Effectiveness of Extracorporeal Therapy in the Treatment of Patients with Severe Acute Pancreatitis

The research is devoted to the study of the effectiveness of extracorporeal therapy in the treatment of severe acute pancreatitis accompanied by endogenous intoxication. The work develops and substantiates the concept of a 'therapeutic window' within the 6–24-hour interval from disease onset, within which pathogenetically justified detoxification intervention is performed using therapeutic plasmapheresis and a detoxification transfusion operation. Special attention is given to the mechanisms of action of extracorporeal methods on the development of disseminated pancreatic necrosis, peripancreatitis, and multiple organ failure, as well as the evaluation of the impact of fractional gravity plasmapheresis on the levels of cytokines and mediators of inflammation. The aim of the work is to improve treatment outcomes through early extracorporeal detoxification intervention aimed at preventing fatal outcomes and the development of multiple organ failure.

In the 1960s, acute pancreatitis (AP) was an 'outsider' among acute surgical diseases of the abdominal organs (AO). Subsequently, the number of hospitalizations due to AP continued to increase, exceeding the growth rate of this indicator for other forms of 'acute abdomen.' Thus, at the turn of the third millennium, the number of hospitalizations due to acute pancreatitis in Saint Petersburg exceeded the corresponding indicator for acute appendicitis and took first place in the structure of hospitalizations of patients with the 'acute abdomen' syndrome (Bagnenko S.F. et al., 2004; 2005).

Similar trends were also noted in other cities of Russia, Ukraine, and Belarus (Anisimov A.A. et al., 2000; Galperin E.I. et al., 2000).

At the same time, by the mid-1990s, acute pancreatitis in Saint Petersburg had taken first place also in terms of mortality, surpassing acute appendicitis, acute cholecystitis, strangulated hernia, and perforative ulcer, taken together.

The 'pancreatological epidemic' in major cities of the Russian Federation, Ukraine, and Belarus requires a rational explanation.

Available data allow the well-founded assumption that the increase in the flow of hospitalized patients with a diagnosis of 'acute pancreatitis' is caused, first and foremost, by repeated hospitalizations of patients with mild forms of this disease and a significant number of patients suffering from relapses of pain in the upper abdomen against the backdrop of pronounced signs of alcoholism and chronic pancreatitis, accompanied by deformation of the ductal system of the pancreas (PD), confirmed by ultrasound examination (US) results. Hyperdiagnosis of acute pancreatitis at the prehospital stage and in emergency departments of hospitals; ignoring the diagnostic criteria of acute pancreatitis, consisting of no less than a fourfold increase in amylase activity and/or a twofold increase in the upper range of lipase activity in combination with a characteristic pain syndrome, the use of which identifies acute pancreatitis in only 3% of patients with various forms of 'acute abdomen' in other countries.

Thus, with a less strict approach to primary diagnosis and subsequent verification of the diagnosis of acute pancreatitis, the number of hospitalizations for this disease turns out to be substantially inflated, which occurs year after year in domestic hospitals, creating an illusion of an 'epidemic' of acute pancreatitis.

At the same time, acute pancreatitis, undoubtedly, is one of the least studied acute inflammatory diseases of the abdominal organs, accompanied by high mortality, severe complications, and significant socio-economic losses. It is this factor, and not the stunning increase in the number of hospitalizations, that determines the scientific and practical importance of the problem under consideration.

The relevance of the research is determined by the consideration of insufficiently studied issues of treatment of severe acute pancreatitis accompanied by endogenous intoxication (EI) — a multicomponent systemic inflammatory syndrome that often leads to a fatal outcome due to the development of multiple organ failure. To date, issues of treatment and prevention of destructive forms of acute pancreatitis remain insufficiently developed, primarily through the early preemptive application of a complex of extracorporeal methods of pathogenetic therapy. All of the above objectively testifies to the relevance and social significance of the acute pancreatitis problem, the need for further improvement of diagnosis and expansion of the arsenal of pathogenetically justified methods of intensive therapy.

Among patients hospitalized for various forms of 'acute abdomen,' acute pancreatitis most often leads to a severe course, early and late complications, and high mortality (Ermolov A.S. et al., 2000).

The issues of criterion-based assessment of the severity of GN, optimal choice of methods and tactics of treatment, prevention of shock, disseminated pancreatic necrosis, purulent complications (PC), and sepsis, which collectively determine the unquestionable significance of the chosen research topic, remain relevant.

Goal of the Research

To improve the results of treatment of severe acute pancreatitis through extracorporeal detoxification intervention within the first 6–24 hours from the onset of the disease, aimed at preventing the development of disseminated pancreatic necrosis, endotoxemia, multiple organ failure (MOF), and fatal outcomes.

Tasks of the Research

1. To develop a pathogenetically justified and effective methodology for urgent detoxification transfusion operation (DTO) combining forced rehydration, reduction of mediastinitis, restoration of diuresis, and extracorporeal 'interruption' in the enzymatic phase of development of destructive acute pancreatitis and peripancreatitis (PP).

2. To evaluate the effectiveness of performing a detoxification transfusion operation at various time points from the onset of the disease.

3. To study the effectiveness of fractional gravity therapeutic plasmapheresis (TPl) in the treatment and prevention of enzymatic peripancreatitis.

4. To assess the impact of the extracorporeal 'interruption' method on the overall results of treatment of severe acute pancreatitis.

Scientific Novelty

The work presents a new concept consisting of targeted manipulation of intravascular and interstitial fluid volumes, allowing not only to reduce mediastinitis but also to exert an effective effect on the pancreas parenchyma and peripancreatic adipose tissue in the initial phase of development of severe acute pancreatitis.

The effectiveness of the application of extracorporeal treatment methods that allow counteracting the mechanisms of progression of damage not only to the pancreas parenchyma but also to the retroperitoneal tissue (RT), saturated with enzymatic histotoxic exudate, has been demonstrated.

Practical Significance of the Work

The performance of fractional gravity therapeutic plasmapheresis in the enzymatic phase of severe acute pancreatitis made it possible to achieve a significant detoxification effect caused by the targeted creation of osmolality gradients in order to maximize the elimination of toxic substrates of intoxication and suppress the developing syndrome of systemic inflammatory response (SIRS), primarily through the reduction of the level of cytokines and other mediators of inflammation (Bone R.S., 1995).

As a result, a methodology for performing a detoxification transfusion operation within the first 6–24 hours from the onset of the disease has been developed, allowing the extracorporeal 'interruption' of destructive acute pancreatitis.

The application of the methodology makes it possible to refuse early surgical interventions and perform sanitizing interventions at time points coinciding with those recommended by the participants of the consensus conference in Atlanta in 1992.

The development of new treatment methods made it possible to reduce early and overall mortality in severe acute pancreatitis.

A comparative evaluation of the effectiveness of fractional centrifugal and continuous apparatus therapeutic plasmapheresis has been conducted.

Positions for Defense

1. The time interval from 6 to 24 hours from the onset of the disease, designated as the 'therapeutic window' (Murr M.M., 2002), provides the opportunity to carry out pathogenetically justified extracorporeal interventions aimed at the 'interruption' of the development of destructive acute pancreatitis.

2. The 'interruption' of severe acute pancreatitis in the enzymatic phase is achieved through a preemptive detoxification transfusion operation, at which therapeutic plasmapheresis should be performed as early as possible within the chronological limits of the 'open therapeutic window.'

3. The method of fractional centrifugal plasmapheresis allows reducing productive EI, primarily through the elimination of mediators of inflammation and cytokines: tumor necrosis factor (TNF), interleukin (IL)-1, and interleukin-2.

4. A high level of cytokines: tumor necrosis factor, interleukin-1, and interleukin-2 is a prognostically favorable factor for achieving the 'interruption' of acute pancreatitis through the course of extracorporeal therapy.

5. The level of interleukin-6 cytokine is prognostically not a favorable criterion for determining indications for performing sessions of therapeutic plasmapheresis with the aim of achieving the 'interruption' of acute pancreatitis.

6. Achieving the 'interruption' of acute pancreatitis is possible even with low cytokine activity at early stages of acute destructive pancreatitis.

7. Timely performed therapeutic plasmapheresis favorably affects the subsequent course of severe acute pancreatitis in the reactive phase of the disease, which manifests itself in a reduction in the frequency of development of infiltrate and purulent complications.

8. A detoxification transfusion operation based on therapeutic plasmapheresis allows performing anti-inflammatory action not only on the pancreas but also on peripancreatic adipose tissue ('interruption' of acute pancreatitis and reduction in the extent of peripancreatitis).

9. Widespread implementation of therapeutic plasmapheresis with timely initiation of treatment makes it possible to reduce early mortality in patients with severe acute pancreatitis to 3.12%, and late mortality — to 4.68%.

Author's Contribution

The author took direct part in the process of examination and treatment of 423 patients with severe acute pancreatitis, as well as performed statistical processing and analysis of the entire prospective (253 cases) and retrospective clinical material (170 observations from the archive).

Research results have been implemented in the practical activities and educational process of surgical clinics of the State Educational Institution of Higher Professional Education 'Saint Petersburg State Medical University named after Academician I.P. Pavlov' of the Federal Agency for Healthcare and Social Development, the Saint Petersburg State Research Institute of Emergency Medicine named after I.I. Janelidze, and City Hospital No. 9 of Saint Petersburg.

Eight printed works have been published on the topic of the dissertation research, including two manuals for physicians, and a report was made at the All-Russian Scientific and Practical Conference 'Organ-Saving Principles in Surgery of Acute Conditions' (Krasnodar, 2001).

Structure and Volume of the Dissertation

The dissertation is presented on 116 pages of typed text and consists of an introduction, four chapters, conclusion, conclusions, practical recommendations, and a list of literature comprising 112 domestic and 90 foreign sources. The work is illustrated with 35 tables and 5 figures.