Quantifying the intensity of adverse events with ibuprofen and oxycodone: an observational cohort study.

OBJECTIVE: To quantify the frequency and intensity of adverse events (AEs), commonly known as side effects, experienced by children receiving either ibuprofen or oxycodone for pain management following an acute fracture. Secondary objectives were to quantify functional outcome impairment and describe demographic and clinical characteristics associated with AEs. DESIGN: Observational cohort study. SETTING: Paediatric emergency department. PATIENTS: Patients (n=240) aged 4-16 years diagnosed with an acute fracture. INTERVENTION: Prescribed either ibuprofen (n=179) or oxycodone (n=61) for pain. MAIN OUTCOME MEASURES: Families were called for the first 3 days after discharge to report the presence and intensity of AEs and their child's functional outcomes (ability to eat, sleep, play or attend school). RESULTS: On day 1, children using oxycodone were more likely to report any AE (χ2 1=13.5, p<0.001), nausea (χ2 1=17.0, p<0.001), vomiting (χ2 1=11.2, p<0.001), drowsiness (χ2 1=13.7,p<0.001), constipation (χ2 1=8.9, p=0.003) and dizziness (χ2 1=19.1, p<0.001), compared with those using ibuprofen. Children receiving oxycodone reported greater severity of abdominal pain (oxycodone: mean 5.4 SD 3.1; ibuprofen mean 2.5 SD 1.4, F1 13=6.5, p=0.02) on day 1 and worse intensity of constipation (oxycodone: mean 4.9 SD 2.1; ibuprofen mean 3.2 SD 2.2, F1 33=4.5, p=0.04) over all 3 days. Use of oxycodone was associated with an increased odds of experiencing an AE on day 1 (OR=1.31 (95% CI 1.13 to 1.52)). Higher pain scores (OR=1.50 (95% CI 1.12 to 2.01)), lower extremity fracture (OR=1.25 (95% CI 1.07 to 1.47)) and undergoing ED sedation (OR=1.16 (95% CI 1.01 to 1.34)) were associated with missing school. Higher pain scores (OR=1.50 (95% CI 1.14 to 1.97)) and lower extremity fractures (OR=1.23 (95% CI 1.07 to 1.43)) were also associated with less play. CONCLUSIONS: Oxycodone is associated with more frequent AEs overall, higher intensity gastrointestinal AEs and greater functional limitations compared with ibuprofen. Lower extremity fractures cause more functional limitations than upper extremity fractures. Clinicians should consider these differences when providing fracture pain care for children.

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

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.

Paediatric hanging and strangulation injuries: A 10-year retrospective description of clinical factors and outcomes.

OBJECTIVE: To identify early clinical factors that are correlated with death or severe disability in paediatric patients who have sustained an injury by hanging or strangulation. METHODS: A retrospective review of all patient records from January 1, 1997, to September 30, 2007, was conducted. Patient records were identified by International Classification of Diseases and Related Health Problems, Tenth Revision, Canada diagnostic codes for asphyxia, strangulation, hypoxic-ischemic encephalopathy, hanging, hypoxemia, hypoxia or anoxia. RESULTS: A total of 109 records were identified. Of these, 41 met the inclusion criteria for the study. Of 19 (46%) children who were pulse-less and received cardiopulmonary resuscitation, 16 died and the survivors were severely disabled. Of the 22 (54%) children who were found with a pulse, 18 made a full recovery. CONCLUSIONS: Children who are pulseless at discovery for hanging injuries are at high risk of death or severe disability. Early clinical and neurophysiological indicators should be applied systematically to best guide clinicians and parents in their decision making.