RU2556198C1 - Method for prevention of postpericardiotomy syndrome in patients with ischemic heart disease after coronary bypass surgery - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: early postoperative period involves administering low-molecular heparins and anti-inflammatory agents. Anti-inflammatory therapy requires administering cycloferon according to the schedule: 2 tablets of cycloferon 0.15 mg on the first preoperative day, 2 tablets on the first postoperative day, 2 tablets in the morning on the 2^nd, 4^th, 6^th postoperative day, and further, every third day throughout 1 postoperative month (on the 9^th, 12^th, 15^th, 18^th, 21^st, 24^th, 27^th, 30^th day).

EFFECT: method provides the effective prevention of postpericardiotomy syndrome with a lower risk of side effects by administering cycloferon according to the developed schedule requiring non-steroidal anti-inflammatory agents and glucocorticosteroids.

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Description

The invention relates to medicine, specifically to cardiology.

Postpericardial syndrome (PCTS) is the most common complication of open heart surgery and occurs according to foreign authors in 10-40% of cases (1), according to various Russian clinics - in 16-68% (2). Despite the fact that the incidence of serious complications, such as cardiac tamponade, constrictive pericarditis, and early shunt occlusion is relatively low, even the favorable course of PCT significantly increases the patient's postoperative rehabilitation time.

In Russia at the moment there are no recommendations, and, accordingly, a single tactic for the management of patients undergoing surgical revascularization.

A known method of treating PCT in accordance with the practical recommendations of the European Society of Cardiology using non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticosteroid drugs (GCS) and a combination of NSAIDs with colchicine in case of recurrent forms of the syndrome; For the prevention of thromboembolic complications, low molecular weight heparins are used in full therapeutic doses (3).

This method is the closest to the claimed technical essence and the achieved result and is selected as a prototype.

The disadvantage of the method of treating PCT in accordance with the practical recommendations of the European Society of Cardiology is a large number of side effects. The use of non-selective cyclooxygenase inhibitors is accompanied by many undesirable effects; leads to an increased risk of cardiovascular complications in patients undergoing coronary artery bypass grafting, increases the risk of shunt thrombosis. The use of corticosteroids is also quite unsafe and entails such unpleasant consequences as poor healing of the postoperative wound, the development and aggravation of metabolic disorders, exacerbation of gastric and duodenal ulcer, lowering the body's resistance to infections, hypercoagulation with a risk of thrombosis.

At the same time, there is currently no pharmacological strategy with proven effectiveness for the prevention of PCTD: there are conflicting and ambiguous data on the preventive use of NSAIDs and GCS (2, 4, 5), the use of NSAIDs together with colchicine did not reduce the risk of complications. In the COPPS study, which evaluated the effect of colchicine therapy without NSAIDs as the primary prevention of PCTs (6), encouraging results were obtained, which nevertheless require further confirmation.

The problem solved by this invention is the optimization of pre- and postoperative management of patients undergoing coronary artery bypass grafting.

The problem is solved by using in patients who underwent surgical intervention on the heart, in the early postoperative period, therapeutic doses of low molecular weight heparins and anti-inflammatory therapy, an endogenous interferon inducer, cycloferon, is prescribed as an anti-inflammatory drug according to the scheme: 2 tablets of cycloferon 0 a day before surgery, 15 g, the day after surgery - 2 tablets, the following doses - in the morning, 2 tablets on the 2nd, 4th, 6th day after the intervention Twa, then - after 2 days on the third duration up to 1 month after surgery (9, 12, 15, 18, 21, 24, 27, 30 hours).

The anti-inflammatory effect of interferon is based on inducing the production of anti-inflammatory cytokines (IL-10, a transforming growth factor) in combination with inhibition of the synthesis of anti-inflammatory cytokines (IL-1, IL-8, TNF), on the activation of the cellular and humoral immune response (Th1-type immune response associated with the production of IFN-γ, interleukin-2 and TNF; Th2-type - with an increase in the production of IL-4, 5, 6, 10). (7, 8, 9, 10). With high immunomodulatory activity, the drug is practically devoid of side effects; no clinically significant interactions with other drugs have been described for it (11). The use of cycloferon allows you to abandon the planned use of NSAIDs in the early postoperative period.

New in the proposed method is the use as an anti-inflammatory agent of the inducer of endogenous interferon - cycloferon.

Distinctive features showed in the inventive combination of new properties that are not explicitly derived from the prior art in this field and are not obvious to a specialist. An identical set of properties was not found in the patent and medical literature. Proposed as an invention, the method can be applied in medical practice to optimize the pre- and postoperative management of patients with coronary heart disease.

Based on the foregoing, the proposed invention should be considered as relevant to the patentability conditions “Novelty”, “Inventive step”, “Industrial applicability”.

The method is as follows: a day before surgery - 2 tablets of cycloferon 0.15 g, the day after surgery - 2 tablets after the intervention (in the probe), the following doses - in the morning, 2 tablets on 2, 4, 6 days after interventions. Further, the drug is taken after 2 days - duration up to 1 month after surgery (9, 12, 15, 18, 21, 24, 27, 30 days).

Low molecular weight heparins used on the 1-7th day after the intervention were used in therapeutic doses (fraxiparin 86 anti-Xa IU / kg, clexane-1 mg / kg).

To accomplish this task, we examined 48 patients with coronary artery disease who underwent surgical treatment of coronary artery disease - coronary artery bypass grafting in conditions of cardiopulmonary bypass and cardioplegia. Patients were comparable in age and gender, severity of coronary heart disease, intracardiac hemodynamics, and the volume of surgical intervention - all of them underwent mammary coronary artery bypass grafting with 1-3 coronary artery bypass grafting without aneurysmectomy and valve prosthetics. The analysis took into account the time of IR and the fact of perioperative blood transfusion, as a factor significantly contributing to the development of PCT.

In the postoperative period, they all received standard basic therapy (aspirin, beta-blockers, ACE inhibitors, statins), antibiotics for the prevention of mediastinitis / perioperative infections. Initially, patients were randomized into 2 groups depending on the use of NSAIDs: 1 group (n = 21); or cycloferon - group 2 (n = 27) as a drug for the treatment of PCT. In case of treatment failure in patients of both groups, the use of corticosteroids was allowed.

Such indicators as the frequency of postoperative pleurisy, pericarditis, the number of pleural punctures, including repeated ones, the frequency of forced use of corticosteroids, and the number of days spent by the patient in the clinic were analyzed. Puncture was performed in the presence of 300 or more ml of fluid according to ultrasound. The patient was discharged from the clinic only in the absence of the need for stationary monitoring by a cardiologist.

The clinical characteristics of the patients and the results of the analysis are shown in table 1.

In group 1 of the standard treatment, a greater number of complications was noted - pleural punctures were required in 47% (in 10 patients, while 4 patients had punctures 2 or more times), pericarditis developed in 23.8% of cases (in 5 patients).

In group 2, with the use of cycloferon, the frequency of pleural punctures was 18.5% (5 patients, 2 of whom needed repeated puncture), the incidence of pericarditis was also lower - 11.1% (3 patients). In this group, there was less need for the use of corticosteroids compared with group 1 (11.1% versus 52.4%, respectively), there was earlier removal of sutures and a significantly shorter hospital stay.

In accordance with the recommendations of European countries for the prevention of thromboembolic complications (12, 13) in group 2, we distinguished 2 subgroups: in one group (n = 14), cycloferon was used without NSAIDs, anticoagulant therapy was carried out with a maintenance dose of LMWH; the other group (n = 13) also received cycloferon without NSAIDs, however, anticoagulant therapy was carried out with a full therapeutic dose of LMWH.

In the group of patients receiving cycloferon and LMWH in prophylactic doses, pleural puncture was performed in 28.6% of cases (n = 4), in one case repeated puncture was required, pericarditis developed in 14.3% of patients (n = 2).

In the group receiving cycloferon and LMWH in the therapeutic dose, pleural puncture was required only in 7.6% (in 1 patient), in 7.6% (n = 1) pericarditis was noted.

Since in the group receiving NSAIDs, the frequency of perioperative blood transfusion was higher than in the group receiving cycloferon, we conducted an additional analysis of the subgroups taking into account these factors (see table 3).

In this version of the analysis, the group of patients with and without perioperative blood transfusion who received cycloferon also showed significantly better results relative to the corresponding subgroups who received NSAIDs as planned.

Example 1. Patient Sh., 66 years old (No. 3382), was admitted on 03.24.13 with complaints of shortness of breath of a mixed nature when climbing to the 3rd floor, interruptions in the work of the heart. Previously, in-patient examination and treatment took place, during which stenosing atherosclerosis was revealed according to the results of CVH, surgical treatment of coronary artery disease - coronary artery bypass grafting was recommended. This hospitalization is planned for surgical intervention. An objective examination: a pulse of 60 beats / min, blood pressure of 120/80 mm Hg, respiratory rate of 17 per minute, no peripheral edema. The main clinical and laboratory characteristics upon admission: a general blood test, a general urinalysis, a biochemical blood test, a coagulogram - without features, an ultrasound examination of the heart MJP = 12.5 mm; ZSLZH = 10 mm; MM = 205 g; KDR = 53 mm; DAC = 34 mm; BWW = 128 ml; CSR = 49 ml; PV (B) = 62%; UO = 79 ml; PL (4k) = 50 × 56 mm; PP (4k) = 52 × 56 mm.

Pharmacological history at the time of admission: concor 10 mg, hypothiazide 25 g, losap 25 mg, simvastatin 20 mg.

Clinical diagnosis: CHD: angina pectoris FC III. Stenosing atherosclerosis of the coronary arteries (PNA 75%, PKA 75%, VTK 75%, 1DA 40%). Paroxysmal form of atrial fibrillation. NK I. FC II (NYHA). Background: GB III art., Risk 4.

The patient underwent mammakoronar bypass surgery of the anterior descending artery, coronary artery bypass surgery of the obtuse margin and posterior interventricular vein under IR and cardioplegia 05/08/2013

In the postoperative period, the patient was treated with: cardiomagnyl 75 mg / day, coronal 10 mg / day, amlodipine 5 mg / day, atorvastatin 20 mg / day, cefazolin 3 g / day - 8 days, fraxiparin 1, 2 ml / day - 7 days , cycloferon 0.15 g: a day before surgery - 2 tablets, the day after surgery - 2 tablets (into the probe), 2 tablets on 2, 4, 6, 9, 12 days (on the 13th day the patient was discharged , taking cycloferon on days 15, 18, 21, 24, 27, 30 is recommended on an outpatient basis). The postoperative period proceeded safely: there were no infectious complications, there were no phenomena of postpericardiotomy syndrome (pleurisy, pericarditis according to objective and ultrasound data), sutures were removed on the 12th day, the patient was discharged after the operation on the 13th day.

Example 2. Patient I., 65 years old (No. 3510), was admitted with complaints of shortness of breath of a mixed nature when walking 50 meters, discomfort behind the sternum, stopping NTG. An objective examination: a pulse of 68 beats / min, the rhythm of atrial fibrillation. HELL 110/70 mm RT. Art., respiratory rate 18 per minute, no peripheral edema.

The main clinical and laboratory characteristics upon admission: General blood test, general urinalysis, coagulogram - without features, in a biochemical blood test: total bilirubin 16.6 mmol / L, urea 7.8 mmol / L, ACT 29 U / L, ALT 29 U / L total protein 83 g / l; creatinine 122 μmol / l, total cholesterol 3.7 mmol / l, glucose 13.6. Ultrasound examination of the heart: MJP = 10 mm; ZSLZH = 10 mm; MM = 252 g; KDR = 72 mm; DAC = 63.5 mm; BWW = 240 ml; CSR = 180 ml; PV (B) = 25%; UO = 60 ml; PL (4k) = 55 × 66 mm; PP (4k) = 51 × 53 mm. Coronoventriculography: PNA pr \ 3 s \ t stenosis, 1 YES 75%, OA pr \ 3 75%, PKA sr \ 3 75%, d \ 3 PKA 30%.

Clinical diagnosis: CHD: angina pectoris FC III. PEAKS 2005. A persistent form of atrial fibrillation. Ventricular extrasystole IV (Lown). NK I. FC II ab NYHA. Background: GB III, target BP achieved. Residual effects of cerebrospinal cord ischemic type from 2012. Type 2 diabetes mellitus, target glycated hemoglobin less than 6.5%. Obesity 1 tbsp. Risk 4.

Surgical intervention was performed: aorto-coronary artery bypass grafting of 1 median artery, 2 median arteries, diagonal artery and mammary coronary artery bypass graft bypass graft surgery IMA, 2MA, YES, and MKSH PNA under cardiopulmonary bypass and cardioplegia (05.06.2013). In the postoperative period, on the 1st day, a single-group erythrocyte mass was transfused in order to replenish the volume of circulating fluid. Prescribed treatment: diuver 2.5 mg, enalapril 2.5 mg / day, veroshpiron 25 mg, cordarone 200 mg, diabeton MB 60 mg / day, atorvastatin 20 mg / day, cefazolin - 3 g / day 10 days, fraxiparin - 1 , 2 ml / day for 7 days, cycloferon 0.15 g: a day before surgery - 2 tablets, the day after surgery - 2 tablets (into the probe), 2 tablets for 2, 4, 6, 9, 12 days ( on the 14th day the patient was discharged, taking cycloferon on the 15th, 18th, 21st, 24th, 27th, 27th, 30th days is recommended on an outpatient basis).

The postoperative period was uneventful: there were no infectious complications, objective and ultrasound pericarditis was not observed, on the 6th day 100 ml of fluid was noted in the left pleural cavity, and on the 8th day no fluid was found. The sutures were removed on the 11th day, the patient was discharged on the 14th day after the operation.

Thus, the addition of cycloferon and LMWH in standard doses to standard basic therapy contributed to a more effective early postoperative rehabilitation of the patient without the use of NSAIDs and GCS.

The proposed method was tested in the heart failure department of the FSBI Research Institute of Cardiology SB RAMS in 48 patients and allows to reduce the risk of developing postoperative pleurisy and pericarditis, improve the postoperative period and reduce the time of postoperative hospitalization in patients with coronary artery bypass grafting.

Bibliography

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Claims (1)

A method for preventing the development of postpericardiotomy syndrome in patients with coronary heart disease who underwent coronary artery bypass grafting, which consists in prescribing therapeutic doses of low molecular weight heparins and anti-inflammatory therapy, characterized in that an inducer of endogenous interferon-cycloferon is prescribed as an anti-inflammatory drug according to the scheme: 2 days before surgery - 2 cycloferon tablets 0.15 g, the day after surgery - 2 tablets, the following doses - morning m 2 tablets at 2, 4, 6 day after intervention, then - after 2 days on the third duration up to 1 month after surgery (9, 12, 15, 18, 21, 24, 27, 30 hours).