Characterizing re-triage guidelines: A scoping review of states' rules and regulations.

BACKGROUND: State guidelines for re-triage, or emergency inter-facility transfer, have never been characterized across the United States. METHODS: All 50 states' Department of Health and/or Trauma System websites were reviewed for publicly available re-triage guidelines within their rules and regulations. Communication was made via phone or email to state agencies or trauma advisory committees to obtain or confirm the absence of guidelines where public data was unavailable. Guideline criteria were abstracted and grouped into domains of Center for Disease Control Field Triage Criteria: pattern/anatomy of injury, vital signs, special populations, and mechanisms of injury. Re-triage criteria were summarized across states using median and interquartile ranges for continuous data and frequencies for categorical data. Demographic data of states with and without re-triage guidelines were compared using the Wilcoxon rank sum test. RESULTS: Re-triage guidelines were identified for 22 of 50 states (44%). Common anatomy of injury criteria included head trauma (91% of states with guidelines), spinal cord injury (82%), chest injury (77%), and pelvic injury (73%). Common vital signs criteria included Glasgow Coma Score (91% of states) ranging from 8 to 14, systolic blood pressure (36%) ranging from 90 to 100 mm Hg, and respiratory rate (23%) with all using 10 respirations/minute. Common special populations criteria included mechanical ventilation (73% of states), age (68%) ranging from <2 or >60 years, cardiac disease (59%), and pregnancy (55%). No significant demographic differences were found between states with versus without re-triage guidelines. CONCLUSION: A minority of US states have re-triage guidelines. Characterizing existing criteria can inform future guideline development.

Is state trauma funding associated with mortality among injured hospitalized patients?

BACKGROUND: We sought to quantify the association between state trauma funding and (1) in-hospital mortality and (2) transfers of injured patients. METHODS: We conducted an observational cross-sectional study of states with publicly available trauma funding data. We analyzed in-hospital mortality using linked data from the Nationwide Inpatient Sample (NIS), American Hospital Association (AHA) Annual Survey, and these State Department of Public Health trauma funding data. RESULTS: A total of 594,797 injured adult patients were admitted to acute care hospitals in 17 states. Patients in states with >$1.00 per capita state trauma funding had 0.82 (95 â€‹% CI: 0.78-0.85, p â€‹< â€‹0.001) decreased adjusted odds of in-hospital mortality compared to patients in states with less than $1.00 per capita state trauma funding. CONCLUSIONS: Increased state trauma funding is associated with decreased adjusted in-hospital mortality.

Re-triage moderates association between state trauma funding and lower mortality of trauma patients.

BACKGROUND: Severely injured patients who are re-triaged (emergently transferred from an emergency department to a high-level trauma center) experience lower in-hospital mortality. Patients in states with trauma funding also experience lower in-hospital mortality. This study examines the interaction of re-triage, state trauma funding, and in-hospital mortality. STUDY DESIGN: Severely injured patients (Injury Severity Score (ISS) >15) were identified from 2016 to 2017 Healthcare Cost and Utilization Project State Emergency Department Databases and State Inpatient Databases in five states (FL, MA, MD, NY, WI). Data were merged with the American Hospital Association Annual Survey and state trauma funding data. Patients were linked across hospital encounters to determine if they were appropriately field triaged, field under-triaged, optimally re-triaged, or sub-optimally re-triaged. A hierarchical logistic regression modeling in-hospital mortality was used to quantify the effect of re-triage on the association between state trauma funding and in-hospital mortality, while adjusting for patient and hospital characteristics. RESULTS: A total of 241,756 severely injured patients were identified. Median age was 52 years (IQR: 28, 73) and median ISS was 17 (IQR: 16, 25). Two states (MA, NY) allocated no funding, while three states (WI, FL, MD) allocated $0.09-$1.80 per capita. Patients in states with trauma funding were more broadly distributed across trauma center levels, with a higher proportion of patients brought to Level III, IV, or non-trauma centers, compared to patients in states without trauma funding (54.0% vs. 41.1%, p < 0.001). Patients in states with trauma funding were more often re-triaged, compared to patients in states without trauma funding (3.7% vs. 1.8%, p < 0.001). Patients who were optimally re-triaged in states with trauma funding experienced 0.67 lower adjusted odds of in-hospital mortality (95% CI: 0.50-0.89), compared to patients in states without trauma funding. We found that re-triage significantly moderated the association between state trauma funding and lower in-hospital mortality (p = 0.018). CONCLUSION: Severely injured patients in states with trauma funding are more often re-triaged and experience lower odds of mortality. Re-triage of severely injured patients may potentiate the mortality benefit of increased state trauma funding.

The Association of Limited English Proficiency With Morbidity and Mortality After Trauma.

INTRODUCTION: Disparities following traumatic injury by race/ethnicity and insurance status are well-documented. However, the relationship between limited English proficiency (LEP) and outcomes after trauma is poorly understood. This study describes the association between LEP and morbidity and mortality after traumatic injury. METHODS: A retrospective cohort study was conducted of adult trauma patients admitted to a level 1 trauma center from 2012 to 2018. Morbidity (length of stay [LOS], intensive care unit admission, intensive care unit LOS, discharge destination) and in-hospital mortality for LEP and English proficient (EP) patients were compared using univariate and multivariable logistic and generalized linear models controlling for patient demographics (age, sex, race/ethnicity, insurance) and clinical characteristics (mechanism, activation level, Glasgow Coma Scale, Injury Severity Score, traumatic brain injury). RESULTS: Of the 13,104 patients, 16% were LEP patients. LEP languages included Chinese (44%) and Spanish (38%), and 18% categorized as "Other," including 33 languages. In multivariable models, LEP was statistically significantly associated with increased hospital LOS (P = 0.003) and increased discharge to home with home health services (P = 0.042) or to skilled nursing facility/rehabilitation (P = 0.006). Mortality rate was 7% for LEP versus 4% for EP patients (P < 0.0001). In multivariable analysis, speaking an LEP language other than Chinese or Spanish was statistically significantly associated with increased mortality compared to EP (P = 0.006). CONCLUSIONS: Following traumatic injury, LEP patients experience increased hospital LOS and are more frequently discharged to home with home health services or to skilled nursing facilities/rehabilitation. LEP patients speaking languages other than Chinese or Spanish experience increased mortality compared to EP patients.

Pelvic fracture pattern predicts the need for hemorrhage control intervention-Results of an AAST multi-institutional study.

BACKGROUND: Early identification of patients with pelvic fractures at risk of severe bleeding requiring intervention is critical. We performed a multi-institutional study to test our hypothesis that pelvic fracture patterns predict the need for a pelvic hemorrhage control intervention. METHODS: This prospective, observational, multicenter study enrolled patients with pelvic fracture due to blunt trauma. Inclusion criteria included shock on admission (systolic blood pressure <90 mm Hg or heart rate >120 beats/min and base deficit >5, and the ability to review pelvic imaging). Demographic data, open pelvic fracture, blood transfusion, pelvic hemorrhage control intervention (angioembolization, external fixator, pelvic packing, and/or REBOA [resuscitative balloon occlusion of the aorta]), and mortality were recorded. Pelvic fracture pattern was classified according to Young-Burgess in a blinded fashion. Predictors of pelvic hemorrhage control intervention and mortality were analyzed by univariate and multivariate regression analyses. RESULTS: A total of 163 patients presenting in shock were enrolled from 11 Level I trauma centers. The most common pelvic fracture pattern was lateral compression I, followed by lateral compression I, and vertical shear. Of the 12 patients with an anterior-posterior compression III fracture, 10 (83%) required a pelvic hemorrhage control intervention. Factors associated with the need for pelvic fracture hemorrhage control intervention on univariate analysis included vertical shear pelvic fracture pattern, increasing age, and transfusion of blood products. Anterior-posterior compression III fracture patterns and open pelvic fracture predicted the need for pelvic hemorrhage control intervention on multivariate analysis. Overall in-hospital mortality for patients admitted in shock with pelvic fracture was 30% and did not differ based on pelvic fracture pattern on multivariate analysis. CONCLUSION: Blunt trauma patients admitted in shock with anterior-posterior compression III fracture patterns or patients with open pelvic fracture are at greatest risk of bleeding requiring pelvic hemorrhage control intervention. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.

The Triage of Injured Patients: Mechanism of Injury, Regardless of Injury Severity, Determines Hospital Destination.

The target rate for trauma undertriage is <5 per cent, but rates are as high as 30 to 40 per cent in many trauma systems. We hypothesized that high undertriage rates were due to the tendency to undertriage injured elderly patients and a growing elderly population. We conducted a retrospective analysis of all hospital visits in California using the Office of Statewide Health Planning and Development Database over a 5-year period. All hospital admissions and emergency department visits associated with injury were longitudinally linked. The primary outcome was triage pattern. Triage patterns were stratified across three dimensions: age, mechanism of injury, and access to care. A total of 60,182 severely injured patients were included in the analysis. Fall-related injuries were frequently undertriaged compared with injuries from motor vehicle collisions (MVCs) and penetrating trauma (52% vs 12% and 10%, respectively). This pattern was true for all age groups. Conversely, MVCs and penetrating traumas were associated with high rates of overtriage (>70% for both). In conclusion, in contrast to our hypothesis, we found that triage is largely determined by mechanism of injury regardless of injury severity. High rates of undertriage are largely due to the undertriage of fall-related injuries, which occurs in both younger and older adults. Patients injured after MVCs and penetrating trauma victims are brought to trauma centers regardless of injury severity, resulting in high rates of overtriage. These findings suggest an opportunity to improve trauma system performance.

Current management of hemorrhage from severe pelvic fractures: Results of an American Association for the Surgery of Trauma multi-institutional trial.

BACKGROUND: There is no consensus as to the optimal treatment paradigm for patients presenting with hemorrhage from severe pelvic fracture. This study was established to determine the methods of hemorrhage control currently being used in clinical practice. METHODS: This prospective, observational multi-center study enrolled patients with pelvic fracture from blunt trauma. Demographic data, admission vital signs, presence of shock on admission (systolic blood pressure < 90 mm Hg or heart rate > 120 beats per minute or base deficit < -5), method of hemorrhage control, transfusion requirements, and outcome were collected. RESULTS: A total of 1,339 patients with pelvic fracture were enrolled from 11 Level I trauma centers. Fifty-seven percent of the patients were male, with a mean ± SD age of 47.1 ± 21.6 years, and Injury Severity Score (ISS) of 19.2 ± 12.7. In-hospital mortality was 9.0 %. Angioembolization and external fixator placement were the most common method of hemorrhage control used. A total of 128 patients (9.6%) underwent diagnostic angiography with contrast extravasation noted in 63 patients. Therapeutic angioembolization was performed on 79 patients (5.9%). There were 178 patients (13.3%) with pelvic fracture admitted in shock with a mean ± SD ISS of 28.2 ± 14.1. In the shock group, 44 patients (24.7%) underwent angiography to diagnose a pelvic source of bleeding with contrast extravasation found in 27 patients. Thirty patients (16.9%) were treated with therapeutic angioembolization. Resuscitative endovascular balloon occlusion of the aorta was performed on five patients in shock and used by only one of the participating centers. Mortality was 32.0% for patients with pelvic fracture admitted in shock. CONCLUSION: Patients with pelvic fracture admitted in shock have high mortality. Several methods were used for hemorrhage control with significant variation across institutions. The use of resuscitative endovascular balloon occlusion of the aorta may prove to be an important adjunct in the treatment of patients with severe pelvic fracture in shock; however, it is in the early stages of evaluation and not currently used widely across trauma centers. LEVEL OF EVIDENCE: Prognostic study, level II; therapeutic study, level III.

Beyond emergency surgery: redefining acute care surgery.

BACKGROUND: Considerable debate exists regarding the definition, skill set, and training requirements for the new specialty of acute care surgery (ACS). We hypothesized that a patient subset could be identified that requires a level of care beyond general surgical training and justifies creation of this new specialty. MATERIALS AND METHODS: Reviewed patient admissions over 1-y to the only general surgical service at a level I trauma center-staffed by trauma and/or critical care trained physicians. Patients classified as follows: trauma, ACS, emergency general (EGS), or elective surgery. ACS patients are nonelective, nontrauma patients with significantly altered physiology requiring intensive care unit admission and/or specific complex operative interventions. Differences in demographics, hospital course, and outcomes were analyzed. RESULTS: In-patient service evaluated approximately 5500 patients, including 3300 trauma patients. A total of 2152 admissions include 37% trauma, 30% elective, 28% EGS, and 4% ACS. ACS and trauma patients were more likely to require multiple operations (ACS relative risk [RR] = 11.5; trauma RR = 5.7, P < 0.0001), have longer hospital and intensive care unit length of stay, and higher mortality (P < 0.0001). They were less likely to be discharged home (ACS RR = 0.75; trauma RR = 0.67, P < 0.0001) compared with that of the EGS group. EGS and elective patients were most similar to each other in multiple areas. CONCLUSIONS: ACS and EGS patients represent distinct patient cohorts, as reflected by significant differences in critical care needs, likelihood of multiple operations, and need for postdischarge rehabilitation. The skills required to care for ACS patients, including ability to rescue from complications and provide critical care, differ from those required for EGS patients and supports development of ACS training and regionalization of care.

Recent developments in the assessment of the multiply injured trauma patient.

PURPOSE OF REVIEW: To provide an update on the recent developments and controversies in the assessment of the traumatically injured patient. RECENT FINDINGS: Recent literature suggests that: whole-body computed tomography (CT) is an effective strategy in more severely injured blunt trauma patients; 64-slice CT scanning now provides an effective noninvasive screening method for blunt cerebrovascular injury; the need for MRI imaging, in addition to CT, for the diagnosis of occult ligamentous injury of the cervical spine remains an unresolved controversy; point-of-care testing has made significant improvements in our ability to predict which patients will need a massive transfusion; and thromboelastography has enhanced our ability to tailor a hemostatic resuscitation more accurately. SUMMARY: The recent advances in the assessment of the multiply injured patient allow clinicians to more efficiently diagnose a patient's injuries and implement treatment in a more timely manner.

Service: 2010 Western Trauma Association presidential address.

Service is central to the mission of a trauma surgeon and inextricably interwoven into our professional lives and activities. It is important to recognize the role that professional associations play in leveraging service as well as the need to continue to cultivate the ethic of service in medical education and in our training programs.

Prospective randomized trial of LC+LCBDE vs ERCP/S+LC for common bile duct stone disease.

OBJECTIVE: To compare outcome parameters for good-risk patients with classic signs, symptoms, and laboratory and abdominal imaging features of cholecystolithiasis and choledocholithiasis randomized to either laparoscopic cholecystectomy plus laparoscopic common bile duct exploration (LC+LCBDE) or endoscopic retrograde cholangiopancreatography sphincterotomy plus laparoscopic cholecystectomy (ERCP/S+LC). DESIGN: Our study was a prospective trial conducted following written informed consent, with randomization by the serially numbered, opaque envelope technique. SETTING: Our institution is an academic teaching hospital and the central receiving and trauma center for the City and County of San Francisco, California. PATIENTS: We randomized 122 patients (American Society of Anesthesiologists grade 1 or 2) meeting entry criteria. Ten of these patients, excluded from outcome analysis, were protocol violators having signed out of the hospital against medical advice before 1 or both procedures were completed. INTERVENTIONS: Treatment was preoperative ERCP/S followed by LC, or LC+LCBDE. MAIN OUTCOME MEASURES: The primary outcome measure was efficacy of stone clearance from the common bile duct. Secondary end points were length of hospital stay, cost of index hospitalization, professional fees, hospital charges, morbidity and mortality, and patient acceptance and quality of life scores. RESULTS: The baseline characteristics of the 2 randomized groups were similar. Efficacy of stone clearance was likewise equivalent for both groups. The time from first procedure to discharge was significantly shorter for LC+LCBDE (mean [SD], 55 [45] hours vs 98 [83] hours; P < .001). Hospital service and total charges for index hospitalization were likewise lower for LC+LCBDE, but the differences were not statistically significant. The professional fee charges for LC+LCBDE were significantly lower than those for ERCP/S+LC (median [SD], $4820 [1637] vs $6139 [1583]; P < .001). Patient acceptance and quality of life scores were equivalent for both groups. CONCLUSIONS: Both ERCP/S+LC and LC+LCBDE were highly effective in detecting and removing common bile duct stones and were equivalent in overall cost and patient acceptance. However, the overall duration of hospitalization was shorter and physician fees lower for LC+LCBDE. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00807729.

Pitfalls in the evaluation and resuscitation of the trauma patient.

The management of the trauma patient presents the practitioner with a host of challenges, and the pace, variety of venues, and multidisciplinary nature of the field combine to create a system complexity that is laden with potential pitfalls. This review summarizes some of the general principles of medical errors and examines some of the more common pitfalls encountered in the initial resuscitation and evaluation of the major trauma patient.

Where do we go from here? Interim analysis to forge ahead in violence prevention.

BACKGROUND: The severity and disparity of interpersonal violent injury is staggering. Fifty-three per 100,000 African Americans (AA) die of homicide yearly, 20 per 100,000 in Latinos, whereas the rate is 3 per 100,000 in Caucasians. With the ultimate goal of reducing injury recidivism, which now stands at 35% to 50%, we have designed and implemented a hospital-based, case-managed violence prevention program uniquely applicable to trauma centers. The Wraparound Project (WP) seizes the "teachable moment" after injury to implement culturally competent case management (CM) and shepherd clients through risk reduction resources with city and community partners. The purpose of this study was to perform a detailed intermediate evaluation of this multi-modal violence prevention program. We hypothesized that this evaluation would demonstrate feasibility and early programmatic efficacy. We looked to identify areas of programmatic weakness that, if corrected, could strengthen the project and enhance its effectiveness. METHODS: We performed intermediate evaluation on the 18-month-old program. We selected the Centers for Disease Control and Prevention-recommended instrument used for unintentional injury prevention programs and applied it to the WP. The four sequential stages in this methodology are formative, process, impact, and outcome. To test feasibility of WP, we used process evaluation. To evaluate intermediate goals of risk reduction and early efficacy, we used impact evaluation. RESULTS: Four hundred thirty-five people met screening criteria. The two case managers were able to make contact and screen 73% of gun shot victims, and 57% of stab wound victims. Of those not seen, 48% were in the hospital for 6 h/wk with the client. Forty-one percent of the time, they spent 3 hours to 6 hours. Seventeen of 18 people who required >6 hours had two to three needs. Attrition rate is only 4%. The table demonstrates percent success thus far in providing risk reduction resources. CONCLUSIONS: WP case managers served high-risk clients by developing trust, credibility, and a risk reduction plan. Cultural competency has been vital. Six of seven major needs were successfully addressed at least 50% of the time. The value of reporting these results has led WP to gain credibility with municipal stakeholders, who have now agreed to fund a third CM position. Intermediate evaluation provided a framework in our effort to achieve the ultimate goal of reducing recidivism through culturally competent CM and risk factor modification.

Acute coagulopathy of trauma: hypoperfusion induces systemic anticoagulation and hyperfibrinolysis.

BACKGROUND: Coagulopathy is present at admission in 25% of trauma patients, is associated with shock and a 5-fold increase in mortality. The coagulopathy has recently been associated with systemic activation of the protein C pathway. This study was designed to characterize the thrombotic, coagulant and fibrinolytic derangements of trauma-induced shock. METHODS: This was a prospective cohort study of major trauma patients admitted to a single trauma center. Blood was drawn within 10 minutes of arrival for analysis of partial thromboplastin and prothrombin times, prothrombin fragments 1 + 2 (PF1 + 2), fibrinogen, factor VII, thrombomodulin, protein C, plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), tissue plasminogen activator (tPA), and D-dimers. Base deficit was used as a measure of tissue hypoperfusion. RESULTS: Two hundred eight patients were studied. Systemic hypoperfusion was associated with anticoagulation and hyperfibrinolysis. Coagulation was activated and thrombin generation was related to injury severity, but acidosis did not affect Factor VII or PF1 + 2 levels. Hypoperfusion-induced increase in soluble thrombomodulin levels was associated with reduced fibrinogen utilization, reduction in protein C and an increase in TAFI. Hypoperfusion also resulted in hyperfibrinolysis, with raised tPA and D-Dimers, associated with the observed reduction in PAI-1 and not alterations in TAFI. CONCLUSIONS: Acute coagulopathy of trauma is associated with systemic hypoperfusion and is characterized by anticoagulation and hyperfibrinolysis. There was no evidence of coagulation factor loss or dysfunction at this time point. Soluble thrombomodulin levels correlate with thrombomodulin activity. Thrombin binding to thrombomodulin contributes to hyperfibrinolysis via activated protein C consumption of PAI-1.

The spontaneous breathing pattern and work of breathing of patients with acute respiratory distress syndrome and acute lung injury.

BACKGROUND: The spontaneous breathing pattern and its relationship to compliance, resistance, and work of breathing (WOB) has not been examined in patients with acute respiratory distress syndrome (ARDS) or acute lung injury (ALI). Clinically, the ratio of respiratory frequency to tidal volume (f/VT) during spontaneous breathing may reflect adaptation to altered compliance, resistance, and increased WOB. We examined the relationship between f/VT, WOB, and respiratory system mechanics in patients with ARDS/ALI. METHODS: Data from spontaneous breathing trials were collected from 33 patients (20 with ARDS, 13 with ALI) at various points in their disease course. WOB and respiratory system mechanics were measured with a pulmonary mechanics monitor that incorporates Campbell diagram software. Differences between the patients with ARDS and ALI were assessed with 2-sided unpaired t tests. Multivariate linear regression models were constructed to assess the relationship between f/VT and other pulmonary-related variables. RESULTS: Patients with ARDS had significantly lower compliance than those with ALI (24 +/- 6 mL/cm H2O vs 40 +/- 13 mL/cm H2O, respectively, p < 0.001), but this did not translate into significant differences in either WOB (1.70 +/- 0.59 J/L vs 1.43 +/- 0.90 J/L, respectively, p = 0.30) or f/VT (137 +/- 82 vs 107 +/- 49, respectively, p = 0.23). Multivariate linear regression modeling revealed that peak negative esophageal pressure, central respiratory drive, duration of ARDS/ALI, minute ventilation deficit between mechanical ventilation and spontaneous breathing, and female gender were the strongest predictors of f/VT. CONCLUSION: The characteristic rapid shallow breathing pattern in patients with ARDS/ALI occurs in the context of markedly diminished compliance, elevated respiratory drive, and increased WOB. That f/VT had a strong, inverse relationship to peak negative esophageal pressure also may reflect the influence of muscle weakness.

Acute traumatic coagulopathy: initiated by hypoperfusion: modulated through the protein C pathway?

OBJECTIVES: Coagulopathy following major trauma is conventionally attributed to activation and consumption of coagulation factors. Recent studies have identified an acute coagulopathy present on admission that is independent of injury severity. We hypothesized that early coagulopathy is due to tissue hypoperfusion, and investigated derangements in coagulation associated with this. METHODS: This was a prospective cohort study of major trauma patients admitted to a single trauma center. Blood was drawn within 10 minutes of arrival for analysis of partial thromboplastin and prothrombin times, prothrombin fragments 1+2, fibrinogen, thrombomodulin, protein C, plasminogen activator inhibitor-1, and D-dimers. Base deficit (BD) was used as a measure of tissue hypoperfusion. RESULTS: A total of 208 patients were enrolled. Patients without tissue hypoperfusion were not coagulopathic, irrespective of the amount of thrombin generated. Prolongation of the partial thromboplastin and prothrombin times was only observed with an increased BD. An increasing BD was associated with high soluble thrombomodulin and low protein C levels. Low protein C levels were associated with prolongation of the partial thromboplastin and prothrombin times and hyperfibrinolysis with low levels of plasminogen activator inhibitor-1 and high D-dimer levels. High thrombomodulin and low protein C levels were significantly associated with increased mortality, blood transfusion requirements, acute renal injury, and reduced ventilator-free days. CONCLUSIONS: Early traumatic coagulopathy occurs only in the presence of tissue hypoperfusion and appears to occur without significant consumption of coagulation factors. Alterations in the thrombomodulin-protein C pathway are consistent with activated protein C activation and systemic anticoagulation. Admission plasma thrombomodulin and protein C levels are predictive of clinical outcomes following major trauma.

Early coagulopathy after traumatic brain injury: the role of hypoperfusion and the protein C pathway.

INTRODUCTION: Early coagulopathy after traumatic brain injury (TBI) is thought to be the result of injury-mediated local release of tissue factor, although the precise mechanisms that cause hypoperfusion and early systemic coagulopathy in TBI patients are unknown. We have previously reported that early systemic coagulopathy after trauma is present only when tissue injury is associated with severe hypoperfusion leading to the activation of the protein C pathway. However, the role of hypoperfusion as an important mechanism for the development of coagulopathy early after TBI is unclear. The objective of the present study was to determine the importance of hypoperfusion and protein C activation in causing early coagulopathy in TBI patients. MATERIALS: We performed a prospective cohort study including patients with isolated brain injury admitted to a single trauma center. Blood was drawn on average 32 minutes after injury. Plasma samples were assayed for protein C and thrombomodulin by standard laboratory techniques. Routine coagulation measures (prothrombin time, partial thromboplastin time) and arterial blood gas analysis were performed concurrently. Severe hypoperfusion was evidenced by the presence of an arterial base deficit greater than 6. RESULTS: Thirty-nine TBI patients were included in the study during a 15-month period. TBI patients without concurrent hypoperfusion (n = 28) did not develop an early coagulopathy after trauma, no matter the severity of injury. In contrast, patients with TBI who also had severe hypoperfusion (BD >6) (n = 11) were coagulopathic early after injury. Indeed, these patients had higher prothrombin time and partial thromboplastin time, compared with those with TBI and a BD <6 (17.6 +/- 3.6 vs. 14.3 +/- 2.3, p < 0.005; and 43.13 +/- 18.3 vs. 27.4 +/- 3.8, p < 0.0001). Unactivated protein C levels were lower in the TBI group with BD >6 (56 +/- 32 vs. 85 +/- 35, p = 0.03) and thrombomodulin levels were significantly higher (48 +/- 26 vs. 35 +/- 10, p = 0.04). Without hypoperfusion, there was no effect of increasing brain injury on protein C pathway or fibrinolysis pathway mediators. CONCLUSIONS: TBI alone does not cause early coagulopathy, but must be coupled with hypoperfusion to lead to coagulation derangements, associated with the activation of the protein C pathway. This novel finding has significant implications for the treatment of coagulopathy after severe brain injury.