Dobson, Geoffrey P., Morris, Jodie L., and Letson, Hayley L. (2023) Adenosine, lidocaine and Mg2+ update: teaching old drugs new tricks. Frontiers in Medicine, 10. 1231759.

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Abstract

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 Mg2+ (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 O2 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).

Item ID:	80666
Item Type:	Article (Research - C1)
ISSN:	2296-858X
Keywords:	adenosine, lidocaine, magnesium, trauma, hemorrhage, inflammation, coagulopathy
Copyright Information:	© 2023 Dobson, Morris and Letson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Funders:	USAMRMC
Projects and Grants:	SO130004 under Award No. W81XWH-15-1-0002, SO150053 under Award No. W81XWH-USSOCOM-BAA-15-1, MB210101 under Award No. W81XWH-21-MBRP-IDA, OR190008 under Award No. W81XWH-20-1-0931
Date Deposited:	09 Oct 2023 03:53
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320207 Emergency medicine @ 50% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320199 Cardiovascular medicine and haematology not elsewhere classified @ 20% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3208 Medical physiology > 320803 Systems physiology @ 30%
SEO Codes:	20 HEALTH > 2001 Clinical health > 200102 Efficacy of medications @ 20% 20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions @ 80%
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