Acute lung injury and inhaled NO

Few bioactive molecules have attracted more attention these last years than nitric oxide (NO) after being identified (1) as the elusive endothelium-derived relaxing factor (EDRE) first described by Furchgott & Zadawski 1980 (2). One of many aspects of NO in medicine is the capacity for vasodilatation through an increase of cyclic guanosine monophosphate (cGMP) concentration in smooth muscle (3). This and other areas of activity were recently well reviewed (4). Since 1991 intensive care physicians and anaesthesiologists have been aware that minute amounts of NO gas mixed into inspired gases act as a selective pulmonary vasodilator (5, 6). In 1993 Rossaint et al. in addition, described how inhaled NO in acute lung injury (ALI) might act as a microselective pulmonary vasodilator (7) , reducing intrapulmonary shunting by redistribution of blood flow from poorlyto well-ventilated lung regions. The reduction of shunting in ALI has since been confirmed by several groups (8-1 1). In this issue of Acta Anaesthesiologica Scandinavica, Benzing & Geiger add important and new data on inhaled NO in ALI, which support the rationale for using inhaled NO in this condition. They have studied the influence of NO inhalation on longitudinal distribution of pulmonary vascular resistance (PVR) in 18 patients with ALI. PVR was divided up into arterial (PVRa) and venous (PVRv) components by measuring pulmonary capillary pressure (PCP) with visual analysis of the decay profile following pulmonary artery balloon inflation. Their data demonstrate that inhaled NO in ALI reduces both PVRa and, more importantly, the PVRv. If inhaled NO would dilate only PVRa, an increase of oedema formation in lung tissue could be feared in ALI. On the other hand, as rightly pointed out in the paper by Benzing & Geiger, already a small reduction of PVRv by a few mmHg may markedly increase the reabsorption rate of pulmonary oedema. That would be a clinically desirable effect as early acute lung injury is often associated with an increase of extravascular lung water (oedema). An increased reabsorption rate, if confirmed by further studies over lung fluid balance during NO inhalation, could enhance the clinical rationale for inhaled NO in ALI more than the already reported improvement of gas exchange. As an example, others have studied arterial and venous components of PVR during thromboxane analog infusions in animals, and observed elevations of both PVRa and PVRv (1 2). This is of clinical interest, as thromboxane release is implicated in several types of acute lung injury. The above mentioned paper by Rossaint et al. 1993 ( 7 ) has triggered widespread use of inhaled NO as an addition to therapy in ALI, especially in European countries. In addition, an increasing number of paediatric ICU's have started to treat infants with persistent hypertension of the newborn (PPHN) with inhaled NO, since reports by Kinsella et al. (13) and Roberts et al. (14) first demonstrated how this could make extracorporeal membrane oxygenation (ECMO) treatment unnecessary in some patients. Finally, a steady flow of small clinical reports and anecdotes (1 5) describe the beneficial effect of adding NO to therapy during various other clinical conditions. This current enthusiasm surrounding NO inhalation is in reality troublesome for several reasons. Firstly, NO gas is not registered as a drug anywhere in the world, which makes further clinical use of industrial gas questionable from a medico-legal point of view