Clinical trial NCT02402868: Intranasal Versus Intravenous Ketamine for Procedural Sedation in Children
Official title: Intranasal Ketamine Versus Intravenous Ketamine for Procedural Conscious Sedation in Children: a Multi-centre Randomized Controlled Non-inferiority Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bone Fractures
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
First posted: 2015-03-30
Enrollment: 17
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 5-17 years of age who require a simple orthopaedic reduction. Following a double dummy approach to overcome the difficulty in masking interventions, each participant will recieve both IV and IN interventions, only one of which will be the real drug. Procedural conscious sedation (PCS) will be assessed using the University of Michigan Sedation Scale (UMSS).

Detailed description: Randomization and concealment of allocation will be pharmacy-controlled using a computer-based random number generator. The treating physician, 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 six to either (1) IN ketamine (each single dose, 8 mg/kg prepared in 0.9% NS in 3 mL syringe and atomizer, to a maximum of 1.5 mL) PLUS IV 0.9% NS 0.02 mL/kg or (2) IV ketamine (single dose, 1 mg/kg, to a maximum 100 mg) PLUS intranasal 0.9% NS 0.08 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. Adjuctive sedation will be given as needed in the form of IV ketamine, 1 mg/kg every 10 minutes for participants who do not achieve adequate sedation at 20 minutes (UMSS score of 4). A figure of the atomizer device used to deliver the IN agent has been uploaded. Eligible participants (defined in section 2.5 above) 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 PCS and a pre-anesthetic assessment will be performed by the treating physician in accordance with the usual standard of care. UMSS scores will be obtained by a trained RA at 5 minutes pre-intervention, intervention (0 minutes) and every 5 minutes thereafter for 60 minutes post-intervention or until the participant is ambulatory and drinking well, whichever is longer. 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. Immediately prior to discharge, the RA will also record the duration of stay in the ED and parental satisfaction with PCS. 1. Chiaretti et al. 2011. Intranasal lidocaine and midazolam for procedural sedation in children. Arch Dis Child. 96;160-163

Eligibility criteria: Inclusion Criteria:

* Patients 5-17 years (up to 80 kg) presenting to the paediatric ED who require a PCS for an acute simple orthopedic injuries who require a procedural sedation and analgesia (PSA). A "simple" injury is defined as a fracture or dislocation that: 1) Angulated with or without displacement but is not shortened) 2) Non-comminuted

Exclusion Criteria:

* 1) Previous hypersensitivity reaction to ketamine including rash, difficulty breathing, hypotension, apnea, or laryngospasm 2) Globe rupture 3) Traumatic brain injury with intracranial hemorrhage 4) History of uncontrolled hypertension 5) Nasal bone deformity 6) Fracture reduction expected to require \> 20 minutes 7) Poor English fluency 8) American Society of Anesthesiologists (ASA) class of 3 or greater 9) Previous sedation with ketamine within 24 hours of index visit 10) Known diagnosis of schizophrenia or active psychosis 11) Pregnancy

Primary outcomes:
measure: University of Michigan Sedation Score
timeFrame: From the time the IV intervention is given to 60 minutes post intervention or when drinking, whichever is longer
Secondary outcomes:
measure: Onset of sedation
timeFrame: Within 1 hour following intervention
measure: Duration of sedation
timeFrame: Within 2 hours following sedation
measure: Adverse events
timeFrame: Within 2 hours following sedation
measure: Length of stay
timeFrame: Within 3 hours of intervention
measure: Length of stay due to sedation
timeFrame: Within 3 hours of intervention
measure: Duration of procedure
timeFrame: Within 3 hours of intervention
measure: Parental satisfaction
timeFrame: Within 2 hours of sedation
measure: Child satisfaction
timeFrame: Within 2 hours of sedation
measure: Sedating physician satisfaction
timeFrame: Duration of ED visit
measure: Adjunctive sedative medication
timeFrame: Duration of ED visit
measure: Analgesic medication
timeFrame: Duration of ED visit
measure: Pain
timeFrame: 15 minutes prior to and 2 hours post intervention
measure: Emergence Agitation
timeFrame: Every 5 minutes for 60 minutes starting 20 minutes post IV intervention
measure: Nasal Irritation
timeFrame: Within 1 hour of intervention
measure: Successful sedation
timeFrame: From time of first IN spray to when participant is fully awake (UMSS score of 0 for 15 minutes)
Other outcomes:
Locations:
city: London
country: Canada
facility: Children's Hospital, London Health Sciences Centre
state: Ontario
Study officials:
affiliation: Western University
name: Naveen Poonai, MD
role: PRINCIPAL_INVESTIGATOR
References: