Extracorporeal cardiopulmonary resuscitation: a national study on the association between favourable neurological status and biomarkers of hypoperfusion, inflammation, and organ injury

Abstract

Background In refractory out-of-hospital cardiac arrest (OHCA) with prolonged whole-body ischemia, global tissue injury proceeds even after establishment of circulation with extracorporeal cardiopulmonary resuscitation (ECPR). We aimed to investigate the role of biomarkers reflecting hypoperfusion, inflammation, and organ injury in prognostication of patients with refractory OHCA managed with ECPR. Methods This nationwide retrospective study included 226 adults with refractory OHCA managed with ECPR in Denmark (2011-2020). Biomarkers the first days after ECPR-initiation were assessed. Odds ratio of favorable neurological status (Cerebral Performance Category 1-2) at hospital discharge were estimated by logistic regression analyses. Cut-off values were calculated using the Youden’s index. Results Fifty-six patients (25%) survived to hospital discharge, 51 (91%) with a favorable neurological status. Factors independently associated with favorable neurological status were low flow time <81 minutes, admission leukocytes ≥12.8 × 109/L, admission lactate <13.2 mmol/L, alkaline phosphatase (ALP) < 56 (day1) or <55 U/L (day2), and day 1 creatine kinase MB (CK-MB) < 500 ng/mL. Selected biomarkers (leukocytes, C-reactive protein, and lactate) were significantly better predictors of favorable neurological status than classic OHCA-variables (sex, age, low-flow time, witnessed arrest, shockable rhythm) alone (p = 0.001) after hospital admission. Conclusion Biomarkers of hypoperfusion (lactate), inflammation (leukocytes), and organ injury (ALP and CK-MB) were independently associated with neurological status at hospital discharge. Biomarkers of hypoperfusion and inflammation (at hospital admission) and organ injury (days 1 and 2 after ECPR) may aid in the clinical decision of when to prolong or terminate ECPR in cases of refractory OHCA.

Inflammatory response after out‐of‐hospital cardiac arrest—Impact on outcome and organ failure development

“…Three studies demonstrated an association of higher CRP levels at admission with mortality but no independent association in multivariable model (not tested in two and not significant in the third), 25,33,42 and two found no difference between neurological outcome groups 21,46 . Gregers et al reported that lower CRP levels at admission and on day one independently predict poor neurological outcome at hospital discharge in a study where all patients underwent extracorporeal cardiopulmonary resuscitation 45 . Studies on later time points reported conflicting results: Kim et al reported unadjusted association with outcome on days one to three, 44 Andersson et al on day one, 20 Chong et al and Kim et al on day three and Ristagno et al an independent association on day two, 16,48,49 whereas three studies found no association at any time point 12,13,19,47 .…”

“…We found no studies focusing primarily on WBC as a marker after OHCA. Three studies reported independent prognostic value; lower WBC at admission was associated with poor neurological outcome at hospital discharge in a study where all patients underwent extracorporeal cardiopulmonary resuscitation, 45 and higher WBC and neutrophils on day one were associated with poor six‐month neurological outcome in another study 46 . Higher WBC on day one independently predicted poor neurological outcome at hospital discharge 51 .…”

“…CRP is an acute-phase protein released by hepatocytes, where its transcription is induced mainly by IL-6 and IL-1β. 41 Thirteen individual studies with a total of 3005 patients evaluated CRP as a prognostic marker, 12,13,16,20,21,25,27,33,[42][43][44][45][46][47] and four studies with 792 patients assessed high-sensitivity CRP (hsCRP). 19,39,48,49 While conventional CRP assays have a detection limit of 3 to 8 mg/L, hsCRP assays can detect CRP levels as low as 0.3 mg/L.…”

“…21,46 Gregers et al reported that lower CRP levels at admission and on day one independently predict poor neurological outcome at hospital discharge in a study where all patients underwent extracorporeal cardiopulmonary resuscitation. 45 Studies on later time points reported conflicting results: Kim et al reported unadjusted association with outcome on days one to three, 44 an independent association on day two, 16,48,49 whereas three studies found no association at any time point. 12,13,19,47 Most of these studies also reported negative results for other time points.…”

“…IL-6, PCT and CRP at different time points after ROSC in poor outcome (CPC 3-5 or nonsurvivor) and good outcome (CPC 1-2 or survivor) groups. Data were extracted from studies where inflammatory marker concentrations were available for both outcome groups 3,16,[19][20][21][22][23][24][25][26]33,36,37,40,[42][43][44][45]47,49. Concentrations were calculated as sample size weighted means of median values.…”