Practice Variation, Costs and Outcomes Associated with the Use of Inhaled Nitric Oxide in Pediatric Heart Transplant Recipients.

Abstract

Right ventricular (RV) failure is a potentially fatal complication following heart transplantation (HTx). Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that is used to decrease pulmonary vascular resistance immediately post-HTx to reduce the risk of RV failure. The aim of this study was to describe utilization patterns, costs, and outcomes associated with post-transplant iNO use in children. All pediatric HTx recipients (2002-2016) were identified from a unique linked PHIS/SRTR dataset. Post-HTx iNO use was determined based on hospital billing data. Utilization patterns and associated costs were described. The association of iNO support with post-HTx survival was assessed using the Kaplan-Meier method and a multivariable Cox proportional hazards model was used to adjust for risk factors. A total of 2833 pediatric HTx recipients from 28 centers were identified with 1057 (36.5%) receiving iNO post-HTx. Post-HTx iNO use showed significant increase overall (17.2-54.7%, p < 0.001) and wide variation among centers (9-100%, p < 0.001). Patients with congenital heart disease (aOR 1.4, 95% CI 1.2, 1.6), requiring mechanical ventilation at HTx (aOR 1.3, 95% CI 1.1, 1.6), and pre-transplant iNO (aOR 9.3, 95% CI 5.4, 16) were more likely to receive iNO post-HTx. The median daily cost of iNO was $2617 (IQR $1843-$3646). Patients who required > 5days of iNO post-HTx demonstrated inferior 1-year post-HTx survival (p < 0.001) and iNO use > 5days was independently associated with worse post-HTx survival (AHR 1.6, 95% CI 1.2, 2.1; p < 0.001). There is wide variation in iNO use among centers following pediatric HTx with use increasing over time despite significant incremental cost. Prolonged iNO use post-HTx is associated with worse survival, likely serving as a marker of residual illness severity. Further research is needed to define the populations that derive the greatest benefit from this costly therapy.