CHAPTER 3ISOFLURANE AND SEVOFLURANE

(HALOGENATED COMPOUNDS)NITROUS OXIDE AND DESFLURANE

ENFLURANEHALOTHANE

METHOXYFLURANEDIETHYL ETHER

Inhalation Anesthetics

Diethyl Ether

1st inhaled anestheticNo longer used as an anesthetic agent, as

well as Chloroform and NO Classic stages and planes of anesthesia

described using etherDesirable characteristics

Stable cardiac output, rhythm, and blood pressure Stable respirations Good muscle relaxation

Diethyl Ether (Cont’d)

Undesirable characteristics Tracheal and bronchial mucosal irritation Prolonged induction and recovery Postoperative nausea and vomiting Flammable and explosive

Halogenated Organic Compounds

Isoflurane and sevoflurane are the most commonly used agents in this class

Also Desflurane, Halothane, Methoxyflurane, and Enflurane

Liquid at room temperatureStored in a vaporizer on an anesthetic

machineVaporized in oxygen that flows through the

vaporizer Exception being Desflurane- has a special injection

type vaporizer

Uptake and Distribution ofHalogenated 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

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

wallsDepth 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 alveoliMaintenance of anesthesia is dependent on

sufficient quantities of anesthetic delivered to the lungs

Elimination of Halogenated Organic Compounds

Reducing amount of anesthetic administered reduces amount delivered to the alveoli

Blood level is initially higher than alveolar levelConcentration gradient now favors anesthetic

diffusion from blood into the alveoliBlood levels drop quickly as patient breathes

out anesthetic from the alveoliBrain levels drop as less anesthetic is delivered

by bloodPatient wakes up

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

Adverse Effects ofHalogenated 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 flowRespiratory system

Hypoventilation Carbon dioxide retention and respiratory acidosis

Physical and Chemical Propertiesof Inhalant Anesthetics

Important properties to consider Vapor pressure Partition coefficient Minimum alveolar concentration (MAC) Rubber solubility

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

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 agentNonvolatile 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

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

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

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?

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 anesthesiaThe 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

Isoflurane

Most commonly used inhalant agent in North America

Approved for use in dogs and horses; commonly used in other species

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

Effects and Adverse Effects

Maintains cardiac output, heart rate, and rhythm Fewest adverse cardiovascular effects

Depresses the respiratory systemMaintains cerebral blood flow Almost completely eliminated through the lungs-

0.2% metabolized by the liverInduces adequate to good muscle relaxationProvides little or no analgesia after anesthesiaDifficult to mask patient Can produce carbon monoxide when exposed to a

desiccated carbon dioxide absorbent

Sevoflurane

High vapor pressure: need a precision vaporizer

Blood:gas partition coefficient: rapid induction and recovery

Good for induction with a mask or chamberHigh controllability of depth of anesthesiaMAC = 2.34% to 2.58% Cost about 10x more the IsofluraneEasier to mask a patient, more pleasantsmelling

Effects and Adverse Effects of Sevoflurane

Minimal cardiovascular depression Depresses respiratory systemEliminated by the lungs, minimal hepatic metabolism-

2-5%Maintains cerebral blood flowInduces adequate muscle relaxationSome paddling and excitement during recoveryNo post of analgesiaCan react with potassium hydroxide (KOH)or sodium hydroxide (NaOH) in desiccated CO2 absorbent to produce a chemical(Compound A) that causes renal damage

Desflurane

Closely related to isofluraneExpensiveLowest blood:gas partition coefficient: very

rapid induction and recoveryUsed with a special heated electronic

precision vaporizerMAC = 7.2% and 9.8%

Least potent inhalant agentEliminated by the lungs- 0.02% metabolized

in liver

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

Other Halogenated Inhalation Agents

Halothane (Fluothane) Not commonly used anymore Being replaced by isoflurane and sevoflurane

B:G -2.5420-46% metabolized in the liverMAC- 0.87-1.19

Sensitizes heart to catecholamine and induces arrhythmias

Cardiac, respiratory depressionIncreased cerebral blood flowIncreased temperature- malignant hyperthermia-

Dantrolene

Methoxyflurane

Methoxyflurane No longer available in North America

B:G- 151!Used in a non precision vaporizer- wick50-75% 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

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 Methoxyfluraneto reduce the adverse effects of these gases

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 effectsWide margin of safetyHyperventilation and hypertensionLowers seizure thresholdCNS damage

Use of Doxapram

Repeat injections may be necessaryReverses respiratory depression from

inhalant agents and barbiturates1-5 ggt under the tongue of a puppy, or 1-2

ggt in a kitten if needed after C-section or dystocia