Diagnosis and Treatment of Intestinal Failure Syndrome in Patients with Diffuse Peritonitis

The research is dedicated to the diagnosis and treatment of intestinal failure syndrome in patients with diffuse peritonitis. The work addresses the pathogenesis, diagnosis, and correction of metabolic disturbances developing in the context of diffuse peritonitis, as well as acute erosive-ulcerative lesions of the upper gastrointestinal tract that manifest as intestinal failure syndrome. Methods of ultrasonographic diagnosis, laser Doppler flowmetry, endoscopic examination, and experimental models of ischemic-reperfusion gastric injury are employed. An algorithm for early diagnosis and correction of intestinal failure syndrome was developed, and approaches to nutritional support for patients with diffuse peritonitis were substantiated.

The dissertation contains clinical and experimental investigations aimed at studying microcirculatory disturbances in the gastroduodenal zone, mechanisms of ischemic-reperfusion injury of the gastric mucosa, and the effectiveness of antioxidant protection. Practical recommendations on ultrasonographic diagnosis of intestinal failure syndrome in peritonitis and organization of enteral nutrition in intensive care conditions were obtained.

Relevance of the problem.

To date, peritonitis remains one of the most frequent and dangerous complications of acute inflammatory diseases and traumatic injuries of abdominal organs. Despite the availability of new surgical technologies and effective methods of modern intensive therapy, the results of peritonitis treatment remain unsatisfactory. The formation of multiple organ failure syndrome leads to increased mortality, which, according to literature data, reaches 28–37.8% in diffuse forms of peritonitis and 52–72% in the development of septic shock. (Timirbulatov V.M. et al., 1992; Gelfand E.B. et al., 2000; Prudkov M.I. et al., 2001).

The prognosis in diffuse forms of peritonitis depends equally on the timing and method of surgical intervention and on timely and adequate compensation of metabolic disturbances caused by peritonitis and the resulting organ dysfunction syndrome. Metabolism in diffuse peritonitis is characterized by pronounced catabolism, rapid depletion of nutrient reserves. Amino acids formed as a result of protein oxidation become one of the main sources of energy in hypercatabolism. Progressive loss of body muscle mass occurs — the syndrome of "autocannibalism" or hypermetabolism. Therefore, an important factor for patient survival is achieving an adequate energy balance and, especially, a positive nitrogen balance, as the final product of protein oxidation (Leiderman I.N., 1999).

In the system of impact on disrupted metabolic processes and the development of energy deficit in peritonitis, enteral and parenteral methods of nutritional correction occupy the most important place. Given the high energy expenditure and pronounced protein deficiency, it becomes clear why nutritional support of a patient with developing multiple organ failure syndrome in diffuse forms of peritonitis is one of the most difficult components of the intensive therapy program (Popova T.S. et al., 2002).

Enteral nutrition in diffuse forms of peritonitis encounters certain difficulties. The complexity of implementing enteral nutrition is associated with the developing intestinal failure syndrome (IFS), one of the main components of multiple organ dysfunction in diffuse forms of peritonitis, which is characterized by a combination of motor, evacuatory, secretory, digestive, and absorptive dysfunction of the gastrointestinal tract. Another factor hindering the use of early enteral tube feeding is dysfunction of the upper gastrointestinal tract segments (Luft V.M. et al., 2003).

Despite the successes of modern surgery, anesthesiology-reanimatology, and other fields of medicine, many researchers continue to be interested in questions of pathogenesis, diagnosis, prevention, and treatment of acute erosive-ulcerative lesions of the upper gastrointestinal tract. In the pathogenesis of the acute erosive-ulcerative process in the mucosa of the stomach and duodenum, as in the pathogenesis of peptic ulcer disease, many unresolved and disputed questions remain to this day. There are numerous theories: vascular, humoral, neurogenic, peptic, thromboembolic, theory of acute energy deficit, hormonal, dystrophic, and others, which testify to the absence of a clear understanding of the pathogenesis of this disease (Kurypsh A.A., Skryabin O.N., 1996). No single theory fully explains the occurrence, development, and course of acute erosive-ulcerative lesions of the stomach and duodenum. In this regard, questions of pathogenesis, prevention, and treatment of acute erosive-ulcerative lesions of the upper gastrointestinal tract remain relevant at the present time.

In recent times, concepts of mechanisms of damage to ischemic organs have undergone substantial changes. Upon restoration of blood circulation in an organ, destructive processes in tissues not only fail to resolve but progress as a result of reperfusion. The basis of this phenomenon lies in molecular destruction of membrane cell structures and organelles arising from disruption of energy metabolism, intensification of membrane phospholipid hydrolysis, and intensification of lipid peroxidation processes. Tissue structures altered as a result of ischemia lead to activation of phagocytosis. Activated neutrophils are powerful generators of reactive oxygen species, which can not only exert a protective effect (microbicidal and antiblastic) but also cause alteration of their own cells through enzyme inactivation, destruction of basal and cellular membranes, and alteration of DNA structure, ultimately leading to cell destruction. This creates a clear picture of ischemia as a complex two-stage process in which destruction arising during ischemia is aggravated and in most cases acquires an irreversible character upon restoration of blood circulation in the organ. Publications exist on reperfusion injury of the brain, liver, kidneys, and heart (Bilenko M.V., 1989). However, in the available literature, we did not find works dedicated to studying these processes in the gastroduodenal zone. Presumably, in the presence of ischemia, as in other organs, reperfusion pathological processes also occur in the gastric wall. As a result of disruption of systemic hemodynamics (cardiovascular insufficiency, reduction in arterial pressure, stress, shock of various etiologies, clinical death with a favorable outcome, etc.) or local disruption of blood circulation (surgeries and various pathological processes in the abdominal cavity), arising ischemic-reperfusion gastric injury should subsequently lead to the appearance of an erosive-ulcerative process. To study the changes occurring in the gastric wall during ischemia-reperfusion, the creation of adequate experimental models reflecting the diversity of situations encountered in clinical practice is relevant. This is also necessary for the development and study of new directions for prevention and treatment of acute erosive-ulcerative lesions of the stomach and duodenum.

Based on the above, the goal and objectives of the investigation were formulated:

Goal: 1. Improvement of treatment results for patients with diffuse peritonitis based on early diagnosis and correction of intestinal failure syndrome. Objectives of the investigation:

1. To conduct an analysis of ultrasonographic semiotics of intestinal failure syndrome in patients with diffuse peritonitis.

2. To study the endoscopic picture of the gastric and duodenal mucosa in patients with intestinal failure syndrome.

3. To investigate microcirculatory disturbances in the gastric and duodenal mucosa in patients with intestinal failure syndrome.

4. To assess the influence of the reperfusion syndrome on the processes of formation of acute stress erosive-ulcerative lesions of the stomach and duodenum.

5. To analyze the features of hypermetabolic reorganization of metabolism in patients with intestinal failure syndrome.

6. To optimize methods of decompression and stimulation of motility and evacuation of the upper gastrointestinal tract in intestinal failure syndrome in patients with diffuse peritonitis.

7. To develop and implement in clinical practice an algorithm for early diagnosis and correction of intestinal failure syndrome in patients with diffuse peritonitis.

8. To evaluate the clinical effectiveness of the developed algorithm for early diagnosis and correction of intestinal failure syndrome in patients with diffuse peritonitis.

SCIENTIFIC NOVELTY

1. For the first time, using laser Doppler flowmetry, patterns of microcirculatory disturbances in the gastroduodenal zone in intestinal failure syndrome were identified.

2. For the first time, an experimental model of ischemic-reperfusion gastric injury was developed, which allows reproduction of the picture of acute erosive-ulcerative lesions of the upper gastrointestinal tract.

3. The role of ischemic-reperfusion disturbances in the genesis of acute erosive-ulcerative lesions of the gastroduodenal zone was demonstrated, and the influence of antioxidants on the degree of reperfusion gastric injury was assessed.

4. For the first time, a morphopathological justification for the application of antioxidants for protection of the upper gastrointestinal tract from reperfusion injury was provided.

5. New techniques for gastroduodenal decompression, stimulation of small bowel motility ("internal drainage" of the stomach when its evacuation is impaired), and protection of the esophageal and gastric mucosa in the erosive-ulcerative process were developed — "Four-channel tube for enteral feeding with balloon fixation" (invention patent No. 2226411), "Single-use set for nasoenteric feeding" (certificate for utility model No. 26743).

6. An algorithm for early diagnosis and correction of intestinal failure syndrome in patients with diffuse peritonitis was proposed.

PRACTICAL SIGNIFICANCE

1. Based on the conducted investigations, ultrasonographic diagnostic criteria for intestinal failure syndrome in peritonitis were developed and implemented in practice.

2. Using laser Doppler flowmetry, it was revealed that the degree of microcirculation pathological changes in the gastroduodenal zone corresponds to the stages of intestinal failure syndrome in diffuse peritonitis.

3. It was demonstrated that the model of ischemic-reperfusion gastric injury is convenient for studying the influence of new pharmaceutical agents used for prevention of erosive-ulcerative lesions of the upper gastrointestinal tract.

4. Experimental confirmation of the effectiveness of antioxidant application in the prevention of acute erosive-ulcerative lesions of the upper gastrointestinal tract was obtained.

5. The developed nutritional support algorithm allows timely selection of the optimal scheme for correction of protein-energy balance in patients with acute surgical diseases complicated by diffuse peritonitis and, thereby, increases the effectiveness of the conducted treatment and reduces mortality in this category of patients.

MAIN PROVISIONS FOR DEFENSE

1. Intestinal failure syndrome is a pathognomonic manifestation of diffuse peritonitis and has a clearly expressed staged character. Its ultrasonographic structure changes depending on the stage of the disease and the etiological factor.

2. Ultrasonography is an objective method for diagnosing the severity of intestinal failure syndrome manifestations, allows study of its dynamics and prediction of the disease course.

3. Erosive-ulcerative lesion of the gastroduodenal zone in diffuse peritonitis is a manifestation of intestinal failure syndrome.

4. Pathological changes in the microcirculation system of the gastric mucosa have a sequential character and correspond to the stages of intestinal failure syndrome in diffuse peritonitis.

5. Ischemic-reperfusion injuries underlie acute erosive-ulcerative lesions of the upper gastrointestinal tract.

6. One of the possible routes of gastrointestinal protection from ischemia-reperfusion is early application of antioxidants.

7. Early initiation of enteral nutrition affects the severity of the patient's condition and contributes to reduction of the mortality level in diffuse peritonitis.

IMPLEMENTATION IN PRACTICE

The topic of the work was included in the plan of scientific investigations of the Bashkir State Medical University. The results of the conducted investigations were implemented in surgical departments and intensive care units of the Emergency Hospital, City Clinical Hospital No. 8, and City Clinical Hospital No. 18 of Ufa. Methodological recommendations "Enteral Nutrition in Intensive Therapy of Abdominal Sepsis" and "Ultrasonic Diagnosis of Intestinal Failure Syndrome in Peritonitis" were published. An invention patent No. 2226411 "Four-channel tube for enteral feeding with balloon fixation" and a certificate for utility model No. 26743 "Single-use set for nasoenteric feeding" were obtained, as well as a certificate for a rationalization proposal "Method of intestinal stimulation in dynamic intestinal obstruction" (certificate No. 2405 issued by the Bashkir State Medical University on October 25, 2001).

The main provisions of the dissertation were presented at the fifth All-Russian conference "New Technologies in Surgery" (Ufa, 2001), at the V International Congress "Parenteral and Enteral Nutrition" (Moscow, 2001), at the International Congress of Surgeons (Petrozavodsk, 2002), at the third interregional conference of the Ural-Siberian Association of Enteral and Parenteral Nutrition (Ufa, 2003), and at meetings of the Association of Surgeons of the Republic of Bashkortostan (Ufa, 2002, 2004).

VOLUME AND STRUCTURE

The dissertation consists of an introduction, 8 chapters, conclusion, conclusions, practical recommendations, and a bibliography. The research materials are presented across 227 pages of typed text, illustrated with 66 figures and 48 tables. The bibliography includes 350 sources (207 domestic and 143 foreign authors).