Blood Purification With CytoSorb in Critically Ill Patients: Single‐Center Preliminary Experience

Calabrò, Maria Grazia; Febres, Daniela; Recca, Giuseppe; Lembo, Rosalba; Fominskiy, Evgeny; Scandroglio, Anna Mara; Zangrillo, Alberto; Pappalardo, Federico

doi:10.1111/aor.13327

Cited by 67 publications

(69 citation statements)

References 17 publications

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“…The reduced scale device used in this study is based on the 300 mL CytoSorb ® adsorber, a CE-Mark certified device approved for use as an extracorporeal cytokine adsorber. The indications for use have been expanded to include the adsorption of myoglobin 19 and bilirubin 20 . The device has been shown to adsorb a number of small lipophilic molecules from blood in vitro including amitriptyline, diazepam, digoxin, quetiapine, and rivaroxaban 21 as well as aflatoxin and T-2 toxin 16 , which prompted this investigation.…”

Section: Discussionmentioning

confidence: 99%

Hemoadsorption Improves Survival of Rats Exposed to an Acutely Lethal Dose of Aflatoxin B1

Ruggeberg

O’Sullivan

Kovacs

et al. 2020

Sci Rep

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Mycotoxins, such as aflatoxin B 1 (AFB 1), pose a serious threat as biological weapons due to their high toxicity, environmental stability, easy accessibility and lack of effective therapeutics. This study investigated if blood purification therapy with CytoSorb (CS) porous polymer beads could improve survival after a lethal aflatoxin dose (LD 90). The effective treatment window and potential therapeutic mechanisms were also investigated. Sprague Dawley rats received a lethal dose of AFB 1 (0.5-1.0 mg/ kg) intravenously and hemoperfusion with a cS or control device was initiated immediately, or after 30, 90, or 240-minute delays and conducted for 4 hours. The CS device removes AFB 1 from circulation and significantly improves survival when initiated within 90 minutes of toxin administration. Treated subjects exhibited improved liver morphology and health scores. changes in the levels of cytokines, leukocytes and platelets indicate a moderately-severe inflammatory response to acute toxin exposure. Quantitative proteomic analysis showed significant changes in the level of a broad spectrum of plasma proteins including serine protease/endopeptidase inhibitors, coagulation factors, complement proteins, carbonic anhydrases, and redox enzymes that ostensibly contribute to the therapeutic effect. Together, these results suggest that hemoadsorption with cS could be a viable countermeasure against acute mycotoxin exposure. Aflatoxins are toxic secondary fungal metabolites (mycotoxins) produced by fungus from the genus Aspergillus that cause severe acute reactions that can be lethal. Aspergillus species are important human pathogens and the toxic metabolites appear to act as virulence factors to suppress the immune system in invasive aspergillosis 1. Aflatoxins cause damage to the liver resulting in hemorrhagic liver necrosis, steatosis, bile duct proliferation and subsequent organ failure and have been detected in pulmonary lesions of immune-compromised patients with systemic aspergillosis 2. Aflatoxin B 1 (AFB 1), the most potent toxin of the 14 naturally occurring aflatoxin variants, is extremely cytotoxic, genotoxic, and carcinogenic 3,4. In the liver, cytochrome P450-modified AFB 1 forms DNA adducts that lead to impaired cellular function, carcinogenesis and/or cell death and organ failure 5,6. Acute aflatoxin poisoning from mold contaminated foods has been linked with numerous deaths in several instances 7,8. Importantly, mycotoxins pose a serious threat as potential biowarfare agents due to their inherent stability and ease of manufacture. The toxins can be readily weaponized into aerosol form and dispersed over a wide area to elicit mass casualties through both inhalation and dermal exposure 9. There have been several reported incidents of use of mycotoxins as bioweapons in Southeast Asia and the Gulf States 10,11. Early symptoms of mycotoxin exposure in bio-warfare manifest rapidly in minutes to hours and can include burning, pain, wheezing, nausea, vomiting, tearing, weakness, bleeding and a host of other symptoms...

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Section: Discussionmentioning

confidence: 99%

Hemoadsorption Improves Survival of Rats Exposed to an Acutely Lethal Dose of Aflatoxin B1

Ruggeberg

O’Sullivan

Kovacs

et al. 2020

Sci Rep

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“…During ECMO therapy, a CytoSorb hemoadsorption device (CytoSorbents Europe, Berlin, Germany) was integrated into the ECMO circuit (SCPC, Sorin Munich Germany). The CytoSorb adsorber was connected at the arterial oxygenator (EOS ECMO, LivaNova Mirandola, Italy) outlet via an 3-way stop-cock (tube length 50 cm, inner diameter 4.8 mm) and was returned into the venous line before the centrifugal pump (Revolution, LivaNova Mirandola, Italy) (Figure 1) as reported previously (16, 17). Blood flow rates through the CytoSorb device were between 150 and 300 ml/min as calculated from blood flow rates before and after return into the venous line (Figure 1).…”

Section: Methodsmentioning

confidence: 99%

Cytokine Adsorption in Critically Ill Patients Requiring ECMO Support

Lother

Benk

Staudacher

et al. 2019

Front. Cardiovasc. Med.

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Systemic inflammation is a key characteristic of sepsis but also also in non-infectious conditions such as post-cardiac arrest syndrome. Cytokine adsorption and extracorporeal membrane oxygenation are emerging therapies applied in these critically ill patients, but the experience with their concurrent use is limited. We evaluated cytokine adsorption in critically ill patients requiring support with either veno-venous (vv) or veno-arterial (va) extracorporeal membrane oxygenation (ECMO) support and hypothesized that adsorber incorporation into the ECMO circuit was technically feasible and not associated with imminent risk. We analyzed data from the first six cases of a prospective single-center registry of patients undergoing veno-venous (vv) or veno-arterial (va) ECMO therapy. While in most published cases cytokine adsorbers were inserted into a hemofiltration circuit, we directly incorporated the adsorber into the ECMO circuit without interruption of continuous ECMO support. We observed no relevant side effects attributable to cytokine adsorption. Thirty-day mortality was 83% (predicted mortality 87%), indicating that the decision for adding cytokine adsorption may have been considered as an ultima ratio decision in severe cases with poor prognosis. Vasopressor or inotrope use, lactate level, and fluid balance did not change significantly when comparing pre- vs. post-cytokine adsorption values. Interestingly, the real-time course of the mentioned three surrogate parameters remained unaltered in all but two cases, regardless of cytokine removal. Beneficial effects of cytokine adsorption are plausible in two va-ECMO-treated patient, where increasing lactate began to drop after initiation of cytokine adsorption. Taken together, these data suggest that incorporation of cytokine adsorption into the management of critically ill patients requiring continued ECMO support is feasible and easy to handle. Whether cytokine removal improves clinical outcome in ECMO-treated patients should now be investigated in randomized controlled trials.

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“…The largest case series study published in 2019, included 40 patients with different primary diseases, mainly cardiac. The study showed a significant reduction in bilirubin, lactates, creatine phosphokinase and lactate dehydrogenase serum concentrations [38]. To our knowledge, there are no results of studies comparing the effectiveness of Cytosorb with other methods used to lower bilirubin serum concentration.…”

Section: State Of Knowledgementioning

confidence: 82%

Applications of Cytosorb in clinical practice

Kutnik¹,

Borys²

2019

J Pre Clin Clin Res.

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Introduction and objective. Cytososorb is haemadsorption device approved in the European Union in 2011 for cytokine adsorption. Recently, in 2018, new indications for the device use have been added, including bilirubin and myoglobin removal. This study aimed to present the results of studies pertaining to Cytosorb use in clinical practice. In subsequent sections of this review, indications for Cytosorb therapy and clinical relevance of presented evidence are listed. State of knowledge. In clinical practice, Cytosorb has been reported as one of potential supportive therapies in patients with septic shock. There is evidence of significant reduction of interleukin 6 and vasopressors when Cytosorb is implemented. However, the decreased mortality after Cytosorb has yet to be reported. Besides cytokine adsorption, Cytosorb also collects drugs, a property that can have a beneficial effect on acute drug poisoning (anticoagulants). However, Cytosorb lowers the plasma concentration of some antibiotics which might affect the outcome of patients in septic shock. The haemadsorption device has also been researched in cardiac patients, and some reports suggest a reduced need for vasopressors and blood transfusions when therapy is installed during surgery. Other indications for Cytosorb are also reported, especially the effectiveness in decreasing bilirubin serum concentrations as treatment or bridge therapy, without affecting the albumins. Cytosorb might also be the last resort treatment in acquired haemophagocytic lymphohistiocytosis. Conclusions. The evidence supporting the use of CytoSorb remains elusive. There is lack of large prospective studies which could provide definitive answers about the place of Cytosorb in clinical practice. There are no reports of safety and feasibility issues in all presented studies.

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Blood Purification With CytoSorb in Critically Ill Patients: Single‐Center Preliminary Experience

Cited by 67 publications

References 17 publications

Hemoadsorption Improves Survival of Rats Exposed to an Acutely Lethal Dose of Aflatoxin B1

Hemoadsorption Improves Survival of Rats Exposed to an Acutely Lethal Dose of Aflatoxin B1

Cytokine Adsorption in Critically Ill Patients Requiring ECMO Support

Applications of Cytosorb in clinical practice

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