1. 
   

   How should a clinician rapidly assess the severity and stability of a patient with acute respiratory distress?

   
   
2. 
   

   How can principles of respiratory physiology be effectively applied to guide diagnosis and therapy?

   
   
3. 
   

   What are the indications and contraindications for noninvasive positive pressure ventilation (NPPV), and what outcomes does this intervention affect?

   
   
4. 
   

   When does a patient require advanced airway management?

Acute respiratory failure, a common inpatient medical emergency, mandates rapid assessment of the patient and initiation of appropriate and potentially life-saving therapy. Treatment decisions often must be made with limited information and well before a definitive diagnosis can be established. In this time-pressured, high-risk environment, clinicians must develop a diagnostic and therapeutic schema that facilitates a rapid and comprehensive approach to the patient with acute respiratory failure. The four key steps to approaching the patient with acute respiratory failure are

1. 
   

   Rapid assessment of the severity of the presentation and of the patient’s stability

   
   
2. 
   

   Determination of the likely cause or causes

   
   
3. 
   

   Initiation of treatment

   
   
4. 
   

   Assessment of the efficacy of treatment

Understanding the pathophysiologic underpinnings of acute respiratory failure simplifies and increases the accuracy of the diagnostic approach and the likelihood of choosing a successful therapeutic intervention. The five main etiologies of acute respiratory failure are

• Shunt
  
• Ventilation/perfusion (V/Q) mismatch
  
• Impaired diffusion
  
• Decreased mixed venous oxygen saturation
  
• Alveolar hypoventilation

Shunt

Shunt occurs when a portion of pulmonary blood flow does not participate in gas exchange. Physiologic shunt, the most common cause of acute hypoxemia in the hospitalized patient, develops when pulmonary perfusion is inappropriately maintained to injured, atelectatic or collapsed alveolar units. A relatively small area of infiltrate or atelectasis may cause profound hypoxemia if there is significant shunt to that area. Anatomic shunts describe physical conduits that divert deoxygenated blood into the systemic circulation, as occurs with right to left intracardiac shunt or intrapulmonary shunt. In both anatomic and physiologic shunts, deoxygenated blood enters the systemic circulation. As the degree of shunt (shunt fraction) increases, the partial pressure of arterial oxygen (PaO2) becomes increasingly independent of the fraction of inspired oxygen (FiO2), and once the shunt fraction exceeds 50%, increasing FiO2 does not increase PaO2. In conditions characterized by high shunt fractions, the FiO2 can often be lowered without compromising the PaO2.

Ventilation/Perfusion Mismatch

V/Q mismatch describes lung ventilation in excess of perfusion. Any process that increases dead space ventilation, such as alveolar overdistension (auto-PEEP), lung parenchymal destruction (emphysema), hypoperfusion (hypovolemia, acute RV failure), or obstruction of the pulmonary arterial circulation (pulmonary embolus) will generate V/Q mismatch. V/Q mismatch is characterized primarily by hypercapnia rather than hypoxemia. As a case in point, although tachypnea and respiratory distress are common clinical manifestations of acute pulmonary embolism (PE), marked hypoxemia is uncommon. Patients who become markedly hypoxemic after an acute PE generally have a secondary lung process or may have developed right-to-left intracardiac shunting due to acute right ventricular pressure overload.

Impaired Diffusion

Processes that damage or thicken the alveolar-capillary membrane, such as pulmonary edema, inflammation, fibrosis, or hemorrhage, increase the time required for gas to move between the alveolus and the pulmonary capillary. Under normal circumstances, gas exchange occurs very early as blood transits the pulmonary microcirculation. However, as cardiac output increases to meet metabolic demand (eg, during sepsis or exercise), blood spends proportionately less time in the pulmonary microcirculation. Impaired diffusion capacity will become clinically evident when the time required for gas exchange exceeds the amount of time that blood spends in the pulmonary capillary bed. This phenomenon explains why measuring exercise capacity remains the most sensitive and predictive indicator of disease progression in disorders characterized by progressive loss of diffusing capacity, such as pulmonary fibrosis.

Decreased Mixed Venous Oxygen Saturation

Mixed venous oxygen saturation (MvO2) reflects tissue oxygen extraction (VO2), or whether oxygen delivery is meeting metabolic demands. Oxygen delivery (DO2) is dependent upon cardiac output, hemoglobin level, and oxygen saturation. Decreases in any of these variables may significantly compromise oxygen delivery. When impaired oxygen delivery is coupled with increased metabolic demand (eg, septic shock), oxygen consumption will exceed oxygen delivery, at which point the MvO2 will decrease; normal MvO2 is 70%. If highly deoxygenated blood is returned to the right heart and gas exchange is impaired, blood may not fully oxygenate in the pulmonary circuit. Consequently, as gas exchange worsens, the MvO2 plays an increasingly important role in dictating the PaO2. Theoretically, the MvO2 can be increased by manipulating oxygen delivery with red blood cell transfusion or treatment with inotropic agents. Studies in which DO2 has been manipulated have demonstrated conflicting outcomes, and this practice remains controversial.

Alveolar Hypoventilation

Finally, alveolar hypoventilation may also cause acute respiratory failure if minute ventilation decreases below a patient’s minimum metabolic requirements.

The etiology of acute respiratory failure is often multifactorial, and physiologic derangements can be synergistic. A patient with a simple opiate overdose may initially present with hypoventilatory respiratory failure, but subsequent atelectasis or aspiration may cause physiologic shunting and impaired gas exchange.

V/Q mismatch, shunt, and diffusion abnormalities all reflect derangements in pulmonary gas exchange, while hypoventilation reflects abnormalities with the mechanics or control of ventilation. The arterial blood gas and calculation of the alveolar-arterial (A-a) gradient effectively differentiate impaired gas exchange from impaired ventilatory control. The A-a gradient is widened by processes that impair gas exchange, but remains normal in pure hypoventilatory respiratory failure.

A-a gradient = FiO2 × (Pbarometric – PH2O) – PaO2 + PaCO2/0.8

At sea level breathing room air:

A-a gradient = 0.21 × (760 – 50) – PaO2 – (PaCO2 × 1.25)

Simplified:

At sea level: A-a gradient = 150 – PaO2 – (PaCO2 × 1.25)

Normal A-a gradient = (Age/4) + 4

The A-a gradient increases by approximately 6 mm Hg for every 10% increase in FiO2, presumably due to blunting of physiologic pulmonary hypoxic vasoconstriction. Thus, a healthy patient with a baseline A-a gradient of 10 mm Hg on room air will develop an A-a gradient of 60 mm Hg when breathing 100% oxygen. As a result, the A-a gradient becomes progressively more difficult to interpret as the FiO2 increases. In patients with high FiO2 requirements, the ratio of oxygenation to supplementation (PaO2/FiO2 ratio) is a better and more reliable gauge of gas-exchange impairment.

Despite its limitations in severely hypoxemic states, the A-a gradient is a useful first step to a physiologic approach to acute respiratory failure (Figure 137-1). While it is helpful to approach respiratory failure based on physiologic principles, it is equally instructive to assess the primary anatomic systems required for effective respiration—specifically, the control of respiration, the airway, chest mechanics, the lung parenchyma, and vascular perfusion (Table 137-1). These complimentary physiologic and anatomic approaches to acute respiratory failure facilitate a rapid and comprehensive approach to diagnosis and treatment. Once a provisional diagnosis has been established, clinicians must initiate therapy that is specifically targeted to reversing the pathophysiology. A full discussion of these interventions is beyond the scope of this chapter, but rapid initiation of effective adjunctive therapy may prevent progression to acute intubation and ventilation.