Effect of Remote Ischemic Conditioning on Trauma Patients With Hemorrhagic Shock

Effect of Remote Ischemic Conditioning on Neutrophil Function and the Immune-Inflammatory and Coagulation Profiles in Trauma Patients With Hemorrhagic Shock

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.

Study Overview

• Status: Completed
• Conditions: Hemorrhagic Shock
• Intervention / Treatment: Device: Pneumatic tourniquet

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B1W8
      • St. Michael's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Sham Remote Ischemic Conditioning; Sham 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	Device: Pneumatic tourniquet; Four cycles of brief occlusion of bloodflow to the thigh (5 minutes) followed by reperfusion (5 minutes) using a pneumatic tourniquet Remote Ischemic Conditioning
Experimental: Remote Ischemic Conditioning; Inflation 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	Device: Pneumatic tourniquet; Four cycles of brief occlusion of bloodflow to the thigh (5 minutes) followed by reperfusion (5 minutes) using a pneumatic tourniquet Remote Ischemic Conditioning

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutrophil Adhesion Molecule Expression (CD11b)	Change in neutrophil adhesion molecule (CD11b) expression over 24 hours from admission. Measured by flow cytometry using whole blood samples.	0 (Admission), 1, 3, 24 hours after intervention
Endothelial Injury (Hyaluronan)	Change in plasma levels of endothelial injury marker Hyaluronan over 24 hours from Admission	0 (Admission), 1, 3, 24 hours
Plasma IL-6	Change in plasma levels of inflammatory mediator IL-6 over 24 hours from Admission	0 (Admission), 1, 3, 24 hours
Plasma IL-8	Change in plasma levels of inflammatory mediator IL-8 over 24 hours from Admission	0 (Admission), 1, 3, 24 hours
Plasma IL-10	Change in plasma levels of anti-inflammatory mediator IL-10 over 24 hours from Admission	0 (Admission), 1, 3, 24 hours
ROTEM EXTEM CT	Change in ROTEM parameter Clotting Time (CT) over 24 hours from Admission	0 (Admission), 1, 3, 24 hours
ROTEM EXTEM CFT	Change in ROTEM parameter Clot Formation Time (CFT) over 24 hours from Admission	0 (Admission), 1, 3, 24 hours
ROTEM EXTEM A10	Change in ROTEM parameter A10 over 24 hours from Admission	0 (Admission), 1, 3, 24 hours
ROTEM EXTEM Alpha Angle	Change in ROTEM parameter Alpha Angle over 24 hours from Admission	0 (Admission), 1, 3, 24 hours
ROTEM EXTEM ML	Change in ROTEM parameter maximum lysis (ML) over 24 hours from Admission	0 (Admission), 1, 3, 24 hours
Plasma D-Dimer	Change in plasma D-Dimer levels over 24 hours from Admission	0 (Admission), 1, 3, 24 hours
Plasma Protein C	Change in plasma Protein C levels over 24 hours from Admission	0 (Admission), 1, 3, 24 hours
Plasma Fibrinogen	Change in plasma fibrinogen levels over 24 hours from Admission	0 (Admission), 1, 3, 24 hours
Neutrophil Oxidative Burst Activity	Change in neutrophil oxidative burst activity (dihydrorhodamine, DHR) over 24 hours from admission. Measured by flow cytometry using whole blood samples.	0 (Admission), 1, 3, and 24 hours after intervention
Neutrophil Oxidative Burst Activity (PMA Stimulated)	Change in PMA stimulated neutrophil oxidative burst activity (dihydrorhodamine, DHR) over 24 hours. Measured by flow cytometry using whole blood samples.	0 (Admission), 1, 3, and 24 hours after intervention
Neutrophil Adhesion Molecule Expression (CD62L)	Change in neutrophil adhesion molecule (CD62L) expression over 24 hours from admission. Measured by flow cytometry using whole blood samples.	0 (Admission), 1, 3, and 24 hours after intervention
Endothelial Injury (Heparan Sulfate)	Change in plasma levels of endothelial injury marker Heparan Sulfate over 24 hours from Admission	0 (Admission), 1, 3, and 24 hours after intervention
Endothelial Injury (Syndecan-1)	Change in plasma levels of endothelial injury marker Syndecan-1 over 24 hours from Admission	0 (Admission), 1, 3, and 24 hours after intervention
Plasma TNF-α	Change in plasma levels of inflammatory mediator TNF-α over 24 hours from Admission	0 (Admission), 1, 3, and 24 hours after intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilator Free Days	Secondary clinical outcomes	up to 28 days or discharge
ICU Free Days	Secondary clinical outcomes	up to 28 days or discharge
Hospital Free Days	Secondary clinical outcomes	up to 28 days or discharge
Nosocomial Infections	Secondary clinical outcomes	up to 28 days or discharge
24 Hour Mortality	Secondary clinical outcomes	up to 28 days or discharge
28 Day Mortality	Secondary clinical outcomes	up to 28 days or discharge

Collaborators and Investigators

• Sponsor: Unity Health Toronto
• Investigators: Principal Investigator: Ori D Rotstein, MD, Unity Health Toronto

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2015
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: February 18, 2014
• First Submitted That Met QC Criteria: February 24, 2014
• First Posted (Estimated): February 25, 2014

Study Record Updates

• Last Update Posted (Actual): June 7, 2023
• Last Update Submitted That Met QC Criteria: May 10, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Remote Ischemic Conditioning; Hemorrhagic Shock
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Shock; Shock, Hemorrhagic
• Other Study ID Numbers: SMH-RIC-01