Other: Long term stability of clonidine in clonidine-hydromorphone mixture in implanted intrathecal infusion pumps

Abstract

Clonidine is frequently added to opioid in implantable intrathecal infusion pumps for the management of chronic pain, especially in those with chronic neuropathic pain. Previous studies on the clonidine stability conducted in vitro with the solution inside the infusion pump at body temperature suggested that clonidine was stable in mixture with morphine under this condition. When applying this data to clinical settings, two concerns remain. There is a non-retrievable volume of 2.4 ml in the reservoir, which has potential for degradation over months or years. Moreover, the stability of clonidine when mixed with other opioids such as hydromorphone is unknown. The aim of the present study was to examine the long-term stability of clonidine when administered with hydromorphone in implanted intrathecal pumps to non-cancer, chronic pain patients. Following REB approval and informed consent, samples were taken from hydromorphone-clonidine mixtures collected before pump refill and from the residual solution in the subsequent refill. The clonidine concentration used were 150mcg/ml in all patients. Following collection, the samples were frozen and transferred to the laboratory for analysis of clonidine concentration by High Performance Liquid Chromatography. Data are presented as mean+SD and compared with paired Student t-test. Twenty paired samples from 3 patients with refilling interval of 35+13days were analyzed. All 3 patients had SyncroMed® implanted for a duration ranging from 3-5 years. There was no statistical difference in clonidine concentration before and after refill (145.6+5.6 vs 145.6+7.1 mcg/mL respectively). Based on our data, only 5 paired samples were required to show a difference of 15% with type I and II error of 0.05 and 0.2. Clonidine, when mixed with hydromorphone, is stable when delivered by implantable intrathecal pump for long term use.