The effects of flumazenil on ventilatory and recovery characteristics in horses following midazolam‐ketamine induction and isoflurane anaesthesia

Abstract

Background: Flumazenil antagonises the actions of benzodiazepines. There has been no prior research specifically investigating this anaesthetic reversal agent for horses.Objectives: To determine the effects of flumazenil administration in horses on (a) ventilatory parameters after midazolam-ketamine induction and maintenance with isoflurane in oxygen and on (b) the characteristics of recovery from general anaesthesia.Study design: Blinded, randomised, crossover experiment.Methods: Six horses were randomly assigned to receive high-dose flumazenil (F high , 20 µg/kg), low-dose flumazenil (F low , 10 µg/kg) and saline (control). Cardioventilatory parameters were monitored. After 90 minutes of isoflurane anaesthesia, a bolus of F high , F low or saline was administered i.v. The horses were recovered using head and tail rope assistance. The times to first movement, to achievement of sternal recumbency, to the first attempt to stand and the total recovery time were determined.The recovery quality was evaluated using a 115-point recovery scoring system. The cardioventilatory parameters and recovery times were analysed using mixed-effects regression analyses. Intraclass correlation (ICC) analysis was used to evaluate the recovery scores. A Mann-Whitney U test assessed the relationship between recovery score and flumazenil administration.Results: A significant difference with flumazenil administration was found for SpO 2 , mean arterial pressure, I:E ratio, minute volume of ventilation (MV) and peak inspiratory pressure. There was a significant difference with flumazenil administration for the time to sternal recumbency, the time to the first attempt to rise and the total recovery time. There was no significant difference in total recovery score with flumazenil administration.Main limitations: Plasma levels of midazolam and flumazenil were not obtained.Conclusions: Flumazenil has a dose-dependent effect on MV and recovery time, which may make it useful in cases for which a prolonged anaesthetic recovery is undesirable.

Recovery of horses from general anaesthesia: A systematic review (2000‐2020) of risk factors and influence of interventions during the recovery period

“…The administration of benzodiazepine antagonist flumazenil before anaesthetic recovery resulted in shorter recovery times but no difference in quality of recovery compared to a control group 13 . Horses treated with flumazenil did exhibit a higher minute ventilation which may, in part, explain a faster recovery time due to more rapid elimination of inhalation agent 13 .…”

“…The CSS examines quantitative and qualitative aspects of each recovery phase and may offer greater sensitivity than the SDS. The CSS contains more categories which may indicate that aspects such as ataxia may be specifically examined, however, in one study, the authors considered the CSS to be too subjective after failing to detect differences in ataxia between groups in their study and suggested that a more objective assessment of ataxia and muscle weakness could be offered with the use of accelerometry 13 . However, there may be practical limitations associated with accelerometry given the wide variation in movement that a horse is capable of.…”

Recovery after General Anaesthesia in Adult Horses: A Structured Summary of the Literature

“…Eighteen publications fell into this category [299][300][301][302][303][304][305][306][307][308][309][310][311][312][313][314][315][316]. Most of the studies were published after the year 2000 and the main inhalant agent used was isoflurane, followed by sevoflurane.…”

“…A recent study reported the use of flumazenil to counteract the effects of benzodiazepines due to their long plasma half-lives [316]. In that randomised, blinded, crossover, experimental study with six horses, flumazenil shortened recovery times without influencing quality of recovery.…”

“…305] (8) Effect of administration of propofol and xylazine hydrochloride on recovery of horses after four hours of anesthesia with desflurane[306] (9) Comparison of the effects of xylazine and romifidine administered perioperatively on the recovery of anesthetized horses[307] (10) Evaluation of infusions of xylazine with ketamine or propofol to modulate recovery following sevoflurane anesthesia in horses[308] (11) Effects of postanesthetic sedation with romifidine or xylazine on quality of recovery from isoflurane anesthesia in horses[309] (12) Assessment of unassisted recovery from repeated general isoflurane anesthesia in horses following post-anesthetic administration of xylazine or acepromazine or a combination of xylazine and ketamine[310] (13) Effect of postoperative xylazine administration on cardiopulmonary function and recovery quality after isoflurane anesthesia in horses[311] (14) Recovery from desflurane anesthesia in horses with and without post-anesthetic xylazine[312] (15) Comparison between the effects of postanesthetic xylazine and dexmedetomidine on characteristics of recovery from sevoflurane anesthesia in horses[313] (16) Pharmacokinetics and clinical effects of xylazine and dexmedetomidine in horses recovering from isoflurane anesthesia[314] (17) Recovery quality following a single post-anaesthetic dose of dexmedetomidine or romifidine in sevoflurane anaesthetised horses[315] (18) The effects of flumazenil on ventilatory and recovery characteristics in horses following midazolam-ketamine induction and isoflurane anaesthesia[316] drugs before/during recovery publications = 18 LoE: level of evidence.…”