| 1.1 Substance|
| 1.2 Group|
| 1.3 Synonyms|
| 1.4 Identification numbers|
| 1.4.1 CAS number|
| 1.4.2 Other numbers|
| 1.5 Brand names, Trade names|
| 1.6 Manufacturers, Importers|
| 2.1 Main risks and target organs|
| 2.2 Summary of clinical effects|
| 2.3 Diagnosis|
| 2.4 First-aid measures and management principles|
|3. PHYSICO-CHEMICAL PROPERTIES|
| 3.1 Origin of the substance|
| 3.2 Chemical structure|
| 3.3 Physical properties|
| 3.4 Other characteristics|
|4. USES/CIRCUMSTANCES OF POISONING|
| 4.1 Uses|
| 4.2 High risk circumstance of poisoning|
| 4.3 Occupationally exposed populations|
|5. ROUTES OF ENTRY|
| 5.1 Oral|
| 5.2 Inhalation|
| 5.3 Dermal|
| 5.4 Eye|
| 5.5 Parenteral|
| 5.6 Others|
| 6.1 Absorption by route of exposure|
| 6.2 Distribution by route of exposure|
| 6.3 Biological half-life by route of exposure|
| 6.4 Metabolism|
| 6.5 Elimination by route of exposure|
| 7.1 Mode of Action|
| 7.2 Toxicity|
| 7.2.1 Human data|
| 126.96.36.199 Adults|
| 188.8.131.52 Children|
| 7.2.2 Relevant animal data|
| 7.2.3 Relevant in vitro data|
| 7.2.4 Workplace standards|
| 7.2.5 Acceptable daily intake (ADI) and other guideline levels|
| 7.3 Carcinogenicity|
| 7.4 Teratogenicity|
| 7.5 Mutagenicity|
| 7.6 Interactions|
|8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS|
| 8.1 Material sampling plan|
| 8.1.1 Sampling and specimen collection|
| 184.108.40.206 Toxicological analyses|
| 220.127.116.11 Biomedical analyses|
| 18.104.22.168 Arterial blood gas analysis|
| 22.214.171.124 Haematological analyses|
| 126.96.36.199 Other (unspecified) analyses|
| 8.1.2 Storage of laboratory samples and specimens|
| 188.8.131.52 Toxicological analyses|
| 184.108.40.206 Biomedical analyses|
| 220.127.116.11 Arterial blood gas analysis|
| 18.104.22.168 Haematological analyses|
| 22.214.171.124 Other (unspecified) analyses|
| 8.1.3 Transport of laboratory samples and specimens|
| 126.96.36.199 Toxicological analyses|
| 188.8.131.52 Biomedical analyses|
| 184.108.40.206 Arterial blood gas analysis|
| 220.127.116.11 Haematological analyses|
| 18.104.22.168 Other (unspecified) analyses|
| 8.2 Toxicological Analyses and Their Interpretation|
| 8.2.1 Tests on toxic ingredient(s) of material|
| 22.214.171.124 Simple Qualitative Test(s)|
| 126.96.36.199 Advanced Qualitative Confirmation Test(s)|
| 188.8.131.52 Simple Quantitative Method(s)|
| 184.108.40.206 Advanced Quantitative Method(s)|
| 8.2.2 Tests for biological specimens|
| 220.127.116.11 Simple Qualitative Test(s)|
| 18.104.22.168 Advanced Qualitative Confirmation Test(s)|
| 22.214.171.124 Simple Quantitative Method(s)|
| 126.96.36.199 Advanced Quantitative Method(s)|
| 188.8.131.52 Other Dedicated Method(s)|
| 8.2.3 Interpretation of toxicological analyses|
| 8.3 Biomedical investigations and their interpretation|
| 8.3.1 Biochemical analysis|
| 184.108.40.206 Blood, plasma or serum|
| 220.127.116.11 Urine|
| 18.104.22.168 Other fluids|
| 8.3.2 Arterial blood gas analyses|
| 8.3.3 Haematological analyses|
| 8.3.4 Interpretation of biomedical investigations|
| 8.4 Other biomedical (diagnostic) investigations and their interpretation|
| 8.5 Overall Interpretation of all toxicological analyses and toxicological investigations|
| 8.6 References|
|9. CLINICAL EFFECTS|
| 9.1 Acute poisoning|
| 9.1.1 Ingestion|
| 9.1.2 Inhalation|
| 9.1.3 Skin exposure|
| 9.1.4 Eye contact|
| 9.1.5 Parenteral exposure|
| 9.1.6 Other|
| 9.2 Chronic poisoning|
| 9.2.1 Ingestion|
| 9.2.2 Inhalation|
| 9.2.3 Skin exposure|
| 9.2.4 Eye contact|
| 9.2.5 Parenteral exposure|
| 9.2.6 Other|
| 9.3 Course, prognosis, cause of death|
| 9.4 Systematic description of clinical effects|
| 9.4.1 Cardiovascular|
| 9.4.2 Respiratory|
| 9.4.3 Neurological|
| 22.214.171.124 CNS|
| 126.96.36.199 Peripheral nervous system|
| 188.8.131.52 Autonomic nervous system|
| 184.108.40.206 Skeletal and smooth muscle|
| 9.4.4 Gastrointestinal|
| 9.4.5 Hepatic|
| 9.4.6 Urinary|
| 220.127.116.11 Renal|
| 18.104.22.168 Others|
| 9.4.7 Endocrine and reproductive systems|
| 9.4.8 Dermatological|
| 9.4.9 Eye, ears, nose, throat: local effects|
| 9.4.10 Haematological|
| 9.4.11 Immunological|
| 9.4.12 Metabolic|
| 22.214.171.124 Acid-base disturbances|
| 126.96.36.199 Fluid and electrolyte disturbances|
| 188.8.131.52 Others|
| 9.4.13 Allergic reactions|
| 9.4.14 Other clinical effects|
| 9.4.15 Special risks|
| 9.5 Others|
| 9.6 Summary|
| 10.1 General principles|
| 10.2 Relevant laboratory analyses and other investigations|
| 10.2.1 Sample collection|
| 10.2.2 Biomedical analysis|
| 10.2.3 Toxicological analysis|
| 10.2.4 Other investigations|
| 10.3 Life supportive procedures and symptomatic treatment|
| 10.4 Decontamination|
| 10.5 Elimination|
| 10.6 Antidote treatment|
| 10.6.1 Adults|
| 10.6.2 Children|
| 10.7 Management discussion|
|11. ILLUSTRATIVE CASES|
| 11.1 Case reports from literature|
| 11.2 Internally extracted data on cases|
| 11.3 Internal cases|
|12. ADDITIONAL INFORMATION|
| 12.1 Availability of antidotes|
| 12.2 Specific preventive measures|
| 12.3 Other|
|14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESSES|
azoto protossido (Budavari, 1989; Reynolds, 1989)
hyponitrous acid anhydride
1.4 Identification numbers
1.4.1 CAS number
1.4.2 Other numbers
1.5 Brand names, Trade names
To be completed by each centre
1.6 Manufacturers, Importers
To be completed by each centre
2.1 Main risks and target organs
The main complication following inhalation of nitrous oxide is
varying degrees of hypoxia, affecting the functions of the
heart and the brain. Chronic exposure can cause neurological
and haematological changes.
2.2 Summary of clinical effects
Nitrous oxide poisoning mainly causes varying degrees of
hypoxia. This may be associated with hypotension, fatal
cardiac arrhythmias, headache, dizziness, anoxic brain damage,
cerebral oedema and permanent mental deficit. Chronic
exposure can cause megaloblastic erythropoiesis and
neurological features similar to subacute combined
degeneration of the
Symptoms of poisoning include hypotension, fatal cardiac
arrhythmias, headache, dizziness, anoxic brain damage,
cerebral oedema and permanent mental deficit
Measurement of nitrous oxide levels in blood is of no
therapeutic value. In cases of acute toxicity, arterial blood
gas analysis may be helpful. Full blood counts are useful in
2.4 First-aid measures and management principles
Remove the patient from the source of exposure.
Establish and maintain adequate airway by removing secretions
from mouth and trachea.
Maintain respiration. Respiratory depression should be treated
with assisted respiration.
Maintain blood pressure.
Maintain body warmth.
Treat cerebral oedema.
Symptomatic and supportive therapy.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
Nitrous oxide is a synthetic substance.
It can be prepared by the following methods:
A. Decomposition of ammonium nitrate by heat
NH4NO3 = N2O + H2O
B. Decomposing an equimolecular mixture of ammonium
sulphate and sodium nitrate at 240°C.
C. A number of methods have been described for the
preparation of nitrous oxide by reduction of nitric acid or
nitrates. The chemicals used are stannous chloride, anhydrous
formic acid and oxalic acid.
2HNO3 + SnCl2 + 8HCl = 4SnCl4 + 5H2O + N2O
2KNO3 + 6H.COOH = N2O + 4CO2 + 2H.COOK
2KNO3 + H2SO4 + 4 (COOH)2 = N2O + 8CO2 +
K2SO4 + 5H2O
D. Nitric acid when reduced with hydrazine or hydroxylamine
yields nitrous oxide.
HNO2 + N2H4 = N2O + NH3 + H2O
HNO2 + NH2OH = N2O + 2H2O
E. It is also possible to isolate nitrous oxide produced
directly by the union of its elements in the nitrogen-oxygen
3.2 Chemical structure
Molecular weight: 44.02
As the nitrous oxide molecule is linear it must have either
two double links or a single and a triple. There are two
N <-- N = O+ and N+ = N --> O (Sidgwick, 1962)
3.3 Physical properties
A stable, non-irritating colourless gas with slightly
sweetish odour and taste (Reynolds, 1989; Budavari,
Solubility - freely soluble in alcohol and chloroform
and also soluble in ether and oils (Reynolds, 1989;
The solubility of nitrous oxide in aqueous salt
solutions and in solutions of aqueous glycerol are
lower than those in water (Prideaux and Lambourne,
Solubility in water - 1 litre of gas in 1.5 litre of
water at 20°C and 2 atm.
Boiling point: -88.46°C (at atmospheric pressure)
Melting point: -90.81°C (at atmospheric pressure)
Density as a gas: 1.997 mg/cm3 at 0°C at atmospheric
Vapour pressure: 4.93 pascals (at 20°C)
Relative molecular mass: 44.02
Viscosity: 1488.99 poise (at 27°C)
Specific gravity: 1.529 at 0°C, at atmospheric
3.4 Other characteristics
4. USES/CIRCUMSTANCES OF POISONING
Nitrous oxide is used for induction and maintenance of
anaesthesia and, in sub-anaesthetic concentrations, for
analgesia in a variety of situations. For anaesthesia,
it is commonly used in a concentration of 50-70% in
oxygen as part of a balanced technique in association
with other inhalation or intravenous agents.
A mixture of nitrous oxide and oxygen containing 50% of
each gas (Entonox) is used to produce analgesia without
loss of consciousness. Self-administration, using a
demand valve, is popular and may be appropriate in
obstetric practice, for changing painful dressings, as
an aid to post-operative
physiotherapy, and in emergency ambulances (Prasad,
4.2 High risk circumstance of poisoning
Using a suitable anaesthetic apparatus, a mixture with 20-30%
oxygen for induction and maintenance of light anaesthesia.
For analgesia, as a mixture with 50% oxygen, according to the
4.3 Occupationally exposed populations
Nitrous oxide is not recommended for anaesthesia and analgesia
in patients with head injuries, impaired consciousness,
facial injuries, the very young and the very old,
pneumothorax, decompression sickness and heavy sedation
including the effects of alcohol (Johnson, 1979; Reynolds,
Nitrous oxide diffuses into gas-filled body cavities and care
is essential when using it in at-risk patients (eg. gaseous
abdominal distension, pneumothorax, or similar cavities in
pericardium or peritoneum) (Reynolds, 1989).
Nitrous oxide should not be administered for more than 24
hours because of the risk of bone marrow depression (Reynolds,
Anaesthesia may be obtained, with some sub-oxygenation, with
alveolar concentrations of 85-90% (625-650 mm/Hg). These
concentrations are not safe and nitrous oxide is therefore
unsuitable as a sole agent for surgical anaesthesia (Adriani,
5. ROUTES OF ENTRY
The main route of exposure is through inhalation.
6.1 Absorption by route of exposure
Nitrous oxide is rapidly absorbed on inhalation (Reynolds,
6.2 Distribution by route of exposure
As a result of lower tissue/blood partition coefficients, the
equilibration of nitrous oxide in most tissues occurs rapidly.
6.3 Biological half-life by route of exposure
Nitrous oxide is not metabolized in the body.
6.5 Elimination by route of exposure
The blood/gas partition coefficient is low and most of the
inhaled nitrous oxide is rapidly eliminated through the lungs,
though small amounts diffuse through the skin (Reynolds,
7.1 Mode of Action
Nitrous oxide is 35 times more soluble than nitrogen. The gas
exchanges with nitrogen and diffuses into hollow viscera and
body spaces potentially containing air such as pneumothorax,
paranasal sinuses and pneumoperitoneum or into the cerebral
ventricles following pneumoencephalography. This expands the
body of trapped air and increases the pressure within such
closed spaces. When administration is discontinued, nitrous
oxide is released into the alveoli, diluting the alveolar
gases. A reduction in alveolar oxygen tension may result.
This is referred to as diffusion anoxia (Adriani, 1983).
Because of the high concentration of nitrous oxide required to
produce and maintain anaesthesia, hypoxia is an unavoidable
accompaniment to its use. During induction with high
concentrations of nitrous oxide, the oxygen in the lungs is
rapidly used up and the anoxia with increased respiratory
effort causes rapid depletion of carbon dioxide in the
Absence of carbon dioxide and depression of the medullary
centres by the anaesthetic quickly lead to respiratory failure,
and rarely, the patient's cerebral function fails to recover
from cerebral damage caused by the prolonged anoxia. The
brain suffers anoxia from the very beginning of the
administration of the gas, and not from just the moment of
cessation of respiratory movements. Thus, the period of
anoxia may be five minutes or more, sufficient to cause
permanent brain damage in the susceptible individual. The
arbitrary "safe period" of eight minutes may be too long for
some patients (Thienes and Haley, 1972).
Nitrous oxide induces inconsistent changes in the basal levels
of the thalamic nuclei. The mechanism of analgesia is
believed to involve a direct intraspinal anti-nociceptive
action rather than depression of limbic function. In the
brain stem, responses evoked by pain stimulation are
depressed, although the extent of depression may be variable.
Nitrous oxide in anaesthetic doses increases cerebral blood
flow and intracranial pressure (Frost, 1985).
7.2.1 Human data
Nitrous oxide is harmless and non-irritating to
the respiratory tract, but concentrations over
50 ppm reduce dexterity, cognition and motor
and audiovisual skills (Adriani, 1983;
Ellenhorn and Barceloux, 1988).
Neurological manifestations similar to subacute
combined degeneration of the spinal cord were
reported following prolonged heavy exposure to
nitrous oxide in 15 patients
Poisoning manifested by symptoms such as
cyanosis, hypotension and methaemoglobinaemia
occurred in two patients anaesthetized with
nitrous oxide contaminated with nitric oxide
Psychological dependency on nitrous oxide may
occur (Adriani, 1983).
Prolonged as well as intermittent repeated
exposure to nitrous oxide may cause
megaloblastic haemopoiesis (Amess et al,
1978; Nunn et al, 1982).
Malignant hyperpyrexia induced by nitrous oxide
anaesthesia was reported in an eleven year-old
girl (Ellis et al 1974).
7.2.2 Relevant animal data
Exposure of pregnant rats to nitrous oxide has caused
foetal death, skeletal malformations and various
macroscopic lesions (Reynolds, 1989).
Physical dependency and withdrawal have been
demonstrated in mice (Adriani, 1983).
7.2.3 Relevant in vitro data
7.2.4 Workplace standards
7.2.5 Acceptable daily intake (ADI) and other guideline levels
In the USA, the FDA considered that there was sufficient
evidence to cause concern about the carcinogenic and
teratogenic potential of nitrous oxide (Reynolds, 1982).
However, no convincing evidence of carcinogenicity in
man has been shown by epidemiological studies (Baden, 1985).
The incidence of spontaneous abortion is increased among women
exposed to nitrous oxide. It has been suggested, but not
proven, that there is an increased incidence of congenital
anomalies in the offspring of women exposed during pregnancy
and of spontaneous abortion in the wives of exposed men
(Baden, 1985). No adverse effects were found in a etrospective
study of 175 pregnancies during which nitrous oxide was
administered. However, all anaesthesias were of short duration
(20 to 30 minutes ) and 97% were administered during the
second trimester (Aldridge and Tunstall, 1986).
Nitrous oxide is not mutagenic (Baden, 1985).
There are conflicting reports that nitrous oxide can reduce or
enhance therapeutic effects of methotrexate (Reynolds, 1989).
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
184.108.40.206 Toxicological analyses
220.127.116.11 Biomedical analyses
18.104.22.168 Arterial blood gas analysis
22.214.171.124 Haematological analyses
126.96.36.199 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
188.8.131.52 Toxicological analyses
184.108.40.206 Biomedical analyses
220.127.116.11 Arterial blood gas analysis
18.104.22.168 Haematological analyses
22.214.171.124 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
126.96.36.199 Toxicological analyses
188.8.131.52 Biomedical analyses
184.108.40.206 Arterial blood gas analysis
220.127.116.11 Haematological analyses
18.104.22.168 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
22.214.171.124 Simple Qualitative Test(s)
126.96.36.199 Advanced Qualitative Confirmation Test(s)
188.8.131.52 Simple Quantitative Method(s)
184.108.40.206 Advanced Quantitative Method(s)
8.2.2 Tests for biological specimens
220.127.116.11 Simple Qualitative Test(s)
18.104.22.168 Advanced Qualitative Confirmation Test(s)
22.214.171.124 Simple Quantitative Method(s)
126.96.36.199 Advanced Quantitative Method(s)
188.8.131.52 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
184.108.40.206 Blood, plasma or serum
220.127.116.11 Other fluids
8.3.2 Arterial blood gas analyses
8.3.3 Haematological analyses
8.3.4 Interpretation of biomedical investigations
8.4 Other biomedical (diagnostic) investigations and their
8.5 Overall Interpretation of all toxicological analyses and
9. CLINICAL EFFECTS
9.1 Acute poisoning
As the main complications are those due to varying
degrees of hypoxia, administration of nitrous oxide
without adequate oxygen can cause hypotension, cardiac
arrhythmias and anoxic brain damage with headache,
cerebral oedema, and permanent mental deficit.
9.1.3 Skin exposure
9.1.4 Eye contact
9.1.5 Parenteral exposure
9.2 Chronic poisoning
Chronic exposure to nitrous oxide may have adverse
effects on rapidly dividing cells such as those of the
bone marrow, germ plasma and foetal tissues. A
transient leukopenia may follow prolonged use (24 hours
or more). Chronic exposure affects vitamin B12
metabolism, resulting in bone marrow and neurological
changes. Neurological changes in dentists have been
reported that are strongly suggestive of combined
degeneration of the spinal cord similar to that
occurring in pernicious anaemia (Adriani, 1983).
9.2.3 Skin exposure
9.2.4 Eye contact
9.2.5 Parenteral exposure
9.3 Course, prognosis, cause of death
Recovery from respiratory depression is usually complete.
Deaths have been reported from use for non-medical purposes or
for "entertainment". These have been ascribed to asphyxia
from inadequate ventilation of areas in which high
concentrations may develop from inhalation of mixtures with
insufficient oxygen or from suicide (Adriani, 1983; Suruda and
McGlothin, 1990). The cause of death may be cardiac
arrhythmia (Ellenhorn and Barceloux, 1988).
9.4 Systematic description of clinical effects
Recovery from respiratory depression is usually
Deaths have been reported from use for non-medical
purposes or for "entertainment". These have been
ascribed to asphyxia from inadequate ventilation of
areas in which high concentrations may develop from
inhalation of mixtures with insufficient oxygen or from
suicide (Adriani, 1983; Suruda and McGlothin, 1990).
The cause of death may be cardiac arrhythmia (Ellenhorn
and Barceloux, 1988).
During anaesthesia, nitrous oxide decreases tidal volume,
increases respiratory rate and minute ventilation, and
pCO2 is normally unchanged. It depresses ventilatory
response to hypoxia and
tracheal mucociliary flow.
Exposure to nitrous oxide can cause headache,
dizziness, euphoria, excitation, depression and
raised intracranial pressure as a result of
Six patients experienced psychotic sensations of
varying severity during anaesthesia with
nitrous oxide and oxygen for caesarean section
18.104.22.168 Peripheral nervous system
Severe neurological symptoms in 15 patients (all
but one of whom were dentists) following
prolonged heavy exposure to nitrous oxide
associated with professional use, self-
administration, or both, have been reported.
Initial symptoms were usually numbness or
tingling in the hands or legs. Later symptoms
included: Lhermitte sign (12 patients), numbness
of trunk (10 patients), impairment of
equilibrium or gait (12 patients), inability to
walk unassisted (7 patients), impotence (7
patients), sphincter impairment (4 patients),
mental changes (7 patients), dysarthria (2
patients), and impairment of smell or taste.
Ten patients were forced to stop work.
Symptoms resembled those of subacute
combineddegeneration of the spinal cord, and it
was considered possible that nitrous oxide
interfered with the action of vitamin B12 on
the nervous system. All improved on stopping
exposure to nitrous oxide and regained the
ability to walk unaided, but 6 patients had a
relapsing course associated with re-exposure to
nitrous oxide. Administration of
corticosteroids to 6 patients, and vitamin B12
to 4 patients did not appear to influence the
extent of recovery (Layzer, 1978).
22.214.171.124 Autonomic nervous system
Autonomic manifestations may vary depending on
the levels of nitrous oxide. During analgesia,
there is a predominance of alpha-adrenergic
stimulation (increased peripheral vascular
resistance and blood pressure); by contrast,
during anaesthesia there is a predominance of
beta-adrenergic activation (raised cardiac
output, heart rate, blood pressure, muscle
blood flow and reduced systemic vascular
resistance) occurs (Eger, 1985). As a result of
increased sympathetic activity nitrous oxide
may increase heat production and reduce heat
loss by causing cutaneous soconstriction,
contributing to malignant hyperthermia in
susceptible individuals (Brodsky, 1985).
126.96.36.199 Skeletal and smooth muscle
Nitrous oxide increases skeletal muscle activity,
and has little if any effect on neuromuscular
blockade produced by non-depolarising muscle
relaxants (Miller, 1985).
Rarely nausea and vomiting may occur following exposure
to nitrous oxide.
Nitrous oxide inactivates methionine synthetase in the
liver. Although this and other unknown factors may lead
to hepatic injury there is no definite evidence of
clinically significant liver damage (Brodsky,
A small but significantly increased incidence of
renal stones was found in male dentists exposed
to nitrous oxide (Cohen, 1980).
9.4.7 Endocrine and reproductive systems
Impotence associated with nitrous oxide-induced
myeloneuropathy has been reported (Layzer, 1978).
9.4.9 Eye, ears, nose, throat: local effects
Hearing acuity was reduced in a few patients after
anaesthesia with nitrous oxide for adenotonsillectomy
Bone marrow depression
In a prospective study of patients undergoing cardiac
by-pass surgery, 8 patients who received a mixture of
nitrous oxide 50% and oxygen 50% continuously for 24
hours suffered megaloblastic changes in their bone
marrow and abnormal deoxyuridine suppression tests
(indicative of abnormal vitamin B12 metabolism). Of 9
similar patients who received the nitrous oxide and
oxygen mixture for 5 - 12 hours only during the
operation, 3 had mildly megaloblastic erythropoiesis
and 2 of these and 1 other patient had abnormal
deoxyuridine suppression tests. In a further 5 similar
patients who had not received nitrous oxide, the bone
marrow was normoblastic and deoxyuridine suppression
tests were normal (Amess, 1978).
Although nitrous oxide appears to depress the
production, motility and chemotactic response of
leukocytes, the significance of nitrous oxide in
interfering with the cell mediated immunity is not
known (Brodsky, 1985).
188.8.131.52 Acid-base disturbances
184.108.40.206 Fluid and electrolyte disturbances
9.4.13 Allergic reactions
9.4.14 Other clinical effects
9.4.15 Special risks
10.1 General principles
A patient with nitrous oxide poisoning should be removed
from the source of exposure. Establish airway and maintain
respiration. Administer oxygen. Maintain blood pressure .
10.2 Relevant laboratory analyses and other investigations
10.2.1 Sample collection
10.2.2 Biomedical analysis
10.2.3 Toxicological analysis
Measurement of nitrous oxide concentrations in blood
or urine has no value in the management of a
patient. Arterial blood gases, complete blood counts
and bone marrow biopsies may be indicated depending
10.2.4 Other investigations
10.3 Life supportive procedures and symptomatic treatment
Remove the patient from further exposure. Then establish
airway and maintain respiration. Administer 100% oxygen.
Respiratory depression should be treated with assisted
Maintain blood pressure.
Maintain body warmth.
Treat cerebral oedema.
Eye contact: Not relevant.
Ingestion: Not relevant.
Skin contact: Not relevant.
Inhalation: Remove patient from the source of exposure.
Maintain adequate airway and assist respiration if
impaired. Administer 100% oxygen.
Eye contact: not relevant.
Ingestion: not relevant.
Skin contact: not relevant.
Inhalation: Nitrous oxide may be removed by forced
Eye contact: Not relevant.
Ingestion: Not relevant.
Skin contact: Not relevant.
10.6 Antidote treatment
There is no specific antidote.
There is no specific antidote.
10.7 Management discussion
Artificial respiration with oxygen and carbon dioxide can
also be used. If pure carbon dioxide is used, the mask or
tube must be held some distance from the subject's face to
allow free mixing with air to achieve adequate oxygenation.
A high concentration of carbon dioxide is itself
depressant and anaesthetic. Adrenaline (epinephrine) should
not be used to treat shock because of the risk of
ventricular fibrillation (Thienes and Haley, 1972).
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
In a study where information was recorded on every occasion
Entonox was administered, no side effects were experienced
on 61 occasions. But on 30 further occasions there were
minimal side effects, although never sufficient to stop the
use of Entonox. Side effects included drowsiness (10
patients), dizziness (13 patients), tingling of fingers and
toes (5 patients), disorders of smell or taste (3 patients),
and nausea (2 patients), one patient said he felt "stoned",
and another "disembodied". A few patients experienced
more than one symptom (Johnson, 1979).
Irritating oxides occur rarely in the nitrous oxide
formulations now marketed for anaesthesia. However,
atmospheric nitrogen is present in excessive amounts more
frequently than is generally appreciated. Because of the
greater volatility of nitrogen, it escapes from the
liquefied gases in the cylinders more rapidly than nitrous
oxide. Therefore, the first patient anaesthetized from
such cylinders suffers a dangerous degree of asphyxia as
anaesthesia is induced. The delayed toxic effect of nitrous
oxide anaesthesia occasionally seen in large hospitals may
be attributable to the prolonged cerebral anoxia due to
the free nitrogen present in nitrous oxide. Degeneration of
the basal ganglia and cortex has been demonstrated in fatal
cases (Thienes and Haley, 1972).
11.2 Internally extracted data on cases
11.3 Internal cases
To be completed by each centre
12. ADDITIONAL INFORMATION
12.1 Availability of antidotes
12.2 Specific preventive measures
No data available.
To some extent, the use of basal anaesthetics along with
nitrous oxide allows a lower concentration of the gas to be
used for induction, so that the degree of induced asphyxia
is lower. The continued cyanosis is responsible for most of
the toxic effects of these gases and contraindicates their
prolonged use (Thienes and Haley, 1972).
Adriani J (1983). General Anaesthetics. In: Haddad LM,
Winchester JEF. Clinical Management of Poisoning and Drug
Overdose. Canada, WB Saunders Company, 762-763.
Aldridge LM & Tunstall ME (1986). Br J Anaesth 58: 1348.
Amess JAL, Burman JF, Rees GM, Nancekievill DG, Mollin DL (1978).
Megaloblastic erythropoiesis in patients receiving nitrous
oxide. Lancet 2: 339-342.
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14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
Authors: Dr Ravindra Fernando
National Poisons Information Centre
Faculty of Medicine
Miss Shiromini Nissanka
National Poisons Information Centre
Faculty of Medicine
Date: December 1991
Peer Review: Newcastle-upon-Tyne, United Kingdom, February 1992