Abstract 428: Clinical and Molecular Characterization of Post-Resuscitation Phenotypes: Cardiac vs. Neurorespiratory Etiology

Abstract

Background: Establishment of clinical and molecular phenotypes is needed to individualize post-resuscitation cardiac arrest (CA) care. Leukocyte subpopulations may characterize ongoing organ injury, and strongly correlate with outcomes. We analyzed patients determined to have a cardiac (COR) vs. neurorespiratory (NR) etiology of CA. Hypothesis: Clinical and molecular phenotypes differ according to the etiology of CA. Goals: Prospectively characterize clinical and molecular phenotypes of patients with cardiac or neurorespiratory etiology of CA. Methods: After IRB approval and informed consent, we collected blood samples at 24, 48, and 72 hours after return of spontaneous circulation. We excluded patients <18 years of age, moribund, Hgb <7mg/dL, or whose CA etiology could not be determined. Flow cytometry was performed on fresh blood; outcomes were established by 6-month telephone call. Results: Among patients with COR (n=61) vs. NR (n=42) etiology of CA, COR patients were older (61±14 vs 54 ±14, P=0.021), more often had shockable rhythm (74% vs. 7.1%, P<0.001), had higher initial blood glucose (227±89 vs 195±95, P=0.046), higher incidence of moderate or severe left ventricular dysfunction on presentation (67% vs 33.5%, P=0.004), lower EEG suppression ratio at 6 hours [22 (4,84) vs. 88 (66,93), P<0.001), lower NSE levels [30 (19,140) vs 104 (33,268), P=0.034], higher in-hospital survival (64% vs. 33%, P=0.002), less neurological-etiology death (25% vs 55%, P<0.001) and more CPC 1-2 at 6 months (49% vs 12%, P<0.001). There were no differences in total number of leukocytes, but flow cytometry revealed leukocyte subsets, characterized by variable expression of CD4, CD8, CD10, CD14, CD16, CD54, CXCR1 and other surface proteins, indicating a trend toward enhanced neutrophil maturation and a preserved pool of circulating T cells in COR vs. NR patients. Conclusions: Separating CA survivors into a cardiac vs. neurorespiratory etiology reveals different clinical risk profiles and inflammatory responses during the acute phase after resuscitation. Further research should evaluate how specific interventions affect patients with dissimilar risk profiles, and how various therapies modulate the immuno-inflammatory response.