RESPIRATORY FAILURE

Respiratory failure refers to the inadequate exchange of gas by the cardiopulmonary system. In order to distinguish between the types of respiratory failure it is useful to determine the difference between the alveolar partial pressure of oxygen (PAO₂ ) and the arterial partial pressure of oxygen (PaO₂ ), or P(A-a)O₂ . The PaCO₂ is obtained from an arterial blood gas, whereas the PAO₂ is calculated from the alveolar gas equation:

PAO₂ = (PB − PH₂ O)FIO₂ − PaCO₂ /RQ

where PB is the barometric pressure, PH₂ O is the partial pressure of water in the alveoli (47 mm Hg at body temperature), FIO₂ is the inspired fraction of oxygen, PaCO₂ is the partial pressure of CO₂ measured on an arterial blood gas, and RQ is the respiratory quotient (usually assumed to be 0.8). A normal P(A-a)O₂ when a person is breathing room air is less than 15 mm Hg and increases linearly with age and FIO₂ . In a person 80 years of age breathing room air, a normal P(A-a)O₂ is 25 mm Hg; when breathing an FIO₂ of 1.0, a P(A-a)O₂ of 60 is normal.^[1]

Respiratory failure can be classified into three categories:

1. Ventilatory failure, or a decrease in the bulk flow of gas in and out of the lungs resulting in alveolar hypoventilation and retention of CO₂ . This rise in CO₂ is frequently accompanied by a drop in the PaO₂ but with a normal P(A-a)O₂ .
2. Hypoxic respiratory failure, or a significant impairment in the molecular exchange of oxygen across the pulmonary alveolar-capillary membrane, causing a decrease in PaO₂ and an increase in P(A-a)O₂ .
3. Combined ventilatory and hypoxic respiratory failure, which manifests with a low PaO₂ , an elevated PaCO₂ as well as an increased P(A-a)O₂ . ^[2] Respiratory failure can thus be conceptualized as having components of ventilatory pump failure (failure to adequately move

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   gases in and out of the pulmonary system) and/or lung failure ( Fig. 75-1 ).

Figure 75-1 Schematic representation of the pathogenesis of acute respiratory failure (ARF). The ventilatory pump is composed of the chest cage, ventilatory muscles, and nervous system elements involved in respiration. The pump primarily affects carbon dioxide excretion (CO₂ ). The lung involves the elements that allow inspired gas to exchange with pulmonary blood flow and primarily affects blood oxygenation (O₂ ). The large arrow from lung to pump represents the finding that lung disease often increases the work of the pump.

Ventilation is the bulk movement of gas into and out of the tracheobronchial tree. Failure of the ventilatory pump can occur due to (1) fatigue of the ventilatory muscles (e.g., in cardiopulmonary disease with increased dead-space ventilation), (2) decreases in chest wall compliance (e.g., scoliosis, kyphosis, pain and splinting after abdominal or thoracic surgery), (3) neuromuscular disease (e.g., muscular dystrophy, Guillain-Barré syndrome, amyotrophic lateral sclerosis), and (4) central nervous system (CNS) dysfunction (e.g., traumatic injury, pharmacologic depression, electrolyte abnormality). Ventilatory failure frequently requires treatment with PPV to improve the bulk movement of gas into and out of the pulmonary system and thus to facilitate adequate ventilation and elimination of CO₂ .

Hypoxemia manifests as a PaO₂ of less than 60 mm Hg. Hypoxemia can be considered due to a combination of six factors that can be grouped according to the P(A-a)O₂ ( Table 75-1 ).^[1] Tissue oxygenation is primarily dependent on oxygen delivery. Oxygen is transported from the alveoli to tissues in two forms: (1) oxygen that is dissolved in the blood plasma, and (2) oxygen that is bound to hemoglobin (Hb) in the red blood cell. The oxygen content of blood is the sum of the Hb-bound O₂ and the dissolved O₂ . The Hb-bound O₂ is a function of arterial oxygen saturation (SaO₂ ), whereas the dissolved component is a function of the arterial partial pressure of oxygen (PaO₂ ). When fully saturated, 1.34 mL of oxygen is bound to each gram of Hb. Because oxygen is not very

TABLE 75-1 -- Causes of hypoxemia

Causes	P(A-a)O2
Decreased barometric pressure	Normal
Decreased FIO2	Normal
Hypoventilation	Normal
Shunting (high s/t)	Increased
Ventilation-perfusion mismatch	Increased
Diffusion impairment	Increased
s/t, shunted blood flow/cardiac output ratio.

soluble in plasma, the dissolved component of blood oxygen is much less than the Hb-bound component. For each mm Hg of arterial partial pressure of oxygen, 1 dL of plasma will contain 0.003 mL of dissolved oxygen. The content of arterial oxygen (CaO₂ ) can therefore be expanded to:

CaO₂ = [(1.34)[Hb](SaO₂ )] + [(PAO₂ )(0.003)]

Oxygen delivery is the product of blood oxygen content and the cardiac output. Hypoxia is clinically defined as inadequate oxygen delivery at the tissue level, whereas hypoxemia refers to a deficiency of oxygen in arterial blood. Thus, tissue hypoxia can result from hypoxemia or impaired perfusion. The physiologic responses to tissue hypoxia are, primarily, to increase oxygen delivery by increasing cardiac output and, secondarily, to increase ventilation. The primary goal of oxygen therapy is to increase the alveolar oxygen content, thus increasing the alveolar partial pressure of oxygen (PAO₂ ). When hypoxemia results from a low PAO₂ , increasing the fraction of inspired oxygen (FIO₂ ) will result in an increase in PaO₂ . On the other hand, when hypoxia results from ventilatory demands that exceed the ability of the cardiac output to increase oxygen delivery, mechanical ventilation may not only improve PaCO₂ but also improve PaO₂ by decreasing oxygen consumption. The benefits of supplemental oxygen therapy must be weighed against the potential adverse physiologic effects of prolonged administration of a high FIO₂ , including denitrogenation absorption atelectasis and direct cytotoxic effects.^{[3] [4]}