Principle of oxygen therapy

in the newborn
Thrathip Kolatat M.D.
Neonatal Intensive Care Unit
Department of Pediatrics
Faculty of Medicine Siriraj Hospital
Oxygen
to achieve adequate delivery oxygen to
tissues without creating oxygen toxicity
The most common drugs used in NICU
Goal
Oxygen
The biomedical double-edged sword
lenergy source of cellular life
lrisk for oxygen toxicity
There must be an oxygen pressure at
which biological activity is optimal
Physiologic consideration
l External respiration
l transfer oxygen molecules from the
atmosphere to blood
l Blood oxygen transport
l movement of oxygen from blood to the site
of intracellular utilization
l Internal respiration
l oxygen consumption
External respiration
l definition: transfer oxygen
molecules from
atmosphere to the blood
l factors influence external
respiration
l fraction of inspired
oxygen
l distribution of
ventilation
l alveolar gas exchange
l mixed venous-oxygen
content
Unloading oxygen capabality
(Term and Preterm)
Preterm 1000-1500 g. Term
Blood oxygen transport
l definition: movement of oxygen from the
blood to the site of intracellular
utilization
l factors influence blood oxygen transport
l cardiac output
l hemoglobin concentration
l hemoglobin oxygen affinity
Factors affected oxygen transport
l amount of oxygen in blood
l hemoglobin concentration
l partial pressure of oxygen
l oxygen-hemoglobin affinity
l delivery of oxygen
l blood pressure and blood volume
l cardiac output and distribution of flow
l viscosity
l abnormalities in cellular metabolism
l increased oxygen requirement e.g.
hyperthermia, hypothermia
Hemoglobin-oxygen dissociation curve
l Shift to the left
l increased oxygen affinity
l less oxygen delivering to
the tissue
l increased oxygen content
l Shift to the right
l decrease oxygen transport
capability
l enhance movement of
oxygen from blood to tissue
l decrease oxygen supply to
tissue
l decrease oxygen content
Hemoglobin-oxygen dissociation curve
Blood oxygen transport
l oxygen content (OC)
l amount of hemoglobin
l hemoglobin-oxygen
dissociation curve
l OC = oxy hemoglobin
+ dissolved oxygen
Side chains
Methyl, -CH
3
Vinyl, -CH-Ch
2
Proprionic acid,-CH
2
-CH
2
-COOH
Internal respiration
l definition: oxygen consumption
l factors influence internal respiration
l capillary perfusion
l diffusion of oxygen to tissue
l tissue oxygen utilization
Oxygen tension in cord blood and arterial
blood at different postnatal age
0
20
40
60
80
100
120
U
A
U
V
5
-
1
0
m
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2
0
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3
0
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6
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5
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4
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r
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2
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s
3
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4
d
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s
5
d
a
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s
6
d
a
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s
7
d
a
y
s
min
mean
max
Method to delivery oxygen
l simple oxygen mask
l oxygen cannula
l oxygen hood
l oxygen box
l oxygen via incubator
l continuous positive airway pressure
(CPAP)
Oxygen mask and cannula
l simple oxygen mask
l apply in an emergency
situation
l provide a concentration of
50-90%
l recommended flow 3-6 LPM
l oxygen cannula
l provide a fixed concentration
which vary on flow rate
l require a specific type of
flow meter
Oxygen hood
l provide a stable
concentration, visibility and
access to most of the body
l recommend for acutely ill
or unstable infants who
require a FiO
2
> 0.40
l a minimum flow rate of
3 LPM is recommended
in order to prevent CO
2
retention
Oxygen box
l provide a stable
concentration,
visibility and access
to most of the body
l recommend for a
FiO
2
< 0.40
l suitable for a
chronically ill or stable
infant in the crib
Oxygen via incubator
l provide a stable
concentration,
visibility and access
to most of the body
l recommend for a
FiO2 < 0.40
l recommend for a
stable infant in the
incubator
Oxygen monitoring
Oxygen analyzer
Arterial PaO
2
VS Oxygen saturation
Oxygen monitoring
l PaO
2
l transcutaneous oxygen monitoring (SpO
2
)
l oxygen content
l PO
2
100 mm Hg hemoglobin carries approx.
100 times more oxygen in plasma
l 2 components of oxygen load
loxygen bound to hemoglobin
(1g. of Hb binds 1.34 ml. oxygen)
loxygen dissolved in plasma
(0.3 ml O
2
/100 ml)
Arterial PaO
2
l tissue oxygenation
depends on PaO
2
or the
saturation between tissue
and blood
l in term of the saturation,
change from fetal
hemoglobin to adult
hemoglobin should be
considered in the
newborn infants
l naturally occurred
l repeated transfusion during
intensive care period
Oxygen saturation
l limitation to detect
hyperoxia (PaO
2
>12
kPa;SpO
2
> 97%)
l sensitive to detect tissue
hypoxemia when PaO
2
is
at the critical level (PaO
2
is on the steep portion of
the curve)
Oxygen saturation: limitation
and recommendation
l no definite criteria for hypoxia
l to avoid hypoxia, saturation should be kept
at the level of PaO
2
50 kPa
l saturation should be intermittently compared
with PaO
2
obtained from ABG
l lower acceptable limit of saturation: 85%
l upper acceptable limit of saturation: 97%
Oxygen saturation
l advantages
l noninvasive
l rapid response time
l no tissue damage
l sensitive to detect hypoxia
l disadvantages
l varied with patient activity
l influenced by edema, phototherapy, perfusion
l insensitive to detect hyperoxia
Complications
l l burns burns
l l factors influence factors influence
l l skin maturation skin maturation
l l tightness tightness
l l duration of probe duration of probe
attachment attachment
Oxygen toxicity
Oxygen toxicity
Development of oxygen radical
defense systems
l concentration of oxygen scavengers and anti-
oxienzymes increase in lungs and kidney
during pregnancy
l level of total antioxidant was lower in the
preterm infants than the adult or term infants
l VLBW infants have a higher capacity to
produce oxygen radicals by the respiratory
burst than term infants
Oxygen free radical reperfusion injury
l accumulation of lipid peroxidation products
following reperfusion
l protection by the administration of nonenzymatic
antioxidants including vitamim E, glutathione,
dimethylsulfoxide or enzymatic antioxidants
l the direct identification of free radicals by
electron spin resonance spectroscopy
Actions of free radicals
Role of hypoxanthine -xanthine oxidase
system
l l hypoxanthine is the end product of the hypoxanthine is the end product of the purine purine
catabolism in most human organs catabolism in most human organs
l l hypoxanthine is a break down product from hypoxanthine is a break down product from
ATP, AMP ATP, AMP
l l during hypoxia, hypoxanthine is accumulated during hypoxia, hypoxanthine is accumulated
l l when hypoxanthine is oxidized to uric acid, when hypoxanthine is oxidized to uric acid,
oxygen radicals are formed oxygen radicals are formed
Mechanism for
ischemia/reperfusion injury
hypoxanthine
ATP
i
s
c
h
e
m
i
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oxygenation
AMP
XD
XO
O
2
protease
O
2
+ H
2
O
2
+ urate
-
Oxygen toxicity
Neonatal free radical disease
l l respiratory tract: respiratory tract: bronchopulmonary bronchopulmonary dysplasia dysplasia
l l retina: retinopathy of prematurity retina: retinopathy of prematurity
l l brain: brain: intraventricular intraventricular hemorrhage, PV L hemorrhage, PV L
l l gastrointestinal tract: necrotizing gastrointestinal tract: necrotizing enterocolitis enterocolitis
l l KUB: acute tubular necrosis KUB: acute tubular necrosis
Oxygen free radicals
O
2
+ 4 H + 4 e 2 H
2
O
+
O
2
+ e O
2
_
_
(superoxide radical)
O
2
+ e H
2
O
2
_
(hydroxyl radical)
(hydrogenperoxide)
H
2
O
2
+ e .OH
_
.HO + e H
2
O
_
(water)
Chemical mechanism of oxygen toxicity
Principle mechanism
l univalent reduction of molecular oxygen
l formation of free radical intermediates
Reactive O
2
metabolites
l Superoxide free radical (O
-
2
)
l Hydrogen peroxide (H
2
O
2
)
l Hydrogen free radical (OH
-
)
l Singlet oxygen (
1
O
2
)
Actions of free radicals
linjure biological membranes by lipid
peroxidation
linactivate enzyme
ldenature proteins
lbreak double strand of DNA
Antioxidant enzyme defense system
l l Superoxide Superoxide dismutase dismutase (SOD) (SOD) detoxified O detoxified O
- -
2 2
l l Catalase Catalase detoxified H detoxified H
2 2
O O
2 2
l l Glutathione Glutathione peroxidase peroxidase (GP) detoxified H (GP) detoxified H
2 2
O O
2 2
l l G G- -6 6- -PD provided NADPH reduced glutathione PD provided NADPH reduced glutathione
Actions of free radicals
Role of Iron
l nutritional iron deficiency in premature infants
may be protective in oxygen radical-mediated
injury
l lactoferrin and transferrin-like-iron-binding
proteinpresent in breast milk may have
protection from oxygen radical injury
l low serum level of apotransferrin and
ceruloplasminin the premature infants may
potentiate this type of injury
Actions of free radicals
Role of the activated leukocyte
l l on exposure to bacteria, the oxygen uptake of on exposure to bacteria, the oxygen uptake of
neutrophils is increased as much as 50 neutrophils is increased as much as 50- -fold fold
l l a large amount of a large amount of superoxide superoxide and hydrogen and hydrogen
peroxide radicals are formed peroxide radicals are formed
l l leukocytes attack bacteria with oxygen leukocytes attack bacteria with oxygen
radicals radicals
l l this phenomenon is called respiratory burst this phenomenon is called respiratory burst
Effects of alveolar macrophage
proteolytic proteolytic damage in alveolar wall damage in alveolar wall
Exposure to prolonged high inspired oxygen Exposure to prolonged high inspired oxygen
influx of
polymorphonuclear
leukocytes
impaired
antiprotease
defense
system
release of
proteolytic
enzyme
Pulmonary change of oxygen toxicity
l l atelectasis atelectasis (surfactant inactivation) (surfactant inactivation)
l l edema edema
l l alveolar hemorrhage alveolar hemorrhage
l l inflammation inflammation
l l fibrin deposition fibrin deposition
l l thickening and hyalinization of alveolar thickening and hyalinization of alveolar
membrane membrane
l l tracheal, bronchiolar and type 1 alveolar tracheal, bronchiolar and type 1 alveolar
lining cells were damaged lining cells were damaged
Free radical scavengers and
antioxidants
Antioxidants
l l vitamin E vitamin E
l l bilirubin bilirubin
Free radical scavengers and
antioxienzymes
Free radical scavengers
l l mannitols mannitols
l l superoxide superoxide dismutase dismutase
l l bilirubin bilirubin
l l uric acid uric acid
l l dimethyl dimethyl sulphoxide sulphoxide
Factors that determine oxygen toxicity
l l maturation maturation
l l nutritional and endocrine status nutritional and endocrine status
l l duration of expose to oxygen duration of expose to oxygen
l l other oxidants other oxidants
A safe level of inspired oxygen has not been A safe level of inspired oxygen has not been
established, any concentration in excess of room established, any concentration in excess of room
air may increase the risk of lung damage when air may increase the risk of lung damage when
administered over a period of time administered over a period of time
Policy for preventing ROP
l l all all infants infants who who are are at at risk risk will will be be monitored monitored with with a an n
oxygen oxygen saturation saturation monitor monitor
l l the the upper upper limits limits for for the the monitor monitor alarm alarm will will be be routinely routinely
set set at at 95% 95%
l l daily daily attempts attempts should should be be made made to to lower lower the the FiO FiO2 2in in
stable stable, , convalescing convalescing infants infants with with O O2 2saturations saturations in in
the the low low to to mid mid 90 90 s s
l l correlating correlating arterial arterial samples samples will will be be obtained obtained/ /attempted attempted
twice twice weekly weekly
ROP: oxygen monitoring policy
l l a administer dminister oxygen oxygen via via a a hood hood as as a a primary primary mode mode of of
delivery delivery for for infants infants < <1500 1500 g g
l l u use se oximetry oximetry to to determine determine the the optimum optimum flow flow and and distance distance
from from the the face face when when using using short short term term blow blow by by O O2. 2.
l l m monitor onitor infants infants at at risk risk by by setting setting a a strict strict upper upper limit limit for for the the
oximeter oximeter of of 95% 95%
l l If If possible possible a a calibration calibration PaO PaO2 2should should be be obtained obtained twice twice
weekly weekly; ; simultaneous simultaneous FiO FiO2, 2, SaO SaO2 2and and PaO PaO2 2will will be be recorded recorded
l obtain an arterial blood gas when an "at-risk"infant
who was previously in roomair is retreated with
oxygen.
l if the arterial PaO2>90 mmHg, notify a physician and
document the response
l adjust FiO2based on ordered parameters using
oximetry and/or transcutaneous monitoring.
l ensure that an ROP check has been done at six
weeks of age on infants <1500 g.
ROP: oxygen monitoring policy
Prognostic factors
l P(A-a)O
2
difference
l in infants with PPHN, the mortality was
79% if P(A-a)O
2
was equal to 610 mm
Hg for 8 consecutive hrs
l Oxygen index (OI)
l definition: MAP x FiO
2
/ PaO
2
l OI>40: 80% mortality
l OI>25: 50% mortality
Alveolar-arterial oxygen pressure
difference
l determine ventilation/perfusion (V/Q)
mismatch
l normal value for adult in RA: 10-20 mm Hg
l normal value in the neonate
l 40-50 mm Hg at birth
l 300 mmHg (FiO
2
1.0)
Alveolar-arterial Oxygen
Pressure Difference
l P(A-a)O
2
alveolar-arterial oxygen
pressure difference
l correlate with severity of lung disease
l method of calculation
l PAO
2
= [FiO
2
x (P
atm
- P
H
2
O
)] - PCO
2
l Exp. PaO
2
= 673 mm Hg
(FiO
2
1.0; PCO
2
40 mmHg)
Etiology of high P(A-a)O
2
difference
l diffusion block at the alveolar-capillary
level
l V/Q mismatch in the lung
l a result of ventilated areas poorly perfusion
l perfused areas poorly ventilated intracardiac
l fixed right-to-left shunt
Graph for estimation the shunt at different
inspired oxygen
Graph for estimation the shunt at different
inspired oxygen
0 10 20 30 40 50
0
100
200
300
400
500
600
700
800
60%inspired oxygen
80%inspired oxygen
100%inspired oxygen