麻醉方案对脑肿瘤对流增强给药的影响

Effect of anesthesia schemes on convective enhancement delivery in brain tumors

目的对流增强给药技术可直接将抗癌药物输注到脑肿瘤组织局部区域,在治疗脑胶质瘤疾病具有广泛的应用前景。给药之前通常患者处于麻醉状态,当前缺乏评估不同麻醉方案对对流增强抗癌药物传输过程的方法。拟通过数值模拟揭示麻醉方案对药物传递的影响。方法通过CT重构建立脑结构及肿瘤组织的物理模型,进而将复杂的脑部组织看作多孔介质,建立组织间液和药物传输的数学模型。以紫杉醇(对照组)为抗癌药,研究对照组及丙泊酚和右美托咪定两种麻醉方案对紫杉醇传输的影响。分析24 h药物传输过程的给药区流场、脑部压力场及药物传递的浓度场。结果台盼蓝染料的扩散系数设置为1.1×10^(-10)m^(2)/s,模型预测的渗透的深度与实验测量结果吻合得很好;对流速度Q=1μL/min,直径0.41 mm和0.31 mm两种输液管产生不同的染色渗透,较小的导管导致了更大渗透深度,但是要求更高的渗透压力。紫杉醇传递过程中2~24 h给药期间,压力分布较为稳定,几乎没有发生变化,但是增加速率逐渐降低。麻醉剂存在的情况,药物传输的深度和传输体积要高于对照组,24 h后,右美托咪定组传输深度相比对照组增加了4.5%,丙泊酚组增加了9.0%。对照组和两种麻醉组速度和压力分布均呈现从针管中心向外逐渐减小的趋势,在对数坐标下,速度与传输深度呈现线性下降关系。结论麻醉方案通过影响脉压而增加了针管附近组织间液的流动速度,进而促进了药物传递。

Objective To discuss the evaluation method in different anesthesia schemes on convection enhanced delivery(CED)process,and study the effect of anesthesia regimen on drug delivery by numerical simulation,under the consideration that CDE technology provide direct injection of anticancer drugs into local brain tumor tissue,which broads application prospects in treatment of glioma diseases.Methods The physical model of brain structure and tumor tissue was established and reconstructed by CT.The complex brain tissue was regarded as porous medium,the mathematical model of interstitial fluid and drug transport was established.The paclitaxel(control group)was set as anticancer drug,the effects of control group and 2 anesthesia regimens(propofol and dexmedetomidine)on paclitaxel transmission were studied.The flow field delivery area,brain pressure field and concentration field of drug delivery within 24-hour were studied.Results The diffusion coefficient of trypan blue was set to 1.1×10^(-10)m^(2)/s,and penetration depth predicted by model was consistent with experimental measurement results.The convection speed was Q=1μL/min,two infusion tubes with diameters of 0.41 mm and 0.31 mm were produced with different dye penetrations.The smaller catheters lead to greater penetration depth and required higher penetration pressure.During administration of paclitaxel for 2-24 hours,the pressure distribution was relatively stable and almost unchanged,but the increase rate was gradually decreased.Under anesthetics situation,the depth and volume of drug delivery were higher than that of control group.After 24 hours,the depth of drug delivery increased by 4.5%in dexmedetomidine group and 9.0%in propofol group.The speed and pressure of each group was gradually decreased from the center of needle tube,and in the logarithmic coordinate,the speed and transmission distance were reduced linearly.Conclusion It is demonstrated that anesthesia regimen increases the flow velocity of interstitial fluid near the needle by affecting the blood vessel pressure,which pro-motes the drug delivery.