Ketamine Pharmacokinetics in Children Having Heart Surgery

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Arkansas Children's Hospital Research Institute
ClinicalTrials.gov Identifier:
NCT00598195
First received: December 26, 2007
Last updated: February 26, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention
C.Surgical Procedure; Cardiac
Drug: Ketamine

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Arkansas Children's Hospital Research Institute:

Primary Outcome Measures:
  • 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 ]

Enrollment: 18
Study Start Date: June 2006
Study Completion Date: December 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Other Name: 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.

  Eligibility

Ages Eligible for Study:   up to 6 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00598195

Locations
United States, Arkansas
Arkansas Children's Hospital
Little Rock, Arkansas, United States, 72202
Sponsors and Collaborators
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
  More Information

No publications provided

Responsible Party: Arkansas Children's Hospital Research Institute
ClinicalTrials.gov Identifier: NCT00598195     History of Changes
Other Study ID Numbers: 57839
Study First Received: December 26, 2007
Last Updated: February 26, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Arkansas Children's Hospital Research Institute:
Ketamine
Phamacokinetics
Cardiopulmonary bypass (CPB)
ketamine/norketamine pharmacokinetic parameters

Additional relevant MeSH terms:
Ketamine
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on April 17, 2014