Inhalation anesthesia

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Inhalation anesthesia
2013-07-09 14:44:28

inhalation anesthesia
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  1. General Anesthesia is a irreversible depression of the CNS resulting in...
    the loss of perception of, and response to, all external stimuli
  2. 4 quality of complete anesthetics ["balance" technique]
    —Analgesia: reduced perception of and response to noxious stimuli

    —Amnesia: loss of memory of surgical experience

    —Unconsciousness: loss of awareness of environment

    —Muscle relaxation: flaccid paralysis and loss of response to muscle stretching/cutting
  3. "balance" technique
    • multiple drugs to give complete anesthetics 
    • e.g complete awareness but feel no pain and ms relaxation
  4. Potency measure by MAC.  MAC is...
    • —Alveolar concentration of anesthetic at which 50% of patients are unresponsive to a
    • standard surgical stimulus.
  5. MAC is used for
    quantifying the potency of inhaled anesthetics
  6. MAC is usually expressed as
    • as the percentage of gas in a mixture required to achieve the effect
    • e.g
  7. Numerically, small MAC vs large MAC. which is one is more potent
    smaller one
  8. MAC(awake) = 0.3 MAC
    Dose for 50% Amnesia and/or awakening
  9. —MAC95% = 1.3 X MAC
    Dose for lack of incision movement for 95%
  10. —MACBAR = 1.5 X MAC
    Dose for 50% block adrenergic response
  11. —MACintubation = 2 X MAC
    ◦Dose for 50% block movement to intubation
  12. Alveolar concentration represents... after a short period of equilibration
    —brain concentration
  13. N2O is ....
    • not a true anesthetic. can never achieve true general anesthesia
    • only MAC awake
  14. drug more lipid-soluble. Potency?
    more potency
  15. Meyer-Overton Rule
    ---—Anesthesia commences when a chemical substance reaches a certain molar concentration in the lipophilic phase, i.e., cell membrane

    • —---Oil/gas partition coefficient
    • Lipid solubility correlates with
    • anesthetic potency

    —---Anesthetics disorder membrane lipids and/or increase membrane volume
  16. Criticisms of Lipid Theories
    • —Membrane
    • expansion, fluidization equaled by increase in body temperature of 1°C

    • —Doesn’t
    • account for stereoisomeric differences in anesthetics

    • —Doesn’t
    • account for lipophilic molecules that are not anesthetic
  17. Membrane Proteins --- mechanism
    —Consistent with the mode of action of most drugs that influence the CNS

    • —Allosteric regulation of a protein by binding of even a single small molecule can affect
    • protein function

    • —Explains the difference in action among various anesthetics by assuming that these
    • agents exert different effects on the same protein or different ones.

    —Meyer/Overton rule also applies to hydrophobic sites on proteins
  18. Resistance to anesthesia
    —genetic polymorphisms in mitochondria and synaptosomal proteins
  19. Location of action
    Mesencephalic reticular formation and dorsal lamina of the SC
  20. Mesencephalic Reticular Formation
    ---—Major center supporting consciousness and alertness in higher brain centers

    • —---When activity is depressed, the ascending influences on the limbic system are
    • reduced and unconsciousness occurs

    • —---This complex of neurons may also respond differently to different anesthetics
    • Nitrous oxide - alters firing pattern
    • Most others - depress firing

    —---All agents block neuronal responses to sensory input
  21. Dorsal Lamina of the Spinal Cord
    —An area implicated in the primary action of anesthetics

    —Gateway for nociceptive impulses into the CNS
  22. receptors involves in anesthesia
    GABA receptor (agonist), NMDA receptor (antagonist)
  23. Behavioral Manifestations of Anesthesia
    • —Progressive depression
    • ◦Guedel’s scheme of progressive depression
    • Seen with volatile anesthetic
    • agents

    ◦4 stages, with the third stage having 4 planes
  24. Guedel’s Stages of Anesthesia
    —Stage 1: Analgesia

    ◦decreased awareness of pain, amnesia

    —Stage 2: Delirium (short) 

    ◦delirium & excitation, enhanced reflexes, retching, incontinence, irregular respiration

    —Stage 3: Surgical Anesthesia

    ◦unconscious, no pain reflexes, respiratory and CV depression in deeper planes

    —Stage 4: Medullary Paralysis

  25. Physiology of Stage 1 - analgesia
    • normal respiration
    • normal BP 
    • normal reflexes
    • Pupil site: normal 
    • normal muscle tone
  26. Physiology of stage 2: delirium
    • inc respiration
    • inc HR
    • Reflex: swallow, retch, vomit and eyelid 
    • dilated pupil
    • inc ms tone
  27. Physiology of Stage 3: surgical anesthesia
    • progressive decrease of respiration
    • progressive decrease of HR
    • Reflex: laryngeal bronchiol, conjuntival, corneal, pupil light reflex 
    • Pupil get progressively larger
    • decrease ms tone
  28. Physiology of stage 4: Medullary paralysis
    oh well
  29. Uptake and Distribution: goal
    • To develop and maintain a satisfactory partial pressure or tension of
    • anesthetic at the site of anesthetic action in brain
  30. Uptake and distribution: brain and perfusion
    high and equilibrates with anesthetic PP in blood
  31. Uptake and distribution: Dosage
    —Dose of An Oral Drug is “Concentration”

    • —Dose of Inhalation Anesthetic Measured in % Volume
    • (Partial pressure ÷ barometric pressure)
    • x100
  32. Distribution
    —Delivered > Inspired > Alveolar > Arterial > Brain
  33. Partition Coefficient
    —An expression of the relative concentrations of a substance in two immiscible phases at equilibrium. It compares the amount of gas dissolved, for example, in blood with the concentration in air.

    —e.g., 2% (air) x 2.3 (P.C. blood:air) = 4.6% in blood
  34. Henry's law describes
  35. Dalton's law describe
    aveolar drug %
  36. Blood:Gas Partition Coefficient
    —Assume B:G coefficient of 2.5 (not 2.3)

    • —The blood really holds on to the gas and
    • equilibration is very slow

    • --->high BG PC is slower onset and higher solubility
    • ---> only describe how fast achieve equilibrium not potency
  37. Onset of Anesthesia
    —Speed at which this is achieved is influenced by:

    ◦Concentration in inspired air

    ◦Ventilation rate and depth

    ◦Cardiac output and regional blood flow

    ◦Solubility in blood

    ◦Concentration and second gas effects
  38. Anything that increases delivery of anesthetic to the alveoli
    thus increasing partial pressure, will hasten anesthesia
  39. Anything that prevents a rise in partial pressure
    —will delay anesthesia
  40. Anything that enhances overall systemic uptake—and removal of anesthetic from the lungs—
    will lower alveolar partial pressure and delay anesthesia
  41. inc CO in blood to the brain and inc onset of the anesthetics
  42. The greater the ventilation
    —the more anesthetic that is delivered to the lungs, the more rapid the induction
  43. hyperventilation inc delivery of drugs
  44. The greater the inspired anesthetic concentration
    —the more rapid the induction
  45. Fat patient & onset of anesthesia
  46. NO with low BG PC
    only drug allow pt to drive home bc of fast onset and removal
  47. high CO  and onset of anesthesia
    • delayed onset of anesthesia bc Removes
    • large quantities of gas from alveoli, lowers alveolar tension
  48. Fat pt: which drugs to choose, low or high BG PC?
    low BG PC --> quicker onset
  49. Low BG PC means high potency
  50. Second Gas Effect
    • —Potent agents are administered with nitrous oxide so that the potent agent will be
    • delivered in increased amounts to the alveoli as gas rushes to replace the nitrous oxide absorbed by pulmonary blood
    • e.g usually O2 or other gas
  51. Concentration Effect
    • —Occurs when nitrous oxide is administered in high concentration during induction. It
    • is taken up rapidly and more gas rushes in to take its place, effectively increasing alveolar ventilation
  52. Desflurane in 65% N2O vs 5% N2O
    quicker onset bc of 2nd gas effect and concentration effect
  53. Redistribution, Metabolism and Elimination
    —Elimination mirrors uptake except that:

    Muscle and fat groups may continue to absorb anesthetic for a time after the halt of administration after short cases, helping to lower blood concentrations and hasten recovery
  54. Metabolism and Elimination
    • —Most inhalation anesthetics undergo small amounts of biotransformation in the liver
    • note: halothane hepatitis
  55. Characteristics of “An Ideal Inhalation Agent”
    —Stable and nonflammable

    —Highly potent (can give with ample O2)

    —Low blood and tissue solubility

    —No biotransformation

    —No toxicity


    —Minimal CV and respiratory effects
  56. Nitrous Oxide
    —First general anesthetic

    —Inorganic gas

    —Very low B/G solubility = 0.47

    • —MAC = 105%
    • ◦Weak anesthetic

    —Strong analgesia

    —Low CV and respiratory depression

  57. Ether (diethyl ether)
    —First successful anesthetic

    —High B/G solubility = 12.1

    —MAC = 1.92


    —Strong analgesia

    —Low CV and resp. depression

    —Good muscle relaxation

    —Flammable, explosive
  58. Halothane (halogenated hydrocarbon)
    • —First “modern" anesthetic
    • ◦Potent, nonflammable
    • ◦Ethane

    —No longer used because:

    ◦CV - myocardial depression, high arrhythmogenic potential

    ◦Significant hepatic metabolism, sometimes causing acute hepatitis

    ◦Modest analgesia
  59. Isoflurane (halogenated ether)
    —B/G solubility =1.4

    —MAC = 1.15%,

    —CV - dose dependent myocardial depression, but much less than halothane; vasodilation; low risk of arrhythmia

    • —Respiratory - moderately irritating
    • ◦Not used for mask induction

    —0.2% metabolized --> hepatitis

    —Moderate analgesia

  60. Desflurane
    —Very low B/G solubility = 0.42

    • —MAC = 6% 
    • Least potent of “potent” inhalation agents

    —0.02% metabolized

    —CV - similar to isoflurane

    • —Not useful for inhalation induction
    • ◦Very irritating to airways

    —Moderate analgesia
  61. Sevoflurane
    —Low B/G solubility = 0.68

    —MAC = 2%

    —4% metabolized but no risk of hepatitis

    —CV - similar to isoflurane

    —Useful for mask inductions

    —Moderate analgesia and muscle relaxation

    Notes: could be turn to 8% MAC to produce quicker onset
  62. —Pharmacologic Effects: Cardiovascular system
    ◦All agents decrease blood pressure (except nitrous oxide)

    • ◦Myocardial depression (esp. halothane) and vasodilation (all others) contribute to
    • hypotension
  63. Pharmacologic Effects:—Respiratory system
    Respiratory depression
    –Desflurane > Isoflurane > Sevoflurane
  64. Pharmacologic Effects:—Respiratory system
    ◦Depress ventilatory responses to hypercarbia and hypoxia in a dose dependent manner
  65. ◦Respiratory Irritation:
    Sevoflurance is the best
  66. Pharmacologic Effects: —Hepatic
    • ◦Correlates with extent of oxidative
    • metabolism

    ◦Halothane > Enflurane > Isoflurane > Desflurane

    • ◦Numerous reports of “halothane
    • hepatitis”

    ◦50 case reports with enflurane

    ◦Fewer case reports with isoflurane

    ◦One case report with desflurane
  67. Pharmacologic Effects: renal
    • ◦All agents decrease renal blood 
    • flow
  68. Pharmacologic Effects: —Nephrotoxicity
    • ◦Related
    • to inorganic fluoride

    • ◦Subclinical:
    • 50-80 uM/L; Overt: 80-175 uM/L

    ◦Isoflurane/Desflurane – Minimal, if any


    • –1-2 MAC-hr:
    • 10-20 uM/L; 2-7 MAC-hr:
    • 20-40 uM/L

    • –15% sevoflurane anesthetics →
    • >50 uM/lit

    • –Absence
    • of sevoflurane
    • nephrotoxicity contradicts classical fluoride hypothesis of 50 uM
    • toxic threshold
  69. Pharmacologic Effects: CNS
    • ◦↓EEG
    • wave frequency

    • ◦Higher
    • conc. (2 MAC) → Isoelectric
    • EEG

    • ◦Protect
    • against ischemia by↓CMRO2

    • ◦Cerebral
    • vasodilation leading to↑ICP

    • ◦Enflurane,
    • and sevoflurane
    • to a lesser extent, can cause convulsions

    • ◦Dose related↓amplitude
    • and↑latency
    • of evoked potentials
  70. Pharmacologic Effects: —Malignant
    ◦All volatile agents may increase metabolic rate in genetically susceptible individuals (1:25,000)

    ◦Treated with dantrolene (skeletal muscle calcium channel blocker)