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Functional cerebral monitoring in patients with critically illness
Anne-Marie Guerguerian MD PhD Assistant Professor of Critical Care Medicine & Pediatrics
Scientist in Neurosciences & Mental Health, Research Institute Hospital for Sick Children, University of Toronto
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Disclosure
• No financial conflict of interest
• Research funding
– SickKids Research Institute Funds
– Ontario Neurotrauma Foundation
– Canadian for Funds for Innovation
• Devices & technologies approved for use in human subjects ± children, Health Canada ± special access, FDA, European CE
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Objectives
(1) Provide an overview of current & innovative approaches available for the assessment of the critically ill patient at risk of neurological injury
(2) Review some indications, potential complications, and expected results
(3) Highlight the exciting potential implementing neuromonitoring using an integrated interdisciplinary approach at the bedside.
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How close are we to a brain global functioning positioning system?
Brain global FPS?
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Outline
• Preclinical and clinical rationale for measuring cerebral function during critical illness
• What’s feasible with research vs. clinical resources?
• Why it’s important at an
– Individual level: What does it mean for the patient now and later?
– Collective level: What can it tell us about the care we deliver?
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• Are important but have intrinsic limitations
– Intended to examine very specific mechanisms & hypotheses, e.g., isolated pathway
– Specific to species, insult paradigm, outcomes
– Fail to reproduce duration of critical illness and management
Preclinical experimental models of
acquired brain injury
Acquired brain injury
time
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Clinical rationale for integrated neuromonitoring = clinical reality
• Clinical reality = patient
– Genotype
– Phenotype
– Exposure to disease (s) with underlying conditions
– Exposure therapy (ies)
time
Acquired brain injury
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Preclinical to clinical translation
• Single
• Discrete in time
• Clear developmental or age stage
• Pharmacological & environmental exposure are systematic and consistent
• Genetically homogeneous
• Complex
• Continuous and/or repeated
• Age with maturation modifications
• Pharmacological & environmental exposure are variable
• Genetically ?
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Cerebral function monitoring
Assumptions about measurement:
Physiologic brain activity = wellness
– Communication
– Sleep
– Pressure regulation
Pathologic brain activity (or change) = badness
– Coma
– Delirium
– Seizure
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Magistretti & Pellerin Science 1999
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Magistretti & Pellerin Science 1999
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Functional Neuromonitoring • Clinical Examination
• SBP, DBP, MBP, CVP
• Sp02, SaO2, SvO2
• PaO2, PaCO2, ETCO2
• Core Temperature
• ECG
• Blood/Serum chemistry – Glucose
– Lactate
– CPK, Troponin, LFTs
• Blood/Serum biomarkers
• VO2, DO2, ERO2
• Echo
• Imaging
• Clinical Neurofunctional Examination
• ICP, CPP
• ETCO2, cerebral rSO2
• Brain tissue oxygenation PbtiO2
• Core or Brain Temperature
• EEG
• Cerebral extracellular chemistry – Glucose
– Lactate/Pyruvate
– Glutamate & Glycerol
• Cerebral biomarkers
• Transcranial Doppler Ultrasonography
• Imaging CMRO2
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Computing set up
Dong Joo Kim PhD
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Domains & Devices integrated for critically ill patients
Patient & Family
Ventilator & ECLS
Bedside Monitor Pulse Oxymeter
Cerebral oximetry ICP
Capnograph
Transcranial Doppler ultrasonography
EEG
RN Clinical Laboratory
Metabolic cart Extracellular chemistry Cerebral microdialysis
Judy VanHuyse, Vera Nenadovic &
Karen Dryden Palmer
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CUMULATIVE EXPOSURE
Going beyond the absolute values
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ICP - responses to changes in intracranial compliance
• Absolute values - guide surgical evacuation of intracranial hemorrhages & space occupying lesions
• Repeated values - “ICP and CPP guided” management
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Cumulative exposure to secondary injury Pressure-time index: time x magnitude quantification of secondary CPP insults
Jones 2005, Lo 2009
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Cerebral Oxygenation Direct Brain Tissue
• Tunneled probe inserted into the brain tissue by neurosurgeons
• Probe: thermocouple sensors for O2 and Temperature that measures O2 diffusing from tissue
• PbtiO2 > 25-30 mmHg
• Device:
Monitor & Probes by Licox®
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Hyperventilation associated with: decreased cerebral blood flow and brain tissue hypoxemia
Gopinath 1999
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Survival & Duration of time below PbtiO2
Adults after Subarachnoid Hemorrhage
Ramakrishna & Leroux 2008
Survivors spend less time at a low PbtiO2
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NEUROVASCULAR UNIT FUNCTION?
Going beyond the absolute values
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Magistretti & Pellerin Science 1999
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Brady 2009
Continuous monitoring of cerebrovascular pressure reactivity after traumatic brain injury
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Brady 2009
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100
200
ABP[mmHg]
0
0
1
-1
PRx
10:00 14:00 16:00 18:00 20:00 22:0012:00Time
PRx
36.5
37.5
37
38
38.5
T[C ]
25
50
ICP[mmHg]
0
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ATBI Study Funded ONF Hutchison et al Dong Joo Kim PhD
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BEDSIDE TCD & CEREBRAL OXIMETRY
Beyond the absolute values
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Cerebral blood flow velocity and autoregulation index after pediatric traumatic brain injury MCA flow velocity & ABP
• Autoregulation index testing & Cerebral hemodynamic predictors of poor 6-month Glasgow Outcome Score in severe pediatric traumatic brain injury
Aaslid Vavilala 2006 + Chawait 2009, + Udumphorn 2008, (-) Figaji 2009
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Impaired pressure regulation during CPB rewarming using MXa
Joshi 2010
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Regional cerebral oxygenation saturation estimated by near infrared technology
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Noninvasive infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters
Jobsis 1977
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Cerebral oxygen saturation rScO2 Methodology: NIRS Near Infrared Spectroscopy Device: INVOS
Ⓣ
Unit: % Expected Normal: 50-90 %
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Pressure regulation estimated with cerebral oxygenation measured by near-infrared spectroscopy
Lee 2009
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18:40
40
50
CBFv[cm/s]
30
0
100
50
ABP[mmHg]
150
30
60
0
EtCO2[mmHg]
19:00 19:10 19:20 19:30 19:4018:50
0
1
-1
MxA
36.76
36.78
36.80
36.74
Time
T[C ]
72.5
75
70
SPO2[%]
CBFv
Early efficacy endpoints ? RCT surgical managements in neonatal congenital heart disease
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CONTINUOUS EEG
Beyond the absolute values
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Magistretti & Pellerin Science 1999
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Coma and seizures after hypoxic ischemic injury from cardiac arrest
Mueller 1968…Sherman 1999; Agnew 2003, Shahwan 2010
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EEG monitoring during hypothermia after pediatric cardiac arrest
Abend 2009
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Quantitative EEG correlates of low cerebral perfusion in severe stroke
Diedler 2009
Left stroke
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Nenadovic 2008
Fluctuations in cortical synchronization in pediatric traumatic brain injury
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Nenadovic 2008
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Can extracellular milieu inform us on cerebral function?
• Cerebral tissue oxygen levels • Brain tissue extracellular space chemistry with cerebral
microdialysis – Glucose: energy substrate – Lactate/ Pyruvate: indicator of anaerobic metabolism & ischemia – Glutamate: indicator of synaptic dysfunction or cell damage – Glycerol: indicator of cell membrane breakdown
• Bedside clinical applications was pioneered in Sweden • 2004 FDA Workshop: role to enhance preclinical to clinical
transition of therapy development? • Pharmacology Bullock
• Biomarkers… cytokines C. Roberston
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Cyclosporin A Preserves Mitochondrial Function after Traumatic Brain Injury in the Immature Rat and Piglet Kilbaugh et al 2011
Lactate/Pyruvate Ratio Axonal Injury & Ischemic Volume
Metabolism Anatomical structure
Cerebral blood flow
Cerebral blood flow
CxA
CxA
CxA
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Remaining Limitations and Challenges
• Uncertainty
– validity, reliability, assumptions, generalizability
– risks, Hawthorn effects…
• Practical considerations:
– Computing challenges
– Complexity at the bedside
– Costs
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André-Philippe Coté, Lapresse 2010
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Exposure to disease & exposure to care
Protocol for intervention & co-interventions
Acquired Brain Injury & Critical Illness Management
Clinical guideline for intervention and co-interventions
Acquired Brain Injury & Critical Illness Management
Acquired brain injury
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Acknowledgements
Acquired Brain Injury Research Team
Dong Joo Kim
Jamie Hutchison
Judith Van Huyse
Jura Augustinavicius
Sumaira Hussain
Karen Dryden Palmer