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 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.

Predictors of muscle protein synthesis after severe pediatric burns

“…Interestingly, MPS rates appear to peak at the time of discharge from the ICU, suggesting that protein turnover increases until wounds are largely closed, underscoring the importance of early wound closure and strategies that accelerate wound healing in mitigating the pathophysiologic response to burn injury. These data show that much like the hypermetabolic inflammatory response to burn injury, (34, 35) skeletal MPS and thus protein turnover, are chronically elevated for at least one year following burn injury. Indeed, whole body protein synthesis is thought to account for as much as 30% of the resting energy expenditure in healthy individuals.…”

Prompt Myocardial Damage Contributes to Hepatic, Renal, and Intestinal Injuries Soon After a Severe Burn in Rats

“…37 These results have no contradiction with our results, because the protection effects mostly result from its negative inotropic and chronotropic functions, that is cardiac depression. Furthermore, its pharmacological actions are dose dependent 38 and the different methods of administration may also have very different effects. While after treatment with cedilanid, the cardiac function was significantly improved, and early hepatic, renal, and intestinal injuries were mitigated due to improved cardiac function and increased organ perfusion and thus decreased levels of organ ischemia/hypoxia.…”

Effect of Therapeutic Dietary Regimen on Wound Healing For Patients with Moderate Degree Burn

“…Also, Young et al and Ryan (1995) concluded that burned patients had 50% higher use rates of essential and nonessential amino acids than healthy individuals. Similarly, Matthews et al (1993) and Saffle (2007) showed that burned patients require a minimum of 1.5 to 2 g/kg body weight per day protein intake for improving wound healing and reduced catabolic state (48)(49)(50)(51) . Furthermore, Adams 2002 and Shewry 2009 explained that wheat germ was considered good source of caloric, protein, minerals, B-group vitamins and dietary fiber.…”