Inhalation anesthesia

the loss of perception of, and response to, all external stimuli

—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

• multiple drugs to give complete anesthetics 
• e.g complete awareness but feel no pain and ms relaxation

• —Alveolar concentration of anesthetic at which 50% of patients are unresponsive to a
• standard surgical stimulus.

quantifying the potency of inhaled anesthetics

• as the percentage of gas in a mixture required to achieve the effect
• e.g

smaller one

Dose for 50% Amnesia and/or awakening

Dose for lack of incision movement for 95%

Dose for 50% block adrenergic response

◦Dose for 50% block movement to intubation

—brain concentration

• not a true anesthetic. can never achieve true general anesthesia
• only MAC awake

more potency

---—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

• —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

—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

—genetic polymorphisms in mitochondria and synaptosomal proteins

Mesencephalic reticular formation and dorsal lamina of the SC

---—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

—An area implicated in the primary action of anesthetics

—Gateway for nociceptive impulses into the CNS

GABA receptor (agonist), NMDA receptor (antagonist)

• —Progressive depression
• ◦Guedel’s scheme of progressive depression
• Seen with volatile anesthetic
• agents

◦4 stages, with the third stage having 4 planes

—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

◦death

• normal respiration
• normal BP 
• normal reflexes
• Pupil site: normal 
• normal muscle tone

• inc respiration
• inc HR
• Reflex: swallow, retch, vomit and eyelid 
• dilated pupil
• inc ms tone

• progressive decrease of respiration
• progressive decrease of HR
• Reflex: laryngeal bronchiol, conjuntival, corneal, pupil light reflex 
• Pupil get progressively larger
• decrease ms tone

oh well

• To develop and maintain a satisfactory partial pressure or tension of
• anesthetic at the site of anesthetic action in brain

high and equilibrates with anesthetic PP in blood

—Dose of An Oral Drug is “Concentration”

• —Dose of Inhalation Anesthetic Measured in % Volume
• (Partial pressure ÷ barometric pressure)
• x100

—Delivered > Inspired > Alveolar > Arterial > Brain

—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

aveolar drug %

—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

—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

thus increasing partial pressure, will hasten anesthesia

—will delay anesthesia

will lower alveolar partial pressure and delay anesthesia

false

—the more anesthetic that is delivered to the lungs, the more rapid the induction

false

—the more rapid the induction

delayed

only drug allow pt to drive home bc of fast onset and removal

• delayed onset of anesthesia bc Removes
• large quantities of gas from alveoli, lowers alveolar tension

low BG PC --> quicker onset

false

• —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

• —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

quicker onset bc of 2nd gas effect and concentration effect

—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

• —Most inhalation anesthetics undergo small amounts of biotransformation in the liver
• note: halothane hepatitis

—Stable and nonflammable

—Highly potent (can give with ample O2)

—Low blood and tissue solubility

—No biotransformation

—No toxicity

—Nonirritating

—Minimal CV and respiratory effects

—First general anesthetic

—Inorganic gas

—Very low B/G solubility = 0.47

• —MAC = 105%
• ◦Weak anesthetic

—Strong analgesia

—Low CV and respiratory depression

—Nonflammable

—First successful anesthetic

—High B/G solubility = 12.1

—MAC = 1.92

—Irritating

—Strong analgesia

—Low CV and resp. depression

—Good muscle relaxation

—Flammable, explosive

• —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

—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

—

—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

—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

◦All agents decrease blood pressure (except nitrous oxide)

• ◦Myocardial depression (esp. halothane) and vasodilation (all others) contribute to
• hypotension

–Desflurane > Isoflurane > Sevoflurane

◦Depress ventilatory responses to hypercarbia and hypoxia in a dose dependent manner

Sevoflurance is the best

• ◦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

• ◦All agents decrease renal blood 
• flow

• ◦Related
• to inorganic fluoride

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

◦Isoflurane/Desflurane – Minimal, if any

◦Sevoflurane

• –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

• ◦↓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

◦All volatile agents may increase metabolic rate in genetically susceptible individuals (1:25,000)

◦Treated with dantrolene (skeletal muscle calcium channel blocker)