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


METHODS
Prospective randomized laboratory investigation.


METHODS
A total of 68 male Sprague Dawley Rats.


METHODS
Post-hemorrhagic shock treatment for acute traumatic coagulopathy.


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.
Heart Research Laboratory, Department of Physiology and Pharmacology, School of Biomedical Sciences, James Cook University, Queensland, Australia.
Hayley L
HL
Letson
Natalie M
NM
Pecheniuk
Lebo P
LP
Mhango
Geoffrey P
GP
Dobson
D000241:Adenosine / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001778:Blood Coagulation Disorders / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D004338:Drug Combinations; D006439:Hemodynamics / Q000187:drug effects; D008012:Lidocaine / Q000008:administration & dosage / Q000627:therapeutic use*; D008274:Magnesium / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D051381:Rats; D012151:Resuscitation / Q000379:methods; D012771:Shock, Hemorrhagic / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D012965:Sodium Chloride / Q000008:administration & dosage / Q000627:therapeutic use
D004338:Drug Combinations; C572495:adenocaine; D012965:Sodium Chloride; D008012:Lidocaine; D008274:Magnesium; D000241:Adenosine