Science Articles

According to different authors the rate of mortality from acute generalized peritonitis is from 24.4% to 55% [4,5]. One of the main reasons for this is impaired motor-evacuation function of the large intestine [1,2] and as a consequence, the development of endogenous intoxication syndrome (EIS), which determines to a large extent the severity of the disease.

Therefore the clinician is faced by the necessity to conduct detoxification actions among the patients with acute generalized peritonitis as soon as possible.

Enterosorbtion conducted in early postoperative period can be one of such actions.

P.K. Zagniboroda (1994) using the models of obturated and strangulated intestinal obstruction of dogs showed high efficiency of intraoperative enterosorbtion using enterosorbent POLYSORB MP.

For evaluation of clinical efficacy of POLYSORB MP in intensive care we used the medicine on 11 patients with acute generalized peritonitis of different ethiology (acute intestinal obstruction - 4 patients, perforation of the hollow organ - 4 patients, penetrating ballistic wounds of abdomen - 3 patients). The condition of patients and wounded was estimated as grave and very grave.

Technology. Through polyfunctional probes set intraoperatively into initial sections of small gut, during first hours after the operation lavage and enterosorbtion were conducted. Electrolytic solution with addition of POLYSORB MP with dose of 300 mg/kg/day was used as lavage medium. Enterosorbtion was done fractionally 4 times per day. Solution made with rated dose of POLYSORB MP was administered with Janet's syringe into the gut through the probe and then the probe was clamped with exposure time 40 minutes, and then at the time of active aspiration the gut contents were removed.

When using the medicine it was noticed that POLYSORB MP is easily suspended in indoor temperature water without flocculation, this gives the possibility to deliver it into sounds of any diameter.

At the ground of conducted enterosorbtion during 3-5 days of postoperation period was noticed the decrease of the level of intoxication markers (LII, leucocytosis, stab shift, the level of middle-molecular peptides). The efficiency of enterosorbtion was proved by decrease of the level of GOT, GPT, creatinine, urea nitrogen and bilirubin in blood serum. This fact proves that usage of the POLYSORB MP at the time of enterosorbtion improves detoxication function not only of digestive tract but also of the detoxication organs (liver, kidneys). It should be noted that detoxication function was improved due to the strengthening of the barrier function of intestinal tract, normalization of indestinal flora and decrease of bacterial translocation. The other remarkable fact is that the level of creatinine in blood serum lowered almost in two times among patients with intact nephatony in comparison with control group (without usage of POLYSORB MP), this fact allows to advertise this medicine among patients with acute and chronic kidney disease in interdialysis period and in some cases even avoid hemodialysis.

Therefore, enterosorbent POLYSORB MP (CJSC Polysorb, the city of Chelyabinsk) is high-efficiency medicine for complex therapy of difficult cases of generalized peritonitis that is accompanied by frank organ disorders.

References:

1.Belyakov N.A. and others. Intraoperative decompression and sorption dialysis of small intestine in case of peritonitis: Manual for medical practitioners. St. Petersburg, 1998.p.3.

2.Burnevich S.Z. and others. The condition of barrier function of digestive tract in case of generalized peritonitis// Endointoxications. Thesis of international symposium. St. Petersburg,1994.p.23.

3.Zagniboroda P.K. The efficiency of intraoperational enterosorbtion with usage of Polysorb in cases of acute intestinal obstruction. ib, p.219.

4. Popova Т. S. and others. Intestinal obstruction syndrome in surgery. Мoscow, 1991.

5. Shorokh G.P. and others. Complex approach to detoxication of organism in case of generalized peritonitis // Endointoxications. Thesis of international symposium. St. Petersburg,1994. P.58.

Under the Approval of Main Army-Medical Direction of Ministry of Defence of RF №161/7/1/1859 dated 07.04.2000г. in Hematological Center (HC) named after the acad. N.N. Burdenko from 10.04. 2000 to 05.05.2000 Clinical enterosorbent absorbation was carried out POLYSORB MP (CJSC Polysorb, Chelyabinsk).

In order to achieve the assigned objective this medicine was administrated in the organism of 77 patients. These patients are undergoing treatment in different units of HC named after N.N. Burdenko in the following groups:

1)        15 patients with coronary disease which were cardia bypass open-heart operated;

2)       42 patients with infectual diseases (acute enteric infection, virus hepatitis, yersinia infections, pseudotuberculosis);

3)       10 patientwithheroinintoxication.

For POLYSORB clinical effect appraisal different clinical tests besides clinical methods were carried out (leucocytosis, band changes, blood-sedimentation test, leucocytal intoxication quotient, medium molecules levels, glucose, creatinine, GOT, GPT, urea nitrogen, bilirubin in blood, urea and blood diastase).

Open-heart surgery usesfactors of considerable force and depth: cardia bypass, total body hypothermia, pharmaco hypothermic cardioplegia, anoxic myocardial ischemia. In post-operation period some patients had considerable changes in phlogistic response, and life support can be affected (heart-vascular system, GI tract, eliminative organs and detoxication), it leads to endotoxemia progression. Fifteen patients with coronary heart disease underwent myocardial revasculization surgery and used POLYSORB MP. There were twenty patients in the control group; these patients received a course of congestive heart failure operative therapy. Both groups were strictly randomized (randomization tests: coronary affection, pumping ability affection of left ventricle, age of patients, associated diseases, extent and character of operational intervention; exception criteria: perioperative acute myocardial infarction, severe acute cardiovascular collapse, profuse blood loss).

Technology. Enteral use of medicine was prescribed in the form of aquatic suspension after extubation in early postoperative period. Drug dose made 200 mg/kg/day, is used 3 times per day 2 hours after meals and other medicine use. Enterosorbent course takes 5 days.

POLYSORB MP has no taste and odor, that’s why tolerance is good.

Enterosorbent presentation of POLYSORB MP consists in:

1)       improvement of subjective general mend (1-2 day before than subjective results in control group);

2)       absence of dyspeptic disorder in post-operation period (in control group 5 patients felt sick and voimit);

3)       lower intensity of postpericardiac syndrome.

After laboratory findings analysis in both groups where patients used enterosorbent POLYSORB MP, vitalses normalization is earlier (4-5 days) than it is in control group (8-10 days): creatinine, urea nitrogen, glucose, blood serum diastase, medium molecules levels, intoxication leukocytic index. Four patients with diabetes mellitus of second stage showed positive results in enterosorbent use, consisting in carbohydrate metabolism subcompensation, the second day after post-operation period and during 5-8 days after post-operation period carbohydrate metabolism subcompensation was still evident in control group analyses.

Consequently, enterosorbent POLYSORB MP was used by patients who underwent bypass open-heart operation. This medicine is an active and harmless component in post-operation treatment, optimizes base treatment, considerably improves post-operation results. Patients quickly recover and leave surgical hospital (2 days before than patients of control group).

Acute infectious diseases. Forty-two patients with intermediate and severe forms of acute infectious diseases used POLYSORB MP. There are thirty-five patients in control group, these patients didn’t use enterosorbent.

Technology. After admission, medicine in the form of aquatic suspension is prescribed to take in orally. Daily dose makes 200 mg/kg/day. A patient with acute diarrheal syndrome takes in daily dose during 5 hours every hour. Further medicine is prescribed to be taken four times per day 1.5-2 hours after meals and after other medicine. Enterosorbent POLYSORB MP was used in combination with eubiotics, probiotics treatment (bifidumbacterin forte (Probifor), Flonivin, Bactisubtil, Normoflor).

Twenty patients with acute enteric infection (salmonellosis, shigellosis, colibacillosis, bacterial food poisoning) shown the following results:

1)      diarrheal syndrome period decreased for 2 days (in control group 4-5 days);

2)      there was no meteorism the second day after enterosorbent was taken in. But 40 % of patients had symptoms of meteorism during 7 days of base therapy after admission;

3)      general intoxication syndrome decreased for 1-2 days with POLYSORB MP use (for 4-5 days in control group);

4)      there was no anorexia the first day after POLYSORB MP use (in control group 50 % patients suffered from loss of appetite during treatment of 6-7 days).

Enterosorbent POLYSORB MP use quickly reduced endointoxication and anorexia syndrome in the organism of 15 patients with virus hepatitis А and В (clinical overt forms of severe and intermediate forms). In the period of fast recovery 7 patients with Yersinia syndrome and pseudotuberculosis deceases shown fast antibiotic colitis resolution caused by dysbacteriosis.

Therefore POLYSORB MP is high-effective enterosorbent used in acute infectious disease complex therapy.

POLYSORB MP was used to treat 10 patients with heroin intoxication in order to prepare them for pharmacologic detoxication. Fourteen patients with heroin intoxication formed the control group, they didn’t take in enterosorbent.

Technology. Probe with aquatic suspension was administrated in stomach during the period when the patient was under anaesthesia and after intubation of trachea and APV. Daily dose of POLYSORB MP was administrated each 2,5 hours. After pharmacological detoxication under anaesthesia the probe was pulled out with active aspiration of gastric contents. Patients which used POLYSORB MP showed the following results:

1)      there is no dyspeptic disorder (sickness, vomiting, loose stool);

2)      negative tests in 100 %, there are no opioids in urine after pharmacological detoxication under anaesthesia (in control group these tests were positive in 30 %). GI tract absorbs and eliminates a portion of heroin. 

  The rate of rotavirus infections in the structure of AEI varies from 9 to 73%, and in respect of all the children, hospitalized on the occasion of enteric disorders, it makes 20—60%.

  Change of aetiologic structure and pathogenesis of AEI of children (increase of the number of virus diarrhea), resistance increase of bacteria to antimicrobials, increase of the number of unfavorable outcomes in recent years, connected with burdened preclinical background of patients, dictate terms of search for new etiopathogenesis medicines and development of therapy for patients with acute enteric infections.

  Basic directions of pathogenetic therapy for the treatment of acute enteric infectious diseases accompanied by diarrhea syndrome, are as follows:

deintoxication;

aquatic-electrolytic disorder correction;

motor-secretory disorder correction of gastro-intestinal tract;

correction of gut organisms disorders;

reinforcement of reparative processes in mucous membrane of large bowel;

enterosorption.

   Enterosorption in case of infectious diseases is not just pathogenetic therapy method, but also aetiologic, as sorbing agents can uptake not just endo- and ectotoxind of causative agents, but also detect at its surface causative agents of bacterial and viral nature, thus excluding them from pathologic process. The ability of enterosorbents to bind endo- and ectotoxins of causative agents contributes much to the macroorganism deintoxication.

  At the pharmaceutical market of Russia various groups of enterosorbents are presented by absorbent carbons, lignines, ion exchanger resins, which have quite different clinical effect, sometimes unpleasant organoleptical properties (Polyphepan), different level of solubility, various aromatic flavorings, which are vital in case of children treatment with allergic diseases and, of course, possible traumatic impact on mucous membrane of the intestinal tract. In this respect the problem of use of new medicine – enterosorbents, which meets modern requirements, especially in respect of children, is quite vital.

  One of new medicines is native drug POLYSORB MP, manufactured by Polysorb CJSC, city of Cheliabinsk, produced from fine silicon, meeting all basic requirements in respect of enterosorbents: non toxic, does not traumatize mucous membrane of gastro-intestinal tract, can be easily removed from gastro-intestinal tract, has good sorption and organoleptical properties.

  The results of using enterosorbent POLYSORB MP for the treatment of acute enteric infections of children were included into this work.

Purpose:

  Estimation of clinical efficiency of the medicine-enterosorbent POLYSORB MP, development of pathogenetic therapy of acute enteric infections of children, followed by diarrhea syndrome.

Materials and methods:

  In compliance with the work purpose in 2005-2006 65 children were examined, who underwent hospital treatment at MMPI (Municipal Medical and Preventive Treatment Institution) City Clinical hospital №1, City of Smolensk, department №5 (intestinal infections). Clinical information on intoxication phenomena estimation was used for the medicine efficiency estimation: duration of sickness, vomit, dysorexia; evidence of disease clinical features: feverish period, abdominal syndrome, diarrhea period, presence of abnormal foreign substances in the stool; laboratory evaluation of causative agent release –bacteriological and serologic methods were used.

  2 groups of children were selected, group “А” - 35 children apart from traditional basis therapy (including specific antimicrobial or antiviral) underwent the treatment with the help of the enterosorbent POLYSORB MP and control group “B” - 30 children who underwent the traditional basis (including specific antimicrobial or antiviral) therapy.

  Total absence of intoxication syndromes in the group examined stated at the 4^th day with maximum fading at the 1^st and the 2^nd day, and in the control group – intoxication symptoms preserved to the 7^th day with maximum fading at the 2^nd and the 4^th.

  Abdominal syndrome cut shorted in the research group with the overwhelming majority up to the 3^rd day, in the control set in 25% preserved up to the 4^th day.

  In the research group with the overwhelming majority up to the 3^rd day the stool was formed, in the control group in 3.3% it was preserved to be liquid to the 8^th day of disease.

  In the research group abnormal foreign substances disappeared up to the end of the 2-3^rd day, in the control group preserved up to 5 days.

 The following dynamics was formed in the process of obtained data analysis:

 DYNAMICSOFclinical symptoms

According tolaboratory findings:

laboratory findings dynamics

  In the group “А” out of 2 cases of shigellosis (released Shigella Flexneri 2а), in control inoculations of fecal masses after the therapy held only negative findings were detected.

  Out of 18 cases of rotavirus infection (laboratory certified) in the control studies of fecal masses the rotavirus was not detected.

  In the group “B” out of 2 cases of shigellosis Shigella Flexneri 2а was released, in control inoculations after therapy only negative findings were detected.

  Positive control inoculations of fecal masses for rotaviruses were detected in 5 out of 13 cases of rotavirus infection (laboratory certified).

  In both the groups 15 children were made a diagnosis of acute enteric infection, not certified laboratory.

  Development of adverse reactions and hyperresponsiveness to the enterosorbent used in the range of patients were not detected.

Conclusions:

Therefore, the information received shows that:

1. In the process of using enterosorbent POLYSORB MP by children with acute enteric infection there was determined quick intoxication syndrome reduction dynamics, stool normalization and disappearance of abnormal foreign substances in comparison with the control group.

2.  On the back of therapy held in the examined group, better intestinal tract sanitation from pathogenic causative agents (in case of rotavirus infection) was achieved.

3. Therapeutic action of POLYSORB with reduction of infectious disease duration, terms of hospitalization and lower cost of the medicine (in comparison with analogue) presupposes possible positive benefits.

4. Enterosorption method with the use of POLYSORB MP can be recommended for the treatment of children acute enteric infections with the syndrome of intoxication and diarrhea. 

  Endogenous intoxication based on bacteriotoxemia, increase in average mass molecules, andhemostasis abnormality accompanied by haemodynamics disorders predetermine the search of methods of artificial detoxification with high efficacy and minimal damaging action. One of the possible methods of detoxification is enterosorbents.

  This work includes the results of Polisorb MP therapy in children with acute enteric infections. Polisorb MP is a novel enterosorbent which is manufactured by ZAO Polisorb, Chelyabinsk.

  25 children aged from 2 months to 6 years were administered the drug and the majority of  the children (21) were infants. The diagnosis of acute enteric infection was made on the ground of clinical, epidemiological, and laboratory data. 

  Polisorb MP was administered at the moment of admission with dose 100 mg/kg/day. The children took the sorbent in the form of water mixture (50 ml) 4 times a day 1 hour before meal and drugs.

  The following results were obtained:

1. Stool came to normal after 2.5±1.1 days of the therapy and after 7.3±1.9 days in control group.

2. Signs of intoxication persisted for 1.7±0.2 days in patients who took Polisorb MP and for 7.1±1.3 days in patients who did not take the drug.

  Hence, available data suggest that Polysorb MP as a part of complex treatment is useful for acute enteric infections in children with treatment course of 3 – 5 days.  

  Acute enteric infections and viral hepatitides are still among the most common diseases with higher incidence only for acute respiratory infections. Containment efforts are associated with some difficulties due to inadequate efficacy or absence of etiotropic drugs. Antibiotics and chemotherapeutic agents are unsafe and should be administered only in case of severe shigellosis and generalized infection. However if only pathogenetic therapy is used there is a risk of chronic infection and bacteria carrying.

  The possible solution for the problem would be enterosorbents which would bind pathogenic agents, and toxic substances and have no negative properties of antibiotics. Sorbents are successfully used for diarrhea and viral hepatitis. However many of them show necessary therapeutic effect only when administered in high doses (up to 100 g/day) causing disorders of morphology and function of bowels.

  A novel enterosorbent Polisorb MP was developed on the basis of fine-grained silica. Due tio its hydrophilia, high sorption activity towards microbes, and affinity to some biologically active substances the drug is supposed to be efficient in the treatment for acute enteric infections and viral hepatitides.

  Our studies were aimed to evaluate action of Polisorb MP as a part of complex therapy for acute enteric infections and viral hepatitides and to specify contraindications and possible side-effects.

  The results of treatment of 125 patients with acute gastroenterocolitis of various etiology and degree of severity and 46 patients with viral hepatitis were analyzed. The results of treatment of patients with acute enteric infections were compared between three groups. The first (control) group included 55 patients who were treated with traditional methods. The second group included 16 patients who were treated with traditional methods and bolus alba (comparator drug). The third group included 54 patients who were treated with traditional methods and Polisorb MP.

  All the patients were administered standard-dose antibiotics (furazolidone 0.1 g 4 times a day; phthalazolum 1.0 g 4 times a day; laevomycetin 0.5 g 4 times a day) for the average of 3 – 7 days and oral rehydratation (Phillips solution number 1, rehydron, 5 % glucose solution). If a patient experienced marked dehydratation, he/she was administered intravenous therapy. Some patients (9 – 11 %) were made gastric lavage. During the treatment the patients took calcium gluconate and vitamins. The second group was also administered bolus alba 20 g 4 times a day and the third group – Polisorb MP 100 mg/kg 3 times a day. The sorbent was taken in the form of water suspension not more than 3 days.

  Every group was divided into subgroups according to degree of severity and clinical entity of enteric infection. The diagnosis was made on the basis of clinical presentation, epidemiological anamnesis, the results of bacteriological examination, coprogram, and indirect hemagglutination test with appropriate diagnosticum. Patients with unspecified causative agent were included in the subgroup with diagnosis: mild or moderate to severe acute gastroenterocolitis of unknown etiology. Opportunistic pathogens, Shigella and Salmonella were identified in other patients. Treatment efficacy was assessed by rate of signs regression.

  Polisorb MP 100 mg/kg 2 times a day was administered as a part of complex therapy for viral hepatitis. 21 patients took oral 3 % water suspension of sorbent for 7 days in average. 25 patients who were administered conventional therapy without enterosorbents were used as controls. The treatment depends on degree of severity of viral hepatitis. So the patients of these two groups were divided into three subgroups: 8 patients of the control group and 6 patients of the experimental group (1^st subgroup) were administered baseline therapy (diet, vitamins, and choleretics); 12 patients of control group and 11 patients who took Polisorb MP (2^nd subgroup) were additionally administered infusion solutions (5 % glucose solution, hemodez, and Phillips solution), antihistamines, and spasmolytics; 5 patients of control group and 4 patients of experimental group (3^d subgroup) were additionally administered prednisolone. Standardtreatmentsanddrugsdoseswereused.

  The diagnosis was made on the basis of clinical presentation and results of biochemical tests. The diagnosis was confirmed by identification of Australia antigen in 44 % of patients of control group and 42.9 % of patients who were administered the sorbent. Treatment efficacy was assessed by rate of evolution of clinical signs (jaundice, skin itching, color of urine and stool), serum bilirubin level, activity of aminotransferases and alkaline phosphatase.

  Groups were formed using random sampling technique, and they were not significantly varied in gender, age, and pre-morbid background. Frequency and intensity of signs before treatment was nearly equal in all compared subgroups. Average values were calculated using the data of patients who had analyzed feature.

  The studies revealed high efficacy of Polisorb MP as a part of complex therapy for acute enteric infections and viral hepatitis which was confirmed by significant regression of clinical and laboratory signs.

  Bolus alba as a part complex therapy for acute enteric infections does not have significant additional therapeutic effect comparing with control. However Polisorb MP stops diarrhea faster than conventional therapy and bolus alba (for example, 2.9 and 2.6 times faster in patients with mild undifferentiated gastroenterocolitis respectively) and improve other signs (nausea, vomiting, colics, appetite loss). Coprogram was normalized significantly faster.

  Neither bacteria carrying nor chronic infection were identified in any of 125 patients. Opportunistic pathogens were found in two patients with history of salmonellosis (3.6 %) at re-examination.

  Slight stool retention (up to 2 days) before its normalization was observed in each group. Perhaps, this is a variant of normal course of recovery period. In the control group constipation developed in 4 patients (7.3 %) who were administered conventional therapy and in 2 patients (12.5 %) who were administered bolus alba. Stool retention over 2 days was not observed in patients who were administered Polisorb MP 100 mg/kg/day for 3 days.

Table 1. Evolution of clinical signs of salmonellosis during complex therapy using Polisorb MP (М±m)

Table 2. Evolution of clinical signs of dysentery during complex therapy using Polisorb MP (М±m)

  Polisorb MP as a part of complex therapy for viral hepatitis significantly accelerates the recovery: jaundice and skin itch disappear by 4 – 6 and 6 – 7 days earlier, and color of urine and stool improves faster. Blood values, serum bilirubin level and activity of aminotransferases (Table 3), normalizes in these patients earlier. Polisorb MP had no side-effects.

Table 3. Evolution of laboratory signs of liver damage during complex therapy using Polisorb MP (М±m)

Note: significance of difference is showed between groups “before treatment” and “10 days after”

  Comparison of the results of the Polisorb MP therapy with available literature data on therapeutic activity of other sorbents show that antidiarrheal action of Polisorb MP exceeds comparator sorbents and its therapeutic effect in patients with viral hepatitides is not inferior to modern coal sorbents and lignin derivates.

Method of administration of Polisorb MP:

  Our experience indicates that Polisorb MP is better to be administered in the form of water suspension. To prepare the suspension the appropriate amount of drug is adjusted with boiled water to mark 250 ml. The drug is administered at daily dose of 100 mg/kg 2 – 3 times a day. Patients with acute enteric infections are recommended to take the drug as early as possible. The first dose can be increased to 5 g (100 ml of water suspension). If a patient has vomiting the drug is given through gastric tube. 2-day therapy of Polisorb MP is sufficient in most of the cases of acute enteric infections. 5-7-day therapy of Polisorb MP (6 – 9 g per day) significantly improves the state of patient with viral hepatitis and shortens the duration of hospital stay.

  A separate study is devoted to the investigation of Polisorb MP efficacy in 144 children with severe enteric toxicosis who stayed in the Intensive Care Department of Khmelnitsk Infectious Diseases Hospital. The results of clinical observation and laboratory tests (P-proteins, immune complexes, erythrocyte index of endogenous intoxication, average mass molecules, malonic dialdehyde, diene conjugates, and dieneketones) showed high therapeutic activity of Polisorb MP 150 -200 mg/kg/day 3 – 4 times a day as a part of complex therapy for enteric toxicosis in children. For example, diarrhea stopped more than 2 days earlier comparing with the control group (children who were not administered Polisorb MP). Neurotoxicosis, microcirculation disorders, etc. resolved significantly faster, and laboratory values were normalized 1.5 – 2 times quicker. If the patients had vomiting they were given enemas with Polisorb MP. When vomiting stopped the patients were transferred to oral therapy. The duration of enterosorption depended on child’s state and averaged 2 – 3 days for moderate to severe toxicosis and 3 – 4 days for severe toxicosis. Polisorb MP did not cause any side-effects or complications.

Conclusions:

1. Polisorb MP as a part of complex therapy for acute enteric infections and viral hepatitis has a marked therapeutic effect.
2. Polisorb MP did not promote chronic infection and bacteria carrying.