Management of the patients with pleural effusion

 

Pleurisy

Pleurisy – inflammation of pleura, usually producing an exudative pleural effusion and stabbing chest pain worsened by respiration and cough.

 

Etiology

Pleurisy may result from an underlying lung process (eg, pneumonia, infarction, irritating substance into the pleural space (eg, with a ruptured esophagus, amebic empyema, or pancreatic pleurisy); transport of an infectious or noxious agent or neoplastic cells to the pleura via the bloodstream or lymphatics; parietal pleural injury (eg, trauma, especially rib fracture, or epidemic pleurodynia /due to coxsackievirus B/); asbestos-related pleural disease in which asbestos particles reach the pleura by traversing the conducting airways and respiratory tissues; or, rarely, pleural effusion related to drug ingestion.

 

Pathology

The pleura usually first becomes edematous and congested. Cellular infiltration  follows, and fibrinous exudate develops on the pleural surface. The exudate may be reabsorbed or organized into fibrous tissue resulting in pleural adhesions. In sme diseases (eg, epidemic pleurodynia), the pleurisy remains dry or fibrinous, with no significant exudaiton of fluid from the inflamed pleura. More often, pleural exudate develops from an outpouring of fluid rich in plasma proteins from damaged capillaries. Occasionally, marked fibrous or even calcific thickening of pleura (eg, asbestos pleural plaques, idiopathic pleural calcification) develops without an antecedent acute pleurisy.

 

Symptoms and Signs

Sudden pain is the dominant symptom of pleurisy. Typically, pleuritic pain is a stubbing sensation aggravated by breathing and coughing, but it can vary. It may only a vague discomfort, or it may occur only when the patient breathes deeply or coughs. The visceral pleura is insensitive; pain results from inflammation of parietal pleura, which is mainly innervated by intercostal nerves. Pain is usually felt over the pleuritic site but may be referred to distant regions. Irritation of posterior and peripheral portioms of the diaphragmatic pleura, which are supplied by the lower six intercostal nerves, may cause pain referred to the lower chest wall or abdomen and may simulate intra-abdominal disease. Irritation of the central portion of the diaphragmatic pleura, innervated by the phrenic nerves, causes pain referred to the neck and shoulder.

Respiration is usually rapid and shallow. Motion of the affected side may be limited. Breath sounds may be diminished. A pleural friction rub, although infrequent, is the characteristic physical sign.It may not be accompanied by pleuritic pain, but it usually is. The friction rub varies from a few intermittent sounds that may simulate crackles to a fully developed harsh grating, creaking, or leathery sound synchronous with respiration, heard on inspiration and expiration. Friction sounds due to pleuritis adjacent to the heart (pleuropericardial rub) may vary with the heart beat as well.

When pleural effusion develops, pleuritic pain usually subsides. Percussion dullness, absent tactile fremitus, decreased or absent breath sounds, and egophony at the upper border of the fluid are theoticeable. The larger the effusion, the more obvious the above signs. A large effusion may produce or contribute to dyspnea through diminished lung volume, especially if there is underlying pulmonary disease, mediastinal shift to the contralateral side, and diminished function and recruitment of inspiratory muscles due to an expanded thoracic cage.

 

Diagnosis

Pleurisy is readily diagnosed when characteristic pleuritic pain occurs. A pleural friction rub is pathognomonic. Pleurisy that produces referred abdominal pain is usually differentiated from acute inflammatory abdominal disease by x-ray and clinical evidence of a respiratory process; absence of nausea, vomiting, and disturbed bowel function; marked aggravation of pain by deep breathing or coughing; shallow rapid breathing; and a tendency toward relief of pain by pressure on the chest wall or abdomen. Intercostal neuritis may be confused with pleurisy, but the pain is rarely related to respiration and there is no friction rub. With herpetic neuritis, development of the characteristic skin eruption is diagnostic. Miocardial infarction, spontaneous pneumothorax, pericarditis, and chest wall lesions may simulate pleurisy. A plueral friction rub may be confused with a friction rub of pericarditis (pericardial rub), which is heard best over the left border of the sternum in the third and forth interspaces, is characteristically a to-and-fro sound synchronous with the heartbeat, and is not influenced significantly by respiration.

Chest x-rays are of limited value in diagnosing fibrinous pleurisy. The pleural lesion causes no shadow, but an associated pulmonary or chest wall lesion may. The presence of a pleural effusion, generally small, confirms the presence of acute pleurisy (picture 14).

 

 

Picture 14. Right sided exudative pleuritis

 

Treatment

Treatment of the underlying disease is essential.

Chest pain may be relieved by wrapping the entire chest with two or three 6-in-wide nonadhesive elastic bandages, which must be reapplied once or twice daily. Acetaminophen 0.65 g qid or an NSAID is often effective. Oral narcotics may be necessary, but cough suppression may be not desired.

Adequate bronchial drainage must be provided to prevent pneumonia. A patient receiving narcotics should be urged to breathe deeply and cough when pain relief from the drug is maximal. Antibiotics and bronchodilators should be considered for treatment of associated bronchitis.   

 

 

 

LUNG ABSCESS

Essentials of Diagnosis

• Development of pulmonary symptoms about 1-2 weeks after possible aspiration, bronchial obstruction, or previous pneumonia.

• Septic fever and sweats, and periodic sudden ex­pectoration of large amounts of purulent, foul-smelling, or “musty” sputum. Hemoptysis may occur.

• X-ray density with central radiolucency and fluid level.

 

General Considerations

Lung abscess develops wheecrosis and liquefaction occur in an area where necrotizing pneumonia is present (picture 1-3). Symptoms and signs occur 1-2 weeks after the following events: (1) massive-aspira­tion of upper respiratory tract secretions and microbial flora, especially during profound suppression of cough reflex (eg, with alcohol, drugs, unconsciousness, anesthesia, brain trauma); (2) bronchial obstruction (eg, by atelectasis, foreign body, neoplasm); (3) pres­ence of pneumonias, especially those caused by gram-negative bacteria or staphylococci; or (4) forma­tion of septic emboli from other foci of infection, or, during bacteremia, with pulmonary infarcts. Abscess is more commonly in the lower dependent portions of the lung. The main etiologic organisms are related to the underlying condition, but a dense mixed anaerobic flora is often prominent, particularly when aspiration has occurred.

Picture 1. Low magnification view of an abscess in the lung. Note well-circumscribed fibrous connective ‘capsule’ (arrowheads) and central area of mineralization.

 

Picture 2. Higher magnification of the same abscess.

 

Picture 3. Lung abscess

 

For more detailed information about Lung abscess go to:

www.ecureme.com/atlas/data/Lung_Abscess550_ab.htm

 

 

Clinical Findings

      A. Symptoms and Signs: Onset may be abrupt or gradual. Symptoms include septic fever, sweats,  cough, and chest pain. Cough is ofteonproductive at onset. Expectoration of foul-smelling brown or gray sputum (anaerobic flora) or of purulent sputum without odor (pyogenic organism) may occur abruptly and  in large quantity. Blood-streaked sputum is also common.

 Pleural pain, especially with coughing, is common because the abscess is often subpleural.     Weight loss, anemia, and pulmonary osteoarthropathy may appear when the abscess becomes chronic (8-12 weeks after onset).

Physical findings may be minimal. Consolidation due to pneumonitis surrounding the abscess is the most frequent finding. Rupture into the pleural space produces signs of fluid or pneumothorax.

B. Laboratory Findings: Sputum cultures are usually inadequate in determining the bacterial cause of a lung abscess. Transtracheal aspirates should be obtained with the proper technique employed to cul­ture anaerobic organisms in addition to the usual aerobic cultures. Special methods of transporting specimens are required for anaerobic organisms, and appropriate culture media and methods must be employed.

Smear and cultures for the tubercle bacilli are required, especially in lesions of the upper lobe and in chronic abscess.

C. X-Ray Findings: A dense shadow is the initial finding. A central radiolucency, often with a visible fluid level, appears as surrounding densities subside. Computerized tomography can supply the detailed lo­calization of the abscess and may also reveal primary lesions (eg, bronchogenic carcinoma) and provide guidance for contemplated surgery. Various x-ray pro­cedures also permit localization of pleural involvement to facilitate drainage. See pictures 4-7.

 

 

Picture 4. PA chest X-ray examination: A well-defined area of increased transparency can be seen in the left upper lobe (white arrow). More than half of the cavity is filled with fluid and air (black arrow). (=> picture)

 

Picture 5.  Lateral view: The cavity in the left upper lobe is depicted, with the air-fluid interface (arrow).

 

 

 

 

 

Picture 6. CT scan of a lung abscess inside (middle bottom: spine, midline top: heart, left, in black: left lung, left: complex solid/liquid/air lesion = abscess)

 

Picture 7. Lung abscess in right upper part of the lungs.

 

D. Instrumental Examination: Fiberoptic bronchoscopy may help to ‘diagnose location and na­ture of obstructions (foreign body, tumor), obtain specimens for microbiologic and pathologic examina­tion, and, occasionally, aid drainage.

Differential Diagnosis

Differentiate from other causes of pulmonary cavitation: tuberculosis, bronchogenic carcinoma, mycotic infections, and staphylococcal or gram-nega­tive bacterial pneumonia.

Treatment

Postural drainage and bronchoscopy are impor­tant to promote drainage of secretions.

A. Acute Abscess: Intensive antibacterial ther­apy is necessary to prevent further destruction of lung tissue. While cultures and sensitivity tests are pending, treatment should be started with penicillin G, 2-6 million units daily. In penicillin hypersensitivity clindamycin and chloramphenicol are alternatives. If the patient improves on antimicrobial drugs (and postural drainage),

 the drugs should be continued for 4—8 weeks. If the patient fails to respond significantly to the initial treatment, laboratory results may suggest other antimicrobials, eg, nafcillin for staphylococci, cefotaxime for Klebsiella, cefoxitin or metronidazole for mixed anaerobes. Postural drainage is important adjunctive treatment. Percutaneous catheter drainage has been used successfully in selected cases. Surgical therapy is indicated mainly for severe hemoptysis and for me infrequent abscesses that fail to respond to antimicrobial management. Failure of fever to subside after 2 weeks of therapy, abscess diameter of more than 6 cm, and very thick cavity waits are all factors that lessen the likelihood of success with nonsurgical treatment alone.

B. Chronic Abscess: After acute systemic man­ifestations have subsided, the abscess may persist. Although many patients with chronic lung abscess can be cured with  long-term treatment with antibacterial agents, surgery may occasionally be required.

Complications

Rupture of pus into the pleural space (empyema) causes severe symptoms: increase in fever, marked pleural pain, and sweating; the patient becomes “tox­ic” in appearance. Adequate drainage of empyema is mandatory. In chronic abscess, severe and even fatal hemorrhage may occur. Metastatic brain abscess is a well-recognized complication, and the infection may seed other organ sites. Bronchiectasis may occur as a sequela to lung abscess even when the abscess itself is cured.

Prognosis   

The prognosis in acute abscess is excellent with prompt and intensive antibiotic therapy. About 80% of patients are healed within 7-8 weeks. The incidenee of chronic abscess is consequently low; In chronic cases, surgery is curative.

 

Real life situation to be solved (picture 8)

Picture 8.   A 45-year-old white woman with no significant past medical history presented with a 2- to 3-week history of malaise, night sweats, and a cough that produced dark green, malodorous sputum. She reported no other symptoms. The patient’s social history was significant for consumption of three drinks per day and weekend bingeing.

Physical examination revealed a low-grade fever (temperature, 38.1°C [100.5°F]), respiration rate of 16 to 18/min, and oxygen saturation of 98% while breathing room air. Crackles were noted in the left lung field. The patient’s white blood cell count was 14.7 x 10³/microliter with a left shift. A chest film was taken.

What is your answer?

a. Community-acquired pneumonia
b. Pulmonary embolism
c. Lung abscess
d. Empyema

Go for answer and discussion on:

www.postgradmed.com/…/09_02/pdq_question.htm

Picture 9. X-ray and CT scan of lungs with abscess. Lung tissue of patient is presented.

Go also to www.indstate.edu/thcme/micro/staph/sld020.htm if you are interested in pulmonology.

BRONCHIECTASIS

Essentials of Diagnosis:

• Chronic cough with expectoration of large amounts of purulent sputum; hemoptysis.

• Rales and rhonchi over lower lobes.

• X-ray of chest reveals little; bronchograms show characteristic dilatations.

General Considerations

Bronchiectasis is a dilatation of small and medium-sized bronchi resulting from destruction of bronchial elastic and muscular elements. It may be, caused by pulmonary infections (eg, pneumonia, per­tussis, tuberculosis) or by a bronchial obstruction (eg, foreign bodies or extrinsic pressure). In many patients, a history of onset following one or more episodes of pulmonary infection, usually in early childhood, is obtained. However,since infection does not regularly produce significant bronchiectasis, unknown intrinsic host factors presumably are present. The incidence of

the disease has been reduced by treating pulmonary infections with antibiotics.

Clinical Findings

A. Symptoms and Signs: Most patients with bronchiectasis have a history of chronic cough with expectoration of large volumes of sputum, especially upon awakening. The sputum has a characteristic qual­ity of “layering out” into 3 layers upon standing, a frothy top layer, a middle clear layer, and a dense particulate bottom layer. It is usually purulent in ap­pearance and foul-smelling.

Intermittent hemoptysis, occasionally in dangerous proportions, is often combined with intercurrent respiratory infections. Symptoms occur most often in patients with idiopathic bronchiectasis (ie, childhood respiratory infections). However, patients who have bronchiectasis secondary either to tuberculosis or chronic obstruction may not exhibit characteristic symptoms. Idiopathic bronchiectasis occurs most fre­quently in the middle and lower lobes and posttuberculous bronchiectasis in the upper lobes. Hemoptysis is thought to result from erosion of bronchiolar mucosa with resultant destruction of un­derlying blood vessels. Pulmonary insufficiency may result from progressive destruction of pulmonary tis­sue.

Physical findings consist primarily of rales and rhonchi over the affected segments. If the condition is far-advanced, emaciation, cyanosis, and digital club­bing may appear.

B. Laboratory Findings: There are no charac­teristic laboratory findings. If hypoxemia is chronic and severe, secondary polycythemia may develop. There may be either restrictive or obstructive pulmo­nary function defects associated with bronchiectasis. Hypoxemia and hypocapnia or hypercapnia may also be associated with the disease, depending on the se­verity of the underlying condition. .

C.X-Ray Findings (figure 1-6): Plain films of the chest often show increased bronchopulmonary markings in af­fected segments; in severe cases there may be areas of radiodensities surrounding portions of radiolucency. Early in the course of bronchiectasis, however, the chest x-ray may be normal.

Iodized contrast media instilled into the bronchial tree (a bronchogram) demonstrates saccular, cylindric, or fusiform dilatation of small and medium bronchi with consequent loss of the normal branching pattern. Cylindric changes of bronchiectasis that may result from acute pneumonia will revert to normal after 6-8 weeks, but saccular dilatations represent long-standing damage and permanent disease.     

 

 

Figure 1. PA (1A) and Lateral chest (1B) radiographs in a 64 year old lady with a chronic cough secondary to MAC. There is air space opacity in the middle lobe (solid arrows) and lingula (dashed arrows)

Figure 2. 83 year old lady with a chronic cough. CT scan at the level of the pulmonary artery demonstrates bronchiectasis (solid arrow)and tree-in-bud nodules (dashed arrows) involving the middle lobe, lingula and lower lobes, secondary to MAC

Figure 3. 83 year old lady with a chronic cough. Coronal reformat CT scan through the airways demonstrates extensive bronchiectasis, tree-in-bud nodules (dashed arrow) and right upper lobe segmental atelectasis (solid arrow) secondary to MAC

 

Figure 4. Bronchiectasis Radiograph Endobronchial radiographic dye is used to demonstrate the dilated bronchi in bronchiectasis.

Figure 5: Bronchogram showing extensive bronchiectasis of left lung

 

Figure 6: CT scan showing extensive bronchiectasis of left lung.

 

Differential Diagnosis

The differential diagnosis includes other disorders that lead to chronic cough, sputum produc­tion, and hemoptysis, ie, chronic bronchitis, tuber­culosis, and bronchogenic carcinoma. The diagnosis of bronchiectasis is suggested by the patient’s history and can be confirmed only by bronchographic examination or histopathologic examination of surgically removed tissue.

Complications

Recurrent infection in poorly drained pulmonary segments leads to chronic suppuration and may cause pulmonary insufficiency. Complications include hemoptysis, respiratory failure, chronic cor pulmonale, and amyloidosis. There is also an increased incidence of brain abscess, which is thought to be secondary to abnormal anastomoses between bron­chial (systemic) and pulmonary venous circulation. These anastomoses produce right-to-left shunts and allow for the dissemination of septic emboli.

Treatment

.  A. General Measures and Medical Treatment:

1. Environmental changes– The patient should  avoid exposure to all common pulmonary irritants such as smoke, fumes, and dust and should stop smoking cigarettes.

2. Control of bronchial secretions (improved drainage)–

a. Postural drainage often gives effective relief of symptoms and should be utilized in every case. The patient should assume the position that gives maximum drainage, usually lying on a bed in the prone, supine, or right or left lateral decubitus position with the hips elevated on several pillows and no pillow under the head. Any effective position should be main­tained for 10 minutes, 2-4 times a day. The first drainage should be done upon awakening and tee last drainage at bedtime. Family members can be trained in the art of chest percussion to facilitate drainage of secretions.

b. Liquefaction of thick sputum may be pro­moted by inhaling warm mists and, in some cases, mucolytic agents such as acetylcysteine or 5% sodium bicarbonate given by aerosol may also be helpful.

 3. Control of respiratory infection-Exposure to respiratory infections should be minimized and the patient should be vaccinated against influenza and pneumococcal pneumonia. Antibiotic therapy is indi­cated for acute exacerbations (ie, increased production of purulent sputum, hemoptysis, etc). Long-term or prophylactic antibiotic therapy is controversial, since it has not been conclusively shown to be of lasting benefit. Therefore, it seems rational to treat acute exacerbations in order to control infection but mini­mize  the  emergence of resistant strains. Because the bacteria most commonly involved are H inftuenzae and S pneumoniae, the drug most commonly employed is ampicillin, 250-500 mg orally every 6 hours for 5 days. Alternative therapies for the penicillin-allergic patient are erythromycin, given in the same dosage schedule as ampicillin, or trimethoprim-sulfamethoxazole, 2 double-strength tablets twice a day for 5 days.

    B. Surgical Treatment: Surgical treatment is most often employed when hemoptysis with bron-chiectasis is recurrent and severe. Despite antibiotic therapy, localized bronchiectasis (eg, in a lower lobe or segment) with progressive uncontrolled infection and sputum production may be an indication for surgical removal of the affected segments.

 

Other Considerations

Bronchiectasis is also associated with mucoviscidosis. It is thought to be secondary to the thick viscid secretions that cannot be cleared by normal cough mechanisms and that  lead to stasis of. sputum and chronic infection. This disorder, usually associated with sinusitis, may be accompanied by other manifes­tations of mucoviscidosis. Its most common organisms are S aureus or Pseudomonas aeruginosa.

Bronchiectasis is also associated with certain ab­normalities of cellular ciliary function, the most common  of which is Kartagener’s syndrome, a combina­tion of sinusitis, situs in versus, and bronchiectasis. Patients with this disorder show immotile cilia second­ary to ultrastructural abnormalities, stasis of sputum, failure to clear secretions, and chronic pulmonary infection that results in bronchiectasis.           

Antibiotic treatment of mucoviscidosis and Kartagener’s syndrome must be guided by sensitivity studies of organisms cultured from sputum.

 

 

CHRONIC COR PULMONALE

Picture 10. Patients with Cor Pulmonale

Background: Cor pulmonale is defined as an alteration in the structure and function of the right ventricle caused by a primary disorder of the respiratory system. Pulmonary hypertension is the common link between lung dysfunction and the heart in cor pulmonale. Right-sided ventricular disease caused by a primary abnormality of the left side of the heart or congenital heart disease is not considered cor pulmonale, but cor pulmonale can develop secondary to a wide variety of cardiopulmonary disease processes. Although cor pulmonale commonly has a chronic and slowly progressive course, acute onset or worsening cor pulmonale with life-threatening complications can occur.

Pathophysiology: Several different pathophysiologic mechanisms can lead to pulmonary hypertension and, subsequently, to cor pulmonale. These pathogenetic mechanisms include (1) pulmonary vasoconstriction due to alveolar hypoxia or blood acidemia; (2) anatomic compromise of the pulmonary vascular bed secondary to lung disorders, eg, emphysema, pulmonary thromboembolism, interstitial lung disease; (3) increased blood viscosity secondary to blood disorders, eg, polycythemia vera, sickle cell disease, macroglobulinemia; and (4) idiopathic primary pulmonary hypertension. The result is increased pulmonary arterial pressure.

The right ventricle (RV) is a thin-walled chamber that is more a volume pump than a pressure pump. It adapts better to changing preloads than afterloads. With an increase in afterload, the RV increases systolic pressure to keep the gradient. At a point, further increase in the degree of pulmonary arterial pressure brings significant RV dilation, an increase in RV end-diastolic pressure, and circulatory collapse. A decrease in RV output with a decrease in diastolic left ventricle (LV) volume results in decreased LV output. Since the right coronary artery, which supplies the RV free wall, originates from the aorta, decreased LV output diminishes blood pressure in the aorta and decreases right coronary blood flow. This is a vicious cycle between decreases in LV and RV output.

Right ventricular overload is associated with septal displacement toward the left ventricle. Septal displacement, which is seen in echocardiography, can be another factor that decreases LV volume and output in the setting of cor pulmonale and right ventricular enlargement. Several pulmonary diseases cause cor pulmonale, which may involve interstitial and alveolar tissues with a secondary effect on pulmonary vasculature or may primarily involve pulmonary vasculature. Chronic obstructive pulmonary disease (COPD) is the most common cause of cor pulmonale in the United States.

Cor pulmonale usually presents chronically, but 2 main conditions can cause acute cor pulmonale: massive pulmonary embolism (more common) and acute respiratory distress syndrome (ARDS). The underlying pathophysiology in massive pulmonary embolism causing cor pulmonale is the sudden increase in pulmonary resistance. In ARDS, 2 factors cause RV overload: the pathologic features of the syndrome itself and mechanical ventilation. Mechanical ventilation, especially higher tidal volume, requires a higher transpulmonary pressure. In chronic cor pulmonale, right ventricular hypertrophy (RVH) generally predominates. In acute cor pulmonale, right ventricular dilatation mainly occurs (picture 11).

Picture 11. The globular heart shows right ventricular dilatation, a sign of chronic cor pulmonale.

Frequency:

• In the US: Cor pulmonale is estimated to account for 6-7% of all types of adult heart disease in the United States, with chronic obstructive pulmonary disease (COPD) due to chronic bronchitis or emphysema the causative factor in more than 50% of cases. Although the prevalence of COPD in the United States is about 15 million, the exact prevalence of cor pulmonale is difficult to determine because it does not occur in all cases of COPD and the physical examination and routine tests are relatively insensitive for the detection of pulmonary hypertension. In contrast, acute cor pulmonale usually is secondary to massive pulmonary embolism. Acute massive pulmonary thromboembolism is the most common cause of acute life-threatening cor pulmonale in adults. In the United States, 50,000 deaths are estimated to occur per year from pulmonary emboli and about half occur within the first hour due to acute right heart failure.

• Internationally: Incidence of cor pulmonale varies among different countries depending on the prevalence of cigarette smoking, air pollution, and other risk factors for various lung diseases.

Mortality/Morbidity: Development of cor pulmonale as a result of a primary pulmonary disease usually heralds a poorer prognosis. For example, patients with COPD who develop cor pulmonale have a 30% chance of surviving 5 years. However, whether cor pulmonale carries an independent prognostic value or it is simply reflecting the severity of underlying COPD or other pulmonary disease is not clear. Prognosis in the acute setting due to massive pulmonary embolism or ARDS has not been shown to be dependent on presence or absence of cor pulmonale.    

History: Clinical manifestations of cor pulmonale generally are nonspecific. The symptoms may be subtle, especially in early stages of the disease, and mistakenly may be attributed to the underlying pulmonary pathology.

• The patient may complain of fatigue, tachypnea, exertional dyspnea, and cough.

• Anginal chest pain also can occur and may be due to right ventricular ischemia (it usually does not respond to nitrates) or pulmonary artery stretching.

• Hemoptysis may occur because of rupture of a dilated or atherosclerotic pulmonary artery. Other conditions, such as tumors, bronchiectasis, and pulmonary infarction, should be excluded before attributing hemoptysis to pulmonary hypertension. Rarely, the patient may complain of hoarseness due to compression of the left recurrent laryngeal nerve by a dilated pulmonary artery.

• Variety of neurologic symptoms may be seen due to decreased cardiac output and hypoxemia.

• In advanced stages, passive hepatic congestion secondary to severe right ventricular failure may lead to anorexia, right upper quadrant abdominal discomfort, and jaundice.

• Syncope with exertion, which may be seen in severe disease, reflects a relative inability to increase cardiac output during exercise with a subsequent drop in the systemic arterial pressure.

• Elevated pulmonary artery pressure can lead to elevated right atrial pressure, peripheral venous pressure, and then capillary pressure and by increasing the hydrostatic gradient, it leads to transudation of fluid, which appears as peripheral edema. Although this is the simplest explanation for peripheral edema in cor pulmonale, other hypotheses explain this symptom, especially in a fraction of patients with COPD who do not show increase in right atrial pressure. A decrease in glomerular filtration rate (GFR) and filtration of sodium and stimulation of arginine vasopressin (which decreases free water excretion) due to hypoxemia play important pathophysiologic roles in this setting and may even have a role for peripheral edema in patients with cor pulmonale who have elevated right atrial pressure.

Physical: Physical findings may reflect the underlying lung disease or pulmonary hypertension, RVH, and RV failure.

• On inspection, an increase in chest diameter, labored respiratory efforts with retractions of chest wall, distended neck veins with prominent a or v waves, and cyanosis may be seen.

• On auscultation of the lungs, wheezes and crackles may be heard as signs of underlying lung disease. Turbulent flow through recanalized vessels in chronic thromboembolic pulmonary hypertension may be heard as systolic bruits in the lungs. Splitting of the second heart sound with accentuation of the pulmonic component can be heard in early stages. A systolic ejection murmur with sharp ejection click over the region of the pulmonary artery may be heard in advanced disease, along with a diastolic pulmonary regurgitation murmur. Other findings upon auscultation of the cardiovascular system may be third and fourth sounds of the heart and systolic murmur of tricuspid regurgitation.

• RVH is characterized by a left parasternal or subxiphoid heave. Hepatojugular reflex and pulsatile liver are signs of RV failure with systemic venous congestion.

• On percussion, hyperresonance of the lungs may be a sign of underlying COPD; ascites can be seen in severe disease.

Causes:

• Disorders with primary involvement of pulmonary vasculature and circulation

• Repeated pulmonary emboli

• Pulmonary vasculitis

• Pulmonary veno-occlusive disease

• Congenital heart disease with left-to-right shunting

• Sickle cell disease

• High altitude disease with pulmonary vasoconstriction

• Primary pulmonary hypertension

• Disorders with secondary involvement of pulmonary vasculature and circulation

• Parenchymal lung diseases (interstitial lung diseases, chronic obstructive lung diseases)

• Neuromuscular disorders (eg, myasthenia gravis, poliomyelitis, amyotrophic lateral sclerosis)

• Obstructive and central sleep apnea

• Thoracic deformities (eg, kyphoscoliosis)

Other Problems to be Considered:

Congestive (biventricular) heart failure
Primary pulmonic stenosis
Primary pulmonary hypertension
Right-sided heart failure due to congenital heart diseases
Right heart failure due to right ventricular infarction

Lab Studies:

• A general approach to diagnose cor pulmonale and to investigate its etiology starts with routine laboratory tests, chest radiography, and electrocardiography. Echocardiography gives valuable information about the disease and its etiology. Pulmonary function tests may become necessary to confirm the underlying lung disease. Ventilation/perfusion (V/Q) scan or chest CT scan may be performed if history and physical examination suggest pulmonary thromboembolism as the cause or if other diagnostic tests do not suggest other etiologies. Right heart catheterization is the most accurate but invasive test to confirm the diagnosis of cor pulmonale and gives important information regarding the underlying diseases. Any abnormal result in each of these tests may need further diagnostic evaluation in that specific direction.

• Laboratory investigations are directed toward defining the potential underlying etiologies as well as evaluating complications of cor pulmonale. In specific instances, appropriate lab studies may include the following: hematocrit for polycythemia (which can be a consequence of underlying lung disease but can also increase pulmonary arterial pressure by increasing viscosity), serum alpha1-antitrypsin if deficiency is suspected, and antinuclear antibody level for collagen vascular disease such as scleroderma. Hypercoagulability states can be evaluated by serum levels of proteins S and C, antithrombin III, factor V Leyden, anticardiolipin antibodies, and homocysteine.

• Arterial blood gas tests may provide important information about the level of oxygenation and type of acid-base disorder.

• Elevated braiatriuretic peptide (BNP) level alone is not adequate to establish presence of cor pulmonale, but it helps to diagnose cor pulmonale in conjunction with other noninvasive tests and in appropriate clinical settings. An elevated BNP level may actually be a natural mechanism to compensate for elevated pulmonary hypertension and right heart failure by promoting diuresis and natriuresis, vasodilating systemic and pulmonary vessels, and reducing circulating levels of endothelin and aldosterone.

Imaging Studies:

• Imaging studies may show evidence of underlying cardiopulmonary diseases, pulmonary hypertension, or its consequence, right ventricular enlargement.

• Chest roentgenography: In patients with chronic cor pulmonale, the chest radiograph may show enlargement of the central pulmonary arteries with oligemic peripheral lung fields. Pulmonary hypertension should be suspected when the right descending pulmonary artery is larger than 16 mm in diameter and the left pulmonary artery is larger than 18 mm in diameter. Right ventricular enlargement leads to an increase of the transverse diameter of the heart shadow to the right on the posteroanterior view and filling of the retrosternal air space on the lateral view. These findings have reduced sensitivity in the presence of kyphoscoliosis or hyperinflated lungs.

• Echocardiography (picture 12): Two-dimensional echocardiography usually demonstrates signs of chronic right ventricular pressure overload. As this overload progresses, increased thickness of the right ventricular wall with paradoxical motion of the interventricular septum during systole occurs. At an advanced stage, right ventricular dilatation occurs and the septum shows abnormal diastolic flattening. In extreme cases, the septum may actually bulge into the left ventricular cavity during diastole resulting in decreased diastolic volume of LV and reduction of LV output.     
  Doppler echocardiography is used now to estimate pulmonary arterial pressure, taking advantage of the functional tricuspid insufficiency that is usually present in pulmonary hypertension. Doppler echocardiography is considered the most reliable noninvasive technique to estimate pulmonary artery pressure. The efficacy of Doppler echocardiography may be limited by the ability to identify an adequate tricuspid regurgitant jet, which may be further enhanced by using saline contrast.

Picture 12. Examples of two-dimensional still frames obtained from hand-held echocardiographic examinations of four distinct patients. (A) Parasternal long axis view obtained from a patient admitted for septic shock secondary to a severe aortic endocarditis (arrows indicate vegetations) associated with a massive regurgitation and dilated left ventricle. (B) Parasternal short axis view obtained from a patient with an acute respiratory distress syndrome and associated cor pulmonale. The right ventricle was markedly enlarged and the ventricular septum bulged towards the left ventricular cavity at end systole, due to severe pulmonary hypertension (arrow). (C) Apical four-chamber view obtained from a ventilated patient with refractory hypoxemia. The contrast study (intravenous injection of saline microbubbles) revealed a large interatrial right-to-left shunt through a patent foramen ovale, which participated to persistent hypoxemia: left cardiac cavities were filled up by the microbubbles within two cardiac cycles. (D) Subcostal view obtained from a patient presenting with shock and pulsus paradoxus. A mild pericardial effusion responsible for prolonged right atrial collapse during the cardiac cycle (arrow) was consistent with a tamponade, and the patient underwent successful pericardotomy. LV, left ventricle; RV, right ventricle; LA, left atrium; RA, right atrium; Ao, ascending aorta.

• Ventilation/perfusion (V/Q) lung scanning, pulmonary angiography, and chest CT scanning may be indicated to diagnose pulmonary thromboembolism as the underlying etiology of cor pulmonale. These tests may be performed early in the diagnostic workup if any evidence of pulmonary embolism appears in history and physical examination. The test may also be considered later in the workup if other tests are not suggestive of any other etiology. Pulmonary thromboembolism has a wide range of clinical presentations from massive embolism with acute and severe hemodynamic instability to multiple chronic peripheral embolisms that may present with cor pulmonale.

• Ultrafast,
  
  ECG-gated CT

  scanning has been recently evaluated to study RV function. In addition to estimating right ventricular ejection fraction (RVEF), it can estimate RV wall mass. Its use is still experimental, but with further improvement, it may be used to evaluate the progression of cor pulmonale in the near future.

• Magnetic resonance imaging (MRI) of the heart is another modality that can provide valuable information about RV mass.

• Radionuclide ventriculography can determine RVEF noninvasively.

Other Tests:

• Electrocardiography (ECG): ECG abnormalities in cor pulmonale reflect the presence of RVH, RV strain, or underlying pulmonary disease. These electrocardiographic changes may include right axis deviation, R/S amplitude ratio in V1 greater than 1 (increase in anteriorly directed forces may be a sign of posterior infarct), R/S amplitude ratio in V6 less than 1, P-pulmonale pattern (an increase in P wave amplitude in leads 2, 3, and aVF), S₁Q₃T₃ pattern and incomplete (or complete) right bundle branch block, especially if pulmonary embolism is the underlying etiology, low-voltage QRS because of underlying COPD with hyperinflation and increased AP diameter of the chest. Severe RVH may reflect as Q waves in the precordial leads that may be interpreted as anterior myocardial infarction by mistake (on the other hand, since electrical activity of the RV is significantly less than the LV, small changes in RV forces may be lost in ECG). See picture 13.

 

Picture 13. ECG of patient with Cor Pulmonale.

Criteria of Cor Pumonale

I. QRS morphology

• Limb leads

1.     Right axis deviation

2.     S > R in lead I

• Precordial leads

1.     S > R in V5 – V6

2.     S > R in V2

3.     Lead V1 rs, Rs, or rS

• Orthogonal leads

1.     S > R in lead X

2.     Tall R wave in lead II

II. T wave variable

III. P wave

• Limb leads

1.     Vertical axis

2.     P > 3 mm in lead II or III

• Precordial leads

1.     Negative P in lead V1

 

• Additionally, many rhythm disturbances may be present in chronic cor pulmonale; these range from isolated premature atrial depolarizations to various supraventricular tachycardia, including paroxysmal atrial tachycardia, multifocal atrial tachycardia, atrial fibrillation, atrial flutter, and junctional tachycardia. These dysrhythmias may be triggered by processes secondary to the underlying disease, (eg, anxiety, hypoxemia, acid-base imbalance, electrolyte disturbances, excessive use of bronchodilators, heightened sympathetic activity). Life-threatening ventricular tachyarrhythmias are less common.

• In selected cases, pulmonary function testing may be indicated to determine underlying obstructive or interstitial lung disease.

Procedures:

• Cardiac catheterization: Right-heart catheterization is considered the most precise method for diagnosis and quantification of pulmonary hypertension. It is indicated when echocardiography cannot assess the severity of a tricuspid regurgitant jet, thus excluding an assessment of pulmonary hypertension. Right-heart catheterization is occasionally important for differentiating cor pulmonale from occult left ventricular dysfunction, especially when the presentation is confusing. Another indication may be for evaluation of the potential reversibility of pulmonary arterial hypertension with vasodilator therapy or when a left-side catheterization is indicated.

• Lung biopsy occasionally may be indicated to determine underlying etiology.

Medical Care: Medical therapy for chronic cor pulmonale is generally focused on treatment of the underlying pulmonary disease and improving oxygenation and RV function by increasing RV contractility and decreasing pulmonary vasoconstriction. However, the approach might be different to some degree in an acute setting with priority given to stabilizing the patient.

Cardiopulmonary support for patients experiencing acute cor pulmonale with resultant acute RV failure includes fluid loading and vasoconstrictor (eg, epinephrin) administration to maintain adequate blood pressure. Of course, the primary problem should be corrected, if possible. For example, for massive pulmonary embolism, consider administration of anticoagulation, thrombolytic agents or surgical embolectomy, especially if circulatory collapse is impending, consider bronchodilation and infection treatment in patients with COPD and consider steroid and immunosuppressive agents in infiltrative and fibrotic lung diseases.

Oxygen therapy, diuretics, vasodilators, digitalis, theophylline, and anticoagulation therapy are all different modalities used in the long-term management of chronic cor pulmonale.

• Oxygen therapy is of great importance in patients with underlying COPD, particularly when administered on a continuous basis. With cor pulmonale, the partial pressure of oxygen (PO₂) is likely to be below 55 mm Hg and decreases further with exercise and during sleep.

Oxygen therapy relieves hypoxemic pulmonary vasoconstriction, which then improves cardiac output, lessens sympathetic vasoconstriction, alleviates tissue hypoxemia, and improves renal perfusion. The Nocturnal Oxygen Therapy Trial (NOTT), a multicenter randomized trial, showed that continuous low-flow oxygen therapy for patients with severe COPD resulted in significant reduction in the mortality rate. In general, in patients with COPD, long-term oxygen therapy is recommended when PaO₂ is less than 55 mm Hg or O₂ saturation is less than 88%. However, in the presence of cor pulmonale or impaired mental or cognitive function, long-term oxygen therapy can be considered even if PaO₂ is greater than 55 mm Hg or O₂ saturation is greater than 88%.

Although it is not clear whether oxygen therapy has a mortality rate benefit in patients with cor pulmonale due to pulmonary disorders other than COPD, it may provide some degree of symptomatic relief and improvement in functional status. Therefore, oxygen therapy plays an important role in both the immediate setting and long-term management, especially in patients who are hypoxic and have COPD.

• Diuretics are used in the management of chronic cor pulmonale, particularly when the right ventricular filling volume is markedly elevated and in the management of associated peripheral edema. Diuretics may result in improvement of the function of both the right and left ventricles; however, diuretics may produce hemodynamic adverse effects if they are not used cautiously. Excessive volume depletion can lead to a decline in cardiac output. Another potential complication of diuresis is the production of a hypokalemic metabolic alkalosis, which diminishes the effectiveness of carbon dioxide stimulation on the respiratory centers and lessens ventilatory drive. The adverse electrolyte and acid-base effect of diuretic use can also lead to cardiac arrhythmia, which can diminish cardiac output. Therefore, diuresis, while recommended in the management of chronic cor pulmonale, needs to be used with great caution.

• Vasodilator drugs have been advocated in the long-term management of chronic cor pulmonale with modest results. Calcium channel blockers, particularly oral sustained-release nifedipine and diltiazem, can lower pulmonary pressures, although they appear more effective in primary rather than secondary pulmonary hypertension. Other classes of vasodilators, such as beta agonists, nitrates, and angiotensin-converting enzyme (ACE) inhibitors have been tried but, in general, vasodilators have failed to show sustained benefit in patients with COPD and they are not routinely used. A trial of vasodilator therapy may be considered only in patients with COPD with disproportionately high pulmonary blood pressure.

Beta-selective agonists have an additional advantage of bronchodilator and mucociliary clearance effect. Right heart catheterization has been recommended during initial administration of vasodilators to objectively assess the efficacy and detect the possible adverse hemodynamic consequences of vasodilators. The Food and Drug Administration (FDA) has approved epoprostenol, treprostinil, bosentan, and iloprost for treatment of primary pulmonary hypertension. Epoprostenol, treprostinil, and iloprost are prostacyclin PGI2 analogues and have potent vasodilatory properties. Epoprostenol and treprostinil are administered intravenously and iloprost is an inhaler. Bosentan is a mixed endothelin-A and endothelin-B receptor antagonist indicated for pulmonary arterial hypertension (PAH), including primary pulmonary hypertension (PPH). In clinical trials, it improved exercise capacity, decreased rate of clinical deterioration, and improved hemodynamics. PDE5 inhibitor sildenafil has also been intensively studied and recently approved by the FDA for treatment of pulmonary hypertension based on a large randomized study. Sildenafil promotes selective smooth muscle relaxation in lung vasculature. Not enough data are available regarding the efficacy of these drugs in patients with secondary pulmonary hypertension such as in patients with COPD.

• The use of cardiac glycosides, such as digitalis, in patients with cor pulmonale has been controversial, and the beneficial effect of these drugs is not as obvious as in the setting of left heart failure. Nevertheless, studies have confirmed a modest effect of digitalis on the failing right ventricle in patients with chronic cor pulmonale. It must be used cautiously, however, and should not be used during the acute phases of respiratory insufficiency when large fluctuations in levels of hypoxia and acidosis may occur. Patients with hypoxemia or acidosis are at increased risk of developing arrhythmias due to digitalis through different mechanisms including sympathoadrenal stimulation.

• In addition to bronchodilatory effect, theophylline has been reported to reduce pulmonary vascular resistance and pulmonary arterial pressures acutely in patients with chronic cor pulmonale secondary to COPD. Theophylline has a weak inotropic effect and thus may improve right and left ventricular ejection. As a result, considering the use of theophylline as adjunctive therapy in the management of chronic or decompensated cor pulmonale is reasonable in patients with underlying COPD.

• Anticoagulation with warfarin is recommended in patients at high risk for thromboembolism. The beneficial role of anticoagulation in improving the symptoms and mortality in patients with primary pulmonary arterial hypertension clearly was demonstrated in a variety of clinical trials. The evidence of benefit, however, has not been established in patients with secondary pulmonary arterial hypertension. Therefore, anticoagulation therapy may be used in patients with cor pulmonale secondary to thromboembolic phenomena and with underlying primary pulmonary arterial hypertension.

Surgical Care:

• Phlebotomy is indicated in patients with chronic cor pulmonale and chronic hypoxia causing severe polycythemia, defined as hematocrit of 65 or more. Phlebotomy results in a decrease in mean pulmonary artery pressure, a decrease in mean pulmonary vascular resistance, and an improvement in exercise performance in such patients. There is, however, no evidence of improvement in survival. Generally, phlebotomy should be reserved as an adjunctive therapy for patients with acute decompensation of cor pulmonale and patients who remain significantly polycythemic despite appropriate long-term oxygen therapy. Replacement of the acute volume loss with a saline infusion may be necessary to avoid important decreases in systemic blood pressure.

• No surgical treatment exists for most diseases that cause chronic cor pulmonale. Pulmonary embolectomy is efficacious for unresolved pulmonary emboli, which contribute to pulmonary hypertension. Uvulopalatopharyngoplasty in selected patients with sleep apnea and hypoventilation may relieve cor pulmonale. Single-lung, double-lung, and heart-lung transplantation are all used to salvage the terminal phases of several diseases (eg, primary pulmonary hypertension, emphysema, idiopathic pulmonary fibrosis, cystic fibrosis) complicated by cor pulmonale. Apparently, lung transplantation will lead to a reversal of right ventricular dysfunction from the chronic stress of pulmonary hypertension. Strict selection criteria for lung transplant recipients must be met, however, because of the limited availability of organ donors.

Diuretics are used to decrease the elevated right ventricular filling volume in patients with chronic cor pulmonale. Calcium channel blockers are pulmonary artery vasodilators that have proven efficacy in the long-term management of chronic cor pulmonale secondary to primary pulmonary arterial hypertension. New FDA-approved prostacyclin analogues and endothelin-receptor antagonists are available for treatment of PPH. The beneficial role of cardiac glycosides, namely digitalis, on the failing right ventricle are somewhat controversial; they can improve right ventricular function but must be used with caution and should be avoided during acute episodes of hypoxia.

In the management of cor pulmonale, the main indication for oral anticoagulants is in the setting of an underlying thromboembolic event or primary pulmonary arterial hypertension. Methylxanthines, like theophylline, can be used as an adjunctive treatment for chronic cor pulmonale secondary to COPD. Besides the moderate bronchodilatory effect of methylxanthine, it improves myocardial contractility, causes mild pulmonary vasodilatory effect, and enhances the diaphragmatic contractility.

Drug Category: Diuretics — Are used to decrease the elevated right ventricular filling volume in patients with chronic cor pulmonale.

Drug Category: Calcium channel blockers — These agents inhibit movement of calcium ions across the cell membrane, depressing both impulse formation (automaticity) and conduction velocity.

Drug Category: Cardiac glycosides — These agents decrease AV nodal conduction primarily by increasing vagal tone.

Drug Category: Anticoagulants — These agents may reduce incidence of embolisms when used fast, effectively, and early.

Drug Category: Methylxanthines — Potentiate exogenous catecholamines and stimulate endogenous catecholamine release and diaphragmatic muscular relaxation, which, in turn, stimulates bronchodilation.

Drug Category: Endothelin receptor antagonists — Competitively bind to endothelin-1 (ET-1) receptors ET_A and ET_B causing reduction in pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), and mean right atrial pressure (RAP).

Further Inpatient Care:

• Appropriate treatment is directed both at the underlying etiology and at correction of hypoxia when present.

Further Outpatient Care:

• Patients with cor pulmonale generally require close attention in the outpatient setting.

• Regular assessment of oxygeeeds and pulmonary function are appropriate.

• Many patients benefit from a formal program of pulmonary rehabilitation.

Complications:

• Complications of cor pulmonale include syncope, hypoxia, pedal edema, passive hepatic congestion, and death.

Prognosis:

• The prognosis of cor pulmonale is variable depending upon underlying pathology.

• Patients with cor pulmonale due to COPD have a high 2-year mortality.

Patient Education:

• Patient education regarding the importance of adherence to medical therapy is vital because appropriate treatment of both hypoxia and underlying medical illness can improve mortality and morbidity.

Medical/Legal Pitfalls:

• Making a diagnosis of cor pulmonale should be followed by further investigation to determine the underlying lung pathology. Sometimes a common lung disease such as COPD is not the only lung pathology as the cause of cor pulmonale; other lung diseases may coexist.

• When diagnosing cor pulmonale, considering the possibility of thromboembolic disease and primary pulmonary hypertension as possible etiologies is important.

• Note the importance of continuous supplemental oxygen therapy in appropriate patients, as well as the dangers of cigarette smoking while using supplemental oxygen. Elevation of carboxyhemoglobin in the blood due to smoking can significantly decrease the effect of O₂ on arterial O₂ content.

 

THERAPEUTIC ALTERNATIVES

Cor pulmonale is not a disease, per se, but a manifestation common to many disease states. Accordingly, a variety of medical and surgical treatments are available, but therapy must be based on the etiologic and pathophysiologic factors responsible. In addition, therapy must be individualized, taking into account the severity of symptoms and prognosis. Treatment of the underlying disorder, if one can be identified, is the first approach to the treatment of cor pulmonale. Improving airflow, alveolar ventilation, and gas exchange through the use of bronchodilators, corticosteroids, mucolytics, and, occasionally, assisted ventilation often ameliorates the pulmonary hypertensive state in patients with parenchymal disease. Supple-mental oxygen therapy reduces the degree of pulmonary hypertension in hypoxemic cor pulmonale by abolishing hypoxic vasoconstriction; indeed, low-flow continuous On therapy is the only modality that has been proven to prolong life in cor pulmonale due to chronic obstructive lung disease.

 

Because of the ominous prognosis associated with pulmonary hypertension from any cause, an aggressive approach to treatment is warranted as soon as a clinical diagnosis is made. It should be emphasized that physical findings and noninvasive studies alone are insufficient to confirm the presence and severity of pulmonary hypertension; right-heart catheterization is necessary both to establish the diagnosis and to monitor therapeutic responses.

As stated previously, therapy directed at improving gas exchange and alleviating hypoxic vasoconstriction is the initial step in the treatment for cor pulmonale secondary to parenchymal lung disease, and it should be initiated at the earliest sign of cor pulmonale. Although this approach is often successful, the maximal effects may not be clinically apparent for several months.

Patients with PPH should also be considered candidates for aggressive therapy immediately upon the establishment of a diagnosis. However, patients with severe, overt right-heart failure pose the greatest risk for adverse effects and are less likely to derive benefit from medical therapy.

Mechanisms of Action of Drugs Used

Oxygen. Low-flow supplemental oxygen therapy alleviates hypoxic pulmonary vasoconstriction and may halt the progressive vascular remodeling that is seen inpatients with cor pulmonale due to severe parenchymal lung disease. Whereas it may relieve the subjective sensation of dyspnea in patients with non hypoxemic cor pulmonale, supplemental oxygen does not usually pro-duce hemodynamic improvement in these patients

Methylxanthines. Theophylline, the most widely used methytxanthine derivative, has several potentially beneficial effects in cor pulmonale: Theophylline improves airflow by its bronchodilator effects and by a direct enhancement of mucociliary clearance. In addition, theophylime enhances diaphragmatic contractility, decreasing the work of breathing. It has also been suggested that theophylline improves right ventricular function in patients with chronic obstructive pulmonary disease with cor pulmonale, possibly by a direct vasodilator effect on the pulmonary circulation. Finally, the modest diuretic effects of theophylline may limit fluid retention in patients with right ventricular dysfunction.

Vasodilators. The rationale for the use of vasodilators in pulmonary hypertension is based on the suggestion that pulmonary vasoconstriction is present, to varying degrees, and that systemic vasodilators exert comparable effects on pulmonary vascular smooth muscle. Reduction in vascular smooth muscle tone would reduce right ventricular afterload, thereby improving right ventricular function and oxygen transport to the peripheral tissues. A variety of vasodilators have been shown to reduce pulmonary vasoconstriction in experimental and clinical conditions, including the calcium channel blockers, prostaglandins I and E, nitrates. Other agents, such as the angiotensin converting enzyme inhibitors, appear far less active on the pulmonary vascular bed. It should also be emphasized that the presence or degree of reversible vasoconstriction is variable in cor pulmonale. It may be a predominant factor in some patients, especially those with hypoxemic lung disease and primary pulmonary hypertension, but it is unlikely to contribute substantially to the hypertensive state in patients with chronic thrombotic pulmonary hypertension or cor pulmonale due to connective tissue disease.

Dosage, Routes of, and Practical Considerations in Drug Administration

Oxygen. Patients with hypoxemic cor pulmonale should be treated with low-flow oxygen delivered via nasal cannula and to achieve an arterial Po greater than 60 to 65 torr. Oxygen therapy should be used for at least 18 hours per day, and preferably for 24 hours per day; even intermittent alveolar hypoxia is sufficient to promote ongoing pulmonary vasoconstriction. Some authors have suggested empirically increasing the flow rate by 1 liter per minute during sleep because hypoventilation with resultant hypoxemia is common in patients with cor pulmonale due to obstructive lung disease Although oxygen concentrators are efficient and cost effective devices for the delivery of continuous supplemental oxygen, they are of limited benefit in ambulatory patients because of their size and electrical requirements. Liquid oxygen systems, which are portable albeit more expensive, allow patients to ambulate while still receiving supplemental oxygen.

In some patients with pulmonary hypertension, arterial hypoxemia may be due to right-to-left shunting through a patent foramen ovale. Such patients may not substantially increase arterial Po in response to sup-plemental oxygen, but dyspnea and activity tolerance may nevertheless be improved.

Methylxanthines. I prefer to use theophylline inpatients with cor pulmonale due to chronic obstructive pulmonary disease in doses that achieve low therapeutic levels. Higher serum levels (15 to 20 u,g per milliliter) may be associated with adverse effects, such as tachycardia, arrhythmias, nausea, and tremors. Oral sustained-release preparations, titrated to achieve the desired serum concentration, can be administered twice daily and provide reliable bioavailabity.

Vasodilators. The use of vasodilators in pulmonary hypertension should be considered experimental, and their role in management is unclear. My approach is to withhold their use in patients with cor pulmonale due to lung disease until conventional therapy has proven in adequate. In contrast, patients with primary pulmonary hypertension are viewed as potential candidates for vasodilator therapy as soon as the diagnosis is established because no other modality of treatment has proven any more successful. Prostacyclin (PGI) is well suited for this purpose in that it is a potent, titratabic, short-acting agent. Individuals who manifest reductions in pulmonary artery pressure and pulmonary vascular resistance in response to the acute intravenous infusion of prostacyclin are more likely to respond in a similar fashion to oral or transdermal vasodilators. As of this writing, prostacyclin is an experimental agent that has not been approved by the Food and Drug Administration for general use; commercially available intravenous agents, may be suitable alternatives, although they may be less potent than prostacyclin.

Individuals who manifest beneficial responses to intravenous prostacyclin are treated with oral or topical vasodilators. The calcium channel blockers appear to be the most potent agents, although side effects are common and may preclude their use Nifedipine and diltiazem hydrochloride appear equally effective; verapamil is generally not used because it is less potent in the pulmonary vascular bed and it possesses negative effects. I usually begin therapy with sustained-release nifedipine in doses of 30 mg once daily, increasing the dose as tolerated; sustained-release diltiazem hydrochloride therapy is instituted in doses of 120 mg once daily, increasing as tolerated. Studies have suggested that large doses of these agents may be necessary to produce sustained responses in pulmonary hypertension, although side effects may limit the doses that can be achieved. Survival is improved in patients who are responsive to calcium channel blocking therapy.

If calcium channel blockers cannot be used because of adverse effects, I consider nitrates as a second line of therapy in patients with demonstrated pulmonary vasoreactivity. I prefer to use topical nitroglycerin ointment,  every 6 hours,increasing as tolerated.

Patients who are refractory to these approaches may be considered candidates for continuous intravenous infusion of prostacyclin. This approach, which is still experimental, may be particularly useful as a bridge to transplantation in severely impaired individuals. Prostacyclin is delivered intravenously from a portable syringe pump connected to a chronic indwelling central venous catheter.

Anticoagulation. Recent experience suggests that PPH patients who arc treated with anticoagulants tend to live longer. I treat patients with PPH or chronic thrombotic pulmonary vascular disease with warfarin, adjusting the dose to achieve a prothrombin time of approximately 1 5 times control I generally do not treat patients with other causes of cor pulmonale with anticoagulants unless a specific indication exists.

Cardiac Glycosides and Diuretics. Cardiac glycosides appear to be of limited usefulness in cor pulmonale due to parenchymal lung disease unless left vcntricular dysfunction is present. Furthermore, the risk of digitalis toxicity is increased in the setting of chronic lung disease, in part because of the presence of hypoxemia, and diuretic-induced hypokalemia. Accordingly, I use cardiac glycosides in this setting only when supraventricular tachyarrhythmias requiring atrioventricular node blockade are present; verapamil may bean alternative, although its other hemodynamic effects may limit its usefulness

Some authors have advocated combining cardiac glycosides with calcium channel blocker therapy inpatients with primary pulmonary hypertension to counteract the negative inotropic effects of nifedipine or diltiazem hydrochloride.

Diuretics should be used cautiously in patients with cor pulmonale because excessive reduction in right-heart preload may actually compromise right ventricular function. In addition, the hypokalemia and metabolic alkalosis that may result from diuretic use are poorly tolerated by patients with severe chronic lung disease. Finally, many patients with hypoxemic cor pulmonale experience a gradual hemodynamic response to supple-mental oxygen therapy, precluding the need for diuretics.

Despite these caveats, patients with persistent or severe volume overload attributable to right-heart failure should be treated with diuretics. Furoscmide, doses of 40 to 120 mg per day, are usually sufficient. In refractory situations, potent diuretics, such as metolazone in doses of 2.5 to 5 mg, may be added. Monitoring of serum electrolytes is mandatory when these agents are used, and aggressive potassium or magnesium replacement may be necessary.

Side Effects of the Drugs Used

Low-flow supplemental oxygen therapy is generally safe and is well tolerated by most patients with hypoxemic lung disease. Modest increases in PCo can accompany its use in hypercapnic individuals with chronic obstructive pulmonary disease, but overt suppression of respiratory drive is unlikely unless very high flow rates are used or other factors precipitating acute respiratory failure are present. The use of nasal cannulas can produce nasal mucosal drying and irritation, which can be minimized by keeping flow rates lower than 4 to5 liters per minute and applying topical lubricants to the mucosa.

Side effects from bronchodilators are generally minor and include tachycardia, tremor, and nervousness. Selective beta-agonists and cholinergic agonists administered by inhalation are better tolerated than oral beta-agonists. Oral theophylline preparations should be given in doses that achieve scrum levels and that arc not accompanied by side effects.

The major adverse effects of vasodilators are systemic hypotension, deterioration in gas exchange, and depression of cardiac contractility. Because there is noselective pulmonary vasodilator, most patients with cor pulmonale experience some degree of systemic vasodilation in response to the administration of a vasodilator. Patients with “fixed” pulmonary vascular disease are more likely to experience hypotension with vasodilators because cardiac output is unlikely to increase.

Some vasodilators, particularly calcium channel blockers and nitrates, can worsen gas exchange by increasing perfusion to poorly ventilated lung units. The hypoxemia may be poorly tolerated by individuals with underlying parenchymal lung disease and pre-existent impaired gas exchange. Careful monitoring of arterial blood gases or saturation is important in this setting.

The calcium channel blocking agents may also precipitate a deterioration in right-heart function as a result of their negative inotropic properties. The phenomenon is more common with verapamil than with either nifedipine or diltiazem hydrochloride, but it can occur with any of these compounds and at any dose. Differentiating drug-induced heart failure from disease progression or drug-induced fluid retention (which occurs in up to 30 percent of patients taking calcium channel blockers) is often difficult and may require empirically reducing the dose or repeated right-heart catheterization.

Assessment of Therapeutic Responses

Although improvement in symptoms, such as decreased exertional dyspnea, is suggestive of a beneficial therapeutic response, evaluation by invasive or noninvasive techniques is usually required. Echocardiography and radionuclide ventriculography are useful in providing a qualitative assessment of right ventricular function. Right ventncular catheterization, is the preferred approach in monitoring therapy.

The debate regarding the definition of a beneficial response to vasodilator therapy remains unsettled. I treat patients with vasodilators if they experience a sustained reduction in pulmonary vascular resistance greater than 25 to 30 percent, which is produced by a reduction in pulmonary artery pressure, increase in cardiac output, or both. An increased pulmonary artery pressure, decreased cardiac output, symptomatic systemic hypotension, or substantial deterioration in gas exchange (usually due to either right-to-left shunting through a patent foramen ovale or increased V/Q mismatching) constitute contraindications to vasodilator therapy.

 

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Real life situation to be solved.

 

Clinical presentation (see picture above):
58 year old man, smoker, with a 20 year history of chronic productive cough. Elevated haemoglobin level.

The lungs are large volume. The diaphragm appears low and flat. There are bullae in both lowerlobes. The proiximal hilar vessels arelarge, but taper rapidly. The heart is enlarged, relative to the large volume lungs. There is a bulge in the region of the main pumonary artery. There is no indication of pulmonary oedema in the current view.

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PULMONARY INSUFFICIENCY, (RESPIRATORY FAILURE)

Pulmonary insufficiency or some degree of respiratory failure occurs when the exchange of respiratory gases between the circulating blood and the ambient atmo­sphere is impaired. The terms are used synonymously though the term respiratory failure generally refers to more severe lung dysfunction. The gaseous composition of arterial blood with respect to 0₂ and C0₂ pressures is normally maintained within restricted limits; pulmonary insufficiency occurs when the Pao₂ is < 60 mm Hg and the Paco₂ is > 50 mm Hg, but pulmonary insufficiency or respiratory failure may be manifested by a reduced Pao₂, with a normal, low, or elevated Paco2.

There are 3 pathogenic categories of diseases of the respiratory apparatus: (1) those manifested mainly by airways obstruction; (2) those largely affecting the lung parenchyma but not the bronchi; and (3) those in which the lungs may be anatomically intact but the regulation of ventilation is defective because of abnor­mal musculoskeletal structure and function of the chest wall or primary dysfunc­tion of the CNS respiratory center. The etiology and mechanisms of disease leading to the physiologic disturbances in each of these categories may differ, but the pattern of physiologic disturbance of lung function is quite similar. Lists the most commonly recognized chronic lung disorders in these catego­ries. These and acute disorders (e.g., pulmonary edema, pneumonia, shock lung) which may lead to pulmonary insufficiency.

 

DISORDERS CAUSING CHRONIC PULMONARY INSUFFICIENCY:

PATHOGENIC CLASSIFICATION

1. Airways Obstruction

Chronic bronchitis (figure 1)

Emphysema

Cystic fibrosis (mucoviscidosis) (figure 2)

Asthma

2. Abnormal Pulmonary Interstitium (Pulmonary Alveolitis, Interstitial Fibrosis)

Sarcoidosis

Pneumoconiosis

Progressive systemic sclerosis

Rheumatoid lung

Disseminated carcinoma

Idiopathic fibrosis (Hamman-Rich syndrome)

Drug sensitivity (hydralazine, busulfan, etc.)

Hodgkin’s disease

Systemic lupus erythematosus

Histiocytosis

Radiation

Leukemia (all cell types)

3. Alveolar Hypoventilation Without Primary Bronchopulmonary Disease

Functional: Sleep, chronic exposure to CO₂, metabolic alkalosis Anatomic abnormal respiratory center (Ondine’s curse), abnormal chest cage (kyphoscoliosis, fibrothorax) Disordered neuromuscular function: Myasthenia gravis, infectious potyneuritis, muscular dystrophy, poliomyelitis, polymyositis Obesity. Hypothyroidism.

Figure 1.  X-ray of patient with chronic bronchitis (COPD) and respiratory failure. The signs are characteristic to main disease.

 

Figure 2.  X-ray of patient with cystic fibrosis and respiratory failure. The signs are characteristic to main disease.

 

Pathophysiologic Changes in Airways Obstruction

The diseases in this category induce an abnormally high resistance to airflow in the bronchial tree. The causes vary with the etiology but include secretions, bron­chial mucosal edema, bronchial smooth muscle spasm, or structural weakness of bronchial wall supports. An abnormally high effort, and therefore energy expendi­ture, is required for ventilation to produce the necessary pressure differences be­tween the mouth and alveoli during expiration and inspiration. The high resistance to airflow can profoundly affect the gas exchanging function of the lung in the alveoli by disturbing the distribution of ventilation to various parts of the lung with respect to regional perfusion by mixed venous blood.

The ventilation/perfusion ratio must be close to 1 for Pao2; and Paco₂  to remaiormal (80 to 100 mm Hg for Pao₂; 40 ± 4 mm Hg for Paco₂). Paco2 is below normal if there is high alveolar ventilation for the level of perfusion; high regional perfusion with respect to ventilation reduces 0₂ tension and content of pulmonary capillary blood, a more dire occurrence. The mixing of blood from such over-perfused regions with blood from regions with a normal ventilation/perfusion ratio causes hypoxemia, which is determined quantitatively by the proportion and composition of blood mixing with the normally oxygenated blood. A true shunt of 50% of mixed venous blood (0₂; saturation 75%) mixing with a similar proportion of fully oxygenated blood results in an Sao2 of 87% or a Pao2 of 53 mm Hg. Hypercapnia or a high Paco2 will not occur as long as regions of the lung are over-ventilated with respect to the regional perfusion (a high ventilation/perfusion ratio) so that C02 is expelled from the blood in large volumes and the regional capillary Pco2 is below the normal 40 mm Hg. The net mixed Paco2 remains normal in the presence of persistent hypoxemia. Arterial hypercapnia develops when total ventilation or regional ventilation is depressed so that regional hyperventilation sufficient to maintain the Paco2 at normal cao longer occur. Hyper­capnia may occur with exacerbations of bronchitis, pneumonia, or status asthmaticus, or suppression of total pulmonary ventilation due to pharmacologic depression of the respiratory center by such agents as codeine, morphine, barbitu­rates, or other sedatives.

The characteristic changes in lung volumes and ventilatory tests in intrathoracic airways obstruction are (1) reduced VC, (2) increased RV and FRC so that TLC may be normal or increased, and (3) reduced MW, FEV₁, and airflow rates on expiration at all phases of the forced expiratory volume.

 

Diffuse Interstitial Fibrosis and Alveolitis

The pattern of physiologic abnormality in these diseases is strikingly different from that in airways obstruction. VC is reduced, usually with reduced RV, so that TLC is also reduced. However, tests of airways obstruction (e.g., the FEV₁ and the MW) are usually normal. The Paco2 is usually normal and often below nor­mal because of hyperventilation, and is almost never elevated. The Pao2, however, is mildly to moderately reduced at rest and more markedly reduced during exercise. The hypoxemia is caused by ventilation/perfusion imbalance and diffusion limitation by the structurally abnormal alveolar capillary membrane or by reduc­tion in the total lung area for diffusion. Lung diffusing capacity for CO2 or O2 is characteristically low at rest and during exercise.

Unlike the case in obstuctive lung diseases, the major mechanical abnormality is increased lung stiffness (reduced lung compliance) with normal airway resist­ance. Ventilatory drive is also increased, frequently causing hyperventilation at rest and during exercise, with associated hypocapnia. The reduced lung compli­ance and the increased ventilatory drive and hypoxemia contribute to dyspnea, the outstanding symptom in this group of diseases.

 

Alveolar Hypoventilation Without Primary Bronchopulmonary Disease

Alveolar hypoventilation of this type occurs when pulmonary structure is intact but the regulatory function of ventilation in relation to whole body metabolism is disturbed. The pathognomonic manifestation of this imbalance between ventila­tory and metabolic function is an elevated Paco2 (normal = 40 ± 4 mm Hg) and a concomitantly reduced PaO2 (PaO2 falls as alveolar Pco2 rises). Ventilation/perfu­sion imbalances are usual in addition to alveolar hypoventilation. The alveolar to arterial 02 tension difference is therefore increased, contributing further to arte­rial hypoxemia. Sometimes (e.g., in central depression of the respiratory center), the elevated Paco2 also results from a total alveolar hypoventilation; other times (e.g., in obesity and severe kyphoscoliosis), elevated Paco2 may result from both ventilation/perfusion imbalance and reduced overall alveolar ventilation.

The pathologic basis of alveolar hypoventilation in the presence of normal lung structure (see table ) vanes from weakness or paralysis of the ventilatory muscles (as in myasthenia gravis and infectious polyneuritis) to acquired or con­genital damage to the medullary respiratory center. In most cases except obesity, lung compliance and airway resistance are unimpaired and voluntary hyperventi­lation usually markedly improves blood gas composition.

 

Consequences of Respiratory Failure

Depressed arterial and tissue O2 tensions affect the cellular metabolism of all organs and, if severe, can cause irreversible damage in minutes. In addition, even moderate (< 60 mm Hg) alveolar hypoxia over days or weeks can induce pulmo­nary arteriolar vasoconstriction and increased pulmonary vascular resistance which leads to pulmonary hypertension, right ventricular hypertrophy (cor  pulmonale), and eventually right ventricular failure.

Elevated arterial and tissue CO2 tensions, however, affect mainly the CNS and the acid-base balance. Paco2 elevations, usually > 70 mm Hg, are associated with marked cerebral vasodilation, increased CSF pressure, and changes in sensorium ranging from confusion to narcosis. Papilledema occurs at these levels of hypercapnia when they persist for many days; it is reversed on lowering of the Paco2.

Ventilatory responsiveness to CO2 as a stimulus to breathing is diminished by persistent hypercapnia, largely due to the increase in blood and tissue buffers resulting from the generation of bicarbonate by the kidney in response to the elevated Paco2. The increased buffering capacity which also occurs in the CNS diminishes the decrease in pH which occurs with increases in plasma and tissue C02 levels. The contribution of pH to the ventilatory stimulus of CO2 is therefore diminished. This can be seen in the relationship between pH, bicarbonate concen­tration, and Paco2 in the Henderson-Hasselbalch equation. This effect on ventila­tory responsiveness is reversed when the Paco2 returns to normal.

Sudden rises in Paco2 occur much faster than compensatory rises in extracellu­lar buffer base; this causes marked acidosis (pH < 7.3), which additionally contributes to pulmonary arteriolar vasoconstriction, reduced myocardial contractility, hyperkalemia, hypotension, and cardiac irritability. This type of acidosis is rapidly reversed by increasing alveolar ventilation by mechanical hy­perventilation if necessary and rapidly lowering Paco2 to normal levels.

 

Clinical classification of pulmonary insufficiency

Stage I– the breastlessness occurred in case of usual physical activity that previously didn’t course it (running, going upstears). Hemoglobin saturation by O₂ no less than 80%.

Stage II– the breastlessness occurred in case of low physical activity (walking on plain surface). Hemoglobin saturation by O₂ near about 60– 80%.

Stage III– the breastlessness occurred in rest. Hemoglobin saturation by O₂ less than 60%.

 

Pulse oxymetry

Objective measures of monitoring for hypoxaemia include pulse oximetry. This is a good bedside monitor if its limitations are recognised. It is a continuous and non-invasive monitor. Its principal limitation is that, in patients who are receiving supplemental oxygen, it will not reliably detect hypoventilation. Hypoventilation must, in the clinical environment, usually be confirmed by measurement of the PaCO2 by arterial blood gas analysis.

Infrequently, inadequate oxygenation with normal oxygen saturation may occur in cases with very gross anaemia or in situations where the cells are unable to utilise oxygen such as severe sepsis or cyanide poisoning. Mixed venous oxygen saturation measurements may be helpful in these situations but this is only practical in an intensive care setting with a pulmonary artery catheter in situ. Inaccurate readings may also be obtained in patients who have high carboxyhaemoglobin or methaemoglobin concentrations, high concentrations of endogenous or exogenous pigments such as bilirubin or methylene blue as well as with cold extremities and movement artifact.

In most circumstances, the trend in oxygen saturation is more important than the value per se as this can indicate whether the patient is responding to therapy or deteriorating.

Arterial blood gases

This is the ‘gold standard’ monitor of ventilation. Arterial blood gases are needed to obtain accurate data, in particular, evidence of hypoventilation (raised PaCO2) as a reason for hypoxaemia. Arterial blood gases may also give an indication of the metabolic effects of clinically important hypoxaemia. Formal blood gas analysis may also afford accurate estimates of carboxyhaemoglobin and methaemoglobin, the former being particularly important in patients rescued from fires. However, a blood gas is a painful, invasive and intermittent procedure that is time consuming in the setting of a busy ward.

A spectrum of treatments exist for the hypoxic patient. These range from supplemental oxgyen therapy and simple measures such as altering posture. Even sitting a patient up improves FRC, compared with the patient lying down. Physiotherapy can be useful, but most specifically in those patients with copious airways secretions. If the patient is still hypoxic after these ward-based treatments, measures such as continuous positive airway pressure, non-invasive ventilation or invasive ventilation may be required, usually in the setting of an intensive care unit.

 

Therapy of Respiratory Failure

The detection of respiratory failure from any cause and its therapy depend on analysis of arterial blood Po2, Pco2. and pH; faculties for such analyses are essential for effective therapy.

When the Paco2 is not elevated and only hypoxemia exists, the therapy of respi­ratory failure may be different than when both blood gas abnormalities are pres­ent. All available technics for reducing airways obstruction (i.e., bronchodilators, tracheal suction, moisturization, and chest physiotherapy) may be required in the treatment of respiratory failure. Ultimate recovery demands recognition of every factor leading to respiratory failure and use of therapeutic agents that can reverse these factors while the patient receives respiratory support by mechanical ventila­tion and high O2  mixtures.

Oxygenation: The concentration of enriched O2 selected to overcome hypoxe­mia should be the lowest concentration that will provide an acceptable Pao2. Inspired O2 concentrations exceeding 80% have significant toxic effects on the alveolar capillary endothehum and bronchi and should be avoided unless neces­sary for the patient’s survival. Concentrations of inspired O2 of < 60% are well tolerated for long periods without manifest toxicity. Most patients tolerate a Pao2 > 55 mm Hg quite well. However, Pao2 values in the range of 60 to 80 mm Hg are most desirable for adequate delivery of 0₂ to tissues and prevention of increases in pulmonary artery pressure from alveolar hypoxia. Pao2 values between 55 and 80 mm Hg are acceptable. For pulmonary insufficiency resulting from ventila­tion/perfusion imbalances as associated with obstructive lung disease or with combined diffusion limitation and ventilation/perfusion imbalance, inspired O2 concentrations of > 40% are usually not required. Most patients with these types of physiologic dysfunctions receive adequate oxygenation with 25 to 35% inspired O2. Such concentrations can be given readily by face masks designed to deliver specific concentrations at the mouth, or by nasal cannulas. With face masks, the flow of O2 required for a given percentage is predetermined by the mask design.

With nasal cannulas, the flow of 02 can only be estimated. Such estimates require knowledge of the total minute ventilation of the patient in room air and the duration of inspiration and expiration. If the time m both phases of ventila­tion is equal, only half the flow of 100% 02 from the 02 reservoir can be assumed to be delivered to the patient. Thus, for a ventilatory rate of 10 L/min and a 4 L/min flow of 100% 02 through nasal cannulas, the 02 concentration delivered to the patient would be estimated at

If the minute ventilation rises and the 02 flow is unchanged, the inspired concen­tration of O2 decreases. Because of the uncertainties in such estimates (including the admixture of 02 with room air, mouth breathing, varying respiratory rate), the actual Pao2 tension must be monitored regularly to determine the results of ther­apy.

When higher concentrations of 02 must be delivered at the nose and mouth to achieve acceptable Pao2 levels (e.g., in severe pulmonary infection, shock lung, pulmonary edema), concentrations of O2 delivered by nasal cannulas are inadequate and tight-fitting face masks capable of delivering up to 100% inspired O2 may be necessary.

If adequate oxygenation by face mask requires continuous administration of O2 concentrations of more than 80%, tracheal intubation and mechanical ventilation can usually provide adequate oxygenation with a lower concentration of inspired O2, minimizing the risk of O2 toxicity. This provides larger tidal volumes and a more favorable ventilation/perfusion ratio than does spontaneous breathing.

No matter which technic of O2 delivery is used, the patient’s comfort and bron­chial clearance demand that the inspired gas be moisturized by passing it through a water trap.

Managing elevated PaCO2: In airways obstruction or when the ventilatory appa­ratus or its CNS control fails, elevated blood and tissue Pco2, as well as hypoxemia, must be treated. The urgency and necessity of rapid lowering of an abnormally elevated arterial and tissue Poo2 may be questioned when respiratory acidosis is compensated. Elevated Paco2, whatever the primary cause, indicates low alveolar ventilation with respect to body metabolism. A Paco2 even to levels of 70 or 80 mm Hg is generally well tolerated as long as compensated by an increase in buffer base, which keeps arterial pH near normal; the primary consid­eration must always be adequate oxygenation and the state of acidosis of the blood. If supplying enriched 02 during spontaneous ventilation leads to a continuously rising Paco2 and acidosis, then mechanical ventilatory assistance is required to control the Paco2.

Mechanical ventilation: Ionacutely ill patients with respiratory failure, an IPPB apparatus can be applied by a mouthpiece and nose clip or a face mask for intermittent therapy throughout the day. This technic is not effective if respiratory failure is acute and severe. If continuous mechanical ventilatory assistance is re­quired, the patient should have tracheal intubation through either the mouth or nose. Intubation allows easier suctioning and a wide variety of technics of me­chanical ventilation to be applied as required. After the trachea is intubated, the tube may be left in place for as long as 10 to 14 days if necessary before a tracheostomy must be performed or the patient returns to spontaneous ventila­tion. Short-term tracheal intubation without tracheostomy may be adequate for treating acute episodes of respiratory failure due to pulmonary infection, severe left heart failure, pulmonary edema, inadvertent depression of ventilation by sedatives and analgesic agents, uncontrolled bronchospasm, pneumothorax, or combinations of the above.

Any mechanical ventilator, particularly if the driving pressure into the lung is high, may cause reduced venous return to the thorax, reduced cardiac output, and a consequent drop in systemic BP. This is particularly common when inspiratory positive pressures are high, hypovolemia is present, and vasomotor control is inadequate due to drugs, peripheral neuropathy, or muscle weakness.

There are 3 main types of mechanical ventilators for treating acute respiratory failure: (1) pressure-controlled, (2) volume-controlled, and (3) body-tank-type.

Intermittent positive pressure breathing (IPPB) apparatus: Ventilation is induced with a mechanical ventilator which delivers positive pressure during inspiration but allows the pressure in the airway to return to atmospheric pressure during the expiratory phase by spontaneous exhalation (see above). Various kinds of appara­tus will introduce gas into the lungs by delivering the desired inspired mixture at a higher than atmospheric pressure through a face mask, mouthpiece, or intratracheal tube. All have similar features of control and performance. Ventilatory as­sistance is provided only during inspiration; expiration is passive. A slight inspiratory effort by the patient (about 1 cm H₂0 negative pressure) opens a valve that initiates the flow of gas from the apparatus to the lungs. In most types of apparatus, a sensitivity control knob determines the ease with which inspiratory effort initiates inspiratory flow. Flow ceases when the pressure in the mouth or intratracheal tube reaches a positive pressure that has been preset by the pressure control on the apparatus. When inspiratory flow ceases, expiration occurs pas­sively through an expiratory valve. The tidal volume delivered to the patient de­pends on the preset pressure at which the inspiratory flow ceases. Iormal individuals, peak positive pressures of 15 cm H₂0 usually provide tidal volumes of 800 to 1000 ml. If bronchial obstruction, obesity, stiff lungs, or thoracic deformity is present, positive pressures > 20 cm H20 may be required to achieve normal tidal volumes. Newer devices can achieve inspiratory pressures of up to 60 cm H20. Such pressures may be required under circumstances of severely reduced lung compliance or increased airway resistance.

Moisture in the inspired gas or aerosol medications can be delivered by a nebu­lizer connected to the inspired gas flow.

Inspired gas flow rates of about 40 to 60 L/min are usually adequate, even in tachypndc states in which higher thaormal flows are required. Excessively high flow rates may accentuate uneven distribution of inspired gas, especially in bron­chial obstruction, and may result in high positive pressures in the proximal bron­chi before an adequate tidal volume can be introduced. The inspiratory phase may then be unnecessarily short and the tidal volume inadequate for effective gas exchange.

In pressure-controlled ventilators, breathing frequency may be determined by allowing the patient to initiate the inspiratory effort and determine his own rate, or, wheecessary, an automatic frequency control predetermines a rate and will initiate breathing automatically. The frequency control on most apparatus also allows automatic initiation of a tidal volume in a patient breathing spontaneously if a period of apnea longer than a preset duration occurs.

Volume-controlled ventilators: A preset tidal volume is delivered to the patient regardless of the pressure required to deliver the inspiratory volume. Expiration is passive. Controls vary the inspired 02 mixture, inspiration and expiration time, and ventilatory frequency. Humidification and nebulization are provided. These ventilators are particularly useful for maintaining adequate alveolar ventilation regardless of rapid changes in the airway resistance or pulmonary compliance while the patient is being ventilated. Volume-controlled ventilators are in general selected most commonly for ventilatory support in the setting of intensive care.

Tank-type body ventilators: These can be used when ventilation is to be me­chanically maintained for a prolonged period and when tracheostomy or tracheal intubation is not indicated. Such ventilators were commonly used prior to the availability of the mechanical ventilators discussed above. A new type of thoracic ventilator allows the patient to lie in a flexible plastic garment extending from the neck to the thighs with a rigid support overlying the thorax only, leaving the patient’s arms free.

Positive end-expiratory pressure (PEEP): This term refers to ventilation in which a positive pressure is imposed in the airway at the end of expiration. Thus with PEEP, inspiration proceeds by imposing a positive pressure in the airway. After peak pressure and tidal volume are reached, expiration proceeds unobstructed. However, exhalation ceases at a preset expiration pressure that is set by an exha­lation valve sensitive to pressure and placed in the exhalation part of the ventila­tor or tracheal tube. If a Pao2 of 50 to 70 mm Hg cannot be achieved with 60% inspired 02 using positive pressure ventilatory assistance, a continuous PEEP of 3 to 15 cm H20 may be tried to induce further expansion of the lung, improve the ventilation/perfusion ratio, and reduce shunting. Since the procedure is not innocuous and complications are directly related to the magnitude of the endexpiratory pressure, the lowest level of PEEP that achieves an adequate Pao2 should be applied. The major complications of PEEP are decreased venous return, reduced cardiac output, and pneumothorax. Application of PEEP to a severely ill patient is best done by an individual experienced with this technic.

Continuous positive airway pressure (CPAP): In this technic, during spontane­ous breathing, a positive pressure is applied during the entire respiratory cycle (during inspiration and expiration). In this regard, exhalation bears some rela­tionship to pursed-Up breathing. The technic may be applied by a head canopy that controls the ambient airway pressure with or without intubation. When the patient has an intratracheal tube, CPAP can be applied by a specially modified T piece in which a reservoir bag is placed in the expiratory line and the expiratory pressure is controlled by varying the degree of occlusion of the tailpiece of the bag. The term continuous positive pressure breathing (CPPB) is synonymous with CPAP and the term continuous positive pressure ventilation (CPPV) has been used instead of CPPB when ventilation is controlled by a mechanical ventilator rather than spontaneously (picture 1).

 

 

 

 

 

 

 

Picture 1. Continuous Positive Airway Pressure (CPAP) devices maintain open airways in patients who have been diagnosed with Obstructive Sleep Apnea (OSA). This device provides airflow at pressures prescribed by a patient’s doctor during sleep. MedNow carries many different brands of CPAP machines and masks for machines and masks for your individual needs. A Staff Respiratory Therapist will work with you to determine the best CPAP machine and masks for your needs and will be available for any questions or concerns after your initial set-up.

 

Aerosols: When bronchospasm or bronchial edema is a factor, airway resist­ance can be reduced and ventilation/perfusion relationships improved by admin­istering aerosolized bronchodilators. Such solutions may be given by a positive pressure breathing apparatus or by hand or mechanical nebulizers (picture 2).

 

 

 

 

 

 

 

 

Picture 2. The nebulizer is designed for inhalation therapy and treatment of asthma, bronchitis, emphysema and upper respiratory tract disorders. A mouthpiece for adults and children or a mask for infants accompanies the machine

 

Maintenance of clear airways: Clearing of secretions from upper and lower air­ways is crucial to treating respiratory failure. Since alveolar gas is 100% humidi­fied at body temperature, room air or inspired gas delivered from a tank tends to dry out mucous membranes and add to the difficulty of raising secretions. The inspired stream delivered through a positive pressure breathing apparatus must be fully moisturized to ensure reduced viscosity of secretions. This can sometimes be achieved by heated nebulization, which highly moisturizes the inspiratory stream.

Physical therapy technics such as chest percussion several times/day in severely ill patients loosen secretions, allowing their removal by tracheal suction or spon­taneous cough.

Tracheal suction should be performed frequently through the mouth, nose, or tracheal tubes using sterile catheters and following other such precautions to minimize infection. In general, tracheal and lower airways suction without an intratracheal tube or tracheostomy by insertion of the suctioning catheter into the posterior pharynx is usually unsuccessful because of the difficulty of introducing the catheter past the vocal cords. Inadequate removal of secretions is an indica­tion for tracheal intubation, which allows easy access to the upper and lower airways and minimizes the risk of aspiration of stomach contents.

 

SOME DEVICES THAT ARE USEFUL IN PATIENTS

WITH CHRONIC RESPIRATORY FAILURE

Long Term Oxygen Therapy (picture 3) relates to the provision of oxygen therapy for continuous use at home for patients with chronic hypoxaemia (PaO2 at or below 7.3kPa (55mg). The oxygen flow rate must be sufficient to raise the waking oxygen tension above 8 KPa, (60mmHg).

Clincians usually prescribe LTOT where this is needed for at least 15 hours per day. For children this may cover 24 hours per day, but often apply to sleeping periods only.

Ambulatory oxygen may also be indicated in patients on LTOT to facilitate their mobility and quality of life.

Vitalair’s dedicated oxygen concentrator service is there to help and support patients undergoing Long Term Oxygen Therapy. Having a ready supply of oxygen at home will help improve patients’ quality of life, allowing them to enjoy the benefits of living at home.

Vitalair has invested in new concentrator technologies capable of delivering up to 5 litres per minute of therapeutic oxygen in the home. Each unit is known for its high performance, easy maintenance, and unmatched reliability.

Vitalair  (picture 4) has also developed a longer-lasting high capacity cylinder, which can provide up to 20 hours of back-up oxygen supply. The size makes it easier to handle and to store, while the capacity means fewer changeovers are needed when administering oxygen. The permanently live contents gauge allows patients to see how much gas is left in the cylinder at all times.

Since patients only use back-up cylinders very occasionally, we cannot predict when a cylinder replacement is needed.

Picture 3. Patient on Long Term Oxygen Therapy

 

 

Picture 4. The internal auto-recharge power cartridge enables easy movement between AC power outlets without interruption of oxygen therapy and can keep the oxygen flowing for up to 5.1 hours. Long lengths of tangled oxygen tubing are no longer needed to move about the house. The Eclipse means extended travel without the fear of running out of oxygen. Just plug the Eclipse into your auto accessory (lighter) outlet and go as far and as long as you like. 

 

Some devices useful in continuous oxygenating are presented in the table below and picture 5.

 

A Oxygen Concentrator Now you can have the freedom to travel with ease or relax at home in comfort with a portable, reliable and quiet oxygen concentrator. B Devilbiss Pulse Dose Oxygen Conserving Device Pulse dose oxygen conserving technology is on the leading edge of oxygen therapy. Unlike other oxygen regulators that simply limit the flow of oxygen, the Devilbiss Pulse Dose delivers a consistent dose of oxygen at the very moment it is most beneficial. C Portable Compressed Oxygen System Using light weight aluminum cylinders, portable compressed oxygen systems can meet the needs of ambulatory patients or for short trips in the outdoors. D Invacare HomeFill Oxygen System The HomeFill oxygen system allows patients to fill there own high pressure cylinders from a concentrator. The HomeFill is a multi-stage pump that simply and safely compresses oxygen from a specially equipped concentrator into oxygen cylinders.
A Devilbiss 9000D CPAP The quietest CPAP available. Convenient touch keypad control. Operating pressure range. 0, 10, 20, 30 or 45 minute pressure delay options. Push button altitude compensation. Monitors compliance while breathing. Includes travel bag for transporting. B HC220 Fisher & Paykel The HC220 humidified CPAP system offers an adjustable range of warm to heated humidification. Heated humidification with CPAP provides more effective treatment, so you too can have the lifestyle only a good night’s sleep can bring. C Remstar® Plus CPAP System Full featured unit. All-new icon based display. Integrated humidification controls. Easy set-up. Unique new session meter records number of sessions that last more than 4 hours.

 

 

 

 

 

 

Picture  5 Liquid oxygen is another type of oxygen therapy alternative. It consists of a stationary unit that is filled with oxygen that is cooled to below zero then is given to the patient in a comfortable gas form. Liquid oxygen has portable units as well that can be filled from the stationary unit a the patient in a comfortable gas form. Liquid oxygen has portable units as well that can be filled from the stationary unit and carried over the shoulder or strapped to a belt. nd carried

CPAP Moisture Therapy

Apply CPAP Moisture Therapy to facial area where mask meets the skin and inside the the nasal passage before beginning therapy (picture 6).

Repeat this process as often as needed to maintain soft skin and eliminate discomfort from dry/cracking skin.

Technology using CPAP therapy to assist those who have been diagnosed with sleep apnea problems may often result in skin irritation and discomfort in the nasal area. For this reason, CPAP Moisture Therapy may be useful to reduce this trauma.

CPAP Moisture Therapy is offered as a preventative to the skin irritation that may accompany this therapy for sleep apnea and may promote a greater compliance to treatment.

 

 

 

 

 

 

Picture 6. CPAP Moisture Therapy gel

DRY NOSE

The problem with dry nose associated with oxygen delivery by means of plastic cannula has been well documented by care givers at every level for decades.

Nasal dryness as well as other skin dryness can occur apart from the use of oxygen or continuous positive airway pressure (CPAP) devices due to dry climates as well as changing seasons. It may be useful in addressing these issues (picture 7).

 

Picture 7. This is a Non-Petroleum-Based Skin Care Emollient with Aloe Vera, Emu Oil, Vit. A & E to prevent the skin lesions in oxygen therapy.

Oxygen users
Apply RoEzIt Dermal Care before beginning oxygen therapy and at intervals as needed during treatment to lubricate nasal passages, as well as over the ear where friction from tubing may cause discomfort.

Main forms of respiratory insufficiency (according to B. E. Votchal).

1.     Central form – is the result of inhibition of respiratory center (narcosis, drugs, trauma, atherosclerosis, stroke etc.).

2.     Neuro–muscular form – is the result of disturbance of  conduction of signals from central nervous system to muscules (miastenia, poliemielitis etc.).

3.     Thoraco-diafragmal form – is the result of reduction of chest movements (chest degormation, kifoscoliosis etc.).

4.     Pulmonary form – is the result of pulmonary problems:

a)     decrease of pulmonary tissue (pneumonia, tumor);

b)    decrease of pulmonary tissue elasticity (fibrosis);

c)     narrowing of bronchial system (asthma, stenosis).

 

Clinical and instrumental characteristics of main types of ventilation insufficiency: obstructive, restrictive and mixed.

1.     Obstructive type is caused by:

a)     spasm; b) mucous odema; c) hypersecretion; d) scar narrowing;  e) endobronchial tumor; f) external pressuring of bronchus.

Diagnostic crireria: dyspnoe after physical execiesing, dry cough, dry rales. Increasing of expiration period, on spirography– decrease of FEV₁.

2.     Restrictive  type is caused by:

a) fibrosis; b) pleural disorders; c) pleural exudation; d) pneumoconiosis; e) tumors of lungs; f) pulmonectomia.

Diagnostic crireria: on spirography– decrease of VC.

3.     Mixed type: both causes are aviable.

 

 

HYPERBARIC OXYGEN THERAPY      

We can better understand the concepts behind hyperbaric oxygen (HBO) therapy by first gaining an understanding of some basic terms:

Hyperbaric Oxygen Therapy   
Hyperbaric oxygen therapy describes a person breathing 100 percent oxygen at a pressure greater than sea level for a prescribed amount of time—usually 60 to 90 minutes.        

Atmospheric Pressure      
The air we breathe is made up of 21 percent oxygen, 78 percent nitrogen and 1 percent carbon dioxide and all other gases. The air exerts pressure because air has weight and this weight is pulled toward the earth’s center of gravity. This pressure is expressed as atmospheric pressure. Atmospheric pressure at sea level is 14.7 pounds per square inch (psi).     

Hydrostatic Pressure       
As we climb above sea level the atmospheric pressure decreases because the amount of air above us weighs less. When we dive below sea level the opposite occurs (the pressure increases) because water has weight that is greater than air. Thus, the deeper one descends under water the greater the pressure. This pressure is called hydrostatic pressure.       

Atmospheres Absolute (ATA)  
The combination (or the sum) of the atmospheric pressure and the hydrostatic pressure is called atmospheres absolute (ATA). In other words, the ATA or atmospheres absolute is the total weight of the water and air above us.       

Terms Used to Measure Pressure       
We use various terms to measure pressure. HBO therapy involves the use of pressure greater than that found at the earth’s surface at sea level. This is called hyperbaric pressure. The terms or units used to express hyperbaric pressure include millimeters or inches of mercury (mmHg, inHg), pounds per square inch (psi), feet or meters of sea water (fsw, msw), and atmospheres absolute (ATA).     

One atmosphere absolute, or 1-ATA, is the average atmospheric pressure exerted at sea level, or 14.7 psi. Two-atmosphere absolute, or 2-ATA, is twice the atmospheric pressure exerted at sea level. If a physician prescribes one hour of HBO treatment at 2-ATA, the patient breathes 100 percent oxygen for one hour while at two times the atmospheric pressure at sea level. The devices for HBO are presented on pictures 8-9.

 

Picture 8. Hyperbaric oxygen therapy device

 

 

Picture 9. Hyperbaric oxygen therapy device in action

 

While some of the mechanisms of action of HBO, as they apply to healing and reversal of symptoms, are yet to be discovered, it is known that HBO:

1) greatly increases oxygen concentration in all body tissues, even with reduced or blocked blood flow;

2) stimulates the growth of new blood vessels to locations with reduced circulation, improving blood flow to areas with arterial blockage;

3) causes a rebound arterial dilation after HBOT, resulting in an increased blood vessel diameter greater than when therapy began, improving blood flow to compromised organs;

4) stimulates an adaptive increase in superoxide dismutase (SOD), one of the body’s principal, internally produced antioxidants and free radical scavengers; and,

5) aids the treatment of infection by enhancing white blood cell action and potentiating germ-killing antibiotics.

While not new, HBO has only lately begun to gain recognition for treatment of chronic degenerative health problems related to atherosclerosis, stroke, peripheral vascular disease, diabetic ulcers, wound healing, cerebral palsy, brain injury, multiple sclerosis, macular degeneration, and many other disorders Wherever blood flow and oxygen delivery to vital organs is reduced, function and healing can potentially be aided with HBO. When the brain is injured by stroke, CP, or trauma, HBO may wake up stunned parts of the brain to restore function.

References:

A – Basic:

1.                 Davidson’s Principles and practice of medicine (21^st revised ed.) / by Colledge N.R., Walker B.R., and Ralston S.H., eds. – Churchill Livingstone, 2010. – 1376 p.

2.                 Harrison’s principles of internal medicine (18^th edition) / by Longo D.L., Kasper D.L., Jameson J.L. et al. (eds.). – McGraw-Hill Professional, 2012. – 4012 p.

3.                 The Merck Manual of Diagnosis and Therapy (nineteenth Edition) / Robert Berkow, Andrew J. Fletcher and others. – published by Merck Research Laboratories, 2011.

4.                 Web -sites:

a)      www.tdmu.edu.ua: Management of the patients with pleural effusion

b)    http://emedicine.medscape.com/

c)     http://meded.ucsd.edu/clinicalmed/introduction.htm

 

B – Additional:

1.     Respiratory diseases /  Ghanei M. – In Tech, 2012. – 242 p.

2.     Clinical respiratory medicine / Spiro S., Silvestri G., Agustí A. – Saunders, 2012. – 1000 p.  

3.     Principles and practice of interventional pulmonology / Ernst A., Herth F. –Springer, 2012. – 757 p.

4.     Chest x-rays for medical students / Clarke C.,  Dux A. – Wiley-Blackwell, 2011.  – 134 p.

 

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