1. Paediatric Applications

2. Scale of Problem
Brain injury kills five times more children than cancer
Nearly 25% PICU adm: risk of acute neurological injury
High incidence of traumatic brain injury (TBI)
In US: 35,000 severe TBI and 7440 deaths/yr (CDC)
Apprx 50% poor neurological outcomes at 6 mo
Mean age ~ 9 yrs, productive life-years 1.3 million/yr
PCCM 2011;12:601-2
Neurotherapeutics 2012;9:3-16

3. Cerebrovascular Dynamics in Children
Age/gender related differences: ICP, CBF, CA
LLA may not be lower in lower age groups
Association of autoregulation with outcome
Age-related changes in mean flow velocity of middle cerebral artery (VMCA) in both genders, cerebral blood flow (CBF), cerebral metabolic rate of glucose (CMRglu)
(Adult values: VMCA ∼ 50 cm/sec, CBF 50 ml/100g/min, CMRglu μmol/100g/min)
Pediatr Neurol 2008;38:225-34

4. Secondary Brain Injury
Cerebral Blood Flow
Impaired autoregulation
Brain oedema
Increased ICP
Energy Flow
Glucose utilization
Glucose availability
Mitochondrial failure
Secondary Brain Injury
Oxygen
Hypoxia/Ischaemia
Impaired O2 Regulation
Impaired microcirculation
Excitotoxicity
Excessive neurotramitter release
Spreading cortical depolarisations
Seizures

7. N=12 (8 survivors)

14. N=36 (23 favourable outcome, 7 unfavourable outcome)

17. Sample Size
Mean (± SD) PRx of 0.03 ± 0.13 for favourable outcome and mean (± SD) PRx of 0.10 ± 0.17 (SD) for unfavourable outcome
One sided analysis, favourable: unfavourable ratio of 0.77 (80% power and alpha error of 5% & allowance for losses (protocol violations, withdrawal of consent, or loss of FU)
Total: 135 patients.

18. IRAS:
REC: 18/SW/0053
Funded by AMRC and ACT
Sponsored by Cambridge University Hospitals

19. Current Status Multicentre UK study: 10 sites
Funded by Action Medical Research and ACT
135 patients over 3 years with one year follow-up
Consent waiver for acute data collection
Objectives:
Primary: Optimal PRx with 12 mo outcome (GOSE peds)
Secondary: Optimal CPP

20. shruti.agrawal@addenbrookes.nhs.uk, sa882@cam.ac.uk, mc916@cam.ac.uk
16 years or younger admitted to PICU
TBI confirmed on CT or MRI
Clinical requirement for monitoring ICP &ABP
No exclusion criteria
Consent for Follow-up before hospital discharge

21. Birmingham Children’s Hospital: Cambridge University Hospitals
Great Ormond Street Hospital
King’s College Hospital
Leeds Children’s Hospital
Manchester Children’s Hospital
Nottingham Children’s Hospital
Royal London Hospital
Sheffield Children’s Hospital
Southampton Children’s Hospital

22. Data Collection Schedule: Acute Data
Data Elements
Acute data (PICU stay)
ICM + data collection (till ICP monitoring stops)
As soon as possible after ICP bolt and arterial line insertion
CRF- Once per admission
Demographics √
Pre-PICU events
Neuro-monitoring
Severity scores (PIM 2 and AIS)
Discharge
CRF- Daily (till ICP monitoring stops)
Laboratory Values
TBI: Medical interventions
TBI: Surgical interventions
PICU complications/events (as required)

23. Data Collection Schedule: Follow-up
CRF for Outcomes Assessment
6 Months
12 months
Parents
Teachers
GOSE- Peds
√ (telephone) X
BRIEF
√ (questionnaire)
SDQ
PedsQL
CASP
CCC
RCADS x

24. STARSHIP: CUH Team PICU:
Shruti Agrawal (chief Investigator) & Ricardo Branco (co-investigator)
Deborah White & Esther Daubney (PICU research nurses)
Phil Castle (ODP for technical support)
Paediatric Neurology:
Dr Anna Maw
Dr Suzanna Watson (Neuropsychologist)
Brain Physics:
Manuel Cabeleira (Research Assistant)
Dr Peter Smielewski & Prof Marek Czosnyka
Neurosurgery
Prof Peter Hutchison
Ms Helen Fernandes & Mr Matthew Garnett
Mr Adam Young

25. shruti.agrawal@addenbrookes.nhs.uk, sa882@cam.ac.uk, mc916@cam.ac.uk
Progress (10th September 2018)
8 site initiation completed, 6 sites live. Recruited: 3
Collaboration with KidsBrainIT: BIR, NOT, MAN
Future Directions
Ongoing national and international collaboration
Database to study age/gender related differences

26. ???? Brain Physics Group members Acknowledgments:
Brain Physics Department:
Professor Marek Czosynka
Dr Peter Smielewski
Mr Manuel Cabeleira
Dr Joseph Donnelly
PhD students & research staff
Academic Neurosciences
Professor Peter Hutchison
Mr Matthew Garnett
Mrs Helen Fernandez
Mr Adam Young
????