RU2553427C1 - Diagnostic technique for infected pancreonecrosis with establishing indications for surgical intervention - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention describes a diagnostic technique for infected pancreonecrosis with establishing the indications for a surgical intervention by examining a patient, wherein acetic, propionic, butyric and isovaleric acids are measured in the blood by gas chromatography, and if the acetic acid concentration is more than 0.11 mmole/l enables stating infected pancreonecrosis, and if the concentration of any of three acids: propionic more than 0.095 mmole/l, butyric more than 0.0035 mmole/l, isovaleric acid more than 0.0003 mmole/l enables stating infected pancreonecrosis with active development of an anaerobic infection requiring one of versions of the surgical intervention.

EFFECT: invention enables providing the objective and accurate diagnosing of pancreonecrosis transformation into the stage of infection by using the qualitative parameters with no undesired side effects.

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Description

The invention relates to medicine, namely to surgery.

In recent decades, acute pancreatitis in terms of growth began to come out on top among urgent surgical diseases. In 10-20% of cases, the course of acute pancreatitis is severely destructive. Its prognosis largely depends on the volume of pancreatic necrosis and its infection. Septic complications resulting from infection of foci of necrosis remain one of the main causes of death. The identification of the transition of pancreatic necrosis to the infected form is carried out according to clinical and laboratory data, markers of pancreatic damage, systems for assessing the severity of the patient, the results of instrumental examination methods (Savelyev BC, Filimonov MI, Burnevich SZ Pancreatonecrosis. M .: Honey. Inf Ag., 2008. P.36-49).

However, these criteria are not always specific and sensitive for the early diagnosis of an infectious process. Therefore, to date, timely diagnosis of infected pancreatic necrosis presents significant difficulties. Diagnostic errors in infectious complications of pancreatic necrosis occur in 40% of cases, which leads to a delay in surgery, the development of sepsis and high mortality. Therefore, it is urgent to develop and put into practice new effective markers of infection in the comprehensive diagnosis of infected pancreatic necrosis.

In recent years, much attention has been paid to the determination in patients with various pathologies of the content of volatile fatty acids, which are metabolites of anaerobic and aerobic microorganisms. The method of gas-liquid chromatography for determining the concentration of volatile fatty acids in various biosubstrates is characterized by high accuracy, sensitivity, accessibility, and speed of obtaining the result (Minushkin O.N., Ardatskaya M.D. Possibilities and prospects of studying short-chain fatty acids in the pathology of the gastrointestinal tract by the example of diseases intestines and organs of the hepatobiliary system // Clin. laboratory diagnostics. 2004. No. 2. S.19-20, 31-36).

It has been established that volatile fatty acids suppress immunity, reducing the activity of the main links of anti-infection protection: epithelium, tissue macrophages, T and B cells, as well as intercellular interactions and the production of anti-inflammatory mediators (Beloborodova N.V., Beloborodov SM. Metabolites of anaerobic bacteria and macroorganism reactivity // Antibiotics and chemotherapy. 2000. No. 2. P.28-36).

The studies of the content of volatile fatty acids and other toxic metabolites by gas chromatography with mass spectrometry in biopsy samples of the pancreas and blood proved the role of anaerobic non-clostridial infection in the development of infected pancreatic necrosis. However, only the total concentration of volatile fatty acids, which are metabolites of only anaerobic microorganisms, was studied in peripheral blood. At the same time, the value of individual volatile fatty acids, which are metabolites of not only anaerobic, but also aerobic microflora, which also takes an active part in the infection of foci of pancreatic necrosis, has not been determined. In addition, a complex and inaccessible chromato-mass spectrometric method was used. Therefore, the determination of the values of the indices of individual volatile fatty acids for the timely diagnosis of infected pancreatic necrosis and the establishment of indications for a particular type of surgical intervention have not yet been carried out.

The technical result of the proposed method is achieved by the fact that they determine the content of acetic, propionic, butyric and isovaleric acids in the blood. At a concentration of acetic acid greater than 0.11 mmol / L, the presence of infected pancreatic necrosis is established, and at a concentration of any of the three acids: propionic is greater than 0.0095 mmol / L, butyric is greater than 0.0035 mmol / L, isovalerianic is greater than 0.0003 mmol / L - establish the presence of infected pancreatic necrosis with the active development of anaerobic infection, requiring one of the options for surgical intervention.

The authors determined by gas chromatography the concentration of acetic, propionic, butyric and isovalerianic acids in the blood of patients with a verified diagnosis of pancreatic necrosis. The authors found a statistically significant significant increase in the average concentrations of these acids in the blood in patients with infected pancreatic necrosis compared with a group of patients with sterile pancreatic necrosis (p <0.05). The most informative indicators were M-m (differences in mean concentration values and standard error). They were selected as diagnostic criteria.

Comprehensive treatment in the intensive care unit remains a priority for pancreatic necrosis. Performing surgical intervention with sterile pancreatic necrosis is erroneous, since it often leads to serious complications. At the same time, despite conservative treatment, the transition of pancreatic necrosis to the stage of infection can become an indication for minimally invasive or open extensive intervention, the timely implementation of which greatly improves the prognosis of this serious disease. To determine the indications for surgical treatment for infected pancreatic necrosis, research is ongoing aimed at developing the most informative criteria for the timeliness and validity of the intervention.

Volatile fatty acids (VFAs) are the main waste products of bacteria. Therefore, they are used as markers of infection. The leading role in the infection of pancreatic necrosis is played by the aerobic-anaerobic association of microorganisms, coming through translocation from the gastrointestinal tract. Acetic acid is produced by aerobic and anaerobic flora, and propionic, butyric, and isovaleric acids are mainly metabolic products of anaerobic bacteria. The onset of pancreatic necrosis infection is accompanied by an increase in the number of VFA in the affected foci of the pancreas and in the blood. The level of VFA can control the effectiveness of conservative treatment: a persistent decrease in VFA indicators indicates the effectiveness of exposure to foci of infection, and their further increase indicates the progression of the infection process. Therefore, the determination of the level of VFA, which is a marker of infection, may be a diagnostic criterion for the stage of pancreatic necrosis requiring surgical treatment.

The method is as follows. After a detailed examination and diagnosis of fasting pancreatic necrosis, venous blood is taken from a peripheral vessel in a volume of 0.5 ml. Then, against the background of the treatment, in the dynamics (after 5-7 days and according to indications), repeated blood sampling is performed. Sample preparation involves adding 1 drop of 10% sulfuric acid to the indicated amount of blood. Gas-liquid chromatography for the quantitative determination of acetic, propionic, butyric and isovalerianic acids is performed on a glass column 1 m long, 3 mm in diameter, filled with Porapak Q (USA) with phosphoric acid deposited on it, in isothermal mode at a temperature of 200 ° C. The MOZKh chromatograph, model 3700. The flame-ionization detector, the carrier gas is helium. The identification and quantification of acids was carried out using analytical standards.

The method used makes it possible to objectify the stage of pancreatic necrosis and determines the algorithm for further surgical tactics: the continuation of intensive care or surgical intervention. Using the method improves the accuracy of diagnosis of infected pancreatic necrosis due to quantitative parameters, and in addition, this diagnosis does not entail complications.

To prove the accuracy of diagnosis of infected pancreatic necrosis, we compared the results obtained using the proposed method and generally accepted methods. The diagnosis of pancreatic necrosis and its complications was established in accordance with modern domestic and foreign guidelines.

45 patients with a confirmed diagnosis of pancreatic necrosis were examined: 25 patients with a sterile form of pancreatic necrosis and 20 patients with infected pancreatic necrosis. In 26 patients, various surgical interventions were performed. The age of the patients ranged from 21 to 72 years.

The proposed method made it possible to establish the transition of pancreatic necrosis to the stage of infection of pancreatic necrosis in 19 of 20 patients (95% coincidence with the final diagnosis).

Therefore, the concentration of acetic, propionic, butyric and isovaleric acid in the blood can be used to diagnose the transition of pancreatic necrosis to the stage of infection. An example of the application of the method in a patient with sterile pancreatic necrosis.

Patient S., 24 years old. He was admitted to the hospital with a diagnosis of "sterile pancreatic necrosis", parapancreatic infiltrate. Disease duration - 10 days: suddenly after drinking alcohol, intense pain appeared in the upper abdomen, nausea, repeated vomiting, weakness began to grow. From the onset of the disease, he was treated in the Central District Hospital at the place of residence.

Ultrasound revealed changes in the pancreas according to the type of acute pancreatitis, infiltration in the projection of the omental bursa and left mesogastric region. Against the background of conservative therapy, the condition is not improved. The patient was sent to the Ivanovo Regional Clinical Hospital for further treatment.

On admission, the general condition is serious, complaints of severe weakness, moderate persistent pain in the upper abdomen. Body temperature - 37.6 C °, heart rate (HR) - 100 per minute, respiratory rate - 24 per minute, blood pressure (BP) - 140/80 mm Hg On palpation, the abdomen is swollen, moderately painful and tense in the epigastrium and left hypochondrium, where the infiltrate is palpated. In the general blood test: erythrocytes - 4.1 · 10 ¹² / l, hemoglobin - 114 g / l, white blood cells - 23.5 · 10 ⁹ / l (eosinophils - 4%, stab neutrophils - 2%, segmented neutrophils - 81% monocytes - 3%, lymphocytes - 10%), toxic granularity of neutrophils +++, ESR - 30 mm / h. Blood amylase - 252 units, C-reactive protein - 100 mg / l. The severity of the condition on the APACHE II scale is 11 points. Ultrasound, MSCT (with intravenous contrasting) revealed a picture of large focal pancreatic necrosis with an infiltrative-exudative component that spreads to the omental bursa and the left pararenal space with a transition to the transverse colon with signs of fluid lumping in these areas.

The content of acetic, propionic, butyric and isovalerianic acids was also determined by gas chromatography in blood. The following results were obtained: acetic acid - 0.1 mmol / L, propionic - 0.0056 mmol / L, butyric - 0.0025 mmol / L, isovalerianic - 0.00015 mmol / L. After complex intensive care, including in the intensive care unit, the patient's condition improved significantly: pain and fever disappeared, weakness decreased significantly. Amylase levels decreased to 54 units. and C-reactive protein up to 5 mg / l, blood leukocytes up to 5.5 · 10 ⁹ (eosinophils - 2%, stab neutrophils - 0%, segmented neutrophils - 63%, monocytes - 8%, lymphocytes - 27%). Ultrasound and MSCT control visualized positive dynamics in the form of a significant decrease in the infiltrative-exudative component, the formation of parapancreatic pseudocysts along the front edge of the body and in the region of the pancreas tail was noted.

The content of volatile fatty acids was re-examined every 7 days, their significant decrease was noted: acetic acid - up to 0.015 mmol / L, propionic - up to 0.001 mmol / L, butyric - up to 0.00052 mmol / L, isovalerianic - up to 0.000077 mmol / l The patient was discharged from the hospital on the 28th day in a satisfactory condition. According to clinical, instrumental, laboratory and chromatographic data, the patient has a sterile form of pancreatic necrosis, which confirms the results of the claimed diagnostic method.

An example of the application of the method in a patient with infected pancreatic necrosis.

Patient P., 38 years old. He was transferred to the Ivanovo Regional Clinical Hospital from the surgical department of the NRB at the place of residence, where he underwent treatment with a diagnosis of “infected pancreatic necrosis, omental abscess”. Disease duration - 12 days: after drinking alcohol, I first noted severe pain in the upper abdomen of herpes zoster, nausea, repeated vomiting. A day after the onset of the disease, he was hospitalized in the Central District Hospital in serious condition with a clinic of pancreatogenic shock. Conservative therapy was carried out, against the background of which from 10 days the patient developed febrile fever, abdominal pain and weakness began to increase. Ultrasound revealed fluid formation in the projection of the stuffing bag.

Upon admission to the Ivanovo Regional Clinical Hospital, the general condition is serious, complaints of moderate weakness, constant pain in the upper abdomen, fever up to 39.0 ° C with chills. Body temperature - 38.0 C °, heart rate - 96 per minute, respiratory rate - 20-22 per minute, blood pressure - 130/70 mm Hg. On palpation, the abdomen is swollen, moderately painful in the epigastrium and left hypochondrium. In the general blood test: erythrocytes - 2.86 · 10 ¹² / l, hemoglobin - 100 g / l, white blood cells - 19.8 · 10 ⁹ / l (eosinophils - 1%, stab neutrophils - 10%, segmented neutrophils - 78% monocytes - 6%, lymphocytes - 11%), ESR - 56 mm / h. Blood amylase - 148 units, C-reactive protein - 152 mg / l. The severity of the condition on the APACHE II scale is 12 points. When MSCT (with intravenous contrasting) revealed a picture of subtotal pancreatic necrosis with infiltration of parapancreatic fiber, smeared with fluid in the stuffing bag, left-sided pleurisy.

The determination of the content of acetic, propionic, butyric and isovalerianic acids in the blood was carried out by gas chromatography. The following results were obtained: acetic acid 0.29 mmol / L, propionic acid 0.084 mmol / L, butyric acid 0.0042 mmol / L, isovalerianic 0.00043 mmol / L.

Considering persistent hyperthermia and the ineffectiveness of conservative therapy, an operation was performed on the 3rd day after the transfer as an emergency - double-rib laparotomy, omenobursostomy, necsecvestrectomy, drainage and plugging of the omental bursa and abdominal cavity. An intervention revealed: there is no effusion in the abdominal cavity, a large number of steatonecrosis in the region of the small and large omentums. An abscess with purulent contents of up to 800 ml was opened in the stuffing bag. Most of the body and tail of the pancreas are necrotic with sequestration, sequestration removed. The rest of the gland is enlarged, with areas of black necrosis, contact bleeds. Parapancreatic fiber with patches of necrosis and copious, thick, purulent discharge. Conclusion: infected subtotal pancreatic necrosis, parapancreatic phlegmon, abscess of the omental bursa. The result of inoculation of pancreatic biopsy samples: Escherichia coli, Bacteroides fragilis.

A day after the operation, a significant decrease in the content of volatile fatty acids in the blood was noted: acetic acid - 0.11 mmol / L, propionic - 0.036 mmol / L, butyric - 0.0019 mmol / L, isovalerianic - 0.00023 mmol / L. Subsequently, five reorganization programmatic relaparotomies were performed with an interval of 2-3 days. Also, in the intensive care unit, complex intensive therapy was carried out, including the use of antibacterial drugs: meronem, ciprofloxacin, metrogil (in connection with the aerobic-anaerobic association of microorganisms in the foci of destruction). Gradual cleansing from necrosis was noted, the wound was actively granulated with scanty serous discharge. With the last relaparotomy, partial suturing of the postoperative wound with drainage of the residual cavity was performed. The patient's condition improved significantly: pain and fever disappeared. Amylase levels decreased to 33 units. and C-reactive protein up to 2 mg / l, blood leukocytes up to 5.5 · 10 ⁹ / l (eosinophils - 1%, stab neutrophils - 2%, segmented neutrophils - 78%, monocytes - 6%, lymphocytes - 11%) . With ultrasound and MSCT control, a positive dynamics was visualized in the form of the absence of osmotic fluid in the abdominal cavity and retroperitoneal space.

Repeated studies of the content of volatile fatty acids were carried out every 7 days, there was a significant decrease in the level of acetic acid to 0.048 mmol / L, propionic to 0.0058 mmol / L, butyric to 0.0015 mmol / L, isovalerianic to 0.0002 mmol / l. The patient was discharged from the hospital on the 37th day in satisfactory condition for outpatient aftercare. According to clinical, instrumental, laboratory and chromatographic data, the patient was diagnosed with infected pancreatic necrosis with the active development of anaerobic infection, which confirms the result of the application of the claimed diagnostic method.

Therefore, the claimed method is objective and informative. Using the clinical signs of the disease and the concentration of acetic, propionic, butyric and isovalerianic acids in the blood, it is possible to diagnose infection of foci of pancreatic necrosis.

This method allows to increase the objectivity and accuracy of the diagnosis of the transition of pancreatic necrosis to the stage of infection through the use of quantitative parameters without the appearance of undesirable side effects.

Claims (1)

A method for diagnosing infected pancreatic necrosis with indications for surgical intervention by examining a patient, characterized in that the gas content of acetic, propionic, butyric and isovaleric acid in the blood is determined by a gas chromatographic method and the presence of infected pancreatic necrosis is established with a concentration of acetic acid greater than 0.11 mmol / l, and when the concentration of any of the three acids: propionic is greater than 0.0095 mmol / l, butyric is greater than 0.0035 mmol / l, isovalerianic is greater than 0.0003 mmol / l - set to the presence of infected pancreatic necrosis with the active development of anaerobic infection, requiring one of the options for surgical intervention.