Ketamine Pharmacokinetics in Children Having Heart Surgery
What are the pharmacokinetics of ketamine in infants and children requiring ketamine for induction of anesthesia for cardiac surgery that requires CPB? Specific Aim 1: To determine the pharmacokinetic parameters of a single intravenous bolus dose of ketamine in infants and children undergoing cardiac surgery with and without CPB (cardio-pulmonary bypass).
Specific Aim 2: To describe the disposition of ketamine's primary active metabolite, norketamine,following a single intravenous bolus dose of ketamine in infants and children undergoing cardiac surgery with and without CPB.
Specific Aim 3: To determine the relationship between ketamine and norketamine pharmacokinetic parameters and age as well as CPB time.
|Study Design:||Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
|Official Title:||Ketamine Pharmacokinetics in Children Undergoing Cardiac Surgery|
- To measure how long ketamine remains in blood after a single dose of ketamine is given (venous) to children undergoing cardiac surgery on cardiopulmonary bypass (CPB)compared to levels of children undergoing cardiac surgery without CPB. [ Time Frame: Length of time ketamine remains in the blood ] [ Designated as safety issue: No ]
|Study Start Date:||June 2006|
|Study Completion Date:||December 2009|
|Primary Completion Date:||January 2009 (Final data collection date for primary outcome measure)|
No Intervention: Ketamine Pharmacokinetics
The pharmacokinetic action of Ketamine used in Children having heart surgery.
subject will then receive an intravenous bolus dose of ketamine 2 mg/kg as a rapid intravenous bolus, over less than two minutes just prior to CPB. In the non-CPB patients, ketamine will be administered just prior to the skin incision. All doses will be rounded to the nearest tenth of a milligram. Timed blood samples will be collected at standardized times after the completion of the ketamine infusion and samples will be obtained from an indwelling arterial line. Each blood sample for pharmacokinetic analysis will be 1 mL.
The role of ketamine in pediatric anesthesia is well established. It is one of the most commonly used agents for conscious sedation in pediatrics. Its widespread use stems for its abrupt onset of action and brief duration of sedation. There is limited ketamine pharmacokinetic data in children and none to our knowledge in infants and young children who will be given an intravenous bolus dose before a surgical procedure that includes cardiopulmonary bypass.
Ketamine is marketed as a racemic mixture (50:50 mixture of S- and R-ketamine enantiomers).
Ketamine undergoes N-demethylation (CYP3B6, 2C9, and 3A4) to its primary active metabolite,norketamine, with minor inactive metabolites, dehydroxynorketamine, generated secondary to direct oxidation. Ketamine exhibits a high intrinsic clearance with hepatic clearance dependent on hepatic blood flow under normal circumstances. One inherent disadvantage associated with the use of cardiopulmonary bypass (CPB) is the potential for organ dysfunction post-operatively.
We propose an open-label controlled study describing the disposition of ketamine in 28 infants and children who will be undergoing cardiac surgery with (n=16) and without (n=12) CPB. We anticipate that cardiopulmonary bypass alters the pharmacokinetics of ketamine.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00598195
|United States, Arkansas|
|Arkansas Children's Hospital|
|Little Rock, Arkansas, United States, 72202|
|Principal Investigator:||Adnan T Bhutta, M.D.||Arkansas Children's Hospital and University of Arkansas for Medical Sciences|