Mesure du

Débit Sanguin Cérébral Cerebral hemodynamics

Pierre Pandin MD
Dept Anesthesiology & Critical Care
CUB Erasmus Hospital
Brussels, Belgium

Pierre Pandin, Dpt Anesthésie-Réanimation, CUB Hôpital Erasme, 16 mai 2018

Cardiorespiratory Physiology /PostGraduate Refresher Course

Thursday December 5th 2019

 Preamble – Definition…

Cerebral Blood Flow…

CBF = CmrO2 / (CaO2-Cv02)
CBF = CPP / CVR

Cerebral Blood Flux…

Cerebral Blood Supply…
Cerebral perfusion…
Cerebral arterial perfusion…
Cerebral arterio-venous perfusion…
 CBF heterogeneity
Difference regarding the sensibility to
the hypoxia and the ischemia
 Peripheral compartment
Convexity and cerebral lobes (grey matter)

Central compartment
Circle of Willis
 Anterior high Posterio low
perfusion pressure perfusion pressure
compartment compartment
(carotid supply) (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 circulatory
physiology
Neural dysfunction thresholds…
 Cerebral Blood Flow Regulation

Humoral and Automatic, Nervous extrinsic

chimical sympathetic nerve (superior cervical
ganglion, sphenopalatine
(H+, K+, Ca2+, adenosine, system (auto- & otical ganglions,
osmolarity…) regulation) peptidergic fibers…)
 Cerebral Blood Flow Regulation

Cerabral vascular CO2 Metabolic

autoregulation Vasoreactivity coupling
Cerebral Blood Flow Control
Ø arteriolar
Cerebral Autoregulation

Vasodilation Vasoconstriction

CBF (mL.100g-1.min-1)

100 Child

CPP = MAP – CerebralVP

CPP = MAP – ICP 75

CPP = MAP – CVP [CVP>ICP]

CPPadult = 80-100 mmHg 50 Adult
CPPpedia = 65-85 mmHg

25 Infant

MAP 60 160
(mmHg)

CPP 50 130
(mmHg)
Pressure regulation
CEREBROVASCULAR RESERVE
« Non-pressure » regulation

Taccone, Curr Vasc Pharm 2012

CBF oxygen reactivity

Haggendal, Acta Physiol Scand 1965

Cerebral Blood Flow Control
Ø arteriolar
Cerebral Autoregulation

Vasodilation Vasoconstriction
Physiological mechanisms
- Myogenic (rapide but inaccurate) CBF (mL.100g-1.min-1)
- Metabolic (NO, adenosine, prostaglandines –
accurate but delayed)
Child
- Neurogenic (accurate but delayed) 100

Physiopathology
75
- Arterial hypertension (reversible right shift)

Therapeutic application 50 Adult

-Controlled hypertension (Rosner J et al
Trauma 1990, J Neurosurg 1995)
25 Infant
Anesthesia
- Halogenated: dose-dependante alteration
0
- Intravenous: conservation
- Concept of MAP maintenance MAP 60 160
(mmHg)

CPP 50 130
(mmHg)
Cerebral Blood Flow Control
Ø artériolar
CO2 vasoreactivity

Vasodilation Vasoconstriction

CBF (mL.100g-1.min-1)

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) Enfant

Therapeutic applications Adulte

Rapid & simple for decreasing CBF in neuroanesthesia
et neuroICU

PaCO2 20 40 50 80 100
(mmHg)
CO2 vasoreactivity
CO2 vasoreactivity
Oxygen/CO2 vasoreactivity relationship

Hypoxemia

Normoxemia

Exp Physiol 2014

 Ø arteriolar
Cerebral Blood
Flow Control
In practice Vasodilation Vasoconstriction

CBF (mL.100g-1.min-1)
CPP (PAM)
PaCO2
100
Normal

75

50 PaO2

25 Adulte

0
PAM 60 160
(mmHg)
PPC 50 130
(mmHg)
PaCO2 10 85
(mmHg)
PaO2 20 125
(mmHg)
Cerebral Blood Flow Control
Ø arteriolar
Metabolic coupling

Vasodilation Vasoconstriction
Physiological mechanism
- Δ 1°C = Δ 5-7% DSC CBF (mL.100g-1.min-1)

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 Adult
- Barbiturates Child
- Others
(coupling maintenance, ↓metabolism CMRO2 3,5 5
(mL.100g-1.min-1)
& ↓ CBF et ICP)
CMRglu 5 6,5
(mg.100g-1.min-1)
 Cerebral Blood Flow Regulation

Triple control: Arteriolo-capillary

- Autorégulation Smaller caliber
- CO2 vasoreactivity Distal arteries
- Metabolic coupling
To be seen…

Distributive
large caliber
proximal arteries
Oui
 Myogenic regulation
Cannulated Arterial Segments

Intrinsic property of smooth muscle to

respond to changes in mechanical load or
intravascular pressure

Bayliss, J Physiol 1902

Exists in arteries and arterioles denuded

of endothelium and in sympathetically
denervated animals

Busija, Rev Physiol Biochem Pharamacol 1984

Ca2+ and Cl- channels / K+Ca channels

Osol, Am J Physiol Heart Circ Physiol 2002
Endothelial biochemical regulation

Endothelium-Derived
Nitric Oxide PGI2 Hyperpolarizing Factor
 Neural regulation
Large and small pial arteries
a-receptors
SCG = superior cervical ganglia
SPG = sphenopalatine ganglion
5-HT1B OG = otic ganglion
TG = trigeminal ganglion

Rostral vs. caudal increase

Reactivity to NE is greater in ACA

compared to MCA (cats)
 Metabolic regulation
High levels of CBF
Cochlear nucleus, mammillary body, cortex

Baron, EMC 2001

Low levels of CBF

Edvinsson, 1993 Hypothalamus, cerebellum, medulla
 Metabolic regulation
Dependence to the metabolic threshold

Healthy Volunteers
TCD

20% of maximal 40% of maximal

oxygen uptake oxygen uptake
 Other influences on Cerebral Blood Flow

Partial pression
of oxygen – Temperature Hematocrit
PaO2
Multimodal regulation / reactivity
Neural
Myogenic Extrinsic Regulation Intrinsic
Regulation Brain
metabolism

Endothelium
Brain
activity

Metabolic
Regulation
NO
Adenosine
L-arg K
+
VI H+
P

PaCO2
Perivascular
MAP pH

Adenosine
Chemical
MAP-based Regulation
Regulation
Carotid sinus, aortic Brian Stem
arch (Baroreceptors) Chemoreceptors
Multimodal regulation / reactivity
 Cerebral blood flow assessment
Techniques of reference

Original dilution method Kety & Schmidt (1945)

Inhalation – dilution of N20
Arterio-venous difference during a 30min long period

Scintigraphy Xe 133
Especially regarding the regional cerebral blood flow

Positron Emission Tomography

O15
Cerebral blood flow imaging

Perfusion
Global regional &CTscan
vascular
(coupled to parameters:
territories AngioScan)

- 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
Perfusion MRI
-1
Blood Flow, ml.min .100g ) -1
But in the real live, at the patient’s bedside…
Cerebral blood flow assessment at the patient’s bedside…

Tissular thermo-dilution Neurosonology Tissular oximetry

(thermo-dilution probe) Cerebral oximetry
Transcranial Doppler (rSO2, SctO2)
Minimal invasive Transcranial Duplex
Continuous / Monitoring Transcranial Triplex Non invasive
Regional Cerebral Blood Tissular microDoppler Regional Cerebral Blood
Flow Flow
Non invasive
Continuous vs
discontinuous
Time-to-time exam vs
monitoring
Regional Cerebral Blood
Flow
 Regional Cerebral Blood Flow
From the origin to the concept…

• 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 Flow

l’Amnésie induite
Regional vs local thermo-dilution tissular probe

par l’Anesthésie
Mécanisme de
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 Cerebral Blood Flow

l’Amnésie induite
Regional vs local thermo-dilution tissular probe

par l’Anesthésie
Mécanisme de
The Bowman perfusion monitor connected to the Qflow probe to monitor continuously the rCBF in absolute units
(ml.100g-1.min-1) and temperature

Tunneled Bolt

Insertion 2.5cm below the dura in the white matter and CT-Scan checked
 Regional tissular CBF – Early validation

n=16 adult farm-bred sheep

16 adult farm-bred sheep

 Regional Cerebral Blood Flow

l’Amnésie induite
Regional vs local thermo-dilution tissular probe

par l’Anesthésie
Mécanisme de
Multimodality:
- Spherical rCBF measurement at the catheter tip
- Recommendation = close to ICP or as much as possible (systematically) combined to PbtO2/ICP catheter
 Regional tissular CBF – integration in practice

n= 20 adult patients
with severe TBI

Hyperventilation Challenge MAP Challenge

Cerebral CO2 vasoreactivity preservation Cerebral autoregulation preservation
 Local/Regional CBF vs Transcranial Doppler

l’Amnésie induite
par l’Anesthésie
Mécanisme de
Neurol Res 2010; 32: 425-428
N=29 adult patients with severe TBI

- 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)
 Neurosonology
2011 international American recommendations

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)
 Neurosonology
2012 international European (ESNCH) recommendations

Structured systematized
multiplane approach (temporal
window):

5 axial US views vs planes

1 coronal US view vs plane (basilar
pre-brainstem)
Neurosonology / Auto-regulation

Sundgreen, Stroke 2001

Neurosonology / Auto-regulation

90

60
MCA MV

30

0
30 40 50 60 70 80 90 100
MAP (mmHg)
 Cerebral oximetry: the reality in some numbers…

Normal SctO2 between 60 and 75% (algorithmic reasonning & contextualizing)

Smith M et al. Near Infrared spectroscopy: shedding light on the injured brain. Anesth Analg 2009; 108: 1055-1057

Baseline variation as high as 10%, may be 20%

(individual and disease-specific thresholds)
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 ischemia

Al-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 deficits

Kurth 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
Threshold Anesthesiology 2016; 124: 826-836

10%
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
autoregulation
Brady KM et al. Stroke 2007; 38: 2818-2825
Smith M et al. Philos Transact A Math Phys Eng Sci 2011; 369: 4452-4469

- Particular validation in neonates and children

Knirsch W et al. Acta Anaesthesiol Scand 2008; 52: 1370-1374

- Very variable correlation for SjvO2 and biomarkers

(S100β) with conflicting results
Knirsch W et al. Acta Anaesthesiol Scand 2008; 52: 1370-1374
Adelson PD et al. Acta Neurochir Suppl 1998; 71: 250-254
Subbaswamy 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: 522-528
Pïcton P et al. Anesth Analg 2010; 110: 581-587
Stoneham 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 guidelines
Vohra HA et al. Interact Cardiovasc Thorac Surg 2009; 9: 318-322
Murkin JM et al. Br J Anaesth 2009; 103Suppl1: i1-i13
Selnes 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 discussion
Smith 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 evidence
D’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 development

Csipo 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: 142-147
Leal-Noval SR et al. Intensive Care Med 2010; 36: 1309-1317
 Cerebral oximetry & at risk patients: infants…

n = 44
Up to 3 months of age
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)

 Coming back home messages…

- Physiology of the cerebral hemodynamics: complexe anatomy with vascular

specificities

- Cerebral hemodynamics: multiples regulations & reactivities

Several mechanisms working simultaneously
Predominance of Pressure (MAP) and CO2 (vasoreactivity

- Assessment / Monitoring
- Imaging (not for monitoring)
- PtiO2 / Pb02
- Neurosonology
- Cerebral oximetry SctO2 / rS02
 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 - basic Step 2 - intermediate Step 3 - advanced

Cerebral oximetry Neurosonology Tissular thermo-dilution
Non-invasive Non-invasive Minimal-invasive
Remain to be refined and Operator dependent Catheter combined with
defined regarding patients Structural, hmdy and ICP ICP (only ICU)
and indications information Optimal insertion site
ICP evaluation
Peripheral Central > peripheral Regional peripheral
 Cerebral Blood Flow Monitoring
Neurosono (TCCS) + rSO2 / Sct02 (NIRS): THE solution to be developed regarding either
intraoperative period or ICU