Burns
Conditions
Brief summary
Severe burn is associated with a wide array of stress, metabolic, and physiologic processes in an attempt to restore homeostasis. The catecholamine induced stress response following severe burns is particularly exaggerated and manifests detrimentally as inflammation, insulin resistance, hypermetabolism, and associated profound protein catabolism. The investigators hypothesize that catecholamine blockade will lead to restored IR signaling and result in improved post-burn morbidity. The investigators will further determine the molecular mechanisms mediating these effects.
Interventions
DRUGplacebo
identically packed placebo
DRUGpropranolol
20-40 mg q6-8h
Sponsors
Sunnybrook Health Sciences Centre
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Patients between 18 and 90 years of age * \>25% TBSA burn
Exclusion criteria
* Death upon admission * Decision not to treat due to burn injury severity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Perform oral glucose tolerance test | Conduct at week 1 post admission | Standard fasting oral glucose tolerance test with an intake of 75 g of glucose. Subsequent measurements (in mg/dl) of glucose in blood, insulin and c-peptide will be conducted over 2 hours. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measure concentrations of serum cytokines | weekly until discharge (1-4 months post admission depending on severity) | Inflammatory response will be assessed by measuring the concentrations (pg/ml) of a panel of serum cytokines (IL-1, IFN, TNF etc.) using the Bio-Plex 17-Plex Suspension assay. |
| Record the episodes of Pneumonia | daily until discharge (1-4 months post admission depending on severity) | Pneumonia is defined by the following criteria: new progressive and persistent infiltrate, consolidation, or cavitations, in light of the baseline evaluation for inhalational injury on chest X-ray, along with signs of sepsis, worsening gas exchange (decreased P/F ratio), increased O2, and change in the sputum, e.g. purulent or increased sputum production. |
| Record the episodes of sepsis | daily until discharge (1-4 months post admission depending on severity of injury) | Patients are evaluated daily and the number of episodes of sepsis or bloodstream infection will be recorded |
| Measure the levels of activated signaling proteins using protein blotting | assess at 1st operation (week 1-2 post admission on average) and 3rd operation (week 3-4 post admission on average) | The level of activation of a protein signaling cascade (fold change compared to control), as indicated by the amount of phosphorylated protein substrates (e.g. p-Akt/Akt), will be measured in tissue obtained at operation using protein blotting techniques in the laboratory. |
Countries
Canada
Outcome results
None listed