Abstract
BackgroundLong-acting local anaesthetics (e.g. bupivacaine hydrochloride) or sustained-release formulations of bupivacaine (e.g. liposomal bupivacaine) may be neurotoxic when applied in the setting of diabetic neuropathy. The aim of the study was to assess neurotoxicity of bupivacaine and liposome bupivacaine in streptozotocin (STZ) - induced diabetic mice after sciatic nerve block. We used the reduction in fibre density and decreased myelination assessed by G-ratio (defined as axon diameter divided by large fibre diameter) as indicators of local anaesthetic neurotoxicity.ResultsDiabetic mice had higher plasma levels of glucose (P < 0.001) and significant differences in the tail flick and plantar test thermal latencies compared to healthy controls (P < 0.001). In both diabetic and nondiabetic mice, sciatic nerve block with 0.25% bupivacaine HCl resulted in a significantly greater G-ratio and an axon diameter compared to nerves treated with 1.3% liposome bupivacaine or saline (0.9% sodium chloride) (P < 0.01). Moreover, sciatic nerve block with 0.25% bupivacaine HCl resulted in lower fibre density and higher large fibre and axon diameters compared to the control (untreated) sciatic nerves in both STZ-induced diabetic (P < 0.05) and nondiabetic mice (P < 0.01). No evidence of acute or chronic inflammation was observed in any of the treatment groups.ConclusionsIn our exploratory study the sciatic nerve block with bupivacaine HCl (7 mg/kg), but not liposome bupivacaine (35 mg/kg) or saline, resulted in histomorphometric indices of neurotoxicity. Histologic findings were similar in diabetic and healthy control mice.
Highlights
IntroductionLong-acting local anaesthetics (e.g. bupivacaine hydrochloride) or sustained-release formulations of bupivacaine (e.g. liposomal bupivacaine) may be neurotoxic when applied in the setting of diabetic neuropathy
Long-acting local anaesthetics or sustained-release formulations of bupivacaine may be neurotoxic when applied in the setting of diabetic neuropathy
Patients with diabetes require surgical procedures more frequently than healthy patients, and due to their comorbidities, peripheral nerve blocks are often recommended as an alternative to general anaesthesia, for lower extremity surgery [3]
Summary
Long-acting local anaesthetics (e.g. bupivacaine hydrochloride) or sustained-release formulations of bupivacaine (e.g. liposomal bupivacaine) may be neurotoxic when applied in the setting of diabetic neuropathy. A prolonged application of high doses of local anaesthetics perineurally has been associated with neurotoxicity [4,5,6] In humans, it is not well-established if nerve blocks can exacerbate a pre-existing diabetic neuropathy [7]. Long-acting local anaesthetics (e.g. bupivacaine HCl) or sustained-release formulations of bupivacaine (e.g. liposome bupivacaine) could prove neurotoxic in the presence of a pre-existing neuropathy [5]. The aim of this study was to assess the neurotoxic effects of liposome bupivacaine and bupivacaine hydrochloride (HCl) following perineural injection for sciatic nerve block in streptozotocin (STZ)-induced diabetic mice. We hypothesized that perineural injections of bupivacaine HCl and liposome bupivacaine would result in a reduction of fibre density and decreased myelination in diabetic nerve
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