S 1

PREVENTION AND THERAPY OF WOUND INFECTION THROUGH THE CENTURIES

S. Geroulanos
Prof. of Surgery and of History of Medicine
Onassis Cardiac Surgery Center, Athens, Greece

The history of wound infection is as old as the history of the human race itself.
About the cleaning of the wound with beer or wine and then applying on it a poultice there are mentions already in Assyrian, Egyptian texts, the Old Testament and Homer’s “Iliad”. Healing herbs, such as dictamon, an antistypticon and chemotherapeuticon are still in use today. We find the inscript dictamon already in the Linear B script, that is 3,500 years ago.
Throughout the “Iliad” and “Odyssey” suppuration was not recorded as a problem, except for the chronic festering wounds of Philoctetes who was bitten by a snake and had to be marooned in the island of Lemnos, where Fango earth is still today used for medical purposes.
In the chapters of Corpus Hippokraticum, the famous maxim: Ubi pus, ibi evacua is to be found. Hippocrates recommended cleaning of the wound with wine, bandaging it with fresh washed and sun-dried clean clothes, which were soaked in wine.The antiseptic qualities of wine were proven by Nichol to be not only the alcohol but mainly the polyphenols.
Contrary to Hippocrates, Galen believed that suppuration of a wound is absolutely necessary for its healing, so he formulated his doctrin of: Pus bonum et laudabile, which marked a retrogression of the wound-healing for more than 1,300 years.
Hand-washing as an essential preventive measure for wound infection is generally believed to have been introduced by I. Semmelweis (1847); however, byzantine emperor John II Komnenos had ordered by decree (Oct. 1135) that all physicians had to wash their hands from one patient to another. Going back to the 3rd c. BC we can also see that Erassistratos recommends before the operation disinfection of the surgeon’s hands with vinegar, which also contains polyphenols.
Pasteur’s discovery of pathogenic bacteria, Lister’s carbolic acid spray, Trendelenburg’s and Bergmann’s sterilization techniques, Halsted’s introduction of gloves, Domagk’s discovery of sulphonamids and Fleming’s discovery of Penicillin, all these further reduced wound infection, making thus major surgical procedures possible.

S 2

CURRENT APPROACHES IN THE THERAPY OF SEPSIS

C.J. Wiedermann
Innsbruck, Austria

Numerous treatments other than antibiotics and supportive care for severe sepsis and septic shock have been tested in clinical trials. These include neutralisation of microbial toxins such as lipopolysaccharide, non-specific anti-inflammatory and immunosuppressive drugs, neutralisation of pro-inflammatory cytokines, and correction of abnormalities in coagulation. The results have been mixed, although several recent clinical trials have given encouraging results. Coagulation abnormalities, especially disseminated intravascular coagulation, are common in patients with sepsis and microvascular thrombosis. The ensuing tissue damage may have an important role in the pathophysiology of organ dysfunction. Glucocorticoids exert broad metabolic and immunomodulating effects and have been used to treat several inflammatory diseases. Although high doses of steroids have no clinical benefit, a recent multicentre trial found that a seven day course of low doses of hydrocortisone and fludrocortisone reduced mortality in patients with septic shock and relative adrenal insufficiency. Finally, two studies of supportive care, one focusing on early therapy with fluids, vasopressors, and transfusions and the other on meticulous control of glycaemia with insulin, have shown reduced mortality in patients with severe sepsis and septic shock.

S 3

ADJUNCTIVE THERAPY OF SEPSIS, SEVERE SEPSIS AND SEPTIC SHOCK - CURRENT KNOWLEDGE AND NEW APPROACHES

G. Huhle
Medical manager Critical Care Europe, Eli Lilly and Company and Scientific Associate Ist Department of Medicine, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Mannheim, Germany

Sepsis is a disease within a mortality comparable to acute myocardial infarction. Currently, we might stand at the beginning of a new era for sepsis treatment. Trials using daily ”stress-dose” steroids (more physiologic doses of glucocorticoids with or without mineralocorticoids) have suggested an improved outcome of patients with vasopressor dependent septic shock.
It has been long recognised that inflammation and coagulation are strongly connected. The haemostasis is balanced by three major components, antithrombin, protein C and tissue factor pathway inhibitor (TFPI). A placebo-controlled, randomised, multicenter trial (KYBERSEPT) of antithrombin in severe sepsis was disappointing in its results showing no positive effect on the outcome in the overall population (28 day mortality). However, subgroup analysis proposed a beneficial effect in patients without heparin co-medication.
Tissue factor activates the extrinsic coagulation pathway and is inhibited by TFPI. Recombinant TFPI was investigated in a large phase III trial during the last couple of years but no benefit of rTFPI-treatment could be demonstrated.
Protein C is the zymogen of activated protein C (APC). APC inhibits factor Va and VIIIa and enhances fibrinolysis by plasminogen activator inhibitor (PAI)-neutralisation. It also demonstrated antiinflammatory properties by inhibiting E-selectin mediated cell adhesion, blocking NF-kB translocation and decrease of TNF-alpha, IL-1 and TF expression. The recent PROWESS study showed the significant improvement in the outcome of severe sepsis. Bernard and colleagues reported on a placebo-controlled, randomised, double-blind, multicenter trial comparing recombinant human activated protein C (Xigris®, Drotrecogin alpha (activated)) and placebo in 1,690 patients with severe sepsis. The study was stopped at the second interim analysis due to a mortality relative risk reduction of 19.4% (95% CI 6.6 – 30.5, p=0.005) with an absolute risk reduction of 6.11% in patients treated with Xigris®. Xigris® has been approved for the therapy of severe sepsis and multiorgan failure in Europe.