This document provides information on nitrous oxide, oxygen, and hyperbaric oxygen. It discusses the discovery and early uses of nitrous oxide as an anesthetic. It describes the preparation, properties, administration and physiological effects of nitrous oxide. Potential side effects are outlined including effects on the central nervous system, circulation, ventilation, and bone marrow. The document also discusses the discovery, production, transport and cascade of oxygen in the body. Various methods of oxygen therapy are described.

1. Nitrous oxide, Oxygen and
Hyperbaric Oxygen
Dr Ashton
Resident Anaesthesia

2. Nitrous Oxide
1771-1772: Oxygen and nitrous
oxide were discovered by Joseph
Priestley.
1799: Sir Humprey Davy discovered
the euphoric effects and called it
“laughing gas”.
1884: Gardener Quincy Colton a
travelling showman conducted a
demonstration exhibiting the
intoxicating effects of nitrous oxide

3.  Horace wells a young dentist saw this
and used nitrous oxide to extract one
of his own teeth and felt no pain.
 January 20,1845: Horace Wells public
demonstration was a failure.
 1863: Introduced into dental practice
on a large scale by Gardener Quincy
Colton.

4. Preparation
 In laboratory: by allowing iron to react
with nitric acid, Nitric oxide is produced
first which is then reduced to nitrous
oxide by an excess of iron.
 Commercially: By Heating ammonium
nitrate to between 245 to 270C.
 This produces ammonia, nitrous oxide,
nitrogen and nitrogen dioxide.
 Gases are passed through water
scrubbers to remove ammonia and nitric
acid.

5.  Then acid scrubbers remove nitrogen
dioxide.
 The gases then dried in an aluminium
drier.
 The compressed and dried gases are
then expanded in a liquifier with
resultant liquefaction of nitrous oxide
and escape of gaseous nitrogen.
 Purified nitrous oxide is now evaporated
compressed into a liquid and passed to
a second aluminium drier to the cylinder
filling line

6. Physical Properties:
 Only inorganic gas in clinical use.
 Colorless and odorless.
 Non explosive and non combustible
yet supports combustion.
 It exists as a gas at room temperature
and ambient pressure
 Its critical temperature lies above
room temperature.

7. Physical properties( contd…. )
-molecular weight - 44
-MAC -105
-Blood gas partition coefficient - 0.47
-critical temperature - +36.5C

8. N2O Cylinder
 N2O cylinder, color-blue,
Pin index - 3,5
 Stored as a liquified gas.
 Pressure depends on vapor pressure
of the liquid and is not an indication of
the amount of gas in the cylinder as
contents are in the liquid phase.
 The pressure remains nearly constant
until all the liquid is evaporated after
which it decreases till the cylinder is
exhausted.

10. Concentration effect
 N2O is about 20 times more soluble than
O2 and N2.
 During induction the volume of N2O
entering the pulmonary capillaries is
greater than the N2 leaving the blood and
entering the alveolus. As a result the
volume of the alveolus
decreases, thereby increasing the
fractional concentration of the remaining
gases. This process augments
ventilation as bronchial and tracheal gas
is drawn into the alveolus to make good
the diminished alveolar volume.

11. Second gas effect
 Rapid absorption from alveoli causes
an rise in the alveolar concentration of
the other inhalational anaesthetic
agent administered at the same time.

12. Diffusion hypoxia
 First described by Fink in 1955
 The elimination of nitrous oxide may
proceed at a greater rate as its uptake
 The volume of N2O entering the
alveolus from blood is greater than the
volume of N2 entering the pulmonary
capillary blood.
 Effectively dilutes alveolar air, and
available oxygen, so that when room
air is inspired hypoxia may result

13. SYSTEMIC EFFECTS
CENTRAL NERVOUS SYSTEM
-EEG: Frequency is decreased and voltage
is increased
-SEIZURE ACTIVITY: It may increase motor
activity with clonus and opisthotonus, even
tonic clonic seizure has been described
-AWARENESS: Requires greater than 0.5 to
0.6MAC to prevent it.
-CEREBRAL BLOOD FLOW: Increased
-INTRACRANIAL PRESSURE: Increased

14. CIRCULATORY EFFECTS
-SYSTEMIC BLOOD PRESSURE:,
HEART RATE, CARDIAC OUTPUT:
No change or modest increase
-RIGHT ATRIAL PRESSURE: Increased
-SYSTEMIC VASCULAR
RESISTANCE: No change
-PULMONARY VASCULAR
RESISTANCE:
-Increased
-This mild sympathomimetic activity
may be due to central effect regulating
beta adrenergic outflow.

15. VENTILATION EFFECTS
-FREQUENCY: Increased,
- TIDAL VOLUME: Decreased
-VENTILATORY RESPONSE TO
HYPOXIA: Depressed

16. BONE MARROW FUNCTION
- Megaloblastic changes and
agranulocytosis.
PERIPHERAL NEUROPATHY
-Ataxia and spinal cord and peripheral
nerve degeneration causing
sensorimotor polyneuropathy.

17. METABOLISM
- About 0.004% of absorbed dose of
nitrous oxide undergoes reductive
metabolism to nitrogen in the
gastrointestinal tract.
- Anerobic bacteria are responsible for
this
- Oxygen concentration of >10% in
GIT and antibiotics inhibit its
metabolism by anerobic bacteria

18. SIDE EFFECTS
HEMATOLOGIC: Mild Megaloblastic
changes.(due to irreversible oxidation
of cobalt atom in Vit B12 –affects
methionine synthetase)
NEUROTOXICITY: Sub acute
combined degeneration of spinal cord.
REPRODUCTION AND
DEVELOPMENT:
- Reduced fertility and increased
spontaneous abortion rate in operation
theatre personal.

19. OXYGEN

20. INTRODUCTION
- Independently discovered by CARL WILHELM
SCHEELE in 1773 and JOSEPH PRIESTLY
in 1774.
- Name OXYGEN was coined by ANTOINE
LOVOISIER in 1777.
- Atomic number-8, atomic weight-
15.9994g/mol
- Critical temperature- -119C
- Colourless, odourless, tasteless diatomic gas
with the formula O2.
- Oxygen cylinder, color - Black with white
shoulder
pin index-2,5

21. Production:
 By Fractional Distillation of liquid air
1.Liquefaction of air: Air is compressed
heat thus produced is got rid of and air is
allowed to expand.
As it expands it cools.(Joule Thompson
Effect)
By repetition of this there is a progressive
fall in temp till it cools enough to liquefy.

22.  Distillation of liquid air:
In liquid air, nitrogen and oxygen can be
separated as the more volatile nitrogen
(boiling pt at 760mmHg= -1960C) is
siphoned at the top
Oxygen is separated at the bottom

23. Oxygen Cascade
 The O2 content in air (at sea level) is
about 159.6mm Hg. (760 mm Hg x
0.21), falling to 10-15 mm Hg. (0.5
KPa) in the mitochondria where it is
utilized. The transport of O 2 down this
concentration gradient is described as
"Oxygen cascade".

24. 1.Starting point
At sea level, the atmospheric pressure is
760mmHg, and oxygen makes up 21%
(20.094% to be exact) of inspired air: so
oxygen exerts a partial pressure of 760
x 0.21 ≈ 160mmHg.
2.First drop
Water vapor, humidifies inspired air, and
dilutes the amount of oxygen, by
reducing the partial pressure by the
saturated vapor pressure (47mmHg).
PIO2 (the partial pressure of inspired
oxygen), (760 - 47) x 0.2094

25. 3.ALVEOLI
Alveolar oxygen tension(PAO2) is less
than PiO2 because some oxygen is
absorbed in exchange for CO2.
By the Alveolar Gas Equation.
PAO2 =PiO2-(PACO2/RQ)=103.5mmHg
R is the respiratory quotient, which
represents the amount of carbon
dioxide excreted for the amount of
oxygen utilized, and this in turn
depends on the carbon content of food
(carbohydrates high, fat low).
RQ≈8

26. 4.ALVEOLI TO BLOOD
FICKS LAW OF DIFFUSION
Rate of gas transfer= (k * A) ∆P/∆D
K is a constant called the diffusion
coefficient
A is the cross sectional area across
which diffusion is taking place
∆P/∆D is the concentration gradient
(any factor that increases the thickness of
membrane such as pulmonary edema
interferes with diffusion of oxygen more
than with that of CO2)

27.  In alveolar air, the O 2 tension is 106 mm
Hg and in venous blood entering the
pulmonary capillary is 40mm Hg.
(pressure gradient difference of 66 mm Hg)
 O 2 diffuses rapidly across the AC-
membrane, on reaching the blood, the O 2
first dissolves in plasma and finally
combines with Hb for its carriage to the
tissues.

28. Arterial Pao2 is now roughly100mmof Hg
The difference between alveolar and
arterial PO2 (A-a gradient) is 5-10mmHg
Increase in the difference between
alveolar and arterial PO2 is due to
1. Increased PIO2
2. V/Q mismatch
3. Rt to Left shunting

29. 5.Artery to tissue.
 The PO2 falls progressively form the arterial to
the venous end of the capillaries and from
capillaries to the cell and is lowest in the
mitochondria.
 O2 tension in tissue is 40mm of Hg.
(O2 transfers via plasma from RBC to tissue via
diffusion)
About 30% of O2 is liberated from blood to supply
the tissue
 O2 consumption cannot take place below a
mitochondrial PO2 of 1 -2 mmHg is known as

30. Oxygen Transport

31. Oxygen carriage by the blood
The amount of oxygen in the
bloodstream is determined by
 the oxygen binding capacity of
hemoglobin
 the serum hemoglobin level,
 the percentage of this hemoglobin
saturated with oxygen
 the amount of oxygen dissolved

32.  Dissolved O2 in plasma
Small quantity of O2 about (3%)
0.3ml/100ml of blood at a PaO2 of 100
mm Hg is physically dissolved in the
plasma.
i) It reflects the tension of oxygen (PO2) in
the blood
ii) Acts as a pathway for supply of O2 to
Hb.
PO2 in the blood is first transferred to the
cells, while its place is rapidly being taken
up by more O2 liberated from the Hb.

33.  b) O2 combined with Hb:
Most of the O2 (97%) in the blood is
transported in combination with Hb.
Hemoglobin: Consists of the protein globin
joined with the pigment haem, which is a
Fe- containing porphyrin.
Normal adult Hb consists of: Hb (A 1 ):
98% and Hb (A 2 ): 2%.
Hb has 4 binding sites for oxygen.
Each gram of Hb can carry 1.34ml of
oxygen.
With a Hb concentration of 15g/dl, the O2

34. Oxygen flux:
 The amount of O2 leaving the Lt. Ventricle per
minute in the arterial blood has been termed
the "oxygen flux".
 It represents O2 delivers to the tissues.
O 2 flux =
CO x Arterial O2 saturation x Hb conc x 1.31.=
5000 ml/min x 98/100 x 15.6/ 100g / ml x 1.31
ml/gm. = l000ml/min.
Normally about 250ml of this O2 is used up in
cellular metabolism and the rest returned to the
lungs in the mixed venous blood

35.  The 3 variables in the equation:
 Cardiac output, arterial O2 saturation and Hb
concentration are multiplied together
 Trivial reduction of any may result in a
catastrophic reduction in O2 flux.
 Lowest tolerable value of O2 flux is 400 ml/min.
 Oxygen flux decreased in anaemia, CCF,
metabolic acidosis, respiratory acidosis
 Oxygen flux is increased in exercise,
thyrotoxicosis, halothane shakes, pain and
shivering.

36. OXYHAEMOGLOBIN
DISSOCIATION CURVE(ODC)
 The percent of Hb saturation with oxygen
(PO2) at different partial pressures of O2 in
blood is described by the “ODC”.
 It expresses the relation between oxygen
tension taken on the X axis and % of Hb
saturation taken on the Y axis at 37° C, pH:
7.4, PCO2 40 mmHg.
 It is a sigmoid curve.

38. Bohr Effect:
 EFFECT-shift in position of ODC caused by
CO2 entering or leaving blood.
CO2+H2OH+ +HCO3.
A fall in pH shift the ODC to the "right" and a
rise a shift of the ODC to the left
Double Bohr Effect:
The transfer of H+ ions from the fetal blood into
the maternal intervillous spaces causes the
fetal pH to rise and increase the affinity of fetal
blood to O 2 (shift to left).
H + ions acids passing to the maternal
circulation causes the maternal pH to fall,
reducing the affinity of maternal blood for O 2
(shift to right) so further O 2 is released to the
fetus.

39. Oxygen content of blood
=(SO2*1.34*Hb*0.01)+(0.023*PO2)
Arterial blood(CaO2)=20.4ml/100ml
Venous blood(CvO2)=15.2ml/100ml
O2 Delivery(DO2) and O2 Uptake(VO2)
DO2=CaO2 * CO(cardiac output)
=1005ml/min
VO2=DO2-oxygen return
=DO2-(CvO2*CO)
=245ml/min
O2 Extraction Ratio=VO2/DO2=25%
Increased tissue demand  increase in CO
Extreme conditionsCvO2 falls, extraction
ratio increases

40. HYPOXIA
Hypoxia, is a pathological condition in which
the body as a whole (generalized hypoxia)
or a region of the body (tissue hypoxia) is
deprived of adequate oxygen supply.
CLASSIFICATION
-hypoxemic hypoxia
-hypemic hypoxia
-histotoxic hypoxia
-ischemic or stagnant hypoxia

41. HYPOXEMIC HYPOXIA:
Reduction in PO2
-high altitude
-switching from inhaled anesthesia
atmospheric air-FINK EFFECT
-sleep apnea
-COPD or pulmonary arrest
-shunts
HYPEMIC HYPOXIA: O2 content of
arterial blood is reduced
-carbon monoxide poisoning
-methhemoglobinemia

42. HISTOTOXIC HYPOXIA:Poisoning of the
electron transfer chain
-cyanide poisoning
ISCHEMIC OR STAGNANT HYPOXIA
-cerebral ischemia, IHD.
SYMPTOMS OF HYPOXIA
-headaches,fatigue
-shortness of breath
-feeling of euphoria and nausea
-changes in level of conciousness
-seizures
-coma
-death

43. OXYGEN THERAPY
INDICATIONS
 In adults and infants > 1 months
SPO2<90% or PaO2< 60mmHg
 In neonates: SPO2 <88% and
PaO2<50mmHg and Capillary
PCO2>40mmHg

44. METHODS OF O2 THERAPY
 Low Flow/ Variable Perfomance Devices:
Nasal Cannula, Nasal Catheter, Face
Mask(Simple/ with reservoir bags)
 High Flow/ Fixed Perfomance Devices:
Venturi mask, O2 Hood, Hyperbaric O2
 Intravenous O2 Therapy
 Extracorporeal Membrane Oxygenation

45. Nasal Cannula
 Most widely used device.
 Prongs are inserted 1 cm
inside nares and other end
is attached to O 2 source.
Continuous flow of O 2 ,
fills the anatomic reservoir
(50ml). which empties into
lungs with each inspiration,
even when the mouth is
wide open
 Flow rate commended =
1-6l/min

46.  Gases should be humidified to prevent
mucosal drying if the oxygen flow
exceeds 4 L/min.
 For each 1 L/min increase in flow, the
Fio2 is assumed to increase by 4%
 Advantages: Simple, Cheap,
Comfortable, Well tolerated as it can
be worn during eating , drinking,
talking and coughing.
 Disadvantages: Irritation of nasal
mucosa. Drying and crusting of nasal
cavity. Unpredictable FiO2 .

47. Nasal catheters
 It appears like a suction
catheter with multiple
openings at its distal end
 Size 8-14 FG
 Length: From tip of a nose
to tragus
 The tip of the catheter is
advanced up to the fold of
the soft palate and then
pulled back slightly so that it
just lies beyond the posterior
nares above the uvula. Has
to be changed from one
nostril to other every 8 hours

48.  Flow rate = 3L min in conscious
patients and can go upto 6L in
unconscious patients.
 FiO2 upto 0.4
 Advantages: Because of presence of
multiple opening, the gas flow doesn’t
impinge on any one area of the
nasopharynx and hence comfortable
to the patient.

49. Face Mask/ Marcy Catteral
mask/Hudsons Mask
 A simple and
transparent device
 O2 flows into mask
through the tubing and
exhaled gases leave
through holes at the
side of the mask.
 F.R= 6 - I0L/min
 Min 4 L/min to avoid
rebreathing CO2

50.  FiO2=0.35 – 0.55 but depends on
patients ventilator pattern, size of the
mask and O 2 flow rate.
 Reservoir =100-200ml mask itself and
totally 150-250ml
 Has to be removed during eating,
coughing respiratory care etc.

51. Partial Rebreathing Mask
 A combination of face
mask and a collapsible O
2 reservoir bag.
 Oxygen flows
continuously to the bag

52.  Inspired O2 consists of O2 from the
reservoir bag, together with some air
entrained through the side ports and the
small space between the mask and the
skin of the face.
 The patient re-breathes some of the
exhaled air also
 Flow rate=5-7 L/min
 FiO 2 = 0.35-0.75
 If the O2 inflow rate adjusted so that the
bag doesn’t collapse during inhalation,
the amount of CO2 contamination in the
bag is negligible.

53. Non rebreathing mask
 Combines face mask with an O 2 reservoir
bag and a unidirectional valve in between.
This valve prevents re-breathing. Another one
way valve seals the side holes of the mask
during inhalation

54.  FR-upto 6-10L/min. FiO2 -0.60-0.80 but
upto 0.95 to 1.00 can be achieved
 Reservoir = 750-1250ml

55. 55
Oxygen Hood
High oxygen device
 Clear plastic shell encompasses the baby's head
 Well tolerated by infants
 Size of hood limits use to younger than age 1 year
 Allows easy access to chest, trunk, and extremities
 Allows control of Oxygen Delivery:
◦ Oxygen concentration
◦ Inspired oxygen temperature and humidity
 Delivers 80-90% oxygen at 10-15 liter per minute

56. Venturi Mask
 Venturi mask
incorporate a
venturi tube,
working on
Bernoulli principle.
 When a stream of gas is pushed through a
narrow orifice, the pressure on the outside
of the stream falls as a result of increased
velocity of gas passing through the
restricted orifice.

57.  Altering the gas orifice or entrainment port
size causes the Fio2 to vary.
 It provides predictable and reliable Fio2
values of 0.24 to 0.50 that are independent
of the patient's respiratory pattern.

58.  Two varieties
 1. A fixed Fio2 model, which requires
specific inspiratory attachments that are color
coded and have labeled jets that produce a
known Fio2 with a given flow.
 2. A variable Fio2 model which has a graded
adjustment of the air entrainment port that
can be set to allow variation in delivered Fio2.

59.  Indications:
 Patients with Inadequate ventilatory
efforts
 Increased shunt e.g. COPD patients
Pulmonary oedema
 Pulmonary consolidation
 ARDS

60. HYPERBARIC OXYGEN THERAPY:
 It means administration of O2 at higher than
atmospheric pressure more than 1atm
Higher the PIO2, higher is the PAO2 .
Higher the PAO2, higher is the actual amount of
O2 carried in physical solution
 Hence by increasing PIO2 we can increase
the amount of dissolved O2. For e.g. O2
dissolved in plasma at 1atm press =0.3
volumes% and at 3 atm press it is 6 volumes
% (6ml/100ml of blood)
 Usually administered btw 2 and 3 atm.

61. Indications of Hyperbaric O2
Therapy
Regional hypoxia: Acts by two
mechanisms
1. Large O2 gradient, allows at least
some degree of O2 delivery by
increasing PaO2 in the hypoxia zone,
unless there is a complete absence of
BF.
2. Repeated therapies with HBO will
stimulate angiogenesis because of
improved macrophage and fibroblast

62.  CO poisoning:
CO has high affinity for Hb and shifts ODC
to the left.
It inhibits cytochrome oxidase enzyme.
Hyperbaric O2 in CO poisoning acts by
three mechanisms
1. Compete with CO molecules for Hb
binding sites on COHb and eliminates
CO.
2. Provides sufficient dissolved O 2 for
tissue use
3. Moves ODC to the right

63.  In severe anaemia: By increasing
dissolved O2 content, it improves tissue
oxygenation
 Infections:
Inhibits Clostridial alpha toxins.
Aerobic organisms which are sensitive to
HBO are Staphylococcal aureus
Pseudomonas Pyocyaneus
Leukocyte oxidative killing mechanisms
operate, when the O 2 tensions >
30mmHg. Improve osteoclastic function
therefore useful in osteomyelitis
 Inhibits growth of anaerobic organisms e.g.

64.  Osteomyelitis: Improve osteoclastic
function therefore useful in
osteomyelitis.
 Gas lesions:
1. By increasing arterial hydrostatic
pressure, decrease the volume of
emboli
2. Produce hyperoxia which improves O
2 delivery to tissue downstream of the
obstructing emboli.
3. also maximizes the gradient for
elimination of gas in the emboli

65.  Cancer: Potentiate radiation therapy by
improving oxygenation of hypoxic
tumour cells thus restoring their
sensitivity to the radiation (hypoxic cells
are less sensitive to radiation )
 Plastic surgery: Reduce the area of
ischemia and permits improvements of
collateral flow.

66. Methods of administration:
1.Single person chamber /Monoplace
 Only the patient is subject to compression
and the staff remains outside.
 It is made up of transparent acrylic.

67. Large operating room pressure
chamber / multiplace
 Encloses both the patient and medical
attendants. Can be used for surgery.
Medical attendants breathe compressed
air, while patient breaths 100% O 2 at
pressure from a mask/ETT.
 Suitable for the patients who are
critically ill and require constant
attendance.
 Made up steel/aluminum.

69. COMPLICATIONS
-tympanic membrane rupture
-nasal sinus trauma
-pneumothorax
-air embolism
-central nervous system toxicity
-oxygen toxicity

70. Oxygen Toxicity
O 2 molecule is capable of subtle
modifications, which transforms it into a range
of free radicals and other highly toxic
substances.
e.g. superoxide ions activated hydroxyl
ions, hydrogen peroxide etc.
 When there is over production of these
reactive species, overwhelming the normal
protective mechanisms of the body, O2 toxicity
results. The free radical cause damage to the
 DNA
 Lipids

71.  The oxygen toxicity can present as Pulmonary
toxicity (Lorraine-Smith effect)
Occurs after approximately 30 hrs exposure to
PIO2 of 100kPa
Mech: Oxidation of SH groups on essential
enzymes e.g. CO-A.
Loss of syntheses of pulmonary surfactant,
encouraging the development of collapse and
alveolar oedema.
 Signs and symptoms: Earliest symptom is
substernal distress, cough and chest pain
Decrease in vital capacity is the most sensitive
indicator. As toxicity progresses MV, Respiratory
rate/Compliance of lung etc. all will deviate from

72.  CNS toxicity (Paul-Bert effect)
 Exposure to oxygen at partial pressure in
excess of 2 ATA result in convulsions.
 Frank convulsions are preceded by
warning signs as-twitching of muscles
around the eyes, mouth and forehead,
dilation of pupils, visual “dazzle” vertigo
or nausea etc.
Mechanism: In activation of SH
containing enzymes controlling levels of
GABA
Treatment: Gradual /sudden withdrawal of
high pressure O 2 and allowing the
patient to breath room air.

73. Retrolental fibroplasia in neonates / retinopathy
of prematurity (RLF / ROP).
RLF is the result of O2 induced retinal
vasoconstriction.
It occurs in premature neonates especially < 30
weeks gestation, with birth weight <1200gm,
exposed to high concentration of O2 i.e. 150
mmHg for >2 hrs.
Hyperoxia constricts retinal arterioles and causes
swelling and degeneration of the endothelium of
the arterioles and capillaries.
Spindle cells in the retina when get stressed by
one of several factors including O 2 , they secrete
angiogenic factor which is responsible for
vascular proliferation between the vascular and

75. References
 Benumoffs Airway Management, 2nd
Edition.
 Lee’s synopsis of anesthesia, 13th
edition.
 Wylie Churchill Davidson – A Practice of
Anesthesia – 5th Edition
 Egan’s fundamentals of respiratory care
– 9th edition
 Morgans - Clinical Anesthesiology – 4th
Edition
 Dorsch – Understanding Anesthesia
Equipment - 5th Edition