Correct!
5. All of the above

Refractory hypoxemia occurs in patients who are on ventilator support, and alternative therapies can be tried when there is no clinical improvement with standard care (22).

One of the most popular modalities is extracorporeal membrane oxygenation (ECMO), which is commonly used in patients with severe hypoxemia with maximum mechanical ventilation. Oxygenation and carbon dioxide exchange occur in the extracorporeal circuit in ECMO and damaged lung can be protected with low tidal volumes and lower positive pressure minimizing atelectrauma and volutrauma (23). Two recent studies, one retrospective and the other a prospective randomized trial, demonstrated significant survival benefit in ECMO patients (24,25). Although these studies are limited by their incapability to differentiate the effect of ECMO from the one from higher level of care at tertiary centers, ECMO is a reasonable option in patients with refractory hypoxemia who do not respond to standard ventilator care.

Inhaled nitric oxide (INO) is known as a selective pulmonary vasodilator and shown to be effective in improving gas exchange. However, the PaO2 improvement is transient and the positive effect mostly disappears in 48~72 hours. Moreover, the benefit in oxygenation with INO failed to translate into benefit of survival in many trials (26,27). Currently, routine use of INO is not recommended, however short term improvement in oxygenation can be expected in patients with refractory hypoxemia.

Supine position increases the risk of atelectasis in dependent lung regions and it exacerbates intrapulmonary shunting. Prone positioning can obviate the effect of gravity minimizing compression of lung with other organs and preventing atelectasis. Many studies demonstrate the benefit of prone position in oxygenation (28, 29), and a recent meta-analysis showed a significant survival benefit in selected patients with severe hypoxemia (30).

High flow oscillatory ventilation (HFOV) is an alternative mode of mechanical ventilation. It delivers 300-900 breaths/min to maximize lung protection and alveolar recruitment with relatively less tidal volume compared to conventional ventilator (31). Previous studies have shown oxygenation improvement with HFOV (32), and a recent meta-analysis demonstrate a significant survival benefit in patients with refractory hypoxemia receiving HFOV (33).

Our patient’s family declined the use of ECMO, but INO and prone positioning were tried with PaO2 improvement. However, the patient developed multiple tension pneumothoraces and chest tubes were placed with no clinical improvement. Sadly, the family decided on comfort care and patient passed away the same day.

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