5-HT3 Receptor Antagonist and Respiratory Drive in Patients With ARDS

Inclusion Criteria:

• Adult patient (18-75 years old)
• Berlin Criteria for Acute Respiratory Distress Syndrome (ARDS) (1):
• Hypoxemic respiratory failure with a patrial pressure of arterial oxygen tofraction of inspired oxygen ratio (PaO2:FiO2 ratio) < 300
• Bilateral opacities not fully explained by effusions, lung/lobar collapse, ornodules on chest imaging that appeared within 7 days of a known clinical insult
• Respiratory failure not fully explained by cardiac failure or fluid overload
• Has been mechanically ventilated > 48 hours
• Planned to remain mechanically ventilated for the next 24 hours
• Currently on Pressure Support Ventilation or planning to go on pressure supportventilation in the next 24 hours

Exclusion Criteria:

• Having received a 5-HT3 antagonist in the last 24 hours, or planning to use one in thenext 24 hours
• Recently treated for bleeding varices, stricture, hematemesis, esophageal trauma,recent esophageal surgery or other contraindication for nasogastric tube placement
• Severe coagulopathy (platelet count< 10 000 or International Normalized Ratio (INR) >

• Neuromuscular disease that impairs ability to ventilate spontaneously (including C5 orhigher spinal cord injury, amyotrophic lateral sclerosis, Guillain-Barre syndrome ormyasthenia gravis)
• Treating clinician refusal, or unwillingness to commit to pressure support ventilationfor at least 6 hours.
• Pregnancy
• Liver cirrhosis (Child B or C) or other severe impairment of hepatic function
• Congestive heart failure
• Bradyarrhythmia (baseline pulse<55/min)
• Known long QT syndrome
• QTc prolongation>450 msec, noted on prior or screening ECG, or who are takingmedication known to cause QT prolongation
• Hypersensitivity or other known intolerance to ondansetron or other 5-HT3 antagonists