title: Towards optimized anesthesia protocols for stereotactic surgery in rats: Analgesic, stress and general health effects of injectable anesthetics. A comparison of a recommended complete reversal anesthesia with traditional chloral hydrate monoanesthesia.
abstract: Although injectable anesthetics are still widely used in laboratory rodents, scientific data concerning pain and distress during and after stereotactic surgery are rare. However, optimal anesthesia protocols have a high impact on the quality of the derived data. We therefore investigated the suitability of recommended injectable anesthesia with a traditionally used monoanesthesia for stereotactic surgery in view of optimization and refinement in rats. The influence of the recommended complete reversal anesthesia (MMF; 0.15mg/kg medetomidine, 2mg/kg midazolam, 0.005mg/kg fentanyl; i.m.) with or without reversal and of chloral hydrate (430mg/kg, 3.6%, i.p.) on various physiological, biochemical and behavioral parameters (before, during, after surgery) was analyzed. Isoflurane was also included in stress parameter analysis. In all groups, depth of anesthesia was sufficient for stereotactic surgery with no animal losses. MMF caused transient exophthalmos, myositis at the injection site and increased early postoperative pain scores. Reversal induced agitation, restlessness and hypothermia. Even the low concentrated chloral hydrate led to peritonitis and multifocal liver necrosis, corresponding to increased stress hormone levels and loss in body weight. Increased stress response was also exerted by isoflurane anesthesia. Pronounced systemic toxicity of chloral hydrate strongly questions its further use in rodent anesthesia. In view of undesired effects of MMF and isoflurane, thorough consideration of anesthesia protocols for particular research projects is indispensable. Reversal should be restricted to emergency situations. Our data support further refinement of the current protocols and the importance of sham operated controls.
authors.affiliation: Institute of Pharmacology, Pharmacy and Toxicology, Veterinary Faculty, University Leipzig, Germany.
authors.forename: Christin
authors.initials: C
authors.lastname: Hüske
authors.affiliation: Institute of Pharmacology and Toxicology, Department of Veterinary Medicine, Freie Universität Berlin, Germany. Electronic address: svenja.sander@fu-berlin.de.
authors.forename: Svenja Esther
authors.initials: SE
authors.lastname: Sander
authors.affiliation: Institute of Pharmacology and Toxicology, Department of Veterinary Medicine, Justus-Liebig-Universität Gießen, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Hamann
authors.affiliation: Institute of Veterinary Pathology, Department of Veterinary Medicine, Freie Universität Berlin, Germany.
authors.forename: Olivia
authors.initials: O
authors.lastname: Kershaw
authors.affiliation: Institute of Pharmacology, Pharmacy and Toxicology, Veterinary Faculty, University Leipzig, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Richter
authors.affiliation: Institute of Pharmacology, Pharmacy and Toxicology, Veterinary Faculty, University Leipzig, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Richter
mesh_terms: D000758:Anesthesia / Q000009:adverse effects / Q000379:methods*; D000777:Anesthetics / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D002697:Chloral Hydrate / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage; D007267:Injections / Q000009:adverse effects; D007530:Isoflurane / Q000008:administration & dosage; D008297:Male; D020926:Medetomidine / Q000008:administration & dosage; D008874:Midazolam / Q000008:administration & dosage; D023421:Models, Animal; D010149:Postoperative Pain / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D051381:Rats; D013238:Stereotaxic Techniques; D013315:Stress, Psychological / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D000777:Anesthetics; D002697:Chloral Hydrate; D007530:Isoflurane; D020926:Medetomidine; D008874:Midazolam; D005283:Fentanyl
keywords: Chloral hydrate; Complete reversal anesthesia; Injectable anesthetic; Refinement