Inhaled Anesthetics Anesthesia 2024
Inhaled Anesthetics RESP 5018
History of Inhalational Anesthetics
1842: Dr. Crawford Long experimented with ether, leveraging its stimulating effects during "Ether Frolics."
Used ether for the first time in surgery to anesthetize a friend for neck tumor excision (report published in 1849).
1845: Dentist Horace Wells successfully utilized nitrous oxide for dental extractions, but public demonstrations were unsuccessful.
1846: Dr. Morton demonstrated ether in public at what is now known as the "Ether Dome" at Massachusetts General Hospital (MGH).
Dr. Warren, initially skeptical, labeled Morton’s claims as “Humbug.”
Dr. Morton collaborated with Dr. Gould to develop an ether delivery device and arrived late for surgery.
After successful use of the Morton Inhaler, Dr. Morton retorted, reinforcing the efficacy of inhaled anesthesia.
Timeline of Inhaled Anesthetics
Ether and N2O introduced before the 1850s, followed by Chloroform, Halothane, and others into the late 20th century.
Key anesthetics introduced:
Sevoflurane - 20
Desflurane - 15
Isoflurane
Nitrous Oxide (N2O) - 0
Earliest agents initiated use around 1830, reaching modern compounds by the mid to late 20th century.
Inhaled Agents
Administered via the respiratory tract affecting the brain and CNS.
Uptake: From alveoli into systemic circulation to reach the site of action within the brain.
Maintaining a constant brain partial pressure (Pbr) is crucial for effective anesthesia.
This involves creating a gas concentration gradient from the machine to the brain (PA ↔ Pa ↔ Pbr).
Pharmacokinetics of Inhaled Agents
Critical factors:
Uptake: Rate at which inhaled agents enter the alveoli.
Distribution: Targeting the CNS for anesthesia.
Elimination: Primarily through the lungs, minimal metabolism occurs in the liver.
The goal is to establish a gas partial pressure in the alveoli that equilibrates with the CNS for effective anesthesia.
Note: Partial Pressure drives effect, not just concentration.
Atmospheric pressure impacts anesthetic efficacy at higher altitudes.
Solubility Factors
Blood-Gas Solubility
Influences uptake from alveoli into blood and induction time.
Low blood-gas partition coefficient leads to faster onset of action.
Brain-Gas Solubility
Affects time needed for equilibrium of partial pressures between blood and brain.
Blood Gas Partition Coefficient
Defines gas solubility in blood, affecting induction and recovery rates.
Compares drug concentration in blood to that in alveolar gas.
Lower coefficients equate to quicker induction of anesthesia.
Solubility's Impact on Anesthesia
Insoluble agents induce rapid effects by concentrating in the brain.
Soluble agents dissolve in the bloodstream, causing delayed onset as they distribute to muscle and fat.
Partial Pressure Dynamics
Transfer from gas machine to alveoli (PA) influenced by:
Inspired concentration, alveolar ventilation, and breathing system characteristics.
From alveoli to blood (Pa) impacted by:
Blood gas partition coefficient and cardiac output.
Arterial blood to brain (Pbr):
Determined by cerebral blood flow and arterial to venous partial pressure difference.
Concentration and Second Gas Effect
FI and FA impact anesthetic uptake and alveolar concentration.
The second gas effect enhances uptake speed of one gas in the presence of another (e.g., N2O).
Rapid uptake of N2O increases relative concentration of the secondary agent.
Minimum Alveolar Concentration (MAC)
A vital measure for evaluating inhaled anesthetics, defining the concentration required to prevent movement in response to surgery in 50% of patients.
MAC correlates inversely with anesthetic potency; higher MAC indicates lower potency.
MAC Values for Various Agents
Halothane - 0.75%
Isoflurane - 1.2%
Sevoflurane - 2.0%
Desflurane - 6.0%
Nitrous Oxide (N2O) - 104%
Xenon - 0.71%
Agent Comparisons
Isoflurane - Potent, slow (1.2, 1.46)
Sevoflurane - Good potency, relatively quick (2.0, 0.65)
Desflurane - Weaker potency, rapid onset/clearance (6.0, 0.45)
N2O - Poor potency, rapid onset/clearance (104, 0.46)
Factors Affecting MAC
Increasing MAC
Stimulants (Amphetamines, Cocaine)
Alcoholism
Young age (<6 months)
Hyperthermia
Hair Color (Red Heads)
Decreasing MAC
Hypnotics (e.g. Propofol)
Older age
Pregnancy
Certain medications (e.g., Lithium, Opioids)
Pharmacodynamics of Inhaled Anesthetics
Two primary effects: immobility and amnesia.
The mechanisms remain multifactorial involving both enhanced inhibitory and diminished excitatory channels in the CNS.
Theories of Action
Volume Expansion Theory
Inhaled agents induce membrane expansion in neuronal membranes, blocking ion channels necessary for action potentials.
GABA Interaction
Reduction of neuronal activity via GABA, the fundamental inhibitory neurotransmitter in the brain.
Stages of Inhalational Anesthesia
Four stages, identifying levels of CNS depression:
Stage 1: Analgesia
Stage 2: Excitement
Stage 3: Surgical Anesthesia
Subdivided into four planes based on respiratory patterns and responses.
Stage 4: Impending death / Medullary Depression.
Shared Properties of Inhalational Agents
Cardiovascular effects: dose-dependent SVR decrease.
Pulmonary effects: diminish Tidal Volume (Vt), enhance respiratory rate (RR).
Renal impact: reduced blood flow and GFR.
Muscle relaxing properties, except N2O.
Specific Agents
Nitrous Oxide (N2O)
Low potency, low solubility, rapid uptake, and elimination.
Potential for diffusion hypoxia post-surgery.
Isoflurane
Highly pungent, the most potent among common anesthetics.
Can cause vasodilation and decreased blood pressure.
Desflurane
Lowest blood-gas solubility coefficient, quick induction and emergence.
Not recommended for inhalational induction due to side effects.
Sevoflurane
Preferred for inhalational induction due to rapid uptake and non-pungent smell.
Elimination of Inhaled Anesthetics
Primarily exhaled through the lungs, minor hepatic metabolism, with some metabolites excreted through the kidney.
Notable that N2O can diffuse through the skin.