Hypertonic Saline FAQ's

How may people experience Trauma?

Trauma is the leading cause of death among Americans between the ages of 1 and 44 years. Blunt trauma includes motor vehicle collisions, pedestrians and bicyclists struck by cars, falls, and assaults with blunt objects. Penetrating trauma includes bullet or stab wounds. The majority of deaths after trauma results from hypovolemic shock (low blood pressure from blood loss) and severe brain injury. Patients in hypovolemic shock develop a state of systemic tissue ischemia (decreased oxygen and blood flow to the tissues) with a subsequent reperfusion injury at the time of fluid resuscitation. 

What's the immediate treatment for a trauma?

Conventional resuscitation of these patients involves the intravenous administration of a large volume of isotonic or slightly hypotonic (lactated ringers) solutions beginning in the pre-hospital environment. Previous studies have suggested that an alternative resuscitation fluid, hypertonic saline with dextran (HSD) may reduce mortality in these patients; but these have not been conclusive. Furthermore, HSD may have specific advantages in the brain-injured patient, as it may aid in the rapid restoration of cerebral perfusion, prevent extravascular fluid sequestration, and thus, limit secondary brain injury. In addition, recent studies have demonstrated that hypertonicity significantly alters the activation of inflammatory cells, which may result in a reduction in subsequent organ injury following whole body ischemia/reperfusion and ultimately decrease nosocomial infection rates.

This study is designed to evaluate the clinical outcome of patients following blunt traumatic injury with hypovolemic shock, who receive lactated ringers (LR) vs. HSD resuscitation. In addition, we plan to focus specifically on neurologic outcome in the subset of patients with brain injury and on the effect of HSD resuscitation on the responsiveness of inflammatory cells.

How can the survival rate be improved?

Most deaths after trauma result from blood loss or severe brain injury thus we need better therapies to support patients with severe blood loss and reduce injury to the brain. HSD or HS has the potential to help in both these circumstances, but more study is needed. Patients that survive their initial injury are also at risk to develop excessive activation of their immune system than can result in injury to their organs, most commonly the lungs. This is called Acute Respiratory Distress Syndrome (ARDS). HSD has been shown to alter the inflammatory response early after injury and thus may reduce the risk of ARDS as well.

Why are we doing another study?

HSD has been successfully used on humans in Europe and in small clinical trials in the US. In fact a hypertonic saline with dextran study was completed in July of 2005. The study was conducted here in King and Snohomish County. There were 209 patients enrolled in the study and while the numbers were too small to show any impact in mortality and there was no difference in the development of adult respiratory disease syndrome (ARDS) between those who did get HSD and those who did not. HSD did help those patients who were severally injured and required 10 or more units of blood in the first 24 hours after their injury. The information obtained in this Seattle trial was used in the design of a large-scale, North American hypertonic saline study. This hypertonic saline study of severely injured trauma victims in the United States and Canada, will be conducted by the Resuscitation Outcomes Consortium (ROC). The ROC is a research group that involves 11 different communities in the United States and Canada, including University of Washington physicians at Harborview Medical Center. Over 5000 trauma patients will be enrolled in the ROC study; approximately 500 patients will be enrolled here in Seattle and King County. 

How will the Resuscitation Outcomes Consortium study at the University of Washington be conducted?

Trauma victims with low blood pressures will be identified by pre-hospital providers (paramedics and flight nurses) and randomized either to receive 250 cc HSD, 250 cc HS, or 250 cc of isotonic solution (normal saline). Normal Saline is the current standard of care. The ambulances and helicopters will be supplied with the IV bags from the pharmacy.

The US Food and Drug Administration and the National Institutes of Health approved this study. The Human Subject Ethics Review Board of the University of Washington is currently reviewing the research proposal and the study will not start until it is approved by the committee. 

Which trauma victims will be treated with HSD/HS?

This will be a randomized study. One third of the patients in the study will receive hypertonic saline with dextran, one third will receive hypertonic saline without dextran and one third will receive normal saline. Neither the victim nor the physician or paramedic will know whether the hypertonic saline or the normal saline was given. Randomization is necessary to assure that research findings do not occur from bias or chance. 

Who will be included in the study?

• The trauma victims must be at least 15 years old. 
• Must have had a blunt, penetrating or a traumatic brain injury.
• Have hypovolemic shock defined as a systolic blood pressure less than 70mmHg or between 70 and 90mmHg with tachycardia (HR >108 beats/ min) 
• Have an altered mental status (unconscious) 
• The participant must be transported directly to Harborview Medical Center either by ambulance or helicopter.  

Are there potential risks in the study?

• HSD administration has been tested in eight previous clinical trials (over 500 subjects) with no adverse effects reported.

Theoretical (but not reported) risks associated with HSD therapy:

• Anti-platelet effect of dextran could potentially impair coagulation. The reported effects of dextran on coagulation occur with significantly higher doses than proposed in this study.
• Allergic reaction to dextran.
• Seizure activity from severe hypernatremia (Serum sodium = 170 meq/L). Levels this high are rarely seen.

Will a trauma victim's records be kept confidential?

Yes, information gathered in the process of this study will remain confidential by the University of Washington research team, the King County area paramedics, the National Institutes of Health (NIH) and the Food and Drug Administration (FDA). The NIH is funding this study, along with the Department of Defense and other agencies here in the United States and Canada. There is also a Federal Certificate of Confidentiality to protect the data from this study. 

How are trauma victims and their families informed about this research?

Obtaining an “informed consent” from victims of serious trauma is difficult as the participant is often unconscious and the family is not immediately available. To allow researchers to possibly improve the survival rate of individuals suffering from life-threatening injury, the US Food and Drug Administration (FDA) has issued guidelines for the waiver of consent under emergency circumstances, as long as the research has the prospect of direct benefit to the patient. However, consent information is provided to the patient, legal representative and the family as soon as possible.

In an attempt to inform as many people as possible before the research begins, the researchers are required to disclose to the public the nature, risks and benefits of the study. This is being done through a variety of means:

• This website
• Advertising on public buses
• News stories
• Consultation with the administrative staff of the King County area paramedics
• Consultation with community leaders
• Community survey

A random sample of 500 King County area households were called in March 2006 and asked their opinion of waiver of consent and whether or not they would want hypertonic saline given to them without their consent. 77% of respondents indicated that they would like to be enrolled in the trial. 

Why has the FDA changed its rules on informed consent?

The FDA has issued these regulations to allow research, designed to improve medical treatment, to occur under emergency circumstances in which obtaining informed consent is not feasible while doing everything possible to protect the rights and safety of human subjects.

Does the HSD/HS study meet the FDA requirements for waiver of informed consent?

Yes, the University of Washington research study meets these requirements:

• A life-threatening situation with unproven or unsatisfactory treatment where research is necessary to improve outcome. Blunt trauma causing hypovolemic shock is an immediately life-threatening condition with unsatisfactory treatment.
• Obtaining informed consent is not feasible because the patient is unresponsive and treatment must begin immediately if there is any hope for survival.
• Participation in research has the prospect of direct benefit because the situation necessitates an intervention, science supports the potential of direct benefit and the risks of the research are reasonable compared to the medical condition.
• The research could not practicably be done without waiver of informed consent.
• The potential therapeutic window is short (in the case of resuscitative fluid must be given within minutes)
• The University of Washington's Human Subject's Ethics Review Board approves the consent document and procedures for the subject or legal representative.

Will the victim's family know that the patient was part of the HSD/HS study?

Information will be provided to the participant, legal representative and the family as soon as possible. Documentation will be kept on file according to federal regulations.

Additional protections provided by FDA regulations include public disclosure prior to starting the study, public disclosure after completion of the study, and an attempt to contact family members whenever possible.

Who are the investigators for this study?

Principal Investigators:
Peter Kudenchuck, MD
Professor of Medicine
University of Washington Medical Center

Eileen M. Bulger, MD
Associate Professor of Surgery
Associate Director of Emergency Surgical Services
Harborview Medical Center

Tom Rea, MD
Assistant Professor of Medicine
Harborview Medical Center

What does it mean to opt-out of this study?

 
If you do not want to participate in this study you can request to “opt-out.” If you choose to opt-out we will mail you a Medic-Alert type bracelet with the words “No Study” engraved on it. You will have to wear this bracelet during the time the study is being conducted – through 2010. Even if you wear this bracelet there is no guarantee that under emergency circumstances the bracelet will be read by those providing care for you. You might still get the enrolled in the study. In the unlikely event you are treated in this trial after you have requested to not be enrolled we will not use any of the information collected about you; such information will be destroyed.

How can I opt-out of this study?

 
If you would like to opt-out of participation in this trial please send your request to the following email address: kcroc@u.washington.edu. Be sure to include your name and mailing address so we can mail you the opt-out bracelet.