NEUROTOXICOLOGICAL ASSESSMENT AFTER INTRACISTERNAL INJECTION OF LIPOSOMAL BUPIVACAINE IN RABBITS

Experiments were performed on rabbits randomly assigned to intracister nally receive 0.3 mL of plain bupivacaine 5 mg/mL, liposomal bupivacai ne 5 mg/mL, bupivacaine-free liposomes, or isotonic phosphate-buffered saline. Mechanical ventilation was initiated or intravenous dopamine was infused when respiratory depression or hypotension occurred. Seven days after the injection, the whole spinal cord was removed and histo pathologic characteristics were studied on transverse sections. All pr eparations were devoid of phosphatidylcholine hydrolysis or oxidation compounds. Solutions without bupivacaine produced transient irritative signs that required sedation in most rabbits. Despite the similar dur ation of respiratory depression in groups receiving liposomal or plain bupivacaine, liposomes produced significantly prolonged motor blockad e (126 vs 70 min). Correction of hypotension after plain bupivacaine r equired a longer dopamine infusion and larger doses than after liposom al bupivacaine (28 vs 18 min and 74 vs 47 mg). Necrosis was observed i n the cervical area of two rabbits (one in the liposomal bupivacaine g roup and another in the phosphate buffer group). No demyelinated areas were noted in spinal cord examinations. We conclude that liposomal bu pivacaine leads to a less severe sympathetic block and to a prolonged motor block, whereas histologic changes are not significantly differen t among groups. Implications: Multilamellar liposomes containing bupiv acaine administered intracisternally to rabbits produce spinal cord hi stopathologic changes not significantly different from those observed with plain bupivacaine. Sustained release of bupivacaine from liposome s is suggested by the prolonged motor blockade and the reduced severit y of arterial hypotension. Use of these Liposomes could prolong the lo cal anesthetic effects of bupivacaine.