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Midazolam

Grade

Sedation/Anxiolytic/AED

Therapeutics

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Evidence

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Rabbit Midazolam Evidence Base

  1. Astuto, M., Sorbello, M., Zirilli, V., Russo, M., La Greca, G., Di Cataldo, A., 2001. Experimental anaesthesiologic protocol for porto-intracaval shunt for liver total vascular exclusion: preliminary study in the rabbit. Microsurgery 21, 127–130. https://doi.org/10.1002/micr.1023

  2. Atalan, Güneri, Atalan, Gültekin, Erol, H., Erol, M., Atasever, A., Doğan, Z., Güneş, V., Yönez, M.K., Keleş, I., 2019. Comparison of Systemic Effects of Midazolam, Ketamine, and Isoflurane Anaesthesia in Rabbits. J Vet Res 63, 275–283. https://doi.org/10.2478/jvetres-2019-0035

  3. Baumgartner, C., Bollerhey, M., Ebner, J., Schuster, T., Henke, J., Erhardt, W., 2010. Effects of medetomidine-midazolam-fentanyl IV bolus injections and its reversal by specific antagonists on cardiovascular function in rabbits. Can J Vet Res 74, 286–298.

  4. Bellini, L., Banzato, T., Contiero, B., Zotti, A., 2014. Evaluation of sedation and clinical effects of midazolam with ketamine or dexmedetomidine in pet rabbits. Vet Rec 175, 372. https://doi.org/10.1136/vr.102595

  5. Bernards, C.M., Artu, A.A., 1991. Hexamethonium and midazolam terminate dysrhythmias and hypertension caused by intracerebroventricular bupivacaine in rabbits. Anesthesiology 74, 89–96. https://doi.org/10.1097/00000542-199101000-00015

  6. Bienert, A., Płotek, W., Wiczling, P., Kostrzewski, B., Kamińska, A., Billert, H., Szczesny, D., Zaba, C., Teżyk, A., Buda, K., Bednarek, E., Kaliszan, R., Grześkowiak, E., 2014. The influence of the time of day on midazolam pharmacokinetics and pharmacodynamics in rabbits. Pharmacol Rep 66, 143–152. https://doi.org/10.1016/j.pharep.2013.06.009

  7. Blake, D.W., Van Leeuwen, A.F., Petring, O.U., Ludbrook, J., Ventura, S., 1995. Haemodynamic response to simulated haemorrhage in the rabbit: interaction of i.v. anaesthesia and hypoxia. Br J Anaesth 75, 610–615. https://doi.org/10.1093/bja/75.5.610

  8. Borkowski, G.L., Danneman, P.J., Russell, G.B., Lang, C.M., 1990. An evaluation of three intravenous anesthetic regimens in New Zealand rabbits. Lab Anim Sci 40, 270–276.

  9. Botman, J., Hontoir, F., Gustin, P., Cambier, C., Gabriel, F., Dugdale, A., Vandeweerd, J.-M., 2020. Postanaesthetic effects of ketamine-midazolam and ketamine-medetomidine on gastrointestinal transit time in rabbits anaesthetised with isoflurane. Vet Rec 186, 249. https://doi.org/10.1136/vr.105491

  10. Bozkurt, P., Tunali, Y., Kaya, G., Okar, I., 1997. Histological changes following epidural injection of midazolam in the neonatal rabbit. Paediatr Anaesth 7, 385–389. https://doi.org/10.1046/j.1460-9592.1997.d01-107.x

  11. Bradley, M.P., Doerning, C.M., Nowland, M.H., Lester, P.A., 2019. Intramuscular Administration of Alfaxalone Alone and in Combination for Sedation and Anesthesia of Rabbits (Oryctolagus cuniculus). J Am Assoc Lab Anim Sci 58, 216–222. https://doi.org/10.30802/AALAS-JAALAS-18-000078

  12. Calvo, R., Suárez, E., Rodríguez-Sasiain, J.M., Martínez, I., 1992. The influence of renal failure on the kinetics of intravenous midazolam: an “in vitro” and “in vivo” study. Res Commun Chem Pathol Pharmacol 78, 311–320.

  13. Cardoso, C.G., Ayer, I.M., Jorge, A.T., Honsho, C.S., Mattos-Junior, E., 2020. A comparative study of the cardiopulmonary and sedative effects of a single intramuscular dose of ketamine anesthetic combinations in rabbits. Res Vet Sci 128, 177–182. https://doi.org/10.1016/j.rvsc.2019.11.016

  14. Chen, J., Yu, T., Longhini, F., Zhang, X., Liu, S., Liu, L., Yang, Y., Qiu, H., 2018. Midazolam increases preload dependency during endotoxic shock in rabbits by affecting venous vascular tone. Ann Intensive Care 8, 59. https://doi.org/10.1186/s13613-018-0403-9

  15. Crawford, M.E., Jensen, F.M., Toftdahl, D.B., Madsen, J.B., 1993. Direct spinal effect of intrathecal and extradural midazolam on visceral noxious stimulation in rabbits. Br J Anaesth 70, 642–646. https://doi.org/10.1093/bja/70.6.642

  16. Demirel, E., Ugur, H.C., Dolgun, H., Kahilogullari, G., Sargon, M.E., Egemen, N., Kecik, Y., 2006. The neurotoxic effects of intrathecal midazolam and neostigmine in rabbits. Anaesth Intensive Care 34, 218–223. https://doi.org/10.1177/0310057X0603400204

  17. Dupras, J., Vachon, P., Cuvelliez, S., Blais, D., 2001. [Anesthesia of the New Zealand rabbit using the the combination of tiletamine-zolazepam and ketamine-midazolam with or without xylazine]. Can Vet J 42, 455–460.

  18. Elbarbry, F., Attia, A., Shoker, A., 2009. Validation of a new HPLC method for determination of midazolam and its metabolites: application to determine its pharmacokinetics in human and measure hepatic CYP3A activity in rabbits. J Pharm Biomed Anal 50, 987–993. https://doi.org/10.1016/j.jpba.2009.07.004

  19. Engbers, S., Larkin, A., Rousset, N., Prebble, M., Jonnalagadda, M., Knight, C.G., Pang, D.S.J., 2017. Comparison of a Supraglottic Airway Device (v-gel®) with Blind Orotracheal Intubation in Rabbits. Front Vet Sci 4, 49. https://doi.org/10.3389/fvets.2017.00049

  20. Erdine, S., Yücel, A., Ozyalçin, S., Ozyuvaci, E., Talu, G.K., Ahiskali, B., Apak, H., Savci, N., 1999. Neurotoxicity of midazolam in the rabbit. Pain 80, 419–423. https://doi.org/10.1016/s0304-3959(98)00240-1

  21. Flecknell, P.A., Liles, J.H., Wootton, R., 1989. Reversal of fentanyl/fluanisone neuroleptanalgesia in the rabbit using mixed agonist/antagonist opioids. Lab Anim 23, 147–155. https://doi.org/10.1258/002367789780863655

  22. Flecknell, P.A., Mitchell, M., 1984. Midazolam and fentanyl-fluanisone: assessment of anaesthetic effects in laboratory rodents and rabbits. Lab Anim 18, 143–146. https://doi.org/10.1258/002367784780891406

  23. Fontes-Sousa, A.P., Moura, C., Carneiro, C.S., Teixeira-Pinto, A., Areias, J.C., Leite-Moreira, A.F., 2009. Echocardiographic evaluation including tissue Doppler imaging in New Zealand white rabbits sedated with ketamine and midazolam. Vet J 181, 326–331. https://doi.org/10.1016/j.tvjl.2008.02.022

  24. Freitag, F.A.V., Ferreira, A.A., Teixeira, W.T., Kerr, C.L., Duque, J.C.M., 2022. Sedative effects of an intramuscular or intranasal combination of sufentanil and midazolam in New Zealand White rabbits. Vet Anaesth Analg S1467-2987(22)00072–1. https://doi.org/10.1016/j.vaa.2022.04.006

  25. Giuliani, E., Manenti, A., Barbieri, A., Farinetti, A., Mattioli, A.V., 2018. Propofol: a safe anaesthetic drug in experimental cardiac surgery in rabbits. Ann Ital Chir 89, 92–94.

  26. Grint, N.J., Murison, P.J., 2008. A comparison of ketamine-midazolam and ketamine-medetomidine combinations for induction of anaesthesia in rabbits. Vet Anaesth Analg 35, 113–121. https://doi.org/10.1111/j.1467-2995.2007.00362.x

  27. Grint, N.J., Murison, P.J., 2007. Peri-operative body temperatures in isoflurane-anaesthetized rabbits following ketamine-midazolam or ketamine-medetomidine. Vet Anaesth Analg 34, 181–189. https://doi.org/10.1111/j.1467-2995.2006.00319.x

  28. Hedenqvist, P., Edner, A., Fahlman, Å., Jensen-Waern, M., 2013. Continuous intravenous anaesthesia with sufentanil and midazolam in medetomidine premedicated New Zealand White rabbits. BMC Vet Res 9, 21. https://doi.org/10.1186/1746-6148-9-21

  29. Hedenqvist, P., Edner, A., Jensen-Waern, M., 2014. Anaesthesia in medetomidine premedicated New Zealand White rabbits: a comparison between intravenous sufentanil-midazolam and isoflurane anaesthesia for orthopaedic surgery. Lab Anim 48, 155–163. https://doi.org/10.1177/0023677213516311

  30. Hedenqvist, P., Jensen-Waern, M., Fahlman, Å., Hagman, R., Edner, A., 2015. Intravenous sufentanil-midazolam versus sevoflurane anaesthesia in medetomidine pre-medicated Himalayan rabbits undergoing ovariohysterectomy. Vet Anaesth Analg 42, 377–385. https://doi.org/10.1111/vaa.12207

  31. Henke, J., Astner, S., Brill, T., Eissner, B., Busch, R., Erhardt, W., 2005. Comparative study of three intramuscular anaesthetic combinations (medetomidine/ketamine, medetomidine/fentanyl/midazolam and xylazine/ketamine) in rabbits. Vet Anaesth Analg 32, 261–270. https://doi.org/10.1111/j.1467-2995.2005.00242.x

  32. Hexeberg, E., Hexeberg, S., Hessevik, I., Fosse, R.T., 1995. Midazolam in combination with fentanyl/fluanisone and nitrous oxide as anaesthesia in rabbits--cardiovascular parameters. Lab Anim 29, 400–406. https://doi.org/10.1258/002367795780740069

  33. Hyatt, J., Coro, C., Bergman, S.A., Wynn, R.L., 1989. Effects of midazolam on fentanyl antinociception and respiration in a rabbit model. J Oral Maxillofac Surg 47, 1298–1302. https://doi.org/10.1016/0278-2391(89)90728-3

  34. Jaček, M., Matějčková, J., Málek, J., Hess, L., Samcová, E., 2013. Determination of midazolam in rabbit plasma by GC and LC following nasal and ocular administration. J Sep Sci 36, 3366–3371. https://doi.org/10.1002/jssc.201300401

  35. Kim, C., Shvarev, Y., Takeda, S., Sakamoto, A., Lindahl, S.G.E., Eriksson, L.I., 2006. Midazolam depresses carotid body chemoreceptor activity. Acta Anaesthesiol Scand 50, 144–149. https://doi.org/10.1111/j.1399-6576.2005.00896.x

  36. Kirihara, Y., Takechi, M., Kurosaki, K., Matsuo, H., Kajitani, N., Saito, Y., 2019. Effects of an anesthetic mixture of medetomidine, midazolam, and butorphanol and antagonism by atipamezole in rabbits. Exp Anim 68, 443–452. https://doi.org/10.1538/expanim.18-0183

  37. Ko, J.C., Thurmon, J.C., Tranquilli, W.J., Benson, G.J., Olson, W.A., 1992. A comparison of medetomidine-propofol and medetomidine-midazolam-propofol anesthesia in rabbits. Lab Anim Sci 42, 503–507.

  38. Kohjitani, A., Miyawaki, T., Funahashi, M., Higuchi, H., Matsuo, R., Shimada, M., 2003. Ketamine and midazolam differentially inhibit nonadrenergic noncholinergic lower esophageal sphincter relaxation in rabbits: role of superoxide anion and nitric oxide synthase. Anesthesiology 98, 449–458. https://doi.org/10.1097/00000542-200302000-00026

  39. Lee, L.Y., Lee, D., Ryu, H., Han, J.H., Ko, J., Tyler, J.W., 2019. Capnography-guided Endotracheal Intubation as an Alternative to Existing Intubation Methods in Rabbits. J Am Assoc Lab Anim Sci 58, 240–245. https://doi.org/10.30802/AALAS-JAALAS-17-000150

  40. Ma, D., Sapsed-Byrne, S.M., Chakrabarti, M.K., Whitwam, J.G., 1998. Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits. Acta Anaesthesiol Scand 42, 670–677. https://doi.org/10.1111/j.1399-6576.1998.tb05300.x

  41. Malinovsky, J.M., Cozian, A., Lepage, J.Y., Mussini, J.M., Pinaud, M., Souron, R., 1991. Ketamine and midazolam neurotoxicity in the rabbit. Anesthesiology 75, 91–97. https://doi.org/10.1097/00000542-199107000-00015

  42. Marques, A.E.G.W., Marques, M.G., Silveira, B.C.R., Oliveira, S.P., Ferraz, I.G., Ventricci, A.B.G., Silva, N.C., Nagata, W.B., Floriano, B.P., Ferreira, W.L., Santos, P.S.P., 2020. Lidocaine administered at a continuous rate infusion does not impair left ventricular systolic and diastolic function of healthy rabbits sedated with midazolam. Vet Anim Sci 10, 100151. https://doi.org/10.1016/j.vas.2020.100151

  43. Martinez, M.A., Murison, P.J., Love, E., 2009. Induction of anaesthesia with either midazolam or propofol in rabbits premedicated with fentanyl/fluanisone. Vet Rec 164, 803–806. https://doi.org/10.1136/vr.164.26.803

  44. Momota, Y., Artru, A.A., Powers, K.M., Mautz, D.S., Ueda, Y., 1998. Posttreatment with propofol terminates lidocaine-induced epileptiform electroencephalogram activity in rabbits: effects on cerebrospinal fluid dynamics. Anesth Analg 87, 900–906. https://doi.org/10.1097/00000539-199810000-00029

  45. Odou, P., Barthélémy, C., Chatelier, D., Luyckx, M., Brunet, C., Dine, T., Gressier, B., Cazin, M., Cazin, J.C., Robert, H., 1999. Pharmacokinetics of midazolam: comparison of sublingual and intravenous routes in rabbit. Eur J Drug Metab Pharmacokinet 24, 1–7. https://doi.org/10.1007/BF03190004

  46. Oguntoye, C.O., Oyewande, O.A., Afolabi, O.O., 2018. Evaluation of Tramadol-Midazolam-Ketamine Anaesthesia in Rabbits. Niger J Physiol Sci 33, 145–149.

  47. Orszulak-Michalak, Daria, Owczarek, J., Wiktorowska-Owczarek, A.K., 2002. Influence of midazolam on pharmacokinetics of verapamil in rabbits. Pol J Pharmacol 54, 501–506.

  48. Orszulak-Michalak, D., Owczarek, J., Wiktorowska-Owczarek, A.K., 2002. The influence of midazolam on plasma concentrations and pharmacokinetic parameters of lidocaine in rabbits. Pharmacol Res 45, 11–14. https://doi.org/10.1006/phrs.2001.0879

  49. Petry, L., Thirion, B., Frisoni, A., Boudigues, O., Lesure, P., George, J.L., 1990. [A new anesthetic protocol in experimental ocular surgery in rabbits]. Bull Soc Ophtalmol Fr 90, 637–641.

  50. Raulic, J., Leung, V.S., Doss, G.A., Graham, J.E., Keller, K.A., Mans, C., Sadar, M.J., Vergneau-Grosset, C., Pang, D.S., 2021. Development and Testing of a Sedation Scale for Use in Rabbits (Oryctolagus cuniculus). J Am Assoc Lab Anim Sci 60, 549–555. https://doi.org/10.30802/AALAS-JAALAS-21-000002

  51. Rivo, J., Raphael, J., Drenger, B., Berenshtein, E., Chevion, M., Gozal, Y., 2006. Flumazenil mimics whereas midazolam abolishes ischemic preconditioning in a rabbit heart model of ischemia-reperfusion. Anesthesiology 105, 65–71. https://doi.org/10.1097/00000542-200607000-00014

  52. Robertson, S.A., Eberhart, S., 1994. Efficacy of the intranasal route for administration of anesthetic agents to adult rabbits. Lab Anim Sci 44, 159–165.

  53. Rousseau-Blass, F., Cribb, A.E., Beaudry, F., Pang, D.S., 2021. A Pharmacokinetic-Pharmacodynamic Study of Intravenous Midazolam and Flumazenil in Adult New Zealand White-Californian Rabbits (Oryctolagus cuniculus). J Am Assoc Lab Anim Sci 60, 319–328. https://doi.org/10.30802/AALAS-JAALAS-20-000084

  54. Rózańska, D., 2009. Evaluation of medetomidine-midazolam-atropine (MeMiA) anesthesia maintained with propofol infusion in New Zealand White rabbits. Pol J Vet Sci 12, 209–216.

  55. Sakamoto, M., Yasumoto, M., Ohsumi, H., Choi, H., Shibata, Y., Kano, T., 1994. Effects of midazolam and flumazenil on carotid sinus baroreflex control of circulation in rabbits. Br J Anaesth 73, 384–387. https://doi.org/10.1093/bja/73.3.384

  56. Santangelo, B., Micieli, F., Marino, F., Reynaud, F., Cassandro, P., Carfora, A., Petrella, R., Borriello, R., Cataldi, M., Vesce, G., 2016a. Plasma concentrations and sedative effects of a dexmedetomidine, midazolam, and butorphanol combination after transnasal administration in healthy rabbits. J Vet Pharmacol Ther 39, 408–411. https://doi.org/10.1111/jvp.12282

  57. Santangelo, B., Micieli, F., Marino, F., Reynaud, F., Cassandro, P., Carfora, A., Petrella, R., Borriello, R., Cataldi, M., Vesce, G., 2016b. Plasma concentrations and sedative effects of a dexmedetomidine, midazolam, and butorphanol combination after transnasal administration in healthy rabbits. Journal of Veterinary Pharmacology and Therapeutics 39, 408–411. https://doi.org/10.1111/jvp.12282

  58. Santangelo, Bruna, Micieli, F., Mozzillo, T., Reynaud, F., Marino, F., Auletta, L., Vesce, G., 2016. Transnasal administration of a combination of dexmedetomidine, midazolam and butorphanol produces deep sedation in New Zealand White rabbits. Vet Anaesth Analg 43, 209–214. https://doi.org/10.1111/vaa.12278

  59. Scherschlicht, R., Marias, J., 1983. Effects of oral and intravenous midazolam, triazolam and flunitrazepam on the sleep-wakefulness cycle of rabbits. Br J Clin Pharmacol 16 Suppl 1, 29S-35S. https://doi.org/10.1111/j.1365-2125.1983.tb02268.x

  60. Schroeder, C.A., Smith, L.J., 2011a. Respiratory rates and arterial blood-gas tensions in healthy rabbits given buprenorphine, butorphanol, midazolam, or their combinations. J Am Assoc Lab Anim Sci 50, 205–211.

  61. Schroeder, C.A., Smith, L.J., 2011b. Respiratory rates and arterial blood-gas tensions in healthy rabbits given buprenorphine, butorphanol, midazolam, or their combinations. J Am Assoc Lab Anim Sci 50, 205–211.

  62. Troitzsch, D., Peukert, A., Vogt, S., 1995. [Ketamine-midazolam combination for anesthesia of rabbits--results of neuroelectrophysiologic studies using evoked potentials]. Berl Munch Tierarztl Wochenschr 108, 143–147.

  63. Ugur, B., Basaloglu, K., Yurtseven, T., Ates, U., Aydin, O.N., Ozenç, D., Yurtseven, M., Gürel, A., 2005. Neurotoxicity with single dose intrathecal midazolam administration. Eur J Anaesthesiol 22, 907–912. https://doi.org/10.1017/S0265021505001547

  64. Vachon, P., Dupras, J. e, Prout, R., Blais, D., 1999. EEG Recordings in Anesthetized Rabbits: Comparison of Ketamine-Midazolam and Telazol With or Without Xylazine. Contemp Top Lab Anim Sci 38, 57–61.

  65. Watts, A.D., Eliasziw, M., Gelb, A.W., 1998. Propofol and hyperventilation for the treatment of increased intracranial pressure in rabbits. Anesth Analg 87, 564–568. https://doi.org/10.1097/00000539-199809000-00012

  66. Whelan, G., Flecknell, P.A., 1995. Anaesthesia of laboratory rabbits using etorphine/methotrimeprazine and midazolam. Lab Anim 29, 83–89. https://doi.org/10.1258/002367795780740384

  67. Wiktorowska, A., Owczarek, J., Orszulak-Michalak, D., 1999. The influence of lidocaine and verapamil on haemodynamic parameters after intravenous administration of midazolam in rabbits. Pharmacol Res 39, 421–429. https://doi.org/10.1006/phrs.1998.0464

  68. Wiktorowska-Owczarek, A., Owczarek, J., Obolewska, A., Orszulak-Michalak, D., 2000. Effect of propranolol and midazolam therapy on hemodynamic parameters in rabbits. Med Sci Monit 6, 896–900.

  69. Yamaguchi, S., Kanmura, Y., Yoshimura, N., 1997. Effects of midazolam on contractions in smooth muscle of the rabbit mesenteric artery. Anesth Analg 84, 199–205. https://doi.org/10.1097/00000539-199701000-00036

  70. Yanmaz, L.E., Okur, S., Turgut, F., Golgeli, A., 2022. Effects of intramuscular and intranasal administration of midazolam-dexmedetomidine on sedation and some cardiopulmonary variables in New Zealand White rabbits. Vet Anaesth Analg 49, 113–117. https://doi.org/10.1016/j.vaa.2021.10.003

  71. Zhu, Y.-M., Yuan, Z.-Y., Wu, H., Zhou, D.-D., Jing, G.-X., 2011. Midazolam in rabbits terminates dysrhythmias caused by intracerebroventricular ropivacaine. J Zhejiang Univ Sci B 12, 668–676. https://doi.org/10.1631/jzus.B1000337

Expert Opinion

  1. 1317822* |  221003 Extrapolation of pharmacological properties in man and veterinary species. Some material employed in collating the data displayed here was taken from veterinary product datasheets or extrapolated from pharmacology texts.


Last Update 1317822 | 221003

Monograph Details

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