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Background: The 'CPPopt-Guided Therapy: Assessment of Target Effectiveness' (COGiTATE) randomised controlled trial demonstrated the feasibility and safety of targeting an automated cerebral perfusion pressure (CPP) tailored to optimize cerebrovascular autoregulation (CPPopt) in patients with traumatic brain injury (TBI) requiring intracranial pressure management. The average values of the autoregulation index known as the pressure reactivity index (PRx) were not different between the intervention (CPP target = CPPopt) and control (CPP target = 60-70 mmHg) groups of the trial. This secondary analysis was performed to investigate whether: (1) in the intervention group, PRx was closer to PRxopt (PRx at CPPopt) values, indicating a more preserved reactivity, as opposed to in the control group; (2) in the intervention group, patients experienced lower hourly PRx when CPP was close to the CPPopt-based target., Methods: We analyzed data from the 28 and 32 patients randomized to the control and intervention groups of the COGiTATE study, respectively. We compared hourly averaged ΔPRx (PRx minus PRxopt, where PRxopt is PRx at CPPopt) between the two groups, focusing on periods of globally preserved/homogeneous autoregulation (negative PRxopt). For each patient in the intervention group, PRx values in periods when ΔCPP (CPP minus CPPopt target) was between -5 and + 5 mm Hg were compared to values in periods when ΔCPP was outside this range., Results: The median ΔPRx was significantly lower in the intervention group for negative PRxopt (Mann-Whitney U-test, p < 0.001). For each patient in this group, the median PRx was lower in periods when CPP was close to the CPPopt-based target (Wilcoxon test, p < 0.001)., Conclusions: Despite no statistically significant difference in the grand mean PRx, our results suggest that targeting CPPopt does provide a way of improving cerebrovascular reactivity in patients with TBI, offering a rational intervention for trials that address this issue. We also bring insight into aspects of the PRx/CPP relationship that should be considered for autoregulation-guided management for future clinical protocols and trials design., Competing Interests: Conflicts of Interest: PS and MC receive part of the licensing fees for multimodal brain monitoring software ICM + , licensed by Cambridge Enterprise Ltd, University of Cambridge, UK. DKM reports research funding or consultancy agreements with the following entities: Calico Inc; GlaxoSmithKline Ltd; Integra LifeSciences; Lantmannen AB; NeuroTrauma Sciences; and PressuraNeuro Ltd. All the other authors report no conflicts of interest. Ethical Approval/Informed Consent: This analysis was a secondary analysis on the data of the COGiTATE trial. The main study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Maastricht University Medical Center (December 29, 2017/METC171023), the Health Research Authority National Health System United Kingdom (October 30, 2017, Research Ethics Reference 17/LO/119), the Ethics Committee of Academic Hospital Leuven (January 9, 2018, B322201834820), and the Ethics Committee of Radboud University Medical Center (February 20, 2019, RvB19.51633). For the COGiTATE study, informed consent was obtained from individual participants included in the study or their legal representatives according to the local country laws., (© 2024. The Author(s).)

Managing traumatic brain injury (TBI) patients with a cerebral perfusion pressure (CPP) near to the cerebral autoregulation (CA)-guided "optimal" CPP (CPPopt) value is associated with improved outcome and might be useful to individualize care, but has never been prospectively evaluated. This study evaluated the feasibility and safety of CA-guided CPP management in TBI patients requiring intracranial pressure monitoring and therapy (TBIicp patients). The CPPopt Guided Therapy: Assessment of Target Effectiveness (COGiTATE) parallel two-arm feasibility trial took place in four tertiary centers. TBIicp patients were randomized to either the Brain Trauma Foundation (BTF) guideline CPP target range (control group) or to the individualized CA-guided CPP targets (intervention group). CPP targets were guided by six times daily software-based alerts for up to 5 days. The primary feasibility end-point was the percentage of time with CPP concordant (±5 mm Hg) with the set CPP targets. The main secondary safety end-point was an increase in therapeutic intensity level (TIL) between the control and intervention group. Twenty-eight patients were randomized to the control and 32 patients to the intervention group. CPP in the intervention group was in the target range for 46.5% (interquartile range, 41.2-58) of the monitored time, significantly higher than the feasibility target specified in the published protocol (36%; p  < 0.001). There were no significant differences between groups for TIL or for other safety end-points. Conclusively, targeting an individual and dynamic CA-guided CPP is feasible and safe in TBIicp patients. This encourages a prospective trial powered for clinical outcomes.