APPROACHES TO TREATING PERSISTENT PULMONARY HYPERTENSION IN THE

NEWBORN

Josef Symon Concha

ANTICIPATION and TRANSITION

• Anticipating at risk infants– MAP, sepsis, CDH, etc– Prompt treatment and evaluation

• Ensuring appropriate transition from fetal to extrauterine circulation– BE READY FOR: Thermoregulation, glucose control,

homeostasis, blood pressure, antibiotics

PRINCIPLES OF TREATMENT

• Restore cardiopulmonary transition while avoiding lung injury

• Maintain adequate oxygenation while avoiding oxygen toxicity

• Minimize oxygen consumption• Avoid compromise of systemic perfusion

INITIAL TREATMENT

• Correct underlying metabolic derangements– Body Temperature– Acidosis ALKALOSIS*– Glucose homeostasis– Electrolyte abnormalities: Hypocalcemia, etc.– Treat anemia

• Optimize lung recruitment– Mechanical ventilation, surfactant

INITIAL TREATMENT

• Optimize cardiac output, and left ventricular function– Vasopressors– Inotropic agents

• Sedation*• Medications*

Specifics…

VENTILATION

• Hyperventilation helps promote pulmonary vasodilation

• Traditionally, we aim for high PaO2 (>100) as possible and low normal PaCO2

• TCPLV (time cycled pressure limited ventilation) may be used

• Some authors: does not improve outcomes; potentially toxic to lung and cerebral perfusion

Mechanical Ventilation

• Almost always necessary• The goal of mechanical ventilation should be

to maintain normal functional residual capacity (FRC) by recruiting areas of atelectasis, as well as to avoid overexpansion.

• Adjust ventilator settings to maintain normal expansion (ie, of approximately 9 ribs) on chest radiography.

Mechanical Ventilation

• A frequent concern is determining the target arterial PaO2 level.

• Little is known about what oxygen concentrations maximize benefits and minimize risks.

• Levels of 50 mm Hg or more? • Aiming for high PaO2 may lead to increased ventilator

support and barotrauma. • Extreme hyperoxia may be toxic to the developing

lung owing to the formation of reactive oxygen species.

VENTILATION

• High frequency oscillatory ventilation (HFOV)– Decrease risk of barotrauma– Effective alveolar ventilation– Alveolar recruitment

• HFOV more effective in PPHN babies WITH lung disease

During Hyperventilation….

• Babies often become agitated INCREASES oxygen consumption! So minimize stimulation…

• Must be kept in a quiet place• Minimize movement• There may be a need to administer muscle

relaxants and induce sedation– Pancuronium 0.1-0.2 mg/kg q 1-3 hrs IV– Morphine 10 mcg/kg/hr continuous infusion– NOT TESTED in RCTs! Debatable clinical significance

ALKALOSIS

a. Establish the critical pH- preferably 7.45 but may be higher. If there is no dramatic improvement in PaO2 at a pH >7.6, the infant can be deemed to be "pH unresponsive".

b. Use small boluses of bicarbonate (1-2 mmol/kg) or a continuous infusion (0.5mmol/kg/hour initially). Liberal bicarbonate use may result in hypernatremia and hypokalemia.

INHALED NITRIC OXIDE (iNO)

• Results in selective pulmonary vasodilatation• Potent agent– Decreases pulmonary artery pressure– Increases PaO2

• Dose: 20 ppm for 6 hours initially• Does not cause systemic hypotension• More effective in PPHN babies WITHOUT lung

disease

INHALED NITRIC OXIDE (iNO)

However…• Baby must be weaned off iNO slowly to avoid

REBOUND hypertension (due to suppressed production of endogenous NO)

• iNO is metabolized to nitrogen dioxide (NO2) which is potentially toxic and cause acute lung injury

• iNO reacts with hemoglobin to form methemoglobin

Thus… Monitor for toxic levels of NO2 and methemoglobin!

INHALED NITRIC OXIDE

• Large placebo-controlled trials demonstrated that iNO significantly decreased the need for ECMO in newborns who had PPHN, although iNO did not reduce mortality or length of hospitalization.

• iNO did not reduce the need for ECMO in infants who had unrepaired Congenital Diaphragmatic Hernia.

VASODILATOR DRUGS

• Tolazoline (Priscoline)– Pulmonary and systemic vasodilator– On starting: assess if with pulmonary response by

giving 1-2 mg/kg through peripheral scalp vein• If positive response: start continuous infusion of 0.5-1.0

mg/kg/hr

– Monitor closely for GI bleeding, pulmonary hemorrhage, systemic hypotension

VASODILATOR DRUGS

• Epoprostenol• Sildenafil • Milrinone • Magnesium sulfate– Common side effect: Systemic hypotension, which

may need emergency correction with colloid

When all these interventions failed….

ECMO

• Extracorporeal membrane oxygenation• Form of cardiorespiratory support that allows

the lungs to rest: so also called EXTRACORPOREAL LIFE SUPPORT (ECLS)

• Shown to increase survival rate significantly• First utilized in the 1970s– Used as rescue therapy for neonates with greater

than 80% predicted mortality

ECMO

• However, this should NOT be a replacement for EARLY, OPTIMIZED therapy for PPHN

• Must be given as LAST RESORT when everything else failed

• Requirements:– >33 weeks gestational age: complications greater

if less mature– Potentially REVERSIBLE lung disease– No bleeding disorders/ intracranial hemorrhage

ECMO

• Two routes:– Venovenous route- blood taken from R jugular

vein and return to venous system– Venoarterial route- returned through R carotid

artery• Gas exchange takes place as the blood is

pumped through a membrane oxygenator