A factorial study of ondansetron, metoclopramide, and dexamethasone for emesis prophylaxis after adenotonsillectomy in children

Background: We conducted a factorial study of emesis prophylaxis with ondansetron (OND), metoclopramide (MET), and dexamethasone (DEX).

Methods: After informed parental consent, 240 children having adenotonsillectomy were randomized to one of 15 combinations of OND (0–60 μg·kg⁻¹), MET (0–400 μg·kg⁻¹), and/or DEX (0–500 μg·kg⁻¹). Using multivariable logistic regression, models were generated for the probability of emesis before discharge, after discharge and overall for 24 h.

Results: Odds of emesis increased by a factor of three to four for children older than 7 years. Before discharge, odds of emesis decreased by factors of 0.29 for each 15 μg·kg⁻¹ of OND and 0.37 for each 100 μg·kg⁻¹ of MET. After discharge, odds of emesis decreased by a factor of 0.67 for each 125 μg·kg⁻¹ of DEX and increased by a factor of 3.5 for emesis before discharge. Over 24 h, odds of emesis decreased with OND, MET, and DEX (ORs as above). A negative interaction between OND and MET was seen before discharge and over 24 h, reducing the efficacy of their combination.

Conclusions: We present novel study design and methods of analysis which are uniquely suited to studies of multiple interventions. Factorial design was a powerful tool, allowing simultaneous determination of dose–response relationships for three drugs and identifying a previously unreported negative interaction between OND and MET.