European Heart Journal (1992) 13, 1271-1276
Haemodynamic effects of different doses of dopexamine hydrochloride in low cardiac output states following cardiac surgery N. FRIEDEL, R. WENZEL, G. MATHEIS, H. KUPPE, H. BITTNER, S. FILCEK* AND R. HETZER
German Heart Institute Berlin, 1000 Berlin 65, Germany; *Fisonsplc Pharmaceutical Division, R&D Laboratories, Loughborough, U.K. KEY WORDS: Dopexamine hydrochloride, vasodilator, low cardiac output syndrome, cardiac surgery. We studied the haemodynamic effects of dopexamine hydrochloride, a $2-adrenergic agonist with dopaminergic (DA,) activity, in 20 patients with low cardiac output following surgery for coronary artery bypass grafting and/or valve replacement or repair. Following titration of four doses (I, 2, 4 and 6 fig . kg~'. min~'), the dose producing the optimal response was infusedfor up to 48 h (five patients). During the infusion, significant increases in cardiac index and stroke volume were accompanied by significant decreases in systemic vascular resistance. Heart rate increased significantly up to 6 h and thereafter returned to control levels. Mean bloodpressure was reduced but did notfall below 60 mmHg. However, in five patients treated for 48 h mean blood pressure had returned to control levels. Unwanted effects (tachycardia and hypotension) were seen chiefly at higher doses, leading us to conclude that infusion rates of 4 fig . kg~'. min ~' or less will be useful in the treatment of low cardiac output following cardiac surgery.
following cardiac surgery for coronary artery bypass grafting (CABG) or valve replacement.
Introduction
Low cardiac output syndrome following cardiac surgery typically comprises a depression of myocardial contractility and increased preload and afterload. Various causative factors include anaesthesia, myocardial ischaemia, cellular oedema, intra-operative cooling, and the stress response to surgery11-21. Cardiac arrhythmias are also common postoperatively, and contribute to inadequate ventricular filling. Positive inotropic agents may be used in this situation to improve cardiac output but potential arrhythmogenic and chronotrophic side-effects are a subject of concern'31. The use of vasodilators such as nitroprusside postoperatively is also common, but limited by hypotension and tachycardia'41. Agents that combine positive inotropy with systemic vasodilatation may overcome these problems. Dopexamine hydrochloride is a vasodilating adrenergic agent which stimulates /?2-adrenoceptors and dopamine DA, and DA2 receptors. It also has an indirect effect on /7,-adrenoceptors by inhibiting neuronal reuptake of endogenous catecholamines (uptake-1). Unlike dopamine, it has no effects on a-adrenoceptors'5"81. Previous studies in post-cardiac surgical patients have shown that, acutely, dopexamine increases cardiac output and renal blood flow and markedly reduces afterload19"13'. In heart failure patients, increases in hepatic-splanchnic blood flow have been noted'14'. We report here on the efficacy and tolerability of dopexamine infusions given for up to 48 h in 20 patients Submitted for publication on 9 January 1991, and in revised form 2 December 1991. Correspondence: Dr N. Friedel, Deutsches Herzzenlrum Augustenburgcr Platz 1, D-1000 Berlin 65, Germany. 0195-668X/92/091271 + 06 $08.00/0
Berlin,
Patients and methods
Twenty patients, 10 female and 10 male, aged 39-73 (mean 57-8) years, entered the study. They all had a history of chronic heart failure due, singly or in combination, to coronary artery disease, mitral valve disease and aortic valve dysfunction. All were in the intensive care unit following surgery for CABG (eight patients), mitral valve replacement or reconstruction (MVR) (nine patients), aortic valve replacement (AVR) (one patient), AVR + MVR (one patient) or CABG + AVR (one patient). Cardiac index was low enough (
Haemodynamic effects of different doses of dopexamine hydrochloride in low cardiac output states following cardiac surgery N. FRIEDEL, R. WENZEL, G. MATHEIS, H. KUPPE, H. BITTNER, S. FILCEK* AND R. HETZER
German Heart Institute Berlin, 1000 Berlin 65, Germany; *Fisonsplc Pharmaceutical Division, R&D Laboratories, Loughborough, U.K. KEY WORDS: Dopexamine hydrochloride, vasodilator, low cardiac output syndrome, cardiac surgery. We studied the haemodynamic effects of dopexamine hydrochloride, a $2-adrenergic agonist with dopaminergic (DA,) activity, in 20 patients with low cardiac output following surgery for coronary artery bypass grafting and/or valve replacement or repair. Following titration of four doses (I, 2, 4 and 6 fig . kg~'. min~'), the dose producing the optimal response was infusedfor up to 48 h (five patients). During the infusion, significant increases in cardiac index and stroke volume were accompanied by significant decreases in systemic vascular resistance. Heart rate increased significantly up to 6 h and thereafter returned to control levels. Mean bloodpressure was reduced but did notfall below 60 mmHg. However, in five patients treated for 48 h mean blood pressure had returned to control levels. Unwanted effects (tachycardia and hypotension) were seen chiefly at higher doses, leading us to conclude that infusion rates of 4 fig . kg~'. min ~' or less will be useful in the treatment of low cardiac output following cardiac surgery.
following cardiac surgery for coronary artery bypass grafting (CABG) or valve replacement.
Introduction
Low cardiac output syndrome following cardiac surgery typically comprises a depression of myocardial contractility and increased preload and afterload. Various causative factors include anaesthesia, myocardial ischaemia, cellular oedema, intra-operative cooling, and the stress response to surgery11-21. Cardiac arrhythmias are also common postoperatively, and contribute to inadequate ventricular filling. Positive inotropic agents may be used in this situation to improve cardiac output but potential arrhythmogenic and chronotrophic side-effects are a subject of concern'31. The use of vasodilators such as nitroprusside postoperatively is also common, but limited by hypotension and tachycardia'41. Agents that combine positive inotropy with systemic vasodilatation may overcome these problems. Dopexamine hydrochloride is a vasodilating adrenergic agent which stimulates /?2-adrenoceptors and dopamine DA, and DA2 receptors. It also has an indirect effect on /7,-adrenoceptors by inhibiting neuronal reuptake of endogenous catecholamines (uptake-1). Unlike dopamine, it has no effects on a-adrenoceptors'5"81. Previous studies in post-cardiac surgical patients have shown that, acutely, dopexamine increases cardiac output and renal blood flow and markedly reduces afterload19"13'. In heart failure patients, increases in hepatic-splanchnic blood flow have been noted'14'. We report here on the efficacy and tolerability of dopexamine infusions given for up to 48 h in 20 patients Submitted for publication on 9 January 1991, and in revised form 2 December 1991. Correspondence: Dr N. Friedel, Deutsches Herzzenlrum Augustenburgcr Platz 1, D-1000 Berlin 65, Germany. 0195-668X/92/091271 + 06 $08.00/0
Berlin,
Patients and methods
Twenty patients, 10 female and 10 male, aged 39-73 (mean 57-8) years, entered the study. They all had a history of chronic heart failure due, singly or in combination, to coronary artery disease, mitral valve disease and aortic valve dysfunction. All were in the intensive care unit following surgery for CABG (eight patients), mitral valve replacement or reconstruction (MVR) (nine patients), aortic valve replacement (AVR) (one patient), AVR + MVR (one patient) or CABG + AVR (one patient). Cardiac index was low enough (
