Background
Severe burn is followed by profound cardiac stress. Propranolol, a non selective β1, β2-receptor antagonist, decreases cardiac stress, but little is known about the dose necessary to cause optimal effect. Thus, the aim of this study was to determine in a large prospective randomized controlled trial the dose of propranolol that would decrease heart rate at least 15% of admission heart rate and improve cardiac function. Four-hundred six patients with burns >30% total body surface area (TBSA) were enrolled and randomized to receive standard care (controls, n=235) or standard care plus propranolol (n=171).
Methods
Dose-response and drug kinetics of propranolol were performed. Heart rate and mean arterial pressure were measured continuously. Cardiac output (CO), cardiac index (CI), stroke volume (SV), rate pressure product, and cardiac work (CW) were determined at regular intervals. Statistical analysis was performed using ANOVA with Tukey and Bonferroni corrections and Student’s t-test when applicable. Significance was accepted at p<0.05.
Results
Propranolol given initially at 1 mg/kg/day decreased heart rate by 15% compared to control patients but was increased to 4 mg/kg/day within the first 10 days to sustain treatment benefits (p<0.05). Propranolol decreased CO, rate pressure product, and CW without deleterious effects on mean arterial pressure. The effective plasma drug concentrations were achieved in 30 minutes, and the half-life was 4 hours.
Conclusions
The data suggest that propranolol is an efficacious modulator of the post-burn cardiac response when given at a dose of 4 mg/kg/day, which decreases and sustains heart rate 15% below admission heart rate.