Regional Citrate Anticoagulation During Coupled Plasma Filtration and Adsorption May Increase Survival in Septic Shock

Dear Editor, We read with great interest the paper by Berlot et al. [1] published in the July 2018 issue of your journal. These authors concluded that a reduced volume of treated plasma was significantly associated with mortality and particularly mentioned that the mean volume of treated plasma was less than 0.20 L/kg/session in non-survivors (0.17 L/kg/session). Available evidence suggests that any effective volume of treated plasma less than 0.18 L/kg/day is too low to have any impact in any multivariate analysis. Indeed, the COMPACT trial, which is a Bellco-funded investigation designed to evaluate hospital mortality in septic shock, compared patients treated with coupled plasma filtration and absorption (CPFA) with similar patients treated with standard care [2]. The study was prematurely stopped due to technical difficulties associated with the technique. Forty-eight percent of patients were undertreated, as they did not reach the target goal of treatment. The main reason for this was the clotting of the circuit because the machine used in the study did not support regional citrate anticoagulation (RCA). Although the trial failed to show any statistical difference in hospital mortality between 2 arms, in a priori subgroup analysis, they did observe a plasma-dose related survival benefit in patients who received at least 0.18 L/kg/day of treated plasma (OR 0.36, 95% CI from 0.13 to 0.99). We believe that in the COMPACT trial and in the study by Berlot et al. [1] CPFA might have had an “all or none” effect. Alternatively, when the volume of treated plasma becomes less than 0.18 L/kg/day, the experimental design requires larger cohorts in order to avoid underpowering. In our consideration, if CPFA was administered using RCA, the volume of treated plasma would have been much higher, thereby providing statistically significant survival benefit. Using the volume of treated plasma ≥0.18 L/kg/day as a categorical variable in multiple logistic regression, its impact on survival benefit might have been more evident. In a feasibility study carried out in 15 septic shock patients, RCA was associated with significantly lower number of clotted CPFA compared to those used with heparin [3]. This initial experience in patients with septic shock demonstrates that a much higher volume of plasma can be safely treated when RCA is used during CPFA, which has been performed successfully using the Bellco machine [3]. For the reasons explained above, we suggest that the volume of treated plasma be increased over 18 L/kg/day using RCA which, to our understanding and as per available evidence, can show survival benefit. Thus, we strongly propose a future study based on this recommendation before we can fully reject CPFA in sepsis.