Potential Early Predictors for Outcomes of Experimental Hemorrhagic Shock Induced by Uncontrolled Internal Bleeding in Rats

Zaid A Abassi,Mike Fitzpatrick,Ahmad Mahajna,Hoda Awad,Aaron Hoffman,Gadi Campino,Niroz Abu Salah,Yossi Mandel,Joseph Winaver,Marina Okun-Gurevich,Giora Z Feuerstein,John Calvert

doi:10.1371/journal.pone.0080862

Abstract

Uncontrolled hemorrhage, resulting from traumatic injuries, continues to be the leading cause of death in civilian and military environments. Hemorrhagic deaths usually occur within the first 6 hours of admission to hospital; therefore, early prehospital identification of patients who are at risk for developing shock may improve survival. The aims of the current study were: 1. To establish and characterize a unique model of uncontrolled internal hemorrhage induced by massive renal injury (MRI), of different degrees (20-35% unilateral nephrectomy) in rats, 2. To identify early biomarkers those best predict the outcome of severe internal hemorrhage. For this purpose, male Sprague Dawley rats were anesthetized and cannulas were inserted into the trachea and carotid artery. After abdominal laparotomy, the lower pole of the kidney was excised. During 120 minutes, hematocrit, pO2, pCO2, base excess, potassium, lactate and glucose were measured from blood samples, and mean arterial pressure (MAP) was measured through arterial tracing. After 120 minutes, blood loss was determined. Statistical prediction models of mortality and amount of blood loss were performed. In this model, the lowest blood loss and mortality rate were observed in the group with 20% nephrectomy. Escalation of the extent of nephrectomy to 25% and 30% significantly increased blood loss and mortality rate. Two phases of hemodynamic and biochemical response to MRI were noticed: the primary phase, occurring during the first 15 minutes after injury, and the secondary phase, beginning 30 minutes after the induction of bleeding. A Significant correlation between early blood loss and mean arterial pressure (MAP) decrements and survival were noted. Our data also indicate that prediction of outcome was attainable in the very early stages of blood loss, over the first 15 minutes after the injury, and that blood loss and MAP were the strongest predictors of mortality.

Highlights

Uncontrolled hemorrhage, resulting from traumatic injuries, continues to be the leading cause of death in civilian and military environments [1,2,3]
Several parameters were proposed as indicators of the patient's condition after traumatic hemorrhage and currently used as end-points of resuscitation: mean arterial pressure (MAP), heart rate, urine output, cardiac index, oxygen consumption, oxygen delivery, base excess (BE) or base deficit, lactate, and mucosal gastric pH [7]
In preliminary experiments conducted in our laboratory using models of splenic injuries, we found that maximal hemorrhage volume in these models did not exceed 25% of calculated total blood volume

Summary

Introduction

Uncontrolled hemorrhage, resulting from traumatic injuries, continues to be the leading cause of death in civilian (accounting for 40% of total deaths) and military (accounting for 50% of total deaths) environments [1,2,3]. According to Coburn, injury to the kidneys occurs in up to 10% of all abdominal injuries [9], in search for models of uncontrolled hemorrhage reaching high bleeding volumes we embarked on developing the model of partial ablation of the kidney. This model was used previously in studies aimed at developing hemostatic agents, and was applied mostly in heparinized rats [10,11,12]. The unheparinized model is suitable for examining potential anticoagulant therapies, whereas the heparinized one may interfere with efficacy of these agents, masking their real hemostatic properties

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