Inhaled Anesthetics

Inhaled Anesthetics
• Volatile
• e.g. Halothane, Enflurane, Isoflurane, Desflurane, Sevoflurane
• Low vapor pressures, high boiling point
• Liquid at room temperature (20°C) or sea-level ambient pressure

• Gaseous
• e.g. Nitrous oxide, Xenon
• High vapor pressure, low boiling point
• Gas at room temperature
Pharmacokinetics
• Uptake occurs via gas exchange in the alveoli of the lung into the
blood

• An ideal anesthetic has rapid onset (induction) and offset

(emergence)
Pharmacokinetics
Speed of induction depends on the following factors:
• Solubility
• Inspired Gas Partial Pressure
• Ventilation Rate
• Pulmonary Blood Flow
• Arteriovenous Concentration Gradient
Solubility
• more rapidly a drug equilibrates
with the blood, the more quickly
the drug passes into the brain to
produce anesthetic effects

• a low blood:gas partition

coefficient (eg, nitrous oxide)
equilibrate more rapidly than
those with a higher blood
solubility
Inspired Gas Partial Pressure
• high partial pressure of the gas in the lungs results in more rapid
achievement of anesthetic levels in the blood

• initial administration of gas concentrations higher than those required

for maintenance of anesthesia
Ventilation Rate
greater ventilation →

rapid rise in alveolar and blood

partial pressure of the agent →

rapid onset of anesthesia

Pulmonary Blood Flow
• At high pulmonary blood flows, the gas’s partial pressure rises at a
slower rate; thus, the speed of onset of anesthesia is reduced

• low flow rates, onset is faster

Arteriovenous Concentration Gradient
• Uptake of soluble anesthetics into highly perfused tissues may
decrease gas tension in mixed venous blood

• Rate of onset of anesthesia is influenced because equilibrium is

dependent on the difference in anesthetic tension between arterial
and venous blood
ELIMINATION
• via the lungs

• Through redistribution of the agent from the brain to the blood, and
from the blood to the alveolar air

• Rate of recovery is faster in agents with low blood:gas partition

coefficient than those with high solubility
MINIMUM ALVEOLAR ANESTHETIC
CONCENTRATION
• determines the potency of inhaled anesthetics

• “alveolar concentration required to eliminate the response to a

standardized painful stimulus in 50% of patients”

• value may vary among patients depending on age, cardiovascular

status, and use of adjuvant drugs
EFFECTS OF INHALED ANESTHETIC
• Central Nervous System
• ↓ brain metabolic rate
• ↓ vascular resistance → ↑ cerebral blood flow (may lead to ↑ ICP)

• Enflurane – uniquely cause spike-and-wave activity & muscle twitching, at

high concentrations

• Nitrous oxide – exerts marked analgesia and amnestic actions but has low
potency (high MAC)
EFFECTS OF INHALED ANESTHETIC
• Levels of CNS depression (Guedel’s signs)

• Stage I (Analgesia): initially experiences analgesia without amnesia; later,

analgesia with amnesia

• Stage II (Excitement): patient appears delirious and may vocalize but is

completely amnesic; respiration is rapid, and heart rate and blood pressure
increase.
EFFECTS OF INHALED ANESTHETIC
• Levels of CNS depression (Guedel’s signs)

• Stage III (Surgical Anesthesia): begins with slowing of respiration and heart
rate and extends to complete cessation of spontaneous respiration (apnea).

• Stage IV (Medullary Depression): represents severe depression of the CNS;

vasomotor center in the medulla and respiratory center in the brainstem.
Aglio, Linda S.; Lekowski, Robert W.; Urman, Richard D. (2015). Essential Clinical Anesthesia Review (Keywords, Questions and Answers for the
Boards) || Administration of general anesthesia. , 10.1017/CBO9781139584005(Chapter 47), 164–165. doi:10.1017/CBO9781139584005.049 
EFFECTS OF INHALED ANESTHETIC
• Cardiovascular Effects
• most inhaled anesthetics decrease arterial blood pressure moderately

• Enflurane and halothane - myocardial depressants that decrease cardiac

output

• Isoflurane, desflurane, and sevoflurane - peripheral vasodilation

• Nitrous oxide is less likely to lower blood pressure than are other inhaled
anesthetics
EFFECTS OF INHALED ANESTHETIC
• Respiratory Effects
• ↑respiratory rate, dose-dependent ↓tidal volume and minute ventilation →
↑arterial CO2 tension

• Inhaled anesthetics decrease ventilatory response to hypoxia even at

subanesthetic concentrations (eg, during recovery)

• Nitrous oxide has the smallest effect on respiration

EFFECTS OF INHALED ANESTHETIC
• Respiratory Effects
• Most inhaled anesthetics are bronchodilators, but desflurane is a pulmonary
irritant and may cause bronchospasm

• The pungency of enflurane causes breath-holding, which limits its use in

anesthesia induction
EFFECTS OF INHALED ANESTHETIC
• Hepatic & Renal Effects
• blood flow to the liver and kidney is decreased by most inhaled agents

• ↓portal vein blood flow parallels the decline in cardiac output

• ↓renal blood flow, GFR and urine flow; preserved filtration fraction
EFFECTS OF INHALED ANESTHETIC
• Uterine Smooth Muscle
• Nitrous oxide appears to have little effect on uterine musculature

• Halogenated anesthetics are potent uterine muscle relaxants and produce

this effect in a concentration-dependent fashion
TOXICITIES OF INHALED
ANESTHETIC AGENTS
• Postoperative hepatitis has occurred (rarely) after halothane
anesthesia in patients experiencing hypovolemic shock or other
severe stress.

• Fluoride released by metabolism of methoxyflurane (and possibly

enflurane and sevoflurane) may cause renal insufficiency after
prolonged anesthesia
TOXICITIES OF INHALED
ANESTHETIC AGENTS
• Prolonged exposure to nitrous oxide decreases methionine synthase
activity and may lead to megaloblastic anemia

• Susceptible patients may develop malignant hyperthermia when

anesthetics are used together with neuromuscular blockers
(especially succinylcholine)