CytoSorb Rescue for COVID-19 Patients With Vasoplegic Shock and Multiple Organ Failure: A Prospective, Open-Label, Randomized Controlled Pilot Study*

Abstract

OBJECTIVES: To investigate the effect of extracorporeal cytokine reduction by CytoSorb (CytoSorbents, Monmouth Junction, NJ) on COVID-19–associated vasoplegic shock. DESIGN: Prospective, randomized controlled pilot study. SETTING: Eight ICUs at three sites of the tertiary-care university hospital Charité—Universitätsmedizin Berlin. PATIENTS: COVID-19 patients with vasoplegic shock requiring norepinephrine greater than 0.2 µg/kg/min, C-reactive protein greater than 100 mg/L, and indication for hemodialysis. INTERVENTIONS: Randomization of 1:1 to receive CytoSorb for 3–7 days or standard therapy. To account for inadvertent removal of antibiotics, patients in the treatment group received an additional dose at each adsorber change. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was time until resolution of vasoplegic shock, estimated by Cox-regression. Secondary endpoints included mortality, interleukin-6 concentrations, and catecholamine requirements. The study was registered in the German Registry of Clinical Trials (DRKS00021447). From November 2020 to March 2021, 50 patients were enrolled. Twenty-three patients were randomized to receive CytoSorb and 26 patients to receive standard of care. One patient randomized to cytokine adsorption was excluded due to withdrawal of informed consent. Resolution of vasoplegic shock was observed in 13 of 23 patients (56.5%) in the CytoSorb and 12 of 26 patients (46.2%) in the control group after a median of 5 days (interquartile range [IQR], 4–5 d) and 4 days (IQR, 3–5 d). The hazard ratio (HR) for the primary endpoint, adjusted for the predefined variables age, gender, extracorporeal membrane oxygenation-therapy, or time from shock onset to study inclusion was HR, 1.23 (95% CI, 0.54–2.79); p = 0.63. The mortality rate was 78% in the CytoSorb and 73% in the control group (unadjusted HR, 1.17 [95% CI, 0.61–2.23]; p = 0.64). The effects on inflammatory markers, catecholamine requirements, and the type and rates of adverse events were similar between the groups. CONCLUSIONS: In severely ill COVID-19 patients, CytoSorb did not improve resolution of vasoplegic shock or predefined secondary endpoints.

Is This the Beginning of the End of Cytokine Adsorption?*

“…Indeed, systemic concentrations of pro-inflammatory cytokines in patients with severe COVID-19 are not as high as has been reported in patients with other causes of acute respiratory distress syndrome. The study results by Stockmann et al ( 1 ) are in line with the results of another randomized controlled study in patients with septic shock and multiple organ failure in which CytoSorb removed IL-6, but the removal had no effect on systemic IL-6-levels ( 10 ). So calming the storm, as one of the miracles of Jesus in a fierce storm sailing the Sea of Galilee, seems to be a challenging endeavor.…”

“…“However beautiful the strategy, you should occasionally look at the results.” is a famous saying by Sir Winston Churchill. In this issue of Critical Care Medicine , Stockmann et al ( 1 ) did exactly that by looking at the result of a well-performed randomized controlled trial in which they investigated an intriguing strategy, namely the use of a cytokine adsorber, in patients with COVID-19 in vasoplegic shock ( 2 ). In contrast to a growing popular belief, they neither showed any difference in the need for catecholamines nor in the mortality nor in other secondary outcomes, including interleukin (IL)-6 and C-reactive protein (CRP) levels.…”

“…In the single-center pilot trial, Stockmann et al ( 1 ) enrolled 50 severely ill patients with need for norepinephrine greater than 0.2 µg/kg/min to maintain mean arterial pressure greater than or equal to 65 mm Hg, a CRP greater than 100 mg/L, and an acute kidney injury (AKI) stage 3 with need for kidney replacement therapy (KRT) ( 2 ). The median time to resolution of vasoplegia, the primary endpoint, was similar between both groups as was the secondary endpoint mortality rate.…”

“…What could have prevented the success of the intervention by cytokine adsorption in the study by Stockmann et al ( 1 )?…”

Application of Extracorporeal Apheresis in Treatment of COVID-19: a Rapid Review

“…Stockmann et al [ 55 ] noted that the removal of cytokines using CytoSorb in critically ill COVID-19 patients with suspected generalized inflammation and shock can be an excellent way of stabilizing hemodynamics and improving the clinical outcome. However, in a large open-label randomized controlled trial involving patients with severe COVID-19, they showed that the use of CytoSorb did not prevent the development of Vasoplegic shock; moreover, mortality level in the CytoSorb and control groups was almost the same at 78% and 73%, respectively [ 56 ].…”