Therapeutic review: The role of tranexamic acid in management of traumatic brain injury, nontraumatic intracranial hemorrhage, and aneurysmal subarachnoid hemorrhage.

PURPOSE: To summarize current literature evaluating tranexamic acid in the management of intracranial bleeding associated with traumatic and nontraumatic brain injuries and implications for clinical practice. SUMMARY: Intracranial hemorrhage, regardless of etiology, is associated with high morbidity and mortality. Tranexamic acid is an antifibrinolytic with anti-inflammatory properties shown to reduce mortality in trauma patients with extracranial injuries. In traumatic brain injury, a large randomized trial found no difference in outcomes when tranexamic acid was compared to placebo; however, subgroup analyses suggested that it may reduce head injury-related mortality in the context of mild-to-moderate injury if treatment occurs within 1 hour of symptom onset. More recent out-of-hospital data have disputed these findings and even suggested harm in severely injured patients. In spontaneous, nontraumatic intracranial hemorrhage, treatment with tranexamic acid did not result in a difference in functional status; however, rates of hematoma expansion, even though modest, were significantly reduced. In aneurysmal subarachnoid hemorrhage, tranexamic acid may prevent rebleeding, but has not led to improved outcomes or reduced mortality, and there is concern for increased incidence of delayed cerebral ischemia. Overall, tranexamic acid has not been shown to result in increased risk of thromboembolic complications across these classes of brain injury. CONCLUSION: Despite its favorable safety profile overall, tranexamic acid does not seem to improve functional outcomes and cannot be routinely recommended. More data are needed to determine which head injury subpopulations are most likely to benefit from tranexamic acid and which patients are at increased risk for harm.

Evaluation of Levetiracetam Dosing Strategies for Seizure Prophylaxis Following Traumatic Brain Injury.

BACKGROUND: Although levetiracetam has been increasingly used as an alternative to phenytoin for early posttraumatic seizure prophylaxis following traumatic brain injury (TBI), an optimal dosing strategy has not been elucidated. The objective of this study is to determine whether different dosing strategies of levetiracetam are associated with the incidence of early posttraumatic seizures when used as prophylaxis following TBI. METHODS: This retrospective single-center cohort study included admitted patients ≥ 18 years of age with a diagnosis of TBI and receiving levetiracetam for early posttraumatic seizure prophylaxis between July 1, 2013, and September 1, 2019. The primary outcome of this study was to evaluate three different dosing strategies of levetiracetam (≤ 1000 mg/day, 1500 mg/day, and ≥ 2000 mg/day) and associated rates of early posttraumatic seizures. Secondary outcomes were to summarize absolute total daily maintenance doses of levetiracetam among patients who experienced early posttraumatic seizures compared with those who did not, to determine the impact of three different dosing strategies on hospital length of stay and in-hospital mortality, and to assess patient-specific variables on the occurrence of posttraumatic seizures. Overlap propensity score weighting was used to address the potential for confounding. RESULTS: Of the 1287 patients who received levetiracetam for early posttraumatic seizure prophylaxis during the study time frame, 866 patients met eligibility criteria and were included in the study cohort (289 patients in the ≤ 1000 mg/day group, 137 patients in the 1500 mg/day group, and 440 patients in the ≥ 2000 mg/day group). After weighting, the cumulative incidence of early posttraumatic seizure was 2.9% in the ≤ 1000 mg/day group, 8.8% in the 1500 mg/day group, and 9% in the ≥ 2000 mg/day group. The 1500 mg/day and ≥ 2000 mg/day levetiracetam groups had a 209% and 216% increase in the subdistribution hazard of early posttraumatic seizures compared with the ≤ 1000 mg/day levetiracetam group, respectively, but these differences were not statistically significant. CONCLUSIONS: In conclusion, the results of this study demonstrate no statistically significant difference in the cumulative incidence of early posttraumatic seizures within 7 days of TBI between three different levetiracetam dosing strategies. After weighting, the ≤ 1000 mg/day levetiracetam group had the lowest rates of early posttraumatic seizures, death without seizure, and in-hospital mortality.

Assessment of Acute Kidney Injury in Neurologically Injured Patients Receiving Hypertonic Sodium Chloride: Does Chloride Load Matter?

Background: Increasing evidence suggests that large-volume infusions of 0.9% sodium chloride (NaCl) for resuscitation are associated with hyperchloremic metabolic acidosis, renal vasoconstriction, and increased risk of acute kidney injury (AKI). Patients with neurological injury may require hypertonic NaCl for therapeutic hypernatremia, treatment of cerebral salt wasting, hyponatremia, or elevated intracranial pressure. Consequently, this increased exposure to chloride may result in an increased risk for development of AKI. Objective: The primary aim of this study was to describe the risk for development of AKI in neurologically injured patients receiving large volumes of intravenous hypertonic NaCl. Methods: This single-center, retrospective study looked at neurologically injured patients who received hypertonic NaCl and sodium acetate. Data were collected to assess renal function, hyperchloremia, and acidemia. Receiver operating characteristic (ROC) curve analysis was used to determine the predictive association between the amount of daily and overall chloride exposure and development of AKI. Results: A total of 301 patients were screened, and of those, 142 were included. Of the 142 patients included, 13% developed AKI, and 38% developed hyperchloremia. Additionally, 32% of patients were switched from NaCl to sodium acetate after an average of 3.4 ± 1.5 days of NaCl therapy. The ROC curve demonstrated that if patients received greater than 2055 mEq of chloride over 7 days, they were more likely to develop AKI (sensitivity 72%, specificity 70%; P = 0.002; area under the curve = 0.7). Conclusion and Relevance: Neurologically injured patients receiving hypertonic sodium therapy with a high chloride load are at risk of developing hyperchloremia and AKI.