In the last 5 years DW has contributed to a number of trials of activated protein C in severe sepsis which have been sponsored by Eli Lilly. He has also received honoraria from Eli Lilly (the manufacturers of activated protein C) for speaking at educational meetings.
Severe acute pancreatitis (SAP) is characterized by an unregulated systemic proinflammatory response secondary to activation of trypsin within the pancreatic tissue, resulting in multiple organ failure. This dysregulated inflammation leading to organ dysfunction also characterizes severe sepsis. Activated protein C (APC) has pleotropic effects on the immune, coagulation, inflammatory and apoptotic pathways, and has been postulated to benefit acute pancreatitis - although concerns of possible retroperitoneal bleeding remain. Currently, experimental studies and subgroup data on patients with pancreatitis from a randomized controlled trial of APC in severe sepsis form the literature on the possible role of APC in SAP. We review the first randomized controlled trial of APC in acute pancreatitis published in the present issue of Critical Care.
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Alfasser G, Warshaw AL, Thayer SP, Antoniu B, Laposata M, Lewandrowski KB, Fernandez-del Castillo C: Decreased inflammation and improved survival with recombinant human activated protein C treatment in experimental acute pancreatitis. Arch Surg 2006, 141: 670-676. 10.1001/archsurg.141.7.670 CrossRef
Khan A, Agarwal R, Aggarwal AN, Gupta D: Prevalence of serious bleeding events and intracranial hemorrhage in patients receiving activated protein C: a systematic review and meta-analysis. Respir Care 2010, 55: 901-910. PubMed
Levi M, Levy M, Williams MD, Douglas I, Artigas A, Antonelli M, Wyncoll D, Janes J, Booth FV, Wang D, Sundin DP, Macias WL, Xigris and prophylactic heparin Evaluation in Severe Sepsis (XPRESS) Study Group: Prophylactic heparin in patients with severe sepsis treated with drotrecoginalfa (activated). Am J Respir Crit Care Med 2007, 176: 483-490. 10.1164/rccm.200612-1803OC CrossRefPubMed
Finfer S, Ranieri VM, Thompson BT, Barie PS, Dhainaut J-F, Douglas IS, Gardlund B, Marshal JC, Rhodes A: Design, conduct, analysis and reporting of a multi-national, placebo-controlled trial of activated protein C for persistent septic shock. Intensive Care Med 2008, 34: 1935-1947. 10.1007/s00134-008-1266-6 PubMedCentralCrossRefPubMed
- Activated protein C in severe acute pancreatitis without sepsis? Not just yet ...
- BioMed Central
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