OBJECTIVE
To examine the effect of dose and route of administration on the sedative-hypnotic effects of midazolam.
DESIGN
Prospective randomized controlled study ANIMALS: Six indigenous, African bred goats.
METHODS
Pilot studies indicated that the optimum dose of midazolam for producing sedation was 0.6 mg kg-1 for intramuscular (IM) injection, while the optimum intravenous (IV) doses causing hypnosis without, and with loss of palpebral reflexes were 0.6 mg kg-1 and 1.2 mg kg-1, respectively. These doses and routes of administration were compared with a saline placebo in a randomized block design in the main experiment, and the sedative-hypnotic effects evaluated according to pre-determined scales.
RESULTS
Intramuscular midazolam produced sedation with or without sternal recumbency in all animals with the peak effect occurring 20 minutes after administration. The scores for IM sedation with midazolam were significantly different (p < 0.05) from placebo. Intravenous midazolam at 0.6 mg kg-1 resulted in hypnosis, and at 1.2 mg kg-1 increased reflex suppression was observed. The maximum scores for hypnosis at both doses were obtained 5 minutes after IV injection. The mean (± SD) duration of lateral recumbency was 10.8 (± 3.8) minutes after IV midazolam (0.6 mg kg-1) compared to 20 (± 5.2) minutes after midazolam at 1.2 mg kg-1. Compared to baseline, the heart rate increased significantly (p < 0.05) after high dose IV midazolam.
CONCLUSION
Intramuscular midazolam (0.6 mg kg-1) produced maximum sedation 20 minutes after injection. Intravenous injection produced maximum hypnosis within 5 minutes. Increasing the IV dose from 0.6 to 1.2 mg kg-1 resulted in increased reflex suppression and duration of hypnosis.
CLINICAL RELEVANCE
For a profound effect with rapid onset midazolam should be given IV in doses between 0.6 and 1.2 mg kg-1.
[1]
G. Stegmann.
Observations on the use of midazolam for sedation, and induction of anaesthesia with midazolam in combination with ketamine in the goat.
,
1998,
Journal of the South African Veterinary Association.
[2]
A. Waterman,et al.
Antinociceptive activity of midazolam in sheep.
,
1995,
Journal of veterinary pharmacology and therapeutics.
[3]
J. Gross,et al.
Slow injection does not prevent midazolam-induced ventilatory depression.
,
1992
.
[4]
P. Taylor.
Anaesthesia in sheep and goats
,
1991,
In Practice.
[5]
K. T. Dodd,et al.
The cardiorespiratory effects of diazepam-ketamine and xylazine-ketamine anesthetic combinations in sheep.
,
1989,
Laboratory animal science.
[6]
A. Waterman,et al.
The effects of alpha 2 adrenoceptor agonists on airway pressure in anaesthetized sheep.
,
1986,
Journal of veterinary pharmacology and therapeutics.
[7]
J G Reves,et al.
Midazolam: Pharmacology and Uses
,
1985,
Anesthesiology.
[8]
A. Uggla,et al.
Acute pulmonary oedema as an adverse reaction to the use of xylazine in sheep
,
1983,
Veterinary Record.
[9]
P. Lebowitz,et al.
Comparative Cardiovascular Effects of Midazolam and Thiopental in Healthy Patients
,
1982,
Anesthesia and analgesia.
[10]
S. Carlyle,et al.
Cardiovascular and respiratory effects of xylazine in sheep.
,
2010,
Zentralblatt fur Veterinarmedizin. Reihe A.