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.