Two large studies have come to conflicting conclusions about whether emergency medical technicians should give plasma to severely bleeding trauma patients who are on their way to the hospital. But the disparity may be a function of the time it takes to get there.
The first, involving 125 trauma patients with presumed hemorrhagic shock and published in The Lancet, found that plasma administration did not improve mortality when the hospital was nearby.
The second, involving 501 patients who were airlifted to trauma center hospitals and released today in The New England Journal of Medicine (NEJM), found that giving plasma reduced the rate of death at 30 days by nearly 10 percentage points.
The authors of the Lancet study, known as COMBAT, speculated that plasma might be beneficial with longer transport times. That study was done in an urban area where it typically took less than 20 minutes to get to the hospital.
In the PAMPer study of patients taken to the hospital by helicopter, the trip typically took about 40 minutes.
The U.S. Department of Defense funded both trials. About 50,000 Americans die from injury-related hemorrhage each year, usually within two hours after their injury.
The results from the airlifted patients “should motivate trauma center personnel and air medical crews across the country to consider implementing this lifesaving approach,” said Dr. Jeremy Cannon of the University of Pennsylvania in a NEJM editorial.
“These results have the power to significantly alter trauma resuscitation,” co-author Jason Sperry, professor of surgery and critical care medicine at the University of Pittsburgh School of Medicine, said in a news release and video interview released by the school.
Adding 10 percentage points to the odds of survival “is going to have a robust benefit and it will change the way we practice pre-hospital care for the injured patient,” said Dr. Sperry, who was in Africa and unavailable for an interview.
The findings mean “it’s definitely feasible and it’s safe to administer blood products such as frozen plasma” in a pre-hospital setting, COMBAT co-author Dr. Michael Chapman of the University of Colorado School of Medicine told Reuters Health in a telephone interview.
“However, whatever benefits that can be seen probably won’t be realized in the short transport time to an urban trauma center,” he said. “But it seems reasonable to look at rural areas, developing countries and a military setting, where these benefits could realize themselves when ground transportation times are longer.”
In the PAMPer study of airlifted patients, mortality at 30 days was 23.2 percent among the people who received two units of thawed plasma versus 33.0 percent with standard care (P=0.03).
The research team estimated that when other factors such as prehospital red-cell transfusion are taken into account, the administration of prehospital plasma cut the risk of death by 39 percent compared with standard care (P=0.02).
The improvement in survival became clear three hours after plasma administration began. Mortality at 24 hours and in-hospital mortality were also lower, they said.
In addition, the plasma group also had a lower median prothrombin time upon arrival at the trauma center and less need for a blood transfusion.
The PAMPer researchers found no evidence that prehospital plasma administration reduced the odds of multiorgan failure, transfusion-related reactions, respiratory distress syndrome, or nosocomial infections.
“Prespecified subgroup analyses showed a consistent survival benefit in the plasma group across various injury types, which suggests broad generalizability of the results,” the team concluded.
The 501 cases, most the result of a shooting, were taken from a pool of 7,275 patients transported from 27 air medical bases to nine trauma centers in five states.
Five patients who received plasma had a transfusion-related reaction or allergic reaction versus one patient who received standard care.
The process of giving plasma did not delay transport time to the hospital, which was a median of 42 minutes with plasma and 40 minutes with standard care.
In contrast, in the COMBAT study, 28-day mortality was 15 percent with plasma and 10 percent with control (P=0.37).
In all, 65 patients received plasma and 60 got saline, with 56 percent ultimately requiring a blood transfusion within six hours of injury.
All had a systolic blood pressure below 71 mmHg. Median transport time to the Denver Health Medical Center in Colorado was 19 minutes with plasma and 16 minutes with saline.
“Due to the consistent lack of differences in the analyses, the study was stopped for futility after 144 of 150 planned enrollments,” the researchers said.
“Blood products might be beneficial in settings with longer transport times, but the financial burden would not be justified in an urban environment with short distances to mature trauma centers,” they said.
COMBAT is the first randomized controlled test of prehospital plasma administration in an urban setting where a trauma center is nearby.
Twenty-one percent of the patients in the plasma group and 19 percent in the control group developed infections. The rate of thrombotic events did not differ between the two groups.
Dr. Chapman said plasma administration needs to be studied in a broader range of settings where emergency treatment is not so homogeneous.
It’s a challenging proposition but “the logistics might get easier when freeze-dried plasma becomes approved for use,” he said.
The studies used thawed plasma, which has a shelf life of just five days once thawed. Never-frozen plasma is good for 30 days. Freeze-dried plasma, with a virtually unlimited shelf life, is not available in the U.S. but has been approved for use in France.
It would also be helpful if researchers could come up with a better system to identify which patients are in hemorrhagic shock, he said. Dr. Chapman and his colleagues are actively working on that challenge.