Current evidence does not support the use of human recombinant activated protein C in adults or children with severe sepsis or septic shock; moreover, there is an increased risk of bleeding associated with its use.
Sepsis is a major cause of death in the intensive care unit. It is a complex syndrome resulting from a presumed or known infection and its pathogenesis involves interactions between inflammation and blood clotting pathways. This serious medical condition is characterized by an inflammatory response to an infection which can affect the whole body. Patients with sepsis may have developed the inflammatory response because of microbes in their blood, urine, lungs, skin or other tissues. Severe sepsis can lead to multiple organ failure due to blood clotting in the finer blood vessels. This reduces the amount of blood reaching the organs. Protein C reduces the clotting process and a lack of protein C can lead to an exaggeration of blood clotting phenomena. Sepsis decreases protein C levels in the body. It has been suggested that treatment with human recombinant activated protein C (APC) will increase the levels and prevent multiple organ failure. In this updated review we included five randomized controlled trials which included 5101 participants with either a high or low risk of death. We found no evidence suggesting that APC reduced the risk of death in adults or children with severe sepsis. Unless additional RCTs provide evidence of a treatment effect, policy-makers, clinicians and academics should not promote the use of APC in patients with severe sepsis.