The Science Journal of the American Association for Respiratory Care
Long-term inhaled nitric oxide (INO) is being investigated as a therapy in the management of chronic pulmonary hypertension1. We evaluated the use of INO in a child with pulmonary hypertension in order to determine the feasibility of long-term therapy in the home. A 4 year old male was diagnosed with an atrial septal defect (ASD) and patent ductus arteriosus (PDA), with pulmonary artery pressures (PAP) equal to systemic arterial pressure (SAP), and right-to-left shunting in room air. Following demonstration of pulmonary vascular reactivity with INO, the PDA was closed with a device and PAPs decreased to 2/3 of SAP. In preparation for later closure of the ASD, INO in conjunction with Heparin, was started with the hypothesis that this therapy would aid in the remodeling of pulmonary vessels and effect further reduction of PAP. INO at 50 ppm, by nasal cannula (NC), was administered by mixing 0.5 L/min of O2 with 0.5 L/min of nitric oxide (NO) from a 100 ppm NO cylinder. In the event of an inadvertent cylinder leak, a 100 ppm source was deemed safe for a non-ICU setting. Echocardiography demonstrated left-to-right shunt flow through the ASD while on INO, SpO2 was 92-98%. Anticipating home therapy, daily simulations of INO disconnection were performed and resulted in acute decreases in SpO2 to 50-60% despite O2 therapy. Echocardiography and cardiac catheterization subsequently showed PAP > SAP during INO withdrawal. Trial doses of Sildenafil2 and Dipyridamole3, both cGMP degradation inhibitors, were administered to minimize the rebound effect. Sildenafil blunted the rebound with SpO2 > 90% off INO, but Dipyridamole did not. After 7 days a cardiac catheterization demonstrated that PAPs equaled SAP. To optimize INO delivery, 40 ppm by a tight-fitting mask replaced the NC, and the PAPs decreased to < 1/2 SAP. The ASD was left open. The patient was intubated and ventilated with 40 ppm INO in order to ensure adequate alveolar concentrations of NO. After 5 days the patient was extubated and continued on INO at 50 ppm by NC. INO was weaned over the next 7 days to a dose of 9 ppm. Once off INO, the patient's SpO2 was 92-96% on 0.5 L/min O2 with no acute changes in SpO2. The maximum methemoglobin during INO therapy was 2.2%. The maximum nitrogen dioxide concentration during bench testing of the NC system, and during mechanical ventilation, was < 1 ppm. Follow-up echocardiography continued to suggest evidence of pulmonary hypertension. This patient was treated with INO for 21 days in the hospital which was originally intended to be accomplished in the home. The significant rebound observed when INO was disconnected, demonstrates the importance of simulating INO disconnections and testing for rebound when anticipating home INO therapy. It is unclear if continued use of Sildenafil or Dipyridamole is feasible and will safely protect patients from adverse effects of inadvertent INO withdrawal. The patient was discharged with home O2 and will be re-evaluated for ASD closure in the future. Domiciliary use of INO is investigational therapy. Safety and efficacy trials must evaluate known and unknown toxicities, adequacy and availability of home monitoring, limitations of NC delivery and physiologic response to inadvertent withdrawal. 1. Atz AM, Wessel DL. Inhaled nitric oxide and heparin for infantile pulmonary hypertension. Lancet 1998;351:1701. 2. Atz AM, Wessel DL. Sildenafil ameliorates the effects of inhaled nitric oxide withdrawal. Anesthesiology 1999;90 (in press). 3. Dunbar DD, Kinsella JP, et al. Dipyridamole attenuates rebound pulmonary hypertension after inhaled nitric oxide withdrawal in postoperative congenital heart disease. J Thorac Cardiovasc Surg 1998;115:875-82.