Cardiac Electrophysiologic and Hemodynamic Effects Related to Plasma Levels of Bupivacaine in the Dog

Hotvedt, Ragnar; Refsum, Helge; Helgesen, Knut G.

doi:10.1213/00000539-198504000-00003

Cited by 61 publications

(14 citation statements)

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“…The variables of ventricular conduction used were HV interval as the evaluation of His-Purkinje conduction and QRS duration as the evaluation of ventricular conduction. The dose of bupivacaine, 4 mg/ kg, induced alterations similar to those reported in other studies (17,(28)(29)(30)(31)(32)(33). Moreover, Nattel and Jing (27) confirmed that antiarrhythmic drug-induced changes in QRS duration are highly correlated with simultaneous changes in ventricular conduction velocity and V, , , of action potentials measured by epicardial mapping, indicating the validity of QRS duration as an index of drug effects on ventricular conduction.…”

Section: Discussionsupporting

confidence: 82%

Receptor Mechanisms for Clonidine Reversal of Bupivacaine-Induced Impairment of Ventricular Conduction in Pentobarbital-Anesthetized Dogs

Coussaye

Eledjam

Bassoul

et al. 1994

Anesthesia & Analgesia

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Possible mechanisms of the ability of clonidine to correct bupivacaine-induced ventricular electrophysiologic impairment were evaluated in an electrophysiologic model on closed-chest dogs. Nine groups (n = 6) of pentobarbital-anesthetized dogs were given atropine, 0.2 mg/kg intravenously (i.v.), and bupivacaine, 4 mg/kg i.v., over a 10-s period. Group 1 was then given only saline solution. Group 2 was given clonidine, 0.01 mg/kg i.v., over a 1-min period. Group 3 was given clonidine followed by i.v. administration of yohimbine, 1 mg/kg, an alpha 2-antagonist. Group 4 was given carbachol, 1 mg/kg i.v., a long-lasting cholinergic agonist, over a 1-min period. Group 5 was given electrical stimulation of the left vagus nerve. Group 6 was given physostigmine, 0.1 mg/kg i.v., known to inhibit cholinesterase degradation, 5 min before bupivacaine administration, and Group 7 received a combination of physostigmine pretreatment and electrical vagal stimulation. Group 8 was given physostigmine, 0.1 mg/kg i.v., and pancuronium bromide, 1 mg/kg i.v., known to inhibit nicotinic receptors, 5 min before bupivacaine administration. Then electrical stimulation of the left vagus nerve was performed. Group 9 was given nicotine, 0.1 mg/kg i.v., 1 min after bupivacaine injection over 1 min. Bupivacaine induced bradycardia, markedly increased the His-Purkinje conduction time (HV interval) and QRS duration. Bupivacaine decreased the peak of first derivative of left ventricle pressure (LVdP/dtmax) and increased left ventricular end-diastolic pressure (LVEDP). Clonidine improved QRS duration and HV interval. Yohimbine did not modify the effects of clonidine. QRS duration and HV interval were significantly improved in Groups 4-7. In Group 8, pancuronium pretreatment inhibited the beneficial effects of the combination of physostigmine pretreatment and electrical vagal stimulation. In contrast, in Group 9, like clonidine, nicotine improved QRS duration and HV interval. Three other groups of anesthetized dogs (n = 6) were then studied. All dogs were given hexamethonium, 10 mg/kg i.v. Then, Group 10 was given only saline solution; Group 11 was given bupivacaine, 4 mg/kg, and Group 12 was given bupivacaine and nicotine as in Group 9. In Group 11, bupivacaine induced its usual alterations. In contrast, nicotine did not modify the cardiotoxic profile of bupivacaine after hexamethonium pretreatment. We conclude that the beneficial effect of clonidine on the variables of ventricular conduction altered by bupivacaine 1) is not mediated by central alpha 2-activation, 2) is mediated by the activation of parasympathetic pathways, and 3) is indirect and not mediated by acetylcholine release but is mediated by the activation of parasympathetic ganglionic nicotinic receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Discussionsupporting

confidence: 82%

Receptor Mechanisms for Clonidine Reversal of Bupivacaine-Induced Impairment of Ventricular Conduction in Pentobarbital-Anesthetized Dogs

Coussaye

Eledjam

Bassoul

et al. 1994

Anesthesia & Analgesia

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“…31,32 Depression of SA and AV nodal activity is further manifested by bradycardia and partial or complete atrioventricular block. With high blood levels of racemic bupivacaine, the heart is predisposed to re-entrant arrhythmias (prolongation of QT interval) as the incidence of ventricular tachycardia and ventricular fibrillation increase.…”

Section: Arrhythmogenicitymentioning

confidence: 99%

Central nervous system and cardiac effects from long-acting amide local anesthetic toxicity in the intact animal model

Groban

2003

Regional Anesthesia and Pain Medicine

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With the development of the newer long-acting amide local anesthetics,ropivacaine and levobupivacaine, numerous animal studies of LA systemic toxicity have emerged. Because of the complex nature of the human response to LA intoxication, the task of designing and interpreting these animal studies of LA toxicity can be difficult. Accordingly, this report will review the selection of an animal model for the study of LA toxicity; examine the pertinent in vivo animal studies that compare the central nervous system toxicity, cardiovascular toxicity, and the ease of resuscitation of the single enantiomer local anesthetics to racemic bupivacaine; and extrapolate these findings to the clinical setting.

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“…Electrophysiologic and hemodynamic responses to plasma bupivacaine levels are minimal at IT analgesia doses. In the dog model (11), no effect was seen on impulse conduction, atrial and AV nerve root refractoriness, or ventricular refractoriness at systemic doses producing plasma levels less than 1 μg/ml. Plasma levels greater than 2 μg/ml, which is unlikely with IT dosing, resulted in inotropic decrease with maintained ventricular refractoriness.…”

Section: Bupivacaine Overviewmentioning

confidence: 86%

“…The final preclinical evaluation of any pharmaceutical agent prior to human use is well designed and involves controlled animal studies to identify potential toxicity associated with the drug. Animal studies (6–18) have reported mostly safe results. In neural toxicity studies in both rabbits (8) and pigs (9), bupivacaine at 0.5% appeared to be safe at continuous epidural infusion for periods up to two months.…”

Section: Bupivacaine Overviewmentioning

confidence: 99%

“…In neural toxicity studies in both rabbits (8) and pigs (9), bupivacaine at 0.5% appeared to be safe at continuous epidural infusion for periods up to two months. A dog‐spinal injury model study (10,11) suggested bupivacaine might improve functional recovery in spinal cord injury attributed to decreased catecholamine‐induced necrosis. Li and colleagues (12) reported dose‐dependent neurologic toxicity including paralysis with chronic subarachnoid infusion of bupivacaine in a rat model, although the concentrations used to produce toxicity were not clinically relevant.…”

Section: Bupivacaine Overviewmentioning

confidence: 99%

See 1 more Smart Citation

Intrathecal Bupivacaine for Chronic Pain: A Review of Current Knowledge

Deer

Serafini²,

Ferrante

et al. 2002

Neuromodulation: Technology at the Neural Interface

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Cardiac Electrophysiologic and Hemodynamic Effects Related to Plasma Levels of Bupivacaine in the Dog

Cited by 61 publications

References 0 publications

Receptor Mechanisms for Clonidine Reversal of Bupivacaine-Induced Impairment of Ventricular Conduction in Pentobarbital-Anesthetized Dogs

Receptor Mechanisms for Clonidine Reversal of Bupivacaine-Induced Impairment of Ventricular Conduction in Pentobarbital-Anesthetized Dogs

Central nervous system and cardiac effects from long-acting amide local anesthetic toxicity in the intact animal model

Intrathecal Bupivacaine for Chronic Pain: A Review of Current Knowledge

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