High dose coupled plasma filtration and adsorption in septic shock patients. Results of the COMPACT-2: a multicentre, adaptive, randomised clinical trial.

PURPOSE: This study aimed at evaluating the efficacy and safety of high-dose (> 0.2 L/kg of treated plasma per day) coupled plasma filtration-adsorption (CPFA) in treating patients with septic shock. METHODS: Multicentre, randomised, adaptive trial, performed in 12 Italian intensive care units (ICUs). Patients aged 14 or more, admitted to the ICU with septic shock, or had developed it during the stay were eligible. The final outcome was mortality at discharge from the last hospital at which the patient received care. RESULTS: Between May 2015, and October 2017, 115 patients were randomised. The first interim analysis revealed a number of early deaths, prompting an unplanned analysis. Last hospital mortality was non-significantly higher in the CPFA (55.6%) than in the control group (46.2%, p = 0.35). The 90-day survival curves diverged in favour of the controls early after randomisation and remained separated afterwards (p = 0.100). An unplanned analysis showed higher mortality in CPFA compared to controls among patients without severe renal failure (p = 0.025); a dose-response relationship was observed between treated plasma volume and mortality (p = 0.010). CONCLUSION: The COMPACT-2 trial was stopped due to the possible harmful effect of CPFA in patients with septic shock. The harmful effect, if present, was particularly marked in the early phase of septic shock. Patients not requiring renal replacement therapy seemed most exposed to the possible harm, with evidence of a dose-response effect. Until the mechanisms behind these results are fully understood, the use of CPFA for the treatment of patients with septic shock is not recommended.

Chemical and microbiological stability, anticoagulant efficacy and toxicity of 35 and 90†mM trisodium citrate solutions stored in plastic syringes.

BACKGROUND: Trisodium citrate is an interesting alternative to heparin for the prevention of circuit clotting during extracorporeal procedures, but some protocols require non-commercially available citrate concentrations. Little published information is available about the stability of diluted citrate solutions. OBJECTIVES: To evaluate the long-term stability, efficacy and toxicity of 35 mM and 90 mM trisodium citrate solutions prepared by diluting a commercially available sterile solution, stored in plastic syringes and used as an anticoagulant during citrate bag changes in the coupled plasma filtration adsorption (CPFA) technique in the COMPACT-2 clinical trial. METHODS: The chemical stability of trisodium citrate solutions was evaluated by high-performance liquid chromatography after 7, 14, 21 and 28 days of storage. Sterility tests were performed both immediately after preparation and after 28 days of storage. RESULTS: After 28 days of storage, the concentration of trisodium citrate had not changed in comparison with day 1, and both solutions passed the sterility test. A preliminary test indicated that a 35 mM solution is insufficient to ensure an effective anticoagulant action on an extracorporeal circuit, but the 90 mM solution was successfully used for 7 CPFA treatments in 2 patients, without clinical signs of toxicity. CONCLUSIONS: Both the 35 mM and 90 mM solutions are chemically and microbiologically stable for 28 days when stored at room temperature in 50 mL syringes protected by light. The 90 mM solution is an effective and safe regional anticoagulant in the CPFA protocol. TRIAL REGISTRATION NUMBER: NCT01639664.