The low-tidal-volume strategy, which uses 6 mL/kg of predicted body weight, has become the standard of care for patients with ARDS, following the Acute Respiratory Distress Syndrome Network (ARDS Network) publication in 2000.¹² The ARDS Network prospectively studied intubated patients with acute lung injury (ALI) or ARDS to determine whether a low-tidal-volume strategy, compared with a traditional-tidal-volume strategy, could improve mortality and decrease the total number of ventilator days. The final analysis showed a 23% reduction in all-cause mortality and a 9% absolute decrease in mortality with the use of a tidal volume of 6 mL/kg of predicted body weight and plateau pressures of 30 cm H₂O or less, compared with the usual practice of 12 mL/kg of predicted body weight and plateau pressures of 50 cm H₂O or less. Low tidal volume or so-called lung protective ventilation is recommended for all patients with ARDS. In patients without ARDS, a retrospective review demonstrated the relationship between ALI and the use of tidal volumes greater than 10 mL/kg of predicted body weight.¹³ Considering the current evidence, tidal volumes greater than 10 mL/kg of predicted body weight should not be routinely used in the care of the mechanically ventilated patient.^12,¹³

B Respiratory Rate

The respiratory rate setting depends on the desired minute ventilation. Minute ventilation is a product of the respiratory rate and the tidal volume, and it is expressed in liters per minute. After a patient is intubated and placed on the mechanical ventilator, it is important to ensure adequate minute ventilation since the underlying pathophysiology or pharmacologic interventions can suppress the patient’s ability to compensate for metabolic demands. In most scenarios, the rate is determined by observing the patient’s native respiratory rate before intubation. The normal rate of minute ventilation is 5 to 7 L/min. In patients with sepsis or diabetic ketoacidosis, the native minute ventilation may be as high as 12 to 15 L/min, requiring a high respiratory rate. To adequately compensate for the acid-base derangements and ensure adequate minute ventilation, it is necessary to titrate the set respiratory rate until the desired pH and PaCO₂ goals are met. Permissive hypercapnia (i.e., allowing the PaCO₂ to increase intentionally to achieve other goals) may be appropriate in certain clinical conditions. Auto-PEEP (i.e. intrinsic PEEP) must be evaluated to ensure it remains at less than 5 cm H₂O. After the goal is achieved, it is a safe practice to set the rate at 4 breaths/min below the spontaneous breathing rate in the event that intrinsic or extrinsic factors suppress respiration. In patients on SIMV, the rate is initially set to meet up to 80% of the minute ventilation demands. Initial respiratory rates are usually 12 to 16 breaths/min, but rates of breaths per minute in the high 20s to low 30s may be required in patients with ARDS. In those with obstructive lung disease (e.g., asthma), a lower respiratory rate is desired, with significant risk of developing auto-PEEP. Assessment and management of auto-PEEP are discussed separately.

C Positive End-Expiratory Pressure

PEEP is the alveolar pressure above the atmospheric pressure at end-expiration. Applied PEEP (i.e., extrinsic PEEP) through mechanical ventilation allows delivery of positive pressure at the end of expiration to keep the unstable lung units from collapse.¹⁴ PEEP increases the peak inspiratory pressure, which directly overcomes the opening pressure of the unstable lung units. Low levels of PEEP (3 to 5 cm H₂O) are routinely used in patients on mechanical ventilation. It can decrease alveolar collapse at end-expiration and may reduce the incidence of ventilator-associated pneumonia.¹⁵ Higher levels of PEEP are employed to improve oxygenation in patients with hypoxic respiratory failure. Goals in managing ARDS are to optimize alveolar recruitment and decrease cycles of recruitment and derecruitment of alveolar lung units. Several strategies are used to determine optimal PEEP, but there are limited data to support their routine use. Determining the lower inflection point of the pressure-volume curve (P_flex), which reflects the transition from low to higher compliance, and applying PEEP of 2 cm H₂O greater than this point may be used to estimate the appropriate level of applied PEEP (Fig. 48-1).¹⁶

Figure 48-1 Calculation of optimal positive end-expiratory pressure (PEEP). Mechanical ventilation delivers low levels of PEEP to keep unstable alveoli from collapse at end expiration. The volume-pressure curve can be used to assess changes in lung compliance and to determine a ventilation strategy by identifying the lower inflection point, which is the critical opening pressure of collapsed alveoli, and the upper inflection point, which indicates a state of lung overinflation.

(From Haitsma JJ: Physiology of mechanical ventilation. Crit Care Clin 23:117–134, 2007.)

Because it is often impractical to routinely obtain pressure-volume curves, algorithms have been developed (e.g., in ARDS Network trials), with PaO₂/FIO₂ ratios to set the recommended PEEP (Table 48-1).¹² Measuring esophageal pressures to estimate transpulmonary pressures has been studied as a method to determine the appropriate applied PEEP in patients with ARDS, and this approach has demonstrated improvement in oxygenation and compliance.¹⁷ Trials of increasing or decreasing PEEP can also be used.^18,¹⁹ Higher levels of PEEP in postoperative patients have had no benefit.²⁰

TABLE 48-1 Combinations of PEEP and FIO₂ Used in the ARDS Network Trials

Lung injury in patients with hypoxic respiratory failure is heterogeneous. Since the collapse and repeated opening and closing of unstable lung units leads to further injury, its prevention would be the optimal ventilator strategy. High PEEP has been used mitigate alveolar collapse and cyclic alveolar stress. Several trials demonstrated that high PEEP increased oxygenation but did not improve mortality rates.^21,²² However, a meta-analysis of high PEEP trials indicated a mortality benefit for patients with a PaO₂/FIO₂ ratio of less than 200.²³ The optimal method of applying adequate PEEP has not been established.¹⁴ Trials in ARDS patients demonstrate PEEP requirements are usually between 12 and 20 cm H₂O.

D Fraction of Inspired Oxygen

On initiation of mechanical ventilation, the FIO₂ usually is set at 1.0. The goal is to rapidly reduce the FIO₂ to the target PaO₂ and SpO₂ to limit the consequences of supplemental oxygen. In most patients, a target PaO₂ of 60 mm Hg and SpO₂ of 90% meets oxygenation requirements. However, some patients may have higher PaO₂ targets based on their underlying cardiopulmonary status (e.g., myocardial ischemia, pulmonary hypertension). In patients with ARDS, targeting a PaO₂ as low as 50 mm Hg may be appropriate to limit alveolar injury.²⁴ A prolonged high level of FIO₂ has been associated with airway and parenchymal injury, atelectasis from nitrogen washout, and increased risk of diffuse alveolar damage, which is even higher in patients receiving bleomycin therapy.^25,²⁶ If the need for supplemental FIO₂ remains greater than 0.6, FIO₂ should be reduced with strategies such as applied PEEP and alternative ventilator modes.

E Peak Pressure

Peak airway pressure is a measurement of the maximum pressure felt by the airways on inspiration. In the passive patient, peak airway pressure, or peak pressure, depends on the respiratory rate, tidal volume, and inspiratory flow rate in volume-targeted modes of mechanical ventilation. When awake and active, the patient’s effort contributes to the peak pressure. In pressure-targeted ventilator modes, the peak pressure is directly related to the inspiratory pressure that is set and the inspiratory flow rate.²⁷ Studies have not consistently shown barotrauma to be an adverse consequence of increased peak pressures.^28,²⁹ The peak airway pressure typically is higher than the plateau pressure, and the difference indicates airway resistance.

F Plateau Pressure

Plateau pressure is the pressure that is applied by the mechanical ventilator to the small airways and alveoli. The plateau pressure is measured at end-inspiration with an inspiratory hold maneuver on the mechanical ventilator that is 0.5 to 1 second. Meta-analysis demonstrated a significant correlation between plateau pressures greater than 35 cm H₂O and the risk of barotrauma.³⁰ In the ARDS Network trial, lower tidal volume ventilation with plateau pressures less than 30 mm Hg was associated with a lower mortality rate than that found for conventional tidal volume using plateau pressures less than 50 mm Hg.¹²

Common reasons for increased plateau pressures are the use of high PEEP, inspiratory flow, and tidal volume. Adverse consequences of high plateau pressures are barotrauma, resulting in ventilator-associated lung injury, pneumothorax, pneumomediastinum, and subcutaneous emphysema. If barotrauma develops, it may be beneficial to reduce the plateau pressures further by decreasing the tidal volume, PEEP, or flow or by increasing the patient’s sedation.

G Trigger Sensitivity

Sensors on the ventilator detect the patient’s effort in terms of negative inspiratory pressure applied to the circuit by the patient or inspiratory flow of air from the patient. This is referred to as “triggering the ventilator” or “triggering a breath.” Pressure trigger sensitivity typically is set between −1 and −3 cm H₂O, and a breath is triggered when a negative inspiratory effort is greater than the set sensitivity. A flow-triggered breath is delivered when the return flow is less than the delivered flow. When the patient does not provide adequate negative inspiratory pressure or flow rate to trigger breaths, the ventilator provides mandatory breaths to the patient at the set parameters. The breaths are initiated by the ventilator at the set time, as determined by the set respiratory rate, and it delivers the breath at the prescribed flow rate until the desired tidal volume has been achieved, after which the ventilator cycles off for passive exhalation.

H Flow Rate

Flow rate, or peak inspiratory flow rate, is the maximum flow at which a set tidal volume breath is delivered by the ventilator. Most modern ventilators can deliver flow rates between 60 and 120 L/min. Flow rates should be titrated to meet the patient’s inspiratory demands.³¹ If the peak flow rate is too low for the patient, dyspnea, patient-ventilator asynchrony, and increased work of breathing may result. High peak flow rates increase peak airway pressures and lower mean airway pressures, which may decrease oxygenation.²⁷

In most patients, peak flow rates of 60 L/min are adequate. Higher flow rates are required in patients with higher ventilator demands.³¹ Higher peak flow rates may also be necessary in patients with obstructive lung disease to decrease inspiratory time, thereby increasing the expiratory time and reducing the risk of developing auto-PEEP.^32,³³

I Flow Pattern

Modern mechanical ventilators can deliver various inspiratory flow patterns. The constant or square waveform is a description of the inspiratory flow that is delivered by the mechanical ventilator. It correlates with volume-cycled breaths, in which the inspiratory flow remains constant until the desired tidal volume is delivered and then remains at that level until expiration. In this pattern of inspiratory flow, the airway pressure varies and depends on the patient’s effort and compliance of the lung. The sinusoidal wave flow gradually increases and decreases throughout the respiratory cycle. In the decelerating ramp wave (i.e., saw-tooth wave), the flow rate begins maximally and decreases until the end of inspiration. It parallels normal inspiratory pattern most closely. The ramp wave yields the most homogenous distribution of ventilation in most conditions, decreases peak airway pressures, and improves carbon dioxide (CO₂) elimination.³⁴ For patients who are triggering the ventilator, this strategy of ventilation is recommended (Fig. 48-2).

Figure 48-2 The three most common inspiratory flow patterns in humans (left) are compared with their corresponding pressure versus time curves (right).

(From Yang SC, Yang SP: Effects of inspiratory flow waveforms on lung mechanics, gas exchange and respiratory metabolism in COPD patients during mechanical ventilation. Chest 122:2096–2104, 2002.)

III Common Modes of Mechanical Ventilation

The three most commonly used modes of mechanical ventilation are ACV, SIMV, and PSV. Each mode describes whether breaths are volume constant or pressure constant; which are mandatory or spontaneous, or both; and which variables determine a change in function. All three modes have uses throughout the spectrum of stabilization of ventilation, maintenance of ventilation, and weaning from mechanical support.

Choice of the type of mechanical ventilation is most often determined by whether resting of respiratory muscles is indicated. Patients who are hemodynamically compromised, patients with severe oxygenation or ventilation derangements, and those undergoing general endotracheal anesthesia qualify for a rest of respiratory muscles. In these cases, it is prudent to choose a mode of ventilation that accomplishes ventilation without the need for spontaneous respirations; ACV is most often used. However, if use of muscles of respiration is desired, SIMV or PSV should be considered. Patients in whom the use of respiratory muscles is desired are usually those being weaned from mechanical ventilation or undergoing assessment of muscle strength and adequacy of spontaneous work of breathing. PSV is the only mode of the three that entirely relies on the patient spontaneously breathing. Table 48-2 shows the set and variable parameters in each common mode of ventilation. Control mode of ventilation (CMV) is the original mode of ventilation. In CMV, the patient receives a positive-pressure breath at a set rate without the ability to influence how it is delivered.

TABLE 48-2 Set and Variable Parameters for Common Modes of Mechanical Ventilation

A Assist-Control Ventilation

Volume assist-control ventilation (VACV) is the most frequently used initial mode of ventilation, and it has several advantages in stabilization and maintenance of adequate ventilation. Using VACV allows adequate oxygenation and ventilation, and it decreases the work of breathing while treating a pathologic process. It is commonly used in patients expected to be passive, as in routine use in the operating room for general anesthesia and in comatose patients.

VACV is a combination mode of ventilation in which the preset tidal volume is delivered in response to the inspiratory effort or if no patient effort occurs within a set period of time. The period is determined by the backup respiratory rate set on the ventilator. A patient-triggered breath is sensed by a change in airway flow or pressure. When the change reaches the trigger threshold, the ventilator delivers the predetermined tidal volume. In ACV, the limit variable that increases to the set threshold before inspiration ends is volume or flow, or both. The cycle variable that ends inspiration is volume or time. Peak inspiratory airway pressure and plateau pressure are variable in this setting. In patients with deep sedation or neuromuscular blockade, the ACV mode functions like CMV. The advantage of ACV is that it substantially decreases the work of breath and decreases myocardial oxygen demand. The disadvantages of ACV in the active patient are that it is less comfortable than spontaneous breathing and that it can induce respiratory alkalosis and breath-stacking (Table 48-3).

TABLE 48-3 Advantages and Disadvantages of Conventional Modes

Ventilation Mode	Advantages	Disadvantages
ACV	Predictable tidal volumes Mandatory respiratory rate Useful for reliable ventilation Good for stabilization of hypoxemia Decreases work of breathing

Uncomfortable for the awake patient

Respiratory alkalosis possible

Breath-stacking, auto-PEEP

Not a weaning mode

Usually requires sedation

SIMV

More comfortable

Allows respiratory muscle work

Spontaneous breaths vary

Increases weaning time

PSV

More comfortable

Allows for evaluation of spontaneous work of breathing

Weaning mode

No guaranteed respiratory rate

No guaranteed tidal volume

Apnea can be disastrous

ACV, Assist-control ventilation; PEEP, positive end-expiratory pressure; PSV, pressure-support ventilation; SIMV, synchronized intermittent mandatory ventilation.

When ACV is used in a volume-targeted mode, airway pressures vary. When patients with severe hypoxemia (e.g., ARDS) require high PEEP and FIO₂ settings to maintain adequate oxygenation, the airway pressures that are generated to deliver the desired tidal volume increase. This increasing pressure can be measured as the peak inspiratory pressure, the mean airway pressure, or the plateau pressure, all of which attempt to describe the pressures that are transmitted through the airways at different levels and at different points in the respiratory cycle. As the plateau pressures increase, reflecting increasing alveolar pressure, it may be prudent to use a pressure-control variant of the ACV mode.

TABLE 48-4 Comparison of Volume-Targeted and Pressure-Targeted Assist-Control Ventilation

Parameter	Volume-Targeted Ventilation	Pressure-Targeted Ventilation
Frequency (rate)	Set	Set
Tidal volume	Set	Variable
Inspiratory flow	Set	Set
Peak inspiratory pressure	Variable	Set
PEEP	Set	Set
FIO₂	Set	Set

PEEP, Positive end-expiratory pressure; FIO₂, fraction of inspired oxygen.

Figure 48-3 Graphs of airway pressure versus time and airflow versus time compare volume assist-control ventilation (VACV) and pressure assist-control ventilation (PACV).

(From Marini JJ: Point: Is pressure assist-control preferred over volume assist-control mode for lung protective ventilation in patients with ARDS? Yes. Chest 140:286–290, 2011.)

ARDS is commonly seen in medical and surgical patients and presents dilemmas in treatment.³⁶ According to the 1994 American-European Consensus Conference definition, ARDS is recognized as a spectrum, which includes ALI, as defined by a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO₂/FIO₂) of 300 or less, and ARDS, which is defined as a PaO₂/FIO₂ ratio of 200 or less. Other characteristics of ARDS are the acute onset of bilateral pulmonary infiltrates and a pulmonary capillary wedge pressure of less than 18 mm Hg (or no evidence of elevated left atrial pressure). ARDS is synonymous with noncardiogenic pulmonary edema.³⁷ ALI has many direct and indirect causes. Examples of direct injury are pneumonia, orogastric fluid aspiration, and inhalation injury; indirect causes of injury include severe sepsis, shock, pancreatitis, blood product transfusion, and narcotic overdose.³⁸

Ventilatory strategies for the management of ARDS rest on the results of the ARDS Network studies, which demonstrated that patients given tidal volumes of 6 mL/kg of predicted body weight had improved mortality rates compared with patients with tidal volumes of 12 mL/kg of predicted body weight. Another finding was that plateau pressures less than 30 cm H₂O protect the lung (Fig. 48-4 and Table 48-5).¹² In 1998, Amato and colleagues demonstrated the mortality benefit of lower tidal volumes and a lower rate of barotraumas (Fig. 48-5).¹⁶ Two meta-analyses demonstrated decreased mortality rates with the use of low tidal volume ventilation (i.e., lung-protective ventilation).^39,⁴⁰ In ARDS management, plateau pressures should be less than or equal to 30 cm H₂O or the lowest possible level. A high-PEEP strategy decreased the mortality rate in a meta-analysis of 2299 ARDS patients.²³ Randomized trials of ventilation in ARDS patients are summarized in Table 48-6.

Figure 48-4 The Kaplan-Meier curve from the ARDS Network study compares survival to 180 days and discharge to home without breathing assistance in the lower tidal volume group and the traditional tidal volume group.

(From Acute Respiratory Distress Syndrome Network: Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 342:1301–1308, 2000.)

TABLE 48-5 Main Outcome Variables in the Acute Respiratory Distress Syndrome (ARDS) Network Trial of Low Tidal Volumes versus Traditional Tidal Volumes in Patients with ARDS

Figure 48-5 Comparison of the 28-day survival of patients with acute respiratory distress syndrome (ARDS) assigned to protective or conventional mechanical ventilation.

(From Al-Saady N, Bennett ED: Decelerating inspiratory flow waveform improves lung mechanics and gas exchange in patients on intermittent positive-pressure ventilation. Intensive Care Med 11:68-75, 1985.

TABLE 48-6 Summary of Randomized, Controlled Trials of Ventilatory Strategies Used for Adult Patients Who Have or Are at Risk for Acute Respiratory Distress Syndrome to Prevent Ventilator-Associated Lung Injury

B Synchronized Intermittent Mandatory Ventilation

SIMV is a frequently used mode of ventilation in hospital medical and surgical units. SIMV has some features that incorporate characteristics of ACV and PSV. SIMV uses the same settings as ACV: frequency, tidal volume, PEEP, and FIO₂, but it also has a setting for a prescribed pressure support for a spontaneous breath. The purpose of the two types of breaths (i.e., mandatory and spontaneous) is to allow increased diaphragmatic activity and increased work of breathing by the patient when triggering spontaneous breaths. SIMV is sometimes used as a weaning mode, but it can prolong mechanical ventilation and is therefore not routinely recommended for weaning.⁴¹

When a patient is deeply sedated or paralyzed, SIMV functions the same as ACV. The patient receives the set number of mandatory breaths as determined by the set frequency at the prescribed tidal volume with the set PEEP and FIO₂. However, in patients who are more awake, SIMV can assist the patient when he or she triggers a mandatory breath and can support the patient with the prescribed pressure support and PEEP in spontaneous breaths that are above the number of mandatory breaths set. The advantage of this mode is that it allows the patient to get the set number of mandatory breaths by controlling the breaths (if the patient is not initiating inspiration) or assisting breaths (if the patient is triggering the start of inspiration), and the patient is allowed to make an effort at spontaneous breaths. The use of SIMV also may reduce sedation requirements (see Table 48-3).⁴²

C Pressure-Support Ventilation

PSV is used for patients who are awake enough to accomplish spontaneous breathing. PSV was initially developed to reduce work of breathing in SIMV but evolved into a stand-alone mode of ventilation. PSV augments the patient’s spontaneous inspiratory efforts with the selected level of positive airway pressure. The inspiratory pressure is delivered until the flow decreases to a predetermined level (usually 25% of peak flow). PSV allows the user to control the desired pressure support, PEEP, and FIO₂. This mode relies entirely on spontaneous breaths by the patient, who must have an intact ventilatory drive. The work of breathing of PSV is inversely proportional to the level of pressure support and the flow rate.⁴³ Because no tidal volume is guaranteed by this mode of ventilation, pressure support must be titrated to help the patient achieve an adequate tidal volume. However, any change in lung compliance or airway impedance results in a change in tidal volume. A certain level of pressure support is needed to overcome the resistance of the ventilator circuit and endotracheal tube. This typically is less than 10 cm H₂O, but it can be higher with narrower endotracheal tubes.⁴⁴ Pressure support above that needed to overcome resistance supplements the achieved tidal volumes. Typical pressure support settings are 5 to 25 mm H₂O. When full ventilator support is needed for the patient, PSV may not be the ideal mode because it requires a higher work of breathing and minute ventilation is not guaranteed (see Table 48-3).

D Pressure-Regulated Volume Control

Pressure-regulated volume control (PRVC) can be employed with ACV or SIMV. With PRVC, the ventilator monitors the patient’s effort and varies the peak inspiratory pressure that is allowed with the inspiratory flow to achieve the set tidal volume. The ventilator provides a breath at a low pressure and then calculates the peak pressure necessary to deliver the set tidal volume. That pressure level is delivered during the next breath. If the target is not attained, the peak pressure is adjusted by 1 to 3 cm H₂O for the next breath. This allows breath-to-breath correction and enables increased airway pressure control. Because the inspiratory time and flow are autoregulated, it results in a smaller increase in plateau airway pressures with a given tidal volume. Because the ventilator responds to the patient’s effort in PRVC, as the patient’s ventilator demand increases, the inspiratory pressure decreases, thereby increasing the patient’s work of breathing.⁴⁵

IV Uncommon Modes of Ventilation

A Inverse-Ratio Ventilation

Inverse-ratio ventilation (IRV) is positive-pressure ventilation with an inspiratory-expiratory (I : E) ratio of greater than 1. It has been used in the management of severe ARDS to improve oxygenation when PEEP has been optimized.⁴⁶ I : E ratios usually range from 1.2 to 1.5, whereas in IRV, they may be 1 : 1, 2 : 1, or higher. Increasing the inspiratory time increases mean airway pressure without increasing the inspiratory plateau pressure, which may improve oxygenation.^47,⁴⁸ This application is most commonly used with time-cycled pressure-control ventilation (PCV), but it can also be used with volume-cycled ventilation. The improvements in oxygenation are modest, and carbon dioxide elimination is preserved or enhanced^48,⁴⁹; however, not all studies have shown benefit.⁵⁰ Development of auto-PEEP is common in IRV, and it may be responsible for some of the improvements in oxygenation, but it also increases the risk of barotrauma. Because the benefits of IRV are controversial, it should be limited to use in patients with severe ARDS with refractory hypoxemia.⁵¹

B Airway Pressure–Release Ventilation

Airway pressure–release ventilation (APRV) is similar to a blend of inverse-ratio PCV and SIMV. APRV offers two levels of continuous positive airway pressure (CPAP) ventilation, in which it uses high and low pressures to aid in recruitment of atelectatic lung units and allows spontaneous breathing.^52,⁵³ The continuous high positive pressure (P_high) is delivered by the ventilator for a prolonged duration (T_high) and then drops to the lower pressure (P_low) for a short duration (T_low). Spontaneous breathing can occur during high and low pressures. Overall, the lower pressure is set to manage hypoxemia and the upper level to promote CO₂ elimination. When the patient cannot initiate breaths, the mode is identical to inverse-ratio PCV.⁵⁴ One study of 24 patients with ARDS showed that when APRV was compared with PSV, APRV improved oxygenation and cardiac parameters, along with improvements in ventilation-perfusion matching in the lung.⁵⁵

APRV can decrease peak airway pressures, improve oxygenation, improve alveolar recruitment, and improve cardiac output, but the findings have been inconsistent, and there has been no evidence of mortality benefit.⁵⁶^–⁵⁹ During periods of transition between low and high pressures, patient ventilator dyssynchrony can occur. APRV is not recommended for patients with obstructive lung disease or high levels of minute ventilation (Figs. 48-6 and 48-7).

Figure 48-6 Inspiratory and expiratory flow of gas in airway pressure release ventilation. T High, Number of seconds spent at the higher pressure; T Low, number of seconds spent at the lower pressure.

(From Frawley PM, Habashi NM: Airway pressure release ventilation: Theory and practice. AACN Clinical Issues 12:234–246, 2001.)

Figure 48-7 Pressure-time curve for airway pressure release ventilation. Paw, Airway pressure; P High, higher pressure used for respiration on bilevel (e.g., 30 cm H₂O); P Low, lower pressure used on bilevel (e.g., 0 cm H₂O); T High, number of seconds in the respiratory cycle spent at the higher pressure; T Low, number of seconds spent at the lower pressure.

(From Frawley PM, Habashi NM: Airway pressure release ventilation: Theory and practice. AACN Clinical Issues 12:234–246, 2001.)

Bi-level ventilation is similar to APRV but has additional features.⁶⁰ The transitions from low and high pressures are coordinated with the patient’s effort to reduce dyssynchrony. T_low usually is longer in bi-level ventilation, which allows for more spontaneous breaths to occur at this pressure level. As in APRV, bi-level ventilation has been used primarily in patients with ALI or ARDS, and it should be avoided in patients with obstructive lung disease because of the risk of auto-PEEP due to shortened expiratory times.

C High-Frequency Ventilation

There are many types of high-frequency mechanical ventilation. High-frequency ventilation is positive-pressure ventilation with tidal volumes near the anatomic dead space and flow rates greater than 60 breaths/min. The theoretical advantages over conventional ventilation are that the tidal volumes of 1 to 3 mL/kg and the higher levels of PEEP reduce the risk of cyclical alveolar injury and collapse and limit alveolar overdistention. The ability to maintain high mean airway pressures and lower plateau pressures can improve oxygenation.

High-frequency oscillatory ventilation (HFOV), sometimes called the oscillator, is a means of improving oxygenation by providing an oxygen-rich and CO₂-poor gas at high respiratory rates that rapidly mixes with sinusoidal flow at stroke volumes that approximate anatomic dead space. HFOV is the most commonly used high-frequency ventilator in adults. HFOV uses a pump to generate a respiratory frequency of 3 to 6 Hz or 180 to 360 breaths/min. In a 1984 publication, Chang described five mechanisms of oxygen delivery by high-frequency oscillation: direct alveolar ventilation of proximal airways; bulk convective gas mixing in conductive airways by recirculation of air among neighboring airways in different cycles of opening and closing of the alveolus; convective transport of gases; longitudinal dispersion by airway turbulence; and molecular diffusion.⁶¹ Additional work is needed to delineate the exact mechanisms involved in gas exchange in high-frequency ventilation.

Selection guidelines for HFOV do not exist, but patients with ARDS who develop refractory hypoxemia on conventional ventilation are sometimes considered.⁶²^–⁶⁴ In patients with ALI that progresses to ARDS, high PEEP and FIO₂ values may be required to sustain oxygenation. HFOV uses high airway pressures during very short time intervals to help recruit and oxygenate atelectatic lung. The mean airway pressure is set by manipulation of the inspiratory flow rate and an expiratory back-pressure valve. A multicenter trial of 148 patients with ARDS compared conventional ventilation with high-frequency oscillatory ventilation. Patients were randomized to receive conventional mechanical ventilation or high-frequency oscillatory ventilation and were followed to compare 30-day ventilator-free survival. Results demonstrated improved 30-day mortality rates in the HFOV group, but it did not rise to statistical significance, nor did various secondary end points, including rates for 6-month mortality and duration of mechanical ventilation.⁶³ HFOV in patients with obstructive lung disease (e.g., COPD, asthma) may lead to significant auto-PEEP.

The oscillator requires vigilance on the part of the physician and respiratory therapist because patients are usually hypoxemic at the initiation of HFOV. Because the oscillator is uncomfortable for patients, they usually require increased sedation and often need pharmacologic paralysis. Careful titration of inspiratory pressure and frequency are needed to obtain optimal settings. During HFOV, ventilation is a passive process, and the patient must have the endotracheal tube cuff deflated to allow for passive exhalation of CO₂. Overall, HFOV appears to be equivalent to conventional ventilation in ARDS patients and useful in the management of refractory hypoxemia and severe air leaks (Fig. 48-8).⁶⁵

Figure 48-8 The pressure-time curve for high-frequency oscillatory ventilation (HFOV) is superimposed on the tracing for pressure-control ventilation (PCV) for comparison.

(From Chang KP, Stewart TE, Mehta S: High-frequency oscillatory ventilation for adult patients with ARDS. Chest 131:1907–1916, 2007.)

In high-frequency jet ventilation (HFJV), a pressurized gas is introduced by inserting a cannula from the HFJV device into the endotracheal tube. An initial pressure of 35 pounds per square inch is set with a rate of 100 to 150 breaths/min and an inspiratory fraction of 30%.⁶⁶ HFJV is more commonly employed in pediatric patients, but it has some use in laryngeal surgery. The drawback of conventional jet ventilators is there is not an adequate measure of intrapulmonary pressure in the circuit, and the patient may be at risk for volutrauma from overdistention of distal airways.

High-frequency pressure ventilation (HFPV) is a time-cycled, pressure-limited mode of ventilation that delivers subphysiologic tidal volumes at rates as high as 500 breaths/min.⁶⁷ HFPV has been used in burn units, specifically for patients with inhalation lung injury, and for salvage therapy in patients with severe ARDS.⁶⁸ The basic tenets are the same as for HFOV, but it oscillates at two different pressure levels. A Phasitron valve at the end of the endotracheal tube delivers small tidal volumes at frequencies of 200 to 900 breaths/min superimposed on PCV. Whereas the HFOV uses rapid oscillations of small volumes at high frequencies that transiently reach high airway pressures, the HFPV prolongs the application of high airway pressure at high frequencies to assist in clearance of mucus and in sloughing airway secretions. A single-center, prospective, randomized trial comparing HFPV with low tidal volume ventilation in burn patients with ALI demonstrated no difference in mortality rates or ventilator-free days.⁶⁹

V Noninvasive Ventilation

NIPPV provides ventilatory support through an external interface such as a nasal or oronasal mask that is firmly secured to the face. The physiologic effect of NIPPV rests in its ability to provide positive pressure into the nasopharynx or oropharynx that splints open the airway and is then transmitted downstream to the lungs, where it increases lung volume. Several cardiovascular effects are seen with NIPPV in this setting. Decreased venous return occurs, and the increased intrathoracic pressure can decrease afterload and thereby increase cardiac output. Figure 48-9 details the interaction of the effects of NIPPV on the cardiopulmonary system.

Figure 48-9 Physiologic effects of positive airway pressure.

(Adapted from Antonescu-Turcu A, Parthasarathy S: CPAP and Bi-level PAP therapy: New and established roles. Respir Care 55:1216–1228, 2010.)

Patient selection is paramount in the decision to initiate NIPPV. NIPPV is not recommended for patients with upper airway obstruction, cardiac arrest, hemodynamic instability, respiratory arrest, injury of the face, massive gastrointestinal bleeding, a high risk of aspiration, significantly depressed mentation, or an inability to clear secretions (Table 48-7).⁷⁰^–⁷²

TABLE 48-7 Factors for Success or Failure of Noninvasive Positive-Pressure Ventilation

Success	Failure
• High PaCO₂ with low A-a gradient • Improvement in pH, PaCO₂, and decreased respiratory rate after 1 hour of NIPPV • Good level of consciousness

• High APACHE score

• Pneumonia on chest radiograph

• Copious secretions

• Edentulous

• Poor nutrition status

• Confusion or delirium

A-a, Alveolar to arterial; APACHE, Acute Physiology and Chronic Health Evaluation; PaCO₂, arterial partial pressure of carbon dioxide; NIPPV, noninvasive positive-pressure ventilation.

NIPPV has been useful in many situations, including exacerbations of COPD with hypercapnia,⁷³^–⁷⁵ cardiogenic pulmonary edema,⁷⁶^–⁷⁹ hypercapnic respiratory failure (i.e., Glasgow Coma Scale score greater than 10), and hypoxic respiratory failure.

NIPPV can be delivered by a standard ventilator through a face mask, nasal mask, or nasal plugs. Heated humidification increases the patient’s comfort.⁸⁰ Common modes of ventilation used to deliver NIPPV are CPAP, bi-level positive airway pressure (BPAP), PSV, proportional-assist ventilation (PAV), and ACV. Modes of NIPPV may be selected on the basis of patient characteristics. For example, patients who require greater support in reducing the work of breathing should be placed on ACV mode, or the patient’s comfort may be increased with PSV.⁸¹ There was no difference in mortality rates between these modalities for various disease states.⁸²^–⁸⁵ The patient should be monitored very closely after initiation of NIPPV. If prompt improvement is not evident within 1 or 2 hours, the physician should proceed to intubation.⁸⁶ In a prospective, multicenter, cohort study, NIPPV failed in 30% of patients. The highest intubation rates occurred in patients with ARDS (51%) or community-acquired pneumonia (50%), and the lowest rates were for those with pulmonary contusion (18%) or cardiogenic pulmonary edema (10%) (Fig 48-10).⁸⁷

Figure 48-10 Airflow, volume, and airway pressure (Paw) versus time tracings for continuous positive airway pressure (CPAP) and bi-level positive airway pressure (Bi-level PAP).

(From Antonescu-Turcu A, Parthasarathy S: CPAP and Bi-level PAP therapy: New and established roles. Respir Care 55:1216–1228, 2010.)

NIPPV improves mortality rates and length of stay for patients with severe COPD exacerbations.⁴ A meta-analysis of patients with severe COPD exacerbations and mild COPD exacerbations demonstrated no mortality benefit for the patients with milder COPD exacerbations.⁷⁴ In cases of cardiogenic pulmonary edema, NIPPV decreases the rate of intubation, but the mortality benefit is uncertain because of conflicting study results.^3,⁸⁸ Patients with hypoxic respiratory failure and asthma exacerbations may benefit from NIPPV. NIPPV use in post-extubation failure has been studied.^89,⁹⁰ If NIPPV is used immediately on extubation in patients with hypercapnia during the spontaneous breathing trial, it may prevent reintubation and is associated with a reduction in mortality rates.⁹¹ NIPPV use in patients after the development of post-extubation failure did not reduce reintubation rates and increased mortality rates, with a longer median time from failure to reintubation in the NIPPV group.⁹²

In patients with severe COPD exacerbations and cardiogenic pulmonary edema, NIPPV should be attempted if no contraindications exist. In other causes of respiratory failure, such as hypoxic respiratory failure, NIPPV can be considered if the patient does not meet the criteria for intubation. However, if the patient does not stabilize in the first 2 hours, management should rapidly progress to intubation and invasive mechanical ventilation.

VI Weaning From Mechanical Ventilation

The process of weaning from mechanical ventilation is a continuum from decreasing support provided by the ventilator to assessment of readiness using multiple variables, and discontinuation from the mechanical ventilator.

In 2001, a collective task force from the American College of Chest Physicians, the American Association of Respiratory Care, and the American College of Critical Care Medicine examined the issue of discontinuation of mechanical ventilation and defined patients who required prolonged mechanical ventilation and strategies to liberate them from the mechanical ventilator. They found that patients who are mechanically ventilated spend approximately 42% of their ventilator time undergoing the weaning process. The task force offered 12 recommendations to standardize practice for discontinuing mechanical ventilation, including searching for causes of respiratory failure; early discontinuation of sedation of postoperative patients; ensuring daily spontaneous breathing trials for patients who meet the criteria for hemodynamic, pulmonary, and mental stability; outlining criteria for evaluation of patients on a spontaneous breathing trial; and strategies for prolonged weaning and daily spontaneous breathing trials assisted by nonphysician practitioners within the health care organization.⁹³ The clinical criteria outlined by the task force includes clinically improving cause of respiratory failure, adequate oxygenation (defined as PaO₂/FIO₂ greater than 150 mm Hg or oxyhemoglobin saturation greater than 90%, while receiving FIO₂ less than or equal to 0.4 and a PEEP less than or equal to 5 cm H₂O); hemodynamic stability (absent or low-dose vasopressors and no signs of myocardial ischemia); arterial pH greater than 7.25; and a patient that is able to initiate a spontaneous inspiratory effort.⁹³

A study of 300 patients published in 1996 demonstrated the value of daily screening of patients by trials of spontaneous breathing. In the study, patients were assessed daily by the nurse and respiratory therapist, and if preset guidelines were met, patients underwent a 2-hour spontaneous breathing trial. If the patient passed the trial, the physician was notified, and the patient was extubated. The study demonstrated a decrease in ventilator days; a decrease in the number of complications, including reintubation; and lower hospital cost.⁹⁴ Another study showed a decrease in the number of ventilator days and ICU days with daily weaning of sedation.⁹⁵

In 2007, a second task force produced the Statement of the Sixth International Consensus Conference on Intensive Care Medicine, which answered five important questions about ventilator weaning: What is known about the epidemiology of weaning problems? What is the pathophysiology of weaning failure? What is the usual process of initial weaning from the ventilator? Is there a role for different ventilator modes in more difficult weaning? How should patients with prolonged weaning failure be managed? Based on the answers to these questions, important recommendations were made to help identify the characteristics that predicted favorable and unfavorable weaning outcomes and determine which modes of ventilation should be used when a patient fails the spontaneous breathing trial.

The task force also addressed the use of noninvasive ventilation and prolonged ventilator dependence. Successful weaning was defined as 48 hours free of the ventilator; weaning as early as possible, using spontaneous breathing trials; avoidance of SIMV as a weaning mode; and use of PSV or AC after a failed weaning attempt. NIPPV should not routinely be used after failed extubation; it should be used only in patients with hypercapnia, although CPAP may be useful in preventing hypoxemia in postoperative patients (Table 48-8).⁹⁶

TABLE 48-8 Time from Initiation of Weaning to Successful Extubation with Various Ventilation Modes

In 1995, the Spanish Lung Failure Collaborative Group prospectively compared the use of intermittent mandatory ventilation (IMV), PSV, intermittent trials of spontaneous breathing, and once-daily spontaneous breathing trials. The study showed that spontaneous breathing trials in either form were superior to IMV or PSV in terms of time from initiation of weaning to successful extubation and probability of successful weaning (Fig 48-11).⁴¹

Figure 48-11 The Kaplan-Meier curve shows the probability of successful weaning from mechanical ventilation for pressure-support ventilation versus intermittent mandatory ventilation and for intermittent trials of spontaneous breathing versus once-daily trials of spontaneous breathing.

(From Esteban A, Frutos F, Tobin MJ, et al: A comparison of four methods of weaning patients from mechanical ventilation. Spanish Lung Failure Collaborative Group. N Engl J Med 332:345–350, 1995.)

To illustrate the interaction of spontaneous breathing trials with daily interruption of sedation, the Awakening and Breathing Trial in 2008 showed that after randomizing 336 patients to the standard protocol or to daily discontinuation of sedation and daily spontaneous breathing trials, the intervention group had 3 fewer days on the mechanical ventilator, fewer ICU days, shorter hospital days, and improved survival rates compared with the standard protocol (Figs. 48-12 and 48-13).⁹⁷ Numerous weaning parameters have been studied to hasten liberation from mechanical ventilation, but none have been shown to be superior to using clinical criteria combined with an algorithmic approach to discontinuation of sedation and ventilation.

Figure 48-12 Survival at 1 year after randomization to usual care with trails of spontaneous breathing (SBT) or to trials of spontaneous awakening (SAT) with SBT.

(From Girard TD, Kress JP, Fuchs BD, et al: Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care [Awakening and Breathing Controlled trial]: A randomised controlled trial. Lancet 371:126–134, 2008.)

Figure 48-13 Probability of successful extubation (A), discharge from intensive care (B), or discharge from hospital (C) within the first 28 days after randomization. SAT, Spontaneous awakening trials; SBT, spontaneous breathing trials.

VII Complications of Mechanical Ventilation

A Mechanical Complications

Mechanical ventilation may produce complications from use of an orotracheal or nasotracheal tube and complications of using positive-pressure ventilation. Common complications of artificial airways are laryngeal edema and irritation, tracheal stenosis, sinusitis, vocal cord damage, and paralysis. Complications of positive-pressure ventilation include barotrauma, which may lead to alveolar rupture and a continuum of pneumothorax, pneumomediastinum, and subcutaneous emphysema. The lungs are susceptible to alveolar distention due to high tidal volumes delivered by the ventilator to alveoli as a result of preset volumes. Due to the heterogenous nature of the lung, even lower volumes may be disproportionally delivered to open alveoli. Atelectotrauma, or cyclic atelectasis, is sheer-force trauma resulting from repeated opening and collapsing of the alveolus in response to positive-pressure ventilation (Fig. 48-14).

Figure 48-14 A telectotrauma (i.e., cyclic atelectasis) results from the sheer forces generated by repeated opening and collapsing of the alveoli in response to positive-pressure ventilation.

(From Papadokos PJ, Lachmann B: The open lung concept of mechanical ventilation: The role of recruitment and stabilization. Crit Care Clin 23:241–250, 2007.)

Volutrauma and atelectotrauma are within the spectrum of ill-defined entities of ventilator-associated lung injury (VALI), which appears to be more common in lungs of patients with ARDS or ALI. Although causation has not been determined, VALI has been observed in patients who have undergone mechanical ventilation. VILI is an entity well described in animal models. It is a syndrome of diffuse alveolar damage that is morphologically identical to ARDS and that is caused by mechanical ventilation.⁹⁸ Alveolar injury results in increased permeability, loss of functional surfactant, release of cytokines, and alveolar collapse (Fig. 48-15). Other factors that may be associated with an increased risk for VALI include immunosuppression,⁹⁹ high ventilator rates,¹⁰⁰ supine body position, and hyperthermia.¹⁰¹

Figure 48-15 Downstream effects of lung injury from mechanical ventilation.

(From Papadokos PJ, Lachmann B: The open lung concept of mechanical ventilation: The role of recruitment and stabilization. Crit Care Clin 23:241–250, 2007.)

1 Auto-PEEP

Intrinsic PEEP or auto-PEEP results from incomplete alveolar emptying before the initiation of the next breath.¹⁰² The alveolar pressures remain positive relative to atmospheric pressures at end-expiration. High minute ventilation from high tidal volumes or respiratory rates is a common cause. When high respiratory rates exist, expiratory time may be decreased to a point at which the full tidal volume is not exhaled before the next breath. High tidal volumes are less likely to be exhaled entirely before the next breath. Patients with obstructive lung diseases such as COPD and asthma often have auto-PEEP while on mechanical ventilation due to disease-related limited expiratory flow.¹⁰³ Expiratory resistance from any obstruction of the endotracheal tube (e.g., kinks, secretions) or patient-ventilator asynchrony can lead to auto-PEEP. Auto-PEEP can result from high tidal volumes, a high respiratory rate, or a decreased expiratory time relative to inhalation time in any disease state (Table 48-9).

TABLE 48-9 Auto-PEEP Factors

Causes of Auto-PEEP	Factors
High minute ventilation	High tidal volume
High minute ventilation	High respiratory rate
Expiratory flow limitation	Airway narrowing from bronchospasm, collapse, inflammation, or remodeling
Expiratory resistance	Patient-ventilator asynchrony
	Narrow or obstructed endotracheal tube
	Secretions

PEEP, Positive end-expiratory pressure.

2 Consequences of Auto-PEEP

Auto-PEEP can decrease venous return, reduce ventricular compliance, and induce hypotension.¹⁰⁴ Hypovolemic patients are at increased risk for PEEP-related hypotension. Alveolar distention from auto-PEEP can lead to barotrauma, worsening oxygenation from ventilation-perfusion () mismatch, and VALI. Auto-PEEP increases the work of breathing by raising the pressure the patient must generate to trigger a ventilator breath. If the breath is triggered at −2 cm H₂O and the auto-PEEP is 6 cm H₂O, the patient needs to overcome both (−8 cm H₂O of negative pressure) to initiate a breath. Auto-PEEP increases peak and plateau pressures in volume-controlled modes and decreases tidal volume in pressure-cycled ventilation.²⁴ Auto-PEEP also increases peak and plateau pressures, which can lead to an overestimation of thoracic compliance. Increased plateau pressures can be transmitted to the intrathoracic vessels and can lead to an overestimation of the central venous pressures and the pulmonary artery occlusion pressure (Table 48-10).

TABLE 48-10 Consequences of Auto-PEEP

Affected System	Consequences
Cardiac	Decreases venous return Hypotension Overestimation of CVP and PCWP

Pulmonary

Alveolar overdistention

Barotrauma or pneumothorax

Increases peak and plateau in pressure ventilation

Increases work of breathing

Underestimation of thoracic compliance

CVP, Central venous pressure; PCWP, pulmonary capillary wedge pressure; PEEP, positive end-expiratory pressure.

Auto-PEEP can be monitored in several ways but sometimes can be difficult to detect. The graphs of flow versus time demonstrate initiation of a new breath before the expiration reaches zero flow. End expiratory alveolar pressure, measured by introducing an end-expiratory breath-hold and subtracting applied PEEP, can quantitate auto-PEEP. The breath-hold allows the pressure in the proximal airways to equilibrate with alveolar pressure. Auscultation for airflow at the end of expiration is also useful.¹⁰⁵

Management of auto-PEEP is targeted at promoting alveolar emptying and increasing expiratory time. Reducing minute ventilation by targeting tidal volume or the respiratory rate, or both, and by increasing inspiratory flow can be effective measures in reducing auto-PEEP. Management of the underlying condition is important, especially for patients with obstructive lung diseases treated with bronchodilators, steroids, and antimicrobial therapies. In patients with COPD or asthma, the limited expiratory flow can be counterbalanced by application of extrinsic PEEP.¹⁰⁶ Small amounts of extrinsic PEEP can decrease intrinsic PEEP by keeping the small airways open at end-expiration. However, the applied PEEP should be less than intrinsic PEEP to prevent an increase in alveolar pressures.¹⁰⁷

B Infectious Complications

Ventilator-associated pneumonia (VAP), a type of hospital-acquired pneumonia (HAP), is defined as a diagnosis of pneumonia 48 to 72 hours after endotracheal intubation. Studies of management with noninvasive ventilation show a decreased incidence of pneumonia when endotracheal intubation is avoided.⁹¹ The earlier pneumonia is diagnosed after onset of mechanical ventilation, the better the prognosis. Pneumonia diagnosed later in the course of mechanical ventilation is more likely to be caused by a drug-resistant organism and carries a worse prognosis. Several practices can help to minimize the occurrence of pneumonia on the ventilator, including elevating the head of the bed to the semirecumbent position of 30 to 45 degrees, aggressive weaning of sedation, use of orotracheal and orogastric tubes to decrease the potential for sinusitis, daily assessments to liberate from mechanical ventilation, avoiding gastric overdistention, avoiding unplanned extubations, oral care with antiseptic solution, and limiting contamination of ventilator tubing.^108,¹⁰⁹ Once a VAP occurs, there is no difference in mechanical ventilation–free days, the length of ICU days, the number of organ failure–free days and mortality rates on day 60 between the groups receiving between 8 days and 15 days of treatment with appropriate antibiotics.¹¹⁰