RU2379034C1 - Method of treating haemorrhagic fever with renal syndrome - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to inflectional diseases, and can be applied for treatment of patients with haemorrhagic fever with renal syndrome of medium- severe forms. For this purpose traditional basic therapy is carried out and since first day of disease additionally by intravenously drip introduced is medication emoxypin. Since 6-th day of therapy 1% emoxypin is introduced intramuscularly in amount 0.5 ml 2 times per day during 10 days.

EFFECT: method insures reduction of treatment terms, also due to improvement of nitrogen-excretion renal function, reduction of endotoxicosis, improvement of oxidative reactions and immunomodulaton.

7 tbl, 2 ex

Description

The invention relates to medicine, namely to the treatment of infectious diseases, and can be used in the treatment of patients with hemorrhagic fever with renal syndrome (HFRS) of moderate and severe forms.

It is known that the infection process in HFRS is accompanied by the development of oxidative stress and depletion of the antioxidant defense system, the objective criteria of which are preserved by the period of early convalescence, which justifies the use of drugs with an antioxidant mechanism of action (Pavelkina V.F., Laseeva MG, Pak S .G., Erovichenkov AA Intoxication syndrome in patients with hemorrhagic fever with renal syndrome. // Infectious diseases. - 2008. - T. 6, No. 1. - P.41-46).

The effectiveness of emoxipin in the treatment of HFRS of moderate severity has been proved (Pavelkina V.F., Laseeva M.G., Ampleeva N.P. Results of a study of the effectiveness of emoxipin in hemorrhagic fever with renal syndrome. // Infection in clinical practice. Antibacterial and long-term therapy and the hospital stage: Materials of scientific-practical conferenceii with international participation. - Kharkiv, 2008. - P.32-33). In addition to basic treatment, patients received emoxipin in a short course - 1% intravenously, 15.0 ml in 200 ml of a 0, 9% sodium chloride solution, 1 time per day for 5 days (daily).

The disadvantage of this method is the following: emoxipin at a specified dose had a certain detoxification and antioxidant effect, however, many objective indicators of intoxication syndrome remained elevated by the period of early convalescence, which indicates the preservation of the pathological process and the possible development of complications, which indicates an insufficient course of treatment and continued correction the above processes.

The technical result consists in increasing the efficiency of treatment of patients with hemorrhagic fever with moderate and severe renal syndrome due to a positive effect on the course of the disease (reduction of disease periods), improvement of the nitrogen excretory function of the kidneys, indicators of endotoxemia, oxidative reactions, stimulation of antioxidant defense factors and the functional state of albumin .

The essence of the invention lies in the fact that in the method of treating hemorrhagic fever with renal syndrome, which includes basic therapy from the first day of the disease and the introduction of an intravenous drip of the drug emoxipin, an additional intramuscular injection of emoxipine is administered for 6 days 1% - 5.0 ml, 2 times a day over the next 10 days.

The method is as follows. From the first day of hospitalization, patients with HFRS of moderate to severe forms of the disease receive 15 ml of a 1% solution of emoxipine in 200 ml of a 0.9% solution of sodium chloride for 5 days intravenously every day, once a day, during basic therapy. Then emoxipin is administered intramuscularly 1% - 5.0 ml, 2 times a day, for 10 days (daily). The total course of treatment is 15 days.

To assess the effectiveness of therapy, patients were divided into 2 groups. The first group - 50 patients (35 with moderate and 15 with severe HFRS) received basic therapy and made up the comparison group. The second (main) group of 30 patients (20 with moderate and 10 with severe HFRS), in addition to the basic treatment, was prescribed the antioxidant drug emoxipin with a general course of 15 days. To control the laboratory parameters, a group of practically healthy individuals (30 people) was examined.

Basic therapy:

Since all patients were admitted to the hospital on day 4-5 of the disease, at the end of the febrile period, etiotropic therapy was not prescribed.

Pathogenetic therapy was as follows: in the oliguric period (from the moment of admission), patients with moderate flow received intravenous drip of 200 - 400 ml of 0.9% sodium chloride solution with 5.0 ml of 5% ascorbic acid solution, 200-400 ml of 5% solution glucose with 5 ml of a 2.4% solution of aminophylline, lasix 20-40 mg, diazolin 100 mg 3 times a day, ascorutin 1 tablet 3 times a day; patients with severe course received an additional 60 mg intravenous prednisone. Symptomatic therapy is represented by antipyretic drugs - paracetamol 200 - 400 mg with an increase in body temperature above 38.5 ° C, in the absence of effect, a lytic mixture was injected intramuscularly - 2 ml of a 50% solution of dipyrone and 1 ml of a 1% solution of diphenhydramine, antispasmodics - 2 ml 2% a solution of papaverine hydrochloride intramuscularly, 2 times a day, with vomiting intramuscularly, 2 ml of cerucal was prescribed, inside a 0.25% solution of novocaine 1 tablespoon 3 times a day. In order to prevent bacterial complications, ampicillin 1000 mg 4 times a day was administered intramuscularly.

During the polyuric period, diuretics were canceled and intravenous administration of a 0.9% solution of sodium chloride and complex salt solutions — Trisol and Chlosol — were prescribed.

The following indicators were determined as criteria for evaluating the effectiveness of antioxidant therapy:

1) clinical - the duration of fever, weakness, oliguria, polyuria;

2) biochemical - the level of urea, creatinine;

3) the dynamics of indicators of endotoxemia - medium-weight molecules (MSM at λ 254 and 280 nm), circulating immune complexes (CIC), the functional state of albumin - the total and effective concentration of albumin (OCA, ECA); albumin binding capacity (CCA), albumin toxicity index (IT);

4) the dynamics of indicators of oxidative reactions and antioxidant protection - malondialdehyde (MDA), plasma catalase and red blood cells.

The proposed method allows to reduce the duration of symptoms such as fever, weakness, oliguria, polyuria in comparison with a group of patients who received only conventional pathogenetic therapy.

When studying the effect of emoxipin therapy on the clinical course in patients with moderate forms of HFRS, it was noted that the duration of fever in both groups was different. So, in the comparison group it was 6.13 ± 0.74 days, and in the main group it was 4.20 ± 0.43 days (p <0.05); the duration of general weakness was 23.10 ± 1.30 days with basic therapy and 18.70 ± 1.50 days with additional use of emoxipin (p <0.05). The duration of the oliguric period also changed under the influence of emoxipin, in the comparison group it was 5.10 ± 0.67 days, and in the main group - 3.40 ± 0.43 days (p <0.05). The polyuric period was significantly shorter in the main group than in the comparison group — 3.20 ± 0.50 and 4.80 ± 0.58 days, respectively (Table 1).

In patients with severe HFRS, the duration of fever was reduced from 9.78 ± 0.65 days in the comparison group to 7.90 ± 0.53 days in the main (p <0.05), general weakness, respectively, from 26.80 ± 1 , 10 days to 23.10 ± 1.25 days (p <0.05), oliguria - from 7.99 ± 0.77 days to 6.00 ± 0.47 days (p <0.05), polyuria - from 7.90 ± 1.10 to 5.04 ± 0.63 days (Table 1).

When emoxipin was used in the complex therapy of patients with HFRS, positive dynamics of laboratory parameters of the nitrogen-excreting function of the kidneys (urea and creatinine) was observed compared with patients who did not receive emoxipin. By the period of early convalescence, the values of these indicators significantly differed in the studied groups and were lower in the group with the appointment of emoxipin (Tables 2, 3).

In the analysis of endotoxemia indicators for the period of early convalescence, the antioxidant and detoxifying effect of emoxipin was revealed in patients with moderate to severe HFRS. It has been established that with the additional use of emoxipin in the complex therapy of HFRS to the period of early convalescence, the content of medium-weight molecules (MSM ₂₅₄ and MSM ₂₈₀ ), malondialdehyde are normalized, circulating immune complexes are reduced compared to the group receiving only basic therapy. When studying the effect of emoxipin on antioxidant defense indices in patients with moderate to severe HFRS, normalization of plasma catalase and red blood cells was revealed (Table 4).

In severe HFRS, emoxipin additionally applied to basic therapy helped normalize MSM ₂₅₄ , MDA, decrease MSM ₂₈₀ , CEC, increase antioxidant potential (CP, CE) (Table 5).

When studying the effect of emoxipin on the parameters of albumin tests in patients with moderate severity of HFRS, normalization of the functional properties of albumin (OCA, ECA, CCA, IT) in the main group to the period of early convalescence was revealed (Table 6).

In severe HFRS, emoxipin additionally applied to basic therapy helped to improve the functional properties of albumin - OCA, which did not differ from the level of healthy individuals, normalize ECA, increase CCA, and decrease IT in albumin (Table 7).

A clinical example illustrating the results in a group of patients with moderate to severe HFRS.

Patient P., 43 years old, was in ward №7 of the Municipal Clinical Hospital "GIKB" in Saransk from 11/06/07 to 11/23/07 with a diagnosis of hemorrhagic fever with renal syndrome, moderate severity. The diagnosis was confirmed by the serological method, in the reaction of indirect immunofluorescence (RNIF) with the HFRS virus antigen dated 11/12/07 (10th day of illness), antibodies were detected in titer 1: 256 of 11/19/07 (17th day of illness) in titer 1: 1024. He was admitted to the hospital on the 4th day of illness with complaints of weakness, fever up to 39 ° C with chills, dry mouth, headache, pain with eye movement. He became ill sharply, on November 3, 2007, when his body temperature increased to 39 ° C, which remained at a high level in the following days, a headache periodically occurred, and on the 3rd day of the disease, back pain appeared. On the 4th day of the disease, he turned to a local therapist, was sent to the Municipal Clinical Hospital "GIKB" with a diagnosis of "Acute respiratory viral infection."

Epidemiological history: works in OJSC “Saransk factory of dump trucks”, where there are mice.

Upon admission to the hospital, the patient’s state of moderate severity continues to be in a fever, body temperature 38.1 ° C, back pain, visual impairment in the form of fog before the eyes. Marked vascular injection of the sclera, moderate hyperemia of the posterior pharyngeal wall, single petechilic elements in the soft palate. A pulse of 100 beats per minute, blood pressure - 130 and 80 mm Hg The tongue is dry, slightly coated with a white coating. The abdomen is swollen, painful in the epigastric region, lateral parts. The liver is enlarged, protrudes from under the edge of the costal arch by 3 cm. Rattling along the lumbar region is slightly painful on both sides.

In addition to the basic therapy, the patient was prescribed a 1% solution of emoxipin 15 ml in 200 ml of a 0.9% sodium chloride solution for 5 days. Then emoxipin was administered intramuscularly 1% - 5.0 ml, 2 times a day, for 10 days (daily). The total course of treatment was 15 days.

During therapy, the fever decreased on the 2nd day of treatment, oliguria kept up to 750 ml for 3 days, lower back pain - 3 days, polyuria up to 3.5 liters per day - 4 days, general weakness - 17 days. The further course was smooth, no complications were observed, and the patient was discharged in satisfactory condition.

Laboratory data - on the day of admission and after 15 days of treatment:

November 6, 2007: General blood test: hemoglobin - 136 g / l, white blood cells - 10.5 × 10 ⁹ / l, ESR - 36 mm / h. General urine analysis: protein - 756 mg / l, specific gravity -1009, white blood cells - 3-4 in the field of view, red blood cells - 4-6 in the field of view.

11/22/07: General blood test: hemoglobin - 145 g / l, white blood cells - 6.1 × 10 ⁹ / l, ESR - 11 mm / h. General urine analysis: protein - no, specific gravity - 1004, white blood cells - 1-2 in the field of view, red blood cells - 0-1 in the field of view.

Blood chemistry:

November 6, 2007: Urea - 12.4 mmol / L, creatinine - 173 μmol / L, Alt - 0.83 mmol / (L · h), ACT-0.41 mmol / (L · h), total bilirubin - 8.5 μmol / L.

11/22/07: Urea - 6 mmol / L, creatinine - 101 μmol / L, Alt - 0.73 mmol / (L · h), AcT - 0.49 mmol / (L · h), total bilirubin - 8 , 08 μmol / L.

Endotoxemia indicators:

November 6, 2007: MSM ₂₅₄ - 0.432 cu, MSM ₂₈₀ - 0.397 cu, CEC small - 130 cu

11/22/07: MSM ₂₅₄ - 0.232 cu, MSM ₂₈₀ - 0.265 cu, small CEC - 85 cu

Albumin tests.

November 6, 2007: OKA - 39 g / l, ECA - 35 g / l, SSA - 89.74%, IT - 0.12.

11/22/07: OKA - 46 g / l, ECA - 44.5 g / l, SSA - 96.73%, IT - 0.03.

Indicators of oxidative reactions and antioxidant protection:

November 6, 2007: MDA - 6.89 μmol / L, plasma catalase - 2.63 μkat / L, erythrocyte catalase - 2.19 μkat / L.

11/22/07: MDA - 2.88 μmol / L, plasma catalase - 4.95 μkat / L, erythrocyte catalase - 4.12 μkat / L.

A clinical example illustrating the results in a group of patients with severe HFRS.

Patient E., 50 years old, was treated in the 7th department of the Municipal Clinical Hospital “GIKB” from 10.30.07 to 11.19.07. Clinical diagnosis: Hemorrhagic fever with renal syndrome, severe course. Infectious toxic shock of the 1st Art. The diagnosis was confirmed by the serological method - an increase in the titer of antibodies to HFRS virus in RNIF in paired sera (1: 64-1: 256).

The patient was admitted to the hospital on the 4th day of illness with complaints of severe weakness, headache, abdominal and lower back pain, visual impairment, dry mouth, and a decrease in urine. From the anamnesis: she became acutely ill, her body temperature increased to 40 ° C with chills, a headache appeared, and in the evening repeated vomiting. On the third day of the disease, back pain joined, noted a deterioration in vision, a decrease in the amount of urine. She took antipyretics at home, and did not seek medical help. 10.30.07, she went to the clinic, was sent to a hospital with a diagnosis of "Hemorrhagic fever with renal syndrome", was hospitalized.

Epidemiological history: In mid-October, I went to the countryside, where I cleaned the cellar.

An objective examination at the time of admission of the patient to the hospital is in serious condition, temperature 39.2 ° C, the patient is sluggish. The face, neck, upper half of the body are hyperemic, the face is puffy. Sclera are injected, single small hemorrhages, hemorrhagic enanthema on the mucosa of the hard palate. In the lungs, vesicular breathing, wheezing is not heard. Heart sounds are muffled, systolic murmur at the apex, heart rate of 120 beats / min, blood pressure of 100 and 80 mm. Hg. Art. The tongue is dry, densely coated with a white coating. The abdomen is moderately swollen, with palpation of a painful side, in the epigastric region. The symptom of lumbar effusion is positive on both sides. Diuresis 650 ml / day.

The patient was prescribed, in addition to basic therapy, a 1% solution of emoxipin 15 ml in 200 ml of a 0.9% solution of sodium chloride for 5 days. Then, emoxipin is administered intramuscularly 1% - 5.0 ml, 2 times a day, for 10 days (daily). The total course of treatment was 15 days.

On the 5th day of illness (10/31/07), the patient's condition remained severe, the temperature remained up to 38.7 ° C, dry mouth, pain in the lumbar region and abdomen, decreased urine (less than 500 ml). The next day, the temperature dropped to 37.5 ° C, there was a decrease in daily urine output to 370 ml, the general condition worsened, an infectious-toxic shock of the 1st stage was detected, the patient was transferred to the intensive care unit. Since November 2, temperature has returned to normal. The manifestations of intoxication and pain were gradually reduced. General weakness persisted for 23 days. Oliguria lasted 6 days, from November 3, 07, diuresis began to increase to 850 ml and reached 3.5 liters in two days, the period of polyuria lasted 5 days. The period of early convalescence proceeded normally, without complications, a large one was discharged in satisfactory condition.

Laboratory data - on the day of admission and after 15 days of treatment:

10/30/07: General blood test: hemoglobin - 135 g / l, white blood cells -13.0 × 10 ⁹ / l, ESR - 31 mm / h. Urinalysis: protein - 1792 mg / l, specific gravity - 1010, white blood cells - 5-6 in the field of view, red blood cells - 3-4 in the field of view.

11/15/07: General blood test: hemoglobin - 154 g / l, white blood cells 7.5 × 10 ⁹ / l, ESR -19 mm / h. General urine analysis: protein - 36 mg / l, specific gravity - 1002, white blood cells - 1 - 2 in the field of view, red blood cells - 0-1 in the field of view.

Blood chemistry:

10/30/07: Urea - 20.4 mmol / L, creatinine - 385 μmol / L, Alt - 0.85 mmol / (L · h), AcT - 0.83 mmol / (L · h), total bilirubin - 8.1 μmol / L.

11/15/07: Urea - 6.3 mmol / L, creatinine - 120.0 μmol / L, Alt - 0.25 mmol / (L · h), AcT - 0.42 mmol / (L · h), total bilirubin 5.4 - mcmol / l.

Endotoxemia indicators:

10.30.07: MSM ₂₅₄ - 0.532 cu, MSM ₂₈₀ - 0.708 cu, small CEC - 200 cu

11/15/07: MSM ₂₅₄ - 0.262 cu, MSM ₂₈₀ - 0.325 cu, small CEC - 105.0 cu

Albumin tests.

10/30/07: OKA - 34 g / l, ECA - 28 g / l, SSA - 82.35%, IT - 0.21.

11/15/07: OKA - 42 g / l, ECA - 40 g / l, SSA - 95.24%, IT - 0.05.

Indicators of oxidative reactions and antioxidant protection:

10/30/07: MDA - 10.86 μmol / L, plasma catalase - 1.3 μkat / L, erythrocyte catalase - 1.4 μkat / L.

11/15/07: MDA - 3.17 μmol / L, plasma catalase - 3.99 μkat / L, erythrocyte catalase - 3.5 μkat / L.

The inclusion of additional emoxipin for 10 days intramuscularly had a positive effect on the clinical course of the disease, indicators of endotoxemia, oxidative-antioxidant status and functional state of albumin.

Thus, the use of emoxipin in the complex treatment of patients with moderate to severe HFRS according to the proposed method significantly reduces the duration of the intoxication syndrome and has a normalizing effect on endotoxemia, oxidative reactions, antioxidant protection and functional properties of albumin.

Table 1
The duration of individual clinical manifestations in patients with HFRS against the background of various methods of therapy Indicator (days) The main group n = 35 Comparison Group n = 20 R Moderate form Fever 4.20 ± 0.43 6.13 ± 0.74 <0.05 General weakness 18.70 ± 1.50 23.10 ± 1.30 <0.05 Oliguria 3.40 ± 0.43 5.10 ± 0.67 <0.05 Polyuria 4.80 ± 0.58 3.20 ± 0.50 <0.05 Heavy form The main group n = 15 Comparison Group n = 10 Fever 7.90 ± 0.53 9.78 ± 0.65 <0.05 General weakness 23.10 ± 1.25 26.80 ± 1.10 <0.05 Oliguria 6.00 ± 0.47 7.99 ± 0.77 <0.05 Polyuria 5.04 ± 0.63 7.90 ± 1.10 <0.05

table 2
Dynamics of indicators of nitrogen-excreting renal function in HFRS of moderate severity during various types of therapy (n = 55) Indicators Healthy (n = 30) Comparison Group (n = 35) The main group (n = 20) P ₁ P ₂ P ₃ Urea mmol / L 5.18 ± 0.42 7.60 ± 0.41 5.76 ± 0.53 <0.001 <0.05 p> 0.05 Creatinine μmol / L 52.00 ± 10.00 130.70 ± 4.07 97.50 ± 7.12 <0.001 <0.001 p <0.01 Note: Here and in Tables 2-7: p ₁ - significance of differences between the comparison group and healthy; p ₂ - significance of differences between the main and the comparison group; p ₃ - significance of differences between the main group and donors.

Table 3
Dynamics of indicators of nitrogen-excreting renal function in HFRS of severe course on the background of various types of therapy (n = 25) Indicators Healthy (n = 30) Comparison Group (n = 15) The main group (n = 10) P ₁ P ₂ P ₃ Urea mmol / L 5.18 ± 0.42 8.17 ± 1.24 6.12 ± 0.61 <0.05 > 0.05 p> 0.05 Creatinine μmol / L 52.00 ± 10.00 151.60 ± 6.8 118.20 ± 4.27 <0.001 <0.01 p <0.001

Table 4
The dynamics of some indicators of ET and AOD in HFRS of moderate severity against the background of various types of therapy (n = 55) Indicators Healthy (n = 30) Comparison Group (n = 35) The main group (n = 20) P ₁ P ₂ P ₃ MSM ₂₅₄ 0.218 ± 0.005 0.288 ± 0.006 0.220 ± 0.010 <0.001 <0.001 p> 0.05 MCM ₂₈₀ 0.255 ± 0.004 0.348 ± 0.009 0.261 ± 0.017 <0.001 <0.001 p> 0.05 CEC small 73.10 ± 3.60 105.68 ± 2.27 94.21 ± 4.72 <0.001 <0.05 p <0.01 MDA 2.18 ± 0.02 5.91 ± 0.24 3.07 ± 0.53 <0.001 <0.001 p> 0.05 Plasma catalase 5.10 ± 0.10 2.69 ± 0.14 4.88 ± 0.10 <0.001 <0.001 p> 0.05 Red blood cell catalase 4.23 ± 0.16 2.66 ± 0.13 4.12 ± 0.10 <0.001 <0.001 p> 0.05

Table 5
The dynamics of some indicators of ET and AOZ in HFRS of severe course on the background of various types of therapy (n = 25) Indicators Healthy (n = 30) Comparison Group (n = 15) The main group (n = 10) P ₁ P ₂ P ₃ MSM ₂₅₄ 0.218 ± 0.005 0.404 ± 0.026 0.259 ± 0.027 <0.001 <0.01 p> 0.05 MSM ₂₈₀ 0.255 ± 0.004 0.419 ± 0.016 0.326 ± 0.020 <0.001 <0.01 p <0.01 CEC small 73.10 ± 3.60 130.50 ± 2.77 103.13 ± 5.71 <0.001 <0.01 p <0.01 MDA 2.18 ± 0.02 6.89 ± 0.26 3.17 ± 0.61 <0.001 <0.001 p> 0.05 Plasma catalase 5.10 ± 0.10 1.66 ± 0.12 4.30 ± 0.19 <0.001 <0.001 p <0.01 Red blood cell catalase 4.23 ± 0.16 1.78 ± 0.15 3.36 ± 0.25 <0.001 <0.001 p <0.05

Table 6
The dynamics of some indicators of the functional state of albumin in HFRS of moderate severity against various types of therapy (n = 55) Indicators Healthy (n = 30) Comparison Group (n = 35) The main group (n = 20) P ₁ P ₂ P ₃ OKA 45.80 ± 1.02 40.97 ± 1.31 44.71 ± 1.09 <0.05 <0.05 p> 0.05 ECA 45.15 ± 0.96 37.00 ± 1.31 43.37 ± 0.87 <0.001 <0.001 p> 0.05 SSA 98.58 ± 0.23 90.31 ± 0.68 97.00 ± 1.29 <0.001 <0.001 p> 0.05 IT 0.01 ± 0.002 0.11 ± 0.010 0.03 ± 0.015 <0.001 <0.001 p> 0.05

Table 7
The dynamics of some indicators of the functional state of albumin in HFRS of severe course on the background of various types of therapy (n = 25) Indicators Healthy (n = 30) Comparison Group (n = 15) The main group (n = 10) P ₁ P ₂ P ₃ OKA 45.80 ± 1.02 37.40 ± 0.82 43.78 ± 0.53 <0.001 <0.001 p> 0.05 ECA 45.15 ± 0.96 33.20 ± 0.93 41.78 ± 1.37 <0.001 <0.001 p> 0.05 SSA 98.58 ± 0.23 88.77 ± 1.38 95.43 ± 0.87 <0.001 <0.01 p <0.01 IT 0.01 ± 0.002 0.13 ± 0.020 0.05 ± 0.010 <0.001 <0.01 p <0.01

Claims (1)

A method for the treatment of hemorrhagic fever with renal syndrome, including basic therapy and from the first day of the disease, the introduction of an intravenous drip of the drug emoxipin, characterized in that an additional 6% are administered intramuscularly emoxipine 1% - 5.0 ml, 2 times a day for the next 10 days .