Pharmacokinetics of Dexmedetomidine in Children During Cardiopulmonary Bypass (CPB)

Dexmedetomidine is increasingly used for sedation in children placed on cardiopulmonary bypass for heart surgery. It is also often used after surgery and may be particularly helpful for children with heart disease. In order for this medication to be helpful and to minimize risks associated with taking the medication, it is important to provide correct dosing for this medication. Based on evidence from studies of other medications used during heart surgery, it is likely that dosing of dexmedetomidine while on cardiopulmonary bypass is different from dosing in other settings. The purpose of this study is to evaluate how the heart-lung bypass machine affects dexmedetomidine levels in the body.

Study Overview

• Status: Completed
• Conditions: Children; Pharmacokinetics; Cardiopulmonary Bypass

• Study Type: Observational
• Enrollment (Actual): 18

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population will include children less than or equal to 2 years of age who undergo cardiopulmonary bypass and receive dexmedetomidine per standard of care during the bypass session.

Description

Inclusion Criteria:

• < 2 years of age
• Sufficient venous access to permit administration of study medication.
• Supported with cardiopulmonary bypass (CPB)
• Receiving dexmedetomidine per standard of care.
• Availability and willingness of the parent/legal guardian to provide written informed consent.

Exclusion Criteria:

• <38 weeks post menstrual age
• Any concomitant condition, which in the opinion of the investigator would preclude a subject's participation in the study.
• Previous participation in this study
• CPB circuit primed with clear fluid

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
age less than or equal to 2 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma pharmacokinetics (clearance, volume of distribution, area under the curve, oxygenator extraction efficiency) of dexmedetomidine in children supported with cardiopulmonary bypass	The plasma pharmacokinetics of dexmedetomidine will include; Clearance (CL); Volume of distribution (V); Area under the curve (AUC); Oxygenator extraction efficiency	Data will be collected at the following approximate time points: 0h, 0.5h, 0.75h, and 2h after infusion initiation; 0.25h, 0.75h, and 2h after bypass initiation; 0.5h prior to bypass termination, 0.25h, 1h, 3h, 7h, and 10h after bypass termination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
COMFORT behavioral score as a measure of dexmedetomidine pharmacodynamics		assessed at time 0, upon presentation to the intensive care unit after surgery, and 12-24 hours from study drug initiation.
Accessory sedative and analgesic use as a measure of dexmedetomidine pharmacodynamics	We will monitor sedatives and analgesics used in addition to dexmedetomidine. Quantification of use of other drugs will allow an indication of the sedative effects of dexmedetomidine.	up to 48 hours after study drug initiation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vital sign variation as a measure of safety	Adverse events of special interest will be evaluated. These will include the presence of bradycardia, hypertension, and hypotension that occur after administration of dexmedetomidine	up to 48 hours after study drug initiation

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Kevin Watt, MD, Duke University

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: February 5, 2014
• First Submitted That Met QC Criteria: February 7, 2014
• First Posted (Estimate): February 11, 2014

Study Record Updates

• Last Update Posted (Estimate): November 24, 2014
• Last Update Submitted That Met QC Criteria: November 21, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: safety; children; pharmacokinetics; dexmedetomidine; cardiopulmonary bypass; pharmacodynamics
• Other Study ID Numbers: Pro00049942; K24HD05873505 (Other Grant/Funding Number: NICHD)