Enoximone Treatment Cardiac Surgery:
of Impaired Myocardial Function During Combined Effects With Epinephrine
Joachim Boldt, MD, Dieter Kling, MD, Rainer Moosdorf, MD, and Gunther Hempelmann, MD Enoximone belongs to a new class of noncatecholamine-positive inotropes, which selectively inhibit phosphodiesterase type Ill and increase cyclic AMP (CAMP]. This study was performed in 30 coronary artery surgery patients with impaired myocardial function (ejection fraction [EF] < 50%). The study’s two purposes were to investigate the hemodynamic effects of enoximone, 0.5 mg/kg, administered following induction of anesthesia (phase I), and to assess whether enoximone can potentiate the actions of sympathomimetic agents during weaning from cardiopulmonary bypass (CPB) (phase II). Starting with already reduced hemodynamics, induction of anesthesia led to a further deterioration of blood pressure and cardiac output (CO). Administration of enoximone produced a significant increase in cardiac index (Cl) (+47%), whereas pulmonary capillary wedge pressure (PCWP) (-37%). pulmonary artery pressure (PAP) (- 17%). and systemic vascular resistance (SVR) (-17%) were significantly reduced.
M
OST CARDIAC surgical procedures are free of complications. Nevertheless, preexisting impaired ventricular function or deterioration of myocardial function during and after cardiopulmonary bypass (CPB) still can result in an increased morbidity and mortality rate.’ The treatment of myocardial failure in these patients remains one of the major therapeutic challenges. The use of sympathomimetic amines, such as epinephrine, isoproterenol, dopamine, or dobutamine, is the established therapy, which produces hemodynamic benefits from their positive inotropism. However, their use may also be associated with severe adverse effects that sometimes limit their role in these patients.2V3 Moreover, the positive inotropic response to catecholamines is diminished in patients with marked hemodynamic dysfunction, most likely because of the down-regulation of myocardial /3-adrenoceptors produced by elevated norepinephrine
From the Departments of Anesthesiology and Zntensive Care Medicine and Cardiovascular Surgery, JustusLiebig-University, Giessen, West Germany. Address reprint requests to Joachim Boldt. MD, Department of Anesthesiology and Intensive Care Medicine. Klinikstr. 29. Justus-Liebig-University Giessen. D-6300 Giessen. FRG. o 1990 by W.B. Saunders Company. 088%-6296/90/0404-0008$03.00/0 462
Heart rate (HR) was not increased, and no dysrhythmias occurred during the investigation. The hemodynamic effects were maintained for 30 minutes until the start of the operation. In phase II. where weaning from CPB was not possible without pharmacological support, either enoximone (0.5 mg/kg) + epinephrine (0.1 pg/kg/min) or only epinephrine (same dosage) was randomly selected. Weaning was successful in both groups, but the combined therapy produced a larger increase in Cl and a more pronounced decrease of the elevated filling pressure (PCWP]. PAP was not changed in the combined therapy group, but increased in the patients receiving epinephrine alone. It is concluded that enoximone has beneficial hemodynamic effects in the perioperative period, and that potentiation of the effects of epinephrine in severe heart failure may be one of the drug’s most useful features. 0 1990 by W.B. Saunders Company.
plasma levels or by sustained @-adrenoreceptor therapy itself.“6 For these reasons, new therapeutic approaches are of major interest. Cardioactive drugs that activate adenyl cyclase or inhibit phosphodiesterase (PDE) are useful in improving myocardial function in patients with cardiac dysfunction because of their action at a site distal to the fl-adrenergic receptor.‘j Amrinone was the first PDE inhibitor approved by the Food and Drug Administration, in 1984, for intravenous use.’ However, its inotropic properties have been and its adverse effects have limquestioned,‘-” ited its clinical use. Enoximone, an imidazole derivative, is a newer PDE-III inhibitoriiV’* that has proven beneficial in patients suffering from severely impaired myocardial function during short- or long-term therapy.13-16 This study’s purpose was to investigate the hemodynamic effects of enoximone in cardiac surgical patients with impaired myocardial function before and after CPB, and to test the efficacy of this drug in combination with epinephrine. MATERIALS AND METHODS A total of 30 patients undergoing elective coronary artery bypass grafting (CABG) were investigated. All gave informed consent to participate in the investigation and the study had been approved by the local ethics committee. Enoximone was studied in two different phases as an intravenous bolus of 0.5 mg/kg: phase I, after induction of
Journal of Cardiothoracic Anesthesia, Vol4. No 4 (August),1990: pp 462-468
ENOXIMONE
463
AND CARDIAC SURGERY
anesthesia, but before the start of the operation (n = 10); and phase II, in patients in whom weaning from CPB was not possible without pharmacological support. In a random sequence, 10 patients received enoximone along with epinephrine (0.1 rg/kg/min; group IIa; E + Ep-patients) and were compared with 10 patients in whom only epinephrine was given at the same dosage (group IIb; Ep-patients). Phase I (group I) patients had impaired left ventricular function by preoperative catheterization (ejection fraction [EF] t50%, and left ventricular end-diastolic pressure [LVEDP] ~20 mm Hg). Premeditation consisted of 0.15 mg/kg of morphine sulfate and 0.025 mg/kg of intramuscular (IM) flunitrazepam given 1 hour before entering the operating room. All monitoring catheters were placed before induction of anesthesia under local anesthesia, and the following hemodynamic measurements were performed: mean arterial pressure (MAP), heart rate (HR), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), right atria1 pressure (RAP), and cardiac index (CI). Total systemic resistance (TSR) was calculated. A CI ~2.5 L/min/m’ and a PCWP >20 mm Hg following induction of anesthesia were the criteria for administration of enoximone. Hemodynamic measurements were performed at 5, 10, 20, and 30 minutes postinjection of 0.5 mg/kg of enoximone, but before the start of the operation and during a steady state of anesthesia (fentanyl, 7 fig/kg; midazolam, 0.15 mg/kg; pancuronium, 0.15 mg/kg). During this period, patients were ventilated mechanically with an F,O, of 0.5 (oxygen/air) and a positive end-expiratory pressure (PEEP) of 5 cm H,O. Phase II of the investigation included 20 patients in whom weaning from CPB was not possible without pharmacological support (MAP ~60 mm Hg; PCWP >25 mm Hg). A second attempt at weaning from CPB was then performed with a period of controlled reperfusion at a flow of 2.4 L/min/m’ after either administration of enoximone, 0.5 mg/kg, and epinephrine, 0.1 pg/kg/min (n = lo), or only epinephrine in the same dosage (n = lo), done in a random sequence. Hemodynamics were measured during controlled reperfusion (before therapy), and 5, 10, and 15 minutes after successful weaning from CPB (after decannulation, before protamine sulfate was given). All data are expressed as mean values (x) + standard deviation (SD). One- and two-factorial analyses of variance were used for statistical interpretation. P values less than 0.05 were considered significant.
RESULTS
Demographic and preoperative catheterization data are listed in Table 1. Group IIa and IIb patients did not differ with regards to preoperative myocardial function, duration of ischemia (cross-clamping of the aorta), or number of grafts. Administration of enoximone following induction of anesthesia resulted in a marked increase in CI (+47%), whereas HR and RAP did not change (Fig 1). MAP also increased and was restored to the level before induction of anesthe-
Table 1. Groun Data (X f SD)
GroupI 10)
(n =
Age W Height (cm1 Weight (kg) LVEF t%) LVEDP (mm Hg)
68.2 173 76.5 41.4 25.5
+ f f * f
3.3 5.3 3.8 3.9 2.7
Group 11s (n =
65.8
101
* 4.8
174 + 3.0
78.9 + 6.9 40.4
+ 4.6
28.1
+ 3.3
GroupIlb In = 10)
67.8 176 78.0 42.0 24.2
f + f f +
5.5 6.0 4.4 3.3 5.9
Myocardial infarctions CPB time (min) lschemia time (min) Grafts performed
1013
1013
1o/3
114.9
* 7.3
109.2
f 8.8
79.5
+ 8.8
85.3
f 4.0
4.8 f 0.9
4.4 + 0.6
Abbreviations: LVEF, left ventricular ejection fraction; LVEDP, left ventricular end-diastolic pressure: CPE, cardiopulmonary bypass.
sia (Fig 1). PAP (- 17%), PCWP (-37%), and TSR (- 17%) decreased significantly after injection of enoximone (Fig 2). Dysrhythmias were not observed during the investigation. Two patients required additional volume replacement because their PCWP decreased below 10 mm Hg. Results from the patients studied during and after weaning from CPB (group II) are shown in Figs 3 and 4. Starting at 2.4 L/min/m2 during the controlled reperfusion period, CI in the patients receiving enoximone and epinephrine increased significantly (+20%) when compared with the group of patients receiving only epinephrine. The PCWP also differed significantly between the groups: epinephrine-treated patients (IIb) had an increase (+ 15%), whereas there was a reduction (- 3 1%) in the patients who also received enoximone. TSR increased significantly in Ep-patients (+9%) in contrast to the E + Ep-patients (-31%). Vasodilator therapy (nitroglycerin) was necessary only in the Ep-patients (n = 4). No significant differences between the two groups could be observed regarding MAP, RAP, and HR. None of the patients had dysrhythmias during the whole investigation and weaning was successful in all patients in both groups. DISCUSSION
Induction of anesthesia is an especially critical period in patients with impaired myocardial function. A deterioration of hemodynamics may result from the effects of anesthetic drugs on myocardial performance and the peripheral circulation, the start of positive-pressure ventilation,
464
BOLDT ET AL
80
t:
enoxlmone 0.5 mg/kg
Lv.
t
P t so
?? p < 0.05
70
3.5
3.5
3.0
3.0
2.5
2.5
2.0
2.0
8 below
altu
5
10
20
and ablation of sympathetic outflow.” All patients investigated in this study had impaired preoperative myocardial function (EF ~50%; LVEDP >20 mm Hg) and depressed hemodynamics, which were further impaired by induction of anesthesia. A number of different drugs including epinephrine, norepinephrine, dopamine, and dobutamine have been advocated to support and improve hemodynamics. These sympathomimetic amines predominantly stimulate production of intracellular CAMP, which increases the intracellular Ca++ inward current and improves myocardial contractility.18919 HOWever, their effectiveness in patients with severely impaired cardiac function is diminished because of the down-regulation of the myocardial fi4-6 It has been demonstrated in adrenoreceptors. patients with heart disease that the degree of P-receptor down-regulation is proportional to the degree of clinical cardiac dysfunction.4*5 Because reduced responsiveness of P-receptor agonists may be anticipated in these patients, it is reason-
30
min
Fig 1. Changes in mean arterial pressure (MAP), heart rate (HRI, and cardiac index (Cl) after enoximone before the start of the operation.
able to select a therapeutic strategy that bypasses the ,&receptor or acts by additional mechanisms to increase calcium availability at the level of the myofilaments.20 Furthermore, patients with ischemic heart disease may be especially sensitive to the tachycardic and arrhythmogenic effects of catecholamines.3*21 New alternatives for treatment of depressed ventricular function include the PDEinhibitors. “Thisclasso f c o m p ounds acts primarily through an inhibition of PDE type III, resulting in an increased CAMP level.” Amrinone was the first of these new cardiotonic agents with combined inotropic and vasodilatory properties.’ However, its inotropic effect has been questioned, lo and severe side effects such as thrombocytopenia have limited its clinical use.22S23 Enoximone is a new member of this class of selective PDE-III inhibitors that possess positive inotropic and vasodilating properties.” It is an imidazole derivative structurally unrelated to digitalis, catecholamines, or amrinone. Several
465
ENOXIMONE AND CARDIAC SURGERY
35
30
25
25-
zo-
20
1:enoxh~one 0.5 mg/kg I.v. I
25-
PCWP (mm Hg)
I
r25
-20
zo-
-15
IS-
-_
??
??
* -10
IO]
*
.I500 .I400
.1300 .I200 -1100 ~1000
Fig 2. Changes in pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), and total systemic resistance (TSR) after enoximone before the start of the operation.
??
??
10
20
??
-900
t before
clinical reports have described beneficial effects of enoximone in patients with heart failure.15*‘6,24 Coagulation studies including platelet counts have not been compromised, which is of special importance in cardiac surgery procedures.25 In this study, decreasing the elevated preload (PCWP) and increasing CO without changing HR were the predominant results of a bolus dose of enoximone following induction of anesthesia. Thus, patients’ hemodynamics were stabilized or even improved for 30 minutes until the start of the operation. Moreover, no additional positive inotropic therapy was necessary until the beginning of CPB. Because of the fact that the patients in this study required positive inotropic therapy postinduction, a placebo control group was considered to be unethical. The second part of the investigation was focused on another problem during cardiac surgery. Termination of CPB and the immediate postbypass period are sometimes complicated by
alter
5
30 mh
depressed cardiovascular dynamics resulting from preoperative inotropic abnormalities and/or the postischemic state of the myocardium.‘7 In this situation, the heart requires additional inotropic support to generate an adequate CO. However, in patients with a limited ability to improve myocardial oxygen supply, special interest has to be concentrated on the impact of inotropic therapy on myocardial oxygen demand.2,25 In this situation, it is controversial as to which is the optimal treatment. 2,26Epinephrine is a very effective positive inotropic drug whose beneficial effects in this situation have been demonstrated in several previous studies.26 Potentiation of the effects of @-adrenergic agents by noncatecholamine drugs is a new technique that may be very useful after CPB. Patients in phase II of this study had impaired myocardial function preoperatively (EF
of Impaired Myocardial Function During Combined Effects With Epinephrine
Joachim Boldt, MD, Dieter Kling, MD, Rainer Moosdorf, MD, and Gunther Hempelmann, MD Enoximone belongs to a new class of noncatecholamine-positive inotropes, which selectively inhibit phosphodiesterase type Ill and increase cyclic AMP (CAMP]. This study was performed in 30 coronary artery surgery patients with impaired myocardial function (ejection fraction [EF] < 50%). The study’s two purposes were to investigate the hemodynamic effects of enoximone, 0.5 mg/kg, administered following induction of anesthesia (phase I), and to assess whether enoximone can potentiate the actions of sympathomimetic agents during weaning from cardiopulmonary bypass (CPB) (phase II). Starting with already reduced hemodynamics, induction of anesthesia led to a further deterioration of blood pressure and cardiac output (CO). Administration of enoximone produced a significant increase in cardiac index (Cl) (+47%), whereas pulmonary capillary wedge pressure (PCWP) (-37%). pulmonary artery pressure (PAP) (- 17%). and systemic vascular resistance (SVR) (-17%) were significantly reduced.
M
OST CARDIAC surgical procedures are free of complications. Nevertheless, preexisting impaired ventricular function or deterioration of myocardial function during and after cardiopulmonary bypass (CPB) still can result in an increased morbidity and mortality rate.’ The treatment of myocardial failure in these patients remains one of the major therapeutic challenges. The use of sympathomimetic amines, such as epinephrine, isoproterenol, dopamine, or dobutamine, is the established therapy, which produces hemodynamic benefits from their positive inotropism. However, their use may also be associated with severe adverse effects that sometimes limit their role in these patients.2V3 Moreover, the positive inotropic response to catecholamines is diminished in patients with marked hemodynamic dysfunction, most likely because of the down-regulation of myocardial /3-adrenoceptors produced by elevated norepinephrine
From the Departments of Anesthesiology and Zntensive Care Medicine and Cardiovascular Surgery, JustusLiebig-University, Giessen, West Germany. Address reprint requests to Joachim Boldt. MD, Department of Anesthesiology and Intensive Care Medicine. Klinikstr. 29. Justus-Liebig-University Giessen. D-6300 Giessen. FRG. o 1990 by W.B. Saunders Company. 088%-6296/90/0404-0008$03.00/0 462
Heart rate (HR) was not increased, and no dysrhythmias occurred during the investigation. The hemodynamic effects were maintained for 30 minutes until the start of the operation. In phase II. where weaning from CPB was not possible without pharmacological support, either enoximone (0.5 mg/kg) + epinephrine (0.1 pg/kg/min) or only epinephrine (same dosage) was randomly selected. Weaning was successful in both groups, but the combined therapy produced a larger increase in Cl and a more pronounced decrease of the elevated filling pressure (PCWP]. PAP was not changed in the combined therapy group, but increased in the patients receiving epinephrine alone. It is concluded that enoximone has beneficial hemodynamic effects in the perioperative period, and that potentiation of the effects of epinephrine in severe heart failure may be one of the drug’s most useful features. 0 1990 by W.B. Saunders Company.
plasma levels or by sustained @-adrenoreceptor therapy itself.“6 For these reasons, new therapeutic approaches are of major interest. Cardioactive drugs that activate adenyl cyclase or inhibit phosphodiesterase (PDE) are useful in improving myocardial function in patients with cardiac dysfunction because of their action at a site distal to the fl-adrenergic receptor.‘j Amrinone was the first PDE inhibitor approved by the Food and Drug Administration, in 1984, for intravenous use.’ However, its inotropic properties have been and its adverse effects have limquestioned,‘-” ited its clinical use. Enoximone, an imidazole derivative, is a newer PDE-III inhibitoriiV’* that has proven beneficial in patients suffering from severely impaired myocardial function during short- or long-term therapy.13-16 This study’s purpose was to investigate the hemodynamic effects of enoximone in cardiac surgical patients with impaired myocardial function before and after CPB, and to test the efficacy of this drug in combination with epinephrine. MATERIALS AND METHODS A total of 30 patients undergoing elective coronary artery bypass grafting (CABG) were investigated. All gave informed consent to participate in the investigation and the study had been approved by the local ethics committee. Enoximone was studied in two different phases as an intravenous bolus of 0.5 mg/kg: phase I, after induction of
Journal of Cardiothoracic Anesthesia, Vol4. No 4 (August),1990: pp 462-468
ENOXIMONE
463
AND CARDIAC SURGERY
anesthesia, but before the start of the operation (n = 10); and phase II, in patients in whom weaning from CPB was not possible without pharmacological support. In a random sequence, 10 patients received enoximone along with epinephrine (0.1 rg/kg/min; group IIa; E + Ep-patients) and were compared with 10 patients in whom only epinephrine was given at the same dosage (group IIb; Ep-patients). Phase I (group I) patients had impaired left ventricular function by preoperative catheterization (ejection fraction [EF] t50%, and left ventricular end-diastolic pressure [LVEDP] ~20 mm Hg). Premeditation consisted of 0.15 mg/kg of morphine sulfate and 0.025 mg/kg of intramuscular (IM) flunitrazepam given 1 hour before entering the operating room. All monitoring catheters were placed before induction of anesthesia under local anesthesia, and the following hemodynamic measurements were performed: mean arterial pressure (MAP), heart rate (HR), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), right atria1 pressure (RAP), and cardiac index (CI). Total systemic resistance (TSR) was calculated. A CI ~2.5 L/min/m’ and a PCWP >20 mm Hg following induction of anesthesia were the criteria for administration of enoximone. Hemodynamic measurements were performed at 5, 10, 20, and 30 minutes postinjection of 0.5 mg/kg of enoximone, but before the start of the operation and during a steady state of anesthesia (fentanyl, 7 fig/kg; midazolam, 0.15 mg/kg; pancuronium, 0.15 mg/kg). During this period, patients were ventilated mechanically with an F,O, of 0.5 (oxygen/air) and a positive end-expiratory pressure (PEEP) of 5 cm H,O. Phase II of the investigation included 20 patients in whom weaning from CPB was not possible without pharmacological support (MAP ~60 mm Hg; PCWP >25 mm Hg). A second attempt at weaning from CPB was then performed with a period of controlled reperfusion at a flow of 2.4 L/min/m’ after either administration of enoximone, 0.5 mg/kg, and epinephrine, 0.1 pg/kg/min (n = lo), or only epinephrine in the same dosage (n = lo), done in a random sequence. Hemodynamics were measured during controlled reperfusion (before therapy), and 5, 10, and 15 minutes after successful weaning from CPB (after decannulation, before protamine sulfate was given). All data are expressed as mean values (x) + standard deviation (SD). One- and two-factorial analyses of variance were used for statistical interpretation. P values less than 0.05 were considered significant.
RESULTS
Demographic and preoperative catheterization data are listed in Table 1. Group IIa and IIb patients did not differ with regards to preoperative myocardial function, duration of ischemia (cross-clamping of the aorta), or number of grafts. Administration of enoximone following induction of anesthesia resulted in a marked increase in CI (+47%), whereas HR and RAP did not change (Fig 1). MAP also increased and was restored to the level before induction of anesthe-
Table 1. Groun Data (X f SD)
GroupI 10)
(n =
Age W Height (cm1 Weight (kg) LVEF t%) LVEDP (mm Hg)
68.2 173 76.5 41.4 25.5
+ f f * f
3.3 5.3 3.8 3.9 2.7
Group 11s (n =
65.8
101
* 4.8
174 + 3.0
78.9 + 6.9 40.4
+ 4.6
28.1
+ 3.3
GroupIlb In = 10)
67.8 176 78.0 42.0 24.2
f + f f +
5.5 6.0 4.4 3.3 5.9
Myocardial infarctions CPB time (min) lschemia time (min) Grafts performed
1013
1013
1o/3
114.9
* 7.3
109.2
f 8.8
79.5
+ 8.8
85.3
f 4.0
4.8 f 0.9
4.4 + 0.6
Abbreviations: LVEF, left ventricular ejection fraction; LVEDP, left ventricular end-diastolic pressure: CPE, cardiopulmonary bypass.
sia (Fig 1). PAP (- 17%), PCWP (-37%), and TSR (- 17%) decreased significantly after injection of enoximone (Fig 2). Dysrhythmias were not observed during the investigation. Two patients required additional volume replacement because their PCWP decreased below 10 mm Hg. Results from the patients studied during and after weaning from CPB (group II) are shown in Figs 3 and 4. Starting at 2.4 L/min/m2 during the controlled reperfusion period, CI in the patients receiving enoximone and epinephrine increased significantly (+20%) when compared with the group of patients receiving only epinephrine. The PCWP also differed significantly between the groups: epinephrine-treated patients (IIb) had an increase (+ 15%), whereas there was a reduction (- 3 1%) in the patients who also received enoximone. TSR increased significantly in Ep-patients (+9%) in contrast to the E + Ep-patients (-31%). Vasodilator therapy (nitroglycerin) was necessary only in the Ep-patients (n = 4). No significant differences between the two groups could be observed regarding MAP, RAP, and HR. None of the patients had dysrhythmias during the whole investigation and weaning was successful in all patients in both groups. DISCUSSION
Induction of anesthesia is an especially critical period in patients with impaired myocardial function. A deterioration of hemodynamics may result from the effects of anesthetic drugs on myocardial performance and the peripheral circulation, the start of positive-pressure ventilation,
464
BOLDT ET AL
80
t:
enoxlmone 0.5 mg/kg
Lv.
t
P t so
?? p < 0.05
70
3.5
3.5
3.0
3.0
2.5
2.5
2.0
2.0
8 below
altu
5
10
20
and ablation of sympathetic outflow.” All patients investigated in this study had impaired preoperative myocardial function (EF ~50%; LVEDP >20 mm Hg) and depressed hemodynamics, which were further impaired by induction of anesthesia. A number of different drugs including epinephrine, norepinephrine, dopamine, and dobutamine have been advocated to support and improve hemodynamics. These sympathomimetic amines predominantly stimulate production of intracellular CAMP, which increases the intracellular Ca++ inward current and improves myocardial contractility.18919 HOWever, their effectiveness in patients with severely impaired cardiac function is diminished because of the down-regulation of the myocardial fi4-6 It has been demonstrated in adrenoreceptors. patients with heart disease that the degree of P-receptor down-regulation is proportional to the degree of clinical cardiac dysfunction.4*5 Because reduced responsiveness of P-receptor agonists may be anticipated in these patients, it is reason-
30
min
Fig 1. Changes in mean arterial pressure (MAP), heart rate (HRI, and cardiac index (Cl) after enoximone before the start of the operation.
able to select a therapeutic strategy that bypasses the ,&receptor or acts by additional mechanisms to increase calcium availability at the level of the myofilaments.20 Furthermore, patients with ischemic heart disease may be especially sensitive to the tachycardic and arrhythmogenic effects of catecholamines.3*21 New alternatives for treatment of depressed ventricular function include the PDEinhibitors. “Thisclasso f c o m p ounds acts primarily through an inhibition of PDE type III, resulting in an increased CAMP level.” Amrinone was the first of these new cardiotonic agents with combined inotropic and vasodilatory properties.’ However, its inotropic effect has been questioned, lo and severe side effects such as thrombocytopenia have limited its clinical use.22S23 Enoximone is a new member of this class of selective PDE-III inhibitors that possess positive inotropic and vasodilating properties.” It is an imidazole derivative structurally unrelated to digitalis, catecholamines, or amrinone. Several
465
ENOXIMONE AND CARDIAC SURGERY
35
30
25
25-
zo-
20
1:enoxh~one 0.5 mg/kg I.v. I
25-
PCWP (mm Hg)
I
r25
-20
zo-
-15
IS-
-_
??
??
* -10
IO]
*
.I500 .I400
.1300 .I200 -1100 ~1000
Fig 2. Changes in pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), and total systemic resistance (TSR) after enoximone before the start of the operation.
??
??
10
20
??
-900
t before
clinical reports have described beneficial effects of enoximone in patients with heart failure.15*‘6,24 Coagulation studies including platelet counts have not been compromised, which is of special importance in cardiac surgery procedures.25 In this study, decreasing the elevated preload (PCWP) and increasing CO without changing HR were the predominant results of a bolus dose of enoximone following induction of anesthesia. Thus, patients’ hemodynamics were stabilized or even improved for 30 minutes until the start of the operation. Moreover, no additional positive inotropic therapy was necessary until the beginning of CPB. Because of the fact that the patients in this study required positive inotropic therapy postinduction, a placebo control group was considered to be unethical. The second part of the investigation was focused on another problem during cardiac surgery. Termination of CPB and the immediate postbypass period are sometimes complicated by
alter
5
30 mh
depressed cardiovascular dynamics resulting from preoperative inotropic abnormalities and/or the postischemic state of the myocardium.‘7 In this situation, the heart requires additional inotropic support to generate an adequate CO. However, in patients with a limited ability to improve myocardial oxygen supply, special interest has to be concentrated on the impact of inotropic therapy on myocardial oxygen demand.2,25 In this situation, it is controversial as to which is the optimal treatment. 2,26Epinephrine is a very effective positive inotropic drug whose beneficial effects in this situation have been demonstrated in several previous studies.26 Potentiation of the effects of @-adrenergic agents by noncatecholamine drugs is a new technique that may be very useful after CPB. Patients in phase II of this study had impaired myocardial function preoperatively (EF
