Oxygen Therapy

Generally, oxygen therapy is used to maintain a PaO₂ of at least 60 mm Hg (which corresponds to an oxygen saturation in arterial blood [SaO₂] of approximately 90%).¹ However, in anemia, cardiac insufficiency, and coronary artery disease (hypoxic heart muscle), it is overly conservative to limit arterial oxygenation to these levels, especially if the F_IO₂ required to achieve a PaO₂ of 100 mm Hg (SaO₂ = 98%) is 0.40 or less. The nearly 10% increase in arterial oxygen content accompanying a PaO₂ increase from 60 mm Hg to 100 mm Hg is clinically significant in such instances.

Oxygen therapy is effective in < ?xml:namespace prefix = "mml" />V._A/Q._C mismatch but not if a large amount of absolute shunting is present (see Chapter 12). Oxygen therapy is also effective in diffusion defects and hypoventilation. However, oxygen therapy is not the appropriate way to treat hypoventilation because inadequate alveolar ventilation is the primary problem, not inability to oxygenate; that is, oxygen transfer across the alveolar capillary membrane is not impaired in pure uncomplicated hypoventilation.

Oxygen therapy must be closely monitored when treating patients who are chronically hypoxemic and hypercapnic (e.g., patients with severe chronic obstructive pulmonary disease [COPD]) because it can cause acute carbon dioxide retention and acidosis through mechanisms described in Chapter 11. However, oxygen should never be withheld from severely hypoxemic individuals, regardless of the cause. Hypercapnia and respiratory acidosis are of secondary importance if cerebral oxygenation is threatened. Oxygen should be administered to hypercapnic patients with COPD via devices that can produce relatively low, fixed, inspired oxygen concentrations not influenced by the patient’s ventilatory pattern. In patients with severe hypoxemia, low inspired oxygen concentrations are effective because arterial hemoglobin saturation is located on the steep part of the oxygen-hemoglobin equilibrium curve. For example, a relatively large amount of oxygen is added to the blood when PaO₂ is increased from 30 to 60 mm Hg (see Chapter 8). A periodic PaCO₂ analysis is important in monitoring oxygen-induced hypercapnia.

Body Position

A simple change in body position may improve oxygenation by improving the match between ventilation and blood flow. Gravity affects the distribution of ventilation and perfusion, as discussed in Chapters 3 and 6. For example, cardiac output is greater in the supine than in the sitting position because venous blood does not have to be pumped “uphill,” from the trunk and lower extremities up to the heart. The supine position improves venous return, pulmonary blood flow, and PaO₂ in patients with hypovolemic shock. The same position decreases PaO₂ in patients with congestive heart failure because increased venous return overwhelms the heart’s pumping capacity, causing pulmonary edema (see Chapter 6).

The sitting or standing position usually improves PaO₂ over the supine position in obese patients and patients with obstructive lung disease. An upright position allows gravity to pull down on the diaphragm, expanding the lungs and increasing functional residual capacity (FRC). For this reason, it is common practice to get surgical patients out of bed, even on the same day of a major surgery, so that they can stand or walk; this improves overall ventilation and oxygenation because it improves lung mechanics.

Patients with unilateral lung disease (e.g., one lung with pneumonia) should be positioned in bed with the healthy lung down. Gravity causes blood to flow preferentially to the healthy lung, improving V._A/Q._C and PaO₂.

Treatment of Shunting in Acute Lung Injury

Acute lung injury (ALI) is characterized by alveolar inflammation, alveolar-capillary membrane injury, high-permeability pulmonary edema, widespread atelectasis, and low lung compliance; the end result is severe shunting and refractory hypoxemia. Acute respiratory distress syndrome (ARDS) is the most severe form of ALI. According to the American-European Consensus Conference on ARDS, the PaO₂/F_IO₂ in ALI, regardless of applied positive end expiratory pressure (PEEP), is 300 mm Hg or less, whereas it is 200 mm Hg or less in ARDS.² ARDS is not a single disease entity; rather, it is a syndrome set in motion by any one of a wide variety of physiological insults to the lung (Table 14-1). The pathological feature common to each of these insults is injury to and increased permeability of the alveolar capillary membrane; the injury can be either direct (e.g., aspiration of gastric contents) or indirect (e.g., circulating bacterial endotoxins in sepsis).

Any of the risk factors listed in Table 14-1 can initiate the release of inflammatory mediators that attract and activate neutrophils (neutrophils are circulating white blood cells essential for phagocytosis and destruction of bacteria and other pathological substances). Prostaglandins, endotoxins, and cytokines are examples of inflammatory mediators. Prostaglandins are substances that can change capillary permeability, cause platelet aggregation (which increases the risk for intravascular clotting), and change vascular smooth muscle tone. Endotoxins are contained in the cell walls of gram-negative bacteria and when released can injure the vascular endothelium and induce inappropriate synthesis of nitric oxide; the result is massive vasodilation (septic shock). Cytokines are any of several regulatory proteins released by immune system cells (e.g., T cells) in generating an inflammatory response. Interleukins are a subgroup of cytokines produced mainly by T cells (T cells are thymus-derived lymphocytes of the body’s immune system that destroy or neutralize foreign substances); interleukins are signaling molecules that facilitate communication among neutrophils, causing them to migrate to the site of injury. Interleukins are thus important in mounting the inflammatory response.

Circulating neutrophils contain an array of toxic substances essential for destroying bacteria and other microorganisms. A hallmark of ARDS is the adherence of neutrophils to the pulmonary capillary endothelium (neutrophils become “sticky”).² Toxic compounds released by neutrophils damage and increase the permeability of the capillary endothelium and alveolar epithelium as neutrophils transmigrate from the bloodstream into the alveoli. Among these compounds are reactive oxygen ions and proteolytic enzymes that degrade and destroy tissues (Figure 14-1). The end result is increased alveolar capillary membrane permeability and flooding of the alveolar airspaces with protein-rich fluids. These fluids interfere with surfactant function, increasing surface tension and inducing widespread atelectasis. Shunting is the result of both alveolar filling and alveolar collapsing processes. The loss of alveolar airspace greatly reduces FRC and lung compliance in ARDS.

The hypoxemic effect of shunt in ARDS is especially severe because the normal hypoxic pulmonary vasoconstriction (HPV) mechanism is severely blunted.3,4 As noted in Chapter 6, the physiological function of HPV is to match blood flow and ventilation better. HPV normally reduces blood flow to nonventilated alveoli, lessening the hypoxemic effect they can exert on arterial blood. In ARDS, blood flows more freely through the capillaries of nonventilated alveoli, contributing to the profound refractory hypoxemia characteristic of ARDS.

ARDS does not affect the lung uniformly; computed tomography scans reveal that both normal-appearing lung and heavily consolidated lung coexist.² ARDS is often characterized as a heterogeneous disease (i.e., interspersed normal and abnormal regions) as opposed to a homogeneous disease. In effect, reduced open airspace creates a “small” lung in ARDS; in other words, one can think of the ARDS lung as a relatively small “normal” lung sharing the same major airways with an abnormal consolidated or atelectatic lung. This means the ARDS lung has marked regional differences in lung compliance, which presents an especially difficult challenge in mechanical ventilation of these patients. A mechanical positive pressure breath preferentially inflates the most compliant lung areas, potentially overdistending and damaging these “normal” regions. Thus, much attention has been given to the phenomenon of ventilator-induced lung injury (VILI) and to protective ventilation strategies. The remaining sections of this chapter address the physiological rationale for various therapeutic strategies designed to improve oxygenation and to protect the mechanically ventilated ARDS lung from further injury.

Positive End Expiratory Pressure

FRC in ARDS is greatly reduced because of widespread atelectasis and lung consolidation; it makes sense to use techniques that either reopen collapsed alveoli or prevent their collapse in the first place. Positive end expiratory pressure (PEEP) is aimed at accomplishing this effect. PEEP refers to airway pressure that remains above atmospheric levels at the end of expiration. PEEP is generally applied to the airway in conjunction with endotracheal intubation and positive pressure mechanical ventilation.

Mechanism of Action

In the atelectatic lung, PEEP increases FRC and lung compliance by increasing transpulmonary pressure (P_A − P_pl) at the end of expiration. This effect is beneficial only in people who already have abnormally low FRC and low lung compliance. In such individuals, PEEP may prevent alveolar collapse at the end of expiration and at sufficiently high levels may help to reopen collapsed alveoli.⁵ The reopening of previously collapsed alveoli reduces intrapulmonary shunt and improves PaO₂. In addition, PEEP improves lung compliance (i.e., less pressure is required to inflate the lung to a given volume) by restoring the FRC of the diseased lung; that is, PEEP places the tidal volume on a steeper portion of the lung compliance curve (Figure 14-2), requiring less pressure to achieve a given tidal volume. As collapsed alveoli are reopened, the lung’s compliance curve shifts back toward its normal position.

Continuous Positive Airway Pressure

A variation of PEEP that produces the same effect is continuous positive airway pressure (CPAP), which is applied to spontaneously breathing individuals. In CPAP, a relatively constant positive airway pressure is maintained throughout inspiration and expiration. CPAP can be applied through a facemask or an endotracheal tube. The beneficial effects of CPAP are similar to the effects of PEEP; alveolar collapse is prevented, and collapsed alveoli may be recruited. The improved lung compliance illustrated in Figure 14-2 decreases the patient’s work of breathing. The major difference between CPAP and PEEP is that airway pressure does not increase during inspiration with CPAP as it does with PEEP. Therefore CPAP is associated with lower mean airway pressure than PEEP. Figure 14-3 illustrates PEEP and CPAP pressure waveforms.

How PEEP and CPAP Devices Work

It is beyond the scope of this chapter to review PEEP and CPAP devices in detail. However, a basic understanding of the mechanical principles involved helps one understand how PEEP and CPAP produce their physiological effects.

Modern mechanical ventilators use sophisticated microprocessor-controlled exhalation valves through which the patient exhales. As expiration proceeds, pressure in the ventilator tubing decreases until it reaches a preselected level, at which point the exhalation valve abruptly closes and traps positive pressure in the patient’s lungs. In other words, the pressure in the patient’s lungs is not allowed to decrease to atmospheric levels, which means the end expiratory volume of the lung (FRC) is increased, and alveolar collapse is presumably prevented. An ideal PEEP valve does not resist expiratory gas flow; instead, it establishes an end expiratory threshold pressure that abruptly stops exhalation (i.e., PEEP does not resist expiratory flow above the preset threshold pressure). Sometimes PEEP is misunderstood to be a pressure that is forced into the lungs, but PEEP is not an inspiratory phenomenon; PEEP is applied at the end of expiration and simply prevents the patient from exhaling to his or her natural resting level.

A CPAP device may consist of a continuous flow apparatus or a demand valve system. In a continuous flow device, a source gas flows through a tube past the patient’s airway (either through a mask or, as shown in Figure 14-4, through an adapter attached to an endotracheal tube) and out of a CPAP valve that can be adjusted to release gas at a given pressure threshold. A CPAP valve functions in a manner similar to a PEEP valve. For example, if the CPAP valve allows gas to escape only when the tubing pressure exceeds 10 cm H₂O, this pressure is maintained in the breathing circuit as long as the source gas flow rate exceeds the patient’s peak inspiratory flow demand.

An example of a demand valve device is an electronically controlled inspiratory valve that senses pressure in the circuit; this valve opens to allow gas to flow to the patient when the patient’s inspiratory effort causes the circuit pressure to drop. In this way, gas flow meets the patient’s inspiratory “demand.” When the patient exhales, the inspiratory demand valve closes, and exhaled gas is directed through the expiratory valve, or CPAP valve. Thus, in a demand CPAP system, source gas flow is not continuous—it is present only during inspiration. A constant airway pressure is maintained in the breathing circuit as long as the inspiratory flow of the source gas meets the patient’s inspiratory flow demands.