Pediatric Idiopathic Pulmonary Artery Hypertension Treatment & Management

Updated: Feb 07, 2023
  • Author: Stuart Berger, MD; Chief Editor: Girish D Sharma, MD, FCCP, FAAP  more...
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Approach Considerations

General medical care for this group of children is very important, and should include annual influenza vaccination. Also consider immunization with palivizumab in infants and young children with idiopathic pulmonary artery hypertension (IPAH).

In addition, treat respiratory illnesses aggressively in order to minimize or prevent increases in pulmonary bed reactivity from ventilation-perfusion mismatching and/or hypoxia. Fevers should be aggressively treated to reduce the metabolic demands. Any infectious illness can potentiate pulmonary hypertensive crises requiring maximization of vasodilator therapy.

Go to Primary Pulmonary Hypertension and Persistent Newborn Pulmonary Hypertension for more complete information on these topics.


Pharmacologic Therapy

The usual regimen for patients with IPAH includes warfarin, digoxin, and vasodilators, such as nifedipine, intravenous prostacyclin, or both.


Adult studies have suggested that long-term anticoagulation with warfarin to achieve an international normalized ratio (INR) of 2.5-3 decreases the morbidity and mortality rates associated with IPAH. This is based on the pathologic finding of microthrombi in the pulmonary vasculature. Whether this is a primary or secondary finding is not known. The major precautions relate to bleeding risks. Warfarin appears to be more effective than aspirin for long-term anticoagulant effect.


The use of digoxin, an oral inotropic agent, is advocated in patients with right ventricular dysfunction associated with IPAH. The efficacy of digoxin in this clinical situation is somewhat controversial.


The rationale for the use of vasodilators is to counteract vasoconstriction and is based on theory as well as pathologic studies that implicate medial hypertrophy and vessel constriction in the pathogenesis of IPAH. Early in IPAH, most pulmonary vessel constriction is believed to be reversible. Subsequently, the changes become fixed and irreversible. Acute vasodilator trials in the catheterization laboratory should be performed to determine pulmonary vascular reactivity.

Acute drug testing is performed in the catheterization laboratory with inhaled nitric oxide (titrated to 40 ppm) or with intravenous prostacyclin in incremental doses starting at 2 ng/kg/min. The dose is titrated until either a favorable effect on the pulmonary hemodynamics is noted or systemic hypotension occurs. Children may require doses of up to or more than 20 ng/kg/min to observe an effect. Adults generally do not tolerate doses higher than 8-10 ng/kg/min.

Favorable response to short-term drug testing (ie, inhaled nitric oxide, prostacyclin) is defined by a 20% decrease in the mean pulmonary artery pressure and/or no change or an increase in cardiac output. In addition, an immediate response to inhaled nitric oxide or prostacyclin tends to predict the response to nifedipine, although acute testing of nifedipine in the catheterization laboratory may also be performed.

In the patient who responds to acute vasodilator testing, vasodilators are administered long-term. The drugs that have been most useful include oral calcium channel blockers (eg, nifedipine) and continuous intravenous prostacyclin, although other drugs are currently available with some promising early results. The latter may be recommended for the patient with right heart failure and/or symptoms that may include syncope.

Studies in children by Barst and colleagues have shown that long-term vasodilator therapy increases the short-term survival rate. [8] The acute responder group had a trend toward long-term survival when compared with the nonresponder group. The 5-year survival rate was 86% in the responders compared with 33% in the nonresponder group.

Patients not responding to acute prostacyclin therapy may also be placed on long-term intravenous prostacyclin therapy, although the long-term results are not as favorable. The rationale for this approach is that some degree of pulmonary vascular remodeling may occur with long-term vasodilator therapy, especially in children. Additionally, this palliative measure may be reasonable while other newer therapeutic approaches are under development.

Finally, this approach may allow extra time before lung transplantation. Because of the long wait for an organ, listing nonresponders for lung transplantation at the time of that determination is reasonable. In addition, an important aspect of the rationale for vasodilator therapy is that some patients, especially children, may not respond to short-term drug testing but may nevertheless undergo vascular remodeling with long-term vasodilator therapy.

Other vasodilators are used. These include prostacyclin via alternative routes, such as treprostinil, which is primarily delivered via an intermittent subcutaneous delivery system but can also be delivered via continuous intravenous administration; beraprost, an oral prostacyclin analogue; and iloprost, an inhaled form of prostacyclin. Very little experience is reported with beraprost and iloprost, although studies are currently available.

Endothelin receptor blockers have also been used. The largest experience has been with the dual endothelin receptor–blocker bosentan. Studies have suggested that exercise tolerance and time to clinical worsening have been favorably impacted in patients with IPAH. In September 2017, the FDA approved bosentan (Tracleer) for idiopathic or congenital PAH in children aged ≥3 years, to improve pulmonary vascular resistance (PVR), which is expected to result in an improvement in exercise ability. The FUTURE-2 trial, was a phase III, open-label, long-term extension study aimed to provide long-term tolerability, safety, and exploratory efficacy data for bosentan. Children (2-12 years) with idiopathic or heritable PAH, who completed 12-week treatment in FUTURE-1 and for whom bosentan was considered beneficial were enrolled, and continued to receive bosentan 4 mg/kg twice-daily, which could be down-titrated to 2 mg/kg if not tolerated. The overall median duration of exposure to bosentan was 27.7 months. The pediatric bosentan formulation was generally well tolerated, and its safety profile was comparable to that of the adult formulation when used in children. The results are in line with the efficacy profile of bosentan in previous pediatric and adult PAH studies of shorter duration. [9]

Sildenafil (Revatio) is indicated in pediatric patients 1 to 17 years old for the treatment of pulmonary arterial hypertension (PAH) (WHO Group I) to improve exercise ability and, in pediatric patients too young to perform standardized exercise testing, pulmonary hemodynamics thought to underlie improvements in exercise. [10]  Approval was based on the STARTS-1 AND STARTS-2 trials. Although children randomized to higher compared with lower sildenafil doses had an unexplained increased mortality, all sildenafil dose groups displayed favorable survival for children with pulmonary arterial hypertension. Most patients who died (28/37) had idiopathic/heritable pulmonary arterial hypertension (76% versus 33% overall) and baseline functional class III/IV disease (38% versus 15% overall) and worse baseline hemodynamics. [11]

Sitaxsentan (Thelin), an alternative endothelin receptor–blocker, is currently undergoing clinical trials.

There is theoretical support for the use of combination vasodilator therapy in patients with IPAH. Combinations of prostacyclin analogues, endothelin receptor inhibition, and/or phosphodiesterase-5 inhibition may have a synergistic effect by working on the multiple pathways that may promote vasoconstriction.


Diet and Activity

No specific diet is recommended other than one that prevents constipation. Valsalva maneuvers can reduce venous return to an already dysfunctional right ventricle, with resultant syncope.

Many children with idiopathic pulmonary artery hypertension are activity restricted and not allowed to participate in competitive athletics. In some instances, children may be allowed to participate in activities. This is more likely the case in a child with a pop-off lesion who has no adverse cardiopulmonary effects at exercise testing. This decision must only be made by a specialist familiar with pulmonary hypertension in children and only after a complete evaluation, including a progressive exercise test.


Supplemental Oxygen

Oxygen is certainly well known as a pulmonary vasodilator. Some authors recommend that supplemental oxygen be available at all times for emergency use and in the presence of an intercurrent pulmonary infection that might potentially result in systemic desaturation, even if treated in the outpatient setting.

Additionally, some children demonstrate desaturation with sleep secondary to hypoventilation. This group of patients may also benefit from nocturnal supplemental oxygen therapy. Note that a current recommendation suggests performing a sleep study as part of the diagnostic workup for patients with IPAH to rule out sleep apnea and/or upper airway obstruction as the underlying cause for pulmonary hypertension.


Palliative Surgery

Patients with severe pulmonary hypertension resulting in recurrent syncope or right-to-left intracardiac shunting have a poor prognosis. The former group does not have an intra-atrial communication.

Syncopal spells are often exercise related and are a result of systemic vasodilation with the concomitant inability to augment cardiac output because of IPAH and right heart dysfunction. This group of patients may benefit from palliation with blade atrial septostomy or balloon dilation of the atrial septum. This procedure can be performed in the cardiac catheterization laboratory. Although the arterial oxygen saturation decreases, cardiac output and oxygen delivery increase with successful decompression of the atrial septum. The procedure is not without risk but is a very good palliative bridge for the symptomatic patient with idiopathic pulmonary artery hypertension.

For those children who truly do not respond to long-term therapy and who are symptomatic, lung transplantation should be considered. [12] Although transplantation is also a palliative therapy, trading one disease for another, it often results in improvement of symptoms and quality of life. Living lobar lung donation may offer some benefits as compared with traditional cadaveric transplantation.


Long-Term Monitoring

Patients with IPAH may require inpatient care for any intercurrent illness that might result in significant hypoxemia or decreased cardiac output.

Patients are observed on an outpatient basis with a regular, but somewhat variable, schedule. Follow-up echocardiography is recommended on a variable schedule, depending on the degree of pulmonary hypertension and the clinical status of the patient.

In addition, follow-up cardiac catheterization and drug testing are also recommended. The latter can be performed in an outpatient setting, and its frequency depends on the clinical circumstances.