Cardiology – ClinCaseQuest

Acute Pulmonary Edema: Emergency Care Algorithm – Should We Remove or Redistribute the Fluid?

Nataliia Lopina — Sat, 05 Oct 2024 10:41:49 +0000

Case Presentation:

A 64-year-old man was transported to the emergency department by ambulance due to a progressively worsening shortness of breath over the past two weeks. He also noticed swelling in his legs. The patient reports feeling breathless when climbing stairs or walking more than two blocks. Approximately one month ago, he suffered an ST-elevation myocardial infarction, which required the implantation of a stent in the left anterior descending artery.

On physical examination, elevated jugular venous pressure was noted, along with bilateral lower extremity edema. Lung auscultation revealed bilateral crepitation in the basal regions. A chest X-ray showed bilateral pleural effusion and the presence of Kerley B lines.

Pulmonary edema

Acute pulmonary edema is a life-threatening emergency that requires immediate medical intervention. It is characterized by secondary shortness of breath and hypoxia, resulting from fluid accumulation in the lungs, which disrupts gas exchange.

Acute heart failure (HF) typically manifests as “acute decompensated heart failure” (ADHF), secondary chronic heart failure (CHF), or de novo heart failure. The most severe complications of acute heart failure are acute pulmonary edema and cardiogenic shock. According to the EuroHeart Failure Survey II, 37% of patients hospitalized with heart failure presented with de novo acute heart failure, and 16% had acute pulmonary edema.

Acute pulmonary edema has a high mortality rate, requiring urgent care and often hospitalization. The one-year mortality rate for patients hospitalized with acute pulmonary edema is as high as 40%.

The most common causes of acute pulmonary edema include myocardial ischemia, arrhythmias (e.g., atrial fibrillation), acute valvular dysfunction, and fluid overload. Other contributing factors can include pulmonary embolism, anemia, and renal artery stenosis. Non-adherence to treatment plans and adverse drug effects may also precipitate pulmonary edema.

General practitioners are typically familiar with the classic presentation of acute pulmonary edema—severe dyspnea, distress, pallor, sweating, tachycardia, and decreased peripheral perfusion. However, in primary care settings, the clinical manifestations of acute heart failure may be less pronounced or atypical (e.g., delirium or falls in the elderly), making timely diagnosis more challenging.

Pulmonary edema is the accumulation of fluid in the interstitial space and air spaces of the alveoli, impairing normal gas exchange.

Types of Pulmonary Edema

Cardiogenic Pulmonary Edema
This occurs due to a sharp increase in left ventricular filling pressure and left atrial volume, leading to increased pulmonary capillary pressure.
- Atrial Outflow Obstruction
  Pulmonary edema can result from mitral stenosis or, more rarely, from conditions like atrial myxoma, thrombosis of a prosthetic valve, or a congenital membrane in the left atrium (e.g., cor triatriatum). Mitral stenosis, often a consequence of rheumatic fever, gradually causes pulmonary edema. Other factors commonly accompany mitral stenosis in acute pulmonary edema, such as reduced left ventricular filling caused by tachycardia in arrhythmias (e.g., atrial fibrillation) or fever.
- Causes of Left Ventricular Dysfunction:
  - Ischemic heart disease
  - Hypertension
  - Acute and chronic heart valve disease (e.g., aortic stenosis, aortic regurgitation, mitral regurgitation)
  - Dilated cardiomyopathy
  - Metabolic conditions (e.g., hypothyroidism)
  - Myocarditis
  - Myocardial toxins (e.g., alcohol, cocaine, chemotherapeutic agents such as doxorubicin, trastuzumab)
  - Ventricular hypertrophy
  - Outflow obstruction
  - Left ventricular diastolic dysfunction (ischemia and infarction can cause diastolic dysfunction in addition to systolic dysfunction). Similarly, myocardial injury can cause systolic or diastolic dysfunction.
- Arrhythmias
  Tachysystolic atrial fibrillation and ventricular tachycardia can precipitate pulmonary edema.
- Non-Compliance with Dietary or Medication Guidelines
  Failure to adhere to dietary salt restrictions or prescribed medications (e.g., diuretics) can lead to fluid retention and pulmonary edema.
Non-Cardiogenic Pulmonary Edema
Pulmonary edema with normal pulmonary artery pressure (≤ 18 mm Hg).
- Causes include:
  - Acute respiratory distress syndrome (ARDS)
  - High-altitude pulmonary edema (HAPE)
  - Opioid overdose
  - Hypoxia, shortness of breath, and dry cough due to altitude exposure in cases of altitude sickness.

Symptoms

Sudden onset of severe shortness of breath.
Anxiety and a feeling of drowning.
Profuse sweating.
Patients with a gradual onset of symptoms (e.g., over 24 hours) often report dyspnea on exertion, orthopnea, and paroxysmal nocturnal dyspnea.
Cough is a common symptom. Pink, frothy sputum may occur in severe cases. Occasionally, hoarseness (Ortner’s sign) can result from compression or recurrent paralysis of the laryngeal nerve by an enlarged left atrium, as seen with mitral stenosis.
Chest pain should raise suspicion for acute ischemia, myocardial infarction, or aortic dissection with acute aortic regurgitation causing pulmonary edema.

Physical Examination

Tachypnea and tachycardia are often present. Patients may adopt an upright position (orthopnea) and become agitated or confused. They usually appear anxious, with profuse sweating.
Hypertension is commonly seen in the hyperadrenergic state.
Hypotension indicates severe left ventricular (LV) systolic dysfunction and the possibility of cardiogenic shock.
Cool extremities may signal low cardiac output and poor peripheral perfusion.
Lung auscultation typically reveals fine crackles (rales), often starting in the lung bases. As the condition worsens, the crackles progress toward the upper lung fields. Wheezing may also be present. Jugular venous distention may indicate increased right heart pressures.
Heart auscultation can aid in diagnosing acute valvular disorders that manifest with pulmonary edema:
- Aortic stenosis is associated with a crescendo-decrescendo systolic murmur, best heard at the upper sternal border, radiating to the carotid arteries.
- Acute aortic regurgitation presents with a short, soft diastolic murmur.
- Acute mitral regurgitation produces a loud systolic murmur, best heard at the apex or lower left sternal border. In the context of ischemic heart disease, this may indicate acute myocardial infarction with rupture of the mitral valve chordae.
Rust-colored sputum may result from ruptured pulmonary capillaries due to increased hydrostatic pressure.
Pallor or mottled skin can result from peripheral vasoconstriction, low cardiac output, and blood shunting to the central circulation in patients with poor LV function and increased sympathetic tone. Mottled skin is an independent predictor of increased in-hospital mortality.
In patients with concomitant right ventricular failure, hepatomegaly, hepatojugular reflux, and peripheral edema may be observed.
Severe acute pulmonary edema may be associated with altered mental status, often due to hypoxia or hypercapnia. Although acute pulmonary edema is typically associated with hypocapnia, hypercapnia and respiratory acidosis can occur in patients with severe or underlying chronic obstructive pulmonary disease (COPD).

Differential Diagnosis

Pneumonia
Diffuse opacification of lung fields due to atelectasis without fluid accumulation

Additional Examination Methods

Chest X-ray
Signs of increased left atrial pressure, Kerley B lines, and pleural effusion.
Echocardiography
- Reduced or preserved left ventricular ejection fraction (LVEF)
- Valvular abnormalities, chordal or papillary muscle rupture
- Mitral regurgitation
- Aortic stenosis

Causes of Acute Pulmonary Edema

Cardiogenic pulmonary edema must be distinguished from pulmonary edema caused by damage to the alveolar-capillary membrane, which can result from various etiologies. Damage to this barrier may occur in several direct lung injuries (such as pneumonia, aspiration pneumonitis, toxin inhalation, radiation exposure, drowning, or fat embolism) as well as in indirect lung injuries (such as sepsis, shock, multiple blood transfusions, acute pancreatitis, or anaphylactic shock).

The most common cause of heart failure is myocardial dysfunction, which can arise due to one or more of the following factors:

Hypertension (present in over 60% of patients with heart failure)
Ischemic heart disease (present in over 50% of patients with heart failure)
Idiopathic dilated cardiomyopathy (seen in approximately 10% of patients with heart failure)
Diabetes mellitus
Excessive alcohol consumption
Obesity
Drug toxicity

Other cardiac causes of heart failure include arrhythmias, valvular dysfunction, and pericardial disease.

Non-cardiac causes of heart failure include hypovolemia (due to dehydration or hemorrhage), pulmonary embolism, and conditions associated with increased cardiac output (such as anemia, sepsis, and thyrotoxicosis).

Cardiogenic pulmonary edema is defined as pulmonary edema caused by elevated capillary hydrostatic pressure, which is secondary to increased pulmonary venous pressure. It reflects the accumulation of low-protein fluid in the pulmonary interstitium and alveoli as a result of cardiac dysfunction.

Stages of Development of Pulmonary Edema

The progression of fluid accumulation in acute pulmonary edema can be described in three physiological stages:

Stage 1
In the initial stage, increased pressure in the pulmonary artery leads to the stretching and opening of small pulmonary vessels. At this stage, gas exchange is not significantly impaired and may even slightly improve. This is due to the redistribution of blood flow within the lungs, enhancing perfusion in certain areas.

Stage 2
In stage 2, fluid and colloids begin to move from the pulmonary capillaries into the pulmonary interstitium. Initially, the lymphatic system compensates by increasing lymphatic outflow to efficiently remove the excess fluid. However, continued fluid filtration can overwhelm the drainage capacity of the lymphatic system. Fluid first accumulates in the compliant interstitial compartments, especially around large vessels in dependent zones (such as the perivascular tissue).

At this stage, the accumulation of fluid in the interstitium can start to affect the function of small airways, leading to mild hypoxemia. However, the hypoxemia is usually not severe enough to cause significant tachypnea. Any tachypnea that does occur is mainly due to the stimulation of juxtapulmonary capillary (J-type) receptors, which are unmyelinated nerve endings near the alveoli. These receptors are involved in reflexes that regulate respiration and heart rate.

Stage 3
In the final stage, as fluid filtration continues and the loose interstitial space becomes filled, excess fluid crosses into the alveolar spaces. The interstitial space can accommodate up to approximately 500 mL of fluid. Once the interstitial capacity is exceeded, fluid moves across the alveolar epithelium into the alveoli. At this stage, gas exchange is noticeably impaired, vital capacity and other lung volumes are significantly reduced, and hypoxemia becomes more pronounced. This is when patients typically experience more severe respiratory distress and worsening oxygenation.

Diagnostics

Laboratory tests and imaging are essential for evaluating patients with cardiogenic pulmonary edema. The following diagnostic tools are commonly used:

Complete Blood Count (CBC)
A CBC is useful for detecting severe anemia and may reveal signs of sepsis or infection, particularly if there is a significantly elevated white blood cell count.

Serum Electrolytes
Measuring serum electrolytes is important because patients with chronic heart failure often take diuretics, making them prone to electrolyte imbalances, especially hypokalemia and hypomagnesemia. Patients with chronic renal failure are at high risk for hyperkalemia, particularly if they are not undergoing regular hemodialysis.

Blood Urea Nitrogen (BUN) and Creatinine Levels
These tests assess kidney function, which is crucial for evaluating the patient’s potential response to diuretics and identifying any underlying renal failure.

Pulse Oximetry
Pulse oximetry is used to assess hypoxia, providing insight into the severity of acute pulmonary edema. It is also helpful for monitoring the patient’s response to supplemental oxygen therapy and other treatments.

Arterial Blood Gas (ABG) Analysis
ABG analysis offers a more precise measurement of oxygen saturation compared to pulse oximetry. While the decision to initiate mechanical ventilation is usually based on clinical findings, ABG results may be considered in more complex cases.

Electrocardiography (ECG)
An ECG can detect acute tachyarrhythmias or bradyarrhythmias, as well as signs of acute myocardial ischemia or myocardial infarction, which may be contributing factors to pulmonary edema.

Chest Radiography (X-ray)
A chest X-ray helps differentiate cardiogenic pulmonary edema from other pulmonary causes of severe dyspnea. Key features of cardiogenic pulmonary edema on a chest X-ray include:

Enlarged heart (cardiomegaly)
Redistribution of blood flow
Kerley B lines (indicative of interstitial edema)
Edema in the basal parts of the lungs (contrasted with diffuse edema)
Absence of air bronchograms
Presence of pleural effusion, particularly bilateral and symmetrical, which is more common in acute presentations of chronic heart failure

Table: Differential Diagnosis of Acute Shortness of Breath and Causes of Acute Pulmonary Edema

Category	Conditions
Primary Causes of Breathing Disorders	– Exacerbation of chronic obstructive pulmonary disease (COPD) – Acute asthma – Pneumothorax – Pneumonia
Primary Cardiac Causes	– Acute coronary syndrome / myocardial infarction – Arrhythmia – Pericarditis – Acute valve dysfunction (e.g., aortic stenosis, mitral regurgitation) – Endocarditis
Fluid Overload	– Anaphylaxis – Hypervolemia due to excessive fluid intake or renal failure – Medication effects (e.g., NSAIDs, non-dihydropyridine calcium channel blockers such as verapamil and diltiazem)
Non-Cardiogenic Causes of Acute Pulmonary Edema	– Drowning – Laryngospasm / upper airway obstruction – Toxic inhalation
Pulmonary Embolism	– Acute pulmonary embolism with sudden onset of dyspnea
Acute Renal Failure	– Fluid overload and electrolyte imbalances associated with acute renal failure
Conditions with Increased Cardiac Output	– Septicemia – Anemia – Thyrotoxicosis

Table: Differential Diagnosis of Acute Pulmonary Edema

Condition	Key Features
Cardiogenic Pulmonary Edema	– Increased pulmonary capillary pressure
	– Symptoms: shortness of breath, orthopnea, cough, anxiety
	– Signs: crackles on auscultation, jugular venous distension
Pneumonia	– Symptoms: cough, fever, chills, pleuritic chest pain
	– Chest X-ray: localized infiltrates, air bronchograms
Acute Respiratory Distress Syndrome (ARDS)	– Symptoms: severe dyspnea, rapid onset
	– Chest X-ray: bilateral infiltrates, often with a history of trauma or sepsis
Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	– Symptoms: increased sputum production, wheezing, prolonged expiratory phase
	– History of smoking or prior lung disease
Pulmonary Embolism	– Symptoms: sudden onset of dyspnea, chest pain, hemoptysis
	– Risk factors: recent surgery, prolonged immobility
	– Chest X-ray: may be normal; CT pulmonary angiography is diagnostic
Acute Kidney Injury (AKI)	– Symptoms: fluid overload, electrolyte imbalances
	– Elevated BUN and creatinine levels
Anaphylaxis	– Symptoms: urticaria, angioedema, hypotension, wheezing
	– History of exposure to allergens

Echocardiography

Bedside echocardiography in patients with decompensated congestive heart failure (CHF) is an essential diagnostic tool for determining the etiology of pulmonary edema. This imaging modality can assess left ventricular (LV) systolic and diastolic function, as well as evaluate valvular function and pericardial disease.

The identification of new wall motion abnormalities may suggest an acute myocardial infarction. Echocardiography is particularly valuable in diagnosing the mechanical causes of pulmonary edema, including the following conditions:

Acute rupture of the papillary muscle
Acute ventricular septal defect
Cardiac tamponade
LV rupture
Valve vegetation leading to acute severe mitral or aortic regurgitation

Treatment

The management of both acute heart failure and acute pulmonary edema is primarily based on clinical experience rather than randomized controlled trials.

The algorithm for providing medical care can be conditionally divided into two stages:

Pre-Hospital Care: This involves immediate assistance to stabilize the patient before they reach the hospital.
Hospital Care: This stage focuses on comprehensive treatment and monitoring of the patient after admission.

While there are various clinical guidelines for treating acute pulmonary edema, the general principles across these guidelines remain consistent. The goals of therapy for acute pulmonary edema include:

Improving oxygenation
Maintaining adequate blood pressure to ensure perfusion of vital organs
Reducing excess extracellular fluid

Additionally, it is crucial to address the underlying cause of the condition or mitigate its impact on the patient’s status.

Evaluation of a Patient with Acute Pulmonary Edema

Entry Level

Quickly alert relevant personnel (doctors, nurses, clinic staff).
Initiate oxygen therapy.
Establish intravenous access.
Start treatment during patient examination.

Patient History

Previous cardiorespiratory complaints (e.g., nocturnal dyspnea, orthopnea).
List of medications taken.

Objective Review

Vital Signs:
- Temperature
- Pulse (frequency, rhythm)
- Blood pressure
- Respiratory rate (frequency, character)
- Oxygen saturation
Targeted Cardiorespiratory Examination:
- Skin color
- Sweating
- Jugular venous pulse
- Apical impulse (displacement, load)
- Heart sounds (e.g., gallop rhythm)
- Murmurs (e.g., mitral regurgitation, aortic stenosis)
- Peripheral perfusion and edema
- Auscultation for crepitations and wheezing

Monitoring

Blood pressure
ECG monitoring (lead II), if possible
Oxygen saturation
Automated external defibrillator on standby
Urinary catheter

Additional Research Methods (Depending on Availability)

12-lead ECG
Chest X-ray
Laboratory tests (if available):
- Troponin
- Natriuretic peptide (BNP)
Other tests: blood urea nitrogen, electrolyte levels, arterial blood gases
Echocardiogram at the earliest opportunity (depending on patient stability and availability)

Drugs Used in Treatment

The medications commonly used in the management of acute pulmonary edema include nitrates, diuretics, morphine, and inotropes. Some patients may also require ventilatory support.

Strongest Evidence

Nitrates and noninvasive ventilation have the strongest evidence for efficacy in treating acute pulmonary edema. Diuretics are indicated only for patients with fluid overload; furosemide should be administered slowly via intravenous infusion. The most common causes of cardiogenic pulmonary edema include excessive venous return (fluid overload), increased systemic vascular resistance (e.g., after exercise), and left ventricular dysfunction, which can involve contractility disorders, rhythm disturbances, and frequency issues.

Continuous use of morphine is not recommended due to its potential adverse effects. Oxygen should be administered only in cases of hypoxemia.

Inotropic agents should be initiated only when hypotension is present with reduced organ perfusion. In such cases, dobutamine is usually the first-line treatment.

Table. Treatment of acute pulmonary edema

Therapy / Tactics	Dosage	Clarification
Position		– Vertical position of the patient while sitting.
		– Lying on the back if unconscious or in cardiogenic shock.
Oxygen (corrects hypoxemia)	10–15 L/min via mask with reservoir bag.	– Once stable, reduce to 2–6 L/min via nasal cannula or 5–10 L/min via mask.
		– COPD patients should ideally receive controlled oxygen therapy via mask (flow rate 4 L/min).
		– Titrate to oxygen saturation of 94–96% (non-COPD) or 88–92% (COPD).
Glyceryl Trinitrate (venodilator, reduces preload)	400 mcg sublingually every 5 minutes (up to three doses).	– Maintain systolic blood pressure above 100 mm Hg.
	Intravenous infusion starting at 10 mcg/min.	– Double the infusion rate every 5 minutes according to clinical response (maintain SBP above 90 mm Hg).
		– Contraindicated within 48 hours after using phosphodiesterase 5 inhibitors.
Positive Airway Pressure Support	CPAP: Constant positive pressure of 10 cm H2O.	– BiPAP: Inspiratory pressure of 15 cm H₂O, expiratory pressure of 5 cm H2O to prevent alveolar collapse.
		– Contraindicated if: SBP <90 mm Hg; loss of consciousness.
		– Clinical improvement can occur within 10 minutes; duration of use depends on effectiveness and tolerability.
Frusemide (loop diuretic, reduces congestion)	20–80 mg IV bolus.	– Followed by IV infusion at 5–10 mg/h (total dose <100 mg during the first 6 hours and <240 mg during the first 24 hours).
		– Consider repeating the bolus dose in 30–60 minutes if no clinical improvement is observed.
		– High risk of hypovolemia and negative hemodynamic effects; avoid unless there is evidence of fluid overload.
Morphine	1–2 mg IV.	– Does not improve pulmonary edema and is associated with an unfavorable prognosis.
		– Use according to individual indications.
Other Medications		– Low Molecular Weight Heparin (Prophylaxis of venous thromboembolism): Enoxaparin 40 mg/day. Start if there is risk.
		– Digoxin: 500 mcg IV (over 5 or more minutes). Only for patients with tachysystolic atrial fibrillation who have not previously received digoxin.
		– Spironolactone: 25–50 mg orally. Consider in cases of fluid overload with poor response to IV furosemide.
Other Methods of Therapy (ICU)		– Adrenaline infusion.
		– Vasopressin antagonists (conivaptan, tolvaptan).
		– Vasodilators (sodium nitroprusside).
		– Inotropes: for cardiogenic shock or hypoperfusion with BP <90 mmHg (dobutamine, dopamine).
		– Phosphodiesterase inhibitors (milrinone, enoximone).
		– Ultrafiltration.
		– Mechanical Support (e.g., intra-aortic balloon counterpulsation) in cardiogenic shock.

Nitrates

The mechanism of action of nitrates involves the relaxation of smooth muscle, leading to the dilation of veins and a consequent reduction in preload at low doses. At higher doses, nitrates also cause the dilation of arterioles, which results in decreased preload and blood pressure. In the coronary arteries, this dilation enhances coronary blood flow. Collectively, these actions improve oxygenation and decrease the workload on the heart.

In clinical practice, nitrates are often prescribed sublingually. Intravenous infusions of nitroglycerin are also used, as this route allows for rapid onset of action and precise dose titration.

Advantages of using nitro preparations for acute pulmonary edema:

Fast and reliable reduction of preload.
Medium to high doses decrease systemic vascular resistance (afterload), helping to maintain or improve stroke volume and cardiac output.
Various routes of administration: sublingual and intravenous.
Short duration of action and rapid metabolism (approximately 60 mcg per minute).

Therefore, nitroglycerin is considered a first-line medication during both the pre-hospital and early hospital stages for patients with acute pulmonary edema.

Contraindications: The use of nitrates should be avoided if the patient has taken phosphodiesterase inhibitors (e.g., sildenafil, vardenafil, tadalafil) within the last 48 hours, as these medications are commonly prescribed for erectile dysfunction and pulmonary hypertension. Additionally, avoid the intravenous administration of eprostenol or treprostinil, which are used in the treatment of pulmonary hypertension.

Nitrates are also not recommended for patients with myocardial infarction of the inferior wall or for those suspected of having an ST-segment elevation myocardial infarction affecting the right ventricle, as these patients require adequate preload for the right ventricle. Moreover, nitrates should not be used in patients with aortic stenosis, hypotension, or acute mitral insufficiency.

Recommended Modes of Use of Nitro Preparations

Drug/Mode of Administration	Dosage	Frequency	Maximum Dose
Glyceryl Trinitrate Spray	400 micrograms (2 sprays)	Repeat every 5 minutes	1200 micrograms
Sublingual Tablet of Glyceryl Trinitrate	300-600 micrograms	Repeat every 5 minutes	1800 micrograms
Intravenous Infusion of Glyceryl Trinitrate	5–10 micrograms/min	Doubling every 5 minutes if SBP is stable	200 micrograms/min

In the conducted studies, a high efficacy of sublingual administration of nitroglycerin at a dose of 0.4 mg every 5 minutes was demonstrated until the onset of a pronounced clinical effect. The administration of the drug according to this regimen is recognized as equivalent to intravenous administration of nitroglycerin at a rate of 60 μg/min.

Diuretics

The use of furosemide is not recommended at the pre-hospital stage. Pulmonary edema is more commonly related to volume distribution rather than volume overload; therefore, furosemide does not provide improvement in most patients.

The administration of furosemide can lead to increased afterload due to vasoconstriction and decreased renal blood flow. In some patients, this may result in a significant drop in cardiac output and systemic pressure, potentially increasing the risk of fatal arrhythmias.

An incorrect diagnosis of chronic congestive heart failure, coupled with excessive diuresis, can lead to complications and fatalities. This is because the use of furosemide:

Reduces preload through increased diuresis, but has a delayed effect.
Causes an initial negative hemodynamic response, characterized by increased systemic vascular resistance, decreased stroke volume, and reduced cardiac output.
Can be detrimental when administered to patients with severe cardiogenic pulmonary edema in the first minutes of medical assistance.

Diuretics are indicated only for patients who exhibit signs of fluid overload. Intravenous administration of furosemide in doses of 40 to 80 mg is preferred. Higher doses may be required for patients already on oral diuretics or those with chronic kidney disease. The initial bolus can be administered slowly via intravenous infusion and repeated after 20 minutes if necessary. Following the bolus, a continuous intravenous infusion can be considered, starting at a rate of 5–10 mg per hour. Higher doses have been associated with better results in alleviating dyspnea but also with worsening renal function and increased hospitalizations in intensive care units. However, this association likely reflects the presence of more severe comorbidities and underlying diseases that contribute to the development of acute pulmonary edema. An indwelling urinary catheter should be placed to monitor urine output volume.

Recommended Dosage Regimens of Furosemide

Drug, Mode of Administration	Dosage	Frequency
Slow intravenous bolus	4 mg/min	Repeat after 20 minutes if necessary
Normal kidney function: 40–80 mg	40–80 mg	–
Kidney failure or severe heart failure	Up to 160–200 mg	–
Chronic use of loop diuretics	Initial IV dose equal to oral maintenance dose* Titrate in response to clinical need
Intravenous infusion	5–10 mg per hour	Continuously

*The bioavailability of the oral preparation of furosemide (frusemide) is approximately half that of the intravenous form.

Morphine

Morphine was traditionally part of the treatment regimen for acute pulmonary edema due to its ability to reduce shortness of breath. It also lowers sympathetic nervous system activity, which may help alleviate anxiety and distress associated with dyspnea.

However, the use of morphine carries several side effects, including respiratory and central nervous system depression, decreased cardiac output, and hypotension. Approximately one-third of patients experience nausea, and morphine can increase the risk of aspiration, especially when continuous positive airway pressure (CPAP) is needed, due to its suppression of the respiratory center. Furthermore, its use in acute pulmonary edema has been linked to a higher incidence of mechanical ventilation, intensive care unit admissions, and mortality.

In the absence of high-quality data from randomized trials, current evidence suggests that morphine may cause harm in this context. As a result, it is no longer recommended for routine use in acute pulmonary edema.

However, administration of morphine may be justified in patients with persistent, intense chest pain that is resistant to nitrates. In such cases, low doses of morphine (1–2.5 mg) may help facilitate the tolerability of invasive ventilation; close monitoring for sedation is essential.

Ventilation Support

The first step in improving ventilation for patients with acute pulmonary edema is to ensure they are in a sitting position, which helps reduce the ventilation-perfusion mismatch.

Oxygen Therapy:
Oxygen is not recommended for routine use in patients without hypoxemia because hyperoxemia can lead to vasoconstriction, decreased cardiac output, and increased short-term mortality. Administering oxygen to a patient who is asphyxiating without hypoxemia may mask clinical deterioration and delay necessary treatment. Supplemental oxygen and assisted ventilation should only be used if oxygen saturation falls below 92%.

When necessary, oxygen should be administered to achieve a target oxygen saturation of 92–96% (with a guideline of 94–98% from the Ministry of Health of Ukraine). Depending on the clinical scenario, oxygen titration can be performed using various delivery devices, including:

Up to 4 L/min via nasal cannulas
5–10 L/min via a face mask
15 L/min via a non-rebreather mask
High-flow nasal cannulas with a fraction of inspired oxygen greater than 35%

For patients with chronic obstructive pulmonary disease (COPD), the target oxygen saturation is 88–92%, and a Venturi mask with inspired oxygen set at 28% is recommended.

Noninvasive Ventilation:
If the patient experiences respiratory distress, acidosis, or hypoxia despite supplemental oxygen, noninvasive ventilation is indicated. There is no significant clinical advantage of bi-level positive airway pressure (BiPAP) over continuous positive airway pressure (CPAP), so the choice of ventilation mode may depend on the specific characteristics of the care center and local availability. Noninvasive ventilation should be initiated with 100% oxygen, with recommended initial settings of 10 cm H2O for CPAP and 10/4 cm H2O (positive inspiratory pressure/expiratory positive airway pressure) for BiPAP. Contraindications to noninvasive ventilation include hypotension, potential pneumothorax, vomiting, and altered levels of consciousness.

Intubation:
If persistent hypercapnia, hypoxemia, or acidosis occurs despite noninvasive ventilation, intubation should be considered. Other indications for intubation include signs of physical exhaustion, decreased level of consciousness, or cardiogenic shock. Endotracheal intubation is indicated only in a limited number of cases and carries significant risks and complications. After intubation, continuous suctioning is often required, and ventilation may be challenging. Additionally, positive pressure ventilation can exacerbate hypotension.

Drug	Bolus	Infusion
Dobutamine	No	2-20 mcg/kg/min (beta+)
Dopamine	No	3-5 mcg/kg/min (beta+) >5 mcg/kg/min (beta+, alpha+)
Milrinone	25-75 mcg/kg for 10-20 minutes	0.375-0.75 mcg/kg/min
Levosimendan	12 mcg/kg for 10 minutes	0.1 μg/kg/min (can decrease to 0.05 or increase to 0.2 μg/kg/min)
Norepinephrine	No	0.2-1.0 mcg/kg/min
Epinephrine	1 mg IV during resuscitation measures Repetition in 3-5 minutes	0.05-0.5 mcg/kg/min

S	Site (Localization)	Ask about the location of the pain	“Where does it hurt?” “Can you tell me precisely where you feel the pain?” “Can you show me where it hurts?” “Where is the pain localized?”
O	Onset	Specify how and when the pain occurred	“Did the pain come on suddenly or develop gradually?” “When did the pain first occur?” “When did the symptoms first appear?” “Did the pain occur at rest or during physical activity?” “How long did the pain last?” “How and when did it start?” “Did the pain start suddenly, or did it develop gradually?” “What were you doing precisely when the pain began?” “What triggers the onset of pain for you?” “When does the pain typically occur?” “Under what circumstances does the pain worsen?”
C	Character	Ask about specific characteristics of the pain	“How would you describe this pain?” “Is the pain continuous or does it come and go?” “Could you describe the pain to me?” “Can you describe the nature of the pain?”
R	Radiation (Irradiation)	Ask if the pain is radiating	“Does the pain radiate elsewhere?” “Does it spread or radiate?” “Where exactly does the pain spread?” “To which part of the body does the pain radiate?”
A	Associated symptoms	Ask if there are any symptoms related to pain	“Are there any other symptoms associated with the pain?” “Do you experience any other symptoms besides pain?” “What other symptoms are you experiencing?” “Are there any other symptoms apart from the pain?”
T	Time course ( dynamics over time )	Find out how the pain has changed over time	“Has the pain changed over time?”
E	Exacerbating or relieving factors	Ask if there is anything that makes the pain worse or worse	“Does anything exacerbate the pain?” “Does anything alleviate the pain?”
S	Severity	Determine the intensity of the pain by asking the patient to rate it on a scale of 0 to 10	“How would you rate the pain on a scale of 0 to 10, where 0 is no pain and 10 is the worst pain you have ever felt?” “Please rate the intensity of the pain on a scale from 0 to 10, where 0 means no pain and 10 represents the most severe pain you have ever experienced.” “On a scale of 1 to 10, how severe is the pain?” “Could you rate the intensity of the pain on a scale from 1 to 10?”

S	Site (Localization)	–	–
O	Onset	Specify how and when the shortness of breath occurred	“Did the shortness of breath come on suddenly or gradually?” “When did you first experience shortness of breath?” “What do you think caused the shortness of breath to start?”
C	Character	Assess the nature of shortness of breath	“How would you describe your experience of shortness of breath?” “Can you describe in detail how you feel when you experience shortness of breath?” “Could you describe specifically what sensations you feel?”
R	Radiation (Irradiation)	–	–
A	Associated symptoms	Ask if there are other symptoms associated with shortness of breath	“Do you experience any other symptoms alongside the shortness of breath?” “Have you noticed any coughing along with the shortness of breath?” “Do you feel any chest pain when experiencing shortness of breath?” “Have you noticed any blood in your sputum when experiencing shortness of breath?”
T	Time course ( dynamics over time )	Find out if the shortness of breath has changed over time	“Has the shortness of breath changed over time?”
E	Exacerbating or relieving factors	Ask if there is anything that makes the shortness of breath worse or worse	“What can cause an increase in shortness of breath?” “What exacerbates shortness of breath?” “What relieves shortness of breath?” “Under what conditions does shortness of breath increase?” “Does shortness of breath worsen when lying down?” “Does shortness of breath increase during physical exertion?” “Does changing body position affect the severity of shortness of breath?”
S	Severity	Determine the intensity of dyspnea by asking the patient to rate it on a scale of 0 to 10	“Estimate the severity of shortness of breath on a scale from 0 to 10, where 0 is the absence of shortness of breath, and 10 is the strongest shortness of breath at rest.” “Can you describe the intensity of shortness of breath on a scale of 1 to 10?”

Reflections	Explore the patient’s perception of the current problem	“What do you think could have caused these symptoms?” “Do you have any guesses as to the cause of these symptoms?”
Concern	Explore the patient’s current concerns	• “Is there something that bothers you?” • “How do you cope with everyday activities?” “Is there anything you and I haven’t discussed yet?”
Expectation	Ask what the patient hopes to gain from the consultation	• “How can I help you today?” • “What do you expect from today’s consultation?” • “What do you think would be the best course of action?”

System	Symptoms
General manifestations	fever, weight change, fatigue, sweating, general weakness
Respiratory	shortness of breath, cough, sputum, wheezing, hemoptysis, pleuritic chest pain
Cardiovascular	chest pain, shortness of breath, heart failure, palpitations, swelling of the lower extremities
Gastrointestinal	dyspepsia, nausea, vomiting, dysphagia, abdominal pain, stool disorders
Genitourinary	oliguria, polyuria, nocturia, pain during urination
Neurological	changes in vision, motor or sensory disturbances, headache
Locomotor	pain in the chest wall, bone pain, trauma
Skin	rashes, ulcers, hemorrhages, petechiae, bruises, hemorrhages, neoplasms

Criteria	Points
Female gender	25
Emotional trigger	24
Physical trigger	13
Absence of ST segment depression (except AVR)	12
Psychiatric disorders	11
Neurological disorders	9
Prolongation of the corrected QT interval (women > 460 ms, men > 440 ms)	6

Inform the patient about the disease	“Mr./Ms…., I’d like to discuss your diagnosis with you. You’ve been diagnosed with Takotsubo syndrome. This condition occurs when the heart temporarily loses its ability to function normally due to severe emotional stress”.
Explain to the patient the possible causes of the disease	“There are several factors that can contribute to the development of Takotsubo syndrome. These include emotional stress, mental health disorders, hormonal imbalances, certain medications, genetic predisposition, among others. Emotional stress is often the primary trigger, leading to the release of large amounts of catecholamines such as adrenaline and norepinephrine. These chemicals can constrict blood vessels and disrupt normal heart function. To determine the exact cause of Takotsubo syndrome, further examinations will be necessary. Once we identify the underlying cause, we can determine the most appropriate treatment approach.”
Inform the patient of the symptoms that may occur with the identified disease	“The symptoms of Takotsubo syndrome can resemble those of a heart attack. Typically, patients experience intense chest pain that persists even after taking nitrates, along with shortness of breath. In severe cases, patients may also develop rhythm disturbances and thromboembolic complications.”
Discuss the results of the examinations with the patient	“Mr./Ms. [Last Name], I’d like to discuss the results of your examinations with you. During the electrocardiography, we observed changes similar to those seen in myocardial infarction. However, further examinations did not confirm this diagnosis. Coronary angiography showed no evidence of thrombosis in the heart arteries, which would typically indicate a myocardial infarction. Additionally, echocardiography revealed transient heart contractility, characteristic of Takotsubo syndrome rather than myocardial infarction. To confirm the diagnosis, we performed ventriculography, which revealed changes in heart shape during contraction typical of Takotsubo syndrome. Do you have any questions or concerns about what I’ve just explained?”
Explain to the patient the possible consequences of the disease	“The prognosis for Takotsubo syndrome is generally favorable, as heart contractility issues are temporary and typically resolve within 2-3 weeks. However, during this period, it’s crucial to adhere to the doctor’s recommendations aimed at reducing strain on the weakened heart and preventing complications.”
Educate the patient about available treatments	“I’d like to discuss the available treatment methods for Takotsubo syndrome, aiming primarily at maintaining blood circulation until the heart’s normal function is restored. The choice of treatment method depends on the severity of the syndrome. Patients without signs of heart failure typically receive beta-blockers, angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers. For those exhibiting lung congestion without low blood pressure, diuretics and nitrates are prescribed to alleviate congestion, reduce cardiac workload, and regulate blood pressure. If there’s unstable circulation, intravenous solutions and/or inotropic drugs may be administered to enhance myocardial contractility. In cases where drug therapy proves ineffective, mechanical circulatory support using various devices may be employed“.
Help the patient understand the risks and benefits of different treatments	“Although the medications used to treat Takotsubo syndrome are well-studied, effective, and generally safe, there is a possibility of side effects with therapy. However, I want to assure you that we will take every precaution to minimize these risks.”
Answer the patient’s questions	“If you have any further questions regarding the causes of the disease, its symptoms, diagnosis, or treatment, please feel free to ask. It’s crucial that you understand what’s happening and what steps we’ll be taking next.”
Provide an explanation of the extent of monitoring during and after treatment	“Monitoring, or observing the main parameters of your body, is crucial for timely assessment of your condition, correction of detected changes, and evaluating the effectiveness of treatment. During monitoring, we will carefully observe your general condition, blood oxygen saturation level, blood pressure, heart rate, and myocardial contractility. Pulse oximetry is performed to determine the level of blood oxygen saturation. A special pulse oximeter device will be worn on your finger to constantly monitor the oxygen level in your blood. Blood pressure monitoring allows us to assess how well your heart is functioning and make corrections if there is a significant decrease or increase in blood pressure. We will use electrocardiography to evaluate heart rhythm by placing special electrodes on the front chest wall to record the electrical activity of your heart. This will enable us to monitor the effect of the treatment. To assess myocardial contractility, we will repeat echocardiography.”
Schedule regular check-ups and follow-up to assess the effectiveness of treatment and changes in the patient’s condition	“After discharge from the hospital, it’s important to monitor your well-being and avoid emotional and physical stress. If you experience anxiety, depression, or other mental health disorders, it’s advisable to consult a psychotherapist to determine the appropriate course of action. Your emotional well-being is crucial to prevent the recurrence of Takotsubo syndrome.”

Criteria	Points
Female sex	25
Emotional trigger	24
Physical trigger	13
Absence of ST segment depression (except AVR)	12
Psychiatric disorders	11
Neurological disorders	9
Prolongation of the corrected QT interval (women > 460 ms, men > 440 ms)	6

Most Frequent Complications:	Less Common Complications:	Rare Complications:
Acute heart failure (12-45%) Left ventricular outflow tract obstruction (10-25%) Mitral regurgitation (14-25%) Cardiogenic shock (6-20%)	Atrial fibrillation (5-15%) Left ventricular thrombus (2-8%) Sinus node arrest (4-6%) AV block (5%)	Tachyarrhythmia (2-5%) Bradyarrhythmia (2-5%) Ventricular tachycardia of the pirouette type (2-5%) Death (1-4.5%) Ventricular tachycardia/fibrillation (3%) Acute defect of the interventricular membrane (up to 1%)

Clinical picture	Treatment of choice	Alternative treatment
Erythema migrans	Doxycycline 100 mg 2 times a day orally (PO) for 10 days or Amoxicillin 500 mg 3 times a day PO for 14 days or Cefuroxime 500 mg 2 times a day PO for 14 days	Azithromycin 500 mg once a day p/o for 5-10 days
Damage to the nervous system	Ceftriaxone 2 g once a day IV for 14-21 days or Cefotaxime 2 g 3 times a day IV for 14-21 days or Benzylpenicillin sodium salt 2.4 g every 4-6 hours IV or IV for 14-21 days
Heart damage (without clinical manifestations of myopericarditis, without arrhythmia, without AV block II or III degree, without block I degree with PR interval ≥0.3 sec.)	Doxycycline 100 mg 2 times a day orally (p/o) for 14-21 days or Amoxicillin 500 mg 3 times a day p/o for 14-21 days or Cefuroxime 500 mg 2 times a day p/o for 14-21 days	Azithromycin 500 mg once a day p/o
Heart damage (with clinical manifestations of myopericarditis, with arrhythmias, with II or III degree AV block, with I degree AV block with a PR interval ≥0.3 sec.)	Ceftriaxone 2 g once a day IV for 14-21 days or Cefotaxime 2 g 3 times a day IV for 14-21 days or Benzylpenicillin sodium salt 2.4 g every 4-6 hours IV or IV for 14-21 days
Damage to the joints	Doxycycline 100 mg 2 times a day orally (PO) for 28 days or Amoxicillin 500 mg 3 times a day PO for 28 days or Cefuroxime 500 mg 2 times a day PO for 28 days
Borreliosis lymphocytoma	Doxycycline 100 mg 2 times a day orally (PO) for 14 days or Amoxicillin 500 mg 3 times a day PO for 14 days or Cefuroxime 500 mg 2 times a day PO for 14 days
Chronic atrophic acrodermatitis	Doxycycline 100 mg 2 times a day orally (p/o) for 21-28 days or Amoxicillin 500 mg 3 times a day p/o for 21-28 days or Cefuroxime 500 mg 2 times a day p/o for 21-28 days

H-Hypoxia	hypoxia	shortness of breath, tachypnea, cyanosis, low blood oxygen saturation
H-Hydrogen ion	excess hydrogen ions (acidosis)	low QRS amplitude on the ECG
H-Hypokalemia	hypokalemia	hypokalemia, flat T waves on the ECG, the appearance of a U wave
H- Hyperkalemia	hyperkalemia	hyperkalemia, high-amplitude T waves on the ECG, widening of QRS complexes
H-Hypothermia	hypothermia	staying in conditions of low temperatures, low body temperature
T-Tension pneumothorax	tension pneumothorax	progressive difficulty breathing, shortness of breath, tachypnea, cyanosis, X-ray signs of air accumulation in the pleural cavity
T- Tamponade	cardiac tamponade	Beck’s triad – enlargement of jugular veins, deafness of heart sounds, hypotension; fluid accumulation in the pericardial cavity
T-Toxins	toxins	As a rule, a prolonged QT interval is registered on the ECG; neurological symptoms may be observed
T-Thrombosis	thrombosis (myocardial infarction)	increased markers of myocardial necrosis, ECG signs of acute myocardial ischemia, angiographic confirmation of coronary artery occlusion

Risk factors	Score	Level of evidence
Previous cardiovascular disease
Heart failure or cardiomyopathy	Very high	B
Severe valvular heart disease	High	C
Myocardial infraction or previous coronary revascularization (PCI or CABG)	High	C
Stable angina	High	C
Baseline LVEF <50%	High	B
Borderline LVEF 50-54%	Medium²	C
Cardiac biomarkers (where available)
Elevated baseline troponin	Medium¹	C
Elevated baseline BNP or NT-proBNP	Medium¹	C
Demographic and cardiovascular risk factors
Age ≥80 years	High	B
Age 65–79 years	Medium_²	B
Hypertension	Medium¹	B
Diabetes mellitus	Medium¹	C
Chronic kidney disease	Medium¹	C
Previous cardiotoxic cancer treatment
Previous anthracycline exposure	High	B
Prior radiotherapy to left chest or mediastinum	High	C
Previous non-anthracycline-based chemotherapy	Medium¹	C
Lifestyle risk factors
Current smoker or significant smoking history	Medium¹	C
Obesity (BMI >30 kg/m²)	Medium¹	C

no risk factor OR one medium¹ risk factor	Low risk	<2%
medium risk factors with a total of 2–4 points	Medium risk	2-9%
medium risk factors with a total of ≥5 points OR any high risk factor	High risk	10-19%
any very high risk factor	Very high risk	>20%

Variable	Points
Surgery within 90 days	+2
Mongoloid race	-3
History of VTE	+3
Age ≥ 80 years	+1
Dexamethasone (dosage regimen): • Standard dose (120-160 mg/cycle) • High dose (>160 g/cycle)	+1 +2

Inform the patient about the disease	“Mr./Ms. [Last Name], I would like to inform you of your diagnosis. You have a significant slowing of the heart rate, known as bradycardia. Bradycardia results from a malfunction of the heart’s conduction system, such as sinus node weakness syndrome or atrioventricular block. With sinus node weakness syndrome, the generation or conduction of electrical impulses to the atria is disrupted, leading to a slower heart rate. With atrioventricular block, electrical impulses are generated normally but may be significantly delayed or completely blocked from reaching the ventricles. Due to inadequate oxygen and nutrient supply, all organs and systems suffer, particularly the brain and heart.”
Explain to the patient the possible causes of the disease	“There are various reasons for conduction system disorders of the heart, categorized as internal (cardiac) or external (extracardiac). Common causes include myocardial ischemia, elevated blood potassium levels, certain medications, or central nervous system damage. Less frequent causes include hypothermia, hypothyroidism, myocardial inflammation, and sleep apnea syndrome. Additional examinations will be needed to pinpoint the specific cause of your bradycardia, enabling us to determine the most effective treatment.”
Inform the patient of the symptoms that may occur with the identified disease	“Bradycardia may often be asymptomatic, but significant slowing of the heart rate can lead to noticeable complaints. Mild cases may cause feelings of fatigue, weakness, or reduced tolerance to physical exertion. Severe cases can result in shortness of breath, chest pain, or even loss of consciousness due to impaired blood supply to the heart and brain.”
Discuss the results of the examinations with the patient	“Mr./Ms. [Last Name], I want to share the results of your examinations with you. Electrocardiography revealed a significant slowing of the heart rate, stemming from impaired electrical impulse conduction through the heart. Blood tests showed normal laboratory parameters. To assess your heart’s blood supply, we conducted a coronary angiography, which revealed minor cholesterol deposits in your blood vessels, but they do not significantly affect blood flow to the heart. Do you have any questions about the information I’ve provided?”
Explain to the patient the possible consequences of the disease	“The severity of the consequences of bradycardia depends on the heart rate. Heart rates above 50 beats per minute typically do not result in negative consequences. However, heart rates below 50 beats per minute may lead to decreased blood pressure, altered consciousness, and heart ischemia, which pose significant health risks.”
Educate the patient about available treatments	“I’d like to discuss the treatment options for bradycardia. If your bradycardia is asymptomatic or mildly symptomatic, observation may suffice without intervention. However, in cases of life-threatening symptoms like loss of consciousness or chest pain, treatment is necessary. Initial treatment often involves atropine to improve electrical impulse conduction in the heart. If atropine is ineffective, other medications like epinephrine or dopamine may be used. Electrical cardiostimulation is commonly employed if medications are ineffective. If bradycardia is due to a reversible cause, temporary transcutaneous cardiostimulation may be sufficient until normal heart rhythm is restored. For irreversible cases, permanent pacemaker implantation is recommended. A pacemaker generates electrical impulses, ensuring the heart beats at the correct rate.”
Help the patient understand the risks and benefits of different treatments	“Although electrical cardiostimulation is generally safe when performed by experienced medical professionals, there is a small risk of complications such as infection or bleeding at the electrode insertion site, perforation of the heart, or electrode displacement. However, we will take all necessary precautions to minimize these risks.”
Answer the patient’s questions	“If you have any questions about the causes, symptoms, diagnosis, or treatment of your condition, please don’t hesitate to ask. It’s essential that you understand your condition and the next steps in your care.”
Provide an explanation of the extent of monitoring during and after treatment	“Monitoring your condition is crucial for timely assessment and correction of any changes and evaluating treatment effectiveness. We will monitor your general condition, blood oxygen saturation, blood pressure, and heart rate. Pulse oximetry will assess blood oxygen saturation, while blood pressure monitoring helps evaluate heart function. Electrocardiography will monitor heart rhythm. Regular follow-ups with your family doctor and arrhythmologist are essential for ongoing monitoring and pacemaker assessment.”
Schedule regular check-ups and follow-up to assess the effectiveness of treatment and changes in the patient’s condition	“After discharge, it’s important to monitor your well-being. Keep a diary noting any changes in symptoms, pulse, or blood pressure. Regular visits to your family doctor for electrocardiogram monitoring and arrhythmologist appointments, initially every 4-6 weeks and later every 6-12 months, are recommended. Modern pacemakers may include remote monitoring systems, enabling your doctor to assess pacemaker function remotely and detect any issues.”

*Individual Risk Factors*	Points	Myeloma risk scores	Points
Positive Factors
Central venous catheter/tunneled central catheter	+2	Immunomodulator (IM)	+4
Fracture of the pelvis, hip joint, or femur	+4	A drug that stimulates erythropoiesis	+1
Obesity (body mass index ≥ 25)	+1	Dexamethasone < 160 mg per month	+2
Previous VTE	+5	Dexamethasone > 160 mg per month	+4
		Doxorubicin or multicomponent chemotherapy	+3
Negative Factors
Ethnicity/Race – Mongoloid/Pacific Islander	-3
Current thromboprophylaxis: low molecular weight heparin (LMWH) at prophylactic doses or aspirin	-3
Current thromboprophylaxis: LMWH at prophylactic doses or warfarin	-4