Importance Current prehospital traumatic brain injury guidelines utilize a systolic blood pressure threshold of <90mmHg for treating hypotension (age≥10) based on studies showing higher mortality when blood pressure drops below this level. However, the guidelines also acknowledge the weakness of the supporting evidence. Objective In a statewide, multisystem study of traumatic brain injury, to evaluate whether any statistically supportable systolic pressure-versus-mortality threshold emerges from the data, a priori, without assuming that a cut-point exists. Design Observational evaluation of a large prehospital database established as a part of the Excellence in Prehospital Injury Care (EPIC) Traumatic Brain Injury Study (NIH/NINDS-1R01NS071049). The generalized additive model and logistic regression were utilized to determine the relationship between systolic pressure and probability of death, adjusting for significant/important confounders. Setting The pre-implementation cohort (1/1/2007–3/31/2014) of the EPIC Study. Participants Patients (age≥10) with moderate/severe traumatic brain injury (Barell Matrix-Type 1 and/or International Classification of Disease-9 head region severity ≥3 and/or Abbreviated Injury Scale head-region severity ≥3) and lowest prehospital systolic pressure between 40 and 119mmHg were included. Main Outcome Measure The main outcome measure was in-hospital mortality. Results Among the 3,844 included cases, the model revealed a monotonically-decreasing relationship between systolic pressure and adjusted probability of death across the entire range (40–119mmHg). Each ten-point increase of systolic pressure was associated with a decrease in the adjusted odds of death of 18.8% (aOR=0.812; 95% confidence interval: 0.748–0.883). Thus, the adjusted odds of mortality increase as much for a drop from, say, 110 to 100mmHg as for 90 to 80mmHg, and so on, throughout the range. Conclusions and Relevance We found a linear relationship between lowest prehospital systolic blood pressure and severity-adjusted probability of mortality across an exceptionally wide range. There is no identifiable threshold or inflection point between 40 and 119mmHg. Thus, in traumatic brain injury, the concept that 90mmHg represents a unique or important physiological “cut-point” may be wrong. Furthermore, clinically-meaningful “hypotension” may not be as low as current guidelines suggest. Randomized trials evaluating treatment levels significantly above 90mmHg are needed.

IMPORTANCE Traumatic brain injury (TBI) is a massive public health problem. While evidence-based guidelines directing the prehospital treatment of TBI have been promulgated, to our knowledge, no studies have assessed their association with survival. OBJECTIVE To evaluate the association of implementing the nationally vetted, evidence-based, prehospital treatment guidelines with outcomes in moderate, severe, and critical TBI. DESIGN, SETTING, AND PARTICIPANTS The Excellence in Prehospital Injury Care (EPIC) Study included more than 130 emergency medical services systems/agencies throughout Arizona. This was a statewide, multisystem, intention-to-treat study using a before/after controlled design with patients with moderate to critically severe TBI (US Centers for Disease Control and Prevention Barell Matrix-Type 1 and/or Abbreviated Injury Scale Head region severity Ն3) transported to trauma centers between

BACKGROUND Survival is significantly reduced by either hypotension or hypoxia during the prehospital management of major traumatic brain injury (TBI). However, only a handful of small studies have investigated the influence of the combination of both hypotension and hypoxia occurring together. Objective: In patients with major TBI, we evaluated the associations between mortality and prehospital hypotension and hypoxia, both separately and in combination. METHODS All moderate/severe TBI cases in the pre-implementation cohort of the Excellence in Prehospital Injury Care (EPIC) Study (a statewide, before/after, controlled study of the impact of implementing the prehospital TBI treatment guidelines) from 1/1/07–3/31/14 were evaluated [exclusions: age<10 years; prehospital oxygen saturation ≤10%; prehospital systolic blood pressure (SBP) <40 or >200mmHg]. The relationship between mortality and hypotension (SBP <90mmHg) and/or hypoxia (saturation <90%) was assessed using multivariable logistic regression, controlling for Injury Severity Score, head region severity, injury type (blunt versus penetrating), age, sex, race, ethnicity, payer, inter-hospital transfer, and trauma center. RESULTS Among the 13,151 cases that met inclusion criteria [Median age: 45; Male: 68.6%], 11,545 (87.8%) had neither hypotension nor hypoxia, 604 (4.6%) had hypotension only, 790 (6.0%) had hypoxia only, and 212 (1.6%) had both hypotension and hypoxia. Mortality for the four study cohorts was 5.6%, 20.7%, 28.1%, and 43.9%, respectively. The crude and adjusted odds ratios (cOR/aOR) for death within the cohorts, utilizing the patients with neither hypotension nor hypoxia as the reference, were 4.4/2.5, 6.6/3.0, and 13.2/6.1, respectively. Evaluation for an interaction between hypotension and hypoxia revealed that the effects are additive on the log odds of death. CONCLUSION In this statewide analysis of major TBI, combined prehospital hypotension/hypoxia were associated with dramatically increased mortality. This effect on survival persisted even after controlling for multiple potential confounders. In fact, the adjusted odds of death in patients with both hypotension and hypoxia was more than two times greater than those with either hypotension or hypoxia alone. These findings seem supportive of the emphasis on aggressive prevention and treatment of hypotension and hypoxia reflected in the current EMS TBI treatment guidelines but clearly reveal the need for further study to determine their impact on outcome.

Traumatic brain injury (TBI) exacts a great toll on society. Fortunately, there is growing evidence that the management of TBI in the early minutes after injury may significantly reduce morbidity and mortality. In response, evidence-based prehospital and in-hospital TBI treatment guidelines have been established by authoritative bodies. However, no large studies have yet evaluated the effectiveness of implementing these guidelines in the prehospital setting. This article describes the background, design, implementation, emergency medical services (EMS) treatment protocols, and statistical analysis of a prospective, controlled (before/after), statewide study designed to evaluate the effect of implementing the EMS TBI guidelines—the Excellence in Prehospital Injury Care (EPIC) study (NIH/NINDS R01NS071049, “EPIC”; and 3R01NS071049-S1, “EPIC4Kids”). The specific aim of the study is to test the hypothesis that statewide implementation of the international adult and pediatric EMS TBI guidelines will significantly reduce mortality and improve nonmortality outcomes in patients with moderate or severe TBI. Furthermore, it will specifically evaluate the effect of guideline implementation on outcomes in the subgroup of patients who are intubated in the field. Over the course of the entire study (~9 years), it is estimated that approximately 25,000 patients will be enrolled.

Background Out-of-hospital hypotension has been associated with increased mortality in traumatic brain injury (TBI). The association of TBI mortality with the depth or duration of out-of-hospital hypotension is unknown. Methods We evaluated adults and older children with moderate/severe TBI in the pre-implementation cohort of Arizona’s statewide Excellence in Prehospital Injury Care (EPIC) Study. We used logistic regression to determine the association between the depth-duration dose of hypotension [depth of systolic blood pressure <90 mmHg integrated over duration (minutes) of hypotension] and odds of in-hospital death, controlling for significant confounders. Results There were 7,521 TBI cases included [70.6% male, median age 40 (interquartile range 24, 58)]. Mortality was 7.8% (95%CI: 7.2–8.5%) among the 6982 cases without hypotension (SBP≥90 mmHg) and 33.4% (95%CI: 29.4–37.6%) among the 539 hypotensive cases (SBP<90 mmHg). Mortality was higher with increased hypotension dose: 0.01–14.99 mmHg*min, 16.3%; 15–49.99, 28.1%; 50–141.99, 38.8%; ≥142, 50.4%. Log2 (the logarithm in base 2) of hypotension dose was associated with TBI mortality [adjusted odds ratio 1.19 (95% CI: 1.14–1.25) per two-fold increase of dose]. Conclusion In this study, the depth and duration of out-of-hospital hypotension were associated with increased TBI mortality. Assessments linking out-of-hospital blood pressure with TBI outcomes should consider both depth and duration of hypotension.