FRC in acute lung injury. Experimental and clinical studies

Sammanfattning: Respiratory failure due to acute lung injury (ALI) of diffuse inflammatory origin is a major cause of respiratory failure treated in intensive care units. In ALI, FRC is reduced by various mechanisms associated with hypoxemia and consolidation of the lung. Increasing FRC by use of positive-pressure ventilation without causing side effects from raised pressure and volume in the lungs is critical when managing patients with ALI. The overall aim of this thesis was to elucidate the pathophysiology of acute lung injury using inert gas methods and CT analysis to assess lung volumes. Three experimental studies involving 32 anaesthetised pigs and one clinical study involving 20 healthy subjects and 25 mechanically ventilated patients with ALI were undertaken. Gas volume, tissue volume and the mechanical properties of the lung were measured using computed tomography (CT), inert gas dilution techniques and the inspiratory occlusion technique, respectively. CT analysis was used as a reference method for quantifying lung perturbations and as a tool to detect regional conditions within the lung. In summary, the early phase of experimental ALI was characterised by rapidly appearing consolidation and loss of aeration that were established within one hour, and the degree of consolidation was reflected in reduced arterial oxygenation. Despite significant loss of aeration, the dimensions of the injured lung were preserved or even slightly increased. The tidal volume was redistributed from basal dependent to apical lung regions but neither overall nor regional gas trapping could be demonstrated. The evolution of lung injury was accompanied by reduced FRC as well as increased resistance and reduced compliance of the respiratory system. FRC appeared to be the more sensitive indicator of the effects of changed PEEP. Further evolution of the lung injury after one hour was not affected by changes in PEEP of limited duration. The expiratory time constant was shortened in injured dependent lung regions and limiting the expiratory time did not provoke gas trapping. In contrast to the findings in early experimental ALI, sedated patients with established ARDS showed evidence of considerable gas trapping while mechanically ventilated. The study findings imply that alveolar flooding is a more important contributor than alveolar collapse to loss of aeration and lung consolidation in early experimental ALI. FRC monitoring as an adjunct to monitoring of arterial oxygenation may be of clinical value when judging the progress of ALI and the effects of changed PEEP. Furthermore, airflow obstruction and gas trapping are not prominent features of injury to dependent lung regions in early ALI. In the patients, however, mechanical heterogeneity of the injured lung with maldistribution of ventilation and gas trapping, possibly due to airway closure and/or obstruction, mandates for further confirmative studies. Future development of CT systems with increased resolution will be of value when investigating regional properties of the lung and structural correlates to the loss of aeration and consolidation seen in ALI.