Hemmorhagic Shock During Air Medical Transport
Conditions
Keywords
hemmorhagic shock, plasma, air medical transport, randomized, multicenter
Brief summary
To determine the effect of the prehospital infusion during air transport of 2 units of AB plasma on 30 day mortality in patients with hemorrhagic shock as compared to conventional care.
Detailed description
Background: Although advances in the care of the severely injured patient have occurred over the last decade, patients continue to be plagued with uncontrolled hemorrhage resulting in significant early mortality and the development of multiple organ failure and associated complications. A primary driving force for this unbridled hemorrhage has been shown to be the early coagulopathy which complicates severe injury. Increasing evidence suggests that blood component transfusion protocols that address this early coagulopathy, once a patient arrives at a trauma center, are associated with lower mortality and a reduction in blood component transfusion requirements. Prehospital interventions which quell this early coagulopathy in an earlier setting have the potential to minimize or even prevent this vicious hemorrhagic cascade, further lowering blood component transfusion requirements and reducing the resultant morbid sequelae which complicates severe injury. Objective/Hypothesis: The primary hypothesis will be that prehospital infusion of plasma during air medical transport in patients with hemorrhagic shock will lower 30 day mortality. The secondary hypotheses include that prehospital infusion of plasma will reduce 24 hour blood transfusion, multiple organ failure, nosocomial infection, and acute lung injury, reduce or prevent the early coagulopathy as demonstrated by improving presenting coagulation and thromboelastography parameters, and reduce the early inflammatory cytokine response, thrombomodulin and increase protein C levels.
Interventions
BIOLOGICALinfusion of 2 units of plasma
infusion of 2 units of plasma
Sponsors
University of Texas
University of Louisville
Vanderbilt University
Case Western Reserve University
The University of Tennessee, Knoxville
JPS Health Network
The Methodist Hospital Research Institute
Jason Sperry
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
Hemorrhagic shock not responsive to crystalloid infusion -
Exclusion criteria
Isolated Fall, Cervical cord injury, prisoner, pregnant patient, traumatic arrest \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Our Primary Outcome for the Proposal Will be 30 Day Mortality | 30 days | All cause 30 day mortality using imputation for those with missing 30 day mortality. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Twenty Four-Hour Blood Transfusion Requirements | at twenty four hours | 24-hour blood transfusion requirements will be determined by recording blood volume (mls) and number of Units transfused from the time of trauma bay arrival or upon completion of pre-hospital initiated plasma infusion. For survival bias analysis, volumes and number of blood transfusion Units received at 3, 6, 12, and 18 hours will also be recorded. |
| In-hospital Mortality | during hospitalization | In hospital mortality will be prospectively recorded from the time of trauma bay arrival. Over the first 24 hours we will document and record the time of death in hours, while after the 24 hour time point, we will document and record the time of death in days from arrival. We suspect that patients in hemorrhagic shock will have a significant percentage of mortality occurring in the first 24 hour period. |
| Multiple Organ Failure | during hospitalization | Organ dysfunction will be evaluated via a well-validated scoring system referred to as the Multiple Organ Dysfunction Score (MODScore). Patients who are never admitted to the ICU or those with a length of ICU stay of less than 48 hours will be considered to have a MODScore of 0. A summary of the MODScore may be calculated by summing the worst scores of each of the individual systems over the course of the ICU stay (Table 1). A summary MODScore \> 5 will be classified as multiple organ failure (MOF). Scores will be determined daily up until post injury day 28 or ICU discharge. |
| Acute Lung Injury (ALI) and Transfusion Related Acute Lung Injury (TRALI) | hospitalization | Development of ALI will be assessed which includes: 1) bilateral infiltrates on chest x-ray, 2) a capillary wedge pressure \< 18mmHg, and 3) Pao2/Fio2 ratio \< 300 via blood gas analysis. In those patients without a Swan-Ganz catheter to determine capillary wedge pressure, the absence of signs of, or clinical concern, for elevated left sided atrial pressures will be used for the diagnosis. All patients who remain intubated beyond the first 24 hours post-injury will be evaluated using blood gas analysis and chest x-ray evaluation. Those patients who remain intubated at 48 hours through 7 days will be reevaluated for this outcome at these time points. The diagnosis of TRALI will be defined as when ALI occurs within the first 6 hours from arrival at the trauma center as it is clinically defined. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Plasma infusion of 2 units of plasma
infusion of 2 units of plasma: infusion of 2 units of plasma | 230 |
| Standard Air Medical Care control group | 271 |
| Total | 501 |
Baseline characteristics
| Characteristic | Plasma | Total | Standard Air Medical Care |
|---|---|---|---|
| Age, Continuous | 44 years | 45 years | 46 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 43 Participants | 29 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 22 Participants | 13 Participants |
| Race (NIH/OMB) White | 207 Participants | 435 Participants | 228 Participants |
| Region of Enrollment United States | 230 Participants | 501 Participants | 271 Participants |
| Sex: Female, Male Female | 66 Participants | 137 Participants | 71 Participants |
| Sex: Female, Male Male | 164 Participants | 364 Participants | 200 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 53 / 220 | 89 / 261 |
| other Total, other adverse events | 5 / 220 | 2 / 261 |
| serious Total, serious adverse events | 1 / 220 | 2 / 261 |
Outcome results
Primary
Our Primary Outcome for the Proposal Will be 30 Day Mortality
All cause 30 day mortality using imputation for those with missing 30 day mortality.
Time frame: 30 days
Population: 10 patients in each arm were lost to follow-up for 30-day mortality and 22 patients total, 8 in the plasma arm and 12 in the standard care arm withdrew consent and 1 patient in each arm was a prisoner and could not be included in the analysis cohort. We compared 30-day mortality using a two sided pooled z test with continuity correction.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Plasma | Our Primary Outcome for the Proposal Will be 30 Day Mortality | 53 Participants |
| Standard Air Medical Care | Our Primary Outcome for the Proposal Will be 30 Day Mortality | 89 Participants |
Secondary
Acute Lung Injury (ALI) and Transfusion Related Acute Lung Injury (TRALI)
Development of ALI will be assessed which includes: 1) bilateral infiltrates on chest x-ray, 2) a capillary wedge pressure \< 18mmHg, and 3) Pao2/Fio2 ratio \< 300 via blood gas analysis. In those patients without a Swan-Ganz catheter to determine capillary wedge pressure, the absence of signs of, or clinical concern, for elevated left sided atrial pressures will be used for the diagnosis. All patients who remain intubated beyond the first 24 hours post-injury will be evaluated using blood gas analysis and chest x-ray evaluation. Those patients who remain intubated at 48 hours through 7 days will be reevaluated for this outcome at these time points. The diagnosis of TRALI will be defined as when ALI occurs within the first 6 hours from arrival at the trauma center as it is clinically defined.
Time frame: hospitalization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Plasma | Acute Lung Injury (ALI) and Transfusion Related Acute Lung Injury (TRALI) | 48 Participants |
| Standard Air Medical Care | Acute Lung Injury (ALI) and Transfusion Related Acute Lung Injury (TRALI) | 50 Participants |
Secondary
In-hospital Mortality
In hospital mortality will be prospectively recorded from the time of trauma bay arrival. Over the first 24 hours we will document and record the time of death in hours, while after the 24 hour time point, we will document and record the time of death in days from arrival. We suspect that patients in hemorrhagic shock will have a significant percentage of mortality occurring in the first 24 hour period.
Time frame: during hospitalization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Plasma | In-hospital Mortality | 51 Participants |
| Standard Air Medical Care | In-hospital Mortality | 88 Participants |
Secondary
Multiple Organ Failure
Organ dysfunction will be evaluated via a well-validated scoring system referred to as the Multiple Organ Dysfunction Score (MODScore). Patients who are never admitted to the ICU or those with a length of ICU stay of less than 48 hours will be considered to have a MODScore of 0. A summary of the MODScore may be calculated by summing the worst scores of each of the individual systems over the course of the ICU stay (Table 1). A summary MODScore \> 5 will be classified as multiple organ failure (MOF). Scores will be determined daily up until post injury day 28 or ICU discharge.
Time frame: during hospitalization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Plasma | Multiple Organ Failure | 145 Participants |
| Standard Air Medical Care | Multiple Organ Failure | 156 Participants |
Secondary
Twenty Four-Hour Blood Transfusion Requirements
24-hour blood transfusion requirements will be determined by recording blood volume (mls) and number of Units transfused from the time of trauma bay arrival or upon completion of pre-hospital initiated plasma infusion. For survival bias analysis, volumes and number of blood transfusion Units received at 3, 6, 12, and 18 hours will also be recorded.
Time frame: at twenty four hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Plasma | Twenty Four-Hour Blood Transfusion Requirements | 3 units of blood |
| Standard Air Medical Care | Twenty Four-Hour Blood Transfusion Requirements | 4 units of blood |