Non-pharmacological interventions in traumatic brain injury: an update Dr Matt Wiles Department of Neuroanaesthesia & Neurocritical Care Sheffield Teaching Hospitals NHS Foundation Trust, sthjournalclub.wordpress.com

“….there are known knowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know. But there are also unknown unknowns – the ones we don't know we don't know.”

ParameterBTFEBICAAGBI RespiratoryAVOID SpO 2 <90% PaO 2 <8 kPa PaCO 2 <3.3 kPa TARGET SpO 2 >95% PaO 2 >10 kPa PaCO kPa TARGET PaO 2 >13 kPa PaCO kPa CardiovascularAVOID SBP <90mmHg TARGET MAP >90 mmHg SBP >120 mmHg TARGET MAP >80 mmHg NeurologicalICP <20 CPP (probably 60) ICP <20-25 CPP ICP <20-25 CPP 60-70

Changing TBI Population YearNumberMedian age% aged > 50 years Traumatic Coma Data Bank UK Four Centre Study EBIC Core Data Survey Rotterdam Cohort Study Austrian Severe TBI Study (mean)45 TARN Review (mean)Not reported Italian TBI Study RAIN Study (UK) Not reported

Objectives To examine recent developments in traumatic brain injury with respect to the use of: Intracranial pressure monitoring Decompressive craniectomy Osmotherapy Therapeutic targets (MAP) & Fluids Prognostication tools

ICP Monitoring Chesnut RM et al. A trial of intracranial-pressure monitoring in traumatic brain injury. New England Journal of Medicine 2012; 367:

ICP Monitoring Su S-H et al. The Effects of Intracranial Pressure Monitoring in Patients with Traumatic Brain Injury. PLoS ONE 2014; 9: e Meta-analysis of 9 studies (n=11,038) ICP monitoring no effect on outcome or mortality Significant heterogeneity in papers

ICP Monitoring Alali AS et al. Intracranial Pressure Monitoring in Severe Traumatic Brain Injury: Results from the American College of Surgeons Trauma Quality Improvement Program. Journal of Neurotrauma 2013; 30: 1737–1746. n=10,068 with severe TBI Only 17.6% had ICP monitors

ICP Monitoring Gerber LM et al. Marked reduction in mortality in patients with severe traumatic brain injury. J Neurosurg 2013; 119: 1583–1590. Retrospective analysis of severe TBI ( ) Primarily Level 1 Trauma Centres

ICP Monitoring Kosty JA et al. Brief report: a comparison of clinical and research practices in measuring cerebral perfusion pressure: a literature review and practitioner survey. Anesth Analg 2013; 117: Survey of Neurocritical Care Society Atrium (74%) Tragus (16%) Conflicted (10%)

ICP Monitoring Kosty JA et al. Brief report: a comparison of clinical and research practices in measuring cerebral perfusion pressure: a literature review and practitioner survey. Anesth Analg 2013; 117: 694-8

content/uploads/2015/03/Final_Revised_Joint_CPP_ statement_Aug_2014.pdf

ICP Monitoring Stocchetti N et al. Clinical applications of intracranial pressure monitoring in traumatic brain injury. Acta Neurochir 2014; 156: 1615–1622 No ICP bolt: Normal CT brain ICP bolt: Cerebral contusions and remained sedated After decompressive craniectomy After evacuation of supratentorial haematoma and at risk of raised ICP GCS ≤ 5, midline shift > 5mm, abnormal pupils etc..

Decompressive Craniectomy Cooper DJ et al. Decompressive Craniectomy in Diffuse Traumatic Brain Injury. New England Journal of Medicine 2011; 364:

Decompressive Craniectomy Hartings JA et al. Surgical management of traumatic brain injury: a comparative-effectiveness study of 2 centers. Journal of Neurosurgery 2014; 120:

Cranioplasty Bender A et al. Early cranioplasty may improve outcome in neurological patients with decompressive craniectomy. Brain Injury 2013; 27: 1073–79.

Osmotherapy: Mannitol Wakai A et al. Mannitol for acute traumatic brain injury. Cochrane Database Syst Rev. 2013; 8: CD Only able to identify 4 trials (n=197) Insufficient reliable evidence to make recommendations for its use in TBI Further high-quality RCTs needed despite the widespread use of mannitol

Osmotherapy: HTS vs. Mannitol Rickard AC et al. Salt or sugar for your injured brain? A meta-analysis of randomised controlled trials of mannitol versus hypertonic sodium solutions to manage raised intracranial pressure in traumatic brain injury. Emerg Med J 2013; 31: Six studies (n=171) Variety of solutions ICP difference 1.34 mmHg No outcome measures More work needed….

Fluid Therapy Cooper DJ et al. Albumin Resuscitation for Traumatic Brain Injury: Is Intracranial Hypertension the Cause of Increased Mortality? Journal of Neurotrauma 2013; 30: Post hoc analyses of SAFE study (n=321)

Permissive Hypotension Maas AI et al. Advancing care for traumatic brain injury: findings from the IMPACT studies and perspectives on future research. Lancet Neurol 2013; 12: Hypotension increases mortality & poor outcomes

Permissive Hypotension Wiles MD. Blood pressure management in trauma: from feast to famine? Anaesthesia 2013; 68: 445–452 “Trials” of permissive hypotension excluded patients with TBI Evidence of reduction in haemorrhage with permissive hypotension is lacking in clinical studies Much (all) is extrapolated from animal models

Permissive Hypotension Berry C et al. Redefining hypotension in traumatic brain injury. Injury 2012; 43: 1833–1837 Retrospective analysis of patients with moderate/severe TBI North American study (n=15733)

Permissive Hypotension Hassler RM et al. Systolic blood pressure below 110 mmHg is associated with increased mortality in penetrating major trauma patients: Multicentre cohort study. Resuscitation 2012; 83: patients with penetrating trauma (TARN) 1

Permissive Hypotension Hassler RM et al. Systolic blood pressure below 110 mmHg is associated with increased mortality in blunt major trauma patients: Multicentre cohort study. Resuscitation 2011; 82: patients with blunt trauma (TARN) 1

Outcome Prediction Roe C et al. Severe traumatic brain injury in Norway: impact of age on outcome. J Rehabil Med 2103; 45: years (n=156) ≥ 65 years (n=22) 90-day mortality24%67% Returned to own 90 days53%68%

Outcome Prediction Stevens RD, Sutter R. Prognosis in severe brain injury. Crit Care Med 2013; 41:

Outcome Prediction Mercier E et al. Predictive value of S-100β protein for prognosis in patients with moderate and severe traumatic brain injury: systematic review and meta-analysis. BMJ 2013; 346: f1757

Outcome Prediction Turgeon AF et al. Determination of Neurologic Prognosis and Clinical Decision Making in Adult Patients With Severe Traumatic Brain Injury: A Survey of Canadian Intensivists, Neurosurgeons, and Neurologists. Crit Care Med 2013; 41: 1087–1093

Outcome Prediction Turgeon AF et al. Determination of Neurologic Prognosis and Clinical Decision Making in Adult Patients With Severe Traumatic Brain Injury: A Survey of Canadian Intensivists, Neurosurgeons, and Neurologists. Crit Care Med 2013; 41: 1087–1093

“The lack of improvement in head injured patients is typified by the apparent overall lack of progress in head injury care, which is suggested by the failure to identify a single therapy to improve outcome despite over 250 randomised controlled trials. However, several studies have shown that the institution of packages of specialist neurosurgical or neurocritical care is associated with improved outcomes.”

Summary Therapeutic targets Hypotension still bad for brains Intracranial pressure monitoring Just a number but (probably) useful as part of neurocritical care package Decompressive craniectomy Size may matter; await RESCUEICP Osmotherapy HTS or mannitol will lower ICP but not alter outcomes Prognostication S-100β protein shows promise