Monitoring the Brain
Petra Lemmers
neonatologist
Introduction
Last decades survival of infants needing large
surgery in the neonatal period has increased
– Prenatal diagnosis/perinatal care
– Minimal invasive-more precise procedures
– Intensive care
More attention for morbidity, but excluded from
follow up studies because of congenital
malformations.
Until now only scarce literature available
Introduction
• Outcome following cardiac surgery
• Increased risk of neurodevelopmental
impairment
• Brain injury
• White matter injury and stroke like lesions
Kabra et al 2007
Block et al 2010
Andropoulos eat al 2010
• Outcome following non-cardiac surgery
• Impairment in motor function
• Cognitive impairment
Mazer et al Dev Med Child Neurol 2010
Madderom et al Arch Dis Child Fetal Neonatal Ed 2012
Introduction
• Outcome following cardiac and non-cardiac surgery
– Mental and motor delay
38%
45%
26%
26%
Laing et al J Paediatr Child Health 2011
Walker et al J Pediatr 2012
Introduction
Long term follow up neonatal surgery non
cardiac malformations
• Ludman et al (London) n= 30
– 1 and 3 year: DQ scores significantly lower than controls
• NL, Rotterdam n= 80
– 5 jaar
– IQ 36% low normal range
– more children with MDI < 85 compared with normal
population.
– 30% emotional /behaviour problems
Ludman et al J Pediatr Surg 1990, 1993
Mazer P et al, Developmental medicine and child
neurology 2010
Risk neonatal brain damage
• Transition from fetal life
• Immaturity of organ systems
– Hypoxic/ischemic damage
– Hyperoxic damage
• Neurotoxicity anesthetics
Monitoring vital parameters:
(HR, BP, SaO2, pCO2, Hb, etCO2, SjO2)
• No direct information
• Cerebral oxygenation
• Brain Perfusion
• Brain activity
Monitoring the neonatal brain
Can we do more?
More direct monitoring parameters are needed:
• Stable and recognizable parameters
• Bedside monitoring possible for extended periods
of time
Monitoring the brain
• Near Infrared Spectroscopy (NIRS)
• 1 or 2 channel EEG: aEEG
Near Infrared Spectroscopy (NIRS)
•
•
•
•
Monitoring technique for cerebral oxygenation and
haemodynamics
Based on absorption of near-infrared light by
oxygenated [O2Hb] and deoxygenated Hb [HHb]
Absorption-changes in NIR-light ( ODs) can be
converted in changes of [O2Hb] and [HHb]
Regional (mixed) cerebral O2-saturation: rScO2
Reproducibility is good when used for trend
monitoring Fronto-parietal position
rScO2-Left (%)
(r= 0.88, p<0.01)
rScO2-Right (%)
Menke et al, Biol Neon 2003
Lemmers et al, Pediatr Res, 2009
Interpretation of rScO2 values
rScO2 %
100
High values (> +2SD)
90
80
70
Expected “normal” values (±2SD)
60
50
Low values (< -2SD)
40
30
20
Avoid if possible!1,2,3
10
1) Hou, Physiol Meas 2007; 2) Kurth, J Cereb Blood Flow Metab 2005;
3) Dent, J Thorac Cardiovasc Surg 2002
29
26
23
20
32
3:
3:
3:
3:
3:
14
17
3:
3:
08
05
02
59
11
3:
3:
3:
3:
2:
53
50
47
44
56
2:
2:
2:
2:
2:
38
41
2:
2:
32
29
26
23
35
2:
2:
2:
2:
2:
17
14
11
08
05
20
2:
2:
2:
2:
2:
2:
2:
02
0
aEEG
•
•
•
•
•
•
Filtered (2-15 Hz)
Amplification
Compressed (6 cm/hr)
Semilogarithmic scale
1 channel (2 parietal leads)
1 channel for impedance
aEEG
signalfiltered
aEEG
signalrectified, smoothed
aEEG
aEEG
signalcompressed in time
aEEG
aEEG
signalcompressed in time
aEEG
signalcompressed in time
Thanks to M Toet
Background patterns
Continuous
Burst Suppression
= 10 min
Discontinuous
Cont. Low Voltage
Flat Trace
Thanks to LdeVries/MToet
aEEG
Seizures
Thanks to LdeVries/MToet
Has cerebral monitoring additional value
in clinical care in the neonate in the perisurgical period?
• No randomised trials
• Scarse data available (cardiac patients)
• Conclusions are experience based
:
Brain monitoring in clinical practice
non<32
invasive
Preterm infants
wks monitoring
Preterm
wks for
72 h
Term infants
afterinfants
hypoxic<32
ischemic
events
Neonates after perinatal asphyxia
Brain monitoring in clinical practice
•
Arterial saturation (pulse
oxymetry)
•
Arterial blood pressure
•
Heart rate
•
Cerebral oxygenation by
NIRS (rScO2)
•
aEEG
Collected on a PC for offline analysis with
Signalbase®
Signalbase/bedbase: collecting and analyzing data
Monitoring the neonatal brain
•
aEEG and NIRS in clinical practice
• Relation with other clinical conditions
• Blood pressure
• Patent ductus arteriosus
• Autoregulatory ability
• (Mechanical) ventilation
• Surgery
Relation brain monitoring
• Blood pressure
• Patent ductus arteriosus
• Autoregulatory ability
• (Mechanical) ventilation
• Surgery
Limits of normal blood pressure in neonates
•
•
•
•
•
Not well defined
Mostly used definition MABP (mmHg)<GA (wks)
Hypotension is related with brain damage
Hypotension is not directly related to outcome
(Dammann 2002; Limperopoulos 2007)
Recent papers show good outcome when accepting
lower limits for MABP (Dempsey 2009)
Dopamine
5µg/kg/min
*
$
$
N=38
N=39
$ p<0.05 vs controls;
* p<0.05 vs before dopa
Bonestroo et al, Pediatrics 2011
Surgical closure of PDA
Term infant with severe anaemia and hypotension at birth;
Bowel perforation of antenatal onset
Thanks to Toet/ de Vries
Conclusion
aEEG should be continued for at least 48 hrs to be able
to detect late onset seizure after HI
Extensive watershed injury Ri > Le
Suggestion
•
Brain monitoring by NIRS and aEEG could be a
useful approach to judge the need of blood pressure
support in infants with low blood pressures
Relation brain monitoring
• Blood pressure
• Patent ductus arteriosus
• Autoregulatory ability
• (Mechanical) ventilation
• Surgery
Hemodynamically important PDA
• Ductal steal phenomenon in cerebral arteries
is a risk factor for cerebral damage in the
preterm infant (Perlman 1981)
PDA surgery after failure medication
GA 26.7 ±1.8 wks
PNA 7 days [4-39]
surgery
*
p<0.05 vs pre-clip
PDA surgery
• Advanced MRI techniques
8 brain structures
•cortical gray matter (cGM)
•central gray matter/basal ganglia (BG)
•ventricles (VENT)
•cerebrospinal fluid (CSF)
•myelinated white matter (MWM)
•unmyelinated white matter (UWM)
•brainstem (BS)
•cerebellum (CB)
Cerebellar volume smaller at term equivalent age
p<0.05 (Zethof/Lemmers/Benders submitted)
Suggestions
•
•
Monitoring of rScO2 during surgical ductal closure
can prevent surgery-related brain damage
Cerebral oxygenation should play a role in the
ultimate decision to close of a hemodynamically
important ductus arteriosus
Relation brain monitoring
• Blood pressure
• Patent ductus arteriosus
• Autoregulatory ability
• (Mechanical) ventilation
• Surgery
Autoregulatory ability
(corr)
rScO2
Cerebral blood flow
(no corr)
(corr)
Stroke 2007/2010
Cerebral perfusion
MABP Brady,
Wong, Pediatrics 2008
pressure
De Smet Adv Exp Med Biol. 2010
Aciado Ped Res 2011
21
:0
21 0
:1
21 8
:3
21 6
:5
22 4
:1
22 2
:3
22 0
:4
23 8
:0
23 6
:2
23 4
0: :42
00
0: :07
18
0: :07
36
0: :07
54
1: :07
12
1: :07
30
1: :07
48
2: :07
06
2: :07
24
2: :07
42
3: :07
00
3: :07
18
3: :07
36
3: :07
54
4: :07
12
4: :07
30
4: :07
48
5: :07
06
5: :07
24
5: :07
42
:0
7
Absence of cerebral autoregulation
200
160
120
80
20
♂, sepsis, †
180
HR
(b/min)
140
SaO2 (%)
100
rScO2 (%)
60
40
MABP (mmHg)
0
Erythrocytes
Dopamine 10
Thrombo+FFP
Dopamine 15
Dobutamine and steroids
40
1 9 :2 0
1 9 :1 8
1 9 :1 6
1 9 :1 4
1 9 :1 2
1 9 :1 0
1 9 :0 8
60
1 9 :0 6
1 9 :0 4
1 9 :0 2
1 9 :0 0
1 8 :5 8
1 8 :5 6
1 8 :5 4
1 8 :5 2
1 8 :5 0
1 8 :4 8
1 8 :4 6
1 8 :4 4
1 8 :4 2
1 8 :4 0
1 8 :3 8
1 8 :3 6
1 8 :3 4
1 8 :3 1
1 8 :2 9
1 8 :2 7
1 8 :2 5
1 8 :2 3
1 8 :2 1
1 8 :1 9
1 8 :1 7
1 8 :1 5
1 8 :1 3
1 8 :1 1
1 8 :0 9
1 8 :0 7
80
1 8 :0 5
100
1 8 :0 3
1 8 :0 1
Presence cerebral autoregulation
♂, 30 wk 945 g, day 1
SaO2 (%)
50
90
40
rScO2 (%)
70
30
MABP (mmHg)
20
50
10
Suggestions
•
•
Monitoring MABP and rScO2 can, within certain limits,
identify infants with absence of autoregulatory ability
Identification of absence of autoregulatory ability may
help to prevent brain damage
Relation brain monitoring
• Blood pressure
• Patent ductus arteriosus
• Autoregulatory ability
• (Mechanical) ventilation
• Surgery
Ventilation: pCO2
/rScO2
r=0.26
p<0.05
Vanderhaegen et al. Eur J Paediatr Neur 2008
Ventilation: pCO2
Victor et al : Pediatr 2005
15
:3
0
15
:5
0
16
:1
0
16
:3
0
16
:5
0
17
:1
0
17
:3
0
17
:5
0
18
:1
0
18
:3
0
18
:5
0
19
:1
0
19
:3
0
19
:5
0
20
:1
0
20
:3
0
20
:5
0
21
:1
0
21
:3
0
21
:5
0
22
:1
0
22
:3
0
22
:5
0
23
:1
0
23
:3
0
Ventilation: pCO2
100
90
80
70
60
10
rScO2
50
40
30
20
pCO2 (mmHg)
0
Ventilation: pCO2
♀ 26 4/7 wks; 925 g; chorioamnionitis
PV cysts
Ventilation: pCO2
pCO2 107
mmHg
pCO2 68
Toet/ de vries
mmHg
Ventilation: pO2
rScO2 (%)
fiO2
1.0
Suggestion
• Brain monitoring during (artificial) ventilation can
help to
prevent hypo/hyper perfusion and hyper/hypoxemia and so
brain damage
Relation brain monitoring
 Hypotension
 Patent ductus arteriosus
 Autoregulatory ability
 (Mechanical) ventilation
 Surgery
Neonatal cardiac surgery
Low cerebral saturations (<35%-45% ) related with
adverse outcome
Toet et al Exp Brain Res 2009
Phelps et al 2009
Sood et al J Thorac Cardiovasc surg 2013
Preliminary data
• 20 infants monitoring data: no analysis
• 11 infants MRI 4-7 days after surgery
• 4 normal
• Cerebellar hemorrhages; infarction
basal ganglia; white matter lesions
– acute brain damage? or already there
prenatally?
– due to hypoperfusion? or neurotoxicity?
– relation with outcome?
ADC-MAP
Thanks to M Benders
T2-W
Conclusions
• The current results of our studies in neonates strongly
suggest that SaO2 does not always reflect oxygenation of
the neonatal brain.
• Thus monitoring of cerebral oxygenation by NIRS and
brain function by aEEg in addition to SaO2 and blood
pressure, can help to prevent brain damage but also
prevent unnecessary treatment.
Limitations
• No randomised trials, so scarse proven data
•
are available of benefits in infants undergoing
surgical procedures
Conclusions are experience based
However:
•
•
The number of infants with (minor) neurodevelopmental
problems is high in infants undergoing surgical
procedures in neonatal period
So
Neurodevelopmental delay needs to be investigated in
relation to brain injury :
• brain monitoring
• (pre-existing) riskfactors
• brain injury by neuro-imaging
• longterm follow-up
• larger cohorts
• collaboration between disciplines in hospitals and
multi-center
Study design
Antenatally
Post partum
• Obstetrics
• Diagnosis congenital anomaly
• Pediatrics and neonatology
• cUS + aEEG + NIRS
Perioperatively
• Surgery and anesthesiology
• aEEG + NIRS + vitals + biomarkers
Postoperatively
• Pediatrics and neonatology
• aEEG + NIRS + biomarkers + cUS + MRI
Follow up at 2
and 5 years
• Psychology and physical therapy
• Neurodevelopmental outcome
Cerebral monitoring during neonatal
surgery: a first step to improve
outcome
Thank you
•
•
•
•
•
Anesthesiologists:
• Jurgen de Graaff
• Desiree vd Werff
• Ton Schouten
Pediatric Surgery:
• Maud van Herwaarden
• David van der Zee
Psychology
• Monica Uniken Venema
• Mijntje van der Linden
Pediatric intensive care
• Koos Jansen
Neonatology
– Manon Benders
– Kristin Keunen
– Mona Toet
– Floris Groenendaal,
– Linda de Vries
– Frank van Bel
Interventions
• A low rStO2 reflects a low oxygen supply to the brain (or
a high use of oxygen by the braintissue)
• If rStO2 < 55%:
– Assess cardiovascular status (BP; systemic circulation)
– Assess oxygen transport (Hb)
– Assess respiratory status (SaO2; pCO2; MAP)
Interventions
• A high rStO2 reflects a high oxygen supply to the brain
(or less oxygen use by the brain)
• If rStO2 > 85%:
– Assess respiratory status (SaO2; pCO2)
Recommendations if rScO2 is out of
expected range
•
Check sensor
• Which sensor is used?
• Position
Introduction
Preterms undergoing surgery
Filan et al, J of Pediatr 2011
Neonatal brain damage
•
Leading to neuro
developmental
problems
•
•
Cerebral palsy
Behaviour/school
problems