OXYGEN THERAPY AND

TOXICITY
[Link]
POST GRADUATE
MGMCRI
SYNOPSIS

 INTRODUCTION
 HISTORY
 PATHOPHYSIOLOGY
 INDICATIONS FOR OXYGEN THERAPY
• ACUTE
• LONG TERM
 OXYGEN SOURCE
 OXYGEN DELIVERY DEVICES
• LOW FLOW DEVICES
• HIGH FLOW DEVICES
 OXYGEN TOXICITY
 SUMMARY
INTRODUCTION

 Oxygen was discovered in the late 18th century

 Oxygen is colorless, odorless, tasteless gas that is essential for the body to function
properly and to survive

 The air that we breath in contains approximately 21% oxygen and the heart relies on
oxygen to pump blood
 Supplemental oxygen is used to treat medical conditions in which the tissues of body do
not have enough oxygen

 Oxygen is gas , but when administered as a supplement to normal atmospheric air may
also be considered as medication or drug.

 Often given without careful evaluation of its potential benefits and side effect.
 Like any drug there are clear Indication for treatment with oxygen and appropriate
methods of delivery.
 Inappropriate dose and failure to monitor treatment can have serious consequences.
 To ensure safe and effective treatment prescriptions should cover
• The flow rate
• Delivery system
• Duration
• Monitoring of treatment.
HISTORY

 Joseph priestly discovered oxygen in 18th century

 Lavoisier demonstrated respiratory gas exchange

 In 1899 ,Lorrain- smith confirmed the potential toxicity of inhaled oxygen.

PATHOPHYSIOLOGY
TISSUE OXYGENATION

 The final link in the transport of oxygen from the atmosphere to the cells is known as
internal respiration or tissue oxygenation, which involves the exchange of gases
between capillaries and tissue cells
CONTD..
CONTD…

 Primary goal of supplemental oxygen therapy is to ensure appropriate oxygen delivery to

vital end-organ tissues.
CARDIAC
OUTPUT
(Q)
OXYGEN
DELIVERY

ARTERIAL
TISSUE
OXYGEN
OXYGENATION
CONTENT
(CaO2)
OXYGEN
UTILISATION
OXYGEN DELIVERY(DO2)

DO2 = Q x CaO2

 Normal range for DO2 is 520–570 ml/min/m2

 DO2 is considerably in the excess of the oxygen consumption (110–160 ml/min/m2)

 This “spare capacity” enables the body to cope with a fall in oxygen delivery without

initially compromising aerobic respiration.

FACTORS INFLUENCING DO2:-
CaO2 & CO

Arterial O2 Content (CaO2):

 It is the total amount of O2 present in blood, i.e. combined with hemoglobin (Hb) and

dissolved in plasma.

CaO2 = (1.34 x Hb x SaO2) + (0.0031 x PaO2)

CONTD..

Cardiac output:

Measurement:

 Invasive: Direct and Indirect FICKS Method

 Non-Invasive: Electrical Impedance Cardiography (EIC) and Transesophageal

Echocardiography (TEE).

CO= Heart rate* Stroke volume

 Stroke volume depends on Preload, Afterload, Contractility

OXYGEN UTILIZATION/
CONSUMPTION(VO2)

 Refers to the rate of uptake of O2 by tissues from the microcirculation.

 It is a product of the cardiac output and the difference in oxygen content between arterial
and venous blood.
MEASUREMENT:

[Link]’S EQUATION: VO2 = Q x (CaO2-CvO2)

VO2 = Q x 1.34 x Hb x (SaO2-SvO2)
The normal range for VO2 is 110–160 ml/min/m2
2. VO2 = (Vi x FiO2) – (Ve x FeO2)
3. Rebreathing spirometer
O2 Extraction Ratio (O2ER)

 It is the ratio of oxygen uptake to oxygen delivery (VO2/ DO2), and reflects the fraction
of O2 delivered to the microcirculation that is taken up by the tissues.

 O2ER varies between different organs.

 Eg: Brain: 34%, exercising muscle-100%

 Normal O2ER is 20 to 30%

The DO2-VO2 Curve
CONTD..

Causes of poor oxygen delivery can be narrowed to three categories:

 Low cardiac output states (i.e., various forms of shock)

 Low hemoglobin concentration states (i.e., anemia)

 Low SaO2 states (i.e., arterial hypoxemia or hemoglobinopathies)

CONTD..

 Supplemental oxygen therapy addresses only arterial hypoxemia.

 Tissue hypoxia - more specific therapies are required, such as vasoactive agents or
intravenous fluid administration to reverse shock, and blood transfusions for anemia.
ARTERIAL HYPOXEMIA:

HYPOXIA
• Functional equivalent of HYPOXEMIA
ischemia • Deficiency of oxygen
• Lack or misuse of tension in the blood.
oxygen at the tissue • Low PaO2/SaO2
level

 Arterial hypoxemia is a major cause of tissue hypoxia

OTHER ASSESSMENTS OF HYPOXEMIA

 PaO2/FiO2
 Alveolar-arterial(A-a) difference
 Oxygenation index
Alveolar hypoventilation Diffusion defect Ventillation-perfusion Shunt
mismatch

• Reduced PAO2 • Defects in diffusion of oxygen • Results when focal (or • Occurs when a fraction of
• Reduced PaO2 and SaO2 across the alveolar–capillary sometimes diffuse) areas of pulmonary blood flow
• Leads to hypoxia and membrane. diminished ventilation arise effectively bypasses the
hypercapnia • Detected as reduced DLCO. relative to persistent alveolar compartment
• Found in pulmonary and non • coexists with ventilation– pulmonary capillary blood • Refractory to the use of
pulmonary disorders like perfusion mismatch flow. supplemental oxygen.
(Narcotic overdose, • Eg: pulmonary edema, acute
abdominal compartment syn, lung injury, and pneumonia
OSA) • characterized by alveolar
filling, reduced ventilation,
and continued perfusion.
• Overcome by increased Fio2
• If no adequate supplemental
O2-> hypoxic pulmonary
vasoconstriction-> PHTN
-> Cor pulmonale
CLINICAL ASSESSMENT OF TISSUE
HYPOXIA

 Clinical manifestation
 Laboratory assessment
CLINICAL MANIFESTATIONS
Laboratory assessment:

 Mixed venous oxygen saturation(SVO2)

 Dual oximetry
 DO2/VO2 measurements
 Blood lactate level
 Gastric tonometry
 Sublingual Capnography
 Nuclear Magnetic Resonance Spectrometry
SVO2:

 It is obtained from the distal end of the pulmonary artery with the help of a specialized
pulmonary artery catheter, the tip of which emits infrared light and records light reflected
back from hemoglobin in circulating erythrocytes - Reflectance spectrophotometry.

 Marker of the balance between whole body oxygen delivery and O2 demand

 Normal SVO2- between 65 to 75%

Dual oximetry

 By simultaneously measuring SaO2 (Pulse oximetry) and SVO2

 Normal value is 20 to 30%.
BLOOD LACTATE LEVELS

 Blood lactate levels increase when tissue hypoperfusion results in anaerobic metabolism.
 This is known as Type A lactic acidosis
 Blood lactate > 4 mmol/L –abnormal.
 Prognostic indicator
OTHERS

 Gastric Tonometry- To measure regional perfusion in the gut that employs a balloon in

the stomach to measure intramucosal pH (pHi)

 Sub-lingual Capnography - yield tissue PCO2 measurements that correlate with those

obtained by gastric tonometry.

 Nuclear Magnetic Resonance Spectrometry - can measure biochemical processes at the

cellular level, e.g. levels of ATP, NADH and cytochrome oxidase

INDICATIONS FOR OXYGEN THERAPY

 ACUTE

 LONG-TERM

 AIR TRAVEL
ACUTE INDICATIONS:
INDICATIONS FOR LTOT
LTOT

 NOTT Trial(1980) - Patients who received nocturnal oxygen therapy alone had a higher
mortality at both 12 and 24 months (40.8% at 24 months) compared with those who
received continuous oxygen therapy (22.4% at 24 months).

 BMRCD trial (1981) - 87 patients with hypoxemia and COPD were randomized to
receive either no oxygen therapy or at least 15 h/d of supplemental oxygen. Mortality was
significantly higher in the no-oxygen group.
NOCURNAL OXYGEN THERAPY
IN AIR TRAVEL

 In patients with lung disease, reduced PIO2 during air travel may result in marked
reductions in PAO2 and PaO2, placing the patient at risk for hypoxemia.

 Patient should have a thorough medical evaluation-Spirometry , DLCO, ABG, 6 MWT

 Hypoxia altitude simulation test (HAST) –ABG drawn just prior to administration of a
gas mixture with an FIO2 of 15.1%. Another ABG is drawn 20 minutes later, while the
patient breathes the hypoxic gas mixture. If the PaO2 is <50 mm Hg, administration of
supplemental oxygen during flight is recommended. If the PaO2 is between 50 and 55
mm Hg, further testing should be considered, including a 6-minute walk test
PULSE OXIMETRY

 Beer’s law - Concentration of an unknown substance dissolved in a solvent can be

determined by its light absorption.
Lout= (Lin * e)- (D*C*A)
OXYGEN SOURCE

 Oxygen from wall source provide 50 psi (pounds per square inch ) of pressure.

Oxygen Cylinder :

 Operate at 1800 – 2400 psi

 Cannot be directly delivered to patient

 Needs down regulating valve

 Flow meter to manipulate the flow rate

PRESSURE REGULATOR WITH FLOW
METER

 Pressure regulator controls the pressure coming

out of the cylinder and is indicated on the gauge in
psi.

 Flow meter controls the oxygen flow from the

cylinder/ wall source to the patient.

 Flow rate can be set from 1 – 25 L/ min

OXYGEN DELIVERY DEVICES

 Devices used to administer , regulate and supplement oxygen to increase the arterial
oxygenation

 System entrains oxygen and / or air to provide a fixed concentration required for
administration.

 Tubing carries the oxygen from the regulator/ flow meter to the delivery device.
CLASSIFICATION:

 Low flow or Variable performance devices

 High flow or fixed performance devices

CONTD..

Low flow or Variable performance High flow or fixed-performance

devices oxygen devices
 Nasal cannula  Venturi mask
 Simple oxygen mask  High flow nasal cannula
 Reservoir mask  High flow generators
LOW FLOW OR VARIABLE
PERFORMANCE DEVICES

 Provides oxygen at flow rates lower than patients’ inspiratory demands

 Fio2 delivered depends on the demand of patient, size of oxygen reservoir and rate at
which reservoir is filled

 When total ventilation exceeds capacity of the oxygen reservoir , room air is entrained.

 Include Nasal cannula , Simple face mask , Partial rebreathing mask, Non rebreathing
mask
HIGH FLOW OR FIXED PERFORMANCE
DEVICES

 Provides a constant Fio2 by delivering the gas at flow rates that exceed the patients’ peak

inspiratory flow rate.

 Devices entrain a fixed proportion of room air.

 Reliable fio2.

 Includes Venturi mask ,Oxygen hood, Face tent ,Oxygen tent, high flow nasal prongs
CHOICE OF DELIVERY DEVICE

 Patient’s oxygen requirement

 Efficacy of the device

 Reliability

 Ease of application

 Patient acceptance and tolerance

NASAL CANNULA

 Simple plastic tubing and prongs with an over the ear adjustments.

 Variable sizes are available

 Used to deliver low and medium o2 concentrations.

 Nasal cannulae at 1- 4 L / min have effects approximately equivalent wit 24 – 40%

oxygen from Venturi mask

 Fio2 increases approximately 1-2% with every increase in o2 flow / litre

 Flow > 5L/ min is less tolerated due to flow jet in nasal cavity.
CONTD…

Advantages Disadvantages
 Patient comfort & preference  Causes nasal irritation or soreness
 No claustrophobic sensation  May not work if nose is severely congested
 Less affected by movement of face  Actual concentration of Fio2 cannot be
predicted
 No interference while eating & talking
 No risk of rebreathing of carbon dioxide
 Cheaper
MOUSTACHE-STYLE RESERVOIR

 Contains a soft, inflatable reservoir with a volume

of approximately 20 mL.

 During inspiration, the patient initially draws from

the reservoir and then, when the reservoir is
depleted, from the continuous flow of the cannula.

 Acts to deliver a bolus of oxygen early in the

course of the inspiration, while reducing wasted
oxygen during expiration.
PENDANT RESERVOIR CANNULA.

 Consists of a reservoir worn on the chest like a

pendant.

 The reservoir is attached to a nasal cannula

with tubing of slightly greater diameter than
normal.

 Pendant reservoir cannula provides a similar

function to the moustache-style cannula.
 SIMPLE FACE MASK

 Disposable plastic device that covers both nose

and face

 Volume : 100 – 300ml

 Delivers oxygen concentration between 40% and

60%

 Vents in the mask allows for dilution of oxygen

 Perforations acts as exhalation ports.

 Air entrained through ports if o2 flow does not

meet peak inspiratory flow.

CONTD..

Advantages Disadvantages
 Less expensive  Uncomfortable
 Can be used in mouth breathers  Requires tight seal
 Difficult to keep in position for long
 Interfere with eating and talking
 Skin breakdown
RESERVOIR MASK

Two types are used

 Partial rebreathing mask

 Non rebreathing mask

PARTIAL REBREATHING MASK

 Simple masks with additional reservoir that allows accumulation of oxygen enriched gas
for rebreathing.
 O2 directed into reservoir.

 Inspiration : draw gas from bag & entrains room air

 First 1/3 of exhaled gas goes into bag

 Flow rates of 6 – 15 L/min.

 Delivers approximately fio2 35% - 60 %.

CONTD..

Advantages Disadvantages
 More oxygen flow does not increase Fio2.
 Inspired gas does not get mixed with room air
 Interferes with eating and talking
 Patient can breath room air through exhalation

ports if oxygen supply gets interrupted

NON REBREATHING MASK

 Oxygen flow into the mask is adjusted to

prevent the collapse of reservoir (12L/ min) &
prevents room air from being entrained

 Flow : 10 – 15 l/ min

 Fio2 : 90 – 100 %
CONTD…

 Valves prevents exhaled gas flow into

reservoir bag.

 Valve over exhalation port prevents air

entrainment
CONTD..

Advantages Disadvantages
 Highest possible Fio2 without intubation.  Requires tight seal & uncomfortable to the
patient.
 Suitable for spontaneously breathing patient
with severe hypoxia.  Malfunction can cause Co build up and
suffocation
 Interferes with eating and talking
VENTURI MASK

 Dilutional mask that works on Bernoulli’s

principle

 As the pressure of a fluid increases , the

pressure exerted by that fluid decreases. Can
be applied for both liquids and gases.
CONTD…

 High velocity o2 entrains ambient air into the

mask due to shearing forces between the gas
travelling through the nozzle and stagnant
ambient air Fio2 depends on size of
entrainment ports, nozzle and flow rate

 Larger the port more room air is entrained and

lower the Fio2
CONTD..

 Final concentration depends on ratio of air drawn in through entrainment ports.

 Due to high fow excess gas flushes out the expired Co2 through the holes on sides of mask.

 Venturi masks are avilable in the following concentartions 24%, 28%, 31%, 35%, 40% and

60%.
CONTD..

Advantages Disadvantages
 Fixed, reliable and precise Fio2  Uncomfortable
 Does not dry mucus membranes  Can not deliver high Fio2
 High flow comes from the air, saving the  Inteferes while eating and talking
oxygen cost.
 Can be used for low Fio2 also
 Helps in deciding whether the oxygen
requirement is increasing or decreasing
OXYGEN HOOD

 Mostly used for newborns and young infants

 Small, clear plastic hood to cover the head .

 O2 and premixed air pass through heated

humidifiers

 Fio2 : 80 -90%; Flow : 10 – 15l/min.

OXYGEN TENT

 Transparent enclosures in larger sizes for adult

patients

 60% - 70% o2 concentration achieved by flow

rates of 10 – 12L/min

 Air changes 20 times/ hour

 Confining & isolating

 Not useful in emergency situation

FACE TENT

 High flow soft plastic bucket like mask

 10 – 15L/min, Fio2 : 40%

 Used mainly for patients who can not tolerate

a mask
HFNC

 Nasal cannulae that can deliver much higher

rates of flow than simple nasal cannulae have
been developed recently.

 Can deliver between 1 and 60 L/min & may

be more comfortable than a facemask.

 In infants, these devices may increase positive

end-expiratory pressures (4 cm H2O or more).

 Clinical benefits must be weighed against the

risk of barotrauma
TOXCITY
OXYGEN TOXICITY

High concentrations for Lower concentrations for

short duration, like in long duration
HBOT

CNS toxicity Pulmonary toxicity

Bert effect Smith effect

FREE RADICALS

 Highly reactive oxygen-derived free radicals- superoxide (O2–), hydrogen peroxide

(H2O2) and the hydroxyl radical (OH–).
 Free radicals are ubiquitously produced during cellular respiration
In hyperoxic states

Excess free radicals

produced

lipid damage, leading to membrane dysfunction; disruption of enzymatic protein function; and
nucleic acids damage

Cell death
CELLULAR ANTI OXIDANT DEFENCES

 Various enzymes and cofactors in cells neutralize free radicals produced normally as a by-
product of metabolism- Anti-oxidants.
Anti-oxidants available:
 Superoxide dismutase
 Glutathione peroxidase
 α-tocopherol (vitamin E) and ascorbate (vitamin C)
 Ceruloplasmin
 Cysteine
TISSUE DAMAGE

Hyperoxic exposure

Generation of free
radicals

Exudative phase -characterized by death of alveolar type 1 and endothelial cells.

Interstitial edema
Exudative alveolar filling. Neutrophil recruitment

Proliferative phase- proliferation of endothelial cells

and type 2 pneumocytes
CLINICAL MANIFESTATIONS OF
PULMONARY OXYGEN TOXICITY

 Absorption atelectasis
 Decrease in vital capacity  Hypercapnic respiratory failure in at-risk
individuals
 Fall in DLCO.  Acute respiratory distress syndrome (ARDS)
 Hyaline membrane disease, leading to
 Lung compliance is diminished.
bronchopulmonary dysplasia (BPD) in
newborns
 Tracheobronchitis
Absorption atelectasis

Complete or partial collapse of an

alveolar unit’s proximal airway
For a patient breathing pure
oxygen, the absence of
nitrogen promotes alveolar
Previously inhaled gas is trapped collapse.
in the distal alveoli

Oxygen passes freely Nitrogen does not diffuse

from alveoli to capillaries easily-alveolar nitrogen
“stents” open the alveoli, Commonly seen:
maintaining patency • Induction of anaesthesia
• Prior to extubation
Hypercapnia in the Setting of Chronic CO2
Retention and Hyperoxia

Suppression of hypoxic
drive to breathe in the Ventilation–perfusion
setting of a blunted mismatch
hypercapnic drive

Haldane effect—the
increased capacity of
High viscosity of pure o2-
deoxygenated blood over
increases work of breathing
oxygenated blood for CO2
binding.
POTENTIATION OF PULMONARY
OXYGEN TOXICITY

 Bleomycin
 Paraqat
Generate free radicals
 Disulfiram
 Nitrofurantoin
 Protein deficiency
 Vitamin A & E deficiency
CNS toxicity

 Twitching of perioral and small muscles of the hand

 Facial pallor and ‘cogwheel’ breathing.
 Vertigo and nausea followed by altered behaviour, clumsiness, and finally convulsions.
 Neurogenic pulmonary oedema

CNS toxicity is mainly due to

oxidation and polymerisation of -
SH groups of enzymes leading to
their inactivation, which in turn
results in cellular damage
Occular toxicity

 Reversible constriction of the peripheral field of vision,

 Progressive but reversible myopia

 Delayed cataract formation

 Retrolental fibroplasia
Others:

 Serous otitis media

 Dysbaric osteonecrosis
 Hemolysis
 Hyperoxic reperfusion injury leading to oxidative stress— specifically worsening
postarrest functioning of the central nervous system
REFERENCES

1. FISHMAN’S Pulmonary diseases and disorders- 5th Edition

2. Textbook of pulmonary and critical care [Link]- 2nd Edition

3. EAGAN’S Fundamentals of respiratory care-11th Edition

4. BTS guidelines for oxygen use in adults in healthcare & emergency settings-2019

5. British Thoracic Society guidelines for home oxygen use in adults -2018

6. Chawla A, Lavania AK. OXYGEN TOXICITY. Med J Armed Forces India. 2001;57(2):131–133.

doi:10.1016/S0377-1237(01)80133-7