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Principle of oxygen therapyin 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 swordlenergy source of cellular lifel risk for oxygen toxicity
There must be an oxygen pressure at which biological activity is optimal
Physiologic consideration
l External respirationl transfer oxygen molecules from the
atmosphere to blood
l Blood oxygen transportl movement of oxygen from blood to the site
of intracellular utilization
l Internal respirationl oxygen consumption
External respiration
l definition: transfer oxygen molecules from atmosphere to the blood
l factors influence external respirationl fraction of inspired
oxygenl distribution of
ventilationl alveolar gas exchangel 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 outputl hemoglobin concentrationl hemoglobin oxygen affinity
Factors affected oxygen transport
l amount of oxygen in bloodl hemoglobin concentrationl partial pressure of oxygenl oxygen-hemoglobin affinity
l delivery of oxygenl blood pressure and blood volumel cardiac output and distribution of flowl viscosity
l abnormalities in cellular metabolisml increased oxygen requirement e.g.
hyperthermia, hypothermia
Hemoglobin-oxygen dissociation curve
l Shift to the leftl increased oxygen affinityl less oxygen delivering to
the tissuel increased oxygen content
l Shift to the rightl decrease oxygen transport
capabilityl enhance movement of
oxygen from blood to tissuel decrease oxygen supply to
tissuel decrease oxygen content
Hemoglobin-oxygen dissociation curve
Blood oxygen transport
l oxygen content (OC)l amount of hemoglobinl hemoglobin-oxygen
dissociation curve
l OC = oxy hemoglobin+ dissolved oxygen
Side chains• Methyl, -CH3• Vinyl, -CH-Ch2• Proprionic acid,-CH2-CH2-COOH
Internal respiration
l definition: oxygen consumptionl factors influence internal respirationl capillary perfusionl diffusion of oxygen to tissuel tissue oxygen utilization
Oxygen tension in cord blood and arterial blood at different postnatal age
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Method to delivery oxygen
l simple oxygen maskl oxygen cannulal oxygen hoodl oxygen boxl oxygen via incubatorl continuous positive airway pressure
(CPAP)
Oxygen mask and cannula
l simple oxygen maskl apply in an emergency
situation
l provide a concentration of 50-90%
l recommended flow 3-6 LPM
l oxygen cannulal 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 FiO2 > 0.40
l a minimum flow rate of 3 LPM is recommended in order to prevent CO2
retention
Oxygen box
l provide a stable concentration, visibility and access to most of the body
l recommend for a FiO2 < 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 PaO2 VS Oxygen saturation
Oxygen monitoringl PaO2
l transcutaneous oxygen monitoring (SpO2)
l oxygen content
l PO2 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 O2/100 ml)
Arterial PaO2
l tissue oxygenation depends on PaO2 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 infantsl naturally occurredl repeated transfusion during
intensive care period
Oxygen saturation
l limitation to detect hyperoxia (PaO2 >12 kPa;SpO2 > 97%)
l sensitive to detect tissue hypoxemia when PaO2 is at the critical level (PaO2
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 PaO2 50 kPa
l saturation should be intermittently compared with PaO2 obtained from ABG
l lower acceptable limit of saturation: 85%
l upper acceptable limit of saturation: 97%
Oxygen saturation
l advantagesl noninvasivel rapid response timel no tissue damagel sensitive to detect hypoxia
l disadvantagesl varied with patient activityl influenced by edema, phototherapy, perfusionl insensitive to detect hyperoxia
Complications
ll burnsburnsll factors influencefactors influencell skin maturationskin maturationll tightnesstightnessll duration of probe duration of probe
attachmentattachment
Oxygen toxicityOxygen 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 nonenzymaticantioxidants 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 oxidasesystem
ll hypoxanthine is the end product of the hypoxanthine is the end product of the purinepurinecatabolism in most human organscatabolism in most human organs
ll hypoxanthine is a break down product from hypoxanthine is a break down product from ATP, AMPATP, AMP
ll during hypoxia, hypoxanthine is accumulatedduring hypoxia, hypoxanthine is accumulatedll when hypoxanthine is oxidized to uric acid, when hypoxanthine is oxidized to uric acid,
oxygen radicals are formedoxygen radicals are formed
Mechanism for ischemia/reperfusion injury
hypoxanthine
ATP
isch
emia
oxygenation
AMP
XD
XO
O2
protease
O2 + H2O2 + urate-
Oxygen toxicity
Neonatal free radical diseasell respiratory tract: respiratory tract: bronchopulmonarybronchopulmonary dysplasiadysplasia
ll retina: retinopathy of prematurityretina: retinopathy of prematurity
ll brain: brain: intraventricularintraventricular hemorrhage, PV Lhemorrhage, PV L
ll gastrointestinal tract: necrotizing gastrointestinal tract: necrotizing enterocolitisenterocolitis
ll KUB: acute tubular necrosisKUB: acute tubular necrosis
Oxygen free radicals
O2 + 4 H + 4 e 2 H2O+
O2 + e O2
_ _(superoxide radical)
O2 + e H2O2
_
(hydroxyl radical)
(hydrogenperoxide)
H2O2 + e .OH_
.HO + e H2O_
(water)
Chemical mechanism of oxygen toxicity
Principle mechanism
l univalent reduction of molecular oxygen
l formation of free radical intermediates
Reactive O2 metabolites
l Superoxide free radical (O-2)
l Hydrogen peroxide (H2O2)
l Hydrogen free radical (OH-)
l Singlet oxygen (1O2)
Actions of free radicals
l injure biological membranes by lipid peroxidation
l inactivate enzyme
ldenature proteins
lbreak double strand of DNA
Antioxidant enzyme defense system
ll SuperoxideSuperoxide dismutasedismutase (SOD) (SOD) detoxified Odetoxified O--22
ll CatalaseCatalase detoxified Hdetoxified H22OO22
ll Glutathione Glutathione peroxidaseperoxidase (GP) detoxified H(GP) detoxified H22OO22
ll GG--66--PD provided NADPH reduced glutathionePD 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 leukocytell on exposure to bacteria, the oxygen uptake of on exposure to bacteria, the oxygen uptake of
neutrophils is increased as much as 50neutrophils is increased as much as 50--foldfoldll a large amount of a large amount of superoxidesuperoxide and hydrogen and hydrogen
peroxide radicals are formedperoxide radicals are formedll leukocytes attack bacteria with oxygen leukocytes attack bacteria with oxygen
radicalsradicalsll this phenomenon is called respiratory burstthis phenomenon is called respiratory burst
Effects of alveolar macrophage
proteolyticproteolytic damage in alveolar walldamage in alveolar wall
Exposure to prolonged high inspired oxygen Exposure to prolonged high inspired oxygen
influx of polymorphonuclear leukocytes
impaired antiproteasedefense system
release of proteolyticenzyme
Pulmonary change of oxygen toxicity
ll atelectasisatelectasis (surfactant inactivation)(surfactant inactivation)ll edemaedemall alveolar hemorrhagealveolar hemorrhagell inflammationinflammationll fibrin depositionfibrin depositionll thickening and hyalinization of alveolar thickening and hyalinization of alveolar
membranemembranell tracheal, bronchiolar and type 1 alveolar tracheal, bronchiolar and type 1 alveolar
lining cells were damagedlining cells were damaged
Free radical scavengers and antioxidants
Antioxidantsll vitamin Evitamin Ell bilirubinbilirubin
Free radical scavengers and antioxienzymes
Free radical scavengersll mannitolsmannitolsll superoxidesuperoxide dismutasedismutasell bilirubinbilirubinll uric aciduric acidll dimethyldimethyl sulphoxidesulphoxide
Factors that determine oxygen toxicity
ll maturationmaturationll nutritional and endocrine statusnutritional and endocrine statusll duration of expose to oxygenduration of expose to oxygenll other oxidantsother 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
ll allall infantsinfants whowho areare atat riskrisk willwill bebe monitoredmonitored withwith aannoxygen oxygen saturationsaturation monitormonitor
ll thethe upperupper limitslimits forfor thethe monitormonitor alarmalarm willwill bebe routinelyroutinelysetset atat 95%95%
ll dailydaily attemptsattempts shouldshould bebe mademade toto lowerlower thethe FiOFiO22 ininstablestable,, convalescingconvalescing infantsinfants withwith OO22 saturationssaturations inin
thethe lowlow toto midmid 9090’’s s
ll correlatingcorrelating arterialarterial samplessamples willwill bebe obtainedobtained//attemptedattempted
twicetwice weeklyweekly
ROP: oxygen monitoring policy
ll aadministerdminister oxygenoxygen viavia a a hoodhood asas a a primaryprimary modemode ofofdeliverydelivery forfor infantsinfants << 1500 1500 gg
ll uusese oximetry oximetry toto determinedetermine thethe optimumoptimum flowflow andand distancedistancefromfrom thethe faceface whenwhen usingusing shortshort termterm blowblow byby OO2.2.
ll mmonitoronitor infantsinfants atat riskrisk byby settingsetting a a strictstrict upperupper limitlimit forfor thethe
oximeteroximeter ofof 95%95%
ll IfIf possiblepossible a a calibrationcalibration PaOPaO22 shouldshould bebe obtainedobtained twicetwice
weeklyweekly;; simultaneoussimultaneous FiOFiO2,2, SaOSaO22 andand PaOPaO22 willwill bebe recordedrecorded
l obtain an arterial blood gas when an "at-risk" infant
who was previously in room air is retreated withoxygen.
l if the arterial PaO2 > 90 mm Hg, notify a physician and
document the response
l adjust FiO2 based on ordered parameters using
oximetry and/or transcutaneous monitoring.
l ensure that an ROP check has been done at sixweeks of age on infants <1500 g.
ROP: oxygen monitoring policy
Prognostic factors
l P(A-a)O2 differencel in infants with PPHN, the mortality was
79% if P(A-a)O2 was equal to 610 mm Hg for 8 consecutive hrs
l Oxygen index (OI)l definition: MAP x FiO2/ PaO2
l OI>40: 80% mortalityl 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 Hgl normal value in the neonatel 40-50 mm Hg at birthl 300 mmHg (FiO2 1.0)
Alveolar-arterial Oxygen Pressure Difference
l P(A-a)O2 – alveolar-arterial oxygen pressure differencel correlate with severity of lung disease
lmethod of calculation
l PAO2 = [FiO2 x (Patm - PH2O)] - PCO2
l Exp. PaO2 = 673 mm Hg (FiO2 1.0; PCO2 40 mmHg)
Etiology of high P(A-a)O2 difference
l diffusion block at the alveolar-capillary level
l V/Q mismatch in the lungl a result of ventilated areas poorly perfusionl perfused areas poorly ventilated intracardiac
l fixed right-to-left shunt
Graph for estimation the shunt at differentinspired oxygen
Graph for estimation the shunt at differentinspired oxygen
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60%inspired oxygen80%inspired oxygen100%inspired oxygen