Abstract
The intravascular injection of a large dose of bupivacaine induces electrophysiological cardiac impairment, mainly by slowing ventricular conduction velocity, and haemodynamic depression, by a decrease in myocardial contractility. When cardiotoxicity occurs, succinylcholine rapidly stops convulsions. However, the possible interactions between bupivacaine and succinylcholine on cardiac electrophysiology and haemodynamic status have never been investigated. Thus, we used an experimental electrophysiological model involving closedchest dogs. Three groups (n = 6) of pentobarbitalanaesthetized dogs were given 0.2 mg · kg−1 atropine iv. Dogs in Group 1 were given saline. The others received 4 mg · kg−1 bupivacaine iv over ten seconds. Dogs in Group 2 were then given saline and those in Group 3 were then given 2 mg · kg−1 succinylcholine iv from one to two minutes after the administration of bupivacaine. The following electrophysiological variables were measured: heart rate represented by RR interval (RR), PR, atria-His (AH), and Hisventricle (HV) intervals, QRS duration, and QT interval corrected for heart rate (QTc). The following haemodynamic variables were measured: mean aortic pressure (MAoP), the peak of the first derivative of left ventricular pressure (LVdP/dt max), and LV end diastolic pressure (LVEDP). Comparison between Groups 1 and 2 showed that bupivacaine induced more than 100% HV interval lengthening and QRS widening (P < 0.01), prolonged QTc interval by more than 25% (P <0.01), and decreased LV dP/dt max by more than 50% (P < 0.01). The only difference between Groups 2 and 3 was a transient shortening of QRS in the group given succinylcholine at four and five minutes (P <0.05) and a shortening of QTc throughout the study period (P < 0.05 at two and three min, P <0.01 at four to 30 min after the end of bupivacaine administration). We conclude that 2 mg · kg−1 succinylcholine did not worsen the previously impaired electrophysiological or a haemodynamic variables produced by a high dose of bupivacaine in anaesthetized dogs.
Résumé
L’injection d’une forte dose de bupivacaïne est responsable d’altérations électrophysiologiques essentiellement dues au ralentissement majeur des vitesses de conduction ventriculaires et à l’atteinte hémodynamique par baisse de l’inotropisme. Lors d’accident toxique, la succinylcholine a été proposée pour supprimer rapidement l’expression des convulsions. Cependant les possibles interactions entre la bupivacaïne et la succinylcholine sur l’électrophysiologie et l’ hémodynamique n’ont jamais été étudiées. Dans ce but, un modèle électrophysiologique de chien anesthésié à thorax fermé a été utilisé. Trois groupes de six chiens anesthésiés au pentobarbital reçoivent tous 0,2 mg · kg−1 iv d’atropine. Le groupe 1 ne reçoit ensuite qu’une perfusion continue de sérum salé isotonique afin de confirmer la stabilité du modèle. Les autres chiens reçoivent ensuite 4 mg · kg−1 iv de bupivacaïne en dix secondes. Le groupe 2 n’est plus perfusé que par du sérum salé isotonique alors que le groupe 3 reçoit en plus 2 mg · kg−1 iv de succinylcholine de la première a la deuxième minute après la fin de l’injection de bupivacaïne. Les paramètres électrophysiologiques mesurés sont les suivants: la fréquence cardiaque représentée par l’intervalle RR (RR), les intervalles PR (PR), AH et HV, la durée du complexe QRS et l’intervalle QT corrigé par la fréquence cardiaque (QTc). Les paramètres hémodynamiques mesurés sont les suivants: la pression aortique moyenne (MAoP), le pic de la dérivée première de la pression ventriculaire gauche (LV dP/dt max) et la pression télédiastolique ventriculaire gauche (LVEDP). La comparaison entre les groupes 1 et 2 montre que la bupivacaïne altère tous les paramètres électrophysiologiques et hémodynamiques. Ainsi, l’intervalle HV est allongé de plus de 100% (P < 0,01), le complexe QRS est élargi de plus de 100% (P < 0,01), l’intervalle QTc est prolongé de plus de 25% (P < 0,01) et LV dP/dt max est diminuée de plus de 50% (P < 0,01). Les seuls paramètres qui varient de manième significative après l’injection de succinylcholine sont le QRS qui se raccourcit à la quatrième et à la cinquième minute suivant la fin de l’injection de bupivacaïne (P <0,05) et le QTc pendant toute l’étude (P < 0,05 à 2 et 3 min, P < 0,01 de 4 à 30 min). En conclusion, l’injection de 2 mg · kg−1 de succinylcholine n’aggrave pas les paramètres électrophysiologiques et hémodynamiques préalablement altérés par la bupivacaïne sur ce modèle de chien anesthésié.
Article PDF
Similar content being viewed by others
References
Albright GA. Cardiac arrest following regional anesthesia with etidocaine and bupivacaine. Anesthesiology 1979; 51: 285–7.
De Jong RH, Ronfeld RA, De Rosa RA. Cardiovascular effects of convulsant and supraconvulsant doses of amide local anesthetics. Anesth Analg 1982; 61: 3–9.
Kotelko DM, Shnider SM, Dailey PA et al. Bupivacaineinduced cardiac arrhythmias in sheep. Anesthesiology 1984; 60: 10–8.
Reiz S, Nath S. Cardiotoxicity of local anaesthetic agents. Br J Anaesth 1986; 58: 736–46.
Moore DC, Crawford RD, Scurlock JE. Severe hypoxia and acidosis following local anesthetic-induced convulsions. Anesthesiology 1980; 53: 259–60.
Sage DJ, Feldman HS, Arthur GR et al. Influence of lidocaine and bupivacaine on isolated guinea-pig atria in the presence of acidosis and hypoxia. Anesth Anal 1984; 63: 1–7.
Bosjnak ZJ, Stowe DF, Kampine JP. Comparison of lidocaine and bupivacaine depression of sino atrial nodal activity during hypoxia and acidosis in adult and neonatal guinea pigs. Anesth Analg 1986; 65: 911–7.
Moore DC. Administer oxygen first in the treatment of local anesthetic-induced convulsions. Anesthesiology 1980; 53: 346–7.
Moore DC. Local anesthetic drugs: tissue and systemic toxicity. Acta Anaesthesiol Belg 1981; 321: 283–300.
Scott DB. Toxicity caused by local anaesthetic drugs. Br J Anaesth 1981; 53: 553–4.
d’Athis F. How should one treat local anaesthetic systemic accidents? Ann Fr Anesth Réanim 1988; 7: 227–32.
Stoelting RK. Neuromuscular blocking drugs.In: Stoelting RK (Ed.). Pharmacology and Physiology in Anesthetic Practice, Philadelphia: Lippincott, 1987: 169–216.
Komai H, Rusy BF. Effects of bupivacaine and lidocaine on A-V conduction in the isolated rat heart: modification by hyperkalemia. Anesthesiology 1981; 55: 281–5.
Avery P, Redon D, Schaenzer G, Rusy BF. The influence of serum potassium on the cerebral and cardiac toxicity of bupivacaine and lidocaine. Anesthesiology 1984; 61: 134–8.
Moore DC, Bridenbaugh LD. Does hyperkalemia contraindicate the use of bupivacaine or the use of succinylcholine to treat bupivacaine-induced toxicity in humans? Anesthesiology 1985; 62: 195–7.
Manders WT, Vatner SF. Effects of sodium pentobarbital anesthesia on left ventricular function and distribution of cardiac output in dogs, with particular reference to the mechanism of tachycardia. Circ Res 1976; 39: 512–7.
Moore EN, Spear JF. Acute and chronic animal models of cardiac arrhythmias.In: Vaughan Williams EM (Ed.). Antiarrhythmic Drugs, Berlin: Springer-Verlag, 1989: 69–85.
Eledjam JJ, de La Coussaye JE, Brugada J et al. Toxicité cardiaque de la bupivacaine et diazepam: étude expérimentale chez le chien anesthésié. Ann Fr Anesth Réanim 1988; 7: 251–6.
de La Coussaye JE, Eledjam JJ, Brugada J et al. Les bêtabloquants aggravent-ils la cardiotoxicité de la bupivacaine? Etude expérimentale. Ann Fr Anesth Réanim 1990; 9: 132–6.
Sassine A, Massé C, Dufour A, Hirsch JL, Cazes M, Puech P. Cardiac electrophysiological effects of cibenzoline by acute and chronic administration in the anesthetized dog. Arch Int Pharmacodyn 1984; 269: 201–18.
Braunwald E. Assessment of cardiac function.In: Braunwald E (Ed.). Heart Disease. A Textbook of Cardiovascular Medicine. Philadelphia: Saunders, 1988: 449–70.
Furukawa Y, Wallick DW, Martin PJ, Levy MN. Chronotropic and dromotropic responses to stimulation of intracardiac sympathetic nerves to sinoatrial or atrioventricular nodal region in anesthetized dogs. Circ Res 1990; 66: 1391–9.
de La Coussaye JE, Eledjam JJ, Brugada J, Sassine A, d’Athis F. Sympathetic tone blockade enhances bupivacaine cardiotoxicity in anesthetized dogs (Abst). Anesthesiology 1988; 69: A870.
Eledjam JJ, de La Coussaye JE, Brugada J et al. Cardiac electrophysiological effects of bupivacaine in the anesthetized dogs: relation with plasma concentration. Arch Int Pharmacodyn 1988; 295: 147–56.
Heavner JE. Cardiac dysrythmias induced by infusion of local anesthetics into the lateral cerebral ventricle of cats. Anesth Analg 1986; 65: 133–8.
Thomas RD, Behbehani MM, Coyle DE, Denson DD. Cardiovascular toxicity of local anesthetics: an alternative hypothesis. Anesth Analg 1986; 65: 444–50.
Bernards CM, Artru AA. Hexamethonium and midazolam terminate dysrhythmias and hypertension caused by intracerebroventricular bupivacaine in rabbits. Anesthesiology 1991; 74: 89–96.
Lacombe P, Blaise G, Loulmet D, Hollmann C. Electrophysiologic effects of bupivacaine in the isolated rabbit heart. Anesth Analg 1991; 72: 62–9.
Hotvedt R, Refsum H, Helgesen KG. Cardiac electrophysiologic and hemodynamic effects related to plasma levels of bupivacaine in the dog. Anesth Analg 1985; 64: 388–94.
Nath S, Häggmark S, Jokansson G, Reiz S. Differential depressant and electrophysiologic cardiotoxicity of local anesthetics: an experimental study with special reference to lidocaine and bupivacaine. Anesth Analg 1986; 65: 1263–70.
Hasselström LJ, Morgensen T, Kehlet H, Christensen NJ. Effects of intravenous bupivacaine on cardiovascular function and plasma catecholamine levels in humans. Anesth Analg 1984; 63: 1053–8.
Liu P, Feldman HS, Covino BM, Giasi R, Covino BG. Acute cardiovascular toxicity of intravenous amide local anesthetics in anesthetized ventilated dogs. Anesth Analg 1982; 61: 317–22.
Sage DJ, Feldman HS, Arthur GR, Doucette AM, Norway SB, Covino BG. The cardiovascular effects of convulsant doses of lidocaine and bupivacaine in the conscious dog. Reg Anesth 1985; 10: 175–83.
Kasten GW. High serum bupivacaine concentrations produce rhythm disturbances similar to torsades de pointe in anesthetized dogs. Reg Anesth 1986; 11: 20–6.
Moller RA, Covino BG. Cardiac electrophysiologic effects of lidocaine and bupivacaine. Anesth Analg 1988; 67: 107–14.
Anderson KP, Walker R, Lux RL et al. Conduction velocity depression and drug-induced ventricular tachyarrhythmias. Effects of lidocaine in the intact canine heart. Circulation 1990; 81: 1024–38.
Buchanan JW Jr,Saito T, Gettes LS. The effects of antiarrhythmic drugs, stimulation frequency, and potassiuminduced resting membrane potential changes on conduction velocity and dV/dtmax in guinea pig myocardium. Circ Res 1985; 56: 696–703.
Clarkson CW, Hondeghem LM. Mechanism for bupivacaine depression of cardiac conduction: fast block of sodium channels during the action potential with slow recovery from block during diastole. Anesthesiology 1985; 62: 396–405.
Nattel S, Jing W. Rate-dependent changes in intraventricular conduction produced by procainamide in anesthetized dogs. A quantitative analysis based on the relation between phase 0 inward current and conduction velocity. Circ Res 1989; 65: 1485–98.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
de La Coussaye, J.E., Bassoul, B.P., Albat, B. et al. Succinylcholine does not worsen bupivacaine-induced cardiotoxicity in pentobarbital-anaesthetized dogs. Can J Anaesth 39, 192–197 (1992). https://doi.org/10.1007/BF03008655
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF03008655