Symposium Papers - Respiratory Care

1 Symposium PapersOxygen Therapy in the Neonatal Care EnvironmentBrian K Walsh RRT-NPS, Toni M Brooks RRT, and Barry M Grenier RRT-NPSI ntroductionPhysiologic Effects of oxygen Therapy: Benefits and Adverse EffectsTreatment of HypoxiaOxidative StressRetinopathy of PrematurityChronic Lung DiseaseLong-Term OutcomesOxygen During ResuscitationOxygen Delivery DevicesBlow-By OxygenOxygen HoodLow-Flow Nasal CannulaHigh-Flow Nasal CannulaDevice-Related ComplicationsAdvances in oxygen TherapyClosed-Loop FIO2 RegulationNew-Generation Pulse OximetryDiscussionUnresolved QuestionsFuture of Neonatal oxygen TherapyThe use of oxygen in the treatment of neonates with Respiratory distress has been reported for morethan a century. oxygen therapy is generally titrated to one or more measures of blood oxygenationand administered to reverse or prevent hypoxia. Individual responses to oxygen therapy varygreatly, depending on the particular cause of hypoxia and the degree of impairment.

2 Despite thisfocused purpose, oxygen administration in this patient population has become complex. The longerwe deliver this drug, the more we discover its beneficial and detrimental effects. New and innovativeways to deliver and monitor this therapy have improved outcomes. Despite this vast experiencethere still remain some unanswered questions regarding the use of oxygen in the neonatal envi-ronment. Nonetheless, oxygen is a major staple in our treatment arsenal for words: oxygen ; neonatal; infant, newborn; retinopathy of prematurity; oxygen inhalation therapy.[Respir Care2009;54(9):1193 1202. 2009 Daedalus Enterprises]IntroductionThe use of oxygen in the treatment of neonates withrespiratory distress has been reported for more than a cen-tury. In 1907, Budin recommended oxygen suppliedthrough a funnel, the large opening of which is placedbeside the infant s face, for the treatment of cyanoticepisodes in the 1930s, Hess2,3developed anincubator (Fig.)

3 1) capable of delivering approximately 40% oxygen for extended periods of time. By the 1940s, aBrian K Walsh RRT-NPS, Toni M Brooks RRT, and Barry M GrenierRRT-NPS are affiliated with the Respiratory Care Department, Chil-dren s Hospital Boston, Boston, authors have disclosed no conflicts of Walsh presented a version of this manuscript at the New HorizonsSymposium, Neonatal Respiratory Care, at the International Respira-tory Congress of the American Association for Respiratory Care, at the54th International Respiratory Congress of the American Association forRespiratory Care, held December 13-16, 2008, in Anaheim, SEPTEMBER2009 VOL54 NO91193commercially available incubator capable of providing ahigh concentration of oxygen facilitated the liberal use ofoxygen for the treatment of cyanosis, apnea, and periodicbreathing in ,4 Throughout this time, oxygenadministration was guided by the clinical observations ofskin color, as well as the rate, regularity, and work ofbreathing.

4 It wasn t until the 1960s and 1970s that tech-nology micro-sampling of blood gases, transcutaneousoxygen monitoring, and, later, pulse oximetry becameavailable for more precise monitoring of physiologic overall goal of oxygen therapy is to achieve ade-quate oxygenation using the lowest concentration of in-spired oxygen . However, achieving this goal is compli-cated by a number of factors. Despite over 75 years ofroutine oxygen administration to newborn infants, the op-timal level of oxygenation one that avoids the detrimen-tal effects of hypoxia on the one hand, and those caused byhyperoxia on the other has not yet been clearly defined,5-7leading to wide variations in the term ad-equate oxygenation is not complicating fac-tors in achieving the goals of neonatal oxygen therapyinclude patient size, tolerance of delivery devices, andvariability in the use of delivery devices, which suggestthat clinicians often lack adequate knowledge in the use ofoxygen delivery equipment,10and the lack of training inthe concepts of neonatal oxygenation and equipment usedto monitor the effects of oxygen Effects of oxygen Therapy.

5 Benefits and Adverse EffectsDespite its universal acceptance as a life-saving therapyfor newborns, oxygen administration is associated withnumerous physiologic effects, particularly when used totreat premature of HypoxiaWhile oxygen therapy is generally titrated to some mea-sure of arterial oxygenation in response to an abnormallyCorrespondence: Brian K Walsh RRT-NPS, Respiratory Care Depart-ment, Children s Hospital Boston, 300 Longwood Avenue, MA-861,Boston MA 02115. E-mail: 1. Hess bed equipped with an oxygen therapy unit (A-side view). 1: Pressure gauge. 2: oxygen flow regulator. 3: Flow meter. 4: Glassand metal hinged door for feeding purposes. 5: Thermometer window. 6: Metal hinged door for purposes of body care of the : Ventilator with small and large exit openings. 8 12:Controls for maintaining temperature in water-jacket of the incubator. (From Refer-ence 3, with permission.)OXYGENTHERAPY IN THENEONATALCAREENVIRONMENT1194 RESPIRATORYCARE SEPTEMBER2009 VOL54 NO9low level of blood oxygen , orhypoxemia, oxygen is ad-ministered to the neonate to reverse or prevent is defined as a deficit of oxygen at the cellularlevel, and is commonly caused by one or more of thefollowing: the reduced availability of oxygen at the alve-olar level, due to pulmonary disease (hypoventilation, un-even matching of ventilation to perfusion, diffusion de-fects); intrapulmonary shunts or right to left cardiacshunts; reduced oxygen carrying capacity due to anemia orabnormal blood hemoglobin; or impaired oxygen deliverydue to shock, heart failure, or localized decreases in ,13 Left untreated, hypoxia can lead to serious andpermanent brain injury and responses to oxygen therapy vary greatly,depending on the particular cause of hypoxia and the de-gree of impairment.

6 Hypoxia caused by hypoventilationand ventilation-perfusion anomalies associated with pul-monary disease will be most responsive to oxygen large increases in FIO2will produce only small in-creases in available oxygen if hypoxia is caused by cardiacshunts, shock, and hemoglobin ,13It should be stressed, however, that even small increases inoxygen availability may prevent life-threatening decom-pensation in the hypoxic StressThe role of oxygen and oxidative stress in the develop-ment of a number of neonatal diseases has generated muchinterest. Oxidative stress has been defined as an imbalancebetween pro-oxidant and anti-oxidant forces in the include oxygen radicals or reactive oxygenspecies, which can be cytotoxic because of their ability toalter cellular components and function. Reactive oxygenspecies are generated as a result of normal mitochondrialrespiration, but also during the reperfusion phase of hy-poxic tissue injury and in association with infection ,16 oxygen is toxic because of the pro-duction of reactive oxygen species; thus oxygen adminis-tration increases oxidative defenses include the enzymes superoxidedismutase, catalase, and glutathione.

7 Nonenzymatic anti-oxidants start to cross the placenta in late gestation, andinclude vitamins A, C, E, and ubiquinone. Premature in-fants are at particular risk from oxidative stress becauseboth endogenous and passively acquired exogenous anti-oxidant defense systems do not accelerate in maturationuntil late in the third ,17,18 Investigators haveattempted to reverse or prevent the damage associated withreactive oxygen species not only by appropriate oxygenadministration but also by administering antioxidants; how-ever, this therapy has not shown to be suggested the termoxygen radical disease of neona-tologyto encompass a variety of newborn diseases whosepathogenesis involves oxidative stress and injury, whichinclude retinopathy of prematurity, bronchopulmonary dys-plasia, necrotizing enterocholitis, and intraventricular of PrematurityThough long recognized as a complication of oxygentherapy, retinopathy of prematurity remains a major causeof morbidity for premature of pre-maturity is a disease limited almost exclusively to prema-ture infants and is characterized by abnormal vasculariza-tion of the retina, causing a range of vision impairment,including blindness.

8 Much has been described in the lit-erature regarding the role of supplemental oxygen in thedevelopment of retinopathy of al-tered regulation of vascular endothelial growth factor hasbeen suggested25,26as one of the factors in the pathogen-esis of retinopathy of prematurity (Fig. 2). In prematureFig. 2. The proposed role of vascular endothelial growth factor(VEGF). A: It is hypothesized that normal retinal vessel develop-ment is stimulated by production of VEGF (red) anterior to thedeveloping vasculature. In addition, maintenance of some retinalvessels is dependent on VEGF. B: In the first phase of retinopathyof prematurity, exposure to relative hyperoxia after birth interruptsthe gradient of physiologic hypoxia in the immature retina, leadingto downregulation of VEGF production, with associated vaso-obliteration and cessation of vessel growth. C: As the metabolicdemand of the developing retina increases, the nonperfused por-tions of the retina become hypoxic and overproduce VEGF.

9 D: Neo-vascularization occurs in response to overproduction of VEGF,producing retinopathy of prematurity. If VEGF production persists,then the retinopathy of prematurity will progress. (From Refer-ence 26, with permission.)OXYGENTHERAPY IN THENEONATALCAREENVIRONMENTRESPIRATORYCAR E SEPTEMBER2009 VOL54 NO91195infants the retina is incompletely vascularized. In utero thearterial oxygen pressure of the fetus is 22 24 mm premature birth, relative hyperoxia may downregu-late vascular endothelial growth factor production. Admin-istration of supplemental oxygen may lead to sustainedhyperoxia, setting the stage for vaso-obliteration of exist-ing vessels and arrest of the vascularization. Over time, asthe metabolic demands of the developing eye increase, theimmature non-perfused area of the retina becomes hypoxicand may overproduce vascular endothelial growth factorpathologically. High levels of vascular endothelial growthfactor stimulate neovascularization of the retina, whichin severe cases may result in retinal fibrosis and studies in the 1950s demonstrated the clearlink between the liberal use of oxygen and the develop-ment of retinopathy of prematurity, or retrolental fibropla-sia, as it was then study by Kinsey et al,in 1956, that was not observation, demonstrated a 17%reduction in retinopathy of prematurity as well as a 9%reduction in blindness when curtailing oxygen therapy toroom air within the first 48 note, these studiesprovoked a drastic decrease in neonatal oxygen use thatwas associated not only with a reduction in retinopathy ofprematurity, but also with an increase in newborn deathsand cerebral ,32 With the improved survival of very-low-birth-weight infants during the past decade, retinopa-thy of prematurity continues to be a source of substantialmorbidity.

10 Wide intercenter variability exists in the inci-dence of severe ( stage 3) retinopathy of prematurity indifferent ,34 These differences could be attributedto the combination of many known and unknown factors;one explanation might be that differences in clinical prac-tices affect the rates of retinopathy of prematurity. Morerecent studies have demonstrated an association betweenretinopathyofprematurityandhighox ygensaturation,8,35,36and several studies suggest that fluctuations in oxygen -ation level may also have a role in its ,37 Itthus is possible that repeated cycles of hyperoxia and hyp-oxia favor the progression of retinopathy of ,39 While hyperoxia clearly plays a role, other riskfactors include growth retardation, male sex, septicemia,and, most significantly, low gestational age and addition, worsening retinopathy of prematu-rity has been linked to the overall severity of illness of thenewborn and the extent of other ,41 Chronic Lung DiseaseOxygen administration was identified as a risk factor inthe development of neonatal chronic lung disease in earlydescriptions of bronchopulmonary ,43In ani-mal studies.