2001B10 Briefly describe the adverse effects of nitrous oxide.

 

List:

·     Pharmaceutical

·     Pharmacokinetic

·     Pharmacodynamics

 

Pharmaceutical:

Impurities

·  Manufactured by superheating NH4NO3 to 250°C

·  Products: N2O plus NH3, N2, NO, NO2

·  Removal of impurities by scrubbers may be incomplete

o e.g. NO2: airway damage, headache, heart failure

Storage

·  Need to reduce filling ratio from 0.75 to 0.67 in hot climates

Entonox lamination

·  Occurs below pseudocritical temperature (~-6°C)

·  Results in delivery of hyperoxic then hypoxic mixture

Supports combustion

·  Like O2

·  Not itself flammable

 

Pharmacokinetics:

Absorption

·  N/A, concentration effect beneficial

Distribution

·  N2O 30x more soluble, BGPC 0.47; diffuses rapidly into air spaces

·  N2 30x less soluble, BGPC 0.014; diffuses slowly from air spaces

·  Hence expansion of existing closed air spaces

o ↑size pneumothorax

o ↑Bowel gas -> difficult laparoscopy

o ↑Ocular gas (of ocular surgery with SF6?)

o ↑Pneumocephalus (if brain surgery)

Metabolism

·  Minimal, 0.004%

Excretion

Diffusion hypoxia:

·  Reverse of the concentration effect

·  Switch from N2O/O2 to N2/O2

·  Rapid output N2O into alveolus, but very slow uptake of N2

·  Dilution of alveolar O2 -> hypoxia

·  Avoided by high %O2 during washout

 

Pharmacodynamics:

Cardiovascular

·  Direct: ↓heart rate, ↓contractility, ↓SVR

·  Via ↑SNS output: ↑HR, ↑contractility, ↑SVR

Respiratory

·  ↑RR, ↓TV

·  ↑SNS output -> ↑PVR -> ↑RV strain

CNS

·  MAC 105%, MAC-awake 67%; cannot be used alone as anaesthetic

·  Pro-emetic

·  ↑CBF, ↑ICP if susceptible

·  Minimal effect on EEG, can’t be monitored with BIS

·  Euphoria, abuse potential

Mutagenesis

·  Oxidises the cobalt atom in Vitamin B12, a cofactor for methionine synthetase

·  Impaired DNA synthesis

·  Teratogenesis

·  Subacute combined degeneration of the cord (chronic abuse)

·  ? ↑Risk abortion in PACU staff