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Are there limits for general anesthesia

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Lectio magistralis 2004,Limits for general anesthesia,inhalation vs tiva,TCI,models,mathematics,etc etc.

Lectio magistralis 2004,Limits for general anesthesia,inhalation vs tiva,TCI,models,mathematics,etc etc.

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  • shows the decrease (from bottom to top) in the effect site concentrations of propofol and alfentanil during the first 40 min after termination of infusions lasting 15, 60, 300, and 600 min, during which constant target propofol and alfentanil concentrations had been maintained at values associated with a 50% probability of no response to surgical stimulation as indicated by the curves in the x—y planes (note that the curve in the x—y plane is identical in all four diagrams in this figure). The bold line over the surface of each of the four diagrams represents the effect site propofol and alfentanil concentrations associated with a 50% probability of awakening and the corresponding times after termination of the infusions. The optimal intraoperative combination of propofol and alfentanil is defined as the combination that, while being associated with a 50% probability of no response to surgical stimuli intraoperatively, results in the fastest possible return of consciousness after termination of the infusion. This combination is represented in each diagram by the lowest point on the bold awakening line. The time to awakening is represented by the distance between this point and the nearest point on the curve in the x—y plane (the bottom of the diagram). The optimal intraoperative effect site EC
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    • 1. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Ci sono limiti alla Anestesia generale? Claudio Melloni Servizio di Anestesia e Rianimazione Ospedale degli Infermi Faenza(RA)
    • 2. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) I limiti della anestesia generale Claudio Melloni Servizio di Anestesia e Rianimazione Ospedale degli Infermi di Faenza Faenza(RA)
    • 3. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Lecture outline What is GA? GA and awareness;skipped! Inhalations vs tiva:experience vs mathematics PK-PD and tiva trainer:from theory to practice From practice to theory and back to practice-………………. We cannot became what we need to be by remaining what we are(Maxwell De Pree,Author and Chairman Emeritus,Hermann Miller Inc,Zeeland .Michigan)
    • 4. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Definitions of anaesthesiaDefinitions of anaesthesia Rees & Gray 1950,Gray 1960Rees & Gray 1950,Gray 1960 Drug induced uncosciousness:the patient does not perceive nor recall noxious stimulationDrug induced uncosciousness:the patient does not perceive nor recall noxious stimulation Prys-Roberts C. Anaesthesia: a practical or impractical construct? [editorial]. Br J Anaesth 1987; 59:1341-5.Prys-Roberts C. Anaesthesia: a practical or impractical construct? [editorial]. Br J Anaesth 1987; 59:1341-5. Paralysis uncosciousness & attenuation of the stress responseParalysis uncosciousness & attenuation of the stress response Pinsker MC. Anesthesia: a pragmatic construct. Anesth Analg 1986; 65:819-20.Pinsker MC. Anesthesia: a pragmatic construct. Anesth Analg 1986; 65:819-20. Sensory block,motor block,block of reflexes,mental blockSensory block,motor block,block of reflexes,mental block WoodbrigeWoodbrige All separate effects useful to protect the patient from the stress of surgeryAll separate effects useful to protect the patient from the stress of surgery Kissin I, Gelman S. Components of anaesthesia. Br J Anaesth 1988; 61:237-42.Kissin I, Gelman S. Components of anaesthesia. Br J Anaesth 1988; 61:237-42. Reversible oblivion and immobilityReversible oblivion and immobility Eger EI II. What is general anesthetic action? [editorial]. Anesth Analg 1993; 77:408.Eger EI II. What is general anesthetic action? [editorial]. Anesth Analg 1993; 77:408.
    • 5. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Modern balanced anesthesiaModern balanced anesthesia Do they fir together?Do they fir together? HypnosisHypnosis AmnesiaAmnesia AnalgesiaAnalgesia Muscle relaxationMuscle relaxation Stress protectionStress protection Reflexes protectionReflexes protection Absence of movementAbsence of movement
    • 6. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) MuscleMuscle relaxationrelaxation Control ofControl of stressstress responseresponse UnconsciousnessUnconsciousness Hypnotics + inhalation agentsHypnotics + inhalation agents Muscle relaxantsMuscle relaxants AnalgesicAnalgesic drugsdrugs Modern balanced anesthesiaModern balanced anesthesia
    • 7. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Assessing anesthetic depthAssessing anesthetic depth Autonomic signsAutonomic signs HR,BP,sweat,tears(PRST score...)HR,BP,sweat,tears(PRST score...) Somatic signsSomatic signs moving,coughing.breathing...moving,coughing.breathing... Response to stimulationResponse to stimulation voice,eyelash reflex,pinprick,incision,intubation,visceral traction voice,eyelash reflex,pinprick,incision,intubation,visceral traction Anesthetic concentrationAnesthetic concentration MAC,plasma conc,effect site conc....MAC,plasma conc,effect site conc....
    • 8. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) MACMAC Mac awake50-95 Mac awake50-95 Anesthetic alveolar concentration preventing awareness in 50% or 95% of subjects…(Stoelting 1970); Anesthetic alveolar concentration preventing awareness in 50% or 95% of subjects…(Stoelting 1970); MACMAC Minimum alveolar concentration of anesthetic preventing movement in response to incision in 50-95% of subjects.. Minimum alveolar concentration of anesthetic preventing movement in response to incision in 50-95% of subjects.. MAC bar50-95MAC bar50-95 Minimum alveolar concentration of anesthetic preventing stress response to surgical stimulation in 50-95% of patients Minimum alveolar concentration of anesthetic preventing stress response to surgical stimulation in 50-95% of patients
    • 9. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) MAC TablesMAC Tables Mac awake Mac awake MAC in O2 MAC in O2 MAC in N2O 60% MAC in N2O 60% MAC bar MAC bar halothanehalothane 0.410.41 0.70.7 0.30.3 1.3Mac1.3Mac isofluraneisoflurane 0.380.38 1.141.14 0.500.50 1.3 Mac1.3 Mac sevofluranesevoflurane 0.620.62 22 0.600.60 1.5 Mac1.5 Mac desfluranedesflurane 2.422.42 66 2.832.83 1.5 Mac1.5 Mac
    • 10. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) MAC PyramidMAC Pyramid Stress response control Stress response control MAC barMAC bar MovementMovement MACMAC UncosciousnessUncosciousness Mac awakeMac awake fraction of MAC 0. 5 1.0 1.5
    • 11. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) MuscleMuscle relaxationrelaxation Control ofControl of stressstress responseresponse UnconsciousnessUnconsciousness Inhalation agents Muscle relaxantsMuscle relaxants Analgesic drugsAnalgesic drugs NeurolepticsNeuroleptics Hypnotics and BDZs Drugs for general anesthesiaDrugs for general anesthesia
    • 12. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) balance of anesthesiabalance of anesthesia AnesthesiaAnesthesia respiratory depression respiratory depression cardiovascular depression cardiovascular depression
    • 13. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Steady state alveolar concentrationSteady state alveolar concentration what does it meanswhat does it means PA=kCAPA=kCA where PA is maintained at a constant value for at least 10 min where PA is maintained at a constant value for at least 10 min PA=CA=BrainPA=CA=Brain
    • 14. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Rate of rise of alveolar(FA) anesthetic concentration toward the inspired (Fi) concentration Min .of administration
    • 15. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Logistic regression curves relating end tidal isoflurane concentrations and multiple stimulations Zbinden AM, Maggiorini M, Petersen-Felix S, Lauber R, Thomson DA, Minder CE: Anesthetic depth defined using multiple noxious stimuli during isoflurane/oxygen anesthesia: I. Motor reactions. ANESTHESIOLOGY 80:253-260, 1994 Tetanic stimulation Intubation Trapezius squeeze Laringoscopy Skin incision
    • 16. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) EFFETTO CONCENTRAZIONE Concentration/effect curves for iv drugs Inclinazione  margine terapeutico EC50  ED50
    • 17. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Probabilityofno-response Cp50 concept
    • 18. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Isobolograms: A: additive B: sinergistic C: infraadditive
    • 19. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Interaction between propofol, midazolam and alfentanil for LOC
    • 20. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) IOT induzione mantenim. risveglio sedazione 0 2 4 6 8 10 12 concentrazioneematicadi propofol(µg/ml) Maitre PO, 1994 ? Propofol: effective Cp50 relative to different stimulations
    • 21. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) 10 8 6 4 2 0 sedazione TIVA: minore: maggiore: TIVA: Propofol- Propofol- Propofol- solo Propofol oppioide N2O N2O Propofol(mg/ml) Propofol: relationship between plasma concentration and CNS depression Shafer SL, Stanski DR, 1991
    • 22. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Loss of consciousnessLoss of consciousness knowledge ofknowledge of LOCLOC time to peak effect time to peak effect haemodynamic effects haemodynamic effects impact of drug combination impact of drug combination
    • 23. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Loading dose correctedLoading dose corrected loading doseloading dose based on Vd incorporating the biophase based on Vd incorporating the biophase drug choice and timing drug choice and timing based on Keo and its time to peak effect based on Keo and its time to peak effect
    • 24. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Vpeak effectVpeak effect Proportionality constant which,when multiplied by the target concentration, should produce the desired peak effect in the number of minutes noted. Proportionality constant which,when multiplied by the target concentration, should produce the desired peak effect in the number of minutes noted. V peak effect(Lt) V peak effect(Lt) Time to peak effect(min) Time to peak effect(min) fentanylfentanyl 7575 3,63,6 alfentanilalfentanil 5959 1,41,4 sufentanilsufentanil 8989 5,65,6 propofolpropofol 2424 22 Shafer SL,Kern DE,Stanki DR .The scientific basis of infusion techniques in anesthesia . North Reading,Ma.Bard Medical Division 1990.
    • 25. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Time course of serum concentration versus EEG spectral edge:Remifentanil (Anesthesiology 84:821-33,1996)
    • 26. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Fentanyl(150 microgr/kg) and EEG (Anesthesiology 90,566-99,1999)
    • 27. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Ausems ME, Vuyk J, Hug CC Jr, Stanski DR. Comparison of a computer assisted infusion versus intermittent bolus administration of alfentanil as a supplement to nitrous oxide for lower abdominal surgery. Anesthesiology 1988; 68:851-61.
    • 28. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA)
    • 29. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) The interaction between fentanyl and isoflurane(BJA 1998,81,38-50)
    • 30. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Interaction between remifentanil and isoflurane Isoflurane concentration reduction by increasing remifentanil whole blood concentration.Anesthesiology 85:721-8, 1996
    • 31. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Mac reduction of desflurane by fentanyl Sebel PS., Glass PSA,Fletcher JE,Murphy M,Gallagher C,Quill T.Reduction of rhe Mac of desflurane with fentanyl. Anesthesiology 76:52-59, 1992
    • 32. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Sevoflurane Mac awake reduction by fentanyl Katoh T,Iked K. The Effects of Fentanyl on Sevoflurane Requirements for Loss of Consciousness and Skin Incision ANESTHESIOLOGY 1998; 88:5—6.
    • 33. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) MAC reduction of isoflurane by sufentanil +:no movement -:movement
    • 34. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Plasma alfentanil vs propofol blood concentrations for 95% probability of no response to surgical stimulation(Vuyk et al.Propofol Anesthesia and Rational Opioid Selection: Determination of Optimal EC50-EC95 Propofol—Opioid Concentrations that Assure Adequate Anesthesia and a Rapid Return of Consciousness Anesthesiology 87:1549-62, 1997
    • 35. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) manual opioid infusion schemesmanual opioid infusion schemes from many sources...from many sources... drugdrug plasma target concentation(ngml) plasma target concentation(ngml) bolus(microgr/kg)bolus(microgr/kg) infusion rate (microgr/kg/min infusion rate (microgr/kg/min fentanylfentanyl 11 33 0.0200.020 fentanylfentanyl 44 1010 0.0700.070 alfentanilalfentanil 4040 2020 0.250.25 alfentanilalfentanil 160160 8080 1.001.00 sufentanilsufentanil 0.150.15 0.150.15 0.0030.003 sufentanilsufentanil 0.500.50 0.500.50 0.0100.010 remifentanilremifentanil 66 11 0.020.02 remifentanilremifentanil 12-2012-20 1-21-2 0.4-1.00.4-1.0
    • 36. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Fiset, P. Practical pharmacokinetics as applied to our daily anesthesia practice .Can J Anesth 1999 / 46 / R122-R126
    • 37. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Finestra terapeuticaFinestra terapeutica oppioidioppioidi fent(ng/ml)fent(ng/ml) alfent(ng/ml)alfent(ng/ml) sufent(ng/ml)sufent(ng/ml) induz & intub con tps induz & intub con tps 3-53-5 250-400250-400 0,4-0,60,4-0,6 induz & intub con N2O induz & intub con N2O 8-108-10 400-750400-750 0,8-1,20,8-1,2 mant con N2O+inhalat mant con N2O+inhalat 1.5-41.5-4 100-300100-300 0,25-0,50,25-0,5 mant con N2O solomant con N2O solo 1.5-101.5-10 100-750100-750 0,25-10,25-1 mant con O2 solomant con O2 solo 15-60 1000-40001000-4000 00 RS suff all'emergRS suff all'emerg 1,5 125125 0,250,25
    • 38. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) TCI systems From clinical experience and literature recommendations to target concentration ,where the system calculates the infusion rate necessary to achieve that concentration over time
    • 39. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Kinetic-dynamic dissociation and the effect compartment
    • 40. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Pharmacokinetic parameters for PropofolPharmacokinetic parameters for Propofol Gepts Anesth Analg 66;1256;1987 & Marsh.BJA 67;41:1991 &Gepts Anesth Analg 66;1256;1987 & Marsh.BJA 67;41:1991 & GeptsGepts MarshMarsh V1V1 767767 228 ml/kg228 ml/kg K10K10 0.0350.035 0.119/min0.119/min KeoKeo 0.630.63 0.26/min0.26/min K12K12 0.28660.2866 0.114/min0.114/min K21K21 0.08660.0866 0.055/min0.055/min K13K13 0.27300.2730 0.0419/min0.0419/min K31K31 0.0360.036 0.0033/min0.0033/min
    • 41. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) PharmacodynamicsPharmacodynamics assumptionsassumptions MEACMEAC fent:0.6 ng/ml fent:0.6 ng/ml Resp depression Resp depression >2 ng/ml>2 ng/ml MAC reduction MAC reduction CSHTCSHT RecoveryRecovery ED95 intraop for surgery/ED95 for recovery of consciousness & spont.resp.ED95 intraop for surgery/ED95 for recovery of consciousness & spont.resp.
    • 42. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Decrement times of desflurane,sevoflurane,isoflurane and enflurane as a function of the duration of anesthetic administration Bailey, J M.Anesth Analg 1997; 85:681-6 50% 80% 90%
    • 43. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Some significant decrement times for the modern inhalatory agents. 0 10 20 30 40 50 60 70 80 90 100 min 50% decr.times 80% decr times after 60 min 90% decr times after 300 min desflurane sevoflurane isoflurane enflurane
    • 44. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Context sensitive half times as a function of infusion duration remifentanil
    • 45. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Three dimensional surface isobolograms relating drugs A & B with probability of no response;two dimensional isobolograms only produces the line at 50% probability…. Minto CF, et al: Anesthesiology 92,1603-15,2000
    • 46. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) The software used in this investigation and other software useful for modeling dose—response surfaces is available via the World Wide Web at URL http://pkpd.icon.palo-alto.med.va.gov in the directory interaction.dir. The Appendices for this article and the data set used for the analysis can be found on the ANESTHESIOLOGY Web site (www.anesthesiology.org). Address reprint requests to Dr. Shafer: Pharsight Corporation, 800 West El Camino Real # 200, Mountain View, California 94040. Address electronic mail to: sshafer@pharsight.com
    • 47. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Response surface for each of the paired interactions.Max effect is failure to open eyes to verbal command Minto CF, et al: Anesthesiology 92,1603-15,2000
    • 48. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) time Propofol blood concOpioid blood concentration Three dimensional planes in the graphs from Vuyk et al.
    • 49. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) time Propofol blood concOpioid blood concentration Three dimensional planes in the graphs from Vuyk et al.
    • 50. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Diprifusor
    • 51. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Calculations behind the target……
    • 52. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) The “Tiva trainer” Blood conc(target ) Effect site concentration
    • 53. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Controlling the effect site concentration of propofol with Diprifusor……….
    • 54. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Graphical TCI
    • 55. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) TCI and monitoring
    • 56. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) PK-PD & surgery…
    • 57. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Closing the loop..
    • 58. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) SurgerySurgery StimulationStimulation ArousalArousal MovementMovement Autonomic effectsAutonomic effects AwarenessAwareness recallrecall analgesics hypnotics anxyolysis Amnesia
    • 59. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Closing the loop:Servoanesthesia(AEP by GC Kenny)
    • 60. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Theory and practice:1
    • 61. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Theory and practice:2
    • 62. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Theory and practice:3
    • 63. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Theory and practice:4
    • 64. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Theory and practice:5
    • 65. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) Theory and practice:6
    • 66. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) New definition of anesthesi..ology Anesthesiology ..is the practice of pharmacology synergism using central nervous system depressant..T.D.Egan ,2003 .
    • 67. Servizio di Anestesia e Rianimazione Ospedale di Faenza(RA) I have made this letter longer than usual, because I lack the time to make it short. I have made this letter longer than usual, because I lack the time to make it short. Blaise PascalBlaise Pascal (lecture)