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Updated: Nov 10, 2025
Author Spotlight: Developing Innovative Therapeutic Strategies for Hemorrhagic Shock Research
Published on: March 22, 2024
Lactate as a mediator of prehospital plasma mortality reduction in hemorrhagic shock
Stephen P Canton1, Waseem Lutfi, Brian J Daley
1From the Division of Trauma and General Surgery, Department of Surgery (S.P.C., J.L.S., J.B.B.), University of Pittsburgh Medical Center, Pittsburgh; Department of Surgery (W.L.), University of Pennsylvania, Philadelphia, Pennsylvania; Department of Surgery (B.J.D.), University of Tennessee Health Science Center, Knoxville, Tennessee; Department of Surgery (R.S.M.), John Peter Smith Health Network, Fort Worth, Texas; Department of Surgery (B.G.H.), University of Louisville, Louisville, Kentucky; Department of Surgery (J.A.C.), MetroHealth Medical Center/Case Western Reserve University, Cleveland, Ohio; Department of Surgery (H.A.P.), Louisiana State University Health Sciences Center-New Orleans, New Orleans, Los Angeles; and Department of Emergency Medicine (F.X.G.), University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Background:
Prehospital plasma transfusion in trauma reduces mortality. However, the underlying mechanism remains unclear. Reduction in shock severity may play a role. Lactate correlates with physiologic shock severity and mortality after injury. Our objective was to determine if prehospital plasma reduces lactate and if this contributes to the mortality benefit of plasma.
Methods:
Patients in the Prehospital Air Medical Plasma trial in the upper quartile of injury severity (Injury Severity Score, >30) were included to capture severe shock. Trial patients were randomized to prehospital plasma or standard care resuscitation (crystalloid ± packed red blood cells). Regression determined the associations between admission lactate, 30-day mortality, and plasma while adjusting for demographics, prehospital crystalloid, time, mechanism, and injury characteristics. Causal mediation analysis determined what proportion of the effect of plasma on mortality is mediated by lactate reduction.
Results:
A total of 125 patients were included. The plasma group had a lower adjusted admission lactate than standard of care group (coefficient, -1.64; 95% confidence interval [CI], -2.96 to -0.31; p = 0.02). Plasma was associated with lower odds of 30-day mortality (odds ratio [OR], 0.27; 95% CI, 0.08-0.90; p = 0.03). When adding lactate to this model, the effect of plasma on 30-day mortality was no longer significant (OR, 0.36; 95% CI, 0.07-1.88; p = 0.23), while lactate was associated with mortality (OR, 1.74 per 1 mmol/L increase; 95% CI, 1.10-2.73; p = 0.01). Causal mediation demonstrated 35.1% of the total effect of plasma on 30-day mortality was mediated by the reduction in lactate among plasma patients.
Conclusion:
Prehospital plasma is associated with reduced 30-day mortality and lactate in severely injured patients. More than one third of the effect of plasma on mortality is mediated by a reduction in lactate. Thus, reducing the severity of hemorrhagic shock appears to be one mechanism of prehospital plasma benefit. Further study should elucidate other mechanisms and if a dose response exists.
Level Of Evidence:
Therapeutic, level II.
