Dose-related cardiovascular effects of amrinone and epinephrine in reversing bupivacaine-induced cardiovascular depression.
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 micrograms.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 micrograms.kg-1 of epinephrine, respectively.


CONCLUSIONS
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 dose-related 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.
Igarashi
T
T
Department of Anesthesiology, Jichi Medical School, Tochigi, Japan.
Hirabayashi
Y
Y
Saitoh
K
K
Fukuda
H
H
Shimizu
R
R
Mitsuhata
H
H
D000676:Amrinone / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002045:Bupivacaine / Q000633:toxicity*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003864:Depression, Chemical; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D000779:Anesthetics, Local; D002316:Cardiotonic Agents; D000676:Amrinone; D002045:Bupivacaine; D004837:Epinephrine