DIPHENHYDRAMINE ENHANCES THE INTERACTION OF HYPERCAPNIC AND HYPOXIC VENTILATORY DRIVE

Background: Although diphenhydramine is frequently used to treat pruri tus and nausea in patients who have received neuraxial opioids, there are no data regarding its effect on ventilatory control. We conducted the current study to evaluate the effects of diphenhydramine on hyperc apnic and hypoxic ventilatory control in healthy volunteers. Methods: First, we measured the steady-state ventilatory response to carbon dio xide during hyperoxia with an end-tidal carbon dioxide tension of 46 o r 54 mmHg (alternate subjects) in eight healthy volunteers. We then de termined the hypoxic ventilatory response during isocapnic rebreathing at the same carbon dioxide tension. After a 10-min recovery period, w e repeated the steady-state and hypoxic ventilatory response measureme nts at the other carbon dioxide tension (54 or 46 mmHg). Ten minutes a fter subjects received diphenhydramine 0.7 mg.kg(-1) intravenously, we repeated this sequence of ventilatory measurements. Results: Under hy peroxic conditions (inspired oxygen fraction > 0.5) diphenhydramine di d not affect the ventilatory response to hypercapnia. Similarly, at an end-tidal carbon dioxide tension of 46 mmHg, neither the slope nor th e position of the hypoxic ventilatory response curve changed significa ntly after diphenhydramine. However, at an end-tidal carbon dioxide te nsion of 54 mmHg, the slope of the hypoxic ventilatory response increa sed from 1.28 +/- 0.33 to 2.13 +/- 0.61 1.min(-1).% Sp(O2)(-1)(mean +/ - standard error), and V-E, at an arterial hemoglobin oxygen saturatio n of 90% increased from 31.2 +/- 3.1 to 43.1 +/- 5.41.min(-1)). Conclu sions: We conclude that although it did not affect the ventilatory res ponse to carbon dioxide during hyperoxia or the ventilatory response t o hypoxia at an end-tidal carbon dioxide tension of 46 mmHg diphenhydr amine augmented the hypoxic response under conditions of hypercapnia i n our young healthy volunteers. Although these findings may help to ex plain the apparent safety of diphenhydramine, they may not be applicab le to debilitated patients or those who have received systemic or neur axial ventilatory depressants.