Dose-related cardiovascular effects of amrinone and epinephrine in reversing bupivacaine-induced cardiovascular depression

• Published in: Acta anaesthesiologica Scandinavica Vol. 42; no. 6; pp. 698 - 706
• Main Authors: Igarashi, T., Hirabayashi, Y., Saitoh, K., Fukuda, H., Shimizu, R., Mitsuhata, H.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.1998; Blackwell
• Subjects: Amrinone - pharmacology; Anesthetics; Anesthetics, Local - toxicity; Animals; Biological and medical sciences; Blood Pressure - drug effects; Bupivacaine - toxicity; cardiac performance; Cardiotonic Agents - pharmacology; catecholamines: epinephrine; complications: intoxication; Depression, Chemical; Dogs; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; Epinephrine - pharmacology; heart; Heart - drug effects; Heart Rate - drug effects; Hemodynamics - drug effects; local: bupivacaine; Medical sciences; Pharmacology. Drug treatments; phosphodiesterase inhibitors: amrinone; Stroke Volume - drug effects; Toxicity: cardiovascular system; Ventricular Function, Left - drug effects; volatile: sevoflurane; Agonist; Cardiotonic agent; Cardiac performance; Intravenous administration; Toxicity; Esterases; Phosphoric diester hydrolases; Amrinone; Dose activity relation; Bupivacaine; Dog; Anilide; Fissipedia; Carnivora; 3',5'-Cyclic-nucleotide phosphodiesterase; Enzyme; Enzyme inhibitor; Catecholamine; Local anesthetic; Epinephrine(drug); Vertebrata; Chemotherapy; Mammalia; Treatment; α-Adrenergic receptor; Animal; Hydrolases; Hemodynamics
• ISSN: 0001-5172; 1399-6576
• DOI: 10.1111/j.1399-6576.1998.tb05304.x

Background: To ascertain the efficacy of amrinone and epinephrine in reversing bupivacaine‐induced cardiovascular depression, we investigated the time course of recovery of cardiac function with 3 doses of both agents after bupivacaine administration. Methods: In sevoflurane‐anaesthetized dogs, bupivacaine was infused intravenously at 1 mg . kg−1 . min−1 until mean arterial pressure fell to 60 mmHg or less. The 3 doses of amrinone (1, 2, and 4 mg . kg−1) or the 3 doses of epinephrine (2, 5, and 10 μg . kg−1) were administered as a bolus in randomized order in each dog. Results: Amrinone improved maximum left ventricular dP/dt, a time constant of left ventricular isovolemic relaxation and cardiac index persistently and dose‐relatedly. Amrinone increased heart rate and decreased left ventricular end‐diastolic pressure and systemic vascular resistance index. Amrinone at 1 and 2 mg . kg−1 significantly increased mean arterial pressure, but amrinone at 4 mg . kg−1 did not. Epinephrine increased mean arterial pressure, maximum left ventricular dP/dt, and systemic vascular resistance dose‐relatedly. The duration of action of epinephrine, peaking at 1 min and subsequently decreasing by 10 min after administration, did not differ among the groups. Epinephrine at all doses failed to improve a time constant of left ventricular isovolemic relaxation and cardiac index. ECG evidence of serious ventricular dysrhythmias was seen in 1 out of 6 dogs after administrating each dose of amrinone and in 3, 3 and 5 out of 6 dogs after administrating 2, 5 and 10 μg . kg−1 of epinephrine, respectively. Conclusion: Bolus amrinone may have a certain efficacy in reversing bupivacaine‐induced cardiovascular depression, and improving cardiac contractility and relaxation dose‐relatedly. In contrast to amrinone, bolus epinephrine remains indispensable for resuscitation, causing a rapid, massive, transient and doserelated rise in blood pressure. However, the use of amrinone may be limited predominantly by a decrease in systemic vascular resistance, while the use of epinephrine may be limited predominantly by the generation of serious ventricular dysrhythmias and lack of effectiveness on cardiac index and on cardiac relaxation.