BACKGROUND: Clinical studies have raised concerns about the safety of 6% hydroxyethylstarch (HES) 130/0.42, but the pathomechanisms of this @entity8 remain unknown. To evaluate the effects of different HES concentrations, molar substitutions and molecular weights in HES-induced @entity8 , we used a porcine two-hit model that combined haemorrhagic and @entity326 . METHODS: We conducted a prospective, randomised, double-blinded, controlled study in a university animal laboratory. Thirty anaesthetised and ventilated @entity1707 were randomised to receive volume replacement therapy using 6% HES130/0.42, 6% HES200/0.5, 10% HES130/0.42 or 10% HES200/0.5, all dissolved in 0.9% @entity4202 rather than 0.9% @entity4202 alone. First, we bled the animals until they reached half of their baseline mean arterial pressure (MAP) for 45 minutes followed by fluid resuscitation. As a second hit, @entity295 was induced using an @entity526 -laden clot 6 hours after @entity548 . Volume resuscitation started with a delay of two hours and a central venous pressure goal of 12 mmHg. RESULTS: At the end of the study, the groups showed no difference in cardiac output or MAP, but the volume balance (mL/kg BW) was significantly higher in the 0.9% @entity4202 group (346  90; P <=0.05) than in the other groups (6% HES130, 125  26; 6% HES200, 105  15; 10% HES130, 114  17; 10% HES200, 96  23). @entity1011 clearance (mL/min) was significantly lower in the 6% HES200 (26  33) and 10% HES200 (15  18) groups compared to the 0.9% @entity4202 group (104  46; P <=0.05) but not in the HES 130 formulations (6% HES130: 64  51; 10% HES130: 58  38) at the end of the study. CONCLUSION: In this porcine two-hit shock model, treatment with 0.9% @entity4202 , HES 130/0.42 or HES 200/0.5 led to a similar maintenance of haemodynamic values. Despite this similar maintenance of the haemodynamic values, volume replacement with 6% and 10% HES 200/0.5 led to an accumulation of HES, higher colloid osmotic pressure and significantly reduced renal function after haemorrhagic and @entity326 . These facts support the presumption that not the concentration but the degree of substitution and the molecular weight play a decisive role in HES-induced @entity8 .

Molecular weight and molar substitution are more important in HES-induced @entity8 than concentration after hemorrhagic and XXXX .

@entity1707 :: ('9823', 'Species') :: ['pigs'] @entity8 :: ('MESH:D007674', 'Disease') :: ['renal impairment'] @entity295 :: ('MESH:D018805', 'Disease') :: ['sepsis'] @entity548 :: ('MESH:D006470', 'Disease') :: ['haemorrhagic shock'] @entity326 :: ('MESH:D012772', 'Disease') :: ['septic shock'] @entity526 :: ('562', 'Species') :: ['Escherichia coli'] @entity1011 :: ('MESH:D003404', 'Chemical') :: ['Creatinine'] @entity4202 :: ('D012965', 'Chemical') :: ['NaCl']
@entity326 :: (MESH:D012772,Disease) :: ['septic shock']
