The cornerstone of current management of ARDS consists of supportive therapy, including lung protective ventilation, and cardiovascular manipulation as needed. Supportive management of ARDS should be joined by aggressive diagnosis and treatment of the predisposing condition since the underlying problem (eg, sepsis) typically requires specific therapy.
The majority of patients with ARDS will require intubation and mechanical ventilation to decrease the work of breathing and to apply PEEP. Some causes of ARDS, such as tocolytic-associated pulmonary edema, postictal pulmonary edema, and pulmonary edema associated with air emboli, tend to have a benign course and may respond simply to supportive therapy. Also, some patients will have rather mild ALI and may be successfully ventilated noninvasively (alert patients with near-drowning).5, 6
Mechanical ventilation has been demonstrated to be injurious to the lung by both (1) overdistention of alveoli and (2) repeated recruitment (opening of closed lung during inspiration) and decruitment (closure of that same lung at end expiration), which amplifies lung injury.7, 8
Volutrauma is defined as overdistention of alveoli (rather than pressure, per se) and causes histopathologic, radiologic, and clinical findings of acute lung injury. It is determined by the transpulmonary pressure in the alveoli of concern. Computed tomographic studies show that in most patients, the ARDS lung is remarkably inhomogeneous, with some normally compliant and likely fragile alveoli (nondependent) and others that are flooded or collapsed (dependent). The loss of functional alveoli necessitates that, if the tidal volume is not reduced, alveoli that are open will be overdistended. Indeed, the apparently “stiff” lung of ARDS is better understood as gross overdistention of a few relatively normal alveoli rather than as caused by generalized parenchymal “stiffness.” The mechanisms by which alveolar overstretching produces damage remain controversial, but inflammatory cytokines are found in lavage fluid and systemic blood following ventilation with excessive tidal volumes.9
The lung pressure-volume relationship in ARDS has a sigmoidal shape, with a lower inflection point (LIP) and an upper inflection zone (UIZ), and exhibits hysteresis (better compliance on the descending limb than the ascending limb) when the inflation and deflation limbs are compared (Figure 37-1). The UIZ signals progressively falling compliance, indicating that many alveoli have reached their normal limits of expansion and overdistention has become the predominant influence on compliance. It has been proposed that when the inflation curve reaches the UIZ, that lung is at risk.
Lung protective strategy. Depicted are the two areas of concern during the mechanical ventilation of acute respiratory distress syndrome (ARDS), both amenable to lung protective strategy. On the lower portion of the pressure-volume curve is the lower inflection point where minimum positive end-expiratory pressure (PEEP) is needed to prevent clinically significant alveolar collapse. On the upper portion of the pressure-volume curve is the upper inflection zone where overdistention and volutrauma may occur. In between is the more compliant area of the pressure-volume curve where tidal excursion is desired. (Courtesy of ARDSNet.)
The ARDS Network (ARDSNet) tested the relevance of overdistention in a clinical study using a simple method: limiting tidal volume to 6 mL/kg ideal body weight (IBW).10 This important study entered 861 patients with both ALI and ARDS and randomized them to 6 versus 12 mL/kg IBW. The primary outcome measure, hospital mortality, markedly favored the lower tidal volume approach (39.8% versus 31.0%). A consequence of limiting the tidal volume in this manner is that the partial pressure of carbon dioxide in arterial blood (Paco2) may rise above 40 mm Hg. Tolerating this respiratory acidosis is called permissive hypercapnia and is preferable to alveolar overdistention. Other ARDSNet ventilator strategies include reducing the tidal volume further, if needed, to keep the plateau pressure (Pplat) less than 30 cm H2O; protocolized PEEP and Fio2 settings to maintain the arterial saturation between 88% and 95%; and rate increases to as high as 35 breaths/min.
The ARDSNet protocol including low tidal volume ventilation has become the benchmark against which alternative approaches are compared.10 The existing data support a dose-response relationship in which the lower the tidal volume, the lower the mortality rate.11 However, very low tidal volumes are poorly tolerated in most patients and require significant sedation, which is problematic.
Recruitment/Derecruitment and the Lower Inflection Point
The LIP of the pressure-volume curve (See Figure 37-1) is the point where lower applied pressures will result in significant lung collapse. Many studies suggest that an appropriate level of PEEP (minimal PEEP) applied at the LIP can protect the injured ARDS lung by preventing repeated deflation-inflation across the LIP and the associated shear force injury. Locating the LIP requires constructing a compliance curve by measuring compliance at various PEEP settings following recruitment maneuvers.7 The ARDS Network has tested a higher PEEP approach (superimposed on low tidal volume ventilation) and found no meaningful benefit or harm in this approach. It remains possible, however, that increasing PEEP only in the presence of improving compliance would be an appropriate, yet unconfirmed strategy.
Historically, physicians first attempted to ventilate patients with ARDS to a normal Paco2. In patients with severe acute lung injury, however, this arbitrary goal has a mechanical cost because of inappropriately sized tidal volume and amplification of lung injury, as described above. Over the past decade, there has been increasing evidence that points to the safety and efficacy of allowing the Paco2 to rise well above 40 mm Hg.12 When patients with severe ARDS are ventilated with a lung protective strategy, Paco2 may rise to 50 to 70 mm Hg (occasionally higher) and the pH falls accordingly. Despite the adverse effects of respiratory acidosis in the nonmechanically ventilated patient, very high levels of Paco2 seem remarkably well tolerated by adequately sedated patients. One may allow the Paco2 to rise gradually (5-10 mm Hg/h) in order to allow time for some cellular compensation. In patients without contraindications, sodium bicarbonate may be infused to raise the blood pH. Sodium bicarbonate delivers a substantial Co2 load to a patient already marginally able to excrete what is produced endogenously and further risks volume overload and potassium depletion. Bicarbonate should be considered when ventilator strategy results in very low pH (ie, < 7.20).
Contraindications to permissive hypercapnia are the presence of increased intracranial pressure or active cardiac ischemia; also, the inspired gas must be oxygen enriched to prevent hypoxemia, and patients would be expected to require more sedation. Over time, in patients with good renal function, the kidney will retain bicarbonate in response to the respiratory acidosis as an endogenous compensation mechanism, making permissive hypercapnia easier to maintain.
Approach to Mechanical Ventilation
The principles that guide our ventilatory management of ARDS are (1) avoid alveolar overdistention targeting an initial tidal volume of 6 mL/kg IBW, tolerating hypercapnia if necessary10; (2) obtain and maintain an Fio2 of less than or equal to 0.6 as soon as feasible; and (3) apply PEEP to avoid deflation/reinflation injury. Either volume- or time-cycled assist-control ventilation (ACV) is used. Since with pressure-control ventilation changes in lung elastance or airway resistance over time cause tidal volume to vary, it is typically deployed in a pressure-regulated volume-control (PRVC) or volume-guaranteed mode. In these circumstances the ventilator software adjusts pressure up or down in an attempt to keep tidal volume constant. PRVC ventilation in the distressed ARDS patient may require significant sedation, which, if necessary, in addition to aiding patient-ventilator synchrony, reduces the oxygen consumption and Co2 production.
One of the management goals is to reduce the Fio2 over the first 24 to 48 hours to less than 0.6 to avoid the potential for oxygen toxicity, and this can usually be accomplished by recruitment and increasing PEEP, using pulse oximetry as a guide. Positive end-expiratory pressure exploits the hysteresis of the inflation and deflation limbs of each breath to recruit alveoli on inspiration (by expanding collapsed units and translocating fluid from flooded units to the interstitial space) and then preventing derecruitment at end expiration. Recruitment maneuvers such as applying 40 cm H2O continuous positive airway pressure for 40 seconds may increase lung opening, which can be held open by increased PEEP settings. The result is increased respiratory system compliance as a result of increased functional residual capacity and improved gas exchange because of oxygenation of perfused recruited air space.13, 14 Positive end-expiratory pressure may be initially set at 12 to 15 cm H2O in a single step and then lowered over time as tolerated, or set lower after initial recruitment maneuvers and sequentially increased if recruitment-induced improvement in oxygenation is not maintained. Both methods require re-recruitment and return to previous PEEP setting if desaturation occurs. PEEP raises pleural pressure, which will produce an increase in juxtacardiac pressure; this raises right atrial pressure (downstream pressure for filling of the heart) and decreases the transmural filling pressure of the left ventricle, and hypotension may result. This, however, is uncommon, perhaps because the pleural pressure increment is slight because of a decrease in lung compliance due to ARDS. Significant hypotension can be treated by reducing the PEEP temporarily and by infusing fluids or vasoactive drugs to restore cardiac output. Just as shunt lesions are poorly responsive to increased Fio2, so are they to reduced Fio2, and it is usually possible to achieve the target of 0.6 early in the management of ARDS. If initial PEEP was set at 15 cm H2O following recruitment and adequate oxygenation was achieved, PEEP can be decreased in steps of 2 cm H2O, allowing at least 15 minutes between steps and seeking the least PEEP that maintains the recruitment-induced oxygenation improvement. An alternative to sustained higher inflation pressure over time for recruitment is incremental increases in PEEP with fixed tidal volume. This is a one-step maneuver that simultaneously increases end- expiratory lung volume (recruiting closed lung), with the increase in PEEP keeping some portion of the newly recruited lung from collapsing at end expiration. Reducing PEEP significantly, even for short periods of time, is often associated with alveolar derecruitment and rapid arterial hemoglobin desaturation. Thus, airway disconnections should be kept to a minimum, and when required or occurring, they should be followed by re-recruitment if recruitment had been used as part of the PEEP-setting strategy. When severely hypoxemic patients fail to respond to PEEP, one should suspect a focal lung process, such as lobar pneumonia or atelectasis. In some patients, PEEP must be raised higher than 15 cm H2O (rarely much higher in order to get the Fio2 below 0.6).
Once the PEEP is adjusted and the Fio2 is lowered to 0.6, the tidal volume and rate should be reevaluated. A 0.3-second end-inspiratory pause should be used to determine Pplat. If Pplat exceeds 30 cm H2O, the tidal volume (initially set at 6 cm H2O IBW) should be reduced progressively, in decrements of 0.5 mL/kg IBW, until this target value of less than or equal to 30 cm H2O is achieved. The initial respiratory rate of 20 breaths/min may need to be raised to reduce the work of breathing and help with Co2 elimination, but the expiratory flow waveform should be inspected for the presence of end-expiratory flow (signaling auto-PEEP), which should be avoided. Respiratory rate should typically not exceed 35 to 40 breaths/min.