乳剂治疗酰胺类局麻药中毒研究新进展

酰胺类局麻药是临床常用的局麻药,其引起的局麻药中毒的并发症一直困扰着临床麻醉师。局麻药中毒一旦出现心血管反应后复苏较难。近年来,脂肪乳对于酰胺类局麻药导致的中毒反应发挥一定的作用,并在许多动物实验中得到证实。目前认为＂脂肪池假说＂及改善心肌能量代谢作为理论依据来证明脂肪乳剂是局麻药中毒后采用常规基本生命支持的一个有效补充,为临床运用局麻药保驾护航。     

硬膜外阻滞计量对穿刺点扩散的影响

用于硬膜外阻滞的局麻药应该具备弥散性强、穿透性强、毒性小,且起效时间短,维持时间长等特点.目前常用的局麻药有利多卡因、罗哌卡因及布比卡因.若无禁忌证,椎管内阻滞的局麻药中可添加肾上腺素(浓度不超过5μg/ml),以延长局麻药的作用时间、减少局麻药的吸收、强化镇痛效果以及作为局麻药误入血管的指示剂.     

局麻药神经毒性影响因素及作用机制研究进展

目的介绍局麻药神经毒性的影响因素及作用机制的研究进展。方法查阅近年来局麻药神经毒性大小的影响因素以及局麻药作用机制的相关文献,并进行归纳总结。结果局麻药的种类、剂量、时间等可影响局麻药的神经毒性,作用机制可能与细胞膜、细胞内钙离子浓度、诱导细胞凋亡炎性反应等相关。结论目前,局麻药均面临着神经毒性问题,随着新型局麻药不断问世,有关局麻药神经毒性作用机制更引人关注,局麻药神经毒性研究的不断深入为局麻药的临床合理应用带来了更为广阔的前景。     

北京市20家医院2008-2011年妇产科局部麻醉药处方情况分析

目的:研究北京市20家医院2008-2011年妇产科局麻药处方情况。方法:对北京市20家医院2008-2011年妇产科局麻药处方进行统计分析。结果:北京市20家医院2008-2011年妇产科局麻药处方按药品名称、给药途径、单价、医保范畴、来源统计结果见正文。结论:利多卡因注射剂在是妇产科局麻药的使用上占主导地位。局麻药的使用与多种因素有关。     

新型缓释剂型局部麻醉药的研究现状

随着药剂学及工艺技术的发展．局麻药的缓释剂型及其它剂型的研究取得了显著的进步。局麻药研究重点已转向控释制剂、靶向制剂和局麻药用途的扩展。本文将综述局麻药微球、脂质体、水凝胶及微囊等的研究进展．并对多种新剂型的长时效特点进行了分析。     

局麻药应用进展

目前新的局麻药陆续问世,使麻醉医生选择局麻药的范围更为广泛。但各种局麻药均有各自的特点,表现在药物的阻滞强度、作用时间长短及它的毒性反应上。布比卡因阻滞效果确切、作用时间长,但它的缺点是机体中枢神经和心脏毒     

局麻药毒性反应的临床观察与处理

目的观察局麻药毒性反应。方法按常规操作方法行硬脊膜外腔麻醉、神经阻滞麻醉。结果局麻药发生轻、中、重不同比例毒性反应。结论局麻药毒性与其血浆浓度过高有关,需结合临床毒性症状及体征相应处理。     

局麻药脊髓神经毒性的研究进展及预防

随着人们对局麻药毒副作用的逐渐认识,局麻药的神经毒性也越来越受到重视.但局麻药的脊髓神经毒性机理仍有待于阐明,可能与局麻药自身毒性有关,也可能与之诱导的神经细胞凋亡有关.局麻药神经毒性在很大程度上与其浓度、剂量及与神经细胞接触时间相关.本文就局麻药脊髓神经毒性发生机制及预防的研究进展做一综述.     

罗哌卡因/左旋罗哌卡因在麻醉和神经阻滞与术后镇痛中的应用进展

布比卡因是临床应用最为广泛的长效局麻药之一。近年来新型长效局麻药罗哌卡因及左旋布比卡因的临床应用,为临床麻醉、神经阻滞和术后镇痛提供了较为理想的选择。罗哌卡因是一种新型长效酰胺类局麻药。为甲哌卡因、丁卡因的左旋异构体。与布比卡因相比,具有感觉阻滞与运动阻滞分离更趋明显,也有代谢快,对心脏毒性小等特点[1]。左旋布比卡因也是长效酰胺类局麻药,是布比卡因的左旋体。布比卡因是左旋体和右旋体等量混合的消旋体型。     

不同PH值盐酸利多卡因溶液的药效学比较

不同ｐＨ值盐酸利多卡因溶液的药效学比较南京市鼓楼医院临床药学室（２１０００８）刘莉，汪小海，葛卫红国内外许多学者提出［１］，ｐＨ是影响局麻药麻醉效能的重要因素，提高局麻药溶液的ｐＨ，即可缩短局麻药的麻醉潜伏期，增强局麻药的麻醉效能。盐酸刮多卡因为临床...     

Literature review of the evidence regarding intravenous lipid administration in drug-induced cardiotoxicity

ABSTRACT

Introduction: Intravenous lipid emulsion (ILE) administration is capable of reversing the acute cardiac and neurological toxicity caused by local anesthetic agents. In recent years, ILE has also been explored as a potential antidote for cardiotoxicity caused by non-anesthetic agents too.

Areas covered: The potential mechanisms, safety, and efficacy of this approach are considered. Data were sought from published reports listed in PubMed and EMBASE, and abstracts of meetings of the North American Congress of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists. There were reports involving 298 patients where ILE has been administered for severe drug toxicity. Clinical improvement was observed in 57 of 59 patients with local anesthetic toxicity (96.6%); there were 239 patients where toxicity was due to non-anesthetic agents, and ILE apparently improved clinical outcome in 215 (72.1%).

Expert opinion: Response rates were similar between ILE treated toxicity caused by lipid soluble and non-lipid soluble drugs. Potential adverse effects of ILE include interference with laboratory assays, acute pancreatitis, and adult respiratory distress syndrome, although the rate of occurrence is difficult to ascertain.     

Intravenous fat emulsion: A potential novel antidote

Intravenous fat emulsions (IFE) are traditionally used as a component of parenteral nutrition therapy. Recently, IFE was used to resuscitate severe local anesthetic drug toxicity. This review focuses on the potential role of IFE in treatment of toxicity due to local anesthetics and other lipid-soluble drugs. The general properties of IFE, metabolic fate, and associated adverse events are described. Cases of local anesthetic toxicity treated with IFE are presented along with a discussion of the possible antidotal mechanisms. Initial investigations into the antidotal use of IFE for lipophilic central nervous and cardiovascular drug toxicity are also reviewed.     

Intravenous lipid emulsion for local anesthetic toxicity: A review of the literature

Introduction

The use of intravenous lipid emulsion (IVLE) has been proposed as a new potential treatment for local anesthetic toxicity. Local anesthetics work through reversible binding at sodium channels, and signs and symptoms of toxicity include central nervous system and cardiovascular effects. Cardiovascular collapse is a potential result of local anesthetic toxicity, and is generally resistant to resuscitation efforts with standard measures.

Discussion

Various animal studies have been published investigating the use of IVLE in local anesthetic toxicity. IVLE has been shown to increase the lethal dose of bupivacaine required, resuscitate animals that underwent local anesthetic-induced cardiovascular collapse, and more quickly reduce the amount of local anesthetic in the myocardium (compared to administration of control solution). Four human case reports utilizing IVLE for presumed local anesthetic toxicity, with varying presentations, are reviewed.

Conclusions

IVLE has shown to be an interesting prospect for local anesthetic toxicity. Human case reports have shown successful resuscitation with use of IVLE, using varying dosing regimens. More studies are needed to determine the optimal dosing regimen, as well as to determine the potential adverse effects of IVLE when used in this setting.     

Benefit and risks of local anesthetics in infants and children

Regional anesthesia has become a routine part of the practice of anesthesiology in infants and children. Local anesthetic toxicity is extremely rare in infants and children; however, seizures, dysrhythmias, cardiovascular collapse, and transient neuropathic symptoms have been reported. Infants and children may be at increased risk from local anesthetics compared with adults. Larger volumes of local anesthetics are used for epidural anesthesia in infants and children than in adults. Metabolism and elimination of local anesthetics can be delayed in neonates, who also have decreased plasma concentrations of alpha(1)-acid glycoprotein, leading to increased concentrations of unbound bupivacaine. Most regional anesthetic procedures in infants and children are performed with the patient heavily sedated or anesthetized; because of this, and because a test dose is not a particularly sensitive marker of intravenous injection in the anesthetized patient, detection of intravascular local anesthetic injection is extremely difficult. The same local anesthetics used in adult anesthetic practice are also used in infants and children. Because of its extremely short duration of action, chloroprocaine has been used primarily for continuous epidural techniques in infants and children. The use of tetracaine has generally been limited to spinal and topical anesthesia. Lidocaine (lignocaine) has been used extensively in infants and children for topical, regional, plexus, epidural and spinal anesthesia. The association between prilocaine and methemoglobinemia has generally restricted prilocaine use in infants and children to the eutectic mixture of local anesthetics (EMLA). Because of its greater degree of motor block compared with other long-acting local anesthetics, etidocaine has generally been limited to plexus blocks in infants and children. Mepivacaine has been used for both plexus and epidural anesthesia in infants and children. Because postoperative analgesia is often the primary justification for regional anesthesia in infants and children, bupivacaine, a long-acting local anesthetic, is the most commonly reported local anesthetic for pediatric regional anesthesia. Given the lower toxic threshold of bupivacaine compared with other local anesthetics, the risk-benefit ratio of bupivacaine may be greater than that of other local anesthetics. Two new enantiomerically pure local anesthetics, ropivacaine and levobupivacaine, offer clinical profiles comparable to that of bupivacaine but without its lower toxic threshold. The extreme rarity of major toxicity from local anesthetics suggests that widespread replacement of bupivacaine with ropivacaine or levobupivacaine is probably not necessary. However, there are clinical situations, including prolonged local anesthetic infusions, use in neonates, impaired hepatic metabolic function, and anesthetic techniques requiring a large mass of local anesthetic, where replacement of bupivacaine with ropivacaine, levobupivacaine or (for continuous techniques) chloroprocaine appears prudent.     

Acute acrylonitrile toxicity: studies on the mechanism of the antidotal effect of D- and L-cysteine and their N-acetyl derivatives in the rat

Thiol-containing antidotes for acute acrylonitrile (AN) toxicity may exert their action by chemically reacting with AN, by replacing critical sulfhydryl groups cyanoethylated by AN, and by detoxifying cyanide produced from AN metabolism. We have evaluated the ability of the optical isomers of cysteine and N-acetylcysteine to act as antidotes against AN toxicity in order to assess the relative importance of each of these three antidotal mechanisms. The toxicity of AN was determined in male Sprague-Dawley rats and compared to the toxicity determined after treatment with 2 mmol/kg of thiol antidote by computing a protective index (median lethal dose with antidote/median lethal dose without antidote). The protective indices of L-cysteine, D-cysteine, N-acetyl-L-cysteine, and N-acetyl-D-cysteine were 2.03, 1.97, 1.76, and 1.25, respectively. Measurements of urinary mercapturates, derived from the non-oxidative pathway of AN metabolism, indicated that none of the antidotes was able to significantly increase the excretion of these metabolites. Blood cyanide generated from the oxidative metabolism of AN and butyronitrile was also determined. All of the antidotes, except N-acetyl-D-cysteine, lowered blood cyanide levels. A comparison of these results with the predicted relative abilities of the enantiomers to participate in each of the three antidotal mechanisms leads to the conclusion that, under these experimental conditions, the best correlation exists with the cyanide detoxification mechanism.     

Life‐Threatening Bupropion Ingestion: Is There a Role for Intravenous Fat Emulsion?

Intravenous fat emulsion (IFE) is emerging as a novel antidote in clinical toxicology. Its current usage is extending beyond local anaesthetic toxicity into management of severe toxicity from some lipophilic drugs. We present a 51-year-old woman with severe bupropion toxicity whose haemodynamic status transiently improved after IFE. Serum analysis demonstrated an increase in serum concentration of hydroxybupropion, an active metabolite of bupropion, after IFE administration, lending support to one of the proposed mechanisms of IFE. A 51-year-old woman presented to the emergency department with generalised tonic-clonic convulsions lasting approximately 30 sec., and a wide complex rhythm on her ECG that was suggestive of myocardial sodium channel blockade. Despite sodium bicarbonate therapy, the patient developed profound hypotension refractory to high-dose norepinephrine. IFE was administered with haemodynamic improvement over the course of 30 min., followed by a significant decrease in norepinephrine requirement. The patient had an episode of ventricular tachycardia 24 hr after presentation, and received a second infusion of IFE. Analysis of serum for a panel of myocardial sodium channel blocking drugs revealed that significant bupropion ingestion had occurred. Bupropion poisoning may produce life-threatening clinical effects, and IFE may be considered in cases of severe haemodynamic instability. Further studies would be instrumental in determining the optimal clinical situations for utilisation of IFE.     

Lipid resuscitation: a life-saving antidote for local anesthetic toxicity

Local anesthetic toxicity is a rare, but potentially lethal, complication of regional anesthesia that cannot be prevented by any single measure. It is associated with CNS excitation and can lead to refractory cardiac dysfunction and collapse. The development of lipid emulsion for the treatment of anesthetic-induced toxicity resulted from a set of observations during a study on the potent, lipophilic drug bupivacaine and its associated clinical risk of intransigent cardiac toxicity in otherwise healthy individuals. Subsequent laboratory studies and clinical reports have shown that infusion of lipid can reliably reverse toxicity from potent local anesthetics as well as other drugs. The underlying mechanisms of lipid resuscitation may be a combination of a 'lipid sink' and metabolic effect. Lipid rescue has led to a reduction in fatalities associated with severe systemic toxicity, but continued research is necessary for a better mechanistic understanding. Increased physician awareness and education, as well as optimized treatment protocols, will significantly reduce the rate of morbidity and mortality from local anesthetic toxicity.     

Pharmacological studies on droxicainide, a new antiarrhythmic agent

The antiarrhythmic, local anesthetic and acute local and systemic toxic effects of DL-N-(2-hydroxyethyl)-pipecolinyl-2,6-dimethylanilide (AL-S-1249, droxicainide) and lidocaine were compared in animals. When given intravenously both substances suppressed ouabain-induced arrhythmias in pentobarbital-anesthetized guinea pigs; they were equipotent in this regard and had the same duration of antiarrhythmic action. Both substances produced generally equivalent sensory anesthesia following intradermal administration in the guinea pig and corneal application in the rabbit and block of motor and sensory function when injected near the sciatic nerve in the rat. In these local anesthetic tests and following intradermal administration to rabbits, droxicainide produced less local tissue irritation than lidocaine. When given intravenously to unanesthetized mice and unanesthetized and pentobarbital-anesthetized rats, the LD50's for droxicainide were consistently higher than those for lidocaine. Since droxicainide has antiarrhythmic and local anesthetic properties that are quantitatively similar to lidocaine but local and systemic toxicity that is relatively weaker, its antiarrhythmic and local anesthetic actions merit further study.     

Preparation and Characterization of Poly(ε-Caprolactone) Nanospheres Containing the Local Anesthetic Lidocaine

The objective of this work was to develop a modified release system for the local anesthetic lidocaine (LDC), using poly(ε‐caprolactone) (PCL) nanospheres (NSs), to improve the pharmacological properties of the drug when administered by the infiltration route. In vitro experiments were used to characterize the system and investigate the release mechanism. The NSs presented a polydispersion index of 0.072, an average diameter of 449.6 nm, a zeta potential of ?20.1 mV, and an association efficiency of 93.3%. The release profiles showed that the release of associated LDC was slower than that of the free drug. Atomic force microscopy analyses showed that the spherical structure of the particles was preserved as a function of time, as well as after the release experiments. Cytotoxicity and pharmacological tests confirmed that association with the NSs reduced the toxicity of LDC, and prolonged its anesthetic action. This new formulation could potentially be used in applications requiring gradual anesthetic release, especially dental procedures.     

Acute oral toxicity of the ethyl acetate fraction of Orostachys japonicus in mice

Context: Orostachys japonicus (Crassulaceae) is referred to as Wa-song in Korea. It is used as an anti-inflammatory, antifebrile, hemostatic, and anti cancer agent, and as an antidote.

Objective: The purpose of this study was to evaluate the acute toxicity of the ethyl acetate fraction of O. japonicus (OJE) after the oral administration in Balb/c mice of both sexes.

Materials and methods: Mice were oral administered a single doses of 500, 1000, and 2000?mg/kg of body weight and were monitored for 14?d. Biochemical parameters [aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), total protein (TP), globulin (GB), total cholesterol (TC), triglyceride (TG), blood urea nitrogen (BUN), and creatinine (CR)] and histopathological examination of liver were performed.

Results and conclusion: No animals died and no toxic changes were observed in clinical signs, body weight, and organ weight. The LD₅₀ of orally administered OJE was higher than 2000?mg/kg/d in both sexes. No toxicological findings were found in biochemical parameters. In histophathological examination, neutrophilic infiltration was observed at a dose of 2000?mg/kg group in both sexes. These finding suggest that oral administration of OJE does not produce acute toxicity. Therefore, these results could provide satisfactory preclinical evidence of safety to launch clinical trials on standardized formulation of OJE to be a biohealth product.