How should an infant with persistent pulmonary hypertension of the newborn and refractory hypotension despite three inotropes be managed, including preparation for extracorporeal membrane oxygenation?

Management of PPHN with Refractory Hypotension and ECMO Preparation

ECMO support is indicated for this infant with severe PPHN and hypoxemia refractory to inhaled nitric oxide and optimization of respiratory and cardiac function, and you should initiate transfer to an ECMO-capable center immediately while optimizing all supportive measures. 1

Immediate Hemodynamic Management

Inotropic Optimization

Since the infant is already on three inotropes with persistent hypotension, consider the following algorithmic approach:

• Add low-dose vasopressin (0.0003 IU/kg/min, range 0.01-0.085 milliunits/kg/h) as rescue therapy for catecholamine-refractory shock. This can improve mean arterial pressure within 1 hour, reduce oxygenation index, and allow weaning of other inotropes 2, 3. Monitor for transient hyponatremia as the primary side effect.

• Intravenous milrinone is reasonable if there are signs of left ventricular dysfunction on echocardiography (Class IIa recommendation) 1. This is particularly important as LV dysfunction commonly complicates PPHN and can worsen with aggressive pulmonary vasodilation.

Pulmonary Vasodilator Therapy

Ensure inhaled nitric oxide (iNO) is optimized at 20 ppm maximum (higher doses increase methemoglobinemia risk without improving outcomes) 1. If not already initiated and oxygenation index exceeds 25, iNO is a Class I indication 1.

Add adjunctive pulmonary vasodilators in this refractory case:

• Sildenafil is a reasonable adjunctive therapy, especially with oxygenation index >25 (Class IIa) 1
• Inhaled prostacyclin analogs may be considered as additional adjunctive therapy (Class IIb) 1
• Intravenous treprostinil (starting at 6 ng/kg/min, titrated to maximum 20 ng/kg/min) can accelerate oxygenation improvement and allow earlier iNO weaning in non-responders 4

Respiratory Optimization

Implement lung recruitment strategies to improve iNO efficacy, particularly if parenchymal lung disease is present (Class I) 1. This includes:

• Optimize PEEP to maintain functional residual capacity
• Avoid both atelectasis and overdistension
• Consider surfactant if lung disease component exists
• Target gentle ventilation to avoid volutrauma

ECMO Preparation and Criteria

Indications for ECMO Transfer

Oxygenation index >40 is a clear indication to transfer to an ECMO center 1. Even with OI 25-40, if the infant is deteriorating despite maximal therapy, initiate transfer discussions.

ECMO is indicated (Class I, Level A) for term and near-term neonates with severe PH or hypoxemia refractory to iNO and optimization of respiratory and cardiac function 1.

Pre-ECMO Considerations

Before initiating ECMO, evaluate for underlying disorders that would make ECMO futile:

• Alveolar capillary dysplasia (Class IIa recommendation) 1
• Genetic surfactant protein diseases
• Severe lung hypoplasia

This evaluation is reasonable for infants failing to improve after vasodilator, lung recruitment, or ECMO therapy 1. One case series noted a neonate with progressive pulmonary artery pressure increase during ECMO who died and was found to have alveolar capillary dysplasia 5.

ECMO Outcomes and Expectations

Expect mean ECMO duration of approximately 81 hours (range 26-185 hours) based on recent experience 5. Successful weaning occurs in approximately 91% of cases with 73% survival 5. Another series showed ECMO was averted in 50% of cases when vasopressin was used as rescue therapy 3.

Monitor closely for ECMO complications:

• Intracranial hemorrhage (most common, ~45% incidence)
• Bleeding at puncture sites
• Disseminated intravascular coagulation
• Pulmonary or gastric hemorrhage
• Renal insufficiency 5

Critical Pitfalls to Avoid

1. Do not delay ECMO referral waiting for additional therapies to work if OI >40 or progressive deterioration occurs
2. Avoid abrupt iNO discontinuation - wean to 1 ppm before stopping to prevent rebound pulmonary hypertension 1
3. Do not use iNO doses >20 ppm - no additional benefit and increased toxicity risk 1
4. Carefully assess for LV dysfunction before aggressive pulmonary vasodilation, as lowering PVR with a dysfunctional LV can worsen pulmonary venous hypertension 1
5. Ensure adequate lung recruitment before concluding iNO failure - up to 30-40% of infants don't respond to iNO alone, but lung recruitment can restore responsiveness 1