RU2638808C1 - Method of laboratory evaluation of extracorporal membrane oxygenation effectiveness in adult patients with acute heart failure after open-heart surgeries - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method for laboratory evaluation of extracorporeal membrane oxygenation effectiveness in adult patients with acute heart failure after open-heart surgeries consists in the fact that in adult patients being on extracorporeal membrane oxygenation due to the acute heart failure after open-heart surgeries, the highly sensitive troponin T is determined daily in blood serum and if the values of the highly sensitive troponin T are from 635 ng/l to 4330 ng/l, the extracorporeal membrane oxygenation is assessed effective, if the values of the highly sensitive troponin T are from 4331 ng/l and above, the extracorporeal membrane oxygenation is assessed ineffective, correction of therapy is necessary.

EFFECT: increased efficiency.

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Description

The invention relates to medicine, namely to cardiac surgery and cardioreanatology, and can be used for laboratory evaluation of the effectiveness of extracorporeal membrane oxygenation in adult patients with acute heart failure after open heart surgery.

The development of cardiovascular surgery has significantly expanded the boundaries of the surgical treatment of coronary heart disease and chronic rheumatic heart disease.

However, despite the use of the latest technologies for protecting myocardium in open heart surgery, acute heart failure remains a formidable complication, the frequency of development of which is 3.6-15.4% of cases, and in 40-80% of cases, acute heart failure leads to fatal the outcome [S.V. Gauthier, V.N. Poptsov, E.A. Spirin. Extracorporeal membrane oxygenation in cardiac surgery and transplantology. - M .: - Tver: LLC Triada. 2013. - 272 p.].

The causes of acute heart failure after open heart surgery are: mechanical myocardial injury, myocardial overload, damage to the conductive system, acute myocardial hypoxia, initial myocardial failure.

The following types of mechanical support of blood circulation are used to treat acute heart failure in patients after open heart surgery:

1) intra-aortic balloon counterpulsation,

2) an artificial ventricle of the heart,

3) venoarterial extracorporeal membrane oxygenation (ECMO).

One of the most effective treatments for acute heart failure after open heart surgery is ECMO.

ECMO improves hemodynamics and gas composition of the blood, as a result of which the rate of development of organ disorders decreases and the clinical condition of patients with acute heart failure improves after open heart surgery.

However, even with a favorable outcome for the treatment of acute heart failure after open heart surgery, there is a high risk of developing infectious and inflammatory diseases, multiple organ failure, and disorders of the hemostatic system, which leads to a delay in the patient’s stay in the intensive care unit and an increase in economic costs of intensive care for patients with this pathology.

In this connection, the development or determination of criteria for evaluating the effectiveness of ECMO in patients with acute heart failure after open heart surgery is currently relevant.

Known methods for assessing the effectiveness of the treatment of acute heart failure. These methods are based on clinical, instrumental and laboratory studies of patients with acute heart failure.

Clinical and instrumental research methods are not always informative, reliable and objective, depending on the level of qualification (knowledge) of specialists performing these types of studies.

Laboratory research methods, unlike clinical and instrumental ones, are standardized and reliably due to internal laboratory quality control in clinical laboratories, validation of research results (samples), participation of clinical laboratories in federal and international laboratory quality control programs, reflecting changes in the human body, correlate with the severity of the patient's condition.

Thus, laboratory studies provide the most reliable information about the development of pathological processes in the human body, the severity of the patient's condition, based on the results of laboratory studies, it is possible to evaluate the effectiveness of the therapy and the outcome of treatment.

A known method for evaluating the effectiveness of the treatment of acute heart failure in cardiac patients. This method uses the data of instrumental (electrocardiography, echocardiography, chest x-ray, angiography) and laboratory studies (blood tests of the marker of myocardial dysfunction - aminoterminal cerebral natriuretic peptide) [Diagnosis and treatment of acute heart failure. Russian recommendations. http://www.cardiosite.ru/medical/recom-dia.asp].

The disadvantages of this method are:

1. It is not possible to use the described method in cardiosurgical patients, since cardiac surgery patients differ from cardiac patients in that patients with cardiovascular pathology underwent heart surgery, which is accompanied by extensive surgical trauma and the development of a systemic inflammatory response to surgery.

2. Amino-terminal cerebral natriuretic peptide is not a marker of myocardial damage, this peptide is a marker of myocardial dysfunction, is synthesized in cardiomyocytes, its concentration increases in the blood with increasing pressure in the heart chambers or with rarefaction of the heart chambers. Amino-terminal cerebral natriuretic peptide correlates with echocardiographic characteristics of left ventricular dysfunction (end diastolic and systolic volumes of the left ventricle, ejection fraction). This laboratory indicator can be used in cardiac surgery patients, but only at the preoperative stage to determine the severity of left ventricular dysfunction and assess the severity of heart failure.

To date, a lot of work has been devoted to the clinical diagnostic value of the amino terminal cerebral natriuretic peptide in patients with cardiovascular diseases, however, all studies have been performed on different analytical systems (analyzers, reagents) and patient groups. In this connection, it is not possible to use the values of the amino terminal cerebral natriuretic peptide obtained on other analytical systems to evaluate the effectiveness of the treatment of acute heart failure using extracorporeal membrane oxygenation in patients after open heart surgery.

In addition, the concentration of the amino-terminal cerebral natriuretic peptide depends on the age, gender, and severity of renal failure. This indicator is very variable, it is impossible to use laboratory indicators with a high coefficient of variability in clinical practice, since the results can lead to incorrect treatment tactics.

A known method for evaluating the effectiveness of ECMO in children and adults with respiratory failure based on a study of the gas composition of the blood and the acid-base balance of the patient [Alsoufi B., Shen I., Karamlou T. et al. Extracorporeal life support in neonates, infants, and children after repair of congenital heart disease: modern era results in a single institution // Ann. Thorac. Surg. 2005. - Vol. 80 (1). - P. 15-21].

The disadvantage of this method is that by studying the gas composition, it is possible to evaluate gas exchange disorders in patients with respiratory failure, but not the degree of damage or recovery of the myocardium after open heart surgery.

There is a method of evaluating the effectiveness of ECMO after open heart surgery in children with congenital heart defects based on the analysis of the use of adrenergic agonists and the amount of hydrobalance, the study of laboratory blood parameters - creatinine and urea, transaminases, free hemoglobin and lactate, as well as the duration of ECMO and pressure in the left atrium . With an inotropic support index of more than 8.5 mcg / kg / min; positive (more than +60 ml) hydro balance in the first day of ECMO application; maximum creatinine concentration of more than 107 mmol / l; the maximum concentration of urea is more than 15 mmol / l; the maximum concentration of AsAT is more than 200 PIECES / l; the maximum concentration of AlAT more than 31 IU / l; the maximum concentration of free hemoglobin is more than 35 mg / dl; maximum lactate concentration of more than 3.85 mmol / l; ECMO procedure duration - more than 6.5 days; pressure in the left atrium of more than 12 mm Hg - ECMO is not effective in children with congenital heart defects [Bokeria L.A., Shatalov K.V., Brodsky A.G. et al. The method of extracorporeal membrane oxygenation in the treatment of heart failure in young children in a heart surgery clinic // Children's heart and vascular diseases. 2012. - No. 1. - S. 19-25].

The disadvantages of this method are:

1. The child’s body is different from the adult, therefore, it is not possible to use the values of laboratory indicators of multiple organ failure (creatinine, urea, transaminases), intravascular hemolysis (free hemoglobin) and tissue hypoxia (lactate), as in adult patients with acute heart failure after open heart surgery, they are significantly higher than in children.

2. In this method, the evaluation of the effectiveness of ECMO is based on the determination of markers of multiple organ failure (creatinine, urea, transaminase), intravascular hemolysis (free hemoglobin) and tissue hypoxia (lactate).

As a rule, multiple organ failure and intravascular hemolysis are secondary manifestations of a systemic inflammatory response and indicate the development of complications amid acute heart failure. Myocardial damage primarily occurs, which leads to the development of acute heart failure, later on, against the background of already existing acute heart failure, other complications develop.

In addition, urea and creatinine in clinical practice (during therapy) change very slowly (within 3-4 days during therapy), therefore, use these indicators to assess the effectiveness of ECMO in adult patients with acute heart failure after open heart surgery is not possible. Patients on ECMO for acute heart failure after open heart surgery need to evaluate the effectiveness of the therapy on a daily basis, and not once every 3-4 days.

None of the methods presented above for assessing the effectiveness of the treatment of acute heart failure used a specific marker of myocardial damage (troponin T), although the main reason for the development of acute heart failure after open heart surgery is myocardial damage of various nature and degree.

The invention is aimed at improving the assessment of the effectiveness of ECMO in adult patients with acute heart failure after open heart surgery based on the study of a specific marker of myocardial damage - highly sensitive troponin T.

The technical result is achieved by the fact that in patients who are on ECMO for acute heart failure after open heart surgery, highly sensitive troponin T is determined in blood serum daily and, with values of highly sensitive troponin T in the range from 635 ng / l to 4330 ng / l, extracorporeal membrane oxygenation effective; with values of highly sensitive troponin T from 4331 ng / l, extracorporeal membrane oxygenation is considered ineffective, therapy correction is necessary.

To date, troponin T is widely used in cardiac surgery to determine and assess the degree of myocardial damage.

Troponin T is involved in the formation of a troponin complex with tropomyosin. Troponin T is a regulatory globular protein, is involved in the process of muscle contraction. The molecular weight of troponin T is 37 kDa. Distinguish between the cytosolic and structural pool of troponin T.

With damage to the myocardium, the release of troponin T in the blood occurs as follows:

- in case of damage to the cytosol of cardiomyocytes, the release of the cytosolic (free, not connected with myofibrils) pool of troponin T is observed. The cytosolic pool of troponin T is a highly sensitive troponin T;

- upon damage to the structures of cardiomyocytes, the release of the structural (associated with myofibrils) pool of troponin T. is noted. The structural pool of troponin T is the “normal” troponin T.

To date, in clinical practice, diagnostic systems (test systems) are used that allow the determination of “normal” troponin T and highly sensitive troponin T in the blood.

The highly sensitive troponin T has a number of advantages over the “usual” troponin T:

- the concentration of highly sensitive troponin T in the blood can be determined from 0 ng / l and higher, and the "usual" troponin T from 100 ng / l;

- The highly sensitive troponin T is a cytosolic pool. In case of damage to cardiomyocytes (myocardium), the highly sensitive troponin T is first found in the blood when damage to cardiomyocytes (myocardium), which is important for early determination of myocardial damage. An early determination of the increase in the concentration of highly sensitive troponin T in the blood reduces the time to start activities, reduces the time spent by patients in the intensive care unit and the economic costs associated with this;

- the dynamics of the levels of highly sensitive troponin T allows us to differentiate acute myocardial damage (cardiomyocytes) from chronic;

- a short period of ischemia, not associated with a clear myocardial infarction, leads to the release of a small amount of highly sensitive troponin T into the blood;

- high levels of highly sensitive troponin T in patients with stable coronary artery disease indicate a high risk of heart failure, but not the risk of developing myocardial infarction;

- the presence of highly sensitive troponin T is a predictor of adverse outcomes.

The method is as follows.

In cardiac surgery patients in the intensive care unit with a complicated postoperative period, blood was taken daily to evaluate the effectiveness of extracorporeal membrane oxygenation to determine the highly sensitive troponin T in the blood serum.

Blood sampling was performed from a peripheral vein into the S-monovetta blood sampling system with a blood coagulation activator. To obtain blood serum, the blood was centrifuged for 10 min at 2500 rpm.

At the prehospital stage, patients were selected for cardiac surgery.

At the time of admission to the hospital, the severity of the patients' condition was due to the severity of heart failure and circulatory disorders.

At the preoperative stage, the concentration of highly sensitive troponin T was within the reference values, which indicated the absence of myocardial damage.

The proposed method has been tested on 28 patients (of which 21 men and 7 women), 26 patients with a diagnosis of coronary heart disease, 2 patients with a diagnosis of chronic rheumatic heart disease. The average age of the patients was 56.5 ± 1.9 years.

Patients diagnosed with chronic rheumatic heart disease underwent valve correction surgery under cardiopulmonary bypass and normothermia.

Patients diagnosed with coronary heart disease underwent coronary artery bypass grafting under cardiopulmonary bypass and normothermia.

Observation (research) was carried out in the period from 2009 to 2015. In the observed patients, the postoperative period was complicated by acute heart failure.

Patients according to the outcome of the postoperative period (acute heart failure) were divided into two groups:

1 group of patients - patients with a favorable course of the postoperative period, surviving patients (n = 11 people). In patients of the 1st group, ECMO was performed on average 4.4 ± 0.5 days, patients in the intensive care unit were on average 14.5 ± 2.5 days, on average, on 24.5 ± 2.63 days, the patients were discharged from the hospital is in satisfactory condition.

2 group of patients - patients with an unfavorable course of the postoperative period, deceased patients (n = 17 people). In patients of the 2nd group of ECMO, an average of 8.33 ± 1.63 days was spent, patients in the intensive care unit were on average 8.33 ± 1.63 days, due to the lack of effect from ECMO (treatment futility), patients on average 8, 33 ± 1.63 days were disconnected from ECMO.

In patients of the 1st group, the concentration of highly sensitive troponin T in the blood serum was in the range from 635 ng / l to 4330 ng / l (median was 1610 ng / l, standard deviation was 1360 ng / l). After open heart surgery, an increase in the concentration of highly sensitive troponin T to 4330 ng / L was observed, and then, against the background of an ECMO, a decrease in the concentration of highly sensitive troponin T to 365 ng / L was observed. An increase in the concentration of highly sensitive troponin T in the blood serum of patients of the 1st group on the first day after surgery indicated myocardial damage. Against the background of ECMO, the concentration of highly sensitive troponin T in the blood serum of patients of the 1st group decreased in the next day, which indicated the reversibility of myocardial damage and the effectiveness of ECMO.

In patients of the 2nd group, the concentration of highly sensitive troponin T in the blood serum was in the range from 4331 ng / l and higher. After open heart surgery, high concentrations of highly sensitive troponin T from 4331 ng / L and higher were observed, indicating myocardial damage. Against the background of ECMO, a further increase in the concentration of highly sensitive troponin T was observed, which indicated the irreversibility of myocardial damage and the absence of the effect of ECMO, an unfavorable outcome of treatment.

Below are the results of testing.

Clinical example 1

Patient I., born in 1957, diagnosis - IHD. Stenosing atherosclerosis of the coronary arteries. Angina pectoris III FC. Postinfarction cardiosclerosis (Q-IM from 01/10/2014). Arterial hypertension of the III stage, risk 4. Mitral valve insufficiency 3 degrees. Pulmonary hypertension 2 degrees. CHF IIa degree.

Before surgery, the concentration of highly sensitive troponin T in the blood serum was 12.2 ng / ml. On admission, the severity of the condition is due to heart failure, circulatory failure.

An operation was performed - mammary coronary artery bypass grafting of the right descending artery, coronary artery bypass grafting of 2 coronary arteries, annuloplasty of the mitral valve by a support ring in the conditions of cardiopulmonary bypass and cardioplegia. The duration of cardiopulmonary bypass was 5 hours 30 minutes. The postoperative period was complicated by acute heart failure - in the first hours after the operation, circulatory arrest. Diagnosed perioperative myocardial infarction of the anterior-septal, apical region.

The development of acute heart failure required resternotomy, repeated coronary artery bypass grafting and ECMO connection.

1st day after surgery, the patient at ECMO. The patient's condition is serious, the severity is due to heart failure. The concentration of highly sensitive troponin T in blood serum was 3657 ng / l. Based on the results of the study of highly sensitive troponin T, the patient undergoes correction of treatment - doses of adrenergic agonists and infusion therapy, acid-base balance.

2nd day after surgery, the patient at ECMO. The patient's condition is serious, the severity is due to heart failure. The concentration of highly sensitive troponin T in the blood serum was 3543 ng / l. Based on the results of the study of highly sensitive troponin T, the patient undergoes correction of treatment - doses of adrenergic agonists and infusion therapy, acid-base balance.

3rd day after surgery, the patient at ECMO. The patient's condition is serious, the severity is due to heart failure. The concentration of highly sensitive troponin T in the blood serum was 2909 ng / l. Based on the results of the study of highly sensitive troponin T, the patient undergoes correction of treatment - doses of adrenergic agonists and infusion therapy, acid-base balance.

4th day after surgery, the patient at ECMO. The patient's condition is serious, the severity is due to heart failure. The concentration of highly sensitive troponin T in the blood serum was 2767 ng / L. Based on the results of the study of highly sensitive troponin T, the patient undergoes correction of treatment - doses of adrenergic agonists and infusion therapy, acid-base balance.

5th day after surgery, the patient at ECMO. The patient's condition is serious, the severity is due to heart failure. The concentration of highly sensitive troponin T in the blood serum was 2305 ng / l. Based on the results of the study of highly sensitive troponin T, the patient undergoes correction of treatment - doses of adrenergic agonists and infusion therapy, acid-base balance.

6th day after surgery, the patient at ECMO. The patient's condition is serious, the severity is due to heart failure. The concentration of highly sensitive troponin T in the blood serum was 1905 ng / l. Based on the results of the study of highly sensitive troponin T, the patient undergoes correction of treatment - doses of adrenergic agonists and infusion therapy, acid-base balance.

Based on the positive dynamics in the blood serum of highly sensitive troponin T and the data of electro- and echocardiography, the patient is disconnected from ECMO on the 7th day after the operation. The patient's condition is serious, the severity of the condition is due to heart failure.

On the 12th day after the operation, the patient’s condition is moderate, the severity is due to heart failure, for further treatment the patient was transferred from the intensive care unit to the cardiac surgery. The concentration of highly sensitive troponin T in blood serum was 341.0 ng / L.

The patient was treated with adrenomimetics (inotropic), infusion therapy to correct the volume of circulating blood and acid-base balance, antibiotics (meropenem, ciprofloxacin), anticoagulants, antiplatelet agents, antiarrhythmic drugs, non-steroidal anti-inflammatory drugs, diuretics, insulinolit, pomulinumolitum , bronchodilators, neuroprotectors, iron preparations, kinetic and respiratory therapy.

Before surgery, the concentration of highly sensitive troponin T in the blood serum was 12.2 ng / L, within the reference values (reference range 0-14 ng / L), which indicated the absence of myocardial damage upon admission.

After surgery, there was a significant increase in the concentration of highly sensitive troponin T in the blood serum by 301.31 times compared with the initial values, which indicates myocardial damage and the development of perioperative myocardial infarction.

Against the background of ECMO and drug therapy, a decrease in the concentration of highly sensitive troponin T in blood serum was noted, and by the 12th day, the concentration of highly sensitive troponin T in blood serum was 341.0 ng / L. A decrease in the concentration of highly sensitive troponin T in the patient's blood serum indicates the reversibility of myocardial damage, the effectiveness of ECMO.

Thus, this clinical example demonstrates the possibility of using the determination of the concentration of highly sensitive troponin T in the blood serum of patients with acute heart failure after open heart surgery to evaluate the effectiveness of ECMO.

Clinical example 2

Patient G., born in 1959, diagnosis - IHD. Stenosing atherosclerosis of the coronary arteries. Angina pectoris III FC. Postinfarction cardiosclerosis (Q-IM from 01/10/2014). Arterial hypertension of the III stage, risk 4. Mitral valve insufficiency 3 degrees. Pulmonary hypertension 2 degrees. CHF IIa degree.

Before surgery, the concentration of highly sensitive troponin T in the blood serum was 10.1 ng / ml. On admission, the severity of the condition is due to heart failure, circulatory failure.

An operation was performed - mammary coronary artery bypass grafting of 4 coronary arteries. The duration of cardiopulmonary bypass was 5 hours 30 minutes.

The postoperative period was complicated by acute heart failure - in the first hours after the operation, circulatory arrest. Diagnosed perioperative myocardial infarction of the anterior-septal, apical region. Against the background of perioperative myocardial infarction, acute heart failure developed, which required a resternotomy, repeated re-coronary artery bypass grafting and ECMO connection.

1st day after surgery. A patient with acute heart failure is on ECMO. The patient's condition is severe, the severity is due to acute heart failure. The concentration of highly sensitive troponin T in serum was 1527 ng / L. Based on the results of the study of highly sensitive troponin T, the patient undergoes correction of treatment - doses of adrenergic agonists and infusion therapy, acid-base balance.

2nd day after surgery. Patient at ECMO. The patient's condition is severe, the severity is due to acute heart failure. The concentration of highly sensitive troponin T in the blood serum was 5285 ng / l. Based on the results of the study of highly sensitive troponin T, the patient undergoes correction of treatment - doses of adrenergic agonists and infusion therapy, acid-base balance.

3rd day after surgery. Patient at ECMO. The patient's condition is extremely serious, the severity is due to acute heart failure. The concentration of highly sensitive troponin T in the blood serum was 18378 ng / l. Based on the results of the study of highly sensitive troponin T, the patient undergoes correction of treatment - doses of adrenergic agonists and infusion therapy, acid-base balance.

4th day after surgery. Patient at ECMO. The patient's condition is extremely serious, the severity is due to acute heart failure. The concentration of highly sensitive troponin T in serum was 22600 ng / l. Based on the results of the study of highly sensitive troponin T, the patient undergoes correction of treatment - doses of adrenergic agonists and infusion therapy, acid-base balance.

Despite the therapy, the patient died on the 5th day after the operation. The cause of the death of the patient is acute heart failure, which subsequently led to renal-hepatic failure, disseminated intravascular coagulation.

The patient was treated with adrenomimetics (inotropic), infusion therapy to correct the volume of circulating blood and acid-base balance, antibiotics (meropenem, ciprofloxacin), anticoagulants, antiplatelet agents, antiarrhythmic drugs, non-steroidal anti-inflammatory drugs, diuretics, insulinolit, pomulinumolitum , bronchodilators, neuroprotectors, iron preparations, kinetic and respiratory therapy.

Before the operation, the concentration of highly sensitive troponin T in the blood serum was 10.1 ng / L, within the reference values (reference range 0-14 ng / L), which indicated the absence of myocardial damage upon admission.

After surgery, there was a significant increase in the concentration of highly sensitive troponin T in the blood serum by 151.2 times compared with the initial values, which indicates myocardial damage and the development of perioperative myocardial infarction.

Against the background of ECMO and drug therapy, on the 3rd day after the operation, a significant increase in the concentration of highly sensitive troponin T in blood serum was noted compared with the previous ones and by the 4th day, the concentration of highly sensitive troponin T in blood serum was 22600 ng / l. An increase in the concentration of highly sensitive troponin T in the patient's blood serum indicates the irreversibility of myocardial damage and the absence of the effect of ECMO.

Thus, this clinical example demonstrates the possibility of using the determination of the concentration of highly sensitive troponin T in the blood serum of adult patients with acute heart failure after open heart surgery to assess the effectiveness of ECMO use.

The advantages of the proposed method are:

- improving the assessment of the effectiveness of ECMO in adult patients with acute heart failure after open heart surgery;

- allows you to assess the degree of myocardial damage after open heart surgery;

- based on the dynamics of changes in the concentration of highly sensitive troponin T in the blood serum of patients with acute heart failure after open heart surgery, it is possible to evaluate the course of the postoperative period (treatment outcome prognosis).

Thus, the claimed method allows to improve the assessment of the effectiveness of ECMO use in adult patients with acute heart failure after open heart surgery: on the basis of a daily determination of the concentration of highly sensitive troponin T in blood serum, with which it is possible to assess the degree of myocardial damage and the course of the postoperative period.

Claims (1)

The method of laboratory assessment of the effectiveness of extracorporeal membrane oxygenation in adult patients with acute heart failure after open heart surgery, which is that in adult patients who are on extracorporeal membrane oxygenation for acute heart failure after open heart surgery, daily in blood serum is determined highly sensitive troponin T and at values of highly sensitive troponin T from 635 ng / l to 4330 ng / l, an extracorporeal membrane is evaluated effective oxygenation, with values of highly sensitive troponin T from 4331 ng / l and higher, extracorporeal membrane oxygenation is considered ineffective, therapy correction is necessary.