Aspects of fluid therapy in the critically ill. Experimental and clinical studies on fluid therapy in the inflammatory conditions

Sammanfattning: Patients suffering from inflammatory conditions often present with severe hypovolemia due to vasodilatation and increased vascular permeability. Early administration of fluids is, therefore, a cornerstone and lifesaving therapy.However, a vigorous and aggressive fluid therapy increases tissue edema, worsen tissue perfusion and organ function. Based on this, the presented studies investigated different aspects of administration and choice of resuscitation fluids with the overall objective to obtain a long-lasting plasma volume expansion with minimalextravasation.Plasma volume expanding efficacy of albumin is suggested to be dependent on microvascular permeability whereas the efficacy of Ringers acetate is independent of permeability. In the first study, plasma volume expansion by 5% albumin was compared to that by Ringers acetate in a condition of normal (after mild haemorrhage) and increased microvascular permeability (in rat sepsis model). The results revealed that, while the efficacy of both albumin and Ringers acetate as plasma volume expanders decreased in sepsis, the ratio between the two as plasma volumeexpanders remained unchanged.In the second study, the objective was to investigate dose-response of a crystalloid in hypovolemia induced by two different etiologies- sepsis and severe haemorrhage. Rats were randomized to resuscitation with Ringers acetate at a dose of 10, 30, 50, 75 and 100 ml/kg in sepsis or after a severe (30 ml/kg) haemorrhage. The results showed that plasma volume expansion was lower than previously realized across those a wide range of doses and that normovolemia was not attained even at the highest doses in any of the conditions. In sepsis, crystalloid resuscitation induced a dose-depended decrease in plasma oncotic pressure which could not be explained only by dilution.The third study was a single-center, assessor-blinded, parallel-group, randomised prospective clinical study. Previous experimental studies showed that plasma volume expansion was greater after slow infusion compared to rapid infusion of a colloid of the same volume. Based on this experimental data the study aimed to test thehypothesis that plasma volume expansion is greater after slow infusion of colloid than after a rapid infusion of a given volume of colloid. A total of 70 patients with signs of hypovolemia after major abdominal surgery were included and a total of 34 and 31 patients completed the protocol in the slow and rapid infusion groups, respectively.The results have shown that a slow infusion of 5% albumin did not give a better plasma volume expansion than a rapid infusion in postoperative patients with suspected hypovolemia.