cytokine storm

1. Role of Extracorporeal
Hemoadsorption in Critically ill
Patients

2. Outline
 CytoSorb
 CytoSorb features
 CytoSorb in Septic Shock
 CytoSorb in other potential indication
 CytoSorb in drug removal

3. Background
 Sepsis and septic shock account for high
morbidity and mortality worldwide in general
and particularly in Southeast Asian countries
 Mortality in India due to sepsis – 213 per
100,000 people
Blue: Mortality
rate due to
sepsis;
Yellow:
Prevalence of
ICU units in
various
Southeast Asian
countries
J Clin Med 2022 Jun 23;11(13):3635

4. In dysregulated host response:
removing cytokines may help to regain control
Organ
dysfunction
+
dysregulated host
response
Cytokine Storm – the body becomes its own enemy
JAMA. 2016 February 23; 315(8): 801–810

5. Pathophysiology of Sepsis
5
Nat Rev Immunol. 2013;13:862-74.
Pro-
inflammation
Anti-
inflammation

6. Immunomodulation is Crucial
https://ars.els-cdn.com/content/image/1-s2.0-S0163725820300048-gr1.jpg

7. Extracorporeal Therapy
for Immunomodulation

8. Rationale of Extracorporeal Therapies

9. ADVANCES IN SEPSIS Vol 4 No 1 2004
MAP improved and the NE requirement
decreased significantly after 10 h of
treatment compared with baseline.
The rate of lipopolysaccharide-induced TNF
production by monocytes improved dramatically,
with a significant improvement in the
phagocytosis capacity.
Hemodynamic and Biological effects of CPFA

10. Ankawi et al. Critical Care (2018) 22:262

11. J. Clin. Med. 2022, 11, 3635.

12. Ideal time for Extracorporeal Therapies
Clinically Unstable

13. Extracorporeal Therapies- Types
J Clin Med 2022 Jun 23;11(13):3635
J Clin Med 2022 Jun 23;11(13):3635

14. Cytokine Hemadsorption Therapy (CytoSorb)

15. CytoSorb
Extracorporeal blood purification therapy designed to reduce
excessive levels of inflammatory mediators such as cytokines, or
“cytokine storm”, from blood.
Used over 200,000 times worldwide in more than 1,000 clinical
departments.
 The CytoSorb adsorber is a standard whole blood perfusion cartridge
that can be used with conventional hemodialysis machines,
hemoperfusion machines, heart-lung machines, and as stand-alone
therapy with many other kinds of blood pumps.
Reference : https://cytosorb-therapy.com/

16. Adsorbs – What and What not?
Removes
Cytokines
Myoglobin
Bilirubin
Bile acids
Plasma free hemoglobin
Rivaroxaban
Ticagrelor
DAMPs & PAMPs
Doesn't remove
 Albumin
 Coagulation factors and
Immunoglobulins
 Physiologic mediators
Only very low loss of platelets
Reference :literature.cytosorb-therapy.com

17. Outline
 CytoSorb
 CytoSorb features
 CytoSorb in Septic Shock
 CytoSorb in other potential indication
 CytoSorb in drug removal

18. The CytoSorb adsorber
• The CytoSorb adsorber is composed of highly biocompatible porous polymer
beads with numerous pores on the surface.
• Each bead, roughly the size of a grain of salt, acts like a tiny sponge to remove
substances from whole blood based on the process of adsorption.
• The relevant surface for adsorption, located in the inner of the beads, is
>45,000 m2.

19. CytoSorb – Adsorber
Adsorption works on the
Membrane Filter
Dialysis works on the principles of the
diffusion of solutes and ultrafiltration of fluid
across a semi-permeable membrane.
principles of the
attraction and binding
CytoSorb Bead Ø 0,45mm
Semipermeable
Membrane
Dialysate
Full Blood
Dialyzable Substances
e.g. Potassium
Non-Dialyzable Substances
e.g. IL6, IL10, TNF-α
Albumin =
Transport device for
lipophilic substances
Filtration Vs Adsorption

20. Concentration Dependant Adsorption
 High concentration of substance -> high removal efficiency
 Low concentration of substance -> low/no removal efficiency
 No complete removal / overtreatment possible
 Restoration of physiological (non overshooting) immune response

21. No elimination of Immuno-Globulins:
IgG:
IgM:
IgE:
IgA:
150KD
971KD
198KD
Monomer: 160 KD
Dimer:
IgD:
385KD
172KD
CytoSorb removes broad spectrum of cytokines through concentration gradient adsorption
Size Selectivity Approach

22. Hemoperfusion
CRRT
CPB ECMO
Pre Filter
Post Filter
Extracorporeal
Circuit
• Blood flow through
CytoSorb 100-700
ml/min
• Anticoagulation as usual
Intermittent
RRT
CytoSorb SET UP Ease of Setup

23. Conditions
 Septic/vasoplesic shock
 COVID-19
 Cardiac surgery
(intra-/postoperative)
 Emergency cardiac surgery
(intraoperative)
 Liver failure
 Rhabdomyolysis
Removal of
o Inflammatory mediators
o Inflammatory mediators
o Inflammatory mediators
o Ticagrelor/Rivaroxaban
o Bilirubin (bile acids)
o Myoglobin
CytoSorb therapy’s fields of indication

24. Outline
 CytoSorb
 CytoSorb features
 CytoSorb in Septic Shock
 CytoSorb in other potential indication
 CytoSorb in drug removal

25. CytoSorb – Adjunctive therapy in Sepsis
PAMPs: Pathogen-associated molecular patterns
DAMPs: Damage-associated molecular patterns
MODS: Multiple organ dysfunction syndrome
IPPV: Intermittent positive-pressure ventilation
 If standard therapy based on guidelines fails
to give sufficient hemodynamic stabilization
within the first 6 to 24 hrs, CytoSorb should
be considered as an adjunctive therapy

26. Potential
Indications in
the ICU
 Refractory septic shock
 Vasoplegic shock (postoperative, with ECMO
therapy)
 Toxic shock syndrome
 Necrotizing fasciitis
 Meningococcal sepsis
 Hemophagocytic lymphohistiocytosis (HLH)
 Pancreatitis
 Burns
 Trauma
 Liver failure
 Rhabdomyolysis
 Dengue
https://cytosorb-therapy.com/wp-content/uploads/2018/07/Therapiekarte-ICU-Englisch_B1053R01EN2018_lr.pdf

27. CYTOSORB in SEPTIC SHOCK
from Austria
 Retrospective single-center
study
 42 septic shock patients with
CRRT and CytoSorb therapy
Compared to 42 matched
control (out of all 2936
patients)
 Matching via generalized
propensity-score and
Mahalanobis distance
matching method (“genetic
matching”)
 1 adsorber/pat for 24 hrs. each
 Start CS < 24 hrs
Biomedicines 2020, 8, 539

28. CYTOSORB in SEPTIC SHOCK
from Austria
While remaining fairly constant in the controls, the catecholamines decreased to 0.26 (0.11–0.40)
μg/kg/min within 24 h after initiation of CytoSorb therapy.
Friesecke et al 2017
Shock reversal Biomedicines 2020, 8, 539

29. CYTOSORB in SEPTIC SHOCK
from Austria
In-hospital as well as 28-day mortality significantly reduced
Biomedicines 2020, 8, 539

30. CytoSorb – Septic shock - Indian experience

31. CytoSorb – Septic shock Indian experience

32. 40 patients survived

33. Early Therapy – Better Treatment Outcomes
It was observed that in the survivor group (n = 40), 70% (n = 28) of patients received CytoSorb® therapy within 48 h of
ICU admission as compared to 72% of non survivors (n = 43/60) in whom CytoSorb® was initiated after 48 h after ICU
admission.

34. Vasopressor Needs Decreased
The study showed a marked reduction in vasopressor therapy in the survivor group over the non-survivor group
indicating recovery in hemodynamic condition

35. World J Crit Care Med 2021 January 9; 10(1): 22-34
CytoSorb – Septic shock Indian experience

36. Outline
 CytoSorb
 CytoSorb features
 CytoSorb in Septic Shock
 CytoSorb in other potential indication
 CytoSorb in drug removal

37. CytoSorb in other potential indication
 Blood purification with Cytosorb® during high-flux dialysis led to a significant reduction of myoglobin in patients with
severe rhabdomyolysis.
 The effect might be obscured by sustained rhabdomyolysis, which was seen in patients with rising CK during treatment.
 Prospective clinical trials would be useful in investigating its benefits in avoiding permanent kidney damage.
Scharf C, et al. Crit Care. 2021 Jan 28;25(1):41..

38. CytoSorb in other potential indication
“The finding of significant bilirubin removal observed in our study could have substantial impact in designing and executing
further studies on the effects of hemadsorption in liver dysfunction, which are certainly warranted”
Ocskay K et al. HemoadsoJ Clin Med. 2021 Nov 5;10(21):5182.

39. CytoSorb in other potential indication
After an 18 hour adsorber time, patient LFTs were improved
 SGOT-8,003(IU/L),
 SGPT-3,573 (IU/L);
 Total bilirubin-4.8 mg/dL with direct bilirubin-2.4
I J M D AT 2 0 2 0 ; 3 : e 2 3 3

40. CytoSorb in other potential indication
 Liver function tests also started decreasing and normalized over 5 days.
 Similarly, significant improvements in the platelet counts were also achieved.
I J M D AT 2 0 2 0 ; 3 : e 2 3 3

41. Outline
 CytoSorb
 CytoSorb features
 CytoSorb in Septic Shock
 CytoSorb in other potential indication
 CytoSorb in drug removal

42. CytoSorb – Removal of P2Y12 inhibitor-ticagrelor intraoperatively
during cardiopulmonary bypass
Reference : Cytosorb Adsorption During Emergency Cardiac Operations in Patients at High Risk of Bleeding

43. CytoSorb – Removal of P2Y12 inhibitor-ticagrelor
intraoperatively during cardiopulmonary bypass

44.  No significant removal of albumin, no removal of coagulation factors and immunoglobulins
 No complete removal of physiologic mediators (restoration of physiologic response)
 Highly biocompatible, porous polymer beads
 No activation of coagulation and complement system
 Only very low loss of platelets
CytoSorb - Favorable safety profile

45. Start Early with CytoSorb Therapy

46. Latest Updates

47. ADQI CONSENSUS (“Acute Disease Quality Initiative”)
Initiation of EBP in sepsis might be considered for immunomodulatory support in patients who meet
explicit and timely clinical and/or biological criteria, such as high concentrations of damage-associated
molecular patterns and pathogen-associated molecular patterns, as well as other targets of systemic
inflammation
Nat Rev Nephrol. 2023 Feb 23.

48. ADQI Consensus (“Acute Disease Quality Initiative”)
EBP for immunomodulatory support can be considered in patients with sepsis as a stand-alone
treatment if kidney support is not required
Stand-alone
Nat Rev Nephrol. 2023 Feb 23
https://cytosorb-therapy.com/wp-content/uploads/2020/04/QuickSetupGuide-Hemoperfusion-ENG-Web.pdf.

49. Patient selection tool- CytoScore

51. Thank you!