What is elevated ICP? and When should it be treated? David Menon Professor of Anaesthesia, University of Cambridge
ICP monitoring recommended to reduce inhospital & 2-wk mortality Rx ICP > 22 mm Hg as higher values associated with increased mortality. Class 3 evidence (9 studies) no clear herniation threshold (18-25). 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 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/
Blood pressure Optimise oxygenation Carbon dioxide Basic intensive care EEG deep sedation Decompressive craniectomy Increasing therapy intensity and side effects
No EBM support for 2 o 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) Increasing therapy intensity and side effects
No EBM support for 2 o 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) Increasing therapy intensity and side effects
No EBM support for 2 o 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? Increasing therapy intensity and side effects
Postmortem: uncal herniation with Duret haemorrhage in brainstem ICP threshold > (?)30mmHg Reduced CBF ICP threshold: (?)20 mmhg Depends on CPP
Different indications to Rx ICP Different risks, thresholds and urgency Different acceptance of iatrogenic risk Calibrate ICP Rx to risk/benefit ratio
Individual titration of CPP and ICP targets using autoregulatory indices and other monitors Titration of therapeutic interventions such as hyperventilation and blood glucose control
Approaches to target refinement Recognise that ICP is more than a single number Consider trends and time post-injury Consider intracranial compliance Consider clinical correlates and pathology location Target optimal range of autoregulation (PRx) Downstream events as a marker Cerebral blood flow Tissue oxygen partial pressure Substrate adequacy (glucose, pyruvate) Metabolic compromise (lactate, lactate/pyruvate) Stress/injury markers (glutamate/glycerol) Blood biomarkers of brain injury (S100B, UCHL-1, SBDP)
Tissue po 2 > 15 mmhg 1 20/25 mmhg 2,3 Lactate/pyruvate < 25 4 (> 40 = late atrophy) 5 (LPR) Brain glucose > 0.5-0.8 mmol 6 PRx (autoreg) <0.0 7 /0.25 7 ; CPPopt 8 Hutchinson Triple Bolt Codman ICP, 100kDa cutoff microdialysis catheter, Licox probe Figures in red Addenbrooke s protocol targets References ICP/CPP targets/thresholds: - More stringent for favourable outcome vs. survival - Vary with age and gender - Potentially patient-specific based on autoregulation? 1. Brain Trauma Foundation Guidelines 2. Spiotta et al (LeRoux). J Neurosurg. 2010;113(3):571 80. 3. Steifel et al (Le Roux). J Neurosurg. 2005;103(5):805 11. 4. Timofeev et al (Hutchinson). Brain 2011;134:484-94. 5. Marcoux et al (Vespa). Crit Care Med 2008;36:2871-7 6. Vespa et al. Crit Care Med 2006; 34:850 856 7. Sorrentio et al (Czosnyka). Neurocrit Care 2012;16:258-66 8. Aries et al (Smielewski). Crit Care Med 2012;40:2456-63 9. Lazarides et al (Czosnyka). J Neurosurg 2014; 120: 893-900 10. Donnely et al (Smielewski). Crit Care Med 2017: 45: 1464-71 Names in italics are senior authors on publications
Monitor Normal Desirable Injury threshold ICP ~10 mmhg <<20 mmhg >>25 mmhg PRx <0 <0.05 <0.25 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
Consideration of clinical context Remove surgical lesions: a chance to cut is a chance to cure! Pathoanatomy of lesion Temporal fossa lesions may herniate at low ICPs Posterior fossa lesions are poorly reflected by supratentorial ICP Any CSF spaces with high ICP = abnormal CSF circulation = EVD Is ICP primarily a cause or a consequence of brain injury? Look at initial GCS, imaging Consider early MRI to look for severe DAI/brainstem injury ICP Rx will not help patients with prognosis-defining primary injury Is there a clinical context that requires specific targets?
Statistical thresholds for <55 years >55years ICP (survival) 23 mmhg 21 mmhg ICP (favourable outcome) 22 mmhg 18 mmhg CPP (survival) 70 mmhg 75 mmhg CPP (favourable outcome) 70 mmhg No clear threshold PRx (survival) 0.3 No clear threshold PRx (favourable outcome) 0.0 No clear threshold Older patients have Lower ICP thresholds for all outcomes tolerate intracranial hypertension less well Higher CPP thresholds for survival tolerate hypotension poorly Less evidence of autoregulation cannot compensate for BP fluctuations
J Neurosurg 2017; 14:1-9.
Stratified medicine
Precision medicine
Mechanistic heterogeneity Classical (CPP mediated) ischaemia Diffusion hypoxia Mitochondrial dysfunction Abnormal glial homeostasis for water/ions Traumatic axonal injury Oxidant injury Neuroinflammation Neurodegeneration (amyloid, tau..)
@Menon_Cambridge Acknowledgements Neuro/Trauma Critical Care Unit Jonathan Coles Ari Ercole Arun Gupta Basil Matta Andrea Lavinio Rowan Burnstein Ronan O Leary Derek Duane Virginia Newcombe Joe Donnelly Neurosurgery John Pickard Peter Hutchinson Marek Czosnyka Peter Smielewski Adel Helmy Peter Kirkpatrick Keri Carpenter The British Oxygen Professorship Beyond Cambridge Luzius Steiner Marcel Aires Nino Stocchetti Giuseppe Citerio Andrew Maas TRACK-TBI CENTER-TBI