Aspects of sepsis/SIRS - An experimental study on fluid therapy, vitamin C and plasma volume in increased permeability

In sepsis, after major surgery or severe trauma, the human body may suffer from various degrees of generalized inflammation, a syndrome called Systemic Inflammatory Response Syndrome (SIRS). One feature of SIRS is increased capillary permeability, caused by disruption of the capillary endothelium due to e.g. bacterial toxins, cytokines, pro-inflammatory hormones and free oxygen radicals. This will result in leakage of plasma fluid to the interstitum with subsequent intravascular hypovolemia and potentially harmful tissue oedema. Restoration of plasma volume with intravenous fluids is a cornerstone in the treatment of SIRS, but the infused fluids would be expected to leak through the capillary membrane to a greater extent, being less effective and further aggravating oedema Thus, an important challenge in patients with increased capillary permeability will therefore be to achieve and maintain normovolemia with as little plasma volume substitution as possible. Also, finding a treatment that could seal the leaking capillaries would be of great value. Study I and II, performed in a sepsis/SIRS animal model, showed that the plasma volume expansion of 5% albumin, 6% HES 130/0.4, 4% gelatin and 6% dextran 70 measured 3 hours after start of infusion was larger when given with a slow infusion rate than when given with a fast infusion rate. This effect was not seen with 0.9% NaCl. In study III, performed in rat models, we compared the initial plasma volume expanding effect of 0.9% NaCl in sepsis/SIRS, after a standardized hemorrhage, and in a normal condition. It showed that the increase in plasma volume in relation to the infused volume of 0.9% NaCl (32 mL/kg) were 0.6% in in sepsis/SIRS, 20% after hemorrhage, and 12% when given to rats in a normal state. This means that efficacy of 0.9% NaCl is highly affected by pathophysiological changes in sepsis/SIRS, e.g. increased capillary permeability. In study IV, two different treatment regimes of high-dose vitamin C, initiated 3 hours after induction of sepsis, were investigated regarding their effect on plasma volume loss. None of the treatment regimes were found to have any effect on the loss of plasma volume, or any of the physiological parameters analysed, in the early stage of severe sepsis/SIRS in the rat