Method of early prognosis of course of acute poisoning with psychotropic drugs

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine, in particular toxicology and resuscitation science and can be used for early prognosis of course of acute poisoning with psychotropic drugs. At the time of patient's admission to hospital albumin fraction of blood serum is isolated. After that, general level of reduced thiols is determined, and if its value is lower than 220 mcmol/l development of negative disease dynamics is predicted.

EFFECT: method allows to increase efficiency of performed treatment in said category of patients.

1 tbl, 8 ex

 

The invention relates to the field of medicine - toxicology, resuscitation.

It is known that Ecotoxicity accompanied by endotoxemia, which exacerbate the disease (Luzhniki E.A. Clinical toxicology. M.: Medicine, 1999). Currently, it is proved that in the pathogenesis of endotoxemia great importance is the state of transport systems in the blood, particularly albumin. This protein is responsible for the transfer of many toxic metabolites and xenobiotics, including drugs. In addition, due to the presence of (usually) free thiol group in the molecule of the protein albumin in the blood makes a significant contribution to antioxidant protection of the organism as a "sacrificial" antioxidant [Century Halliwell, Gutteridge J.M. The antioxidants of human increasing interest among fluids. Arch Biochem Biophys. 1990; v.280 No. 1:1-8; T. Peters, Jr. All about Albumin. Biochemistry, Genetics, and Medical Applications, Academic Press, San Diego, 1996, 452 pp.].

Structure and functions of proteins are interrelated terms, therefore, the research Institute of physical-chemical medicine health Ministry developed and proposed methods of fluorescent probes to study various changes in the structure of certain components of the blood. Using these probes, as well as other physical methods it is shown that under certain pathological processes changes the conformation of the protein globule albumin [Gryzunov Yu.A., Dobretsov G.E. Natural conformation of human serum albumin and its changes in pathology. n: Protein Conformation: New Research/ Editor: L.B. Roswell. Nova Publishers, New York,. 2008, 125-159]. She, in turn, can determine the steric accessibility of drug binding centers and thiol groups of albumin and, therefore, their functional ability. Currently, however, toxicology has only very limited information about the role of albumin concentration, the reactivity of its thiol group and its functional status in patients with endotoxemia and about the possibility of prognosis of acute poisoning with psychotropic drugs with albumen indicators.

We have conducted research albumen fractions of the blood serum in 25 patients with acute poisoning by psychotropic drugs and 21 healthy individuals. Restored thiols were determined using 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) in the reaction of Ellman [Ellman G.L. Tissue sulfhydryl groups. Arch. Biochem. Biophys. 1959; v.82, No. 1:70-77; Ellman G. Lysko H. A precise method for the determination of whole blood and plasma sulfhydryl groups. Anal. Biochem. 1979; v.93 No.1:98-102].

Patients were examined on admission to the hospital on a background of intensive treatment. Studies in healthy individuals (table) revealed a General level of thiols albumen fraction of serum - 780±6 µmol/l on admission of patients with acute poisoning by psychotropic drugs in the hospital (table) General level restore the military bovine serum albumen fraction of serum was 523±8 µmol/L. In the group of patients with subsequent favorable outcome values of this index at admission was 600±8 (µmol/l), and in patients with subsequent fatal General level of thiols albumen fractions of the blood serum was significantly dramatically reduced 4.5 times - on average up to 134±2 (µmol/l). In the group of patients with the level of thiols albumen fraction of serum above 220 µmol/l (18 people) deaths were observed. Level values are recovered were identified in 7 patients, of whom 4 patients died. Thus, the prognostic performance (proportion of correct predictions made among observations) amounted to 0.96 (95%confidence interval from 0.89 to 0.99), i.e. the investigated group of patients method showed the correct results in 96% of cases. The obtained data allowed us to predict adverse outcome in patients with acute poisoning by psychotropic drugs (SFC) with the values in the General level of thiols serum below 220 µmol/l and a favorable outcome at values above 220 µmol/l immediately upon admission to the hospital.

The method is as follows. Blood from patients took no preservative in dry glass tube. Separating the serum by centrifugation for 10 minutes the ri 300 g. Then allocated albumen fraction of blood serum by precipitation of much of the rest of whey proteins using a 30% solution of polyethylene glycol (PEG) with molecular weight of 3000 Da in phosphate buffer solution (pH 6.4) by centrifugation for 10-15 minutes at 600 g. On the photometer KLF-3 was determined by the total concentration of thiols albumen fractions of the blood serum through reaction with 5,5'-dithiobis(2-nitrobenzoic acid) absorption of light at a wavelength of 412 nm taking into account blank sample without albumin in 20 minutes after start of the reaction. The concentration of the recovered SH-groups albumen fraction was calculated in relation to the value of the extinction of the complex DTNB with bovine serum albumin (13000 1/(mol*cm)) [Ellman G. Lysko H. A precise method for the determination of whole blood and plasma sulfhydryl groups. Anal. Biochem. 1979; v.93 No.1: 98-102]. When is the total concentration of thiols albumen fractions of the blood serum is less than 220 µmol/l predicted a high risk of negative dynamics of the disease.

The overall level of thiols albumen fractions of blood serum (µmol/l)in patients with acute poisoning by psychotropic drugs (SFC) at admission
The number of the examined Healthy peopleAll patients SFCPatients SFC survivorsPatients SFC dead
2125214
M±m780 ±6523±8600±8134±2*
range250-125081-1200100-120081-210
Note: * - p≤0,05 significant differences between groups of patients SFC on nonparametric criterion of Wilcoxon-Mann-Whitney.

CLINICAL EXAMPLES

1. Patient K., 70 years. Diagnosis: Acute poisoning fenazepam II-b class. Upon admission to the hospital: coma with respiratory disorders by mixed type, pneumonia, level of consciousness on a scale Glasgow 3 points, a serious condition. The overall level of thiols albumen fraction of serum was 81 µmol/l is below the lower limit of 220 µmol/L. the Patient, in spite of intensive therapy, he died 12 hours later.

2. Patient A., 56 years. Diagnosis: Acute poisoning with a mixture of psychotropic drugs. When is tuplenie in the hospital: coma, complicated by respiratory failure by mixed type, level of consciousness on a scale Glasgow 10 points, Ecotoxicity shock. The condition of the patient is severe. Clinical blood test on admission: hemoglobin 142 g/l, hematocrit 42%, leukocytes 12,0×109/l, stab neutrophils 15%, segmented neutrophils 61%, lymphocytes 16%, monocytes 8%, erythrocyte sedimentation rate (ESR) 24 mm/hour. Biochemical blood test: whole protein 79 g/l, urea 37.5 mmol/l, creatinine 265,5 µmol/l, total bilirubin 9,12 µmol/l, glucose 4,6 mmol/L. Overall level of thiols serum was 125 µmol/l is below the lower limit of 220 µmol/L. the Patient, despite intensive therapy, died within 18 hours of receipt.

3. Patient S., 56 years. Diagnosis: Acute poisoning with a mixture of psychotropic drugs II-b class. Upon admission to the hospital: coma complicated by respiratory failure by mixed type, level of consciousness on a scale Glasgow 3 points. The condition of the patient is severe. Clinical blood test on admission: hemoglobin 100 g/l, hematocrit of 29%, leukocyte count of 4.9×109/l, stab neutrophils 8%, segmented neutrophils 75%, lymphocytes 14%, monocytes 3%, erythrocyte sedimentation rate (ESR) 14 mm/hour. Biochemical blood test: whole protein or 56.1 g/l, urea 5.5 mmol/l, creatinine 95,0 µmol/l, total bilirubin of 9.3 mmol/l, glucose 8,1 is mol/L. The overall level of thiols albumen fraction of serum was 210 µmol/l is below the lower limit of 220 µmol/l, the patient died after 36 hours, despite intensive therapy.

4. Patient K., aged 34. Diagnosis: Acute poisoning with a mixture of psychotropic drugs II-b class. Upon admission to the hospital: coma complicated by respiratory failure by mixed type, level of consciousness on a scale Glasgow 3 points. The condition of the patient is severe. Clinical blood test on admission: hemoglobin 130 g/l, hematocrit 38%, leukocyte count of 6.3×109/l Biochemical blood test: whole protein - 54 g/l, urea - 4.3 mmol/l, creatinine - 124,0 µmol/l, total bilirubin - 5.17 mmol/l, glucose - 8.6 mmol/L. Overall level of thiols serum was 450 µmol/l higher than the boundary 220 µmol/l in the Intensive therapy consisted of: artificial ventilation, active detoxification methods, and the patient was discharged on the 6th day in a satisfactory condition.

5. Patient K., aged 44. Diagnosis: Acute amitriptyline poisoning II-b class. Upon admission to the hospital: coma complicated by respiratory failure on the suction type, level of consciousness on a scale Glasgow 5 points. The condition of the patient is severe. Clinical blood test on admission: hemoglobin 134 g/l, hematocrit 40%, leukocyte count of 7.6×109/l, stab neutrophils 9%, CE is mantadine neutrophils 78%, lymphocytes 8%, monocytes 5%, erythrocyte sedimentation rate of 6 mm/h. Biochemical blood test: whole protein 76 g/l, urea of 8.2 mmol/l, creatinine 99,4 µmol/l, total bilirubin 6.2 mmol/l, glucose of 8.1 mmol/L. Overall level of thiols albumen fraction of serum was 670 µmol/l higher than the boundary 220 µmol/l was a complex of intensive therapy with positive dynamics, and the patient was discharged on the 8th day.

6. Patient W., age 17. Diagnosis: Acute poisoning azaleptinum II and class. Upon admission to the hospital: coma complicated by respiratory failure on mechanical type, level of consciousness on a scale Glasgow 6 points. The patient's state of moderate severity. Clinical blood test on admission: hemoglobin 103 g/l, hematocrit 31%, leukocyte count of 7.6×109/l, stab neutrophils 24%, segmented neutrophils 60%, lymphocytes 12%, monocytes 4%, ESR 13 mm/h. Biochemical blood test: whole protein, 70 g/l, urea of 4.9 mmol/l, creatinine of 80.6 mmol/l, total bilirubin of 7.75 mmol/l, glucose 6.5 mmol/L. Overall level of thiols serum amounted to 552 μmol/l higher than the boundary 220 µmol/l was a complex of intensive therapy with positive dynamics, and the patient was discharged on the 4th day.

7. The patient, 87 years of age. Diagnosis: Acute poisoning by psychotropic drugs II-a degree. Upon admission to the hospital: coma, complicated n is a violation of respiratory mechanical type, the level of consciousness on a scale Glasgow 6 points. The condition of the patient is severe. Clinical blood test on admission: hemoglobin 86 g/l, hematocrit of 23%, leukocyte count of 5.1×109/l, stab neutrophils 20%, segmented neutrophils 61%, lymphocytes 13%, monocytes 6%, ESR 13 mm/h. Biochemical blood test: whole protein of 51.6 g/l, urea of 14.2 mmol/l, creatinine 196 μmol/l, total bilirubin of 9.3 mmol/l, glucose 4,2 mmol/L. Overall level of thiols serum was 221 µmol/l higher than the boundary 220 µmol/l was a complex of intensive therapy with a positive and the patient was discharged on the 14th day.

8. Patient L., aged 57. Diagnosis: Acute poisoning azaleptinum II-b class. Upon admission to the hospital: coma complicated by respiratory failure on the suction type, level of consciousness on a scale Glasgow 5 points. The condition of the patient is severe. Clinical blood test on admission: hemoglobin 156 g/l, hematocrit of 44%, leukocytes to 11.9×109/ l, stab neutrophils 14%, segmented neutrophils 69%, lymphocytes 10%, monocytes 7%, erythrocyte sedimentation rate of 6 mm/h. Biochemical blood test: whole protein 66 g/l, urea 5.3 mmol/l, creatinine 69 µmol/l, total bilirubin 13.3 mmol/l, glucose of 8.2 mmol/L. Overall level of thiols serum was 230 µmol/l higher than the boundary 220 µmol/L. the Patient was conducted intensive tera the Oia and on the 9th day the patient was discharged.

Using the proposed method of early prediction of acute poisoning with psychotropic drugs in the General level of thiols serum of patients on admission to hospital allows the physician to a toxicologist or doctor-the resuscitation accurately assess the patient's condition and to determine the amount of the adequate measures for each patient individually.

The method of early prediction of acute poisoning with psychotropic drugs, including the allocation of albumen fraction from the serum of the patient upon admission to the hospital and determination in her General level of thiols, and when its value is less than 220 µmol/l predict the development of negative dynamics of the disease.



 

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