Ketamine and Propofol for Upper Endoscopy

• Sponsor: The Hospital for Sick Children (Other)
• Overall Status: Completed
• CT.gov ID: NCT02295553
• Collaborator: (none)
• Enrollment: 56
• Location: 1
• Arms: 4
• Actual Duration (Months): 41
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

The purpose of this study is to examine the dose-response relationship of ketamine in combination with propofol.

Condition or Disease	Intervention/Treatment	Phase
Anesthesia	Drug: Ketamine; Drug: Propofol	Phase 4

Detailed Description

Direct visualization of the esophagus, stomach and small intestine is performed using a scope that is inserted while the patient is under under deep sedation or general anesthesia. The most common method of providing general anesthesia for upper endoscopy is intravenous administration of medications such as propofol, often in combination with other medications such as fentanyl, midazolam, remifentanil or ketamine. One study found that the combination of propofol and ketamine provides better conditions (less patient movement, more stable heart and breathing) but more side effects afterwards compared to propofol and fentanyl.

Study Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Co-administration of Ketamine and Propofol for Upper Endoscopy in Children: a Dose-finding Study
• Actual Study Start Date: Jul 1, 2013
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ketamine 0 mg/kg Ketamine dose will be 0 mg/kg. Propofol dose for the first patient will be 4 mg/kg. Doses for the subsequent patients will increase or decrease by 1.6 mg/kg using the Dixon Up and Down method.	Drug: Propofol
Experimental: Ketamine 0.25 mg/kg Ketamine dose will be 0.25 mg/kg. Propofol dose for the first patient will be 3 mg/kg. Doses for the subsequent patients will increase or decrease by 1.2 mg/kg using the Dixon Up and Down method.	Drug: Ketamine; Drug: Propofol
Experimental: Ketamine 0.5 mg/kg Ketamine dose will be 0.5 mg/kg. Propofol dose for the first patient will be 2.5 mg/kg. Doses for the subsequent patients will increase or decrease by 0.8 mg/kg using the Dixon Up and Down method.	Drug: Ketamine; Drug: Propofol
Experimental: Ketamine 1.0 mg/kg Ketamine dose will be 1.0 mg/kg. Propofol dose for the first patient will be 2 mg/kg. Doses for the subsequent patients will increase or decrease by 0.4 mg/kg using the Dixon Up and Down method.	Drug: Ketamine; Drug: Propofol

Outcome Measures

Primary Outcome Measures

1. Dose of Propofol Required to Prevent Movement (Response) to Insertion of Endoscope Into the Patient's Esophagus [This outcome is measured at the time of insertion of the endoscope into the esophagus.]

   The objective is to determine the effective bolus dose in 50% of subjects (ED50) of propofol in combination with ketamine 0, 0.25, 0.5 and 1 mg/kg that produces an adequate depth of anesthesia to prevent minimal or no movement on endoscope insertion in children

Secondary Outcome Measures

1. Duration of Apnea After Propofol Administration [This outcome will be measured after propofol is administered until the end of the procedure.]

   The patient will be observed for apnea after propofol is administered until the endoscopy procedure is complete. Duration of apnea will be recorded.

2. Incidence of Adverse Respiratory Events During the Procedure [From induction of anesthesia until endoscopy procedure is complete]

   Any respiratory adverse event including desaturation <95 requiring oxygen administration or need for airway management maneuvers (jaw thrust, bag/mask ventilation) to relieve upper airway obstruction

3. Incidence of Side Effects and Complications During the Recovery Period [From the time procedure is complete until discharge from hospital with an average time of 1 hour.]

   Side effects including: hallucinations and/or emergence delirium measured by the Pediatric Anesthesia Emergence Delirium (PAED) scale dizziness nausea and/or vomiting administration of antiemetic pain > 3/10 at any site (measured using age appropriate scale) time to discharge readiness using established criteria reasons for delayed discharge (if any)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 13 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 3-13 years

• Receiving general anesthesia for upper endoscopy

Exclusion Criteria:

• Known or possible difficult airway

• BMI > 35

• Weight < 10 kg

• Sedative premedication required

• Known contraindication to ketamine or propofol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8

Sponsors and Collaborators

• The Hospital for Sick Children

Investigators

• Principal Investigator: Jason Hayes, The Hospital for Sick Children

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jason Hayes, Staff Anaesthesiologist, The Hospital for Sick Children
• ClinicalTrials.gov Identifier: NCT02295553
• Other Study ID Numbers: 1000036780
• First Posted: Nov 20, 2014
• Last Update Posted: Jun 10, 2019
• Last Verified: Mar 1, 2019

• Keywords provided by Jason Hayes, Staff Anaesthesiologist, The Hospital for Sick Children: Ketamine; Propofol; Children; Pediatrics; Upper endoscopy
• Additional relevant MeSH terms: Ketamine; Propofol

Study Results

Participant Flow

Arm/Group Title	Ketamine 0 mg/kg	Ketamine 0.25 mg/kg	Ketamine 0.5 mg/kg	Ketamine 1.0 mg/kg
Arm/Group Description	Ketamine dose will be 0 mg/kg. Propofol dose for the first patient will be 4 mg/kg. Doses for the subsequent patients will increase or decrease by 1.6 mg/kg using the Dixon Up and Down method. Propofol	Ketamine dose will be 0.25 mg/kg. Propofol dose for the first patient will be 3 mg/kg. Doses for the subsequent patients will increase or decrease by 1.2 mg/kg using the Dixon Up and Down method. Ketamine Propofol	Ketamine dose will be 0.5 mg/kg. Propofol dose for the first patient will be 2.5 mg/kg. Doses for the subsequent patients will increase or decrease by 0.8 mg/kg using the Dixon Up and Down method. Ketamine Propofol	Ketamine dose will be 1.0 mg/kg. Propofol dose for the first patient will be 2 mg/kg. Doses for the subsequent patients will increase or decrease by 0.4 mg/kg using the Dixon Up and Down method. Ketamine Propofol
Period Title: Overall Study
STARTED	14	14	14	14
COMPLETED	14	14	13	13
NOT COMPLETED	0	0	1	1

Baseline Characteristics

Arm/Group Title	Ketamine 0 mg/kg	Ketamine 0.25 mg/kg	Ketamine 0.5 mg/kg	Ketamine 1.0 mg/kg	Total
Arm/Group Description	Ketamine dose will be 0 mg/kg. Propofol dose for the first patient will be 4 mg/kg. Doses for the subsequent patients will increase or decrease by 1.6 mg/kg using the Dixon Up and Down method. Propofol	Ketamine dose will be 0.25 mg/kg. Propofol dose for the first patient will be 3 mg/kg. Doses for the subsequent patients will increase or decrease by 1.2 mg/kg using the Dixon Up and Down method. Ketamine Propofol	Ketamine dose will be 0.5 mg/kg. Propofol dose for the first patient will be 2.5 mg/kg. Doses for the subsequent patients will increase or decrease by 0.8 mg/kg using the Dixon Up and Down method. Ketamine Propofol	Ketamine dose will be 1.0 mg/kg. Propofol dose for the first patient will be 2 mg/kg. Doses for the subsequent patients will increase or decrease by 0.4 mg/kg using the Dixon Up and Down method. Ketamine Propofol	Total of all reporting groups
Overall Participants	14	14	13	14	55
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.4 (2.8)	8.9 (2.7)	8.9 (2.1)	8.9 (2.5)	8.8 (2.5)
Sex/Gender, Customized (Count of Participants)
Count of Participants [Participants]	NA NaN	NA NaN	NA NaN	NA NaN	NA NaN
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	30.1 (12.4)	28.5 (8.9)	29.5 (0.9)	30.0 (10.7)	29.5 (10.3)

Outcome Measures

1. Primary Outcome

Title	Dose of Propofol Required to Prevent Movement (Response) to Insertion of Endoscope Into the Patient's Esophagus
Description	The objective is to determine the effective bolus dose in 50% of subjects (ED50) of propofol in combination with ketamine 0, 0.25, 0.5 and 1 mg/kg that produces an adequate depth of anesthesia to prevent minimal or no movement on endoscope insertion in children
Time Frame	This outcome is measured at the time of insertion of the endoscope into the esophagus.

Outcome Measure Data

Analysis Population Description

Dose of propofol required to prevent movement upon insertion of endoscope

Arm/Group Title	Ketamine 0 mg/kg	Ketamine 0.25 mg/kg	Ketamine 0.5 mg/kg	Ketamine 1.0 mg/kg
Arm/Group Description	Ketamine dose will be 0 mg/kg. Propofol dose for the first patient will be 4 mg/kg. Doses for the subsequent patients will increase or decrease by 1.6 mg/kg using the Dixon Up and Down method. Propofol	Ketamine dose will be 0.25 mg/kg. Propofol dose for the first patient will be 3 mg/kg. Doses for the subsequent patients will increase or decrease by 1.2 mg/kg using the Dixon Up and Down method. Ketamine Propofol	Ketamine dose will be 0.5 mg/kg. Propofol dose for the first patient will be 2.5 mg/kg. Doses for the subsequent patients will increase or decrease by 0.8 mg/kg using the Dixon Up and Down method. Ketamine Propofol	Ketamine dose will be 1.0 mg/kg. Propofol dose for the first patient will be 2 mg/kg. Doses for the subsequent patients will increase or decrease by 0.4 mg/kg using the Dixon Up and Down method. Ketamine Propofol
Measure Participants	14	14	13	14
Mean (95% Confidence Interval) [mg/kg]	6.1	4.5	4.7	1.1

2. Secondary Outcome

Title	Duration of Apnea After Propofol Administration
Description	The patient will be observed for apnea after propofol is administered until the endoscopy procedure is complete. Duration of apnea will be recorded.
Time Frame	This outcome will be measured after propofol is administered until the end of the procedure.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine 0 mg/kg	Ketamine 0.25 mg/kg	Ketamine 0.5 mg/kg	Ketamine 1.0 mg/kg
Arm/Group Description	Ketamine dose will be 0 mg/kg. Propofol dose for the first patient will be 4 mg/kg. Doses for the subsequent patients will increase or decrease by 1.6 mg/kg using the Dixon Up and Down method. Propofol	Ketamine dose will be 0.25 mg/kg. Propofol dose for the first patient will be 3 mg/kg. Doses for the subsequent patients will increase or decrease by 1.2 mg/kg using the Dixon Up and Down method. Ketamine Propofol	Ketamine dose will be 0.5 mg/kg. Propofol dose for the first patient will be 2.5 mg/kg. Doses for the subsequent patients will increase or decrease by 0.8 mg/kg using the Dixon Up and Down method. Ketamine Propofol	Ketamine dose will be 1.0 mg/kg. Propofol dose for the first patient will be 2 mg/kg. Doses for the subsequent patients will increase or decrease by 0.4 mg/kg using the Dixon Up and Down method. Ketamine Propofol
Measure Participants	14	14	13	14
Mean (Standard Deviation) [seconds]	59 (26)	45 (20)	57 (19)	39 (12)

3. Secondary Outcome

Title	Incidence of Adverse Respiratory Events During the Procedure
Description	Any respiratory adverse event including desaturation <95 requiring oxygen administration or need for airway management maneuvers (jaw thrust, bag/mask ventilation) to relieve upper airway obstruction
Time Frame	From induction of anesthesia until endoscopy procedure is complete

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine 0 mg/kg	Ketamine 0.25 mg/kg	Ketamine 0.5 mg/kg	Ketamine 1.0 mg/kg
Arm/Group Description	Ketamine dose will be 0 mg/kg. Propofol dose for the first patient will be 4 mg/kg. Doses for the subsequent patients will increase or decrease by 1.6 mg/kg using the Dixon Up and Down method. Propofol	Ketamine dose will be 0.25 mg/kg. Propofol dose for the first patient will be 3 mg/kg. Doses for the subsequent patients will increase or decrease by 1.2 mg/kg using the Dixon Up and Down method. Ketamine Propofol	Ketamine dose will be 0.5 mg/kg. Propofol dose for the first patient will be 2.5 mg/kg. Doses for the subsequent patients will increase or decrease by 0.8 mg/kg using the Dixon Up and Down method. Ketamine Propofol	Ketamine dose will be 1.0 mg/kg. Propofol dose for the first patient will be 2 mg/kg. Doses for the subsequent patients will increase or decrease by 0.4 mg/kg using the Dixon Up and Down method. Ketamine Propofol
Measure Participants	14	14	13	14
Desaturation requiring supplemental oxygen	11 78.6%	10 71.4%	11 84.6%	9 64.3%
Need for airway management	1 7.1%	1 7.1%	2 15.4%	1 7.1%

4. Secondary Outcome

Title	Incidence of Side Effects and Complications During the Recovery Period
Description	Side effects including: hallucinations and/or emergence delirium measured by the Pediatric Anesthesia Emergence Delirium (PAED) scale dizziness nausea and/or vomiting administration of antiemetic pain > 3/10 at any site (measured using age appropriate scale) time to discharge readiness using established criteria reasons for delayed discharge (if any)
Time Frame	From the time procedure is complete until discharge from hospital with an average time of 1 hour.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine 0 mg/kg	Ketamine 0.25 mg/kg	Ketamine 0.5 mg/kg	Ketamine 1.0 mg/kg
Arm/Group Description	Ketamine dose will be 0 mg/kg. Propofol dose for the first patient will be 4 mg/kg. Doses for the subsequent patients will increase or decrease by 1.6 mg/kg using the Dixon Up and Down method. Propofol	Ketamine dose will be 0.25 mg/kg. Propofol dose for the first patient will be 3 mg/kg. Doses for the subsequent patients will increase or decrease by 1.2 mg/kg using the Dixon Up and Down method. Ketamine Propofol	Ketamine dose will be 0.5 mg/kg. Propofol dose for the first patient will be 2.5 mg/kg. Doses for the subsequent patients will increase or decrease by 0.8 mg/kg using the Dixon Up and Down method. Ketamine Propofol	Ketamine dose will be 1.0 mg/kg. Propofol dose for the first patient will be 2 mg/kg. Doses for the subsequent patients will increase or decrease by 0.4 mg/kg using the Dixon Up and Down method. Ketamine Propofol
Measure Participants	14	14	13	14
Hallucinations	0 0%	0 0%	1 7.7%	0 0%
Nausea/vomiting	0 0%	0 0%	2 15.4%	4 28.6%
Dizziness	6 42.9%	7 50%	8 61.5%	9 64.3%
Nystagmus/visual disturbance	3 21.4%	5 35.7%	3 23.1%	9 64.3%
Emergence delirium	0 0%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	From the time patient enters recovery room to discharge from hospital
Arm/Group Title	Ketamine 0 mg/kg		Ketamine 0.25 mg/kg		Ketamine 0.5 mg/kg		Ketamine 1.0 mg/kg
Arm/Group Description	Ketamine dose will be 0 mg/kg. Propofol dose for the first patient will be 4 mg/kg. Doses for the subsequent patients will increase or decrease by 1.6 mg/kg using the Dixon Up and Down method. Propofol		Ketamine dose will be 0.25 mg/kg. Propofol dose for the first patient will be 3 mg/kg. Doses for the subsequent patients will increase or decrease by 1.2 mg/kg using the Dixon Up and Down method. Ketamine Propofol		Ketamine dose will be 0.5 mg/kg. Propofol dose for the first patient will be 2.5 mg/kg. Doses for the subsequent patients will increase or decrease by 0.8 mg/kg using the Dixon Up and Down method. Ketamine Propofol		Ketamine dose will be 1.0 mg/kg. Propofol dose for the first patient will be 2 mg/kg. Doses for the subsequent patients will increase or decrease by 0.4 mg/kg using the Dixon Up and Down method. Ketamine Propofol
All Cause Mortality
	Ketamine 0 mg/kg		Ketamine 0.25 mg/kg		Ketamine 0.5 mg/kg		Ketamine 1.0 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/14 (0%)		0/13 (0%)		0/14 (0%)
Serious Adverse Events
	Ketamine 0 mg/kg		Ketamine 0.25 mg/kg		Ketamine 0.5 mg/kg		Ketamine 1.0 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/14 (0%)		0/13 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Ketamine 0 mg/kg		Ketamine 0.25 mg/kg		Ketamine 0.5 mg/kg		Ketamine 1.0 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/14 (50%)		8/14 (57.1%)		10/13 (76.9%)		11/14 (78.6%)
Gastrointestinal disorders
Nausea/vomiting	0/14 (0%)		0/14 (0%)		2/13 (15.4%)		4/14 (28.6%)
Nervous system disorders
Hallucinations	0/14 (0%)		0/14 (0%)		1/13 (7.7%)		0/14 (0%)
Dizziness	6/14 (42.9%)		7/14 (50%)		8/13 (61.5%)		9/14 (64.3%)
Nystagmus/visual disturbance	3/14 (21.4%)		5/14 (35.7%)		3/13 (23.1%)		9/14 (64.3%)
Emergence delirium	0/14 (0%)		0/14 (0%)		0/13 (0%)		0/14 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.