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Neurotoxicity with single dose intrathecal midazolam administration

Published online by Cambridge University Press:  25 November 2005

B. Ugur ,
K. Basaloglu ,
T. Yurtseven ,
U. Ates ,
O. N. Aydin ,
D. Özenç ,
M. Yurtseven  and
A. Gürel
B. Ugur
Affiliation:
Adnan Menderes University Medical Faculty, Department of Anaesthesiology and Reanimation, Aydin, Turkey
K. Basaloglu
Affiliation:
Adnan Menderes University Medical Faculty, Department of Histology and Embryology, Aydin, Turkey
T. Yurtseven
Affiliation:
Ege University Medical Faculty, Department of Neurosurgery, Izmir, Turkey
U. Ates
Affiliation:
Ege University Medical Faculty, Department of Histology and Embryology, Izmir, Turkey
O. N. Aydin
Affiliation:
Adnan Menderes University Medical Faculty, Department of Anaesthesiology and Reanimation, Aydin, Turkey
D. Özenç
Affiliation:
Ege University Medical Faculty, Department of Neurosurgery, Izmir, Turkey
M. Yurtseven
Affiliation:
Ege University Medical Faculty, Department of Histology and Embryology, Izmir, Turkey
A. Gürel
Affiliation:
Adnan Menderes University Medical Faculty, Department of Anaesthesiology and Reanimation, Aydin, Turkey
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Extract

Summary

Background and objective: The aim of study was to investigate the electron microscopic changes in the medulla of the spinal cord that occur with intrathecal midazolam administration. Methods: Twenty-eight albino rabbits of New Zealand type were randomized into two groups. Following anaesthesia, 16 rabbits were given 300 μg of midazolam (Group M) and 12 rabbits were given 0.3 mL of normal saline solution (Group C) intrathecally. Eight rabbits from Group M (Group M1) and 6 rabbits from Group C (Group C1) were sacrificed 24 h after the anaesthesia and 8 rabbits from Group M (Group M2) and 6 rabbits from Group C (Group C2) were sacrificed 6 days after the anaesthesia. The lumbosacral portion was removed by laminectomy and thin sections were examined microscopically. Results: Severe separation in myelin lamella of the large axons, honeycomb appearance, slight separation in myelin lamella of small to moderately large axons, degenerate vacuoles in the cytoplasm and nuclear membrane irregularity were observed in neurons of Groups M1 and M2. Myelin lamella and nuclear membranes were found to be regular, vacuoles and oedema were observed in the neurons in the Groups C1 and C2. Conclusion: Midazolam administered at single dose by the intrathecal route may have neurotoxic effects on the neurons and myelinated axons at 24 h and 6 days following administration.

Keywords

MICROSCOPY ELECTRONMIDAZOLAMINJECTIONS SPINAL, intrathecalNEUROTOXICITYRABBITS
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 22 , Issue 12 , December 2005 , pp. 907 - 912
Copyright
© 2005 European Society of Anaesthesiology

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References

Yanez A, Sabbe MB, Stevens CW, Yaksh TL. Interaction of midazolam and morphine in the spinal cord of the rat. Neuropharmacology 1990; 29: 359–364.Google Scholar
Malinovsky JM, Cozian A, Lepage JY, Mussini JM, Pinaud M, Souron R. Ketamine and midazolam neurotoxicity in the rabbit. Anesthesiology 1991; 75: 91–97.Google Scholar
Valentine JMJ, Lyons G, Bellamy MC. The effect of intrathecal midazolam on postoperative pain. Eur J Anaesthesiol 1996; 13: 589–593.Google Scholar
Cooms DW, Fratkin JD. Neurotoxicology of spinal agents. Anaesthesiology 1987; 66: 724–726.Google Scholar
Abram SE. Spinal cord toxicity of epidural and subarachnoid analgesics. Reg Anaesth 1996; 21: 84–88.Google Scholar
Eisenach JC. Three novel spinal analgesics; clonidine, neostigmin, amitriptyline. Reg Anaesth 1996; 21: 81–133.Google Scholar
Goodchild CS, Noble J. The effects of intrathecal midazolam on sympathetic nervous system reflexes in man: a pilot study. Br J Clin Pharmacol 1987; 23: 279–285.Google Scholar
Young CC, Prielipp RC. Benzodiazepines in the intensive care unit. Crit Care Clin 2001; 17: 843–862.Google Scholar
Liu LL, Gropper MA. Postoperative analgesia and sedation in the adult intensive care unit: a guide to drug selection. Drugs 2003; 63: 755–767.Google Scholar
Niv D, Whitman JG, Loh L. Depression of nociceptive sympathetic reflexes by the intrathecal administration of midazolam. Br J Anaesth 1983; 55: 541–547.Google Scholar
Erdine S, Yücel A, Özyalçin S et al. Neurotoxicity of midazolam in the rabbit. Pain 1999; 80: 419–423.Google Scholar
Bozkurt P, Tunali Y, Kaya G, Okar I. Histological changes following epidural injection of midazolam in the neonatal rabbit. Pediatr Anaesth 1997; 7: 385–389.Google Scholar
Serrao JM, Mackenzie JM, Goodchild CS, Gent JP. Intrathecal midazolam in the rat: an investigation of possible neurotoxic effects. Eur J Anaesthesiol 1990; 7: 115–122.Google Scholar
Nishiyama T, Matsukawa T, Hanaoka K. Acute phase histopathological study of spinally administered midazolam in cats. Anesth Analg 1999; 89: 717–720.Google Scholar
Abolueish E, Barmada BA, Nemato EM et al. Acute and choronic effects of intrathecal morphine in monkeys. Br J Anaesth 1981; 53: 1027–1032.Google Scholar
Madsen JB, Jensen FM, Faber T et al. Choronic catheterization of the spinal epidural space in rabbits: a model for behavioural and histopathologic studies. Examination of meptazinol neurotoxicity. Acta Anaesthesiol Scand 1993; 37: 307–313.Google Scholar
Güleç S, BüyükkMdan B, Oral N, Özcan N, TanrMverdi B. Comparison of caudal bupivacaine, bupivacaine–morphine and bupivacaine–midazolam mixures for postoperative analgesia in children. Eur J Anaesthesiol 1998; 15: 161–165.Google Scholar
Kim MH, Lee YM. Intrathecal midazolam increases the analgesic effects of spinal blockade with bupivacaine in patients undergoing haemorrhoidectomy. Br J Anaesth 2001; 86: 77–79.Google Scholar
Nishiyama T, Hanaoka K. Effect of diluent volume on post-operative analgesia and sedation produced by epidurally administered midazolam. Eur J Anaesthesiol 1998; 15: 275–279.Google Scholar
Serrao M, Marks RL, Morley SJ, Goodchild CS. Intrathecal midazolam for the treatment of choronic mechanical low back pain: a controlled comparison with epidural steroid in a pilot study. Pain 1992; 48: 5–12.Google Scholar
Johansen MJ, Gradert TL, Satterfield WC et al. Safety of continuous intrathecal midazolam infusion in the sheep model. Anesth Analg 2004; 98: 1528–1535.Google Scholar