Inhalant Anesthesia Kinetics DCR 2024 PDF

Inhalant Anesthesia Dave Rankin DVM, MS Diplomate, ACVAA KSU-CVM OBJECTIVES What are and why do we use inhalants Chemical and physical properties of inhalants Pharmacokinetics Circuit concentration Alveolar concentration Factors that affe...

Inhalant Anesthesia Dave Rankin DVM, MS Diplomate, ACVAA KSU-CVM OBJECTIVES What are and why do we use inhalants Chemical and physical properties of inhalants Pharmacokinetics Circuit concentration Alveolar concentration Factors that affect these Inhalants Nitrous Oxide 1790’s “laughing gas” Sir Humphrey Davies Horace Wells 1844 Dentist Inhalants Diethyl ether 1846 William Morton Chloroform 1840’s – 50’s James Simpson Inhalants Liquid (usually) at room temp Alveolus is the “needle” injecting and pressure the drug into the bloodstream Makes a vapor (mixed with air or other medical gas) Easily titratable Inhaled Eventually excreted through Produces a desirable central exhaled gas, or hepatic effect (amnesia, metabolism unconsciousness) Inhalants Modern inhalants require specialized equipment Concern about greenhouse gas effects Can be “toxic” Why Inhalants? Rapid development of unconsciousness Titratable Minimal metabolism Minimal renal clearance Minimal residual effects Chemistry Organic compounds Hydrocarbons Ethers Halogenated Fluorine adds stability Chlorine and bromine add potency Vapor Pressure Vapor Pressure Vapor Pressure TEMPERATURE DEPENDENT!! Pressure vs concentration of inhalant Partial pressure (mmHg) Absolute value Individual pressure of each gas in a mixture Concentration (volumes %) Relative ratio of gas in a mixture Easy to measure, intuitive Vaporizer setting Vapor pressure (Biology loves gradients) Partial Pressure is what produces the effect at a given organ “partial” because there are other gases in play Isoflurane at 2% is part of a gas mix delivered to a patient. It’s partial pressure at sea level is 15.2 mmHg Maximum saturated pressure is 240 mmHg/760 mmHg (at 20C) 32% How to deliver a “safe” concentration??? Pharmacokinetics Vaporizer Temperature compensated (within reason) In circuit vs out of circuit Variable bypass vs measured flow Bubble through vs flow-over Agent Specific: due to vapor pressure Temp compensated Variable bypass Flow over Agent specific Vaporizer Partial pressure is temp dependent Volumes percent is not. Easy to measure and intuitively makes sense. 2% of the gas flow is now isoflurane (or whatever…you get it) Dial adjusts flow through to produce what’s on the dial The circuit Circle Non-rebreathing Pharmacokinetics Gas mixture leaves vaporizer Circuit is attached to a patient Enters circuit Alveolar concentration builds up TIME Eventually reaches a steady state Concentration of anesthetic with blood (and therefore builds in circuit different tissues) The fundamental “unit” Pharmacokinetics THE ALVEOLUS IS THE NEEDLE It ”injects” anesthetic into the bloodstream, which is carried to various tissues ALVEOLAR PARTIAL PRESSURE is responsible for CNS PARTIAL PRESSURE ”as the alveolus goes, so goes the brain” Understanding the inhalant and the circuit is critical Pharmacokinetics Understanding the inhalant… BLOOD:GAS Solubility Pharmacokinetics BLOOD:GAS solubility When the partial pressure of inhalant in blood exerts the same partial pressure as inhalant in the alveolus. It’s a ratio that is specific to each inhalant Helps determine “speed”…whether it’s comparing two drugs, or how quickly a change is made in alveolar PP after changing vaporizer setting, or how quickly an animal is “induced” Pharmacokinetics – Blood/gas solubility All things being equal…sevoflurane is faster than isoflurane in producing a stable alveolar concentration High solubility means longer time to saturate blood and tissues Methoxyflurane 12.0 longer recovery? Nitrogen 0.015 Pharmacokinetics – blood/gas solubility Pharmacokinetics…speed “All things being equal” 1. Vaporizer setting “Overpressure” What are the other things?? 2. Flowmeter setting Time constants 3. Cardiac output and where the blood goes Pharmacokinetics…speed Enflurane MAC 1.7 B:G 1.73 VP. 175 mmHg Vaporizer setting Doesn’t reflect circuit concentration in a circle or alveolar concentration early in an anesthetic Higher vaporizer setting increases circuit concentration and ultimately alveolar concentration Pharmacokinetics…speed Flowmeter setting Larger circle requires more time Various flow settings for different circuits In a circle, higher flow will increase circuit concentration and ultimately alveolar concentration Get ready…time constants The time it takes for flow to equal the volume of a container is 1 time constant If a circuit is 8 liters, and the flowmeter is set at 2 L/min the time constant is 4 minutes  An 86% change takes place in one time constant It takes 3 time constants to get to a 96% change, assuming uptake isn’t happening 8 L circuit @ 2 L/min = 12 min to get close to vaporizer setting  Pharmacokinetics…speed Ventilation If you’re not breathing, you’re not taking up anesthetic…increasing ventilation can increase alveolar concentration Pharmacokinetics …compartments Effect of cardiac output Recovery The reverse of all this Palv and Part need to decrease, allowing Pbrain to decrease Cardiac output, ventilation, vaporizer and B:G solubility all play a role Largely excreted by lung, unchanged The goal is to develop a stable plane of anesthesia! Stability requires stable alveolar concentration of anesthetic DOSE???