Ketamine Pharmacokinetics in Children Having Heart Surgery
Condition: C.Surgical Procedure; Cardiac
Study type: Interventional

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.
    

Intervention name(s): Ketamine
Intervention type(s): Drug
Intervention description(s): 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 MeSH terms: Ketamine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care
Keywords: Ketamine; Phamacokinetics; Cardiopulmonary bypass (CPB); ketamine/norketamine pharmacokinetic parameters