In this episode, I’ll discuss the effect of ondansetron on respiratory drive in patients with acute respiratory distress syndrome.
One of the complicating issues of treating patients with acute respiratory distress syndrome is when they have excessive respiratory effort, which leads to further lung injury. Excessive sedative and paralytic doses are often needed to attempt to prevent this self-inflicted lung injury from occuring, but they are not always successful.
Lung inflammation from ARDS leads to increased stimulation and sensitization of pulmonary vagal afferent C-fibers. Researchers have identified that stimulation of pulmonary C-fibers by serotonin increases respiratory effort through 5-HT3 receptors. If this cycle could be broken by receptor blockade, patients with ARDS could potentially benefit. A group of researchers sought to investigate this and published their findings in the journal Chest.
The authors performed a single-center, single-blind, non-randomized crossover trial of 9 patients with ARDS to determine if ondansetron, through its antagonism of 5-HT3 receptors, would have beneficial effects on surrogate endpoints relevant to ARDS patients. Patients were given placebo followed 3 hours later by 0.15 mg.kg IV ondansetron (max dose = 16 mg).
The authors found that ondansetron reduced many parameters of respiratory drive. Mean inspiratory PTP fell from 108 to 85 cmH2O·s·min-1. Respiratory rate fel by -1.7 breaths/min, minute ventilation fell by 1.0 L/min, peak electrical activity of the diaphgram fell by 2.4 μV. These changes were not accompanied by a change in tidal volume. There was however a small rise in PaCO2 of +3.2 mmHg and a significant improvement of the PaO2:FiO2 ratio by +23.
The authors concluded:
Ondansetron reduces the respiratory drive in invasively mechanically ventilated patients with ARDS.
While mostly hypothesis-generating, these are interesting findings that might be relevant someday to a refractory ARDS patient.
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