Outcomes and physiologic responses associated with ketamine administration after traumatic brain injury in the United States and Canada: a retrospective analysis

Abstract

Purpose: Ketamine has historically been contraindicated in traumatic brain injury (TBI) due to concern for raising intracranial pressure. However, it is increasingly being used in TBI due to the fa-vorable respiratory and hemodynamic properties. To date, no studies have evaluated whether ket-amine administered in subjects with TBI is associated with patient survival or disability. Methods: We performed a retrospective analysis of data from the multicenter Prehospital Tranexamic Acid Use for Traumatic Brain Injury trial, comparing ketamine-exposed and ket-amine-unexposed TBI subjects to determine whether an association exists between ketamine administration and mortality, as well as secondary outcome measures. Results: We analyzed 841 eligible subjects from the original study, of which 131 (15.5%) received ketamine. Ketamine-exposed subjects were younger (37.3±16.9 years vs. 42.0±18.6 years, P=0.037), had a worse initial Glasgow Coma Scale score (7±3 vs. 8±4, P=0.003), and were more likely to be in-tubated than ketamine-unexposed subjects (88.5% vs. 44.2%, P<0.001). Overall, there was no differ-ence in mortality (12.2% vs. 15.5%, P=0.391) or disability measures between groups. Ketamine-ex-posed subjects had significantly fewer instances of elevated intracranial pressure (ICP) compared to ketamine-unexposed subjects (56.3% vs. 82.3%, P=0.048). In the very rare outcomes of cardiac events and seizure activity, seizure activity was statistically more likely in ketamine-exposed subjects (3.1% vs. 1.0%, P=0.010). In the intracranial hemorrhage subgroup, cardiac events were more likely in ketamine-exposed subjects (2.3% vs. 0.2%, P=0.025). Ketamine exposure was associated with a smaller increase in TBI protein biomarker concentrations. Conclusions: Ketamine administration was not associated with worse survival or disability despite being administered to more severely injured subjects. Ketamine exposure was associated with reduced el-evations of ICP, more instances of seizure activity, and lower concentrations of TBI protein biomarkers.