title: Propranolol decreases cardiac work in a dose-dependent manner in severely burned children.
abstract: BACKGROUND
  Severe burn is followed by profound cardiac stress. Propranolol, a nonselective β(1,) β(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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Shriners Hospitals for Children, Galveston, TX, USA.
authors.forename: Felicia N
authors.initials: FN
authors.lastname: Williams
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon
authors.forename: Gabriela A
authors.initials: GA
authors.lastname: Kulp
authors.forename: Marc G
authors.initials: MG
authors.lastname: Jeschke
mesh_terms: D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000367:Age Factors; D001830:Body Surface Area; D002056:Burns / Q000188:drug therapy* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007223:Infant; D008297:Male; D011433:Propranolol / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011446:Prospective Studies; D012727:Sex Characteristics
chemical_list: D000319:Adrenergic beta-Antagonists; D011433:Propranolol