Silverstein B, Witkin K M, Frankos V H, Terr A I
Weinberg Group Inc., Washington, DC 20036, USA.
Regul Toxicol Pharmacol. 1997 Feb;25(1):60-7. doi: 10.1006/rtph.1996.1057.
Landmark midline catheters (Menlo Care, Inc., Palo Alto, CA) provide peripheral venous access for the infusion of medications or fluids. They are constructed of an inner layer of polyurethane and an outer layer of the biomaterial Aquavene, a blend of polyurethane and polyethylene oxide to which butylated hyroxyanisole (BHA), butylated hydroxytoluene (BHT), and triallyl-s-triazine trione (TTT) are added. Once inside the vein, the Aquavene material becomes hydrated and the catheter swells resulting in minimal trauma to the vein. It is well recognized that some patients experience reactions to catheterization. Recent reports of hypersensitivity-like reactions in some patients catheterized with Landmark catheters have prompted the manufacturer to reexamine biocompatibility data and clinical data to assess whether Aquavene was the source of the patient responses. None of the biocompatibility studies provided by Menlo Care in support of U.S. registration and marketing of Aquavene-based catheters demonstrated any tendency for Aquavene or material extracted from Aquavene to invoke an immunological or toxicological response. Examination of potential catheter residuals revealed that significant amounts of BHA and BHT were unlikely to be released from the catheters during expected use. The amounts of polyethylene oxide and TTT expected to be released during the first few minutes after catheter insertion (when most of the patient reactions were reported) are almost 92,500 and 270,000 times lower, respectively, than nontoxic animal exposures. These analyses do not support chemically mediated toxicity as an explanation for the adverse events experienced by some patients. A review of the postmarket surveillance data on Aquavene-based catheters revealed that the reported events were not consistent with a hypersensitivity (immunogenic) response to the biomaterial. The rare reported adverse events tend to occur quickly, most often after flushing of the catheter, and resolve quickly, even when the catheter remains in place. Determining the frequency and severity of adverse events reported in association with the use of Landmark catheters will ultimately require a controlled prospective study, preferably one with a concurrent control group using alternative products.
地标性中线导管（Menlo Care公司，加利福尼亚州帕洛阿尔托）为药物或液体输注提供外周静脉通路。它们由聚氨酯内层和生物材料Aquavene外层构成，Aquavene是聚氨酯和聚环氧乙烷的混合物，并添加了丁基化羟基茴香醚（BHA）、丁基化羟基甲苯（BHT）和三烯丙基-s-三嗪三酮（TTT）。一旦进入静脉，Aquavene材料会水化，导管会膨胀，从而对静脉造成最小的创伤。众所周知，一些患者会对导管插入术产生反应。最近有报道称，一些使用地标性导管的患者出现了类似过敏的反应，这促使制造商重新审查生物相容性数据和临床数据，以评估Aquavene是否是患者反应的根源。Menlo Care公司提供的支持基于Aquavene的导管在美国注册和销售的生物相容性研究中，没有一项表明Aquavene或从Aquavene中提取的材料有引发免疫或毒理学反应的任何倾向。对潜在导管残留物的检查表明，在预期使用期间，大量的BHA和BHT不太可能从导管中释放出来。预计在导管插入后的最初几分钟内（大多数患者反应报告时）释放的聚环氧乙烷和TTT的量，分别比无毒动物暴露量低近92500倍和270000倍。这些分析不支持化学介导的毒性作为一些患者所经历不良事件的解释。对基于Aquavene的导管的上市后监测数据的审查表明，报告的事件与对生物材料的过敏（免疫原性）反应不一致。罕见的报告不良事件往往迅速发生，最常见于导管冲洗后，并且即使导管仍留在原位也会迅速缓解。确定与使用地标性导管相关报告的不良事件的频率和严重程度最终需要进行一项对照前瞻性研究，最好是一项有使用替代产品的同期对照组的研究。
