Dobson Geoffrey P, Morris Jodie L, Letson Hayley L
Heart and Trauma Research Laboratory, College of Medicine and Dentistry, James Cook University, Townsville, QLD, Australia.
Front Med (Lausanne). 2023 Sep 27;10:1231759. doi: 10.3389/fmed.2023.1231759. eCollection 2023.
If a trauma (or infection) exceeds the body's evolutionary design limits, a stress response is activated to quickly restore homeostasis. However, when the injury severity score is high, death is often imminent. The goal of this review is to provide an update on the effect of small-volume adenosine, lidocaine and Mg (ALM) therapy on increasing survival and blunting secondary injury after non-compressible hemorrhagic shock and other trauma and infective/endotoxemic states. Two standout features of ALM therapy are: (1) resuscitation occurs at permissive hypotensive blood pressures (MAPs 50-60 mmHg), and (2) the drug confers neuroprotection at these low pressures. The therapy appears to reset the body's baroreflex to produce a high-flow, hypotensive, vasodilatory state with maintained tissue O delivery. Whole body ALM protection appears to be afforded by NO synthesis-dependent pathways and shifting central nervous system (CNS) control from sympathetic to parasympathetic dominance, resulting in improved cardiovascular function, reduced immune activation and inflammation, correction of coagulopathy, restoration of endothelial glycocalyx, and reduced energy demand and mitochondrial oxidative stress. Recently, independent studies have shown ALM may also be useful for stroke, muscle trauma, and as an adjunct to Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA). Ongoing studies have further shown ALM may have utility for burn polytrauma, damage control surgery and orthopedic surgery. Lastly, we discuss the clinical applications of ALM fluid therapy for prehospital and military far-forward use for non-compressible hemorrhage and traumatic brain injury (TBI).
如果创伤（或感染）超出了身体的进化设计极限，就会激活应激反应以迅速恢复体内平衡。然而，当损伤严重程度评分很高时，死亡往往迫在眉睫。本综述的目的是提供关于小剂量腺苷、利多卡因和镁（ALM）疗法对非可压缩性失血性休克及其他创伤和感染/内毒素血症状态下提高生存率和减轻继发性损伤效果的最新信息。ALM疗法的两个突出特点是：（1）在允许性低血压血压（平均动脉压50 - 60 mmHg）下进行复苏，以及（2）该药物在这些低血压状态下具有神经保护作用。这种疗法似乎会重置身体的压力感受器反射，以产生高流量、低血压、血管舒张状态，并维持组织氧输送。全身的ALM保护似乎是通过一氧化氮合成依赖性途径以及将中枢神经系统（CNS）控制从交感神经主导转变为副交感神经主导来实现的，从而改善心血管功能、减少免疫激活和炎症、纠正凝血障碍、恢复内皮糖萼，并降低能量需求和线粒体氧化应激。最近，独立研究表明ALM可能对中风、肌肉创伤也有用，并且可作为主动脉复苏性血管内球囊阻断术（REBOA）的辅助手段。正在进行的研究进一步表明ALM可能对烧伤多发伤、损伤控制手术和骨科手术有用。最后，我们讨论了ALM液体疗法在院前和军事前沿用于非可压缩性出血和创伤性脑损伤（TBI）的临床应用。
