. 2025 Feb 5:81:103077.

doi: 10.1016/j.eclinm.2025.103077. eCollection 2025 Mar.

Status of cerebrovascular autoregulation relates to outcome in severe paediatric head injury: STARSHIP, a prospective multicentre validation study

Shruti Agrawal^{1

2}, Claudia Smith³, Stefan Y Bogli³, Michal M Placek³, Manuel Cabeleira^{3

4}, Deborah White^{1

2}, Esther Daubney^{1

2}, Adam Young³, Erta Beqiri³, Riaz Kayani², Diarmuid O'Donnell², Nazima Pathan^{1

2}, Suzanna Watson⁵, Anna Maw¹, Matthew Ganrett³, Hari Krishnan Kanthimathinathan⁶, Harish Bangalore⁷, Santosh Sundararajan⁸, Gayathri Subramanian⁹, Dusan Raffaj¹⁰, Avishay Sarfatti¹¹, Simona Lampareillo¹², Anton Mayer¹³, Oliver Ross¹⁴, Marek Czosnyka³, Peter J Hutchinson³, Peter Smielewski³; STARSHIP study team

Collaborators, Affiliations

Collaborators

Affiliations

¹ Department of Paediatrics, University of Cambridge, Cambridge, UK.
² Paediatric Intensive Care, Cambridge University Hospitals, Cambridge, UK.
³ Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
⁴ Department of Mechanical Engineering, University College London, London, UK.
⁵ Paediatric Neuropsychology, Cambridge and Peterborough NHS Foundation Trust, Cambridge, UK.
⁶ Paediatric Intensive Care, Birmingham Children's Hospital, Birmingham, UK.
⁷ Paediatric Intensive Care, Great Ormond Street Hospital, London, UK.
⁸ Paediatric Intensive Care, Leeds Children's Hospital, Leeds, UK.
⁹ Paediatric Intensive Care, Manchester Children's Hospital, Manchester, UK.
¹⁰ Paediatric Intensive Care, Nottingham Children's Hospital, Nottingham, UK.
¹¹ Paediatric Intensive Care, Oxford University Hospitals, Oxford, UK.
¹² Paediatric Intensive Care, Royal London Hospital, London, UK.
¹³ Paediatric Intensive Care, Sheffield Children's Hospital, Sheffield, UK.
¹⁴ Paediatric Intensive Care, Southampton General Hospital, Southampton, UK.

PMID: 39996125
PMCID: PMC11848105
DOI: 10.1016/j.eclinm.2025.103077

Status of cerebrovascular autoregulation relates to outcome in severe paediatric head injury: STARSHIP, a prospective multicentre validation study

Shruti Agrawal et al. EClinicalMedicine. 2025.

. 2025 Feb 5:81:103077.

doi: 10.1016/j.eclinm.2025.103077. eCollection 2025 Mar.

Authors

Collaborators

Affiliations

¹ Department of Paediatrics, University of Cambridge, Cambridge, UK.
² Paediatric Intensive Care, Cambridge University Hospitals, Cambridge, UK.
³ Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
⁴ Department of Mechanical Engineering, University College London, London, UK.
⁵ Paediatric Neuropsychology, Cambridge and Peterborough NHS Foundation Trust, Cambridge, UK.
⁶ Paediatric Intensive Care, Birmingham Children's Hospital, Birmingham, UK.
⁷ Paediatric Intensive Care, Great Ormond Street Hospital, London, UK.
⁸ Paediatric Intensive Care, Leeds Children's Hospital, Leeds, UK.
⁹ Paediatric Intensive Care, Manchester Children's Hospital, Manchester, UK.
¹⁰ Paediatric Intensive Care, Nottingham Children's Hospital, Nottingham, UK.
¹¹ Paediatric Intensive Care, Oxford University Hospitals, Oxford, UK.
¹² Paediatric Intensive Care, Royal London Hospital, London, UK.
¹³ Paediatric Intensive Care, Sheffield Children's Hospital, Sheffield, UK.
¹⁴ Paediatric Intensive Care, Southampton General Hospital, Southampton, UK.

PMID: 39996125
PMCID: PMC11848105
DOI: 10.1016/j.eclinm.2025.103077

Abstract

Background: Continuous assessment of cerebral autoregulation (CA) using pressure reactivity index (PRx), is a promising tool for individualized management to improve outcome after traumatic brain injury (TBI). However, experience with CA in paediatric TBI (pTBI) is limited to retrospective or single-centre studies.

Methods: Studying Trends of AutoRegulation in Severe Head Injury in Paediatrics (STARSHIP) (clinicalTrials.gov identifier-NCT0688462), was a prospective, multicentre, observational, research database study conducted across 10 identified UK Paediatric Intensive Care Units from 01.07.2018 till 31.04.2024. The main objective was to validate and identify optimal thresholds of PRx associated with outcome (as assessed with Glasgow outcome scale extended for Pediatrics at 12 months) in children (<16 years) requiring invasive arterial blood pressure and intracranial pressure monitoring for TBI and establish a comprehensive research database. Apart from high-resolution data, clinical and outcome data up to 12 months post-ictus were collected. Univariable and multivariable analyses including propensity score matching, were employed to determine the effect of PRx on outcome whilst considering covariates, centre-specific differences and other multimodal metrics.

Findings: Out of 153 recruited, 135 children (median age 96 months) with consent and adequate data were included. Overall median PRx of the cohort was -0.09 (IQR -0.19 to 0.08). Both ICP and PRx were elevated in non-survivors and children with unfavourable outcome. PRx retained a significant effect on outcome after adjusting for various clinical and monitoring variables. The critical PRx threshold identified were 0.5 for mortality and 0.0 for favourable outcome.

Interpretation: With STARSHIP, we validate the outcome association of CA derangements as assessed by PRx in pTBI in the first prospective observational multicentre study. This provides additional evidence for the potential use of PRx for individualizing prognosis and treatment and pave way for further research in pTBI with the created database.

Funding: This study was funded by Action Medical Research for Children's Charity and Addenbrookes Charitable Trust, UK (Grant number-GN2609). Cambridge University Hospitals is the study sponsor (Reference: A094693, contact person: Michelle Ellerbeck-michelle.ellerbeck@nhs.net).

Keywords: Cerebral autoregulation; Cerebral perfusion pressure (CPP); Paediatric traumatic brain injury; Pressure reactivity index (PRx).

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Conflict of interest statement

This research was supported by the National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre (NIHR203312∗) and received support from the NIHR Clinical Research Network. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. ICM+ is a software licensed by Cambridge Enterprise Ltd. Marek Czosnyka and Peter Smielewski have a financial interest in a part of licensing fee; the licensing fee was waived for this study. Stefan Y. Bogli is supported by the Swiss National Science Foundation (grant number: 210839/225270). Claudia Smith is supported by the Patrick & Margaret Flanagan Skye Cambridge Trust Scholarship. Erta Beqiri is supported by the Medical Research Council [grant number MR N013433-1] and by the Gates Cambridge Scholarship. Peter J. Hutchinson is supported by the National Institute for Health Research (NIHR) (Senior Investigator Award, Cambridge BRC, NIHR HRC for Brain Injury) and the Royal College of Surgeons of England. None of the other authors have any further declaration of interests.

Figures

**Fig. 1**
Inclusion/exclusion flow chart.

**Fig. 2**
Mean PRx of the entire cohort per day from ictus (day 0) for mortality at discharge (A) and dichotomized outcome (B) as favourable (Glasgow Outcome Scale Extended Pediatrics 1–4) and unfavourable (Glasgow Outcome Scale Extended Pediatrics 5–8). Only the first 8 days shown. PRx, pressure reactivity index.

**Fig. 3**
Critical Thresholds of PRx for mortality and dichotomized outcome. Multiple chi squared tests were used to identify critical thresholds of PRx for the entire cohort and stratified by age group- for mortality (A) and dichotomised outcome (C) as well as for different time periods post ictus- for mortality (B) and dichotomised outcome (D), respectively. The PRx value that corresponded to the highest Chi squared values are the critical thresholds for that cohort or time period. PRx, pressure reactivity index. ∗No thresholds could be calculated for 0–2 years age group due to insufficient number of patients.

See this image and copyright information in PMC

References

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Status of cerebrovascular autoregulation relates to outcome in severe paediatric head injury: STARSHIP, a prospective multicentre validation study

Collaborators

Affiliations

Status of cerebrovascular autoregulation relates to outcome in severe paediatric head injury: STARSHIP, a prospective multicentre validation study

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources

Medical