Unexpected 100% Survival Following 60% Blood Loss Using Small-Volume 7.5% NaCl With Adenocaine and Mg2+ in the Rat Model of Extreme Hemorrhagic Shock

ABSTRACT Hemorrhage is responsible for up to 40% of trauma mortality, and of these deaths, 33% to 56% occur during the prehospital period. In an effort to translate the cardioprotective effects of Adenocaine (adenosine, lidocaine) and Mg2+ (ALM) from cardiac surgery to resuscitation science, we examined the early resuscitative effects of 7.5% NaCl with ALM in the rat model of 60% blood loss. Male Sprague-Dawley rats (250–350 g, n = 40) were anesthetized and randomly assigned to one of five groups: (a) untreated, (b) 7.5% NaCl, (c) 7.5% NaCl/6% dextran 70, (d) 7.5% NaCl/Mg2+, and (e) 7.5% NaCl/ALM. Blood withdrawal occurred over ∼50 min (MAP 30–35 mmHg), and rats were left in shock for 30 min. Total shock time was ∼80 min; 0.3-mL bolus was injected intravenously over 10 s, and hemodynamics monitored for 60 min (phase 1). Shed blood was reinfused and function monitored for a further 60 min (phase 2). Lead II electrocardiogram, arterial pressures, mean arterial pressure (MAP), pulse pressure (PP), heart rate (HR), and rate-pressure product were monitored. Mortality was as follows: untreated (100%), 7.5% NaCl (75%), 7.5% NaCl/6% dextran 70 (87.5%), 7.5% NaCl/Mg2+ (62.5%), and 7.5% NaCl/ALM (0%). Deaths occurred at different times depending on treatment group and paralleled differences in the total number of ventricular arrhythmias with the highest number in untreated animals (49 ± 17) and lowest in 7.5% NaCl/ALM rats (2 ± 1.8) (P < 0.05). At the end of phase 1, MAP of 7.5% NaCl/ALM–treated animals increased from 29 to 40 mmHg (P < 0.05). At the end of phase 2, MAP, PP, HR, and rate-pressure product in the ALM group were 75%, 193%, 96%, and 83% of their preshock values. Small-volume (∼1 mL/kg) i.v. bolus of 7.5% NaCl/ALM led to 100% survival following 60% blood loss with higher MAP than any group, an 89% to 96% reduction in the total number of arrhythmias, and a stable HR.

[1]  Ru-Ping Lee,et al.  Fluvastatin attenuates severe hemorrhagic shock-induced organ damage in rats. , 2009, Resuscitation.

[2]  Ari Leppaniemi,et al.  A profile of combat injury. , 2003, The Journal of trauma.

[3]  G. Dobson Membrane polarity: a target for myocardial protection and reduced inflammation in adult and pediatric cardiothoracic surgery. , 2010, The Journal of thoracic and cardiovascular surgery.

[4]  G. Dobson,et al.  Ultra-small intravenous bolus of 7.5% NaCl/Mg²⁺ with adenosine and lidocaine improves early resuscitation outcome in the rat after severe hemorrhagic shock in vivo. , 2011, The Journal of trauma.

[5]  G. B. West,et al.  Rats resistant to the dextran anaphylactoid reaction. , 1963, British journal of pharmacology and chemotherapy.

[6]  G. Dobson,et al.  Small volume 7.5% NaCl with 6% Dextran-70 or 6% and 10% hetastarch are associated with arrhythmias and death after 60 minutes of severe hemorrhagic shock in the rat in vivo. , 2011, The Journal of trauma.

[7]  S. Stern,et al.  Low-volume fluid resuscitation for presumed hemorrhagic shock: helpful or harmful? , 2001, Current opinion in critical care.

[8]  P. Safar,et al.  A simple survival model of volume-controlled hemorrhagic shock in awake rats. , 1991, Resuscitation.

[9]  G. Dobson Organ arrest, protection and preservation: natural hibernation to cardiac surgery. , 2004, Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology.

[10]  R. Rossaint,et al.  HYDROGEN SULFIDE DOES NOT INCREASE RESUSCITABILITY IN A PORCINE MODEL OF PROLONGED CARDIAC ARREST , 2010, Shock.

[11]  M. Dubick,et al.  HYPOTENSIVE RESUSCITATION OF SEVERE HEMORRHAGE (HEM) IN SWINE WITH 5% SALINE (HS) OR 7.5% SALINE/6% DEXTRAN (HSD) , 2006 .

[12]  Rolf Lefering,et al.  Impact of hemorrhage on trauma outcome: an overview of epidemiology, clinical presentations, and therapeutic considerations. , 2006, The Journal of trauma.

[13]  C. Wade,et al.  Issues of concern regarding the use of hypertonic/hyperoncotic fluid resuscitation of hemorrhagic hypotension. , 2006, Shock.

[14]  M D Blaufox,et al.  Blood volume in the rat. , 1985, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[15]  K. Ward,et al.  LOW-VOLUME RESUSCITATION COCKTAIL EXTENDS SURVIVAL AFTER SEVERE HEMORRHAGIC SHOCK , 2007, Shock.

[16]  Steven B. Johnson,et al.  Association of 6% hetastarch resuscitation with adverse outcomes in critically ill trauma patients. , 2011, American journal of surgery.

[17]  W H Bickell,et al.  Are victims of injury sometimes victimized by attempts at fluid resuscitation? , 1993, Annals of emergency medicine.

[18]  Denis Chemla,et al.  Clinical review: Interpretation of arterial pressure wave in shock states , 2005, Critical care.

[19]  K. Messmer,et al.  Small‐volume resuscitation: from experimental evidence to clinical routine. Advantages and disadvantages of hypertonic solutions , 2002, Acta anaesthesiologica Scandinavica.

[20]  G. Kramer Hypertonic resuscitation: physiologic mechanisms and recommendations for trauma care. , 2003, The Journal of trauma.

[21]  I. Chaudry,et al.  Bench-to-bedside review: Latest results in hemorrhagic shock , 2008, Critical care.

[22]  K. Grathwohl,et al.  The impact of hypothermia on trauma care at the 31st combat support hospital. , 2006, American journal of surgery.

[23]  G. Velmahos,et al.  Surviving blood loss without fluid resuscitation. , 2008, The Journal of trauma.

[24]  G. Kramer,et al.  Small-volume resuscitation with hypertonic saline (2,400 mOsm/liter) during hemorrhagic shock. , 1984, Circulatory shock.

[25]  M. Roth,et al.  Surviving blood loss using hydrogen sulfide. , 2008, The Journal of trauma.

[26]  G. Dobson,et al.  Protection against ventricular arrhythmias and cardiac death using adenosine and lidocaine during regional ischemia in the in vivo rat. , 2004, American journal of physiology. Heart and circulatory physiology.

[27]  G. Velmahos,et al.  Pharmacologic resuscitation promotes survival and attenuates hemorrhage-induced activation of extracellular signal-regulated kinase 1/2. , 2010, The Journal of surgical research.

[28]  P. Lomax Measurement of ‘Core’ Temperature in the Rat , 1966, Nature.

[29]  L. Blackbourne,et al.  Decreasing killed in action and died of wounds rates in combat wounded. , 2010, The Journal of trauma.