title: Injection anaesthesia with fentanyl-midazolam-medetomidine in adult female mice: importance of antagonization and perioperative care.
abstract: Injection anaesthesia is commonly used in laboratory mice; however, a disadvantage is that post-anaesthesia recovery phases are long. Here, we investigated the potential for shortening the recovery phase after injection anaesthesia with fentanyl-midazolam-medetomidine by antagonization with naloxone-flumazenil-atipamezole. In order to monitor side-effects, the depth of anaesthesia, heart rate (HR), core body temperature (BT) and concentration of blood gases, as well as reflex responses, were assessed during a 50 min anaesthesia. Mice were allowed to recover from the anaesthesia in their home cages either with or without antagonization, while HR, core BT and spontaneous home cage behaviours were recorded for 24 h. Mice lost righting reflex at 330 ± 47 s after intraperitoneal injection of fentanyl-midazolam-medetomidine. During anaesthesia, HR averaged 225 ± 23 beats/min, respiratory rate and core BT reached steady state at 131 ± 15 breaths/min and 34.3 ± 0.25℃, respectively. Positive pedal withdrawal reflex, movement triggered by tail pinch and by toe pinch, still occurred in 25%, 31.2% and 100% of animals, respectively. Arterial blood gas analysis revealed acidosis, hypoxia, hypercapnia and a marked increase in glucose concentration. After anaesthesia reversal by injection with naloxone-flumazenil-atipamezole, animals regained consciousness after 110 ± 18 s and swiftly returned to physiological baseline values, yet they displayed diminished levels of locomotion and disrupted circadian rhythm. Without antagonization, mice showed marked hypothermia (22 ± 1.9℃) and bradycardia (119 ± 69 beats/min) for several hours. Fentanyl-midazolam-medetomidine provided reliable anaesthesia in mice with reasonable intra-anaesthetic side-effects. Post-anaesthetic period and related adverse effects were both reduced substantially by antagonization with naloxone-flumazenil-atipamezole.
authors: Division of Surgical Research, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors: Thea
authors: T
authors: Fleischmann
authors: Division of Surgical Research, University Hospital Zurich, University of Zurich, Zurich, Switzerland Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland paulin.jirkof@usz.ch.
authors: Paulin
authors: P
authors: Jirkof
authors: Department of Nonclinical Drug Safety, Biological Laboratory Service, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors: Julia
authors: J
authors: Henke
authors: Division of Surgical Research, University Hospital Zurich, University of Zurich, Zurich, Switzerland Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland.
authors: Margarete
authors: M
authors: Arras
authors: Division of Surgical Research, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors: Nikola
authors: N
authors: Cesarovic
mesh_terms: D000700:Analgesics / Q000009:adverse effects / Q000494:pharmacology; D019162:Anesthetics, Combined / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D005260:Female; D005283:Fentanyl / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005442:Flumazenil / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007274:Injections, Intraperitoneal / Q000009:adverse effects; D020926:Medetomidine / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008874:Midazolam / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D019990:Perioperative Care
chemical_list: D000700:Analgesics; D019162:Anesthetics, Combined; D007093:Imidazoles; D009292:Narcotic Antagonists; D018377:Neurotransmitter Agents; C050701:atipamezole; D009270:Naloxone; D005442:Flumazenil; D020926:Medetomidine; D008874:Midazolam; D005283:Fentanyl
keywords: anaesthesia; antagonization; fentanyl; medetomidine; midazolam; mouse