Inhaled AA - Nitrous oxide (N2O)





PD

Properties

  • Low MW
    • MW = 44
  • Nonflammable
    • But will support combustion
  • Gaseous at room temperature
  • Low potency
    • MAC = 104%
    • i.e. 1 MAC not possible under 1 ATM
  • Low solubility
    • Blood:gas = 0.46
    • c.f. Blood:gas for nitrogen = 0.015
  • Critical temperature = 36.5ºC
  • Critical pressure = 72 bar

⦿ NB:

  • Critical temperature for N2O
    • 36.5ºC [PHW3:p118]
    • 36.4ºC [wikipedia]

MOA

  • Possible NMDA antagonist

Actions

➤ A+B:

  • Small decrease in Vt
  • Small increase in RR
  • MV unchanged

➤ C:

  • Mild direct myocardial depression
  • Mild sympathomimetic effect
  • Overall little change to CO
  • Does NOT sensitise heart to catecholamines
  • Increased pulmonary artery pressure

➤ D:

  • Increased CBF → Increased ICP
  • Analgesia
    • Hard to quantify
    • 70% N2O ≈ Remifentanil 0.085 to 0.17 µg/kg/min ≈ Remifentanil 2 ng/mL
  • Anaesthesia (but high MAC)
    • Cannot reliably prevent recall
    • Cannot be used as sole AA
  • Increased incidence of PONV

➤ Other systems:

  • Minimal skeletal muscle relaxation
  • Toxicity (Interference with vitamin B12 and folate metabolism)
  • Small increase in Hb p50
    • i.e. Decreased affinity of Hb to O2

➤ Misellaneous

  • Supports combustion
  • Theatre pollution
  • Greenhouse gas
    • Absorbs infrared
  • Depletes ozone

PONV

➤ Preventing PONV by avoding N2O [BJA 1996; 76:186-193]:

  • NNT = 13
  • NNT = 5 for high risk patients
  • No difference for low risk patients

Toxicity

N2O...

  • Directly and irreversibly inhibits methionine synthetase
    • 50% reduction in methionine synthetase activity after 2 hours exposure to N2O (BJA 1987;59:3-13)
  • Oxidises the cobalt atom in vitamin B12

Thus,

  • Impaired synthesis of methionine, thymidine, tetrahydrofolate, and DNA
  • Increased level of homocysteine (which is normally converted to methionine)

End results:

  • Haematological issues
    • Megaloblastic changes
      • Megaloblastic anaemia
      • Immunodeficiency
    • Agranulocytosis in more severe cases
  • Impaired wound healing
  • ?Teratogenicity
    • Only inhaled AA with proven teratogenicity in animals
    • Higher risk of spontaneous abortion or low birthweight infants in mothers with occupational exposure
  • Hyperhomocysteinaemia

Toxicity may possibly be avoided with large doses of vitamin B12 and/or folic acid

Physical effects

Includes:

  • Concentration effect
  • Second gas effect
  • Diffusion hypoxia
  • Expansion of air filled space

These effects occur (or becomes clinically significant) due to the high percentage / large volume of N2O used

Concentration effect:

Large volume of N2O is absorbed in the alveoli
→ Gas in the airway is passively drawn into alveoli → Ventilation increased

Second gas effect

Direct result of the concentration effect

Large volume of N2O absorbed in the alveloi → O2 and other volatile agents become more concentrated

Diffusion hypoxia

Reverse of second gas effect

At end of anaesthesia, N2O enters alveoli → Dilution of all alveolar gases (including O2)

Expansion of air filled space

  • Pneumothorax
  • Vascular air embolus
  • Intestinal lumen
  • Sinuses
  • Middle ear post-tympanic surgery
  • Intracranial air
  • Vitrectomy / retinal surgery with intraocular perfluoropropane

PC

Manufacturing

Nitrous oxide is manufactured by heating ammonium nitrate to 250ºC

NH4NO3 → N2O + 2 H2O

➤ Contaminants:

  • include NH3, N2, NO, NO2, and HNO3.
  • Are actively removed

Storage

  • Stored as liquid in French blue cylinders
    • C size = 450 L
    • G size = 9000 L
  • Gauge pressure = 51 bar at 20ºC
  • Pressure has no correlation to cylinder content under all remaining N2O is in gaseous phase
  • Filling ratio
    • Ratio of mass of N2O in cylinder / mass of water that cylinder could hold
    • 0.75 in temperate region
    • 0.67 in tropical region

Entonox / Nitronox

  • 50% of N2O and 50% of O2
  • Two gases effectively dissolve into each other
    • Poynting effect
  • Used for analgesia during painful procedures

Storage

Entonox is stored as a GAS in French blue cylinders with white and blue checked shoulders at 137 bar

  • Size G = 3200 L
  • Size J = 6400 L

Gas separation

Separation...

  • Most likely at -7ºC (pseudo-critical temperature) and at 117 bar
  • Likely at -30ºC (pseudo-critical temperature) when pressure is at 4.1 bar (in pipeline)

If separation occurs in a cylinder, the gas will...

  • Initially contain mostly O2
  • N2O progressively increases
  • Almost 100% N2O as the cylinder empties

Clinical

Safe in malignant hyperthermia

MAC awake is higher than other inhalational anaesthetic agents (> 0.6 MAC)

Contraindication

  • Bowel obstruction
  • Pneumothorax
  • Middle ear tympanic surgery
  • Vitreoretinal surgery (in the last 30 days)
  • Pulmonary HTN

Pros and cons

Pros

  • Cheap
  • Safe
    • Less CVS and resp depression than other inhaled AA
    • No toxic effect on livers and kidney
    • Safe in MH
  • Increases speed of inhalation induction
    • via "second gas effect"
  • Analgesic
  • Short-acting
  • ?Prevention of chronic pain

Con

  • PONV
  • Reduces available O2
  • Increased risk of hypoxia after extubation
    • via "diffusion hypoxia"
  • Increased risk of pulmonary complication
  • Contradicated in certain situations
  • Environmental: Destroys ozone, and also a greenhouse gas
  • Intereference with vitamin B12 and folate metabolism
    • ?? Clinical significance
  • ?? Neurotoxic effects (animal studies)
  • Increased risk of surgical site infection
    • Not in Enigma-II, but in Enigma-I
    • ? Due to effect of lower FiO2 and/or use of N2O