Reversal of acute coagulopathy during hypotensive resuscitation using small-volume 7.5% NaCl adenocaine and Mg2+ in the rat model of severe hemorrhagic shock

Abstract

Objective: Acute traumatic coagulopathy occurs early in hemorrhagic trauma and is a major contributor to mortality and morbidity. Our aim was to examine the effect of small-volume 7.5% NaCl adenocaine (adenosine and lidocaine, adenocaine) and Mg on hypotensive resuscitation and coagulopathy in the rat model of severe hemorrhagic shock.

Design: Prospective randomized laboratory investigation.

Subjects: A total of 68 male Sprague Dawley Rats.

Intervention: Post-hemorrhagic shock treatment for acute traumatic coagulopathy.

Measurements and methods: Nonheparinized male Sprague-Dawley rats (300-450 g, n=68) were randomly assigned to either: 1) untreated; 2) 7.5% NaCl; 3) 7.5% NaCl adenocaine; 4) 7.5% NaCl Mg²⁺; or 5) 7.5% NaCl adenocaine/Mg²⁺. Hemorrhagic shock was induced by phlebotomy to mean arterial pressure of 35-40 mm Hg for 20 mins (~40% blood loss), and animals were left in shock for 60 mins. Bolus (0.3 mL) was injected into the femoral vein and hemodynamics monitored. Blood was collected in Na citrate (3.2%) tubes, centrifuged, and the plasma snap frozen in liquid N2 and stored at -80°C. Coagulation was assessed using activated partial thromboplastin times and prothrombin times.

Results: Small-volume 7.5% NaCl adenocaine and 7.5% NaCl adenocaine/Mg²⁺ were the only two groups that gradually increased mean arterial pressure 1.6-fold from 38-39 mm Hg to 52 and 64 mm Hg, respectively, at 60 mins (p<.05). Baseline plasma activated partial thromboplastin time was 17±0.5 secs and increased to 63±21 secs after bleeding time, and 217±32 secs after 60-min shock. At 60-min resuscitation, activated partial thromboplastin time values for untreated, 7.5% NaCl, 7.5% NaCl/Mg²⁺, and 7.5% NaCl adenocaine rats were 269±31 secs, 262±38 secs, 150±43 secs, and 244±38 secs, respectively. In contrast, activated partial thromboplastin time for 7.5% NaCl adenocaine/Mg²⁺ was 24±2 secs (p<.05). Baseline prothrombin time was 28±0.8 secs (n=8) and followed a similar pattern of correction.

Conclusions: Plasma activated partial thromboplastin time and prothrombin time increased over 10-fold during the bleed and shock periods prior to resuscitation, and a small-volume (~1 mL/kg) IV bolus of 7.5% NaCl AL/Mg²⁺ was the only treatment group that raised mean arterial pressure into the permissive range and returned activated partial thromboplastin time and prothrombin time clotting times to baseline at 60 mins.