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

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 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

Urine biomarkers give early prediction of acute kidney injury and outcome after out-of-hospital cardiac arrest

Background Post-resuscitation care after out-of-hospital cardiac arrest (OHCA) is challenging due to the threat of organ failure and difficult prognostication. Our aim was to examine whether urine biomarkers could give an early prediction of acute kidney injury (AKI) and outcome. Methods This was a prospective observational study of comatose OHCA patients at Oslo University Hospital Ullevål, Norway. Risk factors were clinical parameters and biomarkers measured in spot urine (cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) and the product of tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7)) at admission and day 3. Outcome variables were AKI within 3 days using the Kidney Disease Improving Global Outcomes definition, 6-month mortality, and poor neurological outcome (PNO) defined as cerebral performance category 3–5. Results Among 195 included patients (85 % males, mean age 60 years), 88 (45 %) died, 96 (49 %) had PNO, and 88 (45 %) developed AKI. In univariate analysis, increased urine cystatin C and NGAL concentration sampled at admission and day 3 were independent risk factors for AKI, mortality and PNO. Increased urine TIMP-2 × IGFBP7 levels was associated with AKI only at admission. In multivariate analyses combining clinical parameters and biomarker concentrations, the area under the receiver operating characteristics curve (AuROC) with 95 % confidence interval (CI) were 0.774 (0.700–0.848), 0.812 (0.751–0.873), and 0.819 (0.759–0.878) for AKI, mortality and PNO, respectively. Conclusions In comatose OHCA patients, urine levels of cystatin C and NGAL at admission and day 3 were independent risk factors for AKI, 6-month mortality and PNO. Trial registration Clinicaltrials.gov NCT01239420 . Registered 10 November 2010

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

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

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

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