title: Neurotoxicological assessment after intracisternal injection of liposomal bupivacaine in rabbits.
abstract: Experiments were performed on rabbits randomly assigned to intracisternally receive 0.3 mL of plain bupivacaine 5 mg/mL, liposomal bupivacaine 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 histopathologic characteristics were studied on transverse sections. All preparations were devoid of phosphatidylcholine hydrolysis or oxidation compounds. Solutions without bupivacaine produced transient irritative signs that required sedation in most rabbits. Despite the similar duration of respiratory depression in groups receiving liposomal or plain bupivacaine, liposomes produced significantly prolonged motor blockade (126 vs 70 min). Correction of hypotension after plain bupivacaine required a longer dopamine infusion and larger doses than after liposomal bupivacaine (28 vs 18 min and 74 vs 47 mg). Necrosis was observed in the cervical area of two rabbits (one in the liposomal bupivacaine group and another in the phosphate buffer group). No demyelinated areas were noted in spinal cord examinations. We conclude that liposomal bupivacaine leads to a less severe sympathetic block and to a prolonged motor block, whereas histologic changes are not significantly different among groups.
  
  
  CONCLUSIONS
  Multilamellar liposomes containing bupivacaine administered intracisternally to rabbits produce spinal cord histopathologic changes not significantly different from those observed with plain bupivacaine. Sustained release of bupivacaine from liposomes is suggested by the prolonged motor blockade and the reduced severity of arterial hypotension. Use of these liposomes could prolong the local anesthetic effects of bupivacaine.
authors.affiliation: Service d'Anesthésie et Réanimation Chirurgicale, Hôtel-Dieu, Nantes, France. jmmalino@sante.univ-nantes.fr
authors.forename: J M
authors.initials: JM
authors.lastname: Malinovsky
authors.forename: D
authors.initials: D
authors.lastname: Benhamou
authors.forename: M
authors.initials: M
authors.lastname: Alafandy
authors.forename: J M
authors.initials: JM
authors.lastname: Mussini
authors.forename: C
authors.initials: C
authors.lastname: Coussaert
authors.forename: G
authors.initials: G
authors.lastname: Couarraze
authors.forename: M
authors.initials: M
authors.lastname: Pinaud
authors.forename: F J
authors.initials: FJ
authors.lastname: Legros
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D002045:Bupivacaine / Q000008:administration & dosage / Q000633:toxicity*; D004337:Drug Carriers; D007278:Injections, Spinal; D008081:Liposomes; D009336:Necrosis; D011817:Rabbits; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology
chemical_list: D000779:Anesthetics, Local; D004337:Drug Carriers; D008081:Liposomes; D002045:Bupivacaine