Thread by @nephrosapien

📢 Tweetorial on sepsis -endotoxin- cytokine cascade

👉Pathogen invasion in body

👉Pathogen expresses certain molecular patterns or
endotoxins called pathogen-associated molecular patterns (PAMPs)

👉
PAMPs are recognized by toll-like receptors expressed by
neutrophils

👉 Activation of innate immunity and leukocytes

👉Release of cytokines - pro +
anti-inflammatory(interleukins 1, 6, 8, 10 &
tumor necrosis factor)

👉 Dysregulated host
response to infection - organ failures

👉 Immunoparalysis, reinfection,
hospital-acquired infections

Futher in the thread , extracorporeal therapies targeted at each level of sepsis cascade would be discussed 👇

nejm.org/doi/full/10.10…

ncbi.nlm.nih.gov/pmc/articles/P…

1 - Removal of the pathogen

👉 Seraph 100 Microbind ( Bacteria + Virus )
👉Hemopurifier ( Virus )
👉FcMBL ( Virus )

🌟Seraph-100 Microbind hemoperfusion device- initially used in COVID 19 ,now been explored for bacterial sepsis.

🌟 Polythene beads coated with heparin
1. Mimics as natural cell surface binding the microbe
2. Anticoagulant, reduces hepcidin expression and iron availability

👉 Seraph 100 Microbind hemoperfusion device -mechanism binding the microbes

2 - Endotoxin removal

Hemoperfusion devices available

🌟 Toraymixin ( Polymyxin B hemoperfusion cartridge)

🌟 Alteco LPS absorber device

Polymyxin B cartridge trials-

EUPHAS - mortality and organ score improvement
ABDOMIX , EUPHRATES - no improvement

3 - Removal of activated leucocytes

Selective Cytapheretic Devices ( SCD)

SCD + regional citrate anticoagulation- Change the activity of the bound leukocytes
due to the inhibition of neutrophils by ionized hypocalcemia in
the filter.

SCD use in patients with sepsis & AKI 🌟SCD was not found to be superior to
CRRT alone.

🌟But the subset of patients in whom post filter ionized hypocalcemia of 0.4 mmol/L was maintained ( with use of RCA) , a significant reduction
was observed in the 60-day mortality

4 - Removal of cytokines

Options available
👉Cytosorb
👉 HA -330
👉 Hemofeel
👉CPFA (Coupled Plasma Filtration Adsorption )

CytoSorb - made of polystyrene
divinylbenzene copolymer beads.
🌟Surface area - 45000 m2
🌟Molecular cutoff size of 60 kDa
🌟 Cytokines
,myoglobin, bilirubin, bile acids, PAMPs, and DAMPs
🌟Stand-alone therapy or with HD or CRRT

HA-330/380 , Hemofeel work on similar mechanism.

CPFA - contains a plasma filter+ a resin sorbent cartridge+high-flux dialyzer for convection.

After plasma seperation, cytokines in the plasma is adsorbed through a sorbent cartridge and
the plasma free of cytokines is redirected to the dialyzer for renal
replacement therapy

🌟Advantages of CPFA -
improved biocompatibility , less hemolysis, improved cytokine
clearance and combined cytokine removal with convective RRT.

👉10-hour session, 5 consecutive days

👉Small observational studies showed improved
hemodynamics without survival benefits

5. Removal of Endotoxin + Cytokine both

👉 Oxiris CRRT hemofilter

👉Plasma Exchange

Polyacrylonitrile copolymer on AN69 membrane ( Methylcellulose + Acrylonitrile ) - Negatively charged - removes Cytokines 🌟

Polyethyleneimine polymers - Positively charged - removes Endotoxins 🌟

Heparin grafted🌟

Cytokine + Endotoxin removal+ convective/diffusive clearance

In summary, multiple extracorporeal therapy options are available for use in sepsis patients.

ncbi.nlm.nih.gov/pmc/articles/P…

How do I choose when and which membrane to use for managing such patients ?

Images Source-
Dr Valentine Lobo ( KEMH, Pune )

"Pathogen Reduction via Hemoperfusion: Latest Data & Clinical Experience"

AKI CRRT conference, Jan 2023, Hyderabad

#AKI #CriticalCare #Sepsis