Acute hemodynamic and electrophysiologic effects and safety of high-dose intravenous diltiazem in patients receiving metoprolol.
The anti-ischemic efficacy of diltiazem may improve with increments in dosage and with additional beta-blocking therapy. However, the combined administration could lead to adverse effects through amplification of negative inotropic and chronotropic properties. To evaluate hemodynamic tolerability and safety of high-dose intravenous diltiazem in patients with coronary artery disease receiving long-term metoprolol treatment, 9 such patients were studied for 30 minutes after onset of intravenous diltiazem administration (0.5 mg/kg for 5 minutes, followed by 15 mg/hour). Diltiazem plasma levels peaked at 5 minutes (641 +/- 74 micrograms/liter), decreasing to 177 micrograms/liter at 30 minutes. Average metoprolol levels (43 +/- 12 micrograms/liter) did not change. Diltiazem immediately decreased systemic vascular resistance, left ventricular systolic and mean aortic pressures (29, 21 and 20%, respectively, at 5 minutes), and they remained significantly reduced at 30 minutes. Heart rate initially increased by 11% during the bolus infusion (p < 0.05). Concomitantly, contractility indexes Vmax and Vce40, measured at fixed heart rates, also increased significantly by 11%. Both heart rate and contractility indexes returned to baseline levels thereafter. Cardiac output increased by 10% (p = not significant), stroke index remained unchanged, but stroke work decreased significantly by 20%. Also, the tension-time index was significantly reduced (23%). Diltiazem induced moderate negative lusitropic effects, the first derivative of negative left ventricular pressure decline decreased by 12% and Tau 2 lengthened by 13%. Concomitantly, left ventricular filling pressure increased from 19 +/- 2 to 23 +/- 3 mm Hg, but only at 5 and 15 minutes. PQ, QRS and QTc intervals were not affected.(ABSTRACT TRUNCATED AT 250 WORDS)
Wiesfeld
A C
AC
Cardiovascular Research Foundation, Sticares and Zuiderziekenhuis, Rotterdam, The Netherlands.
Remme
W J
WJ
Look
M P
MP
Kruijssen
D A
DA
van Hoogenhuyze
D C
DC
D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology*; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D008875:Middle Aged; D016277:Ventricular Function, Left / Q000187:drug effects
D004110:Diltiazem; D008790:Metoprolol