title: The effect of intravenous administration of variable-dose midazolam after fixed-dose ketamine in healthy awake cats.
abstract: The effects of intravenous administration of variable-dose midazolam and ketamine (3 mg/kg) were studied in twelve healthy unmedicated cats from time of administration until full recovery. A range of midazolam doses (0.0, 0.05, 0.5, 1.0, 2.0 and 5.0 mg/kg) was chosen, so that beneficial and/or detrimental effects could be documented and the therapeutic window for further study determined. One minute after administration of ketamine, all cats had assumed a lateral position, mostly with head up. Muscle tone was increased (100%), apneustic breathing pattern evident in 92% of cats, chewing without stimulation of the oropharyngeal area was observed in most cats (97%), but most cats did not salivate (87%). At 2.5 min after completion of ketamine injection and 1 min after administration of saline, a similar picture was observed, except that salivation was evident. All cats chewed or swallowed in response to a finger or laryngoscope placed in the oropharyngeal area and, while most cats were not aware of a noxious stimulus to the tail, some cats were aware of a noxious stimulus to the paw. Recovery from ketamine alone was rapid and smooth with cats rolling into sternal recumbency and then cautiously walking with ataxia. Recovery to walking without incoordination was also rapid (< 2 h) and no abnormal behavioural patterns were observed during recovery. Administration of midazolam after ketamine, had beneficial effects and the therapeutic window for midazolam was found to lie between 0.05 mg/kg and 0.5 mg/kg. Administration of any dose of midazolam after ketamine caused a greater proportion of cats to assume a laterally recumbent position with head down compared with ketamine alone, however, the time period of recumbency was only significantly longer with a midazolam dose of 2.0 mg/kg or above. Doses of midazolam of 0.5 mg/kg or above decreased muscle rigidity but did not affect salivation or respiratory pattern observed in cats which received ketamine alone. A significantly greater proportion of cats which received ketamine and midazolam 0.5 mg/kg or above did not swallow in response to a finger or a laryngoscope placed in the mouth compared with that which received ketamine alone. The length of time in which cats did not swallow was only significantly longer at midazolam doses of 1.0 mg/kg and above. At midazolam doses of 0.5 mg/kg or above, the proportion of cats without a nociceptive response to a tail or paw clamp was significantly greater than cats which received ketamine alone. The time period without nociceptive response, however, was not influenced by midazolam administration. The time taken for cats which received ketamine and midazolam 0.05 mg/kg or 0.5 mg/kg to assume sternal position, walk with ataxia, walk without ataxia, behave normally when approached or restrained and recover normal arousal state was not significantly different from cats which received ketamine alone. Ketamine and midazolam 5.0 mg/kg significantly prolonged all recovery times compared with ketamine alone. Unfortunately, a greater proportion of cats which received ketamine and midazolam 0.5 or 5.0 mg/kg exhibited detrimental behavioural effects. These were more likely to be adverse and included restlessness, vocalization and difficulty approaching and restraining cats. In this study, an effect of sex of the cats was found, with male cats taking a significantly longer to recover to sternal recumbency and walk with ataxia, while female cats took longer to recover to a normal arousal state.
authors.affiliation: Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis 95616, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Ilkiw
authors.forename: C M
authors.initials: CM
authors.lastname: Suter
authors.forename: D
authors.initials: D
authors.lastname: McNeal
authors.forename: T B
authors.initials: TB
authors.lastname: Farver
authors.forename: E P
authors.initials: EP
authors.lastname: Steffey
mesh_terms: D000778:Anesthetics, Dissociative / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D001259:Ataxia / Q000139:chemically induced / Q000662:veterinary; D001522:Behavior, Animal / Q000187:drug effects*; D002415:Cats; D016009:Chi-Square Distribution; D004347:Drug Interactions; D005260:Female; D007275:Injections, Intravenous / Q000662:veterinary; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D008874:Midazolam / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D017288:Pain Threshold / Q000187:drug effects; D016683:Supine Position
chemical_list: D000778:Anesthetics, Dissociative; D014151:Anti-Anxiety Agents; D007649:Ketamine; D008874:Midazolam