Hemorrhagic Shock Clinical Trial
Official title:
Field Trial of Hypotensive Resuscitation Versus Standard Resuscitation in Patients With Hemorrhagic Shock After Trauma: A Pilot Trial
Primary Aim: To determine the feasibility and safety of hypotensive resuscitation for the
early treatment of patients with traumatic shock compared to standard fluid resuscitation.
Primary Hypotheses: The null hypothesis regarding feasibility is that hypotensive
resuscitation will result in the same volume of early crystalloid (normal saline) fluid
administration compared to standard crystalloid resuscitation. The null hypothesis regarding
safety is that hypotensive resuscitation will result in the same percent of patients
surviving to 24 hours after 911 call received at dispatch compared to standard fluid
resuscitation. Early resuscitation is defined as all fluid given until 2 hours after arrival
in the Emergency Department or until hemorrhage control is achieved in the hospital,
whichever occurs earlier.
1. Overview This multi-center pilot trial is designed to determine the feasibility and
safety of hypotensive resuscitation for the early resuscitation of patients with
traumatic shock compared to standard fluid resuscitation. Blunt and penetrating trauma
patients with a prehospital systolic blood pressure (SBP) ≤ 90 mmHg will be eligible. In
the hypotensive resuscitation group, an intravenous line (IV) will be placed and a
radial pulse will be palpated. If the radial pulse is present or the SBP is greater than
or equal to 70, a 250 ml bag of normal saline will be hung and maintained at a keep the
vein open rate only. If the radial pulse is absent, the 250 ml of normal saline will be
given as a bolus. This process using small bags of fluid will be repeated until a radial
pulse is palpable or until 2 hours after Emergency Department (ED) arrival or until
hemorrhage control has been achieved. The decision to utilize a SBP versus a radial
pulse will be made a priori. Patients in the standard fluid resuscitation group will
have an IV placed and a 1000 ml bag of normal saline (NS) will be hung. Fluid will be
given as rapidly as possible and continued until hospital arrival. If the prehospital or
hospital fluid resuscitation exceeds 2 liters, it will be stopped when the SBP exceeds
110 mmHg and restarted as necessary to maintain a goal SBP of 110 mmHg. This
randomization scheme will be continued for 2 hours after hospital arrival or until
hemorrhage control is achieved whichever occurs first. The randomization will not affect
the indications for the administration of blood products but we hypothesize that less
blood products and total fluid will be given in the experimental group due to avoidance
of the pop-the-clot phenomenon, less hemodilution and less coagulopathy.
Patients who experience ground level falls are characterized as having low injury
severity scores. (70) Patients with suspected ground level falls will be excluded in an
effort to focus enrollment on the more severely injured patients at risk for trauma
related hemorrhagic shock. Patients with severe traumatic brain injury will be excluded
due to lack of equipoise. In observational studies (1-5) a relationship between
hypotension and poor neurologic outcomes has been observed and EMS personnel as well as
researchers at this time believe that it is unethical to withhold resuscitation fluid
from patients with traumatic brain injury. Patients with suspected spinal cord injury
will also be excluded based on evidence that indicates they are at risk for
cardiovascular failure due to hemodynamic compromise correlated with the presence of
neurogenic hypotension at the time of hospital admission. (69) All enrolled patients
will be retrospectively screened to determine if they had evidence of severe traumatic
brain injury with GCS≤8 or spinal cord injury at the time of enrollment.
Screening information will be obtained for all potentially eligible patients who meet
all inclusion criteria. Screening will also document whether each exclusion criterion is
met. The rate at which screened patients were enrolled and later found to have met one
or more of the exclusion criteria will be assessed to determine if the inclusion and
exclusion criteria need to be adjusted to avoid enrollment of these patients for future
studies. These patients will also be assessed to determine if enrollment in the protocol
potentially harmed these patients.
The study will be a two arm, randomized interventional trial comparing the two
resuscitation strategies. Due to obvious differences in the treatment of enrolled
patients, the study will not be blinded. Nevertheless, treatment bags will be packaged
in containers such that providers will not be able to identify whether treatment
containers house 1000 ml bags or 250 ml bags until the treatment containers are opened.
The patient will be considered randomized at the time a study bag is opened regardless
of whether any fluid is given or not. Hospitals will be provided with 250 ml bags of NS
to continue treatment of those patients randomized to the hypotensive resuscitation arm.
The primary outcomes of the study will be volume of prehospital and in-hospital fluid
administered from time of injury until 2 hours into the hospital stay or until
hemorrhage is controlled to test feasibility and 24 hour survival for the safety
hypothesis. Secondary outcomes will include measures of protocol adherence, 24 hour
fluid volume, 24 hour blood product requirements, ventilator days, hospital length of
stay, intensive care unit (ICU) length of stay, admission base deficit, development of
renal failure, admission hematocrit and admission coagulation parameters. The primary
goals of this pilot study will be to determine if the described model will result in
different early fluid volumes being delivered to the two groups and to determine if
these differing volumes impact mortality. If this pilot study shows that hypotensive
resuscitation is feasible and safe, a larger trial will be planned to determine the
efficacy of hypotensive fluid resuscitation.
This study will be conducted by the Resuscitation Outcomes Consortium (ROC) which is a
collaboration of 7 regional sites in the United States and Canada and a Data
Coordinating Center. This consortium is charged with the task of conducting clinical
trials in patients with life threatening trauma and cardiac arrest. The following ROC
sites have committed to participating in this trial: Alabama, Dallas, Milwaukee, Ottawa,
Pittsburgh, Portland, and Vancouver.
2. Specific Aims and Hypotheses Specific Aim 1: To investigate whether early crystalloid
(normal saline) resuscitation volume can be reduced for trauma patients with hemorrhagic
shock who receive hypotensive resuscitation versus those who receive standard early
resuscitation (feasibility) and whether there are differences in 24-hour survival
between the groups (safety).
Primary Hypotheses: The null hypothesis is that patients who receive hypotensive
resuscitation and patients who receive standard resuscitation will have the same volume of
early crystalloid (normal saline) resuscitation administered and will have the same 24-hour
survival from 911 call received at dispatch time.
Specific Aim 2: To assess protocol adherence and differences in morbidity and adverse events
for hypotensive versus standard resuscitation.
Secondary Hypotheses: The null hypotheses are that protocol adherence is low and that
hypotensive resuscitation versus standard resuscitation will result in the same amount of
total fluid volume and total blood product requirements within 24 hours from 911 call
received at dispatch, the same base deficit, hematocrit and coagulation parameters on
admission to the ED, number of days on a ventilator, duration of hospital stay, ICU length of
stay, and incidence of renal failure.
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