Present treatment of acute respiratory distress syndrome (ARDS) is largely supportive in nature, and unacceptable levels of morbidity and mortality persist [¹]. Traditionally, the definition of ARDS includes bilateral infiltrates on simple chest radiographs [²], but computed tomography scanning has highlighted the patchy, heterogeneous nature of the disease. In particular, the dependent lung regions are often severely affected by alveolar flooding, increased surface tension, and collapse [³]. Gravitational effects directing pulmonary blood flow augment perfusion to these regions, thereby worsening shunt fraction [⁴].

The prone position was reported as early as the mid-1970s to improve oxygenation in patients with hypoxic respiratory failure [⁵], and many investigators have reported that ventilation of ARDS patients in the prone position improves arterial oxygenation [^6-13]. Recently, several studies have suggested that prone positioning, when initiated early and applied for most of the day, may reduce mortality in patients with severe ARDS [¹⁴,¹⁵]. However, prolonged prone positioning frequently requires continuous sedation of the patient, which has been reported to adversely affect critically ill patients [¹⁶,¹⁷]. Thus, if we could predict the effect of prolonged prone positioning in the early stages of the prone position, it may obviate the unnecessarily heavy sedation associated with prone positioning.

There are debatable reports as to whether improvements in gas exchange in response to the prone position are actually associated with an enhanced outcome; however, these studies had methodological differences and patients were positioned for only a few hours each day [¹⁸,¹⁹]. We thus hypothesized that an early gas exchange response to first placement in the prone position might be associated with survival in ARDS patients, as reported previously [¹⁸], especially when the time spent prone is prolonged. Moreover, few studies have evaluated patients with severe ARDS who underwent prolonged prone positioning.

Our aim was to evaluate clinical characteristics, gas exchange responses after first placement in the prone position, outcomes, and the clinical meaning of early gas exchange in patients with severe ARDS under conditions of prolonged prone positioning (≥ 12 hours, whether clinical status improved or not) in a university-affiliated tertiary care hospital.

To our knowledge, this is the first study to investigate clinical characteristics and outcomes in severe ARDS patients under conditions of prolonged prone positioning in Korea. We found that all PaO₂ responders showed oxygenation improvement soon after prone positioning, and those patients who maintained the oxygenation improvement at 8 to 12 hours after first prone positioning seemed to have better outcomes. Some of our study subjects underwent various adjuvant therapies for improved oxygenation, but no significant difference in the number of patients treated with adjuvant therapies or the duration of therapies was found between PaO₂ responders and non-responders. Thus, our findings indicate that the oxygenation improvement was likely primarily due to prone positioning, not to the adjuvant therapies. We also observed a low rate of complications related to prolonged prone positioning, consistent with previously reported clinical trials [¹⁴,¹⁵,²⁴]. Our data suggest that using the prone position for prolonged periods of time is both feasible and safe, and this reinforces the idea that a beneficial effect may be expected if prone oxygenation is applied early and continuously, as has been reported in some clinical studies [¹⁴,¹⁵].

However, these patients with prolonged prone positioning usually require continuous deep sedation using analgesics, sedative agents, and neuromuscular blocking agents, as seen in our study. This continuous deep sedation may be harmful to patients and may be associated with a prolongation of mechanical ventilation, which can increase a patient's likelihood of developing specific complications, including ventilator-associated pneumonia, barotraumas, airway complications (e.g., tracheal stenosis and ulceration), and unanticipated extubation, with resultant arterial oxygenation. It may also be risky because early recognition of brain injury through communication and neurologic examination often is severely limited [¹⁶,¹⁷,²⁵]. Thus, our results may provide tips to physicians for predicting clinical parameter(s) associated with better outcomes in patients with prolonged prone ventilation.

Our data differ in some aspects from those in a previous report; Gattinoni et al. [¹⁸] reported that improved survival at 28 days was significantly associated with decreases in PaCO₂, but not with PaO₂ increases, during first session placement in the prone position. In our study, the PaCO₂ response to the first prone positioning in ARDS patients with prolonged prone positioning was not associated with survival. Unlike the cases studied by Gattinoni et al. [¹⁸], all of our patients had severe ARDS, with much decreased alveolar ventilation and CO₂ elimination. Accordingly, it is possible that our patients had a higher total minute ventilation/PaCO₂ ratio (an approximate surrogate for the dead space tidal volume ratio) before prone positioning than did the patients in the study by Gattinoni et al. [¹⁸]. Also, many of our patients had pulmonary ARDS with increased stiffness of the thorax and insufficient alveolar ventilation.

Our study has several limitations. First, the study was retrospective in design, and we could not strictly control the various factor that affect the gas exchange response during prone ventilation (especially ventilator parameters). Second, we expected that specific subgroups formed by combining PaO₂ and PaCO₂ responders/non-responders to define four subgroups would have differed in outcome, and that those patients who had the most severe form of ARDS (SAPS II score > 49) would benefit from prone positioning; however, we were unable to draw such conclusions, possibly due to the small numbers of enrolled patients. Third, this study was carried out in only one hospital, and it may not represent the general situation.

In summary, we found that improved oxygenation at 8 to 12 hours (PaO₂ response) in patients positioned prone for a long period (≥ 12 hours) was associated with an improved 28-day outcome. Thus, patients with severe ARDS who show initial PaO₂ improvement (more than ≥ 20 mmHg) after prone ventilation seem to be appropriate candidates for prolonged prone ventilation.

No potential conflict of interest relevant to this article was reported.