Effect of ondansetron on respiratory drive in patients with acute respiratory distress syndrome.

Background

Acute respiratory distress syndrome (ARDS) is often accompanied by excessive respiratory effort contributing to patient-self-inflicted lung injury. Lung inflammation leads to increased stimulation and sensitization of pulmonary vagal afferent C-fibers. Stimulation of pulmonary C-fibers by serotonin increases respiratory effort through 5-HT3 receptors. Blocking these receptors could enable safer spontaneous ventilation and mitigate the need for deep sedation or neuromuscular blockade. RESEARCH QUESTION Our objective was thus to evaluate the effect of ondansetron, a 5-HT3 antagonist, on (1) the pressure-time-product (PTP) of esophageal pressure (Peso) per minute and (2) respiratory rate, tidal volume, minute ventilation and electrical activity of the diaphragm (Edi).

Methods

We performed a single-center, single-blind, non-randomized crossover trial, including adults with ARDS (Berlin criteria), ventilated > 48 hours, on pressure-support mode. Participants underwent two consecutive phases: intravenous placebo (10 mL 0.9% saline) followed, 3 hours later, by intravenous ondansetron (0.15 mg/kg; max 16 mg). We continuously recorded airway pressure, flow, Peso, and Edi tracings, comparing respiratory parameters during each 3-hour phase using mixed effect models with participant-specific random intercepts and autoregressive-residual-correlation.

Results

We enrolled ten patients and could carry the experiment in nine. Ondansetron reduced parameters of respiratory drive. Mean inspiratory PTP fell from 108 to 85 cmH2O·s·min-1, yielding a model derived mean difference of -23 cmH2O·s·min-1 (95 % confidence interval (CI95%) [-28, -18]; p<0.001). Respiratory rate (-1.7 breaths/min; CI95% [-2.0, -1.3]), minute ventilation (-1.0 L/min; CI95% [-1.1, -0.8]), peak Edi (-2.4 μV; CI95% [-2.6, -2.2]) all declined, without significant changes in tidal volume. This was accompanied by a modest rise in PaCO2 from (+3.2 mmHg; CI95% [+1.4, +5.1]; p<0.001) and a significant improvement of the PaO2:FiO2 ratio by +23 (CI95% [6, 40] p = 0.009).

Conclusions

Ondansetron reduces the respiratory drive in invasively mechanically ventilated patients with ARDS.