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.