Plasmapheresis in the treatment of acute pancreatitis

Despite of improvements in surgical methods of treatment using the latest anti-protease drugs, treatment of acute pancreatitis is still a difficult problem and is accompanied by a relatively high mortality. This largely depends on what is the disease is at the presence of severe endotoxemia on the basis of sharp increase of proteolytic enzymes and the resulting on increase in the content of some toxic average molecular weight substances, activation of lipid peroxidation with the suppression of the antioxidant defense system. In this first liver takes the brunt of the enzymes in the blood washed out of the pancreas, to a certain point, retaining the ability to inactivate them, and then comes defeat and its functions of detoxification, which defines the transition to the decompensated phase of endotoxemia, increases the level of transferases, amylase, phenol, ammonia, fatty acids and other toxic metabolites. Can join respiratory distress syndrome, which is a toxic pulmonary edema with the development of severe parenchymatous respiratory failure.

Moreover, there is a series of vicious circles when toxic pulmonary edema and hypoxemia stimulate hypoxic disorders of membrane permeability; kidney disorders contributes additional fluid retention (edema stimulated) and toxins (toxemia increases) with the suppression of liver detoxification function as it deepens toxemia; toxic cardiomyopathy worsens organ microcirculation disturbances; toxic encephalopathyalso leads to brain disorders, up to delirious states. And just such "summation" lesions in multiple organ failure determines an extremely high mortality rate - up to 80% [1]. This syndrome of multiple organ failure reflects biological disaster, biological view of suicide that occurs when destructive pancreatitis.

One of the characteristic manifestations of pancreatic necrosis is systemic inflammatory response and sepsis. Septic shock is characterized by persistent hypotension not corrected by adequate completion of CBV, and multiorgan failure accompanied by damage to the functions of vital organs when homeostasis can not be restored without intensive therapeutic interventions [2]. It should be noted that the very development of acute pancreatitis often occurs on the background of the original immunodeficiency that developed as a result of recently transferred other diseases (even the common respiratory viral infections), adverse environmental or social factors, chronic intoxication (alcohol, drugs, etc.). Proof of this is often observed at the initial stage of the disease leukopenia and lymphopenia.

Further is developing a chain of mutually aggravated events. Immune system mobilizes all its reserves to combat infectious and other agents that are not unlimited, and eventually it comes on exhaustion. Increase endotoxemia acts overwhelmingly all components of cellular and humoral immunity leading to an even more profound immunosuppression, which may be described as "immune distress syndrome."

Therefore, in such cases the most pathogenetic justified the use of exchange plasmapheresis when with removed plasma derived products not only toxic, but also all the components of the immune system incompetent. In this case all the available active antibodies already are associated with pathological antigens in the form of inactive immune complexes. All available opsonins and complement already been used in previous reactions phagocytosis, making it impossible to capture pathogens even quite normal phagocytes. Replacement removed plasma of fresh frozen donor plasma allows you to quickly restore the natural protective mechanisms, without which the most powerful super-wide spectrum antibiotics are powerless, and their hepato- or nephrotoxicity may exacerbate the patient's condition. After the massive plasma exchange occures faster turning point in course of diseases and reverses the development of organ disorders [3].

As mentioned above, many biologically active substances such as structural components of endogenous intoxication, possessing membrane-effect, violate the permeability of the vascular endothelium and contribute to toxic interstitial edema with the advent micro-thrombosis and microcirculatory disorders with malnutrition, tissue hypoxia and focal destructive processes. One of the most "weak" and fragile sites of the body are the mucous membranes of the gastrointestinal tract, where they begin to form so-called stressors ulcers. Such ulcers at up to 15-40% there are often formed in severe pancreatitis.

By the time oftheir formation(within 2-4 days of the critical state) phasehypercoagulablereplacedanticoagulationandlocaldestructionof the mucous membranesexposed vessels with their  erosion, which creates prerequisites for the emergenceof bleeding, which due tosystemicanticoagulationmay takeprofusecharacter withhigh (up to40-60%) mortality [2].
At the gastroscopy it revealed the surface pattern of multiple mucosal erosions. Sometimes it is possible to note the signs of the syndrome Mallory-Weiss – cracks gastric mucosa. The rest of the bowel can also attack autolysis massive rejection of the villi and the growth of intoxication.
In such cases also the most pathogenetic justified holding massive plasma exchange, when along with the removal of toxic products is carried out also the replacement of fresh frozen donor plasma with all the normal components of coagulations factors. There is the only way to break the vicious circles formed, do not give the possibility to eliminate manifestations of DIC. Within a few hours after plasma exchange can be observed a tendency to normalization of coagulation and bleeding stops. At the same time, should be resorted to plasma exchange without waiting for a complete picture of the unfolding of DIC with profuse bleeding. Such therapy should be preventive in nature and start at the first signs of impending complications – increased bleeding, identifying erosive changes of gastric mucosa and signs of coagulopathy, detected by laboratory study.

All thisjustifies the need forthe inclusionof efferent therapyat the earlieststages of the disease, as endotoxemiaviolationexacerbatesthe functionalstate of thepancreas, helps to increaselogoffenzymes, thus closing thevicious circle.Applicationof plasmapheresisin1-3rd dayof onsetallows almostrefuse to performearlylaparotomyin severe acutepancreatitis andsignificantlyreduce the frequencyof their performanceinan extremely serious conditionsof it [4, 5, 6, 7, 8]. Plasmapheresiscan significantly reducemortality inhemorrhagicformsfrom 70% to30%, with necrotic – from 49% to25%, andin all forms ofabortiveflowingnecrotizing pancreatitis–from 29% to7% [9]. Even in the contextof regional hospitaluseplasmapheresis in12patients withpancreatic necrosiswaspreventeddeath [10]. 
Plasma exchangeis also usefulin preparation for surgery, at the next dayafter surgery,and after eachextendedrevisionsorrelaparotomy[11]. Even moreeffective wasplasmapheresiswith simultaneousplasma adsorption[12].Moreover, insuch cases,methodsPhoto-hemotherapyandoxidative therapy(UFR and indirect electrochemicaloxidation ofblood)significantlypotentiated theeffectsof detoxification andefferent therapy[13, 14]. Proposedmethodsandhigh-volumeplasmapheresiswith removal of100%CPVwith replacementcrystalloid solutions(1.5 CCPV) and10% sodiumhydroethyl-starch (Pentastarch Infukol) to 0.5CPV [15]. It is noted thatthese patientstoleratedplasmapheresismuch easier thanhemofiltration[15].In addition,if afterplasmapheresiscontent of deadleukocytes invenous bloodwas reducedby an average of39.1%, the prolongedvenovenoushemofiltrationhad no significant effectontheir content[16].

There wasshown also the effect ofbiospecifichemosorptionatdestructive pancreatitis, especially with the useof specialantiproteasehemosorbents"Ovosorb" [17].

Acute pancreatitis isoften arisesat hyperlipidemia(hypertriglyceridemia) and in such casesplasmapheresisexertsa significanteffect oftreatment[18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28].The mostsignificant decreasein the blood levelsof triglycerides(from83.48to4.09mmol/L)was achieved by usingcascade plasmapheresis[29].Usedandselectivelipoproteinapheresis[30].Acute pancreatitiscan be caused bysystemic lupus erythematosusandhereplasmapheresisalsofinds its application[31].

Increasing frequency also primary autoimmune pancreatitis, which is often mistaken as a false inflammatory or neoplastic processes [32].

Among the best methods of plasmapheresis in the treatment of pancreatitis seems membrane plasmapheresis apparatus "Hemofeniks" Russian company "Trackpore Technology" (Moscow) with Plasmofilter "Rosa" by the same company. Small filling volume (70 ml) allows to perform plasmapheresis even at critical severe condition with unstable circulation, when blood pressure is maintained only through sympathomimetics [33]. In these cases,we can only speakaboutplasma exchangewith replacement of1.5-2.5litersof fresh frozenplasma donation. However, evenatincreased bleedingdrainageswith signsDICsyndrome, as well as the presence ofacutegastricerosions and ulcersare not an obstacleforplasmapheresis, because without systemic heparinizationusing as anticoagulantsodium citrate solutiononlythe risk of bleedingin a patientis minimal.

Easy and safetechnique, portable nature ofthe equipmentallow to perform membrane plasmapheresisonurgentindicationevenon the road inother hospitals.

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