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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.

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Analgesia / Nociception Index Calculation


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    1. 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

    2. 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

    3. 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)

    4. Spectral Analysis

    5. HR[bpm2] f [Hz] Spectral Analysis Fast Fourier Transform 0,4 Hz 0,004 Hz 0,04 Hz 0,15 Hz LF HF VLF 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

    6. 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

    7. 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

    8. motif respiratoire 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 In case of nociception or anxiety : respiratory influence is lost, replaced by LF components (sympathetic activation) not visible in the high frequency field

    9. Brain stem vagus node (X) sinus node bronchial strech receptors Para-sympathetic reflex loop

    10. Clinical trialTotal intra venous general anesthesia

    11. 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

    12. Group 3 N=12 Remifentanil 2 µg/kg puis 0.24 µg/kg/min No additionnal opioid n=16 No additionnal opioid n=7 No additionnal opioid n=7 earlylight-lightAnalg n=5; increase of 0.04 µg/kg/min earlylight-lightAnalg n=11; bolus 10 µg/kg earlylight-lightAnalg n=3; bolus 0.1 µg/kg Group 1 N=19 Sufentanil 0.5 µg/kg Group 2 N=18 Alfentanil 30 µg/kg 19 « first » nostim -earlyLight - lightAnalg sequences 1 à 4 sequences per patient Total of 51 sequences

    13. 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

    14. ? Prediction of reactivity during general anesthesia ? • How can we make it simple ?

    15. 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 = S(T1, T2, T3, T4) adequate analgesia inadequate analgesia

    16. 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

    17. Results (2) Correlation between • AUCminnu and HFnu (r2=0,81) • AUCtotnu and HFnu (r2=0,88) • AUCtotnu and AUCminnu (r2=0,92) Linear regression AUCtotnu = 5,1 * AUCminnu + 1,2

    18. ANI = 100 * AUCtotnu / 12.8 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]

    19. ** sensibilité 1-spécificité Results (4) ANI • p<0,0001 (Mann Whitney) • ANI at 48 • sens=76% et spec=72% • ANI at 30 • spec=100% > insuffAnalg • ANI at 82 • sens=100% > adequAnalg surface=0.80

    20. Simulated RR seriesvariable respiratory rate

    21. 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

    22. 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

    23. Simulated RR series • HF spectral measurements are under estimated when resp. rate < 12 c/min

    24. 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

    25. Clinical trialLaparoscopic cholecystectomy

    26. 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

    27. Preliminary results • n=9 patients included • Hemodynamic reactivity is always preceded by an ANI decrease

    28. Case reportMesenteric artery occlusionand general anesthesia

    29. 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

    30. 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 ?

    31. 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 [40-60] range • >> propofol target is maintained constant at 3.5 µg/ml

    32. Future validation...

    33. 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

    34. before induction spontaneous Ventilation with constant tidal vol : ok Irregular tidal volume during induction followed by apnoea ANI non usable controlled ventilation : ok Induction Base Primea controlled ventilation apnoea intubation

    35. 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