Q.

Briefly describe the adverse effect of nitrous oxide

Overview
• nitrous oxide may cause several adverse effect
• due to its physichochemical properties, pharamacokinetic pharamacokinetic proerties and
pharamacodynamic properties

Overview
• CNS
• CVS
• RESP
• Hematology
• Environment

Physichochemical properties
Flammability
•NO2 is not flammable ,
•but, may support combustion of other agent even in the absence of oxygen
•above 450 c it may decomposes to nitrogen and oxygen

Preparation
•nitros oxide is prepared by heating the ammonium nitrate at 270 celcius
•if the reaction is poorly controlled it may cause production of nitrogen dioxide
•the possible contamination of nitrous oxide with these impurities
•NO2 may lead to fatal effect on anethetized patinet

Pollution of environment
•nitorus oxide that is used in nonrebreathing circuit may cause pollution of OT environment

Pharamacokinetic properties
uptake of agent
•nitrous oxide has low blood: gas partition coeeficient ,
•however the 1 MAC of nitrous oxide is 106%
•therefore, nitrous oxide cannot be used as single agent alone during induction
•thus it may not produce induction of anesthesia

Pharamacodynamic effect
CVS
•Mild myocardial depressant with mild indirect symphathomimetic, may be detrimental with patient with
decrease in myocardial disease
•there is also small depression of carotid baroreceptor reflexes that cause slow response to the hypotension

CVS
•Increased Coronary blood flow

Respiratory system
Breathing pattern
•decrease in tidal volume and increase in repiratory rate and minute volume with CO2 ventilation response
maintained
•It may cause alveolar collapse in obstructed lung segment

PVR
•Nitrous oxide may increase the pulmonary vascular resistance
•result in pulmonary hypertension and subsequently increase in right atrial pressure

Diffusion hypoxia
•Diffusion hypoxia is the condition in which the elimination of a poorly soluble gas, such as N2O, from the blood
into the alveoli of lung occur at high rate
•Therefore ,N2O add as much as 1 l/min to alveolar air
•this gas dilutes alveolar air, and available oxygen,
•Therefore , when room air is inspired ,hypoxia may result
•this is usually only mild and rarely clinically significant
•although this may occur with any anaesthetic agent, its magnitude is insignificant unless an insoluble agent,
such as nitrous oxide, has been inhaled for some time
 •under these circumstances as much as 30 l may be dissolved in the blood and tissues
•recommended to continue oxygen after discontinuation of anesthesia see above
Expansion of gas filled cavity
•the blood gas partition coeeficient for nitrous oxide is 0.47
•the blood: gas partition coeffiecient for nitrogen is 0.014
•therefore , it is 34 x more soluble than nitrogen
•the highers soulubility allow nitrous oxide to leave the blood and diffused into air-filled cavity 34 x more
rapidly than nitrogen
•therefore, the diffusion of nitrous oxide into air filled cavity : such as :
•middle ear ( tympanic membrane rupture when the nitrous oxide diffuse into the middle ear with the
eustachian tube blocked )
•intraocular ( the diffusion of nitrous oxide into rigid intraocular cavity may cause retinal artery occlusion and
visual loss ) ,
•air embolus ,
•GIT closed loop bowel obstruction ( enlargement of intestinal gas) ,
•bullae ( diffusion of nitrous oxide into air filled bullae resulting in pneumothorax ) ,
•ETT ( increase in ETT cuff pressure )

CNS
ICP
•Increase ICP secondary to increase in cerebral blood flow

GIT
•Nausea and vomiting 15% of patients postoperative
Impair vitamin B12 synthesis
Overview
•use of nitrous oxide more than six hours may cause inactivation of with vitamin B12 dependent DNA
enzymes
•The vitamin B12 dependent DNA enzymes are methionine synthase and thymidilate synthase

Vitamin B12
•Methionine synthase is the enzyme that catalyze the conversion of monovalent cobalamine to
tetrahydrofolate and methionine
•B12 coenzyme that bound to methionine synthase,
•It comprises of a tetrapyrrole ring and a central cobalt atom
•N2O oxidizes the cobalt from Co+ to Co++,
•as result Co++ cannot function as a methyl carrier and prevent the transmethylation reaction
•therefore , it may cause depletion of tetrahydrofolate and methinone

Methionine & s-adenosylmethionine

Physiological effect of methionine

Overview
•Involve in protein synthesis,
•methionine acts as a precursor to S-adenosylmethionine (SAM)

S-adenosylmethionine
•SAM is a direct methyl donator in a number of important reactions:
1.Conversion of noradrenaline to adrenaline
2.Synthesis of arachidonic acid
3.myelination of nerves

Reaction between N2O and methionine synthase

•after administration of N2O the first detectable changes are a reduction in methionine synthase activity,
•it is then followed by an interference with DNA synthesis
•following very prolonged administration, (>> 4 days), result in agranulocytosis and peripheral
granulocytopenia after 3 days
Physiological of tetrahydrofolate
•Tetrahydrofolate is a compound that bond to precursor for DNA synthesis
•Reduction in tetrahydrofolate interere DNA synthase
•Decrease synthesis of deoxythiamidine to thiamidine > megaloblastic anemia

Prognosis
•hematological changes is reversible