débit sanguin cérébral mesure du cerebral...

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