Inhalational Anaesthetic Agents

Inhalational Anaesthetic Agents
Agents in Common Use
• Halothane
• lsoflurane
• Nitrous oxide
Newer Agents
• Sevoflurane
• Desflurane
Agents Not in Use
• Enflurane
• Ether
• Trilene
• Methoxyflurane
• Cyclopropane
• Chloroform

1. Inhalational
Anaesthetic Agents
Mr. Harshad Khade
MSc. Medical Technology (OTA)
Symbiosis International University, Pune.

2. Inhalational Anaesthetic Agents
Agents in Common Use
•Halothane
•lsoflurane
•Nitrous oxide
Newer Agents
•Sevoflurane
•Desflurane
Agents Not in Use
•Enflurane
•Ether
•Trilene
•Methoxyflurane
•Cyclopropane
•Chloroform

3. Drugs
lsoflurane Sevoflurane
Nitrous oxide Halothane Enflurane
Desflurane
Inhalational Anaesthetic Agents

4. Isoflurane
Class
•Volatile inhaled agent
Uses
1.For the induction and maintenance of general anaesthesia and has been
used.
2.For sedation during intensive care.
Main action
•General anaesthesia (reversible loss of both awareness and recall of
noxious stimuli).

5. Presentation
•As a clear, colourlessliquid with a pungent smell, which is non-flammable;
•The commercial preparation contains no additives or stabilizers and is
supplied in amber-colouredbottles.
•The molecular weight of isoflurane is 184.5, the boiling point 48.5°C, and
the saturated vapourpressure 32 kpaat 20°C.
•The mac of isoflurane is 1.15 (0.50 in 70% N2 O), although it is age-
dependent and ranges from 1.05 in elderly patients to 1.6 in neonates;
•The blood:gaspartition coefficient is 1.4, and the fat:bloodpartition
coefficient is 50.
•The oil:gaspartition coefficient is 97.
•Mechanism of ActionUncertain

6. Mode ofaction
•The mechanism of general anaesthesia remains to be fully elucidated.
•General anaestheticsappear to disrupt synaptic transmission (especially in
the area of the ventrobasalthalamus).
•This mechanism may include potentiation of the gabaaand glycine receptors
and antagonism at nmdareceptors.
•Their mode of action at the molecular level appears to involve the expansion
of hydrophobic regions in the neuronal membrane, either within the lipid
phase or within hydrophobic sites in cell membranes.
Routes ofadministration/dose
•Isoflurane is administered by inhalation;
•The agent has a pleasant, non-irritant odour.
•The concentration used for induction of anaesthesia is quoted as 5–8%.
•Maintenance of anaesthesia is usually achieved using between 0.5 and 3%.

7. Dose
•Titrated to effect; MAC (age 40)=1.15
Onset
•Higher solubility than sevofluraneand desfluranetherefore uptake is
slower than the modern agents.
•Onset of effect is hastened by using higher flows of carrier gases and by
using higher concentrations of volatile agent.
Duration
•Clinical recovery in less than 15 minutes (usually).
•Theoretically a slower wake-up than the modern agents due to higher
solubility.
Elimination
•Pulmonary

8. Effects
•CNS
•Isoflurane produces an additive central nervous system (CNS)-depressant
effect along with other sedative/ hypnotics and analgesics.
•Has the potential to increase intracranial pressure which can be mitigated
with hyperventilation. Delirium.
•CVSDose-related hypotension (vasodilation).
•Respiratory
•Respiratory depression with rapid, shallow respiratory pattern.
•Loss of intercostal muscle function creates a rocking boat appearance.
•Isoflurane is irritating to the airways and can cause breath-holding, cough,
laryngospasm or bronchospasm.
•Its pungent quality makes it unsuitable for use with a mask induction.

9. •GI
•Nausea, vomiting.
•MSK
•Potentiates neuromuscular blockade.
•Malignant hyperthermia trigger.
Contraindications
•Malignant hyperthermia susceptibility

10. Sevoflurane
Class
•Volatile inhaled anesthetic.
Uses
•Used for maintenance of anesthesia.
•Can be used for induction of anesthesia particularly in children.
•Rarely may be used as a treatment for status asthmaticus.
Main action
•General anaesthesia (reversible loss of both awareness and recall of
noxious stimuli).

11. •Presentation
•As a clear, colourlessliquid which is non-flammable;
•The commercial preparation contains no additives or stabilizers and is
supplied in amber-colouredbottles.
•The molecular weight of sevofluraneis 200, the boiling point 58.6°C, and
the saturated vapourpressure 22.7 kpaat 20°C.
•The mac of sevofluraneis age-dependent and ranges from 1.4 in elderly
patients to 3.3 in neonates (0.7–2.0 in the presence of 65% N2 O);
•The blood:gaspartition coefficient is 0.63–0.69, and the fat:bloodpartition
coefficient is 52.
•The oil:gaspartition coefficient is 47–54.
•Degradation of sevofluranemay occur by two pathways in the presence of
warm, dessicatedalkaline co2 absorbants(potassium hydroxide > sodium
hydroxide) at low fresh gas flows

12. Mode ofaction
•The mechanism of general anaesthesia remains to be fully elucidated.
General anaestheticsappear to disrupt synaptic transmission (especially in
the area of the ventrobasalthalamus).
•This mechanism may include potentiation of the GABAA and glycine
receptors and antagonism at NMDA receptors.
•Their mode of action at the molecular level appears to involve the
expansion of hydrophobic regions in the neuronal membrane, either within
the lipid phase or within hydrophobic sites in cell membranes.
Routes ofadministration/dose
•Sevofluraneis administered by inhalation; the agent has a pleasant, non-
irritant odour.
•The concentration used for induction of anaesthesia is quoted as 5–8%.
Maintenance of anaesthesia is usually achieved using between 0.5 and 3%.

13. Dose
•Titrated to effect; MAC (age 40) = 2.1%.
Onset
•Low solubility allows rapid uptake and equilibration.
•Onset of effect is hastened by using higher flows of carrier gases and by
using higher concentrations of volatile agent.
Duration
•Clinical recovery in less than 10 minutes (usually).
•If given for prolonged periods, wake-up will be slower as adipose stores
have been saturated and are slow to offload.
Elimination
•Pulmonary (major); hepatic (2-5%); renal (metabolites excretion only)

14. Effects
•CNS
•Sevofluraneproduces an additive central nervous system (CNS)-
depressant effect along with other sedative/hypnotics and analgesics.
•Has the potential to increase intracranial pressure which can be mitigated
with hyperventilation. Delirium.
•CVSDose-related hypotension (vasodilation).
•Respiratory
•Respiratory depression with a rapid, shallow respiratory pattern.
•Loss of intercostal muscle function creates a rocking boat appearance.
•Causes bronchodilation.
•Sevofluraneis sweet-smelling and not as irritating to the respiratory tract
as desflurane.

15. •GINausea, vomiting.
•MSK
•Potentiates neuromuscular blockade.
•Malignant hyperthermia trigger.
•Misc.
•Potential nephrotoxicity due to Compound A which is produced through
contact with soda lime.
•Compound A can be produced if sevofluraneis used with very low fresh gas
flows or for long MAC-hours.
•Therefore, sevofluranemust be used with a minimum of 2 litres/ minute of
fresh gas flow.
Contraindications
•Malignant hyperthermia susceptibility

16. Desflurane
Class
•Volatile inhaled anesthetic
Uses
•Desfluraneis used for the induction and maintenance of general
anaesthesia
Main action
•General anaesthesia (reversible loss of both awareness and recall of
noxious stimuli).

17. Presentation
•As a clear, colourlessliquid that should be protected from light.
•The commercial preparation contains no additives and is flammable at a
concentration of 17%.
•The molecular weight of desfluraneis 168;
•The boiling point is 22.8°C, and the saturated vapourpressure is 88.5 kpa
at 20°C.
•The mac of desfluraneis age-dependent and ranges from 5.17 ±0.65% to
10.65% (1.67 ±0.4% to 7.75% in the presence of 60% N2 O);
•The blood:gaspartition coefficient is 0.45, and the fat:bloodpartition
coefficient is 29.
•Desfluraneis stable in the presence of moist soda lime.

18. Mode ofaction
•The mechanism of general anaesthesia remains to be fully elucidated. General
anaestheticsappear to disrupt synaptic transmission (especially in the area of
the ventrobasalthalamus).
•This mechanism may include potentiation of the gamma-amino-butyric acid
(GABA) type A(GABAA) and glycine receptors and antagonism at N-methyl-
D-aspartate (NMDA) receptors.
Routs ofadministration/dose
•Desfluraneis administered by inhalation.
•Because of the high saturated vapourpressure, desfluranemust be
administered by a specific pressurized and heated vaporizer.
•The concentration used for induction of anaesthesia is quoted as 4–11%,
although induction is usually achieved using a different agent.
•Maintenance of anaesthesia is usually achieved by using between 2% and 6%.

19. Dose
•Titrated to effect; MAC (age 40) = 6.0%
Onset
•Low solubility allows rapid uptake and equilibration.
•Onset of effect is hastened by using higher flows of carrier gases and
by using higher concentrations of volatile agent.
Duration
•Clinical recovery in less than 10 minutes (2-2.5 x faster washout than
Isoflurane)
Elimination
•Pulmonary (major); negligible hepatic (0.02%)

20. Effects
•CNS
•Desfluraneproduces an additive central nervous system (CNS)
depressant effect along with other sedative/ hypnotics and analgesics.
•Sympatho-excitation can occur with rapid increase in concentration of
desflurane.
•Has the potential to increase intracranial pressure which can be mitigated
with hyperventilation.
•May cause headache, agitation, dizziness
•CVS
•Dose-related hypotension (vasodilation).
•Tachycardia and hypertension may be seen due to sympathetic nervous
system activation.

21. •Respiratory
•Respiratory depression with a rapid, shallow respiratory pattern.
•Loss of intercostal muscle function creates a rocking boat appearance.
•Desfluraneis irritating to the airways and can cause breath-holding,
cough, laryngospasm or bronchospasm in susceptible individuals,
especially if used as sole agent for induction.
•GI
•Potential immune-mediated hepatotoxicity.
•Nausea, vomiting.
•MSK
•Potentiates neuromuscular blockade;
•malignant hyperthermia trigger.

22. •Misc.
•Significant carbon monoxide production occurs on exposure to
dessicatedCO2 absorbing agents therefore must not be used with low-
flow anesthesia.
•Rapid elimination requires initiation of post-operative analgesia prior to
emergence.
Contraindications
•Malignant hyperthermia susceptibility

23. Enflurane
Class
•Volatile inhaled anesthetic
Uses
•Enfluraneis used for the induction and maintenance of general
anaesthesia
Main action
•General anaesthesia (reversible loss of both awareness and recall of
noxious stimuli).

24. •Presentation
•As a clear, colourlessliquid (that should be protected from light) with a
characteristic sweet smell.
•The commercial preparation contains no stabilizers or preservatives; it is
non-flammable in normal anaestheticconcentrations.
•The molecular weight of enfluraneis 184.5, the boiling point 56.5°C, and
the saturated vapourpressure 23.3 kpaat 20°C. The MAC of enfluraneis
1.68 (0.57 in 70% N2 O),
•The oil/water solubility coefficient 120, and the blood/gas solubility
coefficient 1.91.
•The drug is readily soluble in rubber; it does not attack metals.
Mode ofaction
•The mechanism of general anaesthesia remains to be fully elucidated.
•General anaestheticsappear to disrupt synaptic transmission.

25. Routes ofadministration/doses
•Enfluraneis administered by inhalation, conventionally via a calibrated
vaporizer.
•The concentration used for the inhalational induction of anaesthesia is 1–
10% and for maintenance 0.6–3%.
Effects
•CVS
•Enfluraneis a negative inotrope; it also causes a decrease in the systemic
vascular resistance, and these two effects produce a decrease in the mean
arterial pressure.
•Unlike halothane, enfluraneproduces a slight reflex tachycardia.
•The drug decreases coronary vascular resistance;
•it also reduces the rate of phase IV depolarization, increases the threshold
potential, and prolongs the effective refractory period

26. •Rs
•Enfluraneis a powerful respiratory depressant, markedly decreasing the
tidal volume, although the respiratory rate may increase during the
administration of the drug.
•Aslight increase in the paco2 may result in spontaneously breathing
subjects; the drug also decreases the ventilatoryresponse to hypoxia and
hypercapnia.
•Cns
•The principal effect of enfluraneis general anaesthesia; the drug has little
analgesic effect.
•Gu
•Enfluranedecreases the renal blood flow and glomerular filtration rate;
•A small volume of concentrated urine results

27. Halothane
Class
•Volatile inhaled anesthetic
Uses
•Halothane is used for the induction and maintenance of general
anaesthesia
Main action
•General anaesthesia (reversible loss of both awareness and recall of
noxious stimuli).

28. Presentation
•As a clear, colourlessliquid (that should be protected from light) with a
characteristic sweet smell.
•The commercial preparation contains 0.01% thymolwhich prevents
decomposition on exposure to light; it is non-flammable at normal
anaestheticconcentrations.
•The molecular weight of halothane is 197.4, the boiling point 50.2°C, and
the saturated vapourpressure 32 kPaat 20°C.
•The MAC of halothane is 0.75 (0.29 in the presence of 70% N2 O), the
oil/water solubility coefficient 220, and the blood/gas solubility
coefficient 2.5. The drug is readily soluble in rubber;
•It does not attack metals in the absence of water vapourbut will attack
brass, aluminium, and lead in the presence of water vapour.

29. •Mode ofaction
•The mechanism of general anaesthesia remains to be fully elucidated.
General anaestheticsappear to disrupt synaptic transmission (especially
in the area of the ventrobasalthalamus).
•This mechanism may include potentiation of the GABAA and glycine
receptors and antagonism at NMDA receptors.
Routes ofadministration/doses
•Halothane is administered by inhalation, conventionally via a calibrated
vaporizer.
•The concentration used for the inhalational induction of anaesthesia is 2–
4% and for maintenance 0.5–2%.

30. Effects
•CVS
•Halothane causes a dose-related decrease in myocardial contractility and
cardiac output, with an attendant decrease in cardiac work and
myocardial oxygen consumption, possibly by inhibition of Ca2+ flux
within myocardial cells and of the interaction between Ca2+ and the
contractile proteins
•RS
•Halothane is a respiratory depressant, markedly decreasing the tidal
volume, although the respiratory rate may increase.
•CNS
•The principal effect of halothane is general anaesthesia; the drug has
little, if any, analgesic effect.

31. Nitric Oxide
Class
•Nitrous oxide is an inhaled agent but not a volatile agent.
Uses
•It is used as an adjunct to general anesthesia.
•It has a weak effect and therefore cannot be used as the sole agent for
general anesthesia and
•It is most commonly used in combination with a volatile agent.
•It can be used on its own for sedation or analgesia as can be seen in the
obstetric or dental setting.
Main actionsVasodilatation.

32. Presentation
•In aluminiumcylinders containing 100/800 ppm of NO and nitrogen;
•The cylinders may contain either 353 l at standard temperature and
pressure (STP) of NO in nitrogen or 1963 l at STP.
•Pure no is toxic and corrosive.
•No can also be supplied via stainless steel medical gas piping.
Mode ofaction
•No is produced in vivo by no synthase which uses the substrate l-arginine.
•No diffuses to the vascular smooth muscle layer and stimulates guanylate
cyclase;
•The cyclic guanosine monophosphate (cgmp) produced activates a
phosphorylation cascade which leads to smooth muscle relaxation and
vasodilatation.

33. Routes ofadministration/doses
•NO is administered by inhalation in a dose of 5–20 ppm;
•The drug can either be injected into the patient limb of the inspiratory
circuit of a ventilator during inspiration only or administered using a
continuous-flow system which delivers NO throughout the respiratory cycle.
•The former technique reduces a ‘bolus’ effect seen with a continuous-flow
technique, in addition to reducing nitrogen dioxide formation.
•This latter effect is achieved by decreasing the time allowed for oxygen and
no to mix.
•The delivery system is designed to minimize the oxidation of no to nitrogen
dioxide.
•Monitoring of no concentrations can be achieved by a chemiluminescence
monitor or electrochemical detector.

34. Dose
•Delivered in concentrations of up to 70% in oxygen.
•Actual MAC is 104%.
Onset
•Immediate due to very low solubility.
Duration
•Offset of effect is rapid after discontinuation.
Elimination
•Pulmonary

35. Effects
•CNS
•N2O is a potent analgesic.
•It increases cerebral metabolic rate, cerebral blood flow and intracranial
pressure and is therefore not a good choice for patients with decreased
intracranial compliance.
CVS
•N2O has a mild sympathomimetic effect but causes direct myocardial
depression.
•The net effect is a modest decrease in blood pressure and heart rate.
•Increased coronary tone may exacerbate ischemia in susceptible
patients.

36. •Respiratory
•N2O produces mild respiratory depression which is potentiated by
opioids, hypnotics and volatile anesthetics.
•It has no bronchodilatoryeffect.
•It exacerbates pulmonary hypertension.
•Misc.
•N2O expands the volume of gas-containing spaces as N2O diffuses across
membranes more readily than nitrogen can diffuse out.
•Thus the size of a pneumothorax, emphysematous bleb or distended
bowel loop will increase when N2O is used.

37. •Misc.
•Bone marrow suppression due to inhibition of methionine synthetase, can
occur if N2O is used for extended periods.
•N2O enhances opioid-induced rigidity.
•Finally, N2O is an operating room pollutant;
•N2O levels (in parts per million) in the operating room environment are
measured regularly to comply with workplace safety regulations.
Contraindications
•Raised intracranial pressure, pneumothorax or bowel obstruction.
•Should be used with caution in patients with coronary disease or
emphysema.

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