David Menon discusses the complex and fraught world of managing traumatic brain injury (TBI) in the ICU. In particular, David discusses the management of intracranial pressure and cerebral perfusion pressure in these patients. Although the Brain Trauma Foundation provides guidelines for the management of severe TBI, including targets for ICP and CCP, there is no Level 1 recommendation for the use of any intervention to modulate ICP/CCP. General principles remain simple in theory, if not in practice. David describes good basic intensive care, which he describes as doing lots of little things well. The main focuses should be maintaining blood pressure high enough to get oxygen to brain, optimising oxygenation and modulating carbon dioxide. This is in combination with other modalities such as hypertonic saline, cooling people, and using metabolic suppression. The trouble lies in the fact that there is no evidence base for second line therapy. In fact, some of these therapies have been shown to cause harm. When considering a therapy, it boils down to this - is the disease desperate enough and have the benefits and risks of therapy been weighed up. When controlling ICP, the indications for treatment are different so acceptance of iatrogenic risk must also change. Therefore, ICP treatments must be calibrated using a risk benefit ratio. For instance, utilising hyperventilation to decrease intracranial pressure can be a useful lever to pull. However, going too hard can reduce the cerebral blood flow to a detrimental point. The point here is to use it briefly, to make time for another less potentially harmful intervention. Similarly, when considering CCP, targets and protocols use population averages. No single optimal CCP exists across all patients. So, clinicians need a rationale way to titrate treatment to physiology. David suggests using graded thresholds to escalate treatment in an individualised way. Underlying these principles is good detection and minimisations of treatment harm. Underlying all of these principles is a grounding in the data and the utilisation of this data to effectively communicate with families. By doing this you can deliver the treatment and aim for the outcomes deemed most acceptable by the patient and their loved ones. For more like this, head to our podcast page. #CodaPodcast

1. Trying to build a platform to personalise critical care
in TBI.
@Menon_Cambridge
Not all brains are the same…
Human Chimpanzee Baboon Lion Cheetah Dog Cat

2. • ICP monitoring recommended to reduce inhospital & 2-wk mortality
• CPP monitoring is recommended to decrease 2-wk mortality
• Consider maintaining SBP at:
– >100 mm Hg for patients 50 to 69 years old or
– >110 mm Hg or above for patients 15 to 49 or >70 years old
• Rx ICP > 22 mm Hg as higher values associated with increased
mortality.
• Target CPP for survival/favourable outcomes: 60 to 70 mm Hg.
• Whether 60 or 70 mm Hg is the minimum optimal CPP threshold is
unclear; may depend upon the autoregulatory status.
https://braintrauma.org/
No Level I Recommendation for the use
of any intervention to modulate
ICP/CPP

3. Increasingtherapyintensity…andsideeffects
Blood pressure ↑
Optimise oxygenation
Carbon dioxide ↓
Basic
intensive
care
Decompressive craniectomy

4. Increasingtherapyintensity…andsideeffects
No EBM support for 2o
Rx?
•DECRA:
- harm from DC
(as an early Rx)
•Eurotherm3235:
- harm from hypothermia
(as an early Rx)
•BEST TRIP:
- ICP guided Rx no better
(ICP Rx at 20 mmHg)

5. Increasingtherapyintensity…andsideeffects
No EBM support for 2o
Rx?
•DECRA:
- harm from DC
(as an early Rx)
•Eurotherm3235:
- harm from hypothermia
(as an early Rx)
•BEST TRIP:
- ICP guided Rx no better
(ICP Rx at 20 mmHg)
•Was the disease desperate
enough - did we balance
risk and benefit
appropriately?

6. Postmortem: uncal
herniation with Duret
haemorrhage in brainstem
ICP threshold > (?)30mmHg
Reduced CBF
ICP threshold: (?)20 mmHg
Depends on CPP

7. Different indications to Rx ICP
• Different risks, thresholds and urgency
• Different acceptance of iatrogenic risk
• Calibrate ICP Rx to risk/benefit ratio
What about CPP?

8. CPP targets
Protocols use population
averages for CPP targets
But no single optimal CPP
across patients, so
- Some under-treated
- Others over-treated
Need tools to titrate
Rx intensity

9. Hutchinson Triple Bolt
• ICP, 100kDa microdialysis, Licox probe
• Addenbrooke’s protocol targets in red
• Based on associations with outcome
• Aim to titrate Rx to physiology
• No Class I evidence (as yet….)
• BOOST3: RCT of BtpO2 guided Rx
seeking funding from NIH
Autoregulation Keep PRx <0.0/0.25
Target CPPopt
Tissue pO2 > 15 mmHg
20/25 mmHg
Lactate/pyruvate < 25 (> 40 = late atrophy)
(LPR)
Brain glucose > 0.5 - 0.8 mmol
PRx
CPP
“optimal”
autoregulation
PRx
CPP
“optimal”
autoregulation
ICM+
optimal
autoregulation

10. Monitor “Normal” “Desirable” “Injury
threshold”
ICP ~10 mmHg <<20 mmHg >>25 mmHg
BtpO2 ~30 mmHg 20-25 mmHg <15 mmHg
Lactate/Pyruvate <25 <25 >40
Brain glucose >> 1 mmol/l <0.8 mmol/l <0.5 mmol/l
Acceptable Rx
intensity?
LOW HIGH
Make the juice worth the squeeze….
Use graded thresholds to:
•escalate Rx in an individualised way
•detect and minimise Rx harm

11. CBF(ml/100g/min)
50
CBV(ml/100g)
4.0
CBF and CBV reactivity to PaCO2
PaCO2(kPa)
5.02.5 7.5

12. PET CBF maps in TBI: 6 hours post injury
Areas in red show regions with CBF <20 ml/100g/min
0ml/100g/min60
PaCO2: 3.3 kPa (25 mmHg)PaCO2: 5.0 kPa (38 mmHg)
Coles et al. Critical Care Medicine 2002; 30:1950

13. Hyperventilation: The bottom line – avoid harm
• CBF↓ generally more severe < 4.5 kPa (~35 mmHg)
– But patients vary in need/tolerance for hyperventilation
• So if dropping PaCO2 below this level:
– Monitor BtpO2(aim to keep > 15 mmHg)
• Consider why we are using PaCO2 reduction
• if for perfusion pressure elevation, why use an
intervention that drops perfusion?
• if for impending herniation or very high ICP –
hyperventilation is worth the side effects
• Use briefly: make time for another intervention

14. Early decompression
-ICP > 20 mmHg
-For 15 min
-1st
tier Rx failed
Not refractory ICP
Worse outcomes
withDC
Very important paper –
calibrated relative risk of
medical vs. surgical Rx

15. N Engl J Med 2016;375:1119
RESCUEicp – DC for “desperate disease”
•DC as rescue Rx for refractory intracranial hypertension
•ICP > 25 for 1-12 hours
•Refractory to both Stage 1 and Stage 2 therapies
•Follow up at 6 & 12 months
•Dichotomized GOSE between upper/lower severe disability)

16. NS
p <0.01
Pre-specified dichotomisation of GOSE outcome at Upper Severe Disability
USD requires independence at home for at least 8 hours:
A meaningful threshold that allows a partner to hold down a job

17. Some thoughts
• What we need to do is separate two patient groups:
• Intractable ↑ICP as a consequence of devastating brain injury
• Intractable ↑ICP as a possible cause of devastating brain injury
• ICP Rx cannot benefit the 1st
, but may benefit the 2nd
• We don’t know how many patients are in these two
groups in the population we consider for DC
• This distinction important for all ICP Rx in TBI.
• Potential biomarkers: age, initial GCS, severe DAI (MRI)?

18. Talking to families – admitting uncertainty
• DC may be the least worst option in a small group of patients
• I try not to use terms such as “favourable” or “unfavourable”
• I simply state that the best evidence we have suggests that:
– DC as rescue Rx reduces mortality by ~ 20%. Of these 20%:
– ~Half remain severely dependent or do not recover consciousness
– ~Half eventually become independent at home or better
– It takes time (> a year) for the benefit of DC to declare itself
• I offer to provide details of outcome categories & clarify issues
• I say that our prediction of trajectories & outcome is imperfect
• Some families choose decompression, and some do not.

19. Control
Euler Delta Crossings (EuDX) algorithm, DiPy (Diffusion Imaging in Python)
Superior
Inferior
Left
Right
Posterior
Anterior
Colour coding of nerve
fibre directions
Newcombe et al
Neurorehab
Neural Rep 2015
~ 6 weeks ~6 months ~1 year
~ 2 days ~ 1 week
Pattern seen in ~20%
of TBI patients
Correlates with
trajectory of
functional recovery
Potential new
therapy biomarker

20. Menon et al. Lancet 1998; 352: 200
Kate Bainbridge
•26 y old trainee teacher
•Post-viral ADEM
•Prolonged ICU stay
•Diagnosed as VS
•Functional imaging
- “covert cognition”

21. Kate Bainbridge didn’t just recover
from being in vegetative state, but
still thinks of herself as a rock chick!

22. Polly Kitzinger
• Motor vehicle collision, managed elsewhere
• Severe TBI: Aggressively treated
• Minimally Conscious -> now severely disabled
• No Advance Directive, but wishes now clear

23. Reproduced, with permission from Jenny Kitzinger, from http://www.welovepolly.org/
Polly Kitzinger

24. It's my lifeIt's my life
It's now or neverIt's now or never
I ain't gonna live foreverI ain't gonna live forever
I just want to live while I'm aliveI just want to live while I'm alive
(It's my life)(It's my life)
Bon Jovi 2000
We've got to hold on to what we've gotWe've got to hold on to what we've got
Cause it doesn't make a differenceCause it doesn't make a difference
If we make it or notIf we make it or not
We've got each other and that's a lotWe've got each other and that's a lot
For love - well give it a shotFor love - well give it a shot
Bon Jovi 1996