Feasibility of individualised severe traumatic brain injury management using an automated assessment of optimal cerebral perfusion pressure: the COGiTATE phase II study protocol

Erta Beqiri, Peter Smielewski, Chiara Robba, Marek Czosnyka, Manuel Teixeira Cabeleira, Jeanette Tas, Joseph Donnelly, Joanne G Outtrim, Peter Hutchinson, David Menon, Geert Meyfroidt, Bart Depreitere, Marcel J Aries, Ari Ercole, Erta Beqiri, Peter Smielewski, Chiara Robba, Marek Czosnyka, Manuel Teixeira Cabeleira, Jeanette Tas, Joseph Donnelly, Joanne G Outtrim, Peter Hutchinson, David Menon, Geert Meyfroidt, Bart Depreitere, Marcel J Aries, Ari Ercole

Abstract

Introduction: Individualising therapy is an important challenge for intensive care of patients with severe traumatic brain injury (TBI). Targeting a cerebral perfusion pressure (CPP) tailored to optimise cerebrovascular autoregulation has been suggested as an attractive strategy on the basis of a large body of retrospective observational data. The objective of this study is to prospectively assess the feasibility and safety of such a strategy compared with fixed thresholds which is the current standard of care from international consensus guidelines.

Methods and analysis: CPPOpt Guided Therapy: Assessment of Target Effectiveness (COGiTATE) is a prospective, multicentre, non-blinded randomised, controlled trial coordinated from Maastricht University Medical Center, Maastricht (The Netherlands). The other original participating centres are Cambridge University NHS Foundation Trust, Cambridge (UK), and University Hospitals Leuven, Leuven (Belgium). Adult severe TBI patients requiring intracranial pressure monitoring are randomised within the first 24 hours of admission in neurocritical care unit. For the control arm, the CPP target is the Brain Trauma Foundation guidelines target (60-70 mm Hg); for the intervention group an automated CPP target is provided as the CPP at which the patient's cerebrovascular reactivity is best preserved (CPPopt). For a maximum of 5 days, attending clinicians review the CPP target 4-hourly. The main hypothesis of COGiTATE are: (1) in the intervention group the percentage of the monitored time with measured CPP within a range of 5 mm Hg above or below CPPopt will reach 36%; (2) the difference in between groups in daily therapy intensity level score will be lower or equal to 3.

Ethics and dissemination: Ethical approval has been obtained for each participating centre. The results will be presented at international scientific conferences and in peer-reviewed journals.

Trial registration number: NCT02982122.

Keywords: COGiTATE; Optimal CPP; autoregulation; individualised TBI management; intensive care; precision medicine.

Conflict of interest statement

Competing interests: PS and MCz receive part of the licensing fees for multimodal brain monitoring software ICM+, licensed by Cambridge Enterprise Ltd, University of Cambridge, UK. There are no other conflicts of interest to declare.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Flowchart of the patients’ inclusion, randomisation and study procedures in the COGiTATE trial. BTF, Brain Trauma Foundation; CPP, cerebral perfusionpressure; CPPopt, optimal cerebral perfusion pressure; ICP, intracranial pressure; ICU, intensive care unit; TBI, traumatic brain injury.

References

    1. Stocchetti N, Carbonara M, Citerio G, et al. . Severe traumatic brain injury: targeted management in the intensive care unit. Lancet Neurol 2017;16:452–64. 10.1016/S1474-4422(17)30118-7
    1. Carney N, Totten AM, OʼReilly C, et al. . Guidelines for the management of severe traumatic brain injury, fourth edition. Neurosurgery 2016;80:1 10.1227/NEU.0000000000001432
    1. Maas AIR, Menon DK, Adelson PD, et al. . Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research. Lancet Neurol 2017;16:987–1048. 10.1016/S1474-4422(17)30371-X
    1. Menon DK, Ercole A. Critical care management of traumatic brain injury : Handbook of clinical neurology. Elsevier, 2017: 239–74.
    1. Czosnyka M, Smielewski P, Kirkpatrick P, et al. . Continuous assessment of the cerebral vasomotor reactivity in head injury. Neurosurgery 1997;41:11–19. 10.1097/00006123-199707000-00005
    1. Donnelly J, Aries MJ, Czosnyka M. Further understanding of cerebral autoregulation at the bedside: possible implications for future therapy. Expert Rev Neurother 2015;15:169–85. 10.1586/14737175.2015.996552
    1. Czosnyka M, Brady K, Reinhard M, et al. . Monitoring of cerebrovascular autoregulation: facts, myths, and missing links. Neurocrit Care 2009;10:373–86. 10.1007/s12028-008-9175-7
    1. Zweifel C, Lavinio A, Steiner LA, et al. . Continuous monitoring of cerebrovascular pressure reactivity in patients with head injury. Neurosurg Focus 2008;25:E2 10.3171/FOC.2008.25.10.E2
    1. Steiner LA, Czosnyka M, Piechnik SK, et al. . Continuous monitoring of cerebrovascular pressure reactivity allows determination of optimal cerebral perfusion pressure in patients with traumatic brain injury. Crit Care Med 2002;30:733–8. 10.1097/00003246-200204000-00002
    1. Aries MJH, Czosnyka M, Budohoski KP, et al. . Continuous determination of optimal cerebral perfusion pressure in traumatic brain injury*. Crit Care Med 2012;40:2456–63. 10.1097/CCM.0b013e3182514eb6
    1. Needham E, McFadyen C, Newcombe V, et al. . Cerebral perfusion pressure targets individualized to Pressure-Reactivity index in moderate to severe traumatic brain injury: a systematic review. J Neurotrauma 2017;34:963–70. 10.1089/neu.2016.4450
    1. Liu X, Maurits NM, Aries MJH, et al. . Monitoring of optimal cerebral perfusion pressure in traumatic brain injured patients using a Multi-Window weighting algorithm. J Neurotrauma 2017;34:3081–8. 10.1089/neu.2017.5003
    1. Dias C, Silva MJ, Pereira E, et al. . Optimal cerebral perfusion pressure management at bedside: a single-center pilot study. Neurocrit Care 2015;23:92–102. 10.1007/s12028-014-0103-8
    1. Jaeger M, Dengl M, Meixensberger J, et al. . Effects of cerebrovascular pressure reactivity-guided optimization of cerebral perfusion pressure on brain tissue oxygenation after traumatic brain injury. Crit Care Med 2010;38:1343–7. 10.1097/CCM.0b013e3181d45530
    1. Depreitere B, Güiza F, Van den Berghe G, et al. . Pressure autoregulation monitoring and cerebral perfusion pressure target recommendation in patients with severe traumatic brain injury based on minute-by-minute monitoring data. J Neurosurg 2014;120:1451–7. 10.3171/2014.3.JNS131500
    1. Kelly S, Bishop SM, Ercole A. Statistical signal properties of the Pressure-Reactivity index (Prx). Acta Neurochir Suppl 2018;126:317–20. 10.1007/978-3-319-65798-1_62
    1. Ercole A, Smielewski P, Aries MJH, et al. . Visualisation of the 'Optimal Cerebral Perfusion' Landscape in Severe Traumatic Brain Injury Patients. Acta Neurochir Suppl 2018;126:55–8. 10.1007/978-3-319-65798-1_12
    1. Zuercher P, Groen JL, Aries MJH, et al. . Reliability and validity of the therapy intensity level scale: analysis of Clinimetric properties of a novel approach to assess management of intracranial pressure in traumatic brain injury. J Neurotrauma 2016;33:1768–74. 10.1089/neu.2015.4266
    1. R Core Team R: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2013.
    1. Stephane Champely pwr: basic functions for power analysis. R package version 1.2-1, 2017. Available:

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere