Adenosine, lidocaine and Mg²⁺ (ALM)fluid therapy attenuates systemic inflammation, platelet dysfunction and coagulopathy after non-compressible truncal hemorrhage

Letson, Hayley, and Dobson, Geoffrey (2017) Adenosine, lidocaine and Mg²⁺ (ALM)fluid therapy attenuates systemic inflammation, platelet dysfunction and coagulopathy after non-compressible truncal hemorrhage. PLoS ONE, 12 (11). e0188144.

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Abstract

Background: Systemic inflammation and coagulopathy are major drivers of injury progression following hemorrhagic trauma. Our aim was to examine the effect of small-volume 3% NaCl adenosine, lidocaine and Mg2+ (ALM) bolus and 0.9% NaCl/ALM ‘drip’ on inflammation and coagulation in a rat model of hemorrhagic shock.

Methods: Sprague-Dawley rats (429±4 g) were randomly assigned to: 1) shams, 2) no-treatment, 3) saline-controls, 4) ALM-therapy, and 5) Hextend®. Hemorrhage was induced in anesthetized-ventilated animals by liver resection (60% left lateral lobe and 50% medial lobe). After 15 min, a bolus of 3% NaCl ± ALM (0.7 ml/kg) was administered intravenously (Phase 1) followed 60 min later by 4 hour infusion of 0.9% NaCl ± ALM (0.5 ml/kg/hour) with 1-hour monitoring (Phase 2). Plasma cytokines were measured on Magpix® and coagulation using Stago/Rotational Thromboelastometry.

Results: After Phase 1, saline-controls, no-treatment and Hextend® groups showed significant falls in white and red cells, hemoglobin and hematocrit (up to 30%), whereas ALM animals had similar values to shams (9–15% losses). After Phase 2, these deficits in non-ALM groups were accompanied by profound systemic inflammation. In contrast, after Phase 1 ALM-treated animals had undetectable plasma levels of IL-1α and IL-1β, and IL-2, IL-6 and TNF-α were below baseline, and after Phase 2 they were less or similar to shams. Non-ALM groups (except shams) also lost their ability to aggregate platelets, had lower plasma fibrinogen levels, and were hypocoagulable. ALM-treated animals had 50-fold higher ADP-induced platelet aggregation, and 9.3-times higher collagen-induced aggregation compared to saline-controls, and had little or no coagulopathy with significantly higher fibrinogen shifting towards baseline. Hextend® had poor outcomes.

Conclusions: Small-volume ALM bolus/drip mounted a frontline defense against non-compressible traumatic hemorrhage by defending immune cell numbers, suppressing systemic inflammation, improving platelet aggregation and correcting coagulopathy. Saline-controls were equivalent to no-treatment. Possible mechanisms of ALM's immune-bolstering effect are discussed.

Item ID: 51696
Item Type: Article (Research - C1)
ISSN: 1932-6203
Additional Information:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funders: USSOCOM, IACUC protocol A2118, USAMRMC proposal SO13004 under Award No. W81XWH-15-1-0002
Research Data: http://dx.d oi.org/10. 4225/28/59c 44610046 7b
Date Deposited: 22 Feb 2018 02:59
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110305 Emergency Medicine @ 30%
11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110399 Clinical Sciences not elsewhere classified @ 70%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified @ 100%
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