Ketamine Pharmacokinetics in Children Having Heart Surgery

NCT ID: NCT00598195

Last Updated: 2013-02-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-06-30
• Study Completion Date: 2009-12-31

Brief Summary

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.

Detailed 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.

Conditions

C.Surgical Procedure; Cardiac

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Ketamine Pharmacokinetics

The pharmacokinetic action of Ketamine used in Children having heart surgery.

Group Type: NO_INTERVENTION

Ketamine

Intervention Type: DRUG

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.

Interventions

Ketamine

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Arkansas Children's Hospital Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Adnan T Bhutta, M.D.

Role: PRINCIPAL_INVESTIGATOR

Arkansas Children's Hospital and University of Arkansas for Medical Sciences

Locations

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Countries

United States

Other Identifiers

57839

Identifier Type: -

Identifier Source: org_study_id