The effects of prehospital TXA on mortality and neurologic outcomes in patients with traumatic intracranial hemorrhage: a subgroup analysis from the prehospital TXA for TBI trial.

BACKGROUND: In the Prehospital Tranexamic Acid (TXA) for TBI Trial, TXA administered within two hours of injury in the out-of-hospital setting did not reduce mortality in all patients with moderate/severe traumatic brain injury (TBI). We examined the association between TXA dosing arms, neurologic outcome, and mortality in patients with intracranial hemorrhage (ICH) on computed tomography (CT). METHODS: This was a secondary analysis of the Prehospital Tranexamic Acid for TBI Trial (ClinicalTrials.gov [NCT01990768]) that randomized adults with moderate/severe TBI (Glasgow Coma Scale<13) and systolic blood pressure > =90 mmHg within two hours of injury to a 2-gram out-of-hospital TXA bolus followed by an in-hospital saline infusion, a 1-gram out-of-hospital TXA bolus/1-gram in-hospital TXA infusion, or an out-of-hospital saline bolus/in-hospital saline infusion (placebo). This analysis included the subgroup with ICH on initial CT. Primary outcomes included 28-day mortality, 6-month Glasgow Outcome Scale-Extended (GOSE) < = 4, and 6-month Disability Rating Scale (DRS). Outcomes were modeled using linear regression with robust standard errors. RESULTS: The primary trial included 966 patients. Among 541 participants with ICH, 28-day mortality was lower in the 2-gram TXA bolus group (17%) compared to the other two groups (1-gram bolus/1-gram infusion 26%, placebo 27%). The estimated adjusted difference between the 2-gram bolus and placebo groups was -8·5 percentage points (95% CI, -15.9 to -1.0) and between the 2-gram bolus and 1-gram bolus/1-gram infusion groups was -10.2 percentage points (95% CI, -17.6 to -2.9). DRS at 6 months was lower in the 2-gram TXA bolus group than the 1-gram bolus/1-gram infusion (estimated difference -2.1 [95% CI, -4.2 to -0.02]) and placebo groups (-2.2 [95% CI, -4.3, -0.2]). Six-month GOSE did not differ among groups. CONCLUSIONS: A 2-gram out-of-hospital TXA bolus in patients with moderate/severe TBI and ICH resulted in lower 28-day mortality and lower 6-month DRS than placebo and standard TXA dosing. LEVEL OF EVIDENCE: Therapeutic/Care Management, Level II.

Tranexamic acid administration in the field does not affect admission thromboelastography after traumatic brain injury.

BACKGROUND: No Food and Drug Administration-approved medication improves outcomes following traumatic brain injury (TBI). A forthcoming clinical trial that evaluated the effects of two prehospital tranexamic acid (TXA) dosing strategies compared with placebo demonstrated no differences in thromboelastography (TEG) values. We proposed to explore the impact of TXA on markers of coagulation and fibrinolysis in patients with moderate to severe TBI. METHODS: Data were extracted from a placebo-controlled clinical trial in which patients 15 years or older with TBI (Glasgow Coma Scale, 3-12) and systolic blood pressure of ≥90 mm Hg were randomized prehospital to receive placebo bolus/placebo infusion (placebo), 1 g of TXA bolus/1 g of TXA infusion (bolus maintenance), or 2 g of TXA bolus/placebo infusion (bolus only). Thromboelastography was performed, and coagulation measures including prothrombin time, activated partial thromboplastin time, international ratio, fibrinogen, D-dimer, plasmin-antiplasmin (PAP), thrombin antithrombin, tissue plasminogen activator, and plasminogen activator inhibitor 1 were quantified at admission and 6 hours later. RESULTS: Of 966 patients receiving study drug, 700 had laboratory tests drawn at admission and 6 hours later. There were no statistically significant differences in TEG values, including LY30, between groups (p > 0.05). No differences between prothrombin time, activated partial thromboplastin time, international ratio, fibrinogen, thrombin antithrombin, tissue plasminogen activator, and plasminogen activator inhibitor 1 were demonstrated across treatment groups. Concentrations of D-dimer in TXA treatment groups were less than placebo at 6 hours (p < 0.001). Concentrations of PAP in TXA treatment groups were less than placebo on admission (p < 0.001) and 6 hours (p = 0.02). No differences in D-dimer and PAP were observed between bolus maintenance and bolus only. CONCLUSION: While D-dimer and PAP levels reflect a lower degree of fibrinolysis following prehospital administration of TXA when compared with placebo in a large prehospital trial of patients with TBI, TEG obtained on admission and 6 hours later did not demonstrate any differences in fibrinolysis between the two TXA dosing regimens and placebo. LEVEL OF EVIDENCE: Diagnostic test, level III.

Predictors of Definitive Airway Sans Hypoxia/Hypotension on First Attempt (DASH-1A) Success in Traumatically Injured Patients Undergoing Prehospital Intubation.

Background: Prehospital intubation success is routinely treated as a dichotomous outcome based on an endotracheal tube passing through vocal cords regardless of number of attempts or occurrence of hypoxia, or hypotension, which are associated with worse outcomes. We explore patient, provider, and procedure-related variables associated with successful definitive airway sans hypoxia/hypotension on first attempt (DASH-1A) in traumatically injured subjects undergoing endotracheal intubation at the scene of injury by a helicopter EMS system.Methods: This single-center retrospective chart review included patients with traumatic injuries and at least one attempted intubation by helicopter EMS at the scene of injury. Demographic and clinical variables were tested for association with DASH-1A and overall first-attempt success using univariate comparisons and multivariable logistic regression to produce adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Purposeful backwards stepwise elimination was used to develop logistic regression models for outcomes. Initial inclusion of covariates in multivariable models was based on clinical judgement, known or suspected risk factors and confounders for intubation success, and univariate associations.Results: Of 419 subjects screened, 263 met inclusion criteria. Median age was 34 years and the majority of subjects were Caucasian (95%), male (76%), and suffered blunt trauma (90%). The endotracheal tube was successfully placed on the first attempt in 198 (75.3%) of patients, but only 142 (55.3%) had a successful DASH-1A, and overall, 246 (94%) had an endotracheal tube passed successfully before hospital arrival. Factors significantly associated with successful DASH-1A were no ground EMS intubation attempt prior to arrival [aOR 2.2 (CI 1.0-4.9)], lack of airway secretions/blood [1.9 (1.0-3.4)], Cormack-Lehane Score of I and II [12.3 (4.5-33.2) & 3.2 (1.2-9.1), respectively], and bougie use [5.4 (1.8-15.8)]. For endotracheal tube passing only, the following were significantly associated with first pass success: grade of view I and II [aORs 87.3 (CI 25.8-295.7) & 6.8 (2.3-19.5), respectively], lack of secretions/blood [4.9 (2.1-11.2), bougie use [7.8 (2.3-26.3)], direct laryngoscopy [5.1 (1.5-17.0)] and not using apneic oxygenation through a nasal cannula [2.5 (1.1-5.6)].Conclusion: In our helicopter EMS system, successful endotracheal intubation on the first attempt and without an episode of hypoxia was associated with no ground EMS intubation attempt prior to flight crew arrival, lack of airway secretions/blood, Cormack-Lehane Score, and bougie use.

Shorter times to packed red blood cell transfusion are associated with decreased risk of death in traumatically injured patients.

BACKGROUND: Hemorrhage is a leading cause of death in traumatically injured patients. Currently, the importance of earlier administration of packed red blood cells (pRBC) to improve outcomes is limited. We evaluated the association of earlier pRBC administration and mortality when compared with later transfusion initiation. METHODS: This single-center retrospective cohort study of trauma patients transported by a single helicopter service from the scene of injury to an urban academic trauma center included patients receiving at least one unit of pRBC within 24 hours of hospital arrival. The final cohort included patients transported to the trauma center between March 11, 2010, and October 30, 2013. The helicopter service carries two units of pRBC for protocol-driven prehospital transfusion. Logistic regression was used to model odds of death, and 95% confidence intervals were calculated. RESULTS: The 94 patients meeting inclusion criteria had a mean (SD) age of 43 (19) years; 87 (93%) of 94 were white, 66 (70%) of 94 were male, and 88(94%) of 94 sustained blunt force injuries. Median Injury Severity Score was 29 (range, 2-75), and 31 (33%) of 94 died within 30 days. Most patients [82/94 (87%)] received their first pRBC transfusion during transport or within one hour of arrival at the emergency department (ED). For the 82 patients receiving a first pRBC transfusion within one hour of ED arrival, each 10-minute increase in time to transfusion increased the odds of death [OR, 1.27 (95% CI, 1.01-1.62; p = 0.044)], controlling for TRISS. At 30 days, 29/82 (35%) patients who received a pRBC transfusion within one hour of ED arrival, and 2 (16%) of 12 patients who received delayed transfusion were deceased (difference, 19%; 95% CI, -5% to 42%). CONCLUSION: In this study, delays in time to pRBC administration of as short as 10 minutes were associated with increased odds of death for patients receiving ultra-early pRBC transfusion. Expedient prehospital and ED transfusion capabilities may improve outcomes after trauma. LEVEL OF EVIDENCE: Therapeutic/care management study, level III.