Mesure duDébit Sanguin Cérébral
Cardiorespiratory Physiology /PostGraduate Refresher Course
Pierre Pandin, Dpt Anesthésie-Réanimation, CUB Hôpital Erasme, 16 mai 2018
Thursday December 5th 2019
Cerebral hemodynamics
Pierre Pandin MDDept Anesthesiology & Critical CareCUB Erasmus HospitalBrussels, Belgium
Preamble – Definition…
Cerebral Blood Flow…CBF = CmrO2 / (CaO2-Cv02)CBF = CPP / CVR
Cerebral Blood Flux…
Cerebral perfusion…
Cerebral Blood Supply…
Cerebral arterial perfusion…
Cerebral arterio-venous perfusion…
CBF heterogeneity
Difference regarding the sensibility to the hypoxia and the ischemia
Central compartmentCircle of Willis
Peripheral compartmentConvexity and cerebral lobes (grey matter)
Anterior high perfusion pressure
compartment(carotid supply)
Posterio lowperfusion pressurecompartment(basilar trunk supply)
Cerebral Blood Flow in Summary…
Two perconceived ideas:- No energetic reserve YES- Relative constant blood flow NO
Cerebral Hemodynamics - Physiology
Cerebral Blood Flow…CBF = CmrO2 / (CaO2-Cv02)CBF = CPP / CVR
Ohm’s law: CBF = ∆P / R
∆P (CPP) = MAP – CVP
R = arteriolar low vascular résistances(Poiseuille’s law)
50 mL.100g-1.min-1
Li X, Biomed Res Int 2014
Cerebellar CBF values determined by FAIR ASST were 43.8 ± 5.1mL/100 g/min for GM and 27.6 ± 4.5 mL/100 g/min for WM. Quantitative perfusion studies indicated that CBF in cerebellum GM is 1.6 times greater than that in cerebellum WM.
Vascularisation Cérébrale
Brain physiology
Brain circulatoryphysiology
Neural dysfunction thresholds…
Cerebral Blood Flow Regulation
Humoral and chimical
(H+, K+, Ca2+, adenosine, osmolarity…)
Nervous extrinsic(superior cervical
ganglion, sphenopalatine& otical ganglions,
peptidergic fibers…)
Automatic, sympathetic nerve
system (auto-regulation)
Cerebral Blood Flow Regulation
Cerabral vascularautoregulation
Metaboliccoupling
CO2 Vasoreactivity
Cerebral Blood Flow ControlCerebral Autoregulation
CPP = MAP – CerebralVP
CPP = MAP – ICPCPP = MAP – CVP [CVP>ICP]
CPPadult = 80-100 mmHg
CPPpedia = 65-85 mmHg
0
25
50
75
100
Adult
Child
Infant
CBF (mL.100g-1.min-1)
MAP
(mmHg)
CPP
(mmHg)
60 160
50 130
Vasodilation Vasoconstriction
Ø arteriolar
CEREBROVASCULAR RESERVE
Pressure regulation
Taccone, Curr Vasc Pharm 2012
« Non-pressure » regulation
Haggendal, Acta Physiol Scand 1965
CBF oxygen reactivity
Physiological mechanisms
- Myogenic (rapide but inaccurate)
- Metabolic (NO, adenosine, prostaglandines –
accurate but delayed)
- Neurogenic (accurate but delayed)
Physiopathology
- Arterial hypertension (reversible right shift)
Therapeutic application
-Controlled hypertension (Rosner J et al
Trauma 1990, J Neurosurg 1995)
Anesthesia
- Halogenated: dose-dependante alteration
- Intravenous: conservation
- Concept of MAP maintenance
0
25
50
75
100
Adult
Child
Infant
CBF (mL.100g-1.min-1)
MAP
(mmHg)
CPP
(mmHg)
60 160
50 130
Vasodilation Vasoconstriction
Ø arteriolarCerebral Blood Flow ControlCerebral Autoregulation
CBF (mL.100g-1.min-1)
PaCO2
(mmHg)
20 40 80 10050
Adulte
Enfant
CBF changes 2 to 3% for each mmHg of PaCO2
Physiological mechanism - maximum 6-8 hours- Preliminary extracel. & CSF H+ ↘ Secondary HCO3-
reaction
Physiopathology-Ischemia threshold PaCO2 30mmHg?
(PaCO2 20mmHg = flat / suppressed EEG)
Therapeutic applicationsRapid & simple for decreasing CBF in neuroanesthesia
et neuroICU
Vasodilation Vasoconstriction
Ø artériolarCerebral Blood Flow ControlCO2 vasoreactivity
CO2 vasoreactivity
CO2 vasoreactivity
Normoxemia
Hypoxemia
Exp Physiol 2014
Oxygen/CO2 vasoreactivity relationship
0
25
50
75
100
Adulte
CBF (mL.100g-1.min-1)
PAM
(mmHg)
PPC
(mmHg)
60 160
50 130
Vasodilation Vasoconstriction
Ø arteriolar
PaCO2
(mmHg)10 85
PaO2
(mmHg)20 125
CPP (PAM)
PaCO2
PaO2
Normal
Cerebral Blood
Flow ControlIn practice
Physiological mechanism
- Δ 1°C = Δ 5-7% DSC
Physiopathology
- Hyperthermia
- Seizure & convulsions(coupling rupture by intercurrent vasodilation,
↑ CBF et ICP)
Therapeutic applications
- Mild hypothermia (34-35°)(coupling maintenance or recovery,
↓ CBF et ICP)
Anesthesia
- Barbiturates
- Others(coupling maintenance, ↓metabolism
& ↓ CBF et ICP)
CBF (mL.100g-1.min-1)
CMRO2
(mL.100g-1.min-1)
CMRglu
(mg.100g-1.min-1)
3,5
5
5
6,5
Adult
Child
Vasodilation Vasoconstriction
Ø arteriolarCerebral Blood Flow ControlMetabolic coupling
Cerebral Blood Flow Regulation
Triple control:- Autorégulation
- CO2 vasoreactivity- Metabolic coupling
Distributivelarge caliber
proximal arteriesOui
Arteriolo-capillarySmaller caliberDistal arteriesTo be seen…
Intrinsic property of smooth muscle to respond to changes in mechanical load or intravascular pressure
Exists in arteries and arterioles denuded of endothelium and in sympathetically denervated animals
Ca2+ and Cl- channels / K+Ca channels
Bayliss, J Physiol 1902
Busija, Rev Physiol Biochem Pharamacol 1984
Osol, Am J Physiol Heart Circ Physiol 2002
Cannulated Arterial Segments
Myogenic regulation
Nitric OxideEndothelium-Derived
Hyperpolarizing FactorPGI2
Endothelial biochemical regulation
Large and small pial arteries
SCG = superior cervical gangliaSPG = sphenopalatine ganglionOG = otic ganglionTG = trigeminal ganglion
Rostral vs. caudal increase
Reactivity to NE is greater in ACA compared to MCA (cats)
a-receptors
5-HT1B
Neural regulation
Baron, EMC 2001
Low levels of CBFHypothalamus, cerebellum, medulla
High levels of CBFCochlear nucleus, mammillary body, cortex
Edvinsson, 1993
Metabolic regulation
Metabolic regulationDependence to the metabolic threshold
20% of maximaloxygen uptake
40% of maximaloxygen uptake
TCD
Healthy Volunteers
Other influences on Cerebral Blood Flow
Partial pression
of oxygen –
PaO2
HematocritTemperature
Multimodal regulation / reactivity
Adenosine
Metabolic
Regulation
Neural
RegulationMyogenic
Regulation
Chemical
Regulation
Endothelium
NO
L-arg
Extrinsic Intrinsic
Carotid sinus, aortic arch (Baroreceptors)
MAP
MAP-based
Regulation
Brain
metabolism
Brain
activity
Perivascular
pH
Adenosine
H+VI
P
PaCO2
K+
Brian Stem Chemoreceptors
Multimodal regulation / reactivity
Original dilution method Kety & Schmidt (1945)Inhalation – dilution of N20Arterio-venous difference during a 30min long period
Scintigraphy Xe 133Especially regarding the regional cerebral blood flow
Positron Emission TomographyO15
Cerebral blood flow assessmentTechniques of reference
Perfusion MRI
Perfusion CTscan(coupled to AngioScan)Global regional & vascularterritories parameters:
- Maximum time (Tmax, scdes vs
minutes)
- Peak to time (scdes vs minutes)
- Mean transient time to peak(scdes vs minutes)
- Cerebral Blood Volume (ml.100g-1)
- Cerebral Blood Flow (Cerebral
Blood Flow, ml.min-1.100g-1)
Cerebral blood flow imaging
But in the real live, at the patient’s bedside…
Tissular thermo-dilution(thermo-dilution probe)
Minimal invasiveContinuous / MonitoringRegional Cerebral Blood
Flow
Neurosonology
Transcranial DopplerTranscranial DuplexTranscranial Triplex
Tissular microDoppler
Non invasiveContinuous vsdiscontinuous
Time-to-time exam vsmonitoring
Regional Cerebral Blood Flow
Tissular oximetryCerebral oximetry
(rSO2, SctO2)
Non invasiveRegional Cerebral Blood
Flow
Cerebral blood flow assessment at the patient’s bedside…
• In 1956, Clark described the principles of an electrode that could measure
oxygen tension (polaro-graphy) in blood or tissue.
7-15mm3
Regional Cerebral Blood FlowFrom the origin to the concept…
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Regional Cerebral Blood Flow
The Bowman perfusion monitor connected to the Qflow probe to monitor continuously the rCBF in absolute units(ml.100g-1.min-1) and temperature
Insertion 2.5cm below the dura in the white matter and CT-Scan checked
Regional vs local thermo-dilution tissular probe
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Regional Cerebral Blood Flow
The Bowman perfusion monitor connected to the Qflow probe to monitor continuously the rCBF in absolute units(ml.100g-1.min-1) and temperature
Insertion 2.5cm below the dura in the white matter and CT-Scan checked
Regional vs local thermo-dilution tissular probe
Tunneled Bolt
16 adult farm-bred sheep
n=16 adult farm-bred sheep
Regional tissular CBF – Early validation
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Multimodality:- Spherical rCBF measurement at the catheter tip- Recommendation = close to ICP or as much as possible (systematically) combined to PbtO2/ICP catheter
Regional Cerebral Blood FlowRegional vs local thermo-dilution tissular probe
n= 20 adult patientswith severe TBI
Hyperventilation ChallengeCerebral CO2 vasoreactivity preservation
MAP ChallengeCerebral autoregulation preservation
Regional tissular CBF – integration in practice
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Local/Regional CBF vs Transcranial Doppler
- Continuous lCBF and sequential TCD assessment
Cortical autoregulation (lCBF) was worse than autoregulation assessed in the MCA (TCD) during rising ICP and falling CPP
- CPP > 60mmHg, cortical assessed autoregulation (lCBF)
is similar to autoregulation assessed in the MCA (TCD)
Neurol Res 2010; 32: 425-428
N=29 adult patients with severe TBI
Neurosonology
J Neuroimaging 2011; 21: 177-183
The ASNM and ASN strongly support:- Acquisition and interpretation of intraoperative TCD ultrasonograms performed by qualified individuals- Service providers define their diagnostic criteria and develop ongoing self-validation programs of these performance criteria in their practices(Class III evidence, Type C recommendation)
TCD monitoring is an established monitoring modality:- Assessment of cerebral vasomotor reactivity and autoregulation- Documentation of the circle of Willis functional status- Identification of relative cerebral hypo- and hyper-perfusion- Detection of cerebral emboli(Class II and III evidence, Type B recommendation)
2011 international American recommendations
Neurosonology2012 international European (ESNCH) recommendations
Structured systematizedmultiplane approach (temporal window):
5 axial US views vs planes1 coronal US view vs plane (basilarpre-brainstem)
Neurosonology / Auto-regulation
Sundgreen, Stroke 2001
Neurosonology / Auto-regulation
MC
A M
V
MAP (mmHg)
30 40 50 60 70 80 90 100
90
60
30
0
Cerebral oximetry: the reality in some numbers…
Normal SctO2 between 60 and 75% (algorithmic reasonning & contextualizing)
Baseline variation as high as 10%, may be 20%(individual and disease-specific thresholds)
Smith M et al. Near Infrared spectroscopy: shedding light on the injured brain. Anesth Analg 2009; 108: 1055-1057
Thavasothy M et al. A comparison of cerebral oxygenation as measured by the NIRO 300 and the INVOS 5100 near-infrared spectrophotometers. Anesthesia 2002; 57: 999-1006
Reduction of 13% from baseline reflects a threshold of cerebral ischemiaAl-Rawi PG et al. Tissue oxygen index: thresholds for cerebral ischemia using near-infrared spectroscopy. Stroke 2006; 37: 2720-2725
SctO2 of 35% for longer than 2-3h: permanent neurological deficitsKurth CD et al. Cerebral oxygen saturation-time threshold for hypoxic-ischemic injury in piglets. Anesth Analg 2009; 108: 1268-1277
Smith M et al. Near Infrared spectroscopy: shedding light on the injured brain. Anesth Analg 2009; 108: 1055-1057
Clinical change in SctO2 / rSO2
Anesthesiology 2016; 124: 826-836Threshold10%
Cardiopulmonary bypass Carotid cross-clamping
Cerebral Blood Flow vs EEG / SctO2 (rcSO2)
Cerebral oximetry: the great controversy
- Broad validation and use for somatic monitoring of normal brain at risk of injury as measure of autoregulationBrady KM et al. Stroke 2007; 38: 2818-2825Smith M et al. Philos Transact A Math Phys Eng Sci 2011; 369: 4452-4469
- Particular validation in neonates and childrenKnirsch W et al. Acta Anaesthesiol Scand 2008; 52: 1370-1374
- Very variable correlation for SjvO2 and biomarkers(S100β) with conflicting resultsKnirsch W et al. Acta Anaesthesiol Scand 2008; 52: 1370-1374Adelson PD et al. Acta Neurochir Suppl 1998; 71: 250-254Subbaswamy A et al. Neurocrit Care 2009; 10: 129-135
- Poor alternative conclusive informations regarding acute pathological situations (TBI,
stroke, cerebral hemorrhage…)
- May be adapted after acute phase in brain injured patients (TBI, stroke, cerebral
hemorrhage…)Taussky Ph et al. Neurosurg Focus 2012; 32: E2
Cerebral oximetry: some persisting questions…
- Regarding carotid surgery (CEA):« NIRS-guided carotid endarteriectomy always controversed and has to be validated against electrophysiology »Giustiniano E et al. J Cardiovasc Med 2010; 11: 522-528Pïcton P et al. Anesth Analg 2010; 110: 581-587Stoneham MD et al. Anesth Analg 2008; 107: 1670-1675
- Regarding cardiac surgery:« NIRS does not support to prevent significatively POCD & stroke – Probably no powerful enough to characterize a complex and multi-origin problem» - no official guidelinesVohra HA et al. Interact Cardiovasc Thorac Surg 2009; 9: 318-322Murkin JM et al. Br J Anaesth 2009; 103Suppl1: i1-i13Selnes OA et al. N Eng J Med 2012; 366: 250-257
- Possible perspectives:1. Generalization of a systematic use in cerebral at risk patients – Remains under discussionSmith M. Philos Transact A Math Phys Eng Sci 2011; 369: 4452-4469
2. Generalization during sitted or semi-sitted (beach-chair) surgical position (20% of hypotension with ischemia-related cerebrovascular
events / 80% of patients with significant hypo SctO2) – No strong evidenceD’Alessio JG et al. Reg Anesth 1995; 20: 62-68 / Friedman DJ et al. Orthopedics 2009; 32: 256 / Dippmann C et al. Arthroscopy 2010; 26: S148-S150 / Fischer GW et al. Pain Pract 2009; 9: 304-307 / Murphy GS et al. Anesth Analg 2010; 111: 496-505
3. Functional dimension – Further developmentCsipo T et al. GeroScience 2019 https://doi.org/10.1007/s11357-019-00122-x
- Regarding ICU: signification problem remains:« Problem of the NIRS monitoring signification in non-healthy brain remains (problem of reference for the patient)…»Li Z et al. Microvasc Res 2010; 80: 142-147Leal-Noval SR et al. Intensive Care Med 2010; 36: 1309-1317
n = 44Up to 3 months of age
Cerebral oximetry & at risk patients: infants…
SctO2 / rSO2 Hospital stay duration prognosis
Cerebral oximetry: finally, today and after…
- However, the physiological dimension is becoming increasingly clear
- Probably unable to answer questions that are often too complex
- Review how we pose the problem: a simple answer to a simple question
- Brain tolerance to hypotension (intraoperative period)…
- Brain tolerance to PaC02 variations (hypocapnia)…
- Bedside monitoring of cerebral vasoreactivity (triple control)
- Physiology of the cerebral hemodynamics: complexe anatomy with vascularspecificities
- Cerebral hemodynamics: multiples regulations & reactivitiesSeveral mechanisms working simultaneouslyPredominance of Pressure (MAP) and CO2 (vasoreactivity
- Assessment / Monitoring- Imaging (not for monitoring)- PtiO2 / Pb02- Neurosonology- Cerebral oximetry SctO2 / rS02
Coming back home messages…
Coming back home messages…
- Physiology of cerebral blood flow under the triple control
- Central compartment: main vessels and Circle of Willis
- Peripheral compartement: arterio-cappilary tissular compound
Step 1 - basicCerebral oximetryNon-invasiveRemain to be refined and defined regarding patients and indications
Peripheral
Step 2 - intermediate
NeurosonologyNon-invasiveOperator dependentStructural, hmdy and ICP informationICP evaluationCentral > peripheral
Step 3 - advancedTissular thermo-dilutionMinimal-invasiveCatheter combined with ICP (only ICU)Optimal insertion site
Regional peripheral
Cerebral Blood Flow MonitoringNeurosono (TCCS) + rSO2 / Sct02 (NIRS): THE solution to be developed regarding either
intraoperative period or ICU