Open AccessSafety of Continuous Intrathecal Midazolam Infusion in the Sheep Model
Author(s) -
Mary Johansen,
Tamara Lee Gradert,
William C. Satterfield,
Wallace B. Baze,
Keith R. Hildebrand,
Lawrence A. Trissel,
Samuel J. Hassenbusch
Publication year - 2004
Publication title -
anesthesia and analgesia/anesthesia and analgesia
Language(s) - English
Resource type - Journals
eISSN - 1526-7598
pISSN - 0003-2999
DOI - 10.1213/01.ane.0000120086.35289.9d
Subject(s) - medicine , midazolam , saline , anesthesia , toxicity , catheter , cerebrospinal fluid , spinal cord , surgery , pathology , sedation , psychiatry
We investigated the safety of midazolam administered by continuous intrathecal infusion in relevant animal models. Preservative-free midazolam was delivered to sheep and pigs by using implanted infusion systems (SynchroMed pumps plus silicone catheters). Sheep received midazolam 5 mg/d (n = 4) or 15 mg/d (n = 7) or saline (n = 2) for 43 days at 125 micro L/h. One sheep received 10 mg/d. Infusion concentrations ranged from 1.7 to 2.5 mg/mL (5 mg/d) and from 2.5 to 5.0 mg/mL (15 mg/d). Pigs were evaluated for toxicity only and received 15 mg/d (n = 2) or saline (n = 1) for 43 days at 125 micro L/h. Behavior, neurologic function, and vital signs were documented. Serum and cerebrospinal fluid chemistry and cytology were evaluated, and histology was performed on spinal cord tissue. Behavior and neurologic function remained normal in all subjects. Gross and microscopic evaluation of spinal tissue revealed mild inflammation surrounding the catheter tract in both the midazolam-treated and the saline-treated groups. This inflammation was likely attributable to the mechanical presence of the catheter. These data demonstrate that continuous intrathecal infusion of preservative-free midazolam at doses up to 15 mg/d were well tolerated.