Re-evaluating high-frequency oscillation for ARDS: Would a targeted approach be successful?

High-frequency oscillatory ventilation (HFOV) seems ideal for lung protection in acute respiratory distress syndrome, but randomized trials have not shown a mortality reduction. The initial oxygenation response to HFOV appears to be associated with survival. Here, we discuss the mechanisms of oxygenation response to increases in airway pressure and the interpretation of the oxygenation response observed in the present study.

In this issue of Critical Care, Camporota and colleagues [1] report interesting observations on the relationship between the initial gas exchange response to highfrequency oscillatory ventilation (HFOV) and clinical outcomes. HFOV seems ideally suited to protecting the lung during mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). By delivering very small tidal volumes and allowing higher mean airway pressures, HFOV can potentially minimize both volutrauma and atelectrauma [2]. However, the recently published OSCILLATE (OSCillation in ARDS Treated Early) [3] and OSCAR (High-Frequency OSCillation in ARDS) [4] trials -both of which postdate the article by Camporota and colleagues -found that HFOV failed to reduce mortality. In particular, OSCILLATE raised questions of potential harm from HFOV. In the face of these disappointing results, trialists and clinicians alike are left wondering how to reconcile theory to practice. A number of potential mechanisms for harm have been postulated, including (a) the deleterious eff ects of increased sedation, (b) hemodynamic embarrassment due to reduced right ventricular preload or increased right ventricular afterload, or (c) an increase in mechanical alveolar stress and strain within the baby lung [5]. Some combination of these mechanisms is likely to contribute to patient outcome during HFOV.
A critical factor infl uencing the importance of these various mechanisms may be the response of the individual patient to the application of high mean airway pressures. Imaging studies have demonstrated profound heterogeneity in the extent of alveolar recruitment in response to increases in airway pressure [6,7]. In patients with 'recruitable lung' , higher airway pressures increase the size of the functional 'baby lung' , reduce alveolar stress and strain, and may even reduce right ventricular afterload without signifi cantly compromising right ventri cular fi lling [8]. In patients lacking 'recruitable lung' , higher mean airway pressures achieve the opposite: worsened alveolar stress and strain and increased right ventricular afterload. Consequently, the potential for benefi t or harm may depend critically on the degree of lung recruitment in response to increasing mean airway pressure.
Enter the interesting observations of Camporota and colleagues [1], who found that in patients with moderate or severe ARDS who were placed on HFOV by their attending physicians, the change in arterial partial pressure of oxygen/fraction of inspired oxygen (P a O 2 / F i O 2 ) ratio 6 hours after HFOV initiation was associated with 30-day survival. Improvements in oxygenation were also associated with reductions in arterial partial pressure of carbon dioxide (P a CO 2 ), particularly in patients with more severe respiratory failure, contradicting the widely held belief that HFOV inevitably worsens respiratory acidosis.
Th e oxygenation response to increased positive endexpiratory pressure (PEEP) is the product of a complex interplay between alveolar recruitment and cardiac output. Classic physiological studies by Dantzker and colleagues [9] and Lynch and colleagues [10] demonstrated that increased PEEP reduces intrapulmonary shunt both by re-opening collapsed lung units and by reducing cardiac output. In the latter case, non-ventilated lung units are preferentially aff ected by reduced blood

Abstract
High-frequency oscillatory ventilation (HFOV) seems ideal for lung protection in acute respiratory distress syndrome, but randomized trials have not shown a mortality reduction. The initial oxygenation response to HFOV appears to be associated with survival. Here, we discuss the mechanisms of oxygenation response to increases in airway pressure and the interpretation of the oxygenation response observed in the present study.

© 2010 BioMed Central Ltd
Re-evaluating high-frequency oscillation for ARDS: Would a targeted approach be successful? fl ow, possibly because of the eff ects of hypoxic pulmonary vasoconstriction [11]. In the present study, Camporoto and colleagues reported that cardiac output was unchanged; thus, the short-term oxygenation response likely signifi es lung recruitment.
Th e authors speculate that the gas exchange response may be a useful predictor of the utility of HFOV in the diffi cult-to-oxygenate patient and further propose that failure to demonstrate improved oxygenation after a 6-hour trial of HFOV should prompt a consideration of alternative rescue modalities such as extracorporeal life support. It is diffi cult, however, to do anything more than speculate on the basis of these data. First, it is diffi cult to be certain whether the association between early improve ments in oxygenation and reduced mortality arises from the eff ects of HFOV-induced lung recruitment or simply represents the natural history of survivors (whose oxygenation will tend to improve with time) in contrast to non-survivors (whose oxygenation will tend to worsen with time). Second, even if the improvements in oxygenation were directly related to lung recruitment, it is impossible to discern whether oxygenation 'responders' have lower mortality than 'non-responders' because 'responders' have a less fatal form of ARDS or because they accrue greater benefi t from HFOV. Finally, from these data in which all patients received HFOV, it is impossible to know whether increases in mean airway pressure on conventional ventilation would have been equally eff ective.
Such issues can be resolved only by a carefully designed randomized trial of an open-lung ventilation strategy that stratifi es patients by oxygenation response prior to random assignment. In the meantime, in light of the available evidence, HFOV should usually be reserved for patients with refractory hypoxemia. When applying HFOV, clinicians should consider monitoring lung recruitment (by oxygenation response or other means available) and right ventricular function (by echocardiography or other hemodynamic monitoring) to ensure that this unique mode of ventilation is achieving appropriate physiological goals in the individual patient.