MINISTRY OF HEALTH OF UKRAINE

Vinnitsa national medical university of N.I.Pirogova

“Approved"
At methodical meeting of chair
Internal medicine №1
Head of the department

____________ prof. Stanislavchuk M. A.

«30» August 2021

METHODICAL RECOMMENDATIONS
For students

Subject matter Internal medicine

Module Emergencies in the clinic of internal medicine
Substantial module № 1 Emergencies in the clinic of internal medicine
Subject of the lesson Management of a patient with hematemesis, melena, shock.
Course 6
Faculty Medical # 1

Vinnytsya 2021
1. Topicality:
Shock was defined as sustained systolic blood pressure <90 mm Hg with end-organ dysfunction
ascribed to the hypotension. Shock type was classified by site investigators as cardiogenic,
distributive, hypovolemic, or mixed. Among 3049 CICU admissions, 677 (22%) met clinical
criteria for shock. Shock type was varied, with 66% assessed as cardiogenic shock (CS), 7% as
distributive, 3% as hypovolemic, 20% as mixed, and 4% as unknown. Cardiogenic shock (CS),
the most severe form of acute heart failure, is characterized by life-threatening end-organ
hypoperfusion resulting from a low cardiac output state. CS occurs in ≈5% to 7% of patients
presenting with acute myocardial infarction (AMI) and is more common in patients with ST-
segment–elevation MI (STEMI) than non-STEMI.
Distributive shock results from excessive vasodilation and the impaired distribution of blood
flow. Septic shock is the most common form of distributive shock and is characterized by
considerable mortality (treated, around 30%; untreated, probably >80%). In the United States,
this is the leading cause of noncardiac death in intensive care units (ICUs). Sepsis develops in
more than 750,000 patients per year in the United States. Angus and colleagues estimated that,
by 2010, 1 million people per year would be diagnosed with sepsis. From 1979-2000, the
incidence of sepsis increased by 9% per year.

The incidence of acute upper gastrointestinal (GI) bleeding (UGIB) is about 100 per 100,000
adults per year. An estimated 15% of patients with UGIB present with hematochezia. In the
United Kingdom, UGIB accounts for 70,000 hospital admissions each year, with the majority of
cases nonvariceal in origin. In a nationwide study from Spain, UGIB was six times more
common than lower GI bleeding. UGIB is twice as common in men as in women and increases
in prevalence with age (>60 y). However, the death rate is similar in both sexes.
Despite advances in therapy, in-hospital mortality remains high (13%), and rebleeding is
common (15%)

. 2. Educational goal:

2.1. The student must know:

Definition and differentiation of various types of shocks
1. Etiology and pathogenesis of various types of shocks
2. Clinic and course of acute various types of shocks
3. Treatment tactics
4. Etiology and pathogenesis of GIB
5. Clinical symptoms of GIB
6. Modern classification of GIB
7. Methods of diagnostics and differential diagnostic of GIB.
8. Methods of treatment of GIB

2.2. The student must be able:

1. provide emergency care for various types of shocks
2. draw up a scheme for examining a patient using functional methods for examining the
cardiovascular system
3. determine the clinical diagnosis and variant of the disease in the examined patients
4. conduct physical exercise tests and drug tests
5. interpret the main laboratory, instrumental, radiation, radiological, ultrasound examination
methods for patients with coronary artery disease. Identify indications and
contraindications for their conduct
6. formulate a reasonable clinical diagnosis according to the classification requirements
 7. prescribe a differentiated treatment depending on the disease, its variant of the course and
associated diseases, write prescriptions
8. provide emergency care at the prehospital and hospital stages • determine the tactics of the
district doctor of the clinic at different stages of observation
9. prescribe differentiated treatment for elderly patients; • determine tactics for ITU issues,
employment, and prevention.
10. 1.To choose the symptoms of GIB
11. To make the scheme of investigation for the determination of the cause of GIB.
12. To assess the result of lab tests.
13. To determinate the treatment depending on the cause of GIB.
14. To prescribe the proper treatment for the patient with GIB

3. CONTENTS OF THE TRAINING MATERIALS:

Cardiogenic shock is a physiologic state in which inadequate tissue perfusion results from
cardiac dysfunction, most often systolic. It is a major, and frequently fatal, complication of a
variety of acute and chronic disorders, occurring most commonly following acute myocardial
infarction (MI).

Although ST-segment elevation MI (STEMI, previously termed Q-wave MI) is encountered in

most patients, cardiogenic shock may also develop in patients with non ̶ ST-segment elevation
acute coronary syndrome
Types of circulatory shock
Shock is identified in most patients on the basis of findings of hypotension and inadequate organ
perfusion, which may be caused by either low cardiac output or low systemic vascular resistance
(SVR). Circulatory shock can be subdivided into four distinct classes according to the underlying
mechanism and characteristic hemodynamic findings. In all patients, before a definite diagnosis
of septic shock is established, the following four classes of shock should be considered and
systematically differentiated.
Cardiogenic shock characterized by primary myocardial dysfunction renders the heart to be
unable to maintain adequate cardiac output. These patients demonstrate clinical signs of low
cardiac output, with adequate intravascular volume. The patients have cool and clammy
extremities, poor capillary refill, tachycardia, narrow pulse pressure, and low urine output.
Hypovolemic shock results from loss of blood volume, the possible reasons for which include
gastrointestinal bleeding, extravasation of plasma, major surgery, trauma, and severe burns.
Obstructive shock results from impedance of circulation by an intrinsic or extrinsic obstruction.
Pulmonary embolism, dissecting aneurysm, and pericardial tamponade all result in obstructive
shock.
Distributive shock is caused by conditions producing direct arteriovenous shunting and is
characterized by decreased SVR or increased venous capacitance because of the vasomotor
dysfunction. These patients have high cardiac output, hypotension, high pulse pressure, low
diastolic pressure, and warm extremities with good capillary refill. Such findings upon physical
examination strongly suggest a working diagnosis of septic shock.
Etiology
Cardiogenic shock can result from the following types of cardiac dysfunction:
Systolic dysfunction
Diastolic dysfunction
Valvular dysfunction
Cardiac arrhythmias
Coronary artery disease
Mechanical complications
The vast majority of cases of cardiogenic shock in adults are due to acute myocardial ischemia.
Indeed, cardiogenic shock is generally associated with the loss of more than 40% of the LV
myocardium, although in patients with previously compromised LV function, even a small
infarction may precipitate shock. Cardiogenic shock is more likely to develop in people who are
elderly or diabetic or in persons who have had a previous inferior MI.
Complications of acute MI, such as acute mitral regurgitation, large RV infarction, rupture of the
interventricular septum or LV free wall, and tamponade can result in cardiogenic shock.
Conduction abnormalities (eg, atrioventricular blocks, sinus bradycardia) are also risk factors.
Many cases of cardiogenic shock occurring after acute coronary syndromes may be due to
medication administration. The use of beta blockers and angiotensin-converting enzyme (ACE)
inhibitors in acute coronary syndromes must be carefully timed and monitored. [3, 7,
A systemic inflammatory response syndrome–type mechanism has also been implicated in the
etiology of cardiogenic shock. Elevated levels of white blood cells, body temperature,
complement, interleukins, and C-reactive protein are often seen in large myocardial infarctions.
Similarly, inflammatory nitric oxide synthetase (iNOS) is also released in high levels during
myocardial stress. Nitric oxide production induced by iNOS may uncouple calcium metabolism in
the myocardium resulting in a stunned myocardium. Additionally, iNOS leads to the expression
of interleukins, which may themselves cause hypotension.
Left ventricular failure
Systolic dysfunction
The primary abnormality in systolic dysfunction is abated myocardial contractility. Acute MI or
ischemia is the most common cause; cardiogenic shock is more likely to be associated with anterior
MI. The causes of systolic dysfunction leading to cardiogenic shock can be summarized as follows:
Ischemia/MI
Global hypoxemia
Valvular disease
Myocardial depressant drugs (eg, beta blockers, calcium-channel blockers, and antiarrhythmics)
Myocardial contusion
Respiratory acidosis
Metabolic derangements (eg, acidosis, hypophosphatemia, and hypocalcemia)
Severe myocarditis
End-stage cardiomyopathy (including valvular causes)
Prolonged cardiopulmonary bypass.
Cardiotoxic drugs (eg, doxorubicin [Adriamycin])
Diastolic dysfunction
Increased LV diastolic chamber stiffness contributes to cardiogenic shock during cardiac ischemia,
as well as in the late stages of hypovolemic shock and septic shock. Increased diastolic dysfunction
is particularly detrimental when systolic contractility is also depressed. The causes of cardiogenic
shock due primarily to diastolic dysfunction can be summarized as follows:
Ischemia
Ventricular hypertrophy
Restrictive cardiomyopathy
Prolonged hypovolemic or septic shock
Ventricular interdependence
External compression by pericardial tamponade
Greatly increased afterload
Increased afterload, which can impair cardiac function, can be caused by the following:
Aortic stenosis
Hypertrophic cardiomyopathy
Dynamic aortic outflow tract obstruction
Coarctation of the aorta
Malignant hypertension
Valvular and structural abnormality
Valvular dysfunction may immediately lead to cardiogenic shock, or it may aggravate other
etiologies of shock. Acute mitral regurgitation secondary to papillary muscle rupture or
dysfunction is caused by ischemic injury. Rarely, acute obstruction of the mitral valve by a left
atrial thrombus may result in cardiogenic shock by means of severely decreased cardiac output.
Aortic and mitral regurgitation reduce forward flow, raise end-diastolic pressure, and aggravate
shock associated with other etiologies.
Valvular and structural abnormalities associated with cardiogenic shock include the following:
Mitral stenosis
Endocarditis
Mitral aortic regurgitation
Obstruction due to atrial myxoma or thrombus
Papillary muscle dysfunction or rupture
Ruptured septum or free wall arrhythmias
Tamponade
Decreased contractility
Reduced myocardial contractility can result from the following:
RV infarction
Ischemia
Hypoxia
Acidosis
Right ventricular failure
Greatly increased afterload
Afterload increase associated with RV failure can result from the following:
Pulmonary embolism (PE)
Pulmonary vascular disease (eg, pulmonary arterial hypertension and veno-occlusive disease)
Hypoxic pulmonary vasoconstriction
Peak end-expiratory pressure (PEEP)
High alveolar pressure
Acute respiratory distress syndrome (ARDS)
Pulmonary fibrosis
Sleep-disordered breathing
Chronic obstructive pulmonary disease (COPD)
Arrhythmias
Ventricular tachyarrhythmias are often associated with cardiogenic shock. Furthermore,
bradyarrhythmias may cause or aggravate shock due to another etiology. Sinus tachycardia and
atrial tachyarrhythmias contribute to hypoperfusion and aggravate shock.
Pathophysiology
Cardiogenic shock is recognized as a low-cardiac-output state secondary to extensive left
ventricular (LV) infarction, development of a mechanical defect (eg, ventricular septal defect or
papillary muscle rupture), or right ventricular (RV) infarction.
Autopsy studies show that cardiogenic shock is generally associated with the loss of more than
40% of the LV myocardial muscle.
Signs and symptoms
The diagnosis of cardiogenic shock can sometimes be made at the bedside by observing the
following:

Hypotension
Absence of hypovolemia
Clinical signs of poor tissue perfusion (ie, oliguria, cyanosis, cool extremities, altered mentation)
Findings on physical examination include the following:

● Skin is usually ashen or cyanotic and cool; extremities are mottled

● Peripheral pulses are rapid and faint and may be irregular if arrhythmias are present
● Jugular venous distention and crackles in the lungs are usually (but not always) present;
peripheral edema also may be present
● Heart sounds are usually distant, and third and fourth heart sounds may be present
● The pulse pressure may be low, and patients are usually tachycardic
● Patients show signs of hypoperfusion, such as altered mental status and decreased urine
output
● Ultimately, patients develop systemic hypotension (ie, systolic blood pressure below 90
mm Hg or a decrease in mean blood pressure by 30 mm Hg)

Diagnosis
● Laboratory studies
● Biochemical profile
● CBC
● Cardiac enzymes (eg, creatine kinase and CK-MB, troponins, myoglobin, LDH)
● Arterial blood gases
● Lactate
● Brain natriuretic peptide
● Imaging studies
● Echocardiography should be performed early to establish the cause of cardiogenic shock
● Chest radiographic findings are useful for excluding other causes of shock or chest pain
(eg, aortic dissection, tension pneumothorax, pneumomediastinum)
● Ultrasonography can be used to guide fluid management
● Coronary angiography is urgently indicated in patients with myocardial ischemia or MI
who also develop cardiogenic shock
● Electrocardiography
● Perform electrocardiography immediately to help diagnose MI and/or myocardial ischemia
● A normal ECG, however, does not rule out the possibility of acute MI
● Invasive hemodynamic monitoring
●
● Swan-Ganz catheterization is very useful for helping exclude other causes and types of
shock (eg, volume depletion, obstructive shock, and shock)
● The hemodynamic measurements of cardiogenic shock are a pulmonary capillary wedge
pressure (PCWP) greater than 15 mm Hg and a cardiac index less than 2.2 L/min/m 2
● The presence of large V waves on the PCWP tracing suggests severe mitral regurgitation
● A step-up in oxygen saturation between the right atrium and the right ventricle is diagnostic
of ventricular septal rupture
● High right-sided filling pressures in the absence of an elevated PCWP, when accompanied
by ECG criteria, indicate right ventricular infarction
Management
Cardiogenic shock is an emergency requiring the following:
Fluid resuscitation to correct hypovolemia and hypotension, unless pulmonary edema is present
Prompt initiation of pharmacologic therapy to maintain blood pressure and cardiac output
Admission to an intensive care setting (eg, cardiac catheterization suite or ICU or critical care
transport to a tertiary care center)
Early and definitive restoration of coronary blood flow; at present, this represents standard therapy
for patients with cardiogenic shock due to myocardial ischemia
Correction of electrolyte and acid-base abnormalities (eg, hypokalemia, hypomagnesemia,
acidosis)
Invasive procedures include the following:
Placement of a central line may facilitate volume resuscitation, provide vascular access for
multiple infusions, and allow invasive monitoring of central venous pressure
An arterial line may be placed to provide continuous blood pressure monitoring
An intra-aortic balloon pump may be placed as a bridge to percutaneous coronary intervention
(PCI) or coronary artery bypass grafting (CABG)
Pharmacologic therapy
Patients with MI or acute coronary syndrome are given aspirin and heparin
Inotropic and/or vasopressor drug therapy may be necessary in patients with inadequate tissue
perfusion and adequate intravascular volume, so as to maintain mean arterial pressure (MAP) of
60 or 65 mm Hg
Diuretics are used to decrease plasma volume and peripheral edema
Features of dopamine are as follows:
Dopamine is the drug of choice to improve cardiac contractility in patients with hypotension
Dopamine may increase myocardial oxygen demand
Dopamine is usually initiated at a rate of 5-10 mcg/kg/min IV
The infusion rate is adjusted according to the blood pressure and other hemodynamic parameters
Often, patients may require doses as high as 20 mcg/kg/min
Features of dobutamine are as follows:
● Dobutamine may be preferable to dopamine if the systolic blood pressure is higher than 80
mm Hg
● Compared with dopamine, dobutamine has less effect on myocardial oxygen demand
● Tachycardia from dobutamine may preclude its use in some patients
If the patient remains hypotensive despite moderate doses of dopamine, a direct vasoconstrictor
may be administered, as follows:
Norepinephrine is started at a dose of 0.5 mcg/kg/min and titrated to maintain an MAP of 60 mm
Hg
The dose of norepinephrine may vary from 0.2-1.5 mcg/kg/min
Doses as high as 3.3 mcg/kg/min have been used
Phosphodiesterase inhibitors (eg, inamrinone [formerly amrinone], milrinone) are inotropic
agents with vasodilating properties and long half-lives that are beneficial in patients with cardiac
pump failure, but they may require concomitant vasopressor administration

PCI and CABG

Either PCI or CABG is the treatment of choice for cardiogenic shock
PCI should be initiated within 90 minutes after presentation
PCI remains helpful, as an acute intervention, within 12 hours after presentation
Thrombolytic therapy is second best but should be considered if PCI and CABG are not
immediately available
Procedures
● Placement of a central line may facilitate volume resuscitation, provide vascular access for
multiple infusions, and allow invasive monitoring of central venous pressure. Central venous
pressure may also be used to guide fluid resuscitation.
● Although not necessary for the diagnosis of cardiogenic shock, invasive monitoring with a
pulmonary artery catheter may be helpful in guiding fluid resuscitation in situations in which left
ventricular (LV) preload is difficult to determine.
● Pulmonary artery catheter pressure measurements may also be useful in prognosis.
Retrospective evaluation of these measurements from the SHOCK trial demonstrated that stroke
volume index (SVI) and stroke work index (SWI) vary inversely with mortality.
● An arterial line may be placed to provide continuous blood pressure monitoring. This is
particularly useful if the patient requires inotropic medications.
● When immediate stabilization is necessary for recovery cardiac and other organ systems,
consider placing a temporary over durable mechanical circulatory support device (MCS) as the
first-line device. Temporary MCS options include the following:
● Intra-aortic balloon pump (IABP)
● Percutaneous MCS
● Extracorporeal membrane oxygenation (ECMO)
An IABP may be placed in the emergency department (ED) as a bridge to percutaneous coronary
intervention (PCI) or coronary artery bypass grafting (CABG), to decrease myocardial workload,
and to improve end-organ perfusion. [12] Consider placing an IABP in patients with cardiogenic
shock who have acute mitral regurgitation or a ventricular septal defect, as well as select patients
with severe cardiogenic shock when other MCS devices are unavailable. In the setting of poor
oxygenation not expected to quickly improve with an alternative temporary MCS device or during
cardiopulmonary resuscitation, the preferred temporary MCS option may be veno-arterial (VA)
ECMO. [1, 24]
However, consider long-term durable MCS devices in the following patients with cardiogenic
shock: Those unlikely to recover without long-term MCS support
Those can have a meaningful recovery
Those without irreversible end-organ dysfunction, systemic infections, or relative
contraindications to implantation of durable MCS devices
In addition, patients undergoing evaluation for MCS implantation should also concurrently be
assessed for transplantation.

PCI and coronary artery bypass

An early revascularization strategy with either PCI or CABG, in collaboration between
cardiologists and surgeons, is recommended for appropriate patients with suspected cardiogenic
shock related to acute coronary syndrome (eg, those with uncertain neurologic status, those who
received previous fibrinolysis), regardless of the time delay from MI onset. Radial arterial access
is preferred for angiography and PCI, when feasible. When it is not possible to promptly complete
an early invasive approach, consider fibrinolysis in STEMI-associated cardiogenic shock.

Causes of distributive shock include septic shock, systemic inflammatory response syndrome
(SIRS) due to noninfectious inflammatory conditions such as burns and pancreatitis; toxic shock
syndrome (TSS); anaphylaxis; reactions to drugs or toxins, including insect bites, transfusion
reaction, and heavy metal poisoning; addisonian crisis; hepatic insufficiency; and neurogenic
shock due to brain or spinal cord injury.
Pathophysiology
In distributive shock, the inadequate tissue perfusion is caused by loss of the normal responses of
vascular smooth muscle to vasoconstrictive agents coupled with a direct vasodilating effect. The
net result in a fluid-resuscitated patient is a hyperdynamic, hypotensive state associated with
increased mixed venous O2 saturation; however, evidence of tissue ischemia as manifest by an
increased serum lactate, presumably due to intraorgan functional shunts.
Early septic shock (warm or hyperdynamic) causes reduced diastolic blood pressure; widened
pulse pressure; flushed, warm extremities; and brisk capillary refill from peripheral vasodilation,
with a compensatory increase in cardiac output. In late septic shock (cold or hypodynamic),
myocardial contractility combines with peripheral vascular paralysis to induce a pressure-
dependent reduction in organ perfusion. The result is hypoperfusion of critical organs such as the
heart, brain, and liver.
 Etiology
The most common etiology of distributive shock is sepsis. Other causes include the following:

● SIRS due to noninfectious conditions such as pancreatitis, burns, or trauma

● TSS
● Anaphylaxis
● Adrenal insufficiency
● Reactions to drugs or toxins
● Heavy metal poisoning
● Hepatic insufficiency
● Neurogenic shock
All of these conditions share the common characteristic of hypotension due to decreased SVR and
low effective circulating plasma volume.
Septic shock
The most common sites of infection, in decreasing order of frequency, include the chest, abdomen,
and genitourinary tract.
Septic shock is commonly caused by bacteria, although viruses, fungi, and parasites are also
implicated. Gram-positive bacteria are being isolated more, with their numbers almost similar to
those of gram-negative bacteria, which in the past were considered to be the predominant
organisms. Multidrug-resistant organisms are increasingly common.
Systemic inflammatory response syndrome
Causes of SIRS include the following:

● Infection
● Burns
● Surgery
● Trauma
● Pancreatitis
● Fulminant hepatic failure

Toxic shock syndrome

TSS can result from infection with Streptococcus pyogenes (group A Streptococcus) or
Staphylococcus aureus.
Adrenal insufficiency

Adrenal insufficiency can result from the following:

● Destruction of adrenal glands due to autoimmune disease, infection (tuberculosis, fungal

infection, acquired immunodeficiency syndrome [AIDS]), hemorrhage, cancer, or surgical
removal
● Suppression of hypothalamic-pituitary-adrenal axis by exogenous steroid, usually with
doses at 20 mg daily or higher
● Hypopituitarism
● Metabolic failure in hormone production due to congenital conditions or drug-induced
inhibition of synthetic enzymes (eg, metyrapone, ketoconazole)
Anaphylaxis

Anaphylaxis can develop as a result of the following:

● Drugs such as penicillins and cephalosporins

● Heterologous proteins such as Hymenoptera venom, foods, pollen, and blood serum
products
Physical Examination
Cardinal features of distributive shock include the following:

● Change in mental status

● Heart rate - Greater than 90 beats per minute (note that heart rate elevation is not evident
if the patient is on a beta blocker)
● Hypotension - Systolic blood pressure less than 90 mm Hg or a reduction of 40 mm Hg
from baseline
● Respiratory rate - Greater than 20 breaths per minute
● Extremities - Frequently warm, with bounding pulses and increased pulse pressure
(systolic minus diastolic blood pressure) in early shock; late shock may present as critical organ
dysfunction
● Hyperthermia - Core body temperature greater than 38.3°C (101°F)
● Hypothermia - Core body temperate less than 36°C (96.8°F)
● Pulse oximetry - Relative hypoxemia
● Decreased urine output
Clinical symptoms of the underlying infections found in distributive shock include the following:

● Pneumonia - Dullness to percussion, rhonchi, crackles, bronchial breath sounds

● Urinary tract infection - Costovertebral angle tenderness, suprapubic tenderness, dysuria
and polyuria
● Intra-abdominal infection or acute abdomen - Focal or diffuse tenderness to palpation,
diminished or absent bowel sounds, rebound tenderness
● Gangrene or soft-tissue infection - Pain out of proportion to lesion, skin discoloration and
ulceration, desquamating rash, areas of subcutaneous necrosis
Anaphylaxis is characterized by the following clinical symptoms:

● Respiratory distress
● Wheezing
● Urticarial rash
● Angioedema
TSS is characterized by the following clinical symptoms:

● High fever
● Diffuse rash with desquamation on the palms and soles over a subsequent 1-2 weeks
● Hypotension (may be orthostatic) and evidence of involvement of 3 other organ systems
Streptococcal TSS more frequently presents with focal soft-tissue inflammation and is less
commonly associated with diffuse rash. Occasionally, it can progress explosively within hours.
Adrenal insufficiency is characterized by the following clinical symptoms:

● Hyperpigmentation of skin, oral, vaginal, and anal mucosal membranes may be present in
chronic adrenal insufficiency.
● In acute or acute-on-chronic adrenal insufficiency brought on by physiologic stress,
hypotension may be the only physical sign.
Septic shock: management

Initial resuscitation

Septic shock is a medical emergency. Intravenous fluid resuscitation for sepsis-induced

hypoperfusion should consist of at least 30 mL/kg of intravenous crystalloid fluid being given
within the first 3 hours. After initial fluid resuscitation is performed, additional fluids should be
given based on frequent assessment of the patient's hemodynamic status. Dynamic over static
variables are favored in assessing patient response to fluid resuscitation, with a particular goal of
keeping an initial target mean arterial pressure of 65 mm Hg in patients with septic shock requiring
vasopressors. Normalizing elevated lactate levels is also recommended, as lactate levels serve as
a marker of tissue hypoperfusion.
Empiric broad-spectrum intravenous antibiotics should be initiated within 1 hour for both sepsis
and septic shock. The antibiotics should cover all likely pathogens (including bacterial and
potentially fungal or viral coverage). Upon discovery of the offending organism and the
corresponding antibiotic sensitivities result, the antibiotic spectrum should be narrowed. However,
sustained antibiotics should not be given in shock states of known noninfectious origins (eg,
distributive shock due to pancreatitis).
If combination antibiotic therapy is used for septic shock, the recommendation is to discontinue
the combination therapy within the first few days in response to clinical improvement and/or
evidence of infection resolution. This is recommended in both culture-positive and culture-
negative infections. Antimicrobial treatment of 7-10 days is adequate for most serious infections
associated with septic shock; however, certain infections may require longer clinical courses, such
as the case for patients who have a slow clinical response, undrainable foci of infection, bacteremia
with methicillin-resistance Staphylococcus aureus (MRSA), some fungal and viral infections, or
immunologic deficiencies.

Fluid therapy

Crystalloids are the intravenous fluids of choice for initial resuscitation and subsequent
intravascular volume replacement in patients with sepsis and septic shock. Hydroxyethyl starches
for intravascular volume replacement or gelatins are not recommended choices for fluid
resuscitation.

Vasoactive medications

Norepinephrine is the first-choice vasopressor for patients in septic shock. Either vasopressin or
epinephrine can be added to norepinephrine to raise the mean arterial pressure to target. Dopamine
is another alternative vasopressor agent to norepinephrine in patients with low risk of arrhythmias,
although this is a weak recommendation with low quality of evidence. Low-dose dopamine is not
recommended for renal protection.
Dobutamine is another vasopressor that is recommended in patients who show evidence of
persistent hypoperfusion despite adequate fluid loading and the use of vasopressor agents. The
dose of dobutamine should be titrated to the specific endpoint of tissue perfusion. The dose should
also be reduced in the setting of worsening hypotension and arrhythmias. Blood pressure should
be monitored via an arterial line when using vasopressors.

Corticosteroids

The guidelines suggest against using intravenous hydrocortisone to treat septic shock in patients
adequately treated with vasopressors and fluid resuscitation. If this is not possible, 200 mg of
intravenous hydrocortisone is recommended per day to help augment blood pressure to goal.

Blood products

It is recommended that packed red blood cell transfusion occur when the hemoglobin is below 7.0
g/dL. Red blood cell transfusion should occur only when the hemoglobin concentration decreases
to less than 7.0 g/dL in adults in the absence of acute hemorrhage, myocardial ischemia, or severe
hypoxemia. Erythropoietin is not recommended for the treatment of sepsis-related anemia.

Immunoglobulins

The use of intravenous immunoglobulins is not recommended in patients with sepsis or septic
shock.

Glucose control

In septic ICU patients, there should be a protocol for insulin dosing when two consecutive blood
glucose levels are greater than 180 mg/dL, with a target of 110-180 mg/dL. Furthermore, glucose
levels should be monitored every 1-2 hours until stabilization of insulin infusion and glucose
levels.

Renal replacement therapy

Continuous or intermittent forms of renal replacement therapy can be used to facilitate

management of fluid balance in hemodynamically unstable septic patients, or in septic patients
with acute kidney injury who have an increase in creatinine/oliguria.

Bicarbonate therapy

Sodium bicarbonate therapy may improve hemodynamics in patients with lactic acidemia and a
pH of less than 7.15.

Venous thromboembolism prophylaxis

In the absence of contraindications, pharmacologic prophylaxis against venous thromboembolism

(VTE) should be initiated. Low molecular weight heparins are preferred over unfractionated
heparin for VTE. Whenever possible, a combination of pharmacologic and mechanical
prophylaxis is recommended. However, when pharmacologic prophylaxis is not possible (eg,
hemorrhagic shock, intracranial bleeding), mechanical VTE prophylaxis is suggested.

Hypovolemic shock
Hypovolemic shock refers to a medical or surgical condition in which rapid fluid loss results in
multiple organ failure due to inadequate circulating volume and subsequent inadequate perfusion.
Endothelium plays a critical role in vascular physiological, pathophysiological, and reparative
processes. The functions of the endothelium are highly altered following hypovolemic shock due
to ischemia of the endothelial cells and by reperfusion due to resuscitation with fluids. Due to
oxygen deprivation, endothelial cell apoptosis is induced following hypovolemic shock.
Most often, hypovolemic shock is secondary to rapid blood loss (hemorrhagic shock).
Acute external blood loss secondary to penetrating trauma and severe GI bleeding disorders are 2
common causes of hemorrhagic shock. Hemorrhagic shock can also result from significant acute
internal blood loss into the thoracic and abdominal cavities.

Physical
The physical examination should always begin with an assessment of the airway, breathing, and
circulation. Once these have been evaluated and stabilized, the circulatory system should be
evaluated for signs and symptoms of shock.
Do not rely on systolic BP as the main indicator of shock; this practice results in delayed diagnosis.
Compensatory mechanisms prevent a significant decrease in systolic BP until the patient has lost
30% of the blood volume. More attention should be paid to the pulse, respiratory rate, and skin
perfusion. Also, patients taking beta-blockers may not present with tachycardia, regardless of the
degree of shock.
Classes of hemorrhage have been defined, based on the percentage of blood volume loss. However,
the distinction between these classes in the hypovolemic patient often is less apparent. Treatment
should be aggressive and directed more by response to therapy than by initial classification.

Class I hemorrhage (loss of 0-15%)

In the absence of complications, only minimal tachycardia is seen. Usually, no changes in BP,
pulse pressure, or respiratory rate occur.
A delay in capillary refill of longer than 3 seconds corresponds to a volume loss of approximately
10%.

Class II hemorrhage (loss of 15-30%)

Clinical symptoms include tachycardia (rate >100 beats per minute), tachypnea, decrease in pulse
pressure, cool clammy skin, delayed capillary refill, and slight anxiety.
The decrease in pulse pressure is a result of increased catecholamine levels, which causes an
increase in peripheral vascular resistance and a subsequent increase in the diastolic BP.

Class III hemorrhage (loss of 30-40%)

By this point, patients usually have marked tachypnea and tachycardia, decreased systolic BP,
oliguria, and significant changes in mental status, such as confusion or agitation.
In patients without other injuries or fluid losses, 30-40% is the smallest amount of blood loss that
consistently causes a decrease in systolic BP.
Most of these patients require blood transfusions, but the decision to administer blood should be
based on the initial response to fluids.

Class IV hemorrhage (loss of >40%)

Symptoms include the following: marked tachycardia, decreased systolic BP, narrowed pulse
pressure (or immeasurable diastolic pressure), markedly decreased (or no) urinary output,
depressed mental status (or loss of consciousness), and cold and pale skin.
This amount of hemorrhage is immediately life threatening.
Emergency Department Care
Three goals exist in the emergency department treatment of the patient with hypovolemic shock
as follows: (1) maximize oxygen delivery - completed by ensuring adequacy of ventilation,
increasing oxygen saturation of the blood, and restoring blood flow, (2) control further blood loss,
and (3) fluid resuscitation. Also, the patient's disposition should be rapidly and appropriately
determined.

Maximizing oxygen delivery

The patient's airway should be assessed immediately upon arrival and stabilized if necessary. The
depth and rate of respirations, as well as breath sounds, should be assessed. If pathology (eg,
pneumothorax, hemothorax, flail chest) that interferes with breathing is found, it should be
addressed immediately. High-flow supplemental oxygen should be administered to all patients,
and ventilatory support should be given, if needed.
Once IV access is obtained, initial fluid resuscitation is performed with an isotonic crystalloid,
such as lactated Ringer solution or normal saline. An initial bolus of 1-2 L is given in an adult (20
mL/kg in a pediatric patient), and the patient's response is assessed.
If vital signs return to normal, the patient may be monitored to ensure stability, and blood should
be sent for typed and cross-matched. If vital signs transiently improve, crystalloid infusion should
continue and type-specific blood obtained.

Controlling further blood loss

Control of further hemorrhage depends on the source of bleeding and often requires surgical
intervention.
In the patient with GI bleeding, intravenous vasopressin and H2 blockers have been used.
Vasopressin commonly is associated with adverse reactions, such as hypertension, arrhythmias,
gangrene, and myocardial or splanchnic ischemia. Therefore, it should be considered secondary to
more definitive measures. H2 blockers are relatively safe but have no proven benefit.
Somatostatin and octreotide infusions have been shown to reduce gastrointestinal bleeding from
varices and peptic ulcer disease. These agents possess the advantages of vasopressin without the
significant side effects.
In patients with variceal bleeding, use of a Sengstaken-Blakemore tube can be considered. These
devices have a gastric balloon and an esophageal balloon. The gastric one is inflated first, and then
the esophageal one is inflated if bleeding continues. The use of this tube has been associated with
severe adverse reactions, such as esophageal rupture, asphyxiation, aspiration and mucosal
ulceration. For this reason, its use should be considered only as a temporary measure in extreme
circumstances.

Resuscitation

Whether crystalloids or colloids are best for resuscitation continues to be a matter for discussion
and research. Many fluids have been studied for use in resuscitation; these include isotonic sodium
chloride solution, lactated Ringer solution, [5] hypertonic saline, albumin, purified protein fraction,
fresh frozen plasma, hetastarch, pentastarch, and dextran 70.
Proponents of colloid resuscitation argue that the increased oncotic pressure produced with these
substances decreases pulmonary edema. However, the pulmonary vasculature allows considerable
flow of material, including proteins, between the intravascular space and interstitium. Maintenance
of the pulmonary hydrostatic pressure at less than 15 mm Hg appears to be a more important factor
in preventing pulmonary edema
 Gastrointestinal bleeding
Upper gastrointestinal bleeding is a common medical emergency worldwide and refers to
bleeding from the esophagus, stomach, or duodenum. Patients present with hematemesis (bloody
or coffee ground emesis) or melena, although hematochezia can occur in the context of a major
bleed and is typically associated with hemodynamic instability. Patients with melena present
with lower hemoglobin values than patients with hematemesis, probably because presentation is
more likely to be delayed. Therefore, patients with melena more often require transfusion,
although mortality is lower in patients with melena than in those with hematemesis in some
series. Numerous improvements in the management of upper gastrointestinal bleeding have been
incorporated into clinical practice in recent years. However, many patients now have risk factors
for a poorer outcome, including increasing age and major medical comorbidities.
Etiology
Ulcer-related UGIB
Bleeding peptic ulcers account for the majority of patients presenting with acute upper
gastrointestinal (GI) bleeding (UGIB). As previously mentioned, peptic ulcer disease is strongly
associated with H pylori infection. The organism causes disruption of the mucous barrier and has
a direct inflammatory effect on the gastric and duodenal mucosa.
In cases of ulcer-associated UGIB, as the ulcer burrows deeper into the gastroduodenal mucosa,
the process causes weakening and necrosis of the arterial wall, leading to the development of a
pseudoaneurysm. The weakened wall ruptures, producing hemorrhage.
The flow through a vessel varies with the fourth power of the radius; thus, small increases in
vessel size can mean much larger amounts of blood flow and bleeding, with more severe
hypotension and more complications, especially in older patients.
Vomiting-related UGIB
During vomiting, the lower esophagus and upper stomach are forcibly inverted. Vomiting
attributable to any cause can lead to a mucosal tear of the lower esophagus or upper stomach.
The depth of the tear determines the severity of the bleeding. Rarely, vomiting can result in
esophageal rupture, leading to bleeding, mediastinal air entry, left pleural effusion (salivary
amylase can be present) or left pulmonary infiltrate, and subcutaneous emphysema.
Mallory-Weiss tears account for 8%-15% of acute upper GI hemorrhage. Kenneth Mallory and
Soma Weiss first described the syndrome in 1929. The occasionally massive UGIB results from
a tear in the mucosa of the gastric cardia. Like many upper GI tract lesions, the Mallory-Weiss
tear may stop bleeding spontaneously 85%-90% of the time.
Acute stress-related mucosal disease (or stress ulcer) results from predisposing clinical
conditions that have the potential to alter the local mucosal protective barriers, such as mucus,
bicarbonate, blood flow, and prostaglandin synthesis. Any disease process that disrupts the
balance of these factors results in diffuse gastric mucosal erosions.
This is most commonly observed in patients who have undergone episodes of shock, multiple
trauma, acute respiratory distress syndrome, systemic respiratory distress syndrome, acute renal
failure, and sepsis.
The Dieulafoy lesion, first described in 1896, is a vascular malformation of the proximal
stomach, usually within 6 cm of the gastroesophageal junction along the lesser curvature of the
stomach. However, it can occur anywhere along the GI tract. This lesion accounts for 2%-5% of
acute UGIB episodes.
NSAIDs cause gastric and duodenal ulcers by inhibiting cyclooxygenase, which causes
decreased mucosal prostaglandin synthesis and results in impaired mucosal defenses. Daily
NSAID use causes an estimated 40-fold increase in gastric ulcer creation and an 8-fold increase
in duodenal ulcer creation.
Long-term NSAID use is associated with a 20% incidence in the development of mucosal
ulceration. Medical therapy includes avoiding the ulcerogenic drug and beginning a histamine-2
(H2)–receptor antagonist or a proton pump inhibitor that provides mucosal protection.

Gastrointestinal varices are abnormally dilated submucosal veins in the digestive tract due to
portal hypertension and can potentially cause life-threatening bleeding. Prevalence of varices
increases with the severity of liver disease (Child-Pugh class A 42.7%, class B 70.7% and class
C 75.5%). The incidence of esophageal varices in cirrhotic patients is around 5% at the end of
one year and 28% at the end of three years. Small varices progress to large varices at a rate of
10% to 12% annually

Signs and symptoms

Signs and symptoms of acute UGIB include the following:
● Hematemesis
● Melena
● Hematochezia
● Syncope
● Presyncope
● Dyspepsia
● Epigastric pain
● Heartburn
● Diffuse abdominal pain
● Dysphagia
● Weight loss
● Jaundice

Probability of Upper GI Probability of Lower GI

Clinical Indicator
Source Source

Hematemesis Almost certain Rare

Melena Probable Possible

Hematochezia Possible Probable

Blood-streaked stool Rare Almost certain

Occult blood in stool Possible Possible

GI = gastrointestinal.

The clinical presentation of LGIB varies with the anatomical source of the bleeding, as
follows:
● Maroon stools, with LGIB from the right side of the colon
● Bright red blood per rectum with LGIB from the left side of the colon
● Melena with cecal bleeding
In practice, however, patients with UGIB and right-sided colonic bleeding may also present with
bright red blood per rectum if the bleeding is brisk and massive.
The presentation of LGIB can also vary depending on the etiology. A young patient with
infectious or noninfectious (idiopathic) colitis may present with the following:
● Fever
● Dehydration
● Abdominal cramps
● Hematochezia

Physical Examination
The goal of the patient's physical examination is to evaluate for shock and blood loss.
Patients present with an ulcer that has bled or is actively bleeding (although approximately 80%
of ulcers stop bleeding).
Hematemesis and melena are the most common presentations of acute UGIB, and patients may
present with both symptoms.
Assessing the patient for hemodynamic instability and clinical signs of poor perfusion is
important early in the initial evaluation to properly triage patients with massive hemorrhage to
ICU settings.
Worrisome clinical signs and symptoms of hemodynamic compromise include tachycardia of
more than 100 beats per minute (bpm), systolic blood pressure of less than 90 mm Hg, cool
extremities, syncope, and other obvious signs of shock, ongoing brisk hematemesis, or the
occurrence of maroon or bright-red stools, which requires rapid blood transfusion.
Pulse and blood pressure should be checked with the patient in supine and upright positions to
note the effect of blood loss. Significant changes in vital signs with postural changes indicate an
acute blood loss of approximately 20% or more of the blood volume.
Formal risk scoring systems have been validated and are becoming more widely utilized.
Signs of chronic liver disease should be noted, including spider angiomata, gynecomastia,
increased luneals, splenomegaly, ascites, pedal edema, and asterixis.
Signs of tumor are uncommon but portend a poor prognosis. Signs include a nodular liver, an
abdominal mass, and enlarged and firm lymph nodes. The finding of telangiectasias may indicate
the rare case of Osler-Weber-Rendu syndrome.
Diagnosis
Workup may include the following:
● Orthostatic blood pressure
● Complete blood cell count with differential
● Hemoglobin level
● Type and crossmatch blood
● Basic metabolic profile, blood urea nitrogen, and coagulation profile
● Risk scoring assessment
● Calcium level
● Gastrin level
● Endoscopy
● Chest radiography
● Nasogastric lavage
● Computed tomography (CT) angiography (CTA)
● Angiography (if bleeding persists and endoscopy fails to identify a bleeding site)
Standard CT scanning and ultrasonography may be indicated for the evaluation of the
following :
● Liver disease with cirrhosis
● Cholecystitis with hemorrhage
● Pancreatitis with pseudocyst and hemorrhage
● Aortoenteric fistula
Variceal bleeding
Variceal bleeding accounted for 11% of patients admitted to hospital with acute upper
gastrointestinal bleeding in a nationwide UK audit.15 However, the proportion of patients with
variceal bleeding varies widely and is related to the proportion of people with liver disease in the
population served. Patients with variceal bleeding have a higher mortality than those with non-
variceal bleeding, and this is largely related to the severity of underlying liver disease.
The optimal endoscopic therapy for esophageal variceal bleeding is variceal band ligation, which
is associated with less rebleeding and fewer side effects than sclerotherapy.47987 If gastric
varices are found, ligation can be used for gastroesophageal varices type-1, where esophageal
varices extend several centimeters distally along the gastric lesser curve. Injection of tissue
adhesive (eg, N-butyl-cyanoacrylate) is the recommended endoscopic approach for all other
types of gastric varices, although thrombin injection can be considered.Thrombin injection has
been described for gastric variceal bleeding in cohort studies, but to date no RCTs have
compared it with other treatments.
Management
Treatment may include the following:
● Secure the airway
● Insert bilateral, 16-gauge (minimum), upper extremity, peripheral intravenous lines
● Replace each milliliter of blood loss with 3 mL of crystalloid fluid
● In patients with severe coexisting medical illnesses, pulmonary artery catheter insertion
for monitoring hemodynamic cardiac performance
● Foley catheter placement for continuous evaluation of urinary output as a guide to renal
perfusion
● Endoscopic hemostatic therapy for bleeding ulcers and varices
● Surgical repair of perforated viscus
● For high-risk peptic ulcer patients, high-dose intravenous proton pump inhibitors
● Mesenteric angiography with embolization therapy
Indications for surgery in patients with bleeding peptic ulcers include the following:
● Severe, life-threatening hemorrhage not responsive to resuscitative efforts
● Failure of medical therapy and endoscopic hemostasis with persistent recurrent bleeding
● A coexisting reason for surgery (eg, perforation, obstruction, malignancy)
● Prolonged bleeding, with loss of 50% or more of the patient's blood volume
● A second hospitalization for peptic ulcer hemorrhage

Summary of the management of upper gastrointestinal bleeding

Pre-endoscopic management
Hemodynamic assessment and resuscitation as needed
Blood transfusion at a hemoglobin threshold of 70-80 g/L; higher threshold if severe bleeding
with hypotension
Risk assessment:
-If Glasgow-Blatchford score ≤1 consider outpatient endoscopy and management
Erythromycin (as a prokinetic agent) and proton pump inhibitor may be considered
Patients with cirrhosis should receive vasoactive drugs and antibiotics
Endoscopic
Endoscopy is generally recommended within 24 hours in patients admitted to hospital
If the patient has severe bleeding with hemodynamic instability, urgent endoscopy should be
performed after resuscitation
Ulcers with active bleeding and non-bleeding visible vessels should receive endoscopic therapy;
endoscopic therapy may also be used for ulcers with adherent clots
Injection therapy (eg, epinephrine), thermal probes (eg, bipolar electrocoagulation, heater probe),
or clips should be used
Epinephrine injection should always be followed by a second modality
Recurrent bleeding should be treated with repeat endoscopic therapy but subsequent bleeding by
transarterial embolization or surgery
Esophageal variceal bleeding should be treated with ligation and gastric varices with the
injection of tissue adhesive
Refractory variceal bleeding should be treated with transjugular portosystemic shunt
For massive refractory esophageal variceal bleeding a removable covered metal stent is preferred
to balloon tamponade as a temporizing measure
Post-endoscopic management
Patients who have ulcers with high risk lesions (active bleeding, visible vessel, adherent clot)
should receive high dose proton pump inhibitors for 72 h
Patients with cirrhosis should continue antibiotics for up to seven days regardless of the bleeding
source
Variceal bleeding should be treated with vasoactive drugs for up to five days
When used for secondary prevention, aspirin should be continued or reintroduced soon after
hemostasis is achieved
Early reintroduction of other antithrombotic drugs is also recommended after hemostasis is
achieved to reduce thrombotic events and death.

Variceal bleeding - AASLD -20016 guidelines indicate the following :

Conservative transfusion of packed red blood cell (PRBC): Starting to transfuse when the Hb
reaches a threshold of around 7 g/dL, with the goal of maintaining it between 7 and 9 g/dL.
Short-term (maximum 7 days) antibiotic prophylaxis should be instituted in any patient with
cirrhosis and gastrointestinal hemorrhage - Intravenous (IV) ceftriaxone 1 g/24 h is the antibiotic
of choice.
Vasoactive drugs (somatostatin / its analogue, octreotide; vasopressin / its analogue, terlipressin)
should be initiated as soon as bleeding is suspected.
EGD should be performed within 12 hours of admission and once the patient is
hemodynamically stable.
EVL (endoscopic variceal ligation) should be performed.
In patients at high risk of failure or rebleeding (Child-Turcotte-Pugh class C cirrhosis or class B
with active bleeding on endoscopy) who have no contraindications for TIPS, an “early” TIPS
within 72 hours.
For patients in whom an early TIPS is not performed, IV vasoactive drugs should be continued
for 2-5 days and nonselective beta-blockers initiated once vasoactive drugs are discontinued.
In patients in whom TIPS is performed successfully, IV vasoactive drugs can be discontinued.

Management of patient with shock (cardiogenic, septic, obstructive)

Situation task № 1
A 57-year-old male patient had an attack of retrosternal pain that lasted more than 1,5 hours.
Objectively: the patient is inert, adynamic, has pale skin, cold extremities, poor volume pulse,
heart rate - 120/min, AP - 70/40 mm Hg. ECG shows ST elevation in II, III, aVF leads. What
condition are these changes typical for?
1. Make a diagnosis.
2. Emergency treatment.

Situation task № 2
A 64 y.o. patient has developed of squeering substernal pain which had appeared 2 hours ago
and irradiated to the left shoulder, marked weakness. On examination: pale skin, cold sweat.
Pulse- 108 bpm, AP- 70/50 mm Hg, heart sounds are deaf, vesicular breathing, soft abdomen,
painless, varicouse vein on the left shin, ECG: synus rhythm, heart rate is 100 bmp, ST-segment
is sharply elevated in II, III aVF leads. What is the most likely disorder?
1. Make a diagnosis.
2. Emergency treatment.

Situation task №3
43 years old patient complains of thirst, general weakness, dizziness, nausea. The patient feels
chilly. The disease started acutely: 4 hours ago the nonintensive epigastric pain had appeared and
gradually disappeared. 12 hours ago he had a headache and took a tablet of analgin. From history
we know that he has duodenal peptic ulcer for 10 years; exacerbations - every year (up to 2 times
a year.)
On examination: the patient’s nutritional state is satisfactory. The skin and mucous membranes
are pale. The body temperature is 36,0 º C. Pulse - 100/min., low, regular. BP - 80/65 mm Hg (in
horizontal position). In the transition to a vertical position - the pulse - 120/min., BP - 90/65 mm
Hg. Tongue is coated and dry. There is palpatory tenderness in pyloroduodenal zone. Heart – the
1th sound is soft at the apex. All other organs are without pathological changes.
1. Make a preliminary diagnosis.
2. Administer the first aid.

Situation Task №4
The patient aged 42, who 15 years drank alcohol, after an episode of alcohol abuse occurred
vomiting "mouthful." The vomit had a dark cherry colour, and then - bright red. Exam: body
temperature - 36,5 ° C. Pulse – 105 /min, rhythmical, weak. BP - 105/65 mmHg RR - 22/min.
Tongue is furred and dry. Abdomen is enlarged, superficial veins dilated, ascites, enlarged
spleen.
1. Make a diagnosis.
2. Management.

Situation Task №5
During the doctor's round, a 56-year-old male patient with decompensated cirrhosis complains of
dizziness, palpitations, moving black specks seen before the eyes, general weakness. The patient
is pale, Ps- 110/min, AP- 90/50 mm Hg. What complication is most likely to have occurred in
the patient?
1. Make a diagnosis.
2. Emergency treatment.

Recommended literature for students:

А. Main:
1. Davidson’s Principles and Practice of Medicine, 22nd Edition, 2014, P. 542-551.
2. Harrison's Principles of Internal Medicine, 20e J. Larry Jameson, Anthony S. Fauci, Dennis L.
Kasper, Stephen L. Hauser, Dan L. Longo, Joseph Loscalzo) - sec 5-chapter 271; 337
B. Additional:
1 - https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/Acute-and-Chronic-Heart-
Failure
2 - https://www.cardioaragon.com/wp-content/uploads/ejhf.1531.pdf
3 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986746/
4. https://emedicine.medscape.com/article/760145-medication

Methodical recommendation made by Ph.D. Berko G.K.

Ph.D. Ostapchuk O.I.