Chapter 17: Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is a severe lung injury of diverse etiology. It is frequently related to sepsis and multiorgan failure, and is associated with high mortality. ARDS results in diffuse alveolar damage, pulmonary microvascular thrombosis, aggregation of inflammatory cells, and stagnation of pulmonary blood flow. Because many individuals each year develop ARDS in the United States, it consumes much of the time, energy, and resources in the ICU. It is one of the most changeling causes of ventilatory failure to manage and requires adherence to published guidelines.

Clinical Presentation

ARDS is characterized by hypoxemia and decreased pulmonary compliance. Bilateral infiltrates are present on the chest radiograph. Pao₂/Fio₂ less than or equal to 200, and no evidence of left heart failure has been the classic definition of ARDS. Recently ARDS has been categorized as severe (Pao₂/Fio₂ < 100), moderate (Pao₂/Fio₂ 100-200), and mild (Pao₂/Fio₂ > 200). This classification is generally accepted but there is controversy over the conditions that should exist during the assessment. Some suggest that the classification should occur immediately on presentation with a positive end-expiratory pressure (PEEP) more than or equal to 5 cm H₂O without a specific Fio₂ requirement. Others have shown that persistent ARDS requires assessment 24 hours after presentation on a PEEP more than or equal to 10 cm H₂O with an Fio₂ more than or equal to 0.5. Regardless of the approach, the term "acute lung injury," defined by a Pao₂/Fio₂ more than 200 but less than or equal to 300, is no longer used to define the least severe form.

Evaluation of ARDS by chest computed tomography (CT) reveals a very heterogeneous disease with areas of consolidation, areas of collapse that are recruitable, and areas of normal lung tissue. Rather than considering ARDS as low compliance lungs, the gas exchanging areas of the lungs should be considered of small volume when compared with normal lungs.

The pathology of ARDS progresses through two phases, although the process may resolve at any point in either phase. The first phase is characterized by an intense inflammatory response resulting in alveolar and endothelial damage, increased vascular permeability, and increased lung water. This phase lasts about 7 to 10 days and then frequently progresses to extensive fibrosis (Phase 2). ARDS has been categorized as pulmonary and extrapulmonary in origin. With pulmonary ARDS, there is direct injury to the lungs as occurs with aspiration, infectious pneumonia, trauma (lung contusion and penetrating chest injury), inhalation injury, near drowning, and fat embolism. With extrapulmonary ARDS, the initial injury is to an organ system distant from the lungs including sepsis syndrome, multiple trauma, burns, shock, hypoperfusion, and acute pancreatitis. Chest wall effects may be more important for extrapulmonary ARDS and the potential for alveolar recruitment might also be greater for extrapulmonary ARDS.

Ventilator-Induced Lung Injury

As a result of the areas of low lung compliance and the heterogeneous nature of this disease, ARDS is one of the most likely pathologies to develop ventilator-induced lung injury. To avoid ventilator-induced lung injury, a plateau pressure (Pplat) less than or equal to 30 cm H₂O, and as low as possible, along with appropriate PEEP that maintains alveolar recruitment is recommended. Pplat is limited to prevent overdistention, whereas an appropriate level of PEEP is maintained to avoid the injury related to cyclical opening and closing of unstable lung units. It is, however, important to remember that the primary cause of ventilator-induced lung injury is an increased alveolar distending pressure, transalveolar pressure (Pplat minus pleural pressure). Pplat may overestimate the transalveolar pressure when the chest wall is stiff. On the other hand, during pressure-controlled patient-triggered ventilation, the transalveolar pressure may exceed the estimated Pplat with significant inspiratory effort.

Indications

Patients with ARDS present with hypoxemia and increased work-of-breathing. Respiratory support is indicated to reverse hypoxemia with the application of PEEP, delivery of a high Fio₂, and reduction of the work-of-breathing (Table 17-1). The ability to ventilate may become compromised with CO₂ retention. At this stage, mechanical ventilation is indicated because of acute ventilatory failure. The use of mask continuous positive airway pressure (CPAP) and noninvasive ventilation is generally not recommended for patients with ARDS. If noninvasive ventilation is attempted for mild ARDS, there should be a very low threshold for intubation.

Ventilator Settings

The first decision when setting up the ventilator is whether support be provided with full or partial ventilatory support. There is evidence supporting the use of neuromuscular paralysis and appropriate sedation, the first 48 hours after intubation in patients with Pao₂/Fio₂ < 150. In patients with less severe forms of ARDS, sedation but not paralysis is used to facilitate patient-ventilator interaction.

Initial settings and targets when ventilating a patient with ARDS are shown in Tables 17-2 and 17-3. The initiation to mechanical ventilation is shown in Figure 17-1 and the continued approach to ventilation management is shown in Figure 17-2. Two approaches have been advocated for the ventilation of patients with ARDS. The open lung approach uses pressure-controlled ventilation, maintains a low Pplat while monitoring tidal volume, and uses recruitment maneuvers and high levels of PEEP to maximize alveolar recruitment. The ARDSNet approach focuses on maintaining a low tidal volume while monitoring Pplat and sets PEEP based upon the Fio₂ requirement. One approach emphasizes alveolar recruitment and the other prioritizes avoidance of overdistention. Regardless of the approach, there should be an appropriate balance between overdistention and recruitment, as both are important to avoid ventilator-induced lung injury.

Patient triggering may promote alveolar recruitment in dorsal lung regions, it may facilitate venous return, and it may decrease the requirement for sedation. Some clinicians have advocated ventilator modes that allow spontaneous breathing in patients with ARDS, but further study is needed. In the recovery phase and for mild ARDS, pressure support is useful. For severe ARDS, pharmacologic control of ventilation, including paralysis, may be necessary.

The open lung approach (Table 17-4) targets a pressure with pressure-controlled ventilation that ensures a V_T of 4 to 8 mL/kg ideal body weight (IBW) while maintaining peak pressure of less than 30 cm H₂O. Tidal volume is based on IBW, which is determined by measuring the height of the patient (heel to crown with the patient in the supine position). Permissive hypercapnia may be necessary in spite of respiratory rates as high as 35 to 40/min. PEEP is set at 10 to 15 cm H₂O during initial stabilization. After stabilization, PEEP is titrated using a decremental trial following a recruitment maneuver. The goal is to establish the least PEEP that sustains alveolar recruitment. Generally a PEEP of 10 to 20 cm H₂O is set dependent on the severity of the ARDS. After PEEP is set the Fio₂ is decreased to the lowest level that ensures that the Spo₂ and Pao₂ are at or above the target level. The open lung approach emphasizes the role of alveolar recruitment.

The ARDSNet approach prioritizes avoidance of overdistention. For the acute phase, volume-controlled or pressure-controlled continuous mandatory ventilation (assist/control) is used. The target tidal volume is 6 mL/kg IBW and is maintained between 4 and 8 mL/kg IBW. The target Pplat is less than or equal to 30 cm H₂O, and lower if possible. PEEP is set according to the Fio₂/PEEP combination required to maintain the Pao₂ or Spo₂ within the target range (Table 17-5). The low PEEP/Fio₂ table is used for patients with mild ARDS and the high PEEP/Fio₂ table for patients with moderate and severe ARDS. These tables often result in a decremental PEEP titration because high PEEP is required at the onset of intubation and can then be reduced as gas exchange improves. The respiratory rate as high as 35/min is used to maintain pH within the target range. The only factor limiting the setting of rate is the development of auto-PEEP, although auto-PEEP is unusual due to the low compliance and low tidal volume. The primary distinction between the open lung approach and the ARDSNet approach is the focus on lung recruitment maneuvers and decremental PEEP titration with the open lung approach. Both approaches limit V_T and Pplat to avoid overdistention.

Tidal Volume and Plateau Pressure

Avoiding overdistention is key to manage the patient with ARDS. Thus, V_T and Pplat are monitored. The overall goal is to maintain the lowest Pplat possible. It the Pplat is more than 30 cm H₂O with a tidal volume of 6 mL/kg, there should be a reduction in tidal volume to as low as 4 mL/kg IBW. In the setting of severe acidosis or asynchrony, the V_T can be increased to 8 mL/kg IBW provided that Pplat does not exceed 30 cm H₂O. In the setting of asynchrony, the clinician might choose among a higher tidal volume, more sedation, or a mode that promotes synchrony.

Recruitment Maneuvers

The major difference between the ARDSNet approach and the open lung approach is the use of lung recruitment maneuvers and a decremental PEEP trial. The goal of lung recruitment is to maximize the amount of lung volume that can be sustained at a specific PEEP level. The goal of a decremental PEEP trial is to select the minimum PEEP that keeps the lungs open. Once the patient is stabilized after intubation, a lung recruitment maneuver is performed. Stabilization requires hemodynamic stability, because airway pressures 10 to 20 cm H₂O above the normal ventilating pressure are applied for a few minutes. Pulse pressure variation should be less than or equal to 13% before attempting a lung recruitment maneuver. The patient should also be sedated to apnea to ensure synchrony during the recruitment maneuver.

Recruitment maneuvers have been performed using a sustained CPAP (eg, 40 cm H₂O for 40 seconds) or pressure-controlled ventilation. The pressure-controlled approach seems to be better tolerated than the sustained CPAP maneuver. During these maneuvers the patient is carefully monitored and the maneuvers are stopped if the patient becomes hemodynamically unstable, hypoxemic, or develops a cardiac arrhythmia.

A decremental PEEP trial begins at a level higher than the anticipated PEEP needed and then PEEP is decreased. Identification of the lowest decremental PEEP that sustains the benefit of the recruitment maneuver is determined by monitoring dynamic compliance. This is done on a breath-to-breath basis in volume-controlled ventilation. It only requires 3 to 5 minutes for the compliance to stabilize after the PEEP is decreased. If oxygenation is used, it may take 15 to 30 minutes for stabilization of the Pao₂. There is 2 cm H₂O PEEP added to the PEEP determined by best compliance because it underestimates PEEP identified by best oxygenation. As PEEP is decreased, compliance initially increases, and then decreases when PEEP is lower than that necessary to maintain recruitment. Once the best PEEP is determined, the recruitment maneuver is repeated since derecruitment occurred during the decremental PEEP trial.

Other Approaches to PEEP Titration

Perhaps the oldest approach to PEEP titration is based on best compliance. The goal is to identify the PEEP level that maximizes recruitment without causing overdistention. It also recognizes that there are some alveoli that cannot be recruited (consolidation) and some require recruiting pressures so high that there is risk of overdistention of open alveoli. Tidal volume is set at 6 mL/kg and PEEP is increased in 2 to 3 H₂O increments, which results in a stepwise alveolar recruitment. After 3 to 5 minutes at each step, Pplat, Spo₂, and blood pressure are assessed. Best PEEP is identified as the level with the best compliance and Pplat less than 30 cm H₂O.

Another approach uses the stress index. For this approach, the ventilator is set on volume-controlled ventilation with a constant inspiratory flow. Upward concavity of the pressure-time waveform represents overdistention and downward concavity of the pressure-time waveform represents tidal recruitment. PEEP and tidal volume are set so that the increase in pressure is linear, suggesting appropriate recruitment without overdistention. This approach also balances the effects of recruitment against those of overdistention.

The chest wall might affect the PEEP requirement, such as with obesity, high intra-abdominal pressure, fluid overload, or chest wall deformity. These effects increase the pleural pressure, causing alveolar collapse and tidal recruitment/derecruitment. In this case, PEEP is increased to match or exceed the esophageal (eg, pleural) pressure, thus counterbalancing the collapsing effect of the chest wall. The result is that Pplat may exceed 30 cm H₂O. In this case, the esophageal pressure is subtracted from the Pplat to determine alveolar distending pressure (Pplat – esophageal pressure). Pplat more than 30 cm H₂O may be safe if the transalveolar pressure is less than 25 cm H₂O. This approach also attempts to balance recruitment and overdistention.

PEEP can also be titrated to the lowest dead space (ie, lowest Paco₂ for fixed minute-ventilation), but this is not practical because it requires serial blood gas determinations. PEEP can be titrated using the lower inflection point of the pressure-volume curve, although this approach has fallen out of favor in recent years. PEEP can also be titrated by imaging methods such as CT, but this also is not practical. Regardless of the method used to titrate PEEP, higher levels are appropriate for moderate and severe ARDS, whereas modest levels are appropriate for mild ARDS.

Managing Severe Refractory Hypoxemia

When lung-protective ventilation strategies are applied from the onset of mechanical ventilation, the likelihood of severe refractory hypoxemia is often avoided. Much of the ARDS observed in the past was caused by injurious ventilation strategies. Thus, the first step in managing severe refractory hypoxemia is prevention by lung-protective ventilation to all patients from the onset of mechanical ventilation. In addition, hemodynamic instability and asynchrony affect hypoxemia. Alveolar recruitment and appropriate PEEP improves oxygenation and minimizes lung injury due to tidal recruitment/derecruitment.

Prone position may be beneficial in the setting of refractory hypoxemia. The benefit may be greatest for severe hypoxemia (Pao₂/Fio₂ < 150 mm Hg), where being in prone position not only improves oxygenation, but might also afford a survival benefit. If refractory hypoxemia persists despite prone positioning, extracorporeal life support can be considered. Inhaled pulmonary vasodilators may provide short-term improvement in oxygenation, but have not been shown to improve outcome in patients with ARDS. High frequency oscillatory ventilation and airway pressure release ventilation have not been shown to improve outcomes in ARDS.

Monitoring

Hemodynamic monitoring is necessary due to the high PEEP and mean airway pressures sometimes required during ARDS. Pulmonary artery catheters were frequently used in the past to monitor hemodynamic status and to properly titrate fluid therapy and other hemodynamic support. However, pulmonary artery catheters are generally not necessary. Monitoring of arterial blood pressure and central venous pressure is usually adequate to assess fluid status. Daily chest X-rays are used to assess the progression of disease and CT may be helpful. Continuous monitoring of Spo₂ is required, since oxygenation may be difficult to maintain in these patients. Blood gases are indicated when the patient's clinical status changes. Auto-PEEP should be assessed with each ventilator setting change, although it is unusual in patients with ARDS. Reevaluation of Fio₂, PEEP, and Pplat that results in the best gas exchange should occur frequently (Table 17-6).

Liberation

Return to spontaneous breathing following ARDS may be difficult. Patients recovering from ARDS frequently have a high respiratory drive and low lung compliance. Lung function may be compromised for weeks and respiratory muscle weakness may be present. In the recovery phase (ie, when the Fio₂ is 0.40 and the PEEP is 8 cm H₂O with the Pao₂ within the target range), spontaneous breathing trials are initiated. Some patients require tracheostomy. If the patient cannot be extubated, a comfortable level of respiratory support is provided.