Levosimendan as a rescue drug in experimental propranolol-induced myocardial depression: a randomized study.
OBJECTIVE
Severe beta-blocker intoxication remains a clinical challenge despite a variety of treatment options. Because of its unique mechanism of action, the new calcium sensitizer levosimendan may provide more prominent cardiac support compared with current medications used to reverse negative inotropy. We hypothesize that levosimendan could reverse propranolol-induced severe negative inotropy in a porcine model of beta-blocker intoxication.


METHODS
Twenty-four pigs were anesthetized and monitored. After severe propranolol intoxication was completed, animals were randomized into 3 groups. With a double-blind procedure, 9 animals received a 1.25-mg levosimendan bolus, followed by saline solution infusion, 9 animals received mean arterial pressure-targeted dobutamine infusion after saline solution bolus, and 6 animals received a saline solution bolus followed by saline solution infusion. Hemodynamic and laboratory data were collected during a follow-up period of 120 minutes.


RESULTS
All 9 pigs in the levosimendan group survived. In contrast, 4 of 6 (67%) and 7 of 9 (78%) pigs died during the experiment in the placebo and the dobutamine groups, respectively. The levosimendan group showed improved change in the maximum positive slope of the left ventricular pressure, cardiac output, stroke volume, and mean arterial pressure compared with the dobutamine and the placebo groups.


CONCLUSIONS
Levosimendan improved hemodynamic function and survival in this animal model of severe propranolol intoxication. The potential clinical application of levosimendan in propranolol intoxication warrants further investigation.
Leppikangas
Heli
H
Department of Anaesthesia, Tampere University Hospital, Tampere, Finland.
Ruokonen
Esko
E
Rutanen
Juha
J
Kiviniemi
Vesa
V
Lindgren
Leena
L
Kurola
Jouni
J
D000319:Adrenergic beta-Antagonists / Q000506:poisoning*; D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004280:Dobutamine / Q000494:pharmacology / Q000627:therapeutic use; D004311:Double-Blind Method; D062787:Drug Overdose / Q000188:drug therapy; D006333:Heart Failure / Q000139:chemically induced / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects; D006835:Hydrazones / Q000494:pharmacology / Q000627:therapeutic use*; D011433:Propranolol / Q000506:poisoning*; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D000077464:Simendan; D016019:Survival Analysis; D013552:Swine
D000319:Adrenergic beta-Antagonists; D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan; D004280:Dobutamine; D011433:Propranolol