Refractory Hypoxemia – Case Based Approach
Dr Nalinikant PanigrahyMD , DNB Neonatology Consultant Neonatology
Case
• 38 wks ,delivered By LSCS
• Sent to Mother side immediately after birth
• Developed mild respiratory distress @4 hrs
• Started CPAP as Respiratory as Distress increased
• Required Mechanical Ventilation(SIPPV)
• Increased requirement of FIO2 (70 %)
• Ongoing clinical assessment and chest X ray
• ABG – on CPAP - 7.28/pCO2=45/pO2=35/-6 BE
• ABG after 1 hr of SIPPV( PIP=24, PEEP=6, RR=40,FIO2=70%)
• - 7.20/pC02=38/pO2=30/-8 BE
Variations in PVR and SVR During Gestation & at Birth
Embryonal Pseudoglandular Canalicular Saccular Alveolar----
Pulmonary vascular resistance (PVR)
Systemic vascular resistance (SVR)
Severity Assessment
• OI =MAP x FiO2 % / PaO2 mmHg
• AaDO2 = [Patm‐ PH2O] x FiO2‐ PaO2‐ PaCO2/ 0.8
• P/F ratio
• OSI = MAP × FiO2 × 100/Preductal SpO2
140 89
Presentation and Diagnosis of PPHN
140
877
5
Pre-post ductal
oxygenation difference
(R L shunt at PDA)
> 3-5% difference in
SpO2
Predominant shunt at
PFO no differential
cyanosis
Labile
oxygenationHypoxemia disproportional to the degree of parenchymal lung disease
If echo is available,Hyperoxia –Hyperventilation Test?
Presentation and Diagnosis of PPHN
Oxygenation Index
PPHN Mild Moderate Severe Panic!
0 15 25 40OI
100 x MAP x FiO2Postductal PaO2
OI =
MAP
Duct
al
Shun
tPaO2
VentilatorO2
Oxygen Saturation Index (OSI) = 100 x MAP x FiO2Preductal SPO2
Surf iNO +other agentsECMO
HFOV
Modified from Tend and Konduri –Chapter 21. Pulmonary vasodilators in the treatment of PPHN; in Rajiv PK et al –Essentials of Neonatal Ventilation
Etiology of HRF / PPHN
• Transient tachypnea of newborn (TTN)
• Aspiration syndromes -meconium or blood
• Congenital Diaphragmatic Hernia (CDH)
• HYaline membrane disease (RDS)
• PNEumonia / Sepsis
• Asphyxia
– Airleaks– Aspirin– Antidepressants
Pneumothorax
Pulmonary venous hypertension• Mitral stenosis• Disorders of
pulmonary veins• Left ventricular
dysfunction
Prematurity: RDS & BPD
Neonatal X-ray Patterns Associated with HRF
• Seven Dwarfs– Hazy- HMD or pneumonia
– Grainy/ ground glass - HMD
– Patchy - pneumonia
– Streaky - TTN
– Fluffy - MAS
– Bubbly - PIE
– Blacky – idiopathic PPHN
? Cardiac
Dr Bhargavi, Ped CardiollogistContributed
Modified from Tend and Konduri – Chapter 21. Pulmonary vasodilators in the treatment of PPHN; in Rajiv PK et al –Essentials of Neonatal Ventilation
Initial Approac
h in Manage-ment of PPHN
Inhaled NO – Ideal Pulmonary Vasodilator
Selective effect of iNO(only pulmonary vasodilation)
Micro-selective effect of iNO (only adjacent to ventilated alveoli)
Dr Satyan Lakshminrushimha
Starting NO:20-20-20 rule
Sharma et al MHNP journal 2015Lakshminrusimha and Keszler Neoreviews
Wean NO:30-60-90 rule
Weaning iNO30-60-90 ruleWhen? – start 30min after initiating iNO if inspired oxygen is ≤ 60% (50%) and preductal SpO2 is≥90%
Lakshminrusimha et al; Pediatr Res 2007
Sildenafil vs. iNO
• PO 1.0-2.0 mg/kg/dose q 6 to 8 hours
– Oral absorption erratic due to right heart failure
• Intravenous dose (if available)
– load 0.14 mg/kg/h for 3 hours followed by 0.07 mg/kg/h continuous infusion
Sildenafil in Term and Premature Infants: A Systematic Review
Matthew Laughon, Krystle M. Perez 2015
The trials showed improvements in oxygenation index and a reduction in mortality in the sildenafil groups (5.9% vs 44%)
There is currently little evidence to support the use of sildenafil in term or near-term infants with persistent pulmonary hypertension of the newborn in areas in which inhaled nitric oxide is available
Sildenafil for pulmonary hypertension in neonates
2017
Sildenafil in the treatment of PPHN has significant potential especially in resource limited settings. However, a large scale randomised trial comparing sildenafil with the currently used vasodilator, inhaled nitric oxide, is needed to assess efficacy and safety.
NO
NO
NO
NO
NO
NO
NO
NO
sGC
cGMP
PDE5
BNP
cGMP
pGC
Dual source of cGMP
CNP
When systemic
sepsis (including
viral) is suspected, use caution with
sildenafil
Sepsis
Dr Satyan
Surfactant
ECMO 29.3% 40.4%P=0.038
Surfactant Placebo
Lotze et al J Pediatr, 1998 Surfactant replacement therapy. Stevens TP Sinkin RAKonduri et al J Perinatol 2013
In the presence of lung
disease and PPHN (all
causes except
idiopathic or black-
lung PPHN),
administration of
surfactant was
associated with a 3
fold reduction in the
need for ECMO or
death – Dr. Konduri
Choice of Blood Pressure Medication in PPHN
Cardiac Function
Normal Abnormal
Normal blood
pressure
Continue monitoring
Selective pulmonary
vasodilators (iNO)
Milrinone (preferred)
Dobutamine
Epinephrine
Low blood pressure Dopamine (?)
Norepinephrine
Vasopressin
Dopamine
Epinephrine
(High risk of ECMO)Sharma et al MHNP journal 2015Lakshminrusimha and Keszler Neoreviews
Vasopressin: Selective Systemic Vasoconstriction?
Siehr et al PCCM 2016
Pre
ssu
re –
mm
Hg) Systemic BP
Pulmonary arterial pressure
Congenital diaphragmatic herniaInfants of diabetic mothers PPHNAsphyxia and hypothermia
Hydro-cortisone?
Alsaleem et al Clin Med In 2019
MgSo4
Supportive
Endothelin receptor antagonists for persistent pulmonary hypertension in term and late preterm infants
18 August 2016
There is inadequate evidence to support the use of ETRAs either as stand-alone therapy or as adjuvant to inhaled nitric oxide in PPHN. Adequately powered RCTs are needed.
Steinhorn RH, Fineman J, Kusic-Pajic A, Cornelisse P, Gehin M, Nowbakht P,
et al. Bosentan as adjunctive therapy for persistent pulmonary hypertension
of the newborn: results of the FUTURE-4 study. Circulation.
2014;130:A13503.
Bosentan
May be appropriate for PPHN with CDH, BPD
30
Oxygen titrated to preductal SpO2
Hemodynamic management –(dopamine vs. vasopressin)
Inhaled NO or inhaled PGE or inhaled PGI
Brief periods of tolerable
hypoxemia and permissive
hypercapnia do not significantly
increase RV strain
Avoid extremely high doses of pressors to increase systemic blood
pressure to supraphysiological levels
Extreme caution with sildenafil and steroids –
if there is concern about
viral/bacterial/candidalsepsis
Surfactant for parenchymal lung disease (secondary PPHN)
load 0.14 mg/kg/h for 3 hours followed by 0.07 mg/kg/h continuous infusion
Summary
Thank You.
Declining systemic blood flow