A comparison of the actions of pentobarbitone and etomidate on [H]GABA binding to crude synaptosomal rat brain membranes

A study was performed in which both anterograde ([³H]leucine radioautography) and retrograde (horseradish peroxidase (HRP) histochemistry) tracing methods were employed to identify the origin of the fimbrial projection to the nucleus accumbens in the rat. The data reveal that this pathway arises predominantly from layers II–III of the anterior two-thirds of entorhinal cortex rather than from any part of hippocampal formation.     

Cardiovascular effects of xenon and nitrous oxide in patients during fentanyl-midazolam anaesthesia

Xenon anaesthesia appears to have minimal haemodynamic effects. The purpose of this randomised prospective study was to compare the cardiovascular effects of xenon and nitrous oxide in patients with known ischaemic heart disease. In 20 patients who were due to undergo coronary artery bypass graft surgery, 30 min following induction of anaesthesia with fentanyl 30 microg x kg(-1) and midazolam 0.1 mg x kg(-1) but prior to the start of surgery, xenon or nitrous oxide 60% was administered for 15 min. The results showed that xenon caused a minimal decrease in the mean arterial pressure (from 81 (7) to 75 (8) mmHg, mean (SD)), but did not affect the systolic function of the left ventricle, as demonstrated by unchanged left ventricular stroke work index (LVSWI) and the fractional area change of the left ventricle (FAC) derived from transoesophageal echocardiography (TOE). However, in contrast, nitrous oxide was found to decrease the mean arterial pressure (from 81 (8) to 69 (7) mmHg), the LVSWI, and the FAC. The cardiac index, central venous and pulmonary artery occlusion pressures, systemic and pulmonary vascular resistances, and the TOE-derived E/A ratio through the mitral valve were unchanged by xenon or nitrous oxide. We conclude that xenon provides improved haemodynamic stability compared with nitrous oxide, conserving the left ventricular systolic function.     

Maximum recommended doses of local anesthetics: a multifactorial concept

The current recommendations regarding maximum doses of local anesthetics presented in textbooks, or by the responsible pharmaceutical companies, are not evidence based (ie, determined by randomized and controlled studies). Rather, decisions on recommending certain maximum local anesthetic doses have been made in part by extrapolations from animal experiments, clinical experiences from the use of various doses and measurement of blood concentrations, case reports of local anesthetic toxicity, and pharmacokinetic results. The common occurrence of central nervous system toxicity symptoms when large lidocaine doses were used in infiltration anesthesia led to the recommendation of just 200 mg as the maximum dose, which has remained unchanged for more than 50 years. In most cases, there is no scientific justification for presenting exact milligram doses or mg/kg doses as maximum dose recommendations. Instead, only clinically adequate and safe doses (ranges) that are block specific are justified, taking into consideration the site of local anesthetic injection and patient-related factors such as age, organ dysfunctions, and pregnancy, which may influence the effect and the pharmacokinetics of the local anesthetic. Epinephrine in concentrations of 2.5 to 5 microg/mL should be added to the local anesthetic solution when large doses are administered, providing there are no contraindications for the use of epinephrine. As a rule, conditions (eg, end-stage pregnancy, high age in epidural, or spinal block) or diseases (uremia) that may increase the rate of the initial uptake of the local anesthetic are indications to reduce the dose in comparison to one normally used for young, healthy, and nonpregnant adults. On the other hand, the reduced clearance of local anesthetics associated with renal, hepatic, and cardiac diseases is the most important reason to reduce the dose for repeated or continuous administration. The magnitude of the reduction should be related to the expected influence of the pharmacodynamic or pharmacokinetic change.     

The local anesthetic activity of Aconitum alkaloids can be explained by their structural properties: a QSAR analysis

Alkaloids isolated from Aconitum roots exhibit anesthetic effects at peripheral nerves. We performed the present quantitative structure-activity relationship (QSAR) analysis in order to understand the mechanism of action as local anesthetics of 11 Aconitum alkaloids. The alkaloids with the highest anesthetic activity had an aroyl/aroyloxy group at R14 position while the weaker anesthetic alkaloids had the aroyloxy group at R4. The stable compounds exhibited a higher local anesthetic activity than the unstable compounds. In relation to the reactivity indexes of atoms on the aromatic ring, C2' was more reactive while C3' and C5' were less reactive in the compounds with the highest anesthetic activity. Reactivity of N, C1', C4' and C6' was similar between the two groups of alkaloids. The pKa was approximately 7.3 in both groups. The local anesthetic ED50 of alkaloids was significantly inversely related to molecular weight, core-core repulsion energy, steric energy and RI-C2', and directly related to electronic energy, total energy, RI-C5' and to the heat of formation. In conclusion, we identified a set of structural parameters that are related to the local anesthetic activity of Aconitum alkaloids. Our findings are useful to understand the mechanism of action of these alkaloids and to provide a rational for chemical manipulation of the compounds in order to obtain potent derivates with minor toxicity.     

Isoflurane induces dopamine transporter trafficking into the cell cytoplasm

Previous investigations have shown that the binding of a selective hydrophilic positron emission tomography radiotracer for the dopamine transporter (DAT) (2beta-carbomethoxy-3beta-(4-chlorophenyl)-8-(2-18F-fluoroethyl)nortropane) decreased in monkey striatum during deep isoflurane anesthesia. Immunohistochemistry experiments suggested but did not prove that isoflurane induced a decrease in cell surface DAT. The present investigation was undertaken to demonstrate quantitatively the isoflurane-induced internalization of DAT using a rapid and relatively uncomplicated biochemical technique in human embryonic kidney (HEK-293) cells stably expressing the human DAT (h-DAT) protein. Biotinylation followed by Western blot analysis was used to determine the extent of change in cell surface expression of the DAT under control conditions and in the presence of a clinically relevant concentration of isoflurane. Isoflurane treatment for 30 min resulted in a highly significant decrease in the amount of h-DAT on the cell surface (21 +/- 15% of control; P < 0.01) (mean +/- SD; n = 4). These data are consistent with the hypothesis that isoflurane results in internalization of DAT from the cell membrane and further validate our qualitative results reported previously. In addition, the current results confirm the hypothesis that biotinylation can be used to quantitate the extent of disappearance of DAT from the cell surface making dose-response studies and comparisons of DAT internalization with other general anesthetics practical.     

Transient radicular irritation (TRI) after spinal anaesthesia in day-care surgery

Background : A high incidence of backache with radiating pains to the lower extremities, termed transient radicular irritation (TRI), has been reported following the use of 5% hyperbaric lidocaine. This has been attributed to a neurotoxic reaction.
Methods : A retrospective audit has been carried out in our hospital on the postoperative anaesthetic records of all patients from the 1st of January 1993 to the 1st of September 1996, who received spinal anaesthesia with either hyperbaric lidocaine or hyperbaric bupivacaine for day-care surgery.
Results : Backache was reported in 1.9% of patients (6/322) receiving hyperbaric lidocaine and in 2.4% of patients (1/41) receiving hyperbaric bupivacaine. This was not associated with any sensory, motor or sphincter disturbances. One patient complained of backache with bilateral pain referred to the gluteal area (TRI), which was assessed as acute facet joint syndrome. Unilateral accidental block of the femoral nerve was observed in 3 patients, sensory disturbances in the L2/3 dermatome was reported in a further 3 patients at 24 h, following wound infiltration with local anaesthetic during hernia repair.
Conclusions : The low incidence of backache at 24 h and the absence of associated symptoms of neurogenic pain, sensory and motor disturbances, does not support the hypothesis that TRI is a neurotoxic reaction, subsequent to the use of hyperbaric lidocaine.     

急性吸入性氯氰菊酯中毒13例临床分析

目的 通过分析氯氰菊酯吸入中毒的临床特点与救治经验,比较其与口服中毒的不同临床特点.方法 回顾性分析2012年6月群体性5％高效氯氰菊酯可湿粉吸入中毒13例患者的临床表现、影像学、实验室检查、治疗及转归.结果 除神经毒性及消化道损害之外,氯氰菊酯吸入中毒患者中,咽干(61.5％)、咳嗽咳痰(61.5％)、呼吸困难(30.8％)、气短(23.1％)等呼吸道症状明显.结论 氯氰菊酯吸入中毒可以造成明显的呼吸道损害,轻者表现为上呼吸道刺激症状或气管支气管炎症表现.     

七氟烷用于小儿诱导及维持麻醉的临床研究

目的:观察七氟烷用于儿童患者时的诱导和苏醒特征,评估其安全性和麻醉效果.方法:选择40例符合入选标准的患儿,在全麻下行择期手术.所用患儿均不给术前药,入手术室后面罩直接吸纯氧(1 L/min)加七氟烷,逐步升高七氟烷的吸入浓度(最大浓度为7%),直至患儿睫毛反射消失,维持浓度控制在4.0%以下.所有患儿均行气管插管,可合用维库溴胺0.1 mg/kg保证肌松.结果:七氟烷吸入诱导成功率100%,睫毛反射消失时间在60～132 s之间;呼吸道分泌物少,气道耐受性好,术中维持浓度为1.0%～4.0%,麻醉效果满意;血流动力学稳定,无心率减慢、血压下降者;全组患儿体温均正常.结论:七氟烷吸入用于小儿诱导快速,气道刺激小,心血管抑制轻,苏醒迅速,麻醉满意,安全可控.