Diphenhydramine Increases Ventilatory Drive during Alfentanil Infusion

Background: Diphenhydramine is used as an antipruritic and antiemetic in patients receiving opioids. Whether it might exacerbate opioid-induced ventilatory depression has not been determined. Methods: The ventilatory response to carbon dioxide during hyperoxia and the ventilatory response to hypoxia during hypercapnia (end-tidal pressure of carbon dioxide [PET CO2 ] 54 mmHg) were determined in eight healthy volunteers. Ventilatory responses to carbon dioxide and hypoxia were calculated at baseline and during an alfentanil infusion (estimated blood levels 10 ng/ml) before and after diphenhydramine 0.7 mg/kg. Results: The slope of the ventilatory response to carbon dioxide decreased from 1.08 ± 0.38 to 0.79 ± 0.36 1. min -1 . mmHg -1 (X ± SD, P < 0.05) during alfentanil infusion; after diphenhydramine, the slope increased to 1.17 + 0.28 1. min -1 . mmHg -1 (P < 0.05). The minute ventilation (V E ) at PET CO2 46 mmHg (V E 46) decreased from 12.1 ± 3.7 to 9.7 ± 3.6 l/min (P < 0.05) and the V E at 54 mmHg (V E 54) decreased from 21.3 ± 4.8 to 16.6 ± 4.7 l/min during alfentanil (P < 0.05). After diphenhydramine, V E 46 did not change significantly, remaining lower than baseline at 9.9 ± 2.9 l/min (P < 0.05), whereas V E 54 increased significantly to 20.5 ± 3.0 l/min. During hypoxia, V E at S P O 2 = 90% (V E 90) decreased from 30.5 ± 9.7 to 23.1 ± 6.9 l/min during alfentanil (P < 0.05). After diphenhydramine, the increase in V E 90 to 27.2 ± 9.2 l/min was not significant (P = 0.06). Conclusions: Diphenhydramine counteracts the alfentanil-induced decrease in the slope of the ventilatory response to carbon dioxide. However, at PET CO2 = 46 mmHg, it does not significantly alter the alfentanil-induced shift in the carbon dioxide response curve. In addition, diphenhydramine does not exacerbate the opioid-induced depression of the hypoxic ventilatory response during moderate hypercarbia.