Sepsis is one of the main causes of death in critically ill patients worldwide, and in many cases it is associated with renal and/or other organ failure. However, we do not have a unique efficient therapy to reduce this extremely high mortality rate. Both pro-inflammatory and anti-inflammatory mediators participate in the pathogenesis of sepsis and explain the failure of specific therapies to improve survival. Continuous extracorporeal therapies have been proposed as a therapeutic option in sepsis. One of the emerging treatments in patients with sepsis and septic shock is CPFA.CPFA is a technique that separates plasma from the blood using a plasma filter. The plasma is then passed through a synthetic resin cartridge and returned to the blood. A second blood filter is used to remove excess fluid and small molecular weight toxins. The nonselective removal of inflammatory mediators is achieved by hydrophobic styrene resin, which has high affinity and capacity for many cytokines and mediators.In vitro studies have demonstrated the efficacy of CPFA in adsorbing inflammatory mediators like IL-1β, IL-6, IL-8, IL-10, and TNF-α amongst others. CPFA has also been shown to enhance early hemodynamic stability, reduce inotropic support requirement, and improve the immune response in septic patients . However, these trials have so far failed to demonstrate any improvement in hard clinical outcomes.
Our systematic review and meta-analysis of six studies including 537 patients compared CPFA and control group in patients with sepsis or septic shock. We found that the overall all-cause mortality was about 54.2% and there was no statistically significant difference in the all-cause mortality between two groups. Guidelines, for example, state that ‘hemofiltration should not be used in patients with sepsis without renal indications unless ongoing studies provide positive results’ . The role of plasma exchange remains equally controversial[32, 33].The extracorporeal removal of septic mediators is not recommended in the 2016 edition of the Surviving Sepsis Campaign (SSC) due to the absence of large, randomized controlled trials demonstrating its efficacy. Experimental study even showed that treatment with CPFA did not protect from progression of septic hypotension; failed to counteract the progressive alterations in microcirculatory perfusion, energy metabolism, and organ function; and even aggravated the sepsis-induced disturbances in coagulation and oxidative/nitrosative stress.
What are the implications of our meta-analysis’s results? Firstly, CPFA is a blood purification therapy aimed at modulating the host inflammatory response involved in sepsis pathogenesis. One potential drawback of this technique is the unexpected elimination of antibiotics. Any delay in receiving appropriate antibiotic therapy in severe sepsis or septic shock patients is associated with excess mortality[37–39]. Moreover, CPFA removes 50% more antibiotics than does standard continuous renal replacement therapy, increasing the possibility of undertreatment. A significant dose-response effect of treated plasma on mortality was demonstrated in patients without severe renal failure. As a result, monitoring of antibiotics serum concentrations remains essential to avoid antibiotics underdosing. Secondly, even though previous studies have been promising, numerous questions, including the timing, duration, and frequency of these therapies in the clinical setting, remain unanswered. We hypothesize a connection to hemodynamic instability consequent on renal replacement therapy  that has been shown to increase mortality. This instability may complicate the said therapy, especially when patients have not been fully stabilized, and may be related to early commencement of treatment(no more than 12 h from diagnosis) .Thirdly, early treatment with CPFA failed to afford any protection against sepsis-mediated hemodynamic and physiological disturbances and tended to worsen procoagulant state and oxidative stress.Fourthly, they did not take cost into account for each treatment. The cost of new sorbents may be one the main drawbacks in CPFA .
There are several limitations in our meta-analysis. First, the number of included studies is small. Further randomized clinical studies should be conducted in order to confirm the results. Second, many of the clinical outcomes such as ICU length of stay, hospital length of stay, hemodynamic parameters were not included in most of the studies examined in this meta-analysis. Therefore, we were unable to conduct a meta-analysis on secondary outcomes. Third, Organ dysfunction is also a very important clinical outcome. However, few included studies had showed this data. Fourth, although we had performed a subgroup analysis of RCTs and cohort studies, there was still substantial heterogeneity among the included studies. Very heterogeneous populations were included in both observational and randomized studies. In addition, inclusion/exclusion criteria and comorbidities were widely different among included studies which supposed a limitation to interpret results. Therefore, our findings should be interpreted with caution.