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Individualizing Thresholds of Cerebral Perfusion Pressure Using Estimated Limits of Autoregulation

Donnelly, Joseph MBChB1; Czosnyka, Marek PhD1,2; Adams, Hadie MD1; Robba, Chiara MD3,4; Steiner, Luzius A. PhD, MD5; Cardim, Danilo MSc1; Cabella, Brenno PhD1; Liu, Xiuyun MSc1; Ercole, Ari PhD, FFICM3; Hutchinson, Peter John FRCS SN, PhD6; Menon, David Krishna MD, PhD, FMedSci3; Aries, Marcel J. H. MD, PhD1,7; Smielewski, Peter PhD1

doi: 10.1097/CCM.0000000000002575
Clinical Investigations

Objectives: In severe traumatic brain injury, cerebral perfusion pressure management based on cerebrovascular pressure reactivity index has the potential to provide a personalized treatment target to improve patient outcomes. So far, the methods have focused on identifying “one” autoregulation-guided cerebral perfusion pressure target—called “cerebral perfusion pressure optimal”. We investigated whether a cerebral perfusion pressure autoregulation range—which uses a continuous estimation of the “lower” and “upper” cerebral perfusion pressure limits of cerebrovascular pressure autoregulation (assessed with pressure reactivity index)—has prognostic value.

Design: Single-center retrospective analysis of prospectively collected data.

Setting: The neurocritical care unit at a tertiary academic medical center.

Patients: Data from 729 severe traumatic brain injury patients admitted between 1996 and 2016 were used. Treatment was guided by controlling intracranial pressure and cerebral perfusion pressure according to a local protocol.

Interventions: None.

Methods and Main Results: Cerebral perfusion pressure-pressure reactivity index curves were fitted automatically using a previously published curve-fitting heuristic from the relationship between pressure reactivity index and cerebral perfusion pressure. The cerebral perfusion pressure values at which this “U-shaped curve” crossed the fixed threshold from intact to impaired pressure reactivity (pressure reactivity index = 0.3) were denoted automatically the “lower” and “upper” cerebral perfusion pressure limits of reactivity, respectively. The percentage of time with cerebral perfusion pressure below (%cerebral perfusion pressure < lower limit of reactivity), above (%cerebral perfusion pressure > upper limit of reactivity), or within these reactivity limits (%cerebral perfusion pressure within limits of reactivity) was calculated for each patient and compared across dichotomized Glasgow Outcome Scores. After adjusting for age, initial Glasgow Coma Scale, and mean intracranial pressure, percentage of time with cerebral perfusion pressure less than lower limit of reactivity was associated with unfavorable outcome (odds ratio %cerebral perfusion pressure < lower limit of reactivity, 1.04; 95% CI, 1.02–1.06; p < 0.001) and mortality (odds ratio, 1.06; 95% CI, 1.04–1.08; p < 0.001).

Conclusions: Individualized autoregulation-guided cerebral perfusion pressure management may be a plausible alternative to fixed cerebral perfusion pressure threshold management in severe traumatic brain injury patients. Prospective randomized research will help define which autoregulation-guided method is beneficial, safe, and most practical.

1Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom.

2Institute of Electronic Systems, Warsaw University of Technology, Warsaw, Poland.

3Division of Anaesthesia, Department of Medicine, Addenbrooke’s Hospital, University of Cambridge, Cambridge, United Kingdom.

4Department of Neuroscience, University of Genoa, Italy.

5Department of Anesthesia, Surgical Intensive Care, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel, University of Basel, Basel, Switzerland.

6Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke’s Hospital, University of Cambridge, Cambridge, United Kingdom.

7Department of Intensive Care, University of Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.

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Dr. Donnelly received support from a Woolf Fisher scholarship. Dr. Czosnyka has financial interest in a fraction of the licensing fee, and his institution received funding from Cambridge Enterprise, Cambridge, United Kingdom. Dr. Cardim disclosed other support from use of software developed in-house for data analysis. Dr. Liu received support for article research from the Bill & Melinda Gates Foundation. Dr. Hutchinson disclosed that he is a Director of Technicam manufacturer of the Cranial Access Device and he received support from a National Institute of Health Research (NIHR) Research Professorship, Academy of Medical Sciences/Health Foundation Senior Surgical Scientist Fellowship. Dr. Menon received other support from Ornim Medical, Shire Medical, Neurovive, and Calico; he received support for article research from the NIHR; his institution received funding from GlaxoSmithKline and Brainscope; and he received funding from Solvay and the NIHR Cambridge Biomedical Centre (RCZB/004) and an NIHR Senior Investigator Award (RCZB/014). Dr. Smielewski disclosed receiving a fraction of the licensing fees of the software, ICM+ (licensed by Cambridge Enterprise, United Kingdom), used for data collection and analysis in this study. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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