ESCTAIC
Amsterdam
06–09 oct 2010
Analgesia / Nociception Index
Calculation
Dr Mathieu JEANNE – pôle d’anesthésie réanimation R. Salengro – C.H.U. de Lille
contact : mathieu.jeanne@chru-lille.fr
disclaim – conflict of interest
MetroDoloris – startup : bio incubateur Eurasanté
• commercial development of institutionnal research by the
university hospital of Lille
• scientific adviser
www.metrodoloris.com
Heart Rate Variability
Respiratory sinus arrhythmia
• Each respiratory cycle is associated with a fall in paraS tone
• this leads to a brief increase of heart rate (shortening of RR intervals)
• that can be best seen on a bi-dimensionnal RR series as successive local
minima (I)
Spectral Analysis
Spectral Analysis
Fast Fourier Transform
HR
[bpm2]
0,004 Hz
0,04 Hz
VLF
0,4 Hz
0,15 Hz
LF
HF
f [Hz]
Very Low frequencies (0.004-0.04 Hz) express thermoregulatory and endocrine
activities
Low frequencies (0.04-0.15 Hz) are related to sympathetic and parasympathetic
tone modulations, and baroreflex activity
High frequencies (0.15-0.40 Hz) express parasympathetic tone variations only,
mainly in relation with respiratory sinus arrhythmia
Spectral Analysis
Effect of induction of anesthesia
• Propofol (0.3 mg/kg/min) dampen HF content
• but not sevoflurane (5%) in O2 100%
Kanaya et al. Anesthesiology 2003 ; 98 : 34-40
Respiratory sinus arrhythmia
Spectral Analysis
Respiratory sinus arrhythmia plays a prominent role among the various influences
exerted on the sinus node
Example of spectral analysis in a patient during general anesthesia :
the high frequency content is mainly explained by the influence
of ventilation on the RR series
Respiratory arrhythmia and respiratory pattern
Respiratory arrhythmia can be visualized directly on the RR series
In the absence of nociception : respiration is the main influence of variability
motif respiratoire
In case of nociception or anxiety : respiratory influence is lost, replaced by LF
components (sympathetic activation) not visible in the high frequency field
Para-sympathetic reflex loop
Brain stem
vagus node (X)
bronchial
strech
receptors
sinus node
Clinical trial
Total intra venous
general anesthesia
General anesthesia
two components
• Loss of consciousness
– Hypnotic agents (propofol, halogens, …)
– Effect on superficial cortex and thalamo
cortical loops
– measurable on the surface EEG (e.g. BISTM)
• Reactivity
– sub cortex reactions
– Opioids
– measurable on the pupillary response /
diameter
Group 1
Group 2
Group 3
N=19
N=18
N=12
Sufentanil 0.5 µg/kg
Alfentanil 30 µg/kg
Remifentanil 2 µg/kg
puis 0.24 µg/kg/min
No
additionnal
opioid
No
additionnal
opioid
No
additionnal
opioid
n=16
n=7
n=7
earlylight-lightAnalg
earlylight-lightAnalg
earlylight-lightAnalg
n=5;
n=3; bolus 0.1 µg/kg
n=11; bolus 10 µg/kg
increase of 0.04 µg/kg/min
19 « first » nostim -earlyLight - lightAnalg sequences
1 à 4 sequences per patient
Total of 51 sequences
Preliminary results
• TIVA; constant Bispectral index (Aspect A2000)
• objective : anticipate hemodynamic reactivity (20% increase of HR
or SBP)
• total of 51 sequences « noStim – earlyLight – lightAnalg »
Jeanne M et al. Auton Neurosci. 2009;147(1-2):91-6
Prediction of reactivity
during general anesthesia ?
?
• How can we make it simple ?
Respiratory influence on the RR series
adequate analgesia
inadequate analgesia
• Série RR
–
–
–
–
resampled, mean-centered, normalised
band pass filtered [0.15-0.5 Hz] (wavelets transform)
each respiratory cycle leads to a shortening in the RR series
surfaces T1, T2, T3, T4 : measure of respiratory influence on the RR
series
– AUCminnu = min(T1, T2, T3, T4) and AUCtotnu = S(T1, T2, T3, T4)
Results
• n=90 RR series
• Two distinct situations
– A : inadequate analgesia, during 5 min before hemodynamic reactivity
(n=54 series)
– B : adequate analgesia, long before reactivity (n=36 series)
Hemodynamic and HRV results; Mann Whitney U test, non paired test
Results (2)
Correlation between
2.2
• AUCminnu and HFnu (r2=0,81)
• AUCtotnu and HFnu (r2=0,88)
• AUCtotnu and AUCminnu (r2=0,92)
2
1.8
AUCmin(nu)
1.6
1.4
1.2
1
.8
.6
.4
Linear regression
.2
0
0
.2
.4
.6
HF/(HF+LF)
.8
1
AUCtotnu = 5,1 * AUCminnu + 1,2
Results (3)
Analgesia Nociception Index
• The maximum possible surface of respiratory influence is 0.2*64=12.8
• The occupied part of that surface is AUCtotnu / 12.8
ANI = 100 * AUCtotnu / 12.8
or
ANI = 100 * [(5.1*AUCminnu + 1.2) / 12.8]
Results (4)
100
90
80
**
ANI
70
60
ANI
• p<0,0001 (Mann Whitney)
50
40
30
20
10
adequAnalg
insuffAnalg
sensibilité
ANI at 48
• sens=76% et spec=72%
ANI at 30
• spec=100% > insuffAnalg
ANI at 82
• sens=100% > adequAnalg
surface=0.80
1-spécificité
Simulated RR series
variable respiratory rate
Spectral analysis: Fourier transform
Effect a resp. rate change
• A change in respiratory rate leads to a shift of HF
spectral peak
• Two peaks are present during the transition period
Simulated RR series
• Aim : to measure the
performance of HRV
analysis tools (spectral and
graphical)
• Typical respiratory pattern
from a recording during
anesthesia (adequate
analgesia)
• Creation of RR series with different resp. rates
• 8, 10, 12 et 15 c/min
Simulated RR series
• HF spectral
measurements are under
estimated when resp.
rate < 12 c/min
Variable respiratory rate
Graphical measurements are constant
• Graphical measurements (AUCminnu, AUCtotnu)
are constant despite various resp. rates
Jeanne M et al. IEEE EMBS 2009; 1:1840-3
Clinical trial
Laparoscopic cholecystectomy
Protocol
• Adult patients
• Emergency laparoscopic cholecystectomy
• ASA status I or II ; no known alteration of autonomous
nervous system
• TIVA propofol, remifentanil, myorelaxation
• controlled ventilation Vt=8ml/kg – RR 12 c/min
• Bispectral index maintained in [40-60] range
• remifentanil target lowered at 2 ng/ml after tracheal
intubation ; increase in case of hemodynamic reactivity
(20% incrase in HR or SBP)
• ANI measurements
Preliminary results
• n=9 patients included
• Hemodynamic reactivity
is always preceded by an
ANI decrease
Case report
Mesenteric artery occlusion
and general anesthesia
Mesenteric ischemia
• Man, 43 year, no known disease
• Comes to the casualty ward for acute abdominal pain
• abdominal CT scan : upper mesenteric artery occlusion
• first attempt at surgery
– dissection of upper mesenteric artery
– no bypass possible
– conservative treatment (heparin)
• second look after 48h
– small bowel necrosis over 10cm and sub ischemia over 1m
– bowel resection
– ilio-mesenteric bypass
Blind anesthesia
• TIVA
– propofol (Schnider)
– ultiva (Minto)
• Tachycardia from the
beginning (110 / min)
– leading to fluid expansion 2000ml
– increasing remi targets
• After 2h surgery
–
–
–
–
–
persistent tachycardia : 110 / min
BP 98/60 mmHg
total blood loss : 150 ml
ultiva : target = 6 ng/ml
propofol : target = 3.5 µg/ml
Question : are analgesia and hypnosis adequate ?
EEG monitor + ANI monitor
• ANI
– elevated index : 100
– high paraS tone
– > remi target is halved
from 6 to 3 ng/ml
– no effect on HR or BP
during the next hour
• Bispectral index (Aspect
A2000)
– measure is whithin the [4060] range
– >> propofol target is
maintained constant at 3.5
µg/ml
Future validation...
A.N.I.
• Test whether cardiovascular drugs modify ANI
predictibility of hemodynamic reactivity
– beta bloquing drugs
– catecholamines
• Test whether ANI guided opioid delivery during
general anesthesia could prevent hemodynamic
reactivity and opioid overdose ?
– primary endpoint : number of avoided hemodynamic events
• Limitations
– no recording during apnoea
– sinus rythm only
before
induction
Irregular tidal volume during induction
spontaneous
Ventilation
with constant
tidal vol : ok
followed by apnoea
ANI non usable
controlled
ventilation : ok
100
90
80
70
60
50
40
30
20
10
0
0
100
200
300
apnoea
400
500
600
controlled ventilation
Induction
Base Primea
700
intubation
800
Conclusion
• Last years have witnessed the surge of ANS
monitoring, esp. analgesia / nociception
balance.
• Several complementary monitoring techniques
do assess the status of ANS: pupillometry (pS),
skin conductance and Cardean (S), ANI (pS)
• These new monitoring devices underline the role
of anesthesia as an ANS oriented disciplin