• Used for: Airway maintenance
• ❌ Contraindicated in gastric regurgitation risk
• “Brain mask” = LMA

Pharmacodynamics of Nitrous Oxide

Overview

Nitrous oxide (N2O), commonly known as "laughing gas," is an inhalational anesthetic used primarily for its analgesic and anxiolytic properties. Understanding its pharmacodynamics is crucial for safe and effective use in clinical settings.

Pharmacodynamics

1. CNS Depression:

   • Nitrous oxide produces nonspecific central nervous system (CNS) depression.
   • While it is classified as an inhalational general anesthetic, it provides limited analgesia, making surgical anesthesia unlikely unless concentrations that produce anoxia are reached.

2. Potency:

   • Nitrous oxide is the weakest of all inhalation agents, with a minimum alveolar concentration (MAC) of approximately 105%.
   • The MAC is a measure of the potency of an inhalation agent, defined as the concentration required to produce immobility in 50% of patients in response to a surgical stimulus.

3. Effects at Various Concentrations:

   • 30% to 50% Concentration:
     • Produces a relaxed, somnolent patient who may appear dissociated and is easily susceptible to suggestion.
     • Some patients may experience amnesia, but there is typically little alteration in learning or memory.
   • Greater than 60% Concentration:
     • Patients may experience discoordination, ataxia, giddiness, and increased sleepiness.
     • It is recommended that the concentration of nitrous oxide should not routinely exceed 50% to avoid adverse effects.

4. Titration:

   • One of the advantages of nitrous oxide is its ability to be easily titrated.
   • It can be increased for stimulating procedures (e.g., injections) and decreased during less stimulating periods (e.g., restorations).

Physiological Considerations

1. Entrapment in Gas-Filled Spaces:

   • Nitrous oxide can become entrapped in gas-filled spaces such as the middle ear, sinuses, and gastrointestinal tract.
   • This can lead to increased middle ear pressure, which is generally insignificant in patients with normal Eustachian tube function but can induce pain in patients with acute otitis media.

2. Contraindications:

   • Acute Otitis Media: Use should be avoided in patients with this condition due to the risk of increased middle ear pressure and pain.
   • Severe Behavioral Problems and Emotional Illness: Patients who are uncooperative or have a fear of "gas" may not tolerate nitrous oxide well.
   • Claustrophobia: Patients with this condition may feel uncomfortable with the nasal hood placement.
   • Maxillofacial Deformities: Conditions that prevent proper placement of the nasal hood can contraindicate its use.
   • Nasal Obstruction: Conditions such as upper respiratory infections, nasal polyps, or a deviated septum can hinder effective administration.
   • Chronic Obstructive Pulmonary Disease (COPD): Patients with COPD may have difficulty with nitrous oxide due to respiratory issues.
   • Pregnancy: Caution is advised when using nitrous oxide in pregnant patients.
   • High Oxygenation Situations: Situations where high oxygenation is inadvisable, such as during Bleomycin therapy, contraindicate the use of nitrous oxide.

• First Local Anaesthetic: Cocaine
• First Muscle Relaxant: D-Tubocurarine (DTC)
• Intubation Pioneer: Ivan Magill (Magill's forceps)

 Preoperative Considerations

• Stop smoking ideally 8 weeks prior to surgery.
• Urgent warfarin reversal: Fresh Frozen Plasma (FFP).
• Atropine:
  • ↓ Salivation
  • Bronchodilation
  • Flushing in pediatric patients

Stages of General Anesthesia

 Clinical Notes

• Stage I is often brief due to rapid induction agents.

• Stage II is avoided or minimized with modern anesthetics to reduce risk of complications like laryngospasm.

• Stage III is carefully maintained during surgery.

• Stage IV is considered an overdose and must be prevented.

• Stage III Plane 3 → Surgical anaesthesia
• Most reliable indicator: Regular respiration

 Isoflurane

• Agent of choice in Cardiac patients.
•  Vasodilation with least cardiovascular depression.
•  Intracranial pressure (moderate increase).
• Not ideal for asthmatics compared to Sevoflurane.

Desflurane

•  Fastest induction & recovery.
•  Minimally metabolized.
• Preferred in shock & renal failure.

Sevoflurane

•  Induction agent in children.
• Maximum bronchodilation (non-asthmatics).
• More cardiodepressant than Isoflurane.

Ether

• Highly explosive  (not used today).
• Classic: Complete anaesthetic agent.
• Causes max emesis.
• Basis of anaesthesia staging (Guedel’s classification).

1. Refractory periods: absolute (neuron cannot fire) and relative (can fire with greater than normal depolarization)

2. Specific receptor theory: local anesthetics bind inside Na channel, block entry of Na

3. Membrane expansion theory: anesthetics work by disrupting lipid bilayer around ion channel

4. Mechanism of action for local anesthetics: local must be in uncharged form to cross lipid bilayer of axon

a. Locals made as salts (usually mixed with HCl).  [Uncharged form] depends on pH of tissue, pKa of local-found by Henderson-Hasselbach equation- pH = pKa + log ( [RN] / [RNH+] )

b. Once inside axon, only charged form will bind to Na channel.

c. At physiologic pH, enough base exists outside nerve so anesthetic rapidly diffuses into axon.  Rate-limiting step is how much uncharged local is present outside neuron.

d. So, starts with 100 molecules of local, 25 of which are uncharged and 75 charged.  The 25 uncharged enter the neuron, leaving 0 on outside so the remaining 75 re-equilibrate to produce more uncharged which enters neuron .  Inside neuron the reverse happens as converted to ionic form then rapidly binds channel.

5. Inflammatory effects: ® an acidic environment, less of local can be converted to uncharged form (less enters).

6.  Pharmakokinetics: pool of local outside neuron depleted as local diffuses into adjacent muscles, tissues, enters blood vessels.  Since locals are water soluble, they go throughout body (even cross BBB and placenta)

7. Autonomic nervous system: sympathetic and parasympathetic divisions.  Both secrete pre-ganglionic acetylcholine.  Postganglionic NT is acetylcholine for parasympathetic, norepinephrine for sympathetic (also secrete E, dopamine, and seratonin, all are catecholamines).

a. Sympathetic catecholamines affect receptors (local anesthetics affect a1-mediated actions which cause vasoconstriction) ® fight or flight responses (pupil & bronchiole dilation, ­ HR, BP, blood glucose; ¯ GI)

b. Catecholamines inactivated by reuptake, diffusion, or metabolized by monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) then metabolites excreted in urine.

c.  When choosing sympathomimetic drug, consider receptor subtype in tissue and choose drug that affects it.