Martin Smith The management of severe traumatic brain injury (TBI) has undergone extensive revision following evidence that longstanding and established practices are not as efficacious or innocuous as previously believed. Very few specific interventions have been shown to improve outcome in large randomized controlled trials and, with the possible exception of avoidance of hypotension and hypoxaemia, most are based on observational studies or analysis of physiology and pathophysiology. Further, the substantial temporal and regional pathophysiological heterogeneity after TBI means that some interventions may be ineffective, unnecessary or even harmful in certain patients at certain times. Improved understanding of pathophysiology and advances in neuromonitoring and imaging techniques have led to the introduction of more effective and individualised treatment strategies that have translated into improved outcomes for patients. In particular, the sole goal of identifying and treating intracranial hypertension has been superseded by a focus on the prevention of secondary brain insults using a systematic, stepwise approach to maintenance of adequate cerebral perfusion and oxygenation. As well as being used to guide treatment interventions, multimodal neuromonitoring also gives clinicians confidence to withhold potentially dangerous therapy in those with no evidence of brain ischemia/hypoxia or metabolic disturbance. The days of blind adherence to generic physiological targets in the management of severe TBI have been replaced by an individualised approach to optimisation of physiology which has translated into improved outcomes for patients. Mark Wilson The New England Journal of Medicine has published a number of articles recently that demonstrate no benefit from classic neurotrauma interventions (ICP monitoring, cooling, decompression). This is because factors such as ICP and CPP are associated with bad outcome by association rather than causation. This debate will demonstrate that critical care just complicates things and it is high time for the randomised trial between the very best Neurocritical care and NOB therapy (Naso-pharyngeal, Oxygen and a Blanket).

3. When does Primary become Secondary Injury?
On scene ED NCCU
Secondary brain injury occurs after the primary mechanisms of injury have run their course (Gennarelli & Graham, 2005)
often result from complications of the primary mechanism of injury and may occur anywhere from hours to days after the init

4. So at best
Neurocritical Care will only save
neurons that have not died

5. NCCU Has 3 functions
Maintain Airway Good Nursing Care Weaning from Ventilator

7. A S S O O N A S W E G E T I N V O L V E D W E
C A N
E A S I L Y D O H A R M

8. utter cluster
fxxx /
abject harm
perfect
care
/ good outcome
The Spectrum of Neuro Critical Care
The good
perfectionist
The bad
perfectionist Nature
Where most of us practice
{

9. BUT WE MUST STOP SECONDARY INJURY….
Like Hypotension?

11. BUT WE MUST STOP SECONDARY INJURY….
Like ICP?

14. HYPERVENTILATION
1982 Good 2002 Bad

15. C O O L I N G

16. J U G U L A R V E N O U S S A T U R A T I O N
Who regularly does this?

17. B R A I N O X Y G E N A T I O N

18. B R A I N
O X Y G E N A T I O N

19. So we await….

20. S T E R O I D S
2004 Bad1985 Good

21. N E U R O P R O T E C T A N T S … .

22. N T E R V E N T I O N S
T H A T D O H E L P
e.g. Dialysis
….But these are not NCCU specific

23. N T E R V E N T I O N S
T H A T D O H E L P
e.g. Antibiotics
….Probably don’t need ITU

24. The Time to Save neurons is
BEFORE Neurocritical care
Once there… In the spontaneously breathing patient…

25. than NOB THERAPYIs all this really better
Ventilation
Art Line
Central Line
Vasopressors
ICP
Licox
Microdialysis
TPN
Tracheostomy

26. Neurocritical care is no better than

28. W H A T H A P P E N S I F
S H O W S D E C O M P R E S S I O N B A D ?

29. Neurocritical care improves outcome in severe
traumatic brain injury
Martin Smith
Consultant & Honorary Professor in Neurocritical Care
The National Hospital for Neurology & Neurosurgery
University College London Hospitals

30. Diringer et al, Crit Care Med 2001; 29: 635-40
• not being in a neuro ICU is associated with an increase in hospital
mortality after intracerebral haemorrhage
(OR, 3.4; 95% CI, 1.65–7.6)

31. Observational studies comparing outcomes between neurological critical care units and
alternative models of care
Kramer & Zygun, Curr Opin Care 2014;20: 174-81
Mortality
Favourable outcome

32. • treatment guided by ICP monitoring vs. care based on imaging and clinical
examination in absence of ICP monitoring (n=324)
• similar three- and six-month outcomes
Benchmark Evidence from South American Trials: Treatment of
Intracranial Pressure (BEST:TRIP)
Chesnutet al, New Engl J Med 2012;367: 2471-81

33. • moderate hypothermia one of the most effective neuroprotective
strategies in preclinical studies
- translated into humans
Targeted temperature management

34. Andrews et al, New Engl J Med 2015;373: 2403-12
• Eurotherm3235 trial randomized 387 patients from 47 centers in 18 countries
– TTM (32-35˚C) as a component of ICP management of intracranial hypertension
(ICP > 20 mmHg) resistant to initial ICP-lowering therapies
• recruitment suspended early because of safety concerns in the hypothermia
group
– worse functional outcomes (odds ratio 1.53, 95% CI 1.02-2.30)
– higher mortality rates (hazard ratio 1.45, 95% CI 1.01-2.10)

35. Andrews et al, New Engl J Med 2015;373: 2403-12

36. • complex and multifactorial
• several components of key importance
– reduction in substrate delivery below critical thresholds
– failing cellular metabolism
− inability to utilize delivered oxygen & glucose
− profound metabolic crisis
• cerebral ischaemia/hypoxia
– tissue burden related to clinical
outcome
Pathophysiology of traumatic brain injury

37. • secondary insults adversely affect the injured brain
– associated with worse outcomes
– prevention/rapid treatment associated with improved
outcomes
Pathophysiology of traumatic brain injury

38. – hypoxia
– hypotension
– hyper- and hypocarbia
– hyper- and hypoglycaemia
– hyperthermia
– intracranial hypertension
– seizures
Secondary insults

39. McHugh et al, J Neurotrauma 2007;24:287-93
• IMPACT study database
− merged cohort of 7 phase III RCTs with > 9000 patients
• single episode of hypoxia or hypotension strongly associated with worse
outcome
- hypoxia OR 2.1 (95% CI 1.7-2.6)
- hypotension OR 2.7 (95%CI 2.1-3.4)
Systolic BP < 90 mmHg or PaO2
< 8.0 kPa must be avoided or
rapidly corrected after TBI

40. • ABG targets
– PaO2 > 13.0 kPa
– PaCO2 4.5 - 5.0 kPa
• CVS targets
– MAP > 90 mmHg
– volume resuscitation
– vasopressors/inotropes
• glucose 5.0 - 10.0 mmol/l
• core temperature < 37oC
• ICP < 20 cmH20
• CPP 50-70 mmHg
Brain Trauma Foundation, J Neurotrauma 2007; 24: S1-S106
Consensus guidelines

41. Brain Trauma Foundation, J Neurotrauma 2007; 24: S1-S106
Consensus guidelines
• guidelines are a tool, not a goal
• goal is individualised, targeted
treatment
• treatment guided by monitor-derived
physiological variables
• ABG targets
– PaO2 > 13.0 kPa
– PaCO2 4.5 - 5.0 kPa
• CVS targets
– MAP > 90 mmHg
– volume resuscitation
– vasopressors/inotropes
• glucose 5.0 - 10.0 mmol/l
• core temperature < 37oC
• ICP < 20 cmH20
• CPP 50-70 mmHg

42. • multimodal monitoring allows delivery of tailored treatment
regimens
– identify physiological/pathophysiological phenotype
– guide targeted therapy
– assess effects of therapy
– guide decisions about intensity and duration of therapy
– improved patient outcomes
• confidence to withhold potentially dangerous therapy in those
without evidence of brain ischaemia or metabolic disturbance
Individualized therapy

44. ICP-directed management
• greatly elevated ICP is fatal
– ability to control it is limited
• oversimplified concepts surrounding manipulation of ICP and
the association with outcome
– thresholds for initiating medical and surgical management
– cerebral perfusion often not compromised even if ICP is > 20 mmHg
– outcome effects of current treatment probably smaller than we think
– all treatments have side effects
• severe TBI is an overwhelming and complex process
– involves neurones, glia and vasculature
– raised ICP compresses cerebral veins creating a self-regenerating cycle
of even higher pressure

45. Nangunoori etal,NeurocritCare 2012;17:131-8
• brain resuscitation based on control of ICP & CPP alone does
not prevent cerebral hypoxia in some patients
• increased hypoxia burden associated with poor outcome

46. Nangunoori etal,NeurocritCare 2012;17:131-8
(2009)
(2003)
(2009)
(2010)
• brain resuscitation based on control of ICP & CPP alone does
not prevent cerebral hypoxia in some patients
• increased hypoxia burden associated with poor outcome
• PtiO2-directed therapy associated with improved outcome
after severe TBI compared ICP/CPP based therapy alone

47. Marenko et al, J Clin Neurosci 2016; 26: 8-13
• optimal CPP is 92.5
mmHg with an
autoregulatory range
between 80–100 mmHg
• maintenance of CPP
within BTF guidelines
(50–70 mmHg) would
leave this patient at risk
of on-going ischemia

48. • brain tissue destruction caused by acute injury is worsened by
on-going insults
- early, aggressive intervention to minimize secondary insults improves the
outcome trajectory in many patients
- minimizing second insults will minimize residual disability
Critical care management of severe TBI

49. • get all the little things right all the time
- neurocritical care is as much about meticulous systemic physiological
optimization as it is about specific brain-directed therapies
• keep it simple - the six ‘Ns’
– normoxia
– normocapnia
– normovolaemia
– normotension
– normoglycaemia
– normothermia
– normonatraemia
– normomagnesaemia
Critical care management of severe TBI

50. • get all the little things right all the time
- neurocritical care is as much about meticulous systemic physiological
optimization as it is about specific brain-directed therapies
• optimise cerebral haemodynamics and oxygention
– blind adherence to guidelines risks delivering potentially harmful
treatment that is of no benefit
– individualize ICP and CPP-guided therapy
– multimodal physiological monitoring
Critical care management of severe TBI

51. • systemic organs may fail
- sympathetic surge and neuroinflammatory responses can cause
neurogenic pulmonary oedema, stress cardiomyopathy and a general
endocrinopathy
- complications of brain-directed treatment
Critical care management of severe TBI

52. • systemic organs may fail
- sympathetic surge and neuroinflammatory responses can cause
neurogenic pulmonary oedema, stress cardiomyopathy and a general
endocrinopathy
- complications of brain-directed treatment
• complex interaction between brain and systemic physiology
- optimize systemic and intracranial variables
- physiological neuroprotection
Critical care management of severe TBI

53. English et al, NeurocritCare 2013;18: 131-142

54. English et al, NeurocritCare 2013;18: 131-142

55. • burden of neuronal loss directly related to clinical outcomes
– minimize secondary ischaemic brain injury
• clinical guidelines are a useful starting point
• individualized treatment regimens
• neurocritical care does improve outcomes after TBI
Summary

56. THANK YOU!

57. SOCIETY FOR NEUROSCIENCE IN ANESTHESIOLOGY AND
CRITICAL CARE
SNACC 44th Annual Meeting
October 20-21, 2016
Chicago
www.snacc.org