Chapter 13: Fio₂, Positive End-Expiratory Pressure, and Mean Airway Pressure

The principles associated with management of oxygenation are more complex than those associated with ventilation. Provided that cardiovascular function and V̇co₂ are constant, increases in alveolar ventilation generally result in decreases in Paco₂ and vice versa. Oxygenation status, although dependent on Fio₂, is also affected by cardiopulmonary disease, positive end-expiratory pressure (PEEP), and mean airway pressure (P̄aw). In this chapter, the aspects of mechanical ventilation that affect oxygenation are discussed, as well as approaches to these techniques during patient management.

Normal Pao₂ is 80 to 100 mm Hg when breathing room air at sea level, with hypoxemia defined as a Pao₂ of < 80 mm Hg. To maintain normal tissue oxygenation it is necessary to provide an adequate Fio₂, appropriate matching of ventilation and perfusion (V̇/Q̇), sufficient hemoglobin, adequate cardiac output, and appropriate O₂ unloading to the tissue. A breakdown at any stage in this process may result in tissue hypoxia. At sea level, hypoxemia results from one of a number of alterations in cardiopulmonary function. Specifically, hypoxemia is caused by shunt, V̇/Q̇ mismatch, diffusion defect, and hypoventilation. Hypoxemia is also worsened by cardiovascular compromise. A reasonable target Pao₂ in mechanically ventilated patients is 55 to 80 mm Hg (Spo₂ 88%-95%).

Shunt

Shunt is perfusion without ventilation. When present, venous blood (shunted blood) mixes with arterialized blood in the pulmonary veins or left heart causing a decrease in Pao₂ of blood leaving the left heart. Because the majority of O₂ is carried by hemoglobin, even a small shunt (Figure 13-1) can result in significant hypoxemia. Increasing Fio₂ improves oxygenation only in the settings of small shunt. A large shunt is unresponsive to an Fio₂ increase. Improvement in oxygenation in the setting of a large shunt is usually focused on resolution of the shunt (eg, decompression of a pneumothorax, resolution of a pneumonia, re-expansion of atelectasis, diuresis). The use of PEEP, recruitment maneuvers, and maneuvers to elevate P̄aw might improve oxygenation in this setting. A common, but often unrecognized, cause of shunt in mechanically ventilated patients is a patent foramen ovale. A functionally closed foramen ovale may open during mechanical ventilation and acute respiratory failure.

V̇/Q̇ Mismatch

The normal V̇/Q̇ is 0.8. Hypoxemia results when this ratio is low (Figure 13-2). The most effective methods of altering Pao₂ in the presence of V̇/Q̇ mismatch are to improve distribution of ventilation and increase in Fio₂. This is particularly true for patients with chronic obstructive lung disease, where gross mismatching of V̇/Q̇ is present. As illustrated in Figure 13-2, in some settings, minor increases in Fio₂ can markedly increase Pao₂. In many ventilated patients, hypoxemia is caused by both shunt and V̇/Q̇ mismatch. In these patients, management of oxygenation may require increasing Fio₂, PEEP, and P̄aw.

Diffusion Defect

Hypoxemia in this setting is due to the increased time for equilibration of O₂ across the alveolar capillary membrane. This is the result of thickening of the alveolar-capillary membrane or a decrease in surface area available for diffusion. Interstitial fluid, fibrotic changes of the alveolar-capillary membrane, and emphysematous changes of the lung parenchyma are the primary causes of a diffusion defect. Increasing Fio₂ improves oxygenation with a diffusion defect.

Hypoventilation

Elevation of alveolar Pco₂ decreases the alveolar Po₂, as predicted by the alveolar gas equation. The elevated Paco₂ causes the oxyhemoglobin dissociation curve to shift to the right, decreasing Sao₂ but increasing the unloading of O₂ at tissues. Improvement in ventilation is the best treatment for hypoxemia caused by hypoventilation, although this cause of hypoxemia also responds to O₂ administration.

Decreased Cardiovascular Function

With normal lung function, decreased cardiac output does not result in hypoxemia. However, altered cardiovascular function can magnify the hypoxemic effects of either V̇/Q̇ mismatch or shunting. When cardiac output is low, tissue O₂ extraction is high and mixed venous O₂ content is low. When shunt or V̇/Q̇ mismatch is present with low cardiac output, blood with a lower O₂ content from shunted areas mixes with blood from nonshunted areas, resulting in a greater degree of hypoxemia than if the cardiac output were higher. Management of hypoxemia due to cardiovascular dysfunction is corrected by appropriate hemodynamic management. Although increasing Fio₂ is appropriate in this setting, there are certain settings (eg, cardiogenic pulmonary) where moderate levels of PEEP are useful.

Since mechanical ventilation may cause V̇/Q̇ mismatch, even patients without marked cardiopulmonary dysfunction (eg, postoperative, drug overdose) may require an elevated Fio₂ to maintain a normal Pao₂. In these settings, however, rarely is an Fio₂ > 0.40 necessary except during specific procedures (eg, suctioning, bronchoscopy).

O₂ Toxicity

The role of oxygen toxicity in critically ill patients is controversial. In healthy mammals, breathing 100% O₂ for 24 hours results in structural changes at the alveolar-capillary membrane, pulmonary edema, atelectasis, and decreased Pao₂. In healthy humans, the same process has been observed, but requires a longer period of time. Thus, the lowest Fio₂ necessary to maintain the target Pao₂ should always be used. However, in severely diseased lungs, antioxidants capable of minimizing the effect of high Fio₂ may be induced, allowing tolerance to a high Fio₂. For patients with acute lung injury, Fio₂ > 0.60 is generally avoided. However, it is less dangerous to increase the Fio₂ than to expose the lungs to the damaging effects of high alveolar pressure (> 30 cm H₂O).

100% O₂

The continuous use of 100% O₂ should be avoided. In addition to the potential for O₂ toxicity, high Fio₂ may cause absorption atelectasis in poorly ventilated, unstable lung units due to denitrogenation. But this does not mean that 100% O₂ should never be used. Whenever oxygenation status is in question or generalized cardiopulmonary instability occurs, 100% O₂ should be administered, but should be reduced as rapidly as possible to more appropriate levels when the acute issue has resolved. Use of 100% O₂ during procedures such as bronchoscopy is recommended. In addition, 100% O₂ is usually administered during initial ventilator setup and quickly reduced when appropriate Pao₂ and Spo₂ are established.

PEEP is the application of pressures greater than atmospheric to the airway during the expiratory phase. The term continuous positive airway pressure (CPAP) is usually reserved for constant pressures greater than atmospheric applied to the airway of a spontaneously breathing patient. With CPAP, the patient is responsible for ventilation (no additional pressure during inhalation), whereas inspiratory assistance is provided with PEEP.

Physiologic Effects

PEEP increases P̄aw and mean intrathoracic pressure. This has effects on many physiologic functions (Table 13-1). When applied to appropriate levels for the clinical setting, PEEP improves pulmonary mechanics and gas exchange, and may have varying effects on the cardiovascular system.

Pulmonary mechanics Since pressure and volume in the lungs are related, the application of PEEP increases the functional residual capacity (FRC). In the setting of alveolar collapse, PEEP maintains alveolar recruitment. With recruitment of collapsed lung units, lung compliance improves. The increase in lung volume with PEEP can be the result of alveolar recruitment or an increased volume of already open alveoli. If PEEP overdistends already open alveoli, compliance will decrease. Depending on the overall balance between recruitment and overdistention, the application of PEEP may increase, decrease, or not affect tidal compliance. However, the appropriate application of PEEP in a patient with lung injury generally improves lung compliance. An appropriate level of PEEP also decreases work-of-breathing in spontaneously breathing patients. Excessive PEEP places the lung on the upper flat portion of the pressure-volume curve, thus decreasing compliance and increasing work-of-breathing.

Gas exchange In most clinical applications, PEEP is applied to improve Pao₂. This is accomplished through alveolar recruitment and decreasing intrapulmonary shunt. Appropriate PEEP may also improve Paco₂ – Petco₂ (end-tidal CO₂) and Paco₂ by decreasing dead space. Excessive PEEP can decrease perfusion to well-ventilated areas of the lungs, causing an increase in dead space and Paco₂. For patients with unilateral lung disease, PEEP may result in overdistension of healthy lung units with shunting of blood to the diseased lung units, worsening hypoxemia.

Cardiovascular function The effect of PEEP on the cardiovascular system is dependent on the level of PEEP, the compliance of the respiratory system, and the cardiovascular status. Because PEEP increases P̄aw and mean intrathoracic pressure, venous return and cardiac output may decrease as PEEP is applied. PEEP has the greatest effect on cardiac output in a setting where lung compliance is high, chest wall compliance is low and cardiovascular reserve is low. High levels of PEEP decrease right ventricular preload, increases right ventricular afterload (increased pulmonary vascular resistance), and may shift the interventricular septum to the left. This, along with a reduction in pericardial pressure gradient, limits left ventricular distensibility, reducing left ventricular end-diastolic volume and stroke volume. Thus, both pulmonary and systemic vascular pressures are affected by PEEP. Because PEEP increases pressure outside of the heart, it decreases left ventricular afterload. The net result may be a decreased cardiac output, arterial blood pressure, urine output, and tissue oxygenation. Thus, PEEP may increase arterial oxygenation but decrease tissue oxygenation.

Intracranial pressure As PEEP decreases venous return, intracranial pressure may increase with the application of PEEP. This is usually not an issue unless intracranial pressure is already increased. The effect of PEEP is decreased by elevating the head, which is commonly applied in the care of these patients. PEEP should be used cautiously in any patient where increased intracranial pressure is a concern, but levels less than or equal to 10 cm H₂O are usually not a problem.

Barotrauma The amount of overdistention produced with PEEP determines the probability of barotrauma. As lung injury is often heterogeneous, overdistention of an individual lung unit may be achieved at any PEEP level. However, barotrauma occurs due to a high end-inspiratory pressure and, thus, PEEP increases the risk of barotrauma only to the extent that it promotes end-inspiratory overdistention.

Indications

Indications for PEEP are shown in Table 13-2.

Acute respiratory distress syndrome Application of 10 to 20 cm H₂O PEEP is standard practice in patients with early acute respiratory distress syndrome (ARDS) to maintain alveolar recruitment. In later stages of ARDS, however, fibroproliferation is observed and generally 5 to 10 cm H₂O PEEP is used in this setting.

Chest trauma PEEP is used to stabilize the chest wall and prevent paradoxical movement in the setting of flail chest. If ARDS is not present, 5 to 10 cm H₂O PEEP is indicated, provided no pulmonary air leak is present and the patient is hemodynamically stable.

Postoperative atelectasis Use of CPAP by facemask may be beneficial to treat postoperative atelectasis. CPAP can be administered continuously or applied for 15 to 30 minutes every 2 to 6 hours at levels of 5 to 10 cm H₂O.

Cardiogenic pulmonary edema PEEP decreases preload and afterload. The use of PEEP or CPAP at 5 to 10 cm H₂O improves oxygenation, decreases work-of-breathing, increases left-ventricular performance, and improves cardiac output.

Artificial airways Insertion of an artificial airway decreases FRC and may compromise gas exchange. Application of 5 cm H₂O PEEP is typically used with intubated patients unless otherwise contraindicated. However, most patients with long-term tracheostomy do not need PEEP or CPAP.

Auto-PEEP The magnitude of auto-PEEP is dependent on the time constant (resistance and compliance), expiratory time, and tidal volume (V_T). Auto-PEEP is not observed on the ventilator unless an end-expiratory hold is used. The first indication of auto-PEEP may be inability to trigger the ventilator. Applying PEEP in this setting counterbalances auto-PEEP, decreases the effort needed to trigger, and may not affect end-expiratory alveolar pressure. For the patient who is having difficulty triggering the ventilator, PEEP can be slowly increasing until patient is able to comfortably trigger each breath. At the appropriate level of applied PEEP, patient rate decreases and signs of cardiopulmonary stress subside. PEEP counterbalances auto-PEEP with flow limitation (dynamic airway closure). However, PEEP does not affect auto-PEEP when auto-PEEP is due to high minute ventilation. In volume-controlled ventilation (VCV), if the applied PEEP increases end-expiratory alveolar pressure, peak inspiratory pressure (PIP) and plateau pressure (Pplat) increase. If changes in applied PEEP does not affect PIP with VCV, or tidal volume with PCV (and constant PIP), then auto-PEEP is present.

Ventilator-associated pneumonia Because PEEP raises intratracheal pressure, it decreases the amount of microaspiration around the cuff of the artificial airway. In that way, it decreases contamination of lower respiratory tract and decreases the risk of ventilator-associated pneumonia.

PEEP in ARDS

The primary indication for PEEP is ARDS. The goal of PEEP in this setting is prevention of de-recruitment and maintenance of tissue oxygenation. PEEP improves shunt, reverses hypoxemia, and decreases the work-of-breathing. Further, this is accomplished without adversely affecting cardiac output.

The goal is to set PEEP at a level that maximizes alveolar recruitment and avoids overdistention. Higher levels of PEEP may be appropriate for moderate to severe ARDS and modest levels of PEEP may be appropriate for mild ARDS. Because the potential for recruitment is variable among patients with ARDS, it must be titrated for the individual patient. Arterial blood pressure and pulse oximetry are monitored when PEEP is applied. The specific approach used to titrate PEEP is one of the most contentious subjects related to mechanical ventilation. PEEP can be titrated after a recruitment maneuver. Using this approach, PEEP is set higher than necessary to maintain alveolar recruitment and then slowly decreased until the lowest PEEP maintaining the best compliance is identified. Alternatively, PEEP is increased stepwise while monitoring Spo₂, Pplat, compliance, and blood pressure. A decrease in Spo₂, decrease in compliance, decrease in blood pressure, and Pplat more than 30 cm H₂O suggests overdistention. In the setting of a stiff chest wall, PEEP is set to counterbalance the alveolar collapsing effect of the chest wall, and an esophageal balloon may be useful in this setting to estimate pleural pressure. Another approach is to use PEEP/Fio₂ combinations as have been used in the ARDS network studies. PEEP for ARDS is generally set between 10 and 20 cm H₂O. Hemodynamic monitoring is necessary during PEEP titration due to the potential to adversely affect cardiovascular function.

PEEP should not be abruptly withdrawn. If PEEP is reevaluated on a regular basis, there is usually no need to make large changes in PEEP. Of concern is alveolar de-recruitment and hemodynamic instability with the withdrawal of PEEP. If the Spo₂ decreases when PEEP is decreased, the prior level should be re-established rather than increasing the Fio₂.

P̄aw is the average pressure applied over the entire respiratory cycle. P̄aw is dependent on all of the factors that effect ventilation (Table 13-3). Increasing the inspiratory time increases P̄aw without elevating peak alveolar pressure and maintains a constant level of ventilation, provided that auto-PEEP does not occur. If auto-PEEP occurs, either peak alveolar pressure or tidal volume is compromised. With VCV, auto-PEEP increases peak alveolar pressure because V_T is constant. With PCV, tidal volume decreases as auto-PEEP develops. If inspiratory time is increased, it should be limited to the level that does not create auto-PEEP. Auto-PEEP causes a less uniform distribution of PEEP and FRC than applied PEEP. That is, as a result of heterogeneous lung disease, pulmonary time constants can vary considerably from one lung unit to another. With auto-PEEP, FRC and total PEEP will be largest in the most compliant lung units (longest expiratory time constant) and lowest in the least compliant lung unit (shortest expiratory time constant).

Assuming appropriate treatment of the underlying condition, optimization of oxygenation requires the use of PEEP, administration of O₂, and the assurance of adequate cardiovascular function. Management of oxygenation should always be based on the underlying pathophysiology. In diffuse ARDS, high levels of PEEP may be needed, whereas in localized pneumonia, high PEEP may compromise oxygenation. PEEP should be set to balance recruitment against overdistention. Fio₂, PEEP, and P̄aw should target Pao₂ of 55 to 80 mm Hg (Spo₂ 88%-95%).