Management of Severe Sepsis and Septic Shock: Challenges and Recommendations

Despite the advances in the knowledge of the basic processes that trigger and sustain the systemic inflammatory response in sepsis, the search for a "magic bullet" to treat this syndrome has been frustrating. The incidence of severe sepsis and septic shock still remains quite high, as does its mortality, which has decreased very little over the past decades. Advances on pathophysiologic aspects of this syndrome are leading to the discovery of new potential therapeutic targets: studies on Toll-like receptor, a surface receptor present in most of the cells of the immune system, and on the high-mobility group box protein 1, a member of the high-mobility group protein super-family, showed the ability to modulate the inflammatory response after contact with a microbial pathogen [44]. Moreover, an endogenous metabolite, adenosine, has been proposed to play an important role in inflammation. Acting on different receptors (A1, A2a, A2b, and A3) it exerts anti-inflammatory effects by multiple mechanisms including modulation of neutrophil function, endothelial permeability, and collagenase production. The use of adenosine and adenosine kinase inhibitors (an enzyme that increases endogenous adenosine concentration significantly) in the management of sepsis and septic shock has not been investigated in humans, but experimental data seem to be encouraging [45]. The fundamental pillar of the management of sepsis still remains its prevention: an elevated standard of care and hygiene, the selective decontamination of the digestive tract and the source control, together with the administration of appropriate antibiotic treatment when an infection is suspected or documented can surely help to reach this purpose and reduce its incidence. Moreover, an early diagnosis of the syndrome, followed by an early goal-directed therapy for hemodynamic optimization, the use of protective lung strategy, the administration of rhAPC to patients with high risk of death, and low-dose corticosteroids to patients suffering adrenal insufficiency can help in reducing its mortality. The complete understanding of this complex syndrome and its final treatment are still far to come, but the research goes on developing new theories, proposing new experimental therapies, and improving the traditional resources: all of this is encouraging and promising. The priority is to apply evidence-based maneuvers in patients suffering sepsis according to valid recommendations; the importance of bundles represents a new critical point in the early phase. The challenge continues [46]. © 2006 Elsevier Inc. All rights reserved.