Keynote Lecture (S
2 - S 3)
AND THERAPY OF WOUND INFECTION THROUGH THE CENTURIES
Prof. of Surgery and of History of Medicine
Onassis Cardiac Surgery Center, Athens, Greece
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 Homers
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 surgeons
hands with vinegar, which also contains polyphenols.
Pasteurs discovery of pathogenic bacteria, Listers
carbolic acid spray, Trendelenburgs and Bergmanns
sterilization techniques, Halsteds introduction of
gloves, Domagks discovery of sulphonamids and Flemings
discovery of Penicillin, all these further reduced wound
infection, making thus major surgical procedures possible.
APPROACHES IN THE THERAPY OF SEPSIS
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.
THERAPY OF SEPSIS, SEVERE SEPSIS AND SEPTIC SHOCK - CURRENT
KNOWLEDGE AND NEW APPROACHES
Medical manager Critical Care Europe, Eli Lilly and Company
and Scientific Associate Ist Department of Medicine, Faculty
of Clinical Medicine Mannheim, University of Heidelberg,
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.