Document Detail

Hexamethonium and midazolam terminate dysrhythmias and hypertension caused by intracerebroventricular bupivacaine in rabbits.
MedLine Citation:
PMID:  1670915     Owner:  NLM     Status:  MEDLINE    
Previous studies have demonstrated that bupivacaine administered directly into the central nervous system (CNS) is capable of producing signs of bupivacaine cardiovascular toxicity. To investigate the mechanisms by which bupivacaine may act within the CNS to produce cardiovascular toxicity, we studied four groups of halothane-anesthetized rabbits in which infusion of intracerebroventricular (icv) bupivacaine or intravenous (iv) phenylephrine resulted in dysrhythmias and hypertension. In group 1 (n = 5), icv bupivacaine (500 +/- 79 micrograms [mean +/- SEM]) produced dysrhythmias lasting 73 +/- 13 min, whereas icv saline caused no dysrhythmias or hypertension. In group 2 (n = 9), icv bupivacaine-induced hypertension and dysrhythmias were abolished by icv midazolam in 4.4 +/- 0.6 min, and when dysrhythmias and hypertension recurred (22 +/- 0.9 min), hexamethonium (10 mg/kg iv) promptly terminated dysrhythmias and hypertension (14 +/- 1 s). In group 3 (n = 10), icv bupivacaine-induced dysrhythmias and hypertension were not affected by increasing the inspired halothane concentration from 0.8 to 1.6%. In group 4 (n = 6), iv phenylephrine-induced dysrhythmias and hypertension were not affected by icv midazolam. These results suggest that icv bupivacaine produces dysrhythmias and hypertension by increasing autonomic nervous system (ANS) outflow from the brain stem. The finding that peripheral autonomic blockade by hexamethonium rapidly terminated dysrhythmias and hypertension supports this mechanism. We speculate that icv bupivacaine produces an increase in autonomic outflow by blockade of the inhibitory gamma-aminobutyric acid (GABA) neurons that are known to be the principal tonic inhibitors of the ANS.(ABSTRACT TRUNCATED AT 250 WORDS)
C M Bernards; A A Artu
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anesthesiology     Volume:  74     ISSN:  0003-3022     ISO Abbreviation:  Anesthesiology     Publication Date:  1991 Jan 
Date Detail:
Created Date:  1991-02-08     Completed Date:  1991-02-08     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  89-96     Citation Subset:  AIM; IM    
Department of Anesthesiology, University of Washington, Seattle 98195.
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MeSH Terms
Arrhythmias, Cardiac / chemically induced*,  prevention & control
Autonomic Nervous System / drug effects
Blood Pressure / drug effects
Brain / drug effects
Bupivacaine / blood,  toxicity*
Halothane / pharmacology
Hexamethonium Compounds / pharmacology*
Hypertension / chemically induced*,  prevention & control
Injections, Intraventricular
Midazolam / pharmacology*
Phenylephrine / pharmacology
Receptors, GABA-A / drug effects
Reg. No./Substance:
0/Hexamethonium Compounds; 0/Receptors, GABA-A; 151-67-7/Halothane; 2180-92-9/Bupivacaine; 59-42-7/Phenylephrine; 59467-70-8/Midazolam; 60-26-4/Hexamethonium

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

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