Abstract
BackgroundA prospective, randomized, placebo-controlled, blinded clinical study was conducted to determine whether a single dose of midazolam affects the cardiovascular response to surgical manipulation of the ovaries during elective ovariohysterectomy. Thirty-nine client-owned dogs undergoing elective ovariohysterectomy were recruited. After scoring cage demeanour, dogs were premedicated with acepromazine (0.03 mg kg-1) and pethidine (3 mg kg-1) intramuscularly into the quadriceps muscle and 20 min later sedation was scored. Anaesthesia was induced with propofol intravenously (IV) to effect. The study treatment (group M: midazolam (0.25 mg kg-1); or group P: placebo (Hartmann’s solution) (0.125 ml kg-1)) was administered IV before the intra-operative manipulation of the first ovary. Anaesthesia was maintained with isoflurane in oxygen. Morphine (0.3 mg kg-1 IV) was administered prior to the start of surgery. The vaporizer setting was adjusted according to the depth of anaesthesia. If an end-tidal isoflurane concentration (FE’Iso) above 1.6% was required additional analgesia was provided with fentanyl (2 μg kg-1). Dogs received meloxicam (0.2 mg kg-1 IV) at the end of procedure. Heart rate, mean arterial blood pressure, respiratory rate and end-tidal partial pressure of carbon dioxide as well as FE’Iso were recorded and analysed.ResultsA statistical significant difference between groups was detected in FE’Iso, with group M requiring a significantly lower FE’Iso than group P (14.3%) after administration of midazolam. No differences between groups was shown for percentage change in heart rate and mean arterial blood pressure, or end-tidal carbon dioxide and requirement for mechanical ventilation, or rescue analgesia. There was no statistically significant difference in the incidence of complications in group M and P. Group M received significantly more succinylated gelatin solution pre-administration of midazolam than group P, but no differences in fluid administration post-administration of the study treatment (midazolam/placebo) were detected. No statistical significant difference was demonstrated for the use of anticholinergic agents, dobutamine or noradrenaline.ConclusionNo significant effect on cardiovascular parameters could be observed with administration of midazolam, but a modest (14.3%) isoflurane-sparing effect was detected.
Highlights
A prospective, randomized, placebo-controlled, blinded clinical study was conducted to determine whether a single dose of midazolam affects the cardiovascular response to surgical manipulation of the ovaries during elective ovariohysterectomy
The primary objective of the study was to determine the effect of midazolam on the cardiovascular response to the surgical manipulation of the ovaries during elective ovariohysterectomy
Animals The conducted study was approved by the University College Dublin (UCD) Office of Animal Research Ethics and signed, informed owner consent was obtained for all patients included
Summary
A prospective, randomized, placebo-controlled, blinded clinical study was conducted to determine whether a single dose of midazolam affects the cardiovascular response to surgical manipulation of the ovaries during elective ovariohysterectomy. The study treatment (group M: midazolam (0.25 mg kg-1); or group P: placebo (Hartmann’s solution) (0.125 ml kg-1)) was administered IV before the intra-operative manipulation of the first ovary. If an end-tidal isoflurane concentration (FE’Iso) above 1.6% was required additional analgesia was provided with fentanyl (2 μg kg-1). Intra-operative detection of pain relies on the observation and interpretation of autonomic changes, especially cardiovascular and respiratory responses [12,13,14]. Similar to other benzodiazepine agonists it induces anticonvulsant, anxiolytic, sedative/hypnotic, amnesic and centrally mediated muscle relaxant effects [15]. It was shown to cause minimal cardiovascular changes at clinically relevant doses [17] but is associated with a dose-related centrally mediated respiratory depression [18]
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