RU2793647C1 - Method for differential diagnosis of sterile and infected pancreatitis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to diagnostics, abdominal surgery. Upon admission to the hospital in patients with pancreatic necrosis, the concentrations of α₂-macroglobulin and procalcitonin in the blood serum are determined. The ratio of these two proteins is found by dividing the concentration of procalcitonin by the concentration of α₂-macroglobulin, multiplied by 1000. If the coefficient is below 3, sterile pancreatic necrosis is diagnosed, and if the coefficient is 3 or more, infected pancreatic necrosis is diagnosed.

EFFECT: method improves the accuracy and reliability of the differential diagnosis of sterile and infected pancreatic necrosis, even when the diagnosis of other instrumental and laboratory methods is difficult; does not require patient preparation; allows diagnosing latent destructive conditions requiring surgical treatment; eliminates unwanted radiation exposure to the patient and staff.

1 cl, 2 ex

Description

The invention relates to medicine, namely surgery, and can be used for differential diagnosis of sterile and infected pancreatic necrosis.

Diagnosis of acute destructive pancreatitis is a very difficult problem at the present time. Criteria for early preoperative diagnosis of various forms of pancreatic necrosis and indications for surgical treatment have not been sufficiently developed, and therefore unnecessary diagnostic laparotomies and open drainage operations are often performed, which, in turn, increases the incidence of pyoinflammatory diseases and leads to high mortality, 2-3% with edematous form, and from 18-20% to 25-80% with destructive forms of pancreatitis. (Mitkov, V.V. Clinical guide to ultrasound diagnostics / V.V. Mitkov. - M., 1996. - 322 p.). In this regard, it is very important to identify patients with a destructive nature of the course of the disease as early as possible for the entire complex of intensive care measures. Thus, early assessment of the severity of the course of the disease remains an urgent problem and requires further study and correction.

In close connection with these phenomena, the study of the patterns of evolution of destructive pancreatitis from sterile to infected forms remains, which determines increased attention not only to the quality of modern methods of differential diagnosis of the sterile and infected nature of the necrotic process, but also to objective studies of the effectiveness of various components of intensive care and tactics. surgical interventions based on multicenter and evidence-based data.

Therefore, a comprehensive study of the effectiveness of methods of conservative and surgical treatment of pancreatic necrosis in their inseparable essence is possible only with a detailed study of the clinical pathomorphology, pathogenesis and thanatogenesis of destructive pancreatitis in the light of modern ideas about the two-phase development of the disease from aseptic necrosis to its infected forms.

A well-known assessment of the severity of the course of pancreatitis, which is based on the analysis of clinical and laboratory scales, which can improve the accuracy of predicting the outcome of the disease and the development of purulent-septic complications. The most common systems for assessing the severity of the patient's condition and prognosis are scales (Ranson, APACHE II, SOFA, SAPS, MODS) (Banks P.A. Practice Guidelines in Acute Pancreatitis. Am J Gastroenterol 2006; 101: 2379-2400). The evaluation scales use from 34 to 12 parameters that determine the main processes of life. So, Ranson uses 12 parameters, APACHE II - 16 parameters, SOFA - 12 parameters (PaO2 / FiO2, platelet level, μl, bilirubin, mg / dl, mean blood pressure, Glasgow coma scale, scores, creatinine and diuresis), in a simplified SAPS Physiological Disorders Scale - 14

parameters (age, heart rate, systolic blood pressure, mmHg, body temperature, °C, respiratory rate, min, diuresis in 24 hours, l, urea, mg/dl, leukocytes, 1000/l, hematocrit, %, potassium, meq/l, sodium, meq/l, HCO3 meq/l, Glasgow coma scale, points), in the MODS multiple organ failure scale - 14 parameters (PaOgChOz, serum creatinine, mmol/l, serum bilirubin, PAR (mean arterial pressure (MAP) ), central venous pressure (CVP) and heart rate (HR): PAR=4CC x CVP/SBP), Platelets, Glasgow Scale).

However, in duty surgical hospitals it is impossible to determine the main indicators used in these scales upon admission of the patient or in the coming hours, which makes them completely unsuitable for practical use, in addition, these systems for assessing the severity of the patient provide an acceptable accuracy of about 80%, and then only after 48 hours from the onset of the disease, and until that time they are of little information (Kondratenko P.G., Vasiliev A.A., Konkova M.V. Acute pancreatitis. - Donetsk, 2008. - 352 p.).

The disadvantages of methods for assessing the severity of acute pancreatitis using scales are the inability to assess the severity of acute pancreatitis in the first 24 hours and use them in persons under 18 years of age.

A well-known method for laboratory diagnosis of acute pancreatitis is to determine the level of activity of serum amylase or urine diastase (Uhl W., Warshaw A., Imrie C. IAP Guidelines for the Surgical Management of Acute Pancreatitis. Pancreatology 2002; 2(6): 565-73. Banks P.A. Practice Guidelines in Acute Pancreatitis Am J Gastroenterol 2006;101: 2379-2400). At the same time, there is convincing evidence that this indicator is not a reliable marker of pancreatitis. The results of the studies showed the absence of a direct correlation between the activity of these enzymes and the severity of acute pancreatitis, which does not allow the use of this analysis for the choice of treatment tactics (Forsmark S.E. Pancreatitis and Its Complications, 2005: 338. Banks P.A. Practice Guidelines in Acute Pancreatitis. Am J Gastroenterol 2006; 101: 2379-2400).

A method for diagnosing pancreatitis, including taking an anamnesis with an assessment of abdominal pain, conducting a biochemical examination with the determination of serum amylase and lipase. The level of amylase rises already in the first hours of exacerbation of pancreatitis, reaches a maximum by the end of the first day, remaining elevated for 2-3 days. The level of lipase increases from the end of the 4th day, reaches a maximum on the 5th-6th day and is kept elevated for up to 12 days.

The main instrumental method of diagnosis is ultrasound (ultrasound). In the gallbladder or common duct, calculi or various forms of biliary sludge are detected. Conduct a study of the pancreas. With exacerbation of biliary pancreatitis, ultrasound signs of pancreatic tissue edema are detected.

(Biliary pancreatitis. Ilchenko A.A. Central Research Institute of Gastroenterology, Moscow. Portal "Pain" http://www.paininfo.ru/ articles/4076.html)

The disadvantages of the method:

- with a complicated course of pancreatitis, the dynamics of the levels of amylase and lipase can differ significantly;

- normal dimensions of the common bile duct according to ultrasound are not a convincing sign of the absence of pathology:

- ultrasound does not always reveal changes in the pancreatic parenchyma;

- the inability to assess the severity of acute pancreatitis in the first 24 hours.

Other important indicators include C-reactive protein (CRP). (De Campos T., Cerqueira C., Kuryura L. Morbimortality indicators in severe acute pancreatitis. JOP 2008 Nov 3; 9(6):690-7).

However, this analysis becomes reliable from day 3, when the optimal time for choosing treatment tactics remains missed (Schritte K., Malfertheiner P. Markers for predicting severity and progression of acute pancreatitis. Best Pract Res Clin Gastroenterol. 2008; 22 (l): 75 -90).

In practical medicine, the most reliable diagnostic method for detecting destructive pancreatitis is computed tomography (CT), which allows you to establish inflammatory processes in the pancreas in 94% of cases.

However, as it turned out, studies conducted for the first time are absolutely ineffective both in terms of diagnosis and prognosis of the disease, a more or less clear picture using CT can be obtained only by the 7-10th day of the disease. That is why the attitude to this expensive technique, fraught with complications associated with the introduction of a contrast agent, and accompanied by a rather high radiation exposure, has recently become very critical. (Munoz-Bongrand N., Panis Y., Soyer P. et al. (2001) Serial computed tomography is rarely necessary in patients with acute pancreatitis: a prospective study in 102 patients. J. Am. Coll. Surg., No. 193 (2): pp. 146-152.)

The main disadvantages of computed tomography diagnostic methods are:

- undesirable radiation exposure to the patient and staff;

- the complexity of the process of processing the results;

bulky and high cost of equipment and, as a result, high cost of research;

- lack of equipment in small clinics and hospitals, where patients with an acute abdomen are most often hospitalized;

- for a qualitative study, careful bowel preparation (cleansing enemas) is necessary, which can provoke the development of peritonitis, thereby aggravating the patient's condition;

- the inaccessibility of computed tomography in medical institutions of the district, city, and, sometimes, regional subordination, the high cost of research and the patient's unwillingness to undergo radiation exposure encourage many patients to refuse such an examination, and researchers to look for other reliable diagnostic tests.

Currently, the only reasonable indication for surgical treatment of necrotizing pancreatitis is infected pancreatic necrosis in combination with increasing sepsis (Lee V.T., Chung A.Y., Chow R.K.. et al. (2006) Infected pancreatic necrosis - an evaluation of the timing

and technique necrosectomy in a Southeast Asian population. Ann. Acad. Med. Singapore, 35(8): pp.523-530.)

Currently, to control systemic inflammatory and immune responses, septic complications, destructive processes, and multiple organ failure, there is a wide choice of marker proteins of various groups, among which acute phase proteins (APPs) play an important role, associated with inflammation and reflecting different aspects of the pathological process ( Trubnikov G.A., 1975; Merkulov, A.G. 1989; Polevshchikov, A.V. 1997).

As a prototype, we took a method for the differential diagnosis of destructive pancreatitis. Examine the level of C-reactive protein (CRP) and a2-macroglobulin (MG) in the patient's blood serum upon admission to the hospital, determine the ratio of the concentrations of CRP and MG, while the CRP/MG ratio above 2 corresponds to acute destructive inflammation of the pancreas, and the CRP/MG ratio below 2 indicates a decrease or absence of the inflammatory process in the pancreas (Kchibekov E.A., Nikulina D.M. Method for diagnosing destructive pancreatitis// RF Patent No. 2427837).

Given the fact that alpha-2-macroglobulin (MG), being an inhibitor of proteinases, quite clearly shows its properties in acute pancreatitis - its concentration decreases and inversely correlates with the degree of destruction of the pancreas. However, this protein does not correlate with the degree of bacterial contamination, in contrast to procalcitonin (PCT). A significant increase in procalcitonin is found in patients with bacterial sepsis, especially in severe sepsis and/or septic shock. The synthesis of PCT is stimulated by bacterial exo- and endotoxins. (Bohuon C. A Brief history of procalcitonin. Intensive Care Medicine (2000) 26: S146-S147). PCT is more sensitive than CRP, FIO, or IL-6 to detect an infectious nature. This advantage fundamentally distinguishes PCT from other diagnostic markers of inflammation. The sensitivity of the method for determining PCT in bacterial infections in patients in the intensive care unit is similar to SRV or slightly higher, but at the same time, the determination of PCT is more specific (Kishkun A.A. Manual of laboratory diagnostic methods. Educational and practical edition. GEOTAR-Media, 2009 - 800 pp. Higgins K. Decoding of clinical laboratory tests /translated from English, edited by Prof. Emanuel V.L., 5th ed., M.: BINOM Knowledge Lab, 2011, Kamyshnikov VS Doctor's pocket guide for laboratory diagnostics, M.: MEDpress-inform, 2008).

The aim of the invention is to improve the accuracy of the differential diagnosis of sterile and infected pancreatic necrosis.

The technical result is achieved by the fact that upon admission to the hospital in patients with pancreatic necrosis, the concentrations of ar-macroglobulin and procalcitonin in the blood serum are determined, and then the ratio of these two proteins is found by dividing the concentration of procalcitonin by the concentration of ag-macroglobulin, multiplied by 1000, and at the value of the coefficient below 3, sterile pancreatic necrosis is diagnosed, and with coefficient values of 3 or more, infected pancreatic necrosis is diagnosed.

The concentration of ag-macroglobulin and procalcitonin in the serum of patients with acute pancreatitis was studied at admission, immediately on the day of surgery, 3-5 days after surgery and at discharge of patients (53 patients). A clear dependence of the concentration of PCT and MG on the degree of the destructive process in the pancreas was established. Using the electrochemiluminescent method on the analyzer Cobas E 411 (Roshe, Switzerland), the level of procalcitonin (PCT in ng/ml) in the blood serum was determined;

The concentration of ag-macroglobulin in blood serum was determined by the method of radial immunodiffusion (mg/l).

A clear dependence of the concentration of ag-macroglobulin and procalcitonin on the severity of the destructive process in the pancreas was established. A direct correlation of the PCT level in infected pancreatic necrosis and an inverse correlation of the MG level depending on the degree of destruction of the pancreas were obtained.

Statistical processing of the results was carried out using Student's t test. The results of immunochemical testing of MG compared with the data of general clinical examination showed that in patients with sterile pancreatic necrosis, the level of MG was reduced to 931 mg/l (p<0.01), and with infected pancreatic necrosis it decreased to 610 mg/l. The concentration of PCT in sterile pancreatic necrosis did not exceed 1.9 ng/ml, and in infected pancreatic necrosis it was higher than 2.0 ng/ml (p<0.01),

The ratio coefficient was calculated by the formula:

K \u003d PCT / MG * 1000,

Where PCT is procalcitonin, MG-ag-macroglobulin.

The method proposed by us has been introduced into the work of the surgical department of the CHUZ CB "RZD-Medicine" and the City Clinical Hospital No. 3 of Astrakhan and was used in the examination of 53 patients. Below are the test results.

Example #1.

Example 2. Patient X., aged 50, was admitted to the surgical department on the second day after the disease with complaints of pain in the epigastrium, right hypochondrium, radiating to the back, which appeared after an error in the diet, eating fatty foods.

Objectively: a state of moderate severity. Moderate pallor of the skin, dry mouth, single vomiting of bile. Heart tones are rhythmic, muffled, pulse is 88 beats/min, blood pressure is 140/80 mm/Hg. In the lungs, weakened breathing, no wheezing. The abdomen is swollen, painful in the epigastrium and right hypochondrium. The liver and spleen are not enlarged, the gallbladder is not palpable, there are no symptoms of peritoneal irritation. Pasternatsky's symptom is negative on both sides. Stool and diuresis are normal.

Diagnosed with acute pancreatitis. The following examination was carried out: urine diastasis - 124 units, ECG - no features, leukocytosis - 11.6 x 109, ALT, ACT - within normal limits, urinalysis without features, ultrasound - no stones in the gallbladder, walls are not thickened, pancreas gland of reduced echogenicity, enlarged.

Low serum levels of MG - 760 mg/l, PCT -0.91 ng/ml Calculated in the patient's ratio: K=PCT/MGx 1000, and equaled 1.19.

Clinical diagnosis: Acute pancreatitis edematous form.

Treatment was prescribed: Table No. 0, cold on the stomach, bilateral pararenal blockade with a solution of novocaine 25% - 100.0 antispasmodics, infusion therapy, analgesics, heparin, countercal 25,000 units x 2 times a day. After the treatment, the condition improved, the pain disappeared. The restoration of laboratory values by the time of recovery was noted. Discharged on the 11th day in a satisfactory condition.

Example #2

Patient M., aged 54, was admitted on an emergency basis to the surgical department 4 days after the onset of the disease with a diagnosis of acute pancreatitis.

MG - 640 mg/l, PCT -2.8 ng/ml Calculated in the patient's ratio: K=PCT/MG<1000, equal to 4.3.

On admission: the patient's condition is serious. Conscious, contact. The abdomen is tense, with severe pain in the epigastrium on palpation. Shchetkin-Blumberg's symptom is positive. Considering that the ratio is more than 3, the absence of the effect of intensive therapy, as well as CT data (destructive pancreatitis), after preoperative preparation, laparotomy, opening of parapancreatic phlegmon, marsupilization of the omental sac, sanitation and drainage of the abdominal cavity were performed. Intraoperatively: acute destructive pancreatitis, fatty pancreatic necrosis, parapancreatic phlegmon. He received intensive therapy, including detoxification, antispasmodic, antibacterial, antisecretory therapy, as well as RRT procedures (hemodialysis sessions) for health reasons 3 times a week for at least 240 minutes. The postoperative period was uneventful, without complications. The wound healed by first intention. Discharged on the 18th day.

When using the method proposed by us, it is possible to achieve:

• reliable differential diagnosis of sterile and infected pancreatic necrosis even when diagnosis by other instrumental and laboratory methods is difficult;

• for diagnostics special conditions and preparation of the patient are not necessary;

• the method allows diagnosing latent

destructive conditions requiring surgical treatment;

• reduction of economic costs due to the reduction of preoperative preparation, excluding expensive computer examination, attempts of unsuccessful conservative therapy

• exclusion of unwanted radiation exposure to the patient and staff.

Claims (1)

A method for the differential diagnosis of sterile and infected pancreatitis by examining blood serum, characterized in that upon admission to a hospital in patients with pancreatic necrosis, the concentrations of α ₂ -macroglobulin and procalcitonin in the blood serum are determined, and then the ratio of these two proteins is found by dividing the concentration of procalcitonin by the concentration of α ₂ -macroglobulin is multiplied by 1000, and if the coefficient value is below 3, sterile pancreatic necrosis is diagnosed, and if the coefficient is 3 or more, infected pancreatic necrosis is diagnosed.