Precision Medicine in Acute Brain Injury

1. PRECISION CARE
FOLLOWING ACUTE
BRAIN INJURIES IN
ADULTS: WHAT IS THE
LATEST EVIDENCE?
DR XIUXIAN PHAM
MBBS(Hons), BMedSci(Hons)

2. ACUTE BRAIN INJURIES
CHALLENGES
PRECISION MEDICINE

3. NEUROCRITICAL
CARE

4. DOES
SUBSPECIALISED
CARE MAKE A
DIFFERENCE?

5. Systematic review and meta-analysis of 26 studies with
55,792 patients
Study Characteristics
Pham, et al. (2022). DOI:10.1001/jamaneurol.2022.2456
Intervention
15/26 NCC unit
11/26
Neurointensivist
Location
14/26 North
America
5/26 Europe
7/26 Rest of the
world
Risk of bias
22/26 Moderate
4/26 Serious
Study type
All studies were non-randomised observational
cohort studies
23/26 were retrospective; 3/26 were prospective
Study characteristics
Last year of recruitment: from 1988 up to 2018
Participant size: 74 to 13543 participants
Population
9 2 4 4 7
General AIS ICH SAH TBI

6. Systematic review and meta-analysis of 26 studies with
55,792 patients
In critically ill brain-injured adults, association between dedicated
NCC and:
Decreased risk of
mortality
Decreased risk of
poor functional
outcomes
17%
relative risk reduction
(RR 0.83, 95% CI 0.74-0.92)
17%
relative risk reduction
(RR 0.83, 95% CI 0.70-0.97)
Pham, et al. (2022). DOI:10.1001/jamaneurol.2022.2456

7. Are there differences between
unit and personnel level
changes?
Pham, et al. (2022). DOI:10.1001/jamaneurol.2022.2456

8. THINGS TO CONSIDER
Heterogeneity Cost-benefit
What aspect of
NCC?
Additional
benefits

9. WHAT IS THE
AVAILABILITY OF NCC
IN AUSTRALIA?

10. Survey of ICUs across Australia
ICU Characteristics
78 of 175 (44.6%) ICUs across
Australia participated in the
survey.
34.6% (27/78) did not
routinely treat acute brain
injured patients.
Of those that did (n=51), 4 centres
reported specialising in NCC, and 9
centres employed an intensivist
subspecialising in NCC.
60 7 11
Adults Paeds Both
55 23
Public Private
15 13 27 23
Metropolita
n
Private
Rural/
Region
al
Tertiary
*Unpublished

11. Survey of ICUs across Australia
Access to specialties
44.9% (35/78) had a
neurosurgical unit in the
hospital.
48.7% (38/78) had a
neurology unit in the hospital,
and 15.4% (12/78) had a
consulting service only.
A dedicated epilepsy service
was only accessible in 10.3%
(18/78) centres.
CT brain was readily accessible to all centres.
CT perfusion and MRI brain were accessible
in 58/78 and 66/78 respectively.
Interventional radiology for clot retrieval and
other neurovascular procedures were
accessible in 20/78.
0%
20%
40%
60%
80%
100%
CTB CTP MRI B IR ECR IR
Neurovasc
No
Yes
100% 74.4% 84.6% 25.6%
25.6%
Access to imaging

12. Survey of ICUs across Australia
Access to neuromonitoring
Of the ICUs that routinely
treated brain injuries (n=51),
intermittent encephalography,
ICP monitoring and extra-
ventricular CSF drainage devices
were the most frequently
utilised.
Brain tissue oxygen monitors
and optic nerve sheath diameter
assessments were rarely used.
0% 20% 40% 60% 80% 100%
Optic nerve sheath diameter
Partial brain tissue oxygen…
Transcranial Doppler flow…
Near infrared spectroscopy
Pupillometry
Continuous EEG
EVD
ICP monitor
Intermittent EEG
Yes No
82.4% (42/51)
76.5% (39/51)
76.5% (39/51)
33.3% (17/51)
19.6% (10/51)
15.7% (8/51)
7.8% (5/51)
2.0% (1/51)
2.0% (1/51)

13. WHAT IS THE ROLE
OF EEG?

14. How common are seizures?
Depends on patient population
Systematic review and meta-analysis of critically ill adults with EEG
and seizure rates:
• 78 studies with 16,707 patients for pooled prevalence
Nonconvulsive
seizure or status
epilepticus
Routine EEG: 6.3%
Continuous EEG:
15.6%
Limotai, et al. (2019). DOI: 10.1097/CCM.0000000000003641
Post-convulsive
status epilepticus:
32.9%
CNS infection:
23.9%
Post cardiac arrest:
22.6%

15. Routine or Continuous EEG?
Limotai, et al. 2019:
• Pooled OR for NCS/NCSE detected by cEEG vs rEEG
Four studies with patients first
monitored with rEEG then cEEG:
OR 2.57
Two studies with patients either
monitored with rEEG or cEEG:
OR 1.57
Limotai, et al. (2019). DOI: 10.1097/CCM.0000000000003641

16. Routine or Continuous EEG?
Ney, et al. 2013:
• 5949 mechanically ventilated adults with EEG
Hill, et al. 2019:
• 22,728 critically ill patients who had cEEG
cEEG significantly lower in-hospital
mortality
Univariate: OR 0.54 (95% CI 0.45-
0.64)
Multivariate: OR 0.63 (95% CI 0.51-
0.76)
No significant differences in costs or
length of stay.
cEEG significantly lower in-hospital
mortality
Univariate: OR 0.54 (95% CI 0.45-
0.64)
Multivariate: OR 0.63 (95% CI 0.51-
0.76)
cEEG associated with reduced in-
hospital mortality: OR 0.83 (95% CI
0.75-0.93)
Cost and length of hospitalisation
increased for cEEG cohort: OR 1.17
and OR 1.11
Hill, et al. 2019. DOI:10.1212/WNL.0000000000006689
Ney, et al. 2013. DOI:10.1212/01.wnl.0000436948.93399.2a

17. Why is cEEG not utilised universally?
Barriers to access:
• Infrastructure barriers
• Specialised personnel required
Hilkman, et al. (2017). DOI:10.1097/ACO.0000000000000443

18. Why is cEEG not utilised universally?
Barriers to access:
• Infrastructure barriers
• Specialised personnel required
• Terminology for EEG patterns
• Clinical significance of some EEG patterns
• Amount of EEG data to interpret
• Artefact and contribution of medications and machines
• Evidence for improved patient outcome
Hilkman, et al. (2017). DOI:10.1097/ACO.0000000000000443

19. Is this a seizure?
Hilkman, et al. (2017). DOI:10.1097/ACO.0000000000000443

20. Is this a seizure?
Hilkman, et al. (2017). DOI:10.1097/ACO.0000000000000443

21. Is this a seizure?
Hilkman, et al. (2017). DOI:10.1097/ACO.0000000000000443

22. WHAT CAN WE
CONCLUDE?

23. TAKE HOME MESSAGES
1. NEUROCRITICAL CARE HAS THE POTENTIAL TO
IMPROVE OUTCOMES OF BRAIN-INJURED PATIENTS
2. THINK OUTSIDE THE UNIT; PERSONNEL MAKE A
DIFFERENCE TOO
3. EEGS REMAIN THE BEST DIAGNOSTIC TOOL FOR
DETECTING SEIZURES
4. RECOGNISE BARRIERS TO ACCESS AND
COLLABORATE WITH SPECIALTIES TO IMPROVE
AVAILABILITY

24. ACKNOWLEDGEMENTS
SR & MA co-authors:
• Dr Jason Ray
• Dr Ary Serpa Neto
• Dr Joshua Laing
• A/Prof Piero Perucca
• Prof Patrick Kwan
• Prof Terence O’Brien
• Prof Andrew Udy
These projects
were performed as
part of a PhD with
ANZICS-RC,
SPHPM, Monash
University
Survey co-authors:
• Dr David Pilcher
• Dr Ed Litton
• A/Prof Piero Perucca
• Prof Patrick Kwan
• Prof Andrew Udy