Lutz R J, Dedrick R L, Boretos J W, Oldfield E H, Blacklock J B, Doppman J L
J Neurosurg. 1986 Feb;64(2):277-83. doi: 10.3171/jns.1986.64.2.0277.
Sporadic instances of retinal damage and of focal brain toxicity have been observed following intracarotid artery infusions of chemotherapeutic agents (such as BCNU and cis-platinum) for the treatment of glioblastomas. The episodic nature of these toxicities is consistent with the possibility that the drug solutions were streaming from the catheter tip and, therefore, were not well mixed or not uniformly distributed in all branches distal to the catheter tip location. To test this hypothesis, an in vitro system was fabricated which included a transparent model of the human carotid artery and its major branches. These were furnished with pulsatile flow of a blood simulant. Dye solutions infused at several infusion rates through various types of catheters in both supraophthalmic and infraophthalmic positions were monitored and recorded on videotape and photographic film. The effluent streams from distal branches of the model were collected, and the relative concentrations of dye in each branch were determined spectrophotometrically. The results indicate that infusate streaming occurs at low infusion rates. In some cases, the concentration in a given branch can be at least five times the expected concentration. Similar occurrences of streaming in vivo could cause focal toxicity. Methods to improve mixing should be used during intra-arterial administration of drugs; these include increasing the infusion rates and improving catheter tip design.
在经颈内动脉输注化疗药物（如卡氮芥和顺铂）治疗成胶质细胞瘤后，已观察到散发性视网膜损伤和局灶性脑毒性病例。这些毒性的发作性质与药物溶液从导管尖端流出的可能性一致，因此，在导管尖端位置远端的所有分支中，药物溶液混合不佳或分布不均。为了验证这一假设，构建了一个体外系统，其中包括人颈动脉及其主要分支的透明模型。这些模型配备了模拟血液的脉动流。通过各种类型的导管，在眼上和眼下位置以几种输注速率注入染料溶液，并在录像带和摄影胶片上进行监测和记录。收集模型远端分支的流出液，并用分光光度法测定每个分支中染料的相对浓度。结果表明，在低输注速率下会发生输注液流。在某些情况下，给定分支中的浓度可能至少是预期浓度的五倍。体内类似的液流情况可能会导致局灶性毒性。在动脉内给药期间应采用改善混合的方法；这些方法包括提高输注速率和改进导管尖端设计。
