Acute lung injury. Proceedings of the third National Heart and Lung Institute Workshop. 5 May 1989, London

1990 Postgraduate medical journal  
The term adult respiratory distress syndrome (ARDS) defines a group of patients with refractory hypoxaemia, decreased lung compliance and radiological evidence of pulmonary oedema proven to be non-cardiogenic in origin. The term was first coined in 1967, when lung biopsies taken from such patients were shown to be histologically similar to those seen in the infantile distress syndrome.' ARDS is responsible for up to 50,000 deaths per annum in the USA alone and may be precipitated by a wide
more » ... ated by a wide variety of serious medical and surgical problems, most of which do not directly involve the lung. The associated mortality approaches 60% and may be as high as 80% in some circumstances, particularly those involving sepsis.2 Little progress has been made towards the development of therapies aimed at interrupting or reversing the pathophysiology underlying ARDS. However, recent advances in cell biology have increased our understanding of the aetiology of the increased pulmonary vascular permeability that characterizes the syndrome, suggesting that new interventions may not be far away. Furthermore, the growing recognition that ARDS is a complex disorder of peripheral oxygen utilization has lead to a number of developments in the field of ventilatory and circulatory support, making this an opportune time to reassess progress in management. Speculation regarding the aetiology of ARDS has focused increasingly on the role of the neutrophil and the mechanisms leading to its activation by cytokines such as tumour necrosis factor (TNF) and interleukin-1, which are released from macrophages and which can themselves damage vascular endothelial cells.3 Both substances can mimic the haemodynamic and metabolic consequences of septic shock when administered to experimental animals and therapies aimed at preventing cytokine-neutrophil interaction have produced promising preliminary results. Thus the advent of anti-TNF antibodies for clinical use may follow evidence that it can substantially reduce mortality from septic shock in experimental animals. The methylxanthine pentoxifylline has been shown to block cytokine-induced neutrophil adherence to endothelial cells in vitro and to attenuate the mortality associated with experimentally-induced haemorrhagic shock.4 Studies carried out in animal models of ARDS have been useful in defining the pathophysiology of the condition and have enabled the development of techniques for assessing the integrity of the alveolar-capillary membrane. These have varied from measuring the transfer of radiolabelled albumin from the vascular compartment to tracheal aspirate, to more sophisticated dual isotope techniques quantifying the leak of transferrin across the endothelial barrier.5 The increasing awareness that changes in pulmonary vascular permeability may represent the end-stage of a complex inflammatory cascade suggests that such tests may not be useful in the clinical management of patients with ARDS, but they have an important role in the evaluation ofnew and potentially potent interventions. It is in the field of respiratory and circulatory support that most advances have been made in the management of ARDS. The conventional approach has involved the application of continuous positive airways pressure (CPAP) to the spontaneously breathing patient and tidal volumepreset, controlled mandatory ventilation with
doi:10.1136/pgmj.66.773.246 fatcat:z6ydrzcerngn7nfnsjkbq2dz3u