RU2753589C1 - Method for predicting multiple organ failure after heart surgery performed under conditions of artificial blood circulation - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to the field of medicine, in particular to anesthesiology and resuscitation, and is intended for predicting multiple organ failure (MOF) after heart operations performed under conditions of artificial blood circulation. Based on the combination of the concentration of mtDNA in the blood serum of patients more than 10 relative units determined immediately after surgery, and a combination of five clinical events and factors selected from the group: surgery for multifocal atherosclerosis, the combined nature of the operation, acute blood loss during surgery, decreased blood pressure and arterial hypotension, combined vasopressor and inotropic support, increased mtDNA levels on the first day after surgery, acute myocardial infarction, emergency surgery, implantation of a device for mechanical support of blood circulation before surgery, postoperative small cardiac output syndrome, the probability of developing MOF after heart operations performed in conditions of artificial blood circulation is predicted.

EFFECT: invention allows patients with a high probability of developing MOF and a maladaptive course of a systemic inflammatory reaction (SIR) to level the release of alarmins and thereby prevent the further course of SIR.

1 cl, 5 tbl, 2 ex

Description

The invention relates to medicine, in particular to anesthesiology and resuscitation.

The development of modern medicine is determined by the widespread use of invasive surgical medical technologies. In particular, according to the Global Surgery 2030 Initiative: Evidence and Solutions for Health, Well-being and Economic Development and the Lancet panel of 25 experts, it is determined that: (1) investment needs in the organization of surgical care and primarily in low- and middle-income countries, they increase by 10-15% every year, (2) conditions of accessibility of surgical care lead to a loss of at least 12.3 trillion dollars for the period 2015-2030 from outstanding surgical interventions, (3) Investing in anesthesia and surgical infrastructure is cost-effective and profitable for investment compared to other branches of medicine. These provisions determine the fact that surgical care in general and highly specialized surgical care in particular (which includes heart and vascular surgery) will have maximum development not only from a medical and social point of view, but also from the standpoint of profitability for all participants in the healthcare system ( Meara JJ et al, 2015). Any surgical aggression is the sum of mutually potentiating factors and events that contribute to an adaptive or maladaptive individual response to surgery (Baue et al, 1999). Among the factors predisposing to a personalized response to surgical aggression, genetic (genetics of systemic inflammation, genetics of toll-like receptors, their expression and realization of innate immunity, genetics of acute-phase response), age-related (a growing organism and an organism in the stage of involution according to react differently in response to stress), gender (the prevalence of male sex hormones contributes to better adaptation of innate immunity). Events contributing to the individual response of the body - acute massive blood loss perioperatively, acute syndrome of small cardiac output, shock of any genesis.

М. Et al, 2012), уровень мтДНК увеличивается у всехUnder the influence of stress and other pathological events (hypoxia, ischemia and reperfusion), many specific intracellular components are released from the cell, which have the effects of nonspecific stimulation of the family of so-called pattern-recognizing receptors -alarmins. The latter are aimed at activating a nonspecific response of cells of innate immunity, primarily monocytes, for the subsequent activation of specific immunity. Among alarmins, mitochondrial DNA (mtDNA) plays a leading role (Knez J. Et al, 2016). Mitochondria contain several copies of mtDNA, the number of which is interrelated with the size and number of mitochondria, which change depending on the cell's need for energy, oxidative stress, and various pathological conditions. mtDNA can be damaged by reactive oxygen species (ROS), which can lead to mitochondrial dysfunction, inflammation, cell aging, etc. (Bayeva M. et al, 2013). High levels of circulating mtDNA increase inflammation and damage organs (

M. Et al, 2012), the level of mtDNA increases in all

patients without dividing into groups after minimally invasive aortic valve implantation (Estevez-Cid F., et al, 2019).

Mitochondrial DNA, as an alarmmin through the activation of pattern recognition receptors, is involved in the implementation of the systemic inflammatory response. Interaction with TLR9 (Toll-like receptor 9) is one of the main mechanisms for triggering such an immune response of mtDNA (Hemmi H et al, 2005). After interacting with mtDNA, the signal from TLR9 is transmitted via the cytosolic adapter protein MYD88 (myeloid differentiation primary response protein 88) to mitogen activated protein kinase (MAPK) and nuclear factor κB (NF-κB) to initiate an inflammatory response and subsequent chemotaxis of neutrophils (Zhang Q et al , 2006). Another possible mechanism by which mtDNA induces an immune response is interaction with protein complexes - inflammasomes, which modulate inflammatory responses by activating caspase-1 and secreting pro-inflammatory cytokines (interleukin-1 (IL-1β) and interleukin-18 (IL-18 ) (Guo H et al, 2008) In addition, it was obtained that circulating mitochondrial DAMPs lead to neutrophil-mediated organ damage (Zhang Q et al, 2010). In the case of loss of adaptive character, the systemic inflammatory response (SVR) is realized as a failure (PON).

A known method for predicting the development of a complicated systemic inflammatory response in patients with infective endocarditis. The invention relates to medicine, namely to cardiac surgery, and the method can be used to predict the development of a systemic inflammatory response in patients with infective endocarditis. For this, in the preoperative period in the blood of patients, the level of interleukin 1 (3, 4, 10) is determined. ml predict the development of a systemic inflammatory response.Using this method allows you to predict complications in the early postoperative period in patients with infective endocarditis, operated on in cardiopulmonary bypass ("Method for predicting the development of a complicated systemic inflammatory response in patients with infective endocarditis", RF patent 2520753, App. 02/07/2013, publ. 06/27/2014).

The disadvantage of this method is the impossibility of using this method as a bedside one, which requires taking blood, freezing the serum collection and conducting a study of enzyme-linked immunosorbent assay methods.

A known method for predicting the development of multiple organ failure in the postoperative period in cardiac surgery patients operated on in conditions of artificial circulation. The invention relates to medicine, namely to cardiac surgery. The patient's age, duration and minimum temperature of perfusion, the volume of injected colloids, the volume of washed autoerythrocytes transfused, the volume of transfused autologous blood, the volume of urine during perfusion, blood loss in the first 12 hours of the postoperative period are determined, the coefficients K1 and K2 are calculated according to the original formulas and with a value of K1 less K2 predicts multiple organ failure. The method allows to predict the development of multiple organ failure in the postoperative period for pathogenetic therapy ("A method for predicting the development of multiple organ failure in the postoperative period in cardiac patients operated on by cardiopulmonary bypass" RF patent 2343845, declared. 06/28/2007, publ. 01/20/2009).

The disadvantage of this method is the limitation of the use of this method in the development of acute massive blood loss and prediction of complications, in particular, multiple organ failure in this particular variant of the critical condition.

A known method for predicting the course of multiple organ failure during extracorporeal therapy. The invention relates to medicine, in particular to surgery and resuscitation. A method is proposed for predicting the course of multiple organ failure during extracorporeal therapy, including the study of the patient's hemostasis system, while the study is carried out before and after the therapeutic effect, the platelet diameter and the number of activated platelets are determined, and with a decrease in the average value of the platelet diameter by 10-12% from the indicators to effects with a simultaneous decrease in the number of activated platelets by at least 10% predict a favorable outcome of multiple organ failure, and with an increase in the mean platelet diameter by 10-20%) with a simultaneous increase in the number of activated platelets by at least 15% predict the irreversible development of multiple organ failure. The invention makes it possible to reduce mortality, shorten the patient's stay in the intensive care unit and can be considered as a criterion for the effectiveness of extracorporeal detoxification ("Method for predicting the course of multiple organ failure during extracorporeal therapy" RF patent 2377566, declared. 08/20/2008, published on 12/27/2009 ). The disadvantage of this method is the refusal to include in the settlement systems according to this method the possibility of forecasting up to the moment of the session of extracorporeal therapy (forecasting is possible only during the session that has already begun).

The technical result of the invention is preventive therapy to prevent the development of PON (multiple organ failure). Based on the level of mtDNA concentration in the blood serum of patients, determined immediately after surgery and on the basis of a combination of five clinical events and factors selected from the group: surgery for multifocal atherosclerosis, the combined nature of the operation, acute blood loss during surgery, decreased blood pressure and arterial hypotension , combined vasopressor and inotropic support, increased mtDNA level on the first day after surgery, acute myocardial infarction, emergency surgery, implantation of a device for mechanical support of blood circulation before surgery, postoperative small cardiac output syndrome.

The objective of this invention is to determine the indications for the use of extracorporeal correction of homeostasis to prevent the formation of PON (multiple organ failure) after CWC (cardiac surgery).

The task is achieved by the fact that in patients referred for cardiac surgery under cardiopulmonary bypass, a set of events and factors contributing to the development of PN (multiple organ failure) are revealed before surgery, during surgery and after surgery:

1. On the basis of a combination of five clinical events and factors identified in a patient before surgery, the likelihood of developing MOF (multiple organ failure) is determined (Tables 1, 2, 3).

2. The choice of indicators indicated in the scale is based on the maximum contribution made by these five clinical events and factors to the genesis of MOF (multiple organ failure).

3. Each value from the table corresponds to one point.

4. The composition of the diagnostic algorithm is expanded by adding an indicator of mitochondrial DNA (mtDNA) as one of the leading molecular patterns responsible for the initiation of systemic inflammation in conditions of cardiopulmonary bypass surgery.

5. If there is an assessment of the state of 5 points in total and above at any of the stages and an increase in the level of mtDNA above 10 rel. Unit predict the likelihood of developing MOF (multiple organ failure).

6. Based on the events and facts revealed in the patient before the operation in combination with the level of mtDNA, the likelihood of developing MOF (multiple organ failure) is determined (Tables 1, 2, 3) and indications for the use of blood purification methods are established.

7. Indications for the use of blood purification methods are:

- when determining indications for blood purification during surgery - at least 5 points for total events and factors at the preoperative and intraoperative stages - the level of mtDNA during surgery is more than 10 rel. Units, - when determining the indications for blood purification after surgery - at least 5 points for total events and factors at the preoperative, intraoperative and postoperative stages - the level of mtDNA at surgery or after surgery is more than 10 rel. Unit

8. Methods of blood purification can be applied to a patient either during surgery (intraoperatively) or immediately after surgery (postoperatively).

9. Mitochondrial DNA (mtDNA) is being used as a candidate parameter, which is critical to justify the application of treatment methods.

10. Evaluation of the level of mtDNA is carried out in two successive stages (before and after the blood purification procedure), and on the basis of the dynamics of the indicator, the effectiveness of the blood purification procedure can be assessed.

The results obtained showed that, on the basis of five clinical events and factors that, in their isolated application, cannot fully predict the likelihood of developing a maladaptive systemic inflammatory response and the likelihood of developing MOF (multiple organ failure) and the level of the leading alarmmin, mitochondrial DNA, in the next few hours and / or in the first day of the postoperative period, the development of MOF (multiple organ failure) can be predicted in order to carry out preventive therapy at the moment of initiation of the critical state, that is, on the first day, when the maximum probability of the release of alarmines with the formation of the pathophysiological immunobiochemical stage of MOF (multiple organ failure) is observed. This method has several advantages:

- the assessment of the patient's condition is carried out on a combination of factors and events (acute blood loss, shock, prolonged ischemia due to aortic clamping and reperfusion injuries of organs), which can lead to the release of alarms, SVR (systemic inflammatory reaction) and MOF (multiple organ failure),

- there is a cohort of patients who do not develop MOF (multiple organ failure), despite the presence of significant clinical factors and events,

- this cohort requires a more precise method of research and forecasting,

- the use of "primary" or initiating or proximal molecules -alarmins as candidate markers of the likelihood of developing SVR (systemic inflammatory response) and MOF (multiple organ failure) makes it possible to predict and, therefore, to use targeted therapy to remove them on the first day from the moment of realization of the critical state , which makes this therapy preventative.

Example # 1

Patient P., 65 years old, diagnosis: ischemic heart disease (ischemic heart disease). Exertional angina pectoris, FC 2 (functional class 2). CHF II (chronic heart failure II) functional class. History of coronary artery bypass grafting for chronic coronary artery disease (coronary artery disease) in 2008. Established multifocal atherosclerosis (according to color duplex scanning of brachiocephalic vessels revealed stenosis of the right internal carotid artery up to 70%). The indications for the combined operation were determined: coronary artery bypass grafting and carotid endarterectomy on the right. During the operation, the patient experienced acute blood loss of at least 1000 ml. In the postoperative period, the patient required a combined inotropic and vasopressor support to stabilize hemodynamics (arterial hypotension due to postoperative low cardiac output syndrome, confirmed by the data of pulmonary artery catheterization with a Swan-Ganz catheter). Predictable MOF (multiple organ failure) (the presence of five factors and events - surgery for multifocal atherosclerosis, the combined nature of the operation, acute blood loss during surgery, a decrease in blood pressure (blood pressure) and arterial hypotension, combined vasopressor and inotropic support and an increase in the level of mtDNA in the first days after surgery) was realized, which is confirmed by the data of an objective assessment of the severity and severity of MOF (multiple organ failure) by SOFA and the dynamics of the mtDNA indicator (Table 4).

Example No. 2

Patient P., 65 years old, diagnosis: ischemic heart disease (ischemic heart disease). Acute coronary syndrome. Myocardial infarction without ST segment elevation. Acute heart failure according to the Killip III classification. An emergency coronary angiography was performed, which determined hemodynamically significant stenoses of the coronary arteries. Taking into account the severity of the patient's condition, an intra-aortic balloon contrapulsator was installed before the operation. Indications for an emergency operation have been determined: coronary artery bypass grafting. During the operation, the patient experienced acute blood loss of more than 1000 ml while taking antiplatelet drugs followed by blood transfusion. In the postoperative period, the patient required a combined inotropic and vasopressor support to stabilize hemodynamics (arterial hypotension due to postoperative low cardiac output syndrome, confirmed by the data of pulmonary artery catheterization with a Swan-Ganz catheter).

Predictable MOF (multiple organ failure) (the presence of five factors and events - acute myocardial infarction, emergency surgery, implantation of a device for mechanical circulatory support before surgery, acute blood loss during surgery, postoperative small cardiac output syndrome and an increase in the level of mtDNA after surgery) was realized, which is confirmed indicators of MOF (multiple organ failure) SOFA and the dynamics of the mtDNA indicator (Table 5). In order to cleanse the blood, correct the water-electrolyte balance against the background of manifestations of a systemic inflammatory reaction in the first hours after the operation, it was decided to start hemodiafiltration as a method of extracorporeal blood purification, which made it possible to stabilize and further improve the patient's condition (confirmed by a decrease in the SOFA indicator to 2 points by the third day after surgery).

A method for predicting multiple organ failure after heart surgery performed under cardiopulmonary bypass

A method for predicting multiple organ failure after heart surgery performed under cardiopulmonary bypass

A method for predicting multiple organ failure after heart surgery performed under cardiopulmonary bypass

A method for predicting multiple organ failure after heart surgery performed under cardiopulmonary bypass

Claims (1)

A method for predicting multiple organ failure (MOF) after heart surgeries performed under cardiopulmonary bypass, characterized in that, based on the combination of the concentration of mtDNA in the blood serum of patients, more than 10 rel. units, determined immediately after surgery, and a set of five clinical events and factors selected from the group: surgery for multifocal atherosclerosis, combined nature of the operation, acute blood loss during surgery, lowering blood pressure and arterial hypotension, combined vasopressor and inotropic support, an increase in the level of mtDNA on the first day after surgery, acute myocardial infarction, emergency surgery, implantation of a device for mechanical support of blood circulation before surgery, postoperative small cardiac output syndrome, the likelihood of the development of multiple organ failure after heart surgery performed under cardiopulmonary bypass is predicted.