Ketamine Pharmacokinetics in Children Having Heart Surgery

Ketamine Pharmacokinetics in Children Undergoing Cardiac 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 Overview

• Status: Completed
• Conditions: C.Surgical Procedure; Cardiac
• Intervention / Treatment: Drug: Ketamine

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 6 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

No Intervention: Ketamine Pharmacokinetics; The pharmacokinetic action of Ketamine used in Children having heart surgery.

Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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.	Length of time ketamine remains in the blood

Collaborators and Investigators

• Sponsor: Arkansas Children's Hospital Research Institute
• Investigators: Principal Investigator: Adnan T Bhutta, M.D., Arkansas Children's Hospital and University of Arkansas for Medical Sciences

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: December 26, 2007
• First Submitted That Met QC Criteria: January 18, 2008
• First Posted (Estimate): January 21, 2008

Study Record Updates

• Last Update Posted (Estimate): February 27, 2013
• Last Update Submitted That Met QC Criteria: February 26, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: Ketamine; Cardiopulmonary bypass (CPB); Phamacokinetics; ketamine/norketamine pharmacokinetic parameters
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 57839