- Design
- Single-centre, single-blind, non-randomised crossover trial
- Population
- Nine adults with ARDS ventilated over 48 hours on pressure support
- Primary outcome
- Inspiratory pressure-time product of oesophageal pressure
- Effect
- -23 cmH2O·s/min (95% CI -28 to -18), P<0.001; PaO2:FiO2 +23 (6 to 40)
Excessive respiratory effort in ARDS can add to lung injury. Serotonin acting on 5-HT3 receptors on pulmonary C-fibres increases effort, so a 5-HT3 antagonist might lower it. This single-centre, single-blind, non-randomised crossover trial enrolled ten adults with ARDS ventilated for over 48 hours on pressure support; nine completed. Each received intravenous placebo, then 3 hours later ondansetron 0.15 mg/kg (maximum 16 mg).
Inspiratory pressure-time product fell from 108 to 85 cmH2O·s/min, a model-based difference of -23 (95% CI -28 to -18; P<0.001). Respiratory rate fell by 1.7 breaths per minute, minute ventilation by 1.0 L/min and peak diaphragm activity by 2.4 microvolts, with no significant change in tidal volume. PaCO2 rose by 3.2 mmHg and the PaO2:FiO2 ratio improved by 23 (6 to 40).
The placebo always came first, so time and order effects are not separated from the drug. The study was physiological and did not measure clinical outcomes.
- Ondansetron lowered measures of respiratory drive in nine patients; this is hypothesis-generating physiology.
- PaCO2 rose modestly (3.2 mmHg), so watch ventilation if effort falls.
- The study did not test whether lowering effort improves outcomes.
- Do not use ondansetron to reduce respiratory drive outside a trial.
Why it matters
It points to a mechanism-based way of reducing self-inflicted lung injury without deeper sedation.
Don't overread it
Nine patients, no randomisation, no clinical outcomes, and a fixed order of placebo then drug.
The statistics, in plain English
The narrow confidence interval (-28 to -18) reflects many repeated measurements within nine people, not nine independent observations. Because placebo came first every time, a drift over time could contribute to the difference.
Read the rest in the app
You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.
Scan to keep reading on your phone. No account needed to start.
Tomorrow morning, before your first patient
One edition a day for pulmonology, written by the desk, every claim tied to its paper. Six minutes.
Get the app — free