Impact of Continuous Kidney Replacement Therapy and Hemoadsorption with CytoSorb on Antimicrobial Drug Removal in Critically Ill Children with Septic Shock: A Single-Center Prospective Study on a Pediatric Cohort

Abstract

Background: Extracorporeal therapies (ET) are increasingly used in pediatric settings as adjuvant therapeutic strategies for overwhelming inflammatory conditions. Although these treatments seem to be effective for removing inflammatory mediators, their influence on antimicrobials pharmacokinetic should not be neglected. Methods: A prospective observational study of children admitted to the pediatric intensive care unit (PICU) with a diagnosis of sepsis/septic shock. All critically ill children received hemoadsorption treatment with CytoSorb (CS) in combination with CKRT. Therapeutic drug monitoring has been performed on 10 critically ill children, testing four antimicrobial molecules: meropenem, ceftazidime, amikacin and levofloxacin. In order to evaluate the total and isolated CKRT and CS contributions to antibiotic removal, blood samples at each circuit point (post-hemofilter, post-CS and in the effluent line) were performed. Therefore, the clearance and mass Removal (MR) of the hemofilter and CS were calculated. Results: Our preliminary report describes a different impact of CS on these target drugs removal: CS clearance was low for amikacine (6–12%), moderate for ceftazidime (43%) and moderate to high for levofloxacine (52–72%). Higher MR and clearance were observed with CKRT compared to CS. To the best of our knowledge, this is the first report regarding pharmacokinetic dynamics in critically ill children treated with CKRT and CS for septic shock.

Pharmacokinetic/pharmacodynamic issues for optimizing treatment with beta-lactams of Gram-negative infections in critically ill orthotopic liver transplant recipients: a comprehensive review

“…A PK model assessing whether meropenem CL was affected by CytoSorb treatment in 25 critically ill patients found a negligible impact with an increase < 3.7% (Liebchen et al, 2021). Similarly, a prospective observational study carried out in ten critically ill patients undergoing hemoadsorption treatment with CytoSorb reported that drug CL was increased by 43% for ceftazidime and decreased by 57% for meropenem (Bottari et al, 2023). In regard to the use of oXiris high-adsorbent membrane, a prospective population PK study was conducted among 12 critically ill patients treated with meropenem at a dosage of 1000 mg every 8 hours (Padulleś Zamora et al, 2019).…”

“…Finally, the pharmacokinetics of beta-lactams may be affected also by systems providing renal replacement therapy, removing endotoxins, and adsorbing cytokines even simultaneously, namely CytoSorb hemoadsorption device, oXiris hemofilter, or the Molecular Adsorbent Recirculating System (MARS), which are important supportive tools in patients with severe liver failure or OLT recipients (Isoniemi et al, 2005;Li et al, 2022;Bottari et al, 2023;Popescu et al, 2023). Although no specific study was conducted in the setting of OLT recipients, interesting data may be retrieved by preclinical studies and by clinical studies conducted in other settings of critically ill patients.…”