Chapter 8. Acute Respiratory Failure

Acute respiratory failure (ARF) is one of the leading causes of admission to the intensive care unit (ICU). Recently, incidence ranges for ARF, acute lung injury (ALI), and acute respiratory distress syndrome (ARDS) in adults were found to be 77.6–88.6, 17.9–34.0, and 12.6–28.0 cases/100,000 population per year, respectively.1,2 Mortality rates of approximately 40% were reported for patients with ARF, and similar or slightly lower rates for those with ALI and ARDS.3,4

The respiratory system primarily functions to provide adequate blood oxygenation and carbon dioxide elimination for the purposes of sustaining aerobic metabolism and pH homeostasis, respectively. Although the etiologies of respiratory failure are far too numerous to list, the underlying pathophysiologic mechanisms are similar and usually lead to a final common pathway. A consensus definition has not been established for ARF; however, several large studies have defined ARF as a Pao2/FiO2 ratio <200, or Pao2 <60 with either an FiO2 of >0.6 (hypoxemic) or a Paco2 >50 (hypercapnic). Irrespective of the criterion used to establish ARF, it can generally be stated that all patients with respiratory impairment will have either primary ventilatory or primary oxygenation impairment (Figure 8-1).

This chapter will discuss the basic pathophysiologic mechanisms of respiratory failure and the approach to the management of these patients. The most common diseases for respiratory failure are discussed in other chapters and will not be discussed in great detail here. However, two disease processes not discussed elsewhere will be covered in greater detail here as they present their own unique challenges, that is, cervical spinal cord injury (SCI) and neuromuscular diseases.

Hypoxemic respiratory failure is usually the result of hypoventilation, a disorder of alveolar oxygen diffusion, shunting of systemic venous blood to the arterial circuit, or a ventilation–perfusion (V/Q) mismatch. These descriptions provide an accurate depiction of the physiologic mechanisms for hypoxemic respiratory failure and are most useful for understanding how a particular disease causes hypoxemia.5 In a large multicenter international prospective cohort study of patients requiring mechanical ventilation (MV), the most common reported causes of ARF were postoperative respiratory failure, pneumonia, congestive heart failure, sepsis, and trauma.6 In a small prospective cohort study that included 41 patients with hypoxemic respiratory failure, chronic obstructive pulmonary disease and pneumonia were the most common causes.7 Other data from small, randomized controlled trials of noninvasive ventilation identified congestive heart failure, pneumonia, trauma, ARDS, and mucous plugging as the most common causes of respiratory failure.8,9

Hypoventilation

Hypoventilation is a reduction in the volume of gas delivered to the alveoli per unit time (alveolar ventilation). Assuming oxygen consumption remains unchanged, hypoxia then results. Hypoventilation always causes a rise in Paco2. Alveolar hypoventilation of a nonpulmonary etiology is typically characterized by hypercapnia with a normal alveolar–arterial oxygen gradient (A–a gradient) and therefore differs from the other three mechanisms of hypoxemia.10 Hypoventilation or apnea causes the partial pressure of alveolar oxygen to fall faster than the rise of the partial pressure of carbon dioxide. The other three mechanisms are typically characterized by a widening A–a gradient, which is normally less than 20 mm Hg.10

Diffusion

Diffusion typically refers to oxygen transport across the alveolar capillary membrane. In nondiseased states, oxygen transport is diffusion and perfusion limited. The diffusion properties of the alveolar membrane depend on its thickness and area. Thus, the diffusing capacity is reduced by diseases in which the thickness is increased, including acute conditions such as pulmonary edema, or chronic conditions such as diffuse interstitial pulmonary fibrosis, asbestosis, and sarcoidosis (Figure 8-2A). It is also reduced when the area is decreased, for example, by emphysema or pneumonectomy. Theoretically impaired diffusion prevents complete equilibration of alveolar gas with pulmonary capillary blood. The clinical relevance of this, however, is often questioned since most transport is more perfusion limited than diffusion limited. Therefore, in the ICU setting, this mechanism is rarely specifically addressed.

Shunt

The term shunt refers to the percentage of the total systemic venous blood flow that bypasses the gas-exchanging membrane or the lung and transfers venous blood unaltered to the systemic arterial system (Figure 8-2B). Shunting can be intracardiac, as in cyanotic right to left congenital heart disease and opening of a patent foramen ovale due to right ventricular overload, or result from passage of blood through pulmonary arteriovenous malformations. But the most common cause of shunting is pulmonary disease. In lung disease, there may be gas-exchanging units that are completely unventilated because of airway obstruction, atelectasis, or alveolar filling with fluid or cells.

Ventilation–Perfusion

Even in normal subjects, relative ventilation and perfusion in different areas of the lung are unequal, resulting in inefficient gas exchange (Figure 8-2B). This leads to V/Q mismatch. Areas of low ventilation relative to perfusion contribute to hypoxemia and are the most common cause of hypoxemia in lung disease. Furthermore, this is an important cause of hypoxemia affecting patients in the ICU.

The distribution of ventilation even in normal subjects varies depending on the mode of ventilation and position, but even in nonpathologic disease states ventilation is not uniform. The right lung developmentally is larger and therefore receives greater ventilation. The position of the subject also influences ventilation, with the apices of both lungs receiving a greater percentage of ventilation than the bases in the upright position while the lower lung is preferentially ventilated when laying in any horizontal position, irrespective of which side is lain upon (supine, prone, or on a side). This is due to the dependent diaphragm lying higher in the thorax, with increased length of muscle fibers providing more efficient contraction during inspiration. In the sedated and paralyzed patient, however, irrespective of the mode of ventilation, the upper lung receives more gas flow.

Conversely, the bases of both lungs receive more pulmonary blood flow than the apices in the erect subject. Furthermore, the distribution of flow through the lung is uneven due to the relatively low pressures in the pulmonary circulation, so gravity assumes a greater role than in the systemic circulation. While supine or prone gravity assumes a more constant role throughout the lungs, though in a lateral position, the dependent lung is perfused more than the upper lung.

Although both perfusion and ventilation increase from the apices to the bases in a subject lying horizontally, the increase in ventilation is less than that of perfusion. The relationship between the two is described as the V/Q ratio. Resting values are approximately 4 L/min for ventilation and 5 L/min for pulmonary blood flow, giving an overall ratio of 0.8 throughout the whole lung (assuming ventilation and perfusion of all alveoli are equal).

V/Q mismatch is responsible for the hypoxemia seen in pulmonary edema, chronic obstructive airways disease, pulmonary embolism, and interstitial lung disease. The hypoxemia worsens with increasing V/Q mismatch for two reasons. First, with V/Q mismatch, a greater percentage of the cardiac output passes through lung units with lower V/Q ratios (perfusion > ventilation) so that less well-saturated blood makes a greater contribution to total pulmonary blood flow.11 Second, as mentioned above in relation to shunts, the oxygen content of blood from lung units with low V/Q ratios exerts a greater effect on the saturation of blood flowing to the left side of the circulation because of the shape of the oxygen dissociation curve.11 Hypoxic pulmonary vasoconstriction (HPV) is a potent regulator of the distribution of blood flow to match areas of ventilation. It normally acts to improve gas exchange by reducing the blood flow to lung regions with low V/Q ratios. In conditions producing inflammatory mediators—such as sepsis and trauma—HPV is impaired, resulting in blood flowing to poorly ventilated lung, thus causing hypoxia.11 Drugs such as sodium nitroprusside and nitroglycerine can also impair HPV by indiscriminately causing vasodilation. HPV can also be abolished in the presence of raised pulmonary artery pressures leading to V/Q mismatch and hypoxia.

Alveolar ventilation becomes inadequate in relation to carbon dioxide production when either ventilatory demand exceeds the patient's capability (pump failure) or the patient's ventilatory effort is insufficient (drive failure).12–14 These two mechanisms are distinct in their clinical presentation: patients with acute failure of the ventilatory pump are dyspneic and tachypneic with other signs of distress and sympathetic nervous system activation, whereas patients with failure of ventilatory drive are not short of breath and typically demonstrate bradypnea or apnea.

Although acute ventilatory failure is primarily a disorder of alveolar ventilation—as demonstrated by increasing Pco2 and decreasing pH—hypoxemia is also usually present. More than one mechanism may coexist in a given patient at a given time, producing a life-threatening condition even when the individual processes are only moderate in severity.15 For example, in decompensated obesity hypoventilation syndrome, a patient whose underlying respiratory drive is reduced and whose obesity poses an increased elastic load on the ventilatory pump may develop acute-on-chronic ventilatory failure in the presence of a relatively modest increase in the work of breathing (WOB) from the additional restrictive effects of cardiomegaly and pleural effusions.16

In the ICU setting, the most common disorders encountered are:

1. Impairment of ventilatory drive due to sedative drugs

2. Acquired neuromuscular disorders such as cervical SCI, Guillain–Barré syndrome (GBS), acute stroke, or amyotrophic lateral sclerosis (ALS)

3. Restrictive and obstructive diseases such as pulmonary fibrosis, chest wall burns, COPD, and asthma

Cervical Spinal Cord Injury

Cervical SCI effectively disrupts the transmission of neurologic input from the respiratory centers to the ventilatory muscles needed for respiration. The diaphragm is innervated by the phrenic nerve whose root segments originate from C3–C5; therefore, high cervical SCI may result in a permanent need for MV. Although patients with lower cervical SCI may initially require MV, with rehabilitation they may progress to a ventilator-independent lifestyle.

The subacute management phase of cervical SCI may resemble that of most neuromuscular disease patients. The unique aspects are related to the acute management and the impact on the rehabilitation potential. Adverse physiologic effects of cervical SCI in the initial days or weeks after the injury include loss of lung volumes and inability to take deep breaths (which predisposes to atelectasis), inability to cough normally (which predisposes to the development of pneumonia and complicates its management), and impaired HPV (which predisposes to severe and often refractory hypoxemia when atelectasis or pneumonia occurs). Retrospective studies have shown that both mortality17 and ICU length of stay18 for patients with cervical SCI are more strongly influenced by the development of pneumonia and other respiratory complications than by the specific cord injury level.19

In the unintubated patient, initial management should include frequent assessment of forced vital capacity (FVC) and negative inspiratory forces (NIF). A vital capacity (VC) less than 1 L or an NIF >−20 (e.g., −10) despite normal blood gases and oxygenation should warrant early intubation.

Ventilator management principles are also different in these patients. Retrospective studies have demonstrated that high tidal volume ventilation or lung expansion ventilation may impact the duration for which MV is required and decrease the incidence of atelectasis and pneumonia.20 Contradictory to the lung-protective strategies of ARDS/ALI, patients are managed with tidal volumes of 15–20 cm3/kg while maintaining peak inspiratory pressures less than 40 cm H2O. Exceptions to this mode of ventilation include severe traumatic brain injury, chest trauma, bilateral pulmonary contusions, flail chest, pneumothorax/hemothorax, or bullous emphysema. In a recent retrospective study, NIF and FVC were shown to be the best predictors of ventilator weaning in this patient population.21

Neuromuscular Disorders

Neurologic patients can develop respiratory failure from neuromuscular weakness, decreased central respiratory drive, or associated pulmonary complications. In patients with neuromuscular disease, respiratory failure can present as a consequence of progression of a chronic condition such as ALS, exacerbation of a fluctuating disorder such as myasthenia gravis (MG), or sudden onset and fulminant course of an acute illness such as GBS.22 In all these cases, respiratory failure can result from worsening weakness affecting respiratory muscles or from an intercurrent pulmonary complication, typically aspiration, facilitated by concomitant weakness of oropharyngeal musculature or inability to cough up large regurgitated gastric contents.

GBS is the leading cause of nontraumatic acute paralysis in industrialized countries.23 About 30% of the patients have respiratory failure requiring ICU admission and invasive MV.24 The underlying mechanism is progressive weakness of both the inspiratory and expiratory command systems. Several factors that, if present either at admission or during the patient's hospital stay, predict a need for invasive MV; they include rapidly progressive motor weakness, involvement of both the peripheral limb and the axial muscles, ineffective cough, bulbar muscle weakness (dysarthria, dysphagia, impaired gag reflex), or a rapid drop in VC or respiratory pressures.25

Upper airway muscle dysfunction is related to cranial nerve involvement and deserves special attention because impaired coughing is common and increases the risk of aspiration and therefore of aspiration-related complications such as atelectasis and pneumonia. Most commonly, the seventh cranial nerve and the ninth and tenth cranial nerves are involved, manifesting as facial paralysis and swallowing impairment, respectively.26,27 If present, tongue weakness may contribute to the development of respiratory failure by causing upper airway obstruction during sleep, and aspiration during the initial phase of swallowing.28 The result is a combination of inadequate neuromuscular strength leading to alveolar hypoventilation, low tidal volume breathing, and diffuse atelectasis.

MV is frequently required when VC falls below 4–5 mL/kg body weight and there is progressive worsening of bulbar functions.29,30 Therefore, patients with neuromuscular respiratory failure should be closely monitored with frequent measurements of VC, NIF, arterial blood gases, clinical evaluation of their swallowing mechanisms, ability to handle secretions, and presence and strength of cough mechanism.

As with all aspects of acute management of patients, airway, breathing, and circulation should be addressed. After assessing and securing, if necessary, the airway, the next step is to manage and diagnose the etiology of the respiratory failure.

If intubating is not emergently required, evaluation continues with a high clinical suspicion for impending respiratory failure. Early recognition allows for greater therapeutic options. An often underappreciated concept in respiratory system mechanics relates to WOB.

The WOB in normal resting state accounts for approximately 5% of oxygen consumption but dramatically increases in diseased states. Although an oversimplification, WOB typically constitutes airway resistance and chest wall and lung compliance. Airway resistance is a function of airway caliber and flow. Compliance is the change in pressure over volume and encompasses the compliance of both the lungs and chest wall. Therefore, WOB is comprised of the amount of work necessary to overcome resistance of the airways to flow (Figure 8-3) and the elastic recoil of the lungs and chest wall.

Signs of increased WOB include dysconjugate breathing, accessory muscle use, and tachypnea. These signs are compensatory mechanisms and, as such, often exist prior to oxygen desaturation. Systemic signs and symptoms that accompany an increased WOB include restlessness, anxiety, diaphoresis, confusion, seizures, somnolence, tachycardia, bradycardia, and arrhythmias. The key is to suspect and treat the increased WOB prior to the appearance of systemic signs and symptoms.

The goal of managing respiratory failure is to reduce the workload on the pulmonary system while the underlying etiology is resolved. The practitioner must consider early the possibility of respiratory failure. Otherwise a common pitfall is to treat the signs and symptoms and miss the underlying etiology until full respiratory failure has ensued and MV becomes the only treatment option.

Once the respiratory distress/failure has been addressed, the next step is to evaluate the underlying etiology of the respiratory failure through the use of diagnostic aids. An arterial blood gas and a chest x-ray should be the first diagnostic step in addressing a patient in respiratory distress. The ABG (Figure 8-4) and chest x-ray will provide important data as to the potential mechanism for respiratory failure, that is, a primary oxygenation problem (widened A–a gradient), a primary ventilator problem (elevated Pco2 and acidemia), or a combination of both. As respiratory failure ensues and progresses inevitably, the picture is a mixed picture, particularly in the critically ill patient.

Treatment Options

ARF of hypoxemic nature can be addressed with MV but may not be necessary. It is common for practitioners to resolve ARF with noninvasive positive pressure ventilation (NPPV) or conventional MV, but securing the airway and initiating MV has significant complications. Furthermore, prolonged MV increases the incidence of ventilator-associated pneumonia, critical illness polyneuropathy, and ICU morbidity and mortality.

Instead, if the patient's condition allows sufficient time, attempts may be made to maximize all medical options before considering intubation. For instance, supplemental oxygen therapy should be maximized. Supplemental oxygen in excess of 70% oxygen can be provided without the use of a ventilator. Nasal cannula, venturi mask, partial non-rebreather, non-rebreather, and complex air entrapment high-flow systems can be set up to deliver high FiO2. In instances where airway resistance is increased such as COPD or asthma or in upper airway obstructive scenarios such as postextubation stridor, heliox (70:30 or 80:20 mixtures) may facilitate delivery of supplemental oxygen.31

Of course, progressive hypoxic failure will lead to ventilatory failure secondary to fatigue. ARF of a primary ventilator disorder may be managed with close observation in the ICU and NPPV. NPPV has the advantage of improving tidal volume and minute ventilation while delivering high FiO2 without the ventilator circuitry but may be of limited use in some neuromuscular disorders. Relative contraindications to NPPV include decreased mental status and ability to clear secretions since NIV still requires that a patient maintain his or her own airway.

Still, when there is concern for the patient's ability to maintain his or her airway, the primary objective is to protect and maintain the airway and traditional endotracheal intubation and conventional MV should be employed. The decision to intubate and provide MV should not be the first treatment option but should never be delayed and allow for an uncontrolled clinical scenario if avoidable. MV should always be regarded as a temporizing measure while the underlying cause of respiratory failure is addressed.