Cyclosporine A prevents ischemia-reperfusion-induced lymphopenia after out-of-hospital cardiac arrest: A predefined sub-study of the CYRUS trial

摘要

Sir, Resuscitated cardiac arrest (CA) leads severe immune dysfunction, including low monocyte HLA-DR (mHLA-DR) expression and lymphopenia, similar to that observed in septic shock patients. Low lymphocyte count has been described as an independent risk factor for death after CA while accumulating data suggest that preventing lymphopenia may dramatically improve outcomes in critically ill patients. To our knowledge, no treatment has been shown to alter post-CA immune and/or inflammatory response. Cyclosporine A (CsA), independently of its immunosuppressive properties, has potent anti-necrotic and anti-apoptotic properties (via mitochondrial effects) in the context of ischemia-reperfusion (I/R) injury. We recently tested in the Cyclosporine in CA resuscitation (CYRUS) trial, whether CsA could limit the severity of organ failures after non-shockable witnessed CA. Here, we aimed to analyze the effect of CsA on CA-induced immune dysfunction in a predefined sub-study of the CYRUS trial (ClinicalTrials.gov Identifier: NCT01595958). IntheCYRUStrial, patients with non-shockable out-of-hospital CA randomly received either CsA (2.5mg/kg) at the onset of cardiopul-monary resuscitation (Cyclosporine group) or no additional intervention (Control group). Among those included in the coordinating center of the trial, 33 patients (Cyclosporine group: n = 17; Control group: n = 16) had blood samples to evaluate the post-CA immune/ inflammatory response.