RESUMEN
To evaluate safety and clinical outcomes of extracorporeal immunomodulation treatment with a selective cytopheretic device (SCD) in COVID-19 ICU patients with multiple organ failure. DESIGN: Two-center, prospective, single-arm treatment clinical trial. SETTING: ICUs at two academic medical centers between September 2020 and July 2021. PATIENTS: Twenty-two COVID-10 patients in the ICU with acute respiratory distress syndrome who required mechanical ventilation. Nearly all included patients in the intervention group except one had acute kidney injury requiring continuous renal replacement therapy (CRRT). Sixteen subjects meeting enrollment criteria were selected as contemporaneous controls from a concurrent prospective registry CRRT trial. INTERVENTION: Treatment with an SCD integrated into a continuous renal replacement extracorporeal blood circuit for up to 10 days to provide autologous leukocyte cell processing to immunomodulate the hyperinflammatory disease state of COVID-19. MEASUREMENTS AND MAIN RESULTS: SCD treatment in COVID-19 ICU patients with multiple organ failure demonstrated an acceptable safety profile with no device-related serious adverse events. Treatment of these patients resulted in the selective removal of highly activated circulating leukocytes as determined by flow cytometry. Significant reductions were observed in the elevated plasma levels of eight cytokines and biomarkers, including interleukin (IL)6, IL15, IL10, and soluble ST2, which are predictive of mortality in COVID-19 patients. Significant improvements of leukocytosis and Po2/Fio2 ratios occurred during treatment not observed in the control group. SCD-treated subjects had a reduction in 60-day mortality of 50% compared with 81% in the control cohort. The subjects who received greater than 96 hours of SCD treatment, per protocol, had a further reduction in mortality to 31% (p < 0.012). CONCLUSIONS: Extracorporeal immunomodulation therapy with an SCD demonstrated safety without any device-related serious adverse events. As a rescue therapy in COVID-19 ICU patients progressing to multiple organ failure despite maximal pharmacologic and organ support interventions, SCD treatment resulted in improved clinical outcomes. This autologous leukocyte cell processing technology may provide a new approach in the treatment of unremitting hyperinflammation of COVID-19.
RESUMEN
INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic led to increased demand nationwide for dialysis equipment, including supplies and machines. To meet the demand in our institution, our surge plan included rapid mobilization of a novel continuous renal replacement treatment (CRRT) machine named SAMI. The SAMI is a push-pull filtration enhanced dialysis machine that can conjugate extremely high single-pass solute removal efficiency with very precise fluid balance control. MATERIAL AND METHODS: Machine assembly was conducted on-site by local biomedical engineers with remote assistance by the vendor. One 3-h virtual training session of 3 dialysis nurses was conducted before SAMI deployment. The SAMI was deployed in prolonged intermittent replacement therapy (PIRRT) mode to maximize patients covered per machine per day. Live on-demand vendor support was provided to troubleshoot any issues for the first few cases. After 4 weeks of the SAMI implementation, data on treatments with the SAMI were collected, and a questionnaire was provided to the nurse trainees to assess device usability. RESULTS: On-site installation of the SAMI was accomplished with remote assistance. Delivery of remote training was successfully achieved. 23 PIRRT treatments were conducted in 10 patients. 7/10 of patients had CO-VID-19. The median PIRRT dose was 50 mL/kg/h (IQR [interquartile range] 44 - 62 mL/kg/h), and duration of the treatment was 8 h (IQR 6.3 - 8 h). Solute control was adequate. The user response was favorable to the set of usability questions involving user interface, on-screen instructions, machine setup, troubleshooting, and the ease of moving the machine. CONCLUSION: Assembly of the SAMI and training of nurses remotely are possible when access to vendor employees is restricted during states of emergency. The successful deployment of the SAMI in our institution during the pandemic with only 3-h virtual training supports that operating the SAMI is simple and safe.