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Ketamine Pharmacokinetics in Children Having Heart Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00598195
Recruitment Status : Completed
First Posted : January 21, 2008
Last Update Posted : February 27, 2013
Information provided by (Responsible Party):
Arkansas Children's Hospital Research Institute

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.

Condition or disease Intervention/treatment Phase
C.Surgical Procedure; Cardiac Drug: Ketamine Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Ketamine Pharmacokinetics in Children Undergoing Cardiac Surgery
Study Start Date : June 2006
Actual Primary Completion Date : January 2009
Actual Study Completion Date : December 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Surgery
Drug Information available for: Ketamine

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.

Primary Outcome Measures :
  1. 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 6 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00598195

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United States, Arkansas
Arkansas Children's Hospital
Little Rock, Arkansas, United States, 72202
Sponsors and Collaborators
Arkansas Children's Hospital Research Institute
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Principal Investigator: Adnan T Bhutta, M.D. Arkansas Children's Hospital and University of Arkansas for Medical Sciences

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Responsible Party: Arkansas Children's Hospital Research Institute Identifier: NCT00598195     History of Changes
Other Study ID Numbers: 57839
First Posted: January 21, 2008    Key Record Dates
Last Update Posted: February 27, 2013
Last Verified: February 2013
Keywords provided by Arkansas Children's Hospital Research Institute:
Cardiopulmonary bypass (CPB)
ketamine/norketamine pharmacokinetic parameters
Additional relevant MeSH terms:
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Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action