Ketamine Versus Co-administration of Ketamine and Propofol for Procedural Sedation in a Pediatric Emergency Department

Study Overview
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Brief Summary
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The purpose of this study is to compare the effectiveness of the co-administration of intravenous ketamine and propofol to intravenous ketamine as a single agent for procedural sedation in the pediatric emergency department. The investigators hypothesize that patients receiving co-administration of ketamine and propofol will have a lower rate of adverse events, compared to patients receiving ketamine for procedural sedation.

Detailed Description
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Procedural sedation and analgesia (PSA) is a frequent occurrence in pediatric emergency departments. The goals of PSA include maximizing analgesia and amnesia, and minimizing adverse events while ensuring stable cardiopulmonary function. For decades, ketamine has been the main pharmacologic agent used for pediatric PSA. Numerous studies support the use of ketamine for sedation, amnesia, and analgesia on children undergoing painful procedures in the emergency department setting. Research has continually shown ketamine to cause emergence phenomenon, laryngospasm and vomiting. Propofol is a sedative-hypnotic widely used for procedural sedation in adult emergency departments. The advantages of propofol include rapid onset, with quick and predictable recovery time, and antiemetic effects. Disadvantages include dose-dependent hypotension, bradycardia, respiratory depression, as well as pain with injection. In addition, propofol does not provide any analgesia. Ketamine and propofol administered together have been successfully utilized in a variety of settings, including dermatologic, cardiovascular, and interventional radiological procedures in children. The co-administration of ketamine and propofol has been shown to preserve sedation while minimizing the respective adverse events. When used in combination, doses administered of each can be reduced, while producing a more stable hemodynamic and respiratory profile. Furthermore, this combination may reduce the frequency of emergence reactions, vomiting, and the pain of propofol injection. To date, there are no randomized controlled trials evaluating the co-administration of ketamine and propofol versus ketamine monotherapy for PSA in the Pediatric Emergency Department.

Official Title
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Comparison of Ketamine Versus Co-Administration of Ketamine and Propofol for Procedural Sedation in a Pediatric Emergency Department

Conditions
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Procedural Sedation and Analgesia

Intervention / Treatment
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* Drug: Ketamine
* Drug: Ketamine Co-administered with Propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages > 3 years and < 21 years American Society of Anesthesiologists (ASA) class I or II Fracture or dislocation requiring reduction under procedural sedation with ketamine as deemed by the attending emergency medicine physician Parent/Legal Guardian or Patient (if 18 years of age or older) has already given verbal consent for procedural sedation as part of standard care for their condition Exclusion Criteria: Hypertension (Blood Pressure > 95th percentile for age) Glaucoma or acute globe injury Increased intracranial pressure or central nervous system mass lesion Porphyria Previous allergic reaction to ketamine Previous allergic reaction to Propofol or its components including soybean oil, glycerol, egg lecithin, and disodium edentate Disorders of lipid metabolism including primary hyperlipoproteinemia, diabetic hyperlipemia, or pancreatitis Mitochondrial myopathies or disorders of electron transport Pregnancy Parent, guardian or patient unwilling/unable to provide informed consent/assent

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ketamine Alone<br>1.0 milligrams/kilogram (mg/kg) ketamine with additional doses of 0.5 mg/kg ketamine as needed (maximum single dose based on 100 kilogram (kg) person) | Drug: Ketamine<br>* 1.0 milligrams/kilogram (mg/kg) ketamine with additional doses of 0.5 mg/kg ketamine as needed (maximum single dose based on 100 kilogram (kg) person)<br>|
| Experimental: Ketamine Co-Administered with Propofol<br>0.5 mg/kg ketamine and 0.5 mg/kg propofol with additional doses of 0.25 mg/kg ketamine and 0.25 mg/kg propofol as needed (maximum single dose based on 100 kg person) | Drug: Ketamine Co-administered with Propofol<br>* 0.5 mg/kg ketamine and 0.5 mg/kg propofol with additional doses of 0.25 mg/kg ketamine and 0.25 mg/kg propofol as needed (maximum single dose based on 100 kg person)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Adverse Events | We will record all adverse events during the sedation, and then perform a follow-up call to determine if any additional adverse events occured after discharge. | From enrollment through completion of follow-up, up to 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recovery Time | Time until the patient has a Vancouver Sedation Recovery Scale Score of 18 or greater. | Once Vancouver Sedation Recovery Scale Score reaches 18 or greater, on average less than 1 hour | 
| Efficacy of Sedation | Efficacy is defined as: The patient does not have unpleasant recall of the procedure. The patient did not experience sedation-related adverse events resulting in abandonment of the procedure or a permanent complication or an unplanned admission to the hospital or prolonged emergency department (ED) observation The patient did not actively resist or require physical restraint for completion of the procedure. The need for minimal redirection of movements should not be considered as active resistance or physical restraint. The procedure was successful | After procedure is completed, on average less than 1 hour | 
| Parent Satisfaction | Measured on a 10-point scale (1= least satisfied, 10= most satisfied) | After procedure is completed, on average less than 1 hour | 
| Physician Performing Procedure Satisfaction | Measured on a 10-point scale (1= least satisfied, 10= most satisfied) | After procedure is completed, on average less than 1 hour | 
| Nurse Satisfaction | Measured on a 10-point scale (1= least satisfied, 10= most satisfied) | After procedure is completed, on average less than 1 hour | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ketamine, Propofol, Procedural Sedation and Analgesia