If it proves impossible to adequately oxygenate a patient with a high concentration of oxygen delivered at high flow and the underlying disease is likely to be responsive to positive airway pressure (usually diseases with diffuse infiltrates), hypoxaemia on its own may be an indication for ventilation.
If the underlying disease is unilateral (e.g. lobar pneumonia), and especially if shunt is the major component of the pathophysiology, proceed with caution. The situation may not improve, and may worsen, with mechanical ventilation.
If the underlying disease is unlikely to respond to either ventilation or treatment for the underlying condition (e.g. pulmonary fibrosis), ventilation should normally be avoided altogether.
Exhaustion and hypoxaemia can lead to agitation. This can put the patient and staff at risk. In this case (if it is appropriate to invasively ventilate the patient) intubation and ventilation should be offered sooner rather than later. Be aware that this can be a difficult situation to handle and senior help should be sought as soon as possible.