Early Neonatal Research at Wilford Hall US Air ForceMedical Center

The beginning of the many contributions to the field of neonatologyoriginating from Wilford Hall Air Force Medical Center began whenRobert deLemos, MD (Col, retired US Air Force [USAF]), was assigned toLackland Air Force Base (AFB) in the summer of 1969. When Dr deLemoscame to Texas, he was the first and only fully trained Air Force neo-natologist at a time when neonatal medicine was still just in its infancy.Although surfactant deficiency had been described as the cause ofhyalinemembranediseasebyDrAvery inher landmarkarticlepublishedin 1959, surfactant replacement therapy in premature infants did notbegin until the 1980s after the work of Dr Fujiwara et al was reported inLancet.1,2 Morbidity and mortality remained high in premature infants,especially in those under 1500 g with respiratory distress syndrome(RDS). Reports published in the 1960s and 1970s described earlyattempts at the use of mechanical ventilation to rescue neonates withrespiratory failure, but ventilator options were limited and deviceswere not widely available, resulting in minimal success.3,4 Given thisbackdrop, the story of the accomplishments of a relatively small groupof military neonatologists led by Dr deLemos takes on added historicalsignificance.

Some of the most important initial work completed by Dr deLemos andhis colleagues centered on their efforts to improve respiratory supportand cardiovascular monitoring in the critically ill neonate. In the late1960s and early 1970s, physiologic monitoring of the neonate was verydifficult. Blood pressure could only be accurately obtained by usingindwelling arterial lines. Ventilators in this time period only providedflowduring the inspiratory cycle. If patients breathed between ventilatorbreaths, they were rebreathing their own exhaled gas contributing toimpaired ventilation and oxygenation. In neonates this required me-chanical ventilationat rapid rates imposingagreater riskof lung traumaand cardiac and central nervous system complications. Additionally,positive end-expiratory pressure (PEEP) was not a feature of availableneonatal ventilator systems. The end result was that assisted ventilationof the preterm infant with surfactant deficiency was of little to no benefitin improving outcome.

In an effort to comeupwith a better solution, DrdeLemos, alongwith BobKirby, MD (Col, retired USAF), an anesthesiologist, and Jimmy Schultz,RRT, embarked on a course of developing an effective pediatric/neonatalventilator. The initial device was built by Jimmy Schultz by using spareparts from predominantly a Mark II ventilator. The original request fromDrs Kirby and deLemos of Jimmy Schultz was to build a ventilator thatallowed for a continuous flow of fresh gas through all phases of therespiratory cycle, thus allowing for a consistent level of oxygen andhumidification aswell as rapid removal of exhaled CO2. Additionally, theywanted a device capable of providing continuous PEEP during the

AUTHORS: Donald M. Null, MD, FAAP,a Bradley A. Yoder, MD,FAAP,a and Robert J. DiGeronimo, MDb

aDivision of Neonatology, Department of Pediatrics, University ofUtah Health Sciences Center, Salt Lake City, Utah; and bDivision ofNeonatology, Department of Pediatrics, Wilford Hall US Air ForceMedical Center, Lackland Air Force Base, Texas

ABBREVIATIONSAFB—Air Force BaseECMO—extracorporeal membrane oxygenationHFOV—high-frequency oscillatory ventilationHFV—high frequency ventilationIMV—intermittent mandatory ventilationPEEP—positive end-expiratory pressureRDS—respiratory distress syndromeUSAF—US Air Force

The views and opinions expressed in this article are those of theauthors and do not reflect the official policy or position of theAir Force Medical Department, Department of the Air Force,the Department of Defense, or the US Government.

www.pediatrics.org/cgi/doi/10.1542/peds.2010-3797e

doi:10.1542/peds.2010-3797e

Accepted for publication Oct 7, 2011

Address correspondence to Robert J. DiGeronimo, MD (Col,retired US Air Force), 295 Chipeta Way, Salt Lake City, UT 84158-1289. E-mail: robert.digeronimo@hsc.utah.edu

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2012 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE: The authors have indicated they haveno financial relationships relevant to this article to disclose.

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expiratory phase. They also requestedthat the ventilator be able to providea peak pressure up to 80 cm H2O, PEEPup to 20 cm H2O, and rate up to 130breaths per minute to support smallchildren weighing up to 25 kg in addi-tion to premature infants weighing aslittle as 800 g. Because patients sup-ported with this device were able tobreathe fresh (not expired) gas withspontaneous respirations between ma-chine breaths, this meant that fewermechanical breaths could be used. Withthe development of this prototype neo-natal ventilator, intermittent mandatoryventilation (IMV) for the neonate wasborn.

Using their prototype ventilator, Kirbyet al5 went on to demonstrate thatneonates with respiratory failure couldbe kept in a physiologic pH rangewithout the need of paralytic agentsor complex triggering devices. Thisallowed for ease of weaning the venti-lator rate and better determination ofwhen a patient could be extubated. In1970 Kirby et al6 mechanically venti-lated 90 infants with their new device,including 60 infants given a diagnosisof RDS for periods ranging from ,24hours to 31 days. No infant was venti-lated unless the combined pediatricand anesthesia staffs felt they wouldnot survive without support. Criteriafor intubation were a PaO2 of ,40 mmHg on 100% oxygen, a PaCO2 of 70mmHgand rising, and/or repeated apneicepisodes of a life threatening nature.These extreme criteria for intubationwere used as assisted ventilation wasthought to contribute little to the sur-vival of the preterm infant. At a timewhen survival was typically ,30% forinfants with severe RDS, Wilford Hallwas surviving 60% of mechanicallyventilated infants with RDS with birthweights as low as 750 g and up to 80%of infants 1600 g or greater.6

After the early success of the prototypeventilator, individuals from Bourns

(a leading manufacturer of mechanicalventilators during this era) were con-tacted to see if they were interested inhelping to further develop the WilfordHall device; however, as Dr deLemoslater related, they were uninterestedgiven their belief that there was onlya limited need for neonatal ventilatorsin the United States (∼100), and Bournshad close to this number of LS 104devices already built. Shortly there-after, Dr Forrest Bird paid a visit toWilford Hall. Impressed with the suc-cess that Drs deLemos and Kirby had inventilating ill premature infants, hebecame interested in their device. Thisencounter subsequently led to Dr Birdfurther refining the Wilford Hall pro-totype ventilator and eventually mar-keting it as the Baby Bird ventilator.

From the early 1970s into the 1980s, theBaby Bird proved to be the work horsemechanical ventilator used for themanagement of neonates and infantswith RDS and other causes of res-piratory failure. During this time, IMVremained the predominant form ofventilatory support until the devel-opment of synchronous IMV over thelast 15 to 20 years. Nonetheless, to thisday, theuseof bothcontinuousgasflowduring expiration and the inclusionof PEEP remain standard in the designof neonatal ventilatory support. Theventilator initially developed by themilitary team of deLemos, Kirby, andSchultz proved to be an exceptionaldevice that revolutionized mechanicalventilation of the neonate and smallchild. A photograph of Dr deLemos ispictured in Fig 1, the prototype venti-lator built by Jimmy Schulz in Fig 2,and the original Baby Bird device builtby Dr Bird in Fig 3.

During the early days of experimen-tation with assisted ventilation of theneonate at Wilford Hall, additional novelwork was reported by Dr deLemos andcolleagues. Among their many con-tributions, one of the most important

was their landmark article published in1973 describing the beneficial effects ofcontinuous positive airway pressurecombined with mechanical ventilation,what we now call PEEP.7 In this report of25 mechanically ventilated neonates,deLemos et al analyzed the effects ofPEEP by increasing support from 0 to20 cm H2O in 5-cm increments. They

FIGURE 1Dr Robert deLemos, MD (Col, retired USAF)served as the first fully trained USAF neo-natologist at Wilford Hall Medical Center,Lackland AFB, Texas.

FIGURE 2Prototype neonatal and pediatric ventilator builtby Jimmy Schulz, RRT.

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were able to demonstrate improvedoxygenation in 80% of patients withincreasing PEEP. Of particular impor-tance, they also described in this studythe adverse effects of high levels ofPEEP (decreased blood pressure andincreased PaCO2 generally occurringabove 10 cm H2O), noting the principlethat just because some is good, more isnot always better. The authors recom-mended that the level of PEEP selectedmust therefore be individualized foreach patient by careful monitoring ofblood pressure, chest radiographs, andblood gas measurements.

In the1970snoninvasivebloodpressuremeasurement with a stethoscope andsphygmomanometer was ineffective inthe neonate because newborn arteriesdo not generate an adequate sound forauscultation. Systolic blood pressurewas typically estimated by determiningwhen the arm “pinked up” as pressurewas released via the sphygmomanom-eter. This was a very poor technique forthe preterm or ill term infant whoseextremities often looked dusky to beginwith. Among larger patients indwellingcatheters were used to monitor bloodpressure; however, umbilical arteriallines could not be placed in many se-riously ill newborns, and angiocathssmall enough for an infant’s peripheralartery did not exist.

In an effort to improve existing tech-nology to measure blood pressure, DrGary McLaughlan, a fellow at the timeunder Dr deLemos, devised a noveldevice that used Doppler ultrasound toindirectly measure blood pressure inneonates. In 1971, Dr McLaughlanpublished the Wilford Hall experiencewith this device in 15 ill newbornsdemonstrating its accuracy in compar-ison with blood pressures measuredfrom indwelling umbilical catheters.8

Similar to the Baby Bird ventilator, thisearly prototype developed at WilfordHall subsequently led to the marketingof a commercially available device thatgreatly advanced the standard of careavailable at the time for monitoringcritically ill infants. Figure 4 shows theDoppler pressure device used in DrMcLaughlan’s original study.

Transport has always played a vital rolein the military pediatric mission, withmany technological advances in thisarenaoriginating early on in SanAntoniothrough the collaborative efforts ofmilitarypersonnelatWilfordHall,BrookeArmy Medical Center and Brooks AFB.Interest in reliable and safe pediatrictransport grew out of the need to sup-port local, regional, and intercontinentalmovement of critically ill infants fromoutlying military bases to Wilford Halland Brooke Army Medical Center often

fordefinitive life-savingcare.Specifically,in the area of neonatal transport, mili-tary physicians were instrumental indeveloping, testing, and modifying neo-natal equipment ensuring that it per-formed safely while not interfering withaircraft electromechanical operations.9

Howard Heiman, MD (COL, retired USArmy), in conjunction with Airborne LifeSupport and the testing laboratory atBrooks AFB, developed the first fullycontained neonatal transport unit thatcontinues to be the model for systemsroutinely used today. These systemshave been effectively used in the mili-tary neonatal care system for severaldecades, supporting both regional andlong distance transports from as faraway as Asia and Europe.

Over the years, there has remaineda strong interest at Wilford Hall in ad-vancing the management of neonateswith respiratory failure in an effort toreduce acute and chronic lung injury. Intheearly1980sDrsNull, deLemos,Yoder(Col, retired USAF), and Clark beganworkingwithhigh frequency ventilation(HFV) aiming to improve survival andreduce bronchopulmonary dysplasia innewborns. These investigators wereinstrumental in establishing a termandpreterm baboonmodel alongwith theircolleagues at the Southwest Founda-tion for Biomedical Research in SanAntonio that proved to be invaluablefor studying HFV. By using the baboonmodel coupled with clinical experience

FIGURE 3Original Baby Bird neonatal ventilator built by Dr Forrest Bird.

FIGURE 4Doppler blood pressure device designed by GaryMcLaughlan, MD.

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generated from the Wilford Hall NICU,Dr Null and his colleagues were able todevelop an appropriate HFV strategyfor the management of RDS and othercauses of respiratory failure in thenewborn. Numerous publications weregenerated from the Wilford Hall experi-ence with HFV, where the clinical use ofHFV dates back to late 1983.10–26 Of note,HFV research was conducted by usingboth the Bird volumetric diffusive ven-tilation flow interrupter and Texas Re-search high frequency oscillator, thelatter of which served as the prototypefor the Sensormedics 3100A.

One of the first HFV randomized con-trolled clinical trials conducted atWilford Hall was led by Dr Reese Clarkin the mid 1980s involving very low and

extremely low birth weight prematureinfants.27 The findings from this trialwere extremely important at the time inthat they demonstrated that HFV couldbe safely used in premature infants tosignificantly decrease bronchopulmo-nary dysplasia without adverse compli-cations, findings quite disparate fromearlier reported studies involving othercenters. The many studies and publica-tions from the San Antonio militaryneonatal community such as the Clarkstudy were integral to the furtherdevelopment of HFV and ultimate Foodand Drug Administration approval inthe early 1990s, particularly high-frequency oscillatory ventilation (HFOV).Today, HFOV devices are nearly univer-sally present in newborn and pediatricintensive care units not only in theUnited States but throughout the world.It is important to recognize that an un-derstanding of the utility of HFV was onlymade possible by the dedication of manyWilford Hall neonatology staff and fel-lows who spent countless hours at thebedside of critically ill patients, usingtrial and error to gain insight into dif-ferent HFV devices and their effect ontreating varying underlying lung patho-physiology.28 A present day Sensor-medics HFOV 3100A is pictured in Fig 5.

In continuation of the tradition of ex-cellence established early on at Wilford

Hall inmanaging critically ill newborns,especially those with cardiopulmonaryproblems, Devin Cornish, MD, alsoa fellow under Dr deLemos, in late 1984initiated steps to start an extracorpo-real membrane oxygenation (ECMO)program. At this time, ECMO was con-sidered largely an experimental ther-apy and was only being offered at a fewcenterswithin the United States. A storythat very few people know even today,however, is that in 1972 a neonate dyingof respiratory failure was successfullyplaced on extracorporeal bypass witha membrane oxygenator in the NICU atWilford Hall by Dr deLemos (see Fig 6).Even though this patient eventuallydied, this case is remarkable in that DrdeLemos was even able to offer thistherapy several years before the firstsuccessful published use of ECMO in aneonate in 1975.29

Dr Cornish, along with Drs Null anddeLemos, did go on to establish themilitary’s first and only ECMO programat Wilford Hall in 1985. Wilford Hall wasthe 12th center to open in the UnitedStates and the first to open in Texas.Given Wilford Hall’s large catchmentarea and the existence of relatively fewcenters offering ECMO, candidates re-ferred for ECMO were often moribundand too sick to safely transport byconventional means. This resulted in

FIGURE 5Sensormedics 3100A frequency oscillator venti-lator.

FIGURE 6Critically ill neonate placed on ECMO by Dr deLemos in 1972.

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considerable morbidity and mortalityduring the referral process to includechildren dying either before or duringattempted transport to ECMO centers.In an effort to address this problem,especially with regards to militarydependents stationed with their fami-lies at bases where ECMO was notreadily available, Drs Cornish, Null, andNeal Ackerman undertook studies todevelop an ECMO transport system.30

During this process, they workedclosely with the aeromedical researchgroups at Brooks AFB and spent manyhours doing in-flight testing to ensuresafety for the patient, equipment, crew,and aircraft. Their hard work led tothe remarkably quick development ofa safe and reliable ECMO transportsystem, resulting in the first ECMOtransport being done by Wilford Hallshortly after the ECMO programopened. Figure 7 shows a picture ofDr Null with the original ECMO trans-port system.

Wilford Hall remains at present as oneof the world leaders in ECMO transportcapability, being 1 of only 3 centers inthe United States that routinely per-forms regional ECMO transport andthe only one with the technology andresources to routinely perform long-distance missions. The early WilfordHall ECMO transport experience wasinitially described by Dr Cornish in1990.31 Several updates of this experi-ence have been additionally reported,with the most recent publication notingan average distance of 1380 miles pertransport, including several transportsfrom Okinawa, Japan, involving dis-tances of .7500 miles (see Fig 8).32,33

To date, Wilford Hall has performedover 70 ECMO transports, includingmissions involving military dependentsas well as civilian children requiringhumanitarian rescue. All of these trans-ports have been performed successfullyand safely without the occurrence of amajor complication. Given the high risk

nature of ECMO transport, especiallyover extremely long distances often re-quiringmultiple air and ground transfers,this accomplishment is truly remarkable.The success of the Wilford Hall ECMO

transport program is a testament tothe dedicated efforts of the many mili-tary neonatal nurses, respiratory ther-apists, and physicians who have beeninvolved over the years, as well to the

FIGURE 7Dr Don Null (Col, retired USAF) with neonatal patient supported on the original ECMO transport systemdeveloped at Wilford Hall.

FIGURE 8Distribution map of ECMO transport missions done by Wilford Hall. Black lines represent course oftransport. Average distance for all transports was 1380 miles (2220 km).

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commitment by the USAF AeromedicalSystem and Surgeon’s General Office tomake these missions happen.

Uniformed physicians stationed atWilford Hall Air Force Medical Centerand affiliated military institutions in SanAntonio have provided many significantcontributions to the field of neonatology.A test of the success of one’s research is

often the impact it has on its clinicaloutcomes and longevity. Continuous flowventilation is present in all neonatalventilators today having been initiatedby Drs Kirby and deLemos along withJimmy Schultz. Doppler type bloodpressure remains a mainstay in allnewborn intensive care units. High fre-quency ventilation, thought by many to

be a passing fancy, continues to be usedfor the very sickest patients from thesmallest premature neonate to thelargest adult. Wilford Hall remainsas an innovator in ECMO research andextracorporeal support technology andcontinues to be one of the few centersin the world capable of providing ECMOtransport to critically ill children.

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DOI: 10.1542/peds.2010-3797e2012;129;S20Pediatrics 

Donald M. Null, Bradley A. Yoder and Robert J. DiGeronimoEarly Neonatal Research at Wilford Hall US Air Force Medical Center

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