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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control | Placebo Comparator |
| |
| Beta blockade | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| placebo | Drug | identically packed placebo |
| |
| propranolol |
| Measure | Description | Time Frame |
|---|---|---|
| Perform oral glucose tolerance test | 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. | Conduct at week 1 post admission |
| Perform oral glucose tolerance test | 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. | Conduct at week 3 post admission |
| Perform oral glucose tolerance test | 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. | Conduct at discharge (1-4 months post admission depending on severity of injury) |
| Measure | Description | Time Frame |
|---|---|---|
| Measure concentrations of serum cytokines | 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. | weekly until discharge (1-4 months post admission depending on severity) |
| Record the episodes of Pneumonia |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marc G Jeschke, MD PhD | Sunnybrook Health Sciences Centre | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ross Tilley Burn Centre - Sunnybrook HSC | Toronto | Ontario | M4N 3M5 | Canada |
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| ID | Term |
|---|---|
| D002056 | Burns |
| ID | Term |
|---|---|
| D014947 | Wounds and Injuries |
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| ID | Term |
|---|---|
| D011433 | Propranolol |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
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| Drug |
20-40 mg q6-8h |
|
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. |
| daily until discharge (1-4 months post admission depending on severity) |
| Record the episodes of sepsis | Patients are evaluated daily and the number of episodes of sepsis or bloodstream infection will be recorded | daily until discharge (1-4 months post admission depending on severity of injury) |
| Measure the levels of activated signaling proteins using protein blotting | 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. | assess at 1st operation (week 1-2 post admission on average) and 3rd operation (week 3-4 post admission on average) |
| D009930 |
| Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |