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Morphine Distribution in the Spinal Cord After Chronic Infusion in Pigs

Flack, Sean H. MBChB, FCA*,†; Anderson, Christine M. MD; Bernards, Christopher MD*,‡

doi: 10.1213/ANE.0b013e318203b7c0
Analgesia: Pain Mechanisms: Research Reports

BACKGROUND: Continuous intrathecal drug delivery provides new options for chronic delivery of drugs that target the spinal cord, but therapeutic efficacy is highly variable. Using an acute porcine model, we have previously demonstrated that continuous intrathecal drug delivery efficacy may be highly variable because of severely limited drug distribution in the cerebrospinal fluid and spinal cord. We designed this study to determine whether the limited drug distribution observed in our acute studies occurs with chronic administration as well.

METHODS: Four farm-bred pigs were implanted with intrathecal infusion pumps delivering morphine (1 mg/mL) at 20 μL per hour. Because of a programming error, 1 additional pig received intrathecal morphine at 2 μL per hour. Drug infusion continued for 14 days, during which time animal activity was unrestricted. At the end of 2 weeks the animals were anesthetized and euthanized and their spinal cords removed. The spinal cords were divided into 1-cm sections and morphine concentrations measured.

RESULTS: As with previous acute animal studies, drug distribution was extremely limited. Morphine concentration decreased exponentially as a function of distance from the catheter tip, resulting in a 5- to 10-fold decrease over a distance of only 5 to 10 cm.

CONCLUSION: Morphine distribution is very limited during chronic intrathecal delivery in ambulatory pigs, and there are significant spinal cord drug concentration gradients as a function of distance from the infusion point. Consequently, catheter tip position may be critical, particularly when infusing isobaric solutions. These data also support the hypothesis that inflammatory masses complicating chronic intrathecal opioid delivery occur at the catheter tip because limited drug distribution results in extremely high drug concentrations at that point.

Published ahead of print January 6, 2011

From the *Department of Anesthesiology and Pain Medicine, University of Washington; Seattle Children's Hospital; and VA Mason Medical Center.

Funding: Financial support was provided by a competitive grant from the University of Washington, Department of Anesthesiology and Pain Medicine. Medtronic, Inc. (Minneapolis, MN) loaned the investigators 6 Synchromed II pumps for the study.

Conflict of interest: See Disclosures at the end of the article.

Reprints: Reprints will not be available from the authors.

Address correspondence to Christopher Bernards, MD, Clinical Professor, Department of Anesthesiology, B2-AN1100 Ninth Avenue, Seattle, WA 98101. Address e-mail to chrisb@u.washington.edu.

Accepted September 30, 2010

Published ahead of print January 6, 2011

© 2011 International Anesthesia Research Society