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

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 favorable respiratory and hemodynamic properties. To date, no studies have evaluated whether ketamine 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 ketamine-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 intubated than ketamine-unexposed subjects (88.5% vs. 44.2%, P<0.001). Overall, there was no difference in mortality (12.2% vs. 15.5%, P=0.391) or disability measures between groups. Ketamine-exposed 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 elevations of ICP, more instances of seizure activity, and lower concentrations of TBI protein biomarkers. Keywords: Ketamine; Traumatic brain injuries; Biomarkers; Intracranial pressure; Glial fibrillary acidic protein