Ketamine Pharmacokinetics in Children Having Heart 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.

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Key information

Conditions

C.Surgical Procedure; Cardiac

Age range

1 day–6 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

ketamine

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.

Primary outcomes

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

Sponsors and collaborators

Lead sponsor

Arkansas Children's Hospital Research Institute

Other

Registry information

Official study title

Ketamine Pharmacokinetics in Children Undergoing Cardiac Surgery

Important dates

Study start: 2006
Primary completion: 2009
Study completion: 2009
First posted: Jan 21, 2008
Registry last updated: Feb 27, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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