No clinically relevant removal of meropenem by cytokine adsorber CytoSorb® in critically ill patients with sepsis or septic shock

Liebchen, Uwe; Scharf, Christina; Zöller, Michael; Weinelt, Ferdinand; Kloft, Charlotte; Michelet, Robin; Schroeder, Ines; Paal, Michael; Vogeser, Michael; Irlbeck, Michael; Briegel, Josef; Zander, Johannes; Huisinga, Wilhelm

doi:10.1007/s00134-021-06487-y

Cited by 17 publications

(12 citation statements)

References 5 publications

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“…These drugs are presented in Table 1 and include anidulafungin, cefepime, ceftriaxone, ciprofloxacin, clarithromycin, clindamycin, flucloxacillin, ganciclovir, meropenem, metronidazole, and piperacillin. A recently published investigation confirmed the absence of clinically relevant removal of meropenem by CytoSorb in patients with sepsis or septic shock (28).…”

Section: Considerations For the Interpretation Of Available Pharmacok...mentioning

confidence: 84%

Mechanistic Considerations and Pharmacokinetic Implications on Concomitant Drug Administration During CytoSorb Therapy

Scheier

Nelson

Schneider³

et al. 2022

Critical Care Explorations

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The CytoSorb hemoadsorption device (CytoSorbents Inc, Monmouth Junction, NJ) is increasingly used in many critical disease states. The potential impact on the pharmacokinetic (PK) of concomitantly administered drugs must be considered in clinical practice. The current review summarizes relevant mechanistic principles, available preclinical and clinical data, and provides general guidance for the management of concomitant drug administration during CytoSorb therapy.DATA SOURCES: Detailed search strategy using the PubMed and OVID MEDLINE databases, as well as presented congress abstracts for studies on drug removal by the CytoSorb device.STUDY SELECTION: Human, animal, and bench-top studies with PK or drugremoval data during CytoSorb therapy were selected for inclusion. Publications reporting on CytoSorb treatments for drug overdose were not considered.DATA EXTRACTION: Relevant PK data were examined and synthesized for narrative review. DATA SYNTHESIS:To date, PK data during CytoSorb hemoadsorption are available for more than 50 drugs, including analgesics, antiarrhythmics, anticonvulsants, antidepressants, antihypertensives, antiinfectives, antithrombotics, anxiolytics, and immunosuppressants. Based on available PK data, drugs were categorized into low (<30%), moderate (30-60%), or high rates of removal (>60%), or, alternatively, according to clearance increase relative to endogenous clearance: negligible (<25%), low (25-100%), moderate (100-400%), or high (>400%). In most reports, additional impact of the extracorporeal platform where CytoSorb was integrated was not available. Based on available data and considering drug, patient, and setup-specific aspects, general dosing guidance for clinical practice was developed. CONCLUSIONS:CytoSorb therapy may increase drug elimination through active removal. However, the extent of removal is heterogeneous, and its clinical significance, if any, depends on the broader clinical context, including a patient's specific endogenous drug clearance and the underlying extracorporeal platform used. The available data, although not definitive, allow for general guidance on dosing adjustments during CytoSorb therapy; however, any treatment decisions should always be complemented by clinical judgment and therapeutic drug monitoring, when available.

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Section: Considerations For the Interpretation Of Available Pharmacok...mentioning

confidence: 84%

Mechanistic Considerations and Pharmacokinetic Implications on Concomitant Drug Administration During CytoSorb Therapy

Scheier

Nelson

Schneider³

et al. 2022

Critical Care Explorations

View full text Add to dashboard Cite

show abstract

“…An in vitro study suggested the need for administration of an additional antibiotic dose within the first few hours of CytoSorb® treatment and for early therapeutic drug monitoring since all antimicrobial drugs tested were adsorbed by the cartridge in relevant amounts 49 . However, reliable quantitative clinical data is needed to confirm these findings 54 . Another in vitro study found that remdesivir and its main active metabolite were eliminated by CytoSorb® 52 .…”

Section: Discussionmentioning

confidence: 99%

“…49 However, reliable quantitative clinical data is needed to confirm these findings. 54 Another in vitro study found that remdesivir and its main active metabolite were eliminated by CytoSorb ® . 52 Hence, without proper monitoring, some drugs may reach subtherapeutic levels and thus negatively impact patient outcome.…”

Section: Relationship To Previous Studiesmentioning

confidence: 99%

Mortality and adverse events of hemoadsorption with CytoSorb® in critically ill patients: A systematic review and meta‐analysis of randomized controlled trials

Heymann

Schorer

Putzu

2022

Acta Anaesthesiol Scand

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Background: The effects and safety of extracorporeal hemoadsorption with CytoSorb ® in critically ill patients with inflammatory conditions are controversial.Methods: We performed a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized-controlled trials to assess the mortality and safety of CytoSorb ® therapy in critically ill patients with inflammatory conditions. Electronic databases were searched up to April 2022. The primary outcome was mortality at longest follow-up and secondary outcomes included various adverse event (AE) outcomes. Conflict of interest and funding of each trial were assessed. We calculated relative risk (RR) and 95% confidence interval (CI).Results: Fourteen published (n = 764) and 4 unpublished (n = 111) trials were included. Eight trials were performed in medical ICU patients and 10 in complex cardiac surgery. Ten trials had significant industrial funding or an author conflict of interest. Hemoadsorption with CytoSorb ® was associated with higher mortality at latest follow-up (16 trials, n = 807, 120 of 402 [29.85%] patients in the CytoSorb ® group vs. 98 of 405 [24.20%] patients in the control group, RR = 1.24 [95% CI, 1.04-1.49], p = .02, [TSA-adjusted CI, 0.92-1.68]) and at 30-days or in-hospital (11 trials, n = 727; RR = 1.41 [95% CI, 1.06-1.88], p = .02, ). Only one trial reported the definition of adverse event, while detailed results were reported in 3 trials; the risk of adverse events was not higher with CytoSorb ® . Certainty of evidence ranged from low to very low. Conclusion:Low certainty of evidence showed that the use of CytoSorb ® might increase mortality in critically ill patients with inflammatory conditions. Adverse events were frequent but underreported and not systematically evaluated. Industrial funding and conflict of interest were common. Considerable uncertainty about the findings does not allow firm conclusions and suggests a need for high-quality randomized trials to clarify mortality and adverse events related to CytoSorb ® .Editorial Comment: Hemoadsorption with CytoSorb ® have been used in critically ill patients despite lack of high quality data from RCTs suggesting any patient-important benefits. The findings from this systematic review and meta-analysis suggests an

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“…As significant losses of amino acids and several micronutrients, such as vitamins B1 and C, copper and selenium can occur, careful monitoring in prolonged KRT should be considered 156 . Importantly, discrepancies exist in the observed and predicted removal of antimicrobials with haemoadsorption in critically ill patients [157][158][159][160][161][162][163] . In patients undergoing continuous KRT, anti microbial clearance depends on the effluent fluid rate and therapeutic drug monitoring should therefore be considered where available 157 .…”

Section: Delivery and Monitoring Of Extracorporeal Blood Purification...mentioning

confidence: 99%

Sepsis-associated acute kidney injury: consensus report of the 28th Acute Disease Quality Initiative workgroup

et al. 2023

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Sepsis-associated acute kidney injury (SA-AKI) is common in critically ill patients and is strongly associated with adverse outcomes, including an increased risk of chronic kidney disease, cardiovascular events and death. The pathophysiology of SA-AKI remains elusive, although microcirculatory dysfunction, cellular metabolic reprogramming and dysregulated inflammatory responses have been implicated in preclinical studies. SA-AKI is best defined as the occurrence of AKI within 7 days of sepsis onset (diagnosed according to Kidney Disease Improving Global Outcome criteria and Sepsis 3 criteria, respectively). Improving outcomes in SA-AKI is challenging, as patients can present with either clinical or subclinical AKI. Early identification of patients at risk of AKI, or at risk of progressing to severe and/or persistent AKI, is crucial to the timely initiation of adequate supportive measures, including limiting further insults to the kidney. Accordingly, the discovery of biomarkers associated with AKI that can aid in early diagnosis is an area of intensive investigation. Additionally, high-quality evidence on best-practice care of patients with AKI, sepsis and SA-AKI has continued to accrue. Although specific therapeutic options are limited, several clinical trials have evaluated the use of care bundles and extracorporeal techniques as potential therapeutic approaches. Definition and epidemiology of SA-AKI Definition of SA-AKI and sepsis-induced AKICurrently, no universally accepted definition of SA-AKI exists 15 . To support clinical guidelines, quality improvement initiatives, and future research, we propose that the presence of both sepsis (as currently defined in adults by the Sepsis-3 criteria) and AKI (as presently defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria) should define SA-AKI 1,16 (Box 1). SA-AKI is a heterogeneous syndrome that occurs as the consequence of either direct mechanisms related to infection or the host response to infection, or indirect mechanisms driven by unwanted sequelae of sepsis or sepsis therapies 17 . As such, the term SA-AKI operationally unifies the presence of AKI (according to clinical, biochemical and functional criteria) in the context of sepsis as a specific disease phenotype that is characterized by a specific trajectory and outcome 18,19 .Sepsis-induced AKI (SI-AKI) can be considered to be a subphenotype of SA-AKI, in which sepsis-induced mechanisms drive kidney damage directly. Thus, by definition, SI-AKI excludes injury that primarily develops as the indirect consequence of sepsis or sepsis therapies (for example, AKI caused by antimicrobial agent-induced nephrotoxicity or abdominal compartment syndrome) 20,21 . Importantly, mechanisms that underlie cellular and organ injury in ischaemic AKI or nephrotoxic AKI, such as microcirculation failure, inflammation and mitochondrial injury, might also contribute to SI-AKI. The limited availability of clinical tools such as biomarkers that can aid early identification complicate Many aspects of SA-AKI rema...

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No clinically relevant removal of meropenem by cytokine adsorber CytoSorb® in critically ill patients with sepsis or septic shock

Abstract: share senior authorship.The members of the CytoMero collaboration team are listed in the Acknowledgements section of the manuscript.

Cited by 17 publications

References 5 publications

Mechanistic Considerations and Pharmacokinetic Implications on Concomitant Drug Administration During CytoSorb Therapy

Mechanistic Considerations and Pharmacokinetic Implications on Concomitant Drug Administration During CytoSorb Therapy

Mortality and adverse events of hemoadsorption with CytoSorb® in critically ill patients: A systematic review and meta‐analysis of randomized controlled trials

Sepsis-associated acute kidney injury: consensus report of the 28th Acute Disease Quality Initiative workgroup

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