Neurological and histological outcomes after subarachnoid injection of a liposomal bupivacaine suspension in pigs: a pilot study.

BACKGROUND: An injectable liposomal bupivacaine suspension (EXPAREL™) is approved by the US Food and Drug Administration for analgesia by tissue infiltration and interscalene brachial plexus, but not for use in the neuraxial space. This pilot study describes neurological and histological outcomes of escalating doses of this extended-release formulation of bupivacaine after subarachnoid administration. METHODS: Twenty-five pigs (Sus scrofa domesticus) weighing 36.2 (4.4) kg were randomly assigned to one of five groups to receive a subarachnoid injection of sodium chloride 0.9%, 3 ml (negative control), preservative-free bupivacaine hydrochloride 0.5%, 3 ml (positive control), or one of three doses of liposomal bupivacaine suspension 1.33%: 1.5, 3, or 5 ml. After recovering from general anaesthesia, neurological outcomes were assessed by blinded observers. Three weeks later, the animals were sacrificed for histological evaluations of neurotoxicity. RESULTS: Animals that received sodium chloride 0.9%, bupivacaine hydrochloride, or liposomal bupivacaine 1.5 ml recovered within 2, 5, or 4 h, respectively. Animals that received liposomal bupivacaine 3 or 5 ml exhibited signs of neuraxial block (decreased nociception and proprioception) up to 32 h after injection. No histological evidence of neurotoxicity was found in any of the groups. CONCLUSIONS: Subarachnoid administration of liposomal bupivacaine in pigs exhibited a dose-response effect, and resulted in longer duration of neuraxial block than bupivacaine hydrochloride without histological evidence of neurotoxicity. Our study contributes preliminary data to inform further toxicological assessments and regulatory approval before subarachnoid administration in humans.

Step initiation interferes with working memory in nondisabled patients with the earliest multiple sclerosis-A dual-task study.

Balance and cognition are affected by multiple sclerosis (MS). Cognitive-motor interference (CMI) is important for balance impairment in MS, however little is known about CMI at the earliest stages of the disease. Step initiation (SI) with anticipatory postural adjustments (APAs) has been linked to postural instability and falls in subjects with MS, therefore we aimed to assess CMI between SI and the two storage systems of working memory in patients with clinically isolated syndrome (presented as optic neuritis-ON) suggestive of MS. Twenty patients with normal/near normal visual acuity and 20 age-, weight-, height-, sex- and education-matched control subjects were included. APAs were studied using center of pressure measures in three conditions: SI alone, SI+Brooks' spatial- and SI+2-back verbal working memory task. Decrements (% change) in performance on cognitive tasks and in APA parameters were calculated. CMI was assessed combining the two decrements scores. Performance on both cognitive tasks was more affected by dual-tasking in patients compared to healthy subjects. In both groups APA parameters were not influenced by dual-tasking. CMI was higher in patients compared to healthy subjects. Our results suggest that the disease affects CMI in its earliest stages. Since both cognitive tasks were similarly affected by dual-tasking in patients and controls central executive seems to play the major role in CMI between SI and working memory. Patients prioritizing motor over cognitive task for balance maintenance suggests reduced divided attention capacity as a cause of increased CMI in the earliest MS.