Tijdschrift voor geneeskunde vol:61 issue:18 pages:1300-1305
During the past decade, considerable advances have been made in the knowledge of the pathophysiology of severe sepsis. In addition, randomized clinical trials of critical care interventions, such as corticosteroids in sepsis, low tidal volume ventilation, glucose control and appropiate antibiotic strategy, have reduced mortality more effectively than conventional therapy.
Advances in supportive care have not been paralleled by success with antisepsis interventions. Many trials of agents solely targeting the inflammatory cascade have failed to reduce mortality. Knowing that the immune system is closely linked to the coagulation cascade, the antithrombotic approach now offers great promise for bedside application of antisepsis therapy that will improve survival. Treatment with activated protein C decreased the 28-day mortality rate from 30.8% to 24.7%. Whether heparin is of proven benefit in established diffuse intravascular coagulation, and whether it can prevent multiple organ dysfunction in severe sepsis, needs to be proven in ongoing trials. Whether a heparin interaction with activated protein C is responsible for reduced efficacy of activated protein C when combined with heparin as seen in post-hoc analyses, is currently unknown.