The Influence of Diabetic Peripheral Neuropathy on the Duration of Sciatic Nerve Block with 1.3% Liposomal Bupivacaine and 0.25% Bupivacaine Hydrochloride in a Mouse Model.

Little is known regarding the pharmacological properties of extended-release local anesthetics in the setting of diabetic peripheral neuropathy. We investigated and compared the duration of sciatic nerve block following administration of clinically relevant concentrations of liposomal bupivacaine (LB) and bupivacaine hydrochloride (BH) in diabetic mice with peripheral neuropathy. In this prospective, randomized, and double-blind study, twenty-four female C57BL/6J-OlaHsd mice were assigned to a streptozotocin-induced type 1 diabetes group and a control group without diabetes. The presence of peripheral neuropathy was established by assessing the duration of thermal latency of the plantar and tail-flick tests, following which both groups were subdivided into two subgroups in which 35 mg/kg of 1.31% LB and 7 mg/kg of 0.25% BH were respectively administered for sciatic nerve block. The average sensory block duration with BH was 106 min and 117.1 min in the control and diabetic groups, respectively. With LB, the average sensory block duration was 118 min in the control mice, while in mice with diabetic peripheral neuropathy, the average block duration was significantly longer and above the 270 min limit set in our study. Accordingly, sensory block duration was longer with LB compared to BH, and diabetic peripheral neuropathy significantly increased sciatic nerve block duration with LB.

Delivery mode and neonatal morbidity after remifentanil-PCA or epidural analgesia using the Ten Groups Classification System: A 5-year single-centre analysis of more than 10 000 deliveries.

OBJECTIVE: This study aimed to explore the potential association between remifentanil patient-controlled analgesia (RPCA) or epidural analgesia (EA), and caesarean section (CS) rate, operative vaginal delivery rate (OVD), operative delivery (OD) rate (CS or OVD) with pathological cardiotocography (CTG) tracing, Apgar score < 7 at 5 min after birth, incidence of perinatal asphyxia and neonatal intensive care unit (NICU) admission within four groups of the Ten Groups Classification System (TGCS) labour types; group 1: nulliparous, singleton cephalic, ≥37 weeks, spontaneous onset of labour; group 2a: nulliparous, singleton cephalic, ≥37 weeks, induction of labour; group 3: multiparous, singleton cephalic, ≥37 weeks, spontaneous onset of labour; group 4a: multipara, singleton cephalic, ≥37 weeks, induction of labour). We hypothesized that labour and delivery outcomes between RPCA and EA would differ within the different TGCS labour types. STUDY DESIGN: 10,561 deliveries (4876 with RPCA, 5685 with EA) at the University Clinical Centre Ljubljana, Slovenia, from 2015 through 2019 were analysed using the Slovenian National Perinatal Information System data. RESULTS: Compared to EA, RPCA was associated with lower CS and OVD rates in nulliparous women with spontaneous onset of labour (group 1) (CS: 9.9 % vs14.3 %; P < 0.001) (OVD: 5.1 % vs 8.4 %; P < 0.001), in nulliparous women with induced labour (group 2a) (CS: 14.8 % vs 24.2 %; P < 0.001) (OVD: 6.5 % vs 8.9 %; P = 0.036) and in multiparous women with spontaneous onset of labour (group 3) (CS: 1.1 % vs 2.4 %; P = 0.021) (OVD: 0.1 % vs 0.8 %; P = 0.007), respectively. RPCA was associated with a lower incidence of OD with pathologic CTG in all four studied groups (groups 1, 2a, 3, 4a). No differences in APGAR < 7 at 5 min, neonatal asphyxia, and NICU admission were recorded between the two analgesic techniques within any of the TGCS groups. CONCLUSION: Compared to EA, RPCA was not associated with worse delivery and neonatal outcomes within any of the four studied TGCS groups. RPCA could be used for labour analgesia routinely if strict adherence to protocols is ensured and regular staff training is provided.

Neurotoxicity of bupivacaine and liposome bupivacaine after sciatic nerve block in healthy and streptozotocin-induced diabetic mice.

BACKGROUND: 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. 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. RESULTS: Diabetic 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. CONCLUSIONS: In 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.