Vishal Ramteke Profile picture
May 25, 2023 17 tweets 8 min read Read on X
📢 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 Image
👉 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 ImageImage
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… Image
1 - Removal of the pathogen

👉 Seraph 100 Microbind ( Bacteria + Virus )
👉Hemopurifier ( Virus )
👉FcMBL ( Virus ) ImageImage
🌟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 ImageImage
👉 Seraph 100 Microbind hemoperfusion device -mechanism binding the microbes Image
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 ImageImage
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. Image
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 Image
4 - Removal of cytokines

Options available
👉Cytosorb
👉 HA -330
👉 Hemofeel
👉CPFA (Coupled Plasma Filtration Adsorption ) ImageImageImageImage
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. Image
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 Image
🌟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 ImageImage
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 Image
In summary, multiple extracorporeal therapy options are available for use in sepsis patients.

ncbi.nlm.nih.gov/pmc/articles/P… Image
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 Image

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More from @nephrosapien

Oct 11, 2023
In ICU while managing critically ill patients with AKI and -
🔅Septic shock with multiple pressors
🔅Acute liver failure
🔅Cardiogenic shock
🔅Cerebral edema
we all have used the CRRT machines.

Ever wondered how their use started🤔 ???

📍Let's go back to the history of CRRT
Image
Image
🌟The early attempts of continuous hemofiltration were carried out in animals and humans in 1977-78

🌟LW Anderson reported its use in 2 anephric sheeps for 48 and 72 hours

pubmed.ncbi.nlm.nih.gov/715997/
🌟 But the first successful attempt of CAVH in human was done by Dr Peter Cramer in Goettingen, Germany, 1977 in a patient with AKI

🌟 His presentation about the modality in 1982 ASAIO meeting was the inspiration leading to use of CRRT in Intensive care.

pubmed.ncbi.nlm.nih.gov/7164248/
Image
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