Respiratory Failure

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[edit] Respiratory Failure

Kenneth W. Presberg

Respiratory failure is defined as the failure of the respiratory system to provide for adequate gas exchange, that is, adequate oxygenation of the circulating blood for sufficient oxygen (O₂) delivery to tissues and adequate elimination of carbon dioxide (CO₂) produced by cellular metabolism. Arterial oxygen tensions (Pao₂) less than 50 mm Hg and arterial carbon dioxide tensions (Paco₂) greater than 50 mm Hg are generally accepted criteria for the presence of respiratory failure. However, severe abnormalities of the respiratory system's capacity may imminently lead to respiratory failure and may not be reflected in initial measurement of an arterial blood gas (ABG).

Patients may present with the signs and symptoms attributable to the primary process causing the gas exchange abnormality or may have manifestations secondary to the adverse end-organ effects of hypoxemia and hypercapnia. When confronted with a patient with evidence of respiratory failure, the physician must first ascertain whether the process is acute or chronic, then further delineate the cause and initiate treatment. The acute causes will require expeditious evaluation and treatment that is best handled in the inpatient setting. An acute process is often apparent early in the evaluation because of an obvious insult or symptoms that indicate a recent deterioration. Chronic respiratory failure is often suggested by an insidious progression of limitation along with evidence of a chronic thoracic or neuromuscular disorder. At times the patient may not mention any specific complaints, and respiratory failure is apparent after an ABG determination is performed for other reasons. Hypoxemia can be judged to be chronic if no history suggests a recent event, evaluation discloses signs and symptoms of a chronic cardiopulmonary disorder, and other findings of chronic hypoxemia are present (see later discussion). Chronic hypercapnia is easier to judge because it is accompanied by respiratory acidosis that is mild because of renal compensation. When chronic respiratory failure is discovered, evaluation and therapy can often proceed in the outpatient setting; however, daytime hypoxemia should be corrected early. Acute on chronic respiratory failure refers to the acute deterioration in the patient who previously had well-compensated chronic impairment. Severe, life-threatening hypoxemia and worsening hypercapnia with severe respiratory acidosis often occur in this setting.

Many of the chronic pulmonary and neuromuscular disorders are discussed in other chapters. Therefore more attention is given here to the causes of the acute decompensation in chronically impaired patients and the acute, fulminant processes leading to respiratory failure.

[edit] CHRONIC RESPIRATORY FAILURE

[edit] Pathophysiology: Overview of Gas Exchange Abnormalities

The lung can be considered conceptually as an alveolar-capillary gas exchange unit and the respiratory pump. The pump is driven by an integrated control center, the central nervous system (CNS). The pump (muscles of respiration) directs the bulk flow of gas through the airways to the gas exchange unit. Gas exchange failure caused by the respiratory system results from the malfunction of one or more of these many components. Disorders causing respiratory failure are often further categorized by the predominant gas exchange abnormality that is present. Mechanisms for these gas exchange abnormalities are discussed next.

[edit] Tissue Oxygenation Failure.

Inadequate tissue oxygenation can result from other well-known mechanisms quite distinct from the respiratory system. These causes of tissue hypoxia need to be well understood for an expeditious and directed approach to the patient with oxygenation failure (Table 77-1). Failure to correct severe hypoxemia within minutes can result in irreversible organ damage. The CNS and cardiovascular system are particularly affected by hypoxemia. Treatment may require the rapid implementation of mechanical ventilatory and cardiac resuscitative support. Measurement of oxygenation is essential.

Table 77-1 Causes of Tissue Hypoxia

Table 77-2 summarizes and contrasts these various mechanisms of hypoxemia in terms of frequently measured and calculated variables. The degree of hypoxemia is often described by the ratio of Pao₂ to fractional inspired O₂ concentration (Fio₂). Values less than 200 are usually caused by significant degrees of physiologic shunting. Chronic lung disorders usually cause hypoxemia by ventilation/perfusion ( / ) inequality. In contrast, acute lung injuries are associated with severe hypoxemia that is most often secondary to physiologic shunting or increased venous admixture. The hypoxemia in these latter cases often responds poorly to supplemental O₂. Patients with chronic hypoxemia may be relatively asymptomatic until pulmonary vascular, cardiac, and other end-organ sequelae ensue. These include cognitive impairment, weight loss, left-sided heart dysfunction, pulmonary hypertension with cor pulmonale, edema, cyanosis, and polycythemia. Hypoxemia should always be expeditiously corrected when found. If the pulmonary parenchyma appears normal and evaluation is also negative for the common cardiac abnormalities, the physician should consider the possibility of an intracardiac right-to-left shunt, pulmonary arteriovenous malformations, or the hepatopulmonary syndrome.

Table 77-2 Mechanisms of Hypoxemia Caused by Pulmonary Disorders

Condition	Fio2	PAo2	Pao2	Sao2	Paco2	A-a gradient
Normal	0.21 (room air)	100	90	95%	40	Normal
Hypoventilation	0.21	70	60	90%	70	Normal
Ambient hypoxia (low ambient Po2)	0.21	75	60	90%	40	Normal
Shunt	0.21	100	45	75%	40	Increased
	1.00	650	50	80%	40	Increased
Ventilation/perfusion ( / ) inequality	0.21	100	50	85%	40	Increased
	0.50	300	75	93%	40	Increased
Fio2, Fractional inspired oxygen concentration;Po2, oxygen tension;PAo2, alveolar Po2;Pao2, arterial Po2;Sao2, hemoglobin oxygen saturation of arterial blood;Paco2, arterial Pco2; A-a gradient=(PAo2− Pao2). All pressures in mm Hg. Note the different responses to supplemental oxygen between conditions with shunt and those with ( / inequality.

[edit] Mechanisms of Hypoventilatory Failure.

The failure of ventilation to eliminate the CO₂ produced by cellular metabolism (Vco₂) can lead to hypercapnia and respiratory acidosis. Virtually all CO₂ is eliminated from the body through the lungs. Paco₂ is tightly controlled by the regulation of alveolar ventilation under the control of the central chemoreceptors. The failure of the combination of respiratory drive and the respiratory pump to meet the ventilatory requirement for adequate elimination of CO₂ results in hypoventilatory failure. Acute hypercapnia can lead to severe dyspnea, flushing of the skin, and vasodilation of the cerebral vessels, with an increase in intracranial pressure that may result in headache, papilledema, depressed consciousness, and frank coma. For every acute increase in Paco₂ of 10 mm Hg, there is a corresponding pH decrease of 0.08 pH units. Respiratory acidosis leading to a pH less than 7.20 or failure of ventilation to compensate for a metabolic acidosis to a pH greater than 7.20 can adversely affect myocardial function, predisposing the patient to hypotension and dysrhythmias (arrhythmias). The respiratory acidosis from chronic hypoventilatory respiratory failure associated with ongoing CO₂ retention is mild because of renal compensation. However, the renal compensation with the retention of bicarbonate does not totally correct the acidosis under these circumstances. No specific symptoms are related to chronic hypercapnia, and these patients can tolerate marked elevations in Paco₂ without experiencing adverse consequences. Many of the patients with chronic hypoventilation caused by central or extrapulmonary disorders, such as hypothyroidism or sleep apnea, have a blunted respiratory drive response to elevations in Paco₂. These patients also experience chronic hypoxia because of the alveolar gas relation described previously and ( / inequalities. Therefore patients with chronic hypoventilation often have the symptoms and signs related to coexistent hypoxemia described earlier.

Paco₂ is determined by three key factors: CO₂ production (Vco₂), total minute ventilation (Ve), and the physiologic dead space (Vd/Vt). Their relationship is described by the following equation, where k is a constant:

Paco₂=k Vco₂ [1/Ve (1 − Vd/Vt)]

Vco₂ can be increased in hypermetabolic states (e.g., acute illness), which also increase Vo₂. Therefore the acute increase in Paco₂ and decrease in Pao₂ in a patient with respiratory failure who develops a high fever are not necessarily caused by any change in pulmonary gas exchange efficiency or a new mechanical problem and may be secondary to changes in the patient's metabolic state. Dead space is increased in patients with underlying lung disease, particularly in those with chronic obstructive pulmonary disease (COPD). The increase in Vd/Vt increases the basal ventilatory requirement (Ve) needed to maintain a normal Paco₂. Vd/Vt is also increased when positive-pressure ventilation is used and tends to increase as mean airway pressure increases. This increase in Vd/Vt can be mitigated if careful attention is paid to limiting mean airway pressure. Therefore the effect of ventilatory settings on Vd/Vt needs to be considered if the Pco₂ is not responding in the usual way to adjustments of Ve. At times it is not possible to normalize the Paco₂ with mechanical ventilation without incurring prohibitive risks of complications. Certain strategies for mechanical ventilation of patients with severe adult respiratory distress syndrome (ARDS) and asthma have incorporated permissive hypercapnia to avoid barotrauma-related complications (see Acute Respiratory Failure). However, the safe threshold below which an elevation of Paco₂ does not lead to adverse CNS or other organ effects has not been determined.

Hypoventilatory respiratory failure occurs when the normal or increased ventilatory requirement of the patient cannot be met. It results from an imbalance between the work of breathing imposed by respiratory loads and the respiratory capacity, which is determined by the respiratory drive and the respiratory pump (Fig. 77-1). Normally the respiratory capacity reserve is sufficient to accommodate modest increases in respiratory loads (e.g., bronchospasm) without leading to hypoventilatory failure. Acute hypoventilatory failure with an underlying lung or muscular disease is usually caused by respiratory muscle fatigue, which reflects a reversible defect of strength. Treatment strategies for patients with respiratory failure critically depend on reversing respiratory muscle fatigue while reducing respiratory workloads.

Figure 77-1 Abnormalities that can increase the normal respiratory resistive and elastic workloads are listed on the left. Defects of the normal respiratory capacity are noted on the right. Unless respiratory capacity remains sufficient to counterbalance these workloads, respiratory failure will ensue. (From Schmidt GA, Hall JB: JAMA 261:3444, 1989.)

[edit] Pathophysiology and Differential Diagnosis of Chronic Disorders

Box 77-1 lists the common causes of hypoventilatory respiratory failure. A further classification within this group distinguishes between disorders with normal and abnormal respiratory workloads. Those with normal respiratory workloads involve impaired respiratory capacity; these diseases include disorders of CNS control and intrinsic neuromuscular disorders. On the other hand, patients with abnormal respiratory workloads have pulmonary disorders or extrapulmonary thoracic disorders. Fig. 77-1 shows a classification of the abnormalities of respiratory loads and capacity. Table 77-3 further describes these abnormalities of respiratory mechanics, strength, and gas exchange for specific chronic disorders.

Table 77-3 Basic Physiologic Abnormalities Associated with Hypoventilatory Respiratory Failure

Clinical disorder	Mechanical abnormality	Gas exchange
Central nervous system (CNS) insult	Depressed CNS drive	Secondary hypoventilation and hypoxemia
Neuromuscular disease	Respiratory muscle weakness	Same as above
Chronic obstructive pulmonary disease (COPD)	Increased inspiratory airway resistance	Increased dead space (Vd/Vt)
	Increased expiratory airway resistance	Hypoxemia from ventilation/perfusion ( / ) inequality
	Increased compliance
	Dynamic hyperinflation and intrinsic positive end-expiratory pressure
	Abnormal respiratory muscle length-tension relationship
Asthma	Increased large-airways resistance	Hypoxemia from ( / inequality
	Dynamic hyperinflation	Increased Vd/Vt
	Acute change in respiratory muscle configuration
Interstitial lung disease	Increased elastic loads from parenchymal fibrosis	Increased Vd/Vt
		Hypoxemia from ( / inequality
Thoracic cage deformity	Increased elastic loads from atelectasis and chest wall malformations	Secondary hypoventilation
		Hypoxemia from ( / inequality and hypoventilation

[edit] Central Hypoventilation Syndromes.

Chronic central hypoventilation syndromes include acquired processes that result in an abnormal central respiratory drive to common stimuli, including hypoxemia and hypercapnia. This abnormal central regulation can result from specific vascular or anatomic insults, such as midbrain cerebrovascular accidents (CVAs, strokes) and multisystem atrophy syndrome (Shy-Drager syndrome). Metabolic abnormalities (hypothyroidism being the most common) can also lead to hypoventilation. Some patients with morbid obesity may also have chronic daytime hypoventilation, for which the exact cause is unknown, and severe obstructive sleep apnea syndrome. Daytime hypoventilation may improve with treatment of the sleep abnormalities alone. In patients with obesity-hypoventilation syndrome the Pco₂ can be voluntarily decreased with forced tachypnea. These patients may benefit from respiratory stimulants. In all these disorders, respiratory abnormalities and gas exchange may worsen during sleep. These aggravating sleep abnormalities may require specific evaluation and treatment (Box 77-2).

[edit] Neuromuscular Disorders.

Neuromuscular disorders represent a heterogenous group of acute and chronic disorders (see Box 77-1). These diseases can affect the upper motor neurons, lower motor neurons, peripheral nerves, myoneuronal junction, or the muscle itself. Clinical signs and symptoms and patterns of weakness provide critical clues to the diagnosis. These disorders will lead to respiratory failure when muscles controlling the upper airway or the diaphragm or other respiratory muscles are involved. Chronic disorders include the muscular dystrophies, myopathies associated with polymyositis and the collagen vascular diseases, amyotrophic lateral sclerosis, myasthenia gravis, and those with persistent sequelae of the acute neuromuscular disorders. Some patients with chronic impairments do not experience respiratory symptoms with their everyday activities and only show evidence of mild respiratory muscle weakness on formal pulmonary function testing. However, these chronic, compensated patients are predisposed to early respiratory muscle fatigue with acute illnesses that may lead to acute respiratory failure. In contrast, others have significant exertional dyspnea, exercise intolerance, and symptoms attributable to sleep-disordered breathing. This latter group of patients would likely have chronic CO₂ retention, daytime hypoxemia, and little to no respiratory capacity reserve.

[edit] Obstructive and Restrictive Thoracic Disorders.

These diseases are discussed in Chapters 72 to 76. Certain common diseases are readdressed here with regard to the specific mechanisms leading to their presentation with respiratory failure.

[edit] Chronic Obstructive Pulmonary Disease.

It is estimated that more than 10 million Americans have COPD and that the majority of these patients will die of progressive respiratory failure. Patients with COPD can experience, on average, one to four exacerbations per year. An exacerbation is generally defined as an increase in dyspnea that is persistent for a few days and is not readily reversed with acute bronchodilator treatment. An exacerbation is usually accompanied by increased sputum production, sputum purulence, cough, and wheezing. In those with the most severe forms of disease, these episodes may lead to acute on chronic respiratory failure, which in turn requires hospital admission for treatment. Patients with COPD have a number of abnormalities that predispose them to respiratory pump failure (see Chapter 75 and Table 77-3). As a result, the patient with advanced COPD has a limited and often precarious reserve of respiratory capacity.

Box 77-3 lists common causes of a COPD exacerbation and other aggravating conditions that can lead to acute respiratory failure. Overall, more than 50% of COPD patients over age 50 have a coexistent cardiovascular disease. Therefore early recognition of cardiac disease and cor pulmonale is important for directing other specific therapy. Signs of pulmonary hypertension are often difficult to discern in the patient with COPD. Edema is more readily apparent and suggests decompensated cor pulmonale in this patient population.

The severity of the patient's condition can be assessed by evaluating pulmonary function tests (PFTs), exercise capacity, and ABGs; examining for the presence of cor pulmonale; and documenting the frequency of exacerbations and hospital admissions. Recent reports indicate that the mortality rate for COPD patients requiring an intensive care unit (ICU) is only approximately 10%. Furthermore, mortality among patients with COPD who require ICU care for acute respiratory failure is no greater than that observed in patients matched for comparable degrees of respiratory impairment. Previous studies reported a 40% 2-year survival, however, after patients with COPD experienced their first episode requiring mechanical ventilation. Consequently, decisions about when to forego or limit mechanical ventilation remain difficult. A rational decision can often be made with patients using the previous information in conjunction with their beliefs and attitude toward their illness.

[edit] Interstitial Lung Disease.

Patients with interstitial lung disease, especially idiopathic pulmonary fibrosis (IPF), often experience life-threatening respiratory complications, and many will unfortunately die of primary respiratory failure. Right ventricular failure due to pulmonary hypertension and cor pulmonale also contribute to the morbidity and mortality of these patients. Some patients with certain forms of interstitial lung disease, however, may exhibit mild to severe restrictive functional impairment and have a very stable respiratory status over a period of years. This latter course has been frequently described in patients with collagen vascular diseases. (see Chapter 76 ). The physiologic abnormalities include predominantly increased elastic loads that encroach on respiratory capacity, and these patients adopt breathing patterns that seek to decrease the work of breathing (see Table 77-3). Consequently, they function with little respiratory capacity reserve, and events that increase the work of breathing or compromise respiratory muscle strength can quickly lead to respiratory failure.

Common causes of deterioration in patients with interstitial lung disease include pulmonary infection, worsening pulmonary hypertension, decompensated cor pulmonale, and pneumothorax. This latter complication can be more recurrent and troublesome in these patients. Cardiovascular complications, bronchogenic carcinoma, and pulmonary embolism also need to be considered. Other specific causes of deterioration in these patients include adverse reactions to treatment with corticosteroids or cytotoxic agents and opportunistic infections. Fortunately, opportunistic infections still occur infrequently in this patient population despite the frequent use of corticosteroids and immunosuppressive agents. Many of these complications are associated with a more insidious disease process. Others, such as pulmonary embolism, pneumothorax, dysrhythmias, and infection, can be associated with abrupt clinical deterioration. Diagnostic evaluation and treatment need to be approached accordingly.

[edit] Thoracic Cage Abnormalities.

Patients with severe kyphoscoliosis or thoracic cage deformities from trauma or surgery have decreased thoracic compliances primarily because of chest wall abnormalities and associated atelectasis. Given the abnormal configuration of the chest wall, cough and secretion clearance are also compromised. The high-energy cost of breathing from the increased elastic loads results in a pattern of rapid, shallow respirations. Chronic hypoventilation and secondary hypoxemia are common in these patients. Secondary cor pulmonale from hypoxemia and pulmonary vascular remodeling are frequently present. These disorders are also associated with many different respiratory abnormalities during sleep. These patients may have severe central apneas and hypopneas or obstructive events. These abnormalities are worse during rapid eye movement (REM) sleep and can be prolonged and associated with severe O₂ desaturation. These patients may be stable for years and then present with respiratory failure after minor insults such as a viral upper respiratory infection or illnesses that lead to mild decreases in muscle strength.

[edit] Diagnostic Evaluation

[edit] Arterial Blood Gases and Pulse Oximetry.

Early evaluation of gas exchange by ABG analysis is important. The initial measurement of O₂ saturation by pulse oximetry is not sufficient in patients with a chronic respiratory disorder. Accuracy of these devices can vary by up to 5%, and falsely elevated arterial hemoglobin O₂ saturation (Sao₂) values obtained by pulse oximeters can be seen in smokers with elevated carboxyhemoglobin levels. Furthermore, Sao₂ tells the physician nothing about ventilation and the level of Paco₂. Attention to the pH associated with changes in Paco₂ is essential to make correct assessments of the acute gas exchange abnormalities. A pH that cannot be expeditiously corrected to above 7.20 with treatment often signals the need for mechanical ventilatory support. Hypoxemia in these chronic disorders is usually caused by ( / inequality and can be corrected with supplemental Fio₂ gas delivered at a sufficient flow. More severe hypoxemia heralds a complicating pneumonia or cardiac failure.

[edit] Radiologic Studies.

A chest radiograph should be obtained early in all patients to rule out a pneumothorax, confirm the presence of a pneumonia, or detect signs of cardiogenic pulmonary edema. Additionally, the chest film can provide evidence of pulmonary hypertension if there is increased dilation of the pulmonary arterial tree. The value of chest radiograph, computed tomography (CT) scan, and high-resolution CT scan of the thorax in patients with interstitial lung disease is discussed in Chapter 76 . In the patient with severe kyphoscoliosis the chest film can be difficult to interpret, and a chest CT scan may be necessary to evaluate the lung parenchyma adequately. Imaging studies should be considered for the evaluation of deep venous thrombosis and pulmonary embolism if no other apparent cause of respiratory failure is readily discernible (see Chapter 80 ). If necessary, lower extremity duplex Doppler ultrasound and lung perfusion scan can be done at the patient's bedside in most institutions.

[edit] Other Studies.

An electrocardiogram (ECG) is necessary to rule out a dysrhythmia or cardiac ischemia early. Multifocal atrial tachycardia (MAT) is one of the dysrhythmias encountered in this patient group. Early recognition of MAT may lead to a reversal of its metabolic causes and may avoid potentially harmful and ineffective therapy typically used for other supraventricular dysrhythmias. Unfortunately, the ECG is not sensitive (approximately 33%) in detecting cor pulmonale in the COPD patient population. An echocardiogram is more accurate in this regard and is also sensitive for the detection of pulmonary hypertension and cor pulmonale in other chronic cardiopulmonary disorders. Measurements of respiratory muscle strength, spirometry, and lung volumes can be useful if the patient is able to cooperate and reproducible values can be obtained. Emergency clinical decisions are made without these measurements, however, and the physician must rely more on an assessment of the patient's clinical status and gas exchange. Evaluation for bronchitis and pneumonia should follow the guidelines in Chapter 73 . Sputum Gram's stain and culture and blood cultures before antibiotic therapy are essential initial studies. Bronchoalveolar lavage (BAL) and perhaps transbronchial biopsy or open lung biopsy should be undertaken when opportunistic infection needs to be ruled out, most often in the immunocompromised patient. Indications for BAL, transbronchial biopsy, and open lung biopsy in the patient with interstitial lung disease are discussed in Chapter 76 .

[edit] Nocturnal Oximetry and Sleep Studies.

Nocturnal oximetry alone is most often used to detect significant nocturnal desaturation during sleep in patients with chronic pulmonary disorders. Patients with severe limitation or evidence of pulmonary hypertension or cor pulmonale are the best candidates for screening. Desaturation in these conditions usually occurs from worsening ( / inequality or hypoventilation during REM sleep and is readily treated with supplemental O₂. In patients with suspected primary or secondary severe respiratory abnormalities during sleep, however, a four-channel or full polysomnogram is indicated. These studies also include pulse oximetry.

[edit] Treatment

[edit] Oxygen Therapy.

Acute O₂ therapy is often mismanaged in patients with chronic pulmonary disorders because of the concern about the known association between supplemental O₂ and further hypercapnia and respiratory acidosis. Ongoing hypoxemia, however, can result in severe end-organ damage and lead to rapidly progressive deterioration in respiratory muscle and cardiac function. Therefore O₂ should be provided in sufficient amounts to achieve an Sao₂ of at least 85% and preferably 90% saturation. Care must be taken not to decrease or to discontinue supplemental O₂ abruptly if Pco₂ is high, since this may result in a precipitous fall in Po₂. In most instances the Pco₂ will not rise more than 20 mm Hg, and therefore the pH will likely remain above the 7.20 to 7.25 range. If adequate Sao₂ cannot be met without resulting in severe hypercapnia and acidosis, the patient should be assessed for the need for assisted ventilation.

Long-term O₂ therapy (LTOT) has been well studied in the COPD patient population and increases quality of life and survival (see Chapter 75 ). Guidelines for COPD patients are also generally used for patients with other conditions causing chronic hypoxemia, although no similar multicenter trials have documented increased survival in these other groups. Intermittent O₂ therapy for desaturations that occur only at night or during exertion is less studied, and its benefits are not well documented. Nocturnal and exertional desaturation should be treated in patients with chronic pulmonary disorders, however, especially if the patient has any signs of pulmonary hypertension, cor pulmonale, or other coexistent cardiovascular disorder.

[edit] Pharmacologic Treatment.

The standard accepted treatment approach for the patient with an exacerbation of COPD includes (1) maximal inhaled bronchodilator therapy with β₂-agonists and ipratropium bromide alone or in combination; (2) intravenous (IV) corticosteroids in initial doses equivalent to methylprednisolone, 0.5 mg/kg every 6 hours; (3) empiric antibiotics to cover common bacterial pathogens; (4) titrated O₂ therapy; and (5) electrolyte and nutritional supplementation. Theophylline is generally avoided acutely because of associated toxicities. The true efficacy of corticosteroids in this situation is debated, but little harm has been attributable to therapy with the above doses.

Specific pharmacologic treatment for progressive interstitial lung disease in the patient with acute on chronic respiratory failure has unpredictable effects, and unfortunately, benefit is often limited. Patients likely to respond to therapy are usually at a less precarious stage of their disease, and improvement is usually noticed after weeks of treatment. Corticosteroids and cyclophosphamide are typically prescribed for these patients. High-dose corticosteroids are indicated in the patient who experiences rapid deterioration soon after discontinuing or tapering corticosteroids. Other causes of respiratory failure that may mimic progressive interstitial lung disease need to be pursued and treated accordingly. These conditions most often include bacterial, viral, and opportunistic infections or left ventricular failure. Specific treatments for decompensated cor pulmonale may allow stabilization and significant improvement of the patient's condition (see Chapter 80 ).

[edit] Noninvasive Ventilation and Long-term Respiratory Aids.

Noninvasive ventilation has been studied extensively over the last 10 years and has become an important advance in the treatment of patients with acute or chronic respiratory failure, acute pulmonary edema, and sleep-related breathing disorders. Box 77-4 lists the relative contraindications for noninvasive ventilation.

Respiratory assist devices and noninvasive ventilator strategies have been extensively used in patients with chronic neuromuscular impairments and are of proven benefit and generally well tolerated. These treatments can improve daytime Paco₂, decrease dyspnea, resolve symptoms attributed to sleep-disordered breathing, decrease hospitalizations, and improve survival in certain patient groups. Chronic support is frequently provided by positive-pressure assist devices, including intermittent ventilation, conventional ventilation by a tracheotomy or nasal mask, and bilevel positive-airway-pressure (BiPAP) device, also delivered by a nasal adapter. These machines are used intermittently throughout the day or just nocturnally. Other assist devices include rocker beds and externally applied negative-pressure respiratory devices, with the latter rarely used. %Patients with thoracic cage disorders can also benefit from noninvasive respiratory assistance with positive-pressure ventilation, typically delivered by nasal mask. Occasionally the patient must undergo a tracheotomy, and the intermittent ventilatory support must be delivered through the tracheotomy tube. Prolonged improvement in compliance and gas exchange has been reported after brief, intermittent pressure-assisted inflations, which appear to reverse underlying atelectasis. Daytime gas exchange and nocturnal desaturation improve with long-term use of nocturnal or intermittent ventilatory assistance. Noninvasive ventilation is less well tolerated in patients with chronic respiratory failure from parenchymal lung diseases. However, noninvasive positive- pressure assistance can be provided intermittently and at night for select patients. The assist device is usually indicated for relief of symptoms caused by progressive hypercapnia.

[edit] Pulmonary Rehabilitation.

A comprehensive discussion of the proven benefits and costs of pulmonary rehabilitation is beyond the scope of this chapter. Despite being considered essential and routine at some centers, this therapy has not been uniformly accepted by the medical community. However, these programs are integral to any lung transplantation or lung volume reduction surgery program. Pulmonary rehabilitation programs select for the most motivated patients, who in turn derive benefit in terms of increased exercise tolerance and physical conditioning, along with an improved quality of life and increased sense of well-being. Often, however, no other systematic improvements occur in pulmonary function, and no survival benefit has been shown. Variabilities in application and reimbursement and the failure of many patients to quit smoking are important obstacles that impede uniform successful utilization of pulmonary rehabilitation programs for the patient with a chronic pulmonary disorder.

[edit] Lung Transplantation.

Heart-lung, double-lung, and single-lung transplantation are now options for patients with end-stage respiratory failure. Patients who are candidates are generally less than 65 years of age, are free of any significant systemic disorder, and have a poor prognosis related primarily to their underlying lung disease. Patients with COPD, end-stage emphysema from α₁-antitrypsin deficiency, cystic fibrosis, IPF, primary pulmonary hypertension, and pulmonary hypertension secondary to congenital heart defects have accounted for the vast majority of recipients to date. Detailed guidelines for recipient selection have been proposed. Patients with IPF, primary pulmonary hypertension, and cystic fibrosis have the highest mortality rates while awaiting transplantation; early referral of these patients is recommended. The time on the waiting list often exceeds 1 year. Therefore prolonged mechanical ventilatory support is not recommended for potential recipients, although some patients are now receiving transplants after being maintained on mechanical ventilation immediately before transplant.

The 1-year and 2-year posttransplant survival of these patients is about 80% and 70%, respectively. Early mortality is related to immediate postoperative complications and infections. Later mortality is seriously complicated by rejection and bronchiolitis obliterans. Recurrence of the underlying disease has been reported in sarcoidosis, lymphangioleiomyomatosis, giant cell interstitial pneumonitis, and eosinophilic granuloma. The number of lung transplants is increasing worldwide, but experience is more limited with lung transplantation relative to other common organ transplants due to (1) more limited donor acceptability because of pulmonary infection and other environmental exposures and (2) prior complications related to the bronchovascular blood supply and anastomotic healing. Long-term survival remains imperiled by chronic rejection, which manifests as bronchiolitis obliterans. Despite these limitations and the involved posttransplant medical regimen, lung transplantation has allowed for improved quality of life with prolonged survival for many recipients. It is hoped that experience, research, and technical advancements will make this a more successful and less costly option for patients in the future.

[edit] ACUTE RESPIRATORY FAILURE

[edit] Pathophysiology and Differential Diagnosis

Acute respiratory failure is often discussed in terms of the predominant gas exchange abnormality that occurs in the affected patient, that is, acute hypoventilatory failure and acute hypoxemic failure. The chronic lung disorders most often lead to hypoventilatory failure because of acute on chronic respiratory failure, as discussed earlier. In addition, diseases that acutely impair respiratory capacity (CNS drive, neuromuscular strength) also lead to hypoventilation and respiratory acidosis. In contrast, acute hypoxemic failure most often results from an acute parenchymal lung insult that may lead to life-threatening hypoxemia, even in the normal host.

[edit] Acute Hypoventilatory Respiratory Failure.

A failure of ventilation with acute respiratory acidosis represents the predominant abnormality in a number of disorders. In patients with chronic restrictive or obstructive disorders, respiratory muscle fatigue ensues because of further increases in respiratory workloads or from causes that impair the respiratory muscles themselves. Acute asthma will also lead to respiratory muscle fatigue and hypoventilatory failure if the acute, severe bronchospasm cannot be expeditiously reversed. Neuromuscular disorders are not associated with any increased workloads but rather with a decreased capacity. Furthermore, diseased muscles are more prone to early failure leading to hypoventilation. In all these disorders, hypoxemia is often present as well but is caused by ( / inequalities and is often easily corrected with supplemental O₂ at low Fio₂ concentrations.

[edit] Acute on Chronic Respiratory Failure.

The common causes of acute deteriorations in patients with chronic obstructive and restrictive thoracic disorders are discussed in the section on chronic failure. Most often, these patients present with hypoventilatory failure and hypoxemia. However, the hypoventilatory failure is usually the predominant abnormality and is the reason most require mechanical ventilatory support. If the hypoxemia is not readily reversible, causes of hypoxemic respiratory failure, such as pneumonia and cardiac failure, should be suspected.

[edit] Asthma.

Fortunately, only a minority of patients with asthma will develop respiratory failure requiring mechanical ventilatory support. An estimated 4% of hospitalized asthmatic patients will require observation in the ICU, however, and the incidence of near-fatal and fatal asthma has increased in the United States and other countries. Patients with chronic severe disease, steroid dependency, undertreatment, and prior intubation are at particular risk for a severe exacerbation of their asthma. Underuse of corticosteroids and frequent daily treatment with inhaled β₂-agonists have also been associated with near-fatal and fatal presentations. Any asthmatic patient, however, can develop a severe, life-threatening episode of acute bronchospasm, at times linked to acute exposures to specific agents (see Chapter 72 ). Although significant morbidity and mortality are associated with positive-pressure ventilation, ventilator strategies designed to minimize barotrauma and adverse cardiopulmonary interactions have resulted in a very low mortality rate but significant remaining morbidity. Therefore prompt optimization of treatment during a severe exacerbation, careful monitoring for signs of compromise, and judicious use of assisted ventilation are important.

Asthmatic patients have certain physiologic abnormalities (Table 77-3), and common findings are associated with an asthma exacerbation (see Chapter 72 ). Diaphoresis, tachycardia greater than 120 beats/min, a pulsus paradoxus greater than 15 mm Hg, persistent dyspnea at rest, agitation and frequent repositioning, fragmented speech, and delirium are alarming signs of a severe exacerbation of asthma. Barotrauma is a serious complication and is indicated on physical examination by subcutaneous emphysema, tracheal deviation on palpation, and a mediastinal crunch or focal absence of breath sounds on auscultation. When signs and symptoms of a severe attack persist after early aggressive treatment, the condition is often referred to as status asthmaticus.

[edit] Upper Airways Obstruction.

The primary physician may have difficulty distinguishing asthma from mechanical obstruction of the large airways, and the consequences of this missed diagnosis can be severe for the patient. Stridor, or a high-pitched inspiratory wheeze during inspiration, is a critical finding for the patient with a variable, extrathoracic lesion or a fixed trachea or major airways abnormality. If the large-airways obstruction is intrathoracic and is variable, or if it only occurs with expiration, it is often difficult to distinguish from common expiratory wheezing. Often these intrathoracic lesions are caused by bronchogenic carcinoma and occur in patients with underlying obstructive disease. Clues to a major airways obstruction in these patients include focal wheezes and wheezes that are heard best in the upper lung fields relative to the more peripheral areas. Gas exchange abnormalities usually only occur when these lesions are advanced and the narrowing is quite severe. Therefore early diagnosis based on clinical findings is required to avoid acute complications and the need for an emergency surgical airway.

Acute infectious processes leading to stridor from extrathoracic airway obstruction include epiglottitis, supraglottitis, and parapharyngeal abscesses. Symptoms and signs accompanying these acute processes help distinguish them from other causes of upper airway obstruction, which predominantly include tumors of the thyroid, trachea, and major bronchi. Vocal cord paresis, vocal cord dysfunction, and tracheal stenosis from prior intubation are other notable causes.

[edit] Depressed Central Nervous System Drive and Acute Neuromuscular Disorders.

Acute insults to the CNS can impair the respiratory control and integrating center, resulting in ineffective transmission of efferent neurologic impulses to the muscles of respiration. Cranial nerve function and reflexes also may be impaired, leading to aspiration of oropharyngeal secretions. The result is acute hypoventilation, atelectasis, and aspiration pneumonia. Drug overdoses, metabolic encephalopathies, CVAs, and trauma are common causes of hypoventilatory failure. Seizures can also lead to respiratory insufficiency by central depression of the respiratory drive and by respiratory muscle dysfunction. Generalized or partial status epilepticus may also present with generalized, flaccid paralysis or a confusional state, respectively. Furthermore, the pharmacologic agents used to treat convulsions often suppress respiratory drive.

In disorders leading to acute neuromuscular failure (see Box 77-1), patients may have a history that indicates a definite process (e.g., bite, ingestion), or they may show a characteristic pattern of weakness that can help the physician to identify a specific disorder. Symptoms and signs of cholinergic excess can be seen with organophosphate poisoning and cholinergic crisis in patients with myasthenia gravis who are taking cholinesterase inhibitors. Signs include miosis, nausea and vomiting, excess salivation and diaphoresis, bronchorrhea, and bronchoconstriction. Clostridium tetani toxin causes local or generalized muscle rigidity and painful spasms. Sensory deficits should alert the physician to a spinal cord injury or compression or a generalized myelitis. An urgent workup should be undertaken to rule out these latter possibilities and circumvent further neurologic damage. Acute CVAs causing hemiparesis, including the muscles of respiration, do not usually lead to respiratory failure unless there is coexistent cardiopulmonary disease.

[edit] Acute Hypoxemic Respiratory Failure.

In contrast to the causes of hypoventilatory failure, disorders associated with acute hypoxemic failure are often the result of an acute, severe, pulmonary insult (Box 77-5). These insults are sufficient to cause respiratory failure even in patients with previously normal pulmonary function, and life-threatening hypoxemia is often present. Hypoxemia may not be readily corrected with supplemental O₂ by face mask because it is often the result of “shunting.” Therefore these patients may require prompt mechanical ventilation with settings that reduce the “shunt” and increase Pao₂ to mitigate the adverse effects of tissue hypoxia. Because of the occasional prolonged need for high-Fio₂ supplementation, the potential for oxygen toxicity arises. It is not a serious consideration, however, when Fio₂ is less than 0.60 or if levels as high as 1.00 are given for less than 48 hours.

These disorders can be further divided into diffuse and focal processes. This distinction quickly directs the physician's attention to different sets of causes, diagnostic strategies, and treatment. Diffuse lung lesions are usually associated with more pronounced hypoxemia and mechanical abnormalities. Once cardiogenic pulmonary edema is ruled out, ARDS or diffuse lung infection must be considered. Diffuse alveolar hemorrhage is much less common but must not be overlooked. Focal lesions often result from obvious causes. Although hypoxemia is usually less severe than in the diffuse lesions, it may be disproportionate to the degree of lung involvement. Atelectasis is a common focal lesion that can complicate any of these respiratory disorders and should always be considered in any patient with a sudden decline in oxygenation (Fig. 77-2).

Figure 77-2 A, Admission anteroposterior chest radiograph of man being monitored for exacerbation of COPD. He required intubation and later developed acute hopoxemia. B, Repeat chest film revealed silhouette sign of left hemidiaphragm consistent with left lower lobe atelectasis. Oxygenation improved quickly, with reversal of atelectasis.

[edit] Diffuse Processes

[edit] Adult respiratory distress syndrome.

ARDS has many different causes; an estimated 150,000 cases occur annually in the United States. Table 77-4 shows the variation in incidence and mortality among predisposing disorders. Twenty percent of patients with ARDS will experience a primary respiratory death. The mortality rate associated with ARDS has decreased, and younger patients (less than 60 years old) now do much better. Many patients who die from ARDS will succumb to infectious complications and multiorgan system dysfunction. The need for prolonged mechanical ventilation is a likely contributor to the increased incidence of infectious complications and death in these individuals.

Table 77-4 Selected Causes of Adult Respiratory Distress Syndrome (ARDS)

✢Rate among predisposed groups.

†N/A, Not available.

‡Only alveolar hemorrhage reported; see Box 77-5 and text.

ARDS is clinically defined by a limited number of diagnostic criteria that have been slightly modified since the early description of the syndrome. Current criteria for ARDS include (1) compatible clinical history and presentation of a severe lung injury, (2) signs of respiratory distress (tachypnea, dyspnea), (3) severe hypoxemia (Pao₂ less than 50 mm Hg with Fio₂ greater than 0.6, or Pao₂/Fio₂ less than 200), (4) chest x-ray findings with bilateral infiltrates (Fig. 77-3), (5) exclusion of other causes (cardiogenic edema, progressive chronic respiratory failure), and (6) normal pulmonary capillary wedge pressure (PCWP) or no evidence for left atrial pressure elevation. Given the variability in presentation, severity, and course of ARDS, an expanded definition includes (1) a predisposing condition, (2) a lung injury score using physiologic parameters (chest film, Pao₂/Fio₂, PEEP, compliance), and (3) phase of the lung injury (acute or chronic). The criteria reflect a common injury response of the lung to a variety of insults. Box 77-6 lists these common pathophysiologic processes and the phases of ARDS. The key pathophysiologic abnormality is an increase in alveolar- capillary permeability. The Starling equation (see next) describes the forces governing capillary fluid filtration. Normally the hydrostatic forces favor fluid flux out of the capillary and into the perivascular tissues. This movement is usually counterbalanced by the oncotic forces that keep colloid in the vessels and favor fluid movement into the vascular space. The lung injury of ARDS results in an increase in the filtration coefficient, Kf, as follows:

Figure 77-3 A, Chest radiograph of 26-year-old male who developed confusion and ARDS 48 hours after intramedullary rodding procedure for femur fracture. B, Pulmonary artery catheter was placed to aid hemodynamic management. With diuresis the calculated shunt decreased from 35% to 20% over 48 hours, and patient was extubated shortly thereafter.

Capillary fluid flux (edema formation)=

Kf [(P_vascular − P_tissue) − (π_vascular − π_tissue)σ]

where Kf is the filtration coefficient; σ is the reflection coefficient; P is the hydrostatic pressure; and π is the oncotic pressure. Increases in Kf encourage the flow of fluid into the interstitium and alveolar spaces. ARDS is also associated with a decrease in σ, from almost 1 to near 0. This parameter measures the efficiency of plasma proteins in returning fluid to the vasculature; σ decreases as the capillary membrane becomes more permeable to protein. These effects of ARDS result in the formation of exudative pulmonary edema at normal hydrostatic pressures.

In contrast, cardiogenic edema is caused by an increase in capillary hydrostatic pressure that results in the transudation of fluid into the tissues and air spaces of the lungs. Kf and σ remain normal under these conditions. The excess filtered fluid is initially located in the peribronchial tissue space and causes alveolar flooding only if this compartment is overwhelmed. This provides an additional safety factor with cardiogenic edema, unlike increased permeability states, since gas exchange and mechanical abnormalities are only appreciable when edema causes alveolar flooding. When cardiogenic edema results in respiratory failure, the gas exchange and mechanical abnormalities are similar to those seen in early ARDS.

A number of mediators have been implicated in the cellular injury, interstitial inflammation and fibrosis, and pulmonary and systemic hemodynamic changes seen in ARDS (Box 77-7). Survivors of ARDS often recover remarkably. Some patients with the most severe lung injury can recover pulmonary function to within their normal predicted limits. Others may sustain a moderate decrease in function. Fortunately, the vast majority of survivors are not troubled by symptomatic respiratory insufficiency, although neuropsychiatric dysfunction and other limitations may impair their overall health after recovery.

[edit] Alveolar hemorrhage syndromes.

Alveolar hemorrhage can lead to hypoxemia and can be associated with diffuse or focal hemorrhage (Fig. 77-4 and Box 77-8). Diffuse, fulminant alveolar hemorrhage can quickly lead to respiratory failure and death. The triad of hemoptysis, pulmonary infiltrates, and anemia is well described. Since the hemorrhage is distal to the ciliated central airways, however, hemoptysis may be scant or even absent. Patients also often have constitutional or other symptoms suggestive of a systemic disorder. Early recognition allows prompt treatment to prevent severe morbidity from fulminant alveolar hemorrhage, progressive renal failure, and severe anemia. Increasing infiltrates in the face of a rapidly declining hematocrit with no other source of bleeding affords good presumptive evidence of pulmonary hemorrhage. Patients are often misdiagnosed as having an unresolving pneumonia with associated mild hemoptysis and are often treated with repeated antibiotic courses if their disease is mild at onset. Hypoxemia from shunt or increased venous admixture is quite common. If the process is diffuse, patients have the constellation of gas exchange and mechanical abnormalities that also affects patients with ARDS.

Figure 77-4 Anteroposterior chest radiograph (A) and select view of CT scan of lung (B) of 37-year-old male with acute, severe alveolar hemorrhage from limited Wegener's vasculitis. Widespread dense consolidations with upper zone predominance were greatly increased from previous 36 hours, and hematocrit also decreased by 10%. Severe hypoxemia was corrected by using 60% Fio₂ gas by face mask.

[edit] Focal Processes

[edit] Lobar pneumonia.

Patients with lobar or multilobar pneumonia can have life-threatening hypoxemia without developing ARDS. Hypoxemia can be particularly pronounced when the pneumonia is most extensive in the well-perfused, gravity-dependent lung units. In addition, the venous admixture or shunt can be disproportionately elevated relative to the percentage of lung involved, if hypoxic pulmonary vasoconstriction is reversed by other vasoactive mediators of inflammation. Bacterial infection is by far the most likely cause of these consolidative processes (see Chapter 73 ).

[edit] Atelectasis.

This occurs frequently in patients receiving mechanical ventilation with higher Fio₂ gas. Problems with secretion clearance and prolonged supine positioning often lead to left and right lower lobe atelectasis. These changes can often be appreciated on routine daily chest films (see Fig. 77-2). Resorption atelectasis is promoted by high PAo₂ values and low ( / ratios. At high levels of Fio₂, atelectasis of large lung unit areas can be radiographically apparent within minutes and cause hypoxemia from shunting. This needs to be considered in any patient with an abrupt change in Pao₂ without any other apparent clinical cause. Accurate recognition and treatment can quickly reverse the deterioration in Pao₂, can avoid prolonged higher levels of Fio₂ that further predispose to atelectasis, and can obviate the need for investigations into other potential causes of sudden O₂ desaturation, such as pulmonary embolus.

[edit] Diagnostic Evaluation

Arterial blood gases are necessary to determine the severity of hypoxemia and adequacy of ventilation. Once the patient is stable and has achieved an acceptable Sao₂, pulse oximetry can be used to assess the adequacy of oxygenation. The pulse oximeter needs to be intermittently correlated to ABGs. The Paco₂ needs to be measured independently according to the patient's clinical course. Serial ABGs are often necessary for the early evaluation of the patient with a severe asthma exacerbation or acute on chronic respiratory failure. Most patients initially have a respiratory alkalosis. A normal Paco₂ in a patient with persistent signs of respiratory distress indicates the potential for impending respiratory muscle fatigue and exhaustion. As the patient's clinical status improves, the Paco₂ will also naturally normalize. Therefore interpretation of laboratory data always requires close correlation with the patient's clinical condition. A progressively rising Paco₂ in the face of increasing respiratory efforts or signs of fatigue and exhaustion are common indications for assisted ventilation. No specific Pco₂ value, however, is sufficient to make a decision regarding mechanical ventilation without clinical correlation. The ABG may also show evidence of a metabolic acidosis, and the patient's ventilatory requirement may be increased accordingly.

An initial chest radiograph is warranted to delineate the pattern of abnormal pulmonary parenchymal processes, evaluate for pleural abnormalities, and provide information regarding any coexistent cardiac abnormality. Further thoracic imaging is usually not needed in the vast majority of cases. In addition to direct visualization, fluoroscopy and CT imaging of the thorax and neck are helpful in patients with upper airway lesions. Magnetic resonance imaging (MRI) or CT scans of the head are required for patients who have persistent, unexplained focal neurologic abnormalities and depressed CNS drive as the cause of their respiratory failure. Abdominal imaging may be necessary in the patient with ARDS and a likely undiagnosed infection. The lungs and abdomen are the most common sites of infection associated with ARDS.

For the acute neuromuscular disorders the history and clinical pattern of presentation are critical. In some conditions, such as tetanus, they may provide the sole means for diagnosis. Early assessment of respiratory function is essential, and respiratory failure represents the most life-threatening abnormality in these patients. Respiratory muscle weakness does not directly correlate with peripheral muscle strength and needs to be directly assessed (see following discussion). Some patients with Guillain-Barré syndrome may develop apnea at any time during their acute presentation. Therefore these patients require 24-hour monitoring until they start to improve. Early ICU care is justified in other conditions with signs of significant respiratory muscle involvement. ICU care has been clearly shown to decrease mortality in these patients, and a pulmonary or critical care consultant should be contacted early for assisting with respiratory care. Acute ABG abnormalities are a late sign of respiratory insufficiency in these patients. Therefore measurements of strength and mechanics should also be used to determine the need for ICU care. Acute hypercapnia and hypoxemia signal the need for ventilatory assistance.

Bedside measurements of respiratory muscle strength can be performed reproducibly by trained respiratory therapy personnel. Abnormalities of maximal inspiratory and expiratory pressures (MIP, MEP) are the most sensitive tests for respiratory muscle weakness. A MIP less than 15 to 20 cm H₂O is often incompatible with adequate ventilation. The MEP is generated by those muscles that can be recruited for active expiration and cough. A MEP less than 40 cm H₂O is associated with abnormal cough and clearance of respiratory secretions. Inability to clear respiratory secretions and an inadequate cough are common reasons for continued ventilation and reintubation in these patients. The forced vital capacity (FVC) determination is also useful. Values less than 30 ml/kg predispose to atelectasis; values less than 10 ml/kg, or approximately 1 L, are associated with inadequate ventilation. Bedside measurements of strength and volume should be done frequently throughout the day in the patient with an acute illness. Once the patient is at a stable, predictable level of function, treatments can be continued with less monitoring. The edrophonium test is recommended for the diagnosis of myasthenia gravis, but it can be positive in botulism as well.

Peak expiratory flow rates can be useful in the patient with acute asthma, but these data only complement careful clinical assessment (see Chapter 72 ). Values less than 100 L/min or decreased peak flow rates that increase by less than 10% after initial inhaled bronchodilator therapy indicate a severe attack. Patients who do not show significant improvement within the first 1 to 2 hours of treatment require close observation until consistent clinical improvement is noted on a stable treatment regimen. This observation may need to occur in the ICU setting. The flow-volume loop and airways resistance measurements can be helpful in identifying upper airway obstruction. Spirometry and ABGs alone will not identify lesions that cause variable obstruction only during inspiration.

In patients with pneumonia and risk factors or exposures that suggest an opportunistic infection or atypical pneumonia, more definitive diagnostic studies can be pursued. Bronchoalveolar lavage (BAL) can help to diagnose Pneumocystis carinii pneumonia and mycobacterial and fungal infections. Careful examination of the sputum and BAL results in a high yield for the diagnosis of blastomycosis when it leads to ARDS. The yield of sputum and BAL for other fungal infections and for miliary tuberculosis is less certain, and histologic tissue analysis may need to be pursued. Transbronchial biopsy carries a substantial risk of a complicated pneumothorax in a patient supported with mechanical ventilation and high cycling pressures. Open lung biopsy may need to be pursued to confirm or exclude these opportunistic and atypical pulmonary infections.

Fingerstick and serum glucose, basic chemistry and electrolyte panel, urine and blood toxicology screens, and specific serum drug levels are particularly valuable soon after the patient with depressed CNS drive arrives at the hospital. The ABG and electrolyte panel may provide early evidence of a severe underlying metabolic problem with life-threatening acid-base abnormalities. In patients with pulmonary or alveolar hemorrhage syndromes, serial blood counts, urinalysis, and biopsy of a suspicious skin lesion are studies that can be done promptly. Serologic tests should include the antinuclear antibody (ANA), anti–basement membrane antibody, and antineutrophil cytoplasmic antibody (ANCA). The ANCA can be very helpful in confirming a diagnosis of Wegener's vasculitis or an ANCA-associated vasculitis. Transbronchial biopsy is usually not helpful in making a specific histologic diagnosis with the immune alveolar hemorrhage disorders, but an open procedure can be considered for diagnosis.

[edit] Treatment: Pharmacologic and Supportive Care

[edit] Acute Hypoventilatory Respiratory Failure

[edit] Acute Central Nervous System and Neuromuscular Disorders.

Treatment of ingestions may promptly restore consciousness and correct respiratory insufficiency. Rapid recovery may follow the administration of glucose, naloxone, and flumazenil for hypoglycemia, narcotic overdose, and benzodiazepine overdose, respectively. Flumazenil is useful for documenting benzodiazepine overdose but is not recommended in this general patient population because of its propensity to cause seizures. Other toxicology and critical care sources should be consulted for additional guidelines for treatment of these disorders.

The most immediate life-threatening abnormality in these conditions is respiratory insufficiency and hypoventilation. If patients have not responded promptly to a specific antidote or treatment, they should be expeditiously evaluated for airway protection and respiratory support (Box 77-9; see section on mechanical ventilation). Neurologic consultation is needed for all patients in whom a specific diagnosis is not readily apparent. Pulmonary or critical care consultation should be obtained for patients who require prolonged mechanical ventilation, have pulmonary complications, or have persistent problems requiring more expert management in the ICU.

Plasmapheresis for Guillain-Barré syndrome and other specific treatments for these disorders are covered elsewhere in this textbook. Adjunctive preventive therapies are very important for support of these patients. Deep venous thrombosis prophylaxis is essential (see Chapter 80 ). Combination therapy with sequential compression devices and subcutaneous heparin should be strongly considered in patients who cannot raise their legs against gravity. Additional treatments include stress ulcer prophylaxis, prevention of infectious complications, and management of autonomic dysfunction.

[edit] Asthma.

The patient's response to aggressive pharmacologic treatment must be carefully monitored. Specific therapies include aggressive treatment with inhaled bronchodilators and high doses of corticosteroids (see Chapter 72 ). IV aminophylline is generally avoided in the initial treatment of these patients, although ongoing debate surrounds this topic. IV magnesium sulfate, even with normal magnesium levels, may be helpful in improving the status of the patient with an acute exacerbation; however, this reported benefit has not been routinely reproduced. In refractory cases, inhaled general anesthetics and other agents have been employed.

[edit] Acute Hypoxemic Respiratory Failure

[edit] Adult Respiratory Distress Syndrome.

The vast majority of patients with ARDS require mechanical ventilation because of the associated abnormalities (see Box 77-6). The intense supportive treatment needed by these patients requires expertise in mechanical ventilation, management of complications from barotrauma, hemodynamic management, and comprehensive care to avoid infection, gastrointestinal bleeding, and thromboembolic disorders. If these needs cannot be readily met at a certain medical center, it is strongly recommended that the patient be transferred to a center that is so equipped.

Appropriate hemodynamic and fluid management is crucial for the care of ARDS patients. Mechanical ventilation with the associated high levels of positive end-expiratory pressure (PEEP) and mean airway pressure can lead to impaired cardiac filling and a depressed cardiac output. O₂ delivery may fall and tissue hypoxia may ensue even if Sao₂ has been normalized. Volume expansion could lessen the potential for this adverse consequence. Increases in fluid administration and PCWP, however, are associated with increases in edema formation and ventilatory requirements. Diuresis should be initiated and a negative fluid balance targeted if feasible. The physician should consider placement of a pulmonary artery catheter to guide fluid and hemodynamic management if high levels of PEEP are used (greater than 10 cm H₂O) and if hemodynamic instability is present. The goal for fluid management can be simply stated as to achieve the lowest pulmonary capillary filtration pressure associated with an adequate cardiac output and O₂ delivery. Output can be augmented by vasoactive agents to maintain an adequate O₂ delivery. Inotropic agents, such as dobutamine, should be the first-line agents. Increasing cardiac output may increase mixed-venous O₂ saturation and Sao₂ if shunt and O₂ consumption remain constant. This needs to be attempted on a trial-and-error basis, however, because increases in cardiac output may also increase shunt.

Pharmacologic treatments are being studied for ARDS and sepsis syndrome in general. Early administration of short-course, high-dose corticosteroids has been tested in various disorders leading to ARDS. The current consensus is not to give corticosteroids to patients early in their course. Nevertheless, case reports and a small, randomized study indicate that prolonged administration of lower doses of corticosteroids may have some benefit during the fibroproliferative phase of established ARDS in selected patients. Other pharmacologic treatments have failed to improve survival in ARDS and are not recommended. Inhaled nitric oxide given to patients with severe ARDS has decreased shunt, improved oxygenation, and decreased pulmonary artery pressure without systemic hemodynamic effects. No survival benefit has been demonstrated, and study results are pending. Nitric oxide is not approved by the U.S. Food and Drug Administration and is provided as an investigational drug at select medical centers. This therapy may save some patients with severe lung injury who cannot otherwise be oxygenated or who develop severe pulmonary hypertension in association with ARDS.

[edit] Alveolar Hemorrhage Syndromes.

High-dose IV methylprednisolone can ameliorate the ongoing alveolar hemorrhage within 24 hours in most patients with these disorders. Correction of any coagulopathy and thrombocytopenia is an obvious priority. Cyclophosphamide and plasmapheresis can be added for other specific conditions. Prolonged supplemental O₂ may be required for the hypoxemia. If these patients require intubation and mechanical ventilation, they often have widespread hemorrhage, and their ventilator management can follow the guidelines given for the patient with ARDS. The patient must be assisted in the clearance of secretions; in particular, large blood clots may obstruct major airways and endotracheal tubes and may require emergency attention and therapy.

[edit] Atelectasis.

Mechanical and pharmacologic strategies that promote lung inflation and secretion clearance should be vigorously pursued. Previous investigations showed no clear benefit to bronchoscopic treatment vs. these approaches. However, bronchoscopic clearance of tenacious mucus and other materials can be used early in patients with severe hypoxemia and those with unresolving large areas of atelectasis.

[edit] Focal Lesions.

Prolonged administration of supplemental O₂ may be required in these patients. If the shunt is greater than 25%, mechanical ventilation may be necessary to provide adequate oxygenation. The patient can also be positioned more often with the most normal lung units in a gravity-dependent fashion in an attempt to improve ( / matching, but this may lead to atelectasis of these areas. Aggressive chest physiotherapy should be instituted to augment clearance of secretions and inflammatory debris.

[edit] Treatment: Mechanical Ventilation

[edit] Modes.

Once the basic physiologic abnormalities of various disorders causing respiratory failure and the general features of the various modes of mechanical ventilation are understood, it becomes apparent that different modes of therapy may be suitable for the same patient (Tables 77-5 and 77-6). The first principle of using any mode of ventilation is that all operators should be familiar with it.

Table 77-5 Common Modes of Mechanical Ventilation

Table 77-6 Common Ventilator Machine Settings for Disorders Causing Respiratory Failure

✢PEEP added to obstructive disease only in special circumstances.

[edit] Noninvasive Ventilation.

Noninvasive ventilatory strategies have been applied more extensively in patients with acute respiratory failure from various causes over the last 5 years. Recent prospective, randomized studies support the benefit of this strategy for selected patients with an acute exacerbation of COPD. These devices have also assisted select patients in other studied cohorts and have decreased complications relative to invasive ventilation. Assisted ventilation is delivered by nasal BiPAP system or face mask and a conventional mechanical ventilator. Necessary resources, essential monitoring, education, and guidelines for patient selection need to be clarified further before widespread application of this strategy. Randomized, controlled trials have shown noninvasive continuous positive airway pressure (CPAP) to be beneficial for patients with acute pulmonary edema from congestive heart failure (CHF). Most important, CPAP reduces the need for intubation and mechanical ventilatory support. Controlled trials of nasal BiPAP in patients with acute pulmonary edema from CHF showed improvement in respiratory parameters; however, more cardiovascular complications occurred with BiPAP compared with CPAP. Therefore, if used in this patient group, BiPAP should