Synchronized delivery of inspired nitric oxide : Effects on oxygenation and pulmonary tension during artificial ventilation

Abstract: Nitric oxide (NO) is a mediator of vascular smooth muscle tension that metabolises rapidly in blood. NO delivered by inhalation can therefore be used as a selective pulmonary vasodilator to relieve pulmonary hypertension or to improve oxygenation with no systemic effects. In artificial ventilation nitric oxide has been administered in inspiration gas as a continuous gas flow or to form constant inspired concentration. Homogeneous inspired gas mixture has been regarded essential for successful therapy and the therapy has been characterized by the mixture NO concentration. The response in oxygenation on NO therapy has, however, been variable. Administration of NO as a short pulse synchronously with inspiration has been suggested to improve the response. In this study the NO administration was examined theoretically and experimentally with the aim to relieve pulmonary hypertension and improve oxygenation during artificial ventilation. For the experimental study a system for the synchronized administration was developed.The effect on oxygenation was studied during equine anaesthesia where hypoxemia develops regularly secondary to left-to-right shunt caused by atelectasis. By administering the NO as a short pulse in early inspiration to well ventilated lung areas the oxygenation could be effectively improved. Delayed administration to low ventilated lung areas was found possible for a negative contribution on oxygenation, which reduces the improvement gained in the well-ventilated lung areas. When NO is delivered into the whole inspiration, the net effect on oxygenation is the sum of these negative and positive contributions, whereas with pulsed delivery to the early inspiration the negative contribution can be avoided. This finding may be the main explanation for the varying response in oxygenation detected in patients as a response to NO inhalation.When the NO therapy aimed for the relief of induced pulmonary hypertension in pigs, no difference was observed between NO delivery as a short pulse or given to the whole inspiration. Maximum vasodilatation was observed with 105 nmol/min delivery rate. A larger delivery rate only contributed to an abrupt increase in pulmonary pressure at cessation of the delivery.The NO uptake from alveoli to tissue depends on the alveolar NO partial pressure. In a simulation this partial pressure was shown to be independent of the administration mode. Also the relationship between the NO uptake and delivery setting was not explicit. With pulsed delivery, expired NO can be reduced which was confirmed by the experimental results. This is important when the NO therapy is given in rebreathing circuit.