FINAL MASTER THESIS THE USE OF ULTRASOUND IN DIFFERENTIAL DIAGNOSIS OF ACUTE DYSPNEA

(1)

LITHUNIAN UNIVERSITY of HEALTH SCIENCES Department of Emergency Medicine

FINAL MASTER THESIS

THE USE OF ULTRASOUND IN DIFFERENTIAL DIAGNOSIS OF

ACUTE DYSPNEA

Medicine Faculty

(2)

2

1. ABSTRACT

Carles Mallol Blay

The use of Ultrasound in differential diagnosis of acute dyspnea Research aim:

The main aim of this study is to evaluate the efficacy of the US (Ultrasound) in differential diagnosis of the dyspnea. This review analyses the results of previous performed studies evaluating the difference between US and CXR (Chest X-ray) and their sensitivity and specificity.

Objectives:

The objectives of this review are the evaluation of the differential diagnosis of dyspnea, the prevalence of dyspnea worldwide and the causes of it. The evaluation of the US

effectiveness compared to CXR and CT (Computed tomography) and also its diagnostic performance in case of detecting the causes of the dyspnea.

Methodology:

The physiological and diagnostical, as well as some US basis information are taken from different major scientific databases. Epidemiological and also US information are performed from a quantity of 14 studies.

Research results:

Although a minor amount of studies described the differential diagnosis of the dyspnea, the studies demonstrated an increase in sensitivity and specificity while using US for the

diagnosis. US took less time to perform the diagnosis, so a faster treatment could be provided. The heart problems showed the highest causes of dyspnea.

Conclusions:

Cardiological and pulmonary diseases were the major causes of the acute dyspnea causes. The US could replace the radiological in diagnosis of the causes of dyspnea, either by it efficacy and its faster diagnosis.

Recommendations:

Further studies should be evaluated in the differential diagnosis for acute dyspnea, as no sufficient studies are performed on the differential diagnosis as they are more focused on the US diagnosis efficacy.

Conflict of interest:

(4)

4

2. ABBREVIATIONS

- 2D= two-dimension - 3D= three-dimension

- ACEP= American College of Emergency Physicians - AHF= Acute Heart Failure

- AIS= Alveolar-Interstitial Syndrome

- AIUM= American Institute of Ultrasound in Medicine - ARDS= Acute Respiratory Distress Syndrome

- BLUE-protocol= Bedside Lung Ultrasound in Emergency-protocol - BNP= Brain Natriuretic Peptide

- CAD= Coronary Artery Disease

- COPD= Chronic Obstructive Pulmonary Disease - CT= Computed Tomography

- DDx= Differential Diagnosis - DM= Diabetes Mellitus - ECO= Ecography

- ED= Emergency Department - EM= Emergency Medicine - HF= Heart Failure

- ICU= Intensive Care Unit - IVC= Inferior Vena Cava

- LRTI= Lower Respiratory Tract Infections - LUS= Lung UltraSonography

- LVED= Left Ventricular End-Diastolic - LVF= Left-Ventricular Failure

- LVHF= Left Ventricular Heart Failure - min= minutes

- mm= milimeters

- mMRC= modified Medical Research Council - MRC= Medical Research Council

(5)

5 - NYHA= New York Heart Association

- PE= Pulmonary Embolism

- PLUS= Pleural and Lung UltraSound - POCUS= Point Of Care UltraSound

- RADIUS= Rapid Assessment of Dyspnea with UltraSound - SOB= Short Of Breathness

- UK= United Kingdom - US= Ultrasound

- US= Ultrasound/ Ultrasonography - V/Q= Ventilation-Perfusion

(6)

6

3. TERMS

- Air hunger: Kussmaul's respiration, extremely deep ventilation such as occurs in patients with acidosis attempting to increase ventilation of alveoli and exhale more carbon dioxide - J-receptors (juxtacapillary-receptors): sensory nerve endings located within the alveolar walls in juxtaposition to the pulmonary capillaries of the lung and are innervated by fibers of the vagus nerve.

- Acoustic impedance: it is a physical property of the tissue. It describes the resistance that the ultrasound confronts as it passes through the tissue. It depends on the density of the tissue and the speed of the sound wave [13].

(7)

7

4. INTRODUCTION

Ultrasonography is a very wide used instrument, and even more used in the last recent years. Dyspnea causes have a different range for its diagnostical procedure. A rapid diagnostic and treatment are essential to reduce the morbidity and mortality. Lately, US has been used in different departments, ED is one of them. Although US it is not the first choice for the differential diagnosis of the causes of the acute dyspnea, some studies might be demonstrating that US could replace other radiological methods [44,35].

In this review, I tried to had some research in different works already performed in the latest years, from different studies applied on the population and based on the differential diagnosis of acute dyspnea. Whatsmore, some epidemiological data was found which could be

(8)

8

5. AIM & OBJECTIVES

The aim of this thesis is to evaluate the usefulness of the US in the differential diagnosis of acute dyspnea.

(9)

9

6. LITERATURE REVIEW

6.1. Dyspnea and its epidemiological situation

Dyspnea (from Greek dys, meaning “painful” or “difficult” and pneuma, meaning “breath”) is a subjective experience of breathing discomfort (felt as breathlessness) that consists on distinct quality sensations varying in intensity. It is experienced from interactions between different physiological, psychological, social and environmental factors and may induce secondary physiological and behavioural responses [1].

Dyspnea, which is a symptom, must be distinguished from the signs of increased work in breathing.

Dyspnea is a consequence of the normal function deviation in the cardiopulmonary system. These deviations produce the sensation of breathlessness as a consequence of increased drive to breath, increased effort or work of breathing and stimulation of receptors in heart, lungs and vascular system. Most diseases of respiratory system are associated with mechanical properties alterations of the lung or chest wall as a consequence of any disease of the airways or lung parenchyma. On the other way, cardiovascular system disorders more commonly lead to dyspnea by causing gas exchange abnormalities or stimulating pulmonary and vascular receptors.

Dyspnea can be also associated with a normal respiratory and cardiovascular system. Anemia, mild to moderate, is associated with breathing discomfort during exercise. This is thought to be related to stimulation of metaboreceptors, although oxygen saturation is between normal ranges. Obesity associated with breathlessness is probably due to multiple mechanisms, including high cardiac output and impaired ventilatory pump function (decreased compliance of chest wall). Cardiovascular deconditioning (poor fitness) is characterized by the early development of the metabolism which is anaerobic and the stimulation of metaboreceptors and chemoreceptors.

(10)

10 uncomfortable, strained and unsatisfying. These sensations are likely to be linked to physiologic mechanisms. As a symptom, dyspnea can be reported only by the patient and it is completely different from objective findings or signs, such as tachypnea, hyperinflation and cyanosis [2].

M. Johnson collected data from different studies and a study was made: Chronic breathlessness has a prevalence ranging from 9 to 61%. A household survey in South Australia found a prevalence of chronic dyspnea (at least 3 months from the past six ones; modified MRC dyspnea scale >1) of 9%, with symptoms described by the person. The Health Survey for England 2011 found that 15% of men and 26% of women said they had experienced breathlessness (MRC dyspnea scale >2) someday in the previous year. A Norwegian population survey found 13% with moderate dyspnea symptoms on exertion (by using a modified version of the British Medical Research Council‟s Committee on Research into Chronic Bronchitis questionnaire). Dyspnea was more commonly reported by women and older people who were approximately one third of the affected. Some subpopulations seem to have a particularly higher prevalence, for example: older Korean women who smoke have a prevalence of 61%. Breathlessness is a common symptom in some medical conditions and it worsens in the weeks prior to death. Prevalence estimates that for non-malignant cardiorespiratory diseases range 60-88% (in heart failure) and 90-95% (in COPD). In cancer the prevalence varies between 10-79%, depending on the tumor site, stage and context of the study. The most common cause of dyspnea was chronic lung disease (according to other literature). In a national survey of ED in USA, shortness of breath was the primary reason for 2,7% of all presenting patients from all groups of age. In a single hospital study in Norway, dyspnea was the third most common reason to attend with a 9%. Palliative care patients with advanced disease presenting to the ED are even a higher proportion (25%). Patients presenting with breathlessness and HF or COPD are more likely to be hospitalised (88% with HF and 60% with COPD). Breathlessness is a predictor of poor prognosis, for short and long term survival [3].

(11)

11 about 10% [4].

Y. Van Mourik, F. H. Rutten, K. G. M. Moons, L. C. M. Bertens et al. made a study review from a total of 21 articles was performed from 20 different populations. A median sample of 600 patients was taken. A prevalence of 36% had a MRC of ≥2, a 16% had a MRC of ≥3 and a 4% had a MRC ≥4. They also demonstrate that rates were higher in women than in men. Only one of these articles investigated the underlying causes of dyspnea and in the 70% of these, the origin was considered to be cardiac or pulmonary [5].

S. Laribi, G. Keijzers, O. Van Meer, S. Klim, J. Motiejunaite et al. performed an observational prospective study performed in Europe and in Asia-Pacific region. The patients included were presenting to ED with dyspnea as the primary complain. A total of 5.569 patients were admitted in the study. The most common diagnosis in ED were LRTI, with a 25%, HF with a 17%, COPD exacerbation with a 16% and asthma with a 10% [6].

J. P. Stevens, K. Baker, M. D. Howell, R. B. Banzett did a study which was based on a recompilation of 2 studies. The first one was based on 581 studies and the second on 367 who reported dyspnea symptoms. They wanted to estimate the prevalence of dyspnea among hospitalized patients. Prevalence of dyspnea on admission was 13%, while experiencing dyspnea at some time during the hospitalization was 16%. The causes of the dyspnea (rated <4) on the initial patient assessment were: CHF in 16%, valve disease in 6%, pulmonary circulation in 5%, COPD in 14%, DM in 23% and other like hypothyroidism in 12% or RF in 15%. It also concluded that a significant number of patients experienced dyspnea during the hospitalization [7].

Y. S. Punekar, H. Mullerova, M. Small, T. Holbrook et al. took a study performed in 5 different European countries: France, Germany, Italy, Spain and UK. Its objective was to report the prevalence of dyspnea on those countries conducted on 2.531 patients with COPD. About 47% of the patients reported a mMRC ≥2, which was associated with poor health status and sleep quality. The frequency of dyspnea varied from 39,5% in France to 60% in UK (Tab. 1). The study concluded that dyspnea was a highly prevalent symptom in patient with COPD in European countries [8].

(12)

12

EU (n=2531) France Germany Italy Spain UK 0 10 20 30 40 50 60 70 Proportion of patients with mMRC ≥2

Tab. 1 Prevalence of dyspnea in patients diagnosed with COPD [8].

Y. Van Mourik, F. H. Rutten, K. G. M. Moons, L. C. M. Bertens et al. reviewed from a total of 21 articles was performed from 20 different populations. A median sample of 600 patients was taken. A prevalence of 36% had a MRC of ≥2, a 16% had a MRC of ≥3 and a 4% had a MRC ≥4. They also demonstrate that rates were higher in women than in men. Only one of these articles investigated the underlying causes of dyspnea and in the 70% of these, the origin was considered to be cardiac or pulmonary [10].

(13)

13

Tab. 2 Prevalence of mMRC-defined dyspnea grades by site in 15 countries of the COPD study. European countries are underlined [9].

Another study provided some information about the dyspnea in population from Sweden, Australia and also Netherlands (Tab. 3) [12].

The mechanisms to understand the physiologic bases of the dyspnea, four seperate line have evolved [13]:

-VENTILATORY PERFORMANCE:

Some investigations have related the breathlessness sensation to the level of minute ventilation. The correlation is the increased minute ventilation compared to the level of oxygen uptake. This was due to an increase in ventilatory rate, especially if there is lung stiffness. Some patients experiencing breathlessness in the beginning, when they were excessively ventilating for the level of oxygen, noticed that the sensation diminished, suggesting an adaptation to the continued stimulus.

(14)

(15)

15 The third measurement is the breathing-reserve. This value is determined as the difference between the MVV and the actual minute ventilation. The dyspnea symptoms during the performance of any ventilatory task may be related to the fraction of maximum breathing capacity used for force generation by the respiratory system. So, the closer the minute ventilation is to the maximum breathing capacity, the more likely is the patient to feel a shortness of breath. When the actual level of ventilation reaches 30-40% of the maximum breathing capacity, dyspnea is inevitable. Whatsmore, the breathing reserve correlated better with the dyspnea of normal subjects during exertion than with the dyspnea of chronic bronchitis and COPD or LVF (Left-Ventricular Failure). It means that in COPD patients, the minute ventilation may be a very large fraction of MVV (more than 50%) without inducing dyspnea. On the other hand, in acute LVF, a mild increase in ventilation and nearly normal MVV may be associated with considerable breathlessness.

-MECHANICS OF BREATHING:

Concerning the dyspnea is a sensation that prompts an unconscious effort to minimize the work, the energy cost or force of breathing. This, in turn, protects the respiratory system from overwork and inefficient operation. This approach has led the relationships between dyspnea and the work or oxygen cost of breathing.

It has been impossible to identify a critical level of work of breathing at which dyspnea will occur, although a breakdown of the work of breathing into its elastic, resistive and inertial components has helped to relate physiologic disturbances to particular diseases (ex: in chronic MS with pulmonary congestion, the elastic work increases, whereas in obstructive airway disease, resistive work predominates. Those observations have reinforced the concept that patterns of breathing are automatically adjusted to minimize the work done by the respiratory muscles in breathing. The relationship between ventilation and oxygen gas consumed by the respiratory muscles is curvilinear. This oxygen cost of breathing may increase extraordinarily in patients with COPD or with abnormalities of chest wall. In patients with COPD, the quantity of oxygen delivered to the respiratory muscles during the large ventilatory effort may fail to satisfy their aerobic needs, leading to anaerobic metabolism and lactic acidosis. Although the greater the oxygen cost of breathing the likelihood of dyspnea, the determination will not provide any more useful information into the mechanism of the dyspnea.

-CHEMORECEPTION:

(16)

16 for ventilation. The effects of these stimuli on breathing decrease if they continue persist. Additionally, side effects, such as blunting of the sensories during chronic carbon dioxide retention, diminish the likelihood of dyspnea, even if the level of ventilation is increased. Patients with abnormal pulmonary mechanics, the onset of abnormalities in blood gas composition (as in exercise) may aggravate or contribute to dyspnea. So, acute hypercapnia is a stronger stimulus for dyspnea than acute hypoxia is.

-EXERCISE TESTING:

Normally a person is unaware of the fact of breathing and the fact that 500-750 mL of air enters and leaves the lungs 10-15 times per minute. When breathing is perceived to be inappropriate relative to the level of physical activity, dyspnea is felt. Exertional dyspnea is common in patients with heart disease, pulmonary parenchyma or airway disease, pulmonary vascular disease, deformities of chest wall and diseases associated with weakness of the respiratory muscles. An objective and reliable estimation of dyspnea on exertion can be performed from an exercise testing. Dyspnea occurs when minute ventilation flow is excessive relative to oxygen volume flow and when minute ventilation flow is driven by chemical stimuli or altered lung mechanics. Dyspnea with exercise can appear when minute ventilation flow occupies an excessive proportion of MVV. More than 70% of the MVV cannot be sustained by normal subjects for more than several minutes. Consequently, the ventilatory response to exercise associated with dyspnea in patients with heart or lung disease follows a similar pattern of short-lived, near-maximal ventilation.

All these four mechanisms, have a basic relationship which correlates all them with the neurological mechanisms through different outputs or inputs and its mismatches.

It is suggested that the discomfort of dyspnea comprises two primary components: an urge to breathe (referred to as air hunger) and a sense of excessive effort associated with breathing. A third quality is commonly reported by asthmatics, chest tightness.

Dyspnea must result from changes in neural activity within the cortical and subcortical structures of the brain involved in perception. These changes are the consequence of interactions between the efferent (outgoing or motor output) from the brain to the ventilatory muscles (a feed-forward mechanism) and the afferent (incoming or sensory input) from receptors through the body (a feed-back mechanism).

(17)

17 In contrast to painful sensation, which can be attributed to the stimulation of a single nerve ending, dyspnea sensation is viewed as a mixed of different factors producing it.

A disease state may lead to dyspnea by one or more mechanisms, some of which may be present under some circumstances (ex: exercise...), but not others (ex: positional changes...). The inputs and outputs regulating the system are [1]:

Motor outputs or efferents: disorders of the ventilatory pump, most commonly increase airway resistance or stiffness (because of a decreased compliance) of the respiratory system, are associated with a sense of an increased effort to breathe or increased work of breathing. If the muscles are weak or fatigued, greater effort is required, even though the mechanisms of the system are normal. The increased neural output from the motor cortex is sensed via a precipitation discharge, a neural signal that is sent to the sensory cortex at the same time that motor output is directed to the ventilatory muscles.

Sensory inputs or afferents: Chemoreceptors in the carotid bodies and medulla are activated by hypoxemia, acute hypercapnia and acidemia. Stimulation of these (as well as other that could lead to an increase in ventilation), produce the sensation of air hunger. Mechanoreceptors in the lungs, will lead to a sensation of chest tightness when they are stimulated by bronchospasm. J-receptors, which are sensitive to interstitial edema, and pulmonary vascular receptors appear to contribute to air hunger too by its activation by acute changes in pulmonary artery pressure (for example: an hyperinflation is associated with a sensation of increased work of breathing and inability to get a deep breath or an unsatisfying breath. Metaboreceptors (located in skeletal muscles) are activated by changes in the local biochemical milieu of the tissue active during exercise and if it is stimulated, it contributes to a breathing discomfort.

Efferent-afferent mismatch: when there is a mismatch between feed-forward (message to the ventilatory muscles) and feedback (from receptors which monitor the response of ventilatory pump), so the efferent and afferent pathways respectively, increases the intensity of the dyspnea. This is very important, especially when there is a mechanical derangement of ventilatory pump (such as in asthma or chronic obstructive pulmonary disease -COPD-).

6.2. Causes of dyspnea Etiology [14]:

(18)

18 -Respiratory: Foreign body aspiration, glottis edema, COPD (Chronic Obstructive Pulmonary Disease), bronquial asthma, upper or lower airway infection, inhalation of fumes or gaseous substances, pneumonias, athelectasis, respiratory distress syndrome, pneumothorax, pleural effusion, pulmonary thromoembolism, pulmonary hemorrhage, vocal cord dysfunction.

-Mechanical: pulmonary contusion, rib fractures.

-Metabolic diseases: metabolic acidosis, hyper- or hypothyroidism, pregnancy. -Psychogenic: alveolar hyperventilation syndrome, anxiety, depression.

-Others: gastroesophagic reflux, abdominal alterations (ascities, other masses), high altitude exposure, CNS diseases, bad physical shape.

Classification [14]:

Dyspnea can be classified according its pathophysiological mechanism, evolution, NYHA or Medical Research Council (MRC). .

-According its pathophysiological mechanisms

- Increased ventilator demand: which can be due to a physiological process (ex: exercise, pregnancy, high altitude) or due to a pathology (ex: anemia, acidosis, high metabolic index).

- Abnormal mechanics of the lung or chest wall: airway obstruction (asthma, COPD), decreased lung volume (lung fibrosis, pleural effusion, pneumothorax), ventilation-perfusion index alteration (lung edema, athelectasis, pneumonia, lung embolism), neuromuscular pathology (muscular dystrophy, CNS alteration, skeletal deformities).

-According its evolution (Tab. 4).

Tab. 4 According evolution of dyspnea

ACUTE DYSPNEA Pulmonary origin Pneumonia, foreign body aspiration, pleural effusion, asthma, injury intrathoracic structures

Extrapulmonary origin

Cardiogenic pulmonary edema, anemia, metabolic acidosis, injury to chest wall, vocal cord injury

SUDDEN DYSPNEA Pulmonary origin Pulmonary thromboembolism, pneumothorax, nocturnal paroxysmal dyspnea, bronchospasm

Extrapulmonary origin

(19)

19 CHRONIC DYSPNEA (when

it has more than 4 weeks of evolution)

Obstructive

pulmonary diseases

Emphysema, chronic bronchitis, bronquial asthma, vocal cord dysfunction, COPD, asthma Restrictive

pulmonary diseases

Intersticial lung disease, thoracic wall deformities, pleural fibrosis and effusion, phrenic nerve paralysis, left ventricular failure

Others Hyperthyroidism, anemia, CNS disease, hypersensitivity disorders, postintubation tracheal stenosis

-According NYHA classification (cardiac dyspnea) (Tab. 5). Tab. 5 NYHA classification

Class I No symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when walking, climbing stairs, etc.

Class II Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity.

Class III Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m). Comfortable only at rest.

Class VI Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients.

-According MRC (Medical Research Council) dyspnea scale (Tab. 6). Tab. 6 MRC dyspnea scale

Grade 0 Not troubled by breathlessness except on strenuous exercise. Grade 1 Short of breath when hurrying on the level or walking up a slight hill. Grade 2 Walks slower than most people on the level, stops after a mile or so,

or stops after 15 minutes walking at own pace.

Grade 3 Stops for breath after walking about 100 yds (91m) or after a few minutes on level ground.

(20)

20 6.3. Differential diagnosis [1,16]

Shortness of breath is a symptom affecting about the 25% of patients seen in the ED. It can be caused by many different conditions which arise in acute conditions. Clinical presentations occurring at the same time, comorbid diseases makes it more difficult to diagnosis the main cause of dyspnea. The study was based on articles published in PubMed and on different guidelines. The study resulted in that dyspnea was based on a large variety of perceptions, subjective for each patient, and influenced by their emotional state. Acute and chronic dyspnea were, by definition, distinct in the time of symptomatic presence, 4 weeks in chronic dyspnea. Although usually more diagnostic studies are needed, a 30-50% can be correctly diagnosed only by the history, physical examination and observation of breathing pattern. Diagnosis can be more difficult when comorbidities are present. The main causes of dyspnea are cardiac and pulmonary, but also some other conditions. The study concluded that the causes of the dyspnea are a diagnostic challenge and that a rapid evaluation and diagnosis are essential to reduce the mortality and the difficulty of the disease [4].

Acute dyspnea is a serious and possibly lethal medical condition, so it‟s very important to identify it in time and start treatment, however diagnosis is difficult, because there are so many possible causes of such dyspnea. It is the consequence of deviations from normal function in the cardiopulmonary systems. As a consequence of these deviations, breathlessness is produced. Most respiratory system diseases are associated with alterations in mechanical properties of the lungs and/or chest wall, as a consequence of a disease of the airways or parenchyma. Two common pathophysiologic categories are the COPD and the restrictive pulmonary disorders. Whatsmore, disorders of the cardiovascular system often lead to dyspnea by causing gas exchange abnormalities or stimulating pulmonary and/or vascular receptors [15].

Respiratory system dyspnea:

- Diseases of the airways: Asthma and COPD (Tab. 7) are the most common obstructive lung diseases and they are characterized by expiratory airflow obstruction which usually leads to dynamic lung and chest wall hyperinflation. Patients with moderate to severe disease have an increased resistive and elastic load on the ventilatory muscles and increased breathing work. Acute bronchoconstriction suffering patients also complain of tightness and usually hyperventilate too. This is usually due to stimulation of pulmonary receptors. Both asthma and COPD may lead to hypoxemia (usually much more common due to differences on oxygen or carbon dioxide binding to hemoglobin) and hypercapnia from ventilation-perfusion (V/Q) mismatch.

(21)

21 denominator. Patients suffer from this disturbances in breathing, abnormal lung volumes and derangements in gas exchange. The minute ventilation constitutes an abnormally large fraction of the maximum breathing capacity. These mechanical abnormalities are: high resistance to airflow; the thorax assumes an hyperinflated position, placing the inspiratory muscles at mechanical disadvantage; the work of breathing is greatly increased; high oxygen gas cost of breathing; derangement in dead space ventilation and in alveolar-capillary gas exchange add to the afferent stimuli which results in some disturbances in mechanics and gas exchange, large swing in pleural pressure and a considerable muscular effort is expanded in breathing. Oxygen delivery to the overworked muscles is insufficiency, so fatigue and exhaustion may send nervous and chemical signals to the brain. If the patient accumulates excess water in the lungs, the juxtacapillary receptors will provide additional sensory input to the central integrating mechanisms. The convergence of these stimuli upon the sensory-motor cortex may generate an inordinate motor command to the respiratory muscles, which will not be able to mobilize the thorax sufficiently to generate the pleural pressures needed for adequate ventilation.

Asthma mechanism for the dyspnea are exactly the same as described before with COPD. However, these mechanisms do not count for the sensation of the “chest tightness” or the inordinate sense of labored breathing that accompanies the breathlessness in asthma.

- Diseases of the chest wall: conditions which restriction of the ventilator effects are present due to stiffen the chest wall (ex: kyphoscoliosis) or that weaken ventilatory muscles (ex: myasthenia gravis or Guillain-Barré syndrome). Large pleural effusions may contribute to dyspnea by increasing the work of breathing and by stimulating pulmonary receptors if athelectasis is associated. Also encasement of the lung due to pleural thickening. Neuromuscular diseases which affect the inspiratory muscles sufficiently to diminish maximum inspiratory pressures may decrease vital capacity and total lung capacity, leaving functional capacity and residual volume increased. All these abnormal findings are described more precisely with the diseases of the parenchyma.

(22)

22 pulmonary receptors may enhance the hyperventilation characteristic of mild to moderate interstitial disease.

Cardiovascular system dyspnea:

- Diseases of the left heart: diseases of the myocardium resulting from CAD (Coronary Artery Disease) and non-ischemic cardiomyopathies resulting in a greater LVED (Left-Ventricular End-Diastolic) volume and an elevation of the LVED, as well as the pulmonary capillary pressures. The elevated pressures may lead to interstitial edema it stiffens the lung and stimulation of pulmonary receptors happens, thereby causing dyspnea. Long-standing interstitial edema, contributes to stiffen the lung, which in turn increases the airway resistance due to tracheobronchial mucosa edema. Both the lung stiffness and increased airway resistance, swings the pleural pressure during the respiratory cycle. Hypoxemia due to V/Q mismatch may also contribute to breathlessness symptoms. Dyastolic dysfuction (characterized by a very stiff left ventricle) may lead to severe dyspnea with relatively mild degrees of physical activity, even more, if it is associated with MR (mitral regurgitation).

- Diseases of the pulmonary vasculature: primary diseases of the pulmonary circulation (Tab. 7) (primary hypertension and primary vasculitis) and pulmonary thromboembolic disease may cause dyspnea via increased pulmonary-artery pressure and stimulation of pulmonary receptor. Hypoxemia may be present but hyperventilation is common. A low diffusing capacity may be accompanied by normal lung volumes. However, the use of supplemental oxygen has a minimal effect on the severity of dyspnea and hyperventilation.

- Diseases of the pericardium: cardiac tamponade and constrictive pericarditis are both associated with increased intracardiac and pulmonary vascular pressures, which are the likely cause of dyspnea in these conditions. To the extent that cardiac that cardiac output is limited (at rest or with exercise), stimulation of metaboreceptors and chemoreceptors (if lactic acidosis develops) contribute as well.

-Others: in uncomplicated pulmonic stenosis dyspnea is related due to an inadequate cardiac output during exercise. In Tetralogy of Fallot, dyspnea is severe and often relieved by assuming a squatting position. In this form and other cyanotic heart diseases, dyspnea and fatigue appear during exertion when the arterial oxyhemoglobin saturation decreases below the resting level. In anemia (Tab. 7) (where the levels of hemoglobin concentration is under 6-7g/dL) is common the sensation of breathlessness during exercise or excitement; more common in acute than in chronic; although the pathogenesis it is still unclear, inadequate oxygen delivery to the respiratory muscles has been proposed.

Other dyspneas:

(23)

(24)

24 6.4. The use of Ultrasound

6.4.1. US and its applications

All diagnostic procedures of US are based on the detection and representation of the acoustic energy reflexed by the interfaces inside the organism. These interactions provide the necessary information to provide high resolution images of the organism in a grey-colored scale, as well as to represent information related with the blood flow. The properties of the imaging of the US have lead it to be one of the most relevant and versatile methods of image-taking. Unfortunately, the usage of modern ecographic material does not guarantee a high-quality diagnostic studies. The maximum benefits of this complex technology is under the combination of ability and knowledge based on the physical principles of its diagnostic peculiarities. The user should know about the fundamentals of the acoustic energy interactions in the different tissues.

Most of the US use brief discharges or pulses of energy which are transmitted to the body, which spread though the tissues. The acoustic pressure waves can travel perpendicularly to the direction of the moving particles (transversal waves), though in the tissues and fluids the propagation of these waves is moving on the same direction (longitudinal waves). The speed at which the wave is moving through the tissue depends on the physical properties of the tissue, depending on the density of the medium and its rigidity or elasticity. The propagation speed increases by the increase of rigidity and decreases at the increase of elasticity.

The propagation speed is an important value to determine the distance between the interface reflected and the transductor.

The diagnostic ecographs are based on the detection and representation of the reflexed sound or ecos. To produce an eco there should be a reflectant interface. The sound which travels though a complete homogenic medium does not meet interfaces which reflex the sound, so the medium will be anechoic or cystic. When there is a mix of different fisical properties of the tissues or materials, different acoustic interfaces exist. These interfaces are the responsible of the reflexion of a variable proportion of the incident energy. The grade of reflexion is determined according the different acoustic impedances of the materials which forms the interface. This impedance is mainly determined by the density of the medium. That is why the interfaces which are better reflexed are those with air or bone, which in the incident energy is almost all reflexed. On the other side, those tissues with poor acoustic impedance can reflect only a part of this energy, leaving the rest of the energy to go through, as the interface between muscle and fat tissue.

(25)

25 in the alternation between tissues with different acoustic propagation speed either to a higher or lower velocity due to the direction change in the sound wave. The refraction is important because it is one of the most common causes of a wrong register of a structure. When the US apparatus detects an eco assumes that the original eco comes right from the transductor. If the sound suffers refraction, the eco detected and represented on the screen could proceed from a different depth or localization.

The attenuation is present by the acoustic energy resistance while travelling through the mediums. This is an important issue as it influences in the depth from which information can be taken. The sound loses energy while travels through the tissue. The attenuation determines the efficiency in which the ultrasounds penetrate in a specific tissue and changes considerably in normal tissues.

The components used in the US are: a transmissor to refer the energy to the transductor, the ultrasound transductor, a receptor and a processor to detect and amplify the retrodispersed energy and manipulate the reflexed signals for its graphical representation, a screen for its representation and a recorder for the images.

The limitations of the lung ultrasonography are related to 4 different causes: an operator-related, machine-operator-related, documentation-related and miscellanous. When it is due to an operator a specific training acquisition, image interpretation and integration of the results into an effective treatment strategy are required. When it is machine-related it refers to the particular US machines adequate to produce the proper quality images. The documentation-related limitations refers to the insufficient time to label and save the images which are quickly obtained or to issue a complete written report of all findings, documentation problems as the lack of medical-legal documents concern or missed previous lung ultrasound examinations or deficient documentation (on comparison from today‟s results to those from yesterday) for an appropriate treatment application. The fourth limitation is miscellaneous, referring to all those problems that the ultrasonography founds on its diagnostic procedures; lesions surrounded by aerated lung, chest wall dressings, massive edema, obesity and subcutaneous air are those problems which the ultrasonography image founds.

The chest wall is divided into eight areas (2 anterior and 2 lateral on each side).

6.4.2. Biological effects and security

(26)

26 vibrations have any biologic consequence. Those works do not hold true for the ultrasound energy being converted into heat. For example, at soft-bone interface, almost half of the wave is reflected backwards, but the other part of the energy is absorbed by the bone leading to an elevation of that tissue-bone interface. That‟s why the physical effects of the sound are divided mainly in two groups: thermal and non-thermal [19]. This tissue heating is related to intensity and also the focus of the ultrasound beam. The more focused the beam is, the less area of heat production is present, as the surrounding tissues will dissipate the thermal energy.

-The thermal effects: some energy of the ultrasound is absorbed by the tissue structure and converted into heat energy, which is determined by the frequency and intensity of ultrasound dosage and type of tissue. Currently there are no clear guidelines which provide the clinician with protocols about this mechanisms. On the absorption of the ultrasounds along the passage through the tissues the conversion of energy of these ultrasounds to heat is present. Different physical and biological factors control the heat of the tissues and also the capacity of the organism to cool the tissues by the blood perfusion. Mainly two types of tissue have to be focused, bony parts and soft tissues. On the bony part, some studies applied on pregnant women provided that a 3 degree Celsius was increased on the femur of a fetus on the 108th day of gestation [17]. About the soft tissues heating it is related with gynaecological and obstetrical effects.

Whatsmore, a 1982 report demonstrated a direct relationship between the absorption of ultrasound energy and amount of protein. The higher the protein concentration, the higher the ultrasound energy absorption [18].

(27)

27 alterations which, combined, suggest that ultrasound first “injuries” the cell. The result is a growth retardation and a posterior cellular recovery response characterized by an increase in protein production.

This mechanisms prompted the AIUM in 1988 to issue a safety statement which is applicable still nowadays for the usage of diagnostic ultrasound, suggesting [21]:

-no study should be performed without valid reason -no study should be prolonged without valid reason

-the minimal output power should be used to produce the optimal images if the ultrasound machine allows control of output power (known as ALARA principle, As Low As Reasonably Achievable)

6.4.3. Applications in the thorax

The ultrasound is well known to be used to evaluate and diagnose a wide variety of clinical problems in the thorax, in chest wall and pleural and lung lesions adjacent to the chest wall. Although the ribs, the column and the air-filled lung act as barriers at the ecographic visualization, the presence of liquid in the interpleural space, tumors, consolidation, etc. can be evaluated. When a simple chest radiographic image cannot clarify a thoracic anomaly, the ecography can better characterize the anomaly and limit the differential diagnosis. The ecography can be used rather to differentiate between pleural lesions and parenchymal lesions, to visualize the damaged parenchyma hidden by a pleural leakage and other anomalies which cannot be detected or suspected with other radiological modalities.

The ecograph is portable so it is an easy-used instrument. It can be used for those worse-healthy patients in the hospital to be evaluated about their thoracic diseases and to provide an precise and secure guide for the interventional procedures in the intensive care unit. Patients can be examined in any position which facilitates the need to move those patients under life support devices. On the other way, The patients can be positioned differently to optimize the view of the mediastinum or deep thoracic structures.

(28)

(29)

29 6.4.4. US applied on the differential diagnosis of acute dyspnea

D. Berliner, N. Schneider, T. Welte, J. Bauersachs presented that shortness of breath is a symptom affecting about the 25% of patients seen in the ED. It can be caused by many different conditions which arise in acute conditions and can be life-threatening. Clinical presentations occurring at the same time, comorbid diseases makes it more difficult to diagnosis the main cause of dyspnea. The study was based on articles published in PubMed and on different guidelines. The study resulted in that dyspnea was based on a large variety of perceptions, subjective for each patient, and influenced by their emotional state. Acute and chronic dyspnea were, by definition, distinct in the time of symptomatic presence, 4 weeks in chronic dyspnea. Although usually more diagnostic studies are needed, a 30-50% can be correctly diagnosed only by the history, physical examination and observation of breathing pattern. Diagnosis can be more difficult when comorbidities are present. The main causes of dyspnea are cardiac and pulmonary, but also some other conditions. The study concluded that the causes of the dyspnea are a diagnostic challenge and that a rapid evaluation and diagnosis are essential to reduce the mortality and the difficulty of the disease [22].

P. Nazerian, S. Vanni, M. Zanobetti, G. Polidori, et al. proved that cardiac ECO is a necessary tool in diagnosis of acute LVHF, however it is not a routine exam available in every ED. When patients were presenting with acute dyspnea, doppler cardiac ECO was performed for the diagnosis of acute LVHF. For each dyspneic patient, Boston criteria score for HF, N-terminal prohormone BNP and doppler cardiac ECO were performed. The final diagnosis of the patients were established as as a standard criteria. From 145 patients, 64 were finally diagnosed with acute LVHF. The median time used to perform de doppler cardiac ECO was 4 min. The study concluded that doppler cardiac ECO was more specific than the Boston criteria or the N-terminal prohormone BNP and that doppler cardiac ECO of mitral inflow was a rapid and accurate tool in evaluation of acute dyspneic patients [23].

E. Piette, R. Daoust, A. Denault expressed that thoracic and lung US had become a fast and detailed method of diagnosis for hypoxic diseases. The purpose of the study was to review the recent literature on POCUS. Most of the literature on lung US is usually based on studies done in ICU and ED but recently anaesthesiologists have reported the experience on usage of lung US. The study wanted to describe the US technique applied on the lung to diagnose and treat patients with hypoxia. This was mainly found in patients with pneumothorax, alveolar and interstitial lung diseases and pleural effusion.

US descriptions:

(30)

30 sonographic zones and absence of pleural effusions.

-Alveolar interstitial disease: B-lines are the most characteristic findings. B-lines when

separated by less than 3 mm are signs of alveolar interstitium disease, which could be either cardiogenic or non-cardiogenic pulmonary edema such as ARDS, interstitial pneumonias and pulmonary fibrosis. Can be unilateral or bilateral. The constellation of the artifacts will

distributed depending on the spread of the disease. The different findings can help to distinguish among the different cardiogenic or non-cardiogenic causes.

-Pneumothorax: air presence between parietal and visceral (which may not be seen due to air) pleura. The pleural interface should be normal and normal lung sliding should be present. Identification on M-Mode (as a transition from a “seashore“ sign (Fig. 1), on a normal lung, to a “barcode“ sign, when pneumothorax is present) is 100% specific. Pneumothorax is

probable if A-lines are seen with no lung sliding, no B-lines, no lung pulse and no lung point.

Fig. 1 On the left, typical normal lung US image, with “seashore sign“; on the right, typical pneumothorax US image, with “barcode“ image [24].

-Pleural effusions: the air in a normal lung parenchyma will reflect the US waves and create an image identical to liver and spleen. A normal mirror image is lost but liquid is seen.

(31)

31 advantage over CXR or CT. In combination with pulse oxymetry, end-tidal carbon dioxide monitor, mechanical ventilation monitor and bronchoscopy will allow to investigate every cause of hypoxemia. Proper studies in anaesthesiology, ICU and ED medicine will permit a wide and precise use of thoracic and LUS [24].

S.J. Koenig, M. Narasimhan, P.H. Mayo described that thoracic US was a non-invasive and available imaging modality. It was allowing the physicians to diagnose a variety of thoracic disorders. US is still useful in imaging lung consolidation, pleural-based masses, pleural effusions, pneumothorax and diaphragmatic dysfunction. The article summarizes thoracic US applications for the pulmonologist and others procedures. The study concluded that thoracic US was safe, easy-to-learn and portable. The history and physical examination should be performed as an indication from the US exam. US can also be used as a routine in the outpatient settings for a real-time basis. This imaging modality, with a continued decrease in size and cost of US machines, will take its place for the physical examination and to guide thoracic procedures safely [25].

L. Lamsam, L. Gharahbaghian, V. Lobo described that POCUS is being more used as a diagnostic tool in ED. There was a need to validate the efficacy of it in comparison with current diagnostic procedures, as the number and type of POCUS scanings expanded. The study was comparing POCUS to CXR in patients with non-differentiated respiratory or chest complains. Studies showed that CXR, as an initial diagnostic interpretation for a respiratory and chest complains, had a sensitivity of 47% for pleural effusion, 52% for pneumothorax, 77% for pneumonia and 69.5% for pulmonary edema detection [26-28].

The sensitivity findings with the time required to perform the CXR makes it a suboptimal modality.

(32)

32 to modified RADIUS protocol. Modified RADIUS showed a higher sensitivity of 76% compared to CT with a 65% but lower specificity of 71% and compared to CT with a 100%. POCUS scans were interpreted and a 92% of accuracy was achieved. The study concluded that the sensitivity and specificity of POCUS, when modified RADIUS protocol was used, was not significantly different than CXR. POCUS has demonstrated a great value for diagnosing the etiology of undifferentiated acute respiratory and chest complains, but further studies are required [30].

Tab. 8 Modified RADIUS protocol [30] Protocol

Component

Technique

Cardiac examination

Perform with the patient at a 45-degree angle when possible. Include the parasternal long-axis, parasternal short-axis, apical four-chamber and subxiphoid views. Estimate contractility, chamber size and any pericardial fluid

IVC

evaluation

Perform at the subxiphoid view and measure the diameter and percent change with respiration. The right lateral view may be used if the IVC cannot be visualized at the subxiphoid view.

Thoracic cavity evaluation

Assess the costophrenic angles for pleural effusion.

Pleural line assessment

Assess second intercostal spaces for lung sliding using the linear probe. Assess each of the eight Volpicelli lung zones for B-lines, A-lines and comet tails.

(33)

33 evaluation in ED, in identifying cardiac causes of acute dyspnea. 56 patients were enrolled on the study, with the symptoms of breathlessness with a sudden onset with no history of chronic dyspnea, or an increase in severity of chronic dyspnea in the latest 48 hours. At least, one PLUS physician presence was needed. Patients were scanned in a supine or semi-recumbent position. The total of patients examined and diagnosed with cardiac-causing dyspnea was 27 (48,2%), the pulmonary-causing dyspnea patients were 25 (44,6%) and the mixed-causing dyspnea (cardio-pulmonary) were 4 (7,1%). The diffuse AIS had a sensitivity of 93,6% and a specificity of 84%, the pleural effusion a sensitivity of 83.9% and a specificity of 52%, while these both in coexistence had a sensitivity of 81.5% and a specificity of 82.8%. one of the main limitations of this study was the small amount of patients were enrolled. The study concluded that the US examination took a very short time (less than 5 min, as they performed the US just immediately after initial evaluation). They confirmed that B-lines are artifacts that may disappear rapid after edema resolution. The 48% (56 patients) presenting with acute dyspnea had a cardiogenic cause on the final diagnosis; compared to other studies the prevalence of cardiogenic dyspnea was ranging from 37% to 61%. They also demonstrate, by the usage of PLUS, that diffuse AIS was highly predictive for cardiogenic dyspnea to be differentiated from non-cardiogenic dyspnea. High sensitivity but low specificity for cardiogenic dyspnea was showed by pleural effusion in US usage. These results had some disconcordance with a study made by Kataoka and Takada who showed a similar sensitivity but higher specificity, but could be related to the presence of pleural effusion secondary to other diseases, as happens in ED. They noticed that US scanning of a pleural effusion does not allow a reliable differentiation between other causes of acute dyspnea [31].

The study was to ascertain the main diagnostic accuracy of lung and cardiac US in undifferentiated ED patients. The physicians performing the cardiac and LUS, according to the protocol, were blinded to clinical and radiological results. Then the findings were compared with the final diagnosis. The blinded US physician went under more than 20 hours of training on lung and cardiac US or a board-certified emergency physician. The images were reviewed by 2 with a 5 years minimum on US experience (also blinded). The final diagnosis based on history, physical examination, laboratory and radiological findings was performed by 2 other physicians, blinded too. Any discrepancy was revised by a third independent physician. The US was performed in a supine or semi-recumbent position, depending on the breathlessness severity. The BLUE-protocol provided the structure for the modified US protocol on that study [32].

(34)

34 seven profiles:

- The A: profile associates anterior lung-sliding with A-lines. - The A‟: profile is an A-profile with abolished lung-sliding.

- The B: profile associates anterior lung-sliding with lung-rockets. - The B‟: profile is a B-profile with abolished lung-sliding.

- The C: profile indicates anterior lung consolidation, regardless of size and number. A thickened, irregular pleural line is an equivalent.

- The A/B profile: is a half A-profile at one lung, a half B-profile at another.

A total of 231 patients were examined. Mainly, 7 causes for the diagnosis were identified: congestive cardiac failure, pneumonia, asthma, COPD, non-cardiogenic causes leading to fluid overload, pneumothorax and PE. They were grouped in asthma and COPD, pulmonary edema secondary to cardiac or non-cardiac and the last group which was a non-cardiac nor respiratory nature. The results on the DDx for the patients were: for pneumonia (49 patients), the accuracy was on 77,9%, a sensitivity of 65,3% and a specificity of 82%; for pulmonary edema (84 patients), the the accuracy was on 76,9%, a sensitivity of 71,4% and a specificity of 80,9%; for the COPD/asthma (62 patients) the accuracy was on 81,9%, a sensitivity of 64,5% and a specificity of 89,8%. The study showed a lower sensitivities values, but similar specificities for various conditions for POCUS. The limitations affected the results, as a minimum of 250 patients were expected, but only 231 could participate, to simplify the study, only pneumonia, pneumothorax, pulmonary edema, COPD and astham patients were analyzed, lung parenchyma scarring after other diseases if any previously. The study concluded that POCUS could add a value to the clinical evaluation, LUS provided a moderate diagnostic accuracy while the cardiac US for its contractility alone did not adequately differentiate the causes of pulmonary edema. Whatsmore, if complementation with other investigation tools is performed, treatment and accurate disposition of the patient begins earlier [33].

(35)

35 fibrosis or edema and intra-alveolar fluid allowing a DDx between edema and COPD exacerbations. LUS should be taken as a daily practice tool for radiologists, EM physicians, cardiologists, pneumologists and intensivists [34].

Rapid identification of the cause of the dyspnea (either cardiogenic, respiratory or others) is essential for the therapeutical and prognosis purposes. The study evaluated 130 patients in whom LUS scanning were compared to data obtained by clinical examination, medical history, blood analysis and CXR. Etology was classified in three groups, cardiac, respiratory and mixed according to the final diagnosis. It was demonstrated that LUS sensitivity was 91.49% (83.92%–96.25%) and specificity was 75.00% (57.80%–87.88%), while CXR sensitivity was 73.40% (63.29%–81.99%) and specificity was 61.11% (43.46%- 76.86%), and on pulmonary auscultation, sensitivity was 81.91% (72.63%–89.10%) and specificity 36.11% (20.82%- 53.78%). The study had some limitations as an incomplete LUS evaluation of the parenchyma of the lung, supine exmaination (which makes the evaluation incomplete), not a complete evaluation is also important as the results could be better. The study concluded that LUS examination had a great utility in internal medicine department helping with a fast and reliable DDx for the etiology of acute dyspnea. Whatsmore, it also approved the hypothesis that sensibility and specificity of LUS was higher than in CXR fro the identification of the cardiogenic causes, so wider use should be promoted [35].

The differentiation between cardiac from non-cardiac causes of dyspnea takes a huge clinical challenge, since an appropriate diagnosis is the condition needed for an adequate therapy and prognosis. The only structure detected in healthy lungs is the pleura, visualized as a hyperechoic horizontal line, moving with the lung on synchronization. When some pathologies are affecting, for example pneumonia, HF, ARDS, pulmonary fibrosis and others, the volume of air decreases which makes it easy to be visualized. Although it is used for detection of pleural effusions, it is not widely used in ICU yet. One of the main reasons is the requirement of a trained physician, which may take months since the image and diagnosis performed depends only on the person scanning. In the study, LUS was performed on different diseases for an appropriate differential diagnosis. Decompensated HF, COPD, pneumothorax, ARDS, pleural effusions were evaluated with the use of the US. The study concluded that the LUS was a very useful tool in ICU for the differentiation of cardiogenic pulmonary edema from acute lung conditions (ex: ARDS, pneumonia, COPD, pneumothorax and PE) [36].

(36)

36

morbidity and the mortality. The patients were assessed by two expertise, the first one enrolled in performing the sonography evaluation of the lung, the heart and inferior vena cava, and the second (treating) physician performed traditional tests as needed. The time needed for the diagnosis formulation, the accuracy and the concordance were evaluated. 2683 patients were admitted on the study. The differences were remarkable, as the time required for the US diagnosis was lower than that needed for the ED diagnosis, 24+/-10 min and 186+/- 72 min respectively. Diagnosis showed a good overall concordance. Accuracy showed no statistically differences in acute coronary cases, pleural effusion, pneumonia, pericardial effusion, pneumothorax and dyspnea; although that POCUS was more sensitive in HF, while ED diagnosis was more sensitive in COPD, asthma and pulmonary embolism. The study concluded that POCUS is a reliable diagnostic tool for the reduction of its time [37]. POCUS is a clinical tool used in emergency medicine. LUS is a POCUS characterized by a very good accuracy and far better than radiology [38] or auscultation [39]. A POCUS diagnostic evaluation, based on a LUS of patients admitted for acute dyspnea, is concordant with complete diagnostic care and it is much faster [37]. According to the ACEP, the three steps of emergency US skills are the recognition of indications and contraindications, the image acquisition, and image interpretation [40]. The study showed that a higher frequency of ultrasound used by physicians decreased the number of uncertain diagnosis (NUD) in difficult clinical cases with ultrasound information. Also, when physicians had US data and a longer practice history there were fewer NUD. In contrast, if an physician does not practice every day, then POCUS becomes more difficult for them as they assign less importance to the US result in their decision. The study had some limitations as it was based on physicians' diagnostic reasoning, it could be possible that the weight of each argument was different in the clinical situations, the physicians more believing in US could be very cautious when they had the data, that is why the study was completed using typical US syndromes. In conclusion, the physicians did not confirm or eliminate the hypothesis only on clinical examination but the US usage decreased the NUD in difficult acute dyspnea cases with LUS data. An evidence for POCUS, that the weight of US data in decision-making should be important [41].

(37)

37

compared US and radiographic findings independently from the final diagnosis, although the US was used to identify faster the diagnosis and treatment. The most important limitation was that only one experienced physician was in charge of all US examination (if all the physicians working in the ED could have performed the examinations, the accuracy would probably be lower). At least 150 US examinations need to be performed and understood by an expert physician to achieve sufficient aptitudes, these are the recommendations from the American College of Emergency Physicians (ACEP) [42]. The study was based from 404 patients, whom underwent US and CXR examination. In 118 patients, a mismatch between both methods developed, so CT scan was performed. From those 404 patients, 157 had a normal US examination and 141 of these had a normal CXR. When radiography was normal, the most frequent diagnoses were COPD, heart failure, and acute bronchitis. On the other hand, when ultrasound was normal, the most frequent diagnoses were COPD and acute bronchitis. The concordance between both methods overlapped in a 95% in PE, a 87% in pulmonary fibrosis and a 76% in free pleural effusion, a 70% in lung consolidation. The lowest concordance was found in ARDS pattern and loculated pleural effusion. In those 118 patients with discordances between the US and CXR, chest CT scan was performed and confirmed the US-based diagnosis in the majority (63%), exhibiting a greater sensitivity, whereas CXR-based diagnosis was confirmed in 37%. In this clinical study, US provided a correct diagnoses in the 90.5% of cases. In all those cases with concordant results, between US and CXR, were correctly diagnosed, and combining these results with the CT scan findings reflected that the US diagnostic accuracy in the study was more than 90% for all pulmonary diseases investigated causing dyspnea. In conclusion, when US exam was normal, radiographic imaging can be avoided; when discordance between both modalities was present, US was more accurate in free pleural effusion although that in other pathologies both modalities were accurately similar meaning that chest US could be a replacement modality for standard CXR used in patients with dyspnea [43].

(38)

38

(39)

39

7. RESEARCH METHODOLOGY & METHODS

A total of 9 studies were reviewed for its epidemiological information from different sources, some major scientific databases and medicine related books were used to provide some diagnostic information in the study. A total of 14 studies were read and analysed. The works applied on the differential diagnosis of acute dyspnea were less than those expected as more studies are still needed, but some studies evaluating the efficacy of US were found. All

(40)

40

8. RESULTS

STUDY RESULTS

[22]- D. Berliner, N. Schneider, T. Welte, J. Bauersachs. The Differential Diagnosis of Dyspnea. Deutsches Arzteblatt International, 2016. 113(49): 834-845.

Although usually more diagnostic studies are needed, a 30-50% were correctly diagnosed only by the history, physical examination and observation of breathing pattern. Diagnosis was more difficult when comorbidities are present. The main causes of dyspnea were cardiac and pulmonary. A rapid evaluation and diagnosis were essential to reduce the mortality and the difficulty of the disease. [23]- P. Nazerian, S. Vanni, M. Zanobetti, G.

Polidori, et al. Diagnostic Accuracy of Emergency Doppler Echocardiography for Identification of Acute Left Ventricular Heart Failure in Patients with Acute Dyspnea: Comparison with Boston Criteria and N-terminal Prohormone Brain Natriuretic Peptide. Academic Emergency Medicine, 2010. 17: 18-26.

Cardiac ECO was a necessary tool in diagnosis of acute LVHF. The median time used to perform de doppler cardiac ECO was 4 min. Doppler cardiac ECO was more specific than the Boston criteria or the N-terminal prohormone BNP.

[24]- E. Piette, R. Daoust, A. Denault. Basic concepts in the use of thoracic and lung ultrasound. Current opinion in

anaesthesiology, 2013. 26 (1): 20-30.

Thoracic and LUS were very useful tools in evaluation of hypoxic patients. These could be very useful in the operating room, recovery room, ICU and ED because of its easy access, mobility, rapidity, repeatability and lack of radiation. Every cause of hypoxemia would be diagnosed in combination with pulse oxymetry, end-tidal carbon dioxide monitor, mechanical ventilation monitor and bronchoscopy.

(41)

41 Thoracic Ultrasonography for the Pulmonary

Specialist. Chest, 2011. 40 (5): 1332-1341.

outpatient settings for a real-time basis. This imaging modality, with a continued decrease in size and cost of US machines, would take its place for the physical examination and to guide thoracic procedures safely.

[30]- L. Lamsam, L. Gharahbaghian, V. Lobo. Point-of-care Ultrasonography for Detecting the Etiology of Unexplained Acute Respiratory and Chest Complaints in the Emergency Department: A Prospective Analysis. Cureus, 2018. 10 (8).

The modified RADIUS protocol showed a higher sensitivity of 79% compared to CXR with a 67%, while a lower sensitivity showed with a 71% compared to CXR with a 83%. Modified RADIUS showed a higher sensitivity of 76% compared to CT with a 65% but lower specificity of 71% and compared to CT with a 100%. POCUS scans were interpreted and a 92% of a diagnostic accuracy was achieved. The study concluded that the sensitivity and specificity of POCUS, when modified

RADIUS protocol was used, showed non-significant differences compared to CXR. POCUS demonstrated a great value for diagnosing the etiology but further studies were required.

[31]- G. A. Cibinel, G. Casoli, F. Elia, M. Padoan et al. Diagnostic accuracy and reproducibility of pleural and lung ultrasound in discriminating cardiogenic causes of acute dyspnea in the Emergency Department. Internal Emergency Medicine, 2012. 7 (1): 65-70.

(42)

42 had a cardiogenic cause on the final diagnosis. High sensitivity but low specificity for cardiogenic dyspnea was showed by pleural effusion in US usage.

[33]- Y. Koh, M. H. Ho, C. Lee, G. W. H. Chan, W. S. Kuan. Assessment of dyspneic patients in the emergency department using point-of-care lung and cardiac ultrasonography- a prospective observational study. Journal of Thoracic Disease, 2018. 10 (11): 6221-6229.

For pneumonia (49 patients), the accuracy was on 77,9%, a sensitivity of 65,3% and a specificity of 82%; for pulmonary edema (84 patients), the accuracy was on 76,9%, a sensitivity of 71,4% and a specificity of 80,9%; for the COPD/asthma (62 patients) the accuracy was on 81,9%, a sensitivity of 64,5% and a specificity of 89,8%. The study showed a lower sensitivities values, but similar specificities for various conditions for POCUS. LUS provided a moderate diagnostic accuracy while the cardiac US, for its contractility alone, did not adequately differentiate the causes of pulmonary edema (in complementation with other investigation tools, treatment and accurate disposition of the patient begins earlier).

[34]- L. Cardinale, G. Volpicelli, F. Binello, G. Garofalo et al. Clinical application of lung ultrasound in patients with acute dyspnoea: differential diagnosis between cardiogenic and pulmonary causes. La Radiologia Medica. 114 (7): 1053-1064.

Identification of hyperechoic vertical lines artefacts (the B-lines) was necessary for the recognition of diffuse alveolar-interstitial syndrome. Allowing a DDx between edema and COPD exacerbations.

[35]- T. Perrone, A. Maggi, C. Sgarlata, I. Palumbo et al. Lung ultrasound in internal medicine: A bedside help to increase accuracy in the diagnosis of dyspnea. European Journal of Internal Medicine, 2017. 46: 61-65.

FINAL MASTER THESIS THE USE OF ULTRASOUND IN DIFFERENTIAL DIAGNOSIS OF ACUTE DYSPNEA