JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Kroin, J. S. Articles by Ivankovich, A. D. Search for Related Content PubMed PubMed Citation Articles by Kroin, J. S. Articles by Ivankovich, A. D. Related Collections Regional Anesthesia Pain Pharmacology

---

PAIN MEDICINE

Continuous Intrathecal Clonidine and Tizanidine in Conscious Dogs: Analgesic and Hemodynamic Effects

Jeffrey S. Kroin, PhD^*, Robert J. McCarthy, PharmD^*, Richard D. Penn, MD, Timothy J. Lubenow, MD^*, and Anthony D. Ivankovich, MD^*

Departments of *Anesthesiology and Neurosurgery, Rush Medical College, Chicago, Illinois

Address correspondence to Jeffrey S. Kroin, PhD, Department of Anesthesiology, Rush Medical College, 1653 W. Congress Parkway, Chicago, IL 60612. Address e-mail to jkroin{at}rush.edu Reprints will not be available from the author.

Alpha-2-adrenergic agonists, such as clonidine, produce antinociception in animal pain models after intrathecal administration. However, clinical usage is limited by cardiovascular side effects. To investigate alternative ₂-adrenergic agonists as analgesics, we implanted six dogs with an intrathecal catheter and infusion pump. After baseline saline infusion, animals received clonidine or tizanidine (crossover study) each week at escalating doses of 125–750 µg/h. Analgesia, blood pressure, heart rate, respiratory rate, sedation, and coordination were evaluated. A 28-day safety study was performed with another nine dogs receiving intrathecal tizanidine (3 or 6 mg/d) or saline. Equal doses of clonidine and tizanidine produce the same antinociception in thermal withdrawal tests. Blood pressure was reduced with 125–500 µg/h of clonidine, but not with tizanidine at any dose. Clonidine 250 µg/h reduced heart rate by 45.8%, and five of six animals had bradyarrhythmias (marked bradycardia), whereas tizanidine decreased heart rate by 15.1% without arrhythmias, even at the largest dose. Respiratory rate decreased with 250 µg/h of clonidine and larger doses. Sedation or incoordination occurred only at the largest dose for either drug. The safety study indicated that 3 mg/d of tizanidine in dogs produced no side effects or histopathologic changes. Tizanidine may be a useful alternative in patients experiencing cardiovascular side effects with intrathecal infusion of clonidine.

IMPLICATIONS: Clonidine is an effective spinal analgesic, but it is dose-limited by cardiovascular side effects. We compared the analgesic properties and side effects of clonidine with those of a similar drug, tizanidine. Continuous spinal infusion of tizanidine produced similar analgesia as clonidine, but with fewer adverse effects on blood pressure and heart rate.

This article has been cited by other articles:

				C.-D. Kao, J.-B. Chang, J.-T. Chen, Z.-A. Wu, D.-E Shan, and K.-K. Liao Hypotension Due to Interaction Between Lisinopril and Tizanidine Ann. Pharmacother., November 1, 2004; 38(11): 1840 - 1843. [Abstract] [Full Text] [PDF]

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