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.

Keywords: CKRT; CytoSorb; antimicrobials; clearance; extracorporeal therapies; hemoadsorption; mass removal; therapeutic drug monitoring (TDM).

Figure 1

Clearance values for time-dependent antibiotics analyzed in this study (Meropenem and Ceftazidime). Blue bars refer to hemofilter clearance and orange bars to the CytoSorb clearance. y-axis: antibiotic clearance (mL/min); x-axis time points of the day antibiotic’s measurements.

Figure 2

Clearance values for concentration-dependent antibiotics analyzed in this study (Amikacine and Levofloxacine). Blue bars refer to hemofilter clearance and orange bars to the CytoSorb clearance. y-axis: antibiotic clearance (mL/min); x-axis: time points of the day of antibiotic measurements.

Figure 3

Graphical representation of the relationship between pharmacodynamic target attainment (PTA) (red bars) calculated on the basis of MIC and blood concentration (mcg/mL) of each antibiotic tested during the study (blue and orange bars). (a) Ceftazidime MIC for Klebsiella pneumoniae; (b) meropenem for Klebsiella pneumonia in two different patients (blue bars—patient 1 and orange bars—patient 2); (c) amikacin for Klebsiella pneumonia; (d) meropenem for Streptococcal pneumonia.

Figure 4

Graphical illustration of the extracorporeal circuit with blood sampling protocol. The 4 samplings in the patient and along the circuit were the patient’s blood sample (P1), hemofilter outflow = (CS cartridge inflow) (P2), CS cartridge outflow (P3) and effluent line (P4). In the lower section of the figure, the extracorporeal therapy flows are described: (1) hemofilter inlet = (Qin [mL/min]); (2) hemofilter outlet = (Qx [mL/min]) corresponding to CytoSorb inflow; (3) Net Ultrafiltration Rate = (CP [mL/min]); (4) effluent flow = (Qe [mL/min]); (5) CytoSorb outflow = (Qo [mL/min]).