Improving the ventilatory status of a patient with hypercapnic respiratory failure (i.e., reducing the partial pressure of carbon dioxide [PaCO₂] can be accomplished by improving alveolar ventilation, reducing physiological dead space, and reducing carbon dioxide (CO₂) production. Improving oxygenation, on the other hand, involves using various patient management strategies, such as administering enriched oxygen, applying positive end-expiratory pressure (PEEP) and continuous positive airway pressure (CPAP), and patient positioning.

Although the terms hypoxia and hypoxemia are often used interchangeably, it is important to recognize that hypoxia is defined as a reduction in oxygen in the tissues, whereas hypoxemia refers to a reduction in the partial pressure of oxygen in the blood (i.e., PaO₂ <80 mm Hg and SaO₂ <95%). Box 13-1 provides a brief description of the 4 types of hypoxia and Key Point 13-1 provides PaO₂ and SaO₂ values typically used to identify mild, moderate, and severe hypoxemia.

Box 13-1

Types of Hypoxia

• Hypoxemic hypoxia (lower than normal PaO₂, ascent to altitude, hypoventilation)

• Anemic hypoxia (lower than normal red blood cell count [anemia], abnormal hemoglobin, carboxyhemoglobin)

• Circulatory hypoxia (reduced cardiac output, decreased tissue perfusion)

• Histotoxic hypoxia (cyanide poisoning)

Key Point 13-1

Levels of Hypoxemia *

Level*	PaO₂ Value	PaO₂ Range	Saturation (SaO₂)
Mild hypoxemia	<80 mm Hg	60 to 79 mm Hg	90% to 94%
Moderate hypoxemia	<60 mm Hg	40 to 59 mm Hg	75% to 89%
Severe hypoxemia	<40 mm Hg	<40 mm Hg	<75%

The treatment of hypoxia should focus on the cause. For example, hypoxemic hypoxia, which occurs when a person breathes rarefied air at a high altitude (i.e., reduced partial pressure of inspiratory oxygen [P_IO₂]), can be reversed by having the person breathe an enriched oxygen mixture. When hypoventilation causes hypoxemia, increasing minute ventilation generally improves oxygenation (Case Study 13-1). Serious anemia, on the other hand, is treated with the administration of blood products, which in turn improves the patient’s oxygen-carrying capacity (i.e., hemoglobin). Circulatory hypoxia occurs when the patient’s cardiac output is reduced. The treatment of this type of hypoxia typically involves pharmacologic interventions, which normalize the patient’s cardiac output (e.g., administering drugs that increase ventricular contractility or decrease vascular resistance) and therefore improve oxygen delivery to the tissues. With histotoxic hypoxia, cyanide interferes with a person’s ability to utilize oxygen to produce energy (cellular respiration) by uncoupling oxidative phosphorylation (i.e., cytochrome oxidase). Treatment of cyanide poisoning involves administering a cyanide antidote (e.g., hydroxocobalamin) and providing supportive care to maintain oxygenation and acid-base balance.

Case Study 13-1

Myasthenia Gravis

A patient with myasthenia gravis is placed on mechanical ventilation. The chest radiograph is normal. Breath sounds are clear. Initial ABGs on 0.25 F_IO₂ 20 minutes after beginning ventilation are as follows: pH = 7.31; PaCO₂ = 62 mm Hg; bicarbonate = 31 mEq/L; and PaO₂ = 58 mm Hg. What change in ventilator setting might improve this patient’s ABG findings?

See Appendix A for the answer.

Improvement in oxygenation status may require time before the response to treatment is evident. This is particularly important in cases involving hypoventilation, anemia, and circulatory hypoxia. In these cases, it is appropriate to administer supplemental oxygen until the hypoxemia is relieved.

This chapter begins with a discussion of how to make simple adjustments of F_IO₂ to improve oxygenation. It is followed by a discussion of techniques involving the use of PEEP to improve oxygenation. Achieving optimum PEEP requires close monitoring and sometimes the use of either static or dynamic pressure-volume (P-V) loops. Methods used to set optimum PEEP are provided along with a review of P-V loops. Additional uses of PEEP are also discussed in this chapter, along with a description of the effects, complications, and consequences associated with discontinuation of PEEP.

A discussion of the pathophysiology of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is included to provide the reader with an understanding of the complexity of these disorders. Patients with ALI/ARDS are among the most difficult to oxygenate and manage in the critical care unit. The concept of lung-protective strategies and lung-recruitment maneuvers that are currently being evaluated to improve oxygenation, particularly in patients with ARDS, are included along with three clinical scenarios related to the topics discussed in this chapter.

Basics of Oxygenation Using F_iO₂, Peep Studies, and Pressure-Volume Curves for Establishing Optimum Peep

Basics of Oxygen Delivery to the Tissues

The most common parameters used to assess the oxygenation status of patients are the F_IO₂, SpO₂, ABGs, hemoglobin (Hb), abnormal Hb, PaO₂, PaO₂/P_AO₂, PaO₂/F_IO₂, shunt, cardiac output, mixed venous oxygen saturation (), and oxygen content of mixed venous blood (). Measuring oxygen delivery (DO₂) to the tissues provides valuable information about oxygen availability to the tissues. Oxygen utilization by the tissues can be determined by measuring arterial-to-mixed venous oxygen content difference (), oxygen consumption (), cardiac output, and . Table 13-1 provides a list of normal values for the parameters used to evaluate a patient’s oxygen status. Box 13-2 contains a summary of the equations for calculating parameters that are not directly measured, such as the partial pressure of alveolar oxygen (P_AO₂), CaO₂, , and DO₂.

TABLE 13-1

Measures and Values Used in the Evaluation of Oxygenation Status

Term	Abbreviation	Normal Value
Partial pressure of arterial oxygen	PaO₂	80-100 mm Hg
Partial pressure of mixed venous oxygen		40 mm Hg
Alveolar partial pressure of oxygen	P_AO₂	100-673 mm Hg
		F_IO₂ range: 0.21-1.0
Alveolar-arterial oxygen tension gradient	P(A-a)O₂	5-10 mm Hg (F_IO₂ = 0.21)
Alveolar-arterial oxygen tension gradient	P(A-a)O₂	30-60 mm Hg (F_IO₂ = 1.0)
Ratio of PaO₂ to fractional inspired oxygen (PaO₂ range = 80-100 mm Hg; F_IO₂ = 0.21)	PaO₂/F_IO₂	380-475
Ratio of PaO₂ to partial pressure of alveolar oxygen (PaO₂ range = 80-100 mm Hg; F_IO₂ = 0.21)	PaO₂/P_AO₂	0.8-1.0
Saturation of arterial oxygen	SaO₂	97%
Saturation of mixed venous oxygen		75%
Oxygen content of arterial blood	CaO₂	20 vol%
Oxygen content of mixed venous blood		15 vol%
Arterial-to-mixed venous oxygen content difference		3.5-5 mL/dL
Oxygen delivery	DO₂	1000 mL/min
Oxygen consumption		250 mL/min

Box 13-2

Equations Used to Calculate Oxygenation Status: Alveolar Air Equation (Calculation of Alveolar PO₂, P_AO₂)

PAO2=FIO2(PB−PH2O)−[PaCO2×{FIO2+(1−FIO2R)}]

where P_AO₂ = alveolar partial pressure of oxygen (mm Hg)

F_IO₂ = inspired oxygen fraction

P_B = barometric pressure (mm Hg)

= water vapor pressure (at 37° C = 47 mm Hg)

R = respiratory quotient (; R of 0.8 is commonly used)

With an F_IO₂ ≤ 0.6 (low value), the effect of R on P_AO₂ is small.

To estimate the P_AO₂ for F_IO₂ values <0.6: P_AO₂ = F_IO₂(P_B − ) − (1.25 × PaCO₂)

Partial pressure of inspired oxygen: P_IO₂ = F_IO₂ (P_B − )

Arterial oxygen content (CaO₂): CaO₂ = [(Hb × 1.34) × SaO₂] (0.003 mL/dL × PaO₂)

Mixed venous oxygen content (): = [(Hb × 1.34) × ] (0.003 mL/dL × )

Oxygen consumption (): = Cardiac output (C.O.) × (CaO₂ − )

Oxygen delivery (DO₂): DO₂ = C.O. × CaO₂

Evaluating PaO₂, SpO₂, and F_IO₂ in Ventilator Patients

In the clinical setting, the F_IO₂ is measured regularly (at least every 24 hours) and whenever it is changed.1 F_IO₂ is monitored more frequently in neonates and infants (continuously or every 2 to 4 hours). When changes in the F_IO₂ are made for adults or children, ABGs should be measured within 15 minutes, although some institutions wait 30 minutes to do so.²

Every attempt should be made to maintain the F_IO₂ below 0.6 to prevent the complications of oxygen toxicity while keeping the PaO₂ between 60 and 90 mm Hg and the CaO₂ near normal (20 mL/dL). This goal is not always possible, and sometimes a higher F_IO₂ is required.

The SpO₂ can be used to titrate F_IO₂ once the relationship between SaO₂ and SpO₂ has been established. (After mechanical ventilation is initiated, an arterial blood gas sample is obtained and the SaO₂ is compared with the patient’s current SpO₂ to establish this relationship.) A goal for maintaining SpO₂ at greater than 90% is appropriate. It is important to understand, however, that the SpO₂ will not always correlate perfectly with PaO₂. Some patients will have a large discrepancy between SpO₂ and SaO₂ and need to be monitored more carefully³ (see Chapter 11). For example, in patients with chronic obstructive pulmonary disease (COPD), their normal PaO₂ may be near 55 mm Hg (SaO₂ ~80%) and the SpO₂ values may be closer to 88% to 90% on room air.

Although the inspired oxygen percentage can be determined using multiuse oxygen analyzers, most current intensive care unit (ICU) ventilators have built-in oxygen analyzers that can provide continuous measurements of F_IO₂. Examples include the Hamilton Galileo (Hamilton Medical, Bonaduz, Switzerland), the Dräger v500 (Dräger Medical, Inc, Telford, Pa.), the Hamilton G5 (Hamilton Medical, Bonaduz, Switzerland), the Puritan Bennett 840 (Covidien-Nellcor Puritan Bennett, Boulder, Colo.), and the Servoⁱ (Maquet Inc, Wayne, N.J.) to name a few.

Adjusting F_IO₂

The ABGs obtained after mechanical ventilation is initiated are compared with the F_IO₂ being delivered. A linear relationship exists between PaO₂ and F_IO₂ for any patient as long as the person’s cardiopulmonary status remains fairly constant.4–7 In other words, the minute ventilation, cardiac output, shunt, and V_D/V_t must not change significantly between the time the ABG comparison is made and the F_IO₂ is changed. Most of the time, this is the case because ventilator changes are made quickly after blood gas results are obtained.

Because of the linear correlation, the known PaO₂ and the known F_IO₂ can be used to select the desired F_IO₂ necessary to achieve a desired PaO₂:

PaO2(known)F IO2(known)=PaO2(desired)F IO2(desired)

(desired) F IO2=PaO2(desired)×F IO2(known)PaO2(known)

This equation provides a reliable method for making appropriate changes in the F_IO₂ to achieve a desired PaO₂.

Some institutions use the ratio of PaO₂/P_AO₂ for evaluation of oxygenation and for predicting the inspired oxygen concentration.^7–10 The ratio of PaO₂ to F_IO₂ (commonly called the P-to-F ratio [PaO₂/F_IO₂]) has become a very popular way to set F_IO₂ because of its simplicity. However, it is not as accurate as the PaO₂/P_AO₂ because the alveolar PO₂ determination takes PaCO₂ into account. To estimate the a change in F_IO₂, for example, if the PaO₂ is 60 mm Hg with an F_IO₂ of 0.3 and the target PaO₂ is 80 mm Hg, the calculation of F_IO₂ is as follows:

knownPaO2F IO2(known)=desiredPaO2F IO2(desired)

and 60/0.3= 80/X, where X would be the new F_IO₂ setting. In this example, the new setting for F_IO₂ would be 0.4 (Case Study 13-2).^8,9 Making adjustments in F_IO₂ has a greater effect on patients with hypoventilation and reduced , in which higher alveolar oxygen has better access to pulmonary blood flow than situations of pulmonary shunt.

Case Study 13-2

Changing F_IO₂

After being supported on a ventilator for 30 minutes, a patient’s PaO₂ is 40 mm Hg on an F_IO₂ of 0.75. Acid-base status is normal and all other ventilator parameters are within the acceptable range. PEEP is 3 cm H₂O. What F_IO₂ is required to achieve a desired PaO₂ of 60 mm Hg? Is your answer possible? Can you think of another form of therapy to improve oxygenation?

See Appendix A for the answer.

Selection of F_IO₂ or Adjustment of Mean Airway Pressures

Although the exact safe level of F_IO₂ in mechanically ventilated patients is not known at this time, it is generally agreed that maintaining a high F_IO₂ (>0.6) can result in oxygen toxicity.11 Besides the tissue damage associated with the long-term use of 100% oxygen, it also has an additional complication. Breathing 100% oxygen can cause the rapid formation of absorption atelectasis and increase intrapulmonary shunting (i.e., shunt fraction), which further contributes to hypoxemia (Box 13-3).^10,12–14 Thus, F_IO₂ should be kept as low as possible. Although the lower limits of permissive hypoxemia remain controversial, most practitioners agree that a target PaO₂ of 60 mm Hg and a SpO₂ of 90% are acceptable lower limits for most adult patients.¹²

Box 13-3

Pulmonary Shunt: Perfusion Without Ventilation

As the percent of pulmonary shunt increases, hypoxemia worsens. A number of pathologic conditions are associated with an increased shunt fraction. Examples include atelectasis, pulmonary edema, pneumonia, pneumothorax, and complete airway obstruction.

Pulmonary Shunt Calculations

Q˙SQ˙t=(Cc′O2−CaO2)(Cc′O2−Cv¯O2)

where is the shunted portion; is total cardiac output, Cc′O₂ is the content of oxygen of the alveolar capillary (also called pulmonary end-capillary), CaO₂ is the arterial O₂ content, and is the mixed venous oxygen content. Cc′O₂ is calculated based on the assumption that pulmonary end-capillary PO₂ is the same as P_AO₂.

Both arterial and mixed venous blood samples are required for this calculation. As previously mentioned, arterial blood can be obtained from a peripheral artery. Mixed venous blood is taken from the distal port of a pulmonary artery catheter (see Chapter 11).

End-capillary oxygen content (Cc′O₂ = (1.34 × Hb × 1.0) + (0.003 × P_AO₂), arterial oxygen content (CaO₂) = (1.34 × Hb × SaO₂) + (0.003 × PaO₂) and mixed venous oxygen content () = (1.34 × Hb × ) + (0.003 × ).

If the PaO₂ remains very low while the patient is breathing an enriched oxygen mixture, significant shunting, ventilation-perfusion abnormalities, and/or diffusion defects are present. In these cases, other methods to improve oxygenation, besides increasing F_IO₂, must be considered. One approach that can be used to increase the PaO₂ involves increasing the. The is the average pressure above baseline during a total respiratory cycle (I + E) (Fig. 13-1). Box 13-4 provides an equation to estimate . As increases, the PaO₂ increases. Factors that affect during positive-pressure ventilation include peak inspiratory pressure (PIP), total PEEP (or auto-PEEP plus extrinsic or set PEEP [PEEP_E]), inspiratory-to-expiratory (I : E) ratios, respiratory rate (f), and inspiratory flow pattern. For example, as the total PEEP increases, the increases.