The Pk of IV Ketamine in Children With Heart Disease
Conditions
Keywords
anesthesia, children, ketamine, pharmacokinetics
Brief summary
Dosing of medications is based on the plasma level achieved with a given dose and how long the medicine remains in the body. This study is called pharmacokinetics-that is, what the body does to the medication. Ketamine is an intravenous medication used for anesthesia and sedation in children. However the pharmacokinetics of Ketamine has not been systematically studied. We propose to study the pharmacokinetics of ketamine in different age groups of children ranging from infants to teenagers.
Detailed description
This is an open label study that will be conducted in infants and children presenting for procedures (eg., surgery or cardiac catheterization) at Stanford and Lucile Packard Children's hospital in California and at The Children's Hospital in Denver, CO. Patients with abnormal kidney or liver functions will be excluded from the study as the dysfunction in these organs affects the clearance of medications from the body and affects dosing. Preterm neonates will also be excluded. All patients will be premedicated and anesthetised at the discretion of the anesthesia faculty providing clinical care for the child. Once the patient's procedure is underway, a 0.5 cc blood sample will be drawn from an intravenous line. This is the preload blood sample (T0). Following this a 2mg/kg intravenous bolus of Ketamine will be administered over 5 minutes (this is the usual dose and manner in which ketamine is administered). Five minutes after the bolus, timed blood samples will be drawn at the following intervals: 5, 10, 15, 20, 30, 45, 60, 120, 180, 240, 300, 360 and 720 minutes after bolus. (Total 14 blood samples; total blood required is 7 mls for the entire study). When the procedure is completed the anesthesiologist will awaken the patient as per their usual practice. Blood samples that still need drawing will be done in the post-anesthesia recovery room or intensive care or ward-any location where the patient is likely to remain after the surgery.
Interventions
DRUGketamine hydrochloride
Open label pharmacokinetic study to be conducted in infants and children presenting for medical procedures (eg., surgery or cardiac catheterization). After the start of the procedure, a 0.5 cc preload blood sample (T0) will be drawn from an IV line. Then a 2 mg/kg IV bolus of Ketamine will be administered over 5 minutes. Timed 0.5 ml blood samples will be drawn at the following intervals: 5, 10, 15, 20, 30, 45, 60, 120, 180, 240, 300, 360 and 720 minutes after bolus.
Sponsors
University of Colorado, Denver
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 17 Years
Healthy volunteers
No
Inclusion criteria
* Term infants (38 weeks gestation)and infants and children up to age 18 years. * Patients who require procedures that necessitate at least 8 hours in the hospital and those being admitted after procedure will be eligible to participate. * Patients who will receive ketamine as part of their standard anesthesia regimen.
Exclusion criteria
* Preterm neonates * Liver Disease * Kidney disease * Heart failure * Sepsis * Patients receiving anticonvulsants or barbiturates
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Clearance and Intercompartmental Clearance | 5, 10, 15, 20, 30, 45, 60, 120, 180, 240, 300, 360 and 720 minutes after bolus. | pK analysis of ketamine in children with pre-existing congenital heart disease following a single dose of ketamine in order to rationalize an effective 2-h anesthetic medication, personalized based on cardiac function and age. Total Clearance and Intercompartmental Clearance were analyzed using Bootstrap model. |
| Central and Peripheral Volume of Distribution | 5, 10, 15, 20, 30, 45, 60, 120, 180, 240, 300, 360 and 720 minutes after bolus. | pK analysis of ketamine in children with pre-existing congenital heart disease following a single dose of ketamine in order to rationalize an effective 2-h anesthetic medication, personalized based on cardiac function and age. Central and Peripheral Volume of Distribution were analyzed using Bootstrap model. |
| Residual Error | 5, 10, 15, 20, 30, 45, 60, 120, 180, 240, 300, 360 and 720 minutes after bolus. | pK analysis of ketamine in children with pre-existing congenital heart disease following a single dose of ketamine in order to rationalize an effective 2-h anesthetic medication, personalized based on cardiac function and age. Residual Error was analyzed using Bootstrap model. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ketamine Then a 2 mg/kg IV bolus of Ketamine hydrochloride will be given.
ketamine hydrochloride: Open label pharmacokinetic study to be conducted in infants and children presenting for medical procedures (eg., surgery or cardiac catheterization). After the start of the procedure, a 0.5 cc preload blood sample (T0) will be drawn from an IV line. Then a 2 mg/kg IV bolus of Ketamine will be administered over 5 minutes. Timed 0.5 ml blood samples will be drawn at the following intervals: 5, 10, 15, 20, 30, 45, 60, 120, 180, 240, 300, 360 and 720 minutes after bolus. | 21 |
| Total | 21 |
Baseline characteristics
| Characteristic | Ketamine |
|---|---|
| Age, Continuous | 6.44 years STANDARD_DEVIATION 4.59 |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 21 |
| serious Total, serious adverse events | 0 / 21 |
Outcome results
Primary
Central and Peripheral Volume of Distribution
pK analysis of ketamine in children with pre-existing congenital heart disease following a single dose of ketamine in order to rationalize an effective 2-h anesthetic medication, personalized based on cardiac function and age. Central and Peripheral Volume of Distribution were analyzed using Bootstrap model.
Time frame: 5, 10, 15, 20, 30, 45, 60, 120, 180, 240, 300, 360 and 720 minutes after bolus.
Population: Children up to 18 years of age children with pre-existing congenital heart disease
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Single Group Assignment | Central and Peripheral Volume of Distribution | Central Volume of Distribution | 57.6 L/70kg |
| Single Group Assignment | Central and Peripheral Volume of Distribution | Peripheral Volume of Distribution | 149 L/70kg |
Primary
Residual Error
pK analysis of ketamine in children with pre-existing congenital heart disease following a single dose of ketamine in order to rationalize an effective 2-h anesthetic medication, personalized based on cardiac function and age. Residual Error was analyzed using Bootstrap model.
Time frame: 5, 10, 15, 20, 30, 45, 60, 120, 180, 240, 300, 360 and 720 minutes after bolus.
Population: Children up to 18 years of age children with pre-existing congenital heart disease
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Single Group Assignment | Residual Error | 16.1 proportional % |
Primary
Total Clearance and Intercompartmental Clearance
pK analysis of ketamine in children with pre-existing congenital heart disease following a single dose of ketamine in order to rationalize an effective 2-h anesthetic medication, personalized based on cardiac function and age. Total Clearance and Intercompartmental Clearance were analyzed using Bootstrap model.
Time frame: 5, 10, 15, 20, 30, 45, 60, 120, 180, 240, 300, 360 and 720 minutes after bolus.
Population: Children up to 18 years of age children with pre-existing congenital heart disease
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Single Group Assignment | Total Clearance and Intercompartmental Clearance | Total Clearance | 60.0 L/h/70kg |
| Single Group Assignment | Total Clearance and Intercompartmental Clearance | Intercompartmental Clearance | 70.8 L/h/70kg |