A systematic review of clinical study evidence for pulmonary vasodilator therapy following surgery with cardiopulmonary bypass in children with CHD

Objectives: Complications from pulmonary hypertension are one of the leading contributors to morbidity and mortality post-cardiopulmonary bypass surgery in children with CHD. Pulmonary vasodilator therapies are commonly used post-operatively, but the optimal target patient population, therapy choice, timing of therapy initiation, and duration of therapy are not well defined. Methods: We used PubMed and EMBASE to identify studies from 2000 to 2020 investigating the use of pulmonary vasodilator therapy post-cardiopulmonary bypass in children aged 0-18 years. To ensure eligibility criteria, studies were systematically reviewed by two independent reviewers. Results: We identified 26 studies of 42,971 children across four medication classes; 23 were single centre, 14 were prospective, and 11 involved randomisation (four of which employed a placebo-control arm). A disproportionate number of children were from a single retrospective study of 41,872 patients. Definitions varied, but change in pulmonary haemodynamics was the most common primary outcome, used in 14 studies. Six studies had clinical endpoints, with mortality the primary endpoint for two studies. Treatment with inhaled nitric oxide, iloprost, and sildenafil all resulted in improved haemodynamics in specific cohorts of children with post-operative pulmonary hypertension, although improved outcomes were not consistently demonstrated across all treated children. Iloprost may be a cheaper alternative to inhaled nitric oxide with similar haemodynamic response. Conclusion: Studies were predominantly single-centre, a control arm was rarely used in randomised studies, and haemodynamic endpoints varied significantly. Further research is needed to reduce post-operative morbidity and mortality from pulmonary hypertension in children with CHD.

Automated summary

Complications from pulmonary hypertension are a major cause of morbidity and mortality in children with congenital heart disease (CHD) post-cardiopulmonary bypass surgery. The use of pulmonary vasodilator therapy after surgery is common, but the optimal target patient population, therapy choice, timing, and duration are unclear. This review identified 26 studies involving 42,971 children with CHD, and found that inhaled nitric oxide, iloprost, and sildenafil showed improved haemodynamics in specific cohorts of children with post-operative pulmonary hypertension. However, further research is needed to reduce post-operative morbidity and mortality.