4 What is the most common cause and mortality rate for acute respiratory distress syndrome?

In the past sepsis syndrome was the most common risk factor for the development of ARDS. In the 1980s three prospective studies evaluated the risk factors for ARDS, and sepsis was identified as a risk in 43% of the cases. The most common diagnosis associated with ARDS, reported in the National Institutes of Health (NIH) Acute Respiratory Distress Syndrome Network (ARDS NET) study, was pneumonia (incidence = approximately 35%); sepsis as an etiology had an incidence of 27%.

The difficulty with interpreting mortality data is that the definition for this syndrome has changed at least three times. Yet three large randomized trials involving over 2000 patients provided consistent mortality data of between 33.9% and 36.3%.

5 Describe the pathogenesis of acute respiratory distress syndrome

Despite more than 30 years of clinical and basic laboratory work, the genesis for ARDS remains elusive. Common to all inciting risk factors is an intense inflammatory pulmonary reaction initially targeted at the interstitial and alveolar-capillary membrane. As a result of injury to the alveolar epithelial and endothelial membranes, flooding of the alveolar space with proteinaceous exudates containing vast numbers of neutrophils results in severe shunting and altered gas exchange. Attraction of polymorphonuclear leukocytes (PMNs) to the injured lung has been linked to the presence of proinflammatory cytokines, endotoxins, thrombin, compliment, and vascular endothelial growth factor. Lung injury and other organ dysfunction may be exacerbated and perpetuated by inappropriate mechanical ventilation, suggesting that a combined biochemical and biophysical injury from alveolar overdistention and shear injury related to repeated opening and closing of distal airways exacerbates parenchymal damage.

6 Describe the stages of acute respiratory distress syndrome

Regardless of the specific etiology, clinical, radiographic, and histopathologic abnormalities generally progress through three overlapping phases, an acute or exudative phase, a proliferative phase, and finally a fibrotic phase also referred to as late ARDS. Identifying each phase in a particular patient is complicated and may be influenced by other confounding variables such as episodes of ventilator-associated pneumonia and the harmful effects of mechanical ventilation.

7 How do patients who develop acute respiratory distress syndrome typically present?

Within 24 hours of an identified risk factor, 80% of patients present with respiratory dysfunction; and within 72 hours the remaining patients progress to signs of respiratory compromise. Most patients will be receiving mechanical ventilation based on physiologic instability from their injury. The extent of hypoxemia (refractory to supplemental O₂) cannot be predicted but may be exacerbated by the patient’s baseline pulmonary function, intravascular volume status, adequacy of cardiac output, and severity of the inciting risk factor. Concurrent with worsening of intrapulmonary shunting the lung compliance is reduced, as evidenced by rising peak alveolar pressures (static plateau pressure). This reflects that the volume of aerated lung is diminished from persistent edema, atelectasis, and consolidation of the diseased lung. It is important to emphasize that the decreased compliance reflects the poor compliance of the lung tissue that is participating in ventilation and not the fluid-filled, consolidated lung. In the nonsedated patient tachypnea and air hunger with elevated minute ventilation are common. Auscultation of the lungs is surprisingly normal, and as a rule volume of secretions aspirated from the artificial airway is minimal.

8 Do any pulmonary diseases mimic acute respiratory distress syndrome?

Based on the NAECC criteria, a number of diffuse noninfectious parenchymal lung diseases fulfill all of the necessary criteria for ALI/ARDS (Table 41-3). Most of the patients who meet these criteria are initially diagnosed with ALI/ARDS secondary to pneumonia. Although pneumonia is one of the most prevalent causes for ARDS, an infectious etiology can be found in about 50% of the cases. Patients who present without an obvious risk factor for pneumonia should undergo a bronchoscopic alveolar lavage and may require an open lung biopsy to fully exclude a noninfectious etiology for their lung disease. The misdiagnosis of a patient having a noninfectious cause for the onset of acute pulmonary dysfunction may exclude them from receiving appropriate therapy with systemic corticosteroids.

TABLE 41-3 Causes of Acute Noninfectious Lung Diseases

9 Are any drug therapies available to treat acute respiratory distress syndrome?

Unfortunately, despite the establishment of an NIH network (ARDS NET) of interactive critical-care treatment groups involved in performing prospective, randomized, controlled, multicenter trials, no effective drug therapy has been identified. Thromboxane synthetase inhibitors, nitric oxide (NO), corticosteroids, surfactant, N-acetylcysteine, inhaled prostacyclin, liquid ventilation, activated protein C, and other agents have also been trialed but with unconvincing success.

10 Does that mean that none of these agents has a role in patients with refractory acute respiratory distress syndrome?

Because no one pharmacologic agent has demonstrated a reduction in mortality rates doesn’t mean that an individual patient may not respond favorably to a targeted drug therapy. For example, inhaled NO, once considered a promising therapy because of its ability to provide selective pulmonary vasodilation and improve ventilation-perfusion mismatch, has not demonstrated improved mortality outcomes. However, if a patient is dying from refractory hypoxemia, trials of inhaled NO have consistently resulted in improved oxygenation and pulmonary hemodynamics in 60% of patients. These benefits are short lived, diminishing over a 24- to 48-hour period; but this bought time may allow for other therapies such as antibiotics to become effective. Similarly, a recent study from ARDS NET pertaining to the safety and efficacy of corticosteroids in persistent ARDS concluded that the routine use of methylprednisolone was not warranted. Nonetheless, to date there have been five trials consisting of 518 patients who have received corticosteroids as part of an ARDS protocol and have demonstrated significant improvements in gas exchange, reduction in markers of inflammation, and decreased duration of mechanical ventilation and intensive care unit (ICU) days. There is nothing routine about refractory ARDS; therefore decisions regarding advanced pharmacologic therapies must be evaluated in light of the patient’s physiologic status.

11 Is there an optimal fluid strategy in acute respiratory distress syndrome?

Recently the ARDS NET demonstrated that a conservative fluid management approach that resulted in a negative fluid balance at day seven (−136 ± 491 ml) vs. a liberal fluid strategy (6992 ± 502 ml) resulted in fewer ventilator days, fewer ICU days, and no increase in nonpulmonary-organ failures. An aside, the use of a pulmonary artery catheter when compared to a central venous catheter demonstrated no differences in outcome.

12 Can mechanical ventilation exacerbate or delay healing from acute respiratory distress syndrome?

Yes. The syndrome of ALI/ARDS results in a very inhomogeneous pattern of lung consolidation. Early in the course of lung injury these heterogeneous changes in lung morphology may give rise to lung zones that consist of normal lung regions; potentially recruitable lung regions within the mid portion of the lungs; consolidated, gravity-dependent lung; and areas of hyperinflated lung tissue. As a consequence of the ongoing structural changes occurring within the lung parenchyma, a ventilator-associated lung injury (VALI) may result from maldistribution of tidal volumes (V_ts) and high airway pressures creating overdistention of remaing normal, aerated lung regions. This high-volume induced form of lung injury is known as volutrauma. Conversely, parenchymal injury also occurs when the lungs are being ventilated from a low lung volume and with low end-expiratory pressures. Although not completely understood, the formation of this low-volume environment probably occurs as a consequence of the increased shear stress) resulting from repeated opening and closing of occluded bronchioles and alveoli from surfactant deficiency. This low-volume induced region of injury is referred to as atelectrauma. Undoubtedly there needs to be a balance between providing a sufficient inspiratory plateau pressure (peak alveolar pressure) while at the same time avoiding insufficient amounts of end-expiratory pressures.

13 How should patients with acute respiratory distress syndrome be ventilated?

As a result of mounting evidence for increased morbidity and mortality associated with ventilator-induced lung injury, clinicians have focused on providing lung protective strategies in patients with ALI/ARDS. Numerous trials have compared the efficacy of a low V_t approach to more traditional V_t. The largest trial was the ARDS NET study involving 861 patients that compared a V_t of 6 ml/kg of predicated body weight to a V_t of 12 ml/kg. Further reduction in V as low as 4 ml/kg was permitted in the low group if end-inspiratory plateau pressures remained >30 cm H₂O, whereas V_t reduction could not occur in the traditional group unless plateau pressures were >50 cm H₂O. Mortality was 39.8% in the traditional V_t group and 31% in the low V_t patients, resulting in approximately a 20% reduction in mortality. In other words, for every 10 patients ventilated with a lung protective approach, one life will be saved.

14 Define lung recruitment maneuver and the different techniques for performing it

Lung recruitment is defined as the application of a prolonged increase in airway pressure, with the goal being reversal of atelectasis; this is followed by the application of sufficient amounts of PEEP to ensure that the lung stays open. Various techniques are available to accomplish recruitment maneuver (RM) (Table 41-4). Most RMs are performed on an intermittent basis through manipulation of the mechanical ventilator, whereas some other techniques are continuous.

TABLE 41-4 Techniques for Performance of Recruitment Maneuvers

Conventional Ventilation	Unconventional Modes	Positioning
Sustained inflation/CPAP CPAP of 30–40 cm H2O

High-frequency oscillation

Use reverse Trendelenburg position; maintain for PEEP 12–24 hours

Pressure-control inverse ratio ventilation

Maintain head of bed at 30 to 45 degrees with frequent turning

CPAP, Continuous positive airway pressure; I:E, inspiratory-to-expiratory ratio; PCV, pressure-control ventilation; PEEP, positive end-expiratory pressure; PIP, peak inspiratory pressure; RR, respiratory rate.

Although RMs are commonly accepted as part of a lung protective strategy for ALI/ARDS, there is still much to be learned about their use: which patients will benefit, direct vs. indirect lung injury, optimal duration for RM, whether RMs should be applied routinely or only during acute hypoxic events, and whether the baseline PEEP makes a difference in terms of response.

15 How does prone ventilation improve oxygenation?

The primary pulmonary defect based on computed tomographic scans of supine patients with ARDS is the opacification of the gravity-dependent areas of the lung as a result of atelectasis and consolidation. Clearly alveolar flooding from formation of edema fluid is partially responsible for the atelectasis, but mechanical imbalances caused by cephalic displacement of the diaphragm with positive-pressure ventilation, decreased thoracic and abdominal compliance, increased pleural pressure in dorsal lung regions, and the weight of the heart causing compression of the lower lung regions all act in concert to worsen atelectasis and promote ventilation-perfusion mismatching. Interestingly, gravity plays only a minor role in perfusion heterogeneity in the lung; therefore the dorsal regions of the lung, regardless of positioning, always receive preferential perfusion. Improvements in oxygenation by using the prone position probably result from:

Recruitment of collapsed dorsal lung fields by a redistribution of lung edema to ventral regions.

Increased diaphragm motion enhancing ventilation.

Elimination of the compressive effects of the heart on the inferior lower lung fields, thus improving regional ventilation.

Maintenance of dorsal lung perfusion in the face of improved dorsal ventilation leads to improved V/Q matching.

16 Does prone ventilation offer a survival benefit in acute respiratory distress syndrome patients?

Since 2001 there have been over nine randomized prospective trials of prone ventilation in critically ill patients. In 2008 alone there have been four metaanalyses of prone ventilation reporting on approximately 1562 patients. All but two of these trials used some form of lung-protective ventilation strategy. The unwavering findings from all of these reports is that prone ventilation results in a consistent improvement in oxygenation but unfortunately shows no clear impact on mortality.

KEY POINTS: Adult Respiratory Distress Syndrome

1. Historically sepsis has been identified as the most common risk factor for ARDS.

2. VALI is thought to be caused by two mechanisms:

Overdistention of normal aerated lung by using high tidal volumes

Lung collapse that occurs as a result of ventilating the lungs with low end-expiratory volumes and pressures

3. Mechanical ventilation settings for patients with ARDS or ALI include tidal volume at 6 to 8 ml/kg of ideal body weight and limiting plateau pressures to <30 cm H₂O.

4. PEEP should be adjusted to prevent end-expiratory collapse.

5. FiO₂ should be adjusted to maintain oxygen saturations between 88% and 92%.