Skip Navigation LinksHome > March 2012 - Volume 40 - Issue 3 > C1-esterase inhibitor infusion increases survival rates for...
Critical Care Medicine:
doi: 10.1097/CCM.0b013e318236edb8
Clinical Investigations

C1-esterase inhibitor infusion increases survival rates for patients with sepsis*

Igonin, Anton A. MD, PhD; Protsenko, Denis N. MD, PhD; Galstyan, Gennadiy M. MD, PhD; Vlasenko, Alexey V. MD, PhD; Khachatryan, Nana N. MD, PhD; Nekhaev, Igor V. MD, PhD; Shlyapnikov, Sergey A. MD, PhD; Lazareva, Natalya B. MD, PhD; Herscu, Paul ND, MPH

Collapse Box


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.

© 2012 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins

Article Tools


Article Level Metrics

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.