Anesthesia
Conditions
Keywords
Ketamine, Propofol, Children, Pediatrics, Upper endoscopy
Brief summary
The purpose of this study is to examine the dose-response relationship of ketamine in combination with propofol.
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.
Interventions
DRUGKetamine
DRUGPropofol
Sponsors
The Hospital for Sick Children
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
3 Years to 13 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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) |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Propofol | 14 |
| 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.
Ketamine
Propofol | 14 |
| 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.
Ketamine
Propofol | 13 |
| 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.
Ketamine
Propofol | 14 |
| Total | 55 |
Baseline characteristics
| Characteristic | Ketamine 0 mg/kg | Ketamine 0.25 mg/kg | Ketamine 0.5 mg/kg | Ketamine 1.0 mg/kg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 8.4 years STANDARD_DEVIATION 2.8 | 8.9 years STANDARD_DEVIATION 2.7 | 8.9 years STANDARD_DEVIATION 2.1 | 8.9 years STANDARD_DEVIATION 2.5 | 8.8 years STANDARD_DEVIATION 2.5 |
| Sex/Gender, Customized | NA Participants | NA Participants | NA Participants | NA Participants | NA Participants |
| Weight | 30.1 kg STANDARD_DEVIATION 12.4 | 28.5 kg STANDARD_DEVIATION 8.9 | 29.5 kg STANDARD_DEVIATION 0.9 | 30.0 kg STANDARD_DEVIATION 10.7 | 29.5 kg STANDARD_DEVIATION 10.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 14 | 0 / 13 | 0 / 14 |
| other Total, other adverse events | 7 / 14 | 8 / 14 | 10 / 13 | 11 / 14 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 | 0 / 13 | 0 / 14 |
Outcome results
Primary
Dose of Propofol Required to Prevent Movement (Response) to Insertion of Endoscope Into the Patient's 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
Time frame: This outcome is measured at the time of insertion of the endoscope into the esophagus.
Population: Dose of propofol required to prevent movement upon insertion of endoscope
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ketamine 0 mg/kg | Dose of Propofol Required to Prevent Movement (Response) to Insertion of Endoscope Into the Patient's Esophagus | 6.1 mg/kg |
| Ketamine 0.25 mg/kg | Dose of Propofol Required to Prevent Movement (Response) to Insertion of Endoscope Into the Patient's Esophagus | 4.5 mg/kg |
| Ketamine 0.5 mg/kg | Dose of Propofol Required to Prevent Movement (Response) to Insertion of Endoscope Into the Patient's Esophagus | 4.7 mg/kg |
| Ketamine 1.0 mg/kg | Dose of Propofol Required to Prevent Movement (Response) to Insertion of Endoscope Into the Patient's Esophagus | 1.1 mg/kg |
Secondary
Duration of Apnea After Propofol Administration
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine 0 mg/kg | Duration of Apnea After Propofol Administration | 59 seconds | Standard Deviation 26 |
| Ketamine 0.25 mg/kg | Duration of Apnea After Propofol Administration | 45 seconds | Standard Deviation 20 |
| Ketamine 0.5 mg/kg | Duration of Apnea After Propofol Administration | 57 seconds | Standard Deviation 19 |
| Ketamine 1.0 mg/kg | Duration of Apnea After Propofol Administration | 39 seconds | Standard Deviation 12 |
Secondary
Incidence of Adverse Respiratory Events During the Procedure
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
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ketamine 0 mg/kg | Incidence of Adverse Respiratory Events During the Procedure | Desaturation requiring supplemental oxygen | 11 Participants |
| Ketamine 0 mg/kg | Incidence of Adverse Respiratory Events During the Procedure | Need for airway management | 1 Participants |
| Ketamine 0.25 mg/kg | Incidence of Adverse Respiratory Events During the Procedure | Need for airway management | 1 Participants |
| Ketamine 0.25 mg/kg | Incidence of Adverse Respiratory Events During the Procedure | Desaturation requiring supplemental oxygen | 10 Participants |
| Ketamine 0.5 mg/kg | Incidence of Adverse Respiratory Events During the Procedure | Desaturation requiring supplemental oxygen | 11 Participants |
| Ketamine 0.5 mg/kg | Incidence of Adverse Respiratory Events During the Procedure | Need for airway management | 2 Participants |
| Ketamine 1.0 mg/kg | Incidence of Adverse Respiratory Events During the Procedure | Desaturation requiring supplemental oxygen | 9 Participants |
| Ketamine 1.0 mg/kg | Incidence of Adverse Respiratory Events During the Procedure | Need for airway management | 1 Participants |
Secondary
Incidence of Side Effects and Complications During the Recovery Period
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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ketamine 0 mg/kg | Incidence of Side Effects and Complications During the Recovery Period | Nystagmus/visual disturbance | 3 Participants |
| Ketamine 0 mg/kg | Incidence of Side Effects and Complications During the Recovery Period | Nausea/vomiting | 0 Participants |
| Ketamine 0 mg/kg | Incidence of Side Effects and Complications During the Recovery Period | Emergence delirium | 0 Participants |
| Ketamine 0 mg/kg | Incidence of Side Effects and Complications During the Recovery Period | Dizziness | 6 Participants |
| Ketamine 0 mg/kg | Incidence of Side Effects and Complications During the Recovery Period | Hallucinations | 0 Participants |
| Ketamine 0.25 mg/kg | Incidence of Side Effects and Complications During the Recovery Period | Dizziness | 7 Participants |
| Ketamine 0.25 mg/kg | Incidence of Side Effects and Complications During the Recovery Period | Nystagmus/visual disturbance | 5 Participants |
| Ketamine 0.25 mg/kg | Incidence of Side Effects and Complications During the Recovery Period | Emergence delirium | 0 Participants |
| Ketamine 0.25 mg/kg | Incidence of Side Effects and Complications During the Recovery Period | Nausea/vomiting | 0 Participants |
| Ketamine 0.25 mg/kg | Incidence of Side Effects and Complications During the Recovery Period | Hallucinations | 0 Participants |
| Ketamine 0.5 mg/kg | Incidence of Side Effects and Complications During the Recovery Period | Dizziness | 8 Participants |
| Ketamine 0.5 mg/kg | Incidence of Side Effects and Complications During the Recovery Period | Hallucinations | 1 Participants |
| Ketamine 0.5 mg/kg | Incidence of Side Effects and Complications During the Recovery Period | Nausea/vomiting | 2 Participants |
| Ketamine 0.5 mg/kg | Incidence of Side Effects and Complications During the Recovery Period | Nystagmus/visual disturbance | 3 Participants |
| Ketamine 0.5 mg/kg | Incidence of Side Effects and Complications During the Recovery Period | Emergence delirium | 0 Participants |
| Ketamine 1.0 mg/kg | Incidence of Side Effects and Complications During the Recovery Period | Nystagmus/visual disturbance | 9 Participants |
| Ketamine 1.0 mg/kg | Incidence of Side Effects and Complications During the Recovery Period | Nausea/vomiting | 4 Participants |
| Ketamine 1.0 mg/kg | Incidence of Side Effects and Complications During the Recovery Period | Hallucinations | 0 Participants |
| Ketamine 1.0 mg/kg | Incidence of Side Effects and Complications During the Recovery Period | Dizziness | 9 Participants |
| Ketamine 1.0 mg/kg | Incidence of Side Effects and Complications During the Recovery Period | Emergence delirium | 0 Participants |