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Impact of Therapeutic Interventions on Cerebral Autoregulatory Function Following Severe Traumatic Brain Injury: A Secondary Analysis of the BOOST-II Study

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Abstract

Background

The Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II randomized controlled trial used a tier-based management protocol based on brain tissue oxygen (PbtO2) and intracranial pressure (ICP) monitoring to reduce brain tissue hypoxia after severe traumatic brain injury. We performed a secondary analysis to explore the relationship between brain tissue hypoxia, blood pressure (BP), and interventions to improve cerebral perfusion pressure (CPP). We hypothesized that BP management below the lower limit of autoregulation would lead to cerebral hypoperfusion and brain tissue hypoxia that could be improved with hemodynamic augmentation.

Methods

Of the 119 patients enrolled in the Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II trial, 55 patients had simultaneous recordings of arterial BP, ICP, and PbtO2. Autoregulatory function was measured by interrogating changes in ICP and PbtO2 in response to fluctuations in CPP using time-correlation analysis. The resulting autoregulatory indices (pressure reactivity index and oxygen reactivity index) were used to identify the “optimal” CPP and limits of autoregulation for each patient. Autoregulatory function and percent time with CPP outside personalized limits of autoregulation were calculated before, during, and after all interventions directed to optimize CPP.

Results

Individualized limits of autoregulation were computed in 55 patients (mean age 38 years, mean monitoring time 92 h). We identified 35 episodes of brain tissue hypoxia (PbtO2 < 20 mm Hg) treated with CPP augmentation. Following each intervention, mean CPP increased from 73 ± 14 mm Hg to 79 ± 17 mm Hg (p = 0.15), and mean PbtO2 improved from 18.4 ± 5.6 mm Hg to 21.9 ± 5.6 mm Hg (p = 0.01), whereas autoregulatory function trended toward improvement (oxygen reactivity index 0.42 vs. 0.37, p = 0.14; pressure reactivity index 0.25 vs. 0.21, p = 0.2). Although optimal CPP and limits remained relatively unchanged, there was a significant decrease in the percent time with CPP below the lower limit of autoregulation in the 60 min after compared with before an intervention (11% vs. 23%, p = 0.05).

Conclusions

Our analysis suggests that brain tissue hypoxia is associated with cerebral hypoperfusion characterized by increased time with CPP below the lower limit of autoregulation. Interventions to increase CPP appear to improve autoregulation. Further studies are needed to validate the importance of autoregulation as a modifiable variable with the potential to improve outcomes.

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Author notes

  1. Adam de Havenon and Nils H. Petersen contributed equally to this work.

Authors and Affiliations

  1. Division of Neurocritical Care and Emergency, Department of Neurology, Yale University School of Medicine, 15 York St, LCI 1003, New Haven, CT, CT 06510, USA

    Ayush Prasad, Emily J. Gilmore, Jennifer A. Kim, Liza Begunova, Madelynne Olexa, Rachel Beekman, Guido J. Falcone, Adam de Havenon & Nils H. Petersen

  2. Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA

    Charles Matouk

  3. Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA, USA

    Santiago Ortega-Gutierrez

  4. Department of Neurological Surgery, University of Washington, Seattle, WA, USA

    Nancy R. Temkin

  5. Department of Biostatistics, University of Washington, Seattle, WA, USA

    Nancy R. Temkin & Jason Barber

  6. Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    Ramon Diaz-Arrastia

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  1. Ayush Prasad
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Contributions

AP, AdH, and NHP contributed to the study concept and design. NRT, JB, and RDA contributed to data acquisition. AP, EJG, SOG, AdH, and NHP contributed to the analyses and interpretation of data. AP, EJG, JAK, LB, MO, RB, GJF, CM, SOG, NRT, JB, RDA, AdH, and NHP contributed to the drafting and critical revisions of the manuscript. All authors have approved the final manuscript.

Corresponding author

Correspondence to Nils H. Petersen.

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Conflict of interest

NHP is supported by the National Institutes of Health - National Institute of Neurological Disorders and Stroke (NIH-NINDS) (K23NS110980) and has received clinical research funding from Liminal Sciences. ADH is supported by NIH-NINDS (K23NS105924), has received investigator-initiated clinical research funding from the AAN, has received consultant fees from Integra and Novo Nordisk, has equity in TitinKM and Certus, and receives author fees from UpToDate. EJG is supported by NIH-NINDS (R01NS117904) and receives consulting fees from UCB. SOG is supported by NIH-NINDS (R01NS127114, R03NS1202228), industry investigator-initiated grants from Stryker Neurovascular, Medtronic, Microvention, Methinks, and VizAi, and Society of Vascular and Interventional Neurology, and consulting fees from Medtronic, Stryker, and Microvention. CCM is supported by NIH-NINDS R21NS119992, receives consulting fees from Microvention-Terumo and Stryker, and speaker fees from Penumbra and Silk Road Medical. NRT and JB are supported by NIH-NINDS (U01NS099084).

Ethical Approval/Informed Consent

The Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II trial was approved by the local institutional review board at each participating center, and proxy informed consent was obtained from each study participant. This secondary analysis was performed on deidentified data obtained from the Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II investigators under a data use agreement.

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Prasad, A., Gilmore, E.J., Kim, J.A. et al. Impact of Therapeutic Interventions on Cerebral Autoregulatory Function Following Severe Traumatic Brain Injury: A Secondary Analysis of the BOOST-II Study. Neurocrit Care (2023). https://doi.org/10.1007/s12028-023-01896-x

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