Pulmonary hypertension in children is a devastating diagnosis with significant morbidity and mortality. Causes for pulmonary hypertension in children include idiopathic pulmonary arteriolar dysfunction, CHD, and chronic lung disease, especially in premature infants.Reference Simonneau, Gatzoulis and Adatia ¹ Robust laboratory investigations have shown that inflammation disrupts multiple molecular pathways leading to pulmonary hypertension. Inflammatory cell lines and elevated pro-inflammatory cytokines have been identified in tissue and sera from patients with pulmonary hypertension.Reference Price, Wort and Perros ² In rats, dexamethasone has been shown to attenuate the development of pulmonary hypertension and even reverse the pathology.Reference Wang, Wang and Chen ^{3 ,} Reference Price, Montani and Tcherakian ⁴ Human smooth muscle cell growth is inhibited by prednisolone in vitro.Reference Ogawa, Nakamura and Matsubara ⁵ Despite the literature on anti-inflammatory medications in treatment of pulmonary hypertension, limited literature exists on treating pulmonary hypertension with anti-inflammatory medications in humans. In this article, we present the cases of two children with severe pulmonary hypertension that improved when treated with glucocorticoids.

Patient one was a former 31-week-gestation infant with an uncomplicated intensive care course who presented at 6 months of age to an outside hospital with respiratory distress and hypoxia. Support was rapidly escalated with intubation, muscle paralysis, and multiple inotropes. All viral and bacterial cultures were negative. An echocardiogram showed suprasystemic right heart pressures (tricuspid regurgitation jet derived pressure 106 mmHg, systolic blood pressure 60 mmHg, and paradoxical ventricular septal motion with “pancaked” left ventricle), and she was transferred for a lung transplant evaluation. A cardiac catheterisation performed while mechanically ventilated, muscle relaxed, and on 100% oxygen, 20 ppm of inhaled nitrous oxide, oral sildenafil, dopamine, and epinephrine demonstrated suprasystemic right ventricular pressures (right ventricular systolic pressure 103 mmHg, left ventricular systolic pressure 57 mmHg, indexed pulmonary vascular resistance of 25.7 Wood units×m²). Intravenous epoprostenol was subsequently initiated. Over the next 3 days, the child’s clinical condition continued to deteriorate with worsening spells of hypoxia and hypotension. Within 48 hours of initiating methylprednisolone at 2 mg/kg/day, the child’s clinical course improved significantly with no further spells and a reduction in inotropic support and oxygen. An open lung biopsy found non-specific features of diffuse medial hypertrophy, normal venules and capillaries, and rare lymphocytes. After 11 days, she was weaned off steroids with improved right ventricular function and septal position though an insufficient tricuspid regurgitation jet on echocardiograms. The child was transferred out of the ICU on supplemental oxygen, increased dose of epoprostenol, and sildenafil. The child developed worsening respiratory distress and hypoxia 10 days after stopping steroids. Oral prednisone 2 mg/kg/day was again initiated and with notable clinical improvement within 36 hours. The child was discharged home, and steroids were successfully weaned over a 3-month period. The child continues to thrive, and has been weaned off all pulmonary vasodilators in the 9 years since treatment.

Patient two had Trisomy 21, and was initially seen at 1 month of age with a moderate-sized, atrial-level defect, no ventricular septal defect, and evidence of suprasystemic right heart pressures with a pancaked left ventricle. Cardiac catheterisation at 3 months of age showed systemic right ventricular pressures (mean pulmonary arterial pressure 44 mmHg, indexed pulmonary vascular resistance 4.7 Woods units×m²) with minimal responsiveness to inhaled nitric oxide. At 5 months of age, the atrial defect was surgically closed without complications, and he was discharged home on sildenafil. Follow-up at 8 months of age, however, showed pancaked interventricular septum and suprasystemic pulmonary pressures (tricuspid valve regurgitation jet derived pressure of 70 mmHg), and the child clinically had poor feeding and diaphoresis. A 5-day burst of prednisone at 2 mg/kg/day improved clinical symptoms. The child was admitted 2 months later to the ICU with right heart failure, and an echocardiogram showed suprasystemic right heart pressures (tricuspid regurgitation jet 75 mmHg) with decreased right ventricular systolic function. He was initiated on nasal cannula-inhaled nitric oxide, milrinone, and furosemide on admission. The next day, bosentan and intravenous methylprednisone at 4 mg/kg/day were added. Within 72 hours of steroid initiation, milrinone and inhaled nitric oxide were weaned off, and an echocardiogram showed right ventricular pressures that were half systemic (tricuspid regurgitation jet 40 mmHg). The child was discharged home on sildenafil, furosemide, bosentan, and a 2.5-month prednisolone taper. Now at 6 years of age, he is maintained on sildenafil and ambrisentan with no further admissions.