Ketamine Pharmacokinetics in Children Having Heart Surgery

Arkansas Children's Hospital Research Institute

Status

Completed

Conditions

C.Surgical Procedure; Cardiac

Treatments

Drug: Ketamine

Study type

Interventional

Funder types

Other

Identifiers

NCT00598195

57839

Details and patient eligibility

About

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.

Full description

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.

Enrollment

18 patients

Sex

All

Ages

1 day to 6 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

≤ 6 years of age
cardiac surgical procedure
Indwelling arterial line or central venous line for blood sampling

Exclusion criteria

patients with known hepatic dysfunction(>3 times normal AST & ALT)
clinically significant alteration (as determined by the investigator) hemoglobin or hematocrit
patients receiving medications known to be potent inhibitors or inducers of CYP3A4 and CYP2C19
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