Intracranial Pressure (ICP) Trajectories: a Novel Tool that may Inform Outcome and Mortality in Severe Traumatic Brain Injury (P4.299)

Objective: 1) define ICP-trajectories over time in severe TBI, 2) determine whether ICP-trajectory groups predict outcome 3) determine whether ABCC8 -genetic polymorphisms associated with traditional edema-measures differed across ICP-trajectory groups. Background: ICP is dynamic and influenced by genetics, TBI injury complex and medical/surgical treatments. Existing studies use point ICP-measures for patient categorization with important temporal trends potentially lost. ABCC8 , encoding sulfonylurea-receptor-1 is a putative regulator of cerebral edema in TBI and other neurological diseases. Design/Methods: We included prospective observational data from 446 severe TBI patients (GCS≤ 8, 2001–2014). Trajectories were modeled from hourly ICP measurements (hours 1–120 after ventriculostomy/monitor placement). We used Group Based Trajectory Modeling (GBTM) incorporating clinically relevant risk factor adjustment (age, sex, initial GCS score, emergent craniectomy, primary hemorrhage pattern). We employed censored-normal distributions and Bayesian Information Criteria to select best models. We compared 6-month disability, mortality, and relevant ABCC8 tag-single-nucleotide polymorphisms (rs2237982, rs7105832) across ICP-trajectory groups. Results: A six trajectory-group model best fit the data, identifying subcohorts that differed in initial ICP, ICP-evolution/longitudinal trajectory, and number of ICP spikes >20 mmHg. There were pattern differences in age, hemorrhage pattern, and craniectomy rates between groups. Glasgow Outcome Scale score (p=0.006), Disability Rating Scale score (p=0.001), mortality (p Conclusions: We employed a novel dynamic ICP-classification approach to investigate patterns in severe TBI and identified 6 distinct ICP-trajectory groups. Disability, mortality and ABCC8 polymorphism rs2237982 differed across groups. Groups with more favorable outcomes had greater ICP variability. Trajectory modeling may represent a powerful new vista to ICP-directed care. Combining patient characteristics with ICP-trajectory groups may help prognosticate and guide precision-medicine. Study Supported by: Research reported in this publication was supported by the following grants to which we are grateful: NIH(NINDS) K23NS101036 (RMJ), NIH(NINDS) 1K23NS097629 (JE) NINR R01NR013342 (YPC), NINR R00 NR013176 (AMP), NCATS KL2-TR000146 (RMJ), NCATS KL2-TR001856 (RMJ). Disclosure: Dr. Jha has nothing to disclose. Dr. Elmer has nothing to disclose. Dr. Zusman has nothing to disclose. Dr. Puccio has nothing to disclose. Dr. Okonkwo has nothing to disclose. Dr. Park has nothing to disclose. Dr Shutter has nothing to disclose. Dr. Wallisch has nothing to disclose. Dr. Conley has nothing to disclose. Dr. Kochanek has nothing to disclose.