Effectiveness of plasma versus crystalloids in pre-hospital hemorrhagic shock: systematic review and meta-analysis

The impact of prehospital plasma transfusion on survival after major trauma remains uncertain. We conducted a systematic review and meta-analysis (PROSPERO CRD420251027516) following PRISMA 2020 standards. Randomized and comparative observational studies published through [March 8, 2025] were included; alerts/hand-searches to April 15, 2025. Primary outcomes were 24-hour and 28–30-day mortality. Pooled Odds Ratios (ORs) were estimated using random-effects models with restricted maximum likelihood and Hartung–Knapp adjustment. Risk of bias was assessed with RoB 2 and ROBINS-I, and certainty of evidence appraised by GRADE. Three randomised trials (n=760) and two observational cohorts were included. Mortality at 28–30 days did not differ between pre-hospital plasma and crystalloids (OR 0.92; 95% CI 0.49–1.72; I²=50.6%). Twenty-four-hour mortality was not meta-analysed due to heterogeneity. Secondary outcomes showed no clinically significant differences. Observational cohorts were not pooled due to endpoint misalignment and risk of bias. Certainty of evidence ranged from low to very low across outcomes, primarily due to imprecision and inconsistency. Current evidence shows no survival benefit of prehospital plasma over crystalloid resuscitation. The findings remain uncertain, and routine plasma use should be restricted to controlled research or highly structured trauma systems until adequately powered multicenter trials with standardized outcomes confirm benefit. In Emergency Medical Services (EMS) settings, crystalloids remain the pragmatic first-line fluid.