Clinical and immunological features of post-resuscitation care
Maine Medical Center, Medical Education, Maine Medical Center Research Institute, Center for Outcomes Research & Evaluation
Background Patients treated after resuscitation from cardiac arrest (CA) have different levels of neurological, circulatory, and systemic ischemia?reperfusion injuries, as well as variable immune-inflammatory profiles; in some patients, inflammation may be a treatment target. Clinical and immune-inflammatory phenotypes are poorly characterized; our preliminary data show that CD73+ lymphocytes are anti-inflammatory by downregulating neutrophil activation status. We hypothesized that after resuscitation from CA, different profiles of circulating neutrophils, CD73+ lymphocytes and neutrophil/CD73+ lymphocyte ratios would correspond to recognizable clinical phenotypes. The aim of this study was to evaluate how the clinical features differ among groups of patients with different immunological profiles after resuscitation from CA.
Methods We reexamined existing data included in the Post Cardiac Arrest Syndrome (PCAS) study (NCT02664831, MMC IRB#4684) and in Maine Medical Center’s cardiac arrest database. Patients ? 18 years admitted to the intensive care unit after cardiopulmonary arrest, and treated with targeted temperature management were enrolled in the PCAS study after informed consent. Blood samples were collected from enrolled individuals at predetermined intervals over a week after return of spontaneous circulation (ROSC), and analyzed for numbers of white blood cell subtypes. Clinical data were also collected: time to ROSC, initial rhythm, no flow interval, low flow interval, shock, outcomes, and other clinical features. Neutrophils, CD73+ lymphocytes, and the neutrophil/CD73+ lymphocyte ratio at 24 hours after ROSC were measured and tertiles developed. We then evaluated the clinical features of patients within each tertile by calculating the median (IQR), or number (percent) of each. Differences across groups were analyzed using Kruskal-Wallis, Fisher’s exact, or Chi-square tests of independence. All statistical analyses were conducted in R, and p-values ?0.05 considered statistically significant.
Results Forty-eight patients were sorted into tertiles of 16 each. Age, gender, and most elements of the past medical history were not associated with neutrophil levels, CD73+ lymphocytes, or the neutrophil/CD73+ ratio at 24 hours after resuscitation. However, high neutrophils were associated with an increased duration of ischemia, especially prolonged low-flow time (with CPR), a non-shockable rhythm, smoking, and pre-existing renal disease. Low CD73+ lymphocytes were associated with worse outcomes, as was a high neutrophil/CD73+ ratio.
Conclusions Although limited by sample size, we found significant differences in clinical features of patients with different levels of neutrophils, CD73+ lymphocytes and neutrophil/CD73+ ratio. The CD73+ lymphocyte count and the neutrophil to CD73+ ratio may be independent risk factors for poor outcome after resuscitation, unrelated to clinical features like duration of the arrest or an initial shockable rhythm; these classifications may facilitate immunomodulatory therapies for cardiac arrest. In order to gain a better understanding of how clinical features in CA patients differ depending on immunological profiles, further studies with larger study populations are needed.
May, Teresa; Ryzhov, Sergey; Lucas, Lee; Ahlberg, Clara; Rados, Danijela; Dziodzio, John; Williams, Deanna; Hinton, Alexandra; and Seder, David, "Clinical and immunological features of post-resuscitation care" (2020). Costas T. Lambrew Research Retreat 2020. 63.