From the Journals

Prehospital plasma outperforms standard care

Publish date: July 25, 2018
Author(s):
Will Pass

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Prehospital plasma deserves consideration

The Prehospital Air Medical Plasma (PAMPer) trial shows that prehospital plasma improves survival rates in trauma patients at risk for hemorrhagic shock, and its implementation should therefore be considered, according to Jeremy W. Cannon, MD.

“Severe hemorrhage from injury claims the lives of nearly 50,000 Americans every year,” Dr. Cannon wrote in an accompanying editorial. “Because many of these deaths occur in young, vital people, this number translates to an astounding loss of almost 2,000,000 years of productive life.”

Since most deaths occur in less than 2 hours, severe hemorrhage requires rapid intervention; however, the best methods of intervention are unclear. In 1994, Bickell et al. demonstrated that administration of crystalloid-based therapy was more beneficial in a goal-directed, operative setting than it was in transit to a trauma center. Other studies have shown that rapid transport and tourniquet application, when appropriate, are essential.

“But what about patients who have blunt injuries and longer transport times?” asked Dr. Cannon. Recently, damage-control resuscitation has proven effective in the trauma center – a combination of red cells, plasma, and platelets in approximately equal proportions, with minimal nonhemostatic crystalloid solution. Researchers now ask whether this intervention has a place in the prehospital setting.

The PAMPer trial suggests that the number needed to treat is 10 to save one life. These results “should motivate trauma center personnel and air medical crews across the country to consider implementing this lifesaving approach,” Dr. Cannon wrote.

Several blood products are candidates for prehospital resuscitation; their selection depends on both logistical and medical factors. Although fresh-frozen plasma was used in the PAMPer trial, it has a shelf life of only 5 days once thawed, leading to more frequent replenishment. Never-frozen plasma lasts 26 days, which could be easier to keep in stock. Beyond plasma, “refrigerated whole blood has a shelf life of 21 days and offers the benefit of both platelets and oxygen delivery, making it perhaps the ideal product for prehospital resuscitation,” Dr. Cannon wrote.

Jeremy W. Cannon, MD, is at the University of Pennsylvania in Philadelphia and the Uniformed Services University in Bethesda, Md. These comments are adapted from an accompanying editorial (N Engl J Med. 2018 Jul 26;379[4]:387-8). Dr. Cannon reported nonfinancial support from Prytime Medical Devices outside the submitted work and institutional participation in a research network funded by the Department of Defense.


 

FROM THE NEW ENGLAND JOURNAL OF MEDICINE

Prehospital administration of plasma to trauma patients at risk for hemorrhagic shock improves odds of survival, according to the Prehospital Air Medical Plasma (PAMPer) trial.

Patients who received plasma also had a decreased median prothrombin to time ratio, compared with those who received standard-care resuscitation alone.

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Modern trauma patients benefit “from receiving less crystalloid-based therapy and early balanced blood component–based therapy once they arrive at a facility for definitive care,” Jason L. Sperry, MD, of the University of Pittsburgh and his coauthors wrote in the New England Journal of Medicine. These newer strategies aim to mitigate coagulopathy and its associated downstream complications.

Still, “a majority of deaths from traumatic hemorrhage continue to occur in the first hours after arrival at the trauma center, which underscores the importance of the prehospital environment for early interventions that provide benefit,” the investigators noted.

The PAMPer trial (NCT01818427) examined the efficacy and safety of prehospital plasma resuscitation, comparing it with standard-care resuscitation, in severely injured patients. The phase 3, randomized, superiority trial involved 501 trauma patients at risk for hemorrhagic shock who were transported from 27 air medical bases to nine trauma centers. In total, 230 patients received prehospital plasma and standard-care resuscitation, and 271 patients received standard-care alone. Standard-care included infusion of crystalloid fluids in a goal-directed manner. Air medical bases delivered each type of care in 1-month intervals.

Patients were eligible if they exhibited severe hypotension (systolic blood pressure less than 70 mm Hg) or both hypotension (systolic blood pressure less than 90 mm Hg) and tachycardia (greater than 108 beats per minute).

Eligible patients received two units of thawed plasma, which was completely delivered before administration of any other fluids. If infusion of plasma was not complete upon arrival at the trauma center, infusion was completed before any in-hospital fluids were administered. Following preexisting local protocols, 13 of 27 air transport teams carried 2U of red blood cells. If red blood cells were delivered, then this was performed after plasma administration if the patient was still hypotensive or obviously bleeding.

The 30-day mortality rate among all patients was 29.6%. Approximately one in three patients received a prehospital red blood cell transfusion, and nearly 60% underwent surgery within 24 hours of hospital admission.

A greater percentage of patients in the standard-care group were given red blood cell transfusions, compared with those in the plasma group. The standard-care patients also received greater volumes of crystalloid solution than did those receiving plasma.

The primary outcome, 30-day mortality, was 9.8% lower for patients who received plasma, compared with patients who received standard-care alone (23.2% vs. 33.0%; P = .03). Multivariate regression analysis revealed that plasma delivery accounted for a 39% lower risk of death within 30 days, compared with standard care (P = .02). Within 3 hours of randomization, Kaplan-Meier curves revealed a separation between the two treatment groups that persisted until 30 days.

Median prothrombin to time ratio, the only statistically significant secondary outcome, was lower in the plasma group than it was in the standard-care group (1.2 vs. 1.3; P less than .001).

Other measured parameters were similar between the two main treatment groups, including rates of nosocomial infections, allergic or transfusion-related reactions, acute lung injury/acute respiratory distress syndrome, and multiorgan failure.

“Although we cannot determine the independent or additive effects of prehospital administration of plasma and packed red cells, the survival benefits attributable to plasma administration persisted after adjustment for prehospital red-cell administration, and a subgroup analysis showed no heterogeneity of the treatment effect,” the investigators wrote.

The PAMPer trial was supported by a grant from the U.S. Army Medical Research and Materiel Command. One author reported funding from Janssen Pharmaceuticals, CSL Behring, Haemonetics, and Accriva Diagnostics, as well as having been named on a patent on TLR4 inhibitors for the treatment of inflammatory and infectious disorders.

SOURCE: Sperry JL et al. N Engl J Med. 2018 Jul 26;379(4):315-26.

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