ASPECTS OF FLUID THERAPY: An experimental study of the effects of systemic inflammation, microvascular permeability, blood pressure and plasma volume

Abstract: Adequate circulating blood volume is a prerequisite for circulatory stability. Fluid therapy aims at correcting hypovolaemia, and is an important part of the haemodynamic management of perioperative and critically ill patients. The efficacy of plasma volume substitution largely depends on the pharmacological properties of the colloid solutions used. However, according to the 2-pore theory for transvascular exchange of fluid and macromolecules, it can also be influenced by such physiological factors as systemic inflammation, microvascular permeability, blood pressure, and prevailing plasma volume. This doctoral thesis based on 5 experimental studies performed on the rat and on the guinea pig, is aimed at evaluating the plasma volume expanding capacity of currently used colloid solutions and the changes in plasma volume in experimental models representing clinically relevant constellations of the above mentioned physiological factors. It also evaluated and compared the ability of activated protein C and prostacyclin to counteract an increased protein leakage in septic inflammation. Plasma volume expanding capacity of currently used colloid solutions was evaluated in standardized models of hypovolaemia. Plasma volume was measured with a 125I-albumin dilution technique. The studies showed that both during normal and increased microvascular permeability 6% dextran-70 and 5% albumin were more effective plasma expanders than 6% HES 130/0.4 and 4% gelatin. HES and gelatin were equally effective and produced similar increase in plasma volume as did normal saline given in 4-times larger volume. Both dextran and albumin showed an absorbing effect which was still present 3 h after infusion, but abolished when permeability was increased. During increased permeability all studied colloid solutions and normal saline were less effective regarding the plasma volume expanding capacity. The effects of the prevailing plasma volume and the increase in blood pressure accomplished by noradrenalin infusion were also studied regarding the subsequent changes in plasma volume during normal and increased permeability. The results showed that the increase in blood pressure and plasma volume, separately or in combination, was associated with larger plasma volume loss which was consequently larger during increased than during normal permeability. On the other hand, the refill of plasma volume, normally seen in hypovolaemia after haemorrhage, was counteracted by noradrenalin infusion. The physiological mechanisms explaining these findings most likely are associated with the changes in hydrostatic capillary pressure which is dependent on autoregulatory capacity, post-/precapillary resistance ratio, and systemic arterial and venous pressures. In the endotoxin induced inflammation, both activated protein C and prostacyclin reduced protein leakage in the gut and improved arterial oxygenation, and prostacyclin reduced protein leakage in the lung.