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)

Secondary brain injuries often result from complications of the primary mechanism of injury and may occur anywhere from hours to days after the initial injury (Dawodu, 2007)

So at best

Neurocritical Care will only save neurons that have not died

NCCU Has 3 functions

Maintain Airway Good Nursing Care Weaning from Ventilator

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

utter clusterfxxx /

abject harm

perfect care

/ good outcome

The Spectrum of Neuro Critical Care

The goodperfectionist

The bad perfectionist Nature

Where most of us practice

{

BUT WE MUST STOP SECONDARY INJURY….

Like Hypotension?

BUT WE MUST STOP SECONDARY INJURY….

Like ICP?

HYPERVENTILATION1982 Good 2002 Bad

C O O L I N G

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?

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

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

So we await….

S T E R O I D S

2004 Bad1985 Good

N E U R O P R O T E C T A N T S … .

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

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

The Time to Save neurons is BEFORE Neurocritical care

Once there… In the spontaneously breathing patient…

than NOB THERAPYIs all this really better

VentilationArt Line

Central LineVasopressors

ICPLicox

Microdialysis TPN

Tracheostomy

Neurocritical care is no better than

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 ?

Neurocritical care improves outcome in severe traumatic brain injury

Martin SmithConsultant & Honorary Professor in Neurocritical CareThe National Hospital for Neurology & NeurosurgeryUniversity College London Hospitals

Diringer et al, Crit Care Med 2001; 29: 635-40

• notbeinginaneuroICUisassociatedwithanincreaseinhospital

mortalityafterintracerebralhaemorrhage

(OR,3.4;95%CI,1.65–7.6)

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

• treatmentguidedbyICPmonitoringvs.carebasedonimagingandclinical

examinationinabsenceofICPmonitoring(n=324)

• similarthree- andsix-monthoutcomes

Benchmark Evidence from South American Trials: Treatment of Intracranial Pressure (BEST:TRIP)

Chesnut et al, New Engl J Med 2012; 367: 2471-81

• moderatehypothermiaoneofthemosteffectiveneuroprotectivestrategiesinpreclinicalstudies

- translatedintohumans

Targetedtemperaturemanagement

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

• Eurotherm3235trialrandomized387patientsfrom47centersin18countries

– TTM(32-35˚C)asacomponent ofICPmanagementofintracranialhypertension(ICP>20mmHg) resistanttoinitialICP-loweringtherapies

• recruitmentsuspendedearlybecauseofsafetyconcernsinthehypothermiagroup

– worsefunctionaloutcomes (odds ratio1.53,95%CI1.02-2.30)

– highermortalityrates(hazardratio1.45,95%CI1.01-2.10)

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

• complexandmultifactorial

• severalcomponentsofkeyimportance

– reductioninsubstratedeliverybelowcriticalthresholds

– failingcellularmetabolism

− inabilitytoutilizedeliveredoxygen&glucose

− profoundmetaboliccrisis

• cerebralischaemia/hypoxia

– tissueburdenrelatedtoclinicaloutcome

Pathophysiologyoftraumaticbraininjury

• secondaryinsultsadverselyaffecttheinjuredbrain

– associatedwithworseoutcomes

– prevention/rapidtreatmentassociatedwithimprovedoutcomes

Pathophysiologyoftraumaticbraininjury

– hypoxia

– hypotension

– hyper- andhypocarbia

– hyper- andhypoglycaemia

– hyperthermia

– intracranialhypertension

– seizures

Secondaryinsults

McHugh et al, J Neurotrauma 2007; 24: 287-93

• IMPACTstudydatabase

− mergedcohortof7phaseIIIRCTswith>9000patients

• singleepisodeofhypoxiaorhypotensionstronglyassociatedwithworse

outcome

- hypoxiaOR2.1(95%CI1.7-2.6)

- hypotension OR2.7(95%CI2.1-3.4)

SystolicBP<90mmHgorPaO2

<8.0kPamustbeavoidedor

rapidlycorrectedafterTBI

• ABGtargets

– PaO2 >13.0kPa

– PaCO2 4.5- 5.0kPa

• CVStargets

– MAP>90mmHg

– volumeresuscitation

– vasopressors/inotropes

• glucose5.0- 10.0mmol/l

• coretemperature<37oC

• ICP<20cmH20

• CPP50-70mmHg

Brain Trauma Foundation, J Neurotrauma 2007; 24: S1-S106

Consensusguidelines

Brain Trauma Foundation, J Neurotrauma 2007; 24: S1-S106

Consensusguidelines

• guidelinesareatool,notagoal

• goalisindividualised,targeted

treatment

• treatmentguidedbymonitor-derived

physiologicalvariables

• ABGtargets

– PaO2 >13.0kPa

– PaCO2 4.5- 5.0kPa

• CVStargets

– MAP>90mmHg

– volumeresuscitation

– vasopressors/inotropes

• glucose5.0- 10.0mmol/l

• coretemperature<37oC

• ICP<20cmH20

• CPP50-70mmHg

• multimodalmonitoringallowsdeliveryoftailoredtreatmentregimens– identifyphysiological/pathophysiologicalphenotype

– guidetargetedtherapy

– assesseffectsoftherapy

– guidedecisionsaboutintensityanddurationoftherapy

– improvedpatientoutcomes

• confidencetowithholdpotentiallydangeroustherapyinthosewithoutevidenceofbrainischaemiaormetabolicdisturbance

Individualizedtherapy

ICP-directedmanagement

• greatlyelevatedICPisfatal– abilitytocontrolitislimited

• oversimplifiedconceptssurroundingmanipulationofICPandtheassociationwithoutcome– thresholdsforinitiatingmedicalandsurgicalmanagement

– cerebralperfusionoftennotcompromisedevenifICPis>20mmHg

– outcomeeffectsofcurrenttreatmentprobablysmallerthanwethink

– alltreatmentshavesideeffects

• severeTBIisanoverwhelmingandcomplexprocess

– involvesneurones,gliaandvasculature

– raisedICPcompressescerebralveinscreatingaself-regeneratingcycleofevenhigherpressure

Nangunoori et al, Neurocrit Care 2012;17: 131-8

• brainresuscitationbasedoncontrolofICP&CPPalonedoesnotpreventcerebralhypoxiainsomepatients

• increasedhypoxiaburdenassociatedwithpooroutcome

Nangunoori et al, Neurocrit Care 2012;17: 131-8

(2009)(2003)

(2009)(2010)

• brainresuscitationbasedoncontrolofICP&CPPalonedoesnotpreventcerebralhypoxiainsomepatients

• increasedhypoxiaburdenassociatedwithpooroutcome

• PtiO2-directedtherapyassociatedwithimprovedoutcomeaftersevereTBIcomparedICP/CPPbasedtherapyalone

Marenko et al, J Clin Neurosci 2016; 26: 8-13

• optimalCPPis�92.5mmHgwithan

autoregulatoryrange

between80–100mmHg

• maintenanceofCPP

withinBTFguidelines

(50–70mmHg)would

leavethispatientatrisk

ofon-goingischemia

• braintissuedestructioncausedbyacuteinjuryisworsenedbyon-goinginsults- early,aggressiveinterventiontominimizesecondaryinsultsimprovesthe

outcometrajectoryinmanypatients

- minimizingsecondinsultswillminimizeresidualdisability

CriticalcaremanagementofsevereTBI

• getallthelittlethingsrightallthetime- neurocriticalcareisasmuchaboutmeticuloussystemicphysiological

optimizationasitisaboutspecificbrain-directedtherapies

• keepitsimple- thesix‘Ns’– normoxia

– normocapnia

– normovolaemia

– normotension

– normoglycaemia

– normothermia

– normonatraemia

– normomagnesaemia

CriticalcaremanagementofsevereTBI

• getallthelittlethingsrightallthetime- neurocriticalcareisasmuchaboutmeticuloussystemicphysiological

optimizationasitisaboutspecificbrain-directedtherapies

• optimisecerebralhaemodynamics andoxygention

– blindadherencetoguidelinesrisksdeliveringpotentiallyharmful

treatmentthatisofnobenefit

– individualizeICPandCPP-guidedtherapy

– multimodalphysiologicalmonitoring

CriticalcaremanagementofsevereTBI

• systemicorgansmayfail- sympatheticsurgeandneuroinflammatoryresponsescancause

neurogenicpulmonaryoedema,stresscardiomyopathyandageneralendocrinopathy

- complicationsofbrain-directedtreatment

CriticalcaremanagementofsevereTBI

• systemicorgansmayfail- sympatheticsurgeandneuroinflammatoryresponsescancause

neurogenicpulmonaryoedema,stresscardiomyopathyandageneralendocrinopathy

- complicationsofbrain-directedtreatment

• complexinteractionbetweenbrainandsystemicphysiology

- optimizesystemicandintracranialvariables

- physiologicalneuroprotection

CriticalcaremanagementofsevereTBI

English et al, Neurocrit Care 2013; 18: 131-142

English et al, Neurocrit Care 2013; 18: 131-142

• burdenofneuronallossdirectlyrelatedtoclinicaloutcomes

– minimizesecondaryischaemicbraininjury

• clinicalguidelinesareausefulstartingpoint

• individualizedtreatmentregimens

• neurocritical caredoesimproveoutcomesafterTBI

Summary

THANK YOU!

SOCIETY FOR NEUROSCIENCE IN ANESTHESIOLOGY AND CRITICAL CARE

SNACC 44th Annual MeetingOctober 20-21, 2016Chicago

www.snacc.org