RU2348404C1 - Method of treatment of acute destructive pancreatitis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: treatment of acute destructive pancreatitis is ensured with intramuscular introduction of Deferoxamine within complex therapy. If accessory signs of disease severity are observed, while free haemoglobin concentration is up to 0.4 g/l, the preparation is introduced in daily dosage 500 mg. If basic signs of disease severity are observed with haemoglobin concentration over 0.4 g/l, dosage is 1000 mg a day. Course duration is 5-7 days.

EFFECT: effective disintoxication without by-action, prevention and elimination of microcirculation disorders in the present category of patients.

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Description

The invention relates to medicine, in particular to resuscitation and intensive care, and can be used in the treatment of pancreatic necrosis.

Currently, a search is under way for “clipping therapy” that would avoid progressive pancreatitis with an outcome in pancreatic necrosis, in which the mortality rate reaches 50-85%.

A known method of "cutting therapy", comprising the following elements of pathogenetic therapy: rheologically active drugs - refort (Berlin-Chemie AG); antisecretory agents - sandostatin; detoxification procedures: plasmapheresis, peritoneal perfusion; cytokine blockade - antiproteases; elimination of hypoxia and hyperoxidation - olifene [A.D. Tolstoy, R.V. Goltsov. Possibilities of “breaking off" the destructive process in the early stages of pancreatic necrosis. General resuscitation, 2005. - T.1. - No. 5. - S.58-60].

The disadvantages of this method of treatment are: the use of active detoxification methods is possible only after eliminating hypovolemia, organ dysfunctions, of which the correction of central hemodynamics is most difficult to eliminate, lasting up to several hours and days; antiprotease and antioxidant drugs, administered against the background of impaired microcirculation, may not have a sufficient therapeutic effect; according to multicenter randomized trials, the use of antiprotease and antisecretory drugs does not affect the outcome of the underlying disease and mortality in acute pancreatitis.

A known method of correcting microcirculation in pancreatic necrosis by the combined use of intravenous administration of ozonized physiological saline and transcutaneous infrared laser therapy [Yu.S. Vinnik, D.V. Cherdantsev, O.V. Petrova. The methodology of flowmetry. - No. 5. - S.87-99].

The disadvantages of this method are: the mandatory availability of special equipment (ozonizer, infrared transdermal laser), which is not a mandatory part of the equipment of the hospital; the possibility of developing arterial hypotension against the background of the introduction of ozonized physiological saline in patients prone to hypovolemia; there is a risk of potentiation of oxidative stress due to the active production of a superoxide radical against the background of an intense supply of ozonated solution; a significant reduction in the due effect of percutaneous laser therapy in obese patients against obesity, which is a frequent companion of acute pancreatitis.

A known method for the correction of systemic antilipid distress syndrome in acute pancreatitis using emoxipin and fraxiparin [A.P. Vlasov, I.V. Savushev, V.P. Vlasova, S.V. Aksenova, I.V. Atamankin. An integrated approach to the correction of systemic antilipid distress syndrome in acute pancreatitis. Bulletin of Intensive Care, 2006. - No. 5. - S.240-243].

The disadvantages of this method are: emoxipin, being a water-soluble antioxidant drug, administered against the background of impaired microcirculation, may not have a sufficient therapeutic effect; the use of fraxiparin in patients with acute pancreatitis who undergo conservative therapy is contraindicated, since it contradicts the order of the Ministry of Health of the Russian Federation "On the introduction of OST" 91500.11.0007 - 2003

A known method of active detoxification in pancreatogenic sepsis using hemosorption, hemofiltration, hemodialysis, hemodiafiltration in patients with pancreatic necrosis [A.F. Potapov, T.M. Tyaptiryanova, A.N. Kirillin. Detoxification in abdominal sepsis. General resuscitation, 2005. - T.1. - Number 3. - S. 32-35].

The disadvantages of these methods are: erythrocyte trauma and subsequent hemolysis in the process of blood circulation through the cardiopulmonary bypass, which leads to erythropoiesis stress, the entry of young, easily deformed red blood cells and free hemoglobin into the bloodstream and aggravation of microcirculatory circulatory disorders; Requires the availability of expensive equipment and components; requires the use of high doses of anticoagulants, which creates a threat of bleeding and DIC syndrome; the use of these methods is possible only against the background of stable hemodynamics, the absence of hypovolemia.

The objective of the invention is the improvement of the method of treatment in the early period of acute destructive pancreatitis.

The problem is solved in that a patient with acute pancreatitis in the intensive care program includes deferoxamine at a dose of 500 mg IM once or twice a day, taking into account the concentration of free hemoglobin: at a concentration of free hemoglobin up to 0.4 g / l, the daily dose of deferoxamine is 500 mg, with a free hemoglobin concentration of more than 0.4 g / l - 1000 mg. According to the mechanism of pharmacological action, deferoxamine can be attributed to the most active antioxidants, since it allows you to bind free Fe ^{2+ ions} that have pronounced cytoxicity with respect to the endothelium of the blood vessels of the microvasculature, and remove them from participation in free radical oxidation reactions.

Description of the technique: when a patient with acute pancreatitis and the effects of endotoxicosis enters, an assessment of the severity of the condition is necessary according to the prognostic system (Tolstoy A.D., Goltsov R.V., 2005), which takes into account the main signs of the severity and threat of transformation of acute pancreatitis into destructive pancreatic necrosis: marbling integument, pulse rate> 120 per min ^-1 , oligoanuria, hemorrhagic peritoneal exudate, intravascular hemolysis> 0.25 g / l or fibrinolysis, lymphopenia <0.7 × 10 ⁹ / l; and additional signs of severity: body temperature> 38 ° C, white blood cell count> 13 × 10 ⁹ / L, hemoglobin concentration> 140 g / L, hyperglycemia> 7 mmol / L, bilirubinemia> 21 mmol / L, increase in the concentration of AlAT, AsAT more 20% of the norm, hyperfermentemia, dizziness, hyperemia of the face, agitation, pain.

If the patient has the main signs of severity, deferoxamine in a dose of 500 mg IM twice a day is included in the intensive care program. If there are only additional signs of the severity of acute pancreatitis, deferoxamine in a dose of 500 mg IM once a day is included in the intensive care program. If the patient has one of the main signs of severity, deferoxamine at a dose of 500 mg IM twice a day is included in the intensive care program.

EXAMPLE 1: Patient I., 38 years old, was delivered to BSMP No. 1 at ^12:00 04.02.2007 with a diagnosis of acute interstitial pancreatitis; 13 hours after the illness with complaints of pain in the upper abdomen, repeated vomiting. The pains were permanent, radiating to the back. In the emergency room, the patient's condition is regarded as moderate. Consciousness is clear. The position is active. The skin is pale. The tongue is dry. The vesicular breathing is evenly carried out in all departments of the lungs. NPV = 17-18 min ^-1 . Heart sounds are muffled, the rhythm is correct. HELL = 140/100 mm Hg Pulse 80 min ^-1 . The abdomen is soft, participates in the act of breathing, painful in the epigastrium and both hypochondria. The gall bladder is not palpable. Liver at the edge of the costal arch. There are no symptoms of peritoneal irritation. In laboratory tests, it was noted: in a detailed clinical blood test - red blood cells 5.0 × 10 ¹² / l, hemoglobin 166 g / l, white blood cells 8.0 × 10 ⁹ / l, ESR 7 mm / h, in the leukocyte formula - segmented neutrophils 78 %, stab 2%. In blood serum - total protein 80.9 g / l, free hemoglobin 0.21 g / l, sugar 10.8 mmol / l, urea 6.4 mmol / l, creatinine 0.080 mmol / l, total bilirubin 29.0 mmol / L, direct 4.1 μmol / L, AlAT activity 1.3 mmol / L, AcAT 0.75 mmol / L. Hyperfermentemia (blood amylase) 345.4 units. Diastasuria at 12 ⁰⁰ 512 units, at 18 ⁰⁰ 2048 units. According to the ECG - sinus rhythm (65-75 min ^-1 ). The electrical axis of the heart is not deflected. The APACHE II score for general severity was 18 points.

The patient was hospitalized in the intensive care unit and intensive care unit, where conservative basic therapy was started: hunger, infusion therapy in the amount of physiological needs, antispasmodics, antibacterial therapy, deferoxamine at a dose of 500 mg IM once a day. After 2 days, against the background of the therapy, the condition stabilized (pain, hyperfermentemia, hyperglycemia stopped, the parameters of AlAT and AsAT, bilirubin returned to normal), and he was transferred to the specialized department, where he was discharged for 14 days in satisfactory condition.

Example 2: Patient M., 36 years old, was admitted to BMSP №1 in February ²⁰ 10.02.07 with complaints about the temperature of 38.5 ° C, uncontrollable vomiting, dry mucous membranes, intense abdominal pain encircling longer in the left costal margin, decreased diuresis. Diagnosed with acute pancreatitis, she was hospitalized in the intensive care unit and intensive care unit. The general condition is serious. In the mind, inhibited, periodically restless. There is a pronounced marbling of the skin, a symptom of a "white spot"> 8, dry mucous membranes, temperature 38.8 ° C, respiratory rate 20-24 rpm ^-1 , pulse 122 rpm ^-1 , blood pressure 100/60 mm Hg, the abdomen is painful in all departments, moderate intestinal paresis, the symptoms of peritoneal irritation are doubtful. Puncture and catheterization of the right subclavian vein was performed, severe hypovolemia was diagnosed - CVP = 0-1 cm water. Art. According to integral rheography (IRG), stroke volume (UO) of 28 ml, minute volume of blood circulation (IOC) 2.6 l, cardiac index (SI) 1.3 l / min / m ² , total peripheral vascular resistance (OPSS) 2995 dynes · ^S · cm ^-5 , the volume of circulating blood (BCC) of 2.1 liters. In blood tests, signs of endotoxemia (leukocyte count 17.5 × 10 ⁹ / L, nuclear shift of neutrophils to the left to 25% of stab neutrophils, LII 6.5, accelerated ESR up to 26 mm / h, lymphopenia. In a biochemical blood test: sugar 9, 2 mmol / L, free hemoglobin 0.44 g / L, bilirubin 43.3 mmol / L, amylase 455.8 units, AlAT 1.76 mmol / L, AcAT 1.23 mmol / L, creatinine 335.2 mmol / l, urea 11.4 mmol / L. In the general analysis of urine, free hemoglobin 0.55 g / l, protein 2.2 g / l, diastasuria 2768 units. Diagnostic laparoscopy was performed: in the abdominal cavity there is a large amount of hemorrhagic ypot, amylase 5466 units exudate., clinical signs destructive haemorrhagic pancreatic necrosis complicated enzymatic diffuse peritonitis. begun complex intensive therapy including a therapeutic program deferoxamine of 500 mg / m twice daily.

Against the background of the treatment, by 3 days the patient's condition stabilized, water-electrolyte and metabolic disturbances, endotoxemia were stopped, hyperfermentemia, hyperglycemia regressed rapidly. The patient was transferred to the specialized department on the 5th day and was discharged in satisfactory condition on the 16th day from the moment of admission to the hospital.

This method of treatment was used in 14 patients with acute destructive pancreatitis. Using the proposed method allowed to reduce mortality in acute destructive pancreatitis from 26.7 to 14, 2% and the average hospital bed in the intensive care unit from 8.3 to 4.5. The inclusion in the intensive care program of acute pancreatitis of deforaxamine avoided prolonged use of expensive antibacterial drugs and completely excluded expensive antisecretory drugs from the treatment program, which led to an economic effect of 8 thousand rubles per patient.

In the proposed method for the prevention of destructive pancreatitis, the use of deferoxamine allows you to: bind and remove excess ferroions, which contribute to the formation of pancreatic edema due to damage to the endothelium of the microvascular bed; to exclude ferroions from free radical oxidation reactions, which eliminates the phenomena of oxidative stress; elimination of the excess of ferroins makes it possible to actively stop the effects of endotoxicosis, since it eliminates the cytotoxic effect of ferroins on the cell membrane of both the gland itself and other organs. Moreover, our proposed method is easy to use, does not require high material costs, is free from the disadvantages that are found in other methods of prevention of destructive pancreatitis that we studied, does not adversely affect central hemodynamics, and avoids surgical treatment. Deferoxamine when used in the indicated dosages has no toxic effects. The clinical results are confirmed by the data of an experimental study, which revealed the leading pathogenetic role of excess unbound Fe ^{2+ ions} in the formation of pancreatic necrosis and pathogenetically substantiated the inclusion of deferoxamine in the intensive care program for destructive pancreatitis.

Claims (1)

A method of treating acute destructive pancreatitis, characterized in that the complex therapy includes intramuscular administration of deferoxamine in the presence of additional signs of severity and free hemoglobin concentration of up to 0.4 g / l at a dose of 500 mg, in the presence of the main signs and hemoglobin concentration of more than 0.4 g / l - 1000 mg for 5-7 days.