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 [PETCO2] approximate to 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 approximate to 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 l . min(-1) . mmHg(-1) ((x) over bar +/- SD, P < 0.05) during alfentanil infusion; after diphenhydramine, the slope increased to 1.17 +/- 0.28 l . min(-1) . mmHg(-1) (P < 0.05). The minute ventilation ((V) over dot (E)) at PETCO2 approximate to 46 mmHg ((V) over dot (E) 46) decreased from 12.1 +/- 3.7 to 9.7 +/- 3.6 l/min (P < 0.05) and the (V) over dot (E) at 54 mmHg ((V) over dot (E) 54) decreased from 21.3 +/- 4.8 to 16.6 +/- 4.7 l/min during alfentanil(P < 0.05). After diphenhydramine, (V) over dot (E) 46 did not change significantly, remaining lower than baseline at 9.9 +/- 2.9 l/min (P < 0.05), whereas (V) over dot (E) 54 increased significantly to 20.5 +/- 3.0 l/min. During hypoxia, (V) over dot (E) at SpO2 = 90% ((V) over dot (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) over dot (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 PETCO2 = 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.