Skip to main content

Advertisement

Log in

A comparison of midazolam and dexmedetomidine for the recovery of serotonin syndrome in rats

  • Short Communication
  • Published:
Journal of Anesthesia Aims and scope Submit manuscript

Abstract

Serotonin syndrome is a drug-related toxicity caused by excess serotonin within the central nervous system. We recently encountered a case of serotonin syndrome that developed in the early postoperative period that was successfully treated with intravenous dexmedetomidine. Although the prescriptive literature has commonly recommended sedation with benzodiazepines for controlling agitation in serotonin syndrome, the effectiveness of dexmedetomidine has also been reported in several clinical conditions. In the present study, we conducted a reverse translational experiment to compare the efficacy of dexmedetomidine and midazolam, at equi-sedative doses, on serotonergic toxicity-like responses in rats. Animals were subcutaneously injected with 0.75 mg/kg 8-OH-DPAT, a full 5-HT1A agonist. 8-OH-DPAT-treated rats showed serotonin syndrome-like behaviors (low body posture, forepaw treading), hyperlocomotion, and decreased body temperature, which were completely inhibited by pretreatment with WAY 100635, a selective 5-HT1A antagonist (n = 8). Intramuscular injection of midazolam (1.0 mg/kg) or dexmedetomidine (0.01 mg/kg), which comparably induced observable signs of sedation, was tested in the present study. Concomitant treatment with midazolam significantly attenuated the hyperlocomotion, but failed to affect traditional serotonin syndrome behaviors and body temperature in 8-OH-DPAT-treated rats (n = 8). On the other hand, concomitant treatment with dexmedetomidine significantly attenuated all of these parameters (n = 8). The present case and related reverse translational experiment demonstrate that dexmedetomidine may be more beneficial for the treatment of serotonin syndrome compared to the current recommended treatment with benzodiazepines.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

References

  1. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352:1112–20.

    Article  CAS  PubMed  Google Scholar 

  2. Rastogi R, Swarm RA, Patel TA. Case scenario: opioid association with serotonin syndrome: implications to the practitioners. Anesthesiology. 2011;115:1291–8.

    PubMed  Google Scholar 

  3. Gillman PK. Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. Br J Anaesth. 2005;95:434–41.

    Article  CAS  PubMed  Google Scholar 

  4. Altman CS, Jahangiri MF. Serotonin syndrome in the perioperative period. Anesth Analg. 2010;110:526–8.

    Article  PubMed  Google Scholar 

  5. Akingbola OA, Singh D. Dexmedetomidine to treat lisdexamfetamine overdose and serotonin toxidrome in a 6-year-old girl. Am J Crit Care. 2012;21:456–9.

    Article  PubMed  Google Scholar 

  6. Rushton WF, Charlton NP. Dexmedetomidine in the treatment of serotonin syndrome. Ann Pharmacother. 2014;48:1651–4.

    Article  CAS  PubMed  Google Scholar 

  7. Maura G, Gemignani A, Raiteri M. Noradrenaline inhibits central serotonin release through alpha 2-adrenoceptors located on serotonergic nerve terminals. Naunyn Schmiedebergs Arch Pharmacol. 1982;320:272–4.

    Article  CAS  PubMed  Google Scholar 

  8. Hopwood SE, Stamford JA. Noradrenergic modulation of serotonin release in rat dorsal and median raphé nuclei via α1 and α2A adrenoceptors. Neuropharmacology. 2001;41:433–42.

    Article  CAS  PubMed  Google Scholar 

  9. Haberzettl R, Bert B, Fink H, Fox MA. Animal models of the serotonin syndrome: a systematic review. Behav Brain Res. 2013;256:328–45.

    Article  CAS  PubMed  Google Scholar 

  10. Sallinen J, Haapalinna A, Viitamaa T, Kobilka BK, Scheinin M. d-amphetamine and l-5-hydroxytryptophan-induced behaviours in mice with genetically altered expression of the alpha2C-adrenergic receptor subtype. Neuroscience. 1998;86:959–65.

    Article  CAS  PubMed  Google Scholar 

  11. Nisijima K, Shioda K, Yoshino T, Takano K, Kato S. Diazepam and chlormethiazole attenuate the development of hyperthermia in an animal model of the serotonin syndrome. Neurochem Int. 2003;43:155–64.

    Article  CAS  PubMed  Google Scholar 

  12. Carollo DS, Nossaman BD, Ramadhyani U. Dexmedetomidine: a review of clinical applications. Curr Opin Anaesthesiol. 2008;21:457–61.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Takashi Kawano.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 PDF (74 kb)

Supplementary material 2 PDF (620 kb)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kawano, T., Takahashi, T., Kaminaga, S. et al. A comparison of midazolam and dexmedetomidine for the recovery of serotonin syndrome in rats. J Anesth 29, 631–634 (2015). https://doi.org/10.1007/s00540-014-1973-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00540-014-1973-9

Keywords

Navigation