improving neonatal transition by giving ventilatory support … · gestational age neonates ......

DOI: 10.1542/neo.13-6-e3432012;13;e343Neoreviews

Charles C. Roehr, Colin J. Morley and Maximo VentoRoom

Improving Neonatal Transition by Giving Ventilatory Support in the Delivery

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Improving Neonatal Transition by GivingVentilatory Support in the Delivery RoomCharles C. Roehr, MD,

PhD,*† Colin J. Morley,

MD,‡ Maximo Vento, MD,

PhDx

Author Disclosure

Drs Roehr, Morley, and

Vento have disclosed

no financial

relationships relevant

to this article. This

commentary does not

contain a discussion of

an unapproved/

investigative use of

a commercial product/

device.

Educational Gap

With the search on for gentler means of resuscitation support for extremely low

gestational age neonates (ELGANs), clinicians must pay close attention to evidence-

based research on sustained inflations, tidal volume, use of surfactant and CPAP, and less

invasive resuscitation techniques and devices.

AbstractExtremely low gestational age neonates are likely to require help with breathing. Strat-egies to enhance uncomplicated pulmonary transition are critically evaluated in thisarticle. These strategies include antenatal corticosteroid treatment and different respi-ratory support options immediately after birth. Important techniques for providingearly neonatal support include the careful monitoring of the postnatal progressionof heart rate and oxygenation in the delivery room, the provision of continuous dis-tending positive airway pressure with avoidance of high tidal volumes, surfactant treat-ment without intubation, and options for avoiding endotracheal intubation by givingnasal continuous positive airway pressure from birth. We discuss how the less invasivestrategies are likely to reduce iatrogenic neonatal lung injury and may indeed help toreduce the incidence of bronchopulmonary dysplasia.

Objectives After completing this article, readers should be able to:

1. Avoid endotracheal intubation and confidently use nasal continuous positive airway

pressure as primary respiratory support in breathing in extremely low gestational

age neonates.

2. Minimize postnatal lung injury and enhance lung function at term by applying early

continuous positive airway pressure from birth.

3. Assess adequate neonatal transition objectively by checking the progression of

peripheral oxygen saturation and heart rate by using a pulse oximeter.

4. Titrate additional oxygen supplementation via an oxygen blender.

Assisting Transition of Extremely LowGestational Age Neonates in the Delivery RoomGiving respiratory assistance to newborn infants is one of themost common medical interventions. (1) On most occa-sions, all they need is a little help for the transition to airbreathing, although this transition is commonly referredto as “resuscitation.” Even the most immature infants (ex-tremely low gestational age neonates [ELGANs]; ie, lessthan 28 weeks’ gestation) will almost invariably breatheand have a heart rate at birth. (2) Although these immatureinfants require the most support during the transition period,cardiopulmonary resuscitation, including chest compressions,

Abbreviations

CPAP: continuous positive airway pressureELGAN: extremely low gestational age neonateFiO2: fraction of inspired oxygenFRC: functional residual capacityMV: mechanical ventilationnCPAP: nasal continuous positive airway pressurePEEP: positive end expiratory pressurePIP: peak inspiratory pressureVT: tidal volume

*Department of Neonatology, Charite University Medical Center Berlin, Berlin, Germany.†Dieter Scheffner Center for Medical Teaching and Educational Research, Charite University Medical Center Berlin, Berlin, Germany.‡Neonatal Research, The Royal Women’s Hospital, Parkville, Melbourne, Victoria, Australia.xDivision of Neonatology, University & Polytechnic Hospital La Fe, Valencia, Spain.

Article respiratory

NeoReviews Vol.13 No.6 June 2012 e343



is only rarely required, (3) and bradycardia is almost alwayssuccessfully counteracted by effective ventilation. Whencardiopulmonary resuscitation is performed, it is associatedwith poor outcomes. (4)

Strategies to successfully support the ELGAN afterbirth ideally include evidence-based antenatal manage-ment, so before we discuss respiratory support, it is crucialto emphasize the importance of treating all mothers likelyto begin very preterm labor with antenatal steroids at least48 hours before the delivery. The administration of ante-natal steroids is the single most effective treatment to re-duce respiratory problems and to improve the outcomeof very preterm infants. (5)

Once born, the newborn needs to swiftly clear his or herlungs of fluid and aerate them to establish gas exchange.The volume of air with each breath is the tidal volume(VT). The VT varies depending on the breathing effortsof the infant, the compliance of the lungs and chest wall,and the airway resistance. With each breath, more air entersthan leaves the lungs, thus creating the functional residualcapacity (FRC). The FRC is the gas volume in the lungat the end of passive expiration. Infants develop an FRCof w30 mL/kg. After birth, effective ventilation requiresa VT of w5 mL/kg at a rate of at least 60 per minute.(6) The process of complete lung fluid clearance and pul-monary aeration takes several hours, but to achieve ade-quate ventilation, an FRC must be formed within thefirst minutes after birth (7) (Fig 1). Failure to establish

adequate lung aeration results in inadequate gas exchangeand respiratory failure. (8)

In term infants, lung aeration is achieved by large neg-ative inspiratory pressures during the first breaths. (6)ELGANs, however, have a pliable and unstable chest walland underdeveloped respiratory muscles, which make itdifficult for them to take large enough breaths to forman FRC (Table 1). The most important first step to aidthe transition to effective breathing for ELGANs is tohelp them form and maintain a sufficient FRC and a largeenough VT, which is best done by providing positive end-expiratory pressure (PEEP) directly from birth. (9)

Avoiding Lung InjuryDeterminants of Lung Injury

Björklund et al described how preterm lambs’ lungs ven-tilated with just six inflations with a high VT immediatelyafter birth were seriously damaged (the concept of volu-trauma). (10) Dreyfuss and Saumon showed the harmfuleffect of high VT on mature rat lungs and that the injurywas not due to high inflating pressures per se. (11) Jobeet al compared the effects of mechanical ventilation (MV)or continuous positive airway pressure (CPAP) in pre-term lambs and showed that lung volume was higher afterCPAP, with significantly lower inflammatory markerscompared with MV (the concept of barotrauma). (12)

Complications of MV include cardiovascular and cere-brovascular instability during intubation, injury from the

endotracheal tube (subglottic ste-nosis and tracheal lesions), and in-creased pulmonary and systemicinfection, which, together withthe recurrent shear stress occurringwith every inflation (concept of ate-lectotrauma), contribute with volu-trauma and barotrauma to acuteand chronic lung damage. (13)

Avoiding Intubation andVentilation

Twenty-five years ago, Avery et al,reporting outcomes of infants weigh-ing <1500 g, found that those trea-ted from birth with CPAP (withoutsurfactant) had less bronchopulmo-nary dysplasia at 28 days than thosetreated with MV. (14) One explana-tion is that by using CPAP instead ofMV, less volutrauma, barotrauma,and atelectotrauma are being caused.Recent evidence from the CPAP

Figure 1. Progression of functional residual capacity (FRC), lung compliance (CL ), andpulmonary resistance (R).

respiratory ventilatory support

e344 NeoReviews Vol.13 No.6 June 2012



or Intubation of Neonates at Birth (COIN) trial co-hort supports this concept. (15) Following Averyet al’s observation, further studies (16)(17)(18)(19)(20)(21) and large randomized controlled trials (22)(23)(24) confirmed that many ELGANs treated withCPAP from birth have outcomes at least as good as in-tubated ventilated infants, without the complications ofventilation.

Gentle AerationConsidering these facts and the previously described ad-verse effects of MV, nasal CPAP (nCPAP) is now themainstay of gentle ventilation. When providing CPAP orpositive pressure ventilation in the delivery room to verypreterm infants, it is best accomplished with T-piece re-suscitators, because they allow control of the deliveredpressures and are the only devices that can provide positivepressure ventilation with PEEP and CPAP to a breathing

infant. (25)(26)(27) Face masks are currently the preferredpatient interface. Avoidingmask leak by a goodmask hold isa central element of effective respiratory support. (28) Theuse of a PEEP valve on a self-inflating bag will provide onlyvariable decelerating PEEP with ventilation rates >40 perminute. (29)(30) A self-inflating bag cannot provide CPAP.

Facilitating Lung Aeration and AvoidingAtelectasis

For breathing infants, providing a positive distending pres-sure may be enough to effectively assist pulmonary transi-tion. (31) Clinical studies and experimental animal datareveal that initial aeration is best when PEEP is used. (9)An nCPAP pressure of 5 cm H2O is traditionally used inmost NICUs with good results. (32) In the landmark pub-lication on nCPAP for preterm infants, Gregory et al (33)used pressures up to 15 mm Hg. The Cochrane reviewof nCPAP after extubation revealed that pressures

Table 1. Morphologic and Functional Disadvantages of the PrematureLung

Cause Consequence Signs

Morphologic factorsDevelopmental immaturity (saccularstage)

Decreased alveolar surface area for gasexchange (pulmonary side)

Hypoxia

Decreased blood-air surface area withinsufficient vascularization

Decreased alveolar vascular bed for gasexchange (vascular side/blood saturation)

Immature (saccular) vascularization ofalveolar structures

Increased diffusion distance

Reduced number of lymphatic vessels Decreased fluid clearance CrepitationsImmature, saccular alveoli Decreased tolerance for alveolar stretch Alveolar damage, hyaline

membranesDecreased numbers of elastic fibers inalveolar tissue

Cartilaginous rib cage Reduced resistance against atmosphericpressure and pulmonary recoil

Recessions, atelectasis

Small airways Increased resistance Labored breathingBiochemical factorsSmall and insufficient alveolarsurfactant pool and slow surfactantmetabolism

Alveolar collapse Respiratory distress, hypoxia

Imbalance of pro- and anti-inflammatory enzymes

Pulmonary inflammation, destruction ofalveolar and parenchymal structures

Hyaline membranes

Decreased intracellular antioxidativecapacity

Functional factorsDelayed absorption of fetal lung fluid/lung clearance

Delayed establishment of FRC/VT Transient and persistenttachypnea

Immature respiratory muscles Apnea ApneaHigh dead space/FRC ratio Persisting dead space ventilation Hypoxia, hypercarbiaExtracardiac shunting (patentductus arteriosus)

Pulmonary overflow, persisting pulmonarycirculation

Hypoxia, hypercarbia

FRC¼functional residual capacity; VT¼tidal volume.





<5 cm H2O are ineffective. (34) A study of infants withmild respiratory distress syndrome showed the highestFRC and VT, the lowest respiratory rate, and the leastthoracoabdominal asynchrony occurred at a CPAP pres-sure of 8 cm H2O. (35) In infants with low lung compli-ance, the pressure may need to be increased to w10 cmH2O. Conversely, high nCPAP pressures, if used in aninfant with compliant lungs, interfere with pulmonaryblood flow and may cause overdistension, leading to car-bon dioxide retention (Table 2). The decision aboutwhich CPAP pressure to use is difficult and depends onthe infant’s condition. If a very preterm infant has increas-ing fraction of inspired oxygen (FiO2) and an opaque chestradiograph, we would increase the pressure in incrementsof 1 cm H2O and observe the effect. In the absence of ev-idence-based guidelines, we use nCPAP in the range of 5to 8 cm H2O, adjusting it on the basis of FiO2 require-ment and clinical assessment of work of breathing.

Avoiding High VTsThe purpose of gentle assisted ventilation at birth, for ap-neic infants, is to achieve an adequate VT to facilitate gasexchange and reduce lung injury. Traditionally, the judg-ment of sufficient ventilation pressure is made by observ-ing chest wall movement and a rise in oxygen saturationand heart rate. Although guidelines suggest that a peakinspiratory pressure (PIP) between 20 to 40 cm H2Oshould be used for resuscitation, the mere focus on theprovision of a given pressure does not equate to stableVTs, because there is usually a large and variable maskleak, the infant’s breathing may vary from apnea to cry-ing, and the pulmonary compliance and resistance change.(36)(37) Therefore, using a fixed PIP can lead to VTs that

are too high and may damage the lungs or so low that ven-tilation is inadequate. Rapid adjustments of PIP will be re-quired to control the VT and protect against lung damage.(36) Recent studies have shown that resuscitators are un-able to deliver appropriate VT during neonatal training orduring neonatal resuscitation. (38) With in vitro studies,Kattwinkel et al found that showing resuscitators the VT

enabled them to adjust the PIP and achieve the VT moreaccurately than by showing the pressure. (39) In the fu-ture, it will be important that resuscitators of very preterminfants are able to see and control the VT rather than justthe PIP.

CPAP: How Does It Work?nCPAP is now the mainstay of gentle ventilation, becausewhen positive pressure ventilation is used, it is usuallybrief. (40) CPAP effectively supports the breathing of verypreterm infants through several mechanisms. (31) The highflow of gas through the nasopharynx continuously flushesthe dead space, so distension of the upper airway reducesresistance to airflow. It also improves the compliance of stifflungs; regularizes and slows the respiratory rate, therebydiminishing the work of breathing and apnea; and reducesinflammation (Table 2). The continuous pressure in thepharynx aids lung expansion and improves ventilation-perfusion and oxygenation. By supporting end-expiratorylung volume, it reduces repeated alveolar collapse and re-expansion, epithelial injury, and protein leak and helpsconserve endogenous surfactant. A combination of allthese mechanisms reduces the need for ventilation.

There have been many case reports or historical seriesdemonstrating the effectiveness of early CPAP. There arenow four randomized controlled trials that have randomly

Table 2. Potential Advantages and Disadvantages of nCPAP Therapy

Advantages of CPAP Disadvantages of CPAP

Increases FRC and leads to an increase in PaO2 Increases the risk for air leak syndromes (pneumothorax,pneumomediastinum)

Improves pulmonary compliance and the work of breathing High CPAP levels lead to lung overinflation, decreasedcompliance, and increased work of breathing

Splints the airways and diaphragm Lung overinflation decreases the VT and may increase PCO2and the dead-space fraction

Prevents alveolar collapse Increased intrathoracic pressure may reduce venous returnto the heart and decrease cardiac output

Reduces the alveolar-arterial oxygen pressure gradient Air may escape into the stomach, causing gaseousdistension (CPAP-belly syndrome)

Decreases the amount of intrapulmonary shunting Skin excoriation and nasal damage may lead to airwayobstruction and infection

Reduces obstructive and mixed apneaConserves surfactant

CPAP¼continuous positive airway pressure; FRC¼functional residual capacity; nCPAP¼nasal continuous positive airway pressure; VT¼tidal volume.





assigned very preterm infants to continue on nCPAPor receive intubation and ventilation with surfactant.(22)(23)(24)(41) In summary, they show that very pre-term neonates treated with early nCPAP, with or withoutprophylactic surfactant, had outcomes similar to thosetreated with MV. Early CPAP might obviate the needfor MV or surfactant.

nCPAP can be delivered through several different de-vices, but short binasal prongs appear to be more effec-tive than nasopharyngeal tubes. Nasal masks are nowbeing used and may be good alternatives to nasalprongs. Comparisons of devices are few. Analysis ofthe two trials comparing single with double nasal prongsafter extubation of preterm infants confirmed that doubleprongs are better for preventing extubation failure (relativerisk: 0.59; confidence interval: 0.42–0.85). (42) Anothertrial compared the Infant Flow Driver system (EME,Brighton,UK) to Inca prongs (CooperSurgical, Trumbull,USA) and found no difference in rates of extubation fail-ure, death, or bronchopulmonary dysplasia. (42)

Mazzella compared the Infant Flow Driver witha single long nasopharyngeal tube for treating preterminfants with respiratory distress. (43) Although infantstreated with the Infant Flow Driver had lower oxygen re-quirements and respiratory rates, there were no significantdifferences in the need for MV or the duration of CPAP.

The most optimal CPAP pressure has not yet been elu-cidated. To produce the best effect, the pressure should be‡5 cm H2O. It will obviously vary depending on the se-verity of the lung disease being treated and the infant’sweight.

With many very preterm infants being treated withnCPAP from birth, some will fail to respond to CPAP treat-ment and will need MV. At the moment, there is no con-sensus about the definition of CPAP failure. The criteriaused are a high and rising PaCO2, the FiO2, and apnea.Obviously, an infant who has serious apnea must be ven-tilated, so that decision is relatively easy; however, studiesdiffer about the PaCO2 level that defines respiratory failureand the FiO2 level above which an infant should be ven-tilated. (44)(45) The lower the PaCO2 or FiO2 level chosento define failure, the more infants will be ventilated. If theobject of gentle ventilation is to reduce ventilation rates,then the cutoff levels of PaCO2 and FiO2 should be chosenwith care. Whatever cutoffs are chosen, it is importantthat causes of CPAP failure are treated before the deci-sion is made to intubate the infant. These causes includeairway obstruction from secretions and CPAP prongsthat are too small. Treating a large mouth leak and in-creasing CPAP should be tried before accepting thatCPAP has failed.

Surfactant TreatmentHistorically, trials have shown that surfactant reducedmortality and air leaks; however, those studies were donebefore early CPAP was used, most did not involve the useof antenatal steroids, and caesarean deliveries were per-formed with the use of general anesthesia. Therefore, theresults of these trials cannot be applied directly to infantsreceiving modern prenatal and postnatal care. Nonetheless,it is important to decide what the benefit of surfactant is inrelation to the cost and invasiveness of the procedure.Many ELGANs will do well with nCPAP without intuba-tion and surfactant. Some may fail to respond to CPAPtreatment and require ventilation. They should then betreated with surfactant. The question is how to detect, atbirth, those infants who will fail to respond to CPAP andrequire surfactant, with or without subsequent MV, andthose who can manage well with just CPAP.

The Scandinavian approach of combining surfactanttreatment with CPAP is the INSURE procedure: an in-fant is intubated, given surfactant, and then extubatedto CPAP as soon as possible. (46)(47)(48) The INSUREprocedure may reduce the need for MV and oxygen sup-plementation; however, a randomized trial by Sandri et alcompared INSURE with CPAP alone and found no sig-nificant benefits of INSURE. (41) A new idea is for skilledneonatologists to give surfactant slowly to an infant whilehe or she is being treated with CPAP, through a tiny tubeinserted through the larynx. This method has been testedin a small number of trials with promising results, (49)(50)(51) which showed a reduction in rate and duration ofMV and a reduction of pulmonary and extrapulmonarysequelae. More results from prospective studies of theefficacy and safety of this procedure are awaited. A listof further open questions regarding the use of noninva-sive ventilation is found in Table 3.

Supplementation of OxygenAir should be used at the start of resuscitation of terminfants; (51) however there is limited evidence forELGANs. Two randomized, controlled studies of infants<32 weeks’ gestational age on different initial oxygen con-centrations are available. Wang et al investigated startingwith an FiO2 of 0.21, but most infants did not reachthe targeted SpO2 of 85% by 5 minutes and had to be trea-ted with oxygen. (52) Escrig et al and Vento et alshowed that a comparable group of infants reached anSpO2 of 85% by 10 minutes if they started with anFiO2 of 0.30. (53)(54) Stenson et al reported on theBenefits of Oxygen Saturation Targeting Trial II(BOOST-II), which investigated different SpO2 target





ranges (91%–95% or 85%–89%) for infants <28 weeks’gestational age starting several hours after birth, using in-ternally masked monitors. (55) The study was terminatedbecause of higher survival in infants in the higher SpO2 tar-get range. In the Surfactant Positive Airway Pressure andPulse Oximetry Randomized Trial (SUPPORT) trial, (23)infants in the lower SpO2 target group had a slight increasein mortality (19.9% vs 16.2%; P¼ 0.04) but less severe ret-inopathy (8.6% vs 17.9%; P < 0.001). (23) Until furtherevidence becomes available, the need for oxygen duringtransition of ELGANs should be assessed by pulse oxime-try, (56) and the FiO2 titrated according to SpO2.

Table 3. Open Questions Regarding Noninvasive Respiratory Therapy FromBirth for ELGANs

Knowledge Gaps Related Research Issues Proposed Actions

How gentle is "gentle enough"? Methods for identification of sufficienthandling

Qualitative video assessment

Sustained inflations (SIs) Is the concept of SI to minimize lunginjury sufficiently proven?

Clinical trials

What timing, synchronization, and ideallevel of SI pressure would be ideal?

Which pressures are advisable?Do we have suitable devices to realize therecommended strategy?

Which kinds of devices or methodsshould be developed?

Lung volume (FRC) Can FRC be measured during the initialaeration of the lung, and how?

Device to evaluate the pulmonary gascontent

Measurement of VT Can VT be reliably measured while givingnoninvasive respiratory support in thedelivery room?

Device to evaluate VT duringnoninvasive respiratory support

Use of surfactant and CPAP Assessment of need for surfactanttreatment: how to assess?

Clinical studies

Can the addition of antioxidants helpstabilize endogenous and/or exogenoussurfactant?

Laboratory studies

How stable are endogenous andexogenous surfactants under CPAP?

Laboratory studies

Is CPAP equivalent to MV? Do we have sufficient evidence fromcomparative studies regarding CPAPversus modern ventilation techniques?

Clinical studies

Sufficient evidence for practicingINSURE or even less invasivesurfactant application techniques?

Evidence from large enough clinical trialswith sufficient follow-up available?

Clinical studies

Early markers of bronchopulmonarydysplasia (BPD) development

Which markers are available? Animal and human observationalstudies

Will early markers of BPD developmenthave an impact on planning of clinicalstudies?

Is BPD becoming a dispensableoutcome measure?

What could be used as alternativeindices?

Testing of proposed alternatives

CPAP¼continuous positive airway pressure; ELGANs¼extremely low gestational age neonates; FRC¼functional residual capacity; MV¼mechanicalventilation; SI¼sustained inflations. Adapted with permission from Wauer and Roehr 2010. (57)

American Board of Pediatrics Neonatal-PerinatalMedicine Content Specifications

• Know the medications, indications for, andcomplications of drugs used to enhancefetal lung maturity.

• Know indications for and properadministration of supplemental oxygen inthe delivery room.

• Know factors that determine residual lung volume, functionalresidual capacity, and tidal volume, and how they changewith various pulmonary disorders.





References1. Lawn JE, Cousens S, Zupan J; Lancet Neonatal Survival SteeringTeam. 4 million neonatal deaths: when? where? why? Lancet. 2005;365(9462):891 9002. Dawson JA, Kamlin CO, Wong C, et al. Oxygen saturation andheart rate during delivery room resuscitation of infants <30 weeks’gestation with air or 100% oxygen. Arch Dis Child Fetal NeonatalEd. 2009;94(2):F87 F913. Singhal N, McMillan DD, Yee WH, Akierman AR, Yee YJ.Evaluation of the effectiveness of the standardized neonatal resuscitation program. J Perinatol. 2001;21(6):388 3924. Wyckoff MH, Salhab WA, Heyne RJ, Kendrick DE, Stoll BJ,Laptook AR; National Institute of Child Health and HumanDevelopment Neonatal Research Network. Outcome of extremelylow birth weight infants who received delivery room cardiopulmonaryresuscitation. J Pediatr. 2012; 160(2):239 244. e25. Crowley P. Prophylactic corticosteroids for preterm birth.Cochrane Database Syst Rev. 2000; (2):CD0000656. Vyas H, Field D, Milner AD, Hopkin IE. Determinants of thefirst inspiratory volume and functional residual capacity at birth.Pediatr Pulmonol. 1986;2(4):189 1937. Jobe AH, Hillman N, Polglase G, Kramer BW, Kallapur S,Pillow J. Injury and inflammation from resuscitation of the preterminfant. Neonatology. 2008;94(3):190 1968. Dimitriou G, Greenough A, Kavadia V. Early measurement oflung volume a useful discriminator of neonatal respiratory failureseverity. Physiol Meas. 1996;17(1):37 429. Siew ML, Wallace MJ, Kitchen MJ, et al. Inspiration regulatesthe rate and temporal pattern of lung liquid clearance and lungaeration at birth. J Appl Physiol. 2009;106(6):1888 189510. Björklund LJ, Ingimarsson J, Curstedt T, et al. Manualventilation with a few large breaths at birth compromises thetherapeutic effect of subsequent surfactant replacement in immaturelambs. Pediatr Res. 1997;42(3):348 35511. Dreyfuss D, Saumon G. Ventilator induced lung injury: lessonsfrom experimental studies. Am J Respir Crit Care Med. 1998;157(1):294 32312. Jobe AH, Kramer BW, Moss TJ, Newnham JP, Ikegami M.Decreased indicators of lung injury with continuous positive expiratory pressure in preterm lambs. Pediatr Res. 2002;52(3):387 39213. Slutsky AS. Lung injury caused by mechanical ventilation.Chest. 1999;116(1 suppl):9S 15S14. Avery ME, Tooley WH, Keller JB, et al. Is chronic lung diseasein low birth weight infants preventable? A survey of eight centers.Pediatrics. 1987;79(1):26 3015. Roehr CC, Proquitté H, Hammer H, Wauer RR, Morley CJ,Schmalisch G. Positive effects of early continuous positive airway

pressure on pulmonary function in extremely premature infants:results of a subgroup analysis of the COIN trial. Arch Dis ChildFetal Neonatal Ed. 2011;96(5):F371 F37316. De Klerk AM, De Klerk RK. Nasal continuous positive airwaypressure and outcomes of preterm infants. J Paediatr Child Health.2001;37(2):161 16717. Jacobsen T, Grønvall J, Petersen S, Andersen GE. “Minitouch”treatment of very low birth weight infants. Acta Paediatr. 1993;82(11):934 93818. Kamper J, Wulff K, Larsen C, Lindequist S. Early treatmentwith nasal continuous positive airway pressure in very low birthweight infants. Acta Paediatr. 1993;82(2):193 19719. Gittermann MK, Fusch C, Gittermann AR, Regazzoni BM,Moessinger AC. Early nasal continuous positive airway pressuretreatment reduces the need for intubation in very low birth weightinfants. Eur J Pediatr. 1997;156(5):384 38820. Vanpee M, Walfridsson U, Katz Salamon M, Zupancic JA,Pusley D, Jonsson B. Resuscitation and ventilation strategies forextremely preterm infants: a comparison study between two neonatal centers in Boston and Stockholm. Acta Paediatr. 2007;96(1):10 6; discussion, 8 921. te Pas AB, Spaans VM, Rijken M, Morley CJ, Walther FJ.Early nasal continuous positive airway pressure and low thresholdfor intubation in very preterm infants. Acta Paediatr. 2008;97(8):1049 105422. Morley CJ, Davis PG, Doyle LW, Brion LP, Hascoet JM,Carlin JB; COIN Trial Investigators. Nasal CPAP or intubationat birth for very preterm infants. N Engl J Med. 2008;358(7):700 70823. Finer NN, Carlo WA, Walsh MC, et al; SUPPORT StudyGroup of the Eunice Kennedy Shriver NICHD Neonatal ResearchNetwork. Early CPAP versus surfactant in extremely preterminfants. N Engl J Med. 2010;362(21):1970 197924. Dunn MS, Kaempf J, de Klerk A, et al; Vermont OxfordNetwork DRM Study Group. Randomized trial comparing 3approaches to the initial respiratory management of preterm neonates. Pediatrics. 2011;128(5). Available at: www.pediatrics.org/cgi/content/full/128/5/e106925. Bennett S, Finer NN, Rich W, Vaucher Y. A comparison of threeneonatal resuscitation devices. Resuscitation. 2005;67(1):113 11826. O’Donnell CP, Davis PG, Lau R, Dargaville PA, Doyle LW,Morley CJ. Neonatal resuscitation 2: an evaluation of manualventilation devices and face masks. Arch Dis Child Fetal NeonatalEd. 2005;90(5):F392 F39627. Roehr CC, Kelm M, Fischer HS, Bührer C, Schmalisch G,Proquitté H. Manual ventilation devices in neonatal resuscitation:tidal volume and positive pressure provision. Resuscitation. 2010;81(2):202 20528. Wood FE, Morley CJ, Dawson JA, Davis PG. A respiratoryfunction monitor improves mask ventilation. Arch Dis Child FetalNeonatal Ed. 2008;93(5):F380 F38129. Kelm M, Proquitté H, Schmalisch G, Roehr CC. Reliability oftwo common PEEP generating devices used in neonatal resuscitation. Klin Padiatr. 2009;221(7):415 41830. Morley CJ, Dawson JA, Stewart MJ, Hussain F, Davis PG. Theeffect of a PEEP valve on a Laerdal neonatal self inflating resuscitationbag. J Paediatr Child Health. 2010;46(1 2):51 5631. Morley C, Davis P. Continuous positive airway pressure:current controversies. Curr Opin Pediatr. 2004;16(2):141 14532. Roehr CC, Schmalisch G, Khakban A, Proquitté H, Wauer RR.Use of continuous positive airway pressure (CPAP) in neonatal

• Know the clinical strategies and therapies used to decreasethe risk and severity of respiratory distress syndrome (RDS).

• Know the management of RDS, including surfactantreplacement.

• Plan the ventilatory therapy for infants with respiratoryfailure of different etiologies.

• Know the indications for and techniques of continuouspositive airway pressure (CPAP).

• Know the effects and risks of CPAP.• Know the effects and risks of positive pressure ventilation.




http://www.pediatrics.org/cgi/content/full/128/5/



units a survey of current preferences and practice in Germany. EurJ Med Res. 2007;12(4):139 14433. Gregory GA, Kitterman JA, Phibbs RH, Tooley WH, HamiltonWK. Treatment of the idiopathic respiratory distress syndrome withcontinuous positive airway pressure. N Engl J Med. 1971;284(24):1333 134034. Davis PG, Morley CJ, Owen LS. Non invasive respiratorysupport of preterm neonates with respiratory distress: continuouspositive airway pressure and nasal intermittent positive pressureventilation. Semin Fetal Neonatal Med. 2009;14(1):14 2035. Elgellab A, Riou Y, Abbazine A, et al. Effects of nasal continuouspositive airway pressure (NCPAP) on breathing pattern in spontaneously breathing premature newborn infants. Intensive Care Med.2001;27(11):1782 178736. Schmölzer GM, Kamlin OC, O’Donnell CP, Dawson JA, MorleyCJ, Davis PG. Assessment of tidal volume and gas leak during maskventilation of preterm infants in the delivery room. Arch Dis ChildFetal Neonatal Ed. 2010;95(6):F393 F39737. Poulton DA, Schmölzer GM, Morley CJ, Davis PG. Assessment of chest rise during mask ventilation of preterm infants in thedelivery room. Resuscitation. 2011;82(2):175 17938. Schmölzer GM, Roehr CC. Use of respiratory functionmonitors during simulated neonatal resuscitation. Klin Padiatr.2011;223(5):261 26639. Kattwinkel J, Stewart C, Walsh B, Gurka M, Paget Brown A.Responding to compliance changes in a lung model during manualventilation: perhaps volume, rather than pressure, should bedisplayed. Pediatrics. 2009;123(3). Available at: www.pediatrics.org/cgi/content/full/123/3/e46540. Morley CJ, Davis PG. Advances in neonatal resuscitation:supporting transition. Arch Dis Child Fetal Neonatal Ed. 2008;93(5):F334 F33641. Sandri F, Plavka R, Ancora G, et al; CURPAP Study Group.Prophylactic or early selective surfactant combined with nCPAP invery preterm infants. Pediatrics. 2010;125(6). Available at: http://pediatrics.aappublications.org/content/123/3/e46542. De Paoli AG, Davis PG, Faber B, Morley CJ. Devices andpressure sources for administration of nasal continuous positiveairway pressure (NCPAP) in preterm neonates. Cochrane DatabaseSyst Rev. 2002; (4):CD00297743. Mazzella M, Bellini C, Calevo MG, et al. A randomised controlstudy comparing the Infant Flow Driver with nasal continuouspositive airway pressure in preterm infants. Arch Dis Child FetalNeonatal Ed. 2001;85(2):F86 F9044. Ammari A, Suri M, Milisavljevic V, et al. Variables associatedwith early failure of nasal CPAP in very low birth weight infants.J Pediatr. 2005;147(3):341 34745. Fuchs H, Lindner W, Leiprecht A, Mendler MR, HummlerHD. Predictors of early nasal CPAP failure and effects of variousintubation criteria on the rate of mechanical ventilation in preterm

infants of <29 weeks gestational age. Arch Dis Child Fetal NeonatalEd. 2011;96(5):F343 F34746. Verder H, Albertsen P, Ebbesen F, et al. Nasal continuouspositive airway pressure and early surfactant therapy for respiratorydistress syndrome in newborns of less than 30 weeks’ gestation.Pediatrics. 1999;103(2). Available at: http://pediatrics.aappublications.org/content/103/2/e2447. Bohlin K, Gudmundsdottir T, Katz Salamon M, Jonsson B,Blennow M. Implementation of surfactant treatment duringcontinuous positive airway pressure. J Perinatol. 2007;27(7):422 42748. Dargaville PA, Aiyappan A, Cornelius A, Williams C, De PaoliAG. Preliminary evaluation of a new technique of minimally invasivesurfactant therapy. Arch Dis Child Fetal Neonatal Ed. 2011;96(4):F243 F24849. Kribs A, Härtel C, Kattner E, et al. Surfactant withoutintubation in preterm infants with respiratory distress: first multicenter data. Klin Padiatr. 2010;222(1):13 1750. Göpel W, Kribs A, Ziegler A, et al; German Neonatal Network.Avoidance of mechanical ventilation by surfactant treatment ofspontaneously breathing preterm infants (AMV): an open label,randomised, controlled trial. Lancet. 2011;378(9803):1627163451. Saugstad OD, Ramji S, Soll RF, Vento M. Resuscitationof newborn infants with 21% or 100% oxygen: an updatedsystematic review and meta analysis. Neonatology. 2008;94(3):176 18252. Wang CL, Anderson C, Leone TA, Rich W, Govindaswami B,Finer NN. Resuscitation of preterm neonates by using room air or100% oxygen. Pediatrics. 2008;121(6):1083 108953. Escrig R, Arruza L, Izquierdo I, et al. Achievement of targetedsaturation values in extremely low gestational age neonates resuscitated with low or high oxygen concentrations: a prospective,randomized trial. Pediatrics. 2008;121(5):875 88154. Vento M, Moro M, Escrig R, et al. Preterm resuscitation withlow oxygen causes less oxidative stress, inflammation, and chroniclung disease. Pediatrics. 2009;124(3). Available at: http://pediatrics.aappublications.org/content/124/3/e43955. Stenson B, Brocklehurst P, Tarnow Mordi W; U.K. BOOST IItrial; Australian BOOST II trial; New Zealand BOOST II trial.Increased 36 week survival with high oxygen saturation target inextremely preterm infants. N Engl J Med. 2011;364(17):1680168256. Dawson JA, Kamlin CO, Vento M, et al. Defining the referencerange for oxygen saturation for infants after birth. Pediatrics.2010;125(6). Available at: http://pediatrics.aappublications.org/content/125/6/e134057. Wauer RR, Roehr CC. Report on the international seminar onsurfactant and CPAP in extremely low gestational age neonates,Vienna 2009. NeoReviews. 2010;11:e343 348






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NeoReviews QuizNew minimum performance level requirementsPer the 2010 revision of the American Medical Association (AMA) Physician’s Recognition Award (PRA) and creditsystem, a minimum performance level must be established on enduring material and journal-based CME activities thatare certified for AMA PRA Category 1 CreditTM. In order to successfully complete 2012 NeoReviews articles for AMAPRA Category 1 CreditTM, learners must demonstrate a minimum performance level of 60% or higher on thisassessment, which measures achievement of the educational purpose and/or objectives of this activity.

Starting with 2012 NeoReviews, AMA PRA Category 1 CreditTM can be claimed only if 60% or more of the questionsare answered correctly. If you score less than 60% on the assessment, you will be given additional opportunities toanswer questions until an overall 60% or greater score is achieved.

1. You are attending the delivery of a 28-weeks’-gestation preterm infant. Which of the following accuratelyrepresents what should be the normal (physiologic) progression of functional residual capacity (FRC), lungcompliance (CL) and resistance (R) over the first 24 hours?

A. Increasing FRC, decreasing resistance, increasing CL.B. Decreasing FRC, decreasing resistance, increasing CL.C. Decreasing FRC, increasing resistance, decreasing CL.D. Increasing FRC, increasing resistance, increasing CL.E. No change in FRC, resistance, or CL.

2. Your examination right after birth shows this baby is having significant sternal retractions and nasal flaring butis showing no signs of apnea. What is accurate statement about this baby?

A. The respiratory distress would not have been prevented had the mother been administered antenatalglucocorticoids.

B. Immediate intubation and aggressive mechanical ventilation with a peak inspiratory pressure of30 cm and high tidal volumes will avoid later volutrauma and decrease the cytokine responsecompared to early use of continuous positive airway pressure (CPAP).

C. Early CPAP may prevent the need for subsequent mechanical ventilation by forming and maintaininga sufficient FRC and a large enough tidal volume.

D. The single nostril intubation technique is clearly superior to nasal prongs and/or mask CPAP.E. Gaseous distension of the stomach—“CPAP Belly”—does not occur when nasal prongs are used.

3. Regarding oxygen use in this baby, which is correct?

A. The recommendations are the same as in term infants: start with 100% oxygen.B. Use only room air level oxygen.C. Oxygenation of the baby can be assessed accurately by physical exam alone.D. Until further evidence becomes available, the need for oxygen during transition of extremely low

gestational age neonates should be assessed by pulse oximetry and the inhaled oxygen titrated according tothe oxygen saturation provided by a pulse oximeter.

E. Inhaled FiO2 should not exceed 0.4 in this baby.

4. The most important first step to aid transition to effective breathing for extremely low gestational agenewborns is to:

A. Help them form a sufficient functional residual capacity and large enough tidal volume.B. Provide 100% blow by oxygen.C. Place a pulse oximeter on the left hand.D. Perform chest compressions.E. Give endotracheal tube epinephrine.





5. Several studies have confirmed that:

A. Endotracheal intubation with immediate mechanical ventilation after birth is superior to nasal or maskCPAP and is associated with fewer complications.

B. Many extremely low gestational age infants treated with CPAP from birth have outcomes at least as goodas intubated ventilated infants without the complications of ventilation.

C. The use of 100% oxygen in these infants is safer than air.D. Nasal CPAP is not an integral part of gentle ventilation.E. Early CPAP does not obviate the need for mechanical ventilation and/or surfactant.





DOI: 10.1542/neo.13-6-e3432012;13;e343Neoreviews

Charles C. Roehr, Colin J. Morley and Maximo VentoRoom

Improving Neonatal Transition by Giving Ventilatory Support in the Delivery

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