Global decision support for COVID-19 patients
Potential criteria for considering CytoSorb in critically ill COVID-19 patients**
** Experiences showed that the use of CytoSorb can help the body to fight the harmful effects of COVID-19, if one or more of the following criteria is met:
- Pronounced vasoplegia (NE > 0.3 µg/kg/min, lactate ↑ ) without response to standard therapy (start of CytoSorb within the first 6 to maximum 24 hours)
- Moderate ARDS
- AKI III with start of CVVH (CRRT)
- H-Score suggesting diagnosis of secondary HLH
Basic prerequisites for the use of CytoSorb therapy
- CytoSorb is to be employed as an adjunctive therapy to reduce effects caused by a cytokine storm, not as a primary therapy
removing the virus. Due to its concentration dependency CytoSorb does not completely eliminate inflammatory mediators from the body but rebalances the immune system to more physiologic levels.
- CytoSorb can be integrated in many extracorporeal blood circuit: standard clinical renal replacement therapy (CRRT), continuous dialysis and hemofiltration.
Alternatively, use in stand-alone hemoperfusion is possible.
- Treatment duration and indication for exchange of adsorber depends on the clinical course.
It is approved for a maximum treatment time of 24 hours.
- Usual contraindications for extracorporeal blood circuits apply.
- Installation must never be into the main-stream of an ECMO circuit, pressure or flow monitoring of CytoSorb line is recommended.
- Recommended blood flow rate 150-700 ml/min with a minimal flow of 100ml/min. Ideal flow rates using CRRT with systemic heparin anticoagulation were shown to be 200-250 ml/min.
- Higher flow rates generally result in higher adsorption efficacy.
Anticoagulation for CytoSorb therapy
- Clinical experience has shown that critically-ill patients with COVID-19 may be significantly hypercoagulable.
This is supported by a recent publication on COVID-19 patients showing elevated D-Dimer levels in the critically ill.
Standard dosing regimens for therapeutic anticoagulation during CRRT (see e.g. Dickie et al. Critical Care, 2015, 19:376),
however, seem to be still sufficient. Close monitoring of anticoagulation is recommended.
- Therapeutic anticoagulation for CytoSorb is possible with heparin and citrate (if an additional hemofilter is present in the circuit) and must be fully effective at the start of treatment. When using heparin, PTT targets should be at the high end (i.e. PTT 80 sec). Protocol for regional citrate anticoagulation has to be followed.
- Clinical experience of clotting has found to be less of an issue with femoral vascular access, probably due to the generally higher possible flow rates.
- Generally, any decision on regimen, dosage, target values and monitoring intervals is the responsibility of the treating physician.
Follow up / Change of adsorber
- After the start of the CytoSorb therapy, the first adsorber should be preferably replaced after 12 hours.
- Thereafter, the adsorber should be changed every 12-24 hours depending on the clinical course
(e.g. degree of hemodynamic instability, pulmonary dysfunction).
Termination of the therapy
- CytoSorb therapy should be re-evaluated after 2-3 days in cases of primarily respiratory problems.
- In cases of profound vasoplegia as the leading clinical problem, CytoSorb therapy should be continued (with new
adsorbers every 12-24 hrs.) until shock reversal and reduction of vasopressor need is down to <10% of baseline need.
Recommendations general treatment
Recommendations from ESICM / SSC
- In adults with COVID-19 and shock, we suggest using dynamic parameters skin temperature, capillary refilling time, and/or serum lactate measurement over static parameters in order to assess fluid responsiveness (weak recommendation, low quality evidence).
- For the acute resuscitation of adults with COVID-19 and shock
– We suggest using a conservative over a liberal fluid strategy (weak recommendation, very low quality evidence).
– We recommend using crystalloids over colloids (strong recommendation, moderate quality evidence).
– We suggest using buffered/balanced crystalloids over unbalanced crystalloids (weak recommendation, moderate quality evidence).
- For adults with COVID-19 and shock
– We suggest using norepinephrine as the first-line vasoactive agent, over other agents (weak recommendation, low quality evidence).
– We suggest adding vasopressin as a second-line agent, over titrating norepinephrine dose, if target mean arterial pressure (MAP) cannot be achieved by norepinephrine alone (weak recommendation, moderate quality evidence).
– We suggest titrating vasoactive agents to target a MAP of 60-65 mmHg, rather than higher MAP targets (weak recommendation, low quality evidence).
- For adults with COVID-19 and shock with evidence of cardiac dysfunction and persistent hypoperfusion despite fluid resuscitation and norepinephrine, we suggest adding dobutamine, over increasing norepinephrine dose (weak recommendation, very low quality evidence).
Alhazzani et al, Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19)
© European Society of Intensive Care Medicine and the Society of Critical Care Medicine 2020
ARDS Berlin definition
ARDS Definition Task Force, JAMA, June 20, 2012, Vol 307, No.23
Ventilation and ECMO therapy
Recommendations from ELSO
Extracorporeal Life Support Organization COVID-19
Interim Guidelines – A consensus document from an international group of interdisciplinary ECMO providers
Downloaded on April 22nd 2020. A link to the latest version of this document can be found at ELSO.org
Renal replacement therapy
Latest recommendations of the Brescia Renal Covid Task Force (Italy) for the treatment of patients on dialysis and kidney transplantation in the course of COVID-19 infection:
Patients with AKI stage III should receive CVVH.
- Defined as a 3-fold increase in creatinine levels from baseline or creatinine ≥4.0 mg/dl or defined based on amount of diuresis: diuresis <0.3 ml/kg/h for ≥24 h or anuria for ≥12 h) hospitalized in ICU
- Method: CVVH pre- and post-dilution with a prescribed dose >25 ml/kg/h (to obtain an administered dose ≥25 ml/kg/h).
– First choice: regional citrate anticoagulation (RCA).
– Second choice: systemic heparinization with unfractionated heparin (UFH).
– Third choice: treatment with no anticoagulants.
– NOTE: most COVID-19-infected patients requiring intensive care management show altered liver function values secondary to drug-induced hepatotoxicity as well as due to possible liver involvement. This is associated with an increased risk for citrate accumulation.
Diagnosis of secondary HLH
H-Score > 169 points
- 93% sensitive for HLH
- 86% specific for HLH
Mehta P et al., COVID-19: consider cytokine storm syndromes and immunosuppression, Lancet 2020; epub
anti-cytokine storm therapy
Recommendations from China
The recently published manual for prevention and treatment of COVID-19 reads as follows: Critical cases are classified into
early, middle and late stages according to the oxygenation index and respiratory system compliance.
- Early stage: 100 mmHg without organ failure except the lung. The patient has a great chance of recovery through active antiviral,
anti-cytokine storm therapy and supportive treatment.
Recommendations from Italy I
The latest recommendations of the Brescia Renal Covid Task Force (Italy) for the treatment of patients on dialysis and kidney transplantation in the course of COVID-19 infection are as follows:
- Patients with AKI stage III should receive CVVH.
- CytoSorb therapy is recommended for 48 hours (with change of adsorber after 24 hours) in patients for which
tocilizumab (IL-6 receptor blocker) is not indicated or not available
Recommendations from Italy II
In patients who are planned to receive Tocilizumab but haven‘t been given it at the time of CVVH start, CytoSorb therapy should be continued for 24 to 48 hrs. after the beginning of the Tocilizumab treatment.*
* Replace CytoSorb adsorber after every 24 hrs. of use with a new cartridge.
Recommendations from Panama
CytoSorb therapy should be considered if one or more of the following aspects occur:
- Deep vasoplegia with elevated lactate levels and high need for vasopressors (e.g. NE> 0.3 μg / kg / min) that do not respond to standard therapy. Therapy with CytoSorb should begin within the first 6, maximum 24 hours after the start of standard therapy.
- Very severe respiratory distress syndrome, requiring high ventilatory support
- Indication for use of ECMO / ECLS therapy
Reports suggest that COVID-19 is associated with severe disease, that requires intensive care in approximately 5% of proven infections. The virus can result in a dysregulated immune response and this cytokine storm seems to be associated with disease severity, as it can lead to capillary leak syndrome, progressive lung injury, respiratory failure and acute respiratory distress syndrome (ARDS).
In addition to ARDS, further complications in the critically ill include shock, acute cardiac injury and AKI. This is in line with what is known from other viral infections like influenza and previous coronavirus infections (SARS, MERS), as well as with the general fact that infectious and non-infectious triggers can result in a cytokine storm, progressing to vasoplegic shock and finally multi organ dysfunction syndrome.
CytoSorb is a CE-marked extracorporeal cytokine adsorber, designed to broadly reduce inflammatory mediators in the blood that could otherwise lead to uncontrolled systemic inflammation, organ failure, and death in many life-threatening illnesses. CytoSorb has been used safely in more than 143,000 treatments worldwide, primarily in the treatment of systemic hyperinflammation in a wide variety of life-threatening conditions.
Ronco C et al. Coronavirus Epidemic and Extracorporeal Therapies in Intensive Care: si vis pacem para bellum, Blood Purif,
published online March 13,2020
This decision guidance is for health care professionals outside the USA only. It is non-binding and cannot replace the therapy decisions of the treating physician, who is in all cases responsible for the development and implementation of an adequate diagnostic and therapeutic plan for each individual patient.
It is a “best practice” collection, based on the current level of knowledge and expert opinion.
The clinical and preclinical data and results obtained with the CytoSorb adsorber are not transferable to other products. CytoSorb should only be administered by personnel who have been properly trained in administration of extracorporeal therapies.
CytoSorb is not available for commercial sale in USA. CytoSorb and CytoSorbents are trademarks of the CytoSorbents Corporation, USA.
© Copyright 2020, CytoSorbents Europe GmbH. All rights reserved. B2117R01ENG2020