Abstract
Cytokine hemoadsorption might be beneficial in patients with sepsis. However, its effect on anti-infective agents' disposition remains largely unknown. We sought to determine the influence of hemoadsorption on the pharmacokinetics of common anti-infective agents. This is an interventional experimental study, conducted in 24 healthy pigs. Animals were randomly allocated to either hemoadsorption (cases) or sham extracorporeal circuit (controls) and to drug combinations (3 cases and 3 controls for each combination). Hemoadsorption was performed with CytoSorb (CytoSorbents Corporation, USA). We evaluated 17 drugs (clindamycin, fluconazole, linezolid, meropenem, piperacillin, anidulafungin, ganciclovir, clarithromycin, posaconazole, teicoplanin, tobramycin, ceftriaxone, ciprofloxacin, metronidazole, liposomal amphotericin B, flucloxacillin and cefepime). Repeated blood sampling from the extracorporeal circulation (adsorber inlet/outlet, sham circuit) was performed over six hours following administration. Total clearance and adsorber-specific clearance were computed. Hemoadsorption was associated with increased clearance of all study drugs, except ganciclovir. Its impact on total body clearance was considered as moderate for fluconazole (282%) and linezolid (115%), mild for liposomal amphotericin B (75%), posaconazole (32%) and teicoplanine (31%) and negligible for all other drugs. Hemoadsorber clearance declined over time, with even delayed desorption for beta-lactams. It was moderately correlated with drug's lipophilicity (p = 0.01; r2 = 0.43). Hemoadsorption with CytoSorb appears to increase to a clinically significant extent the clearance of five among 17 tested anti-infectives. Studies in human patients are required to confirm the need for dosage adjustment of these agents.
Highlights
Cytokine hemoadsorption might be beneficial in patients with sepsis
Little is known about the effect of CytoSorb on anti-infectives’ pharmacokinetics
We have conducted an experimental study on 24 pigs to assess the impact of hemoadsorption with CytoSorb on the pharmacokinetics of a panel of anti-infective drugs commonly utilized in the management of patients with sepsis
Summary
Cytokine hemoadsorption might be beneficial in patients with sepsis. its effect on antiinfective agents’ disposition remains largely unknown. We sought to determine the influence of hemoadsorption on the pharmacokinetics of common anti-infective agents. Sepsis results from a dysregulated host response to infection[2] Activation of both complement and coagulation systems lead to the massive release of pro- and anti-inflammatory cytokines in the blood, a phenomenon sometimes referred to as "cytokine storm"[3]. The level of evidence supporting the use of CytoSorb in septic shock remains low and largely o bservational[7,8,9,10,11] In their latest statement, experts from the Surviving Sepsis Campaign urged for further research and did not recommend for or against blood purification techniques[12].
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