Critical Care Unit, Memorial Hospital, St Lô, France.
Med Hypotheses. 2010 Dec;75(6):652-6. doi: 10.1016/j.mehy.2010.08.010.
One of the unsolved problems of septic shock is the poor responsiveness, or reduced vascular reactivity, to vasopressors used to increase blood pressure (BP). Attempts to restore vascular reactivity with NO inhibitors or low dose steroids have met with little success. Low vascular reactivity, which may lead to refractory shock and death, is linked to desensitization or down-regulation of alpha-1 adrenergic receptors. Our working hypothesis is that the use of alpha-2 agonists (e.g. clonidine or dexmedetomidine) in septic shock, in addition to the state-of-the-art treatment (including volume load and vasopressors), will reduce the vasopressor requirements needed to restore adequate BP. This counter-intuitive proposal is based on the fact that alpha-2 agonists will reduce the massive release of endogenous catecholamines. A decrease in plasma endogenous catecholamine concentrations will be followed by reduced down-regulation of alpha-1 receptors and/or a gradual re-sensitization of alpha-1 adrenergic receptors. In turn, this will lead to lowered vasopressor requirement, with respect to dose and duration. Our hypothesis, based on a reverse "denervation hypersensitivity", is at variance with accepted treatments, which rest only on volume load and vasopressors and emphasizes restoration of blood pressure per se. Several observations in the cardiology and anesthesia setting have shown increased vascular reactivity following alpha-2 agonist administration. Our preliminary observations in the setting of septic shock again suggest such increased vascular reactivity. Improved outcome was also observed. Rigorous work is warranted to verify reduced vasopressor requirement and improved outcome, when an alpha-2 agonist is combined with state-of -the-art treatment of septic shock.
感染性休克的一个未解决问题是血管对升压药的反应性差或降低，升压药用于升高血压（BP）。使用 NO 抑制剂或低剂量类固醇恢复血管反应性的尝试收效甚微。血管反应性低可能导致难治性休克和死亡，这与α-1 肾上腺素能受体的脱敏或下调有关。我们的工作假设是，在感染性休克中使用α-2 激动剂（例如可乐定或右美托咪定），除了最先进的治疗方法（包括容量负荷和升压药）外，还将降低恢复适当 BP 所需的升压药需求。这个违反直觉的建议基于这样一个事实，即α-2 激动剂将减少内源性儿茶酚胺的大量释放。血浆内源性儿茶酚胺浓度降低后，α-1 受体的下调减少，或α-1 肾上腺素能受体逐渐重新敏感化。反过来，这将导致降低升压药的需求，无论是剂量还是持续时间。我们的假设基于反向“去神经超敏性”，与仅基于容量负荷和升压药的公认治疗方法不同，强调了血压本身的恢复。心血管和麻醉领域的几项观察结果表明，α-2 激动剂给药后血管反应性增加。我们在感染性休克环境中的初步观察结果再次表明血管反应性增加。观察到改善的结果。当α-2 激动剂与感染性休克的最先进治疗方法结合使用时，需要进行严格的工作来验证降低升压药需求和改善结果。
