Background and objective: Amiodarone is very effective against a variety of dysrhythmias but has poor pharmacodynamic properties and many undesired side-effects.Its short- and rapid-acting derivative E 047/1 may circumvent some of these drawbacks.It is easier to titrate while retaining the high efficacy of amiodarone and may have acceptable influences on hemodynamics and cardiac conduction in patients who develop serious, destabilizing ventricular tachydysrhythmias after cardiac surgery.Methods: Testing E 047/1 was performed prospectively in two consecutive phase II open, clin. studies.Out of 504 patients scheduled for surgery using cardiopulmonary bypass for coronary artery grafting and/or valve repair, 35 developed serious, hemodynamically destabilizing ventricular dysrhythmias (Lown 2-Lown 4b) after surgery and were treated with a 1 mg kg-1 (pilot study, n = 15) or randomized to a 2 or 3 mg kg-1 bolus of E 047/1, followed by a 1 mg kg-1h-1 continuous infusion for 2 h (n = 10 in each group).Dysrhythmias, PQ, QTc intervals and hemodynamics using the thermodilution technique were evaluated for up to 24 h after drug initiation.Results: At the time of final inclusion the patients had between 6 and 12 (or more) ventricular ectopics per min.Within the first 2-3 min of application in the pilot trial E 047/1 induced a decrease of ventricular dysrhythmias to between 0 and 4 per min, a decrease that held for the duration of treatment.The area under the curve decreased from 434 (322, 855; median, quartiles) to 114 (9, 477, P < 0.01) events per h.In the randomized trial, E 047/1 administered in either dose rapidly reduced ventricular dysrhythmias at least as effectively as in the pilot trial 565 (478, 701) to 33 (8, 238, P < 0.05) after a 2 mg bolus; 482 (339, 482) to 95 (13, 540, P < 0.01) events per h after a 3 mg bolus.Approx. 4-6 h after drug termination, dysrhythmias reappeared in the majority of patients.In only three patients did the incidence of dysrhythmias return to inclusion criteria levels.In contrast to the pilot trial, in the randomized trial there was a slight increase of mean pulmonary artery pressure, central venous pressure and pulmonary arterial wedge pressure and a slight decrease of LCWI in both groups.E 047/1 did not cause QTc prolongation.Conclusions: E 047/1 appears to be a safe alternative to amiodarone in the perioperative setting of cardiac surgery when serious, destabilizing dysrhythmias occur.