1. CHAPTER 3 ISOFLURANE AND SEVOFLURANE (HALOGENATED COMPOUNDS) NITROUS OXIDE AND DESFLURANE ENFLURANE HALOTHANE METHOXYFLURANE DIETHYL ETHER Inhalation Anesthetics

2. Diethyl Ether 1 st inhaled anesthetic No longer used as an anesthetic agent 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  Others include Desflurane, Halothane, Methoxyflurane, and Enflurane, but these are not commonly used 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 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 of the anesthetic gas  Concentration gradient is greatest during initial induction

6. Uptake and Distribution of Halogenated Organic Compounds Distribution to tissues is dependent on blood supply  Tissues with greater blood flow (brain, heart, kidney) are more quickly saturated with anesthetic gas  Lipid solubility of the gas determines entry into tissues through cell walls 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 in the alveoli Anesthetic will move from the brain into the blood and then into the alveoli where it is finally breathed out Patient wakes up

8. Inhalant Anesthetics EFFECTS: ADVERSE EFFECTS:

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

10. 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

11. Vapor Pressure Volatile 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

12. Blood:Gas Partition Coefficient 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

13. Blood:Gas Partition Coefficient 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

14. Blood:Gas Partition Coefficient 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?

15. 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

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

17. 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

18. 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

19. Sevoflurane High vapor pressure: need a precision vaporizer Low 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 than Isoflurane Easier to mask a patient, more pleasant smelling

20. 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-op 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

21. 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, but the following may be seen: Hyperventilation and hypertension Lowers seizure threshold CNS damage

22. 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

23. UNCOMMONLY USED INHALANT ANESTHETICS

24. 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

25. 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

26. Other Halogenated Inhalation Agents Halothane (Fluothane)  Not available anymore  replaced by isoflurane and sevoflurane B:G -2.54 20-46% metabolized in the liver MAC- 0.87-1.19 Sensitizes heart to catecholamine and induces arrhythmias Cardiac, respiratory depression Increased cerebral blood flow Increased temperature- malignant hyperthermia- Dantrolene is used for treatment

27. 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 toxic metabolites produced by the liver= renal damage Enflurane  Used primarily in human medicine

28. 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