Skip to main content

Advertisement

SpringerLink
Log in

Intravenous buspirone for the prevention of postoperative nausea and vomiting

  • Clinical Trial
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Rationale

Buspirone, a partial 5HT1A agonist and D2 and D3 antagonist, has shown promising antiemetic efficacy when given parenterally in animal models, but its efficacy for the prevention of postoperative nausea and vomiting (PONV) is unknown.

Objective

To study the efficacy and dose-responsiveness of intravenous buspirone for the prevention of PONV.

Methods

A randomised, double-blind, placebo-controlled study was performed in adults at moderate to high PONV risk undergoing surgery with a general anaesthetic. Patients were randomised to receive an intravenous dose of buspirone (0.3, 1.0, 2.0, 3.0 mg) or placebo at the end of surgery. The primary endpoint was the cumulative 24-h PONV incidence (i.e. any nausea and/or vomiting). Vomiting included retching. Nausea was defined as a score of ≥4 on an 11-point verbal rating scale running from zero (no nausea) to ten (the worst nausea imaginable).

Results

A total of 257 patients received the study drug and fulfilled the criteria for inclusion in the primary efficacy and safety analyses. With placebo, the mean 24-h PONV incidence was 49.0 % (90 % confidence interval [CI] 37.5–60.5 %). With buspirone, that incidence ranged from a mean of 40.8 % (29.3–52.4 %) in the 1 mg arm to 58.0 % (46.5–69.5 %) in the 0.3 mg arm (P > 0.05 for all comparisons). There was no difference between placebo and buspirone at any dose for any other efficacy endpoint, nor in the number or severity of adverse events or any other safety measures.

Conclusion

We were unable to show that intravenous single-dose buspirone, at the tested dose-range, was effective at preventing PONV in surgical adult patients. The present study emphasises the difficulty in extrapolating from animal models of emesis to clinical efficacy in PONV.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

D:

Dopaminergic

5HT:

Serotoninergic

NK:

Neurokinin

PONV:

Postoperative nausea and vomiting

PP:

Pyrimidinylpiperazine

References

  1. Kranke P (2011) Effective management of postoperative nausea and vomiting: let us practise what we preach! Eur J Anaesthesiol 28:152–154

    Article  PubMed  Google Scholar 

  2. Pierre S (2011) Risk scores for predicting postoperative nausea and vomiting are clinically useful tools and should be used in every patient: pro–'don't throw the baby out with the bathwater'. Eur J Anaesthesiol 28:160–163

    Article  PubMed  Google Scholar 

  3. Sanger GJ, Andrews PL (2006) Treatment of nausea and vomiting: gaps in our knowledge. Auton Neurosci 129:3–16

    Article  PubMed  CAS  Google Scholar 

  4. Oshima T, Kasuya Y, Okumura Y, Terazawa E, Dohi S (2002) Prevention of nausea and vomiting with tandospirone in adults after tympanoplasty. Anesth Analg 95:1442–1445

    Article  PubMed  CAS  Google Scholar 

  5. Darmani NA, Zhao W, Ahmad B (1999) The role of D2 and D3 dopamine receptors in the mediation of emesis in Cryptotis parva (the least shrew). J Neural Transm 106:1045–1061

    Article  PubMed  CAS  Google Scholar 

  6. Kranke P, Eberhart LH (2011) Possibilities and limitations in the pharmacological management of postoperative nausea and vomiting. Eur J Anaesthesiol 28:758–765

    Article  PubMed  CAS  Google Scholar 

  7. Kooij FO, Klok T, Hollmann MW, Kal JE (2010) Automated reminders increase adherence to guidelines for administration of prophylaxis for postoperative nausea and vomiting. Eur J Anaesthesiol 27:187–191

    Article  PubMed  Google Scholar 

  8. Habib AS, Gan TJ (2005) The effectiveness of rescue antiemetics after failure of prophylaxis with ondansetron or droperidol: a preliminary report. J Clin Anesth 17:62–65

    Article  PubMed  CAS  Google Scholar 

  9. Tramèr MR (2003) Treatment of postoperative nausea and vomiting. Br Med J 327:762–763

    Article  Google Scholar 

  10. Riblet LA, Taylor DP, Eison MS, Stanton HC (1982) Pharmacology and neurochemistry of buspirone. J Clin Psychiatry 43:11–18

    PubMed  CAS  Google Scholar 

  11. Gupta YK, Sharma SS (2002) Involvement of 5-HT1A and 5-HT2 receptor in cisplatin induced emesis in dogs. Indian J Physiol Pharmacol 46:463–467

    PubMed  CAS  Google Scholar 

  12. Lucot JB, Crampton GH (1987) Buspirone blocks cisplatin-induced emesis in cats. J Clin Pharmacol 27:817–818

    PubMed  CAS  Google Scholar 

  13. Lucot JB, Crampton GH (1987) Buspirone blocks motion sickness and xylazine-induced emesis in the cat. Aviat Space Environ Med 58:989–991

    PubMed  CAS  Google Scholar 

  14. Okada F, Torii Y, Saito H, Matsuki N (1994) Antiemetic effects of serotonergic 5-HT1A-receptor agonists in Suncus murinus. Jpn J Pharmacol 64:109–114

    Article  PubMed  CAS  Google Scholar 

  15. Alfieri AB, Cubeddu LX (1995) Comparative efficacy of a single oral dose of ondansetron and of buspirone against cisplatin-induced emesis in cancer patients. Br J Cancer 72:1013–1015

    Article  PubMed  CAS  Google Scholar 

  16. Gammans RE, Mayol RF, LaBudde JA (1986) Metabolism and disposition of buspirone. Am J Med 80:41–51

    Article  PubMed  CAS  Google Scholar 

  17. Center for Drug Evaluation and Research (2005) Guidance for industry: estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. United States Food and Drug Administration, Rockville

    Google Scholar 

  18. Aldrete JA (1995) The post-anesthesia recovery score revisited. J Clin Anesth 7:89–91

    Article  PubMed  CAS  Google Scholar 

  19. Peroutka SJ (1985) Selective interaction of novel anxiolytics with 5-hydroxytryptamine1A receptors. Biol Psychiatry 20:971–979

    Article  PubMed  CAS  Google Scholar 

  20. Romero AG, Leiby JA, McCall RB, Piercey MF, Smith MW, Han F (1993) Novel 2-substituted tetrahydro-3 H-benz.eindolamines: highly potent and selective agonists acting at the 5-HT1A receptor as possible anxiolytics and antidepressants. J Med Chem 36:2066–2074

    Article  PubMed  CAS  Google Scholar 

  21. Newman-Tancredi A, Gavaudan S, Conte C, Chaput C, Touzard M, Verrièle L, Audinot V, Millan MJ (1998) Agonist and antagonist actions of antipsychotic agents at 5-HT1A receptors: a.35SGTPgammaS binding study. Eur J Pharmacol 355:245–256

    Article  PubMed  CAS  Google Scholar 

  22. Yocca FD (1990) Neurochemistry and neurophysiology of buspirone and gepirone: interactions at presynaptic and postsynaptic 5-HT1A receptors. J Clin Psychopharmacol 10:6S–12S

    Article  PubMed  CAS  Google Scholar 

  23. Ministry of Health Labour and Welfare (Japan) (1997) Summary basis of approval, tandospirone citrate tablets. Ministry of Health, Labour and Welfare, Tokyo

    Google Scholar 

  24. Díaz-Mataix L, Scorza MC, Bortolozzi A, Toth M, Celada P, Artigas F (2005) Involvement of 5-HT1A receptors in prefrontal cortex in the modulation of dopaminergic activity: role in atypical antipsychotic action. J Neurosci 25:10831–10843

    Article  PubMed  Google Scholar 

  25. Zhu BT (2005) Mechanistic explanation for the unique pharmacologic properties of receptor partial agonists. Biomed Pharmacother 59:76–89

    Article  PubMed  CAS  Google Scholar 

  26. Seletti B, Benkelfat C, Blier P, Annable L, Gilbert F, de Montigny C (1995) Serotonin1A receptor activation by flesinoxan in humans. Body temperature and neuroendocrine responses. Neuropsychopharmacology 13:93–104

    Article  PubMed  CAS  Google Scholar 

  27. Grof P, Joffe R, Kennedy S, Persad E, Syrotiuk J, Bradford D (1993) An open study of oral flesinoxan, a 5-HT1A receptor agonist, in treatment-resistant depression. Int Clin Psychopharmacol 8:167–172

    Article  PubMed  CAS  Google Scholar 

  28. Lutsep HL (2005) Repinotan, A 5-HT1A agonist, in the treatment of acute ischemic stroke. Curr Drug Targets CNS Neurol Disord 4:119–120

    Article  PubMed  CAS  Google Scholar 

  29. Lucot JB (1994) Antiemetic effects of flesinoxan in cats: comparisons with 8-hydroxy-2-(di-n-propylamino)tetralin. Eur J Pharmacol 253:53–60

    Article  PubMed  CAS  Google Scholar 

  30. Ogren SO, Eriksson TM, Elvander-Tottie E, D'Addario C, Ekström JC, Svenningsson P, Meister B, Kehr J, Stiedl O (2008) The role of 5-HT(1A) receptors in learning and memory. Behav Brain Res 195:54–77

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The study was funded by Acacia Pharma Ltd, the manufacturer of the study drug. The study design was developed by a steering committee (CCA, PD, TJG, PK, MRT) in collaboration with Acacia Pharma Ltd. Acacia Pharma Ltd edited the study protocol in collaboration with the steering committee members, organised meetings for steering committee members and investigators, supplied study drugs and was responsible for data analysis.

Participating study investigators and centres

France: Prof Hervé Bouaziz, Hôpital Central, Nancy; Prof Dominique Chassard, Hôpital Mere Enfant, Bron; Prof Pierre Diemunsch, CHU de Hautepierre, Strasbourg; Prof Gilles Lebuffe, Hôpital Huriez–CHRU, Lille; Dr Ngay Liu, Hôpital Foch, Suresnes; Prof Jean-Marc Malinowsky, Hôpital Maison Blanche–CHRU, Reims; Prof Emmanuel Samain, CHU Besançon, Besançon. Germany: Prof Leopold Eberhart, Philipps Universität Marburg, Marburg; Prof Peter Kranke and Dr Mustafa Rifai, Universitätsklinik Würzburg, Würzburg; Prof Johann Motsch, Universität Heidelberg, Heidelberg; Dr Kerstin D Röhm, Klinikum Ludwigshafen, Ludwigshafen; Prof Claudia Spies and Dr Martin Franck, Charité–Universitätsmedizin Berlin, Berlin; Dr Jan Wallenborn, Universität Leipzig, Leipzig. Switzerland: Prof Martin Tramèr and Dr Georges Savoldelli, Geneva University Hospitals, Geneva. USA: Prof Christian Apfel, UCSF Medical Center at Mt Zion, San Francisco, CA; Prof Tong Joo Gan and Dr Ashraf S Habib, Duke University Medical Center, Durham, NC; Dr Harold S Minkowitz, Memorial Hermann-Memorial City Hospital, Houston, TX

Conflict of interest and disclosure

There was a pre hoc agreement that the investigators would have the right to examine the data independently and to submit a manuscript for publication without first obtaining the consent of the sponsor and that the results of this study would be published as a full report, in their entirety and not as individual centre data, and independent of the result of the study. MRT had full access to all the data and coordinated the decision to submit for publication. All authors participated in writing the manuscript. GMF is an employee of Acacia Pharma Ltd.

Author information

Authors and Affiliations

  1. Department of Anaesthesiology and Critical Care, University Hospitals of Würzburg, 97080, Würzburg, Germany

    Peter Kranke

  2. Department of Anaesthesiology and Intensive Care Medicine, Klinikum Ludwigshafen, 67063, Ludwigshafen, Germany

    Kerstin D. Röhm

  3. Department of Anaesthesiology and Intensive Care, University Hospital of Hautepierre, 67000, Strasbourg, France

    Pierre Diemunsch

  4. Department of Anesthesiology, Duke University Medical Center, Durham, NC, 27710, USA

    Tong J. Gan

  5. Department of Anesthesiology, UCSF Medical Center at Mt Zion, San Francisco, CA, 94115, USA

    Christian C. Apfel

  6. Department of Anaesthesiology and Intensive Care, Philipps University Marburg, 35033, Marburg, Germany

    Leopold Eberhart

  7. Department of Anesthesiology, Memorial Hermann-Memorial City Medical Center, Houston, TX, 77024, USA

    Harold S. Minkowitz

  8. Department of Anaesthesiology and Intensive Care Medicine, University of Leipzig, 04103, Leipzig, Germany

    Jan Wallenborn

  9. Service d’Anesthésie, Hôpital Mère Enfant, 69500, Bron, France

    Dominique Chassard

  10. Department of Anaesthesiology and Intensive Care, Huriez Hospital, University Hospital of Lille, 59037, Lille, France

    Gilles Lebuffe

  11. Acacia Pharma Ltd, Cambridge, CB22 7GG, UK

    Gabriel M. Fox

  12. Division of Anaesthesiology, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1211, Geneva 14, Switzerland

    Martin R. Tramèr

Authors
  1. Peter Kranke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kerstin D. Röhm
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pierre Diemunsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tong J. Gan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christian C. Apfel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Leopold Eberhart
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Harold S. Minkowitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jan Wallenborn
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dominique Chassard
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Gilles Lebuffe
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Gabriel M. Fox
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Martin R. Tramèr
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Martin R. Tramèr.

Additional information

Trial registration

Clinicaltrials.gov identifier: NCT00895830.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kranke, P., Röhm, K.D., Diemunsch, P. et al. Intravenous buspirone for the prevention of postoperative nausea and vomiting. Eur J Clin Pharmacol 68, 1465–1472 (2012). https://doi.org/10.1007/s00228-012-1284-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-012-1284-8

Keywords

Search

Navigation