52 in 52 – #29: The “PAMPer” Study

Welcome back to the “52 in 52” series. This collection of posts features recently published must-know articles. This week the series covers prehospital transfusion of plasma.


Author: Christiaan van Nispen, MD (Emergency Medicine Physician Resident, San Antonio, TX) and Brannon Inman (Chief Resident, Emergency Medicine Physician, San Antonio, TX) // Reviewed by: Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)


Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock

AKA: The “PAMPer” Study

Clinical question:

In patients at risk for hemorrhagic shock, is there a mortality benefit to pre-hospital transfusion of plasma as the initial resuscitation fluid compared to the standard of care?

 

Study design:

  • Multi-centered, cluster-randomization trial

 

PICO:

Population:

  • Inclusion:
    • Patients being transported by one of 27 participating air transportation teams from the scene of blunt or penetrating injury or from a referring ED to one of 9 participating trauma centers
    • At risk for hemorrhagic shock during transport or prior to arrival of transport team, defined as at least one episode of either:
      • Systolic blood pressure < 90 mm Hg AND heart rate > 108 beats per minute
      • Systolic blood pressure < 70 mm Hg irrespective of heart rate
    • Assumed consent for participation in trial unless patient or family voiced opposition; patients could opt out of continued participation later
  • Exclusion:
    • Younger than 18 years or older than 90 years
    • Inability to establish intravenous and/or intraosseous access
    • Isolated fall from standing mechanism of injury
    • Isolated drowning mechanism of injury
    • Isolated hanging mechanism of injury
    • Presence of greater than 20% total body surface area burns
    • Traumatic cardiac arrest lasting longer than 5 minutes
    • Penetrating brain injury
    • Incarcerated patients
    • Pregnant patients

 

Intervention: 

  • Infusion of 2 units of universal donor or group A low titer B (<1:100) thawed plasma to patients at risk for hemorrhagic shock in addition to standard of care
  • Plasma was the initial resuscitative fluid prior to advancing to the erstwhile standard of care for fluid resuscitation.

 

Comparator:

  • Standard of care only with a goal of systolic blood pressure ≥ 90 mm Hg
  • Standard of care varied by air transportation team.
    • 13 of 27 air transportation teams also carried 2 units of universal donor packed red blood cells (pRBCs) which could be infused after a liter of crystalloid if one of the following conditions were present:
      • Systolic blood pressure < 90 mm Hg
      • Heart rate > 120 beats per minute
      • Deteriorating mental status
      • Capillary refill > 2 seconds
    • Remainder of teams used isotonic crystalloid infusion only.

 

Enrollment and Randomization:

  • Initially calculated that 530 screened prehospital patients would lead to 504 eligible patients, which would provide 88% power to detect a 14% difference.
  • 2 years, 8 months into the trial, enrollment was increased to 564 to account for higher-than-expected ineligible patients.
  • Intervention and Comparator arms were demographically well balanced.
  • Enrolled patients were largely men (72.7%), sustained injuries from blunt trauma (82.4%), and appeared at high risk for severe outcomes, given the median prehospital heart rates, systolic blood pressures, and rates of intubation reported.
  • 390 enrolled at scene; 111 enrolled from referring ED.
  • Due to limited shelf life of thawed plasma, randomization was clustered by air medical team base.
    • Each month, each base was randomized to carry or not to carry plasma in addition to their standard of care.
  • Primary outcome data was available for 96% of patients.

Outcome:

  • Statistically significant difference in primary outcome of 30-day mortality
    • 53 deaths in the plasma group
    • 89 deaths in standard of care group
    • 2% vs. 33.0%; difference, −9.8 percentage points; 95% confidence interval, −18.6 to −1.0%; P=0.03
  • There remained a 39% lower risk of death at 30 days in the plasma group when accounting for variations in pre-hospital crystalloid volume infused, pre-hospital pRBC volume infused, and clustering at the base level
  • Statistically significant difference in initial prothrombin time, which was a secondary outcome
    • 1.2 in plasma group
    • 1.3 in control group
  • Other secondary outcomes lacked statistical significance:
    • 24-hour mortality
    • In-hospital mortality
    • Onset of acute lung injury/acute respiratory distress syndrome
    • Onset of multi-organ failure
    • Median total 24-hour volume of pRBCs transfusion
    • Median 24-hour volume of plasma transfusion
    • Median 24-hour volume of platelet transfusion
    • Vasopressor requirement in first 24 hours
    • Onset of nosocomial infection
    • Allergic reaction or transfusion related reaction
    • Median initial results of thromboelastography

Take aways:

  • Positive trial: pre-hospital plasma appears superior to standard of care alone.
  • Intervention group was less likely to be administered prehospital pRBCs (26.1% vs. 42.1%) and received lower median crystalloid volume (500mL vs. 900mL) yet had better 30-day mortality outcomes.
  • Effect was larger in the patients transported from scene compared to patients transported from a referring ED, suggesting that earlier plasma transfusion might be better, though more research is necessary for validation.
  • Though statistically significant, it is unlikely that the 0.1 difference in initial prothrombin time is physiologically or clinically meaningful enough to account for the apparent mortality benefit.
  • The study is appropriately powered and has limited loss to follow-up.

My take:

  • In patients with pre-hospital signs of hemorrhagic shock, pre-hospital plasma transfusion in conjunction with pRBCs and/or crystalloid appears superior to pRBCs and/or crystalloid alone, which tracks with other recent data demonstrating that balanced transfusion and the avoidance of crystalloid are best practices.
  • More research is needed to validate the results of this trial, with better standardized local protocols regarding the transfusion of other blood products and crystalloid.

 

References:

  1. Sperry JL, Guyette FX, Brown JB, et al. Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock. N Engl J Med.2018; 379(18):1783. DOI 10.1056/NEJMc1811315

 

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