Effect of Extracorporeal Blood Purification on Mortality in Sepsis: A Meta-Analysis and Trial Sequential Analysis

Abstract

<b><i>Objective:</i></b> The objective of this study was to conduct a meta-analysis and trial sequential analysis (TSA) of published randomized controlled trials (RCTs) to determine whether mortality benefit exists for extracorporeal blood purification techniques in sepsis. <b><i>Data Sources:</i></b> A systematic search on MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for RCTs was performed. <b><i>Study Selection:</i></b> RCTs investigating the effect of extracorporeal blood purification device use on mortality among critically ill septic patients were selected. <b><i>Data Extraction:</i></b> Mortality was assessed using Mantel-Haenszel models, and <i>I</i><sup>2</sup> was used for heterogeneity. Data are presented as odds ratios (OR); 95% confidence intervals (CIs); <i>p</i> values; <i>I</i><sup>2</sup>. Using the control event mortality proportion, we performed a TSA and calculated the required information size using an anticipated intervention effect of a 14% relative reduction in mortality. <b><i>Data Synthesis:</i></b> Thirty-nine RCTs were identified, with 2,729 patients. Fourteen studies used hemofiltration (<i>n</i> = 789), 17 used endotoxin adsorption devices (<i>n</i> = 1,363), 3 used nonspecific adsorption (<i>n</i> = 110), 2 were cytokine removal devices (<i>n</i> = 117), 2 used coupled plasma filtration adsorption (CPFA) (<i>n</i> = 207), 2 combined hemofiltration and perfusion (<i>n</i> = 40), and 1 used plasma exchange (<i>n</i> = 106). On conventional meta-analysis, hemofiltration (OR 0.56 [0.40–0.79]; <i>p</i> < 0.001; <i>I</i><sup>2</sup> = 0%), endotoxin removal devices (OR 0.40 [0.23–0.67], <i>p</i> < 0.001; <i>I</i><sup>2</sup> = 71%), and nonspecific adsorption devices (OR 0.32 [0.13–0.82]; <i>p</i> = 0.02; <i>I</i><sup>2</sup> = 23%) were associated with mortality benefit, but not cytokine removal (OR 0.99 [0.07–13.42], <i>p</i> = 0.99; <i>I</i><sup>2</sup> = 64%), CPFA (OR 0.50 [0.10–2.47]; <i>p</i> = 0.40; <i>I</i><sup>2</sup> = 64%), or combined hemofiltration and adsorption (OR 0.71 [0.13–3.79]; <i>p</i> = 0.69; <i>I</i><sup>2</sup> = 0%). TSA however revealed that based on the number of existing patients recruited for RCTs, neither hemofiltration (TSA-adjusted CI 0.29–1.10), endotoxin removal devices (CI 0.05–3.40), nor nonspecific adsorption devices (CI 0.01–14.31) were associated with mortality benefit. <b><i>Conclusion:</i></b> There are inadequate data at present to conclude that the use of extracorporeal blood purification techniques in sepsis is beneficial. Further adequately powered RCTs are required to confirm any potential mortality benefit, which may be most evident in patients at greatest risk of death.

Renal Replacement Techniques in Septic Shock

“…However, CytoSorb therapy was not associated with 56-day survival ( p = 0.095) in a multivariable analysis of a subset of patients who received CytoSorb or CRRT and standard care [ 86 ]. Finally, CytoSorb therapy was not associated with improved survival in a recent meta-analysis assessing the effect of different extracorporeal blood purification techniques on mortality in patients with sepsis [ 87 ]. A clinical trial assessing the efficacy of CytoSorb hemoadsorption compared to standard medical therapy in terms of shock reversal in patients with early refractory septic shock is ongoing (ClinicalTrials.gov identifier: NCT04742764).…”

Mortality and adverse events of hemoadsorption with CytoSorb® in critically ill patients: A systematic review and meta‐analysis of randomized controlled trials

“…Removing those proteins from the blood has therefore been hypothesized to be an effective way to improve clinical outcome. Despite the existence of several blood purification devices and their experimental use in the last 30 years in sepsis and septic shock, their effectiveness is inconclusive and these therapies have not entered routine clinical practice 2,3 . Polymyxin B immobilized fiber column hemoadsorption was evaluated in a cumulative population of more than 1100 septic patients without quality evidence supporting a beneficial effect on survival 2–4 .…”

Endotoxin and Cytokine Sequential Hemoadsorption in Septic Shock and Multi-Organ Failure

“…However, the evolution of clinical trials with polymyxin hemoadsorption has allowed the profile of patients who could benefit from this treatment. Also several studies have shown that cytokine elimination can improve the prognosis [12].…”