Neurogenic pulmonary edema

Neurogenic pulmonary edema is a severe and life-threatening pulmonary edema that occurs after injury to the central nervous system (brain and spinal cord) most commonly spontaneous subarachnoid hemorrhage (SAH) and has an acute onset and rapid progression ¹, ², ³, ⁴. Neurogenic pulmonary edema is classified as a subtype of the acute respiratory distress syndrome (ARDS). Any sort of acute central nervous system (brain and spinal cord) injury may trigger neurogenic pulmonary edema including aneurysmal subarachnoid hemorrhage, head trauma, spinal cord injury, stroke, epilepsy and postoperative intracranial injury ⁴. The 3 most common triggers of neurogenic pulmonary edema are: (1) head trauma (open or closed); (2) subarachnoid hemorrhage (counting rupture of an aneurysm where it is found in more than 50% of cases); and (3) epilepsy (generalized seizure) ⁵. Neurogenic pulmonary edema has also been reported in some other pathological situations such as cervical medullary trauma, a postoperative period of intracranial surgery, and meningitis.

Two distinct neurogenic pulmonary edema syndromes have been described based on the time course elapsed from the inciting event, both presenting with signs and symptoms of respiratory distress (e.g. dyspnea, tachypnea, crackles) with subsequent progression to hypoxemic respiratory failure ⁶:

1. “Early” or “Acute” neurogenic pulmonary edema (most common) occurs within the first 4 hours in the majority (71.4%) of patients ⁷. Acute neurogenic pulmonary edema is associated with younger patients and higher serum glucose ⁸. Acute neurogenic pulmonary edema spontaneous resolution within 48 to 72 hours ⁹
2. “Delayed” neurogenic pulmonary edema onset within 12 to 24 hours ¹⁰

Neurogenic pulmonary edema most commonly develops within a few hours after a central nervous system (brain and spinal cord) insult, and is characterized by shortness of breath (dyspnea), bilateral basal pulmonary crackles, and the absence of cardiac failure ¹¹. However, a delayed form of neurogenic pulmonary edema that develops 12 to 24 hours after the central nervous system (brain and spinal cord) insult has been reported ¹⁰. Symptoms often spontaneously resolve within 24 to 48 hours; however, in patients with ongoing brain injury and elevated intracranial pressure (ICP), the neurogenic pulmonary edema often persists ¹².

The diagnosis of neurogenic pulmonary edema is based on the occurrence of pulmonary edema after a central nervous system (brain and spinal cord) event/insult and the exclusion of other plausible causes ⁶. There is no specific laboratory study that can confirm the diagnosis of neurogenic pulmonary edema ¹². Neurogenic pulmonary edema is a diagnosis of exclusion and diagnosis requires exclusion of other causes of pulmonary edema (eg, cardiogenic pulmonary edema or high-altitude pulmonary edema [HAPE]) ¹⁰, ⁵.

The occurrence of neurogenic pulmonary edema in a brain-injured patient is associated with a poor prognosis as the mortality rate is very high (60% to 100%). It is not only attributed to pulmonary involvement but also to primary brain injury ³, ⁴, ¹³.

The treatment of neurogenic pulmonary edema is focused on treating the underlying central nervous system (brain and spinal cord) condition. Treatment efforts to reduce intracranial pressure (ICP), including decompression and clot evacuation, osmotic diuretics, anti-epileptics, tumor resection, and steroids have all been associated with improvements in oxygenation ¹².

Figure 1. Pulmonary edema

Figure 2. Pulmonary edema chest X-ray

Footnote: Acute pulmonary edema showing alveolar edema (white arrows) and interstitial edema (black arrowheads). Alveolar edema manifests as ill-defined nodular opacities tending to confluence (white arrows). Interstitial edema can be seen as peripheral septal lines – Kerley B lines (black arrowheads).

Figure 3. Neurogenic pulmonary edema

Footnote: 40 year old female patient presents with an early hyperacute stroke, with a sudden reduced level of consciousness, and is intubated with the endotracheal tube (ETT) at the carina. This should be retracted. There is minimal left-sided proximal tracheal deviation. There is a normal cardiomediastinal contour. There are overlying ECG leads. There is diffuse, bilateral air space opacification, right greater than left, with bi-apical sparing. MRI of her brain confirmed extensive early hyperacute posterior circulatory non-hemorrhagic infarction. There is a wide differential diagnosis for the above chest X-ray appearance including infection, ARDS, pulmonary edema, pulmonary hemorrhage and aspiration pneumonitis. In this instance, based on the acute presentation, negative past and recent medical history, absence of any causative incidents and the ease and rapidity of intubation suggested a non-cardiogenic cause and specifically likely acute neurogenic pulmonary edema (within 4 hours of the neurological event).

Figure 4. Pulmonary edema CT scan

Footnote: Chest CT showing diffuse bilateral infiltrates but no cardiac dilatation. Laboratory tests showed a decreased total protein (4.9 g/dL) and albumin (2.8 g/dL), suggesting increased vascular leakiness. Serum NT-proBNP (N-terminal-pro brain natriuretic peptide) was normal (60 pg/mL). Her troponin T was negative, and ST-T wave changes were not observed on her ECG. Her echocardiography showed normal left ventricular systolic function. Her white blood cell count was 20 000/µL, and C reactive protein was 0.12 mg/dL. Streptococcus pneumoniae and Legionella pneumophila urinary antigen tests were negative. Only normal flora was cultured from her sputum sample.

What is pulmonary edema?

What’s the difference between pulmonary edema and pneumonia?

Both pulmonary edema and pneumonia involve a buildup of fluid in your lungs. An infection causes pneumonia. The infection can be viral, bacterial or fungal. These organisms can cause infected fluid to fill your air sacs. An infection doesn’t cause pulmonary edema, and the fluid is typically thinner and watery.

What’s the difference between pulmonary edema and pleural effusion?

Pleural effusion is when abnormal amounts of fluid buildup outside of your lungs in the pleura, which is a lining around your lungs. The pleura sits between your lungs and the inside of your chest wall, and usually only has a thin rim of fluid inside it. Pleural effusion is commonly caused by pneumonia, congestive heart failure or cancer. Unlike pulmonary edema, the fluid sits outside of your lungs and can compress your lungs, which are spongy.

Does pulmonary edema require hospitalization?

Pulmonary edema is a serious condition. If you have acute (sudden) pulmonary edema, you need immediate treatment. You may be treated in the emergency room (ER) or intensive care unit (ICU). Chronic pulmonary edema may require hospitalization as well.

Can pulmonary edema cause sudden death?

Severe cases of pulmonary edema can be life-threatening if you don’t receive treatment right away. With immediate treatment, your chances of recovery are higher.

Neurogenic pulmonary edema causes

Any acute central nervous system (brain and spinal cord) insult can result in neurogenic pulmonary edema (NPE) and the 3 most common triggers of neurogenic pulmonary oedema are: (1) traumatic brain injury (open or closed), (2) subarachnoid hemorrhage (counting rupture of an aneurysm where it is found in more than 50% of cases), and (3) epilepsy (generalized seizure) ¹⁸, ¹⁹, ²⁰, ²¹, ²², ⁷, ²³, ²⁴, ²⁵, ²⁶, ²⁷.

Neurogenic pulmonary edema has also been reported in some other pathological situations such as:

• spinal cord infarction
• cervical medullary trauma
• postoperative period of intracranial surgery
• meningitis ²⁸
• viral encephalitis particularly with enterovirus-71 ²⁹, ³⁰
• nonhemorrhagic stroke ³¹
• medication overdose
• arteriovenous malformation

Neurogenic pulmonary edema pathophysiology

The full understanding of the pathophysiology of neurogenic pulmonary edema is still poorly understood ¹¹, ⁵. Two main pathogenic mechanisms have been proposed to underlie neurogenic pulmonary edema: the hemodynamic theory, which theorizes that an increase in pulmonary vascular pressure results from a sudden surge in catecholamines in circulation ³², ³³; and the theory of increased pulmonary permeability, which suggests that direct damage to the lungs is caused by the massive sympathetic discharge and cytokines released as a result of elevated intracranial pressure (ICP) ³⁴.

The central nervous system (brain and spinal cord) disturbance will cause a sympathetic overflow leading to a state of systemic vasoconstriction. This will cause pooling of the blood from the systemic circulation to the pulmonary circulation, hence eliciting an increase in the pulmonary capillary hydrostatic pressure. That change of pressure will cause the leakage of intravascular fluid to both the alveoli and the pulmonary interstitial space through 2 mechanisms: (1) change of pressure across the alveolar bed dictated by Starling forces, (2) the changes in permeability on the capillary walls ⁵.

Figure 6. Neurogenic pulmonary edema pathophysiology

Central Nervous System

• Structural: The injured central nervous system (brain and spinal cord) will initiate a state of sympathetic overflow. Specific centers in the central nervous system (if stimulated) manage autonomic sympathetic system activation. Centers responsible for autonomic contribution to the pathogenesis of neurogenic pulmonary edema are located in specific areas of the central nervous system called trigger zones for neurogenic pulmonary edema. These include rostral ventrolateral medulla, area postrema, nuclei of the solitary tract, nuclei of A1 and A5, and the medial reticulated nucleus, and the dorsal motor vagus nucleus.
• Chemical: The role of neurotransmitters is not clear in the pathogenesis of neurogenic pulmonary edema. Experimental studies relate NMDA receptors and GABA receptors activity in neurogenic pulmonary edema trigger zones to affect the sympathetic flow following central nervous system insult.
• Physiological: Raised intracranial pressure (ICP) is a common encounter in central nervous system injuries. The abrupt increase in intracranial pressure (ICP) will lead to the Cushing triad (increased blood pressure [BP], irregular breathing, and bradycardia). These physiological changes along with sympathetic overflow facilitate the development of pulmonary edema. Experimental studies on animals showed an increase in pulmonary artery pressure and extravascular pulmonary fluid in response to increased intracranial pressure (ICP).

Autonomic Nervous System

• Sympathetic overflow: The sympathetic system is the key player in the pathogenesis of neurogenic pulmonary edema. The sudden over-activation of the neurogenic pulmonary edema trigger zones (either due to direct injury/irritation, activation of ascending neural pathways or as a response to the raised ICP) prompts sympathetic overflow and an outburst of catecholamines initiating 3 important pathophysiological responses; systemic vasoconstriction, increased blood pressure, and increased venous return. In subarachnoid hemorrhage (SAH) patients complicated by neurogenic pulmonary edema, a study conducted by Joji Inamasu et al. ³⁶ observed changes in plasma norepinephrine levels and found that norepinephrine is actively involved in neurogenic pulmonary edema. The study suggested that increased plasma norepinephrine levels may contribute to the development of neurogenic pulmonary edema. Norepinephrine can stimulate alpha1-adrenoceptors, leading to increased permeability and capillary pressure in the pulmonary microvasculature ³⁷. It can also stimulate beta1-adrenoceptors, resulting in overperfusion and edema of the lungs due to increased right ventricular systolic pressure ³⁸. Based on these findings, it is reasonable to assume that neurogenic pulmonary edema develops more frequently in the presence of increased norepinephrine levels. To reduce the incidence of neurogenic pulmonary edema, early adequate sedation, analgesia, and the suppression of sympathetic nervous system activity may be beneficial for subarachnoid hemorrhage (SAH) patients with increased norepinephrine levels ³⁹.
• Parasympathetic contribution: The 10th cranial nerve called the vagus nerve provides the parasympathetic supply to the lungs and heart. Although the effect of vagus nerve rule on the heart during central nervous system (brain and spinal cord) injury is fairly elicited, yet the correlation of vagus nerve with the development of neurogenic pulmonary edema is strongly debatable and lacks clear supporting evidence. It is worth to mention that the hypothetical rationalization of the correlation of the vagus nerve activity to neurogenic pulmonary edema pathogenesis is the question of whether bradycardia is an essential or accessory factor in the development of pulmonary edema.

Cardiovascular and Pulmonary Systems

Sympathetic overflow and catecholamines-surge result in an increase of systemic resistance, venous return, and BP. Knowing this, the proposed theory of the development of neurogenic pulmonary edema falls into one of three supposed explanation:

• Hemodynamic changes: Increased functional demand on the cardiac muscle due to the outcomes of the sympathetic overflow will cause the movement of blood from the systemic highly resistant circulation to the less resistant pulmonary circulation, resulting in an increase in pulmonary capillary positive hydrostatic pressure leading the movement of fluid from the capillaries to the lung tissue and interstitial space.
• Neurogenic heart injury: Mainly dictated by the sudden catecholamine surge ⁴⁰, ⁴¹, ⁴², ⁴³, ⁴⁴. The increase in systemic blood pressure (BP) and venous return will cause an overload on the heart. As the left ventricle fails to meet that loading change functionally, accumulation of blood in the ventricle occurs, causing cardiac damage, hence diastolic dysfunction. This will lead to pulmonary vascular congestion, hereafter pulmonary edema.
• Increased pulmonary capillary permeability is governed by 2 possible causes:
  1. Direct (humoral): Damage to the pulmonary capillaries endothelium in direct response to the catecholamines regardless of hemodynamic changes ⁴⁵, ⁴⁶, ⁴⁷, ⁴⁸
  2. Indirect (physical): Damage to the capillary bed as a mechanical response to the abrupt rise in the pulmonary capillary hydrostatic pressure ⁴⁹, ⁵⁰, ⁵¹

Neurogenic pulmonary edema symptoms

Neurogenic pulmonary edema often occurs within minutes to 48 hours after the central nervous system (brain and spinal cord) insult and is mainly manifested by acute respiratory failure that is is characterized by shortness of breath (dyspnea), bilateral basal pulmonary crackles, and the absence of heart failure ¹¹.

Two distinct neurogenic pulmonary edema syndromes have been described based on the time course elapsed from the inciting event, both presenting with signs and symptoms of respiratory distress (e.g. dyspnea, tachypnea, crackles) with subsequent progression to hypoxemic respiratory failure ⁶:

1. “Early” or “Acute” neurogenic pulmonary edema (most common) occurs within the first 4 hours in the majority (71.4%) of patients ⁷. Acute neurogenic pulmonary edema is associated with younger patients and higher serum glucose ⁸. Acute neurogenic pulmonary edema spontaneous resolution within 48 to 72 hours ⁹
2. “Delayed” neurogenic pulmonary edema onset within 12 to 24 hours

Common patients are usually children or young adults, who must have suffered an intracranial injury recently. In cases of blunt head injuries, neurogenic pulmonary edema may develop in a matter of minutes (acute neurogenic pulmonary edema). There is no specific symptomatology of neurogenic pulmonary edema. It is most often associated with neurological pathology. The clinical signs boil down to classic signs of pulmonary edema with the absence of signs of left ventricular failure usually found in cardiogenic edema. For classic neurogenic pulmonary edema, the manifestation is immediate, and it could be detected clinically within 2 to 12 hours post-injury ⁵.

The symptomatology is that of any pulmonary edema with initially ventilation disorders often accompanied by systolic hypertension probably also testifying to intracranial hypertension. In patients with spontaneous ventilation, dyspnea, tachypnea, cough and rales with auscultation and tachycardia would be early signs, sometimes accompanied by pink foamy sputum or hemoptysis. More discrete symptoms of sympathetic stimulation, such as insomnia, sweating, paralytic ileus, and transient hypertension are also described. Ventilation/perfusion disorders, hypoxemia, and carbon dioxide retention will occur shortly after that.

Physical findings may include the following:

• Abnormally rapid breathing (tachypnea)
• Fast heart rate (tachycardia)
• Bibasilar crackles
• Respiratory distress
• Pulmonary edema occurs but with normal jugular venous pressure and an absence of cardiac gallop, which should raise the possibility of a neurogenic cause
• Fever – May occur secondary to the neurological disturbance (eg, subarachnoid hemorrhage)

Sudden (acute) pulmonary edema symptoms

Sudden (acute) pulmonary edema symptoms may include:

• Difficulty breathing (dyspnea) or extreme shortness of breath that worsens with activity or when lying down
• A feeling of suffocating or drowning that worsens when lying down
• A cough that produces frothy sputum that may have blood in it
• A rapid, irregular heartbeat (palpitations)
• Anxiety, restlessness or a feeling that something bad is about to happen
• Cold, clammy skin
• Wheezing or gasping for breath

Long-term (chronic) pulmonary edema signs and symptoms

Long-term (chronic) pulmonary edema signs and symptoms may include:

• Awakening at night with a cough or breathless feeling that may be relieved by sitting up
• Difficulty breathing with activity or when lying flat
• Fatigue
• More shortness of breath than usual when you’re physically active
• New or worsening cough
• Rapid weight gain
• Swelling in the legs and feet
• Wheezing

Neurogenic pulmonary edema diagnosis

People who have breathing problems should see a doctor. Based on the severity of your symptoms, your doctor may order tests. Tests may include a chest X-ray, brain scan, or electrocardiogram (ECG). These help diagnose the type of illness and decide on a treatment plan. The clinical diagnosis is easy in young patients without a history of cardio-respiratory disorders or direct lesions of these organs. It can be very difficult in poly-trauma patients or older people with pre-existing cardiac or pulmonary insufficiency.

Tests that can help diagnose pulmonary edema or determine the reason for fluid in your lungs include:

• Chest X-ray. A chest X-ray can confirm the diagnosis of pulmonary edema and exclude other possible causes of shortness of breath. It’s usually the first test done when a health care provider suspects pulmonary edema.
• Chest computerized tomography (CT) scan. A chest computed tomography (CT) scan gives more details about the condition of the lungs. It can help a provider diagnose or rule out pulmonary edema.
• Pulse oximetry. A sensor is attached to a finger or ear. It uses light to determine how much oxygen is in the blood.
• Arterial blood gas test. This test measures the amount of oxygen and carbon dioxide in the blood.
• Brain-type natriuretic peptide (BNP) blood test. Increased levels of B-type natriuretic peptide (BNP) may signal a heart condition. Brain-type natriuretic peptide (BNP) is secreted by the heart muscle cells (cardiac myocytes) of the left ventricles in response to stretching caused by increased ventricular blood volume or increased intracardiac pressures. Elevated BNP levels correlate with left ventricular end-diastolic pressure as well as pulmonary occlusion pressure and can be seen in patients with congestive heart failure ⁵². BNP levels less than 100 pg/ml suggest heart failure is less likely, and levels greater than 500 pg/ml suggest a high likelihood of heart failure. Levels between 100 and 500 pg/ml do not help in the diagnosis of heart failure and are often seen in critically ill patients ⁵².
• Troponin elevation is commonly noted in patients with damage to heart muscle cells (cardiac myocytes), such as acute coronary syndrome. They, however, are also noted to be elevated in patients with severe sepsis ⁵².
• Other blood tests. Blood tests to diagnose pulmonary edema and its causes also usually include a complete blood count, metabolic panel to check kidney function and thyroid function test.
  • Hypoalbuminemia (≤3.4 g/dL) is an independent marker of increased in-hospital and post-discharge mortality for patients presenting in acute decompensated heart failure ⁵³. Low albumin in isolation does not lead to pulmonary edema as there is a concurrent drop in pulmonary interstitial and plasma albumin levels preventing the creation of a transpulmonary oncotic pressure gradient ⁵⁴.
  • Obtaining serum electrolyte levels, including renal function, serum osmolarity, toxicology screening, help in patients with pulmonary edema due to toxic ingestion. Obtaining lipase and amylase levels help diagnose acute pancreatitis.
• Electrocardiogram (ECG or EKG). This painless test detects and records the timing and strength of the heart’s signals. It uses small sensors (electrodes) attached to the chest and sometimes to the arms or legs. Wires attach the sensors to a machine, which displays or prints results. An electrocardiogram (ECG) can show signs of heart wall thickening or previous heart attack. A portable device such as a Holter monitor may be used to continuously monitor the heartbeat at home.
• Echocardiogram. An echocardiogram uses sound waves (ultrasound) to create pictures of the beating heart. It can identify areas of poor blood flow, heart valve issues and heart muscle that is not working properly. An echocardiogram can help diagnose fluid around the heart (pericardial effusion).
• Cardiac catheterization and coronary angiogram. This test may be done if other tests don’t show the cause of pulmonary edema, or when there’s also chest pain. It helps health care providers see blockages in the heart arteries. A long, flexible tube (catheter) is inserted in a blood vessel, usually in the groin or wrist. It’s guided to the heart. Dye flows through the catheter to arteries in the heart. The dye helps the arteries show up more clearly on X-ray images and video.
• Ultrasound of the lungs. This painless test uses sound waves to measure blood flow through the lungs. It can quickly reveal signs of fluid buildup and plural effusions.

Cardiac injury enzyme levels are elevated in patients with neurologic injury, especially subarachnoid hemorrhage (SAH). The magnitude of elevation often correlates with the severity of the neurologic event and its effect on cardiac function. In one series, 20% of patients with subarachnoid hemorrhage (SAH) were found to have serum troponin 1 levels greater than 1 mcg/L (range, 0.3-50 mcg/L) ⁵⁵.

Elevated natriuretic peptides, A-type and B-type, have also been reported in patients with subarachnoid hemorrhage, with B-type natriuretic peptide peak levels reported as 355 ± 80 pg/mL ⁵⁶.

Serial monitoring of cardiac function may demonstrate reduced left ventricular function attributed to a neurogenic stress cardiomyopathy. Findings include regional wall motion abnormalities that extend beyond a single vascular bed. Echocardiographic findings may demonstrate a reduced ejection fraction and large areas of akinesis in the setting of modestly elevated serum troponin levels. Normal pulmonary artery capillary wedge pressures may increase and approach high levels.

Recent studies have identified abnormal Q or QS wave and nonspecific ST- or T-wave changes as possible predictors of neurogenic pulmonary edema following subarachnoid hemorrhage ⁵⁷, ⁵⁸.

Coronary angiography, if performed, shows no obstructing lesions.

Hemodynamic measurements with right-sided heart catheterization (ie, Swan-Ganz catheter) may be necessary to differentiate neurogenic pulmonary edema from hydrostatic or cardiogenic pulmonary edema. Systemic blood pressure, cardiac output, and pulmonary capillary wedge pressure are usually normal by the time neurogenic pulmonary edema is diagnosed clinically.

Separating the cardiac effects of the neurologic event from the effect of therapy used in these critically ill patients may be difficult.

Plain radiograph

The chest radiograph (chest X-ray) remains the most practical and useful method of radiologically assessing and quantifying pulmonary edema ⁵⁹, ⁶⁰.

A mnemonic to remember the radiographic signs of pulmonary edema is ABCDE ⁶¹:

• A: alveolar opacification
• B: batwinging
• C: cardiomegaly
• D: diffuse interstitial thickening (septal lines) and diversion (vascular upper zone diversion, cephalisation)
• E: effusions (pleural)

Features useful for broadly assessing pulmonary edema on a plain chest radiograph include ⁶²:

• upper lobe pulmonary venous diversion (stag’s antler sign)
• increased cardiothoracic ratio/cardiac silhouette size: useful for assessing for an underlying cardiogenic cause or association
• features of pulmonary interstitial edema:
  • peribronchial cuffing and perihilar haze
  • septal (Kerley) lines
  • thickening of interlobar fissures
• features of pulmonary alveolar edema:
  • air space opacification classically in a batwing distribution
  • may have air bronchograms
• pleural effusions and fluid in interlobar fissures (including ‘vanishing’ pulmonary pseudotumor)

There is a general progression of signs on a plain radiograph that occurs as the pulmonary capillary wedge pressure (PCWP) increases (see pulmonary edema grading below). Whether all or only some of these features can be appreciated on the plain chest radiograph, depend on the specific cause ¹⁷. Pulmonary edema is usually a bilateral process, but it may uncommonly appear to be unilateral in certain situations and pathologies (unilateral pulmonary edema).

One pulmonary edema grading based on chest radiograph appearances and pulmonary capillary wedge pressure (PCWP) is as follows ⁶³:

• Grade 0: normal chest radiograph, pulmonary capillary wedge pressure (PCWP) 8-12 mmHg
• Grade 1: shows evidence of upper lobe diversion on a chest radiograph, pulmonary capillary wedge pressure (PCWP) 13-18 mmHg
• Grade 2: shows interstitial edema on a chest radiograph, pulmonary capillary wedge pressure (PCWP) 19-25 mmHg
• Grade 3: shows alveolar edema on a chest radiograph, pulmonary capillary wedge pressure (PCWP) greater than 25 mmHg

Pulmonary edema CT

Interstitial pulmonary edema is most commonly demonstrated by the following CT signs ⁶⁴:

• ground glass opacification
• bronchovascular bundle thickening (due to increased vascular diameter and/or peribronchovascular thickening)
• interlobular septal thickening

Alveolar edema is demonstrated by airspace consolidation in addition to the above findings.

Pleural effusions are a frequent accompanying finding in cardiogenic/hydrostatic pulmonary edema.

Pulmonary edema ultrasound

Pulmonary edema ultrasound is a newer technique that is non-invasive and does not involve radiation exposure. It is most commonly used in intensive care units, emergency rooms, and operating rooms. It helps detect the accumulation of extravascular lung water (EVLW) ahead of the clinical manifestations ⁶⁵.

The appearance of pulmonary edema is defined as a function of the perturbation of the air-fluid level in the lung, a spectrum of appearances coined the alveolar-interstitial syndromes.

As subpleural interlobular septa thicken among air-filled alveoli, they create a medium in which incident ultrasound waves will reverberate within, creating a short path reverberation artifact. Referred to as B-lines, these are pathological when more than three appear, garnering the title lung rockets, and consistent with thickened interlobular septa. When spaced 7 mm apart they correlate with radiographic interstitial edema and when 3 mm apart with ground glass opacification. When surrounding alveoli become fluid-filled, the resultant interface assumes a tissue-like pattern. The tissue-like sign and shred sign are pathognomonic ⁶⁶.

Pulmonary artery catheterization

Often considered a gold standard in the determination of the cause of pulmonary edema, it is an invasive test that helps monitor systemic vascular resistance, cardiac output, and filling pressures. This test may be done if other tests don’t show the cause of pulmonary edema, or when there’s also chest pain. It helps health care providers see blockages in the heart arteries. A long, flexible tube (catheter) is inserted in a blood vessel, usually in the groin or wrist. It’s guided to the heart. Dye flows through the catheter to arteries in the heart. The dye helps the arteries show up more clearly on X-ray images and video. An elevated pulmonary artery occlusion pressure over 18 mm Hg is helpful in the determination of cardiogenic pulmonary edema ⁵².

Transpulmonary thermodilution

It is an invasive testing modality performed in patients typically undergoing major cardiac, vascular, or thoracic surgeries. They are also used in septic shock and monitors several hemodynamic indices such as cardiac index, mixed venous oxygen saturation, stroke volume index, and extravascular lung water (EVLW) ⁶⁵.

Neurogenic pulmonary edema treatment

Neurogenic pulmonary edema treatment consists of two interventions: treating the underlying central nervous system (brain and spinal cord) injury to reduce intracranial pressure (ICP) to control sympathetic hyperactivity related to the lung injury, and supportive treatment for pulmonary edema ⁶⁷, ⁶⁸, ⁶⁹, ⁷⁰, ⁷¹. Within the supportive treatment of pulmonary impairment, monitoring of body fluids is difficult because maintaining adequate fluid volume is required for cerebral resuscitation, but the approach to neurogenic pulmonary edema (NPE) requires fluid restriction ⁶⁷, ⁶⁸, ⁶⁹, ⁷⁰. In this context, real-time lung ultrasound allows an assessment of respiratory failure, quantification and monitoring of pulmonary interstitial fluid, contributing to the management of liquid therapy ⁷². Another viable intervention is the transpulmonary thermodilution technique, which consists of administering a saline solution at low temperature through a central venous catheter, then measuring the change in blood temperature and using this to construct a thermodilution curve that allows the calculation of hemodynamic parameters such as cardiac output and the pulmonary extravascular water index ⁷³.

Supportive care involves adequate ventilation to provide sufficient oxygenation to prevent hypoxia and hypercapnia ⁶⁸, ⁶⁹, ⁷⁰, ⁷¹. Therefore, the invasive or noninvasive ventilation technique must be individualized according to the severity of the patient’s cardio-pulmonary and neurological affectation ⁶⁷, ⁶⁸. Since patients present a life-threatening condition, it is important to be strict in the non-invasive monitoring of blood pressure, pulse oximetry, electrocardiography, echocardiography, radiography, among others ⁷⁰, ⁷¹. Extracorporeal membrane oxygenation can be used in patients with acute respiratory failure in whom mechanical ventilation and other therapies do not provide adequate gas exchange ⁷⁴.

The usefulness of pharmacotherapy is varied, although no drug has been officially approved for routine use ⁶⁷, ⁶⁹, ⁷¹. Hemodynamic instability with consequent organ hypoperfusion, metabolic acidosis, and progression of inflammation can be managed with vasoactive drugs ⁷⁵, ⁷⁶, ⁷⁷. Milrinone is used to increase cardiac output and is recommended when systolic blood pressure is > 90 mmHg. Dobutamine is preferred in those patients with blood pressure < 90 mmHg to increase cardiac output ⁷⁵, ⁷⁶, ⁷⁷. Other drugs that could be used according to the patient’s context include diuretics such as furosemide, osmotic diuretics, and alpha-adrenergic blockers ⁷⁸, ⁷⁹.

Pulmonary edema treatment

The first treatment for acute pulmonary edema is oxygen. Oxygen flows through a face mask or a flexible plastic tube with two openings (nasal cannula) that deliver oxygen to each nostril. This should ease some symptoms. A health care provider will monitor your the oxygen level. Sometimes it may be necessary to assist your breathing with a machine such as a mechanical ventilator or one that provides positive airway pressure ⁸⁰, ⁸¹.

Depending on the severity of the condition and the reason for the pulmonary edema, treatment might include one or more of the following medications:

• Diuretics (water pills). Diuretics, such as furosemide (Lasix), decrease the pressure caused by excess fluid in the heart and lungs. Diuretics remain the mainstay of treatment, and furosemide (Lasix) being the most commonly used medication. Higher doses are associated with more improvement in dyspnea; however, also associated with transient worsening of kidney function ⁸².
• Blood pressure drugs. These help manage high or low blood pressure, which can occur with pulmonary edema. A doctor may also prescribe medications that lower the pressure going into or out of your heart. Examples of such medicines are nitroglycerin (Nitromist, Nitrostat, others) and nitroprusside (Nitropress). IV nitroglycerin (NTG) is the drug of choice, and it lowers preload and pulmonary congestion. Nitroglycerin should only be used when the systolic blood pressure (SBP) is > 110 mm Hg. Nesiritide is a recombinant brain natriuretic peptide (BNP) that has vasodilatory properties. It has been shown to reduce pulmonary capillary wedge pressure (PCWP) and filling pressures significantly, but no subsequent improvement in dyspnea has been noted ⁸³. Newer drugs like serelaxin, a recombinant human form of relaxin, induced nitric oxide activation, which causes vasodilation. Clevidipine is an ultra-short-acting calcium channel blocker, initiated very early in the presentation, has been associated with reduced length of stay, improved dyspnea, and less frequent ICU admission ⁸⁴.
• Inotropes. Inotropes such as dobutamine and dopamine improve heart pumping function and maintain blood pressure. This type of medication is given through an IV for people in the hospital with severe heart failure. Significant adverse events include tachyarrhythmias, ischemia, and hypotension. Milrinone is an IV inotrope with vasodilatory properties but is associated with an increase in post-discharge mortality ⁸⁵.
• Morphine (MS Contin, Infumorph, others). Morphine reduces systemic vascular resistance and acts as an analgesic and anxiolytic. It has been used in the management of pulmonary edema secondary to acute coronary syndrome. This narcotic may be taken by mouth or given through an IV to relieve shortness of breath and anxiety. However, it may cause respiratory depression needing intubation, and generally not recommended ⁸². Some doctors believe that the risks of morphine may outweigh the benefits. They’re more likely to use other drugs.
• Other medications, when congestive heart failure isn’t the cause of your pulmonary edema, such as antibiotics and steroids.

It is important to diagnose and treat, if possible, any nervous system problems or causes of heart failure. Treatment of neurogenic pulmonary edema (NPE) centers on resolution of central nervous system (CNS) injury and ventilation support ⁴. Specific treatments have been proposed like endothelin converting enzyme inhibitors or sympathectomy which has been successfully tested in rats ⁸⁶, ⁸⁷; however, the evidence is insufficient for its use as a human treatment ⁸⁸, and seizure control is essential as the only preventable treatment.

Neurogenic pulmonary edema prognosis

Data regarding the prognosis (outcome) following neurogenic pulmonary edema have not been well documented, given the relatively low prevalence and likely underdiagnosis ⁸⁹. Neurogenic pulmonary edema usually is generally well tolerated by the patient, although some patients require ventilatory support. Neurogenic pulmonary edema resolves within 48 to 72 hours in the majority of affected patients ⁸⁹.

The occurrence of neurogenic pulmonary edema in a brain-injured patient is associated with a poor prognosis and has a high mortality (60% to 100%). It is impossible to assess whether the direct cause of this mortality is pulmonary or neurological or even cardiovascular. Recent publications seem to attribute neurogenic pulmonary edema mortality to not only attributed to pulmonary involvement but also to primary brain injury ³, ⁹⁰, ⁹¹, ⁴, ¹³.

Illness related to neurogenic pulmonary edema is reported to be in the range of 40-50%, and reported death rate (mortality) from neurogenic pulmonary edema is low, at approximately 7% ⁸⁹. Overall, patient prognosis (outcome) is usually determined by the underlying neurological insult that led to neurogenic pulmonary edema unless significant respiratory complications develop.

Neurogenic pulmonary edema complications may include but are not limited to the following:

• Prolonged hypoxic respiratory failure
• Hemodynamic instability
• Nosocomial infections (ie, related to prolonged mechanical ventilation and hospitalization)

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