İnvestigation and histopathological evaluation of intradural effect (CSF level) of locally applied vancomycin in experimental laminectomy model in rabbits

OBJECT: The aim of this study was the penetration of vancomycin from the blood-brain barrier of intravenously or directly local application on dura and evaluation of its histopathological effects on the central nervous tissue. METHODS: The study includes a total of 18 rabbits in three groups of 6 rabbits each. (1)Group 1 was determined as the control group and the wound was closed after laminectomy. (2) Local vancomycin (30 mg/kg, total dose 50mg) was applied to the second group after laminectomy.(3) Intravenous vancomycin (10 mg/kg, total dose 30mg) was applied to the third group after laminectomy. CSF and serum samples were taken from the subjects at the 6th, 12th and 24th hours postoperatively. Vancomycin levels were measured in all samples by LC-MS / MS method. In the 4th week after the procedure, the subjects were sacrificed and their lumbar vertebrae were removed as a block. Sections were graded for epidural fibrosis and histopathological analysis was performed. Biochemical analyzes, pathological examinations and statistical analysis of the results were designed as double-blind studies. RESULTS: When the measurement values of the three groups were compared, in the CSF samples taken at the 6th hour, it was found that the level of vancomycin in the intravenous vancomycin group was significantly higher than control-local vancomycin groups statistically (p = 0.035). There was no difference between the three groups in the measurements of CSF vancomycin values at 12th and 24th hours. Similarly, in the paired group comparison, the 6th hour CSF values in the IV vancomycin group were found to be significantly higher than the local vancomycin group (p = 0.025). However, there was no significant difference between the three groups in the 12th and 24th hour measurements. When the serum vancomycin values of the three groups were compared, significantly higher values were found in the intravenously applied vancomycin group in comparison to locally applied vancomycin group and control group at 6, 12 and 24 hours (p <0.05). In the comparison of serum levels between the IV vancomycin group with the local group, it was found that the 6th and 12th hour measurements were significantly higher in the IV vancomycin group (p <0.050), and there was no difference in the 24th hour measurements. In the evaluations of the groups among themselves, CSF values were high at the 6th hour in the IV application and tended to decrease at the 12th and 24th hours. In the local group, CSF values was not detected at the 6th hour, and it was detected in trace amounts at the 12th and 24th hours. The level of serum vancomycin values reached its peak at the 12th hour in the IV group and a significant decrease was found at the 24th hour (p = 0.03). It was observed that serum values in the local group were not very high, but there was an increase tendency from the 6th to the 24th hour. When histopathological evaluation results were evaluated, Grade 1 fibrosis was found in all samples obtained from the IV group, and Grade 0 fibrosis was found in all local application samples. In the control group, 50% of the samples had Grade 3 fibrosis, 16.7% Grade 2 fibrosis and 33.3% Grade 0 fibrosis. There was a statistically significant difference between all three groups (p = 0.01). CONCLUSION: In the intravenous application of vancomycin, it has been shown that the vancomycin molecule crosses the blood-brain barrier at the 6th hour in the rabbit model. Although it is not statistically significant, the local application of vancomycin also contains trace amounts of vancomycin molecules in the cerebrospinal fluid and shows a moderate increase tendency from the 6th to the 24th hour. Epidural fibrosis occurred less frequently in local vancomycin application compared to other groups. The acidic vancomycin molecule may reduce fibrosis by affecting fibroblasts. The data obtained from this study are in favor of the positive effects of vancomycin applied locally and intravenously. In ongoing studies, new treatment guidelines can be developed if local vancomycin dosage changes and long-term release systems are emphasized. Key Words: Laminectomy ,vancomycin, CSF, epidural fibrosis