Persistent Pulmonary

Hypertension of The Newborn

(PPHN)
RSUD KOTA BANDUNG
2017
*Sharma V, Lakshminrusimha S,
et al. Persistent pulmonary
hypertension of the newborn.
2015. DOI: 10.1186/s40748-015-
0015-4
Hipertensi Pulmonal

Gangguan kardiopulmoner serius yang ditandai dengan peninggian

tekanan arteri paru-paru, mengakibatkan paparan kronis dari ventrikel
kanan selama fase afterload tinggi

Tekanan rata-rata arteri pulmonal > 25 mmHg diukur oleh kateterisasi

jantung yang tepat, atau tekanan puncak sistolik arteri paru-paru >
35mmHg yang diukur dengan ekokardiografi
 Peningkatan PVR pada bayi
• Tekanan Oksigen rendah
• Berkurangnya produksi vasodilator, NO, prostasiklin
• Peningkatan produksi prostaglandin (tromboksan)

*Cabral JEB, et al. Persistent pulmonary hypertension of the newborn: recent advances in pathophysiology treatment. J Perdiatr. 2013; 89(3):226-242.
• Sharma V, et al. Persistent pulmonary hypertension of the newborn. Maternal Health Neonatal Perinatol 2015; 1:14.
 Pathophysiology
• Pulmonary Blood Flow (PBF) ↑
(e.g., VSD, ASD)
• Pulmonary Vascular Resistance
(PVR) ↑
• Pulmonary Capillary Wedge
Pressure (PCWP) ↑

*McNamara PJ, et al. Hemodynamics. The Newborn Infant 2015;29:467.

** Lakshminrusimha S, et al. Tracheal suctioning improves gas exchange but not hemodynamics in
asphyxiated lambs with meconium aspiration. Pediatr Res. 2014.
*Jain A, McNamara PJ. Persistent Pulmonary Hypertension of the Newborn.
Seminars in Fetal & Neonatal Medicine 20 (2015) 262-271
 Subjek
• Takipnea
• dyspnoe
• Sianosis progresif saat stimulasi rangsangan pada bayi baru lahir

Objective
KU : Sesak
Nadi : dbn Respirasi : takipnea S : dbn Sp02 : <94%
Kepala : PCH (+), POC (+)
Leher : retraksi suprasternal
Thorax : B/P simetris
: Cor : BJM, regular, S2 >S1, murmur sistolik rendah
Abdomen: Cembung,soepel, BU(+)
Ext : akral hangat, sianosis sentral
Diagnosis : Identify the underlying
etiology
• Chest x-ray and arterial blood gas
Echocardiography: gold • Difference PO2 20 mmHg
standard diagnostic tool in
PPHN  patent foramen • Chest radiography
• underlying parenchymal disease, such as RDS and
ovale and/or PDA MAS; distinguish the idiopathic PPHN
• Measuring pre-ductal (right extremity) and post-
BNP  as a biomarker in ductal (either lower extremity) arterial
PPHN to assess efficacy of oxygenation
treatment and to predict • Oxygen Saturation 5-10%
rebound of PPHN • Labile hypoxemia

*Nair J, Lakshminrusimha S. Update on PPHN: mechanism and treatment in Seminar

Perinatology 38. Elsevier: 2014.
Management

Treat the problem not the consequences

• Optimize lung recruitment

• Effective pulmonary vasodilatation
• Achieve normal cardiac output and blood pressure

*McNamara P. The Critical Neonate with PPHN.2010

Management
General Supportive

•Ventilation •Hypothermia
•Oxygenation •Acidosis
•Maintaining Systemic Blood •Polycythaemia corrected
Pressure •Hypoglycaemia
•Maintaining Homeostasis •Hypocalcaemia
•Hypomagnesaemia
•Minimal handling and judicious
sedation
•Antimicrobial therapy

*S Afr J Child Health 2016;10(4):194-198.

 Surfactant

• Surfactant therapy doesn’t appear to be effective when PPHN is the

primary diagnosis.*

• It should be considered in patients with associated parenchymal lung

disease, in whom there is either a suspected RDS or MAS

* Ostrea EM Jr, Odell GB. The influence of bicarbonate administration on blood pH in a "closed system": clinical implications. J Pediatr 1972; 80:671.
*S Afr J Child Health 2016;10(4):194-198. DOI:10.7196/SAJCH.2016.v10i4.1145
• OI ≥ 25 should receive care in a center where high-frequency
oscillatory ventilation (HFOV), iNO and ECMO are readily available
in addition to general supportive care.

• OI < 25, general supportive care is typically adequate and no further

invasive intervention is usually required.

*Stark AR, Eichenwald EC. Persistent Pulmonary Hypertension of the Newborn.

 PPHN
No Lung Lung
Diseases Diseases
Hypoxemia is caused by right-to- Associated lung disease , atelectasis
left shunting and resulting maldistribution of
 Minimize MAP ventilation may exacerbate high PVR
 low inspiratory pressures and
short inspiratory times or
 Severe : ventilator peak pressures
volume targeted ventilation
reach 28 to 30 cmH2O, use HFOV.

 Maintain adequate lung  HFOV ang iNO in patients with severe

recruitment with modest levels with HFOV
or iNO only*
of PEEP
* Kinsella JP, Truog WE, Walsh WF, et al. Randomized, multicenter trial of inhaled nitric oxide and high-frequency oscillatory ventilation in severe,
persistent pulmonary hypertension of the newborn. J Pediatr 1997; 131:55.
 • Sedation – nyeri dan gelisah pada pasien PPHN dapat meningkatkan
produksi katekolamin yang menyebabkan peningkatan PVR dan right-
to-left shunting.
 Intravenous (IV) morphine sulfate (loading dose of 100-150 mcg/kg over
one hr followed by a continuous infusion of 10-20 mcg/kg per hr) or
fentanyl (1-5 mcg/kh per hr)

* Kinsella JP, Truog WE, Walsh WF, et al. Randomized, multicenter trial of inhaled nitric oxide and high-frequency oscillatory ventilation in severe,
persistent pulmonary hypertension of the newborn. J Pediatr 1997; 131:55.
Mechanical Ventilation and
Oxygenation
• No randomized studies comparing different PaO2 levels in the
management of PPHN in a term infant.
• Brief exposure to 100% oxygen in newborn lambs  increased
contractility of pulmonary arteries, reduces response to iNO and
increases the potential for oxidative stress
• Maintaining preductal oxygen saturations in low to mid-90s with
PaO2 levels between 55 and 80 mmHg

*Nair J, et al. Update On PPHN: Mechanisms and Treatment. Semin Perinatol. 2014 Mar;38(2):78-91
**Jain A, et al. Persistent pulmonary hypertension of the newborn. Maternal Health, Neonatology and Perinatology. 20151:14
Mechanical ventilation and
Oxygenation
• Maintain PaCO2of 40-60 mmHg(5.3–8.0kPa) and PaO2 of 60 – 90
mmHg (8 - 12 kPa) by using gentle ventilation to optimise lung
volume
*S Afr J Child Health 2016;10(4):194-198.

• 70% of the respondents (neonatologists) used higher goal SpO2 >

95% or 95 to 98% and thirty-eight percent of the respondents used
PaO2 > 80 mm Hg.

*Management of Supplemental Oxygen for Infants with Persistent Pulmonary

Hypertension of Newborn: A Survey.Am J Perinatol. 2017
Ventilatory Strategies
• Conventional ventilation • Weaning should be
• Initial rates of 60–80/minute gradual
(I:E ratio of 1:1.2) • pressures are to be decreased
• Sufficient peak pressure to before decreasing the FiO2
achieve a PaCO2 of not greater
than 35–45 mmHg with the pH
between 7.35 and 7.45. • Use of high pressures can
• PaO2 maintained at 80–100 impede venous return to
mmHg initially and 50–60 the heart reducing cardiac
mmHg once stable (usually output and increasing PVR
after 12–24 hours of
ventilation).
* Sharma BM, et al. Persistent pulmonary hypertension of the newborn : a review. MJAFI . 2016. doi: 10.1016/S0377-
1237(11)60082-8
Ventilatory Strategies
• Strategi  mengelola pasien tanpa hiperventilasi dan/atau
alkalinisation.

• Ventilasi yang halus dengan sedikit hypercarbia telah dilaporkan

memiliki hasil yang sangat baik dan insiden rendah dari BPD.
• Jika HFOV tersedia dapat digunakan pada bayi dengan penyakit paru parenchym
al sambil menunggu diberi terapi inhalasi NO

* Sharma BM, et al. Persistent pulmonary hypertension of the newborn : a review. MJAFI . 2016.doi: 10.1016/S0377-
1237(11)60082-8
Pulmonary Vasodilator
*Nair J, Lakshminrusimha S. Update on PPHN:
mechanism and treatment
in Seminar Perinatology 38.
Elsevier: 2014.
 Inhalation Nitric oxide
• Mainstay of PPHN treatment*
• A meta-analysis of seven
randomized trials of iNO use in
newborns with PPHN also
revealed that 58% of hypoxic
near-term and term infants
responded to iNO within 30 to
60 minutes**

* Cochrane Database of Systematic Reviews 2017

** Update on PPHN mechanisms and treatment. Semin Perinatol. 2014
Milrinone
• No studies meeting the criteria for inclusion in this review
• The efficacy and safety of milrinone in the treatment of PPHN are not
known and its use should be restricted within the context of RCTs
Cochrane Database of Systematic Reviews 2010, Issue 11 Art. No.: CD007802.

• Improvement in PaO2 (p = 0.002), reduction in Fio2 (p < 0.001),

oxygenation index (p < 0.001), mean airway pressure (p = 0.03),
inhaled nitric oxide dose (p < 0.001).
• Need for a randomized controlled trial in neonates
Pediatr Crit Care Med 2013; 14:74–84
Inhaled iloprost vs sildenafil

No side effects on blood pressure or homeostasis in any of the patients in the

iloprost group (dose between 1–2.5 mg/kg with an interval of 2–4 hr)
Pediatr Pulmonol. 2014. DOI 10.1002/ppul.22985
Sildenafil
• Sildenafil in the treatment of PPHN has significant potential
especially in resource limited settings
• A large scale randomised trial comparing sildenafil with the currently
used vasodilator, inhaled nitric oxide, is needed to assess efficacy and
safety
Cochrane Database of Systematic Reviews 2011, Issue 8. Art. No.: CD005494.

• Enteral sildenafil, dose range 0,5 - 3 mg/kg every 6 hours,

reduced mortality in resource-limited settings where iNO is not
available
S Afr J Child Health 2016;10(4):194-198.
Magnesium Sulfate
• On the basis of the current lack of evidence, the use of magnesium
sulphate cannot be recommended in the treatment of PPHN.
• Randomised controlled trials are recommended
Cochrane Database of Systematic Reviews 2007
 Magnesium Sulfate vs Sildenafil
• Both groups showed a significant improvement in their pulmonary
artery pressure 48 hours after therapy as compared to their baseline
measurements

MgSO4 at a loading
dose of 200 mg/kg
infused over 30
minutes, followed by
maintenance dose of
20 - 50 mg/kg/hr

Int J Clin Pediatr. 2012;1(1):19-24

Management of Systemic
Hypotension
Sharma BM. MJAFI 2011;67:348–353. 2016.DOI 10.1016/S0377-1237(11)60082-8
*Nair J, et al. Update On PPHN:
Mechanisms and Treatment.
Semin Perinatol. 2014
Mar;38(2):78-91
 Extracorporeal Membrane Oxygenation
(ECMO)
• Criteria for institution of ECMO
include an elevated OI that is
consistently ≥ 40.
• MAPs are higher on HFOV than
conventional ventilation, some
clinicians wait until OI ≥ 60
when HFOV is used.

*Nair J, et al. Update On PPHN: Mechanisms and Treatment. Semin Perinatol. 2014 Mar;38(2):78-91
Summary
• PPHN is a neonatal emergency with a high mortality rate
• Principe therapy including
• Optimize lung recruitment
• Effective pulmonary vasodilatation
• Achieve normal cardiac output and blood pressure
• In term and preterm infants with a GA > 34 weeks severe PPHN,
defined as an OI ≥25, iNO be administered at a dose of 20 ppm is
recommended (Grade 1B).
• Oral sildenafil and Inhale iloprost in the treatment of PPHN has
significant potential especially in resource limited settings
Thank you