Efficacy of high dose tranexamic acid (TXA) for hemorrhage: A systematic review and meta-analysis.

BACKGROUND: Standard dose (≤ 1 g) tranexamic acid (TXA) has established mortality benefit in trauma patients. The role of high dose IV TXA (≥2 g or ≥30 mg/kg as a single bolus) has been evaluated in the surgical setting, however, it has not been studied in trauma. We reviewed the available evidence of high dose IV TXA in any setting with the goal of informing its use in the adult trauma population. METHODS: We searched MEDLINE, EMBASE and unpublished sources from inception until July 27, 2022 for studies that compared standard dose with high dose IV TXA in adults (≥ 16 years of age) with hemorrhage. Screening and data abstraction was done independently and in duplicate. We pooled trial data using a random effects model and considered randomized controlled trials (RCTs) and observational cohort studies separately. We assessed the individual study risk of bias using the Cochrane Risk of Bias for RCTs and the Newcastle-Ottawa Scale for observational cohort studies. The overall certainty of evidence was assessed using the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: We included 20 studies with a combined total of 12,523 patients. Based on pooled RCT data, and as compared to standard dose TXA, high dose IV TXA probably decreases transfusion requirements (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.76 to 0.97, moderate certainty) but with possibly no effect on blood loss (mean difference [MD] 43.31 ml less, 95% CI 135.53 to 48.90 ml less, low certainty), and an uncertain effect on thromboembolic events (OR 1.33, 95% CI 0.86 to 2.04, very low certainty) and mortality (OR 0.70, 95% CI 0.37 to 1.32, very low certainty). CONCLUSION: When compared to standard dose, high dose IV TXA probably reduces transfusion requirements with an uncertain effect on thromboembolic events and mortality. LEVEL OF EVIDENCE: Systematic review and meta-analysis, level IV.

A clinical prediction model for raised intracranial pressure in patients with traumatic brain injuries.

BACKGROUND: Intracranial hypertension is believed to contribute to secondary brain insult in traumatically brain injured patients. Currently, the diagnosis of intracranial hypertension requires intracranial monitoring or advanced imaging. Unfortunately, prehospital transport times can be prolonged, delaying time to the initial radiographic assessment. The aim of this study was to identify clinical variables associated with raised intracranial pressure (ICP) prior to the completion of neuroimaging. METHODS: We performed a retrospective cohort study of head injured patients over a 3-year period. Patients were labeled as having increased ICP if they had a single reading of ICP greater than 20 mm Hg within 1 hour of ICP monitor insertion or computed tomography findings suggestive of raised ICP. Patient and clinical characteristics were analyzed using stepwise multivariable logistic regression with ICP as the dependent variable. RESULTS: Of 701 head injured patients identified, 580 patients met inclusion criteria. Mean age was 48.65 ± 21 years, 73.3% were male. The mean Injury Severity Score was 22.71 ± 12.38, and the mean Abbreviated Injury Scale for body region head was 3.34 ± 1.06. Overall mortality was 14.7%. Only 46 (7.9%) patients had an ICP monitor inserted; however, a total of 107 (18%) patients met the definition of raised ICP. The mortality rate for patients with raised ICP was 50.4%. Independent predictors of raised ICP were as follows: age, older than 55 years (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.35-3.76), pupillary fixation (OR, 5.76; 95% CI, 3.16-10.50), signs of significant head trauma (OR, 2.431; 95% CI, 1.39-4.26), and need for intubation (OR, 3.589; 95% CI, 2.10-6.14). CONCLUSION: This study identified four independent variables associated with raised ICP and incorporated these findings into a preliminary risk assessment scale that can be implemented at the bedside to identify patients at significant risk of raised ICP. Future work is needed to prospectively validate these findings prior to clinical implementation. LEVEL OF EVIDENCE: Prognostic, Epidemiological, level III.