Pharmacodynamics of Midazolam and Reversal with Flumazenil in the Ball Python (Python regius)
2018 Joint EAZWV/AAZV/Leibniz-IZW Conference
Cédric B. Larouche1,2*, DVM, IPSAV; Hugues Beaufrère1, Dr. Med. Vet, PhD, DACZM, DECZM (Avian), DABVP (Avian); Craig Mosley3, DVM, MSc, DACVAA; Nicole Nemeth1, BA, DVM, PhD, DACVP; Christopher Dutton2, BVSc, MSc, DACZM, DECZM (Zoo Health Management)
1Ontario Veterinary College, University of Guelph, Guelph, ON, Canada; 2Toronto Zoo, Toronto, ON, Canada; 3404 Veterinary Emergency and Referral Hospital, Newmarket, ON, Canada


Midazolam is a benzodiazepine with a wide cardiorespiratory safety margin reported to provide adequate sedation in ophidian species.1 The study objective was to evaluate the pharmacodynamics of intramuscular (IM) midazolam and reversal efficacy of flumazenil in ball pythons (Python regius). A blinded randomized crossover trial comparing two dosages, 1 and 2 mg/kg IM, was performed in nine captive bred adults. Flumazenil was administered at 0.08 mg/kg IM 60 minutes following an injection of midazolam at 1 mg/kg IM in a second trial. Each snake was serially monitored until no sedation was noted. Sedation was systematically scored through assessing the righting reflex and reactions to head grabbing. Similarly, muscular relaxation was scored based on muscle tone during manipulations. Other parameters evaluated included heart rate, respiratory rate, and body temperature. Midazolam administered at 2 mg/kg resulted in slightly increased sedation and muscle relaxation scores compared to 1 mg/kg (p=0.005), although both dosages provided moderate to profound sedation. Time to maximal sedation was 60 minutes. The highest sedation scores occurred between 15 and 300 minutes. Sedation scores were significantly higher than baseline until 3 days post-injection, although 2 snakes took more than 6 days to recover. The high dose resulted in more profound and longer-lasting respiratory depression than the lower dose. Flumazenil provided adequate, but short-acting reversal (2–3h) and all snakes renarcotized for several days. Results suggest that midazolam 1 mg/kg IM results in moderate to marked sedation for several days and flumazenil provides short-acting reversal effects in ball pythons.


The authors would like to acknowledge the Toronto Zoo for funding of this research.

Literature Cited

1.  Arnett-Chinn ER, Hadfield CA, Clayton LA. Review of intramuscular midazolam for sedation in reptiles at the National Aquarium, Baltimore. J Herpetol Med Surg. 2016;26(1–2):59–63.


Speaker Information
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Cédric B. Larouche, DVM, IPSAV
Ontario Veterinary College
University of Guelph
Guelph, ON, Canada

Toronto Zoo
Toronto, ON, Canada

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