Intranasal Ketamine for Procedural Sedation
Keywords
Abstract
Description
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
Dates
| Last Verified: | 02/28/2017 |
| First Submitted: | 06/29/2016 |
| Estimated Enrollment Submitted: | 07/06/2016 |
| First Posted: | 07/10/2016 |
| Last Update Submitted: | 08/24/2017 |
| Last Update Posted: | 08/28/2017 |
| Actual Study Start Date: | 09/30/2017 |
| Estimated Primary Completion Date: | 12/31/2018 |
| Estimated Study Completion Date: | 01/31/2019 |
Condition or disease
Intervention/treatment
Drug: IN ketamine and IV saline
Drug: IV ketamine and IN saline
Drug: IV ketamine and IN saline
Drug: IN ketamine and IV saline
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Experimental: IN ketamine and IV saline Ketamine, single dose, 10 mg/kg (0.1 mL/kg) of 100 mg/mL solution delivered intranasally using an atomizer and divided to both nares to a maximum of 800 mg (8 mL) AND 0.9% normal saline (NS) 0.02 to 0.03 mL/kg delivered intravenously to a maximum of 2.4 mL | Drug: IN ketamine and IV saline Intranasal ketamine 100 mg/mL solution (10 mg/kg, maximum 800 mg) |
| Active Comparator: IV ketamine and IN saline Ketamine, single dose, 1 to 1.5 mg/kg (0.02 to 0.03 mL/kg) of 50 mg/mL solution delivered intravenously, to a maximum of 120 mg (2.4 mL) AND 0.9% normal saline (NS) 0.1 mL/kg delivered intranasally using an atomizer and divided to both nares, to a maximum of 8 mL | Drug: IV ketamine and IN saline Intravenous ketamine 50 mg/mL solution (1 to 1.5 mg/kg, maximum 120 mg) |
Eligibility Criteria
| Ages Eligible for Study | 4 Years To 4 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: 1. Age 4 -17 years 2. Up to 80 kg 3. Presenting the paediatric emergency department 4. Require a closed reduction by procedural sedation and analgesia 5. Acute (=< 48 hours) distal radius and/or ulna fracture that is angulated with or without displacement 6. No more than 0.5 cm shortening in either the radius or ulna (not both) Exclusion Criteria: 1. Previous hypersensitivity reaction to ketamine 2. Globe rupture 3. Traumatic brain injury with intracranial hemorrhage 4. History of uncontrolled hypertension 5. Nasal bone deformity 6. Duration of reduction expected to be greater than 20 minutes 7. Poor English or French fluency in the absence of a native language interpreter 8. American Society of Anesthesiologists (ASA) class of 3 or greater 9. Previous sedation with ketamine within 24 hours 10. Previous diagnosis of schizophrenia or psychosis based on DSM-V criteria 11. Pregnancy 12. Neuro-cognitive impairment that precludes informed consent, assent, or ability to self-report pain and satisfaction 13. Multi-limb trauma 14. Hemodynamic compromise 15. Glasgow coma score < 15 16. Fracture is comminuted 17. Fracture is associated with a dislocation 18. Hematoma block at index visit 19. Unilateral or bilateral nasal obstruction (due to infectious or allergic rhinitis, nasal polyps, septal hematoma, or septal deviation) |
Outcome
Primary Outcome Measures
1. Adequacy of sedation [Duration of fracture reduction]
Secondary Outcome Measures
1. Depth of sedation [Duration of fracture reduction]
2. Onset of adequate sedation [Within 1 hour following intervention]
3. Duration of sedation [Within 2 hours following intervention]
4. Proportion of time participant adequately sedated during fracture reduction [Within 2 hours following intervention]
5. Adverse events [Within 2 hours following intervention]
6. Length of stay due to PSA [Within 3 hours of intervention]
7. Duration of procedure [Within 3 hours of intervention]
8. Caregiver satisfaction [Within 2 hours of intervention]
9. Participant satisfaction [Within 2 hours of intervention]
10. Physician satisfaction [Within 2 hours of intervention]
11. Nurse satisfaction [Within 2 hours of intervention]
12. Requirement for additional sedative medication [Within 2 hours of intervention]
13. Analgesic medication [Within 2 hours of intervention]
14. Pain [Within 2 hours of intervention]
15. Emergence delirium [20 to 80 minutes post-IV intervention]
16. Nasal irritation [Within 2 hours following intervention]
17. Successful sedation [Within 2 hours following intervention]
18. Adjunctive IV therapy [Within 2 hours following intervention]
19. Number of IN sprays received / Intended number of sprays [Within 2 hours following intervention]
20. Number of IV attempts [Within 2 hours following intervention]
21. Time to IV insertion [Within 2 hours following intervention]
