Individualising Neurointensive Care of Traumatic Brain Injury: Reduced Signal Complexity Relates to Secondary Insults and Predicts Worse Outcome.

BACKGROUND: Autonomic nervous system (ANS) dysfunction and reduced signal complexity (SC) appear to occur after traumatic brain injury (TBI) and may reflect impaired physiological adaptability. However, their relationships with cerebral physiology and functional outcome during neurointensive care (NIC) remain incompletely understood. This study explores heart rate variability (HRV), baroreflex sensitivity (BRS) and multiscale entropy-derived SC of systemic and cerebral signals in patients with moderate-to-severe TBI during NIC. METHODS: This retrospective, single-centre study included 649 TBI patients with intracranial pressure (ICP) monitoring for longer than 24 h, treated in the NIC unit at Uppsala University Hospital, Sweden (2008-2024). HRV, BRS and SC (multiscale entropy complexity index) of heart rate (HR), mean arterial pressure (MAP), ICP, ICP pulse amplitude (AMP) and cerebral perfusion pressure (CPP), respectively, were analysed over the first 10 days of NIC. Associations with demographics, injury severity, NIC physiology (ICP, CPP, pressure reactivity index [PRx]) and 6-month Glasgow Outcome Scale-Extended (GOSE) were assessed using Spearman's correlations, multivariable ordinal logistic regression and two-variable outcome heatmaps. RESULTS: In multivariable regression (adjusted for age, Glasgow Coma Scale motor score [GCS M], pupillary reactivity, ICP, CPP and PRx) higher HRV and SC of each of HR, ICP, AMP and CPP independently correlated with better functional outcome in separate models. Outcome heatmaps demonstrated that reduced SC combined with high ICP, low CPP or high PRx was particularly associated with poor recovery. Lower admission GCS M, barbiturate use and decompressive craniectomy were generally associated with reduced HRV, BRS and SC. Higher ICP and PRx and lower CPP correlated with reduced systemic and cerebral SC. CONCLUSIONS: Reduced SC and HRV are independently associated with worse outcome after TBI, even when adjusted for conventional NIC predictors. Reduced SC may co-occur with higher ICP and PRx and lower CPP in TBI.