Characterization of Effect of Repeated Bolus or Continuous Intrathecal Infusion of Morphine on Spinal Mass Formation in the Dog. Issue 7 (23rd May 2019)

• Record Type: Journal Article
• Authors: Hildebrand, Keith R.; Page, Linda M.; Billstrom, Tina M.; Steinauer, Joanne J.; Eddinger, Kelly A.; Arjomand, Shervin; Yaksh, Tony L.
• Is Part Of: Neuromodulaton. Volume 22:Issue 7(2019)
• Page Start: 790
• Page End: 798
• Publication Date: 2019-05-23
• Subjects: Bolus delivery -- intrathecal drug -- intrathecal granuloma -- intrathecal pump -- morphine; Central nervous system -- Physiology -- Periodicals; Central nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1111/ner.12963
• Languages: English
• ISSNs: 1094-7159

Abstract

Abstract : Background: We determined whether intrathecally delivering the same daily dose of morphine (MS) at a fixed concentration of 25 mg/mL by periodic boluses versus continuous infusion would reduce intrathecal mass (IMs) formation in dogs. Methods: Adult dogs (hound cross, n = 32) were implanted with intrathecal catheters connected to SynchroMed II infusion pumps. Animals were randomly assigned to receive infusion of 0.48 mL/day of saline or MS dosing (12 mg/day at 25 mg/mL) as boluses: x1 (q24hour), x2 (q12hour), x4 (q6hour), or x8 (q3hour) given at the rate of 1000 μL/hour, or as a continuous infusion (25 mg/mL/20 μL/hour). Results: With IT saline, minimal pathology was noted. In contrast, animals receiving morphine displayed spinally compressing durally derived masses with the maximal cross‐sectional area being greatest near the catheter tip. Histopathology showed that IMs consisted of fibroblasts in a collagen (type 1) matrix comprised of newly formed collagen near the catheter and mature collagen on the periphery of the mass. The rank order of median cross‐sectional mass area (mm 2 ) was: Saline: 0.7 mm 2 ; x2: 1.8 mm 2 ; x4: 2.7 mm 2 ; x1: 2.7 mm 2 ; x8: 4.2 mm 2 ; Continuous: 8.1 mm 2, with statistical difference from saline being seen with continuous ( p < 0.0001) and x8 ( p < 0.05). Bench studies with a 2D diffusion chamber confirmed an increase in dye distribution and lower peak concentrations after bolus delivery versus continuous infusion of dye. Conclusions: Using multiple bolus dosing, IMs were reduced as compared to continuous infusion, suggesting relevance of bolus delivery in yielding reduced intrathecal masses.