Inhalation anaesthetic agents

Inhalational Agents

• Volatile anaesthetic agents are administered via inhalation (vapour or gases). Examples include isoflurane, sevoflurane, and desflurane.
• Gases, such as nitrous oxide, are also administered via inhalation.
• Inhalational agents are used for induction and maintenance of anaesthesia.

Learning Objectives

• The presentation covers the differences between gaseous and volatile anaesthetic agents in terms of administration.
• The presentation describes the various uses of inhalational agents in veterinary anaesthesia, including their pharmacokinetics.
• Key terms like saturated vapour pressure, minimum alveolar concentration, blood gas partition co-efficient and second gas effect are defined.
• The factors affecting the rate of uptake and elimination of inhalational agents are discussed.
• Agent-specific considerations for contemporary veterinary anaesthetic agents are examined.
• Health and safety precautions, including scavenging, are explained for use of inhalational agents.

Inhalational Anaesthetic Agents' Properties

• Saturated Vapour Pressure (SVP): SVP is the pressure exerted by the vapour on its surroundings (liquid) in a closed container at equilibrium at a particular temperature. Higher SVP means more of the agent is delivered to the patient. Isoflurane has a higher SVP than sevoflurane.

• Solubility (Partition Coefficient): The capacity of a solvent to dissolve the anaesthetic gas. The partition coefficient is measured as [inhalant]solvent : [inhalant]gas at equilibrium.

• Blood/Gas Partition Coefficient: Indicates how much of the anaesthetic needs to be dissolved in the blood before equilibrium is reached. A high coefficient means more of the drug needs to dissolve in the blood before equilibration occurs. Isoflurane has an intermediate coefficient. Low blood solubility leads to rapid induction, change of anaesthetic depth and elimination. Nitrous Oxide, sevoflurane and desflurane have a low coefficient.

• Oil/Gas Partition Coefficient: A measure of anaesthetic potency.

• Mechanism of Action: Inhalational agents interact with various components of the nervous system, leading to hypnosis, amnesia, and muscle relaxation.

Minimum Alveolar Concentration (MAC)

• MAC is the minimum alveolar concentration (expressed as a percentage) of an anaesthetic agent at which 50% of patients fail to respond to a standard noxious stimulus (e.g., skin incision).
• Isoflurane is more potent than sevoflurane.
• 1.3 to 1.5 x MAC are usually used with MAC sparing effect techniques.
• MAC sparing effect techniques are used to reduce the amount of anaesthetic required while still achieving the desired level of anesthesia.
• Balanced anesthesia involves using a combination of anaesthetic agents, some of which are MAC sparing agents to decrease the overall amount of anaesthetic required to achieve balanced anesthesia. Specie and individual differences must be considered when choosing an anesthetic agent.

MAC in Different Species

• A table lists MAC values for various animal species (dog, cat, horse, cow, sheep, goat, pig, chicken, rabbit, rat, and man) for isoflurane, sevoflurane, desflurane, and nitrous oxide.

Effect of Different Factors on MAC

• Factors like species size, CNS stimulants, hyperthermia, CNS depressants, pregnancy, age, hypoxaemia, hypercapnia, hypothermia, hypotension, and haemorrhage can affect MAC.

Vaporiser

• The vaporiser converts liquid anesthetic into its vapour form.
• It controls the amount of vapour delivered to the fresh gas flow.
• Annual service is essential for optimal vaporiser function.

End Tidal Concentration of Inhalants

• End tidal concentration measurements are taken and monitored during procedures.

Pharmacokinetics (Uptake)

• Inhalational agents move down a pressure gradient from high to low pressure until reaching equilibrium.
• Depth of anaesthesia depends on the partial pressure of the anaesthetic drugs in the brain (Pbrain).
• Alveolar partial pressure of anaesthetic agents is important for controlling Pbrain.

Pharmacokinetics (Elimination & Recovery)

• Elimination depends on the rate of decrease in Pbrain and return to consciousness.
• Metabolism (primarily by the liver via cytochrome P450 enzymes) is a minor factor for modern inhalational agents.
• Prolonged general anesthesia can result from inhalant accumulation in fat, leading to slow recovery.
• Anesthetic agent can be absorbed or degraded by CO2 absorbers.

Uptake & Elimination Factors

• Factors affecting inhalant uptake include the vaporizer setting, fresh gas flow, volume of the breathing system, alveolar ventilation, dead space ventilation, and the presence of a second gas effect, blood/tissue solubility, and cardiac output. Uptake and elimination are contrasted, with factors that increase or decrease uptake and elimination illustrated in a chart.

Pharmacodynamics: Cardiovascular System

• Inhalational agents decrease myocardial contractility and cause peripheral vasodilation.
• There is attenuation of the baroreceptor reflex.
• The effect on heart rate varies based on species and agent.
• Impaired cardiac conduction and dose-dependent effects are also observed.

Pharmacodynamics: Cerebral System

• Inhalational agents cause reversible, dose-related CNS unresponsiveness.
• Cerebral metabolic rate decreases.
• Cerebral blood flow increases due to vasodilation.
• Intracranial pressure (ICP) may increase.

Pharmacodynamics: Respiratory System

• Inhalational agents decrease alveolar ventilation.
• The response to hypercapnia and hypoxemia decreases.
• Respiratory muscle relaxation may occur.
• Dose-dependent effects on respiratory rate are seen (except with isoflurane).
• Airway irritation is observed, particularly with isoflurane and desflurane.
• There is bronchodilation (increased dead space).
• Hypoxic pulmonary vasoconstriction is impaired.

Pharmacodynamics: Hepatobiliary system

• Decreased hepatic function and hepatocellular injury.
• Inhibitor actions.
• Compounds formed with interaction from CO2 absorbents are at a minimal level.

Pharmacodynamics: Renal System

• A decrease in glomerular filtration rate (GFR), renal blood flow, and potential renal toxicity are observed.
• Mild or reversible dose-related changes are observed.
• Nephrotoxicity is observed, especially with sevoflurane due to metabolites affecting the kidneys.
• Compounds A, generated from CO2 absorber degradation, may contribute to kidney issues.

Pharmacodynamics: Miscellaneous

• Inhalational agents cause myorelaxation.
• They can trigger malignant hyperthermia in susceptible animals.
• They affect uterine contractility and blood flow.
• There is a degree of depression in the immune system.

Environmental Effects

• Inhalational anesthetics include nitrous oxide, halothane, etc., which contribute to ozone depletion. These and nitrous oxide are potent greenhouse gases.
• Desflurane has the most substantial or potent greenhouse gas effect of the inhalational agents.

Second Gas Effect

• The presence of one gas (e.g., nitrous oxide) can accelerate the rise in alveolar concentration of another gas (e.g., volatile anaesthetic). This is due to the first gas's high solubility in plasma, rapidly moving it between the lungs and plasma.
• This can speed up induction of anaesthetic.

Diffusion Hypoxia/Third Gas Effect/ Fink Effect.

• During recovery from nitrous oxide, it diffuses back out of the blood to the alveoli, leading to dilution of the remaining inspired oxygen.
• This effect can result in hypoxia and an increase in respiratory drive.
• Administering 100% oxygen during recovery helps mitigate this effect.

Health & Safety

• Issues like vaporizer filling, leaks in the airway, machine and patient exhalation, short-term exposure effects and chronic exposure risks related to inhalational agents should be considered.
• Mitigation strategies like daily leak testing, use of minimum safe fresh gas flow, squeezing the breathing bag during disconnection, avoiding facemask/chamber induction methods, adequate ventilation during spills and recovery, and monitoring for trace concentrations are recommended.