What is the treatment for a newborn with pulmonary hypertension and hypotension?

Treatment of Neonatal Pulmonary Hypertension with Hypotension

In newborns with pulmonary hypertension and low systolic blood pressure, the priority is to restore adequate systemic perfusion with volume resuscitation and inotropic support before initiating pulmonary vasodilators, as hypotension can worsen right-to-left shunting and tissue oxygen delivery. 1

Initial Hemodynamic Stabilization

Maintain normal systemic blood pressure with volume expansion and cardiotonic therapy to reduce both left and right ventricular dysfunction and enhance systemic oxygen transport. 1 This is critical because:

• Adequate systemic pressure is essential to reduce right-to-left shunting through the ductus arteriosus and foramen ovale 1
• However, avoid increasing blood pressure to supraphysiological levels solely to drive left-to-right ductal shunting, as this may transiently improve oxygenation but will not reduce pulmonary vascular resistance 1

Volume and Inotropic Support

• Administer volume resuscitation first to ensure adequate preload, particularly important as many neonates with PPHN are relatively hypovolemic 2
• Consider intravenous milrinone (Class IIa recommendation) in infants with PPHN and signs of left ventricular dysfunction, as it provides both inotropic support and afterload reduction 3
• Milrinone has been reported to substantially improve oxygenation indices in severe PPHN cases unresponsive to other therapies, though caution is warranted regarding potential complications 4

Optimize Ventilation Before Vasodilators

Establish optimal lung recruitment and ventilation strategies before initiating pulmonary vasodilator therapy, as adequate lung inflation is essential for vasodilator efficacy. 3, 1

• Implement lung recruitment strategies to improve functional residual capacity, particularly in patients with parenchymal lung disease 3
• Avoid both atelectasis and over-distension, as both worsen pulmonary vascular resistance 1
• Consider high-frequency oscillatory ventilation for poor lung compliance and inadequate gas exchange 1

Pulmonary Vasodilator Therapy

Inhaled Nitric Oxide (First-Line)

Inhaled nitric oxide (iNO) is indicated as first-line pulmonary vasodilator therapy to reduce the need for ECMO in term and near-term infants with PPHN and oxygenation index exceeding 25 (Class I recommendation, Level of Evidence A). 3, 5

• Initial dose: 10-20 ppm, as doses >20 ppm do not enhance oxygenation and increase methemoglobinemia risk 1, 5
• Once oxygenation improves, wean relatively rapidly to 5 ppm, then to 1 ppm before discontinuation to avoid rebound pulmonary hypertension 3
• Low-dose iNO (6 ppm) has been shown to cause sustained clinical improvement in severe PPHN 6

Critical caveat: In the presence of significant left ventricular dysfunction, use iNO cautiously, as lowering pulmonary vascular resistance may increase preload to a dysfunctional left ventricle that cannot accommodate increased stroke volume, potentially worsening pulmonary venous hypertension and causing pulmonary edema. 3

Adjunctive Therapies for iNO-Resistant Cases

If hypotension persists or PPHN remains refractory despite iNO and hemodynamic support:

• Sildenafil is a reasonable adjunctive therapy for infants refractory to iNO, especially with oxygenation index >25 (Class IIa recommendation) 3
• Inhaled prostacyclin analogs may be considered as adjunctive therapy for iNO-refractory cases with oxygenation index >25 (Class IIb recommendation) 3
• Intravenous milrinone is particularly reasonable when left ventricular dysfunction is present (Class IIa recommendation) 3

Special Consideration: Prostaglandin E1

In cases of suprasystemic pulmonary hypertension with severe right ventricular failure and persistent hypotension, consider prostaglandin E1 infusion to maintain ductal patency and augment cardiac output through right-to-left ductal shunting (Class IIb recommendation). 3 This strategy:

• Allows the right ventricle to decompress by maintaining right-to-left shunting at the ductal level 3
• May be particularly beneficial when left ventricular dysfunction limits the effectiveness of pulmonary vasodilators 3
• Should be used cautiously and only after establishing that the left ventricle can handle the increased preload 3

ECMO Criteria

ECMO support is indicated for term and near-term neonates with severe pulmonary hypertension or hypoxemia refractory to iNO and optimization of respiratory and cardiac function (Class I recommendation, Level of Evidence A). 3, 1

• Consider ECMO referral when oxygenation index exceeds 40 despite maximal medical therapy 1
• iNO may play an important stabilizing role before ECMO initiation, improving the safety of cannulation 3

Monitoring Priorities

• Continuous assessment of systemic blood pressure and tissue perfusion (capillary refill, urine output, lactate) 2
• Serial echocardiography to evaluate right and left ventricular function, estimate pulmonary artery pressures, and assess for ductal and atrial level shunting 3, 1
• Methemoglobin levels when using iNO, particularly at higher doses 5
• Avoid extreme hyperoxia (FiO₂ >0.6) as it may be ineffective due to extrapulmonary shunt and may aggravate lung injury 1

Common Pitfalls to Avoid

• Never initiate pulmonary vasodilators before establishing adequate systemic blood pressure, as this can precipitate cardiovascular collapse 1
• Do not use aggressive hyperventilation strategies to induce alkalosis, as this causes ventilator-induced lung injury without proven mortality benefit 2
• Avoid abrupt discontinuation of iNO, as rebound pulmonary hypertension can be life-threatening; always wean to 1 ppm first 3
• Recognize that hypotension may indicate underlying left ventricular dysfunction, which fundamentally changes the treatment approach and may limit vasodilator efficacy 3