CYTOKINE REMOVAL

Cytokine removal is an extracorporeal blood-purification approach intended to reduce excessive concentrations of circulating cytokines, which are signalling proteins involved in the body's immune and inflammatory responses. It is not a single drug or molecule; instead, it refers to techniques that use specialised adsorption cartridges or membranes to remove selected substances from blood as it passes through an external circuit. Some devices use porous adsorbent materials that bind inflammatory mediators, while other blood-purification systems may combine cytokine adsorption with renal support or target different substances, such as endotoxins. Cytokine removal has been investigated and used in selected critical-care situations involving severe systemic inflammation, including some cases of septic shock and other conditions associated with an exaggerated inflammatory response. However, reducing cytokine concentrations does not necessarily improve survival or prevent organ failure, and clinical evidence remains mixed. The procedure is considered an adjunct to appropriate treatment, not a replacement for established care such as infection control, antimicrobial therapy when indicated, fluid and circulatory support, and organ support. The choice to use cytokine removal depends on the patient's condition, the specific device's authorised indications, available evidence, and specialist clinical judgement.

Extracorporeal cytokine removal developed from blood-purification technologies used to adsorb selected substances directly from circulating blood. Devices differ in their materials, adsorption mechanisms, target substances, and intended clinical settings. CytoSorb, for example, uses porous polymer beads to adsorb certain cytokines and other molecules; other systems use modified haemofilter membranes or adsorbents designed to target different inflammatory substances. Regulatory authorisation applies to individual devices and specific intended uses, rather than to cytokine removal as one universally approved treatment. CytoSorb received European CE marking and has had authorised uses in selected settings, with indications varying by jurisdiction and product labelling. In the United States, its regulatory status differs from its European status; the device has been used under a past emergency-use authorisation for certain critically ill adults with COVID-19, but it is not generally FDA-approved or cleared for routine cytokine removal. Clinical research includes studies of haemoadsorption in septic shock and cardiac surgery, alongside observational studies and systematic reviews. Results have shown that inflammatory-marker levels can decrease in some settings, but evidence of consistent improvement in major clinical outcomes remains insufficient to support routine use in all patients with sepsis or systemic inflammation.

Cytokine removal may be considered as an adjunctive intervention in selected critically ill patients with severe systemic inflammation, including some patients with septic shock, depending on the device's authorised indications and local clinical protocols. It has also been investigated in conditions such as cytokine release syndrome, severe inflammatory responses associated with extracorporeal life support, and selected cardiac-surgery settings. The evidence and regulatory status differ substantially across these applications. Some devices primarily target cytokines, while others are designed to adsorb endotoxins or combine adsorption with continuous renal replacement therapy. These approaches are not interchangeable. Cytokine removal should not delay established treatments such as prompt antimicrobial therapy and source control in sepsis. Routine use for all patients with sepsis or elevated inflammatory markers is not supported by consistent evidence of improved patient-centred outcomes. The decision to use a device should be based on individual clinical assessment, its approved or authorised purpose, and specialist critical-care input.

Cytokine removal is performed using an extracorporeal circuit, in which blood passes through a specialised adsorption cartridge or membrane and is returned to the patient. Depending on the device and clinical setting, the system may be incorporated into a dedicated haemoperfusion circuit, continuous renal replacement therapy, or another compatible extracorporeal support system. There is no universal drug dose or standard treatment schedule because cytokine removal is a procedure rather than a medicine. Cartridge selection, blood-flow rate, session duration, replacement frequency, and the total course of treatment must follow the specific device's instructions for use and the treating team's protocol. Some systems are used for several hours at a time, while treatment duration and repeat sessions vary according to the technology and patient's response. Anticoagulation may be required to maintain circuit patency, depending on the treatment system and patient factors. Clinical status, circuit function, haemodynamic response, laboratory findings, and possible unintended removal of medications should be assessed throughout treatment.

Potential adverse effects depend on the device, extracorporeal circuit, anticoagulation strategy, and the patient's underlying critical illness. These may include low blood pressure or haemodynamic instability, bleeding associated with anticoagulation, reduced platelet counts, clotting or interruption of the circuit, and complications related to vascular access. Changes in body temperature or other treatment-related disturbances may also occur in critically ill patients. Adsorption cartridges can remove some medicines and other circulating substances in addition to the intended inflammatory mediators, potentially affecting drug exposure. The frequency and severity of these effects vary between devices and clinical settings, and the underlying illness may make it difficult to distinguish treatment-related effects from disease complications. Close monitoring by trained critical-care personnel is essential, with management guided by the patient's clinical condition and the device-specific safety instructions.

Serious potential complications include major bleeding, clinically significant thrombocytopenia, circuit clotting, vascular-access complications, and haemodynamic deterioration. Unintended adsorption of antibiotics, anticoagulants, or other essential medicines may reduce their circulating concentrations and compromise treatment if not recognised. Broad-spectrum adsorption may also remove beneficial inflammatory or other plasma mediators, and the clinical consequences of this are not fully established. The procedure should not be assumed to prevent organ failure or reduce mortality simply because inflammatory-marker levels decrease. Patients with active bleeding, severe coagulation abnormalities, haemodynamic instability, or other relevant risks require careful assessment before treatment. Device-specific contraindications and warnings must be reviewed before use. Treatment may need to be paused or stopped if serious adverse effects occur, the extracorporeal circuit becomes unsafe, or the treating team determines that the potential risks outweigh the expected benefits.

Before treatment, clinicians should assess the underlying diagnosis, haemodynamic status, vascular access, blood counts, coagulation profile, renal and hepatic function, and the need for concurrent organ support. Medication review is particularly important because some adsorption systems can remove drugs from blood, including certain antimicrobials and anticoagulants. Drug exposure may be affected by the device's adsorption characteristics, treatment duration, blood concentrations, and the timing of medication administration. Therapeutic drug monitoring should be considered when available and clinically appropriate, especially for medicines where inadequate exposure could compromise treatment. Anticoagulation should be individualised according to circuit requirements, bleeding risk, and local protocols. There are no universal vaccine-related precautions specific to all cytokine-removal technologies; considerations depend on the patient's underlying illness, immune status, and any concurrent therapies. Device compatibility, sterile handling, circuit integrity, and the manufacturer's instructions must be followed. Treatment should be used only in an appropriately equipped clinical setting with staff trained in extracorporeal therapies.

Confirm the clinical objective before initiating treatment and distinguish cytokine adsorption from devices intended primarily for endotoxin removal or renal replacement therapy. Review the specific device's regulatory status, authorised indications, contraindications, and instructions for use in the relevant jurisdiction. Establish baseline clinical and laboratory measurements, including blood counts and coagulation parameters where appropriate, and document the patient's haemodynamic status and organ-support requirements. Coordinate treatment timing with antimicrobial administration and review whether important medicines may be adsorbed by the selected device. Where therapeutic drug monitoring is available, use it to help guide dosing for medicines at risk of reduced exposure. Monitor vascular access, circuit pressures, anticoagulation, bleeding, platelet counts, and clinical response throughout treatment. Interpret changes in cytokine concentrations or other biomarkers alongside organ function and the patient's overall progress; biomarker reduction alone does not establish clinical benefit. Discuss the uncertainty of outcome evidence with the multidisciplinary critical-care team and reassess the need for continued treatment at regular intervals.