Safety of enteral sildenafil in hemodynamically unstable children

Enteral sildenafil may be used in the intensive care unit for treatment of pulmonary arterial hypertension. We aimed to determine if initial enteral sildenafil dosing is safe in children receiving concurrent vasoactive infusions.

We performed a single-centre retrospective chart review that included patients less than 2 years of age in paediatric and cardiovascular intensive care units at an academic medical centre from 1 January, 2010 to 30 November, 2016. Included patients received concomitant enteral sildenafil and a continuously infused vasoactive agent. Exclusion criteria consisted of mechanical circulatory support, any form of dialysis, or a suspicion of septic shock at the time of sildenafil initiation. We sought to identify patients who developed worsening hemodynamic instability after initiation of enteral sildenafil defined as one or more of the following observations within 24 hours of sildenafil initiation: sildenafil discontinuation, total fluid bolus receipt >10 ml/kg, increased vasoactive support, epinephrine intravenous push administration, and/or the initiation of mechanical circulatory support.

Worsening hemodynamic instability was identified in 35% of the 130-patient cohort. Patients younger than 4 months were at increased risk of further hemodynamic instability compared with older patients (56% versus 44%, p = 0.0003) despite receiving lower median doses (1.28 mg/kg/day versus 1.78 mg/kg/day, p = 0.01).

Critically ill children receiving vasoactive infusions may be at increased risk for further hemodynamic instability after initiation of enteral sildenafil, particularly in younger patients. This population may benefit from lower starting enteral sildenafil doses of 0.25 mg/kg/dose or less every 8 hours to avoid further hemodynamic compromise.