The Experience of Blood Puri fi cation in Sepsis by Coupled Plasma Filtration Adsorption in Thailand

Sepsis is an infl ammation syndrome which is caused by severe infection. This severe infl ammation is characterized by vasodilatation, leukocyte accumulation and increased microvascular permeability. The pathophysiology of sepsis is believed to be due to the dysregulation of the infl ammatory response. The human body generates and releases a massive uncontrolled amount of proinfl ammatory mediators into the blood stream which causes cellular and tissue injury. This injury leads to the development of multiple organ dysfunction syndromes (MODS), and causes life-threatening conditions.


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epsis is an infl ammation syndrome which is caused by severe infection.This severe infl ammation is characterized by vasodilatation, leukocyte accumulation and increased microvascular permeability.The pathophysiology of sepsis is believed to be due to the dysregulation of the infl ammatory response.The human body generates and releases a massive uncontrolled amount of proinfl ammatory mediators into the blood stream which causes cellular and tissue injury.This injury leads to the development of multiple organ dysfunction syndromes (MODS), and causes life-threatening conditions.
The normal host response to infection involves the activation of circulating and fi xed phagocytic cells, the generation of proinfl ammatory and anti-infl ammatory mediators.When the body releases massive cytokines beyond the infection site, sepsis occurs.These mediators cause fever, hypotension, acute phase protein response, induction of interleukin 6, coagulation activation, increased endothelial permeability and so on.These large quantities of proinfl ammatory mediators will cause cellular damage and lead to multiple organ failure.
[7][8] A study from Nakada TA, et al. 9 in 2008 showed a decrease of interleukin 6 and procalcitonin correlated with survival during sepsis.The innovative idea to reduce proinfl ammatory cytokines led to the development of the extracorporeal blood purifi cation technique.Extracorporeal blood purifi cation can be performed in different ways.The treatment restores the normal balance of the targeted substances within the patient's body.
Coupled plasma fi ltration adsorption (CPFA) is a therapeutic extracorporeal blood purifi cation tool combining 3 techniques namely plasma fi ltration, adsorption and hemofi ltration.CPFA is suitable for illnesses involving renal failure together with large molecules, especially if these have a molecular weight close to that of albumin such as infl ammatory substances found in sepsis and in liver failure.The CPFA technique has been performed in animal experimentation and in clinical settings worldwide since 1998.Some CPFA studies have been reviewed (Table 1).
Thanakornyothin N, et, al.The principles of a mechanized CPFA technique CPFA is designed to remove some specifi c large substances by plasma perfusion in-line with continuous veno-venous hemofi ltration (CVVH) which replaces kidney failure.The CPFA machine (blood purifi cation HF 440, Infomed, Switzerland) contains 5 blood pumps and 3 fi lters (Figure 1A-B).
There are 3 steps to the technique.First, blood is passed through a plasma fi lter.The plasma is fi ltered and sent to  a second fi lter (a sorbent cartridge).This sorbent cartridge is important because it absorbs large molecules, in particular interleukin 1β, interleukin 6, interleukin 8, interleukin 10, macrophage infl ammatory proteins (MIP-α, MIP-β), tumor necrosis factor (TNF-α), endotoxin, peptidoglycan, bradykinin, angiotensin, leptin, retinol binding protein, prostanoids, complement factors, coagulation components, nitric acid, oxygen radicals, and bilirubin.The obtained plasma returns to the blood, and together passes through the third fi lter (hemofi lter).The hemofi lter placed on the blood fl ow allows hemofi ltration to be performed which compensates for the kidney failure often associated with the main disease (Figure 1C).

study showed the improvement of mean interval pressure (MAP). The decrease of norepinephrine dosage use, the increase in oxygenation, and the reduction of interleukin 6 and prolactin in 72 hrs after the 3 rd CPFA treatment
In late 2012, at the Bangkok Hospital Medical Center (BMC), a 60-year-old man with a past medical history of diabetes and end stage renal disease on hemodialysis was admitted due to an infected diabetic foot.During hospitalization, he had an ischemic bowel requiring surgery.Later on, he developed sepsis and multiple organ dysfunction syndromes, including acute respiratory distress, hemodynamic instability, liver injury with high bilirubin levels, and bleeding disorders.His proinfl ammatory cytokines were very high especially interleukin 6, procalcitonin, and C-reactive protein.
A BMC medical team decided to perform blood purification by CPFA technique in order to reduce proinfl ammatory cytokines and bilirubin levels.However, he had abnormal coagulopathy so the team decided to use a citrate substrate for anticoagulation instead of heparin.After 3 sessions of 10 hours CPFA with 0.22l/kg/d of plasma purification, the level of interleukin 6, procalcitonin, C -reactive protein, and bilirubin had declined drastically (Table 2).
In Thailand, this was the fi rst case time a coupled plasma fi ltration adsorption treatment was used to reduce cytokines in sepsis.The cooperation between the Bangkok Hospital Medical Center and Infomed gave the team the required knowledge, learning experience, and the necessary additional tools to fi ght this life-threatening disease.

Figure 2 :
Figure 2:The innovative idea to reduce infl ammatory substances in sepsis by CPFA treatment.

Figure 1 :
Figure 1: Shows CPFA Machine (A-B) and the third fi lter (Hemofi lter) (C) A B C

Figure 3 :
Figure 3: This Turani F. study showed the improvement of mean interval pressure (MAP).The decrease of norepinephrine dosage use, the increase in oxygenation, and the reduction of interleukin 6 and prolactin in 72 hrs after the 3 rd CPFA treatment

Figure 4 :
Figure 4:Laboratory data shows a sharp decline of C-reaction protein (CRP) throughout the treatment time (from before the fi rst treatment to after the last treatment).19