Mechanical ventilation is a major component of the treatment of ARDS as it keeps the patient alive and ensures gas exchange despite compromised and injured lungs. Historically, the therapeutic goal was to achieve almost normal blood gas levels, even if this meant using very high tidal volumes during mechanical ventilation. However, mechanical ventilation itself also has the potential to injure the lungs, as implied by the term ‘ventilator-induced lung injury’. The optimal strategy of ventilation is therefore under constant review. In a landmark study by ARDSnet, a strategy of ‘protective ventilation’ using a low tidal volume (6 mL per kg predicted bodyweight) compared with a traditional high tidal volume (12 mL per kg predicted bodyweight) was successful in significantly reducing mortality from 39.8% to 31%. However, since this trial was reported more than 10 years ago, no further change in ventilation strategy has been shown in a multicentre trial to result in lower mortality. Different strategies in the amount of PEEP applied have shown no clear-cut effects on survival. It remains to be determined whether strategies of ultra-protective ventilation (tidal volumes less than 6 mL per kg predicted bodyweight) or high-frequency oscillation ventilation (HFOV) may prove advantageous. This is important, as overdistension of the lung by excessive tidal volumes may be responsible for both inducing and perpetuating lung injury.
The optimal strategy for supplying fluids to the patient with ARDS remains a controversial management issue. Fluid restriction may benefit gas exchange by reducing alveolar oedema, but this must be weighed against the concept that more liberal fluid management improves cardiac output, protects renal function and increases the delivery of oxygen to vital organs. The ARDSnet studies reported a shorter period of ventilation and better oxygenation, but no increase in survival, using a complex algorithm that aimed simultaneously to protect renal function and to secure circulatory function, while employing a policy of restrictive fluid management.
These goals may remain difficult to achieve, since, for example, in the early phase of the sepsis syndrome (which may lead to ARDS) a more liberal fluid strategy has proved successful in reducing mortality.
So far, no pharmacological therapy has been successful in improving the survival of patients with ARDS. Despite numerous strategies appearing to be successful in experimental studies and smaller trials, none has been shown to be successful in multicentre trials. Given the unacceptably high mortality and prevalence of ARDS among critically ill patients, there is an urgent need for a successful pharmacological treatment strategy.
The lung offers the unique possibility of treatment via both the vascular bed (intravascular injection) and via the airways (inhalational approach). Again, several apparently highly successful strategies in experimental studies and smaller clinical trials have not resulted in improved survival of real-world treated patients. Inhalation of gaseous nitric oxide, which was predicted to redirect the blood flow from injured to better ventilated areas of the lung, has been unsuccessful in general ARDS patients and remains only a last-resort option. Supplying surfactant, which, in healthy lungs, maintains the patency of the alveoli and which is destroyed by lung injury, is successful in IRDS but has not improved survival in adults. Despite these frustrating results, treatment of injured lungs via the airways remains a valuable potential approach in further research efforts.
Extracorporeal lung support strategies
The technique of extracorporeal membrane oxygenation (ECMO) allows complete artificial oxygenation of, and removal of carbon dioxide from, the blood by use of a membrane-oxygenator, a pump and two large-bore cannulae. The techniques have been refined in recent years and three different approaches now allow: 1) carbon dioxide removal driven by blood pressure without a pump (extracorporeal lung assist); 2) a step-up solution using the same technique with a pump; and 3) full ECMO. Experience from the most recent influenza epidemic demonstrated successful ECMO treatment of younger patients in specialised centres. The large CESAR (Conventional Ventilation or ECMO for Severe Adult Respiratory failure) trial for the first time showed a survival benefit when treating patients with severe ARDS in a specialised centre using ECMO compared with standard treatment. Due to inherent design limitations, however, the results of this trial have not been accepted unequivocally, but, at least in experienced centres, ECMO therapy may be considered as a valuable treatment option in severe cases. As to the other two above options for extracorporeal lung support, data showing their effectiveness are available but results from larger trials concerning survival, for example, are lacking.
Other supportive measures
Further supportive measures have been evaluated for the treatment of ARDS patients. One option is turning the patient on his stomach while he is being ventilated (prone position). This has attracted considerable interest but has not produced unequivocal results in large trials. It seems to be an option for severely ill patients when they are treated for prolonged periods. In experienced centres, it is a valuable option for maintaining oxygenation. Nutritional approaches have shown promising results in several studies but recent trials have not reproduced the favourable results.