Presented at the 2012 AAPM Annual Meeting « Back

Chronic Intrathecal Morphine Administration: Effects of Continuous Infusion Versus Intermittent Boluses on the Incidence of Inflammatory Mass in a Canine Model

Linda M. Page, PharmD, linda.page@medtronic.com¹, Keith Hildebrand, PhD DVM¹, Tina M. Billstrom, MS¹, Lynette A. Phillips, PhD DVM¹, (1) Medtronic, Inc., Minneapolis, Minnesota

Background: Inflammatory masses (IMs) from chronic intrathecal (IT) infusion were thought to be related to catheter materials. Research has shown that IM is associated with continuous infusion of high concentration opioids. Objectives: Determine if intermittent morphine boluses effects IM incidence compared to same daily dose and concentration infused continuously. Methods: Twenty-two canines (1, 2, 4, & 8 bolus/day) were used to investigate IM incidence compared to historical continuous-infusion controls. Morphine was administered - 12 mg/day @ 25 mg/mL. IT catheters were implanted and connected to a subcutaneous SynchroMed® II pump. Infusion rates were gradually increased until the desired dose was achieved. Animals were euthanized 28 days after dose was reached. Histopathology was performed. Results: IM incidence for 15 dogs completed (1, 2, & 4 bolus/day) averages 23% when two animals are excluded (one infection, one morphine hypersensitivity/early sacrifice). Two animals that completed the study have incipient masses (dural inflammation without extension into the leptomeninges). Including incipient masses, the IM incidence with boluses is 38% versus 100% with continuous infusion. Bolus-induced IMs were smaller than continuous-infusion-induced IMs. The 8-bolus/day animals have been initiated; data and histolopathology of all groups and historical controls will be presented. Conclusions: Intermittent bolus delivery of IT morphine produced marked reduction (> 50%) in IM incidence relative to continuous infusion when daily dose and concentration were constant. Bolus administration may result in greater morphine distribution within the intrathecal space decreasing sustained dural exposure to high morphine concentrations at the catheter tip.

Funding: None