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.

To support adequate elimination performance, the recommended blood flow rate is 150 to 700 mL/min. The minimum blood flow rate is 100 mL/min. Lower flow rates may be associated with increased risk of clotting. Please refer to the instructions for use by the manufacturer of the primary circuit.

CytoSorb needs a vascular access that allows operation of 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.
• For standalone use of CytoSorb, (Hemoperfusion/Hemoadsorption setup) avascular access as for a CRRT treatments is required.

CytoSorb Therapy can be applied in combination with standard hemoperfusion devices, CRRT systems, ECMO/ECLS circuits, or heart–lung machines that are already in clinical use.

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

All personnel involved in the use of CytoSorb Therapy must be appropriately trained by the manufacturer or authorized distributors in accordance with applicable legal and institutional requirements regarding set-up, operation, and safety.

• The timing of CytoSorb Therapy should be determined based on the patient’s clinical condition and overall treatment strategy.
• In contrast, the potential benefit of therapy in patients with long-standing, therapy-refractory shock is considered limited and should be carefully evaluated by the treating physician.
• The final decision regarding indication, timing, and duration always lies with the responsible clinician, based on individual patient factors and institutional protocols.

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.

The assessment of treatment response should be based primarily on the overall clinical course of the patient.
Indicators of clinical stabilization may include:
 
Hemodynamic stability

• Decrease in vasopressor requirements (or no further dose escalation required).
• Reduction in fluid requirements.
• Stabilization or no further increase in lactate levels.

Reduction in inflammatory markers

• Decrease in interleukin-6 (if measured) and other inflammatory/infection parameters such as leukocytes, procalcitonin (PCT), or C-reactive protein (CRP).
• When interpreting PCT levels, note that PCT can be partially adsorbed by CytoSorb; therefore, an increase during ongoing therapy should be evaluated cautiously.

Stabilization of organ function

• No further deterioration in liver function (synthesis or detoxification capacity).
• No increase in respiratory support requirements.
• Improvement in coagulation parameters.

Clinical judgment should always guide interpretation, and no single parameter alone should be used to determine therapeutic success.

The timing of CytoSorb Therapy should be determined based on the patient’s clinical condition and overall treatment concept.
 
Clinical experience and published data suggest that the initiation of hemoadsorption may be considered during the early phase of septic shock or systemic hyperinflammation (early SIRS), when inflammatory processes are still potentially reversible.
 
The potential benefit of therapy may be limited in patients with advanced or irreversible organ failure.
CytoSorbents provides a non-evidence-based “best-practice” guide for clinical decision support.

 
General indicators that may support consideration of CytoSorb Therapy include:

• Clinical signs of systemic hyperinflammation
• Insufficient response to standard medical therapy
• Evidence of capillary leak (e.g., marked positive fluid balance)
• Elevated interleukin-6 (IL-6) levels (e.g., > 500 pg/mL) may support, but are not required for, treatment consideration

In all cases, the patient’s overall clinical picture should remain decisive when determining indication, timing, and assessment of therapy response.

CE-marked intended purpose:
 
CytoSorb Therapy is intended for the reduction of excessive levels of cytokines and/or bilirubin and/or myoglobin from blood or plasma. In addition, the device is indicated for the intraoperative removal of the P2Y12 inhibitor ticagrelor and the factor Xa inhibitor rivaroxaban during cardiopulmonary bypass.

 
Regular clinical application areas include:

• Management of therapy-refractory septic or vasoplegic shock
• Cardiac surgery, intra- and postoperative use

Additional clinical experience:
 
Published case series and reports have described the use of CytoSorb in various hyper-inflammatory and toxin-related conditions, such as:

• Polytrauma and rhabdomyolysis
• Severe burns
• Acute pancreatitis
• Different forms of liver failure
• Severe cardiogenic shock
• Complications following cardiac surgery
• Necrotizing fasciitis
• Systemic hyperinflammation associated with ECMO therapy

Decisions regarding use should always be made by the treating physician, considering the patient’s overall condition and institutional protocols.

The Instructions for Use (IFU) of a medical device are an integral part of the CE-marked approval documentation.
 

They are reviewed by the Notified Body during the conformity assessment process and define the intended purpose, indications, conditions of use, and safety instructions of the device.
 

Accordingly, these specifications are binding for use within the approved indication (“on-label use”).
 

Physicians may, under their own professional responsibility, decide to use a medical device outside its approved indication (“off-label use”) when doing so within the technical specifications of the IFU and based on an individual risk–benefit assessment.
 

In such cases, the treating physician assumes full liability for the medical decision and its outcomes.
 

Use of a medical device outside its technical specifications — for example, a blood flow rate below 100 mL/min or above 700 mL/min during CytoSorb Therapy — is not permitted.
 

Supplementary materials such as Quick Setup Guides or training documents reflect and summarize the content of the official IFU, but do not replace it as the legally binding reference.

From a hygienic perspective, the CytoSorb adsorber should be used as soon as possible after priming.

 

It should be handled according to standard hygienic principles, similar to prepared infusion solutions or extracorporeal circulation systems that are ready for clinical use.
 

When handled under appropriate hygienic conditions, CytoSorb with adapters is comparable to other components of the extracorporeal circuit in terms of material composition and hygiene requirements.
 

Data beyond the maximum treatment duration of 24 hours, as specified in the Instructions for Use (IFU), are not available.

 

Therefore, the adsorber should be replaced after a maximum of 24 hours to maintain performance and compliance with validated use conditions.
 

The CytoSorb Therapy Booklet “Indications & Practical Aspects” specifies that “treatment duration and the indication for adsorber exchange depend on the clinical course; the maximum treatment time per adsorber is 24 hours.”

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.
• 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).

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).

The development of secondary organ dysfunction in systemic inflammation is largely driven by circulating cytokines and inflammatory mediators that can affect tissues distant from the initial site of injury or infection.
 

Current scientific understanding suggests that:

• Removal of cytokines and mediators from blood through hemoadsorption may contribute to a temporary reduction of their circulating concentrations.
• Lower mediator levels have been associated in clinical observations with improved hemodynamic stability and reduced vasopressor demand, although these effects depend on individual patient conditions.
• Stabilization of endothelial integrity and mitigation of capillary leak have been discussed in the literature as potential secondary effects of cytokine reduction.
• By influencing mediator levels, inflammation-related tissue stress may be modulated, which could play a role in supporting organ function during systemic inflammation.
• Experimental studies have described a possible re-balancing of immune cell signaling and chemokine gradients that may help redirect the immune response toward local sites of inflammation.

These mechanisms are based on published experimental and clinical findings and should be interpreted as supporting hypotheses rather than proven therapeutic effects. Clinical decision-making should always rely on the overall patient condition and established treatment protocols.

Yes. CytoSorb is designed to adsorb hydrophobic molecules with a molecular weight of up to approximately 60 kDa. The removal of substances occurs in a concentration-dependent manner, meaning that higher plasma concentrations can lead to proportionally greater adsorption. At lower concentrations, removal efficiency decreases, which contributes to maintaining the physiological balance of circulating mediators.

• The adsorption spectrum includes both pro- and anti-inflammatory mediators that may reach elevated plasma levels during systemic inflammation.
• Published data have shown that physiologically important plasma components such as albumin may also bind to the polymer surface, but typically only in small, clinically non-relevant amounts.

 

• The intended purpose of CytoSorb Therapy is to reduce excessive levels of inflammatory mediators from blood or plasma as part of extracorporeal blood purification, thereby contributing to modulation of dysregulated immune responses.
• Elevated concentrations of both pro- and anti-inflammatory cytokines have been reported in the literature to correlate with adverse outcomes and increased mortality in critical illness.

CytoSorb is a CE-marked whole-blood adsorber designed for the selective reduction of specific substance groups from blood or plasma. CytoSorb is not yet approved or cleared in the United States or Canada for any indication outside an Emergency Use Authorization (EUA) by the US FDA.

• It can be integrated quickly and easily into an existing extracorporeal circulation (ECC), such as CRRT, ECMO, or cardiopulmonary bypass systems.
• The device is designed to adsorb hydrophobic molecules with molecular weights of up to approximately 60 kDa, including various cytokines and inflammatory mediators that can accumulate during systemic inflammation.
• In addition, adsorption of other substances such as free hemoglobin, myoglobin, bilirubin, bile acids, light chains, and certain bacterial toxins has been described in published experimental and clinical studies.

CytoSorb is indicated for intraoperative use during surgical procedures involving cardiopulmonary bypass to remove the P2Y12 inhibitor ticagrelor and/or the factor Xa inhibitor rivaroxaban from blood.