Refractory Hypoxemia Case Based Approach · Based Approach Dr Nalinikant Panigrahy MD , DNB Neonatology Consultant Neonatology. Case ... cyanosis Labile oxygenation Hypoxemia disproportional

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