Interventions for patients with Adult Respiratory Distress Syndrome (ARDS) are mainly dictated by the severity of ARDS defined as mild (PaO2/FiO2 200-300), moderate (PaO2/FiO2 100-200), and severe (PaO2/FiO2 <100). The above infographic illustrates these various interventions visually and the following text explains the evidence supporting these interventions. Of note, text in orange indicates lack of concrete evidence of benefit.
PaO2/FiO2 <300
Many patients with ARDS may be adequately supported by Noninvasive ventilation (HFNC/CPAP/BiPAP). A combination of these modalities may help in lung recruitment (CPAP/BiPAP) alternating with airway clearance (HFNC). The FLORALI trial (25981908) showed that HFNC may reduce mortality among patients with ARDS especially in patients with bacterial pneumonia. The RECOVERY-RS trial found that CPAP compared to HFNC reduced the requirement for intubation among patients with COVID-19. (pre-print)
Protective lung strategy remains the mainstay treatment of all patients with ARDS as it is associated with mortality benefit demonstrated in the original ARDSNet trial and reproduced in multiple other studies. (10793162)
VT 4-6 mL/Kg of ideal body weight (IBW). Start with 6 ml/kg and go gradually down to 4 mL/kg if plateau pressure is not below 30 cm H₂O.
Pplateau <30 cm H₂O, preferably below 28 cm H₂O.
Driving pressure <15 cm H₂O. This is based on retrospective analysis of several ARDS studies showing a strong correlation between lower driving pressure and lower mortality.(25693014) (34090669, 33526308, 32735841)
PEEP as per the Low PEEP/FiO₂ table.
| Standard PEEP | Higher PEEP |
30% | 5 | 5-14 |
40% | 5-8 | 14-16 |
50% | 8-10 | 16-20 |
60% | 10 | 20 |
70% | 10-14 | 20 |
80% | 14 | 20-22 |
90% | 14-18 | 22 |
100% | 18-24 | 22-24 |
PaO2/FiO2 <200
Steroid use in ARDS remains controversial. It is probably of benefit early in the disease process in patients with moderate to severe ARDS ( PaO2/FiO2 <200 mm), who have a steroid-responsive disease process. It is contra-indicated if there is a concern active fungal or mycobacterial infection. We prefer the regimen used in the DEXA-ARDS trial of 20 mg dexamethasone for 5 days, followed by 10 mg dexamethasone for 5 days (stop earlier if extubated).(32043986) Of note, SCCM/ESICM guidelines recommend methylprednisolone 1 mg/kg/day, with a gradual taper over 14 days.(28938253)
The FACTT trial demonstrated an improved lung function and shortened the duration of mechanical ventilation and intensive care without increasing nonpulmonary-organ failures in conservative fluid strategy. However, there was no significant difference in the primary outcome of 60-day mortality. (16714767) We prefer to maintain a euvolemia with a net even fluid balance (or slightly negative fluid balance) by using diuresis as needed once the patient is hemodynamically stable.
Recruitment maneuvers have been traditionally done using 40 cm of pressure for 40 seconds in efforts to recruit the lungs. This has been demonstrated to be either ineffective or harmful in several trials.(14605529, 31356105, 28973363) The high pressure pose a risk for hemodynamic compromise or pneumothorax. In addition, the short period of high pressure does not achieve extensive alveolar recruitment. A safer approach to recruitment is higher mean airway pressure using APRV with gradual recruitment over several hours. (30850004)
Evidence supporting pulmonary vasodilators (i.e., epoprostenol) in ARDS is not robust. These agents can improve the ventilation/perfusion matching and improve oxygen saturation in severe hypoxemia. In addition, they can improve right ventricular function and cardiac output in those patients with right ventricular failure secondary to pulmonary hypertension as the result of hypoxemia and high airway pressures.
PaO2/FiO2 <150
Two large trials examined the benefit of paralysis in moderate to severe ARDS. The ACURASYS trial evaluated early paralysis with cisatracurium for 48 hours among patients and showed a mortality benefit that was only statistically significant within an adjusted analysis.(20843245)
A larger trial (ROSE trial) revealed no benefit of cisatracurium paralysis compared with as-needed paralysis.(31112383)
Paralysis may have a benefit in patients with severe and refractory hypoxemia and in patients with dyssynchrony on the ventilator eliminating large transpulmonary pressures that maybe injurious to the lung.
The PROSEVA trial is the main study that demonstrated a mortality benefit in patients with moderate to severe ARDS when they were proned for 16 hours per day after 12-24 hours of optimization on the ventilator).(23688302)
Certain patients may not be candidates for proning such as severe refractory shock, unstable rhythm that may require cardioversion, unstable spine, femur, or pelvic fracture, massive hemoptysis, open abdomen, increased intracranial pressure, abdominal compartment syndrome, pregnancy, tracheal surgery, sternotomy, facial surgery or trauma within the past two weeks, and restricted mobility of the C-spine or shoulders (may increase risk of pressure ulcerations).
PaO2/FiO2 <80
In cases of severe ARDS that did not respond to the above interventions including neuromuscular blockade and pronging position, Extracorporeal Life Support (ECMO or EcCO2R) maybe indicated (no exclusion criteria is met) if one of the following is fulfilled:
PaO2/FiO2 <50 for more than 3 hours
PaO2/FiO2 <80 for more than 6 hours
pH <7.25 and PaCO2 >60 mm Hg with RR >35 more more than 6 hours.
In a meta-analysis that included patients from the two largest RCTs (CESAR and EOLIA), the 90-day mortality was significantly lowered by ECMO compared with conventional management. (PMC7537368)
De-escalation Considerations:
Proning is the first intervention in de-escalation and may be stopped if the patient is able to maintain a PaO2/FiO2 ratio >150 mm (20 kPa) with an FiO2 ≤0.6, at least four hours after supination.(34090669)
PEEP should be decreased to an acceptable level (<16 cm H2o) before paralysis is weaned off or likely just stopped.
Pulmonary vasodilators (if used) should be weaned gradually for the concern of reactive vasoconstriction and worsening of ventilation/perfusion ratio.
PEEP can be decreased at 2 cm H2O every 12-24 hours as tolerated
Conservative fluid strategy can be continued throughout the de-escalation process.
Dexamethasone (if used) can be decreased after 5 days to 10 mg for 5 additional days or can be stopped if the patient was extubated earlier.
Tidal volume can be liberated to 7-8 mL/kg of IBW only if PaO2/FiO2 >300 and plateau pressure is maintained below 28 cm H2O.
Spontaneous breathing trial can be started once FiO₂ is ≤40% and PEEP ≤8 cm H₂O.
*Infographic idea belongs to Dr. Bahaa Alabid.
Nice review, If APRV is safe and effective at rescuing when the lungs are pretty bad, it would make sense to use early to prevent progression of ARDS (or even use it initially for all intubated patients to reduce incidence of ARDS).
Extremely informative, fluent and organized approach.
Many thanks Dr Mazen