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Anesth Analg 2003;96:159-162
© 2003 International Anesthesia Research Society

ANESTHETIC PHARMACOLOGY

Serum and Cerebrospinal Fluid Concentrations of Midazolam After Epidural Administration in Dogs

Tomoki Nishiyama, MD, PhD, Hisayoshi Tamai, MD, and Kazuo Hanaoka, MD, PhD

Department of Anesthesiology, The University of Tokyo, Japan

Address correspondence and reprint requests to Tomoki Nishiyama, MD, PhD, 3-2-6-203, Kawaguchi, Kawaguchi-shi, Saitama 332-0015, Japan. Address e-mail to nishiyamat-ane{at}h.u-tokyo.ac.jp

The epidural administration of midazolam has analgesic effects that might be mediated by {gamma}-aminobutyric acid type A receptors in the spinal cord. In this study, we examined both serum and cerebrospinal fluid (CSF) concentrations of midazolam after epidural administration to investigate the possibility of midazolam entering CSF directly from the epidural space. Five male mongrel dogs had catheters inserted in a femoral artery, the epidural space at L3-4, and the intrathecal space at the atlanto-occipital region under general anesthesia. Midazolam 1 mg/kg was epidurally administered, and arterial blood and CSF samples were collected until 240 min after the midazolam administration to measure midazolam concentration. Serum midazolam concentration increased and reached a peak at 30 min after the administration (224.8 ± 30.5 ng/mL) and then decreased to 25.8 ± 6.0 ng/mL at 240 min. Midazolam concentration in the CSF was less than the detection limit at 5 min, reached a peak at 30 min after the administration (7.2 ± 4.7 ng/mL), and decreased to 3.6 ± 3.3 ng/mL at 240 min. In conclusion, epidurally administered midazolam enters CSF, but CSF concentrations are only 3% of those in the systemic circulation.

IMPLICATIONS: Midazolam, which has spinally mediated analgesic potency, was epidurally administered in dogs, and serum and cerebrospinal fluid concentrations were measured. Epidurally administered midazolam enters the cerebrospinal fluid, but concentrations are only 3% of those in the systemic circulation.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2003 by the International Anesthesia Research Society.