Pharmacology of
Nitrous Oxide
Aim
The effects of inhalation sedation (N2O)on
the body and its hazards
Learning objectives
By the end the students should know:  The properties & characteristics of N2O
  How is it absorbed/eliminated by body
  Effects of N2O on Organs systems
  The adverse effects/complications of N2O
  Health and safety issues around N2O
  About scavenging – the reason for/types & how
they work
History of Nitrous Oxide - N2O
1771 Joseph Priestley discovered OXYGEN.
1772 Joseph Priestley discovered NITROUS OXIDE.
  1779
Humphrey Davey discovers some of the effects of
Nitrous Oxide
  1840s Horace Wells, a dentist, employed Nitrous
Oxide as anaesthetic
 1888 Liverpool Dental Hospital used Nitrous Oxide
analgesia for cavity preparation on teeth.
 1936 Dr Harry Langa in the USA began using Nitrous
Oxide analgesia. He was later to write the
standard textbook on Relative Analgesia. RA is
inhalation sedation using a mixture of N2O & O2
The patient is awake, but has a reduced level of
fear and anxiety
Manufacture
•  Ammonium Nitrate crystals is heated
between 250 and 270oC,
NH4NO3
N2O + 2H2O
purified, and stored in compressed form in
metal cylinders
Preparation
30% N2O in liquid form in full cylinder
The pressure gauge (800psi) measures the
vapor pressure of the liquid
Weighing the cylinder is the only way of knowing
how much gas is left!!!!!!”!
N20 e size cylinder weighs 5.4kg empty, 3.37 gas = 8.97kg when full
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Physical properties of N20
Physical Properties
 Its one and a half times heavier than air
(specific gravity 1.53)
 Only inorganic substance other than CO2
to have CNS depressant properties
  Only inorganic gas used to produce
anesthesia in humans
 N2O constitutes 0.00005% of the earth’s
atmosphere !!
Physical Properties
SOLUBILITY
  N2O require heat for vaporization into
gaseous state
The Solubility in blood of an agent is expressed as the
 Relatively insoluble in blood : blood-gas solubility
coefficient is 0.47 at 37°C
The “Blood Gas Distribution Coefficient” is the ratio
of the number of molecules of the agent in the blood
phase, to the number of molecules in the gaseous
phase, per unit volume, at equilibrium.
  Nitrous oxide is carried in simple solution in the
body and does not enter into any chemical
combination during administration
SOLUBILITY
“BLOOD GAS DISTRIBUTION COEFFICIENT”
The inhalation agent N2O is administrated as a gas
Inhalation
Absorption
The solubility of Nitrous Oxide in the blood is an important
consideration because it effect the rate of absorption,
distribution and rate of excretion.
BGDC for N2O is 0.47 compared to Halothane which has
BGDC of 2.36 and Diethyl Ether 12.10
Nitrous Oxide is poorly soluble in blood therefore induction
and recovery are rapid.
The Lungs
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Absorption
MOVEMENT OF NITROUS OXIDE DOWN
PARTIAL PRESSURE GRADIENT
CNS saturation occurs by displacement of
N2 by N2O , usually in 3-5 minutes
N2o is rapidly absorbed into the CV due to
large concentration gradient of N2O
between alveolar sacs and blood
Tissues with greater blood flow (brain,
heart, liver, kidney) receive greater
amounts of N2O
N20 reach the brain by crossing alveolar
membranes into the blood
Nitrous oxide is carried in simple solution
in the body and does not enter into any
chemical combination during administration
Absorption
Tissues with poor blood supply (fat, muscle,
connective tissue) absorb small amounts
Alveolar and grey-matter tension during
uptake of 25% nitrous oxide
Proportional saturation
for 25% N2O
1.0
0.8
Slow absorption occurs once primary
saturation has completed
Alveolar tension
Grey-matter tension
0.6
0.4
There is no body reservoir present once N2O
terminated
0.2
0
ELIMINATION OF NITROUS OXIDE
5
10
15
20
Time in minutes
Elimination of N2O
Returning with the
blood to the left side of
the of the heart and
are then distributed
through the arterial
supply to lung.
Hence movement of
N2O down partial
pressure gradient
ELIMINATION
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Biotransformation
•  N2O undergoes no biotransformation in the
body
DIFFUSION HYPOXIA
Rapid diffusion of large volumes of N2O into the
alveoli produces a significant dilution of O2 present.
• In normal alveolus air contains at least 16 % O2.
• For few minutes on termination of RA the O2 may drop to 10% !!
•  Majority of N2O is exhaled unchanged
3-5mins following termination of delivery
•  1% eliminated via skin and lungs in 24hrs
Potency
•  Nitrous oxide is the least potent of all
anaesthetic gases
•  Potency is expressed in terms of a Minimal
Alveolar Concentration for an agent (MAC)
• There is a rapid diffusion of N2O from the blood into the alveoli.
• This decreases CO2 arterial tension with decrease stimulus for
respiration and this also dilutes the O2 present, causes the hypoxia.
• Hypoxia causes headache, nausea, and lethargy-hangover effect.
however
Prevent DIFFUSION HYPOXIA by giving 100%oxygen
for 2 - 3 minutes.
MAC
The concentration of the inhalation
anaesthetic required to abolish the response
to a standard surgical stimulus in 50% of the
patients
Minimal Alveolar Concentration of N2O
is high –about 104%
Potency of N2O
POTENCY
As N2O has a high MAC hence a low
potency probably the lowest potency
value of all the anaesthetic gases
therefore very safe
•  N2O in sub-anaesthetic dosages can
produce analgesia
•  N20 + O2 at 20%/80% mix = to 10-15mg
of morphine
•  Optimal concentration is 35%
.
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Nitrous Oxide has the following properties
and characteristics:-
So what are:-
Anxiolytic properties hence it will reduce the distressing feeling of
tension, anxiety , so inducing a state of relaxation and
panic
Analgesic
It is estimated that a 20% : 80% mixture of N2O - O2
produces the analgesic effectiveness of 10-15mg of
morphine.
Amnesia
Preventing recall of events that occurred after the
sedation was given
The Effects of Nitrous Oxide on
organ systems
Weak anesthetic agent
Actions of Nitrous Oxide on
CNS
•  Nobody really knows the action of N2O on the CNS
•  Latest theory is that it affects the NMDA glutamate receptors
Cardiovascular system
•  No changes in heart rate or cardiac output
•  BP remains stable with only slight decrease
•  N-methyl-D-aspartate excite the nerves
•  N2O blocks their ability to detect a normal signal - sedating
Respiratory System
•  Cutaneous vasodilatation
GI System
•  N2O is non-irritating to pulmonary
epithelium
•  No clinically significant effects unless there
is an obstruction
•  Changes drop in respiratory rate and depth
more likely due to anxiolytic effects
•  N/V rarely seen unless hypoxia present
•  Can be used in hepatic dysfunction
•  Slight elevation of resting respiratory
minute volume at 50%/50% mix
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Hematopoietic System
Musculoskeletal System
•  No direct relaxation of skeletal muscle
•  Long-term exposure greater than 24hrs
can produce transient bone marrow
depression
•  Anxiolytic effects helps relaxation
Reproductive System
•  Uterine contraction not inhibited
•  Pregnancy is a relative contra-indication
(avoid 1st trimester)
Complications and Adverse
Reaction of Nitrous Oxide
Acute Complications
Excessive perspiration
peripheral vasodilatation
2-3% incidence
If pallor, decreased blood pressure,
increased heart rate- consider syncope
(100% O2 )
Treatment - decrease N20%
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Acute Complications
Nausea
Causes
over sedation - especially >50%
long procedures
anxious patients
inherent tendency
full stomach ??
Treatment
decrease N2O
Complications
Vomiting
Signs
pallor
sweating
cold / clammy
increased salivation
active swallowing
Complications
Shivering
Rare
Usually at end of procedure
Treatment
Reassurance, blanket
Complications
Vomiting
Potentially serious
aspiration pneumonia, obstruction
Pediatric more often than adult
Early recognition of nausea is key to
prevention
Complications
Vomiting
Management
100% O2
remove dental instrumentation &
rubber dam
turn head to side
emesis basin - high volume suction
replace nasal hood - 100% 02 3-5 mins
Sexual Phenomena
Sexual hallucination/arousal
Females more frequent
Precautions
Always have assistant present
Avoid concentrations >50%
Never leave patient unattended
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From a Health and Safety
prospective:Is there a problem
With N2O pollution???
Animal studies have demonstrated
adverse effects at exposure to high
levels so the potential for harm cannot
be dismissed
BDA Advise sheet A3 - March 2005
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Retrospective study of 459 dental nurses in
California into the association between N2O
occupational exposure and fertility.
Significant reductions only in those
exposed to unscavenged N2O for more
than 5 hours per week.
Rowland et al, 1992
Adverse reproductive outcomes are linked to
B12 deficient individual and those exposed to
high nitrous oxide levels
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Workforce Exposure Levels (WEL) /
Occupational Exposure Standards (OSEs)
are based on an 8 hour time weighted average (TWA)
In the UK the WEL /OSE for
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8 hour TWA therefore equals
Understanding Time Weighted Average
(TWA)
250 X 3/8 = 93.4ppm
But if operator works 2 sessions per day
TWA = 186.8ppm
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Scavenging
• Not Scavenged but vented into the local environment
What is it?
•  Leakage from breathing delivery system ie mask
Why use it?
•  Leakage from circuit
•  Exhaled breath
What are the benefits?
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MediScav Active Scavenger Unit
Description: Comes complete
with external debris filter/
outlet, one metre 30mm
transfer hose and vent warning
label. Unit is CE marked,
requires a 240v power point
and external wall vent Price: £670.00
Description: The New Miniscav active
scavenger unit Fully sound proofed Carrying
handle The pump requires an exit vent
through an external wall for: waste hose
assembly (£25) Additional 20mm transfer
hose £10/m
Certosimo et al 2002
N2O Scavenging - Device
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Active Scavenging achieves < 100ppm
71%-91%
>50ppm
ACTIVE + PASSIVE
needed to
achieve US standard of
25 ppm TWA
Certosimo et al 2002
•  check (at least once a week) that scavenging and
ventilation equipment are working properly and have it
regularly serviced in accordance with the
manufacturer’s recommendations and at least every
12 months.
•  Periodically review how you operate scavenging
equipment to ensure that it is being used correctly.
•  Make sure your employees are aware of the possible
risks to their health, understand why scavenging and
ventilation are necessary and how
to use the equipment properly
BDA A3 Advise Sheet
Summary
Properties of How does
an ideal sedative
Induction Characteristics
Smooth
Anxiolysis
Yes
Cardiovascular stability Stable
Ease of titration
Easy
Induction and recovery
Rapid
Metabolism
O%
Ease of breathing
Non-pungent
Blood Gas Solubility
Low
Potency (MAC)
Weak
Speed of change in sedation level Rapid
Systemic toxicity
potentially None
Environmental effects
None
Analgesia
Yes
ANY QUESTIONS?
N2O rate?
Yes
Yes
Stable
Easy
Rapid
1%
Non-pungent
Low
Weak
Rapid
Yes prolonged use
Yes
Yes
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