我国10家医院静脉药物调配中心抗肿瘤药物环境污染评估及工作人员防护措施效果比较

目的：以环磷酰胺（cyclophosphamide,CP）和阿糖胞苷（cytarabine,CAR）为标志物评估我国10家医院静脉药物调配中心（pharmacy intravenous admixture services,PIVAS）环境污染情况及工作人员个人防护效果。方法：将同时检测环磷酰胺和阿糖胞苷的UPLC-MS/MS方法用于检测工作环境以及混合调配后的口罩和手套样本。结果：洁净区和一般控制区CP和CAR残留总检出率为73.5%。混合调配以及非混合调配岗位的工作人员口罩以及手套内侧均有残留污染,混合调配岗位污染残留更严重,口罩和手套的内侧污染物检出率分别为47.10%和61.85%。增加口罩和手套的层数同时注意及时更换有助于降低渗透性。结论：现有的不同防护措施表现出不同的防护效果,但并未完全阻隔药物渗透,政府和医院应更加关注PIVAS工作人员职业暴露,优化防护措施,并制订标准操作规程,提升防护效果。     

静脉用药调配中心抗肿瘤药物的职业暴露危害及防护

静脉用药调配中心（pharmacy intravenous admixture service,PIVAS）调配的药品包括全静脉营养液、细胞毒性药物和抗生素等静脉用药.护理人员在病区调配药品的过程中,可能接触到抗肿瘤药物,处于急性刺激、过敏反应、遗传毒性、致癌与致畸等职业暴露危害中.PIVAS对抗肿瘤药物进行集中调配,可减少其对护理人员的暴露危害及对周边环境的污染.对从事药品调剂的药剂人员进行职业防护,是PIVAS必须要解决的一大问题.作者对安徽医科大学第二附属医院PIVAS的相关工作经验做一总结,报道如下.关键词：静脉用药调配中心;抗肿瘤药物;职业暴露;防护分类号：R952 文献标识码：B文章编号：1671-2838（2013）05-0388-03     

抗肿瘤相关的中药注射液在静脉用药集中调配中心的分类调配与职业防护

目的:通过对抗肿瘤相关的中药注射液的调配进行合理分类,为静脉用药集中调配中心(PIVAS)人员的安全防护提供依据。方法:通过数据库和国家医保目录查找抗肿瘤相关的中药注射液品种,对药物活性成分、不良反应、药动学、特殊人群用药和毒理学研究等数据进行分析,作为分类调配的依据。结果:将通关藤注射液(消癌平注射液)、鸦胆子油乳注射液等13种抗肿瘤相关的中药注射液纳入本次研究。除黄芪多糖注射液外,多数抗肿瘤相关的中药注射液存在不同程度毒性,具有剂量和时间相关性。结合国内调配现状建议通关藤注射液、鸦胆子油乳注射液等7个品种按照抗肿瘤药物调配,其余6个品种按照普通危险药物和中药注射液调配,并根据药物的毒性和极性合理安排药物调配顺序。结论:目前国内尚无药品调配安全性分类及防护指南,PIVAS应进一步提高现有防护要求,以减少职业暴露。     

不同医院不同环境表面化疗药物污染情况调查

摘 要 目的：通过监测环境中化疗药物的残留量评估我省化疗药物配置的暴露情况,为政府部门和医疗机构药品风险管理提供依据。方法：将我省已建立静脉药物配置中心(PIVAS)调配化疗药物的5所医院编为PIVAS组,有肿瘤内科病区,但未建立PIVAS的5所医院编为肿瘤内科组,以环磷酰胺和顺铂作为环境监测标志物,对上述10所医院进行环境监测,采用面积为2 cm×2 cm的滤纸定面积（10 cm×10 cm）擦拭不同取样点及手套、口罩内侧的表面,采用高效液相色谱法测定样本中环磷酰胺和顺铂的药物浓度。结果：肿瘤内科组环磷酰胺与顺铂的检出率与总污染量均明显高于PIVAS组,差异有统计学意义（P＜0.05）。其中在污染分布方面,肿瘤内科组在大部分擦拭地点的污染量均明显高于PIVAS组,以操作台面差异最大;在采取不同防护措施上,肿瘤内科组佩戴1层手套、1层口罩时的化疗药物检出率明显高于PIVAS组,PIVAS组一次性口罩检出率又明显高于N95口罩。结论：化疗药物的配置环境中存在不同程度的污染,应加强对化疗药物职业暴露的监测与防范。     

风险管理在预防PIVAS抗肿瘤药物职业危害中的应用

为了减少PIVAS工作人员的抗肿瘤药物职业暴露危害,我院PIVAS应用风险管理的方法,识别、评估抗肿瘤药物的危害及可能导致危害的风险环节,实施防护措施并进行风险监控与系统管理。在集中调配抗肿瘤药物后,未发生一起与抗肿瘤药物相关的职业伤害事件及环境污染事件,职业暴露危害的风险指数明显降低,差异有统计学意义（P <0.05）,操作人员对于风险的认知及防护操作水平均明显提高,差异有统计学意义（P <0.01）。有效保证了PIVAS的工作环境安全及人员健康。     

静脉药物配置中心危害药品调配的职业防护

［摘要］主要从调配人员培训、建立危害药品调配相关的操作规程和规章制度、合理安排调配人员等方面探索静脉药物配置中心（PIVAS）对危害药品调配的职业防护方法; PIVAS自运行以来未发生与危害药品相关的职业伤害,PIVAS为危害药品的调配人员提供了有效的职业防护。     

医院PIVAS洁净区环境监测标准探讨

目的:完善医院静脉药物集中调配中心(PIVAS)洁净区环境监测标准。方法:参考相关国家标准及规范,结合工作实践,探讨《静脉用药集中调配质量管理规范》对已投入使用的PIVAS洁净区环境监控要求存在的问题。结果:《静脉用药集中调配质量管理规范》未对洁净区的检测方法标准作出明确规定;对压差、照度、风速无具体数值规定;未对悬浮粒子的监测进行规定,对沉降菌和浮游菌的规定不明确;缺少对风速、悬浮粒子监测频次的规定。结论:建议《静脉用药集中调配质量管理规范》对洁净区的环境监测标准应单独列出,并对检测方法、监测项目、判定标准及监测频次予以明确规定,使医院药学人员更易操作和执行。     

静脉药物调配中心妊娠期员工岗位设置与职业防护探讨

目的：探讨静脉药物调配中心（PIVAS）妊娠期员工岗位安排及安全防护。方法：通过线上软件（微信）调研不同医院PIVAS的做法,并通过医院信息系统查阅工作量并参考国内外相关研究报道进行粗略计算,从药物暴露角度说明不同岗位的职业风险,并针对性地提出防护的意见。结果：各医院对妊娠期岗位设置具体做法不一。常见普通药物挥发性弱,调配过程药物暴露量有限,但摆药区药物暴露风险仍存在。针对药物暴露的风险,调配间外如摆药区域应做好个人基本防护措施,而在调配间内除优先安排静脉营养调配岗位外,可通过建立《妊娠人员避免调配目录》,提高调配技巧、规范处理医疗垃圾等措施减少暴露机会。针对药物暴露以外的职业风险如消毒剂暴露的风险也提出相应的建议。结论：PIVAS可安排妊娠期员工调配普通药物,根据实际情况灵活安排岗位并做好充足的防护,以提供给妊娠期员工一个洁净舒适的工作环境。     

我国静脉用药集中调配模式的创建与现状

目的:为促进我国静脉用药集中调配工作模式的规范化建设和静脉用药调配中心(PIVAS)健康发展、提升临床输液的合理使用水平提供参考。方法:回顾我国PIVAS的创建与发展过程,分析我国静脉用药集中调配模式的必然性、PIVAS建设现状和需解决的问题。结果与结论:由药师负责的静脉用药集中调配模式因操作流程科学、先进、顺畅,且便于规范化管理,减少了输液调配人员的职业暴露等优势成为我国医院静脉用药调配工作的必然发展方向。我国PIVAS总体运行良好、作用显著,大幅提高了成品输液质量、促进了合理用药,也保护了护士的身体健康和病房(区)环境。这不仅有利于护理专业建设与发展,也有利于提升药学部门自身管理水平的提高。但PIVAS药师的服务价值如何予以体现尚需要合理解决。     

全自动针剂摆药系统在PIVAS抗肿瘤药物摆药中的应用

目的:提升静脉用药调配中心(PIVAS)抗肿瘤药物摆药工作质量,减少摆药差错,减少摆药人员受到的抗肿瘤药物的职业暴露伤害。方法:介绍全自动针剂摆药系统的组成及功能,并将其用于PIVAS抗肿瘤药物的摆药工作中,比较该系统使用前后1个月的各项工作指标。结果:该系统包括用药医嘱信息处理软件、设备控制软件和摆药机硬件,具有自动盘点药品、自动进筐、自动摆药、自动打印瓶签等功能。启用全自动针剂摆药系统后,摆药流程中的输液标签打印、分筐和摆药操作由人工换为自动,节约了人力资源,每张标签平均摆药时间由原来的(33.00±3.31)s缩短为(15.55±1.41)s,摆药差错及破损数量降为0。结论:全自动针剂摆药系统的应用,实现了PIVAS抗肿瘤药物摆药的自动化,减少了摆药差错,减少了工作人员接触抗肿瘤药物的机会,减少了其带来的职业暴露伤害。     

Medical surveillance for antineoplastic-drug handlers

Elements of a medical surveillance program are described, with emphasis on a program for antineoplastic-drug handlers in a hospital setting. There are four data-gathering elements in any medical surveillance program: the history (medical and occupational), the physical examination, laboratory studies, and biological monitoring. Of these, the most useful and cost-effective is the history. The physical examination and laboratory tests should focus on the target organs of the hazardous agent in question. When results of biological monitoring are available for an unexposed control population, results for a group of exposed workers may be interpreted as greater than, similar to, or less than what was expected; thus, groups of unacceptably exposed workers may be identified. For antineoplastic-drug handling, the most important controls are use of a biological-safety cabinet and a worker education program. Estimating the average number of hours of drug handling per shift may serve as a surrogate measure of the potential exposure dose. Health-care professionals examining and testing workers who handle antineoplastic agents should give special emphasis to the skin and the hematopoietic, hepatic, renal, and urinary systems. Because of problems with assay sensitivity, cost, and interpretation of results, biological monitoring is not considered necessary in every medical surveillance program for antineoplastic-drug handlers. The Occupational Safety and Health Administration currently recommends that a permanent registry be maintained of all employees who routinely handle antineoplastic agents. Because of their opportunity for exposure to potentially hazardous drugs, pharmacy professionals should take a leading role in establishing surveillance programs that complement existing drug-handling practices and worker education programs.     

Drugs hazardous to healthcare workers. Evaluation of methods for monitoring occupational exposure to cytostatic drugs.

We review the literature concerning possible health risks for individuals (e.g. healthcare workers and pharmaceutical plant employees) occupationally exposed to cytostatic drugs. Cytostatic drugs possess toxic properties and may therefore cause mutagenic, carcinogenic and teratogenic effects. Hence, individuals handling these drugs in the course of their employment may face health risks. For this reason, it is important to monitor occupational exposure to these drugs. An overview of exposure monitoring methods is presented and their value is discussed. Most studies involve nonselective methods for biological monitoring and biological effect monitoring, such as the urinary mutagenicity assay and analysis of chromosomal aberrations and sister-chromatid exchanges in peripheral blood lymphocytes. The disadvantages of these biological methods are that their sensitivity is low and it cannot be proved beyond any doubt that the results found were caused by occupational exposure to cytostatic drugs. For occupational health services it is important to have sensitive and specific methods for monitoring exposure to cytostatic drugs. One of the most promising methods seems to be the determination of cyclophosphamide in urine using gas chromatography-tandem mass spectrometry. Several studies have demonstrated exposure to cyclophosphamide and other cytostatic drugs, even when protective measures were taken and safety guidelines were followed. To estimate the magnitude of any health effects arising from this exposure, we calculated the risk of cancer due to occupational exposure to cyclophosphamide on the basis of available human and animal dose-response data and the amounts of cyclophosphamide found in urine. The initial results show an extra cancer risk for pharmacy technicians and nurses.     

Evaluation of genotoxicity induced by exposure to antineoplastic drugs in lymphocytes of oncology nurses and pharmacists

The hazards of handling antineoplastic drugs have been raised and discussed in several studies. Introduction of new antineoplastics together with abuse of safety standards have contributed to the exposure risk for personnel who handle these substances. Interactions of antineoplastic drugs with biological structures vary according to the drug(s) and the individual's genetic susceptibility. This study was carried out to evaluate the genome damage induced by exposure to antineoplastic drugs in nurses (n = 20) and pharmacists (n = 18) working in the Oncology Department of Tanta Cancer Center. Thirty subjects matched in age, gender and smoking habit were selected as controls. Both chromosomal aberration analysis and micronucleus assay were used to evaluate genome damage in peripheral blood lymphocytes of the study subjects. The numbers of aberrant lymphocytes, as well as chromosomal aberration and micronuclei frequencies, were significantly increased in exposed personnel in comparison to matched controls. Compared with pharmacists, nurses showed notably higher level of chromosome damage. On the other hand, no significant difference in micronuclei frequency was observed between nurses and pharmacists. Correlation analyses pointed to the influence of age and duration of occupational exposure on the level of chromosome damage among exposed subjects. The results of this study confirmed that handling antineoplastic drugs without appropriate precautions imposed a genotoxic risk for exposed healthcare workers. These results address the need for regular biomonitoring of exposed personnel. In addition, they call attention to the need for proper implementation of intervention measures aiming to eliminate or significantly reduce worker exposure and prevent untoward biological effects. Copyright © 2011 John Wiley & Sons, Ltd.     

静脉用药调配中心洁净室环境动态监测实践

目的:建立静脉用药调配中心洁净室环境动态监测方法。方法:应用营养琼脂培养皿、空气浮游菌采样器及尘埃粒子检测仪对洁净室物体表面微生物、空气浮游菌及悬浮粒子进行动态监测。结果:通过对洁净环境的动态监测并进行评估,指导操作人员规范操作,保证静脉药物调配环境符合要求。结论:该方法可操作性强、结果可靠,可用于静脉用药调配中心洁净环境的动态监测。     

抗肿瘤药物对职业接触护士免疫功能的影响

目的:探讨职业接触抗肿瘤药物对护士免疫功能的影响。方法:选择接触抗肿瘤药物5年以上,每日接触5人次以上护士为接触组;无抗肿瘤药物接触史的健康志愿者为对照组。抽取接触组及正常对照组外周静脉血各3mL,EDTA抗凝血各2mL,利用我院血清免疫球蛋白常规检测方法及流式细胞仪技术观察血清免疫球蛋白及外周血T淋巴细胞亚群的变化。结果:血清免疫球蛋白IgG接触组较正常对照组减少,差异具有显著性(P<0.05);血清免疫球蛋白IgM、IgA接触组与对照组比较,差异无显著性(P<0.05);接触组T淋巴细胞亚群CD4+细胞下降,与对照组比较差异具有显著性(P<0.05)。CD8+有上升趋势,CD4+/CD8+比值有下降趋势,两组比较无显著性差异;CD3+及NK细胞接触组与对照组比较也无显著性差异(P>0.05)。结论:职业接触抗肿瘤药物可能减低护士的体液免疫功能。     

Primary DNA damage in chrome-plating workers

In order to evaluate the primary DNA damage due to occupational exposure to chromium (VI), DNA strand-breaks and apoptosis in peripheral lymphocytes were measured in a group of 19 chrome-plating workers. DNA strand-breaks was assessed by alkaline (pH>13) single-cell microgel electrophoresis ('comet') assay, while apoptosis was measured by flow-cytometry after propidium iodide staining of the cells. Concentrations of chromium in urine, erythrocytes and lymphocytes were investigated as biological indicators of exposure. A group of 18 hospital workers (control group I) and another 20 university personnel (control group II) without exposure to chromium were also studied as controls. The results of the study show that chrome-plating workers have higher levels of chromium in urine, erythrocytes and lymphocytes than unexposed workers. Comet tail moment values, assumed as index of DNA damage, are increased in chromium-exposed workers and results are significantly correlated to chromium lymphocyte concentrations. No difference emerged in the percentage of apoptotic nuclei in exposed and unexposed workers. The study confirms that measurements of chromium in erythrocytes and lymphocytes may provide useful information about recent and past exposure to hexavalent chromium at the workplace. The increase in DNA strand-breaks measured by comet assay suggests this test is valid for the biological monitoring of workers exposed to genotoxic compounds such as chromium (VI).     

Biological Monitoring of Pesticide Exposure: a review. Introduction

Pesticides are used worldwide in agriculture, industry, public health and for domestic applications: as a consequence, a great part of the population may be exposed to these compounds. In spite of this extensive use, knowledge on the health risks associated with prolonged exposure is rather poor, and major uncertainties still exist. Epidemiological observations in man have so far produced little conclusive information, mainly because of weaknesses in exposure assessment. Therefore, information on the type and levels of exposure is fundamental in order to better understand and characterize risk to human health. Exposure assessment can be carried out via measurement of environmental concentrations, as well as via determination of the chemical or its metabolites in body tissues (biological monitoring). Besides indices of internal dose, biological monitoring also includes measurements of early effects attributable to interaction between the chemical agent and the human body. Biological monitoring has the advantage, over environmental monitoring, of determining the dose actually absorbed via any possible route: differences in absorption can be taken into account. whether they are due to biological variability or to use of protective equipment. When, in some cases, a combination of occupational and non-occupational exposure occurs, this also can be taken into consideration by biological monitoring. Few reference documents have been published on biological monitoring of pesticides. For this reason, the Office of Occupational Health of the World Health Organization gave ICPS a mandate to prepare a monograph specifically addressed to reviewing methods for biological monitoring of pesticide exposure. This review is based on more than 300 studies published over the period 1980-1999. For the most representative chemical classes, the available biological exposure indices are reported. Both indices of internal dose and. when available, of early effects are discussed. The reported tests were used to monitor exposure of pesticide applicators in agriculture and public health, manufacturing and formulating workers. subjects poisoned after accidental exposure or attempted suicide, volunteers involved in pharmacokinetic studies, as well as sub-groups of the general population exposed to environmentally persistent pesticides. Single chapters deal with organophosphorus insecticides, carbamate pesticides, dithiocarbamates, phenoxyacids, quaternary ammonium compounds. coumarin rodenticides, synthetic pyrethroids, organochlorine pesticides, chlorotriazines, and pentachlorophenol.     

职业接触抗肿瘤药物对护士外周血淋巴细胞凋亡及Fas bcl-2基因表达的影响

目的探讨职业接触抗肿瘤药物对护士外周血淋巴细胞凋亡及Fas、bcl-2基因表达的影响。方法选择接触抗肿瘤药物5年以上,每日接触5人次以上的护士为接触组;无抗肿瘤药物接触史的健康志愿者为对照组。抽取接触组及正常对照组外周静脉血各2ml,乙二胺四乙酸(EDTA)抗凝,利用流式细胞仪技术观察外周血淋巴细胞凋亡率及Fas、bcl-2基因的表达。结果接触组外周血淋巴细胞凋亡率明显增高(P<0.05);接触组Fas基因的表达明显增高(P<0.01);而bcl-2基因表达差异无统计学意义。结论抗肿瘤药物能促进职业接触护士外周血淋巴细胞的凋亡和Fas基因的表达。     

Assessment of DNA damage in workers occupationally exposed to pesticide mixtures by the alkaline comet assay

The potential genetic hazard of pesticides to human beings is of great concern in occupational and environmental settings because of the widespread use of these chemicals for domestic and industrial applications. Various studies have revealed a significantly elevated risk for particular tumours in humans exposed to some pesticides. Results from the biological monitoring or cytogenetic methods for the detection of health risks to pesticides have given both positive and negative results of mutagenicity. In this study DNA damage in peripheral lymphocytes of 33 pesticide-exposed workers employed in the municipality of Ankara (Turkey) for at least 1 year was examined by alkaline single-cell gel electrophoresis, the 'comet' technique. Results were compared with those from 33 controls of comparable age, sex and smoking habits, which were not occupationally exposed to pesticides. Work characteristics of the exposed workers and the use of personnel protective measures were also investigated. The DNA damage observed in lymphocytes of the workers was significantly higher than that in the controls ( P<0.001). The observed DNA damage was found to be significantly lower ( P<0.001) in workers applying some of the necessary individual safety protections during their work. Cigarette smoking was not related to increases in DNA damage; also, no significant association was found between the duration of occupational exposure to pesticides and the degree of DNA damage.