• Laurent Argaud, Martin Cour, Pierre-Yves Dubien, François Giraud, Claire Jossan, Benjamin Riche, Romain Hernu, Michael Darmon, Yves Poncelin, Xavier Tchénio, QuenotJean-PierreJPCentre Hospitalier Universitaire de Dijon, Hôpital François Mitterand, Service de Réanimation Médicale, Dijon, France., Marc Freysz, Cyrille Kamga, Pascal Beuret, Pascal Usseglio, Michel Badet, Bastien Anette, Kevin Chaulier, Emel Alasan, Sonia Sadoune, Xavier Bobbia, Fabrice Zéni, Pierre-Yves Gueugniaud, Dominique Robert, Pascal Roy, Michel Ovize, and CYRUS Study Group.
• Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Réanimation Médicale, Lyon, France2Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1060, Carmen, Equipe Cardioprotection, Lyon, France3Université de Lyon, Uni.
• JAMA Cardiol. 2016 Aug 1; 1 (5): 557-65.

ImportanceExperimental evidence suggests that cyclosporine prevents postcardiac arrest syndrome by attenuating the systemic ischemia reperfusion response.ObjectiveTo determine whether early administration of cyclosporine at the time of resuscitation in patients with out-of-hospital cardiac arrest (OHCA) would prevent multiple organ failure.Design, Setting, And ParticipantsA multicenter, single-blind, randomized clinical trial was conducted from June 22, 2010, to March 13, 2013 (Cyclosporine A in Out-of-Hospital Cardiac Arrest Resuscitation [CYRUS]). Sixteen intensive care units in 7 university-affiliated hospitals and 9 general hospitals in France participated. A total of 6758 patients who experienced nonshockable OHCA (ie, asystole or pulseless electrical activity) were assessed for eligibility. Analyses were performed according to the intention-to-treat analysis.InterventionsPatients received an intravenous bolus injection of cyclosporine, 2.5 mg/kg, at the onset of advanced cardiovascular life support (cyclosporine group) or no additional intervention (control group).Main Outcomes And MeasuresThe primary end point was the Sequential Organ Failure Assessment (SOFA) score, assessed 24 hours after hospital admission, which ranges from 0 to 24 (with higher scores indicating more severe organ failure). Secondary end points included survival at 24 hours, hospital discharge, and favorable neurologic outcome at discharge.ResultsOf the 6758 patients screened, 794 were included in intention-to-treat analysis (cyclosporine, 400; control, 394). The median (interquartile range [IQR]) ages were 63.0 (54.0-71.8) years for the cyclosporine group and 66.0 (57.0-74.0) years for the control group. The cohorts included 293 men (73.3%) in the treatment group and 288 men (73.1%) in the control group. At 24 hours after hospital admission, the SOFA score was not significantly different between the cyclosporine (median, 10.0; IQR, 7.0-13.0) and the control (median, 11.0; IQR, 7.0-15.0) groups. Survival was not significantly different between the 98 (24.5%) cyclosporine vs 101 (25.6%) control patients at hospital admission (adjusted odds ratio [aOR], 0.94; 95% CI, 0.66-1.34), at 24 hours for 67 (16.8%) vs 62 (15.7%) patients (aOR, 1.08; 95% CI, 0.71-1.63), and at hospital discharge for 10 (2.5%) vs 5 (1.3%) patients (aOR, 2.00; 95% CI, 0.61-6.52). Favorable neurologic outcome at discharge was comparable between the cyclosporine and control groups: 7 (1.8%) vs 5 (1.3%) patients (aOR, 1.39; 95% CI, 0.39-4.91).Conclusion And RelevanceIn patients presenting with nonshockable cardiac rhythm after OHCA, cyclosporine does not prevent early multiple organ failure.Trial Registrationclinicaltrials.gov Identifier: NCT01595958; EudraCT Identifier: 2009-015725-37.

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