Volume Replacement With HES 130/0.4 Attenuates Inflammatory Response to Major Abdominal Surgery Compared to Ringer's Lactate (RL); the Effect on Cytokines and Matrix Metalloproteinases

Various stimuli such as trauma, infection and major surgery may alter the physiologic immune balance and initiate systemic inflammatory processes. This pathophysiological event is characterized by the release of potent inflammatory mediators into the circulation.

Among these, pro- and anti-inflammatory cytokines such as interleukin-6 (IL-6), IL-8 or IL-10, ICAM-1 play a dominant role as local or systemic regulators in the acute inflammatory response. Recent studies have also investigated the role of matrix metalloproteinases (MMPs) in the inflammatory response. The MMPs constitute a family of enzymes that are structurally related neutral proteinases. MMPs can degrade essentially all extracellular matrix (ECM) components and play an important role in wound healing and remodeling of the ECM. The Tissutal Inhibitor MetalloProteine (TIMPs) are important regulator of MMPs activity.

The inflammatory response coming of surgery mainly affects surgical patients' outcome. Many factors may attributed to this response, such as the kind of operation, the extent of surgical trauma, the patient's medical history and therapy, as well as the type of anesthesia used. Apart from that, the kind of fluids administered for volume replacement was revealed to alter the inflammatory processes. Several studies have addressed on this issue mainly involved abdominal surgery and provided compelling evidence that perioperative fluid optimization produces benefits for the patient, with regard to inflammatory biomarkers such as cytokines, matrix metalloproteinases, intercellular adhesion molecule-1(ICAM-1). They support that the different volume replacement strategies, using only crystalloids or combination of crystalloids with colloids (HES 130/0,4), may have important impact on immune response. However, the relevant studies investigated different inflammatory biomarkers, and usually involved either metalloproteinases, and their inhibitors (TIMPs) or cytokines.

In our study we investigated the hypothesis that intra- and postoperative volume replacement with HES attenuates inflammatory response to elective abdominal surgery compared to RL fluid therapy. For this purpose both metalloproteinases, MMP-9, MMP-13, their inhibitor, TIMP-1, cytokines, IL-6, IL-8 and the intercellular adhesion molecule-1, ICAM-1 were investigated postoperatively. Their changes during the first 24 postoperative hours consisted our primary outcomes.