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  1. 1.
  2. 2. Lesson objectives<br />Understand the history of Sevoflurane<br />Recognize the pharmacological properties of Sevoflurane<br />Recognize its specific advantages in neuroanaesthesia<br />Must appreciate unfavourable conditions produced by Sevoflurane<br />
  3. 3. Introduction:<br /><ul><li>History started with inhalational anaesthesia.
  4. 4. Past 50 years- 3 gases,13 inhalational anaesthetics were introduced.
  5. 5. Inhalational anaesthetics are routinely used.
  6. 6. They are potent.
  7. 7. Balanced anaesthesia.</li></li></ul><li>History<br /><ul><li>Development of Sevoflurane is an unusual and truly remarkable story.
  8. 8. 1960’S-Three investigators evaluated halogenated ethers.
  9. 9. Thomas Cook, Richard Mazze & Michael Halsey-on animals.
  10. 10. Bio transformation- increase in inorganic flouride in urine.</li></li></ul><li>History conti….<br /><ul><li>DunkenHoladay& Burnell Brown observed sweet smell,low solubility & no arrhythmias.
  11. 11. 1981- phase 1 trials.
  12. 12. After 10years Yasuda etal compared Sevo with Iso.
  13. 13. Baxter sold sevo to BOC which later became OHMEDA.
  14. 14. OHMEDA sold Sevo to Mariushijapan.</li></li></ul><li>History conti….<br /><ul><li>Mariushi used Sevo in japan .
  15. 15. Approached ABBOTT for FDA approval in USA.
  16. 16. Later phase 2 &3 trials were done.
  17. 17. Approved by FDA in 1994.
  18. 18. Freely available by 1995.</li></li></ul><li>Pharmacolgy<br />It is 1, 1,1,3,3,3,hexafluro-2- fluromethoxy propane.<br />
  19. 19. Physical properties<br /><ul><li>Non flammable
  20. 20. Pleasant smell
  21. 21. Volatile
  22. 22. Molecular weight-200.05
  23. 23. Boiling point(at sea level)-58.6c
  24. 24. Specific gravity at 20c-1.520-1.525
  25. 25. Partition coefficient at 37c</li></ul> water/gas- 0.36<br /> blood/gas-0.63-0.69<br />
  26. 26. Physical properties<br /><ul><li>Refractive index n20-1.2740 - 1.2760
  27. 27. Purity by gas chromatography-99.975% or better</li></li></ul><li>Physical properties<br />
  28. 28. Physical properties<br /><ul><li>Non corrosive to stainless steel, brass, aluminium,nickle plated brass,chrome plated brass.
  29. 29. Stored at 25c not refrigerated.
  30. 30. Tightly closed amber colouredbottles.
  31. 31. Should not be used after expiry date.</li></li></ul><li>Factors to be considered in Neuroanaesthesia<br />Impact on intracranial dynamics<br /><ul><li>Indirect vasoconstriction vs direct vasodilatation.
  32. 32. Effect on ICP& surgical condition.
  33. 33. Effect on auto regulation.
  34. 34. CO2reactivity.
  35. 35. Studies that have compared the use of different agents in patients with intra cranial lesions with a certain degree of increased ICT.</li></li></ul><li>Conti…..<br /><ul><li>The possibility of a quick awakening allowing for rapid post operative neurological assessment.</li></ul> Low solubility of agents such as<br />Sevoflurane.<br /><ul><li>Cytoprotective effect.</li></ul> Animal studies only,at this time.<br />
  36. 36. Critical cerebral blood flow(CBF)<br /><ul><li>Relationship between metabolism and CBF.
  37. 37. Volatile anaesthetics act indirectly on CBF by reducing metabolism.
  38. 38. Directly they are vasodilators.
  39. 39. Net effect depends on agent & dosage used.</li></li></ul><li>CBF CONTI….<br /><ul><li>Sevo is the least vasodilating agent followed by Iso and Des.
  40. 40. Sevo has net vasoconsticting effect.
  41. 41. Preserves autoregulationupto 2 MAC. Iso&Desdisruots auto regulation at 1.5&0.5 MAC.</li></li></ul><li>Critical CBF<br /><ul><li>Threshold under which CBF is not sufficient to meet the cerebral metabolic needs is called critical CBF.
  42. 42. Below critical CBF brain becomes ischemic.
  43. 43. On awake patients it is 25ml/100gms/min.
  44. 44. The critical CBF with Iso 10ml/100gms/min, with Sevo 11.5ml& with Halothane 20ml/100gms/min.</li></li></ul><li>Cytoprotection<br /><ul><li>Strong evidence showing cytoprotection in animal experiments by volatile anaesthetics.
  45. 45. Same applies to Propofol but more benificial if given in reperfusion period.
  46. 46. Volatile anaesthetics shown to have preconditioning in rodents.
  47. 47. They allow ischemic tolerance of brain tissue.
  48. 48. Preconditioning is not seen with Propofol.
  49. 49. The choice of specific agent in anaesthesia in a patient with cerebral ischemia solely depends on CPP,ICP& autoregulation.</li></li></ul><li>WHY SEVO IS THE BEST?<br /><ul><li>Solubility : low blood gas solubility</li></ul>coefficient.<br /><ul><li>Potency : highly potent MAC averaging at 2%</li></ul> can be given with high 02<br /> does not suppress SSEP.<br /><ul><li>Air way properties:</li></ul> pleasant smell,no irritation, fast induction<br /> no laryngospasm.<br />
  50. 50. <ul><li>Circulatory effects:</li></ul> Dose dependent fall in BP<br /> No sensitization to catecholamines<br /> Protective property on myocardium<br /> Coronary vasodilation<br />
  51. 51. <ul><li>Respiratory effects:</li></ul>Dose dependent in tidal volume<br /> Slight in end tidal & arterial co2<br />Bronchodilatation<br /> No irritation<br /> Less effect on HPVC<br />
  52. 52. <ul><li>CNS effects</li></ul> Dose dependent in total &<br /> regional blood flow<br /> CMRO2<br /> Slight in ICP<br /> Protection against ischemia<br /> Preconditioning possible.<br />
  53. 53. <ul><li>Renal effects:</li></ul> 3-5% metobolised .<br /> in inorganic flourides. <br /> Reacts with sodalime and baralime.<br />CompoundA produced.<br /> More in low FGF,when soda lime is dryer& <br /> hotter and also with high Sevo.<br />CompoundA 19 ppm at clinical conditions.<br />
  54. 54. <ul><li>Hepatic :</li></ul> very little effect on hepatic blood flow and function<br />
  55. 55. Conclusions <br /><ul><li>Favourable points</li></ul>Low blood gas solubility co-efficient<br />Rapid induction and recovery<br />Potent, can be used with oxygen only<br />Pleasant,non-irritating to respiratory system<br />Minimal or no stimulation of air way reflexes<br />Laryngospasm uncommon<br />Suitable for all ages<br />Compatable with epinephrine<br />
  56. 56. Conclusions <br />Cerebral autoregulation maintained<br />Coupling of metabolism and o2 demand maintained<br />Rapid recovery and early neurological assessment possible<br />Pre-conditioning of the brain for ischemic attacks<br />Protects brain cells<br />Non-inflammable<br />No long term effects on vital organs<br />Maintains co2 reactivity<br />
  57. 57. Conclusions <br /><ul><li>Unfavourable points</li></ul>Triggering agent for malignant hyperthermia<br />Emergence dysphoria in children<br />Nausea and vomiting<br />Seizures <br />Co production<br />
  58. 58. References<br />
  59. 59. <ul><li>Sevoflurane induces less cerebral vasodilation than isoflurane at the same A-line1autoregressive index level </li></ul> A. HOLMSTRO¨ M and J. A°KESON<br /> Department of Anesthesia and Intensive Care, Malmo¨ University Hospital, Lund University, Malmo¨, Sweden<br /><ul><li>Dynamic Cerebral Autoregulation During SevofluraneAnesthesia: A Comparison with IsofluraneAndrew C. Summors, BSc, MBBS, FRCA, Arun K.Gupta, MBBS, FRCA, and Basil F. Matta, MB, ChB, BA, FRCA</li></li></ul><li><ul><li>Intracranial Pressure, Middle Cerebral Artery FlowVelocity, and Plasma Inorganic Fluoride Concentrations inNeurosurgical Patients Receiving Sevoflurane or lsofluraneAlan A. Artru, MD*, Arthur M. Lam, MD*, Joel 0. Johnson, MD, PhDt, andRichard J. Sperry, MD, PhDtDepartment of Anesthesiology, University of Washington School of Medicine, Seattle, Washington; and tDepartmentofAnesthesiology, University of Utah School of Medicine, Salt Lake City, Utah
  60. 60. Direct Cerebral Vasodilatory Effects of SevofluraneandIsofluraneBasil F. Matta, M.B.B.Ch., B.A., F.R.C.A.,* Karen J. Heath, M.B.B.S., F.R.C.A.,† Kate Tipping, M.B.B.S.,‡</li></ul> Andrew C. Summors, B.Sc., M.B.B.S., F.R.C.A.‡<br />*<br />
  61. 61. <ul><li>Sevoflurane-induced preconditioning of rat brainin vitro and the role of KATP channels</li></ul>Franz Kehla,*, Ralphiel S. Payneb, Norbert Roewera, AvitalSchurrbaDepartment of Anesthesiology, Klinik und Poliklinikfu¨rAna¨sthesiologie, Zentrum Operative Medizin, Julius-Maximilans-Universita¨ t, Oberdu¨rrbacher Str. 6, Wu¨rzburg 97080, Germany<br /><ul><li>Sevoflurane Provides Faster Recovery and PostoperativeNeurological Assessment Than Isoflurane in Long-DurationNeurosurgical Cases</li></ul>Alain Gauthier, MD*, Francois Girard, MD, FRCPC*, Daniel Boudreault, MD, FRCPC*, Monique Ruel, RN*, and AlexandreTodorov, PhD†Department of Anesthesiology, Centre Hospitalier de l’Universite´ de Montre´al, Hopital Notre-Dame, Montre´al, Canada; and †Department of Psychiatry, Washington University Medical Center, St. Louis, Missouri<br />
  62. 62. <ul><li>Desflurane results in higher cerebral blood flow than sevoflurane or isoflurane at hypocapnia in pigsA. HOLMSTRO¨ M 1, I. ROSE ´ N 2 and J. A°KESON Departments of 1Anaesthesia and Intensive Care, Experimental Research and 2Clinical Neurophysiology, Malmo¨ University Hospital, Lund University, Malmo¨, Sweden
  63. 63. The Effects of Prolonged Low-Flow Sevoflurane Anesthesia on Renal and Hepatic Function Ryoji Obata, MD, HiromichiBito, MD, Morihiro Ohmura, GorokuMoriwaki, MD, YukakoIkeuchi, MD, TakasumiKatoh, MD, and Shigehito Sato, </li></ul> MD Department of Anesthesiology and Intensive Care, Hamamatsu University School of Medicine, Hamamatsu, Japan<br />
  64. 64. <ul><li>Comparison of propofol/remifentanil and sevoflurane/remifentanil for maintenance of anaesthesia for elective intracranial surgery J. R. Sneyd1*, C. J. H. Andrews2 and T. Tsubokawa21Peninsula Medical School, C310 Portland Square, University of Plymouth, Drake Circus, Plymouth PL4 8AA, UK. 2Department of Anaesthesia, Pain Management and Critical Care Medicine, Derriford Hospital, Plymouth PL6 8DH, UK
  65. 65. The Long-Term Effect of Sevoflurane on Neuronal Cell Damage and Expression of Apoptotic Factors After Cerebral Ischemia and Reperfusion in Rats Monika Pape, MD*Kristin Engelhard, MD*Eva Eberspa¨cher, Regina Hollweck‡KristineKellermann, DVM‡SusanneZintner, DVM‡PeterHutzler, PhD§Christian Werner, MD</li></li></ul><li><ul><li>A review of recovery from sevofluraneanaesthesia:Comparisons with isoflurane and propofolincludingComparisons with isoflurane and propofolincluding meta-analysis B. J. ROBINSON, T. D. UHRICH and T. J. EBERT Medical College of Wisconsin and VA Medical Center, Milwaukee, Wisconsin, USA
  66. 66. Low-flow Sevoflurane Compared with Low-flow Isoflurane Anesthesia in Patients with Stable Renal Insufficiency</li></ul>Peter F. Conzen, M.D.,* Evan D. Kharasch, M.D., Ph.D.,† Stephan F. A. Czerner, M.D.,‡ Alan A. Artru, M.D.,†Florian M. Reichle, M.D.,‡ PiotrMichalowski, M.D., Ph.D.,§ G. Alec Rooke, M.D., Ph.D.,_ Branko M. Weiss, M.D.,# Thomas J. Ebert, M.D., Ph.D.**<br />