Evaluation of the effect of midazolam on toxicity induced by administration of high doses of lidocaine in chickens (Gallus gallus domesticus)

Document Type : Research Paper


1 DVSc Student in Veterinary Surgery, Faculty of Veterinary Medicine, Shiraz University, Shiraz, Iran

2 Professor, Department of Clinical Sciences, Faculty of Veterinary Medicine, Shiraz University, Shiraz, Iran


    The aim of the present study was to evaluate the effect of midazolam on lidocaine-induced toxicity in chickens. Forty-eight healthy, Lohmann broiler chickens (Gallus gallus domesticus) divided into two groups (n=24) and four subgroups each (n=6). The birds in group I and II received lidocaine with infusion rates of 15 and 25 mg/kg/min, respectively. Ten minutes before lidocaine administration, in each subgroup, one of the treatments of normal saline or midazolam at the dose rate of 0.25, 0.5 and 1.0 mg/kg were injected into the pectoral muscle. With occurrence of the signs related to the toxicity (convulsion and/or respiratory arrest), lidocaine infusion was disrupted and the administered dose of lidocaine was calculated. In group I, convulsion was observed at the dose of 38.0 ± 13.0 mg/kg in the birds received normal saline while in midazolam-treated birds, respiratory arrest without convulsion occurred at the dose of 36.1 ± 12.4, 39.9 ± 15.3, and 37.1 ± 9.1 mg/kg, respectively. In group II, convulsion occurred saline-treated animals at the dose of 23.4 ± 4.8 mg/kg. The birds that received midazolam showed respiratory arrest without convulsion at the dose of 31.1 ± 3.8, 31.3 ± 3.8 and 28.2 ± 5.3 mg/kg, respectively. The birds which received lidocaine at the lower infusion rate showed toxicity signs at the significantly higher doses. Based on the results of the current study, at lower infusion rate, premedication with midazolam protected chickens against convulsion but it had no effect on the threshold of toxicity (respiratory arrest) following administration of high doses of lidocaine.


Main Subjects

Ausiksch, B., Malagodi, M.H., & Munson, E.S. (1976). Diazepam in the prophylaxis of lignocaine seizures. British Journal of Anaesthesia, 48 (4): 309-314.
Becker, D.E., & Reed, K.L. (2006). Essentials of local anesthetic pharmacology. Anesthesia Progress, 53 (3): 98-108.
Beltrame, J., Aylward, P.E., McRitchie, R.J., & Chalmers, J.P. (1984). Comparative haemodynamic effects of lidocaine, mexiletine, and disopyramide. Journal of Cardiovascular Pharmacology; 6 (3):483–490.
Bowles, H., Lichtenberger, M., & Lennox, A.M. (2007). Emergency and critical care of pet birds. Veterinary Clinics North America Exotic Pet Practice, 10 (2): 345–394.
Brandao, J.; da Cunha, A.F.; Pypendop, B.; Stout, R.; Nevarez, J. and Tully Jr, T.N. (2015). Cardiovascular tolerance of intravenous lidocaine in broiler chickens (Gallus gallus domesticus) anesthetized with isoflurane. Veterinary Anaesthesia and Analgesia, 42 (4): 442-448.
Bruguerolle, B., Valli, M., Bouyard, L., Jadot, G., & Bouyard, P. (1983). Effect of the hour of administration on the pharmacokinetics of lidocaine in the rat. European Journal of Drug Metabolism and Pharmacokinetics, 8 (3): 233-238.
Chadwick, H.S. (1985). Toxicity and resuscitation in lidocaine- or bupivacaine-infused cats. Anesthesiology, 63 (4): 385-390.
Da Cunha, A., Messenger, K.M., Stout, R.W., Barker, S.A., Nevarez, J.G., Queiroz-Williams, P., & Tully Jr, T.N. (2011). Pharmacokinetics of lidocaine and its active metabolite monoethylglycinexylidide after a single intravenous administration in chickens (Gallus domesticus) anesthetized with isoflurane. Journal of Veterinary Pharmacology & Therapeutics, 35 (6): 604-607.
Daos, F.G., Lopez, L., & Virtue R.W. (1962). Local anesthetic toxicity modified by oxygen and by combination of agents. Anesthesiology, 23 (6):755-61.
de Jong, R.H., & Bonin, J.D. (1981). Benzodiazepines protect mice from local anesthetic convulsions and deaths. Anesthesia and Analgesia, 60 (6): 385-389.
de Jong, R.H., & Heavner, J.E. (1973). Diazepam and lidocaine-induced cardiovascular changes. Anesthesiology, 39 (6): 633-638.
DiGeronimo, P.M., da Cunha, A.F., Pypendop, B., Brandão, J., Stout, R., Rinaldi, M., & Tully Jr, T.N. (2017). Cardiovascular tolerance of intravenous bupivacaine in broiler chickens (Gallus gallus domesticus) anesthetized with isoflurane. Veterinary Anaesthesia and Analgesia, 44 (2): 287-294.
Divers, S J. (2014) Anaesthesia of zoological species (exotic pets, zoo, aquatic, and wild animals). In: Clarke K.W., Trim C.M. and Hall L.W.: Veterinary Anaesthesia. 11th Ed., Elsevier Ltd., Edinburgh, UK, Pp: 535-569.
Feldman, H.S., Arthur, G.R., & Covino, B.G. (1989). Comparative systemic toxicity of convulsant and supraconvulsant doses of intravenous ropivacaine, bupivacaine, and lidocaine in the conscious dog. Anesthesia and Analgesia, 69 (6): 794-801.
Figueiredo, J.P., Cruz, M.L., Mendes, G.M., Marucio, R.L., Riccó, C.H. & Campagnol, D. (2008). Assessment of brachial plexus blockade in chickens by an axillary approach. Veterinary Anaesthesia and Analgesia, 35 (6):511-518.
Garcia, E.R. (2015). Local Anesthetics. In: Grimm, K.A.; Lamont, L.A.; Tranquilli, W.J.; Greene, S.A. and Robertson, S.A. Veterinary Anesthesia and Analgesia, The Fifth Edition of Lumb and Jones. Pondicherry, India, John Wiley and Sons, Pp: 332-354.
Giaufre, E., Bruguerolle, B., Morisson-Lacombe, G. & Rousset-Rouviere B. (1990): The influence of midazolam on the plasma concentrations of bupivacaine and lidocaine after caudal injection of a mixture of the local anesthetics in children. Acta Anaesthesiologica Scandinavica, 34 (1): 44-46.
Haasio, J., Hekali, R., & Rosenberg, P. (1988). Influence of premedication on lignocaine-induced acute toxicity and plasma concentrations of lignocaine. British Journal of Anaesthesia, 61 (2): 131-134.
Hawkins, M.G., & Pascoe, P.J. Cagebirds. In:  West, G.; Heard, D.J. and Caulkett, N. (2007). Zoo Animal and Wildlife Immobilization and Anesthesia. Victoria, Australia, Wiley-Blackwell, Pp: 269-297.
Horikawa, H., Tada, T., Sakai, M., Karube, T., 7 Ichiyanagi, K. (1990). Effects of midazolam on the threshold of lidocaine-induced seizures in the dog. Journal of Anesthesia, 4 (3): 265-269.
Imani, H., Vesal, N., & Mohammadi-Samani, S. (2013). Evaluation of Intravenous Lidocaine Overdose in Chickens (Gallus domesticus). Iranian Journal of Veterinary Surgery, 8 (1): 9-16.
Kotelko, D.M., Shnider, S.M., 7 Dailey, P.A. (1984). Bupivacaine-induced cardiac arrhythmias in sheep. Anesthesiology, 60 (1): 10-18.
Lee, A., & Lennox, A. (2016). Sedation and local anesthesia as an alternative to general anesthesia in 3 birds. Journal of Exotic Pet Medicine, 25 (2): 100-105.
Lemo, N., Vnuk, D., Radisic, B., Skender, L., Karacic, V., & Brcic, I. (2007). Determination of the toxic dose of lidocaine in dogs and its corresponding serum concentration. Veterinary Record, 160 (11): 374-375.
Liu, P., Feldman, H.S., Covino, B.M., Giasi, R., & Covino, B.G. (1982). Acute cardiovascular toxicity of intravenous amide local anesthetics in anesthetized ventilated dogs. Anesthesia and Analgesia, 61 (4): 317-322.
MacDougall, L.M., Hethey, J.A., Livingston, A., Clark, C.; Shmon, C.L., & Duke-Novakovski, T. (2009). Antinociceptive, cardiopulmonary, and sedative effects of five intravenous infusion rates of lidocaine in conscious dogs. Veterinary Anaesthesia and Analgesia, 36 (5): 512-522.
Machin, K.L. (2005a). Avian analgesia. Seminars in Avain and Exotic Pet Medicine, 14 (4): 236-242.
Machin, K.L. (2005b). Controlling avian pain. Compendium on Continuing Education for the Practicing Veterinarian 27(4), 299-309.
Meyer, G.A., Lin, H.C., Hanson, R.R., & Hayes, T.L. (2001). Effects of intravenous lidocaine overdose on cardiac electrical activity and blood pressure in the horse. Equine Veterinary Journal, 33 (5): 434-437.
Morishima, H.O., Pedersen, H., & Finster, M. (1981). Toxicity of lidocaine in adult, newborn, and fetal sheep. Anesthesiology, 55 (1): 57-61.
Odedra, D., Lyons, G. (2010). Local anaesthetic toxicity. Current Anaesthesia and Critical Care, 21 (1): 52-54.
Orszulak-Michalak, D., Owczarek, J., & Wiktorowska-Owczarek, A. (2002). The influence of midazolam on plasma concentrations and pharmacokinetic parameters of lidocaine in rabbits. Pharmacological Research, 45 (1): 11-14.
Paul-Murphy, J., & Fialkowski, J. (2001). Injectable anesthesia and analgesia of birds. In: Gleed, R.D., & Ludders, J.W. (Eds.). Recent Advances in Veterinary Anesthesia and Analgesia: Companion Animals. International Veterinary Information Service (www.ivis.org), Ithaca, New York, USA.
Pypendop, B.H., & Ilkiw, J.E. (2005) Assessment of the hemodynamic effects of lidocaine administered IV in isoflurane-anesthetized cats. American Journal of Veterinary Research, 66 (4): 661–668.
Rankin, C.D. (2015). Sedative and tranqulizers. In: Grimm, K.A.; Lamont, L.A.; Tranquilli, W.J.; Greene, S.A. and Robertson, S.A. Veterinary Anesthesia and Analgesia, The Fifth Edition of Lumb and Jones. Pondicherry, India, John Wiley and Sons, Pp: 196-206.
Rosen, M.A., Thigpen, J.W., & Shnider, S.M. (1985). Bupivacaine-induced cardiotoxicity in hypoxic and acidotic sheep. Anesthesia and Analgesia, 64 (11): 1089-1096.
Rutten, A.J., Nancarrow, C., Mather, L.E., Ilsley, A.H., Runciman, W.B., & Upton, R.N. (1989). Hemodynamic and central nervous system effects of intravenous bolus doses of lidocaine, bupivacaine, and ropivacaine in sheep. Anesthesia and Analgesia, 69 (3): 291-299.
Sawaki, K., Ohno, K., Miyamoto, K., Hirai, S.; Yazaki, K., & Kawaguchi, M. (2000). Effects of Anticonvulsants on Local Anaesthetic-Induced Neurotoxicity in Rats. Pharmacology and Toxicology, 86 (2): 59-62.
Scott, B.D. (1975): Evaluation of the toxicity of local anaesthetic agents in man. British Journal Anaesthesia, 47 (1): 56–61.
Stewart, P., & Wiley, M. (1981). Structural and histochemical features of the avian blood‐brain barrier. Journal of Comparative Neurology, 202 (2): 157-167.
Torbiner, M.L., Yagiela, J.A., & Mito, R.S. (1989). Effect of midazolam pretreatment on the intravenous toxicity of lidocaine with and without epinephrine in rats. Anesthesia and Analgesia, 68 (6): 744-749.
Wiktorowska, A., Owczarek, J., & Orszulak-Michalak, D. (1999). The influence of lidocaine and verapamil on haemodynamic parameters after intravenous administration of midazolam in rabbits. Pharmacological Research, 39 (6): 421-429.