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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
Recommended