Dynamic versus fixed cerebral perfusion pressure targets in paediatric traumatic brain injury: a STARSHIP analysisResearch in context

Summary: Background: Cerebral perfusion pressure (CPP) represents a key target for intensive care management of paediatric traumatic brain injury (TBI) patients. Current guidelines recommend a CPP target within the range of 40–50 mmHg but emphasise that these may depend on patient age and the state...

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Main Authors: C.A. Smith, S.Y. Bögli, M.M. Placek, M. Cabeleira, D. White, E. Daubney, A. Young, E. Beqiri, R. Kayani, R. O'Donnell, N. Pathan, S. Watson, A. Maw, M. Garnett, H.K. Kanthimathinathan, H. Bangalore, S. Sundararajan, G. Subramanian, D. Raffaj, S. Lampariello, A. Sarfatti, A. Mayer, O. Ross, M. Czosnyka, P.J. Hutchinson, P. Smielewski, S. Agrawal, Shruti Agrawal, Peter Smielewski, Peter J. Hutchinson, Stefan Yu Bögli, Claudia A. Smith, Carly Tooke, Caroline Payne, Holly Belfield, Amisha Mistry, Collette Spencer, Claire Jennings, Lara Bunni, Laura Anderson, Emily Morgan, Melanie James, Rebecca Beckley, Tahnima Khatun, Hafiza Khatun, Olivia Nugent, Richard Aldridge, Ruth Morgan, Julie Morcombe, Martin Quinton, Catherine Postlethwaite, Jenny Pond, Jessica Cutler, Caitlin Oxford, Marek Czosnyka, Michal Placek, Manuel Cabaleira, Deborah White, Esther Daubney, Adam Young, Erta Beqiri, Riaz Kayani, Roddy O'Donnell, Nazima Pathan, Suzanna Watson, Anna Maw, Matthew Garnett, Hari Krishnan Kanthimathinathan, Harish Bangalore, Santosh Sundararajan, Gayathri Subramanian, Dusan Raffaj, Simona Lampariello, Avishay Sarfatti, Anton Mayer, Oliver Ross
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Language:English
Published: Elsevier 2025-08-01
Series:EClinicalMedicine
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589537025003025
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author C.A. Smith
S.Y. Bögli
M.M. Placek
M. Cabeleira
D. White
E. Daubney
A. Young
E. Beqiri
R. Kayani
R. O'Donnell
N. Pathan
S. Watson
A. Maw
M. Garnett
H.K. Kanthimathinathan
H. Bangalore
S. Sundararajan
G. Subramanian
D. Raffaj
S. Lampariello
A. Sarfatti
A. Mayer
O. Ross
M. Czosnyka
P.J. Hutchinson
P. Smielewski
S. Agrawal
Shruti Agrawal
Peter Smielewski
Peter J. Hutchinson
Stefan Yu Bögli
Claudia A. Smith
Carly Tooke
Caroline Payne
Holly Belfield
Amisha Mistry
Collette Spencer
Claire Jennings
Lara Bunni
Laura Anderson
Emily Morgan
Melanie James
Rebecca Beckley
Tahnima Khatun
Hafiza Khatun
Olivia Nugent
Richard Aldridge
Ruth Morgan
Julie Morcombe
Martin Quinton
Catherine Postlethwaite
Jenny Pond
Jessica Cutler
Caitlin Oxford
Marek Czosnyka
Michal Placek
Manuel Cabaleira
Deborah White
Esther Daubney
Adam Young
Erta Beqiri
Riaz Kayani
Roddy O'Donnell
Nazima Pathan
Suzanna Watson
Anna Maw
Matthew Garnett
Hari Krishnan Kanthimathinathan
Harish Bangalore
Santosh Sundararajan
Gayathri Subramanian
Dusan Raffaj
Simona Lampariello
Avishay Sarfatti
Anton Mayer
Oliver Ross
author_facet C.A. Smith
S.Y. Bögli
M.M. Placek
M. Cabeleira
D. White
E. Daubney
A. Young
E. Beqiri
R. Kayani
R. O'Donnell
N. Pathan
S. Watson
A. Maw
M. Garnett
H.K. Kanthimathinathan
H. Bangalore
S. Sundararajan
G. Subramanian
D. Raffaj
S. Lampariello
A. Sarfatti
A. Mayer
O. Ross
M. Czosnyka
P.J. Hutchinson
P. Smielewski
S. Agrawal
Shruti Agrawal
Peter Smielewski
Peter J. Hutchinson
Stefan Yu Bögli
Claudia A. Smith
Carly Tooke
Caroline Payne
Holly Belfield
Amisha Mistry
Collette Spencer
Claire Jennings
Lara Bunni
Laura Anderson
Emily Morgan
Melanie James
Rebecca Beckley
Tahnima Khatun
Hafiza Khatun
Olivia Nugent
Richard Aldridge
Ruth Morgan
Julie Morcombe
Martin Quinton
Catherine Postlethwaite
Jenny Pond
Jessica Cutler
Caitlin Oxford
Marek Czosnyka
Michal Placek
Manuel Cabaleira
Deborah White
Esther Daubney
Adam Young
Erta Beqiri
Riaz Kayani
Roddy O'Donnell
Nazima Pathan
Suzanna Watson
Anna Maw
Matthew Garnett
Hari Krishnan Kanthimathinathan
Harish Bangalore
Santosh Sundararajan
Gayathri Subramanian
Dusan Raffaj
Simona Lampariello
Avishay Sarfatti
Anton Mayer
Oliver Ross
author_sort C.A. Smith
collection DOAJ
description Summary: Background: Cerebral perfusion pressure (CPP) represents a key target for intensive care management of paediatric traumatic brain injury (TBI) patients. Current guidelines recommend a CPP target within the range of 40–50 mmHg but emphasise that these may depend on patient age and the state of cerebrovascular autoregulation. In this analysis, we aimed to compare the fixed targets proposed by the Brain Trauma Foundation to autoregulation-based targets CPPopt (optimal CPP) and LLA (Lower Limit of Autoregulation). Methods: Data were acquired from the STARSHIP study (a prospective, multicentre, observational, research study which enrolled 135 children (median age 96 months (interquartile range 26–152 months)) with TBI between July 2018 and March 2023 across 10 paediatric intensive care units in the UK). In this secondary analysis the dose or percentage time spent below a fixed CPP target of 50 mmHg or CPPopt or LLA (assessed continuously on a minute-by-minute basis and derived by fitting a curve to the relationship between CPP and pressure reactivity index values, as previously described) was compared by outcome using univariable and multivariable methods. ClinicalTrials.gov registration–NCT0688462. Findings: When assessed within ordinal analyses (to account for differences in baseline severity), both hourly dose and percentage time spent below LLA (odds ratio 1.01 [95% CI 1.00–1.02], p = 0.017 and 1.05 [95% CI 1.01–1.08], p = 0.008 respectively) were independently associated with worse outcomes. LLA displayed a dynamic time-trend increasing over time in patients with unfavourable outcome (n = 44, p = 0.003). Overall, LLA exceeded 50 mmHg for more than 45% of the monitoring period across all patients, and for over 35% of the time in the youngest cohort (0–2 years). Interpretation: Dynamic autoregulation monitoring based on LLA was associated with outcomes in paediatric TBI with higher LLA values observed in individuals experiencing unfavourable outcomes. Our findings indicate that the current fixed CPP threshold of 40–50 mmHg may be too low–highlighting the need for further investigation into autoregulation-guided CPP targets. Whether personalised management based on autoregulatory-informed thresholds offers advantages over guideline-based targets remains to be determined and should be investigated in future prospective interventional studies. Funding: Action Medical Research for Childrens' Charity and Addenbrookes Charitable Trust (UK Grant number–GN2609).
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spelling doaj-art-09121d56129d4e25a22fce82d8e021352025-08-20T03:25:05ZengElsevierEClinicalMedicine2589-53702025-08-018610337010.1016/j.eclinm.2025.103370Dynamic versus fixed cerebral perfusion pressure targets in paediatric traumatic brain injury: a STARSHIP analysisResearch in contextC.A. Smith0S.Y. Bögli1M.M. Placek2M. Cabeleira3D. White4E. Daubney5A. Young6E. Beqiri7R. Kayani8R. O'Donnell9N. Pathan10S. Watson11A. Maw12M. Garnett13H.K. Kanthimathinathan14H. Bangalore15S. Sundararajan16G. Subramanian17D. Raffaj18S. Lampariello19A. Sarfatti20A. Mayer21O. Ross22M. Czosnyka23P.J. Hutchinson24P. Smielewski25S. Agrawal26Shruti AgrawalPeter SmielewskiPeter J. HutchinsonStefan Yu BögliClaudia A. SmithCarly TookeCaroline PayneHolly BelfieldAmisha MistryCollette SpencerClaire JenningsLara BunniLaura AndersonEmily MorganMelanie JamesRebecca BeckleyTahnima KhatunHafiza KhatunOlivia NugentRichard AldridgeRuth MorganJulie MorcombeMartin QuintonCatherine PostlethwaiteJenny PondJessica CutlerCaitlin OxfordMarek CzosnykaMichal PlacekManuel CabaleiraDeborah WhiteEsther DaubneyAdam YoungErta BeqiriRiaz KayaniRoddy O'DonnellNazima PathanSuzanna WatsonAnna MawMatthew GarnettHari Krishnan KanthimathinathanHarish BangaloreSantosh SundararajanGayathri SubramanianDusan RaffajSimona LamparielloAvishay SarfattiAnton MayerOliver RossDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UKDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UK; Department for Neurology and Neurocritical Care Unit, University Hospital and University of Zurich, Zurich, Switzerland; Corresponding author. Department of Neurology and Neurocritical Care Unit, University Hospital and University of Zurich, Zurich, Switzerland.Department of Clinical Neurosciences, University of Cambridge, Cambridge, UKDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UK; Department of Mechanical Engineering, University College London, London, UKDepartment of Paediatrics, University of Cambridge, Cambridge, UK; Paediatric Intensive Care, Cambridge University Hospitals, Cambridge, UKDepartment of Paediatrics, University of Cambridge, Cambridge, UK; Paediatric Intensive Care, Cambridge University Hospitals, Cambridge, UKDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UKDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UKPaediatric Intensive Care, Cambridge University Hospitals, Cambridge, UKPaediatric Intensive Care, Cambridge University Hospitals, Cambridge, UKDepartment of Paediatrics, University of Cambridge, Cambridge, UK; Paediatric Intensive Care, Cambridge University Hospitals, Cambridge, UKPaediatric Neuropsychology, Cambridge and Peterborough NHS Foundation Trust, Cambridge, UKDepartment of Paediatrics, University of Cambridge, Cambridge, UKDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UKPaediatric Intensive Care, Birmingham Children's Hospital, Birmingham, UKPaediatric Intensive Care, Great Ormond Street Hospital, London, UKPaediatric Intensive Care, Leeds Children's Hospital, Leeds, UKPaediatric Intensive Care, Manchester Children's Hospital, Manchester, UKPaediatric Intensive Care, Nottingham Children's Hospital, Nottingham, UKPaediatric Intensive Care, Oxford University Hospitals, Oxford, UKPaediatric Intensive Care, Royal London Hospital, London, UKPaediatric Intensive Care, Sheffield Children's Hospital, Sheffield, UKPaediatric Intensive Care, Southampton General Hospital, Southampton, UKDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UK; Institute of Electronic Systems, Warsaw University of Technology, PolandDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UKDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UKDepartment of Paediatrics, University of Cambridge, Cambridge, UK; Paediatric Intensive Care, Cambridge University Hospitals, Cambridge, UKSummary: Background: Cerebral perfusion pressure (CPP) represents a key target for intensive care management of paediatric traumatic brain injury (TBI) patients. Current guidelines recommend a CPP target within the range of 40–50 mmHg but emphasise that these may depend on patient age and the state of cerebrovascular autoregulation. In this analysis, we aimed to compare the fixed targets proposed by the Brain Trauma Foundation to autoregulation-based targets CPPopt (optimal CPP) and LLA (Lower Limit of Autoregulation). Methods: Data were acquired from the STARSHIP study (a prospective, multicentre, observational, research study which enrolled 135 children (median age 96 months (interquartile range 26–152 months)) with TBI between July 2018 and March 2023 across 10 paediatric intensive care units in the UK). In this secondary analysis the dose or percentage time spent below a fixed CPP target of 50 mmHg or CPPopt or LLA (assessed continuously on a minute-by-minute basis and derived by fitting a curve to the relationship between CPP and pressure reactivity index values, as previously described) was compared by outcome using univariable and multivariable methods. ClinicalTrials.gov registration–NCT0688462. Findings: When assessed within ordinal analyses (to account for differences in baseline severity), both hourly dose and percentage time spent below LLA (odds ratio 1.01 [95% CI 1.00–1.02], p = 0.017 and 1.05 [95% CI 1.01–1.08], p = 0.008 respectively) were independently associated with worse outcomes. LLA displayed a dynamic time-trend increasing over time in patients with unfavourable outcome (n = 44, p = 0.003). Overall, LLA exceeded 50 mmHg for more than 45% of the monitoring period across all patients, and for over 35% of the time in the youngest cohort (0–2 years). Interpretation: Dynamic autoregulation monitoring based on LLA was associated with outcomes in paediatric TBI with higher LLA values observed in individuals experiencing unfavourable outcomes. Our findings indicate that the current fixed CPP threshold of 40–50 mmHg may be too low–highlighting the need for further investigation into autoregulation-guided CPP targets. Whether personalised management based on autoregulatory-informed thresholds offers advantages over guideline-based targets remains to be determined and should be investigated in future prospective interventional studies. Funding: Action Medical Research for Childrens' Charity and Addenbrookes Charitable Trust (UK Grant number–GN2609).http://www.sciencedirect.com/science/article/pii/S2589537025003025Paediatric traumatic brain injuryMultimodality neuromonitoringIntensive care managementCerebral perfusion pressureCerebrovascular autoregulation
spellingShingle C.A. Smith
S.Y. Bögli
M.M. Placek
M. Cabeleira
D. White
E. Daubney
A. Young
E. Beqiri
R. Kayani
R. O'Donnell
N. Pathan
S. Watson
A. Maw
M. Garnett
H.K. Kanthimathinathan
H. Bangalore
S. Sundararajan
G. Subramanian
D. Raffaj
S. Lampariello
A. Sarfatti
A. Mayer
O. Ross
M. Czosnyka
P.J. Hutchinson
P. Smielewski
S. Agrawal
Shruti Agrawal
Peter Smielewski
Peter J. Hutchinson
Stefan Yu Bögli
Claudia A. Smith
Carly Tooke
Caroline Payne
Holly Belfield
Amisha Mistry
Collette Spencer
Claire Jennings
Lara Bunni
Laura Anderson
Emily Morgan
Melanie James
Rebecca Beckley
Tahnima Khatun
Hafiza Khatun
Olivia Nugent
Richard Aldridge
Ruth Morgan
Julie Morcombe
Martin Quinton
Catherine Postlethwaite
Jenny Pond
Jessica Cutler
Caitlin Oxford
Marek Czosnyka
Michal Placek
Manuel Cabaleira
Deborah White
Esther Daubney
Adam Young
Erta Beqiri
Riaz Kayani
Roddy O'Donnell
Nazima Pathan
Suzanna Watson
Anna Maw
Matthew Garnett
Hari Krishnan Kanthimathinathan
Harish Bangalore
Santosh Sundararajan
Gayathri Subramanian
Dusan Raffaj
Simona Lampariello
Avishay Sarfatti
Anton Mayer
Oliver Ross
Dynamic versus fixed cerebral perfusion pressure targets in paediatric traumatic brain injury: a STARSHIP analysisResearch in context
EClinicalMedicine
Paediatric traumatic brain injury
Multimodality neuromonitoring
Intensive care management
Cerebral perfusion pressure
Cerebrovascular autoregulation
title Dynamic versus fixed cerebral perfusion pressure targets in paediatric traumatic brain injury: a STARSHIP analysisResearch in context
title_full Dynamic versus fixed cerebral perfusion pressure targets in paediatric traumatic brain injury: a STARSHIP analysisResearch in context
title_fullStr Dynamic versus fixed cerebral perfusion pressure targets in paediatric traumatic brain injury: a STARSHIP analysisResearch in context
title_full_unstemmed Dynamic versus fixed cerebral perfusion pressure targets in paediatric traumatic brain injury: a STARSHIP analysisResearch in context
title_short Dynamic versus fixed cerebral perfusion pressure targets in paediatric traumatic brain injury: a STARSHIP analysisResearch in context
title_sort dynamic versus fixed cerebral perfusion pressure targets in paediatric traumatic brain injury a starship analysisresearch in context
topic Paediatric traumatic brain injury
Multimodality neuromonitoring
Intensive care management
Cerebral perfusion pressure
Cerebrovascular autoregulation
url http://www.sciencedirect.com/science/article/pii/S2589537025003025
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