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Q&A

The CytoSorb Therapy

CytoSorb is the first CE approved whole blood adsorber to remove a wide range of excessively elevated cytokines from the blood. For this purpose, the CytoSorb adsorber is quickly and easily integrated into an extracorporeal circuit.

  • In addition to cytokines, other inflammatory mediators, e.g. chemokines are also adsorbed.
  • Other substances such as free hemoglobin, myoglobin, bilirubin and bile acids, bioactive lipids, antibody light chains, toxins, bacterial enterotoxins (shigatoxin, alpha-hemolysin, gas gangrene toxin, diphtheria toxin) and other toxic metabolites can also be removed by the CytoSorb adsorber.

Yes. CytoSorb can generally remove hydrophobic substances with an average molecular weight of up to 55 kDa. Here, substances with high concentrations are more effectively removed than those at lower levels. This autoregulation protects against uncontrolled removal of endogenous substances.

  • The spectrum of removable substances includes both pro- and anti-inflammatory mediators with elevated plasma levels. Physiologically important plasma constituents such as albumin are only removed in clinically irrelevant quantities (less than 5%).
  • The goal of CytoSorb therapy is to reduce the excess immune response. Inflammatory mediators are reduced and this causes a modulation of the immune system.
  • As described in the literature, high concentrations of both pro-inflammatory and anti-inflammatory cytokines are associated with high mortality.

The key to preventing and treating secondary organ failure is to prevent or minimize the impact of the cytokine storm on primarily non-diseased tissues (remote organs). On the basis of current knowledge, it can be assumed that:

  • Reduction of cytokines and mediators in the plasma occurs through removal and decreased new production
  • The hemodynamics (macro- and micro-circulation) are improved, thereby reducing the catecholamine requirements. A positive effect on capillary leak syndrome can be achieved by reducing cytokine levels (integrity of glycocalyx).
  • Lower levels of cytokines and inflammatory mediators favorably influences the cause of inflammatory tissue damage and any resulting (multiple) organ dysfunction. As a result, the otherwise very high morbidity and mortality can be favorably influenced.
  • The immune response is remodulated and the immune cells redirected to the inflammatory focus: CytoSorb restores the chemokine gradient responsible for the migration of leukocytes to the focus (infection or tissue damage). As a result, the focus of inflammation can be unmasked and the previously systemic immune response can be better directed towards the local focus.

No. CytoSorb does not remove endotoxins, which only occur in gram-negative sepsis.

  • Unlike endotoxin adsorbers, CytoSorb can also be used in Gram-positive bacterial sepsis and other systemic infections (viral, fungal, parasitic).
  • In addition to cytokines, enterotoxins, e.g. Diphtheria toxin, alpha-hemolysin, Clostridium perfringens toxin or Shiga toxin can be effectively removed from the circulation using CytoSorb.
  • In addition, CytoSorb can be used in all non-infectious causes of a systemic hyperinflammatory syndrome (eg: polytrauma, burn injuries, inhalation trauma, pancreatitis).

No. CytoSorb is an adsorbent technology in which substances selectively bind to the adsorbent material (hydrophobic molecules with a molecular weight of up to approx. 55kDa).

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 up to about 55kDa are adsorbed within the porous structure of the polymer beads.

Dialysis Filter:

  • Dialysers are based on the principles of diffusion and convection.
  • Blood components interact with a dialysis fluid through a semi-permeable membrane.
  • Only water-soluble and very small substances (up to 10kD) are selectively removed from the blood.
  • High cut-off membranes have higher thresholds for the elimination of substances. In addition to the desired substances, useful substances such as albumin may also be removed.

The CytoSorb Therapy is the only CE approved procedure for the removal of cytokines. It can be used in all countries where CE approval is required or is basis for registration.

The adsorbers should, if possible, be stored in the original carton at an ambient temperature of 1-40 ° C.

Fields of Application

The use of CytoSorb is approved for all indications in which elevated cytokine levels occur (intended use). This is especially the case in patients with severe hyperinflammation.

CytoSorb is regularly used in two main indications:

  • Septic shock and severe sepsis
  • Severe hyperinflammation in cardiac surgery patients

CytoSorb has also been used successfully in hyperinflammatory conditions from other causes. A number of case reports of early clinical use in some of the areas listed below have been presented or published:

  • Polytrauma and rhabdomyolysis
  • Serious burn injury
  • Severe acute pancreatitis
  • Various types of liver failure
  • Severe cardiogenic shock
  • Complications from cardiac surgery
  • Necrotizing fasciitis
  • Use with ECMO

Previous clinical experience and data suggest that:

  • Treatment should start in the early stages of severe sepsis or hyperinflammation, in which organ dysfunction is still early and therefore reversible.
  • CytoSorb use in already existing irreversible organ failure is less promising.

CytoSorbents provides a “best practice” guide (not evidence-based) for patient selection. Basically, “It is better to prevent organ failure than to treat it.”

General indicators for CytoSorb therapy include:

  • Patient is a non-responder in standard medical care.
  • Clinical picture of hyperinflammation.
  • Onset of shock: norepinephrine> 0.3 μg / kg / min or rapidly increasing requirements within the last 24 hours.
  • Sign of capillary leak – for example, positive fluid balance.
  • Development of at least one other organ dysfunction: – kidney, respiratory, liver, coagulation, neurological deficits.
  • A high interleukin (IL)-6 values (e.g.,> 500 pg / ml) may support the treatment decision, but low values do not exclude treatment.

In case of doubt, the clinical picture of the patient should always be decisive in the indication and effectiveness assessment of CytoSorb therapy.

The assessment of the therapeutic success depends primarily on the clinical course.

Signs of therapy success may for e.g. be:

  • Stabilization in hemodynamics
    – decrease in vasopressor demand (or slowing of dose increase)
    – decrease in fluid requirements.
    – No further increase in lactate levels.
  • Decrease in IL-6 (if measured) and other inflammatory / infection parameters (Leucocytes, Procalcitonin PCT, C-Reactive Protein):
    – When assessing the PCT history, note that PCT is partially removed directly by CytoSorb.

An increase in PCT under ongoing CytoSorb therapy should therefore be evaluated critically.

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

The duration of treatment with CytoSorb depends on the clinical improvement of the patient:

  • CytoSorb treatment should be continued until the patients has stabilized:
    – No need or repadily decreasing catecholamine doses.
    – Reversal of fluid balance.
    – Normalization in the lactate levels.
  • Improvement of impaired organ functions:
    – Significant reduction in ventilation support.
    – return of spontaneous diuresis.
    – improvement in liver function, e.g. Increase in albumin levels and decrease in alkaline phosphatase levels.
  • A deterioration of the condition after the completion of CytoSorb treatment (inadequate recovery or “second hit”) may indicate the need to restart CytoSorb therapy.
  • It must be decided on a patient by patient basis how many days CytoSorb is used.
  • CytoSorb has in most cases a particularly positive effect if therapy can be started as early as possible (i.e. within the first 24 hours after standard therapy has proved inadequate).
  • Please reconsider the use in patients who are already in therapy-refractory shock for several days.

Indication

CytoSorb can be combined with standard continuous renal replacement therapy (CRRT) devices, extracorporeal life support (ECLS) machines or heart lung machines (HLM), available in most hospitals.

  • Preparation and assembly takes only a few minutes.
  • For this purpose, the CytoSorb adsorber cartridge is safely and easily integrated into an existing extracorporeal circulation (ECC).
  • CytoSorb can be used as a stand-alone therapy or in combination with dialysis filters.
  • No special additional equipment is needed.
  • Standardized adapter kits for integration into different ECC systems are available.
  • As far as possible, all employees involved in the CytoSorb therapy should be trained in terms of set-up, operation and safety by qualified personnel.

CytoSorb is always integrated into an extracorporeal circulation. It is up to the doctor to decide where appropriate access is required.

  • The safety and effectiveness of CytoSorb therapy does not depend on the catheter puncture site
  • Any decisive regarding the type of catheterization are for the requirements of the extracorporeal circulation

The blood flow rate should be between 150 and 700 ml/min. Please observe the instructions for use of the primary circuit manufacturer.

Yes, it is possible with a CRRT system.

  • As prescribed by the manufacturer of the CRRT circuit, return the blood from the extracorporeal circuit back to the patient.
  • Let the CRRT device circulate as long as no patient is connected. Local hygiene guidelines and specifications of the machine manufacturer apply
  • Removal of the CytoSorb cartridge (for example from the HLM) and replacement in another system is not permitted for reasons of hygiene.

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

  • The local hygiene guidelines apply.
  • Bacterial colonization of the cartridge contents is not possible when used in septic patients.
  • CytoSorb contains no toxic ingredients that would prevent disposal with standard contaminated waste.
The shelf life is 3 years when stored as recommended

Reimbursement

For Information regarding reimbursement in Germany, please click here. For all other countries please contact us.

Therapy management

Treatment with anticoagulation under CytoSorb therapy does not deviate from the usual strategy for CRRT or HLM treatment.

  • Treatment is possible with both heparin and citrate.
  • An aPTT of 60-80 sec in intensive care patients or an ACT of 160 – 210 sec when used on the HLM is sufficient for CytoSorb
  • The decision on the dosage and the clotting values ​​required is the responsibility of the attending physician.
  • If CytoSorb is used as a stand-alone therapy, only heparin should be used for anticoagulation. Citrate is contraindicated in this situation.
  • In the case of HIT II, ​​Danaparoid (Orgaran) can also be used to replace heparin.
  • In the case of citrate anticoagulation, no special adaptations needs to be made. The citrate and calcium additions are made at the usual sites of the extracorporeal circuit.

It is possible to use IL-6 as a surrogate marker for the follow-up assessment. However, the absolute level of the baseline does not necessarily reflect the severity of the disease. The course of the IL-6 value should always be considered in the context of the clinical picture of the patient.

  • In case of doubt, the clinical picture of the patient should always be decisive in the indication and assessment of the effectiveness of the CytoSorb therapy.
  • Cytokine levels can only be reasonably assessed during the course of the disease, but not on the basis of a single determination.
  • After IL-6 blood sampling, the sample must be cooled immediately for measurement and transported to the laboratory – if measurement is delayed the sample must be frozen
  • IL-6 has a very short half-life (in the minutes only range).
  • The duration of CytoSorb therapy should be based on the clinical development of the patient, not just individual parameters. Significantly decreasing markers of infection and decreasing catecholamine demand, possibility of a negative fluid balance, decreasing ventilation invasiveness and other factors characterize an improvement in the clinical picture.

Yes, this can happen under certain circumstances and be:

  • an indication that the cause of cytokine release persists (e.g., insufficient focus control)
  • or a new trigger for systemic hyperinflammation has occurred.

The CytoSorb therapy itself does not trigger a specific rebound effect.

Studies

A number of studies in different CytoSorb indications (e.g cardiac surgery, sepsis, pancreatitis) are currently underway in cooperation with well-known scientific partners.

  • For additional information see below: – A number of studies in different CytoSorb indications (e.g cardiac surgery, sepsis, pancreatitis) are currently underway in cooperation with well-known scientific partners.
  • Further information also under:
    www.clincal-trials.gov – search term: CytoSorb
    cytosorb-therapy.com/the-studies
  • Further clinical studies are in preparation
  • In the US, the FDA approved a pilot study that was launched at the end of 2015 to prepare for the US approval of CytoSorb in cardiac surgery. This study has now been published and a second study is now well under way.

CytoSorbents is a highly medically-scientifically oriented company. Our team includes physicians and biologists who are intensively involved in clinical research.

  • If you have an idea for a clinical study please contact us.
  • In order to understand more about the effects, benefits and safety of CytoSorb therapy independent of studies, an international CytoSorb registry was established and established in collaboration with the study center of the University Hospital Jena, Germany headed by Prof. Frank Brunkhorst.
  • We invite you to register and participate in the project by sharing your clinical application experience with CytoSorb.
  • More information is available at www.cytosorb-registry.org

Extensive preclinical studies were performed (see our Cytosorb literature database for more details and links to articles).

  • In all clinical publications to date, safety of the procedure has been reported.
  • According to the currently more than 88,000 individual applications in various patient groups, CytoSorb shows a very favorable safety profile. It can be well assumed that CytoSorb therapy is a safe and well tolerated treatment.