Document Detail

Hemodynamic and analgesic actions of epidurally administered clonidine.
MedLine Citation:
PMID:  8439023     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: alpha 2-Adrenergic agonists such as clonidine produce behavioral analgesia and cardiovascular depression in animals, but clonidine's site of action in clinical analgesia and cerebrospinal fluid (CSF) pharmacokinetics have not been defined. METHODS: Clonidine was administered in the lumbar epidural space to nine volunteers while monitoring blood pressure, heart rate, finger and toe blood flow, and response to cold pain testing, and while sampling CSF and arterial plasma for clonidine analysis. Effects were correlated to plasma and CSF clonidine concentrations. Ten other volunteers received stepped intravenous infusions of the opioid alfentanil with similar testing. RESULTS: Clonidine decreased pain report in the foot but not the hand, and this effect correlated stronger with CSF than with plasma clonidine, suggesting a spinal site for analgesia. Extrapolation of CSF clonidine pharmacokinetics suggests the minimum effective CSF clonidine concentration for postoperative pain relief is 76 +/- 15 ng/ml. Clonidine increased finger and toe blood flow, decreased blood pressure and heart rate, produced sedation, and mildly increased arterial PCO2, in most cases correlating better with plasma than CSF clonidine concentrations, suggesting actions at central sites. In 10 other volunteers, intravenous infusion of the opioid alfentanil produced analgesia of similar intensity to clonidine but was accompanied by significant respiratory depression. CONCLUSIONS: These data support previous studies in animals and provide the scientific rationale for this novel analgesic therapy. In comparison to the potent opioid alfentanil, epidural clonidine produces a similar degree of analgesia but less respiratory depression.
J Eisenach; D Detweiler; D Hood
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Anesthesiology     Volume:  78     ISSN:  0003-3022     ISO Abbreviation:  Anesthesiology     Publication Date:  1993 Feb 
Date Detail:
Created Date:  1993-03-25     Completed Date:  1993-03-25     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  277-87     Citation Subset:  AIM; IM    
Department of Anesthesia, Wake Forest University Medical Center, Winston-Salem, North Carolina 27157-1009.
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MeSH Terms
Alfentanil / administration & dosage
Clonidine / administration & dosage*,  pharmacokinetics,  pharmacology
Depression, Chemical
Epidural Space
Epinephrine / blood
Hemodynamics / drug effects*,  physiology
Infusions, Intravenous
Norepinephrine / blood
Pain / prevention & control*
Respiration / drug effects
Grant Support
Reg. No./Substance:
4205-90-7/Clonidine; 51-41-2/Norepinephrine; 51-43-4/Epinephrine; 71195-58-9/Alfentanil

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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