Treatment principle: treat the patients to improve the symptoms and underlying diseases, actively prevent potential complications and secondary infection; provide timely measures to support organ function. Hypoxic respiratory failure and severe ARDS. Give oxygen therapy immediately to patients with ARDS, and closely monitor them for signs of clinical deterioration, such as rapidly progressive respiratory failure. Consider severe hypoxemic respiratory failure when standard oxygen therapy fails. When patients have increased frequency of breathing (> 30 times/min) and hypoxemia (SpO2 < 90% or PaO2 < 60 mmHg) even with oxygen delivered via a face mask and reservoir bag (gas flow of 10~15 L/min, FiO2 0.60–0.95), it may be considered as hypoxic respiratory failure.
ARDS is a status of severe acute hypoxic respiratory failure caused by increased pulmonary capillary permeability and alveolar epithelial cell damage. It can be divided into mild, moderate and severe conditions according to the Berlin definition [38] (Table 6).
Table 6 The Berlin definition for acute respiratory distress syndrome
Item Mild Moderate Severe
Onset time Respiratory symptoms developed/aggravated within 1 week after clinically known damage
Hypoxemia PaO2/FiO2 201–300 mmHg, PEEP or CPAP ≥5 cmH2O PaO2/FiO2 101–200 mmHg, PEEP≥5 cmH2O PaO2/FiO2 ≤ 100 mmHg, PEEP≥10 cmH2O
Causes of pulmonary edema Respiratory failure cannot be completely explained by heart failure or fluid overload. Objective assessment (such as echocardiography) is needed to eliminate the possibility of hydrostatic pulmonary edema if other risk factor is absent.
Abnormality in imaging Decreased transparence of two lungs cannot be completely explained by pleural effusion, atelectasis or nodules.
PEEP positive end-expiratory pressure, CPAP continuous positive airway pressure
HFNO. Under the support of standard oxygen therapy, to maintain SpO2 above 93% stills hard, and the breathing rate increases rapidly, then HFNO should be considered. HFNO can deliver 60 L/min of gas flow and FiO2 up to 1.0. Generally, gas flow is initially set as 30–40 L/min and oxygen concentration 50%–60%, which is well tolerated and coordinated. Then settings can be adjusted according to the oxygenation status of patients. Compared with standard oxygen therapy, HFNO is able to reduce the chance of tracheal intubation. Patients with hypercapnia (like exacerbation of obstructive lung disease, cardiogenic pulmonary edema), hemodynamic instability, multi-organ failure, or abnormal mental status should not be given HFNO. HFNO may be safe in patients with mild-moderate and non-worsening hypercapnia. However, if the respiratory distress still exists or even worsens dramatically under HFNO (FiO2 > 70%, gas flow > 50 L/min for 1 hour), the respiratory supporting strategy should be changed.
NIV. NIV provides a certain positive pressure ventilation effect through the positive pressure formed by the closed mask. HFNO combined with intermittent short-term NIV (1–2 h) support may be useful to reduce respiratory power consumption and improve oxygenation. But NIV guidelines recommend the use of respiratory support therapy in hypoxemic respiratory failure or pandemic viral illness. Limited data showed a high failure rate of NIV in MERS patients. Invasive mechanical ventilation should be considered in case the ARDS still exists and even acutely deteriorates in NIV process (about 1 h). Patients with hemodynamic instability, multiple organ failure, or abnormal mental status should not receive NIV.
Invasive mechanical ventilation. Under the support of HFNO (the demand for FiO2 > 70% and gas flow > 50 L/min) or NIV, ARDS still exists and even acutely deteriorates, invasive mechanical ventilation should be implemented as soon as possible.
Endotracheal intubation should be carried out by trained and experienced provider using airborne precautions, since endotracheal intubation is an operation that may produce a large number of contagious aerosols.
The strategy of protective lung ventilation should be implemented in invasive mechanical ventilation: lower tidal volume (4–6 ml/kg), lower plateau pressure (< 30 cmH2O), and appropriate PEEP. For patients with moderate-severe ARDS (PaO2/FiO2 < 150), it is recommended to use higher PEEP, apply prone ventilation for more than 12 h per day and adopt deep sedation and analgesia muscle relaxation strategy within the first 48 h of mechanical ventilation. For patients with severe acute hypoxic respiratory failure, we should pay attention to and prevent ventilator-associated lung injury after mechanical ventilation.
Extracorporeal Life Support (ECLS). In the process of invasive mechanical ventilation when the patient is still in the state of hypoxia, combined with increased partial pressure of carbon dioxide (excluding ventilation dysfunction, PaCO2 > 60 mmHg), especially after muscle relaxation and prone ventilation, it is necessary to consider to implement ECLS. However, it is suggested that ECLS treatment should only be carried out under the condition that the professional center is with access to expertise. Currently the ECLS in ICU includes VV-ECMO (blood is pumped from femoral vein, and returns to right atrium through internal jugular vein after oxygenation through membrane oxygenator) and VA-ECMO (blood is pumped from femoral vein and directly enters aortic system through femoral artery after oxygenation through membrane oxygenator). For patients with severe refractory hypoxemia, neuromuscular blockade can improve oxygen supply, especially if there is still evidence of ventilator-patient dyssynchrony after the use of sedatives. However, neuromuscular blockade through continuous infusion should not be routinely used in patients with moderate-severe ARDS; Where available, ECMO in conjunction with low tidal-volume mechanical ventilation can be considered in the treatment of patients with severe refractory hypoxemia in whom standard therapy are failing; Routine use of high-frequency oscillatory ventilation (HFOV) in patients with moderate-severe ARDS is not beneficial, but may be harmful. However, HFOV may still be regarded as a rescue therapy for patients with severe ARDS and refractory hypoxemia. ECMO can be used in some severe ARDS patients (lung injury score > 3 or pH < 7.2 due to uncompensated hypercapnia), but it is not recommended for all ARDS patients. It can be considered to use extracorporeal carbon dioxide removal for ARDS patients, if there is more supportive research evidence in the future.