Distribution in Cerebrospinal Fluid, Blood, and Lymph of Epidurally Injected Morphine and Inulin in Dogs

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Abstract
We describe procedures for catheterizing the epidural space, the azygos vein, and the thoracic lymph duct of dogs without using fluoroscopy. The success rates of the procedures were 100, 80, and 50%, respectively (n = 10). To assess the validity of the model, 3H-morphine and unlabeled morphine (2 mg) were injected epidurally in ten dogs. Lumbar cerebrospinal fluid (CSF), azygos venous blood, arterial blood, and lymph were sampled before and 5, 20, 60, 120, 180, 240, 300 and 360 min after injection. During the first 20 min, morphine levels in the azygos vein were about three and ten times greater than arterial and lymphatic levels, respectively (n = 3; P < 0.01). Morphine levels were significantly greater in the azygos vein (n = 8) and the femoral artery (n = 10) during the first 20 and 60 min than they were later, respectively (P < 0.05). In the lymph (n = 5), the levels of morphine at 60 min were statistically greater (P < 0.05) than levels at 4, 5, and 6 hr. At no time were the concurrent arterial and lymph levels different from each other. In the lumbar CSF, the morphine peak concentration was reached 5–60 min after epidural injection and ranged between 5 and 93 μg/ml. In the CSF, the levels of morphine were significantly greater during the first 20 min than later (n = 7; P < 0.05). The washout of the lumbar CSF curve for morphine appeared to be fitted by a two-compartment open model. The t1/2-α and t1/2-β values were 14.7 ± 7.2 min and 106 ± 45 min, respectively (mean ± SD). Cumulative percentages of the epidural dose of morphine passed into the azygos system within the first 5, 20, 60, and 120 min after injection were calculated to be 4.0 ± 2.1, 23.5 ± 14.6, 49.2 ± 34.2, and 55.9 ± 35.3, respectively (mean ± SD; n = 8). Both 14C-inulin and 3H-morphine were injected epidurally in one dog and intrathecally in another dog. In the CSF, morphine appears to be cleared at a rate similar to that of inulin. The fraction of morphine and inulin crossing the dura after epidural injection was calculated to be 0.31% and 0.59%, respectively.