Classification and Pathophysiologic Aspects of Respiratory Failure

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Classification and Pathophysiologic Aspects of Respiratory Failure

Many types of respiratory disease are capable of impairing the normal function of the lung as a gas exchanging organ. In some cases, the degree of impairment is mild, and the patient suffers relatively few consequences. In other cases, dysfunction is marked, and the patient experiences disabling or life-threatening clinical sequelae. When the respiratory system can no longer function to keep gas exchange at an acceptable level, the patient is said to be in respiratory failure, irrespective of the underlying cause.

The tempo for development of respiratory failure varies depending on the nature of the underlying problem. Many of the diseases discussed so far, such as chronic obstructive pulmonary disease (COPD) and interstitial lung disease, are characterized by a chronic clinical course accompanied by relatively slow deterioration of pulmonary function and gas exchange. However, because of limited pulmonary reserve, patients with preexisting pulmonary disease are also susceptible to episodes of acute respiratory failure, either from an intercurrent illness or from transient worsening of their underlying disease. On the other hand, respiratory failure, generally acute or subacute in onset, can develop in individuals without preexisting lung disease. The initiating problem in these patients is often a primary respiratory illness or a disorder of another organ system complicated by major respiratory problems.

This chapter presents an overview of the problem of respiratory failure and discusses the different pathophysiologic types and consequences of respiratory insufficiency. Chapter 28 addresses a specific form of acute respiratory failure known as acute respiratory distress syndrome (ARDS), which does not require the presence of preexisting lung disease. Chapter 29 considers some principles of management of respiratory failure, as well as specific modalities of current therapy.

Definition of Respiratory Failure

Respiratory failure probably is best defined as inability of the respiratory system to maintain adequate gas exchange. Exactly where to draw the line for adequate gas exchange is somewhat arbitrary, but in a previously normal individual, arterial PO₂ less than 60 mm Hg or PCO₂ greater than 50 mm Hg generally is considered evidence for acute respiratory failure. In the individual with preexisting lung disease, the situation is even more complicated because the patient chronically has impaired gas exchange and abnormal blood gas values.

For patients with normal baseline arterial blood gas measurements, criteria for respiratory failure are PO₂ < 60 mm Hg or PCO₂ > 50 mm Hg.

For example, it would not be unusual for a patient with significant COPD to perform daily activities with PO₂ approximately 60 mm Hg and PCO₂ 50 to 55 mm Hg. By the blood gas criteria just mentioned, this patient is always in respiratory failure, but the condition obviously is chronic, not acute. A look at the patient’s pH value shows that the kidneys have compensated for the CO₂ retention, and the pH is not far from the normal value of 7.40.

At what point is the condition called acute respiratory failure? Certainly, if an acute respiratory illness such as an acute pneumonia develops, the patient’s gas exchange becomes even worse. PO₂ falls further, and PCO₂ may rise even higher. In this case, acute respiratory failure is defined as a significant change from the patient’s baseline gas exchange status. If the patient’s usual arterial blood gases are known, the task is easier. If the blood gases are not known, the pH value can provide a clue about whether the patient’s CO₂ retention is acute or chronic. When a patient is seen initially with PCO₂ 70 mm Hg, the implications are quite different if the accompanying pH value is 7.15 as opposed to 7.36.

Classification of Acute Respiratory Failure

Hypoxemic Type

In practice, it is most convenient to classify acute respiratory failure into two major categories on the basis of the pattern of gas exchange abnormalities. In the first category, hypoxemia is the major problem. The patient’s PCO₂ is normal or even low. This condition is the hypoxemic variety of acute respiratory failure. For example, localized diseases of the pulmonary parenchyma (e.g., pneumonia) can result in this type of respiratory failure if the disease is sufficiently severe. However, an even broader group of etiologic factors causes hypoxemic respiratory failure by means of a generalized increase in fluid within the alveolar spaces, often as a result of leakage of fluid from pulmonary capillaries. The latter problem is frequently called ARDS and can be the consequence of a wide variety of disorders that cause an increase in pulmonary capillary permeability.* Because of the importance of this syndrome as a major form of acute respiratory failure, Chapter 28 focuses entirely on the problem of ARDS.

Categories of acute respiratory failure are:

1. Hypoxemic (with normal or low PCO₂)

2. Hypercapnic/hypoxemic

Examples of hypoxemic respiratory failure are:

1. Severe pneumonia

2. ARDS

Hypercapnic/Hypoxemic Type

In the second category, hypercapnia is present. For the respiratory failure to be considered acute, the pH must show absent or incomplete metabolic compensation for the respiratory acidosis. From the discussion of alveolar gas composition and the alveolar gas equation in Chapter 1, it is apparent that hypercapnia is associated with decreased arterial PO₂ because of altered alveolar PO₂. Therefore, even if ventilation and perfusion are relatively well matched and the fraction of blood shunted across the pulmonary vasculature is not increased, arterial PO₂ falls in the presence of hypoventilation and consequent hypercapnia. In fact, many cases of hypercapnic respiratory failure have marked ventilation-perfusion mismatch as well, which further accentuates the hypoxemia. With these concepts in mind, it is clear the hypercapnic form of respiratory failure generally involves not just hypercapnia; it may be more appropriately considered the hypercapnic/hypoxemic form of respiratory failure.

A number of types of respiratory disease are potentially associated with this second form of respiratory failure. How the various disorders result in hypercapnic/hypoxemic respiratory failure is explained in Pathogenesis of Gas Exchange Abnormalities. These disorders primarily include (1) depression of the neurologic system responsible for respiratory control; (2) disease of the respiratory bellows, either the chest wall or the neuromuscular apparatus responsible for thoracic expansion; and (3) COPD. More than one of these three problems commonly is present, compounding the potential for respiratory insufficiency.

Causes of hypercapnic/hypoxemic respiratory failure are:

1. Depression of central nervous system ventilatory control

2. Disease of the respiratory bellows

3. COPD

In the hypercapnic/hypoxemic form of respiratory failure, patients often have preexisting disease that is responsible for either chronic respiratory insufficiency or limitations in respiratory reserve sufficient to make patients much more susceptible to decompensation with an acute superimposed problem. This form of respiratory failure is called acute-on-chronic respiratory failure, obviously reflecting prior problems or limitations with respiratory reserve. This expression has been used especially to describe the patient with COPD in whom acute respiratory failure develops at the time of an infection or another acute respiratory insult.

Presentation of Gas Exchange Failure

When acute respiratory failure develops, the patient’s symptom complex generally includes the manifestations of hypoxemia, hypercapnia, or both, accompanied by the specific symptoms related to the precipitating disorder. Dyspnea is present in the majority of cases and is the symptom that often suggests to the physician the possibility of respiratory failure.

Clinical presentation with respiratory failure consists of:

1. Dyspnea

2. Impaired mental status

3. Headache

4. Tachycardia

5. Papilledema (with ↑ PCO₂)

6. Variable findings on lung examination

7. Cyanosis (with severe hypoxemia)

Impairment of mental abilities is a frequent result of either hypoxemia or hypercapnia. Patients may become disoriented, confused, and unable to conduct their normal level of activity. With profound hypercapnia, patients may become stuporous and eventually lapse into a frank coma. Headache is a common finding in patients with hypercapnia. Dilation of cerebral blood vessels as a consequence of increased PCO₂ is probably an important factor in the pathogenesis of the headache.

Physical findings associated with abnormal gas exchange are relatively few. Patients may be tachypneic, tachycardic, and restless, findings that are relatively nonspecific. Examination of the optic fundi may reveal papilledema (swelling and elevation of the optic disk) resulting from hypercapnia, cerebral vasodilation, and increased pressure at the back of the eye. Findings in the lung are related to the specific form of disease present—for example, wheezing and/or rhonchi in COPD, or crackles due to fluid in the small airways and alveolar spaces. When hypoxemia is severe, patients may become cyanotic, which is apparent as a dusky or bluish hue to the nail beds and lips.

Pathogenesis of Gas Exchange Abnormalities

The basic principles of abnormal gas exchange were discussed in Chapter 1. The focus here is on applying these principles to patients with respiratory failure. A discussion of hypoxemic respiratory failure is followed by a discussion of hypercapnic/hypoxemic failure.

Hypoxemic Respiratory Failure

In the patient with hypoxemic respiratory failure, two major pathophysiologic factors contribute to lowering of arterial PO₂: ventilation-perfusion mismatch and shunting. In the patient with significant ventilation-perfusion mismatch, regions with a low ventilation-to-perfusion ratio return relatively desaturated blood to the systemic circulation. What sorts of problems cause a decrease in ventilation relative to perfusion in a particular region of lung? If an alveolus or a group of alveoli is partially filled with fluid, only a limited amount of ventilation reaches that particular area, whereas perfusion to the region may remain relatively preserved. Similarly, if an airway supplying a region of lung is diseased, either by pathology affecting the airway wall or by secretions occupying the lumen, then ventilation is limited.

When these problems become extreme, ventilation to a region of perfused lung may be totally absent so that a true shunt exists. For example, alveoli may be completely filled with fluid, or an airway may be completely obstructed, preventing any ventilation to the involved area. Although the response of the pulmonary vasculature is to constrict and thereby limit perfusion to an underventilated or unventilated portion of the lung, this protective mechanism often cannot fully compensate for the loss of ventilation, and hypoxemia results.

Alveolar filling with fluid and collapse of small airways and alveoli seem to be the main pathogenetic features leading to ventilation-perfusion mismatch and shunting in ARDS (see Chapter 28). An earlier consideration of the ability of supplemental O₂ to raise PO₂ in conditions of ventilation-perfusion mismatch versus shunt indicated that O₂ cannot improve PO₂ significantly for truly shunted blood (see Chapter 1). Therefore, when the shunt fraction of cardiac output is quite high, oxygenation may be helped surprisingly little by administration of supplemental O₂.

Despite the marked derangement of oxygenation in ARDS, CO₂ elimination typically remains adequate because, at least early in the course of the syndrome, patients are able to maintain alveolar ventilation at an acceptable level. Even when regions of lung have a high ventilation-perfusion ratio and thus effectively act as dead space, patients are generally able to compensate by increasing their overall minute ventilation.

Hypercapnic/Hypoxemic Respiratory Failure

In the hypercapnic form of respiratory failure, patients are unable to maintain a level of alveolar ventilation sufficient to eliminate CO₂ and keep arterial PCO₂ within the normal range. Because ventilation is determined by a sequence of events ranging from generation of impulses by the respiratory controller to movement of air through the airways, there are multiple stages at which problems can adversely affect total minute ventilation. This sequence is shown in Figure 27-1, which also lists some of the disorders that can interfere at each level. Not only is the total ventilation per minute important, the “effectiveness” of the ventilation for CO₂ excretion—that is, the relative amount of alveolar versus dead space ventilation—is also important to ensure proper utilization of inspired gas. If the proportion of each breath going to dead space (i.e., ratio of volume of dead space to tidal volume [VD/VT]) increases substantially, alveolar ventilation may fall to a level sufficient to cause elevated PCO₂, even if total minute ventilation is preserved.

Figure 27-1 Levels at which interference with normal ventilation give rise to alveolar hypoventilation. Factors contributing to decreased ventilation are listed under each level. ARDS = Acute respiratory distress syndrome; CNS = central nervous system.

In the hypercapnic form of respiratory failure, hypoventilation also leads to a decrease in alveolar PO₂. As a result, arterial PO₂ falls even if ventilation-perfusion matching and gas exchange at the alveolar level are well maintained. In practice, however, many of the diseases associated with alveolar hypoventilation, ranging from neuromuscular and chest wall disease to chronic airflow obstruction, are accompanied by significant ventilation-perfusion mismatch. Therefore, patients generally have two major reasons for hypoxemia: hypoventilation and ventilation-perfusion mismatch. Interestingly, true shunts usually play a limited role in causing hypoxemia in these disorders, unlike the situation in ARDS.

Given the causes of hypoxemia in the hypercapnic/hypoxemic form of respiratory failure, patients frequently respond to supplemental O₂ with a substantial rise in arterial PO₂. However, most of these patients have at least mild chronic CO₂ retention, with their acute respiratory failure resulting from some precipitating insult or worsening of their underlying disease. Administration of supplemental O₂ to these chronically hypercapnic patients may lead to a further increase in arterial PCO₂ for a number of pathophysiologic reasons (see Chapter 18). With judicious use of supplemental O₂, substantial additional elevation of arterial PCO₂ can usually be avoided.

An elaboration of further features of the hypercapnic/hypoxemic form of respiratory failure follows.

Clinical and Therapeutic Aspects of Hypercapnic/Hypoxemic Respiratory Failure

Whether the underlying disease is chest wall disease (e.g., kyphoscoliosis) or COPD, this type of respiratory failure often develops in patients who already have some degree of chronic respiratory insufficiency. However, this is not true of all cases. In certain neurologic conditions such as Guillain-Barré syndrome, hypercapnic respiratory failure occurs in a previously healthy individual.

As noted earlier, when the patient has chronic disease upon which acute respiratory failure is superimposed, the phrase acute-on-chronic respiratory failure is frequently used. In such cases, a specific different problem often precipitates the acute deterioration, and identification of the problem is important.

Frequent precipitants of acute-on-chronic respiratory failure are:

1. Respiratory infection

2. Drugs (e.g., sedatives, narcotics)

3. Heart failure

4. Less common: pulmonary emboli, exposure to environmental pollutants

What are some of the intercurrent problems or factors that precipitate acute respiratory failure in these patients? Perhaps the most common is an acute respiratory infection, such as bronchitis, usually but not always caused by a virus. Bacterial causes must always be investigated, however, because often they are amenable to specific therapy. Use of drugs that suppress the respiratory center, such as sedatives or narcotics, may precipitate hypercapnic respiratory failure by depressing central respiratory drive in a person whose condition already was marginal. Other intercurrent problems include heart failure, pulmonary emboli, and exposure to environmental pollutants, each of which may be sufficient to induce further CO₂ retention in the patient with previously borderline compensation.

The general therapeutic approach to these patients involves three main areas: (1) support of gas exchange, (2) treatment of the acute precipitating event, and (3) treatment of the underlying pulmonary disease. Support of gas exchange involves maintaining adequate oxygenation and elimination of CO₂ (see Chapter 29). Briefly, supplemental O₂, generally in a concentration only slightly higher than that found in ambient air, is administered to raise PO₂ to an acceptable level (i.e., > 60 mm Hg). If CO₂ elimination deteriorates much beyond the usual level of PCO₂, then an acute respiratory acidosis is superimposed on the patient’s usual acid-base status. If significant acidemia develops or if the patient’s mental status changes significantly as a result of CO₂ retention, some form of ventilatory assistance, either intubation and mechanical ventilation or noninvasive positive-pressure ventilation with a mask, may be required.

Treating the factor precipitating acute respiratory failure is most successful when bacterial infection or heart failure is responsible for the acute deterioration. Antibiotics for suspected bacterial infection, or diuretics and afterload reduction for heart failure, are appropriate forms of therapy in these circumstances. For patients in whom respiratory secretions seem to be playing a role either chronically or in an acute exacerbation of their disease, attempts to assist in clearance of secretions may be beneficial. In particular, chest physical therapy, in which percussion and vibration of the chest are performed and followed by appropriate positioning to assist gravity in drainage of secretions, may be beneficial.

Treatment of the underlying pulmonary disease depends on the nature of the disease. For patients with obstructive lung disease, intensive therapy with bronchodilators and corticosteroids may be helpful in reversing whatever components of bronchoconstriction and inflammation are present. If neuromuscular or chest wall disease is the underlying problem, specific therapy may be available, as is the case with myasthenia gravis. Unfortunately, for many neuromuscular or chest wall diseases, no specific form of therapy exists, and support of gas exchange and treatment of any precipitating factors are the major modes of therapy.

When patients with irreversible chest wall or neuromuscular disease are in frank respiratory failure, they may require some form of ventilatory assistance on a chronic basis (modalities for chronic ventilatory support are discussed in Chapter 29). It is important to emphasize here that the primary decision is whether chronic ventilatory support should be given to a patient with this type of irreversible disease. In many cases the patient, family, and physician make the joint decision that life should not be prolonged with chronic ventilator support, given the projected poor quality of life and irreversible nature of the process.

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