Complement activation is associated with poor outcome after out-of-hospital cardiac arrest

Viktoriia Chaban; Espen R Nakstad; Henrik Stær-Jensen; Camilla Schjalm; Ingebjørg Seljeflot; Jarle Vaage; Christofer Lundqvist; Jūratė Šaltytė Benth; Kjetil Sunde; Tom Eirik Mollnes; Geir Ø Andersen; Søren Erik Pischke

doi:10.1016/j.resuscitation.2021.05.038

Complement activation is associated with poor outcome after out-of-hospital cardiac arrest

Resuscitation. 2021 Sep:166:129-136. doi: 10.1016/j.resuscitation.2021.05.038. Epub 2021 Jun 11.

Affiliations

¹ Dept. of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway.
² Dept. of Acute Medicine, Oslo University Hospital, Oslo, Norway.
³ Dept. of Anaesthesiology, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway.
⁴ Dept. of Cardiology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁵ Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Dept. of Research and Development, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway; Section of Physiology, Dept. of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
⁶ Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Dept. of Neurology, Akershus University Hospital, Oslo, Norway; Health Services Research Unit, Akershus University Hospital, Oslo, Norway.
⁷ Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Health Services Research Unit, Akershus University Hospital, Oslo, Norway.
⁸ Dept. of Anaesthesiology, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁹ Dept. of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Research Laboratory, Nordland Hospital Bodø, and K.G. Jebsen TREC, University of Tromsø, Norway; Centre of Molecular Inflammation Research, Department of Clinical and Molecular Research, Norwegian University of Science and Technology, Trondheim, Norway.
¹⁰ Dept. of Cardiology, Oslo University Hospital, Oslo, Norway.
¹¹ Dept. of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway; Dept. of Anaesthesiology, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Dept. of Research and Development, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway. Electronic address: s.e.pischke@medisin.uio.no.

PMID: 34126135
DOI: 10.1016/j.resuscitation.2021.05.038

Abstract

Background: Cardiopulmonary resuscitation after cardiac arrest initiates a whole-body ischemia-reperfusion injury, which may activate the innate immune system, including the complement system. We hypothesized that complement activation and subsequent release of soluble endothelial activation markers were associated with cerebral outcome including death.

Methods: Outcome was assessed at six months and defined by cerebral performance category scale (1-2; good outcome, 3-5; poor outcome including death) in 232 resuscitated out-of-hospital cardiac arrest patients. Plasma samples obtained at admission and day three were analysed for complement activation products C3bc, the soluble terminal complement complex (sC5b-9), and soluble CD14. Endothelial cell activation was measured by soluble markers syndecan-1, sE-selectin, thrombomodulin, and vascular cell adhesion molecule.

Results: Forty-nine percent of the patients had good outcome. C3bc and sC5b-9 were significantly higher at admission compared to day three (p < 0.001 for both) and in patients with poor compared to good outcome (p = 0.03 and p < 0.001, respectively). Unadjusted, higher sC5b-9 at admission was associated with poor outcome (odds ratio 1.08 (95% CI 1.01-1.14), p = 0.024). Adjusted, sC5b-9 was still associated with outcome, but the association became non-significant when time to return-of-spontaneous-circulation above 25 min was included as a covariate. Endothelial cell activation markers increased from admission to day three, but only sE-selectin and thrombomodulin were significantly higher in patients with poor versus good outcome (p = 0.004 and p = 0.03, respectively) and correlated to sCD14 and sC5b-9/C3bc, respectively.

Conclusion: Complement system activation, reflected by sC5b-9 at admission, leading to subsequent endothelial cell activation, was associated with poor outcome in out-of-hospital cardiac arrest patients.

Keywords: Cardiopulmonary resuscitation; Endothelial cells; Immune system; Out-of-hospital cardiac arrest; Outcome; Return of spontaneous circulation; SC5b-9 protein complex.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Cardiopulmonary Resuscitation*
Complement Activation
Endothelium
Humans
Out-of-Hospital Cardiac Arrest* / therapy

Substances

Biomarkers