Uniformity of intracarotid drug distribution with diastole-phased pulsed infusion

Abstract

Drug streaming has been implicated in the development of focal necrotic lesions in perfused tissues following intracarotid chemotherapy of brain tumors at low infusion rates. The narrow infusate path characteristic of streaming within laminar blood flow is not observed at high infusion rates such as are typical in contrast injection for angiography. By periodically pulsing the infusate at a high rate, the mechanisms of rapid mixing can be exploited while retaining the practicality of low average infusion rates. This in vitro study demonstrates the effects of the pulse-controlling parameters and the catheter characteristics and placement on mixing effectiveness. An internal carotid artery model including eight cerebral branches was infused with dye through various indwelling catheters, and individual branch effluents were collected and analyzed spectrophotometrically for dye concentration. While catheter placement dominates the factors that control infusate distribution, judicious selection of the pulse parameters can alleviate that dependence. A primary advantage is gained by phasing the pulse to occur during that period of the cardiac cycle when the blood flow is lowest at the injection site. The data clearly showed that diastole-phased pulsed infusions are highly effective in producing a uniform infusate distribution at low average infusion rates.

Selective ophthalmic artery infusion of chemotherapy for advanced intraocular retinoblastoma: initial experience with 17 tumors

“…11 The technique of diastolic-phased pulsed infusion has been shown to reduce this phenomenon, resulting in a more uniformly distributed concentration of drug. 4,16 Conclusions Direct intraophthalmic infusion of chemotherapy is an elegant solution to the difficult problem of advanced macular retinoblastoma with vitreous seeding. While the technical procedure is benign, the effect of direct intraophthalmic infusion of melphalan is not without risk as evidenced by our 15% rate of delayed vitreous hemorrhage.…”

Intraarterial Chemotherapy for Brain Tumors by Using a Spatial Dose Fractionation Algorithm and Pulsatile Delivery

“…Various recommendations have been made to improve mixing of the injected agent with blood. For example, diastolephased pulsatile injection has substantially decreased heterogeneous drug delivery clinically (28,29). Another variable that affects streaming and toxicity is delivery location.…”

A simple catheter‐vessel model for MR assessment of drug distribution in arteries and optimization of catheter design for intraarterial infusion therapy

“…Some investigators have reported the efficacy of special infusion techniques such as pulsed or diastolic infusion (20) and special catheter designs such as multiple side-hole (19), small caliber (13,14), or balloon catheters (14). However, balloon catheters are not suitable for implantation and long-term use, and multiple side holes may cause coagulation inside the implanted catheters.…”