Propranolol decreases cardiac work in a dose-dependent manner in severely burned children

BackgroundSevere burn is followed by profound cardiac stress. Propranolol, a nonselective 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 ≥15% of admission heart rate and improve cardiac function. Four-hundred six patients with burns >30% total body surface area were enrolled and randomized to receive standard care (controls; n = 235) or standard care plus propranolol (n = 171).MethodsDose–response and drug kinetics of propranolol were performed. Heart rate and mean arterial pressure (MAP) were measured continuously. Cardiac output (CO), cardiac index, stroke volume, rate–pressure product, and cardiac work (CW) were determined at regular intervals. Statistical analysis was performed using analysis of variance with Tukey and Bonferroni corrections and the Student t test when applicable. Significance was accepted at P < .05.ResultsPropranolol given initially at 1 mg/kg per day decreased heart rate by 15% compared with control patients, but was increased to 4 mg/kg per day within the first 10 days to sustain treatment benefits (P < .05). Propranolol decreased CO, rate–pressure product, and CW without deleterious effects on MAP. The effective plasma drug concentrations were achieved in 30 minutes, and the half-life was 4 hours.ConclusionThe data suggest that propranolol is an efficacious modulator of the postburn cardiac response when given at a dose of 4 mg/kg per day, and decreases and sustains heart rate 15% below admission heart rate.