Santamaria Claudia M, Zhan Changyou, McAlvin J Brian, Zurakowski David, Kohane Daniel S
From the *Laboratory for Biomaterials and Drug Delivery, Division of Critical Care Medicine, Department of Anesthesiology; †Division of Medicine Critical Care, Department of Medicine; and ‡Department of Anesthesiology, Perioperative, and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts.
Anesth Analg. 2017 Jun;124(6):1804-1812. doi: 10.1213/ANE.0000000000002072.
Chemical permeation enhancers (CPEs) have the potential to improve nerve blockade by site 1 sodium channel blockers such as tetrodotoxin (TTX). Here, we investigated the efficacy and toxicity of CPE-enhanced nerve blockade across a range of TTX concentrations using 2 CPEs (sodium octyl sulfate and octyl trimethyl ammonium bromide). We also tested the hypothesis that CPEs could be used to reduce the concentrations of TTX and/or of a second adjuvant drug (in this case, epinephrine) needed to achieve prolonged local anesthesia METHODS:: Sprague-Dawley rats were injected at the sciatic nerve with combinations of TTX and CPEs, with and without epinephrine. Sensory and motor nerve blockade were assessed using a modified hot plate test and a weight-bearing test, respectively. Systemic and local toxicities of the different combinations were assessed.
Addition of increasing concentrations of TTX to fixed concentrations of CPEs produced a marked concentration-dependent improvement in the rate of successful nerve blocks and in nerve block duration. CPEs did not affect systemic toxicity. At some concentrations, the addition of sodium octyl sulfate increased the duration of block from TTX plus epinephrine, and epinephrine increased that from TTX plus CPEs. The addition of epinephrine did not cause an increase in local toxicity, and it markedly reduced systemic toxicity.
CPEs can prolong the duration of nerve blockade across a range of concentrations of TTX. CPEs could also be used to reduce the concentration of epinephrine needed to achieve a given degree of nerve block. CPEs may be useful in enhancing nerve blockade from site 1 sodium channel blockers.
化学渗透增强剂（CPEs）有可能改善诸如河豚毒素（TTX）等1型钠通道阻滞剂的神经阻滞效果。在此，我们使用两种CPEs（辛基硫酸钠和溴化辛基三甲基铵）研究了在一系列TTX浓度下CPE增强神经阻滞的疗效和毒性。我们还检验了这样一个假设，即CPEs可用于降低达到延长局部麻醉所需的TTX和/或第二种辅助药物（在本研究中为肾上腺素）的浓度。
将TTX与CPEs的组合，以及有无肾上腺素的情况，注射到Sprague-Dawley大鼠的坐骨神经处。分别使用改良热板试验和负重试验评估感觉和运动神经阻滞情况。评估不同组合的全身毒性和局部毒性。
在固定浓度的CPEs中添加不断增加浓度的TTX，在成功神经阻滞率和神经阻滞持续时间方面产生了显著的浓度依赖性改善。CPEs不影响全身毒性。在某些浓度下，添加辛基硫酸钠可延长TTX加肾上腺素的阻滞持续时间，而肾上腺素可延长TTX加CPEs的阻滞持续时间。添加肾上腺素不会导致局部毒性增加，且能显著降低全身毒性。
CPEs可在一系列TTX浓度范围内延长神经阻滞持续时间。CPEs还可用于降低达到给定程度神经阻滞所需的肾上腺素浓度。CPEs可能有助于增强1型钠通道阻滞剂的神经阻滞效果。
