2011A07 Describe the advantages and disadvantages of using nitrous oxide as part of a general anaesthetic.

 

List:

·      PC: pros and cons

·      PK: pros and cons

·      PD: pros and cons

 

Pharmaceutics:

Pros

Cons

·  Liquid form -> efficient storage

·  Impurities from manufacturing: NH3, N2, NO, NO2

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

·  Sweet smell, non irritant -> good for gas induction

·  Set-up and maintenance costs: wall supply, cylinder manifolds etc.

·  Inert: no reaction with rubber, plastic, sodalime

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

·  Low potency (MAC 105%): use as carrier gas

·  Entonox lamination: occurs if below pseudocritical temperature (-6°C)

·  Delivery of hyperoxic then hypoxic mixture

 

·  Supports combustion, although not itself flammable

·  Risk of fire, explosion in airway laser surgery

·  Destructive to ozone layer

 

Pharmacokinetics:

 

Pros

Cons

 

N2O 30x more soluble, blood-gas partition coefficient 0.47; equilibrates across membranes rapidly

N2 30x less soluble, BGPC 0.014; equilibrates across membranes slowly

A

Rapid onset during gas induction:

 

1) Concentration effect:

·  Seen only with high volume carrier gases

·  Switch from N2/O2 to N2O/O2

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

·  ↓ alveolar volume and pressure -> rapid inflow of N2O-rich fresh gas

·  Accelerated ↑ FA/FI N2O

 

2) Second gas effect:

·  Rapid uptake N2O, very slow output of N2

·  Concentration of remaining alveolar gas

·  Accelerated ↑FA/FI volatile drug

-

D

·  Low muscle:blood PC (1.2)

·  Low fat:blood PC (2.3)

·  Minimal accumulation in long case

Expansion of existing closed air spaces:

·  ↑size pneumothorax

·  ↑Bowel gas -> difficult laparoscopy

·  ↑Ocular gas (if surgery using SF6)

·  ↑Pneumocephalus (if brain surgery)

M

·  Minimal (0.004%)

-

E

 

Diffusion hypoxia:

·  Reverse of concentration effect

·  N2O/O2 off, N2/O2 on

·  N2O diffuses rapidly out of blood into alveolus

·  N2 slow to be taken up from alveolus

·  Dilution of alveolar O2 -> hypoxia

 

Pharmacodynamics:

 

Pros

Cons

CVS

·  Stability: ↑SNS offsets ↓inotropy

·  Direct negative inotropy may be unmasked if on exogenous intrope

Resp

·  Mild ↑RR, ↓TV, minimal ↑PaCO2

·  ↑RR, ↓TV

·  ↑SNS output -> ↑PVR -> ↑RV strain

·  Carrier gas -> ↓FiO2

CNS

·  Additive with volatile anaesthetics
 (MAC-sparing)

·  Analgesia (NMDA antagonist), may reduce risk of chronic pain

·  MAC 105%, MAC-awake 67%; inadequate alone for anaesthesia

·  Pro-emetic

·  ↑CBF

·  Minimal effect on EEG; BIS/entropy unhelpful

·  Euphoria, abuse potential

Other

·  No vasodilation, MAC sparing -> ↓bleeding

·  Does not trigger MH

Mutagenesis:

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

·  Impaired DNA synthesis

·  Megaloblastic anaemia

·  Subacute combined degeneration of the cord (chronic abuse)

·  Teratogenesis

·  ? ↑Risk abortion in PACU staff

 

 

 

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