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

• Sponsor: Hennepin Healthcare Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01260662
• Collaborator: (none)
• Enrollment: 271
• Location: 1
• Arms: 3
• Duration (Months): 33
• Patients Per Site Per Month: 8.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Procedural Sedation	Drug: Propofol; Drug: 1:1 Propofol/Ketamine; Drug: 4:1 Propofol/Ketamine	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 271 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Nov 1, 2010
• Actual Primary Completion Date: Aug 1, 2013
• Actual Study Completion Date: Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Propofol Deep sedation using propofol	Drug: Propofol; 1 mg/kg IV bolus followed by 0.5 mg/kg every 3 minutes as need for sedation
Experimental: 1:1 Propofol/Ketamine 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; 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
Experimental: 4:1 Propofol/Ketamine 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; 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

Outcome Measures

Primary Outcome Measures

1. Clinical Interventions During Sedation [From start of sedation procedure to end of sedation procedure, up to 24 hours]

   Add/increase in supplemental oxygen, stimulation to induce respiration, airway repositioning, assisted ventilations, endotracheal intubation

2. Hypoxia [From start of sedation procedure to end of sedation procedure, up to 24 hours]

   Pulse oximetry

Secondary Outcome Measures

1. Respiratory Depression [From start of sedation procedure to end of sedation procedure, up to 24 hours]

   Continuous capnographic monitoring

2. Procedural Recall [Immediately after the end of the procedure, a single time point within 30 minutes of procedures conclusion.]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415

Sponsors and Collaborators

• Hennepin Healthcare Research Institute

Investigators

• Principal Investigator: James R Miner, MD, Hennepin Healthcare Research Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hennepin Healthcare Research Institute
• ClinicalTrials.gov Identifier: NCT01260662
• Other Study ID Numbers: HSR 10-3230
• First Posted: Dec 15, 2010
• Last Update Posted: Jul 14, 2015
• Last Verified: Jun 1, 2015

• Keywords provided by Hennepin Healthcare Research Institute: Deep Procedural Sedation; Propofol; Ketamine; Emergency Department; Monitoring; Capnography; Procedural Sedation in the Emergency Department
• Additional relevant MeSH terms: Emergencies; Ketamine; Propofol

Study Results

Participant Flow

Recruitment Details	300 patients recruited in the Emergency Department from October 24, 2010 to February 4, 2013
Pre-assignment Detail	271 enrolled subjects underwent procedural sedation

Arm/Group Title	Propofol	1:1 Propofol/Ketamine	4:1 Propofol/Ketamine
Arm/Group Description	Deep sedation using propofol (10 mg /mL) Subjects received a 1 mg/kg IV bolus of propofol followed by 0.5 mg/kg every 3 to 5 minutes as needed to achieve and maintain adequate sedation	Deep sedation using 1:1 propofol to ketamine mixture (prepared with propofol 10 mg/mL and ketamine 10mg/mL) Subjects received a 1 mg/kg IV bolus of 1:1 propofol/ketamine mixture followed by 0.5 mg/kg every 3 to 5 minutes as needed to achieve and maintain adequate sedation	Deep sedation using 4:1 propofol to ketamine mixture (prepared with propofol 10 mg/mL and ketamine 10mg/mL) Subjects received a 1 mg/kg IV bolus of 4:1 propofol/ketamine mixture followed by 0.5 mg/kg every 3 to 5 minutes as needed to achieve and maintain adequate sedation
Period Title: Overall Study
STARTED	90	85	96
COMPLETED	90	85	96
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Propofol	1:1 Propofol/Ketamine	4:1 Propofol/Ketamine	Total
Arm/Group Description	Deep sedation using propofol (10 mg /mL) Subjects received a 1 mg/kg IV bolus of propofol followed by 0.5 mg/kg every 3 to 5 minutes as needed to achieve and maintain adequate sedation	Deep sedation using 1:1 propofol to ketamine mixture (prepared with propofol 10 mg/mL and ketamine 10mg/mL) Subjects received a 1 mg/kg IV bolus of 1:1 propofol/ketamine mixture followed by 0.5 mg/kg every 3 to 5 minutes as needed to achieve and maintain adequate sedation	Deep sedation using 4:1 propofol to ketamine mixture (prepared with propofol 10 mg/mL and ketamine 10mg/mL) Subjects received a 1 mg/kg IV bolus of 4:1 propofol/ketamine mixture followed by 0.5 mg/kg every 3 to 5 minutes as needed to achieve and maintain adequate sedation	Total of all reporting groups
Overall Participants	90	85	96	271
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	40	39	36	38
Sex: Female, Male (Count of Participants)
Female	43 47.8%	40 47.1%	45 46.9%	128 47.2%
Male	47 52.2%	45 52.9%	51 53.1%	143 52.8%
Region of Enrollment (participants) [Number]
United States	90 100%	85 100%	96 100%	271 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

100 subjects were randomized to each group, 90 subjects in the propofol arm completed the study, 85 in the 1:1 propofol/ketamine arm, and 96 in the 4:1 propofol/ketamine arm

Arm/Group Title	Propofol	1:1 Propofol/Ketamine	4:1 Propofol/Ketamine
Arm/Group Description	Deep sedation using propofol (10 mg /mL) Subjects received a 1 mg/kg IV bolus of propofol followed by 0.5 mg/kg every 3 to 5 minutes as needed to achieve and maintain adequate sedation	Deep sedation using 1:1 propofol to ketamine mixture (prepared with propofol 10 mg/mL and ketamine 10mg/mL) Subjects received a 1 mg/kg IV bolus of 1:1 propofol/ketamine mixture followed by 0.5 mg/kg every 3 to 5 minutes as needed to achieve and maintain adequate sedation	Deep sedation using 4:1 propofol to ketamine mixture (prepared with propofol 10 mg/mL and ketamine 10mg/mL) Subjects received a 1 mg/kg IV bolus of 4:1 propofol/ketamine mixture followed by 0.5 mg/kg every 3 to 5 minutes as needed to achieve and maintain adequate sedation
Measure Participants	90	85	96
Number [Clinical interventions performed]	41	33	48

2. Primary Outcome

Title	Hypoxia
Description	Pulse oximetry
Time Frame	From start of sedation procedure to end of sedation procedure, up to 24 hours

Outcome Measure Data

Analysis Population Description

100 subjects were randomized to each group, 90 subjects in the propofol arm completed the study, 85 in the 1:1 propofol/ketamine arm, and 96 in the 4:1 propofol/ketamine arm

Arm/Group Title	Propofol	1:1 Propofol/Ketamine	4:1 Propofol/Ketamine
Arm/Group Description	Deep sedation using propofol (10 mg /mL) Subjects received a 1 mg/kg IV bolus of propofol followed by 0.5 mg/kg every 3 to 5 minutes as needed to achieve and maintain adequate sedation	Deep sedation using 1:1 propofol to ketamine mixture (prepared with propofol 10 mg/mL and ketamine 10mg/mL) Subjects received a 1 mg/kg IV bolus of 1:1 propofol/ketamine mixture followed by 0.5 mg/kg every 3 to 5 minutes as needed to achieve and maintain adequate sedation	Deep sedation using 4:1 propofol to ketamine mixture (prepared with propofol 10 mg/mL and ketamine 10mg/mL) Subjects received a 1 mg/kg IV bolus of 4:1 propofol/ketamine mixture followed by 0.5 mg/kg every 3 to 5 minutes as needed to achieve and maintain adequate sedation
Measure Participants	90	85	96
Number [Patients which experienced hypoxia]	11	6	18

3. Secondary Outcome

Title	Respiratory Depression
Description	Continuous capnographic monitoring
Time Frame	From start of sedation procedure to end of sedation procedure, up to 24 hours

Outcome Measure Data

Analysis Population Description

100 subjects were randomized to each group, 90 subjects in the propofol arm completed the study, 85 in the 1:1 propofol/ketamine arm, and 96 in the 4:1 propofol/ketamine arm

Arm/Group Title	Propofol	1:1 Propofol/Ketamine	4:1 Propofol/Ketamine
Arm/Group Description	Deep sedation using propofol (10 mg /mL) Subjects received a 1 mg/kg IV bolus of propofol followed by 0.5 mg/kg every 3 to 5 minutes as needed to achieve and maintain adequate sedation	Deep sedation using 1:1 propofol to ketamine mixture (prepared with propofol 10 mg/mL and ketamine 10mg/mL) Subjects received a 1 mg/kg IV bolus of 1:1 propofol/ketamine mixture followed by 0.5 mg/kg every 3 to 5 minutes as needed to achieve and maintain adequate sedation	Deep sedation using 4:1 propofol to ketamine mixture (prepared with propofol 10 mg/mL and ketamine 10mg/mL) Subjects received a 1 mg/kg IV bolus of 4:1 propofol/ketamine mixture followed by 0.5 mg/kg every 3 to 5 minutes as needed to achieve and maintain adequate sedation
Measure Participants	90	85	96
Number [number of respiratory depression events]	15	16	21

4. Secondary Outcome

Title	Procedural Recall
Description	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.
Time Frame	Immediately after the end of the procedure, a single time point within 30 minutes of procedures conclusion.

Outcome Measure Data

Analysis Population Description

100 subjects were randomized to each group, 90 subjects in the propofol arm completed the study, 85 in the 1:1 propofol/ketamine arm, and 96 in the 4:1 propofol/ketamine arm

Arm/Group Title	Propofol	1:1 Propofol/Ketamine	4:1 Propofol/Ketamine
Arm/Group Description	Deep sedation using propofol (10 mg /mL) Subjects received a 1 mg/kg IV bolus of propofol followed by 0.5 mg/kg every 3 to 5 minutes as needed to achieve and maintain adequate sedation	Deep sedation using 1:1 propofol to ketamine mixture (prepared with propofol 10 mg/mL and ketamine 10mg/mL) Subjects received a 1 mg/kg IV bolus of 1:1 propofol/ketamine mixture followed by 0.5 mg/kg every 3 to 5 minutes as needed to achieve and maintain adequate sedation	Deep sedation using 4:1 propofol to ketamine mixture (prepared with propofol 10 mg/mL and ketamine 10mg/mL) Subjects received a 1 mg/kg IV bolus of 4:1 propofol/ketamine mixture followed by 0.5 mg/kg every 3 to 5 minutes as needed to achieve and maintain adequate sedation
Measure Participants	90	85	96
Number [percentage report recall of procedure]	6	14	11

Adverse Events

Arm/Group Title	Propofol		1:1 Propofol/Ketamine		4:1 Propofol/Ketamine
Arm/Group Description	Deep sedation using propofol (10 mg /mL) Subjects received a 1 mg/kg IV bolus of propofol followed by 0.5 mg/kg every 3 to 5 minutes as needed to achieve and maintain adequate sedation		Deep sedation using 1:1 propofol to ketamine mixture (prepared with propofol 10 mg/mL and ketamine 10mg/mL) Subjects received a 1 mg/kg IV bolus of 1:1 propofol/ketamine mixture followed by 0.5 mg/kg every 3 to 5 minutes as needed to achieve and maintain adequate sedation		Deep sedation using 4:1 propofol to ketamine mixture (prepared with propofol 10 mg/mL and ketamine 10mg/mL) Subjects received a 1 mg/kg IV bolus of 4:1 propofol/ketamine mixture followed by 0.5 mg/kg every 3 to 5 minutes as needed to achieve and maintain adequate sedation
All Cause Mortality
	Propofol		1:1 Propofol/Ketamine		4:1 Propofol/Ketamine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Propofol		1:1 Propofol/Ketamine		4:1 Propofol/Ketamine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/90 (0%)		0/85 (0%)		0/96 (0%)
Other (Not Including Serious) Adverse Events
	Propofol		1:1 Propofol/Ketamine		4:1 Propofol/Ketamine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/90 (0%)		0/85 (0%)		0/96 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.