Pharmacokinetics of Low Dose Ketamine Infusion
Opioids, such as fentanyl, are commonly used in PICU patients to provide comfort and pain control. Opioid tolerance, the need to increase the dose of medication to achieve the same effect,is seen in PICU children who require opioid infusions. Animals and human studies have shown that activation of the N-methyl-D-aspartate (NMDA) receptor is involved in the development of opioid tolerance and that deactivation of this receptor can slow the development of tolerance. Ketamine, an NMDA receptor antagonists, turns off the NMDA receptor. Ketamine is used to provide sedation and anesthesia in children. Its use in inhibiting the development of opioid tolerance has not been tested in children. We aim to determine ketamine's effectiveness in the treatment of tolerance in PICU patients who require fentanyl infusions to treat pain and discomfort .
Some physicians have reported using ketamine doses of 0.04mg/kg/hr to 0.5mg/kg/hr to inhibit opioid tolerance. We propose to study the sedative effect, and the metabolism of, three doses of ketamine, 0.1mg/kg/hr, 0.3mg/kg/hr, and 0.5mg/kg/hr.
Patients admitted to the PICU, requiring a breathing machine and fentanyl infusion for discomfort or pain control will be enrolled. Patients' age three to eighteen years will be enrolled. Patients will receive a ketamine infusion once their COMFORT scores indicate an adequate sedation/comfort level on their current sedation regimen. The COMFORT score is a validated scale that measures distress in PICU patients. The COMFORT score will be continued for the twelve hours the patient receives the ketamine to test whether the ketamine adds to the level of sedation. Blood samples during and following the ketamine infusion will be taken to determine how ketamine and norketamine (one of ketamine's metabolites) are used in the body.
To determine the effect of ketamine on tolerance it must be a ketamine dose that does not cause additional sedation. The goal of this study is to define a non-sedating dose of ketamine and define how it is used by the body. A non-sedating ketamine dose could be added to current sedation regimens allowing us to monitor the development of tolerance without the confusion of added sedation. The data obtained in this study will be used to design a study to further investigate the effect of ketamine on opioid tolerance.
|Study Design:||Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
|Official Title:||Phase I Trial to Determine Steady State Pharmacokinetics and Sedative Effects of Low Dose Ketamine Infusion|
- To establish if continuous infusions of ketamine in doses of 0.01mg/kg/hr, 0.1mg/kg/hr and 0.5mg/kg/hr cause serum levels > 1 mcg/ml. [ Time Frame: 6 and 12 hours after begining infusion ] [ Designated as safety issue: Yes ]
- To define the pharmacokinetics of continuous infusion ketamine in doses of 0.01mg/kg/hr, 0.1mg/kg/hr and 0.5mg/kg/hr. [ Time Frame: 6 and 12 hours after infusion ] [ Designated as safety issue: No ]
|Study Start Date:||June 2006|
|Study Completion Date:||June 2015|
|Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Experimental: Arm 1
Ketamine will be administered in doses of 0.01mg/kg/hr, 0.1mg/kg/hr and 0.5mg/kg/hr to in PICU patients that meet eligibility criteria.
Ketamine administered in doses of 0.01mg/kg/hr, 0.1mg/kg/hr and 0.5mg/kg/hr to PICU patients.
Other Name: Brand Name - ketalar
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00618397
|United States, Texas|
|Children's Medical Center Dallas, University of Texas Southwestern|
|Dallas, Texas, United States, 75235|
|Principal Investigator:||Cindy Darnell, MD||University of Texas|