| C1-esterase inhibitor infusion increases survival rates for patients with sepsis. | |
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MedLine Citation:
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PMID: 22080632 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVES:: Systemic inflammatory response variability displays differing degrees of organ damage and differing outcomes of sepsis. C1-esterase inhibitor, an endogenous acute-phase protein, regulates various inflammatory and anti-inflammatory pathways, including the kallikrein-kinin system and leukocyte activity. This study assesses the influence of high-dose C1-esterase inhibitor administration on systemic inflammatory response and survival in patients with sepsis. DESIGN:: Open-label randomized controlled study. SETTING:: Surgical and medical intensive care units of nine university and city hospitals. PATIENTS:: Sixty-one patients with sepsis. INTERVENTIONS:: Patients were randomized to receive either 12,000 U of C1-esterase inhibitor infusions in addition to conventional treatment or conventional treatment only (n = 41 C1-esterase inhibitor, 20 controls). Blood samples for measurement of C1-esterase inhibitor, complement components C3 and C4, and C-reactive protein concentrations were drawn on days 1, 3, 5, 7, 10, and 28. MEASUREMENTS AND MAIN RESULTS:: Quartile analysis of C1-esterase inhibitor activity in sepsis subjects revealed that the lowest quartile subgroup had similar activity levels (0.7-1.2 U/L), when compared to healthy volunteers (p > .05). These normal-level C1-esterase inhibitor sepsis patients nevertheless displayed increased C-reactive protein (p = .04) production and higher likelihoods of a more severe sepsis (p = .001). Overall, infusion of C1-esterase inhibitor increased C1-esterase inhibitor (p < .005 vs. control on days 2, 3, and 5) functional activity, resulted in higher C3 levels (p < .05 vs. control on days 2 and 3), followed by decreased C-reactive protein (p < .05 vs. control on days 3 and 10). Simultaneously, C1-esterase inhibitor infusion in sepsis patients was associated with reduced all-cause mortality (12% vs. 45% in control, p = .008) as well as sepsis-related mortality (8% vs. 45% in control, p = .001) assessed over 28 days. The highest absolute reduction risk of 70% was achieved in sepsis patients with Simplified Acute Physiology Score II scores >27. CONCLUSION:: In the present study, patients in the lowest quartile of C1-esterase inhibitor activity in combination with high C-reactive protein demonstrated a higher risk of developing severe sepsis. In general, high-dose C1-esterase inhibitor infusion down-regulated the systemic inflammatory response and was associated with improved survival rates in sepsis patients, which could have important treatment and survival implications for individuals with C1-esterase inhibitor functional deficiency. |
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Authors:
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Anton A Igonin; Denis N Protsenko; Gennadiy M Galstyan; Alexey V Vlasenko; Nana N Khachatryan; Igor V Nekhaev; Sergey A Shlyapnikov; Natalya B Lazareva; Paul Herscu |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-10 |
Journal Detail:
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Title: Critical care medicine Volume: - ISSN: 1530-0293 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0355501 Medline TA: Crit Care Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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From the Department of Clinical Pharmacology (AAI, NBL), Sechenov Moscow Medical University; Intensive Care Unit (DNP), Clinical City Hospital #7; Intensive Care Unit (GMG), Hematology Research Centre; Intensive Care Unit (AVV), S.P. Botkin Clinical City Hospital; Department of Surgery (NNK), Moscow State Medical and Dental University; and Intensive Care Unit (IVN), Russian Cancer Research Centre, Moscow, Russia; Department of Surgical Infections and Sepsis (SAS), Institute of Emergency Care, Saint Petersburg, Russia; Research Division (PH), Herscu Laboratory, Amherst, MA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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