Understand the history of Sevoflurane
2. Recognize the pharmacological properties
of Sevoflurane
3. Recognize its specific...
History started with inhalational
anaesthesia.
 Past 50 years- 3 gases,13 inhalational
anaesthetics were introduced.
 In...
Development of Sevoflurane is an unusual
and truly remarkable story.
 1960’S-Three investigators evaluated
halogenated et...
Dunken Holaday& Burnell Brown observed
sweet smell,low solubility & no
arrhythmias.
 1981- phase 1 trials.
 After 10year...
Mariushi used Sevo in japan .
 Approached ABBOTT for FDA approval in
USA.
 Later phase 2 &3 trials were done.
 Approved...
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...
Refractive index n20-1.2740 - 1.2760
 Purity by gas chromatography-99.975% or
better


Vapour
pressure

Temp°C

mmHg

20...
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
...
Non corrosive to stainless
steel, brass, aluminium,nickle plated
brass,chrome plated brass.
 Stored at 25c not refrigerat...
Impact on intracranial dynamics






Indirect vasoconstriction vs direct
vasodilatation.
Effect on ICP& surgical con...
The possibility of a quick awakening
allowing for rapid post operative
neurological assessment.
Low solubility of agents s...


Relationship between metabolism and CBF.



Volatile anaesthetics act indirectly on CBF
by reducing metabolism.



Di...


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



Sevo has net vasoconsticting effect.



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

Strong evidence showing cytoprotection in
animal experiments by volatile anaesthetics.
Same applies to Propof...


Solubility : low blood gas solubility
coefficient.



Potency : highly potent MAC averaging at 2%
can be given with hi...
 Circulatory

effects:

Dose dependent fall in BP
No sensitization to catecholamines
Protective property on myocardium
Co...
 Respiratory

effects:

Dose dependent in tidal volume

Slight in end tidal & arterial co2
Bronchodilatation
No irritatio...
 CNS

effects

Dose dependent in total &
regional blood flow
CMRO2
Slight in ICP
Protection against ischemia
Precondition...
 Renal

effects:

3-5% metobolised .
in inorganic flourides.
Reacts with sodalime and baralime.
CompoundA produced.
More ...
 Hepatic

:

very little effect on hepatic blood flow
and function

1.
2.
3.
4.
5.
6.
7.
8.

Favourable points
Low blood gas solubility co-efficient
Rapid induction and recovery
Potent, ca...
Cerebral autoregulation maintained
10. Coupling of metabolism and o2 demand
maintained
11. Rapid recovery and early neurol...


Unfavourable points
1. Triggering agent for malignant
hyperthermia
2. Emergence dysphoria in children
3. Nausea and vom...
 Sevoflurane

induces less cerebral
vasodilation than isoflurane at the same
A-line1autoregressive index level
A. HOLMSTR...


Intracranial Pressure, Middle Cerebral Artery
FlowVelocity, and Plasma Inorganic Fluoride
Concentrations inNeurosurgica...


Sevoflurane-induced preconditioning of rat
brainin vitro and the role of KATP channels

Franz Kehla,*, Ralphiel S. Payn...
 Desflurane

results in higher cerebral
blood flow than sevoflurane or isoflurane
at hypocapnia in pigs A. HOLMSTRO¨ M 1,...


Comparison of propofol/remifentanil and
sevoflurane/remifentanil for maintenance of
anaesthesia for elective intracrani...


A review of recovery from sevoflurane
anaesthesia:Comparisons with isoflurane and
propofol includingComparisons with is...
Sevo in neuro anesthesia
Sevo in neuro anesthesia
Sevo in neuro anesthesia
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Sevo in neuro anesthesia

  1. 1. Understand the history of Sevoflurane 2. Recognize the pharmacological properties of Sevoflurane 3. Recognize its specific advantages in neuroanaesthesia 4. Must appreciate unfavourable conditions produced by Sevoflurane 1.
  2. 2. 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. 
  3. 3. 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. 
  4. 4. 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. 
  5. 5. 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. 
  6. 6. It is 1, 1,1,3,3,3,hexafluro-2- fluro methoxy propane.
  7. 7. 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 
  8. 8. 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
  9. 9. 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%
  10. 10. Non corrosive to stainless steel, brass, aluminium,nickle plated brass,chrome plated brass.  Stored at 25c not refrigerated.  Tightly closed amber colouredbottles.  Should not be used after expiry date. 
  11. 11. 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.
  12. 12. 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. 
  13. 13.  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.
  14. 14.  Sevo is the least vasodilating agent followed by Iso and Des.  Sevo has net vasoconsticting effect.  Preserves autoregulation upto 2 MAC. Iso&Des disruots auto regulation at 1.5&0.5 MAC.
  15. 15. 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. 
  16. 16.       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.
  17. 17.  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.
  18. 18.  Circulatory effects: Dose dependent fall in BP No sensitization to catecholamines Protective property on myocardium Coronary vasodilation
  19. 19.  Respiratory effects: Dose dependent in tidal volume Slight in end tidal & arterial co2 Bronchodilatation No irritation Less effect on HPVC
  20. 20.  CNS effects Dose dependent in total & regional blood flow CMRO2 Slight in ICP Protection against ischemia Preconditioning possible.
  21. 21.  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.
  22. 22.  Hepatic : very little effect on hepatic blood flow and function
  23. 23.  1. 2. 3. 4. 5. 6. 7. 8. Favourable points Low blood gas solubility co-efficient Rapid induction and recovery Potent, can be used with oxygen only Pleasant,non-irritating to respiratory system Minimal or no stimulation of air way reflexes Laryngospasm uncommon Suitable for all ages Compatable with epinephrine
  24. 24. Cerebral autoregulation maintained 10. Coupling of metabolism and o2 demand maintained 11. Rapid recovery and early neurological assessment possible 12. Pre-conditioning of the brain for ischemic attacks 13. Protects brain cells 14. Non-inflammable 15. No long term effects on vital organs 16. Maintains co2 reactivity 9.
  25. 25.  Unfavourable points 1. Triggering agent for malignant hyperthermia 2. Emergence dysphoria in children 3. Nausea and vomiting 4. Seizures 5. Co production
  26. 26.  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
  27. 27.  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.‡ *
  28. 28.  Sevoflurane-induced preconditioning of rat brainin vitro 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
  29. 29.  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
  30. 30.  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
  31. 31.  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 Lowflow 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.**

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