52 in 52 – #29: The “PAMPer” Study

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.

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

• 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