Randomized Clinical Trial of Propofol, 1:1 and 4:1 Combination of Propofol and Ketamine for Procedural Sedation

Study Overview
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Brief Summary
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This will be a randomized trial of propofol versus the combination of propofol and ketamine for procedural sedation for procedures in the Emergency Department (ED). Propofol produces sedation, hypnosis, and dense amnesia, and is commonly used in the ED at Hennepin County Medical Center (HCMC) for procedural sedation. Ketamine is a dissociative anesthetic that is also frequently used in the ED in children and sometimes in adults. It has been proposed that by combining the two agents, the negative side effects of respiratory depression and hypotension associated with propofol, and the negative effects of dysphoria and vomiting associated with ketamine, can be avoided. In the proposed study, patients seen in the ED who will require procedural sedation for a painful procedure will be randomized to receive either propofol or propofol and ketamine. During the procedure, patients will be monitored per the standard of care, including use of a cardiac monitor, non-invasive blood pressure monitoring, pulse oximetry, nasal sample end-tidal carbon dioxide, and physician assessment. Once the procedure is successfully completed and the patient has returned to his/her baseline mental status, the patient will be asked to mark a 100 mm visual analog scale regarding perceived pain during the procedure, memory of the procedure, and overall satisfaction with the procedure.

Official Title
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Randomized Blinded Three Arm Trial of Propofol, 1:1 Combination of Propofol and Ketamine, and 4:1 Combination of Propofol and Ketamine for Procedural Sedation in the Emergency Department

Conditions
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Procedural Sedation

Intervention / Treatment
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* Drug: Propofol
* Drug: 1:1 Propofol/Ketamine
* Drug: 4:1 Propofol/Ketamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients undergoing procedural sedation for an urgent procedure in the Emergency Department Exclusion Criteria: Allergy to propofol or ketamine, intoxication, altered mental status, ASA physical status score >2

Ages Eligible for Study
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Minimum Age: 1 Year

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Propofol<br>Deep sedation using propofol | Drug: Propofol<br>* 1 mg/kg IV bolus followed by 0.5 mg/kg every 3 minutes as need for sedation<br>|
| Experimental: 1:1 Propofol/Ketamine<br>Propofol and ketamine mixed 1:1, given at 0.1 cc/kg as initial bolus, followed by 1/2 that dose every 3 minutes as need for sedation | Drug: 1:1 Propofol/Ketamine<br>* Propofol and ketamine mixed 1:1, given at 1 mg/kg IV bolus followed by 0.5 mg/kg every 3 minutes as need for sedation<br>|
| Experimental: 4:1 Propofol/Ketamine<br>Propofol and ketamine mixed 4:1, given at 0.1 cc/kg as initial bolus, followed by 1/2 that dose every 3 minutes as need for sedation | Drug: 4:1 Propofol/Ketamine<br>* Propofol and ketamine mixed 4:1, given at 1 mg/kg IV bolus followed by 0.5 mg/kg every 3 minutes as need for sedation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Interventions During Sedation | Add/increase in supplemental oxygen, stimulation to induce respiration, airway repositioning, assisted ventilations, endotracheal intubation | From start of sedation procedure to end of sedation procedure, up to 24 hours | 
| Hypoxia | Pulse oximetry | From start of sedation procedure to end of sedation procedure, up to 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory Depression | Continuous capnographic monitoring | From start of sedation procedure to end of sedation procedure, up to 24 hours | 
| Procedural Recall | After patients returned to baseline mental status they were asked whether they were able to recall any of the procedure. Question was answered in a yes or no format. | Immediately after the end of the procedure, a single time point within 30 minutes of procedures conclusion. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Deep Procedural Sedation, Propofol, Ketamine, Emergency Department, Monitoring, Capnography, Procedural Sedation in the Emergency Department