- Email: [email protected]
Long term effects of dopexamine hydrochloride in low cardiac output states following cardiac surgery
80
LONG TERM EFFECTS OF DOPEXAMINE HYDROCHLORIDE IN LOW CARDIAC OUTPUT STATES FOLLOWING CARDIAC SURGERY N. Friedel, G. Matheis, H. Kuppe, H. Bittner, R.Hetzer Deutsches Herzzentrum Berlin, D-1000 Berlin 65, Augustenburger Platz 1 Introduction: The treatment of postoperative mvocardial failure is based on the use of inotropes and vasodilators. Dopexamine hydrochloride, a new beta-2 adrenergic and dopaminergic agonist with mild inotropic and vasodilating properties, has been shown to exert beneficial haemodynamic effects in the immediate postoperative period following cardiac surgery (1,Z). In this study, we investigated the long-term effects of dopexamine hydrochloride in patients with low cardiac output status after cardiac surgery. Methods: After informed consent 10 patients undergoing coronary bypass or valvular sugery entered the study. The admission criteria included a cardiac index of less than 2,5 L/min/m2 and a wedge pressure greater than 15 mmHg prior to anaesthesia. No other inotropic or vasodilator therapy was permitted in the early postoperative period. Followino a dose titration ohase. where dopexaminea was infused at increasing doses of 1,2,4, and 6 ug/kg/min, the dose was adjusted to provide the maximum increase in cardiac index without increasing heart rate by more than 20%. This "optimal dose", which could be varied according to the progress of the patient, was infused for at least 36 hours, Haemodynamic variables were measured before and 12, 24, and 36 hours after starting dopexamine infusion. Results: During the dose titration, a si nificant increase in cardiac index (CIB was associated with a marked decrease in systemic vascular resistance (SVR). Mean atria1 blood pressure (MAP), however, remained unchanged. A dose-dependent increase in heart rate was significant except with the lowest dose. The "optimal" dose was 4.0 mg/kg/min. During the 36 hour infusion period, dopexamine was downtitrated to a final mean-dose of 2.0 ,ug/kg/min. The long-term effects of dopexamine hydrochloride are summarized below: Controls &rnin~&~~
12h
3.24* 875*
24h 3.72"
732* (dynesl;lsec x~;;-~) 75* MAP &tllmHg) 86 (beats/min)
95
89
* Significantly different (pcO.05) from controls
36h 3.50* 885* 82* 94
The increase in cardiac index was maintained during the entire infusion period and remained significantly different from control values at all times. This effect was accompanied by a profound and sustained fall in systemic vascular resistance resulting in a significant decrease in mean arterial pressure during the infusion period. However, MAP values never dropped below 60 mmHg. Although heart rate showed a dose dependent increase during the dose titration phase, the values declined during extended infusion and remained within the limits of clinical acceptability. Discussion: Dopexamine hydrochloride produced a marked increase in cardiac index, primarily in response to the reduction of systemic vascular resistance. These beneficial haemodynamic effects were well maintained during extended infusion up to 36 hours with no indication of tolerance or an effect attenuation. The results indicate that satisfactory hemodynamic responses during long-term infusion of dopexamine can be obtained even at doses below 4 uglkglmin. At these low doses, the positive chronotropic responses to the drug should not result in any adverse effect on myocardial oxygen consumption because of its additional vasodilating properties that result in a reduction of myocardial wall stress. It can be concluded that long-term infusion of dopexamine hydrochloride provides low-dose useful hemodynamic support in patients with low output states following cardiac surgery. References: 1. Brown RA. Dixon J. Farmer JB. et al: Depoxamine: a novel agonist at peripheral dopamin and beta-2 adrenoreceptors. Br J Pharmacol 85 (1985): 599-606. 2. Van der Starre PJA, Rosseel PMJ: Dopexamine hydrochloride after coronary artery bypass grafting. Am J Cardiol 62 (1988): 786-826.
LONG TERM EFFECTS OF DOPEXAMINE HYDROCHLORIDE IN LOW CARDIAC OUTPUT STATES FOLLOWING CARDIAC SURGERY N. Friedel, G. Matheis, H. Kuppe, H. Bittner, R.Hetzer Deutsches Herzzentrum Berlin, D-1000 Berlin 65, Augustenburger Platz 1 Introduction: The treatment of postoperative mvocardial failure is based on the use of inotropes and vasodilators. Dopexamine hydrochloride, a new beta-2 adrenergic and dopaminergic agonist with mild inotropic and vasodilating properties, has been shown to exert beneficial haemodynamic effects in the immediate postoperative period following cardiac surgery (1,Z). In this study, we investigated the long-term effects of dopexamine hydrochloride in patients with low cardiac output status after cardiac surgery. Methods: After informed consent 10 patients undergoing coronary bypass or valvular sugery entered the study. The admission criteria included a cardiac index of less than 2,5 L/min/m2 and a wedge pressure greater than 15 mmHg prior to anaesthesia. No other inotropic or vasodilator therapy was permitted in the early postoperative period. Followino a dose titration ohase. where dopexaminea was infused at increasing doses of 1,2,4, and 6 ug/kg/min, the dose was adjusted to provide the maximum increase in cardiac index without increasing heart rate by more than 20%. This "optimal dose", which could be varied according to the progress of the patient, was infused for at least 36 hours, Haemodynamic variables were measured before and 12, 24, and 36 hours after starting dopexamine infusion. Results: During the dose titration, a si nificant increase in cardiac index (CIB was associated with a marked decrease in systemic vascular resistance (SVR). Mean atria1 blood pressure (MAP), however, remained unchanged. A dose-dependent increase in heart rate was significant except with the lowest dose. The "optimal" dose was 4.0 mg/kg/min. During the 36 hour infusion period, dopexamine was downtitrated to a final mean-dose of 2.0 ,ug/kg/min. The long-term effects of dopexamine hydrochloride are summarized below: Controls &rnin~&~~
12h
3.24* 875*
24h 3.72"
732* (dynesl;lsec x~;;-~) 75* MAP &tllmHg) 86 (beats/min)
95
89
* Significantly different (pcO.05) from controls
36h 3.50* 885* 82* 94
The increase in cardiac index was maintained during the entire infusion period and remained significantly different from control values at all times. This effect was accompanied by a profound and sustained fall in systemic vascular resistance resulting in a significant decrease in mean arterial pressure during the infusion period. However, MAP values never dropped below 60 mmHg. Although heart rate showed a dose dependent increase during the dose titration phase, the values declined during extended infusion and remained within the limits of clinical acceptability. Discussion: Dopexamine hydrochloride produced a marked increase in cardiac index, primarily in response to the reduction of systemic vascular resistance. These beneficial haemodynamic effects were well maintained during extended infusion up to 36 hours with no indication of tolerance or an effect attenuation. The results indicate that satisfactory hemodynamic responses during long-term infusion of dopexamine can be obtained even at doses below 4 uglkglmin. At these low doses, the positive chronotropic responses to the drug should not result in any adverse effect on myocardial oxygen consumption because of its additional vasodilating properties that result in a reduction of myocardial wall stress. It can be concluded that long-term infusion of dopexamine hydrochloride provides low-dose useful hemodynamic support in patients with low output states following cardiac surgery. References: 1. Brown RA. Dixon J. Farmer JB. et al: Depoxamine: a novel agonist at peripheral dopamin and beta-2 adrenoreceptors. Br J Pharmacol 85 (1985): 599-606. 2. Van der Starre PJA, Rosseel PMJ: Dopexamine hydrochloride after coronary artery bypass grafting. Am J Cardiol 62 (1988): 786-826.