The Science Journal of the American Association for Respiratory Care
Introduction: A positive response to inhaled nitric oxide (NO) is a predictive screening tool for long-term treatment of primary pulmonary hypertension (PPH). This treatment consists of calcium channel blockers or prostacyclin. Both of these pharmaceuticals are not without side effects and limitations. Chronic administration of inhaled nitric oxide (NO) may be a beneficial alternative in treating PPH due to its vasodilator action, improvement of right ventricular performance and its antiproliferative effect on the pulmonary vascular smooth muscle. Evaluation of the safety and efficacy for long-term use of NO in treating patients with PPH has been hindered by the lack of information about NO delivery methods to spontaneously breathing humans. Objectives: The purpose of this study was to analyze the NO concentration profile in the human lung during both continuous and intermittent nasal cannula delivery during spontaneous breathing.
Methods: Seven healthy volunteers (Ages 19 - 74, 5 males and 2 females) underwent bronchoscopy in order to sample baseline endogenous NO levels in the right middle lobe (RML), right upper lobe (RUL) and carina of the right lung with a rapid response chemiluminescence analyzer (280NOA, Sievers, Colorado, USA). The bronchoscope was in place in the right middle lobe during exogenous NO administration. NO was then delivered with a prototype delivery device (Pulmonox, Alberta, Canada) designed for the study. A source NO cylinder of 80 parts per million (Matheson, Alberta, Canada) was used in conjunction with the device to deliver NO via nasal cannula (Softech Bi-Flo cannula, Hudson RCI, California, USA) continuously (1.5 Lpm) or intermittently (0.8 s @ 5 Lpm) during normal tidal breathing. Additional data was collected to evaluate baseline lower airway NO utilizing the restrictive exhaled breath (REB) technique as described elsewhere in the literature.
Results: An initial inspiratory NO peak was found in all breathing cycles during continuous and intermittent NO administration. The peak during continuous NO delivery was not significantly different (46.1; SD=21.8 parts per million) than during intermittent NO delivery (55.8; SD=24.8 parts per million). After the initial inspiratory peak during continuous NO delivery, a relatively stable plateau was observed in late stage expiration. This plateau was significantly lower with intermittent (0.7; SD=0.4 parts per million) as opposed to continuous (8.2; SD=3.2 parts per million) NO administration. Endogenous NO REB was significantly lower (16.4; SD=4.5 parts per billion) than endogenous NO at the RML (56.5; SD=20.1 parts per billion), RUL (71.4; SD=22.4 parts per billion) and carinal level (65.5; SD=24.3 parts per billion) of the lung. There was no significant difference between endogenous NO levels at the RML, RUL and carina (p>0.05). Conclusion: These results suggest that NO delivered during intermittent NO delivery effectively delivers a dosage beyond the RML similar to continuous NO delivery. This technique would reduce NO consumption and lower the overall exposure of the lung to NO during long-term NO administration to PPH patients.