Twenty-seven patients of either sex, aged 48-84 years with ongoing
chest pain upon arrival to the Coronary Care Unit (CCU) were subdivided into two groups: (1) patients with ECG signs of threatening transmural myocardial damage (n = 15); and (2) patients without such ECG signs (n = 12).
Pain intensity was assessed by a numerical rating scale (NRS) and venous blood was obtained for determination of plasma
catecholamine and NPY concentrations. A continuous infusion of
metoprolol (3 mg.min-1 i.v) was started and serial blood samples for plasma
catecholamines, NPY as well as
metoprolol and its major metabolite
alpha-hydroxymetoprolol were obtained from the contralateral arm.
RESULTS: Initial
pain intensity was 5.9 (arbitrary units) and 5.4 in the groups with and without signs of transmural myocardial damage, respectively. One third of the patients with ST changes reported full
pain relief (NRS = 0) within 70 min after starting
metoprolol infusion (accumulated dose, 15-180 mg). Among the patients without ST changes upon arrival, full
pain relief was obtained in 70% (accumulated dose, 30-120 mg). There was a dose-dependent relation between accumulated
metoprolol dose and
pain relief. The diagnosis of acute
myocardial infarction (AMI) was confirmed in all 15 patients with ECG signs on arrival of transmural myocardial damage. The mean
metoprolol dose in this group was 91(12) mg. The mean
metoprolol dose in the 12 patients without ST changes was 64(8) mg. In all, seven of these patients developed definite AMI. The terminal half-life of unchanged
metoprolol ranged from 2.5 to 8.5 h in group 1 and from 2.2 to 5.2 h in group 2. In group 1,
metoprolol half-life was 4.5 h and total plasma clearance (CL) 54.1 1.h-1. In group 2, the
metoprolol half-life was 3.7 h and total plasma clearance 75.4 1.h-1. There was a significant difference in clearance between the groups. After the intravenous
metoprolol infusion,
alpha-hydroxymetoprolol concentrations increased gradually. In groups 1 and 2, maximal concentrations in plasma (Cmax) were 143 and 135 nmol.1(-1) for
alpha-hydroxymetoprolol and 2830 and 1653 nmol.1(-1) for
metoprolol, respectively. Plasma NA or NPY did not differ between the groups. In contrast, plasma A was significantly higher during the initial 90 min of observation in patients with ECG signs of transmural myocardial damage.
CONCLUSION: High-dose intravenous
metoprolol was well tolerated in patients with suspected AMI. There was a more rapid and almost complete
pain relief in patients without signs of transmural ischaemia compared with the patients with ECG signs of transmural AMI at arrival. In the later group of patients, plasma clearance of
metoprolol was significantly reduced.