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Analgesia / Nociception Index Mathieu JEANNE, MD, PhD Anesthesia & Intensive Care Cic-It 807 Inserm University Hospital Lille, France.

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Presentation on theme: "Analgesia / Nociception Index Mathieu JEANNE, MD, PhD Anesthesia & Intensive Care Cic-It 807 Inserm University Hospital Lille, France."— Presentation transcript:

1 Analgesia / Nociception Index Mathieu JEANNE, MD, PhD Anesthesia & Intensive Care Cic-It 807 Inserm University Hospital Lille, France

2 Conflict of interest Mathieu JEANNE is consultant for MetroDoloris®

3 State of the art

4 Current understanding of general anesthesia Cortical reactions –consciousness –hypnosis > EEG assessment of depth of hypnosis (bispectral index, entropy, etc) Sub cortical reactions : autonomous nervous system eye heart rate blood pressure sweat (> pain monitor) analgesia / nociception balance evaluation through ANS reactions assessment State of art

5 Autonomous nervous system parasympathetic system sympathetic system pupil contraction slowing of heart rate bronchial constriction digestive system pupil dilation lacrimation increased heart rate and blood pressure bronchial dilation sweating

6 Why use the ECG signal ? electrical signal easy to measure on the skin surface used for standard clinical monitoring standard during anesthesia practice / ICU / neo natalogy non invasive provides continuous monitoring and assessment of ANS reactions to stress / nociception still usable in case of : –hypovolemia –shock (hypovolemic, septic, cardiogenic...) –hypothermia State of art

7 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) State of art

8 Spectral Analysis using Fourier transform Fourier transform has been widely used for heart rate variability analysis –spectral powers measured on the RR series result from various actions of the ANS –ANS sympathetic and paraS tones can be measured in the low (LF) and high frequency (HF) fields –Very Low Frequencies (VLF) are influenced by thermo regulation and the endocrine system Bpm Time 70 90 50 instantaneous heart rate Fourier transform Power spectrum Quantification LFHF Frequency VLF State of art

9 0,04 Hz0,15 Hz 0,4 Hz HR [bpm 2 ] f [Hz] VLF LF HF 0,004 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 paraS tone modulations, and baroreflex activity High frequencies (0.15-0.40 Hz) express parasympathetic tone variations only, mainly in relation with respiratory sinus arrhythmia Fourier Transform Power Spectrum State of art

10 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 rate Respiratory spectral peak State of art

11 Why is Fourier transform not used routinely ? The increase of respiratory rate from 8 to 12 cpm leads to two respiratory spectral peaks during the 5 min transition in the analyzing window ANS assessment is not possible during that period State of art

12 Main disavantages of the fourrier transform analysis -Just applicable for stable signals -Needs 5 minutes of recording to be accurate

13 Pichot et al. J Appl Physiol 1999 ; 86:1081-91 Fast wavelet transform Mallat S. Une exploration des signaux en ondelettes. Ed Ecole Polytechnique R&D

14 Main advantages: - applicable with unstable signals - Provide a reliable countinuous assessment

15 Focused on the high frequencies range analysis of the HRV, the ANI technology objectively assess the parasympathetic reflex loop ANS Sinu s node Stretch receptor s Limitatio n: Apnea Limitation: Sinusal rythm only Technology

16 Respiratory arrhythmia and respiratory pattern ventilatory pattern 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 State of art

17 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. BIS TM ) Reactivity –sub cortex reactions –opioids dampen reactivity –measurable on ANS reactions HF measurements of HRV provide direct paraS evaluation hypothesis / clinical research

18 From ECG to ANI 1 2 3 hypothesis / clinical research

19 1

20 12

21 1 2 3

22 Instead of the former methodology, here are our main advantages: 1: Exclusion of all artefacts from the ECG signal 2: Normalization 3: Fast wavelet transform analysis 4: Graphical measurement 5: Simple index

23 Change in respiratory rate : graphic measure not altered The change in respiratory rate does not lead to a change in graphical measurements. Simulated RR series during an increase of respiratory rate hypothesis / clinical research

24 Adult patients scheduled for surgery Total intra venous anesthesia : propofol + opioid; propofol adapted in order to keep Bispectral index in the predefined range [40-60] ECG recordings and post hoc processing of RR series in order to obtain «noStim – earlyLight – lightAnalg» sequences primary objective : anticipate hemodynamic reactivity (defined as a 20% increase of HR or SBP) Clinical setting hypothesis / clinical research

25 Patients and anesthetic protocol 49 patients included –sufentanil : 19 patients (0.3 µ -1 at induction and 0.1 µ -1 in case of reactivity) –alfentanil : 18 patients (30 µ -1 at induction and 10 µ -1 in case of reactivity) –remifentanil : 12 patients (0.24 µ -1.min -1 decreasing until reactivity) 30 patients do not present reactivity 19 patients present reactivity –total : 51 sequences of reactivity –1 to 4 sequences per patient hypothesis / clinical research

26 Results RR series in two distinct situations –adequate analgesia, long before reactivity –5 min before hemodynamic reactivity Hemodynamic and HRV results; Mann Whitney U test adequate analgesia reactivityp HR 59 (60-68)72 (69-81) < 0.001 SBP (mmHg) 98 (89-126)130 (113-142) < 0.001 HFnu 0.64 (0.46-0.74)0.42 (0.30-0.51) < 0.001 AUCmin (nu) 1.33 (0.97-1.66)0.82 (0.65-0.96) < 0.001 AUCtot (nu) 8.48 (6.13-10.41)5.69 (4.39-6.67) < 0.001 hypothesis / clinical research

27 Results (2) Correlation between AUCmin nu and HF nu (r 2 =0,81) AUCtot nu and HF nu (r 2 =0,88) AUCtot nu and AUCmin nu (r 2 =0,92) Linear regression AUCtot nu = 5,1 * AUCmin nu + 1,2 hypothesis / clinical research ANI p<0,0001 (Mann Whitney) **

28 Results (3) Analgesia Nociception Index The maximum possible surface of respiratory influence is 0.2*64=12.8 AUCtot = T1 + T2 + T3 + T4 AUCmin = min (T1, T2, T3, T4) The occupied part of that surface is AUCtot nu / 12.8 orANI = 100 * [(5.1*AUCmin nu + 1.2) / 12.8] ANI = 100 * AUCtot nu / 12.8 hypothesis / clinical research

29 How to interpret ANI ? Recommended target range based on available clinical data : 50-70 Actual thresholds - 48 se=76% sp=72% - 30 se=100% > reactivity - 82 se=100% > adequate Analg 0 50 100 70 1-spécificité sensibilité Sensitivity 1-Specificity surface = 0.80 hypothesis / clinical research

30 clinical setting

31 ANI : relative paraS measurement


33 Clinical trial Laparoscopic cholecystectomy

34 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% increase in HR or SBP) ANI measurements

35 Preliminary results n=9 patients included Hemodynamic reactivity is always preceded by an ANI decrease Data presented as media (interquartile). * p<0.01 vs AprInd (after induction). + p<0.01 vs AprChir (after surgery)

36 Clinical trial: Tetanic stimulation at 2 remifentanil targets during TIVA

37 Neurosurgery Preliminary results Adults ASA I or II ; no know ANS alteration TIVA propofol + remifentanil + myorelaxation controlled ventilation Vt=8ml/kg – RR 12 c/min Bispectral index maintained in [30-50] Remifentanil target at 3 ng/ml after tracheal intubation 3 stimuli before incision –TET1 : remifentanil Ce = 3 ng/ml (tetanic stimulation) –TET2 : remifentanil Ce = 6 ng/ml –head holder insertion : remifentanil Ce = 6 ng/ml ANI Papillary dilation reflex (Neurolight, IDMED)

38 Results N=14 patients included Propofol Ce = 2.6 (2.5-3.0) µg/ml Heart rate (FC), blood pressure (PA) and BIS did not change during tetanos and head holder insertion (TAP) ANI decreased significantly after all 3 stimuli vs nostim less ANI decrease after TET2 vs TET1 Pupilary dilation reflex decreased also after TET2 vs TET1

39 Results - propofol target : 2,6 µ (2,5-3,0) RDP (%) NoStim TET 1 TET 2 TAP Example of ANI variation and HR during nociceptive stimuli

40 Case report Mesenteric artery occlusion and general anesthesia

41 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

42 Blind anesthesia TIVA –propofol (Schnider) –remifentanil (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 –remifentanil : target = 6 ng/ml –propofol : target = 3.5 µg/ml Question : are analgesia and hypnosis adequate ?

43 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 within the [40- 60] range –>> propofol target is maintained constant at 3.5 µg/ml

44 Future validation...

45 A.N.I. Test whether cardiovascular drugs modify ANI predictability of hemodynamic reactivity –beta bloquing drugs –catecholamines Limitations –no recording during apnea –sinus rhythm only

46 controlled ventilation Induction Base Primea apnea intubation Irregular tidal volume during induction followed by apnoea ANI non usable controlled ventilation : ok before induction spontaneous Ventilation

47 Conclusion The surge of ANS monitoring devices is probably a promise of personalized anesthetic care in the coming years, esp. analgesia / nociception balance monitoring. These new monitoring devices underline the role of anesthesia as an ANS oriented discipline.

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