Complement activation in emergency department patients with severe sepsis.
OBJECTIVE
This study assessed the extent and mechanism of complement activation in community-acquired sepsis at presentation to the emergency department (ED) and following 24 hours of quantitative resuscitation.


METHODS
A prospective pilot study of patients with severe sepsis and healthy controls was conducted among individuals presenting to a tertiary care ED. Resuscitation, including antibiotics and therapies to normalize central venous and mean arterial pressure (MAP) and central venous oxygenation, was performed on all patients. Serum levels of Factor Bb (alternative pathway), C4d (classical and mannose-binding lectin [MBL] pathway), C3, C3a, and C5a were determined at presentation and 24 hours later among patients.


RESULTS
Twenty patients and 10 healthy volunteer controls were enrolled. Compared to volunteers, all proteins measured were abnormally higher among septic patients (C4d 3.5-fold; Factor Bb 6.1-fold; C3 0.8-fold; C3a 11.6-fold; C5a 1.8-fold). Elevations in C5a were most strongly correlated with alternative pathway activation. Surprisingly, a slight but significant inverse relationship between illness severity (by sequential organ failure assessment [SOFA] score) and C5a levels at presentation was noted. Twenty-four hours of structured resuscitation did not, on average, affect any of the mediators studied.


CONCLUSIONS
Patients with community-acquired sepsis have extensive complement activation, particularly of the alternative pathway, at the time of presentation that was not significantly reversed by 24 hours of aggressive resuscitation.
Younger
John G
JG
Department of Emergency Medicine, Center for Computational Medicine and Biology, University of Michigan, Ann Arbor, MI, USA. jyounger@umich.edu
Bracho
David O
DO
Chung-Esaki
Hangyul M
HM
Lee
Moonseok
M
Rana
Gurpreet K
GK
Sen
Ananda
A
Jones
Alan E
AE
D015415:Biomarkers / Q000032:analysis; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D002496:Central Venous Pressure / Q000502:physiology; D003167:Complement Activation / Q000502:physiology*; D003176:Complement C3 / Q000032:analysis; D015926:Complement C3a / Q000032:analysis; D003182:Complement C5 / Q000032:analysis*; D015936:Complement C5a / Q000032:analysis; D016638:Critical Illness; D004636:Emergency Service, Hospital; D005260:Female; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D012016:Reference Values; D012151:Resuscitation / Q000379:methods; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D016019:Survival Analysis
D015415:Biomarkers; D003176:Complement C3; D003182:Complement C5; D015926:Complement C3a; D015936:Complement C5a; D002097:C-Reactive Protein