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.