Global Differences in Causes, Management, and Survival After Severe Trauma: The Recombinant Activated Factor VII Phase 3 Trauma Trial

Background: Little is known about international variation in mortality after severe trauma. This study examines variation in mortality, injury severity, and case management among countries from a recent prospective multinational trauma trial. Methods: This trauma trial was a prospective, randomized, double-blinded, multicenter comparison of recombinant activated factor VII versus placebo in severely injured bleeding trauma patients. Differences in baseline patient characteristics, case management, and clinical outcomes were examined for the 11 countries recruiting most patients. Between-country differences in mortality were examined using regression analysis adjusting for case mix and case management differences. Global predictors of mortality were also identified using multivariate regression analysis. Results: Significant differences were observed between countries in unadjusted mortality rates at 24 hours (p = 0.025) and 90 days (p < 0.0001). When adjusting for differences in case mix and case management, the between country differences in mortality at 24 hours and 90 days remained significant. Consistent independent predictors of 24-hour, 24-hour to 90-day, and 90-day mortality were admission lactate >= 5 mmol/L (odds ratio: 9.06, 3.56, and 5.39, respectively) and adherence to clinical management guidelines (odds ratio: 4.92, 5.90, and 3.26, respectively). On average, the damage control surgery guideline was less well adhered to than the RBC transfusion and ventilator guidelines. There was statistically significant variation between countries with respect to adherence to the RBC transfusion guideline. Conclusions: Considering international variation in mortality when designing or interpreting results from multinational trauma studies is important. Significant differences in mortality persisted between patients from different countries after case mix and case management adjustment. Adherence to clinical guidelines was associated with improved survival. Stratification, case mix adjustment, and use of guidelines on damage control surgery, transfusion, and ventilation may mitigate country-driven variation in mortality.