Bayesian re-analysis of a randomized 2 × 2 crossover trial of ketamine dose reduction in the ketamine-midazolam combination in uncooperative children: effects on crying and oxygen saturation

Managing fear and uncooperative behavior in pediatric dentistry is challenging. The present study re-analyzed data from a randomized 2 × 2 crossover clinical trial to evaluate whether reducing ketamine dose in an intranasal midazolam–ketamine regimen altered crying and oxygen saturation in young children undergoing dental treatment. Twenty children aged 3–6 years who completed both periods of the original crossover trial received two intranasal sedative combinations across two treatment sessions: midazolam/ketamine 0.4/4 mg·kg⁻¹ and 0.5/3 mg·kg⁻¹. Crying and peripheral oxygen saturation (SpO₂) were measured at baseline, 10 minutes, and 20 minutes. A Bayesian joint modeling approach was used to assess the association between the two longitudinal outcomes. SpO₂ remained within the recorded normal clinical range in both regimens, while crying decreased over time. The estimated association between crying and SpO₂ was weak and negative. No clear evidence of a difference between regimens was observed for either outcome. Within the limits of this small crossover dataset, reducing ketamine from 4 to 3 mg·kg⁻¹ in combination with intranasal midazolam did not materially change the recorded crying or SpO₂ outcomes. Crying was analyzed as a binary outcome, which may not fully capture behavioral control or sedation adequacy. These findings should be interpreted cautiously because this study represents a secondary Bayesian re-analysis of a previously conducted clinical trial.