1. Inhalation Anesthetics
Chapter 3
Isoflurane and sevoflurane
(halogenated compounds)
Nitrous oxide and desflurane
Enflurane
Halothane
Methoxyflurane
Diethyl ether

2. Diethyl Ether 1st inhaled anesthetic
No longer used as an anesthetic agent, as well as Chloroform and NO
Classic stages and planes of anesthesia described using ether
Desirable characteristics
Stable cardiac output, rhythm, and blood pressure
Stable respirations
Good muscle relaxation

3. Diethyl Ether (Cont’d)
Undesirable characteristics
Tracheal and bronchial mucosal irritation
Prolonged induction and recovery
Postoperative nausea and vomiting
Flammable and explosive

4. Halogenated Organic Compounds
Isoflurane and sevoflurane are the most commonly used agents in this class
Also Desflurane, Halothane, Methoxyflurane, and Enflurane
Liquid at room temperature
Stored in a vaporizer on an anesthetic machine
Vaporized in oxygen that flows through the vaporizer
Exception being Desflurane- has a special injection type vaporizer

5. Uptake and Distribution of Halogenated Organic Compounds
Liquid anesthetic is vaporized and mixed with oxygen gas
Mixture is delivered to the patient via a mask or endotracheal tube (ET tube)
Mixture travels to lungs (alveoli) and diffuses into the bloodstream
Diffusion rate is dependent on concentration gradient (alveoli/capillary) and lipid solubility
Concentration gradient is greatest during initial induction

6. Uptake and Distribution of Halogenated Organic Compounds (Cont’d)
Distribution to tissues is dependent on blood supply
Lipid solubility determines entry into tissues through cell walls
Depth of anesthesia is dependent on partial pressure of anesthetic in the brain
Partial pressure in the brain is dependent on partial pressure of the anesthetic in blood and alveoli
Maintenance of anesthesia is dependent on sufficient quantities of anesthetic delivered to the lungs

7. Elimination of Halogenated Organic Compounds
Reducing amount of anesthetic administered reduces amount delivered to the alveoli
Blood level is initially higher than alveolar level
Concentration gradient now favors anesthetic diffusion from blood into the alveoli
Blood levels drop quickly as patient breathes out anesthetic from the alveoli
Brain levels drop as less anesthetic is delivered by blood
Patient wakes up

8. Effects of Halogenated Organic Compounds
CNS
Dose-related reversible CNS depression
Hypothermia
Cardiovascular system
Depress cardiovascular function
Effects on HR variable
Respiratory system
Dose-dependent ventilation depression

9. Adverse Effects of Halogenated Organic Compounds
CNS (Cont’d)
Increased intracranial pressure in patients with head trauma or brain tumors
Considered safe for epileptic animals
Cardiovascular system
Decrease blood pressure and may decrease renal blood flow
Respiratory system
Hypoventilation
Carbon dioxide retention and respiratory acidosis

10. Physical and Chemical Properties of Inhalant Anesthetics
Important properties to consider
Vapor pressure
Partition coefficient
Minimum alveolar concentration (MAC)
Rubber solubility

11. Vapor Pressure
Is the amount of pressure exerted by the gaseous form of a substance when in equilbrium
i.e. – it’s ability to evaporate
Determines how readily an inhalation anesthetic will evaporate in the anesthetic machine vaporizer
Temperature and anesthetic agent dependent

12. Vapor Pressure Volatile agents Nonvolatile agents
High vapor pressure- evaporates readily
Isoflurane, sevoflurane, desflurane, and halothane
Delivered from a precision vaporizer to control the delivery concentration
All precision vaporizers are made to deliver only one specific halogenated agent
Nonvolatile agents
Low vapor pressure- no need for precision vaporizer
Methoxyflurane
*Vaporizers are specific to that gas, and is unacceptable to combine agents in the same vaporizer. Although it is safe to switch patient from one gas to another

13. Blood:Gas Partition Coefficient
Solubility is a ratio of concentration of an agent in 2 substances
The measure of the solubility of an inhalation anesthetic in blood as compared to alveolar gas (air)
Indication of the speed of induction and recovery for an inhalation anesthetic agent
Low blood:gas partition coefficient
Agent is more soluble in alveolar gas than in blood at equilibrium
Agent is less soluble in blood
Faster expected induction and recovery

14. Blood:Gas Partition Coefficient (Cont’d)
High blood:gas partition coefficient
Agent is more soluble in blood than in alveolar gas at equilibrium
Agent is less soluble in alveolar gas
Agent is absorbed into blood and tissues (sponge effect)
Slower expected induction and recovery

15. Blood:Gas Partition Coefficient (Cont’d)
Blood: gas partition coefficient determines the clinical use of the anesthetic agent
Induction: Can a mask be used?
Maintenance: How fast will the anesthetic depth change in response to changes in the vaporizer setting?
Recovery: How long will the patient sleep after anesthesia?

16. Minimum Alveolar Concentration (MAC)
The lowest concentration of which 50% of patients shows no response to a painful stimulus
The measure of the potency of a drug
Used to determine the average setting on the vaporizer that will produce surgical anesthesia
The lower the MAC, the more potent the anesthetic agent and the lower the vaporizer setting
MAC may be altered by age, metabolic activity, body temperature, disease, pregnancy, obesity, and other agents present
Every patient must be monitored as an individual
Age, disease, temperature, pregnancy, obesity, pre medications

17. Isoflurane Most commonly used inhalant agent in North America
Approved for use in dogs and horses; commonly used in other species

18. Isoflurane Properties High vapor pressure: need a precision vaporizer
Low blood:gas partition coefficient: rapid induction and recovery
Good for induction with mask or chamber
MAC = 1.3% to 1.63%: helps determine initial vaporizer setting
Low rubber solubility
Stable at room temperature; no preservatives needed = no build up in the machine

19. Effects and Adverse Effects
Maintains cardiac output, heart rate, and rhythm
Fewest adverse cardiovascular effects
Depresses the respiratory system
Maintains cerebral blood flow
Almost completely eliminated through the lungs- 0.2% metabolized by the liver
Induces adequate to good muscle relaxation
Provides little or no analgesia after anesthesia
Difficult to mask patient
Can produce carbon monoxide when exposed to a desiccated carbon dioxide absorbent

20. Sevoflurane High vapor pressure: need a precision vaporizer
Blood:gas partition coefficient: rapid induction and recovery
Good for induction with a mask or chamber
High controllability of depth of anesthesia
MAC = 2.34% to 2.58%
Cost about 10x more the Isoflurane
Easier to mask a patient, more pleasant
smelling

21. Effects and Adverse Effects of Sevoflurane
Minimal cardiovascular depression
Depresses respiratory system
Eliminated by the lungs, minimal hepatic metabolism- 2-5%
Maintains cerebral blood flow
Induces adequate muscle relaxation
Some paddling and excitement during recovery
No post of analgesia
Can react with potassium hydroxide (KOH)
or sodium hydroxide (NaOH) in desiccated
CO2 absorbent to produce a chemical
(Compound A) that causes renal damage

22. Desflurane Closely related to isoflurane Expensive
Lowest blood:gas partition coefficient: very rapid induction and recovery
Used with a special heated electronic precision vaporizer
MAC = 7.2% and 9.8%
Least potent inhalant agent
Eliminated by the lungs- 0.02% metabolized in liver

23. Effects and Adverse Effects of Desflurane
Strong vapors cause coughing and holding the breath= difficult to mask
Other effects are similar to isoflurane
Transient increase in heart rate and blood pressure (humans)
Produces carbon monoxide with spent soda lyme

24. Other Halogenated Inhalation Agents
Halothane (Fluothane)
Not commonly used anymore
Being replaced by isoflurane and sevoflurane
B:G -2.54
20-46% metabolized in the liver
MAC
Sensitizes heart to catecholamine and induces arrhythmias
Cardiac, respiratory depression
Increased cerebral blood flow
Increased temperature- malignant hyperthermia- Dantrolene

25. Methoxyflurane Methoxyflurane No longer available in North America
B:G- 151!
Used in a non precision vaporizer- wick
50-75% metabolized by the liver, excreted by the kidneys!!
Fluoride ions and other potentially toxid metabolites produced by the liver= renal damage
Enflurane
Used primarily in human medicine

26. Nitrous Oxide Nitrous oxide
Used primarily in human medicine; some veterinary use
A gas at room temperature; no vaporizer is required
Mixed with oxygen at 40-67%, then delivered to patient
Reduces MAC 20-30%
Used with Halothane and Methoxyflurane
to reduce the adverse effects of these gases

27. CNS and Respiratory Stimulants
Doxapram
Analeptic agent (CNS stimulant)
Stimulates respiration and speeds recovery
Acts at the carotid sinus and the aortic arch
Used in neonate puppies and kittens after C-section
IV administration or sublingual drops (neonates)
Adverse effects
Wide margin of safety
Hyperventilation and hypertension
Lowers seizure threshold
CNS damage

28. Use of Doxapram Repeat injections may be necessary
Reverses respiratory depression from inhalant agents and barbiturates
1-5 ggt under the tongue of a puppy, or 1-2 ggt in a kitten if needed after C-section or dystocia