Systemic toxic effects of local anaesthetics

Local anaesthetics are widely used in the provision of local/regional anaesthesia and the management of acute and chronic pain. Their mechanism of action temporarily inhibits voltage gated sodium channels in neuronal plasma membranes. Local anaesthetic systemic toxicity (LAST) is a serious yet largely preventable complication that can occur by any of the multiple routes of administration. LAST predominantly affects the central nervous and cardiovascular systems. Awareness of LAST and vigilance during administration of local anaesthetics may help in early recognition and successful management of the toxicity. Intralipid emulsion (ILE) infusions have been successfully used in reversing local anaesthetic-induced cardiotoxicity. Since 2007 in the UK, ILE infusion has been incorporated into the safety guidelines for management of LAST.     

Transcatheter Arterial Sclerosing Embolization for the Treatment of Giant Propranolol-Resistant Infantile Hemangiomas in the Parotid Region

PurposeTo report the effectiveness and safety of transcatheter arterial sclerosing embolization (TASE) for the treatment of parotid infantile hemangiomas that did not respond appreciably to propranolol.Materials and MethodsA total of 21 infants (12 male and 9 female) with large propranolol-resistant infantile hemangiomas in the parotid region were enrolled in this study. During TASE, the feeding arteries of the lesions were embolized using pingyangmycin-lipiodol emulsion and polyvinyl alcohol particles (300–500 μm) to reduce the blood flow rate. All children were followed up as outpatients at 2 weeks and monthly thereafter. The curative effect was evaluated at the 1- and 3-month follow-up visits.ResultsNine lesions were located on the right side of the parotid gland, whereas 12 were located on the left side. The feeding arteries in all patients originated from branches of the external carotid artery. TASE was technically successful in all patients. The mean (± SD) maximal diameter of the hemangiomas significantly decreased from 6.50 cm ± 2.28 before treatment to 3.56 cm ± 1.84 at 1 month after TASE (P <. 05). Three months after TASE, the mean maximal diameter further significantly decreased to 1.94 cm ± 1.58 (P <. 05). During the follow-up period, 16 cases were rated as excellent and 5 as good; no recurrence or serious complications were noted. Minor side effects, such as slight pain, mild fever, and tissue swelling, were observed.ConclusionsTASE significantly decreased the size of the parotid hemangiomas with minor side effects during a short follow-up period.     

Bupropion Overdose Complicated by Cardiogenic Shock Requiring Vasopressor Support and Lipid Emulsion Therapy

BackgroundBupropion overdose is a commonly encountered presentation in the emergency department (ED). While the majority of cases resolve with supportive care, serious adverse effects, including seizures, cardiogenic shock, and death, can occur. Intravenous lipid emulsion (ILE) therapy has been utilized for a multitude of poisonings with varying levels of success. Although a number of cases suggest the value of ILE therapy in cases of bupropion overdose, more recent data propose that its role may be overstated.Case ReportA young woman presented to the ED with altered mental status complicated by seizure after bupropion overdose. She subsequently developed cardiogenic shock requiring vasopressor support. Bedside echocardiogram revealed a decreased left ventricular ejection fraction (LVEF). She received ILE therapy with significant improvement in both hemodynamic status and LVEF by bedside ultrasound.Why Should an Emergency Physician Be Aware of This?Although the majority of patients presenting with bupropion overdose improve with supportive care, life-threatening sequelae are possible. ILE therapy has shown promise in a variety of different overdose situations, although the evidence in cases of bupropion poisoning has been varied, and it has traditionally been utilized as a last-line rescue modality. Based on hemodynamic parameters and bedside ultrasound, this case suggests that early initiation of ILE therapy should be considered in these cases, as the potential benefits likely outweigh the theoretical risks.     

胆维丁乳对酵母多糖所致多器官功能障碍综合征小鼠肾脏作用的研究

目的研究胆维丁乳对酵母多糖所致多器官功能障碍综合征小鼠肾脏的作用。方法选取C57BL/6源性的野生小鼠36只,随机分为对照组、胆维丁乳组、酵母多糖组、胆维丁乳+酵母多糖组,每组9只,室温饲养,按组别分别自由饮水或添加胆维丁乳喂养14 d。2周后,酵母多糖组、胆维丁乳+酵母多糖组腹腔注射酵母多糖混悬液,对照组、胆维丁乳组腹腔注射等量0.9%氯化钠溶液,18 h后处死各组小鼠,分别进行HE染色,观察肾脏组织病变情况;Western blot技术检测炎症因子蛋白表达;用TRizol法按照试剂说明书提取总RNA,用反转录试剂盒将RNA反转录成c DNA;采用SPSS 16.0进行统计学处理。结果胆维丁乳+酵母多糖组小鼠炎症因子IL-6、IL-18蛋白及mRNA的表达、尿素及肌酐水平高于酵母多糖组(P<0.05),且肾脏组织病理学改变较严重。结论对于正常生长的小鼠,给予胆维丁乳不会加重小鼠的肾脏负担;对于已经发生急性肾损伤的小鼠,胆维丁乳的摄入会加重肾脏损伤。     

A Quantitative Comparison of Physical Accuracy and Numerical Stability of Lattice Boltzmann Color Gradient and Pseudopotential Multicomponent Models for Microfluidic Applications

The performances of the Color-Gradient (CG) and the Shan-Chen (SC) multicomponent Lattice Boltzmann models are quantitatively compared side-by-side on multiple physical flow problems where breakup, coalescence and contraction of fluid ligaments are important. The flow problems are relevant to microfluidic applications, jetting of microdroplets as seen in inkjet printing, as well as emulsion dynamics. A significantly wider range of parameters is shown to be accessible for CG in terms of density-ratio, viscosity-ratio and surface tension values. Numerical stability for a high density ratio $\mathcal{O}(1000)$ is required for simulating the drop formation process during inkjet printing which we show here to be achievable using the CG model but not using the SC model. Our results show that the CG model is a suitable choice for challenging simulations of droplet formation, due to a combination of both numerical stability and physical accuracy. We also present a novel approach to incorporate repulsion forces between interfaces for CG, with possible applications to the study of stabilized emulsions. Specifically, we show that the CG model can produce similar results to a known multirange potentials extension of the SC model for modelling a disjoining pressure, opening up its use for the study of dense stabilized emulsions.     

Pharmacokinetics and Early Tumor Response to Conventional Transarterial Chemoembolization with Sorafenib and Doxorubicin in a VX2 Rabbit Tumor Model

PurposeTo investigate the pharmacokinetics (PK) and early effects of conventional transarterial chemoembolization (TACE) using sorafenib and doxorubicin on tumor necrosis, hypoxia markers, and angiogenesis in a rabbit VX2 liver tumor model.Materials and MethodsVX2 tumor-laden New Zealand White rabbits (N = 16) were divided into 2 groups: 1 group was treated with hepatic arterial administration of ethiodized oil and doxorubicin emulsion (DOX-TACE), and the other group was treated with ethiodized oil, sorafenib, and doxorubicin emulsion (SORA-DOX-TACE). Animals were killed within 3 days of the procedure. Levels of sorafenib and doxorubicin were measured in blood, tumor, and adjacent liver using mass spectrometry. Tumor necrosis was determined by histopathological examination. Intratumoral hypoxia-inducible factor (HIF) 1α, vascular endothelial growth factor (VEGF), and microvessel density (MVD) were determined by immunohistochemistry.ResultsThe median intratumoral concentration of sorafenib in the SORA-DOX-TACE group was 17.7 μg/mL (interquartile range [IQR], 7.42–33.5 μg/mL), and its maximal plasma concentration (C_max) was 0.164 μg/mL (IQR, 0.0798–0.528 μg/mL). The intratumoral concentration and C_max of doxorubicin were similar between the groups: 4.08 μg/mL (IQR, 3.18–4.79 μg/mL) and 0.677 μg/mL (IQR, 0.315–1.23 μg/mL), respectively, in the DOX-TACE group and 1.68 μg/mL (IQR, 0.795–4.08 μg/mL) and 0.298 μg/mL (IQR, 0.241–0.64 μg/mL), respectively, in the SORA-DOX-TACE group. HIF-1α expression was increased in the SORA-DOX-TACE group than in the DOX-TACE group. Tumor volume, tumor necrosis, VEGF expression, and MVD were similar between the 2 groups.ConclusionsThe addition of sorafenib to DOX-TACE delivered to VX2 liver tumors resulted in high intratumoral and low systemic concentrations of sorafenib without altering the PK of doxorubicin.     

脂肪乳剂通过激活自噬流解救布比卡因心肌毒性

目的：探讨自噬在脂肪乳剂解救布比卡因心肌毒性中的作用。方法：取对数生长期的H9C2心肌细胞随机分成空白溶剂组（DMSO组）、布比卡因组（Bup组）、脂肪乳剂组（Lip组）、脂肪乳剂联用布比卡因组（BLp组）,相应药物处理24 h后,CCK8检测细胞增殖抑制率,光镜下观察细胞形态,电镜下观察细胞自噬现象,激光共聚焦显微镜下监测自噬流情况,Western blot和RT-PCR检测LC3II/I、p62蛋白和mRNA表达水平。结果：与DMSO组相比较,Bup组心肌细胞增殖抑制率明显升高（P ＜0.05）,光镜下可见细胞大量死亡皱缩,形态不规则,胞核不清,电镜下见自噬体大量堆积,激光共聚焦显微镜下见自噬流被抑制,LC3II/I、p62蛋白和mRNA表达水平均显著升高（P ＜0.05）。与Bup组相比较,BLp组与Lip组心肌细胞增殖抑制率显著下降（P ＜0.05）;光镜下心肌死亡细胞减少,细胞界限清楚,胞浆清晰,胞核清楚;电镜下自噬体减少;自噬流加快自噬体清除;LC3II/I、p62 蛋白和mRNA表达水平均显著下降（P ＜0.05）。结论：脂肪乳剂可通过激活自噬流来加快自噬体的清除从而解救布比卡因所致心肌毒性。