The critical role of concentration for lidocaine block of peripheral nerve in vivo -: Studies of function and drug uptake in the rat
The critical role of concentration for lidocaine block of peripheral nerve in vivo -: Studies of function and drug uptake in the rat
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DOI：
10.1097/00000542-200311000-00028
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发表时间：
2003-11-01
期刊：
影响因子：
8.8
通讯作者：
Strichartz, GR
中科院分区：
文献类型：
--
作者：
Nakamura, T;Popitz-Bergez, F;Strichartz, GR
背景资料：周围神经阻滞的局部麻醉剂量的调整必须满足两个基本要求：药物浓度足以抑制Na+通道到冲动失败的点，药物体积足以暴露一段长度的神经长于传播失败的“临界长度”。本研究使用相当于2至7 mg/ml浓度的四倍体积范围，检查了大鼠坐骨神经阻滞功能测定的利多卡因剂量要求（mg），并将这些阻滞与注射等效剂量后的神经内利多卡因含量进行了比较。坐骨神经穿刺注射利多卡因0.05ml、0.1ml、0.2ml（均在pH 6.8），并对体重为200至250 g的雄性Sprague-Dawley大鼠进行定量神经行为测定。50%最大可能效应（ED 50）和仅达到完全阻滞（即，90%效果的最小阻断剂量）、完全阻断动物的分数和所有剂量下完全阻断的持续时间评估三种不同功能的抑制：本体感受、运动和疼痛反应活动。在单独的实验中注射放射性标记的（C-14）利多卡因，并在从动物解剖的神经中测定总药物含量及其纵向分布（七氟醚麻醉）在10分钟时，峰值阻滞时间，注射E-50后和三种不同体积的100%效应的最小阻滞剂量。对于所有功能，体积越小，E-50越低，导致几乎恒定的浓度以实现相等程度的阻断。注射体积越小，阻滞持续时间越长，达到完全阻滞的剂量越低。在镇痛等效剂量下，神经内利多卡因与浓度无关，而是随着体积的增加而增加，几乎与给定剂量成比例。利多卡因的纵向蔓延也更大，随着体积的增加利多卡因solution.Conclusion：块更大的深度和更长的持续时间从较小的体积注射，相应地，较高的利多卡因浓度包含相同的剂量。其必然结果是，当注射较小体积时，需要较低的利多卡因剂量才能达到相同的效果。奇怪的是，当注射等量的E-50时，即使功能效应的峰值是相等的，但从较小的体积进入神经的总药物比从较大的体积少。全神经内局部麻醉剂可能不代表包含神经轴突的隔室中的有效药物，神经阻滞的实际位置。
Background: The adjustment of local anesthetic dosage for peripheral nerve block must meet two basic requirements: a drug concentration sufficient to inhibit Na+ channels to the point of impulse failure and a volume of drug sufficient to expose a length of nerve longer than the "critical length" for propagation failure. This study examines the lidocaine dosage requirement, in milligrams, for functionally assayed sciatic nerve block in the rat using a fourfold range of volume corresponding to concentrations from 2 to 7 mg/ml and compares these blocks with the intraneural lidocaine content after injection of equipotent doses.Methods: Lidocaine was injected percutaneously at the sciatic nerve in volumes of 0.05 ml, 0.1 ml, and 0.2 ml (all at pH 6.8), and quantitative neurobehavioral assays were conducted on male Sprague-Dawley rats weighing from 200 to 250 g. The dose requirements for 50% maximum possible effect (ED50) and for just achieving complete block (i.e., minimal blocking dose for 90% effect), the fraction of completely blocked animals, and the duration of complete block at all doses were assessed for the inhibition of three different functions: proprioception, motor, and nocifensive activities. Radiolabeled (C-14) lidocaine was injected in separate experiments, and the total drug content and its longitudinal distribution were determined in nerves dissected from animals (sevoflurane anesthetized) at 10 min, the time of peak block, after injection of the E-50 and minimal blocking dose for 100% effect for the three different volumes.Results: For all functions, the smaller the volume, the lower was the E-50, resulting in a nearly constant concentration to achieve an equivalent degree of block. Durations of block were longer, and the dose to full block was lower for the smaller injected volumes. Intraneural lidocaine, at the equipotent doses for analgesia, was not related to concentration but rather increased with increasing volume, being almost proportional to the given dose. The longitudinal spread of lidocaine was also greater with increasing volume of lidocaine solution.Conclusion: Blocks of greater depth and longer duration result from injection of smaller volumes and, correspondingly, higher lidocaine concentrations containing the same dose. The corollary is that lower lidocaine doses are required to achieve the same effect when smaller volumes are injected. Curiously, when the equivalent E-50 is injected, total drug taken into the nerve is less from the smaller volumes than from the larger volumes, even though the peak functional effects are equal. Total intraneural local anesthetic may not represent the effective drug in the compartment that contains nerve axons, the actual location of neural blockade.