Strengths and limitations
myocardial injury
ADVERSE EVENTS, CHRONIC HEART FAILURE, HYPERTENSION
Besides its randomized design, this study has several strengths. Our efficacy criteria included serial measurements of a large panel of pro- and anti-inflammatory cytokines, at six different time points over 72 h post-randomization. IL-6 plasma measurements were highlighted in view of the amount of data supporting its role in PCAS development and potential interest as a therapeutic target to reduce myocardial injury in PCAS [Certain limitations should also be reported. First, as a pilot study, it was not powered to detect a difference in mortality or in cytokines reduction. Therefore, the small sample size precludes any conclusions on biological and clinical outcomes. In addition, for this reason, we explored cytokines variations mainly through descriptive analysis and simple comparison tests. Our data enable power calculation for further studies, which would ideally include more statistical analyses such as mixed effects models accounting for time effects and baseline characteristics. Second, the randomization was imperfect and CA characteristics associated with worse outcomes (time-to-ROSC, out-of-hospital CA, non-shockable presenting rhythm) as well as certain comorbidities (chronic heart failure, hypertension, aspirin use and smoking) were unbalanced between groups. The exact impact of this imbalance is difficult to estimate as characteristics associated with poor prognosis were distributed between both groups (longer time-to-ROSC and more out-of hospital CA in HA group but more non-shockable rhythm and higher admission lactate in control group). Third, we did not collect neurological outcomes; however, HA may exert beneficial effects on neurological recovery. Previously, elevated IL-6 levels in cerebrospinal fluid (CSF) were found to be associated with poor neurological outcomes [Finally, the study population was highly heterogeneous with respect to IL-6 plasma levels at randomization. Although we applied strict criteria to select the patients with the highest risk to develop PCAS (therefore excluding 30% of patients admitted after CA), IL-6 plasma levels were low (< 100 pg/mL) at randomization in half of our patients. Because hemoadsorption is a concentration-dependent process, its effect on these patients is likely to be negligible and might even “dilute” any potential effect observed in those with the highest levels. Including patients unlikely to benefit from the treatment by nature leads to erroneous conclusions while exposing them to potential adverse events. In the absence of cytokine measurements at the bedside, future research should focus on identifying predictors of elevated cytokines, such as biomarkers or clinical scores.
