Table 1.

Priorities for Fluid Management Research in ARDS.

Important Ongoing Trials	Phase of ARDS
Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) trial  Multicenter trial (NCT03434028) comparing early vasopressors to a liberal fluid strategy in the first 24 hours after development of sepsis-induced hypotension. This trial may provide definitive evidence regarding the effect of early fluid management on the development of ARDS.	Development
High Priority Topics Needing Further Study
Timing of Initiation of Diuresis  The FACTT trial began fluid restriction and diuresis 12 hours after the resolution of shock. Future trials should evaluate the impact of conservative fluid management beginning early after ARDS diagnosis, even among patients who remain in shock. CLASSIC2 (NCT NCT03668236) will investigate use of conservative fluid management during shock, but not specifically for patients with ARDS.	Acute Illness
Extravascular Lung Water (EVLW)  Numerous small trials have demonstrated that measurement of EVLW may predict outcomes of patients with ARDS. Future trials should evaluate the use of EVLW as a bedside measurement to guide volume management (resuscitation and diuresis).	Development and Acute Illness
Albumin  Several small trials have suggested that albumin may improve outcomes in ARDS, particularly when paired with diuretics. Future large trials are needed to evaluate the impact of albumin administration in patients with ARDS. This question could be factorialized with a trial examining timing of diuresis.	Acute Illness
Subphenotyping  Several methods have shown potential in differentiating patients likely to benefit from conservative or liberal fluid management. Prospective trials are needed to validate the use of these markers in guiding fluid management strategy.	Acute Illness
Long-term Outcomes  Recent secondary analyses of the FACTT trial have raised concerns about the long-term impact on cognitive and renal outcomes of conservative fluid management. Future trials of fluid management in ARDS should plan to rigorously and systematically collect these outcomes using valid long-term outcome measures.	Recovery