In the Journals

Plasma during air transport may benefit those at risk for hemorrhagic shock

The use of thawed plasma during prehospital air medical transport appeared safe and led to lower 30-day mortality than standard resuscitation among patients at risk for severe hemorrhage, according to results from the phase 3 Prehospital Air Medical Plasma, or PAMPer, clinical trial.

“These results have the power to significantly alter trauma resuscitation, and their importance to the trauma community cannot be overstated,” Jason L. Sperry, MD, MPH, assistant professor in the departments of surgery and critical care medicine at Clinical and Translational Science Institute of University of Pittsburgh, said in a press release. “This is the first trial in a quarter century to have the potential to alter prehospital care so considerably.”

Previous studies have shown damage-control resuscitation in a prehospital environment could be beneficial and reduce complications attributed to hemorrhage.

Plasma transfusion may assist in changing the inflammatory response after injury, and reduce the permeability of endothelial cells after hemorrhagic shock. However, risks associated with plasma transfusion in this setting are still unknown and data are limited on its efficacy in the prehospital environment.

For this study, researchers used a single-stage cluster randomization scheme due to the limited availability and short shelf life — 5 days — of universal donor thawed plasma.

Sperry and colleagues randomly assigned air medical bases from nine medical institutions to administer two units of plasma (n = 230) or standard-of-care resuscitation (n = 271) at 1-month intervals to patients transported via air medical transport between May 2014 and October 2017.

All patients had suffered blunt trauma — with at least one episode of hypotension and tachycardia, or severe hypotension — prior to arrival of air medical transport or any time before arrival at the trauma center.

Mortality at 30 days served as the study’s primary outcome. Secondary outcomes included mortality at 24 hours and in-hospital mortality; volumes of blood components and resuscitation fluid given within 24 hours after study enrollment; multiorgan failure; incidence of acute lung injury-acute respiratory distress syndrome, transfusion-related acute lung injury or nosocomial infection; indexes of coagulopathy; and results of thromboelastography.

The rate of 30-day mortality was 23.2% among patients who receive plasma, compared with 33% among patients who received standard resuscitation, for a difference of 9.8% points (95% CI, 18.6 to 1).

After adjustment for volume of administered prehospital crystalloid solution and number of patients who received prehospital red-cell transfusion, analyses showed patients who received prehospital plasma had a 39% lower risk for mortality within 30 days after randomization than patients who received standard resuscitation (adjusted OR = 0.61; 95% CI, 0.4-0.91).

Kaplan–Meier curves indicated an early separation of the two treatment groups, which began 3 hours after randomization and remained until 30 days after randomization (log-rank chi-square test = 5.7; P = .02).

Researchers observed a similar treatment effect across nine prespecified subgroups (heterogeneity chi-square test = 12.21).

“We tested the interaction between treatment group and each subgroup variable; no significant interactions were observed after adjustment for multiple comparisons,” the researchers wrote.

After arrival at a trauma center, patients who received plasma had a median prothrombintime ratio of 1.2 (interquartile range [IQR], 1.1-1.4) compared with a ratio of 1.3 (IQR, 1.1-1.6; P < .001) among patients who received standard resuscitation.

Five patients who received plasma had transfusion-related reactions or allergic reactions deemed possibly related to the trial treatment.

Researchers did not observe significant differences between the two groups regarding multiorgan failure, acute lung injury-acute respiratory distress syndrome, nosocomial infections or allergic or transfusion-related reactions.

“Using thawed plasma, like we did in our trial, may not be feasible for all trauma centers,” Sperry said in the release. “But there are alternatives available of that are being approved by regulators soon that can extend the exciting results of our trial to more traumatically injured patients, potentially saving hundreds of lives every year.”

In a related editorial, Jeremy W. Cannon, MD, associate professor of surgery in the division of traumatology, surgical critical care and emergency surgery at Perelman School of Medicine, University of Pennsylvania, agreed that not all trauma centers will be able to use thawed plasma.

Although inexpensive, logistical challenges associated with prehospital administration exist, including careful monitoring of temperature for storage and likelihood of quick resupply.

Still, the study by Sperry and colleagues demonstrates the benefits of plasma for patients at risk for severe hemorrhage, Cannon wrote.

“Although these various alternative products are being explored, the PAMPer trial has shown the benefits and safety of prehospital plasma administration, which should motivate trauma center personnel and air medical crews across the country to consider implementing this lifesaving approach,” Cannon wrote. – by Melinda Stevens

Disclosures: Sperry reports grant support from Department of Defense during the conduct of the study and from NIH outside the submitted work. One author reports consultant/advisory fees from CSL Behring and Janssen Pharmaceuticals; grant support from Accriva Diagnostics, Haemonetics and Janssen Pharmaceuticals; equipment provision from Haemonetics; and that he is named on a patent for TLR4 inhibitors. Cannon reports nonfinancial support from Prytime Medical Devices outside the submitted work.

 

The use of thawed plasma during prehospital air medical transport appeared safe and led to lower 30-day mortality than standard resuscitation among patients at risk for severe hemorrhage, according to results from the phase 3 Prehospital Air Medical Plasma, or PAMPer, clinical trial.

“These results have the power to significantly alter trauma resuscitation, and their importance to the trauma community cannot be overstated,” Jason L. Sperry, MD, MPH, assistant professor in the departments of surgery and critical care medicine at Clinical and Translational Science Institute of University of Pittsburgh, said in a press release. “This is the first trial in a quarter century to have the potential to alter prehospital care so considerably.”

Previous studies have shown damage-control resuscitation in a prehospital environment could be beneficial and reduce complications attributed to hemorrhage.

Plasma transfusion may assist in changing the inflammatory response after injury, and reduce the permeability of endothelial cells after hemorrhagic shock. However, risks associated with plasma transfusion in this setting are still unknown and data are limited on its efficacy in the prehospital environment.

For this study, researchers used a single-stage cluster randomization scheme due to the limited availability and short shelf life — 5 days — of universal donor thawed plasma.

Sperry and colleagues randomly assigned air medical bases from nine medical institutions to administer two units of plasma (n = 230) or standard-of-care resuscitation (n = 271) at 1-month intervals to patients transported via air medical transport between May 2014 and October 2017.

All patients had suffered blunt trauma — with at least one episode of hypotension and tachycardia, or severe hypotension — prior to arrival of air medical transport or any time before arrival at the trauma center.

Mortality at 30 days served as the study’s primary outcome. Secondary outcomes included mortality at 24 hours and in-hospital mortality; volumes of blood components and resuscitation fluid given within 24 hours after study enrollment; multiorgan failure; incidence of acute lung injury-acute respiratory distress syndrome, transfusion-related acute lung injury or nosocomial infection; indexes of coagulopathy; and results of thromboelastography.

The rate of 30-day mortality was 23.2% among patients who receive plasma, compared with 33% among patients who received standard resuscitation, for a difference of 9.8% points (95% CI, 18.6 to 1).

After adjustment for volume of administered prehospital crystalloid solution and number of patients who received prehospital red-cell transfusion, analyses showed patients who received prehospital plasma had a 39% lower risk for mortality within 30 days after randomization than patients who received standard resuscitation (adjusted OR = 0.61; 95% CI, 0.4-0.91).

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Kaplan–Meier curves indicated an early separation of the two treatment groups, which began 3 hours after randomization and remained until 30 days after randomization (log-rank chi-square test = 5.7; P = .02).

Researchers observed a similar treatment effect across nine prespecified subgroups (heterogeneity chi-square test = 12.21).

“We tested the interaction between treatment group and each subgroup variable; no significant interactions were observed after adjustment for multiple comparisons,” the researchers wrote.

After arrival at a trauma center, patients who received plasma had a median prothrombintime ratio of 1.2 (interquartile range [IQR], 1.1-1.4) compared with a ratio of 1.3 (IQR, 1.1-1.6; P < .001) among patients who received standard resuscitation.

Five patients who received plasma had transfusion-related reactions or allergic reactions deemed possibly related to the trial treatment.

Researchers did not observe significant differences between the two groups regarding multiorgan failure, acute lung injury-acute respiratory distress syndrome, nosocomial infections or allergic or transfusion-related reactions.

“Using thawed plasma, like we did in our trial, may not be feasible for all trauma centers,” Sperry said in the release. “But there are alternatives available of that are being approved by regulators soon that can extend the exciting results of our trial to more traumatically injured patients, potentially saving hundreds of lives every year.”

In a related editorial, Jeremy W. Cannon, MD, associate professor of surgery in the division of traumatology, surgical critical care and emergency surgery at Perelman School of Medicine, University of Pennsylvania, agreed that not all trauma centers will be able to use thawed plasma.

Although inexpensive, logistical challenges associated with prehospital administration exist, including careful monitoring of temperature for storage and likelihood of quick resupply.

Still, the study by Sperry and colleagues demonstrates the benefits of plasma for patients at risk for severe hemorrhage, Cannon wrote.

“Although these various alternative products are being explored, the PAMPer trial has shown the benefits and safety of prehospital plasma administration, which should motivate trauma center personnel and air medical crews across the country to consider implementing this lifesaving approach,” Cannon wrote. – by Melinda Stevens

Disclosures: Sperry reports grant support from Department of Defense during the conduct of the study and from NIH outside the submitted work. One author reports consultant/advisory fees from CSL Behring and Janssen Pharmaceuticals; grant support from Accriva Diagnostics, Haemonetics and Janssen Pharmaceuticals; equipment provision from Haemonetics; and that he is named on a patent for TLR4 inhibitors. Cannon reports nonfinancial support from Prytime Medical Devices outside the submitted work.