analgesia / nociception index calculation
DESCRIPTION
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 : [email protected]. disclaim – conflict of interest. - PowerPoint PPT PresentationTRANSCRIPT
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Analgesia / Nociception Index Calculation
Dr Mathieu JEANNE – pôle d’anesthésie réanimation R. Salengro – C.H.U. de Lillecontact : [email protected]
ESCTAIC Amsterdam 06–09 oct 2010
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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
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Heart Rate VariabilityRespiratory 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)
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Spectral Analysis
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0,04 Hz 0,15 Hz0,4 Hz
HR[bpm2]
f [Hz]VLF LF HF0,004 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 AnalysisFast Fourier Transform
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Spectral AnalysisEffect 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
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Respiratory sinus arrhythmiaSpectral 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
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Respiratory arrhythmia and respiratory pattern
motif respiratoire
In the absence of nociception : respiration is the main influence of variability
In case of nociception or anxiety : respiratory influence is lost, replaced by LF components (sympathetic activation) not visible in the high frequency field
Respiratory arrhythmia can be visualized directly on the RR series
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Para-sympathetic reflex loopBrain stem
vagus node (X)
sinus nodebronchial
strech receptors
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Clinical trial
Total intra venous general anesthesia
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General anesthesiatwo 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
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Group 3
N=12
Remifentanil 2 µg/kg puis 0.24 µg/kg/min
Group 2
N=18
Alfentanil 30 µg/kg
Group 1
N=19
Sufentanil 0.5 µg/kg
No additionnal opioid
n=7
No additionnal opioid
n=7
No additionnal opioid
n=16
earlylight-lightAnalg
n=3; bolus 0.1 µg/kg
earlylight-lightAnalg
n=11; bolus 10 µg/kg
earlylight-lightAnalg
n=5;
increase of 0.04 µg/kg/min
19 « first » nostim -earlyLight - lightAnalg sequences
1 à 4 sequences per patient
Total of 51 sequences
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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
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Prediction of reactivity during general anesthesia ?
• How can we make it simple ? ?
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Respiratory influence on the RR series
• 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 = (T1, T2, T3, T4)
adequate analgesia
inadequate analgesia
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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
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Results (2)
Correlation between• AUCminnu and HFnu (r2=0,81)• AUCtotnu and HFnu (r2=0,88)• AUCtotnu and AUCminnu (r2=0,92)
Linear regressionAUCtotnu = 5,1 * AUCminnu + 1,2
0
.2
.4
.6
.8
1
1.2
1.4
1.6
1.8
2
2.2
AU
Cm
in(n
u)
0 .2 .4 .6 .8 1HF/(HF+LF)
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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
or ANI = 100 * [(5.1*AUCminnu + 1.2) / 12.8]
ANI = 100 * AUCtotnu / 12.8
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Results (4)
ANI• p<0,0001 (Mann Whitney)
10
20
30
40
50
60
70
80
90
100
AN
I
adequAnalg insuffAnalg
**
ANI at 48• sens=76% et spec=72%
ANI at 30• spec=100% > insuffAnalg
ANI at 82• sens=100% > adequAnalg
1-spécificité
sensibilité
surface=0.80
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Simulated RR seriesvariable respiratory rate
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Spectral analysis: Fourier transformEffect 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
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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
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• HF spectral measurements are under estimated when resp. rate < 12 c/min
Simulated RR series
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Variable respiratory rateGraphical measurements are constant
• Graphical measurements (AUCminnu, AUCtotnu) are constant despite various resp. rates
Jeanne M et al. IEEE EMBS 2009; 1:1840-3
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Clinical trial
Laparoscopic cholecystectomy
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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
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Preliminary results
• n=9 patients included• Hemodynamic reactivity
is always preceded by an ANI decrease
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Case report
Mesenteric artery occlusionand general anesthesia
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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
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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 ?
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EEG monitor + ANI monitor
• ANI– elevated index : 100– high para 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 [40-
60] range– >> propofol target is
maintained constant at 3.5 µg/ml
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Future validation...
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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
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controlled ventilationInduction
Base Primea
apnoea
intubation
0
10
20
30
40
50
60
70
80
90
100
0 100 200 300 400 500 600 700 800
Irregular tidal volume during induction
followed by apnoea
ANI non usablecontrolled
ventilation : ok
before induction
spontaneous Ventilation
with constant tidal vol : ok
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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 (p), skin conductance and Cardean (, ANI (p
• These new monitoring devices underline the role of anesthesia as an ANS oriented disciplin
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