High Frequency Ventilation in PPHNHigh Frequency Ventilation in PPHNHigh Frequency Ventilation in PPHNHigh Frequency Ventilation in PPHN

Namasivayam Ambalavanan M.D.Namasivayam Ambalavanan M.D.Division of Neonatology,Division of Neonatology,

Department of Pediatrics, Department of Pediatrics,

University of Alabama at BirminghamUniversity of Alabama at Birmingham

Overview of presentation Introduction to PPHNIntroduction to PPHN Types of HFVTypes of HFV Hyperventilation in PPHNHyperventilation in PPHN HFOV, HFJV, and HFFI trialsHFOV, HFJV, and HFFI trials HFV techniquesHFV techniques

What is the problem? PPHN / PFC : persistence of the pattern of fetal circulation PPHN / PFC : persistence of the pattern of fetal circulation

postnatally due to a sustained elevation of pulmonary vascular postnatally due to a sustained elevation of pulmonary vascular resistance, with right-to-left shunt at the ductus arteriosus or resistance, with right-to-left shunt at the ductus arteriosus or foramen ovale in the absence of structural heart diseaseforamen ovale in the absence of structural heart disease

Incidence:1: 522-1454. Exact incidence unknown in the Incidence:1: 522-1454. Exact incidence unknown in the absence of ICD coding or a “gold standard” for diagnosisabsence of ICD coding or a “gold standard” for diagnosis

Mortality and morbidity: mortality > 50% in the absence of Mortality and morbidity: mortality > 50% in the absence of ECMO, and >10-20% with ECMO; >20% severe ECMO, and >10-20% with ECMO; >20% severe handicap/intracranial hemorrhage/deafnesshandicap/intracranial hemorrhage/deafness

(Walsh-Sukys. Clin Perinatol 20: 127-143, 1993)(Walsh-Sukys. Clin Perinatol 20: 127-143, 1993)

Causes of PPHN (Geggel RL, Reid LM:(Geggel RL, Reid LM:

Clin Perinatol 11:525, Clin Perinatol 11:525, 1984)1984)

PPHN

Normal Arterial Number Decreased Arteries e.g. CDH

Normal muscularization Increased muscularization

Developmentalimmaturity

Maladaptation dueto acute injury (commonest) e.g.Sepsis, MAS, asphyxia

Chronic injurywith vascularremodeling

Malform-ation

Current managementConfirm diagnosis of PPHNConfirm diagnosis of PPHN

Correct underlying abnormalities (hypothermia, acidosis, hypocalcemia, hypoglycemia, Correct underlying abnormalities (hypothermia, acidosis, hypocalcemia, hypoglycemia, polycythemia)polycythemia)

Conservative mechanical ventilationConservative mechanical ventilationTrial of hyperventilationTrial of hyperventilation

If low PO2, trial of rescue therapiesIf low PO2, trial of rescue therapies

MetabolicMetabolic HFVHFV SurfactantSurfactant VasodilatorsVasodilators ECMOECMO

AlkalosisAlkalosis NONO, PGD, PGD22,,

PGIPGI22, Tolazoline,, Tolazoline,

AdenosineAdenosine

Pathophysiological basis of current management Mechanical ventilation:Mechanical ventilation:

V/Q matching to improve oxygenationV/Q matching to improve oxygenation respiratory alkalosis to reduce PVRrespiratory alkalosis to reduce PVR

Metabolic alkalosis: effect of pH on PVRMetabolic alkalosis: effect of pH on PVR Vasodilators: specific relaxation of the pulmonary Vasodilators: specific relaxation of the pulmonary

vasculature. Most experience with NO.vasculature. Most experience with NO. ECMO: modified long-term cardio-pulmonary ECMO: modified long-term cardio-pulmonary

bypass bypass

High frequency ventilationHigh frequency ventilation TechniquesTechniques

HFPPV HFJVHFPPV HFJV HFFI HFFI HFOVHFOV

VVTT >dead sp>dead sp > or > or < ds< ds > or > or <ds<ds <ds<ds

ExpExp passive passive passive passive passive passive activeactive

Wave- variableWave- variable triangular triangular triangular triangular sine wavesine wave

formformEntrai- noneEntrai- none possiblepossible none none nonenonementmentFreq.Freq. 60-150 60-150 60-600 60-600 300-900 300-900 300-3000 300-3000

(60-80)(60-80) (350-450) (350-450) (480-720) (600-900) (480-720) (600-900)(/min)(/min)

High frequency ventilationHigh frequency ventilationHFPPVHFPPV

conventional ventilators with low-compliance tubingconventional ventilators with low-compliance tubing ventilatory rates of 60-150/minventilatory rates of 60-150/min not very effective: minute ventilation decreases with not very effective: minute ventilation decreases with

high frequencies [If Thigh frequencies [If TII < 3 TC, V < 3 TC, VTT decreases.] decreases.]

((Boros et al. Pediatrics 74: 487-492, 1984Boros et al. Pediatrics 74: 487-492, 1984 ) )

ventilator and circuit design are not optimal for use at ventilator and circuit design are not optimal for use at frequenciesfrequencies

High frequency ventilationHigh frequency ventilation HFJV (e.g. Bunnell Life Pulse HFJV)HFJV (e.g. Bunnell Life Pulse HFJV)

adequate gas exchange with lower MAPadequate gas exchange with lower MAP Servo pressure reflects volume ventilated:Servo pressure reflects volume ventilated:

increases with improving increases with improving compliance compliance or or resistanceresistance or by or by peri-ET leaksperi-ET leaks

decreased by worsening decreased by worsening compliance, compliance, resistance, obstruction, resistance, obstruction, oror pneumothoraxpneumothorax

Larger babies: 300 bpm; smaller ones: 500 bpmLarger babies: 300 bpm; smaller ones: 500 bpm

High frequency ventilationHigh frequency ventilation HFJV (contd.)HFJV (contd.)

MAPMAP controls PaO controls PaO22, , PP (and frequency) controls (and frequency) controls

PaCOPaCO22 ( (MAP controls lung volume. PaOMAP controls lung volume. PaO22 will not will not

respond to increased MAP if FRC normalrespond to increased MAP if FRC normal)) smaller Vsmaller VTT ( (PP) with higher PEEP better than larger V) with higher PEEP better than larger VTT

with lower PEEP (--> hypoxia with hypocarbia)with lower PEEP (--> hypoxia with hypocarbia) Optimal PEEP: no drop in SpOOptimal PEEP: no drop in SpO22 when CMV off when CMV off Parallel conventional ventilation recruits alveoli (use low Parallel conventional ventilation recruits alveoli (use low

rate : 1-3 bpm; 0-1 bpm if air leak)rate : 1-3 bpm; 0-1 bpm if air leak)

High frequency ventilationHigh frequency ventilation HFOV (e.g. Sensormedics 3100A)HFOV (e.g. Sensormedics 3100A)

MAPMAP controls PaO controls PaO22, , amplitudeamplitude (and frequency) control (and frequency) control PaCOPaCO22

Optimal MAP difficult to determine as CXR “rib space Optimal MAP difficult to determine as CXR “rib space counting” not accuratecounting” not accurate(Thome et al. Pediatr Pulmonol 26:265-72, 1998)(Thome et al. Pediatr Pulmonol 26:265-72, 1998)

Frequency: 5-10 Hz better for COFrequency: 5-10 Hz better for CO22 elimination; 10-15 Hz elimination; 10-15 Hz better for improving oxygenationbetter for improving oxygenation

maybe useful in airleak syndromesmaybe useful in airleak syndromes maybe useful in PPHN; may decrease need for ECMO esp. maybe useful in PPHN; may decrease need for ECMO esp.

if combined with NOif combined with NO

High frequency ventilationHigh frequency ventilation HFFI (e.g. Infant Star with HFFI module)HFFI (e.g. Infant Star with HFFI module)

active expiration in Infant Star model makes active expiration in Infant Star model makes operation more like HFOVoperation more like HFOV

MAPMAP controls PaO controls PaO22, , amplitudeamplitude (and frequency) (and frequency)

controls PaCOcontrols PaCO22

insufficient evidence to show it to be superior insufficient evidence to show it to be superior to conventional ventilationto conventional ventilation

more convenient: single ventilator for CMV more convenient: single ventilator for CMV and HFV makes initiation and weaning easierand HFV makes initiation and weaning easier

High Frequency Ventilation in PPHN V/Q matching to improve oxygenationV/Q matching to improve oxygenation Respiratory alkalosis to reduce PVRRespiratory alkalosis to reduce PVR Improved response to inhaled NOImproved response to inhaled NO ““Rescue” for air leak syndromesRescue” for air leak syndromes

Hyperventilation in PPHN

No HV/Alk No HV/Alk HVHV Alk HV+Alk pAlk HV+Alk p

Mortality%Mortality% 4.4 4.4 6.86.8 9.5 9.5 9.8 9.8 0.670.67

ECMO%ECMO% 33.3 33.3 13.613.6 44.644.6 34.2 34.2 0.0080.008

DurationDuration 7.8 7.8 7.27.2 7.8 12.6 7.8 12.6 0.00130.0013

ventilator (d)ventilator (d)

Duration ODuration O2 2 (d)(d) 11.111.1 11.511.5 11.9 11.9 17.5 0.001 17.5 0.001

OO22 at 28 d at 28 d 2.7 2.7 2.82.8 6.8 16.7 0.1 6.8 16.7 0.1

(Walsh-Sukys et al. Pediatrics 105:14-20, 2000)(Walsh-Sukys et al. Pediatrics 105:14-20, 2000)

HFOV in term infants Early studies:Early studies:

Kohelet et al. Crit Care Med 16: 510-6, 1988Kohelet et al. Crit Care Med 16: 510-6, 1988 HFOV in 41 infants with PPHNHFOV in 41 infants with PPHN 34 showed improved oxygenation and ventilation, and 34 showed improved oxygenation and ventilation, and

decreasing MAPdecreasing MAP

Carter et al. Pediatrics 85: 159-64, 1990Carter et al. Pediatrics 85: 159-64, 1990 50 ECMO referrals with A-a O50 ECMO referrals with A-a O22>>600. 4 died early.600. 4 died early. 21 responded to HFOV and did not require ECMO21 responded to HFOV and did not require ECMO 25 needed ECMO, with more morbidity & 3 died.25 needed ECMO, with more morbidity & 3 died. Infants responding to HFOV more often had pneumoniaInfants responding to HFOV more often had pneumonia

HFOV in term infants

Varnholt et al. Eur J Pediatr 151: 769-74, 1992Varnholt et al. Eur J Pediatr 151: 769-74, 1992 HFOV tried in 50 infants meeting ECMO criteriaHFOV tried in 50 infants meeting ECMO criteria 25 responded to HFOV, 25 needed ECMO25 responded to HFOV, 25 needed ECMO 2 responders subsequently needed ECMO due to 2 responders subsequently needed ECMO due to

air leaksair leaks

Responders in Carter’s and Varnholt’s study Responders in Carter’s and Varnholt’s study tended to be younger (37-38 wks vs. 39-40 wks)tended to be younger (37-38 wks vs. 39-40 wks)

HFOV in term infants Recent studies:Recent studies:

Clark et al. J Pediatr 124: 447-54, 1994Clark et al. J Pediatr 124: 447-54, 1994 GA >34 w, B.wt> 2 kg, < 14 d age on high vent GA >34 w, B.wt> 2 kg, < 14 d age on high vent

settingssettings 81 neonates randomized to HFOV or CV81 neonates randomized to HFOV or CV Patients stratified before admission based on Patients stratified before admission based on

primary diagnosis (pneumonia, MAS, RDS, air primary diagnosis (pneumonia, MAS, RDS, air leak, or other)leak, or other)

HFOV in term infantsClark et al contd.Clark et al contd. Mortality: HFOV 1/39 vs. CV 2/40Mortality: HFOV 1/39 vs. CV 2/40 ECMO need: HFOV: 12/39 vs. CV 6/40 (n.s)ECMO need: HFOV: 12/39 vs. CV 6/40 (n.s) Median days on ventilator: 8 in both groupsMedian days on ventilator: 8 in both groups OO22 reqt at 28 days: HFOV 11/39 vs. CV 5/40 reqt at 28 days: HFOV 11/39 vs. CV 5/40

(n.s.)(n.s.)

This trial was prematurely terminated (needed This trial was prematurely terminated (needed 250) and hence did not have enough power250) and hence did not have enough power

HFJV in term infantsCarlo et al. Am J Dis Child 143: 233-8, 1989Carlo et al. Am J Dis Child 143: 233-8, 1989 14 infants on HFJV compared to 23 infants on CV14 infants on HFJV compared to 23 infants on CV HFJV: reduction in MAP and PaCOHFJV: reduction in MAP and PaCO22

No change in mortality, A-aDONo change in mortality, A-aDO22, air leaks, BPD, , air leaks, BPD, duration of ventilation or Oduration of ventilation or O22 supplementation supplementation

This was a small pilot study, not a randomized trialThis was a small pilot study, not a randomized trialPeters et al. J Perinatol 12: 21-4, 1992Peters et al. J Perinatol 12: 21-4, 1992 2 infants with pulmonary hypoplasia and PPHN 2 infants with pulmonary hypoplasia and PPHN

worsening on CV survived on HFJVworsening on CV survived on HFJV

HFJV in term infantsEngle et al. J Perinatol 17:3-9, 1997Engle et al. J Perinatol 17:3-9, 1997 Small RCT of HFJV (n=11) vs. HFPPVSmall RCT of HFJV (n=11) vs. HFPPV HFJV: Stable MAP and PIP. Improved oxygenation, HFJV: Stable MAP and PIP. Improved oxygenation,

ventilation, and OIventilation, and OI HFPPV: Required higher PIP to maintain same HFPPV: Required higher PIP to maintain same

oxygenation, ventilation, and OI.oxygenation, ventilation, and OI. No difference in survival without ECMO, duration of No difference in survival without ECMO, duration of

ventilation, O2, hospital stay, need for ECMO, or BPD.ventilation, O2, hospital stay, need for ECMO, or BPD.

HFJVStewart et al. Eur Respir J 9:1257-60, 1996Stewart et al. Eur Respir J 9:1257-60, 1996 30 infants meeting criteria for ECMO30 infants meeting criteria for ECMO 22 responded to HFJV, 8 non-responders required 22 responded to HFJV, 8 non-responders required

ECMOECMO Responders showed a decrease in OI without increases in Responders showed a decrease in OI without increases in

MAP within 4 hours MAP within 4 hours Same problem of small sample size, uncontrolled Same problem of small sample size, uncontrolled

observational reportobservational reportMany similar uncontrolled studies and case series exist Many similar uncontrolled studies and case series exist on HFJV, but only a few controlled trials in term infants.on HFJV, but only a few controlled trials in term infants.

HFFI in term infants Very few trials of HFFI in term infantsVery few trials of HFFI in term infantsJirapaet et al. Respir Care 46: 586-94, 2001Jirapaet et al. Respir Care 46: 586-94, 2001 36 infants with PPHN requiring hyperventilation and FiO36 infants with PPHN requiring hyperventilation and FiO22

1.0 with PaO1.0 with PaO22 < 60 torr. HFFI (n=18) or CV (n=18) in < 60 torr. HFFI (n=18) or CV (n=18) in non-non-randomizedrandomized manner. manner.

HFFI: HFFI: Survival 78% vs. 44% on CV (p=0.087)Survival 78% vs. 44% on CV (p=0.087) Less chronic lung disease (1 vs. 5, p 0.02)Less chronic lung disease (1 vs. 5, p 0.02) Faster extubation (8.1 vs. 18.7 d, p 0.03)Faster extubation (8.1 vs. 18.7 d, p 0.03) Improvements in other respiratory variables (less Improvements in other respiratory variables (less

hypocarbia and alkalosis, improved oxygenation)hypocarbia and alkalosis, improved oxygenation)

Comparison of HFV techniques No human comparisonsNo human comparisonsWiswell et al. Am J Dis Child 146: 1287-93, 1992Wiswell et al. Am J Dis Child 146: 1287-93, 1992 56 newborn piglets with meconium instillation56 newborn piglets with meconium instillation Randomized to CV, HFJV, or HFFI for 6 hoursRandomized to CV, HFJV, or HFFI for 6 hours Measures of oxygenation mostly similar Measures of oxygenation mostly similar Lung histologic changes worse on CV compared to HFJV or HFFILung histologic changes worse on CV compared to HFJV or HFFISimma et al. Pediatr Pulmonol 22: 263, 1996Simma et al. Pediatr Pulmonol 22: 263, 1996 More lung injury in animals treated with HFV+CV than HFOV More lung injury in animals treated with HFV+CV than HFOV

alonealone

Comparison of HFV techniquesBancalari et al. J Pediatr 110-617-22, 1987Bancalari et al. J Pediatr 110-617-22, 1987 Animals on HFOV vs. HFJVAnimals on HFOV vs. HFJV More air trapping on HFJV (due to active More air trapping on HFJV (due to active

exhalation on HFOV?) exhalation on HFOV?)

Many centers now use HFOV for term infants with Many centers now use HFOV for term infants with PPHN, rather than HFFI or HFJVPPHN, rather than HFFI or HFJV

Not possible to state if one type of HFV is better in Not possible to state if one type of HFV is better in human infantshuman infants

HFV Indications Usually used as “rescue” therapy for infants not Usually used as “rescue” therapy for infants not

improving/deteriorating on conventional ventilatorimproving/deteriorating on conventional ventilator Response to HFJV or HFOV may depend on disease Response to HFJV or HFOV may depend on disease

pathophysiology:pathophysiology: Pneumonia and RDS more likely to respond (70-90%)Pneumonia and RDS more likely to respond (70-90%) MAS (50%) and CDH (20%) less likely to respondMAS (50%) and CDH (20%) less likely to respond

(Baumgart et al. Pediatrics 89:491, 1992; Paranka et al. (Baumgart et al. Pediatrics 89:491, 1992; Paranka et al. Pediatrics 95: 400, 1995; Stewart et al. Eur Respir J 9:1257, Pediatrics 95: 400, 1995; Stewart et al. Eur Respir J 9:1257, 1996)1996)

HFV techniques HFOV, usually with Sensormedics 3100HFOV, usually with Sensormedics 3100 MAP: 1-3 cm HMAP: 1-3 cm H22O higher than on IMVO higher than on IMV

Frequency: 10-12 HzFrequency: 10-12 Hz Inspiratory time: 33%Inspiratory time: 33% Amplitude: sufficient for visible chest motionAmplitude: sufficient for visible chest motion Target ABG: pH 7.45-7.55, PaCOTarget ABG: pH 7.45-7.55, PaCO22 30-40, PaO 30-40, PaO22

80-100, HCO80-100, HCO33 26-30 26-30

HFV techniques ““High volume strategy” often usedHigh volume strategy” often used

Useful in animal models and preterm infants with RDSUseful in animal models and preterm infants with RDS Assessment of lung volume a problem (chest X-Rays not Assessment of lung volume a problem (chest X-Rays not

accurate)accurate) Initial MAP 10-20% more than MAP on IMV. Initial MAP 10-20% more than MAP on IMV. Increase MAP in 1-3 cm HIncrease MAP in 1-3 cm H22O increments until O increments until

oxygenation and a/A ratio improve or cardiac oxygenation and a/A ratio improve or cardiac compromise occurscompromise occurs

FiOFiO22 can then be weaned. As lungs improve, wean MAP can then be weaned. As lungs improve, wean MAP

slowly (MAP changes may take > 1 hr to affect PaOslowly (MAP changes may take > 1 hr to affect PaO22))

HFV + NO The combination of HFOV and NO is more effective The combination of HFOV and NO is more effective

than HFOV alone or NO alonethan HFOV alone or NO alone

Kinsella et al. J Pediatr 131: 55-62, 1997Kinsella et al. J Pediatr 131: 55-62, 1997 Mulicenter RCT on PPHN with n=205Mulicenter RCT on PPHN with n=205 Randomized to IMV+NO or HFOV aloneRandomized to IMV+NO or HFOV alone If PaOIf PaO22<60, cross-over to other therapy<60, cross-over to other therapy

If PaOIf PaO22 still <60, HFOV+NO still <60, HFOV+NO

Treatment success if PaOTreatment success if PaO22>>60 sustained60 sustained

HFV + NOKinsella et al contd.Kinsella et al contd. 28% responded to NO, 23% to HFOV (100% 28% responded to NO, 23% to HFOV (100%

survival and similar outcome in responders)survival and similar outcome in responders) Non-responders following crossover: 21% Non-responders following crossover: 21%

responded to NO, and 14% to HFOVresponded to NO, and 14% to HFOV 125 did not respond to either NO or HFOV alone: 125 did not respond to either NO or HFOV alone:

32% responded to HFOV+NO32% responded to HFOV+NO Combination works better for those with significant Combination works better for those with significant

parenchymal lung disease (e.g. MAS, RDS)parenchymal lung disease (e.g. MAS, RDS)

HFV + Surfactant Surfactant:Surfactant:

inactivation in MAS and pneumoniainactivation in MAS and pneumonia deficiency in RDS and CDHdeficiency in RDS and CDH

Animal studies Animal studies HFV does not affect delivery of bolus surfactant HFV does not affect delivery of bolus surfactant

(Heldt et al. Pediatr Res 31:270, 1992; Walther et al. (Heldt et al. Pediatr Res 31:270, 1992; Walther et al. Pediatr Res 22:725, 1987)Pediatr Res 22:725, 1987)

HFV and surfactant prevent lung injury synergistically HFV and surfactant prevent lung injury synergistically (Jackson et al. Am J Respir Crit Care Med 150: 534, (Jackson et al. Am J Respir Crit Care Med 150: 534, 1994)1994)

HFV + Surfactant Survanta in term infants study group: Survanta in term infants study group:

Multicenter RCT on infants at risk for ECMO Multicenter RCT on infants at risk for ECMO Surfactant use may reduce need for ECMO, especially when Surfactant use may reduce need for ECMO, especially when

used early (OI 15-22)used early (OI 15-22)

(Lotze et al. J Pediatr (Lotze et al. J Pediatr 132:40-7, 1998) Surfactant in MAS:Surfactant in MAS:

1/20 in surfactant gp vs. 6/20 controls needed ECMO1/20 in surfactant gp vs. 6/20 controls needed ECMO 0/20 in surfactant gp vs. 5/20 controls had air leaks0/20 in surfactant gp vs. 5/20 controls had air leaks

(Findlay et al. Pediatrics 97: 48-52, 1996)(Findlay et al. Pediatrics 97: 48-52, 1996)

HFV + Surfactant No studies focusing on HFV + Surfactant in term No studies focusing on HFV + Surfactant in term

neonatesneonates Studies in preterm neonates indicate that HFV:Studies in preterm neonates indicate that HFV:

prolongs efficacy of surfactantprolongs efficacy of surfactant reduces number of surfactant dosesreduces number of surfactant doses reduces pulmonary morbidityreduces pulmonary morbidity

(Gerstmann et al. Pediatrics 98:1044, 1996; Clark and (Gerstmann et al. Pediatrics 98:1044, 1996; Clark and Gerstman. Clin Perinatol 25: 113-122, 1998)Gerstman. Clin Perinatol 25: 113-122, 1998)

Does HFV “rescue” prevent ECMO but lead to more chronic lung disease?

Vaucher et al. J Pediatr 128: 109, 1996Vaucher et al. J Pediatr 128: 109, 1996 ECMO survivors vs. avoiders: less CLD, shorter ECMO survivors vs. avoiders: less CLD, shorter

ventilation and hospital stayventilation and hospital stay

Walsh-Sukys et al. J Pediatr 125: 104, 1994Walsh-Sukys et al. J Pediatr 125: 104, 1994 ECMO survivors vs. avoiders: less CLD, less ECMO survivors vs. avoiders: less CLD, less

rehospitalizationsrehospitalizations

however,however,

Schwendeman et al. Crit Care Med 20: 372, 1992Schwendeman et al. Crit Care Med 20: 372, 1992 ECMO avoiders had less CLD and neurologic morbidityECMO avoiders had less CLD and neurologic morbidity

Impact of HFV: more recent reports Reduction in ECMO use by HFV + NOReduction in ECMO use by HFV + NO

Magnitude of reduction ranges from 40 to 75%, Magnitude of reduction ranges from 40 to 75%, depending on centerdepending on center

Reduction of ECMO use not associated with Reduction of ECMO use not associated with longer ECMO in those needing itlonger ECMO in those needing it

Shorter hospitalization, lower costsShorter hospitalization, lower costs(Kennaugh et al. J Perinatol 17: 366-9, 1997; Kachel et al. Int J (Kennaugh et al. J Perinatol 17: 366-9, 1997; Kachel et al. Int J Artif Organs 18: 589-97, 1995; Hintz et al. Pediatrics 106: 1339-Artif Organs 18: 589-97, 1995; Hintz et al. Pediatrics 106: 1339-43, 2000)43, 2000)

The current situation:Despite common use of HFV, there is Despite common use of HFV, there is insufficient data from randomized insufficient data from randomized controlled trials to support the routine controlled trials to support the routine use of rescue HFV in term infants with use of rescue HFV in term infants with PPHNPPHN