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

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Summary

Introduction

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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