Method for diagnosing septic process and predicting septic complications development in children

FIELD: medicine.

SUBSTANCE: method involves determining plasminogen/plasmin, α₂-macro-globulin, α₁-antitripsin content at the first, third, fifth and tenth day. The plasminogen/plasmin level being equal to 66-74 mcmole/l or 100-120 mcmole/l, α₂-macro-globulin level of 2.7-3.0 mcmole/l, α₁-antitripsin content of 2.38-3.2 mcmole/l, systemic inflammatory response to purulent infection, light severity degree endotoxicosis is diagnosed and favorable disease outcome is predicted. The plasminogen/plasmin level being equal to 50-65 mcmole/l or 125-160 mcmole/l, α₂-macro-globulin level of 2.3-2.6 mcmole/l, α₁-antitripsin content of 3.3-4.0 mcmole/l, sepsis with organ and system dysfunction, moderate severity degree endotoxicosis is diagnosed and septic complication availability and lingering disease development course is predicted. The plasminogen/plasmin level being equal to 39-40 mcmole/l, α₂-macro-globulin level of 1.58-2.08 mcmole/l, α₁-antitripsin content of 5.0-6.2 mcmole/l, severe sepsis, septic shock, severe degree endotoxicosis is diagnosed and unfavorable disease outcome is predicted.

EFFECT: high accuracy of diagnosis.

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The proposed method relates to medicine, clinical diagnostics, and can be used to adequately assess the severity of patients and early diagnosis of septic complications in children with purulent-septic diseases.

Sepsis and septicemia shock remains one of the main causes of mortality. The development of this terrible complications in critical conditions in children of all ages is often a consequence of late diagnosis and inadequate assessment of the severity of the condition at the onset of disease. Many questions concerning the mechanisms of occurrence and development of sepsis, to date, has not been fully investigated. Leading experts dealing with this issue believe that the most urgent task is to develop uniform criteria for the diagnosis of sepsis timely appointment of adequate therapy (Yu.f.isakov, Nowbelieve. “Sepsis in children. 2001).

Known refractometric method for the diagnosis of endogenous intoxication in children. This method is based on the determination of proteins, products of protein metabolism and decay in plasma by determining the refractive index by refractometry blood plasma, depending on which rank the degree of endotoxemia (Patent No. 2158929. M CL 7 G 01 N 33/68. BIPM No. 31. 2000. S).

The disadvantage of this method is that ISS is adowanie only the degree of endogenous intoxication, without taking into account the functional status of the patient. The degree SEI is not possible to predict the further course of the pathological process, as the syndrome of endogenous intoxication is common in various injuries of the body, regardless of the location and nature of the lesion.

Closest to the claimed is a method of early diagnosis of neonatal sepsis, including determination in serum by enzyme immunoassay of anti-inflammatory cytokines of the tumor necrosis factor (TNF) and interleukin-8 (IL-8) (Patent No. 2180119. M CL 7 G 01 N 33/68. BIPM No. 6 2002. S.255).

The disadvantages of this method are as follows.

1. The presence of symptoms of inflammation does not give us a clear picture of the reaction of organs and systems using existing damage. The emergence of Pro-inflammatory cytokines indicates the beginning of the septic process in the body. In the presence of any pathological lesion in the body are activated protection system, which is inflammation.

2. These signs do not allow to predict the course and outcome of the disease. A well-functioning mechanisms of the immune system to prevent uncontrolled release cytokines and other mediators of inflammation, enable the normal body's response to inflammation.

3. To assess the reversibility of the process without additional m the methods is not possible.

The present invention is to improve the accuracy of determining the stage of the pathological process and the prediction of the development of septic complications in children with purulent-septic diseases.

This object is achieved in that define the content of the plasminogen/plasmin, α₂-macroglobulin, α₁-antitrypsin in 1, 3, 5, 10 day and if plasminogen/plasmin 66-74 µmol/l or 100-120 μmol/l, level, α₂-macroglobulin of 2.7-3.0 µmol/l, level, α₁-antitrypsin 2,38-3.2 µmol/l diagnosed with systemic inflammatory response to the presence of purulent infection, endotoxicosis mild severity and predicts favorable outcome of the disease. When the level of the plasminogen/plasmin 50-65 µmol/l or 125-160 µmol/l, level, α₂-macroglobulin 2,3-2.6 mmol/l, level, α₁-antitrypsin 3,3-4,0 mmol/l diagnosed with sepsis with organ dysfunction and systems, endotoxicosis moderate severity and predict the presence of septic complications and a prolonged course of the disease. When the level of the plasminogen/plasmin 39-45 µmol/l, level, α₂-macroglobulin 1,58-2,08 µmol/l, level, α₁-antitrypsin 5,0-6,2 mmol/l diagnosed with severe sepsis, septic shock, endotoxicosis severe and predict adverse outcome of the disease.

1. Selected as markers of septic process indicators proteins of acute phase of inflammation: the plasminogen/plasmin, α₂-macroglobulin, α₁-antitripsin.

2. Limits to the changes of these indicators of the severity of the pathological process.

3. Changes in the concentration of the plasminogen/plasmin indicates activation of proteolysis. About the state of the inhibiting factors is judged by the degree of changes in the level of α₂-macroglobulin and α₁-antitrypsin, which are natural inhibitors.

Diagnostic criteria specific early signs of sepsis may be used in pediatric practice after appropriate correction. The syndrome of systemic inflammatory response is a response of the organism to the presence of a pathological lesion and does not give a clear idea of the stage of the pathological process and the degree of destructive changes. Any pathological process, not dependent on the localization of the lesion, the body responds physiologically reasonable response aimed at limiting process. However, the inflammatory response only up to a certain time plays the role of protection. When endotoxicosis observed a direct effect of toxins on the vascular wall, which contributes to the activation of cellular proteolysis. Naru is a group of dynamic equilibrium between the activated proteolytic enzymes and their natural inhibitors lead to the development of septic shock, the end result of which is a generalized irreversible proteolysis. Thus, there are certain difficulties in evaluating the severity of the patient and the nature of the pathological process. Assessment of dynamic changes in the concentration of proteins of the acute phase of inflammation allows us to determine not only the stage of the pathological process, but also the nature of its course, and outcome of the disease. Conducted a comprehensive assessment of the severity of the patient, including the assessment of the functional status of the patient, the data analysis of laboratory parameters, calculating indices of intoxication (LII, RON), which allows to evaluate the body's response to the presence of the pathological focus. The assessment takes into account the degree of activation of proteolytic systems and natural inhibitors of this process.

The method consists in the following.

On admission the patient in intensive care unit patients examined the protein level of the acute phase of inflammation: the plasminogen/plasmin, α₂-macroglobulin, α₁-antitrypsin deficiency (low voltage rocket immunoelectrophoresis). The intake of these indicators was conducted at 1, 3, 5, 10 day illness and at discharge from hospital. These are the basic stages in the management of patients in these terms as necessary, conduct an audit of pathologic the ski center with subsequent correction therapy. In combination with clinical data (HR, BH, BP, body temperature, assessment of urine output), data from laboratory studies, the estimated indicators of the degree of endotoxemia (LII, RON) evaluated the severity of the patients predicted the course and outcome of the disease.

Assessment, determination of the stage of the pathological process was carried out for the following data.

1. While reducing the plasminogen/plasmin to 66-74 µmol/l or increased to 100-120 μmol/l, α₂-macroglobulin to 2.7-3.0 mmol/l, increase the level of α₁-antitrypsin to 2.38-3.2 µmol/l was diagnosed with systemic inflammatory response to the presence of purulent infection, endotoxicosis mild severity and predicted a favorable outcome of the disease.

2. While reducing the plasminogen/plasmin to 50-65 µmol/l) or increase to 125-160 µmol/l, reducing α₂-macroglobulin to 2.3-2.6 mmol/l, increase the level of α₁-antitrypsin to 3.3-4.0 mmol/l was diagnosed with sepsis with organ dysfunction and systems, endotoxicosis moderate severity. Predicted presence of septic complications and a prolonged course of the disease.

3. While reducing the plasminogen/plasmin to 39-45 µmol/l, level, α₂-macroglobulin 1.58-2,08 µmol/l, the increase in the level of α₁-antitrypsin to 5,0-6,2 mcmall diagnose severe sepsis, septic shock, endotoxicosis severe and predict adverse outcome of the disease. When the diagnosis in a patient with severe sepsis there is an imbalance of all systems of homeostasis, characterized by uncontrolled aggressive for generalized inflammation and proteolysis. The patient's condition even with adequate therapy is extremely heavy, low reversibility of the process and a high percentage of aircraft outcome.

The definition of early activation of proteolysis and state inhibiting factors allows early to intensify and skorrelirovat therapy. Depending on the stage of the process corrigiola antibacterial therapy, infusion-transfusion and respiratory therapy aimed at improving tissue perfusion, applied inhibitors of proteinases.

Example 1.

Patient C. 3 years(East. disease No. 1067). He enrolled in the intensive care unit with a diagnosis of flegmonoznih appendicitis. Diffuse peritonitis. State upon receipt of moderate severity through mild endotoxemia: heart rate 120-140 min, shortness of breath up to 32-36 min, body temperature 38,0°C, a slight decrease of diuresis. Laboratory: leukocytosis with 9,5 n/I shift in the formula blood up to 20%, LII - 2,3. RON is 9,85. Level ostrofsky proteins were measured in the dynamics. The patient was operated. In the dynamics of indicators of the following:

Conclusion. With a slight decrease in the level of the plasminogen/plasmin in the blood serum level of inhibitory factors - α₂-macroglobulin and α₁-antitrypsin deficiency remains within age norms, diagnosed endotoxicosis mild severity. Classied by us as the development of systemic inflammatory response to inflammation. Treatment is the standard therapy aimed at correction of water-electrolyte metabolism, antibiotic therapy with 2 drugs. The postoperative period is smooth. The normalization parameters to 5 days. The patient was discharged with recovery.

Example 2.

Conclusion.

While reducing the plasminogen/plasmin and α₂-macroglobulin by 30% from age norms, increase the level of α₁-antitripsin to 3.4 in combination with signs of severe endotoxemia condition of the patient is heavy, RSIS with signs of multiple organ dysfunction. The patient was performed correction of fluid and electrolyte status, antibiotic therapy with 2 drugs, twice a revision of the abdominal cavity. Sick threaten in the development of septic complications. It was noted the protracted course of the disease.

Example 3.

Patient R. 2 years 3 months (the ist. disease No. 3589). He enrolled in the intensive care unit with a diagnosis of acute gangrenous-perforated appendicitis. Periappendicular abscess. Diffuse peritonitis. The condition for admission is extremely heavy due to the clear of endotoxemia. Tachycardia up to 180 min, shortness of breath up to 42 min, T 38,2°With, disturbance of microcirculation - marbling, paleness of the skin, dramatically reduced diuresis. Laboratory: leukocytosis up to 17 with p/I shift to 14-20%, LEAH 4,7. RON 46,2. After preoperative preparation of the patient operated on. The patient was observed severe postoperative period. The patient was on a ventilator required Pressor support. The ambiguity of obratno was conducted revision of the abdominal cavity. For a long time preserved signs of multiple organ failure with slow regression process. Was observed following the concentration of proteins of the acute phase of inflammation:

Conclusion. With a sharp lowering of the level of the plasminogen/plasmin and α₂-macroglobulin, more than 50% from age norms, a sharp increase in the level of α₁-antitrypsin can talk about the inadequate response of natural inhibitors have dramatically activated the process of proteolysis. The patient was a long time on a ventilator, was carried out Pressor support, correction of all hemodynamic parameters, water-electrolyte is about sharing, hemostasis, CSR. Repeatedly carried out sanitation of the abdominal cavity, has long been used laparostomy. The phenomenon of functional intestinal obstruction and PON were stopped slowly. In this situation, the patient noted a generalization of infection, sepsis with multi-organ failure. In this category of patients even with adequate therapy high percentage of deaths.

The proposed method is used in MDCB No. 7 core. For the period 2001-2002 investigated more than 30 patients with different severity of the condition and different localization of the nidus, under treatment in the intensive care unit MDCB No. 7.

Example 4.

Sick So 13 years old (case history No. 6942). He enrolled in the intensive care unit with a diagnosis of acute pyelonephritis. State upon receipt of moderate severity through mild endotoxemia: HR 110-112 min, shortness of breath up to 26 min, body temperature of 38.2°C. Laboratory: leukocytosis with a 9.7 n/I shift in the formula blood to 11%, LII - to 3.58. RON - 15,06. Level ostrofsky proteins were measured in the dynamics. In the dynamics of indicators of the following:

Conclusion. With a slight increase at the onset of disease level of the plasminogen/plasmin and lowering α₂-macroglobulin and a slight increase α₁-antitrypsin in serum compared with the age norm diagnosed endotoxicosis mild severity. Classied by us as the development of systemic inflammatory response to the presence of serous inflammation. The patient received standard therapy aimed at correction of water-electrolyte metabolism, antibiotic therapy with 2 drugs. The normalization parameters to 5 days. The patient was discharged with recovery.

Example 5.

Patient 3. 13 years old (case history No. 6197). He enrolled in the intensive care unit with a diagnosis of acute hematogenous osteomyelitis of the tibia. Cellulitis of the lower third of the leg. State when the pic is upline heavy. Endotoxicosis moderate: tachycardia 112-126, shortness of breath up to 30 min, T 38,9-39°C, moderate cyanosis, breathing hard, laboratory: leukocytosis 18 with p/I shift 16%, LEAH 4,27, RON - 44,72, R is a picture of shock lung 2 tbsp. After preoperative preparation of the patient was operated. The postoperative period of severe, signs of multiple organ failure. The patient was repeatedly carried out the reorganization of the nidus. The concentration of acute phase proteins following:

Conclusion. When the level increases, the plasminogen/plasmin and level α₁-antitrypsin and lowering α₂Mac is globulina from age norms in combination with signs of endotoxemia moderate severity was diagnosed with sepsis with evidence of organ dysfunction. The patient was performed correction of fluid and electrolyte status, antibiotic therapy with 3 drugs, repeatedly conducted the audit of the pathological process. Sick threaten in the development of septic complications. It was noted the protracted course of the disease.

The proposed method is used in MDCB No. 7. core.

For the period 2001-2002 investigated more than 30 patients with different severity of the condition and different localization of the nidus, under treatment in the intensive care unit MDCB No. 7.

Method for the diagnosis of septic process and predict the development of septic complications in children, including determination in blood proteins, characterized in that define the content of the plasminogen/plasmin, α₂-macroglobulin, α₁-antitrypsin, 1, 3, 5, 10 day and at the level of the plasminogen/plasmin 66-74 µmol/l or 100-120 μmol/l, level, α₂-macroglobulin of 2.7-3.0 µmol/l, level, α₁-antitrypsin 2,38-3.2 µmol/l diagnosed with systemic inflammatory response to the presence of purulent infection, endotoxicosis mild severity and predicts favorable outcome of the disease, when the level of the plasminogen/plasmin 50-65 µmol/l or 125-160 µmol/l, level, α₂-macroglobulin 2,3-2.6 mmol/l, level, α₁-antitrypsin 3,3-4,0 mmol/l diagnostician who shape the development of sepsis with organ dysfunction and systems endotoxicosis moderate severity and predict the presence of septic complications and a prolonged course of the disease, when the level of the plasminogen/plasmin 39-45 µmol/l, level, α₂-macroglobulin 1,58-2,08 µmol/l, level, α₁-antitrypsin 5,0-6,2 mmol/l diagnosed with severe sepsis, septic shock, endotoxicosis severe and predict adverse outcome of the disease.