Masters D B, Berde C B, Dutta S K, Griggs C T, Hu D, Kupsky W, Langer R
Department of Anesthesia, Children's Hospital, Boston, Massachusetts 02115.
Anesthesiology. 1993 Aug;79(2):340-6. doi: 10.1097/00000542-199308000-00020.
Prolonged nerve blockade is potentially useful in the management of many acute and chronic pain problems. Aside from infusions via an indwelling catheter, most currently available nondestructive techniques for prolonging local anesthetic action cannot provide more than 1-2 days of blockade. Bioerodible polymer matrixes have been used to deliver a variety of drugs in patients and animals for periods lasting weeks to years. Previously, dibucaine and bupivacaine were incorporated into copolymers of 1,3 bis(p-carboxyphenoxy) propane-sebacic acid anhydride (1:4), and demonstrated sustained release in vitro following incubation of the drug-polymer matrixes in phosphate-buffered solution (pH 7.4, 37 degrees C).
In the present study, cylindrical pellets made from polymer matrixes incorporated with bupivacaine-HCl were implanted surgically along the sciatic nerves of rats. Neural block was assessed by direct observation of motor skills and by leg-withdrawal latency to a hot surface. Biochemical and histologic examinations were performed 2 weeks after implantation.
Sensory and motor blockade was produced for periods ranging from 2 to 6 days. Contralateral control legs receiving polymer implants without drug showed no block. Blockade was reversible, and animals appeared to recover sensory and motor function normally. Biochemical indexes of nerve and muscle function were indistinguishable from contralateral controls.
This biodegradable polymer system provides a promising new alternative for the delivery of local anesthetics to peripheral nerves to produce prolonged blockade for the management of acute and chronic pain.
延长神经阻滞在许多急慢性疼痛问题的管理中可能具有重要作用。除了通过留置导管进行输注外，目前大多数可延长局部麻醉作用的非破坏性技术所提供的神经阻滞时间不超过1 - 2天。生物可蚀解聚合物基质已被用于在患者和动物体内递送各种药物，持续时间可达数周甚至数年。此前，丁卡因和布比卡因被掺入1,3 - 双（对羧苯氧基）丙烷 - 癸二酸酐（1:4）的共聚物中，并在药物 - 聚合物基质于磷酸盐缓冲溶液（pH 7.4，37℃）中孵育后，在体外显示出持续释放。
在本研究中，将含有盐酸布比卡因的聚合物基质制成的圆柱形微丸经手术植入大鼠坐骨神经旁。通过直接观察运动技能和测量对热表面的腿部退缩潜伏期来评估神经阻滞情况。植入后2周进行生化和组织学检查。
感觉和运动阻滞持续时间为2至6天。接受不含药物的聚合物植入物的对侧对照腿未出现阻滞。阻滞是可逆的，动物的感觉和运动功能似乎正常恢复。神经和肌肉功能的生化指标与对侧对照无差异。
这种可生物降解的聚合物系统为向周围神经递送局部麻醉药以产生延长的阻滞用于急慢性疼痛管理提供了一种有前景的新选择。
