biostudies-literatureWilliams FNNICHD NIH HHSNIGMS NIH HHSPHS HHS231-9https://www.ebi.ac.uk/biostudies/studies/S-EPMC3008513biostudies-literatureUnknown149(2)Severe burn is followed by profound cardiac stress. Propranolol, a nonselective ?(1,) ?(2)-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).Dose-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.Propranolol 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.The 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.SurgeryPropranolol decreases cardiac work in a dose-dependent manner in severely burned children.PMC3008513T32 GM008256-20R01 HD049471U54 GM062119T32GM08256P50GM60338R01 GM087285-01A2P50 GM060338-01P50 GM060338R01 GM056687R01-HD049471T32 GM008256U54 GM62119R01 GM056687-12R01-VM56687T32 GM008256-19R01 GM087285Kulp GAWilliams FNJeschke MGHerndon DNfalsePropranolol decreases cardiac work in a dose-dependent manner in severely burned children.Severe burn is followed by profound cardiac stress. Propranolol, a nonselective ?(1,) ?(2)-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).Dose-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.Propranolol 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.The 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.2011-01-01T00:00:00Z2011 Feb2021-02-20T00:36:42Z2019-03-27T00:37:36ZS-EPMC30085132059833210.1016/j.surg.2010.05.015