Midazolam as an anaesthetic agent in children
Creators: name: Jones, RDM
Publisher: name: University Of Tasmania
Year: 2023

description: A relatively high dose of midazolam has to be administered orally to achieve the favourable effects of premedication in children and this could be associated with arterial oxygen desaturation. Pethidine has been commonly administered as a premedicant to children for many years, however its association with oximetric desaturation has not previously been investigated. In this thesis the incidence, duration and severity of oximetric desaturation episodes was determined following premedication in children with midazolam and pethidine. To facilitate this research, SatmasterTM, a computer programme which permits storage, retrieval, signal evaluation and data compilation, was developedin conjunction with the software authors and subjected to artefact template analysis to reduce the inclusion of spurious oximetric data in the determination of the incidence of desaturation. It was found that neither pethidine nor midazolam premedication increased the incidence of episodic desaturation when compared to that occurring during normal sleep. If analgesia is not a premedication requirement, oral midazolam confers the advantage over pethidine of avoiding the pain of an intramuscular injection, without compromising oxygen saturation. The availability of flumazenil permits specific reversal of the unconsciousness and reflex depression associated with the hypnotic effect of midazolam administration. The combined pharmacokinetics and pharmacodynamics of midazolam and flumazenil in children have not previously been reported. Midazolam pharmacokinetics were shown to compare favourably with those of propofol in a similar patient population and it was found that midazolam antagonism with flumazenil produced similar clinical awakening rates to those achieved after propofol induction. Blood pressure changes on induction were measured using a standard intermittent noninvasive technique and these were compared with continuous pressure measurements using a Finapres, modified for paediatric use and computerised data acquisition. Propofol induction was associated with hypotension of a significantly greater degree and duration compared to midazolam and thiopentone. Postoperative recovery after anaesthesia is particularly important for ambulatory surgery. The effect of midazolam on psychomotor performance, residual sedation and mood was shown to be related to plasma concentration. These indices were also used to assess recovery after anaesthetic induction with either midazolam, thiopentone or propofol. A post-box toy completion ratio (PBTR) was developed for assessment of psychomotor performance in children and compared with a standard component of the Wechsler intelligence scale (WISC-R). The PBTR was found to be as sensitive as the WISC-R in this assessment, but also has the advantage of ease of administration. The quality and rate of recovery following unantagonised midazolam induction in the immediate postoperative period is inferior to propofol and thiopentone but within one hour of awakening there is no difference in recovery characteristics between the agents. Recovery of orientation, co-operation and comprehension after flumazenil administration would appear to be as rapid as propofol and superior to thiopentone. Midazolam (0.5 mg kg‚ÄövÖ¬™¬¨œÄ) administered orally is a suitable premedicant for children. The drug's bitter taste can be disguised, it is rapidly absorbed, producing peak sedative effects at 60 min, and has residual anxiolytic effects 120 min after administration. Premedication was not associated with episodic oximetric desaturation and the children entered the operating suite without overt distress, appearing calm and co-operative. Intravenous midazolam (0.5 mg kg‚ÄövÖ¬™¬¨œÄ) compares favourably to propofol and thiopentone as an induction agent in some respects, providing a intermediate onset of action, intraoperative amnesia, excellent operating conditions and when reversed with flumazenil, it has a short recovery period without unwanted residual effects. However propofol and thiopentone are both easier to administer because their onset of action occurs in one arm-brain circulation time and they demonstrate a definite end-point. Following anaesthetic induction with midazolam, psychomotor performance returned to preoperative unmedicated levels (recorded the previous evening), without flumazenil administration, within 4 hr of eye opening. There were no adverse side effects associated with the administration of midazolam. Midazolam therefore seems to be a very suitable agent for use in elective surgery in children.