7.5% NaCl Resuscitation Leads to Abnormal Clot Fibrinolysis after Severe Hemorrhagic Shock and its Correction with 7.5% NaCl Adenosine, Lidocaine, and Mg(2+)

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 Mg(2+) (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.