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

Summary 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  μ g·kg −1 ), MET (0–400  μ g·kg −1 ), and/or DEX (0–500  μ g·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  μ g·kg −1 of OND and 0.37 for each 100  μ g·kg −1 of MET. After discharge, odds of emesis decreased by a factor of 0.67 for each 125  μ g·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.