Inhalational
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This document provides an overview of inhalational anesthetics, including: 1. It describes Guedel's stages of anesthesia and theories of anesthetic action such as the Meyer-Overton rule relating lipid solubility to potency. 2. It discusses concepts such as minimum alveolar concentration (MAC) and pharmacokinetics including uptake, distribution, elimination and metabolism of volatile gases. 3. It reviews the pharmacodynamics of inhalational anesthetics on various organ systems and lists properties of common agents like halothane, enflurane, isoflurane, sevoflurane, desflurane and xenon.
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Inhalational
- 2. GUEDEL’S STAGES OF ANESTHESIA S 1- AMNESIA S 2- EXCITEMENT S 3- SURGICAL ANESTHESIA S IMPENDINGD DEATH
- 3. THEORIES OF ANESTHETIC ACTION S Lipid Solubility (Meyer-Overton Rule) S Alterations to lipid bilayer S Alteration to protein inhibition
- 5. MINIMUM ALVEOLAR CONCENTRATION S Produces immobility in 50% of subjects exposed to standard noxious stimuli (surgical incision) S Analogous to ED50 S MAC awake S MAC intubation S MAC bar
- 7. PHARMACOKINETICS UPTAKE AND DISTRIBUTION S SOLUBILITY BLOOD (blood :gas partition coefficient) FAT (oil: gas partition coefficient) S ALVEOLAR BLOOD FLOW ELIMINATION AND RECOVERY S BIOTRANSFORMATION S REDISTRIBUTION S EXHALATION
- 8. PHARMACODYNAMICS CNS S INC CBF S DEC cerebral metabolic rate CVS S DEC SVR, CO S Inc HR
- 9. RENAL S nephrotoxic RESPIRATORY S Bronchodilators S DEC tidal volume S INC RR
- 10. LIVER S Hepatotoxic MUSCULAR S Centrally muscle relaxant S Uterus: relaxes
- 12. VOLATILE GASES S HALOTHANE S ENFLURANE S ISOFLURANE S DESFLURANE S SEVOFLURANE ANESTHETIC GASES S NITROUS OXIDE S XENON
- 13. NITROUS OXIDE S Odorless, tasteless, colorless, non flammable S MAC 105% S Diffusion hypoxia, teratogenic, toxicity, effects on closed spaces
- 14. HALOTHANE S Most potent inhalational anesthetic S MAC 0.75% S Low blood:gas solubility coefficient S Hepatotoxic, arrhythmias
- 15. ENFLURANE S Potent cardiovascular depressant S MAC 1.68%
- 16. ISOFLURANE S Isomer of enflurane S Least soluble S MAC 1.7% S Pungent odor S Coronary steal syndrome
- 17. SEVOFLURANE S Pleasant smell S MAC 2% S Compound A
- 18. DESFLURANE S Special vaporizer S MAC 6% S Irritant
- 20. XENON ADVANTAGES S Inert (probably nontoxic with no metabolism) S Minimal cardiovascular effects S Low blood solubility S Rapid induction and recovery S Does not trigger malignant hyperthermia S Environmentally friendly S Nonexplosive DISADVANTAGES S High cost S Low potency (MAC = 70%)
Editor's Notes
- GENERAL ANESTHESIA- reversible state of unconsciousness with loss of sensation of pain Intravenous- induce anesthesia Inhalational- maintain anesthesia - MOA: despite widespread use current understanding of molecular basis for the action is poorly understood. - Molecular mechanism of GA: 1. Ligand gated - GABA –a, glycine receptor (enhanced by volatile)--- inhibitory postsynaptic channels NMDA (blocked by volatile)--- excitatory channels 2. Voltage gated- blocked Sites of action Anesthesia induced amnesia- hippocampus Anesthesia induced sedation- hypothalamus
- Stages of anesthesia 1 analgesia- beg of administration until LOC, 2 excitement, combative behavior, spasm, heart rate BP rises, 3 surgical anesthesia- regular deep breathing, loss of corneal reflex phase1- light surgical anesthesia: roving of eyeballs then becomes fixed phase 2- moderate surgical anesthesia: loss of corneal and laryngeal reflex phase 3- deep: fixed pupils, light reflex lost phase 4- very deep—apnea: intercostal paralysis 4 medullary paralysis-shallow irregular breathing, non reactive dilated pupils, thready pulse Guedel’s criteria based on: Respiration Eyeball movement Presence or absence of various reflex Gillespie added: Secretion of tears Response to skin incision Evaluation of pharyngeal and laryngeal reflexes Hallmarks of anesthesia: amnesia/uncosciousness Anlagesia Muscle relaxation
- 1.Lipid Solubility - Overton & Meyer 2. Alterations to Lipid Bilayers - lipidperturbation-dimensionalchange lipid phase transition - "lateral phase separation" lipid-proteininteractions 3. Alteration to Protein Function - luciferase inhibition Best correlation with anesthetic potency was nited to be the oil:gas partition coefficient by meyer-overton
- Potency and speed of induction of inhaled agents correlate with their lipid solubility Greater lipid solubility, greater potency
- -Best estimate for potency of inhalational anesthetics The alveolar concentration, at equilibrium, at 1 atm pressure Animals: clamping of tail or passing electric current through subcutaneous electrodes Mac values are remarkably consistent across species and are roughly additive 1.3 MAC would prevent 95% subjects from moving and is equivalent to ED95 MAC awake: a value that would allow response to verbal/tactile stimulation (0.3-0.4) MAC intubation: necessary to prevent laryngeal response to endotracheal intubation (1.3) MAC bar: necessary to blunt the autonomic response to a noxious stimulus (1.5)
- DECREASE IN MAC: hypercarbia PaCo2 >95mmhg, ketamine,barbiturates, bzd, verapamil,amphetamine, hgb <5 INCREASE: cocaine,ephedrine, MAO inhibitors, levodopa NO CHANGES: gender, hypo/hyperthyroidism,hypercalcemia, metabolic alkalosis, duration of inhaled anesthetics
- Vapor pressure- pressure exerted by the molecules -measures the agents ablity to evaporate (volatlity) - greater vp, greater concentration delivered greater temp, greater vp Blood- determines the rate of induction and recovery from inhalational anesthetics (inversely proportional) Fat/ lipid- potency of the agent (directly proportional) BLOOD FLOW Vessel rich group-brain, heart, kidney, liver Muscle group- Fat group- large capcity, minimal flow Vessel poor group-bone, cartilage Redistribution- as long as an arterial to tissue partial pressure exists, muscle and fat will absorb anesthetic, even after discontinuation of anesthesia, it continues until blood/alveolar anesthetic partial pressure falls below tissue partial pressure Recovery- low solubility= fastser recovery, des>sevo>iso greater solubility= greater absorption Increased ventilation help recovery
- Inc CBF (time dependent and dose dependent)=inc ICP (especially halothane) and impair autoregulation of vascular tone=vasodilate Dec ceb met- may increase nitrous oxide Desflurane and isoflurane <1 MAC= suppress status epilepticus Inc sevo= epileptiform waves in EEG Dec SVR, CO Isoflurane best maintains CO==ok in cardiac patients Halothane= dec MAP = dec CO, unchaged SVR
- Nephrotoxic-due to fluoride Most: methoxyflurane Bronchodilates=most is sevo safe for asthmatics Not halothane because of increased arryhthmias with beta agonist All vasodilators except nitrous oxide (constrictor) Dec mucociliary function--- smokers have impaired mucociliary function== inadequate clearing of secretions Sequence of respiratory depression: en>des>iso>sevo
- Hepatotoxic – halothane, chloroform, methoxyflurane Ether based (iso, sevo,des)maintain or inc hepatic artery BF while dec portal vein BF Halothane dec portal vein and hepatic artery blood flow=Inadequate hepatocyte oxygenation Centrilobular area- prone to hypoxia Muscle relaxant except n2o, potentiate action of nmb All are potential to cause MH
- PROVIDE ALL 3 CHARACTERISTICS OF GA: unconsciousness, analgesia, muscle relaxation Ideal inhalational anesthetic gas: Rapid, pleasant induction and emergence Rapid and easily identified changes in depth of anesthesia Adequate relaxation of skeletal muscle Wide margin of safety Absence of toxic adverse effectsat normal dose High degree in specificity in action Easy to administer Useful for all ages
- Physical property, laughing gas, gas at RT, liquid under pressure Pharmacology: low potency, relatively insoluble in blood, does not produce muscle relaxation, but have analgesic effects Side effects inc cerbral oxygen consumption diffusion hypoxia: dec in p02 usually observed in emergence which displaces the oxygen in alveoli megaloblastic anemia: bone marrow depression oxidizes Co in vit B12=inactivates methionine synthetase affects myelin formation=neurotoxic inhibits thymidylate synthetase= teratogenic second gas effect: the inc in partial pressure of of other gases in alveolar mixture resulting from the rapid uotake of high conc of nitrous oxide during induction the ability the large volume uptake of one gas (first gas) to acclerate the rate of rise of alveolar pressure of a concurrent gas (second gas) Closed spaces: 35 times m0re soluble in blood than nitrogen – fills and expands aany air containing spaces= air embolism, pneumothorax, tension pneumocephalus Weakest anesthetic but good analgesic Cylinder: blue
- Synthesized in 1951, halogenated alkene Colorless, pleasant odor, non irritant, non flammable, light sensitive Corrosive- rubber and plastic tubing Rapid induction faster recovery Amber colored bottle with Thymol preservative to prevent spontanoeus oxidative decomposition CV: dec BP, CO, slow conduction=bradycardia Sensitizes the heart to catecholamines Resp: inc RR, dec TV, potent bronchodilator Elimination: liver oxidation= trifluoroacetic acid (TFA) Other meatbolites: bromin, chlorine, Halothane isnot hepatotoxic in children, Potent bronchodilator (asthmatics), used in ob for uterine relaxation only
- Cauttion in renal failure due to fluorine Contraindicated in epileptics: decrease threshold for seizures Sweet, ethereal odor
- Steal:isoflurane induced vasodilation leads to redistribution of Coronoary BF from diseased (maximally dilated ) to normal repsonsive arteries inc in cbf, froom inadeq perf to adeq perf Airway irrittant: spasm, increase in secretions Agent of choice for neuroanesthesia: high conc:inc BF by vasodilattion f cerebral arteries= cns depression, Agent of choice for cardaic anesthesia: maintains baroreceptor reflex == refelex tachy in response to dec BP Substitution with fluoride results in greater stability Ether linkage: dec incidence of cardiac arrhythmias
- 1995, Rapid induction and recovery Agent of choice for pediatric anesthesia 2nd choice for neuro, cardiac, asthmatics Does not sensitize myocardium to catecholamines Metabolites: Inorganic fluoride, hexafluoroisopropanol Compound A- nephrotoxic:
- 1993 Differs from isoflurane: by substitution of fluorine atom to chlorine atom Which increases vapor pressure, enhances molecular stability, decreases potency Produces the highest carbon monoxide next is enflurane and isoflurane Fastest induction, Rapid emergence
- Fastest induction and fastest recovery Mac 70% Most ideal inhalational anesthetic Blood gas coefficient 0.14 Least side effects Expensive