Inhaled nitric oxide treatment of children with pulmonary hypertension after cardiac surgery

The presence of pulmonary hypertension in children with a congenital heart defect carries the risk of considerable problems of management immediately after corrective surgery. To evaluate whether inhaled nitric oxide (NO) complements other routine therapeutic measures to lower pulmonary artery pressure, 28 infants and children (ages, 0.85 +/- 0.19 years) with this condition were studied within the first few days after surgery. Hemodynamics and/or oxygen saturations were significantly improved by NO inhalation (initial concentration, 15 +/- 1.8 ppm) in 27 patients (96%). Mean pulmonary arterial pressure (PAP) declined significantly from 45 +/- 5.8 to 27 +/- 3.1 mmHg, whereas there were significant increases in mean systemic arterial pressure (55 +/- 1.9 to 59 +/- 1.8 mmHg) and arterial oxygen saturation (SaO(2), 90 +/- 1.9 to 97 +/- 1.1%). The changes in PAP (ED50: 0.29 +/- 0.07 ppm NO) and SaO(2) (ED50: 0.21 +/- 0.04 ppm NO) were dose-dependent with no significant difference in ED,, values. The NO-induced pulmonary vasodilation was independent of the concomitant reduction in arterial carbon dioxide tension. In a case-control study of a subgroup of 18 patients and 35 matched controls, inhaled NO significantly reduced the frequency of pulmonary hypertensive crises by 83% and lowered the mortality rate from 14.2% to zero. During low-dose NO inhalation there was no detectable formation of methemoglobin or significant production of nitric dioxide (NO,), and no disturbance of platelet aggregation or leukocyte adhesion. It is concluded that in children undergoing cardiac bypass surgery, low-dose inhaled NO improves hemodynamics and oxygenation, and reduces the frequency, severity, and mortality of pulmonary hypertensive crises during perioperative intensive care. We recommend a dose range of 1-10 ppm NO for routine use, and an absolute upper dose limit of 40 ppm NO to avoid potential adverse side effects. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.