Pharmacokinetics of Low Dose Ketamine Infusion

NCT00618397 | Terminated Phase 1

• 1 other identifier: 042006035
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Sedation; Opioid Tolerance

Keywords

ketamine; pharmacokinetics; sedation; critical care; opioid tolerance; NMDA Antagonist

Outcome Measures

Primary Outcomes (1)

• 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.

  6 and 12 hours after begining infusion

Secondary Outcomes (1)

• To define the pharmacokinetics of continuous infusion ketamine in doses of 0.01mg/kg/hr, 0.1mg/kg/hr and 0.5mg/kg/hr.

  6 and 12 hours after infusion

Study Arms (1)

Arm 1

EXPERIMENTAL

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.

Drug: Ketamine

Interventions

Ketamine DRUG

Ketamine administered in doses of 0.01mg/kg/hr, 0.1mg/kg/hr and 0.5mg/kg/hr to PICU patients.

Also known as: Brand Name - ketalar

Arm 1

Eligibility Criteria

• Age: 3 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients will be eligible if they meet the following criteria:
• Children age one three (3) years to eighteen (18) years, requiring admission to the Pediatric ICU, who require intubation for respiratory failure and continuous infusion fentanyl.
• Patients of both genders, all races and ethnic backgrounds will be eligible.
• Patients will need to have AST and ALT evaluated within the two weeks prior to enrollment, with the result being within two times the normal range. Patients who have not had AST and ALT evaluated within two weeks will have to be evaluated prior to enrollment. Serum will be evaluated for AST and ALT when convenient to other lab testing prior to enrollment.
• Patients meeting the above criteria will be eligible regardless of nutritional status, performance status or recovery from prior medical treatment.
• Patients will not be excluded if they require simultaneous infusions of sedation with benzodiazepine.
• Enrollment will require parental consent.

You may not qualify if:

• Patients will not be eligible if they meet any of the following criteria:
• Patients who are currently on oral analgesia or sedation
• Patients who have a prior history of drug or alcohol dependence/abuse.
• Patients who are allergic to opioids.
• Patients who are allergic to ketamine or any NMDA antagonist. Patients in whom significant elevation of blood pressure would constitute a serious hazard
• Patients with documented or clinical concern for elevated intracranial pressure.
• Patients with known liver dysfunction as evidenced by AST and ALT two times the normal limit within the past two weeks.
• Patients who are being medically paralyzed as part of their current treatment.
• Patients with any underlying neurologic condition, or impairment, which would interfere with their perception of, or response to, pain or discomfort.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

Children's Medical Center Dallas, University of Texas Southwestern

Dallas, Texas, 75235, United States

Location

MeSH Terms

Interventions

Ketamine

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Cindy Darnell, MD

  University of Texas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assisant Professor Pediatrics

Study Record Dates

• First Submitted: February 6, 2008
• First Posted: February 20, 2008
• Study Start: June 1, 2006
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: October 26, 2016

Record last verified: 2016-10

Locations

US (1)