Published Online
on July 8, 2002

A more recent version of this article appeared on July 30, 2002

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Submitted on March 18, 2002
Revised on May 10, 2002
Accepted on May 10, 2002

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

Christophe Adrie MD^*, Minou Adib-Conquy PhD, Ivan Laurent MD, Mehran Monchi MD, Christophe Vinsonneau MD, Catherine Fitting BS, François Fraisse MD, A. Tuan Dinh-Xuan MD, Pierre Carli MD, Christian Spaulding MD, Jean-François Dhainaut MD, and Jean-Marc Cavaillon PhD

From the Medical ICU (C.A., I.L., M.M., C.V., J.-F.D.), Cochin Hospital, Paris, France; General ICU (C.A., F.F.), Delafontaine Hospital, Saint Denis, France; Cytokines and Inflammation Unit (M.A.-C., C.F., J.-M.C.), Pasteur Institute, Paris, France; Laboratory of Respiratory Physiology (A.T.D.-X.), Cochin Hospital, Paris, France; Service d'Aide Médicale Urgente (P.C.), Necker Hospital, Paris, France; and Cardiology Department (C.S.), Cochin Hospital, Paris, France.

^* To whom correspondence should be addressed. E-mail: christophe.adrie{at}wanadoo.fr.

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- 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.

Key words: cardiopulmonary resuscitation • heart arrest • reperfusion • inflammation • interleukins

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