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Potassium haemostasis study after administration of packed red blood cells in hemorrhagic shock: experimental study in pigs

Grant number: 11/20954-3
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): March 01, 2012
Effective date (End): February 28, 2013
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Joel Avancini Rocha Filho
Grantee:Fernando Chuluck Silva
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Hemorrhagic shock (HS) remains a major cause of early death after trauma, accounting for up to 40% of trauma-related deaths. The optimal HS resuscitation strategy still needs to be determined, but it is recognized that it may include the avoidance of cardiac standstill, prevention of progression to untreatable shock and rescue of protracted HS. HS patients are exposed to pathophysiologic processes and therapeutic interventions, mainly blood transfusion, that predispose to hyperkalemia (hyperK), one of the deadliest electrolyte abnormalities. Our previous studies showed that hyperK unrelated accompanies the onset of HS and correlates with the severity of hypoperfusion and early animal mortality. More than a potential marker of acute ischemic insult, hyperK may indicate that the body's ability to manipulate serum K is exhausted. This K homeostasis exhaustion hypothesis may be a critical factor in post-transfusional hyperK genesis and related complications. Several reports describing packed red blood cells (PRBC) related hyperkalemic cardiac arrest have been published. PRBC K concentration is related to processes occurring during processing and storage steps, and is directly proportional to storage time, easily reaching levels higher than 60 mEq/L after 21 days. Our hypothesis is that 21 days-stored PRBC administration during HS is associated with critical increases in serum K and cardiac arrest when compared with washed PRBC or short-storage PRBC infusion. Objectives: Evaluate the immediate effects of transfusion of packed red blood cells on potassium haemostasis in the rescue of the hemorrhagic shock comparing the effects of administration of red blood cells stored for 21 days with the administration of red cells stored for 21 days and washed at the moment of administration and with the administration of red blood cells with a short storage time. Methods: The study will use 48 male pigs of Large White breed weighing 25 to 35 kg. 24 animals will only be used as blood donors (donor animals) and the other 24 animals (receptor animals) will be placed in one of three groups submitted to hemorrhagic shock and fluid resuscitation with blood previously collected and processed from donor animals. The 24 receptor animals will be randomized to receive one of the 3 PRBC tested (3 groups, 8 animals each): Group 1 - 21 days storage PRBC; Group 2 - 21 days-storage washed PRBC; Group 3 - 2-5 days storage PRBC. After anesthesia, mechanical ventilation and monitoring, HS protocolwill start with blood withdrawal at a rate of 50-70 mL/min, adjusted to reach mean arterial pressure (MAP) of 40 mm Hg within 25 minutes. Subsequently animals will be submitted to the randomly selected blood administration in a volume equal to the volume withdrawn during HS.The animals will be studied in 8 moments: baseline, MAP 60 and 40 mm Hg, and at 2, 5, 10, 20 e 30 minutes after blood administration. Variables analyzed:gasometrical analysis from animals and PRBC; biochemical analysis (Hb, Ht, K, Ca, Na, lactate, glycemia) from animals and PRBC; free hemoglobin and haptoglobin levels (from PRBC and animals immediately before and after PRBC administration);hemodynamic analysis (ECG, HR, MAP, CaO2, CvO2, SvO2); serum TNF±, IL-6 e IL-10 levels; mortality.

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