📢 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
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