Hemoadsorption with CytoSorb shows a decreased observed versus expected 28-day all-cause mortality in ICU patients with septic shock: a propensity-score-weighted retrospective study

Abstract

Background and aims Innovative treatment modalities have not yet shown a clinical benefit in patients with septic shock. To reduce severe cytokinaemia, CytoSorb as an add-on to continuous renal replacement therapy (CRRT) showed promising results in case reports. However, there are no clinical trials investigating outcomes. Methods In this investigator-initiated retrospective study, patients with septic shock were treated with CRRT + CytoSorb (n = 67) or CRRT alone (n = 49). The primary outcome was the 28-day all-cause mortality rate. Patients were weighted by stabilized inverse probability of treatment weights (sIPTW) to overcome differences in baseline characteristics. Results At the start of therapy, CytoSorb-treated patients had higher lactate levels (p < 0.001), lower mean arterial pressure (p = 0.007) and higher levels of noradrenaline (p < 0.001) compared to the CRRT group. For CytoSorb, the mean predicted mortality rate based on a SOFA of 13.8 (n = 67) was 75% (95%CI 71–79%), while the actual 28-day mortality rate was 48% (mean difference − 27%, 95%CI − 38 to − 15%, p < 0.001). For CRRT, based on a SOFA of 12.8 (n = 49), the mean predicted versus observed mortality was 68% versus 51% (mean difference − 16.9% [95%CI − 32.6 to − 1.2%, p = 0.035]). By sIPTW analysis, patients treated with CytoSorb had a significantly lower 28-day mortality rate compared to CRRT alone (53% vs. 72%, respectively, p = 0.038). Independent predictors of 28-day mortality in the CytoSorb group were the presence of pneumosepsis (adjusted odds ratio [aOR] 5.47, p = 0.029), higher levels of lactate at the start of CytoSorb (aOR 1.15, p = 0.031) and older age (aOR per 10 years 1.67, p = 0.034). Conclusions CytoSorb was associated with a decreased observed versus expected 28-day all-cause mortality. By IPTW analysis, intervention with CytoSorb may be associated with a decreased all-cause mortality at 28 days compared to CRRT alone.

Hemoadsorption of cytokines by CytoSorb filter: a simulation study without human factor—pilot is the difference

“…We agree however that because of the retrospective nature of our study, a human factor cannot be completely eradicated. Yet, by applying the "inverse probability of treatment weight (IPTW)" method, the patient characteristics at the start of therapy are comparable as shown in Table 1 and by the supplementary figure [1,2,4,5].…”

“…The propensity score (i.e., the probability of being treated, given the set of confounders) is constructed and used as a weighting factor in order to create a comparable set of patients. This means that, after applying the weights, the distribution of the patient characteristics at the start of therapy is now independent of the treatment assignment, such as is the case in a randomized controlled trial [1,2,4,5].…”

“…The weights were normalized using the estimated marginal means of the propensity score, and as a result, there is not an inflated sample size and the confidence intervals are not falsely narrowed. Data with respect to the IPTW and the distribution of the covariates can be found in the supplementary figure [1].…”

“…Lastly, Nadeem et al summarize a list of limitations of our study. We would kindly like to refer the authors to the discussion section of our paper where these limitations had already been thoroughly considered [1].…”

“…We read with great interest the article published in a recent issue of Critical Care by Brouwer et al [1]. Authors showed the beneficial effect of addition of CytoSorb filter to continuous renal replacement therapy (CRRT) for hemoadsorption of cytokines in management of septic shock.…”