Finally, in studying the whole cohort, we did not find any correlation at any time point between mHLA-DR and usual markers of OHCA severity such as no-flow and/or low-flow duration, dose of epinephrine, SAPS II, or SOFA scores (data not shown).
Interestingly, the extent of this immunosuppression evaluated by mHLA-DR appears independent of usual mortality prognostic markers and of multiple organ failure after OHCA. In addition, overtime evolution appeared different between survivors and non-survivors, with non-survivors presenting with persistent mHLA-DR decrease overtime while mHLA-DR values in survivors increased between D1 and D3 after OHCA. Similar differences in mHLA-DR evolution between survivors and non-survivors were, for example, made after ruptured abdominal aortic aneurysms (19). However, mHLA-DR could probably be used as a surrogate marker of the severity of the post-cardiac arrest syndrome but not as a relevant prognostic factor in this field. Thus, mHLA-DR evaluation may represent a novel standardized monitoring tool after OHCA, affordable and readily available in the clinical routine. In particular, it could help clinicians to evaluate the consequences of the systemic ischemia-reperfusion injury and the impact of therapeutic management on immunosuppression after OHCA, independently of multiple organ failure. This is all the more relevant since it has been suggested in other clinical contexts that immunosuppression may participate in an increased risk of nosocomial infections (5, 20). As early infectious complications are frequent in post-OHCA patients since up to two-third of these patients will present with a septic episode within the first 3 days after ICU admission, mHLA-DR measurements at these time points may also represent a new tool to assess the post-OHCA infectious risk (21, 22). For instance, low mHLA-DR could prompt physicians to perform additive bacteriological sampling and/or to initiate early antibiotic treatment. Indeed, mHLA-DR directly measures monocyte anergy and altered functionality and is considered the best marker to date of injury-induced immunosuppression (4, 5). Thus, our study opens up the possibility of using mHLA-DR as a reasonable alternative endpoint to test interventions targeting the post-cardiac arrest syndrome. Obviously, our study has at least one limitation. As a preliminary pilot work, the low number of patients (and their severity) precludes us to perform robust statistical analyses (especially on infectious complications) but these first promising results deserve now to be extended to a larger cohort of patients in a multicentered study.
In summary, our results suggest that OHCA patients develop cardiac arrest-induced immune alterations as illustrated by a decreased mHLA-DR and CD4+ lymphopenia. We also present here preliminary results showing the differential overtime evolution in mHLA-DR between survivors and non-survivors without association with initial prognosis factors after OHCA.
The authors thank Anne Portier (Immunology Laboratory) as well as Sylvie De La Salle (Medical ICU) for their respective great help in experiments performing, clinical data gathering. The authors are also very grateful to Dr Delphine Maucourt-Boulch (Department of Medical Statistics, Hospices Civils de Lyon) for statistical advices.
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