Your Questions. Our Answers.

A collection of publications with varying levels of evidence, abstracts, and article links can be found in the CytoSorb® Literature Database (cytosorbents.com/lit-db).

• To date, published clinical studies have described the safety and performance of CytoSorb® Therapy across different clinical settings.
• As of July 2024, the literature database includes more than 1,100 entries, of which over 600 are peer-reviewed publications.
• Based on post-market experience of over 250,000 individual applications (as of January 2023), no unexpected device-related serious adverse events have been reported.

Published evidence and post-market data collectively describe CytoSorb® Therapy as well characterized from a safety perspective when used according to its intended purpose.

A number of studies on various CytoSorb® indications (e.g., cardiac surgery, sepsis, pancreatitis) are being conducted in collaboration with recognized scientific partners.

For an overview of published literature, please visit our database: cytosorbents.com/lit-db.

Further information is also available at www.clinicaltrials.gov (search term: CytoSorb) or cytosorbents.com/studies-registry.

Additional clinical studies are in preparation.

Information on reimbursement in Germany can be found here, for all other countries please contact us.

This can occur under certain conditions and may indicate that

• the cause of cytokine release persists (e.g., insufficient focal control), or
• a new trigger for systemic inflammation has appeared.

CytoSorb® Therapy itself does not induce a specific rebound effect.

The use of IL-6 as a surrogate marker for clinical monitoring is possible; however, the absolute baseline value does not necessarily reflect disease severity. The course of IL-6 levels should be interpreted in the context of the overall clinical picture.

Treatment is possible with both heparin and citrate. If CytoSorb is used as a stand-alone therapy, only heparin may be used for anticoagulation. Citrate is contraindicated in this setup.

In general, no special protocol adjustments are required for CytoSorb. The instructions by the device manufacturer must be followed.

In case of systemic anticoagulation with heparin the following applies:

As a matter of principle, anticoagulation must be effective before starting treatment. This means to first increase the aPTT to the target value and only then start the extracorporeal procedure.

Recommended target values when using heparin:

• aPTT: 60–80 sec (activated partial thromboplastin time. This value corresponds to 2–3 times the baseline value).
• ACT: 160–210 sec (activated clotting time standard value 100-130 sec)
• AT III: 75–120% (antithrombin III)
• Caution: HIT (heparin-induced thrombocytopenia).

These target values are controlled according to the respective standards of the critical care unit. The decision regarding dosage and target values is always the responsibility of the attending physician.

For regional anticoagulation with citrate, the following applies:

• Initial dose, blood flow rate, control and adjustment of calcium and citrate is according to protocol.
• Citrate and calcium are to be added at the usual points of the extracorporeal circulation.
• Control of ionized calcium (CRRT circuit and patient) a few minutes after the start of treatment and at regular intervals of 8 – 12 hours is recommended.

The decision regarding dosage and target levels is always the responsibility of the treating physician.

Yes, this is possible with a CRRT system.

• CytoSorb is a single use product.
• Interruption of therapy e.g.: in CRRT systems is possible as long as the adsorber remains part of the extracorporeal circuit. Return the blood from the extracorporeal circuit to the patient as prescribed by the CRRT circuit manufacturer. Allow the CRRT device to circulate even while no patient is connected. Local hygiene guidelines and specifications of the machine manufacturer apply.
• Removal of the CytoSorb cartridge (e.g. from the Heart Lung Machine) and reinstallation into another system is not permitted for hygienic reasons.

The recommended blood flow rate is 150 to 700 mL/min. The minimum blood flow rate is 100 mL/min. Please refer to the instructions for use by the manufacturer of the primary circuit.

The same access is needed to basically operate an extracorporeal circuit. Accordingly, the access chosen must be suitable for this. CytoSorb is always integrated into an extracorporeal circuit. It is up to the physician to decide where suitable access is to be established for this purpose.

• The safety and effectiveness of CytoSorb Therapy is not dependent on the puncture site.
• The requirements of the extracorporeal circulation are
  dependent on the type of
  catheterization.
• Ideally, vascular access should allow the extracorporeal circulation to maximize blood flow.

CytoSorb can be combined with standard hemoperfusion devices, CRRT devices, ECMO/ECLS systems or heart-lung machines commonly already available in hospitals.

• Preparation and set-up require only a few minutes.
• For this purpose, the CytoSorb adsorber cartridge is safely and easily integrated into an existing extracorporeal circulation (ECC) system.
• CytoSorb can be used in alone hemoperfusion mode or in combination with dialysis filters.
• Standardized adapter kits for preparation and integration into different ECC systems are available.

All staff involved in CytoSorb Therapy must be trained by the manufacturer or qualified distributors in accordance with legal requirements regarding set-up, operation, and safety.

• CytoSorb has a particularly beneficial effect in most cases if therapy can be started as early as possible.
• Please reconsider the use in patients who are already in therapy-refractory shock for several days.

Duration of any CytoSorb treatment depends on the patient’s clinical improvement:

• CytoSorb treatment should be continued until stabilization:
  – No need or sharply decreasing catecholamine doses.
  – Reversal of fluid balance.
  – Normalization of lactate levels.
• – Improvement in impaired organ function:
  – Significant reduction in ventilatory support.
  – Improvement in liver function.
• Deterioration of the condition after cessation of CytoSorb treatment may indicate the need to resume CytoSorb Therapy (inadequate focal control or “second hit”).
• A patient-specific decision must be made as to how long to treat with CytoSorb.

Evaluation of the therapeutic success is primarily based on the clinical course.

Signs of therapy success can be, for example:
• Stabilization in hemodynamics
– Decrease in vasopressor requirements (or no further dose increases necessary).
– Decrease in fluid requirements.
– No further increase in lactate levels.

• Decrease in Interleukin-6 levels (if measured) and other inflammation/infection parameters (leukocytes, procalcitonin (PCT), C-Reactive Protein):
– When assessing PCT progression, note that PCT is partially removed directly by CytoSorb.
Accordingly, an increase in PCT during ongoing CytoSorb Therapy should be critically evaluated.

• Stabilization in other organ functions:
– No further deterioration in liver function (synthesis and detoxification).
– No increase in respiratory support necessary.
– Improvement of the coagulation situation.

The timing of CytoSorb® Therapy should be determined by the treating physician based on the patient’s clinical condition and institutional protocols. Clinical experience indicates that earlier initiation may be beneficial in cases of severe systemic inflammation, whereas benefit may be limited in late-stage, therapy-refractory shock.
 
Therapy should be continued until sufficient stabilization is achieved as assessed by parameters such as decreasing vasopressor needs, improved fluid balance, and normalization of lactate levels.

• Use of CytoSorb is indicated in the presence of excessive cytokine and/or bilirubin and/or myoglobin levels in the blood. CytoSorb is also indicated for intraoperative removal of the P2Y12 inhibitor ticagrelor and the factor Xa inhibitor rivaroxaban during cardiopulmonary bypass.

CytoSorb is currently used regularly primarily in two main indications:

• Therapy-refractory septic and vasoplegic shock
• Cardiac surgery intra- and postoperatively

CytoSorb has also been used successfully in hyperinflammatory conditions of a non-infectious origin. A number of case series and case reports on the initial clinical use in some of the areas listed below have been presented or published:

• Polytrauma and rhabdomyolysis
• Severe burns
• Severe acute pancreatitis
• Various types of liver failure
• Severe cardiogenic shock
• Complications of cardiac surgery
• Necrotizing fasciitis

Systemic hyperinflammation associated with ECMO therapy.

• The instructions for use (IFU) of a medical device, like those of a drug, are part of the approval documents which are reviewed by the notified body during CE approval and comprise the intended purpose, indication, type of use and safety instructions. Accordingly, these specifications are binding for “on-label use”, i.e. use in accordance with the approval.
• In the case of so-called “off-label use”, physicians can also use a medical device for other indications within its specifications as defined in the IFU and individual risk-benefit considerations. The treating physician assumes liability for the indication.
• Use of a medical device outside its specification – e.g. blood flow rate < 100 mL/min or > 700 mL/min during CytoSorb Therapy – is not permitted.
• Introductions and other sources of information such as Quick Setup Guides map the specifications of the IFU.

• From a hygienic point of view, the adsorber should be used as soon as possible after priming. Basically, the adsorber should be handled according to hygienic guidelines, similar to prepared infusion solutions or extracorporeal circulation systems ready for use.
• When handled hygienically, CytoSorb with the adapters is similar to the extracorporeal system itself. Identical materials are used from the material side.
• Data on hygiene beyond the maximum 24 h specified in the IFU are not available.
• The adsorber should be changed after a maximum of 24 hours to ensure sufficient capacity for adsorption. It may make sense to change the adsorber earlier if the adsorber becomes saturated during therapy in severe cases (e.g.: an increasing need for vasopressors again, …).
• In the current version of the CytoSorb Therapy booklet “Indications & Practical Aspects” it is recommended: “Treatment duration and indication for adsorber exchange depend on the clinical course. The maximum treatment time per adsorber is 24h.”

The shelf life is 3 years.

CytoSorb can be disposed of together with potentially infectious waste, such as dialysis filters and infusion systems.

• Local hygiene guidelines apply.
• Bacterial colonization of the cartridge contents is not a concern, even with septic patients.
• CytoSorb does not contain any toxic ingredients that would prevent disposal with other standard infectious waste.

The adsorber should be stored in its outer packaging, at an ambient temperature of +1 – 40 °C (34 – 104 °F). The adsorber should be stored upright so that gas bubbles, which can arise e.g. due to temperature fluctuations, migrate upwards to the outlet.

CytoSorb is CE-certified and can be used in all countries where this is the basis for use or local registration.

Please check availability and our representative in your country cytosorbents.com/distributors.

No. CytoSorb is an adsorber technology in which substances selectively bind physico-chemically to the adsorbent material (hydrophobic molecules with a molecular weight of up to approximately 60 kDa).

Adsorber:

• CytoSorb is a “blood in – blood out” product (whole-blood adsorber). There is no secondary circulation with albumin, no dialysate, no ultrafiltrate.
• Hydrophobic substances with a molecular weight of up to approx. 60 kDa are adsorbed onto the surface within the porous structure of the polymer beads.

Hemofilter/Dialyzer:

• Water-soluble substances are filtered out of the blood.
• Dialyzers are based on the principles of diffusion and convection.
• Blood components interact with a dialyzing solution through a semipermeable membrane.
• High cut-off membranes have higher thresholds for the elimination of substances. In addition to the desired substances, however, useful molecules such as albumin can also be removed in the process.

No. CytoSorb does not remove endotoxin, which is primarily involved in gram-negative sepsis.

• In contrast to endotoxin adsorbers, CytoSorb can be used for gram-positive bacterial sepsis and other systemic infections (viruses, fungi, parasites) as well.
• In addition to cytokines, exotoxins such as diphtheria toxin, alpha hemolysin, Clostridium perfringens toxin or Shiga toxin can also be effectively removed from the circulation using CytoSorb.
• In addition, CytoSorb can be used for all non-infectious causes of systemic hyperinflammation syndrome (e.g. polytrauma, burn injuries, inhalation trauma, pancreatitis).

Systemic inflammation can lead to circulating cytokines and mediators affecting organs distant from the initial site of injury or infection.

Current scientific understanding suggests that:
• Removal of cytokines and mediators from blood by hemoadsorption may contribute to temporary reduction of their circulating levels.
• Lower mediator levels have been associated in clinical observations with hemodynamic stabilization and reduced vasopressor requirements.
• Stabilization of endothelial integrity and reduction of capillary leak have been discussed in the literature as potential secondary effects.
• These mechanisms are based on published experimental and clinical findings and should be interpreted as supporting hypotheses rather than proven therapeutic effects.

Yes. CytoSorb can generally remove hydrophobic substances with a molecular weight of up to approx. 60 kDa. Due to the concentration-dependent removal, substances at high concentrations are removed more effectively than those at low concentrations are. This autoregulation protects against uncontrolled removal of endogenous substances and helps to maintain the physiological immune response.

• The spectrum of removable substances includes both pro- and anti-inflammatory mediators with elevated plasma levels. Physiologically important plasma components such as albumin are removed – as shown in studies –, but only in clinically irrelevant quantities.
• CytoSorb Therapy is intended to reduce the excessive immune response. Inflammatory mediators are reduced, and thereby modulation of the immune system is achieved.
• As described in the literature, high concentrations of both pro- and anti-inflammatory cytokines are associated with high mortality.

CytoSorb is the only whole-blood adsorber which is explicitly CE approved for the removal of specific substance groups. To achieve this objective, the CytoSorb adsorber is quickly and easily integrated into an extracorporeal circuit.

• Along with cytokines, other inflammatory mediators are also removed.
• Harmful substances such as free hemoglobin, myoglobin, bilirubin and bile acids, bioactive lipids, light chains of antibodies, toxic metabolites, bacterial exotoxins (toxins such as shiga, alpha-hemolysin, gas gangrene, diphtheria) and other toxins can be removed by the CytoSorb adsorber.

CytoSorb is indicated intraoperatively during surgical procedures involving cardiopulmonary bypass for the removal of the P2Y12 inhibitor ticagrelor and/or the factor Xa inhibitor rivaroxaban.