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Midazolam as an anaesthetic agent in children


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Jones, RDM 1995 , 'Midazolam as an anaesthetic agent in children', Coursework Master thesis, University of Tasmania.

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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
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⁻¹) 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⁻¹) 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.

Item Type: Thesis - Coursework Master
Authors/Creators:Jones, RDM
Keywords: Midazolam, Pediatric anesthesia
Copyright Holders: The Author
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Copyright 1993 the Author - The University is continuing to endeavour to trace the copyright
owner(s) and in the meantime this item has been reproduced here in good faith. We
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Additional Information:

Thesis (M.D.)--University of Tasmania, 1995. Includes bibliographical references

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