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.
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
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.
- ≤ 6 years of age
- cardiac surgical procedure
- Indwelling arterial line or central venous line for blood sampling
- patients with known hepatic dysfunction(>3 times normal AST & ALT)
- clinically significant alteration (as determined by the investigator) hemoglobin or
- patients receiving medications known to be potent inhibitors or inducers of CYP3A4
- patients with significant malnutrition (< 1%tile for age-adjusted weight)
- patients enrolled in other studies that require frequent blood sampling during and
after cardiac surgery
- any contraindication for ketamine administration
- ketamine administration within the previous 24 hours
- Patients with known history of pulmonary hypertension