ANAESTHETIC GASES

INHALED NITROUS OXIDE

 Chemical name: dinitrogen monoxide
 Introduced: 1844
 MAC: 105%
 Bld-Gas:0.47..
 Critical Temperature: 36.5°C
 MW 44 gm, Boiling Point: -88°C
 Liquifying Pressure (36.5°C): 72 bar
 Vapour Pressure : 52 bar 39,000 mmHg
 General Characteristics

 N2O is a colorless gas without appreciable odour or

taste

 Marketed in steel cylinders as a liquid under

pressure in equilibrium with the gas phase at
normal room temperature.
 Cont..
 Heat is required to vaporise the liquid-
latent heat of vaporisation

 If this is rapid the cylinder becomes cold

 The gas is neither flammable, nor

explosive, but will support combustion of
flammable agents
 Chemical Preparation

 Prepared commercially by heating ammonium

nitrate between 245-270 °C

 NH4NO3 -----Heat --- N2O + 2H2O

 Contamination with the higher oxides of nitrogen,

nitrogen dioxide or nitric oxide, may lead to-
a. Laryngospasm
b. Cyanosis
c. Chemical pneumonitis and respiratory failure
 Pharmacokinetics
 Nitrous oxide is a potent analgesic but a weak
anaesthetic agent.

 The rate of approach of alveolar to inspired

concentration is rapid due to the low solubility in
blood
 Cont..
 The time taken to reach 90% arterial
saturation is about 20 min

 This large uptake of gas, and rapid egress on

emergence, results in-
a. Concentration effect
b. Second gas effect
c. Diffusion hypoxia
 N2O/O2
 The ability to combine nitrous oxide and oxygen at
high pressure while remaining in the gaseous form is
called Poynting effect.

 Inhalation of pure nitrous oxide over a continued

period would render a human hypoxic and the 50%
oxygen content prevents this from occurring.
 Cont..
 Although N2O has a "low" blood solubility c.f.
other anaesthetic agents, it is considerably
more soluble than nitrogen (0.014) ~ 34
times
 Therefore, any closed, gas-filled cavity will
expand during nitrous oxide anaesthesia as
nitrogen is exchanges for N2O,
e.g
 Pneumothorax
 Occluded middle ear
 Pneumopericardium
 Closed loop intestinal obstruction
 Renal or lung cysts
 Pneumocranium
 Cont..
 N2O may delay return of normal bowel function
after surgery if air is present in the bowel at the
start of surgery.

 The expansion of gas spaces in bowel by N2O may

contribute to the increased risk of Post-operative
Nausea and Vomiting (PONV).
 Cont..
 The main value of nitrous oxide in anaesthesia is as an
adjuvant to the inhalational agents

 With inhalation of 70%-N2O / 30%-O2, the MAC values are

reduced ~ 35-45% as follows-
 Halothane 0.74% -- 0.29%
 Enflurane 1.68% -- 0.58%
 Isoflurane 1.15% --0.50%

NB: smaller doses of the volatile agents, with N2O,

result in equal anaesthesia but less
-Cardio-respiratory depression
-Inhalational Anaesthetics
 CNS
 Depresses the CNS and produces analgesia

 Increases cerebral blood flow and raises ICP

 When used with barbiturate + droperidol/fentanyl +

relaxant, good anaesthesia and a moderate fall in
ICP.
 RES
 Effects on respiratory system are generally
small.

 There is no change in the respiratory

response to CO2.

 There is a decrease in hypoxic drive

when 50% N2O is inspired.
 Interaction with Vitamin B12
 B12 is a bound coenzyme of methionine synthase-
having a tetrapyrrole ring and a central cobalt
atom.
 N O oxidizes the cobalt from Co+ to Co++,
2
which can no longer function as a methyl
carrier.
NB: blockade of this reaction appears to be the
sole metabolic action of N2O, with a
subsequent reduction of the two products-
i. tetrahydrofolate
ii. methionine
 Cont..
 Following very prolonged administration, (> 4 days)
agranulocytosis is an almost universal result.

NB: -"interference with thymidine synthesis is to

be expected in man after 12 hrs of exposure
to N2O, but may appear within 2h or even less
Nunn (BJA 1987)
 Cont..
 Subsequent recommendations (Nunn),
a. N2O > 24h  absolute contraindication
b. N2O ~ 24h  reasonable for healthy patient bone
marrow will be megaloblastic

c. N2O >2h  hepatic methionine synthase will

be depressed effects on DNA synthesis
unpredictable
d. N2O > 0.5h  no measurable effect
 Cont..
 There is irrefutable evidence that N2O is a mild
teratogen and this is undoubtedly due to its
effects on DNA synthesis.

 Therefore, the use of N2O in pregnancy during the

period of organogenesis is inadvisable, if necessary,
cover with folinic acid may offer some protection.

NB:- The possibility of N2O abuse should be

considered in any person with access to the gas
who presents with symptoms & signs resembling
subacute combined degeneration of the cord -
especially dentists!!
 Other Organ Systems
 Skeletal muscle does not relax in the presence of
80% N2O, and muscle blood flow is unaltered

 Unlike the halogenated GA's, N2O is most unlikely to

contribute to malignant hyperpyrexia

 The liver, kidneys, and GIT show no marked effects

in response to N2O, and there is no evidence of
toxicity

 Nausea & Vomiting occur in ~ 15% of patients

postoperative
 Biotransformation

 Rapidly and predominantly eliminated

unchanged through the lungs

 Significant biotransformation is unable

to be assessed
 Advantages
a. Non-flammable & non-explosive
b. Non-irritant
c. Potent analgesic
d. Very rapid onset, changes in depth and
recovery
e. Little or no toxicity during normal
applications
 Disadvantages

a. Weak anaesthetic agent

b. No augmentation of muscle relaxation
c. Diffusion hypoxia on recovery
d. Expansion of closed internal air-spaces
e. Depressed methionine synthase activity

® megaloblastic marrow changes demyelination

of the cord in long term abusers
 OXYGEN TOXICITY
 Oxygen poisoning.
 Second most common gas forming the
normal external air 20.93%
 Preceeded only by Nitrogen 78.10%
 It is vital gas to sustain life
 Partial pressure of O2 in inspired air at
sea level is about 160mmHg
 Cont..
 CNS effects of oxygen toxicity are called
BERT EFFECT named after Paul Bert in
1878…demonstrated convulsions in
Larks
 Pulmonary effects of oxygen toxicity
were named after J.Lorain in 1899…he
found Fatal pneumonia in rats after
after 4 days exposure to 73% O2
 Scenarios
1.High concentrations of oxygen for short
duration of time like-Hyperbaric oxygen
therapy.

2.Lower concentration of the gas are

used for longer durations.
(Fio2>0.60 for 24Hrs or more.)
 Cont..
 Results can be Acute or Chronic

 Acute toxicity-Predominantly CNS

 Chronic toxicity-Predominantly
Pulmonary
 HBOT
 Hyperbaric oxygen is the oxygen
administered at higher than
atmospheric pressure
 Clinical applications
 Carbonmonoxide poisoning
 Decompression sickness
 Respiratory distress of newborn
 Anaerobic infections e.g Gas gangrene
caused by C.welchi
 Refractory chronic osteomyelitis with
draining lesions
 Infected superficial burns
 Sensitization of tumor to radiotherapy
END