Inhalational Agents 2024 - Veterinary Anaesthesia

I N H A L AT I O N A L A G E N T S 27th September 2024 Hanna Machin Dip ACVAA, Dip SIAV, MVetMed, MRCVS Lecturer in Veterinary Anaesthesia LEARNING OBJECTIVES Describe the differences between the gaseous and volatile agents in terms of the practicalities of...

I N H A L AT I O N A L A G E N T S 27th September 2024 Hanna Machin Dip ACVAA, Dip SIAV, MVetMed, MRCVS Lecturer in Veterinary Anaesthesia LEARNING OBJECTIVES Describe the differences between the gaseous and volatile agents in terms of the practicalities of their administration Describe the various ways in which inhalational anaesthetic agents are used in veterinary anaesthesia and explain the relevant pharmacokinetics Define and explain the clinical importance of the terms: saturated vapour pressure, minimum alveolar concentration, blood gas partition co-efficient and second gas effect Describe the factors affecting the speed of uptake and elimination of inhaled anaesthetic agents Describe clinically relevant physical properties and agent specific considerations for the inhaled anaesthetic agents used in contemporary veterinary anaesthesia Explain the health and safety precautions for the use of inhaled anaesthetic agents, including the use of scavenging I N H A L AT I O N A L A N A E S T H E T I C A G E N T S Volatile anaesthetic drugs administered by inhalation Vapour or gases VAPOUR: gaseous phase of a substance which is normally liquid @ room temperature & atmospheric pressure (Isoflurane, Sevoflurane, Desflurane) GAS: substance which is in a gaseous state at room temperature & atmospheric pressure (Nitrous oxide) Indications: Induction & Maintenance of anaesthesia I N H A L AT I O N A L A G E N T S ' P R O P E R T I E S SATURATED VAPOUR PRESSURE (SVP) Pressure exerted by the vapour on its surroundings (liquid) in a closed container at equilibrium at certain temperature Max concentration of molecules in the vapour state that exist for a given liquid for a given temperature, at equilibrium Measure the ability to evaporate ↑ SVP → ↑ [inhalant] delivered to pa ent Isoflurane > Sevoflurane SOLUBILITY Image from: Vapor Pressure (gsu.edu) Measured as PARTITION COEFFICIENT Capacity of a solvent to dissolve the anaesthetic gas [inhalant]solvent : [inhalant]gas at equilibrium I N H A L AT I O N A L A G E N T S ' P R O P E R T I E S BLOOD/GAS PARTITION COEFFICIENT High: a lot of anaesthetic must be dissolved in the blood before equilibrium Intermediate: Isoflurane Low: N20, sevoflurane, desflurane Helps predict speed of induction, recovery, change in anaesthetic depth Low blood solubility → > rapid equilibra on: > rapid induc on, change of anaesthetic depth & elimination OIL/GAS PARTITION COEFFICIENT Anaesthetic potency I N H A L AT I O N A L A G E N T S ’ P R O P E R T I E S Induce a reversible, dose-related state of unresponsiveness of CNS, haemodynamic & endocrine responses to noxious stimuli POOR (apart from Nitrous Oxide) I N H A L AT I O N A L A G E N T S : M E C H A N I S M O F A C T I O N M I M I N U M A LV E O L A R C O N C E N T R AT I O N ( M A C ) Minimum alveolar concentration of anaesthetic agent at which 50 % of patients fails to respond (by purposeful movement) to a standard supramaximal noxious stimulus (i.e., skin incision) Express as a % Potency 1/MAC Isoflurane > potent than Sevoflurane ~ 1.3 X MAC prevent movement in 95% of animals ~ 1.5 X MAC surgical anaesthesia BUT side effects… ~ 1 X MAC ( or less) usually used + MAC sparing effect techniques used MAC determined as a sole agent administered Balanced anaesthesia: ↓ MAC requirements (MAC sparing effect) Species & individual differences → monitoring MAC IN DIFFERENT SPECIES EFFECT OF DIFFERENT FACTORS ON MAC? ↑MAC ↓MAC NO EFFECT Species (body size) Pregnancy Gender Age: neonates, geriatric CNS stimulants drugs: CNS depressant drugs: PH Catecholamines Sedative, injectables, analgesic Sympathomimetics agents Hypertheroidism Hypernatremia Severe Hypoxaemia & Anaemia Hypercapnia Hypo/Hyperkalaemia Hyperthermia Hypothermia Duration of Anaesthesia Severe Hypotension Haemorrhage ≠ depending on the sources  VAPORISER Zzzzzzz 02 +/- medical air Vaporiser converts liquid anaesthetic agent into its vapour form Add a controlled amount of this vapour to fresh gas flow Controls the concentration of anaesthetic delivered to the patient Annual service is a must! (faulty vaporizer can cause ) E N D T I D A L C O N C E N T R AT I O N O F I N H A L A N T S  P H A R M A C O K I N E T I C S ( U P TA K E ) Inhalational agents move down a pressure gradient (from high to low) until equilibrium Depth of anaesthesia depends on Partial Pressure of anaesthetic drugs in the brain (Pbrain) Alveolar partial pressure of anaesthetic agents 15-20 % of important to control Cardiac Output Pbrain 75% of Cardiac Output (CO) P H A R M A C O K I N E T I C S ( E L I M I N AT I O N & R E C O V E R Y ) Depends on rate of decrease of Pbrain : return of consciousness Exhalation Metabolism (liver primarily, Cyt P450 enzymes): Minimal for modern inhalational agents (Isoflurane 0.2%, Sevoflurane 2-5%, Nitrous oxide 0.004%) Prolonged general anaesthesia → inhalant accumula on in fat → slow recovery Inhalant may be lost from breathing circuit (leaks) & patient (open cavities) Adsorption or degradation by CO2 absorber  FA C TO R S T H AT A F F E C T S U P TA K E & E L I M I N AT I O N O F I N H A L AT I O N A L A G E N T S UPTAKE ELIMINATION ↑ [inhala onal agent], vaporiza on/ dial se ng ↑ ↓ ↑ FGF (circle < non-rebreathing) ↑ ↑ ↑ Volume of breathing system (circle > non-rebreathing system) ↓ ↓ ↑ Alveolar ven la on = RR x alveolar volume (TV -dead space volume) ↑ ↑ ↓ Dead space ven la on ↑ ↑ 2nd Gas Effect ↑ ↑ ↑Blood/ ssue solubility ↓ ↓ ↑Cardiac Output → pulmonary & ssue perfusion ↓ ↑ ↑Alveolar- venous blood-tissue partial pressure gradient ↑ ↑  U P TA K E & E L I M I N AT I O N Blood Uptake Equilibrium Elimination  PHARMACODYNAMIC: CARDIOVASCULAR SYSTEM Decrease myocardial contractility Peripheral vasodilation HYPOTENSION Attenuation of baroreceptor reflex ↓CARDIAC OUTPUT Variable effect on HR (species & agent dependent) Impaired cardiac conduction Dose dependant effects PHARMACODYNAMIC: CEREBRAL Reversible, dose related CNS unresponsiveness to noxious stimulation: general anaesthesia Decrease cerebral metabolic rate Increase in cerebral blood flow (CBF): vasodilation Increase ICP P H A R M A C O D Y N A M I C : R E S P I R ATO R Y Decrease alveolar ventilation Decrease response to hypercapnia & hypoxaemia Respiratory muscle relaxation Dose dependent ↑ in RR (not with Isoflurane) but ↓ TV Airway irritation (especially Isoflurane, desflurane) Bronchodilation (increase in dead space) Depression of Hypoxic Pulmonary Vasoconstriction Image from: Lungs Sketch Illustration Hand Drawn Stock Motion Graphics SBV- 308613041 - Storyblocks P H A R M A C O D Y N A M I C : H E PATO B I L I A R Y S Y S T E M Decrease hepatic function Hepatocellular injury Cit P 450 inhibition Sevoflurane: Compound A (hepatotoxic) formed with interaction of CO2 absorbants (minimal level) PHARMACODYNAMIC: RENAL Decrease GFR & renal blood flow (decrease CO, hypotension, splanchnic vasoconstriction) Mild, reversible, dose related Nephrotoxicity : Sevoflurane: - Fluoride metabolites - Compound A (from degradation by CO2 absorbents) PHARMACODYNAMIC: MISCELLANEOUS MUSCLES: Myorelaxation Malignant Hyperthermia (pigs, humans, horses, dogs) All inhalational anaesthetics can trigger Rapid ↑ cellular metabolic activity UTERUS: Decrease contractility & blood flow IMMUNE SYSTEM: Depression Inhibition of INSULIN secretion SECOND GAS EFFECT Ability of one gas (1st gas, soluble in plasma, i.e. nitrous oxide ) to accelerate the rise of alveolar concentration of a 2nd gas (volatile anaesthetic, O2) when administered together “first gas” that is soluble in plasma, moves rapidly from the lungs to plasma. →↑ alveolar concentration and hence rate of uptake into plasma of the “second gas” To speed anaesthetic induction  DIFFUSION HYPOXIA (THIRD GAS EFFECT OR FINK EFFECT) During recovery: Nitrous oxide is discontinued → nitrous oxide (low blood solubility) diffuses rapidly back from blood to alveoli → Dilution of the [inspired 02] & hypoxia → Dilution of [inspired CO2] → decrease in PaCO2 → to ↓in respiratory drive To solve: Administer 100% oxygen on recovery H E A LT H & S A F E T Y Sources of issues: Vaporiser filling Leaks from around the patient’s airway (e.g. mask or ET tube), anaesthetic machine and breathing system, ventilator, scavenging devices & connection tubing Patient exhalation Short term exposure: headache, fatigue, nausea, depression, irritability Chronic exposure: potential mutagenic, carcinogenic, teratogenic effects? H E A LT H & S A F E T Y Mitigation:  Daily leak testing & regular maintenance  Use minimum safe FGF  Squeeze breathing bag into scavenging & flush breathing system with O2/air before disconnecting  Avoid facemask or chamber induction/ maintenance  Spills → PPE, absorbent materials, ven la on  Ventilation of operating & recovery rooms  Scavenging system  Key-indexed vaporizer filling systems  Monitoring for trace concentrations  Education/ training E N V I R O N M E N TA L E F F E C T S Greenhouse gases : Global Warming Potential Index of CO2 & methane >>> desflurane & N2O >> sevoflurane > isoflurane Ozone layer destruction: N2O >> halothane >> isoflurane UVL degrada on → free chlorine Image from: https://www.sciencefacts.net/ozone-layer- depletion.html REFERENCES THANK YOU FOR YOUR AT T E N T I O N. 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