Inhaled nitric oxide (NO) for the treatment of early allograft failure after lung transplantation

Abstract

Objective: Inhalation of high concentrations of nitric oxide (NO) has been shown to improve gas exchange and to reduce pulmonary vascular resistance in individuals with ischemia-reperfusion injury following orthotopic lung transplantation. We assessed the cardiopulmonary effects of low doses of NO in early allograft dysfunction following lung transplantion. Design: Prospective clinical dose-response study. Setting: Anesthesiological intensive care unit of a university hospital. Patients and participants: 8 patients following a single or double lung transplantation who had a mean pulmonary arterial pressure (PAP) in excess of 4.7 kPa (35 mmHg) or an arterial oxygen tension/fractional inspired oxygen ratio (PaO2/FIO2) of less than 13.3 kPa (100 mmHg). Interventions: Gaseous NO was inhaled in increasing concentrations (1, 4 and 8 parts per million, each for 15 min) via a Siemens Servo 300 ventilator. Measurements and results: Cardiorespiratory parameters were assessed at baseline, after each concentration of NO, and 15 min after withdrawal of the agent [statistics: median (25th/75th percentiles: Q1/Q3), rANOVA, Dunnett's test, p < 0.05]. Inhaled NO resulted in a significant, reversible, dose-dependent, selective reduction in PAP from 5.5 (5.2/6.0) kPa at control to 5.1 (4.7/5.6) kPa at 1 ppm, 4.9 (4.3/5.3) kPa at 4 ppm, and to 4.7 (4.1/5.1) kPa at 8 ppm. PaO2 increased from 12.7 (10.4/17.1) to 19.2 (12.4/26.0) kPa at 1 ppm NO, to 23.9 (4.67/26.7) kPa at 4 ppm NO and to 24.5 (11.9/28.7) kPa at 8 ppm NO. All patients responded to NO inhalation (either with PAP or PaO2), all were subject to long-term inhalation (1-19 days). All were successfully weaned from NO and were discharged from the intensive care unit. Conclusion: The present study demonstrates that low-dose inhaled NO may be an effective drug for symptomatic treatment of hypoxemia and/or pulmonary hypertension due to allograft dysfunction subsequent to lung transplantation.