Trial of Therapeutic Hypothermia in Patients With ARDS

Eligibility Criteria

• 1. endotracheal tube or tracheostomy in place and mechanically ventilated for ≤7 days;
• 2. admitted to a participating ICU
• 3. radiologic evidence of bilateral pulmonary infiltrates not fully explained by pleural effusions, atelectasis, or hydrostatic pulmonary edema
• 4. P/F ratio ≤200 with PEEP ≥8 cm H2O; If ABG values are not available, the P/F ratio may be inferred from SpO2 values based on Table 3 from Brown et al as long as following conditions are met:
• 1. SpO2 values are 80-96%
• 2. SpO2 is measured ≥10 min after any change in FIO2
• 3. PEEP is ≥ 8 cm H2O
• 4. the pulse oximeter waveform tracing is adequate
• 5. the qualifying inferred P/F ratio is confirmed 1-6h after initial determination.
• 5. access to an LAR to provide consent.
• 6. Criteria 3 AND 4 must be met within 72h of enrollment and randomization, not be fully explained by hydrostatic pulmonary edema, and must have occurred within 7 days of exposure to an ARDS-risk factor (including continuous exposure to persistent processes (e.g. sepsis, pneumonia, COVID-19).
• * Patients may be enrolled and decision about randomization delayed if all criteria other than P/F ratio ≤ 200 are met and then randomized if and when the P/F ratio ≤200 (as long as this occurs within 72h of randomization). Patients on high flow nasal oxygen or non-invasive pressure ventilation may be consented if they meet criteria for starting the 72h ARDS window but may not be enrolled and randomized until they are intubated.
• 1. Missed moderate-severe ARDS window (\>72hrs) - Window starts when patient is intubated with a qualifying P/F ratio of ≤ 200 with PEEP ≥ 8 cm H2O or on high flow nasal oxygen with well-fitting nasal cannula with flow ≥ 40 LPM and FiO2 ≥ 0.65 or on non-invasive pressure ventilation with PEEP ≥ 8 cm H2O and FiO2 ≥ 0.6.
• 2. Missed NMB window: (\>48 hrs)
• 3. Missed mechanical ventilation window (\>7 days)
• 4. Refractory hypotension (continuous infusion of \>0.3 mcg/kg/min of norepinephrine or equivalent dose of other vasopressors within 2 hours prior to randomization)
• 5. Core temperature \<35°C for ≥6 hours while not receiving CRRT on day of randomization
• 6. Significant, active bleeding (\>3u blood products and/or surgical/IR intervention) on day of randomization
• 7. Platelets \<10K/mm3 (uncorrected) on day of randomization
• 8. Active hematologic malignancy and not expected to survive 6 months
• 9. Skin process that precludes cooling device
• 10. Moribund, not likely to survive 72h
• 11. Pre-morbid condition makes it unlikely that patient will survive 28 days
• 12. Do Not Resuscitate status at time of randomization (excluding patients receiving full support EXCEPT CPR for cardiac arrest)
• 13. Not likely to remain intubated for ≥48h
• 14. Physician of record unwilling to participate
• 15. Severe underlying lung disease
• 1. Needs \> 2 LPM or \>28% continuous home O2 (adjusted for altitude)
• 2. On BIPAP (except for OSA)
• 3. Prior lung transplantation
• 16. Pregnant at time of randomization
• 17. BMI consistently \>50 kg/m2
• 18. Known NYHA class IV heart disease
• 19. Acute Coronary Syndrome (MI, unstable angina) within 30 days of randomization
• 20. Cardiac arrest within 30 days of randomization with sequelae likely to increase mortality and/or time to ventilator liberation.
• 21. Burns over \>20% of the body surface
• 22. Severe chronic liver disease (Child-Pugh score 12-15)
• 23. Previously randomized in CHILL study
• 24. Simultaneous enrollment in another inpatient interventional trial started during the current hospitalization.
• 25. On ECMO during the current hospitalization.