Br. J. clin. Pharmac. (1979), 8, 233S-238S
LABETALOL INFUSION IN ACUTE MYOCARDIAL INFARCTION WITH SYSTEMIC HYPERTENSION P.G. MARX & D.S. REID Regional Cardiothoracic Centre, Freeman Hospital, Freeman Road, Newcastle upon Tyne NE7 7DN, UK
1 Fifteen patients with suspected acute myocardial infarction and systemic BP of greater than 160/110 mmHg were treated with an incremental infusion of labetalol. 2 Systemic BPs were safely and effectively lowered to less than 130 mmHg systolic or 90 mmHg diastolic in all patients. 3 Heart rate, mean pulmonary artery wedge pressure cardiac index and stroke work index were significantly reduced. 4 The dose of labetalol varied from 30 mg-440 mg and was significantly higher (mean 295 mg) in those patients with pre-existing systemic hypertension compared with others (mean 133 mg). 5 No side-effects occurred and all patients survived ito leave hospital.
Introduction
Methods
MYOCARDIAL infarction complicated by systemic hypertension has been associated with a higher incidence of left ventricular failure, major arrhythmia and hospital death (Fox et al., 1975; Rosenbaum & Levine, 1941). The improved coronary perfusion resulting from raised systemic BP in this situation probably does not compensate for the increased myocardial oxygen consumption occasioned by elevated afterload, with consequent impairment of myocardial function. High serum catecholamine levels are found in myocardial infarction (Siggers et al., 1971) which makes adrenoceptor blockade an attractive approach to lowering systemic BP. However, ac-adrenoceptor blockade with phentolamine in these circumstances is relatively ineffective in reducing systemic BP in those patients with pre-existing hypertension and, moreover, while satisfactorily lowering left ventricular end diastolic BP, increases heart rate and can worsen myocardial ischaemia (Kelly et al., 1973). padrenoceptor blockade on the other hand lowers systemic BP and heart rate, but may elevate left ventricular filling pressure (Peter et al., 1978). The combination of a- and f3-adrenoceptor blockade produced by labetalol may combine the benefits of the individual approaches, namely, lowering systemic BP, heart rate and left ventricular filling BP, the major determinants of myocardial oxygen consumption (Braunwald, 1969). The purpose of this study was to determine a suitable infusion regimen for labetalol in hypertensive infarction and to observe its haemodynamic effects.
Patients were admitted to the study if they had a history and/or 12 lead electrocardiogram (ECG) suggestive of acute myocardial infarction, and systemic BPs either greater than 160 mmHg systolic or greater than 110 mmHg diastolic, persisting for 2 h after adequate analgesia. Patients were excluded if they: were over 70 yr of age; had chronic airways disease; had bradycardia of less than 60 beats/min; had X-ray evidence of severe left ventricular failure; or had taken 1 adrenoceptorblocking drugs within the previous 48 hours. All patients gave informed consent, and the studies were carried out in the coronary care unit. Daily 12 lead electrocardiogram and SGOT assays were carried out for at least three consecutive days, and WHO criteria were used for infarct diagnosis (World Health Organization, 1959). The ECG was continuously displayed and the heart rate determined from a recording of ten consecutive beats. A 12 lead ECG was taken before and on completion of labetalol infusion, with the chest lead positions marked by an indelible pen. Systemic BP was measured using a sphygmomanometer cuff. Further haemodynamic measurements were made in seven patients (9-15). A thermistor tipped Swan-Ganz catheter was inserted by way of the brachio-cephalic or an antecubital vein and advanced to a pulmonary artery. If the mean occluded pulmonary arterial BP was the same as pulmonary arterial diastolic BP, the catheter tip was withdrawn to a more central position, and the latter BP used to represent left ventricular end diastolic BP
0306-5251/79/170233-06 $01.00
© Macmillan Journals Ltd 1979
234S
P.G. MARX & D.S. REID
(Bauchard et al., 1971). The catheters permitted simultaneous recording of right atrial pressure. Using Bruch transducers, pulmonary arterial and right atrial pressures were continuously displayed on an S & W oscilloscope. Cardiac output determinations were made using a Cardiovascular Instruments CV 600 cardiac output computer, initially using hand injections of 5% dextrose, but latterly using an OMP thermodilution injector and 5% dextrose cooled in iced water. The mean of three injections was used for these determinations. The observations recorded were: heart rate and systemic BP; and in those patients with Swan-Ganz catheters: cardiac output, and pulmonary arterial and right atrial pressures. Two sets of observations were taken 15 min apart before labetalol infusion, and subsequently observations were recorded every 30 min during infusion. For the first six patients, this was commenced at 10 mg/h with increments every 30 min of 10 mg/hour. For patients 7-15 an initial rate of 30 mg/h with increments of 30 mg/h every 30 min was used. The infusion was continued for 30 min after the systemic systolic BP fell to less than 130 mmHg or the diastolic to less than 90 minHg. If at any time the systemic BP fell to less than 120 mmHg or 80 mmHg diastolic, the infusion was stopped at once. Calculations Mean arterial pressure (MAP, mmHg) = systemic diastolic + 1/3 (systemic systolic-systemic diastolic) (Yang et al., 1971). Cardiac index (CI: 1/min 1 m2)= (cardiac output/body surface area). Stroke index (SI; mI 1m2) = (CI/heart rate). Stroke work index Table 1
Results Fifteen patients were admitted to the study between 8-22 h after the onset of major symptoms. There were eleven men and four women with a mean age of 54 yr (range 37-64 yr). Thirteen were found to have had myocardial infarction (nine anterior, four inferior) and two were considered to have unstable angina. Five patients had previously diagnosed systemic hypertension, the SGOT peak in these patients being no different from the others (Table 1). Results and labetalol dosage are summarized in Table 2. Observations shown were taken immediately before labetalol infusion and at the time of cessation. In all cases a satisfactory fall in systemic BP was obtained, the mean fall in systolic BP being 34% (P
LABETALOL INFUSION IN ACUTE MYOCARDIAL INFARCTION WITH SYSTEMIC HYPERTENSION P.G. MARX & D.S. REID Regional Cardiothoracic Centre, Freeman Hospital, Freeman Road, Newcastle upon Tyne NE7 7DN, UK
1 Fifteen patients with suspected acute myocardial infarction and systemic BP of greater than 160/110 mmHg were treated with an incremental infusion of labetalol. 2 Systemic BPs were safely and effectively lowered to less than 130 mmHg systolic or 90 mmHg diastolic in all patients. 3 Heart rate, mean pulmonary artery wedge pressure cardiac index and stroke work index were significantly reduced. 4 The dose of labetalol varied from 30 mg-440 mg and was significantly higher (mean 295 mg) in those patients with pre-existing systemic hypertension compared with others (mean 133 mg). 5 No side-effects occurred and all patients survived ito leave hospital.
Introduction
Methods
MYOCARDIAL infarction complicated by systemic hypertension has been associated with a higher incidence of left ventricular failure, major arrhythmia and hospital death (Fox et al., 1975; Rosenbaum & Levine, 1941). The improved coronary perfusion resulting from raised systemic BP in this situation probably does not compensate for the increased myocardial oxygen consumption occasioned by elevated afterload, with consequent impairment of myocardial function. High serum catecholamine levels are found in myocardial infarction (Siggers et al., 1971) which makes adrenoceptor blockade an attractive approach to lowering systemic BP. However, ac-adrenoceptor blockade with phentolamine in these circumstances is relatively ineffective in reducing systemic BP in those patients with pre-existing hypertension and, moreover, while satisfactorily lowering left ventricular end diastolic BP, increases heart rate and can worsen myocardial ischaemia (Kelly et al., 1973). padrenoceptor blockade on the other hand lowers systemic BP and heart rate, but may elevate left ventricular filling pressure (Peter et al., 1978). The combination of a- and f3-adrenoceptor blockade produced by labetalol may combine the benefits of the individual approaches, namely, lowering systemic BP, heart rate and left ventricular filling BP, the major determinants of myocardial oxygen consumption (Braunwald, 1969). The purpose of this study was to determine a suitable infusion regimen for labetalol in hypertensive infarction and to observe its haemodynamic effects.
Patients were admitted to the study if they had a history and/or 12 lead electrocardiogram (ECG) suggestive of acute myocardial infarction, and systemic BPs either greater than 160 mmHg systolic or greater than 110 mmHg diastolic, persisting for 2 h after adequate analgesia. Patients were excluded if they: were over 70 yr of age; had chronic airways disease; had bradycardia of less than 60 beats/min; had X-ray evidence of severe left ventricular failure; or had taken 1 adrenoceptorblocking drugs within the previous 48 hours. All patients gave informed consent, and the studies were carried out in the coronary care unit. Daily 12 lead electrocardiogram and SGOT assays were carried out for at least three consecutive days, and WHO criteria were used for infarct diagnosis (World Health Organization, 1959). The ECG was continuously displayed and the heart rate determined from a recording of ten consecutive beats. A 12 lead ECG was taken before and on completion of labetalol infusion, with the chest lead positions marked by an indelible pen. Systemic BP was measured using a sphygmomanometer cuff. Further haemodynamic measurements were made in seven patients (9-15). A thermistor tipped Swan-Ganz catheter was inserted by way of the brachio-cephalic or an antecubital vein and advanced to a pulmonary artery. If the mean occluded pulmonary arterial BP was the same as pulmonary arterial diastolic BP, the catheter tip was withdrawn to a more central position, and the latter BP used to represent left ventricular end diastolic BP
0306-5251/79/170233-06 $01.00
© Macmillan Journals Ltd 1979
234S
P.G. MARX & D.S. REID
(Bauchard et al., 1971). The catheters permitted simultaneous recording of right atrial pressure. Using Bruch transducers, pulmonary arterial and right atrial pressures were continuously displayed on an S & W oscilloscope. Cardiac output determinations were made using a Cardiovascular Instruments CV 600 cardiac output computer, initially using hand injections of 5% dextrose, but latterly using an OMP thermodilution injector and 5% dextrose cooled in iced water. The mean of three injections was used for these determinations. The observations recorded were: heart rate and systemic BP; and in those patients with Swan-Ganz catheters: cardiac output, and pulmonary arterial and right atrial pressures. Two sets of observations were taken 15 min apart before labetalol infusion, and subsequently observations were recorded every 30 min during infusion. For the first six patients, this was commenced at 10 mg/h with increments every 30 min of 10 mg/hour. For patients 7-15 an initial rate of 30 mg/h with increments of 30 mg/h every 30 min was used. The infusion was continued for 30 min after the systemic systolic BP fell to less than 130 mmHg or the diastolic to less than 90 minHg. If at any time the systemic BP fell to less than 120 mmHg or 80 mmHg diastolic, the infusion was stopped at once. Calculations Mean arterial pressure (MAP, mmHg) = systemic diastolic + 1/3 (systemic systolic-systemic diastolic) (Yang et al., 1971). Cardiac index (CI: 1/min 1 m2)= (cardiac output/body surface area). Stroke index (SI; mI 1m2) = (CI/heart rate). Stroke work index Table 1
Results Fifteen patients were admitted to the study between 8-22 h after the onset of major symptoms. There were eleven men and four women with a mean age of 54 yr (range 37-64 yr). Thirteen were found to have had myocardial infarction (nine anterior, four inferior) and two were considered to have unstable angina. Five patients had previously diagnosed systemic hypertension, the SGOT peak in these patients being no different from the others (Table 1). Results and labetalol dosage are summarized in Table 2. Observations shown were taken immediately before labetalol infusion and at the time of cessation. In all cases a satisfactory fall in systemic BP was obtained, the mean fall in systolic BP being 34% (P
