General Anesthesia History

General Anesthesia

• History:
  • Early anesthetic practices relied on alcohol and opium, and strong men to hold patients down while surgeons worked quickly.
  • Amputations were the most common surgeries.
  • Crawford Long used ether for surgery in 1842 on James Venable.
  • William Morton performed a public demonstration of ether at Mass. General Hospital in 1846.
  • Horace Wells demonstrated nitrous oxide in Boston in 1845; deemed a failure at the time.
  • James Simpson utilized chloroform for childbirth in Scotland in 1847. Chloroform offered advantages over ether (less irritating, non-flammable, sweet-smelling).
  • Gardner Colton reintroduced nitrous oxide to dental and surgical procedures in 1863.
  • Nitrous oxide and oxygen were used together in 1868.
  • Cyclopropane (derived as a contaminant in propylene) was introduced in 1929. Used for 30 years but less desirable as electrical equipment in surgery became more common.
  • Halothane was synthesized in 1956, a fluorinated hydrocarbon.

Mechanism of Action for Volatile Anesthetics

• Meyer-Overton theory (1900s): potent anesthetics have high lipid solubility.
• Compounds with higher lipid solubility require lower concentrations to produce anesthesia.
• Anesthetics dissolve in the lipid portions of cell membranes, causing swelling and altering ion channel function, which reduces nerve firing.
• Not all lipid-soluble compounds produce anesthesia.
• Volatile anesthetic mechanism is more complex than simply lipid solubility.
• Volatile anesthetics interact with protein receptors, including ion channels like chloride, potassium, and sodium channels.

General Anesthesia: Important Compounds

Barbiturates

• Thiopental, Thiamyl, Methohexital are compounds in this category
• Barbiturates' pKa is at or above blood pH, resulting in rapid entry into the brain.
• Recovery from anesthesia due to redistribution, not metabolism.
• Side effects include decreased cerebral oxygen consumption, decreased blood pressure, and depressed respiratory response to CO2 levels, potentially causing apnea, especially if used with opiates.
• Mechanism of action involves modulating GABA receptors, enhancing GABA's effects at beta subunits.

Propofol

• Commonly used intravenous anesthetic.
• Emulsion form (very low water solubility).
• Bacterial contamination is a concern, use or discard within 6 hours of opening.
• Mechanism involves interacting with GABA receptors, increasing sensitivity to GABA.
• Fast induction (40 seconds to reach the brain).
• Recovery is primarily via redistribution, different from barbiturates' slower elimination.
• Dose-dependent decrease in blood pressure, slightly elevated risk of respiratory depression compared to barbiturates.

Etomidate

• Commonly used IV anesthetic (D isomer)
• Major drawbacks include nausea, vomiting, inhibition of adrenal enzymes needed for cortisol production (adrenal corticoid stress response).
• This isn't typically problematic for short-term use.
• Poorly water-soluble, formulated as a solution in 35% propylene glycol.
• Typically used in patients likely to have hypotension issues.

Ketamine

• Structurally similar to phencyclidine (PCP).
• Inhibits NMDA receptors by binding to the PCP binding site, the S-isomer being more potent.
• Useful in patients at risk for hypotension, bronchospasms
• Commonly used for pediatric or emergency use.
• Recovery is dependent on redistribution.
• Increases cerebral blood flow, intracranial and intraocular pressure; increases blood pressure and heart rate by inhibiting catecholamine reuptake.
• Characterized by a cataleptic state, accompanied by nystagmus (rapid eye movement), dilation of pupils, salivation, lacrimation and spontaneous limb movements with increased overall muscle tone.
• Post-operative state characterized by delirium, hallucinations, vivid dreams, and illusions. This is more common in initial hours of post-anesthesia and less prevalent in younger patients.

Local Anesthetics

• General properties:
  • Produce loss of sensation or motor function in a defined area.
  • Used for temporary relief of pain in dental and minor procedures and spinal anesthesia.
  • Topical local anesthetics are used to treat minor burns, bites, and allergic reactions, including hemmorhoids and procedures like sigmoidoscopy and intubation.
• Mechanism of Action:
  • Block sodium channel activity, preventing action potential propagation.
  • Affect the inside surface of cell membranes.
  • Lipophilicity (ability to cross membranes) is key to potency and duration of action.
• Ester-type (e.g., cocaine):
  • Cocaine has vasoconstriction which prolongs its duration.
  • Cocaine interacts with α₂ adrenergic receptors, increasing nerve excitability and blood pressure.
  • Other topical anesthetic agents may be used in conjunction with epinephrine to simulate vasoconstrictive effects; however, cocaine use with epinephrine shouldn’t take place to prevent serious consequences.
  • Cocaine use can increase cardiovascular and CNS response.
    • Examples include Hexylcaine, Benzocaine, Procaine, Chloroprocaine, Tetracaine, and Proparacaine
• Amide-type (e.g., lidocaine): - Lidocaine, Xylocaine, Mepivacaine, Carbocaine, Bupivacaine, Prilocaine - Similar to ester types, but amide types are more resistant to hydrolysis. Thus have longer effects.
• Other miscellaneous types: - Examples include, Pramoxine, and Dyclonine

Toxic Side Effects of Local Anesthetics

• CNS and cardiovascular reactions are often seen
• Possible side effects include: excitatory and/or depressive effects such as nervousness, dizziness, blurred vision, tremors, and drowsiness.
• Severe cases may merge into unconsciousness with concomitant respiratory depression.
• Cardiovascular reactions are characterized by hypotension, myocardial depression, bradycardia, and possibly cardiac arrest.