2. Lesson objectives Understand the history of Sevoflurane Recognize the pharmacological properties of Sevoflurane Recognize its specific advantages in neuroanaesthesia Must appreciate unfavourable conditions produced by Sevoflurane

4. Past 50 years- 3 gases,13 inhalational anaesthetics were introduced.

5. Inhalational anaesthetics are routinely used.

6. They are potent.

8. 1960’S-Three investigators evaluated halogenated ethers.

9. Thomas Cook, Richard Mazze & Michael Halsey-on animals.

11. 1981- phase 1 trials.

12. After 10years Yasuda etal compared Sevo with Iso.

13. Baxter sold sevo to BOC which later became OHMEDA.

15. Approached ABBOTT for FDA approval in USA.

16. Later phase 2 &3 trials were done.

17. Approved by FDA in 1994.

20. Pleasant smell

21. Volatile

22. Molecular weight-200.05

23. Boiling point(at sea level)-58.6c

24. Specific gravity at 20c-1.520-1.525

25. Partition coefficient at 37c water/gas- 0.36 blood/gas-0.63-0.69

29. Stored at 25c not refrigerated.

30. Tightly closed amber colouredbottles.

32. Effect on ICP& surgical condition.

33. Effect on auto regulation.

34. CO2reactivity.

37. Volatile anaesthetics act indirectly on CBF by reducing metabolism.

38. Directly they are vasodilators.

40. Sevo has net vasoconsticting effect.

42. Below critical CBF brain becomes ischemic.

43. On awake patients it is 25ml/100gms/min.

45. Same applies to Propofol but more benificial if given in reperfusion period.

46. Volatile anaesthetics shown to have preconditioning in rodents.

47. They allow ischemic tolerance of brain tissue.

48. Preconditioning is not seen with Propofol.

56. Conclusions Cerebral autoregulation maintained Coupling of metabolism and o2 demand maintained Rapid recovery and early neurological assessment possible Pre-conditioning of the brain for ischemic attacks Protects brain cells Non-inflammable No long term effects on vital organs Maintains co2 reactivity

58. References

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.,‡ Andrew C. Summors, B.Sc., M.B.B.S., F.R.C.A.‡ *

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, MD Department of Anesthesiology and Intensive Care, Hamamatsu University School of Medicine, Hamamatsu, Japan

66. Low-flow Sevoflurane Compared with Low-flow Isoflurane Anesthesia in Patients with Stable Renal InsufficiencyPeter 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.**