高效液相色谱法测定碘克沙醇注射剂中碘克沙醇的含量

<正>含碘造影剂已广泛应用于临床多年,随着现代医学的发展,临床研究发现,大部分造影剂具有不同程度的肾毒性。目前离子型含碘造影剂基本上已被淘汰,非离子型含碘造影剂已普遍应用,低渗非离子型含碘造影剂因安全、有效、耐受性好而被大家认可;而碘克沙醇作为一个新型的可溶性非离子型等渗的二聚体六碘X线造影剂,可在血管内应用,研究表明任何浓度的碘克沙醇在血中都是等渗     

非离子型造影剂引起过敏性休克3例报告

常用的碘造影剂分为两大类型：离子型和非离子型。非离子型造影剂是新一代造影剂，可使碘离子不易与血管内皮接触，具有不产生电离、低渗、低黏、不良反应少等优点。文献报道非离子型造影剂的变态反应（过敏反应）发生率非常低，仅为0．04％，严重过敏反应罕见，因而在临床上广泛应用。离子型造影剂在使用前全部需要做过敏试验，而非离子型造影剂相对来说比较安全，一般无需做皮试，     

造影剂在螺旋CT增强扫描中的应用

目的 探讨离子型造影刑与非离子型造影剂在螺旋CT增强扫描中的作用.方法 通过对照组和观察组患者的螺旋CT增强扫描结果,进行增强效果和过敏反应评价.结果 对照组增强合格率99.8%.过敏反应率11.2%.观察组增强合格率100%,过敏反应率4.8%.两组患者增强效果无明显差别,非离子型造影剂过敏反应率明显低于离子型造影剂.结论 在增强扫描中造影剂的合理选择非常重要,对碘过敏反应要积极预防并有效地处理.     

使用紫杉醇注射液致过敏反应危险因素分析

目的:探讨化疗药物紫杉醇注射液致过敏反应的相关危险因素,为有效预防过敏反应的发生提供参考。方法:回顾性分析2012年我院输注紫杉醇注射液致过敏反应的62份临床病历,并随机抽取输注紫杉醇注射液未发生过敏反应的102份病历作为对照,对紫杉醇注射液致过敏反应的可能危险因素进行单因素分析及多因素非条件Logistic回归分析。结果:单因素分析结果显示,药物配制浓度、药物过敏史、滴速和预处理方法几个因素未发生与发生过敏反应组间的差异有统计学意义(P<0.05);多因素非条件Logistic回归分析结果显示,上述4个因素均为紫杉醇注射液致过敏反应的危险因素。结论:使用紫杉醇注射液过程中,应当对其致过敏反应的药物配制浓度、药物过敏史、滴速和预处理方法几个危险因素给予关注和干预,以有效预防过敏反应发生。     

碘造影剂的速发过敏样反应

碘造影剂过敏样反应可分为速发反应(IAR)和迟发反应(LAR).非离子型造影剂应用于临床至今,IAR明显下降,但严重病例及死亡率并未见显著降低.目前对于IAR的机制了解有限,大多数病例病因学呈多因素,极少数严重病例可明确归为IgE Ⅰ型过敏反应.皮试对于预测严重不良反应并无临床价值.重要风险因素为IAR史、哮喘、过敏史等.糖皮质激素单剂量预防用药无效,且其预防作用尚存争议.防范意识和及时识别、救治严重反应病例是避免意外的重要手段.     

冠状动脉介入诊疗中造影剂对肾功能影响的临床观察

目的探讨冠状动脉介入诊疗中造影剂对肾功能影响以及引起造影剂肾病（CIN）的危险因素及其防治。方法行冠状动脉造影和经皮冠状动脉介入术患者980例，术前肾功能正常者969例选用非离子型低渗造影剂碘普罗胺370，术前肾功能异常者11例用等渗造影剂碘克沙醇，均于介入治疗前及治疗后第2、5天分别检查肾功能指标，分析CIN的危险因素及防治方法。结果术前肾功能正常者CIN发生率为2.5％，发生CIN患者与未发生CIN患者在糖尿病、造影剂用量和术前补液量等方面有统计学意义（P〈0．05）。术前肾功能异常者未发生CIN，但例数过少，不具说服力。结论造影剂可引起一过性肾功能改变，CIN与糖尿病、造影剂用量和补液量有关。     

非离子型造影剂优维显变态反应试验400例临床观察

优维显是第二代单体非离子型低渗造影剂,其化学结构为单苯环三碘,亦称磺普罗胺。它化学毒性低、渗透压低、有良好的血管内皮耐受性、副作用小、安全性高,所以一般都没有强调做变态反应试验,但极少数病人使用该造影剂仍可出现变态反应。为了避免严重的变态反应发生,特别是对有药物过敏史的病人应强调在用药前作药物变态反应试验。     

碘过敏试验致呼吸心跳骤停的抢救及护理体会

临床上常用碘化物造影剂作肾脏、胆囊、膀胱、支气管、心血管、脑血管造影,此类药物可发生过敏反应。因此在造影前必须先作过敏试验,阴性者才能作碘造影检查。我院常用的碘造影剂为离子型造影剂：76％复方泛影葡胺,虽过敏反应时有发生．但致呼吸、心跳骤停者却不多见。我院于2003年至今成功抢救了3例碘过敏试验致呼吸心跳骤停的患者,现将护理体会报道如下：     

重视非离子型冠脉造影剂引发的过敏样反应

非离子型碘造影剂可引起过敏样反应,美国放射学会2008年修订最新分类标准,将其分为轻度、中度、重度三类。北京阜外心血管病医院2007-2009年严重过敏样反应发生率0.037%,与国外文献报道相似。预防造影剂导致过敏样反应的关键,是甄别高危人群,并事先给予预防措施,如糖皮质激素和/或抗组胺药等。介入医生应时刻警惕造影剂引发的过敏样反应。中重度过敏样反应需要立即处理,如吸氧、补液、激素治疗和升压药（尤肾上腺素）以及心肺复苏等。非离子型碘造影剂引发的过敏样反应相对少见,及时识别、迅速处理严重过敏样反应是防止患者出现严重不良后果的关键。     

碘普罗胺注射液的不良反应

碘普罗胺注射液是一种非离子型低渗性造影剂。可降低因高渗透压引起的不良反应;溶液呈中性,不会影响带电荷的蛋白质和细胞膜结构,也不干扰体内电解质的平衡;对红细胞、内皮细胞及体液影响小。适用于血管造影、脑和腹部 CT 扫描及尿道造影,因其性质稳定,使用简便,不良反应小于离子型碘造影剂,因而被广泛用于心血管造影。随着使用频率和使用量的增加,碘普罗胺注射液不良反应报告的病例也逐年增加。2012年,国家药品不良反应监测数据库共收到怀疑药品为碘普罗胺注射液的不良反应事件报告709例,其中严重报告157例（22．14％）。其严重报告病例中严重过敏反应较为突出,主要表现为过敏性休克、喉水肿、过敏样反应和呼吸困难等。现将碘普罗胺注射液近年引起的不良反应综述如下。     

Hypersensitivity reactions to iodinated contrast media

Adverse reactions after iodinate contrast media (ICM) administration have been observed, which can be classified as immediate (i.e., occurring within one hour after administration) and delayed or non-immediate (i.e., occurring more than one hour after administration). Even though the incidence of ICM adverse reactions has been significantly reduced by the introduction of non-ionic compounds, immediate reactions still occur in about 3% of administrations. Different pathogenic mechanisms have been suggested for ICM reactions, including immunologic ones. Basophils and mast cells participate in immediate reactions through the release of mediators like histamine and tryptase, whereas a T-cell-mediated pathogenic mechanism is involved in most non-immediate reactions, particularly maculopapular rashes. Skin tests and specific IgE assays are carried out to diagnose immediate hypersensitivity reactions, while both delayed-reading intradermal tests and patch tests are usually performed to evaluate non-immediate reactions. However, in vitro specific IgE assays are not commercially available. As far as in vitro tests are concerned, a response involving ICM-related T-cell activity may be assessed by the lymphocyte transformation test. Allergologic evaluation appears to be indicated in hypersensitivity reactions to ICM, although the sensitivity, specificity, and predictive values of allergologic tests have not yet been established. This paper summarizes the current state of the art and addresses the research that is still needed on the pathogenic mechanisms, diagnosis, and prevention of ICM-induced hypersensitivity reactions.     

碘造影剂过敏样反应发生机制研究进展及防治

目的:综述碘造影剂(ICM)过敏样反应发生机制研究进展。方法:参考国外相关文献,从膜效应、补体系统激活、缓激肽释放、Ig-E介导的抗原抗体反应、T细胞介导的免疫反应这5个方面,对ICM过敏样反应发生机制研究进行综述。结果和结论:ICM过敏样反应中绝大多数属于类过敏反应,真正的过敏反应很少,因此皮肤试验假阴性概率高,大规模推广造影前进行皮试意义不大。     

Immediate reactions to contrast media: mediator release and value of diagnostic testing

Immediate reactions to iodinated contrast media (ICM) resembles anaphylaxis. The recent literature demonstrates that histamine is released in vivo, with a peak concentration correlating within the severity grade of the reaction. Mast cells participate in severe reactions, as shown by several authors through the release of tryptase. In patients with severe reactions, intradermal testing with immediate reading appear positive to the culprit ICM, confirming an immune mechanism. For further procedures, a strict avoidance of the culprit ICM must be observed. The injection of another ICM giving negative skin tests has proved safe in a few patients.     

Current understanding of contrast media reactions and implications for clinical management.

Iodinated contrast media (CM) are an integral part of modern diagnostic medicine. Although these agents are considered to be relatively safe, adverse effects in the form of allergy-like reactions occur in a significant number of exposed patients. These reactions may be divided into immediate and delayed responses. Immediate (within 1 hour of administration) anaphylactic reactions range from urticaria and angioedema to laryngeal oedema, hypotension and even death. Delayed reactions to CM occur from 1 hour to 1 week after administration and usually have mostly cutaneous manifestations. History of prior CM reactions and atopy predispose patients to CM reactions. Despite intense research into the pathogenesis of the immediate anaphylactoid responses, new evidence shows that true IgE type I hypersensitivity mediation occurs only in rare, severe cases. The aetiology appears to be multifactorial in most individuals. There is strong evidence to conclude that type IV hypersensitivity is responsible for the delayed reactions to CM. Although switching to non-ionic agents significantly reduces the incidence of immediate reactions to CM, there is little consensus regarding corticosteroid prophylaxis in high-risk individuals. Skin testing and provocative challenges also provide little security. Therefore, physicians must be better prepared to treat immediate anaphylactoid responses. Preventing delayed CM reactions is best performed with patch and delayed intradermal testing in those with a history of prior reactions, although false-negative results have been reported. Corticosteroids and antihistamines may be required for treatment. Until newer agents are developed that negate these issues, healthcare providers must strive to better understand the risk factors associated with CM reactions, as well as the available prophylactic and treatment options.     

Hypersensitivity reactions to anticoagulant drugs

Drugs with anticoagulant activity, including heparins, hirudins, coumarins, and platelet aggregation inhibitors belong to the most widely used drugs. Hypersensitivity reactions from these agents are rare. However, due to their widespread use, they may have a considerable impact on patient safety and treatment. Accurate diagnosis of potentially life-threatening adverse events and identification of alternatives is mandatory. We review hypersensitivity reactions caused by the different groups of anticoagulant agents and discuss the pathophysiological mechanisms, diagnostic possibilities and management options. According to patients histories the most common hypersensitivity reaction is intolerance to acetylsalicylic acid (ASA). Also localized erythematous plaques, occurring to subcutaneous application of heparins are rather common. Other hypersensitivity reactions are rare but may be life-threatening, e.g. skin necrosis due to heparin-induced thrombocytopenia. Rarely anaphylactoid reactions have been observed to ASA, heparin, and hirudin. Skin and provocation tests with immediate and late readings are the most reliable diagnostic tools for heparin- or hirudin-induced urticaria/anaphylaxis or heparin-induced delayed plaques. Provocation tests may be used to identify safe alternatives. In cases of necrosis from heparins or coumarins, all in vivo tests are contraindicated. Most in vitro tests are not universally available, and with the exception of platelet aggregation tests, they have a low sensitivity. In some anticoagulant-associated hypersensitivity reactions detailed allergologic investigation may help to identify safe treatment alternatives. Typically, several tests are needed, and therefore the test procedures are time consuming.     

Contrast media hypersensitivity--scope of the problem

Hypersensitivity reactions to contrast media (CM) are frequent causes of anaphylactically induced fatalities. Adverse events after CM exposure are classified into immediate and non-immediate reactions, with differing pathomechanisms. In the majority of patients with immediate reactions, IgE-mediated allergy can not be demonstrated and the underlying mechanism remains unknown. However, recent data has provided evidence for skin test positivity and/or specific IgE in some patients with severe reactions. Cell-mediated hypersensitivity is the responsible mechanism for the majority of non-immediate skin eruptions. Skin tests have been employed to confirm this hypersensitivity. Previous reactors have an increased risk to develop new reactions upon repeated exposure, however, other risk factors are poorly defined. The use of skin tests for the selection of a "safe" CM is controversially discussed; information on sensitivity and specificity is lacking. New in-vitro assays have to be developed and/or validated. Premedication of previous reactors is common practice among radiologists, however, its precise role in the prevention of severe CM reactions to lower-osmolality CM has not been demonstrated. Thus, the main future tasks are to develop and validate allergic tests procedures, which may identify patients at risk and/or may confirm CM tolerance, and to reassess the value of different premedications in the prevention of hypersensitivity reactions.     

An IgE immediate reaction to thiocolchicoside

Hypersensitivity reactions due to muscle relaxant drugs may be related either to a nonspecific release of allergic mediators or to allergic reactions induced by the molecules themselves. Rare cases of hypersensitivity reactions have been associated to thiocolchicoside, and no case of IgE-mediated immediate reaction has actually been reported to date. We report the first documented case of immediate anaphylaxis to thiocolchicoside.     

Hypersensitivity reactions to ophthalmic products

Adverse reactions after administration of ophthalmic products have frequently been observed. These reactions can be provoked by both active principles and excipients. Different pathogenic mechanisms have been suggested for such reactions, including immunologic ones. Basophils and mast cells participate in IgE-mediated reactions through the release of mediators like histamine and tryptase, whereas a T-cell-mediated pathogenic mechanism is involved in most delayed reactions, particularly conjunctival ones and eyelid dermatitis. Prick tests and immediate-reading intradermal tests are carried out to diagnose immediate hypersensitivity reactions, while patch tests are usually performed to evaluate delayed reactions. Other diagnostic tests, such as serum-specific IgE assays in immediate reactions, as well as delayed-reading intradermal tests and/or lymphocyte transformation tests in delayed ones, are rarely performed. In this review, particular attention is addressed to the clinical and practical aspects of both cell-mediated and IgE-mediated hypersensitivity reactions to ophthalmic products.     

Skin tests in the diagnosis of drug hypersensitivity reactions

Adverse drug reactions (ADRs) are an area of concern for pharmaceutical drug development. Among these, drug hypersensitivity reactions are neither dose-dependent nor predictable, and affect only predisposed individuals. Clinical and immunological studies suggest that IgE-mediated (type I) and cell-mediated (type-IV) pathogenic mechanisms are involved in many immediate (i.e., occurring within 1 hour after the last drug administration) and non-immediate (i.e., occurring more than 1 hour after the last drug administration) hypersensitivity reactions, respectively. Skin prick, patch, and intradermal tests are the most readily available tools for the evaluation of hypersensitivity drug reactions. The diagnostic value of skin tests for many drugs still has not been fully established. Reliable skin test procedures for the diagnosis of drug hypersensitivity have been defined, and test concentrations have been validated for many drugs. Skin tests should be carried out according to the clinical features of ADRs. In immediate drug reactions, an IgE-mediated mechanism can be demonstrated by a positive skin prick and/or intradermal test after 20 minutes, whereas in non-immediate reactions, a T-cell involvement can be found by a positive patch test and/or a late-reading intradermal test. The predictive value of skin tests varies with the drug tested and is especially high with beta-lactams, muscle relaxants, insulins, platinum salts, streptokinase, and chymopapain. Further diagnostic tests are required in the assessment of drug hypersensitivity reactions. However, skin tests can provide information about the culprit drug and the mechanism involved in certain reactions. The present review addresses literature data regarding the diagnosis of drug hypersensitivity reactions by skin tests.     

Adverse skin reactions to low molecular weight heparins: frequency, management and prevention.

Adverse skin reactions to low molecular weight heparins (LMWH) are rare even though their true incidence is probably underestimated because of under-reporting. These reactions may occur as an urticarial rash, presumably due to local histamine release or have the features of a classic type I immediate hypersensitivity reaction. They can also present as skin necrosis often due to vasculitis (type III Arthus reaction) or heparin-induced thrombocytopenia. Erythematous, well circumscribed lesions without necrosis are usually secondary to a delayed type IV hypersensitivity reaction. Although most LMWH-induced skin lesions are benign, treatment should be discontinued. In type I reactions or in the presence of skin necrosis with or without heparin-induced thrombocytopenia, the LMWH should be replaced by an alternative medication such as danaparoid sodium or hirudin. Platelet counts should be monitored to diagnose heparin-induced thrombocytopenia. In a type IV delayed hypersensitivity reaction, in the absence of severe, extensive, life-threatening mucocutaneous manifestations, a first-line pragmatic approach consists, in our view, of replacing the particular LMWH with another one. If the skin symptoms do not improve, cutaneous tests may help detect the presence of a cross-reactivity between the available preparations of LMWHs and danaparoid sodium. In the presence of a negative subcutaneous provocation test, the compound can be used with little risk. If all types of LMWH and danaparoid sodium are positive in skin testing, mechanical prevention or oral anticoagulants should be used, and intravenous injections of any kind of heparin should be avoided because of the potential risk of anaphylactic shock. Alternatively, hirudin might be administered but experience with this compound is still very limited. Prevention is only possible in type IV hypersensitivity skin reactions, by avoiding long term LMWH therapy, particularly in middle-aged, obese women and during pregnancy. In these patients, oral anticoagulation should be preferred, whenever possible. In conclusion, though rare, skin reactions to LMWH may have important consequences which can be reduced by rapid diagnosis and appropriate management.