Trauma Resuscitation Study to Test Hypothermia
CHANDLER, ARIZ. — The idea of using suspended animation in trauma care was unthinkable just 5 years ago, but surgeons now stand at the cusp of the first clinical trial in humans.
The nonrandomized, phase II trial will use emergency preservation and resuscitation (EPR), as it is now called, to buy surgeons time for victims of blunt or penetrating trauma who have exsanguinated to the point of cardiac arrest.
Hypothermia is achieved via a flush of ice-cold saline pumped into the aorta until the brain is cooled to a tympanic membrane temperature of less than 10°C. Patients can then undergo surgical interventions to control bleeding, followed by rewarming and resuscitation with cardiopulmonary bypass, principal investigator Dr. Samuel Tisherman explained at the annual meeting of the Eastern Association for the Surgery of Trauma.
Patients in the Emergency Preservation and Resuscitation for Cardiac Arrest from Trauma (EPR-CAT) trial must have at least one sign of life present within the 5-minute period prior to ED arrival or in the ED, and have no response to open-chest cardiopulmonary resuscitation with clamping the aorta or remain pulseless for 5 minutes despite aggressive resuscitative efforts.
Informed consent is impossible, said Dr. Tisherman, professor of critical care medicine and surgery and associate director of the Safar Center for Resuscitation Research at the University of Pittsburgh. “Why do it? Because we know our outcomes are so bad. These patients have almost no chance of survival with current therapy,” he said.
Standard resuscitation for patients in cardiac arrest from blunt or penetrating injuries includes emergency department thoracotomy (EDT), open cardiac massage, and fluid resuscitation. A recent analysis of 283 consecutive penetrating injury cases showed that patients with multiple cardiac or great-vessel gunshot wounds, regardless of ED signs of life, were “nearly unsalvageable”; only 1 patient survived EDT (J. Trauma 2009;67:1250–7).
Hypothermia is commonly used in elective pediatric and neurologic surgery, and is effective for cardiac arrest. In trauma care, however, hypothermia has been considered unfeasible because of three hurdles, coinvestigator Dr. Hasan B. Alam said at the meeting. The procedure is performed in a chaotic environment on patients who are typically in shock; it is technically challenging to cool the patient in less than 5 minutes, as opposed to the slow hypothermia induced in elective cases; and hypothermia has long been thought to exacerbate bleeding and coagulopathy in trauma patients.
Active rewarming can actually reverse coagulopathy, and although trauma patients may bleed more during hypothermic arrest, some systems allow for blood to be recirculated back into the patient, said Dr. Alam of Massachusetts General Hospital and Harvard University, both in Boston.
The goal of the multicenter trial is to limit EPR to less than 60 minutes. The hypothesis is that aortic arch flush can be initiated within 5 minutes of pulselessness, decreasing the tympanic membrane temperature to less than 20°C in 15 minutes.
A meeting attendee commented that death isn't the worst or most expensive outcome in these patients, noting the trial's potential for extremely poor outcomes. Data have shown that encephalopathy can begin 4 minutes after the cessation of blood flow in normothermic patients.
“The cheapest thing is a quick death,” Dr. Alam replied. “It's expensive if the heart comes back but the brain does not. But if we don't do this, we won't push ahead.”
The primary end point of the EPR-CAT trial is survival to hospital discharge without major disability, with the secondary outcome being neurologic function at 6 months.
Despite many medical and ethical questions, the trial is moving ahead; medical protocols have been submitted at two of the eight participating centers. Researchers expect to treat the first patient sometime in the second half of 2010, Dr. Tisherman said. The Food and Drug Administration will keep a close eye on the trial.
Disclosures: The trial is sponsored by the University of Pittsburgh. Dr. Tisherman disclosed no financial conflicts of interest.
