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Anesth Analg 2001;93:363-369
© 2001 International Anesthesia Research Society

ANESTHETIC PHARMACOLOGY

Clonidine Suppresses Plasma and Cerebrospinal Fluid Concentrations of TNF-{alpha} During the Perioperative Period

Nader D. Nader, MD, PhD*, Tracey A. Ignatowski, PhD*{dagger}, Carlos J. Kurek, MD*, Paul R. Knight, MD, PhD*, and Robert N. Spengler, PhD*{dagger}

Departments of *Anesthesiology and {dagger}Pathology, SUNY-Buffalo, Buffalo, New York

Address correspondence and reprint requests to Nader D. Nader, MD, PhD, SUNY-Buffalo, Anesthesiology Service (128), Western New York VA Healthcare System, 3495 Bailey Ave., Buffalo, NY 14215. Address e-mail to nnader{at}med.va.gov

The analgesic properties of {alpha}2-agonists are well known. In experimental models, tumor necrosis factor (TNF)-{alpha} regulates adrenergic responses in the brain. Constitutive TNF-{alpha}, in brain regions involved in pain perception, is decreased after the administration of clonidine. We investigated patients undergoing lower-extremity revascularization. Seven patients were treated with clonidine 0.2 mg per os (low), and three patients received 0.4 mg per os clonidine (high) before surgery. Eight patients received placebo and served as controls. Continuous spinal anesthesia was provided by insertion of a pliable catheter into the subarachnoid space. Baseline plasma and cerebrospinal fluid (CSF) samples were obtained before injection of local anesthetic. Samples were analyzed for TNF-{alpha} using a biologic assay. Systemic and central release of catecholamines were assessed by high-pressure liquid chromatography measurement of norepinephrine in plasma and CSF, vanillylmandelic acid and methoxy hydroxyl phenyl glycol in 24-h urinary excretion, respectively. Clonidine 0.2 mg pretreatment decreased TNF-{alpha} concentrations both in plasma and CSF. Patients receiving clonidine had lower pain visual analog scale scores and required less morphine compared with the Placebo group (P < 0.01). Preoperative administration of clonidine decreased catecholamine release in the periphery, as well as in the central nervous system. A smaller norepinephrine concentration in plasma and CSF, and less secretion of vanillylmandelic acid (P < 0.01) and methoxy hydroxyl phenyl glycol in the urine, were observed. Larger dose clonidine (0.4 mg) resulted in no detectable TNF-{alpha} in CSF. These results suggest that an interaction between TNF-{alpha} and the function of adrenergic neurons in the central nervous system may contribute to the sedative and analgesic effects of adrenergic agonists.

IMPLICATIONS: Preoperative administration of clonidine decreases both plasma and cerebrospinal fluid concentrations of inflammatory cytokines, resulting in perioperative analgesia and decreased sympathetic tone.




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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 © 2001 by the International Anesthesia Research Society.