. Patients were allocated randomly to one of three groups: group A ( n =27) received 12.5mg Dolasetron intravenously (i.v.), group B ( n =27) received 1.25mg DHB i.v. and placebo group C ( n =29) received saline 0.9%. If patients complained of retching or vomiting or if patients demanded antiemetics, 20mg metoclopramide (MCP) i.v. was given. Postoperative nausea, postoperative vomiting, or nausea and vomiting was assessed in the postoperative period at 0–4h and overall between 0 and 24h. Results A significant reduction in the incidence of postoperative nausea and/or vomiting was observed in the Dolasetron group (33%) when compared with DHB (81%) and placebo (86%) treated patients. No other significant differences between the DHB and the placebo group were found. Dolasetron (11%) significantly reduced vomiting in comparison with the DHB (52%) and placebo group (52%). The use of postoperative MCP per patient was significantly lower in the Dolasetron group when compared with both other groups. Dolasetron significantly reduced the postoperative nausea and/or vomiting-score when compared with both other groups. There was no significant difference between DHB- and placebo-treated patients with regard to nausea and/or vomiting. Conclusion Intravenous Dolasetron (12.5mg) is more effective than either intravenous DHB (1.25mg) or placebo for preventing PONV after surgery for prognathism. It also was significantly superior to either DHB or placebo concerning nausea and vomiting and the need for MCP rescue medication.

  • Prevention of post-operative nausea and vomiting. Randomised comparison of Dolasetron versus Dolasetron plus dexamethasone
    Der Anaesthesist, 2003
    Co-Authors: Swen N. Piper, J. G. Triem, K. D. Röhm, Peter Kranke, W. H. Maleck, Joachim Boldt
    Abstract:

    BACKGROUND: Postoperative nausea and vomiting (PONV) are frequent complications after operations. The aim of this study was to assess the efficacy of combined Dolasetron plus dexamethasone versus Dolasetron alone with respect to the incidence and severity of emetic symptoms and patients satisfaction. METHODS: In a prospective, randomised, double-blind study, 150 patients scheduled for hysterectomy or breast surgery were allocated to one of the following two groups: group A received 50 mg Dolasetron orally and group B 50 mg Dolasetron orally plus 8 mg dexamethasone intravenously. The follow-up was for 24 h after surgery. RESULTS: In group A PONV was significantly more frequent (28%) compared to group B (12.0%). The incidence of vomiting was significantly lower in patients receiving Dolasetron plus dexamethasone (0%) in comparison to patients receiving Dolasetron (8.0%). Furthermore,patients satisfaction was significantly higher in group B compared to group A. About 6 or 7 patients need to be treated with additional dexamethasone instead of a placebo for one patient to benefit from this intervention (i.e. to stay free from PONV) who otherwise would have suffered from PONV. CONCLUSIONS: Combining oral Dolasetron with intravenous dexamethasone further improves the antiemetic efficacy of Dolasetron. With a number-needed-to-treat of about 6 the additional benefit might be considered clinically relevant.

  • Prophylaxe von postoperativer Übelkeit und postoperativem Erbrechen. Randomisierter Vergleich von Dolasetron versus Dolasetron mit Dexamethason
    Anaesthesist, 2003
    Co-Authors: Swen N. Piper, J. G. Triem, K. D. Röhm, W. H. Maleck, R. Kranke, Joachim Boldt
    Abstract:

    Background. Postoperative nausea and vomiting (PONV) are frequent complications after operations.The aim of this study was to assess the efficacy of combined Dolasetron plus dexamethasone versus Dolasetron alone with respect to the incidence and severity of emetic symptoms and patients satisfaction. Methods. In a prospective, randomised, double-blind study, 150 patients scheduled for hysterectomy or breast surgery were allocated to one of the following two groups: group A received 50 mg Dolasetron orally and group B 50 mg Dolasetron orally plus 8 mg dexamethasone intravenously.The follow-up was for 24 h after surgery. Results. In group A PONV was significantly more frequent (28%) compared to group B (12.0%).The incidence of vomiting was significantly lower in patients receiving Dolasetron plus dexamethasone (0%) in comparison to patients receiving Dolasetron (8.0%). Furthermore, patients satisfaction was significantly higher in group B compared to group A. About 6 or 7 patients need to be treated with additional dexamethasone instead of a placebo for one patient to benefit from this intervention (i.e. to stay free from PONV) who otherwise would have suffered from PONV. Conclusions. Combining oral Dolasetron with intravenous dexamethasone further improves the antiemetic efficacy of Dolasetron. With a number-needed-to-treat of about 6 the additional benefit might be considered clinically relevant.

  • Dolasetron reduces pain on injection of propofol
    Anasthesiologie Intensivmedizin Notfallmedizin Schmerztherapie : AINS, 2002
    Co-Authors: Swen N. Piper, K. D. Röhm, W. H. Maleck, M. Papsdorf, Mattinger P, Joachim Boldt
    Abstract:

    OBJECTIVE Pain on injection is a well known side-effect of propofol. The present study was designed to assess the efficacy of Dolasetron, a 5-HT 3 -antagonist, in prophylaxis of pain on injection of propofol compared with lidocaine and placebo. METHODS Prospective, randomised, double-blinded study including 150 patients randomly assigned to one of three groups: Group A received 12.5 mg Dolasetron, group B 40 mg lidocaine and group C saline 0.9 % as placebo. After occluding the venous drainage the test medication was given. The occlusion was released after 1 min and 2.0 mg/kg Propofol was administered over a period of 30 sec. The patients were asked whether they felt any pain during the administration. Pain on injection was judged by using a four-point scale. RESULTS Incidence of pain on injection as well as the severity of pain was significantly reduced by lidocaine (62 % pain free) compared with placebo (28 %). Severity, but not incidence of pain on injection was significantly reduced by Dolasetron (50 %) compared with placebo. There was no significant difference between Dolasetron and lidocaine. CONCLUSION Dolasetron and lidocaine were effective in preventing pain of injection secondary to propofol.

  • Dolasetron for preventing postanesthetic shivering.
    Anesthesia and analgesia, 2002
    Co-Authors: Swen N. Piper, Kerstin D. Röhm, Wolfgang H. Maleck, Moritz T. Fent, Stefan W. Suttner, Joachim Boldt
    Abstract:

    UNLABELLED We designed this study to assess the efficacy of Dolasetron compared with clonidine and placebo in prophylaxis of postanesthetic shivering. We included 90 patients undergoing elective abdominal or urologic surgery. The patients were randomly assigned to one three groups (each group n = 30) using a double-blinded study protocol: Group A received 12.5 mg Dolasetron, Group B 3 microg/kg clonidine, and Group C saline 0.9% as placebo. The medication was given after the induction of anesthesia. Postanesthetic shivering was judged by using a five-point scale. In the Clonidine group, 86.6% showed no shivering, whereas in the Dolasetron and Placebo groups, only 63.3% and 66.6%, respectively, were symptom free. Only clonidine, but not Dolasetron, significantly reduced the incidence and the severity of shivering. We conclude that clonidine is effective in preventing shivering when given before surgery, whereas Dolasetron, at the dose used, is not effective. IMPLICATIONS Shivering, an irregular muscular fasciculation lasting longer than 15 s, is a common complication secondary to general anesthesia. We compared Dolasetron with clonidine (an established antishivering drug) in the prevention of postanesthetic shivering. Dolasetron 12.5 mg was not effective.

William F. Hahne - One of the best experts on this subject based on the ideXlab platform.

  • Single- and multiple-dose pharmacokinetics of oral Dolasetron and its active metabolites in healthy volunteers: part 2.
    Biopharmaceutics & drug disposition, 1999
    Co-Authors: Dan C. Dimmitt, Lorene A. Martin, William F. Hahne, Thangam Arumugham, Youn Sung Choo, Scott Weir
    Abstract:

    Abstract The single- and multiple-dose pharmacokinetics and dose-proportionality of oral Dolasetron and its active metabolites over the therapeutic dose range was investigated in 18 healthy men. In an open-label, randomized, complete three-way crossover design, each subject received three separate doses: 50, 100, and 200 mg doses of Dolasetron mesylate solution given orally. Each dose was administered on the morning of Days 1 and 3-7 during each of the three treatment periods. Serial blood and urine samples were collected for 48 h after the first and last doses. Blood was analysed for Dolasetron and hydroDolasetron concentrations; urine was analysed for Dolasetron, the R(+) and S(-)-enantiomers of hydroDolasetron, and the 5'-hydroxy and 6'-hydroxy metabolites of hydroDolasetron. Dolasetron was rarely detected in plasma. HydroDolasetron was formed rapidly, with a time to maximum concentration (t(max)) of less than 1 h. Steady-state conditions for hydroDolasetron were reached 2-3 days after starting once-daily dosing. Although statistical significance was found for hydroDolasetron AUC(0->infinity) and C(max) between dose groups after both single and multiple doses of Dolasetron, the differences were small and unlikely to be of clinical significance. About 17-22% of the dose was excreted in urine as hydroDolasetron, with the majority (> 83%) as the R(+) enantiomer.

  • Intravenous pharmacokinetics and absolute oral bioavailability of Dolasetron in healthy volunteers: part 1.
    Biopharmaceutics & drug disposition, 1999
    Co-Authors: Dan C. Dimmitt, Lorene A. Martin, William F. Hahne, Thangam Arumugham, Youn Sung Choo, Scott J. Weir
    Abstract:

    In this first part of a two-part investigation, the intravenous dose proportionality of Dolasetron mesylate, a 5-HT 3 , receptor antagonist, and the absolute bioavailability of oral Dolasetron mesylate were investigated. In an open-label, randomized, four-way crossover design, 24 healthy men between the ages of 19 and 45 years received the following doses: 50, 100, or 200 mg Dolasetron mesylate administered by 10-min intravenous infusion or 200 mg Dolasetron mesylate solution administered orally. Serial blood and urine samples were collected for 48 h after dosing. Following intravenous administration, Dolasetron was rapidly eliminated from plasma, with a mean elimination half-life (t 1/2 ) of less than 10 min. Dolasetron was rarely detected in plasma after oral administration of the 200 mg dose. HydroDolasetron, the active primary metabolite of Dolasetron, appeared rapidly in plasma following both oral and intravenous administration of Dolasetron mesylate, with a mean time to maximum concentration (t max ) of less than I h. The mean t 1/2 of hydroDolasetron ranged from 6.6-8.8 h. The plasma area under the concentration-time curve (AUC (0- ∞ ) ) for both Dolasetron and hydroDolasetron increased proportionally with dose over the intravenous dose range of 50-200 mg Dolasetron mesylate. Approximately 29-33% and 22% of the dose was excreted in urine as hydroDolasetron following intravenous and oral administration of Dolasetron, respectively. For Dolasetron as well as hydroDolasetron, mean systemic clearance (Cl), volume of distribution (V d ), and t 1/2 were similar at each Dolasetron dose. The mean 'apparent' bioavailability of Dolasetron calculated using plasma concentrations of hydroDolasetron was 76 The R(+) enantiomer of hydroDolasetron represented the majority of drug in plasma (> 75%) and urine (> 86%). Dolasetron was well tolerated following both oral and intravenous administration.

  • Rationale for the use of a single fixed intravenous Dolasetron dose for the prevention of cisplatin-induced nausea and vomiting
    Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 1998
    Co-Authors: J. B. Whitmore, Michael B. Cramer, Paul J. Hesketh, Thomas H. Grote, Mark G. Kris, Dawn M. Dubois, William F. Hahne
    Abstract:

    Dolasetron mesilate is a selective 5-HT3 receptor antagonist that prevents chemotherapy-induced and postoperative nausea and vomiting. For the majority of patients in intravenous Dolasetron trials for chemotherapy-induced nausea and vomiting, dosing has been based on body weight (mg/kg). The approved weight-based dose is 1.8 mg/kg based on results of controlled clinical trials. However, trials of Dolasetron evaluating oral doses for prevention of chemotherapy-induced emesis, and intravenous doses for prevention and treatment of postoperative emesis have used a fixed milligram dose. To identify an appropriate intravenous fixed milligram dose for the prevention of chemotherapy-induced nausea and vomiting, this analysis was performed to derive efficacy results for fixed milligram doses from pooled results obtained with dosing based on body weight. Intravenous Dolasetron doses for 1,598 patients treated on a mg/kg basis (0.3, 0.6, 1.2, 1.8, 2.4, 3.0 and 5.0 mg/kg) in 14 clinical trials were converted to fixed milligram doses based on weight. Fixed-dose groups were established at doses of 50, 75, 100, 125, 150, and 200 mg. Doses less than or equal to the midpoint between two dose groups were included in the lower dose group. Pooled results showed that the 100 mg intravenous Dolasetron dose group (who received actual doses of 88–112 mg) produced the highest rate (53%) of complete response (0 emetic episodes and no rescue medication in the 24-h period following initiation of chemotherapy).

  • The effect of food on the bioavailability of Dolasetron mesylate tablets
    Biopharmaceutics & drug disposition, 1998
    Co-Authors: Christina Lippert, William F. Hahne, Thangam Arumugham, Anther C. F. Keung, Mark G. Eller, Scott J. Weir
    Abstract:

    Anzemet (Dolasetron mesylate) is being developed for the prevention of chemotherapy-induced emesis and postoperative nausea and vomiting. Twenty-four healthy male subjects were orally dosed with Dolasetron mesylate, 200 mg, after either an overnight fast or a high-fat breakfast. The ratio of the mean area under the plasma concentration-time curve of the reduced active metabolite (MDL 74,156) to infinity (AUC(0-infinity)) values in fed compared to fasting subjects was 86.3% with a 90% confidence interval for the ratio within (80, 125)%, indicating bioequivalence. The ratio of the mean MDL 74,156 maximum plasma concentration (Cmax) values was 70.6% in fed versus fasted subjects. The time to Cmax was statistically significantly longer after the high-fat breakfast (mean values, 1.11 h fasting and 1.80 h fed), probably due to delayed gastric emptying. It may be concluded that, although the rate of absorption was somewhat delayed, the extent of absorption did not change significantly when Dolasetron mesylate was given with food.

  • Effect of Infusion Rate on the Pharmacokinetics and Tolerance of Intravenous Dolasetron Mesylate
    Annals of Pharmacotherapy, 1998
    Co-Authors: Dan C. Dimmitt, Thomas L. Hunt, Anthony J Spalitto, Michael B. Cramer, Ajit K. Shah, Thangam Arumugham, William F. Hahne
    Abstract:

    OBJECTIVETo evaluate the safety, tolerance, and pharmacokinetics of Dolasetron mesylate and its active metabolite hydroDolasetron when Dolasetron mesylate was administered intravenously at increasing infusion rates.DESIGN:A double-blind, placebo-controlled, parallel-group study.METHODS:Forty-nine healthy nonsmoking male volunteers were randomly assigned to receive intravenous doses of Dolasetron mesylate 100 mg or placebo. Three groups of 16 subjects each (12 Dolasetron mesylate, 4 placebo) received escalating infusion rates (50, 100, then 200 mg/min). Physical examinations, vital signs, laboratory tests, and adverse events were recorded before and after administration of the study drug. Serial blood samples and 12-lead electrocardiogram measurements were obtained for 24 hours after the infusion. Plasma samples were analyzed for Dolasetron and hydroDolasetron.RESULTSDolasetron mesylate was well tolerated, with no apparent differences in vital signs or adverse event profiles among the different rates of in...

Swen N. Piper - One of the best experts on this subject based on the ideXlab platform.

  • Postoperative nausea and vomiting after surgery for prognathism: not only a question of patients' comfort. A placebo-controlled comparison of Dolasetron and droperidol.
    Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery, 2008
    Co-Authors: Swen N. Piper, K. D. Röhm, Peter Kranke, Joachim Boldt, Wolfgang H. Maleck, Rudolf Seifert, Stefan W. Suttner
    Abstract:

    Summary Introduction The aim of this study was to evaluate the efficacy of Dolasetron and droperidol (DHB) for preventing postoperative nausea and vomiting (PONV) in patients undergoing surgery for prognathism. Material and methods In a randomised, placebo-controlled, double-blind trial, the efficacy of 12.5mg Dolasetron i.v. and 1.25mg DHB was evaluated in preventing PONV in 83 patients undergoing surgery for prognathism. Patients were allocated randomly to one of three groups: group A ( n =27) received 12.5mg Dolasetron intravenously (i.v.), group B ( n =27) received 1.25mg DHB i.v. and placebo group C ( n =29) received saline 0.9%. If patients complained of retching or vomiting or if patients demanded antiemetics, 20mg metoclopramide (MCP) i.v. was given. Postoperative nausea, postoperative vomiting, or nausea and vomiting was assessed in the postoperative period at 0–4h and overall between 0 and 24h. Results A significant reduction in the incidence of postoperative nausea and/or vomiting was observed in the Dolasetron group (33%) when compared with DHB (81%) and placebo (86%) treated patients. No other significant differences between the DHB and the placebo group were found. Dolasetron (11%) significantly reduced vomiting in comparison with the DHB (52%) and placebo group (52%). The use of postoperative MCP per patient was significantly lower in the Dolasetron group when compared with both other groups. Dolasetron significantly reduced the postoperative nausea and/or vomiting-score when compared with both other groups. There was no significant difference between DHB- and placebo-treated patients with regard to nausea and/or vomiting. Conclusion Intravenous Dolasetron (12.5mg) is more effective than either intravenous DHB (1.25mg) or placebo for preventing PONV after surgery for prognathism. It also was significantly superior to either DHB or placebo concerning nausea and vomiting and the need for MCP rescue medication.

  • Prevention of post-operative nausea and vomiting. Randomised comparison of Dolasetron versus Dolasetron plus dexamethasone
    Der Anaesthesist, 2003
    Co-Authors: Swen N. Piper, J. G. Triem, K. D. Röhm, Peter Kranke, W. H. Maleck, Joachim Boldt
    Abstract:

    BACKGROUND: Postoperative nausea and vomiting (PONV) are frequent complications after operations. The aim of this study was to assess the efficacy of combined Dolasetron plus dexamethasone versus Dolasetron alone with respect to the incidence and severity of emetic symptoms and patients satisfaction. METHODS: In a prospective, randomised, double-blind study, 150 patients scheduled for hysterectomy or breast surgery were allocated to one of the following two groups: group A received 50 mg Dolasetron orally and group B 50 mg Dolasetron orally plus 8 mg dexamethasone intravenously. The follow-up was for 24 h after surgery. RESULTS: In group A PONV was significantly more frequent (28%) compared to group B (12.0%). The incidence of vomiting was significantly lower in patients receiving Dolasetron plus dexamethasone (0%) in comparison to patients receiving Dolasetron (8.0%). Furthermore,patients satisfaction was significantly higher in group B compared to group A. About 6 or 7 patients need to be treated with additional dexamethasone instead of a placebo for one patient to benefit from this intervention (i.e. to stay free from PONV) who otherwise would have suffered from PONV. CONCLUSIONS: Combining oral Dolasetron with intravenous dexamethasone further improves the antiemetic efficacy of Dolasetron. With a number-needed-to-treat of about 6 the additional benefit might be considered clinically relevant.

  • Prophylaxe von postoperativer Übelkeit und postoperativem Erbrechen. Randomisierter Vergleich von Dolasetron versus Dolasetron mit Dexamethason
    Anaesthesist, 2003
    Co-Authors: Swen N. Piper, J. G. Triem, K. D. Röhm, W. H. Maleck, R. Kranke, Joachim Boldt
    Abstract:

    Background. Postoperative nausea and vomiting (PONV) are frequent complications after operations.The aim of this study was to assess the efficacy of combined Dolasetron plus dexamethasone versus Dolasetron alone with respect to the incidence and severity of emetic symptoms and patients satisfaction. Methods. In a prospective, randomised, double-blind study, 150 patients scheduled for hysterectomy or breast surgery were allocated to one of the following two groups: group A received 50 mg Dolasetron orally and group B 50 mg Dolasetron orally plus 8 mg dexamethasone intravenously.The follow-up was for 24 h after surgery. Results. In group A PONV was significantly more frequent (28%) compared to group B (12.0%).The incidence of vomiting was significantly lower in patients receiving Dolasetron plus dexamethasone (0%) in comparison to patients receiving Dolasetron (8.0%). Furthermore, patients satisfaction was significantly higher in group B compared to group A. About 6 or 7 patients need to be treated with additional dexamethasone instead of a placebo for one patient to benefit from this intervention (i.e. to stay free from PONV) who otherwise would have suffered from PONV. Conclusions. Combining oral Dolasetron with intravenous dexamethasone further improves the antiemetic efficacy of Dolasetron. With a number-needed-to-treat of about 6 the additional benefit might be considered clinically relevant.

  • Dolasetron but not metoclopramide prevents nausea and vomiting in patients undergoing laparoscopic cholecystectomy
    Canadian Journal of Anaesthesia-journal Canadien D Anesthesie, 2002
    Co-Authors: Swen N. Piper, Kerstin D. Röhm, Wolfgang H. Maleck, Stefan W. Suttner, Eberhard Larbig, J Boldt
    Abstract:

    Objectif: Les nausees et vomissements postoperatoires (NVPO) sont une des complications les plus frequentes de l'anesthesie generale. Le but de cette etude etait de comparer l'efficacite antiemetique du Dolasetron et du metoclopramide sous anesthesie avec un agent volatil ou iv (AIV). Methode : Trois cent quatre-vingt-sept patients (ASA I-III) subissant une cholecystectomie laparoscopique ont ete enroles dans cette etude en double-aveugle et controlee par placebo comparant l'efficacite de 12,5 mg de Dolasetron et 20 mg de metoclopramide (MCP) par voie iv comme prevention des NVPO. Les patients etaient randomises en trois groupes : le Groupe D (n = 129) recevait 12,5 mg de Dolasetron iv, le Groupe MCP (n = 129) 20 mg de MCP iv et le Groupe C un placebo (salin 0,9 %). Utilisant un protocole multifactoriel, un tiers de chaque groupe (n = 43) a fait l'objet d'une randomisation additionnelle : anesthesie generale avec desflurane, isoflurane ou AIV avec propofol et remifentanil. L'incidence de NVPO, la consommation de piritramide et de droperidol ont ete documentees. Resultats: Une incidence diminuee des NVPO (19 %), independante du regime d'anesthesie, a ete observee avec le Dolasetron compare au MCP (45 %) ou au placebo (46 %). L'incidence de NVPO etait plus elevee avec l'isoflurane (46 %) qu'avec l'AIV (28 %) mais semblable avec le desflurane (36 %). La consommation postoperatoire de piritramide etait significativement plus elevee dans le groupe AIV que dans les autres groupes. Conclusion : Les resultats de cette etude suggerent que le Dolasetron est plus efficace que le MCP et que le placebo pour prevenir les NVPO. Cet effet est independant de la technique anesthesique utilisee.

  • Dolasetron reduces pain on injection of propofol
    Anasthesiologie Intensivmedizin Notfallmedizin Schmerztherapie : AINS, 2002
    Co-Authors: Swen N. Piper, K. D. Röhm, W. H. Maleck, M. Papsdorf, Mattinger P, Joachim Boldt
    Abstract:

    OBJECTIVE Pain on injection is a well known side-effect of propofol. The present study was designed to assess the efficacy of Dolasetron, a 5-HT 3 -antagonist, in prophylaxis of pain on injection of propofol compared with lidocaine and placebo. METHODS Prospective, randomised, double-blinded study including 150 patients randomly assigned to one of three groups: Group A received 12.5 mg Dolasetron, group B 40 mg lidocaine and group C saline 0.9 % as placebo. After occluding the venous drainage the test medication was given. The occlusion was released after 1 min and 2.0 mg/kg Propofol was administered over a period of 30 sec. The patients were asked whether they felt any pain during the administration. Pain on injection was judged by using a four-point scale. RESULTS Incidence of pain on injection as well as the severity of pain was significantly reduced by lidocaine (62 % pain free) compared with placebo (28 %). Severity, but not incidence of pain on injection was significantly reduced by Dolasetron (50 %) compared with placebo. There was no significant difference between Dolasetron and lidocaine. CONCLUSION Dolasetron and lidocaine were effective in preventing pain of injection secondary to propofol.

Martin Galvan - One of the best experts on this subject based on the ideXlab platform.

  • actions of Dolasetron and its major metabolite on guinea pig papillary muscle fibres and the α subunit of human heart sodium channels expressed in xenopus oocytes
    Drug Development Research, 1996
    Co-Authors: Robert Dumaine, H. A. Hartmann, Derek J. Leishman, Arthur M. Brown, Martin Galvan
    Abstract:

    The present study evaluated the effects of the anti-emetic 5-HT 3 antagonist Dolasetron and its major metabolite MDL 73,405 on guinea-pig papillary muscle fibres and human heart sodium channels expressed in Xenopus oocytes. Dolasetron and MDL 73,405 (3-10 μM) reduced the maximum depolarization rate during phase I of the action potential (Vmax) in papillary muscle fibres without significantly changing the action potential duration. The reduction in Vmax was both use- and concentration-dependent. In Xenopus oocytes expressing the α-subunit of human heart sodium channels, extracellular application of Dolasetron or MDL 73,405 induced only a low affinity tonic block of the sodium channel ; the apparent K d values were 1.1 and 1.2 mM, respectively. In contrast to guinea-pig sodium channels, neither compound induced a marked use-dependent block of the human channel α-subunit at a concentration of 100 μM (3 and 7% block, respectively). Flecainide produced a reversible, tonic, and use-dependent block in the concentration range of 10 to 100 μM ; the K d value for tonic block was 50 μM. The present results demonstrate that Dolasetron and MDL 73,405 do not act directly on the human heart sodium channel α-subunit and further emphasise the need to study drug action on human ionic channels and/or receptors.

  • Actions of Dolasetron and its major metabolite on guinea‐pig papillary muscle fibres and the α‐subunit of human heart sodium channels expressed in Xenopus oocytes
    Drug Development Research, 1996
    Co-Authors: Robert Dumaine, H. A. Hartmann, Derek J. Leishman, Arthur M. Brown, Martin Galvan
    Abstract:

    The present study evaluated the effects of the anti-emetic 5-HT 3 antagonist Dolasetron and its major metabolite MDL 73,405 on guinea-pig papillary muscle fibres and human heart sodium channels expressed in Xenopus oocytes. Dolasetron and MDL 73,405 (3-10 μM) reduced the maximum depolarization rate during phase I of the action potential (Vmax) in papillary muscle fibres without significantly changing the action potential duration. The reduction in Vmax was both use- and concentration-dependent. In Xenopus oocytes expressing the α-subunit of human heart sodium channels, extracellular application of Dolasetron or MDL 73,405 induced only a low affinity tonic block of the sodium channel ; the apparent K d values were 1.1 and 1.2 mM, respectively. In contrast to guinea-pig sodium channels, neither compound induced a marked use-dependent block of the human channel α-subunit at a concentration of 100 μM (3 and 7% block, respectively). Flecainide produced a reversible, tonic, and use-dependent block in the concentration range of 10 to 100 μM ; the K d value for tonic block was 50 μM. The present results demonstrate that Dolasetron and MDL 73,405 do not act directly on the human heart sodium channel α-subunit and further emphasise the need to study drug action on human ionic channels and/or receptors.

  • Pharmacology of the human metabolites of Dolasetron, an antiemetic 5-HT3 receptor antagonist
    Drug Development Research, 1995
    Co-Authors: Marc Bigaud, Jack Elands, Philip R. Kastner, Rick A. Bohnke, Lee W. Emmert, Martin Galvan
    Abstract:

    Dolasetron mesylate (MDL 73, 147EF) is a novel 5-HT3 receptor antagonist under development as an anti-emetic. Dolasetron undergoes rapid and extensive metabolism to form a major metabolite, MDL 74,156; the metabolism is stereoselective, with the [+]-enantiomer (MDL 73,405) predominant. MDL 74,156 is also hydroxylated to form MDL 102, 382 (5′-OH metabolite) and MDL 73,492 (6′-OH metabolite). The present study evaluated the pharmacological properties of Dolasetron and its human metabolites in vitro and following oral and intravenous administration in rats and compared the antiemetic effects of Dolasetron and ondansetron in dogs. Each of the metabolites had high affinity at and was selective for 5-HT3 receptors. In anesthetized rats, the 5-HT-mediated von Bezold-Jarisch reflex was inhibited by 1 mg/kg oral doses of either Dolasetron (3.1 μmol/kg), ondansetron (3.4 μmol/kg), granisetron (3.2 μmol/kg), or tropisetron (3.5 μmol/kg) and by intravenous doses of Dolasetron and ondansetron. Dolasetron had a significantly longer duration of action than ondansetron. In addition, the metabolites MDL 73,405, MDL 102,382, and MDL 73,492 exhibited significant 5-HT3 receptor antagonist activity following intravenous administration, but only MDL 73,405 exhibited significant activity following oral administration. Both Dolasetron mesylate and ondansetron reduced the number of emetic episodes and increased the time to first emetic event in cisplatin-treated dogs. The clinical effects and duration of action observed following administration of Dolasetron mesylate to humans are likely due mainly to MDL 73,405 (the [+]-enantiomer of MDL 74,156). © 1995 Wiley-Liss, Inc.

  • Pharmacological properties of Dolasetron, a potent and selective antagonist at 5-HT3 receptors
    Drug Development Research, 1993
    Co-Authors: Robert C. Miller, Martin Galvan, Maurice W. Gittos, Paul L.m. Van Giersbergen, Paul Moser, John R. Fozard
    Abstract:

    In the rabbit isolated perfused hear, Dolasetron (MDL 73,147) was found to be a potent (PA2 = 9.8) antagonist at 5-hydroxytryptamine3 (5-HT3) receptors present on sympathetic nerve terminals. In anesthetized rats, intravenous (iv), intraduodenal (id), or oral administration of Dolasetron blocked the von Bezold-Jarisch reflex elicited by iv injection of 5-HT; the iv ED50 was approximately 3 μg/kg and following a dose of 140 μg/kg iv the reflex was abolished for >85 min. The compound displayed no significant affinity for 5-HT1, 5-HT2, or a variety of other radioligand binding sites at concentration of 10 μM. In conscious ferrets, Dolasetron suppressed the vomiting induced by an iv injection of the anti-cancer drug cisplatin (10 mg/kg). Intravenous doses (0.05–0.5 mg/kg) administered 30 min before and 45 min prior to cisplatin, were clearly anti-emetic and single oral doses of 0.5 or 2 mg/kg, given 30 min prior to cisplatin were also effective. Minimal changes in the behaviour of mice were observed at doses up to 100 mg/kg given ip or subcutaneously (sc). It is concluded that Dolasetron is a potent, selective, and reversible antagonist at neuronal 5-HT3 receptors, which is well tolerated. The compound is effective at low doses in an animal model predictive of clinical efficacy in cytotoxic drug-induced vomiting. © 1993 Wiley-Liss, Inc.

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  • Prevention of post-operative nausea and vomiting. Randomised comparison of Dolasetron versus Dolasetron plus dexamethasone
    Der Anaesthesist, 2003
    Co-Authors: Swen N. Piper, J. G. Triem, K. D. Röhm, Peter Kranke, W. H. Maleck, Joachim Boldt
    Abstract:

    BACKGROUND: Postoperative nausea and vomiting (PONV) are frequent complications after operations. The aim of this study was to assess the efficacy of combined Dolasetron plus dexamethasone versus Dolasetron alone with respect to the incidence and severity of emetic symptoms and patients satisfaction. METHODS: In a prospective, randomised, double-blind study, 150 patients scheduled for hysterectomy or breast surgery were allocated to one of the following two groups: group A received 50 mg Dolasetron orally and group B 50 mg Dolasetron orally plus 8 mg dexamethasone intravenously. The follow-up was for 24 h after surgery. RESULTS: In group A PONV was significantly more frequent (28%) compared to group B (12.0%). The incidence of vomiting was significantly lower in patients receiving Dolasetron plus dexamethasone (0%) in comparison to patients receiving Dolasetron (8.0%). Furthermore,patients satisfaction was significantly higher in group B compared to group A. About 6 or 7 patients need to be treated with additional dexamethasone instead of a placebo for one patient to benefit from this intervention (i.e. to stay free from PONV) who otherwise would have suffered from PONV. CONCLUSIONS: Combining oral Dolasetron with intravenous dexamethasone further improves the antiemetic efficacy of Dolasetron. With a number-needed-to-treat of about 6 the additional benefit might be considered clinically relevant.

  • Prophylaxe von postoperativer Übelkeit und postoperativem Erbrechen. Randomisierter Vergleich von Dolasetron versus Dolasetron mit Dexamethason
    Anaesthesist, 2003
    Co-Authors: Swen N. Piper, J. G. Triem, K. D. Röhm, W. H. Maleck, R. Kranke, Joachim Boldt
    Abstract:

    Background. Postoperative nausea and vomiting (PONV) are frequent complications after operations.The aim of this study was to assess the efficacy of combined Dolasetron plus dexamethasone versus Dolasetron alone with respect to the incidence and severity of emetic symptoms and patients satisfaction. Methods. In a prospective, randomised, double-blind study, 150 patients scheduled for hysterectomy or breast surgery were allocated to one of the following two groups: group A received 50 mg Dolasetron orally and group B 50 mg Dolasetron orally plus 8 mg dexamethasone intravenously.The follow-up was for 24 h after surgery. Results. In group A PONV was significantly more frequent (28%) compared to group B (12.0%).The incidence of vomiting was significantly lower in patients receiving Dolasetron plus dexamethasone (0%) in comparison to patients receiving Dolasetron (8.0%). Furthermore, patients satisfaction was significantly higher in group B compared to group A. About 6 or 7 patients need to be treated with additional dexamethasone instead of a placebo for one patient to benefit from this intervention (i.e. to stay free from PONV) who otherwise would have suffered from PONV. Conclusions. Combining oral Dolasetron with intravenous dexamethasone further improves the antiemetic efficacy of Dolasetron. With a number-needed-to-treat of about 6 the additional benefit might be considered clinically relevant.

  • placebo controlled comparison of Dolasetron and metoclopramide in preventing postoperative nausea and vomiting in patients undergoing hysterectomy
    European Journal of Anaesthesiology, 2001
    Co-Authors: Swen N. Piper, J. G. Triem, Wolfgang H. Maleck, M T Fent, I Huttner, J Boldt
    Abstract:

    Summary Background and objective  In a randomized, placebo-controlled, double-blind trial, we compared the efficacy of Dolasetron and metoclopramide in preventing postoperative nausea and vomiting in women undergoing hysterectomy. Methods  Patients were allocated randomly to one of three groups: group A (n = 50) received 50 mg Dolasetron orally, group B (n = 50) received 20 mg metoclopramide intravenously and placebo orally, group C (n = 50) received placebo orally. If patients complained of retching or vomiting, or if patients demanded an antiemetic, 1.25 mg droperidol was administrated intravenously. To quantify postoperative nausea and vomiting the following score was used: 0 = no nausea, 1 = nausea, 2 = retching, 3 = single vomiting, 4 = multiple vomiting. The Raatz test was used to analyse postoperative nausea and vomiting (PONV) scores. Results  Dolasetron reduced the postoperative nausea and vomiting score significantly (P < 0.02 vs. metoclopramide; P < 0.0001 vs. placebo). Metoclopramide also reduced the postoperative nausea and vomiting score (P < 0.02 vs. placebo). Fisher's exact test showed a significant reduction of vomiting in the Dolasetron group compared with metoclopramide-treated patients (P < 0.007) and placebo-treated patients (P < 0.000006) and a significantly lower rate of nausea in comparison to the placebo group (P < 0.009). There were no significant differences between the metoclopramide and the placebo groups (in Fisher's exact test). The use of postoperative droperidol per patient was significantly lower in the Dolasetron group (P < 0.04 vs. metoclopramide; P < 0.0001 vs. placebo) than in the metoclopramide (P < 0.02 vs. placebo) and in the placebo groups. Conclusions  Oral Dolasetron is more effective than either metoclopramide given intravenously or placebo for preventing vomiting after hysterectomy. It also was significantly superior to either metoclopramide or placebo concerning the PONV score and the need for droperidol rescue.

  • Placebo-controlled comparison of Dolasetron and metoclopramide in preventing postoperative nausea and vomiting in patients undergoing hysterectomy:
    European journal of anaesthesiology, 2001
    Co-Authors: Swen N. Piper, J. G. Triem, Wolfgang H. Maleck, M T Fent, I Huttner, Joachim Boldt
    Abstract:

    Summary Background and objective  In a randomized, placebo-controlled, double-blind trial, we compared the efficacy of Dolasetron and metoclopramide in preventing postoperative nausea and vomiting in women undergoing hysterectomy. Methods  Patients were allocated randomly to one of three groups: group A (n = 50) received 50 mg Dolasetron orally, group B (n = 50) received 20 mg metoclopramide intravenously and placebo orally, group C (n = 50) received placebo orally. If patients complained of retching or vomiting, or if patients demanded an antiemetic, 1.25 mg droperidol was administrated intravenously. To quantify postoperative nausea and vomiting the following score was used: 0 = no nausea, 1 = nausea, 2 = retching, 3 = single vomiting, 4 = multiple vomiting. The Raatz test was used to analyse postoperative nausea and vomiting (PONV) scores. Results  Dolasetron reduced the postoperative nausea and vomiting score significantly (P 

  • Prevention of postoperative nausea and vomiting after hysterectomy with oral Dolasetron, intravenous dehydrobenzperidol or a combination of both substances
    Anasthesiologie Intensivmedizin Notfallmedizin Schmerztherapie : AINS, 1999
    Co-Authors: J. G. Triem, W. H. Maleck, S N Piper, A Schenck, C C Schmidt, J Boldt
    Abstract:

    PONV is a frequent postoperative complication. The aim of this study was to assess the efficacy of oral Dolasetron in comparison to intravenous droperidol (DHB) and to a combination of both drugs for prophylaxis of PONV. 80 patients (ASA I-III) were randomly allocated to one of four groups and received the following medication: group A: 50 mg Dolasetron was given orally 45-60 minutes before anaesthesia was induced, group B: 2.5 mg i.v. DHB + placebo p.o. was administered while inducing anaesthesia (positive control group), group C: 50 mg Dolasetron was given 45-60 minutes before anaesthesia was induced and 2.5 mg i.v. DHB was given while inducing anaesthesia, group D: placebo tablet was administered 45-60 minutes before anaesthesia was induced (negative control group). PONV was assessed using a 5-point score: 0 = no symptoms, 1 = nausea, 2 = retching, 3 = vomiting, 4 = multiple vomiting. Metoclopramid was given as antiemetic if a patient reached two or more score points. PONV scores were significantly lower in group A and C (p < 0.001) compared to the control group. Patients treated with DHB showed a significantly lower PONV score in comparison to the placebo treated patients (p < 0.05). Between the groups A, B and C we found no significantly different PONV scores. Postoperative consumption of metoclopramid was significantly lower in the groups A (2.4 +/- 5.2 mg) and C (1.0 +/- 3.1 mg) than in the placebo group (6.0 +/- 6.8 mg), whereas between group B (3.0 +/- 5.7 mg) and D we found no significant differences. Single dose of oral Dolasetron and single dose of intravenous DHB reduced PONV effectively, in patients undergoing gynaecologic surgery. A combination of Dolasetron and DHB has no better effect than a single dose of oral Dolasetron. Contrary to DHB the application of Dolasetron decreased the postoperative antiemetic requirement significantly.