The intranasal dexmedetomidine plus ketamine for procedural sedation in children, adaptive randomized controlled non-inferiority multicenter trial (Ketodex): a statistical analysis plan

Abstract

Background Procedural sedation and analgesia (PSA) is frequently required to perform closed reductions for fractures and dislocations in children. Intravenous (IV) ketamine is the most commonly used sedative agent for closed reductions. However, as children find IV insertion a distressing and painful procedure, there is need to identify a feasible alternative route of administration. There is evidence that a combination of dexmedetomidine and ketamine (ketodex), administered intranasally (IN), could provide adequate sedation for closed reductions while avoiding the need for IV insertion. However, there is uncertainty about the optimal combination dose for the two agents and whether it can provide adequate sedation for closed reductions. The Intranasal Dexmedetomidine Plus Ketamine for Procedural Sedation (Ketodex) study is a Bayesian phase II/III, non-inferiority trial in children undergoing PSA for closed reductions that aims to address both these research questions. This article presents in detail the statistical analysis plan for the Ketodex trial and was submitted before the outcomes of the trial were available for analysis. Methods/design The Ketodex trial is a multicenter, four-armed, randomized, double-dummy controlled, Bayesian response adaptive dose finding, non-inferiority, phase II/III trial designed to determine (i) whether IN ketodex is non-inferior to IV ketamine for adequate sedation in children undergoing a closed reduction of a fracture or dislocation in a pediatric emergency department and (ii) the combination dose for IN ketodex that provides optimal sedation. Adequate sedation will be primarily measured using the Pediatric Sedation State Scale. As secondary outcomes, the Ketodex trial will compare the length of stay in the emergency department, time to wakening, and adverse events between study arms. Discussion The Ketodex trial will provide evidence on the optimal dose for, and effectiveness of, IN ketodex as an alternative to IV ketamine providing sedation for patients undergoing a closed reduction. The data from the Ketodex trial will be analyzed from a Bayesian perspective according to this statistical analysis plan. This will reduce the risk of producing data-driven results introducing bias in our reported outcomes. Trial registration ClinicalTrials.gov NCT04195256. Registered on December 11, 2019.

Uso de sedação com cetamina + dexmedetomedina (Ketodex) para reparo endovascular de aneurisma de aorta abdominal – relato de experiência / Use of sedation with ketamine + dexmedetomedine (Ketodex) for endovascular repair of abdominal aortic aneurysms - experience report

“…Li, et al (2021) destacam que esta estratégia analgésica auxilia no encurtamento do início da sedação e recuperação, mantendo a estabilidade hemodinâmica e respiratória. Heath, et al (2021) salientam que a combinação de dexmedetomidina e cetamina, administrada por via intranasal, pode fornecer sedação adequada para reduções fechadas de fraturas e luxações em crianças, evitando a necessidade de administração intravenosa. Contudo, ainda não há uma padronização da combinação ideal de dose para os dois agentes.…”

Uso do Ketodex para sedação em implante dentário no consultório odontológico – relato de experiência / Use of Ketodex for sedation to dental implants in a dental office - experience report

“…Brazilian Journal of Health Review, Curitiba, v.5, n.1, p. 1744-1752 jan./fev. 2022 Heath, et al (2021), mostra que a associação de cetamina e dexmedetomidina quando administrada por via intranasal, pode fornecer sedação adequada para luxações e reduções fechadas de fraturas em crianças. Porém ainda não se sabe uma dose ideal para a combinação das drogas.…”