This study will examine the effectiveness of intranasal (IN) ketamine compared to standard intravenous (IV) ketamine administration for simple reductions of orthopaedic injuries in the paediatric population. The aim is to assess if IN administration is equivalent to the current standard of care, IV. The population to be studied is children 4-17 years of age who require a simple orthopaedic reduction. Following a double dummy approach to overcome the difficulty in masking interventions, each participant will receive both IV and IN interventions, only one of which will be the real drug. Procedural sedation and analgesia (PSA) will be assessed using the Dartmouth Operative Conditions Scale (DOCS).
Randomization and concealment of allocation will be pharmacy-controlled using a computerized central randomization service. The treating physician, bedside nurse, research assistant, and participant will be blinded to the intervention. Eligible participants will be randomized in a 1:1 allocation ratio with a stratified block design of four or six to either (1) IN ketamine (each single dose, 10 mg/kg prepared in 0.9% NS in 3 mL syringe and atomizer, to a maximum of 8 mL) PLUS IV 0.9% NS 0.02 mL/kg or (2) IV ketamine (single dose, 1 mg/kg, to a maximum 80 mg) PLUS intranasal 0.9% NS 0.10 mL/kg divided to both nares. Due to the perceptible differences in interventional routes, each participant will receive both IV and IN interventions using this double-dummy approach. For IN dose volumes less than or equal to 0.5 mL, the entire dose will be delivered into 1 nostril and for doses greater than 0.5 mL, the dose will be divided equally between both nares. Adjunctive sedation will be given as needed in the form of IV ketamine, any dose, for participants who are adequately sedated 1 minute after IV administration at the discretion of the treating physician. Inadequate sedation in this context refers to one of the following: participant's vocalizations are consistent with pain OR participant withdraws or localizes due to pain. Eligible participants will be identified by the treating physician after viewing the radiographs and performing a clinical assessment. The physician will then inform a research assistant (RA) that the participant is eligible. The RA will then seek informed consent and explain the protocol to the family. Baseline demographic information will be obtained. Informed consent for PSA and a pre-anesthetic assessment will be performed by the treating physician in accordance with the usual standard of care. The RA will record a continuous video of the participant's entire body and monitor using an iPad starting immediately after the IV intervention until the participant is awake and able to tolerate oral fluids. DOCS scores will be obtained by two trained outcome assessors every 30 seconds for the entire duration of the video. The outcome assessors will also score the entire video for emergence delirium using the Paediatric Anesthesia Emergence Delirium (PAED) scale every 5 minutes beginning at the completion of fracture reduction until the participant is awake and drinking. Participants will receive standard monitoring of oxygen saturation, blood pressure, respiratory rate, apnea, heart rate, and rash by the attending nurse and physician every 5 minutes as per the usual standard of care. The usual standard of care also includes monitoring post-anesthetic for the presence of known idiosyncratic effects of ketamine that include vomiting, seizure, headache, emergence reaction, and hypersensitivity. The RA will obtain this information from the nursing record at discharge and based on consensus-based Canadian recommendations. Immediately prior to discharge, the RA will also record the duration of stay in the ED, parental, patient, and physician satisfaction with PSA using a 5-item Likert scale, and nasal irritation
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
470
Intranasal ketamine 100 mg/mL solution (10 mg/kg, maximum 800 mg)
Intravenous ketamine 50 mg/mL solution (1 to 1.5 mg/kg, maximum 120 mg)
Intranasal 0.9% normal saline
Intravenous 0.9% normal saline
Adequacy of sedation
Proportion with DOCS score -2 to +2 for duration of fracture reduction
Time frame: Duration of fracture reduction
Depth of sedation
Score using Pediatric Sedation State Scale
Time frame: Duration of fracture reduction
Onset of adequate sedation
Time interval from first IN sprays to first DOCS score between -2 and +2 in minutes
Time frame: Within 1 hour following intervention
Duration of sedation
Duration of time between the first DOCS score -2 to +2 to last DOCS score between -2 and +2 post-fracture reduction
Time frame: Within 2 hours following intervention
Proportion of time participant adequately sedated during fracture reduction
Proportion of time DOCS score is -2 to +2 during fracture reduction.
Time frame: Within 2 hours following intervention
Adverse events
The proportion of participants with adverse effects between groups will be compared. The list of adverse effects was chosen based on known adverse effects associated with ketamine and consensus-based recommendations for reporting for procedural sedation and analgesia in children.
Time frame: Within 2 hours following intervention
Length of stay due to PSA
Time interval from the first pair of IN sprays to discharge
Time frame: Within 3 hours of intervention
Duration of procedure
Time of the first pair of IN sprays to the end of cast or splint application
Time frame: Within 3 hours of intervention
Caregiver satisfaction
Obtained when patient is awake and drinking using a Visual Analog Scale; Parents not wishing to remain in proximity of child for sedation may opt out
Time frame: Within 2 hours of intervention
Participant satisfaction
Obtained when patient is awake and drinking using a Visual Analog Scale; Satisfaction will only be assessed in children at least eight years of age as the VAS has not been validated in younger children.
Time frame: Within 2 hours of intervention
Physician satisfaction
Obtained immediately prior to discharge using a Visual Analog Scale
Time frame: Within 2 hours of intervention
Nurse satisfaction
Obtained immediately prior to discharge using a Visual Analog Scale
Time frame: Within 2 hours of intervention
Requirement for additional sedative medication
Number of doses and type of adjunctive sedative medication required; Deemed inadequate if additional sedative medication given (for IN ketamine group only)
Time frame: Within 2 hours of intervention
Analgesic medication
Number of doses and type of analgesic medication required
Time frame: Within 2 hours of intervention
Pain
Pain scores will be recorded using the FPS-R on arrival and when the child is awake and drinking
Time frame: Within 2 hours of intervention
Emergence delirium
The proportion of children experiencing emergence delirium will be compared using the Paediatric Anesthesia Emergence Delirium (PAED) scale scored from the video every 5 minutes by an outcome assessor starting when fracture reduction is complete to when awake and drinking
Time frame: 20 to 80 minutes post-IV intervention
Nasal irritation
Measured using the Faces Pain Scale - Revised when awake and drinking
Time frame: Within 2 hours following intervention
Successful sedation
Successful sedation - Based on the definition of Bhatt et al., this will be defined as no unpleasant patient recall of the procedure, no resistance or restraint required during the procedure, no permanent sedation-related complication or no sedation-related event requiring abandonment of the procedure. Defined as: no unpleasant patient recall of the procedure, no resistance or restraint required during the procedure, no permanent sedation-related complication or no sedation-related event requiring abandonment of the procedure. Defined as no unpleasant recall of procedure, no resistance or restraint, no permanent sedation related complication, no sedation-related event requiring abandonment of procedure
Time frame: Within 2 hours following intervention
Adjunctive IV therapy
Other reasons for IV insertion (analgesia, anxiolysis, fluids, etc.)
Time frame: Within 2 hours following intervention
Number of IN sprays received / Intended number of sprays
Number of IN sprays received / Intended number of sprays
Time frame: Within 2 hours following intervention
Number of IV attempts
Number of IV attempts and time to IV insertion Number of IV attempts
Time frame: Within 2 hours following intervention
Time to IV insertion
Time from first breakage of skin to establishment of successful flow with a flush
Time frame: Within 2 hours following intervention
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