Successful Cardiopulmonary Resuscitation After Cardiac Arrest as a “Sepsis-Like” Syndrome

TLDR

Cardiac arrest survivors represent a model of whole‑body ischemia/reperfusion syndrome, prompting investigation of their immunoinflammatory profile. The study measured plasma cytokines, endotoxin, and ex vivo whole‑blood cytokine responses in 61, 35, and 11 patients, and used plasma exchange between patients and healthy controls to demonstrate leukocyte‑intrinsic hyporeactivity and plasma‑mediated immunosuppression. Survivors and nonsurvivors differed in admission levels of IL‑6, IL‑8, IL‑10, and soluble TNFRII, with nonsurvivors requiring vasopressors showing higher IL‑1RA, IL‑10, and IL‑6; endotoxin was present in 46 % of patients, and their endotoxin‑induced TNF and IL‑6 production was markedly blunted while IL‑1RA, T‑cell IL‑10, and IFN‑γ production were dysregulated, mirroring the cytokine profile of sepsis.

Abstract

Background — We investigated the immunoinflammatory profile of patients successfully resuscitated after cardiac arrest, representing a model of whole-body ischemia/reperfusion syndrome. Methods and Results — Plasma cytokine, endotoxin, and ex vivo cytokine production in whole-blood assays was assessed in 61, 35, and 11 patients, respectively. On admission, high levels of plasma interleukin (IL)-6, IL-8, IL-10, and soluble tumor necrosis factor (TNF) receptor type II could discriminate between survivors and nonsurvivors. Among nonsurvivors, the initial need for a vasopressor agent was associated with higher levels of IL-1 receptor antagonist, IL-10, and IL-6 on day 1. Plasma endotoxin was detected in 46% of the analyzed patients within the 2 first days. Endotoxin-induced TNF and IL-6 productions were dramatically impaired in these patients compared with healthy control subjects, whereas an unaltered production was observed with heat-killed Staphylococcus aureus . In contrast, IL-1 receptor antagonist productions were enhanced in these patients compared with healthy control subjects. The productions of T-cell–derived IL-10 and interferon-γ were also impaired in these patients. Finally, using in vitro plasma exchange between healthy control subjects and patients, we demonstrated that the endotoxin-dependent hyporeactivity was an intrinsic property of patients’ leukocytes and that an immunosuppressive activity was also present in their plasma. Conclusions — Altogether, the high levels of circulating cytokines, the presence of endotoxin in plasma, and the dysregulated production of cytokines found in these patients recall the immunological profile found in patients with sepsis.