Table 2 Inclusion and exclusion criteria for START

Patients will be eligible for inclusion if they meet all of the below criteria. Criteria 1 to 3 must all be present within a 24-hour time period and at the time of enrollment:

1. Age younger than 18 years

1. A need for positive pressure ventilation by an endotracheal or tracheal tube with a PaO₂/FiO₂ ratio < 200 with at least 8 cmH₂O positive end-expiratory airway pressure (PEEP)

2. Greater than 96 hours since first meeting ARDS criteria per the Berlin definition [19]

2. Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph, and

3. Pregnant or breast-feeding

No clinical evidence of left atrial hypertension, or if measured, a Pulmonary Arterial Occlusion Pressure (PAOP) less than or equal to 18 mmHg

4. Prisoner

5. Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the last two years

6. Any other irreversible disease or condition for which six-month mortality is estimated to be greater than 50%

7. Moderate to severe liver failure (Childs-Pugh Score > 12)

8. Severe chronic respiratory disease with a PaCO₂ > 50 mmHg or the use of home oxygen

9. Patient, surrogate, or physician not committed to full support (exception: a patient will not be excluded if he/she would receive all supportive care except for attempts at resuscitation from cardiac arrest).

10. Major trauma in the prior five days

11. Lung transplant patient

12. No consent/inability to obtain consent

13. Moribund patient not expected to survive 24 hours

14. WHO Class III or IV pulmonary hypertension [27]

15. Documented deep venous thrombosis or pulmonary embolism within past three months

16. No arterial line/no intent to place an arterial line

17. No intent/unwillingness to follow lung protective ventilation strategy or fluid management protocol

18. Currently receiving extracorporeal life support or high-frequency oscillatory ventilation