7.5% NaCl resuscitation leads to abnormal clot fibrinolysis after severe hemorrhagic shock and its correction with 7.5% NaCl adenosine, lidocaine, and Mg2+

Letson, Hayley Louise, and Dobson, Geoffrey Phillip (2018) 7.5% NaCl resuscitation leads to abnormal clot fibrinolysis after severe hemorrhagic shock and its correction with 7.5% NaCl adenosine, lidocaine, and Mg2+. Journal of Emergencies, Trauma, and Shock, 11 (1). pp. 15-24.

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Abstract

Background: Hyperfibrinolysis is a common complication of hemorrhagic shock. Our aim was to examine the effect of small-volume 7.5% NaCl adenosine, lidocaine, and Mg2+ (ALM) on fibrinolysis in the rat model of hemorrhagic shock.

Methods: Rats were anesthetized and randomly assigned to one of four groups: (1) baseline, (2) shock, (3) 7.5% NaCl controls, and (4) 7.5% NaCl ALM. Animals were bled for 20 min (42% blood loss) and left in shock for 60 min before resuscitation with 0.3 ml intravenous bolus 7.5% NaCl ± ALM. Rats were sacrificed at 5, 10, 15, 30, and 60 min for rotation thromboelastometry and 15 and 60 min for ELISA analyses.

Results: After hemorrhagic shock, 7.5% NaCl failed to resuscitate and exacerbated coagulopathy and fibrinolysis. At 15 and 60 min, the activation as extrinsically-activated test using tissue factor (EXTEM) with aprotinin to inhibit fibrinolysis (APTEM) test showed little or no correction of fibrinolysis, indicating a plasmin-independent fibrinolysis. Clots also had ~ 60% lower fibrinogen (fibrin-based EXTEM activated test with platelet inhibitor cytochalasin D A10) and 36%–50% reduced fibrinogen-to-platelet ratio (11%–14% vs. 22% baseline). In contrast, 7.5% NaCl ALM resuscitated mean arterial pressure and attenuated hyperfibrinolysis and coagulopathy by 15 min. Correction was associated with lower plasma tissue factor, higher plasminogen activator inhibitor-1, and lower D-dimers (5% of controls at 60 min). Platelet selectin fell to undetectable levels in ALM animals, which may imply improved endothelial and platelet function during resuscitation.

Conclusions: Small-volume 7.5% NaCl resuscitation exacerbated coagulopathy and fibrinolysis that was not corrected by APTEM test. Fibrinolysis appears to be associated with altered fibrin structure during early clot formation and elongation. In contrast, 7.5% NaCl ALM rapidly corrected both coagulopathy and hyperfibrinolysis.

Item ID: 54548
Item Type: Article (Research - C1)
ISSN: 0974-519X
Keywords: 7.5% NaCl; coagulopathy; fibrinolysis; hemorrhage; rotation thromboelastometry; resuscitation; shock
Additional Information:

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

Funders: James Cook University, US Navy Medical Development Program (USNMDP)
Projects and Grants: N626645-12-C-4033, USNMDP N626645-12-C-4033
Date Deposited: 16 Jul 2018 06:02
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320199 Cardiovascular medicine and haematology not elsewhere classified @ 60%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320207 Emergency medicine @ 15%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320299 Clinical sciences not elsewhere classified @ 25%
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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