Procedural Sedation and Analgesia
Conditions
Keywords
Ketamine, Propofol, Procedural Sedation and Analgesia
Brief summary
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
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.
Interventions
DRUGKetamine
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)
DRUGKetamine Co-administered with Propofol
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)
Sponsors
Colorado Clinical & Translational Sciences Institute
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
3 Years to 21 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Adverse Events | From enrollment through completion of follow-up, up to 7 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Recovery Time | Once Vancouver Sedation Recovery Scale Score reaches 18 or greater, on average less than 1 hour | Time until the patient has a Vancouver Sedation Recovery Scale Score of 18 or greater. |
| Efficacy of Sedation | After procedure is completed, on average less than 1 hour | Efficacy is defined as: 1. The patient does not have unpleasant recall of the procedure. 2. 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 3. 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. 4. The procedure was successful |
| Parent Satisfaction | After procedure is completed, on average less than 1 hour | Measured on a 10-point scale (1= least satisfied, 10= most satisfied) |
| Physician Performing Procedure Satisfaction | After procedure is completed, on average less than 1 hour | Measured on a 10-point scale (1= least satisfied, 10= most satisfied) |
| Nurse Satisfaction | After procedure is completed, on average less than 1 hour | Measured on a 10-point scale (1= least satisfied, 10= most satisfied) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ketamine Alone | 99 |
| Ketamine Co-Administered With Propofol | 84 |
| Total | 183 |
Baseline characteristics
| Characteristic | Total | Ketamine Alone | Ketamine Co-Administered With Propofol |
|---|---|---|---|
| Age, Categorical <=18 years | 183 Participants | 99 Participants | 84 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 6 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 32 Participants | 20 Participants | 12 Participants |
| Race (NIH/OMB) White | 134 Participants | 72 Participants | 62 Participants |
| Region of Enrollment United States | 183 participants | 99 participants | 84 participants |
| Sex: Female, Male Female | 55 Participants | 25 Participants | 30 Participants |
| Sex: Female, Male Male | 128 Participants | 74 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 38 / 99 | 33 / 84 |
| serious Total, serious adverse events | 0 / 99 | 0 / 84 |
Outcome results
Primary
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.
Time frame: From enrollment through completion of follow-up, up to 7 days
Population: Adverse events
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ketamine Alone | Frequency of Adverse Events | Respiratory depression | 12 participants |
| Ketamine Alone | Frequency of Adverse Events | Cardiovascular event | 1 participants |
| Ketamine Alone | Frequency of Adverse Events | vomiting/retching | 21 participants |
| Ketamine Alone | Frequency of Adverse Events | Unpleasant recovery reaction | 4 participants |
| Ketamine Co-Administered With Propofol | Frequency of Adverse Events | Unpleasant recovery reaction | 2 participants |
| Ketamine Co-Administered With Propofol | Frequency of Adverse Events | Respiratory depression | 15 participants |
| Ketamine Co-Administered With Propofol | Frequency of Adverse Events | vomiting/retching | 18 participants |
| Ketamine Co-Administered With Propofol | Frequency of Adverse Events | Cardiovascular event | 0 participants |
Secondary
Efficacy of Sedation
Efficacy is defined as: 1. The patient does not have unpleasant recall of the procedure. 2. 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 3. 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. 4. The procedure was successful
Time frame: After procedure is completed, on average less than 1 hour
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ketamine Alone | Efficacy of Sedation | 97 participants |
| Ketamine Co-Administered With Propofol | Efficacy of Sedation | 81 participants |
Secondary
Nurse Satisfaction
Measured on a 10-point scale (1= least satisfied, 10= most satisfied)
Time frame: After procedure is completed, on average less than 1 hour
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ketamine Alone | Nurse Satisfaction | 10 units on a scale |
| Ketamine Co-Administered With Propofol | Nurse Satisfaction | 8 units on a scale |
Secondary
Parent Satisfaction
Measured on a 10-point scale (1= least satisfied, 10= most satisfied)
Time frame: After procedure is completed, on average less than 1 hour
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ketamine Alone | Parent Satisfaction | 10 units on a scale (1-10) |
| Ketamine Co-Administered With Propofol | Parent Satisfaction | 10 units on a scale (1-10) |
Secondary
Physician Performing Procedure Satisfaction
Measured on a 10-point scale (1= least satisfied, 10= most satisfied)
Time frame: After procedure is completed, on average less than 1 hour
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ketamine Alone | Physician Performing Procedure Satisfaction | 9 units on a scale |
| Ketamine Co-Administered With Propofol | Physician Performing Procedure Satisfaction | 8 units on a scale |
Secondary
Recovery Time
Time until the patient has a Vancouver Sedation Recovery Scale Score of 18 or greater.
Time frame: Once Vancouver Sedation Recovery Scale Score reaches 18 or greater, on average less than 1 hour
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ketamine Alone | Recovery Time | 44 minutes |
| Ketamine Co-Administered With Propofol | Recovery Time | 43.5 minutes |