1. Understand the history of Sevoflurane2. Recognize the pharmacological

properties of Sevoflurane3. Recognize its specific advantages in

neuroanaesthesia4. Must appreciate unfavourable

conditions produced by Sevoflurane

History started with inhalational anaesthesia.

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

Inhalational anaesthetics are routinely used.

They are potent. Balanced anaesthesia.

Development of Sevoflurane is an unusual and truly remarkable story.

1960’S-Three investigators evaluated halogenated ethers.

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

Bio transformation- increase in inorganic flouride in urine.

Dunken Holaday& Burnell Brown observed sweet smell,low solubility & no arrhythmias.

1981- phase 1 trials. After 10years Yasuda etal compared

Sevo with Iso. Baxter sold sevo to BOC which later

became OHMEDA. OHMEDA sold Sevo to Mariushi japan.

Mariushi used Sevo in japan . Approached ABBOTT for FDA approval

in USA. Later phase 2 &3 trials were done. Approved by FDA in 1994. Freely available by 1995.

It is 1, 1,1,3,3,3,hexafluro-2- fluro methoxy propane.

Non flammable Pleasant smell Volatile Molecular weight-200.05 Boiling point(at sea level)-58.6c Specific gravity at 20c-1.520-1.525 Partition coefficient at 37c water/gas- 0.36

blood/gas-0.63-0.69

Refractive index n20-1.2740 - 1.2760 Purity by gas chromatography-99.975%

or better

Vapour pressure

Temp°C mmHg

20 157

25 197

36 317

AGE OF PATIENT(YEARS)

SEVOFLURANE IN O2

SEVOFLURANE IN N2O 65% O2 35%

<3 3.3-2.6% 2.0%

3 - <5 2.5% Not available

5 - 12 2.4% Not available

25 2.5% 1.4%

35 2.2% 1.2%

40 2.05% 1.1%

50 1.8% 0.98%

60 1.6% 0.87%

80 1.4% 0.70%

MAC values

Non corrosive to stainless steel, brass, aluminium,nickle plated brass,chrome plated brass.

Stored at 25c not refrigerated. Tightly closed amber coloured bottles. Should not be used after expiry date.

Impact on intracranial dynamics Indirect vasoconstriction vs direct

vasodilatation. Effect on ICP& surgical condition. Effect on auto regulation. CO2 reactivity. Studies that have compared the use of

different agents in patients with intra cranial lesions with a certain degree of increased ICT.

The possibility of a quick awakening allowing for rapid post operative neurological assessment.

Low solubility of agents such as

Sevoflurane.

Cytoprotective effect. Animal studies only,at this time.

Relationship between metabolism and CBF.

Volatile anaesthetics act indirectly on CBF by reducing metabolism.

Directly they are vasodilators.

Net effect depends on agent & dosage used.

Sevo is the least vasodilating agent followed by Iso and Des.

Sevo has net vasoconsticting effect.

Preserves autoregulation upto 2 MAC. Iso&Des disrupts auto regulation at 1.5&0.5 MAC.

Threshold under which CBF is not sufficient to meet the cerebral metabolic needs is called critical CBF.

Below critical CBF brain becomes ischemic.

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

The critical CBF with Iso 10ml/100gms/min, with Sevo 11.5ml& with Halothane 20ml/100gms/min.

Strong evidence showing cytoprotection in animal experiments by volatile anaesthetics.

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

Volatile anaesthetics shown to have preconditioning in rodents.

They allow ischemic tolerance of brain tissue.

Preconditioning is not seen with Propofol. The choice of specific agent in anaesthesia

in a patient with cerebral ischemia solely depends on CPP,ICP& autoregulation.

Solubility : low blood gas solubility coefficient.

Potency : highly potent MAC averaging at 2%

can be given with high 02 does not suppress SSEP.

Air way properties: pleasant smell,no irritation, fast

induction no laryngospasm.

Circulatory effects:

Dose dependent fall in BP No sensitization to catecholamines Protective property on myocardium Coronary vasodilation

Respiratory effects: Dose dependent in tidal volume

Slight in end tidal & arterial co2 Bronchodilatation No irritation Less effect on HPVC

CNS effects Dose dependent in total & regional blood flow CMRO2 Slight in ICP Protection against ischemia Preconditioning possible.

Renal effects: 3-5% metobolised . in inorganic flourides. Reacts with sodalime and baralime. CompoundA produced. More in low FGF,when soda lime is dryer& hotter and also with high Sevo. CompoundA 19 ppm at clinical conditions.

Hepatic : very little effect on hepatic blood flow

and function

Favourable points1. Low blood gas solubility co-efficient2. Rapid induction and recovery -(Sevoflurane

Provides Faster Recovery and Postoperative Neurological Assessment Than Isoflurane in Long-Duration Neuro surgical Cases)

3. Potent, can be used with oxygen only4. Pleasant,non-irritating to respiratory

system5. Minimal or no stimulation of air way

reflexes6. Laryngospasm uncommon7. Suitable for all ages8. Compatable with epinephrine

9. Cerebral autoregulation maintained (Dynamic Cerebral Autoregulation During SevofluraneAnesthesia: A Comparison

with Isoflurane)

10. Coupling of metabolism and o2 demand maintained

(Intracranial Pressure, Middle Cerebral Artery FlowVelocity, and Plasma Inorganic Fluoride Concentrations inNeurosurgical Patients Receiving Sevoflurane or lsoflurane)

11. Rapid recovery and early neurological assessment possible (A comparative study between Sevo and Propofol for intracranial surgery for assessment of rapid recovery)

12. Pre-conditioning of the brain for ischemic attacks (The Long-Term Effect of Sevoflurane on Neuronal Cell Damage and Expression of Apoptotic Factors After Cerebral Ischemia and Reperfusion in Rats)—(sevoflurane induced preconditioning of rat brain invitro and the role of KATP channels.)

13.Protects brain cells (the effect of Sevoflurane on recovery of brain energy metabolism after cerebral ischmia in the rat)

14.Non-inflammable15.No long term effects on vital organs(Low-flow

Sevoflurane Compared with Low-flow Isoflurane Anesthesia in Patients with Stable Renal Insufficiency) (The Effects of Prolonged Low-Flow Sevoflurane Anesthesia on Renal and Hepatic Function)

16.Maintains co2 reactivity

Unfavourable points

1. Triggering agent for malignant hyperthermia

2. Emergence dysphoria in children3. Nausea and vomiting4. Seizures 5. CO production

Sevoflurane induces less cerebral vasodilation than isoflurane at the same A-line1autoregressive index level

A. HOLMSTRO¨ M and J. A°KESON

Department of Anesthesia and Intensive Care, Malmo¨ University Hospital, Lund University, Malmo¨, Sweden

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

Intracranial Pressure, Middle Cerebral Artery FlowVelocity, and Plasma Inorganic Fluoride Concentrations inNeurosurgical Patients Receiving Sevoflurane or lsoflurane Alan 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 tDepartment ofAnesthesiology, University of Utah School of Medicine, Salt Lake City, Utah

Direct Cerebral Vasodilatory Effects of Sevofluraneand IsofluraneBasil 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.‡*

Sevoflurane-induced preconditioning of rat brain invitro and the role of KATP channels

Franz Kehla,*, Ralphiel S. Payneb, Norbert Roewera, Avital SchurrbaDepartment of Anesthesiology, Klinik und Poliklinik fu¨r Ana¨sthesiologie, Zentrum Operative Medizin, Julius-Maximilans-Universita¨ t, Oberdu¨rrbacher Str. 6, Wu¨rzburg 97080, Germany

Sevoflurane Provides Faster Recovery and PostoperativeNeurological Assessment Than Isoflurane in Long-DurationNeurosurgical Cases

Alain Gauthier, MD*, Francois Girard, MD, FRCPC*, Daniel Boudreault, MD, FRCPC*, Monique Ruel, RN*, and Alexandre Todorov, 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

Desflurane results in higher cerebral blood flow than sevoflurane or isoflurane at hypocapnia in pigs A. 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

The Effects of Prolonged Low-Flow Sevoflurane Anesthesia on Renal and Hepatic Function Ryoji Obata, MD, Hiromichi Bito, MD, Morihiro Ohmura, Goroku Moriwaki, MD, Yukako Ikeuchi, MD, Takasumi Katoh, MD, and Shigehito Sato,

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

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

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‡Kristine Kellermann, DVM‡Susanne Zintner, DVM‡Peter Hutzler, PhD§Christian Werner, MD

A review of recovery from sevoflurane anaesthesia:Comparisons with isoflurane and propofol includingComparisons with isoflurane and propofol including meta-analysis B. J. ROBINSON, T. D. UHRICH and T. J. EBERT Medical College of Wisconsin and VA Medical Center, Milwaukee, Wisconsin, USA

Low-flow Sevoflurane Compared with Low-flow Isoflurane Anesthesia in Patients with Stable Renal Insufficiency

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.,‡ Piotr Michalowski, M.D., Ph.D.,§ G. Alec Rooke, M.D., Ph.D.,_ Branko M. Weiss, M.D.,# Thomas J. Ebert, M.D., Ph.D.**