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

Letson, Hayley L., Pecheniuk, Natalie M., Mhango, Lebo P., and Dobson, Geoffrey P. (2012) Reversal of acute coagulopathy during hypotensive resuscitation using small-volume 7.5% NaCl adenocaine and Mg2+ in the rat model of severe hemorrhagic shock. Critical Care Medicine, 40 (8). pp. 2417-2422.

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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 Mg²⁺ 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 (similar to 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 N-2 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 (similar to 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.

Item ID: 23533
Item Type: Article (Refereed Research - C1)
Keywords: adenocaine, adenosine, coagulopathy, hemorrhagic, hypertonic saline, hypocoagulopathy, lidocaine, magnesium, military, prehospital, resuscitation, shock, small volume, trauma
ISSN: 0090-3493
Date Deposited: 03 Oct 2012 05:33
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110305 Emergency Medicine @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110299 Cardiovascular Medicine and Haematology not elsewhere classified @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 20%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified @ 80%
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