First described in 1967, acute respiratory distress syndrome (ARDS) is one of the leading causes of mortality in intensive care units (ICUs), despite improved treatment modalities within the last 15 years. Acute respiratory distress syndrome is considered the most severe form of hypoxic acute lung injury and results in respiratory failure related to noncardiogenic pulmonary edema.

Etiology

Acute respiratory distress syndrome is caused by either a direct or indirect pulmonary injury (Table 1). The syndrome is most frequently a complication of a systemic process, such as sepsis, severe bleeding, or a traumatic injury resulting in shock. However, direct injury to the lung tissue, such as aspiration or inhalation of toxic substances, may also lead to ARDS. The likelihood of developing ARDS increases with the addition of other direct pulmonary or indirect injuries.1

TABLE 1 Predisposing Factors Leading to Adult Respiratory Distress Syndrome

Pathophysiology

No matter its etiology, the physiological changes to the lung tissue are identical, with symptoms occurring within 4 to 72 hours after the inciting incident.2 During this time, the alveolar-capillary membranes become "leaky," allowing fluids, as well as proteins and blood cells, to enter the interstitial space. Increased interstitial protein levels cause a rise in the space's oncotic pressure, which results in less fluid being "pulled" into the capillaries. If the fluids, proteins, and blood cells accumulate too rapidly for the lymphatic system to remove, the consequence is noncardiogenic pulmonary edema, one of the key findings in ARDS patients.

Diffuse bilateral infiltrates on chest radiograph, secondary to lung tissue inflammation, are also characteristic of ARDS.3 In addition, the lungs experience an increase in hyaline membrane formation, development of fibroblasts, and an increased number of alveolar type II cells, as well as the inactivation of pulmonary surfactant.3,4 Interstitial fibrosis may also develop. Together, these factors worsen gas exchange (particularly intrapulmonary shunting), decrease lung compliance, and produce areas of atelectasis adjacent to normal tissue, which all increase the work of breathing.

Diagnosis and Diagnostic Criteria

Definitive diagnostic criteria have been difficult to determine because the syndrome mimics other acute disorders, such as hemodynamic pulmonary edema and acute interstitial pneumonia. The diagnosis of ARDS is determined after ruling out other potential causes and using the American-European Consensus on ARDS criteria (Table 2).5

TABLE 2 The American-European Consensus on ARDS Diagnostic Criteria

The diagnosis of ARDS is determined after ruling out other potential causes and using the American-European Consensus on ARDS criteria.

Clinical Findings

A progression of deteriorating clinical findings is observed and includes worsening tachypnea, dyspnea, hypoxemia, tachycardia, and the appearance of bilateral infiltrates. Initially, patients may experience respiratory alkalosis as their tachypnea decreases PaCO₂. However, as the syndrome progresses and gas exchange worsens, the arterial blood gasses shift to respiratory acidosis followed by metabolic acidosis due to tissue hypoxia and anaerobic metabolism.3,4 In addition, the ventilation-perfusion mismatch and intrapulmonary shunting lead to severe hypoxia, with a decrease in the ratio of percentage of oxygen in arterial blood to fraction of inspired oxygen (PaO₂/FIO₂ ratio) to less than 200. Another hallmark sign of ARDS is profound hypoxemia despite increasing oxygen delivery.3 This is also known as refractory hypoxemia.

PATIENT MANAGEMENT

Gas Exchange and Ventilator Management

Treatment of ARDS primarily focuses on supporting the patient and maintaining adequate gas exchange. The majority of patients require intubation and mechanical ventilation. As previously discussed, ARDS patients typically experience significant oxygenation problems despite higher-than-normal oxygen concentrations being delivered. The prolonged use of FIO₂ concentration of 60% or greater increases the likelihood of oxygen toxicity, which can lead to further lung damage. For this reason, positive end-expiratory pressure (PEEP) is a mainstay of therapy for the mechanically ventilated ARDS patient.6 Positive end-expiratory pressure prevents the patient from completely exhaling and recruits collapsed alveoli, thereby promoting gas exchange.

Controversy exists as to what level of PEEP (high or low) is best for treating ARDS. Most practitioners use a protocol that adjusts a patient's FIO₂ and PEEP levels to provide acceptable oxygenation, typically considered a PaO₂ of 60 mm Hg. Current trends use higher PEEP levels to promote greater alveolar recruitment, coupled with lower ventilator tidal volumes.

The standard practice of setting tidal volumes in mechanically ventilated patients is between 10 and 12 mL/kg of ideal body weight. In ARDS, because of the fragile lung tissue, these tidal volumes place the patient at risk for developing volutrauma/barotrauma, thus increasing mortality rates.7 Therefore, as the syndrome progresses and lung tissue becomes more damaged, the tidal volume is typically decreased to 4 to 8 mL/kg of ideal body weight.8,9 Lowering tidal volumes often lead to higher set respiratory rates; 15 to 25 breaths/min are common, to maintain an adequate minute ventilation for gas exchange.10 With these higher respiratory rates, patients are more likely to air trap gas resulting in auto-PEEP or intrinsic PEEP.11 This is especially true when the inspiratory-to-expiratory ratio becomes closer to 1:1 or is inversed with inspiration longer than expiration. However, it is hypothesized that auto-PEEP may play a key role in the success of the low tidal volume-high respiratory rate treatment modality.11

Another strategy for the ARDS patient is to maintain mechanical ventilation plateau pressures at less than 30 cm H₂O, although this may prove challenging. Typically, ICUs use volume-target ventilation for the majority of mechanically ventilated patients. In volume-target ventilation, the ventilator delivers a specific tidal volume with little concern as to the pressure required to deliver the breath. Practitioners set a "high pressure limit" to ensure that excessive pressures are not reached. When the ARDS patient's pressures climb and reach or exceed plateau pressures of 30 cm H₂O, the health care team should consider using pressure-target ventilation.10,12 These ventilators deliver a practitioner-set pressure, whereas the tidal volume varies based on the patient's lung compliance and airway resistance. By using a preset pressure, the team can ensure that the ARDS patient maintains safe plateau pressures.

Although the above mechanical ventilation strategies will improve oxygenation for most, these efforts will be insufficient in the most critically ill ARDS patients. Permissive hypercapnia occurs when the health care team allows the carbon dioxide levels to climb, in lieu of further damaging the lungs from excessive ventilation, especially when plateau pressure exceeds 30 cm H₂O.10,13 When using permissive hypercapnia, the health care team typically maintains the Paco₂ less than 80 mm Hg and the pH greater than 7.2. In addition, the PaO₂ should remain greater than 60 mm Hg.

The health care team may also consider using high-frequency oscillation ventilation as a treatment option for the most critically ill. High-frequency oscillation ventilation utilizes a respiratory rate ranging from approximately 240 to 600 breaths/min.14 This ventilation strategy is an "open-lung" technique keeping the lung alveoli well recruited to promote additional gas exchange.14,15 Although studies have not shown large differences in ARDS mortality rates, high-frequency oscillation ventilation is safe and may protect the fragile lungs because of the low tidal volumes used in this form of ventilation.14,16

Pharmacological Management

Controlling an ARDS patient's breathing becomes more important as his/her oxygenation status deteriorates. Patient-ventilator dyssynchrony increases the likelihood of lung tissue damage and exacerbates the patient's oxygenation issues. The effective use of sedatives and analgesics is a key intervention (Table 3). A variety of medication combinations are used with the selection influenced by patient characteristics.17 Many health care teams add neuromuscular-blocking agents (NMBAs) to completely control ventilation and promote oxygenation. However, patients receiving NMBAs, especially those receiving corticosteroids such as asthmatic patients, may develop long-term muscle weakness after their use.18 A 2010 study suggested that NMBAs can be safely used and may actually improve the 90-day survival rate.19 Whether sedation and analgesia are used alone, or in combination with NMBAs, the health care team should ensure that the ARDS patient is comfortable and in synchrony with the ventilator to maximize oxygenation.

TABLE 3 Commonly Used Medications for Ventilated Patients With Adult Respiratory Distress Syndrome

Controlling an ARDS patient's breathing becomes more important as his/her oxygenation status deteriorates.

The administration of corticosteroids intuitively makes sense, as lung tissue inflammation is present in the ARDS patient. Trials investigating the use of corticosteroids in ARDS have shown no improvement in mortality rates.20 Unfortunately, the use of corticosteroids for more than 14 days in patients who have ARDS is associated with higher mortality rates and greater neuromuscular weakness.21,22

The administration of nitric oxide (NO) has demonstrated short-term success. Nitric oxide provides potent pulmonary vasodilation, thereby reducing pulmonary hypertension and redistributing blood flow to better ventilated areas in the lungs.20 Nitric oxide appears to improve oxygenation only for the first few days of administration in the ARDS patient. When comparing conventional treatment with NO administration, no significant difference in mortality exists.20,23 Nitric oxide may be useful in treating the most difficult ARDS patients who have significant oxygenation deficits despite conventional therapy.

Just as with NO, surfactant therapy shows promise in short-term improvement of oxygenation for ARDS patients. The surfactant's purpose is to decrease surface tension in the lungs, thereby preventing alveolar collapse.24 In ARDS, exogenous surfactant improves lung compliance and oxygenation. However, studies, to date, have found that the use of surfactant therapy does not significantly improve mortality rates.20,25

Gas Exchange and Positioning

Prone positioning is a relatively newer treatment modality for ARDS. Traditionally, ICU patients, including those with ARDS, are placed in a semi-Fowler or supine position and, if stable, turned side to side. This positioning may last days or weeks and often leads to a worsening of the ventilation/perfusion matching. The use of prone positioning, typically via a specialized bed, allows the placement of the patient on his/her stomach. Prone positioning leads to improved oxygenation by shifting edema, recruiting alveoli, and changing the pleural pressure gradients.26-28 Similar to NO and exogenous surfactant therapy, prone positioning has not improved overall survivability of ARDS.29 In addition, complications such as tube or line displacement, gastric aspiration, facial edema, and peripheral nerve injury may occur when placing a patient in the prone position; therefore, careful attention when using this intervention is necessary.

Fluid Management

Fluid management strategies for the ARDS patient can be difficult because of the presence of noncardiogenic pulmonary edema and increasing hydrostatic pressures from fluid replacement. A multicenter trial evaluating fluid management for ARDS determined that aggressive fluid resuscitation was appropriate only for patients exhibiting shock symptoms.21 Current evidence supports conservative fluid strategies for hemodynamically stable ARDS patients, including the use of diuretics as needed.20 Maintaining a slightly depleted fluid volume status is hypothesized to minimize leakage of excess fluids through the damaged alveolar-capillary membrane, which worsens pulmonary edema.

Nutritional Support

As with all critically ill patients, providing early nutrition that meets the patient's metabolic needs is important, and with ARDS, it has shown to decrease mortality.1 Caloric, protein, carbohydrate, and fat intake should be determined based on the patient's daily metabolic needs, with most requiring 35 to 45 kcal/kg per day.2 A low-carbohydrate, high-fat enteral regimen, with anti-inflammatory and vasodilating components, leads to improved oxygenation and decreased mortality rates.30

A common nutritional problem with ARDS patients is the lack of bowel motility. The health care team will have to determine whether enteral feedings through a small bowel feeding tube, or parenteral support, are more appropriate. It is hypothesized that enteral feedings reduce the incidence of peritonitis and sepsis by decreasing the bacterial translocation associated with impaired perfusion to the gastrointestinal system. Therefore, enteral feeding alone, or in combination with parenteral support, is the preferred method of nutritional support.2

Therefore, enteral feeding alone, or in combination with parenteral support, is the preferred method of nutritional support.

COMPLICATIONS

Most of the complications related to ARDS are the result of sepsis, treatment interventions, and prolonged immobility. The leading cause of death in ARDS patients is sepsis and resulting multiple organ failure.31 Therefore, the health care team must be vigilant in preventing infections. van Soeren and Hulock-Chorostecki2 suggest implementing sepsis and ventilator-associated pneumonia bundles for ARDS patients in effort to prevent these complications (Table 4).

TABLE 4 Sepsis and Ventilator-Associated Pneumonia "Bundles"

In addition to ventilator-associated pneumonia, mechanical ventilation leads to other complications, including cardiovascular and pulmonary problems. Although the addition of PEEP is vital to improving oxygenation for most ARDS patients, increasing PEEP levels can result in decreased cardiac output and/or blood pressure. The health care team must continually assess for signs of hemodynamic deterioration whenever initiating or increasing PEEP levels (Table 5). A patient who is hemodynamically unstable or who, despite appropriate levels of PEEP, has a low PaO₂ may require increases in FIO₂ to ensure adequate oxygenation and to prevent hypoxic organ damage.32

TABLE 5 Signs and Symptoms of Hemodynamic Deterioration in Adult Respiratory Distress Syndrome

Pulmonary complications related to mechanical ventilation include alveoli damage and volutrauma/barotraum.32 Because of the fragileness of the alveoli, even normal tidal volumes and PEEP levels can lead to pneumothorax and subcutaneous emphysema.2 The health care team must remain attentive for the signs and symptoms of a pneumothorax, which requires immediate chest tube insertion.

CONCLUSION

Although there are many recent advances in the care of ARDS patients, morbidity and mortality remain high, and most interventions remain supportive. Treatment modalities currently being investigated in research trials and studies include noninvasive ventilation; pharmacological support with prostaglandins, statins, and albuterol; the role of recombinant human activated protein C; and extracorporeal membrane oxygenation strategies.24,33-35

References