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Effect of Remote Ischemic Conditioning on Trauma Patients With Hemorrhagic Shock

Not Applicable
Completed
Conditions
Hemorrhagic Shock
Interventions
Device: Pneumatic tourniquet
Registration Number
NCT02071290
Lead Sponsor
Unity Health Toronto
Brief Summary

The purpose of the study is to evaluate whether remote ischemic conditioning is a safe and effective intervention to prevent the development of inflammation and coagulopathy in trauma patients with hemorrhagic shock.

Detailed Description

Dysfunction of vital organs is one of the major reasons why trauma victims die after sustaining a major injury, even though the organs themselves may not have been directly injured. The inability to clot blood as a result of inflammation further contributes to complications in a majority of these patients. One intervention proposed to protect against impaired organ function is called "Remote Ischemic Conditioning", wherein application of intermittent occlusion and release of blood flow to the arm by sequentially inflating and deflating a blood pressure cuff can protect against the development of distant organ injury and inflammation following a severe traumatic event. In a pilot study, we will investigate the effects of remote ischemic conditioning in trauma patients with hemorrhagic shock, with a view to evaluate its effects on the immune system and coagulation profiles, both of which are known to be deranged in these patients. These studies will potentially benefit patients and will serve as a proof of principle for the use of remote ischemic conditioning in the trauma setting.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
50
Inclusion Criteria
  • Age ≥16 years of age or estimated weight ≥50kgs if age is unknown;
  • Victim of blunt or penetrating trauma
  • Hemorrhagic shock defined as:
  • One or more episodes of systolic blood pressure ≤90mmHg at any time prior to enrollment into the study;
  • An identified source of blood loss (abdomen, chest, pelvis/retroperitoneum, extremities, external) or
  • Blood products (RBC, Platelets, Plasma, etc.) has been ordered to the trauma room.
  • Admitted to St. Michael's Hospital directly from the scene of injury within 3 hours of the injury
  • Application and completion of Remote Ischemic Conditioning (RIC) within 4 hours of the injury
Exclusion Criteria
  • Pregnancy
  • Non-hemorrhagic shock (i.e. tension pneumothorax, cardiac tamponade, spinal shock, etc.)
  • Major burns > 20% total body surface area
  • Fracture of both lower extremities (i.e. traumatic amputation, fractures)
  • Absence of vital signs prior to admission, ongoing CPR, possibly dead on admission or not expected to survive beyond a few hours.
  • Injury in both legs (traumatic amputation, fractures, etc.)
  • Patients with a systolic blood pressure above 200mmHg
  • Patients treated with anticoagulants, antiplatelet therapy (Warfarin, Aspirin), steroids or with a known bleeding disorder or known abnormality of blood flow to the limb (if known)
  • Patients with osteoporosis or other bone disorders, peripheral nerve injury, abnormal nerve supply, peripheral neuropathy (if known) or preexisting traumatic injury to the limb.
  • Morbid obesity (largest cuff size won't fit)
  • If RIC is done clinically before research protocol begins.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Sham Remote Ischemic ConditioningPneumatic tourniquetSham inflation of pneumatic tourniquet pressure cuff at 0 mmHg on the thigh for 5 minutes and release for 5 minutes (repeated for 4 cycles) applied to trauma patients on arrival to hospital
Remote Ischemic ConditioningPneumatic tourniquetInflation of pneumatic tourniquet pressure cuff at 250mmHg on the thigh for 5 minutes and release for 5 minutes (repeated for 4 cycles) applied to trauma patients on arrival to hospital
Primary Outcome Measures
NameTimeMethod
Neutrophil Oxidative Burst Activity0 (Admission), 1, 3, and 24 hours after intervention

Change in neutrophil oxidative burst activity (dihydrorhodamine, DHR) over 24 hours from admission. Measured by flow cytometry using whole blood samples.

Neutrophil Oxidative Burst Activity (PMA Stimulated)0 (Admission), 1, 3, and 24 hours after intervention

Change in PMA stimulated neutrophil oxidative burst activity (dihydrorhodamine, DHR) over 24 hours. Measured by flow cytometry using whole blood samples.

Neutrophil Adhesion Molecule Expression (CD11b)0 (Admission), 1, 3, 24 hours after intervention

Change in neutrophil adhesion molecule (CD11b) expression over 24 hours from admission. Measured by flow cytometry using whole blood samples.

Neutrophil Adhesion Molecule Expression (CD62L)0 (Admission), 1, 3, and 24 hours after intervention

Change in neutrophil adhesion molecule (CD62L) expression over 24 hours from admission. Measured by flow cytometry using whole blood samples.

Endothelial Injury (Heparan Sulfate)0 (Admission), 1, 3, and 24 hours after intervention

Change in plasma levels of endothelial injury marker Heparan Sulfate over 24 hours from Admission

Endothelial Injury (Hyaluronan)0 (Admission), 1, 3, 24 hours

Change in plasma levels of endothelial injury marker Hyaluronan over 24 hours from Admission

Plasma TNF-α0 (Admission), 1, 3, and 24 hours after intervention

Change in plasma levels of inflammatory mediator TNF-α over 24 hours from Admission

Plasma IL-80 (Admission), 1, 3, 24 hours

Change in plasma levels of inflammatory mediator IL-8 over 24 hours from Admission

Endothelial Injury (Syndecan-1)0 (Admission), 1, 3, and 24 hours after intervention

Change in plasma levels of endothelial injury marker Syndecan-1 over 24 hours from Admission

Plasma IL-60 (Admission), 1, 3, 24 hours

Change in plasma levels of inflammatory mediator IL-6 over 24 hours from Admission

ROTEM EXTEM CFT0 (Admission), 1, 3, 24 hours

Change in ROTEM parameter Clot Formation Time (CFT) over 24 hours from Admission

Plasma Fibrinogen0 (Admission), 1, 3, 24 hours

Change in plasma fibrinogen levels over 24 hours from Admission

Plasma IL-100 (Admission), 1, 3, 24 hours

Change in plasma levels of anti-inflammatory mediator IL-10 over 24 hours from Admission

ROTEM EXTEM CT0 (Admission), 1, 3, 24 hours

Change in ROTEM parameter Clotting Time (CT) over 24 hours from Admission

ROTEM EXTEM A100 (Admission), 1, 3, 24 hours

Change in ROTEM parameter A10 over 24 hours from Admission

ROTEM EXTEM Alpha Angle0 (Admission), 1, 3, 24 hours

Change in ROTEM parameter Alpha Angle over 24 hours from Admission

ROTEM EXTEM ML0 (Admission), 1, 3, 24 hours

Change in ROTEM parameter maximum lysis (ML) over 24 hours from Admission

Plasma D-Dimer0 (Admission), 1, 3, 24 hours

Change in plasma D-Dimer levels over 24 hours from Admission

Plasma Protein C0 (Admission), 1, 3, 24 hours

Change in plasma Protein C levels over 24 hours from Admission

Secondary Outcome Measures
NameTimeMethod
28 Day Mortalityup to 28 days or discharge

Secondary clinical outcomes

24 Hour Mortalityup to 28 days or discharge

Secondary clinical outcomes

Ventilator Free Daysup to 28 days or discharge

Secondary clinical outcomes

ICU Free Daysup to 28 days or discharge

Secondary clinical outcomes

Hospital Free Daysup to 28 days or discharge

Secondary clinical outcomes

Nosocomial Infectionsup to 28 days or discharge

Secondary clinical outcomes

Trial Locations

Locations (1)

St. Michael's Hospital

🇨🇦

Toronto, Ontario, Canada

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