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Hypertonic Resuscitation Following Traumatic Injury

Phase 3
Terminated
Conditions
Shock, Traumatic
Interventions
Drug: 7.5% hypertonic saline/6% Dextran-70 (HSD)
Drug: 7.5% hypertonic saline (HS)
Drug: 0.9% normal saline
Registration Number
NCT00316017
Lead Sponsor
University of Washington
Brief Summary

The purpose of this study is to determine if hypertonic saline with and without dextran can improve overall survival in victims of trauma with shock.

Injury and lost blood from trauma can cause your body to be in shock (low blood pressure related to blood loss). This decreased blood flow can lead to organ damage. In order to restore the blood pressure and blood flow, the medics give fluids into the patients' veins as soon as possible. This is called "resuscitation." The resuscitation fluid most commonly used is "isotonic" or one that is the same concentration as the blood. The investigators are trying to determine if infusing a "hypertonic" fluid (or one more concentrated than the blood) can increase the blood pressure and restore blood flow more efficiently. The hypertonic fluids the investigators are using are called hypertonic saline with dextran (HSD) and hypertonic saline (no dextran). Hypertonic saline is a salt solution that is slightly more concentrated than your blood. Dextran is a sugar solution.

Detailed Description

Specific Aim: To determine if prehospital administration of 7.5% hypertonic saline /6% Dextran-70 (HSD) OR 7.5% hypertonic saline alone (HS), compared to current standard therapy with normal saline (NS), as an initial resuscitation fluid, affects survival following traumatic injury with hypovolemic shock.

Trauma is the leading cause of death among North Americans between the ages of 1 and 44 years. The majority of these deaths result from hypovolemic shock or severe brain injury. Patients in hypovolemic shock develop a state of systemic tissue ischemia then a subsequent reperfusion injury at the time of fluid resuscitation. Conventional resuscitation involves the IV administration of a large volume of isotonic or slightly hypotonic (lactated ringers, LR) solutions beginning in the prehospital setting. Although not conclusive, prior studies have suggested that alternative resuscitation with hypertonic saline (7.5%) solutions may reduce morbidity or mortality in these patients. Furthermore, hypertonic fluids may have specific advantages in the brain-injured patient, as they may aid in the rapid restoration of cerebral perfusion and prevent extravascular fluid sequestration, thereby limiting secondary brain injury. In addition, recent studies have demonstrated that hypertonicity significantly alters the activation of inflammatory cells, an effect that may reduce subsequent organ injury from ischemia-reperfusion and decrease nosocomial infection. The majority of previous clinical trials have focused on the use of HSD. The potential for 7.5% saline alone (HS) to have similar effects has not been well studied. Removal of the dextran component may enhance the anti-inflammatory effects of this solution, which could improve secondary outcomes such as acute respiratory distress syndrome (ARDS), multiple organ failure syndrome (MOFS) and rates of nosocomial infections.

This study is a randomized, double-blind, three-arm placebo controlled trial designed to evaluate the clinical outcome of trauma patients with hypovolemic shock, as manifested by prehospital hypotension. Patients will be randomized to a single 250cc IV dose of 7.5% saline in 6% Dextran-70 (HSD), 7.5% saline (HS) or normal saline as the initial fluid for prehospital resuscitation. No additional interventions will occur once the patient is admitted to the hospital. In hospital data collection will last up to 28 days.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
895
Inclusion Criteria
  • Blunt or penetrating trauma
  • Prehospital Systolic Blood Pressure (SBP) <= 70;OR
  • Prehospital SBP 71-90 AND Hear Rate (HR) ≥108
  • 15 years of age or older, or 50kg or more if age unknown
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Exclusion Criteria
  • Known or suspected pregnancy
  • Age younger than 15 or less than 50kg if age unknown
  • Ongoing prehospital cardiopulmonary resuscitation (CPR)
  • Administration of more than 2000cc crystalloid or any colloid or blood products
  • Severe hypothermia (suspected Temperature less than 28 degrees celsius)
  • Drowning or asphyxia due to hanging
  • Burns Total Body Surface Area (TBSA) more than 20%
  • Isolated penetrating injury to the head
  • Inability to obtain prehospital intravenous access
  • Time of call received at dispatch to study intervention greater than four hours
  • Known prisoners
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
17.5% hypertonic saline/6% Dextran-70 (HSD)7.5% hypertonic saline/6% Dextran-70 (HSD)
27.5% hypertonic saline (HS)7.5% hypertonic saline (HS)
30.9% normal saline0.9% normal saline
Primary Outcome Measures
NameTimeMethod
28 Day Survival28 days from time of Emergency Department (ED) arrival

The day of episode is counted as "Day 0". So for measures using a 28 day period, the maximum value is 29 (i.e. days 0 through 28).

Secondary Outcome Measures
NameTimeMethod
Adult Respiratory Distress Syndrome(ARDS)-Free Survival Through Day 2828 days from time of ED arrival

Absence of diagnosis of Adult Respiratory Distress Syndrome and alive through day 28

Worst Multiple Organ Dysfunction Score (MODS) Mean Through Day 2828 days from time of ED arrival

Multiple Organ Dysfunction Score is described as:

Six organ systems were chosen, and a score of 0-4 allotted for each organ according to function (0 being normal function through to 4 for most severe dysfunction) with a maximum score of 24. The worst score based on available data (missing values were assumed normal) in each 24-hour period is taken for calculation of the aggregate score.

Presence of Nosocomial Infection Through Day 28Within 28 days of injury, while hospitalized

Includes one or more nosocomial infections from the following list: pneumonia, blood stream infection, urinary tract infection and wound infection

Packed Red Blood Cells (PRBC) First 24 HoursFirst 24 hours from the time of 911 call

The numbers of units of packed red blood cells transfused in the first 24 hours

Total Fluids First 24 HoursFirst 24 hours from the time of of 911 call

The total amount of IV fluids given in the pre-hospital setting and the hospital setting in the first 24 hours following the time of 911 call

Ventilator-free Days Through Day 28Duration of hospital stay through day 28

The number of days beginning with the day of 911 call counted as "Day O" through day 28 that the patient did not require mechanical ventilation

Days Alive Out of the Intensive Care Unit (ICU) Through Day 28First 28 days from the time of 911 call

The number of days the patient is alive and not being cared for in the intensive care unit

Days Alive Out of the Hospital Through Day 28First 28 days from the time of 911 call

The number of days the patient is alive and no longer an inpatient in the hospital through day 28

Survival at Hospital DischargeDuration of hospital stay through to discharge

Alive at the time of discharge from the Level One or Two trauma hospital. This did not include disposition from rehabilitation facilities.

Zero Units PRBC in First 24 HoursFrom the time dispatch received the 911 call to the end of the first 24 hours

This is the total number of subjects who received no blood products in the first 24 hours from the time of the 911 call.

Zero Units PRBC and Died in Field or Emergency Department (ED)From the time dispatch received 911 call to the time of death in the field or ED

This is the total number of subjects who died in the field or the ED from the set of subjects who received no blood products.

Zero Units PRBC and Died Within 6 Hours of Admission to the HospitalThe first 6 hours from the time of admission to the hospital

This is the total number of subjects who died within the first 6 hours from the time of admission to the hospital among the patients who received no blood products.

Zero Units PRBC and Died Within 28 Days From the Time of the 911 CallFrom the time dispatch received the 911 call to 28 days

This is the total number of subjects who died within 28 days from the time of the 911 call among the patients who received no units of PRBC.

1-9 Units PRBC in First 24 HoursFrom the time dispatch received the 911 call to the end of the first 24 hours

This is the total number of subjects who received 1 to 9 units of packed red blood cells (PRBC) in the first 24 hours from the time of the 911 call.

1-9 Units PRBC and Died in Field or EDFrom the time dispatch received 911 call to the time of death in the field or ED

This is the total number of subjects who received 1 to 9 units of packed red blood cells (PRBC) among the patients who died in the field or the ED.

1-9 Units PRBC and Died Within 6 Hours of Admission to the HospitalThe first 6 hours from the time of admission to the hospital

This is the total number of subjects who died within the first 6 hours from the time of admission to the hospital among the patients who received 1 to 9 units of packed red blood cells (PRBC).

1-9 Units PRBC and Died Within 28 Days From the Time of the 911 CallFrom the time dispatch received the 911 call to 28 days

This is the total number of subjects who died within 28 days from the time of the 911 call among the patients who received 1 to 9 units of packed red blood cells (PRBC).

Greater Than 10 Units PRBC in First 24 HoursFrom the time dispatch received the 911 call to the end of the first 24 hours

This is the total number of subjects who received greater than 10 units of packed red blood cells (PRBC) in the first 24 hours from the time of the 911 call.

Greater Than 10 Units PRBC and Died in Field or EDFrom the time dispatch received 911 call to the time of death in the field or ED

This is the total number of subjects who died in the field or the ED among the patients who received greater than 10 units of packed red blood cells (PRBC).

Greater Than 10 Units PRBC and Died Within 6 Hours of Admission to the HospitalThe first 6 hours from the time of admission to the hospital

This is the total number of subjects who died within the first 6 hours from the time of admission to the hospital among the patients who received greater than 10 units of packed red blood cells (PRBC).

Greater Than 10 Units PRBC and Died Within 28 Days From the Time of the 911 CallFrom the time dispatch received the 911 call to 28 days

This is the total number of subjects who died within 28 days from the time of the 911 call among the patients who received greater than 10 units of packed red blood cells (PRBC).

Trial Locations

Locations (10)

Iowa Resuscitation Network, University of Iowa Carver College of Medicine

🇺🇸

Iowa City, Iowa, United States

University of Ottawa/University of British Columbia Collaborative RCC, Ottawa Health Research Institute

🇨🇦

Ottawa, Ontario, Canada

Portland Resuscitation Outcomes Consortium, Oregon Health & Sciences University

🇺🇸

Portland, Oregon, United States

Alabama Resuscitaion Center, University of Alabama

🇺🇸

Birmingham, Alabama, United States

UCSD-San Diego Resuscitation Research Center

🇺🇸

San Diego, California, United States

Seattle-King County Center For Resuscitation Research, University of Washington

🇺🇸

Seattle, Washington, United States

Dallas Center for Resuscitation Research, University of Texas Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

Toronto Regional Resuscitation Research Out-of-Hospital Network, University of Toronto

🇨🇦

Toronto, Ontario, Canada

Milwaukee Resuscitation Network, Medical College of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

The Pittsburgh Resuscitation Network, University of Pittsburgh

🇺🇸

Pittsburgh, Pennsylvania, United States

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