Pulmonary Vasodilator Therapy in Children With Pulmonary Hypertension

Introduction

Pulmonary hypertension is a complex condition described by high blood pressure in the arteries supplying the lungs. This can cause increased stress on the heart and potential damage. While this condition can affect people of all ages, children with pulmonary hypertension encounter distinctive challenges. However, pulmonary vasodilator therapy has shown promising results in research on managing pulmonary hypertension and improving the symptoms in affected children. Pulmonary hypertension is also associated with significant morbidity and mortality.

What Is Pulmonary Hypertension in Children?

Pulmonary hypertension in children is a rare yet severe condition. The most common cause of pulmonary hypertension is congenital heart defects, genetic disorders, or chronic lung diseases. However, in some cases, it can also be idiopathic (unknown cause). In the case of pulmonary hypertension, the raised blood pressure in the pulmonary arteries causes the heart to pump blood more difficult, which may give rise to symptoms including shortness of breath, fatigue, and restricted tolerance to exercise. In addition, diagnosis of pulmonary hypertension in children is also quite difficult because of the similarity of manifestations with other respiratory conditions. Pulmonary hypertension treatment recommendations vary from adults to children population as the etiology of pulmonary hypertension, pharmacodynamics, and pharmacokinetics differ in adults and children.

What Are the Signs and Symptoms of Pulmonary Hypertension in Children?

The most common signs and symptoms of pulmonary hypertension in children include:

• Fainting.

• Abnormal heartbeat.

• Paleness or blue discoloration of the lips and extremities.

• Poor growth.

• Shortness of breath.

• Fatigue.

What Is the Treatment of Pulmonary Hypertension in Children?

Therapeutic options for pulmonary hypertension in children consist of the following:

1. Vasodilators (dilates and widens blood vessel walls).

2. Calcium channel antagonists.

3. Prostacyclin analogs.

4. Endothelin antagonists such as Ambrisentan, Bosentan and Sitaxentan.

What Is Pulmonary Vasodilator Therapy for Pulmonary Hypertension in Children?

Pulmonary vasodilator therapy is an effective medical treatment in the management of pulmonary hypertension in children. This treatment method focuses on the relaxation of the smooth muscle of the pulmonary arteries, which eventually reduces resistance and improves the blood flow of the lung arteries.

There are two main vasodilators for pulmonary hypertension in children, such as the following,

• Phosphodiesterase (PDE)-5 inhibitors such as Sildenafil.

• Inhaled Nitric oxide is used for babies with pulmonary hypertension receiving care in the neonatal intensive care unit. It is not available for treatment at home. Nitric oxide is delivered by either mask or ventilator over 15 minutes.

At present, monotherapy with Sildenafil is the most commonly used drug for the treatment of pulmonary hypertension in children. Sildenafil contributes to improvement from a less than one-year survival in untreated children with pulmonary hypertension to a five-year survival rate in 97 % of children with severe pulmonary hypertension. Sildenafil is most commonly used as an oral preparation in the management of pulmonary hypertension in children. In current guidelines for pulmonary hypertension treatment in children, initial upfront combination therapy is used. Sequential addition of complementary medications from another class of vasodilators is used.

Currently, two better PDE-5 inhibitors that are Tadalafil and Vardenafil, are being evaluated. These newer compounds are more satisfactory than Sildenafil in terms of more selectivity for PDE-5, faster onset of action, longer duration of action, and absence of the influence of food on absorption. In addition to these, Tadalafil has the least impact on PDE-6 and is therefore not associated with any visual disturbances, including blurring and blue-green color traces that may occur with Sildenafil. However, after the use of Tadalafil, backache, and myalgia can occur frequently. Tadalafil is the most laboriously researched alternative to Sildenafil and has demonstrated efficacy at one mg/kg doses in children with pulmonary hypertension. Moreover, its more extended half-life allows once-daily dosing that is fewer daily doses than Sildenafil, enhancing outpatient compliance. In addition, Tadalafil improves oxygen saturation and functional capacity better than Sildenafil.

What Are the Adverse Effects of Vasodilator Therapy in Children With Pulmonary Hypertension?

The followings are the side effects reported in children on Sildenafil,

• Epistaxis (nosebleeds).

• Respiratory symptoms, including cough and nasal congestion.

• Gastroesophageal reflux.

• Abdominal pain.

• Headaches.

• Tremors.

• Diarrhea and vomiting.

• Erections.

• Facial flushing.

• Dizziness.

• Irritability.

• Fever.

• Rarely psychiatric disorders.

• Skin disorders.

• Edema (fluid filled swelling).

• Pain in limbs.

• Photophobia (light sensitivity).

• Retinal dysfunction (problems in function of the retina in the eye).

Adverse effects of nitric oxide in children are not common and may occur only during long-term administration. these adverse effects include:

• Methemoglobinemia.

• Nitrogen dioxide toxicity.

What Are the Contraindications of Using Vasodilator Therapy in Children With Pulmonary Hypertension?

Sildenafil raises the vasodilatory and antihypertensive outcomes of nitrates such as Glyceryl trinitrate and can create profound hypotension resulting in reduced coronary perfusion and myocardial infarction. Thus it is contraindicated in children taking nitrates.

Other contraindications include the following:

• The presence of severe hypotension.

• Pulmonary veno-occlusive disease.

• Left ventricular outflow obstruction.

• Sickle cell anemia associated with pulmonary hypertension.

• Multiple system atrophy.

• Additional caution is needed if the individuals are receiving alpha-blockers.

What Is the Efficacy of Vasodilator Therapy in Children With Pulmonary Hypertension?

Sildenafil improved cardiac output and stroke volume without causing a significant change in heart rate. It decreases pulmonary arterial pressures and increases pulmonary blood flow. Nitric oxide remains the gold standard for the management of acute pulmonary hypertension in children. However, it carries the risk of the development of methemoglobinemia which can be lowered by delivering nitric oxide via inhalation or by administration of Sildenafil concomitantly. However, newborns receiving this combination therapy are closely monitored for the development of systemic hypotension. Moreover, nitric oxide therapy withdrawal is associated with the chance of rebound pulmonary hypertension.

Conclusion

Pulmonary vasodilator therapy represents a substantial advancement in the management of pulmonary hypertension in children. These medications have demonstrated promising outcomes in improving exercise capability and functional status in children with pulmonary hypertension by stimulating vasodilation and decreasing pulmonary artery pressure. However, individualized treatment plans, meticulous monitoring for probable side effects, and a thorough approach are essential. Sildenafil is a cost-effective choice for the treatment of children with pulmonary hypertension currently. However, caution is required regarding its long-term usage with higher doses. Studies show that pulmonary vasodilators reduce mortality, enhance respiratory and hemodynamic parameters, and lessen the duration of mechanical ventilation in children with pulmonary hypertension. Overall, vasodilators in children with pulmonary hypertension are well tolerated.