Acute Hypoxemic Respiratory Failure (AHRF, ARDS)
Acute hypoxemic respiratory failure (AHRF) is severe arterial hypoxemia that is refractory to supplemental O2. It is caused by intrapulmonary shunting of blood resulting from airspace filling or collapse. Findings include dyspnea and tachypnea. Diagnosis is by ABGs and chest x-ray. Treatment usually requires mechanical ventilation.
Airspace filling in AHRF may result from
Elevated alveolar capillary hydrostatic pressure, as occurs in left ventricular failure or hypervolemia
Increased alveolar capillary permeability, as occurs in any of the conditions predisposing to acute respiratory distress syndrome (ARDS)
Blood (as occurs in diffuse alveolar hemorrhage) or inflammatory exudates (as occur in pneumonia or other inflammatory lung conditions)
ARDS is divided into 3 categories of severity: mild, moderate, and severe based on oxygenation defects and clinical criteria ( Berlin Definition of ARDS). The mild category corresponds to the previous category termed acute lung injury (ALI).
Berlin Definition of ARDS
In ARDS, pulmonary or systemic inflammation leads to release of cytokines and other proinflammatory molecules. The cytokines activate alveolar macrophages and recruit neutrophils to the lungs, which in turn release leukotrienes, oxidants, platelet-activating factor, and proteases. These substances damage capillary endothelium and alveolar epithelium, disrupting the barriers between capillaries and airspaces. Edema fluid, protein, and cellular debris flood the airspaces and interstitium, causing disruption of surfactant, airspace collapse, ventilation-perfusion mismatch, shunting, and pulmonary hypertension. The airspace collapse more commonly occurs in dependent lung zones.
Causes of ARDS ( Causes of ARDS) may involve direct lung injury (eg, pneumonia, acid aspiration) or indirect lung injury (eg, sepsis, pancreatitis, massive blood transfusion, nonthoracic trauma). Sepsis and pneumonia account for about 60% of cases.
Causes of ARDS
In both types of AHRF, flooded or collapsed airspaces allow no inspired gas to enter, so the blood perfusing those alveoli remains at the mixed venous O2 content no matter how high the fractional inspired O2(Fio2). This effect ensures constant admixture of deoxygenated blood into the pulmonary vein and hence arterial hypoxemia. In contrast, hypoxemia that results from ventilating alveoli that have less ventilation than perfusion (ie, low ventilation-to-perfusion ratios as occurs in asthma or COPD and, to some extent, in ARDS) is readily corrected by supplemental O2.
Acute hypoxemia (see also Oxygen Desaturation) may cause dyspnea, restlessness, and anxiety. Signs include confusion or alteration of consciousness, cyanosis, tachypnea, tachycardia, and diaphoresis. Cardiac arrhythmia and coma can result. Airway closure causes crackles, detected during chest auscultation; the crackles are typically diffuse but sometimes worse at the lung bases. Jugular venous distention occurs with high levels of positive end-expiratory pressure (PEEP) or right ventricular failure.
Chest x-ray and ABGs
Clinical definition ( Berlin Definition of ARDS)
Hypoxemia is usually first recognized using pulse oximetry. Patients with low O2 saturation should have a chest x-ray and ABGs and be treated with supplemental O2 while awaiting test results.
If supplemental O2 does not improve the O2 saturation to > 90%, right-to-left shunting of blood should be suspected. An obvious alveolar infiltrate on chest x-ray implicates alveolar flooding as the cause, rather than an intracardiac shunt. However, at the onset of illness, hypoxemia can occur before changes are seen on x-ray.
Once AHRF is diagnosed, the cause must be determined, considering both pulmonary and extrapulmonary causes. Sometimes a known ongoing disorder (eg, acute MI, pancreatitis, sepsis) is an obvious cause. In other cases, history is suggestive; pneumonia should be suspected in an immunocompromised patient, and alveolar hemorrhage is suspected after bone marrow transplantation or in a patient with a connective tissue disease. Frequently, however, critically ill patients have received a large volume of IV fluids for resuscitation, and high-pressure AHRF (eg, caused by ventricular failure or fluid overload) resulting from treatment must be distinguished from an underlying low-pressure AHRF (eg, caused by sepsis or pneumonia).
High-pressure pulmonary edema is suggested by a 3rd heart sound, jugular venous distention, and peripheral edema on examination and by the presence of diffuse central infiltrates, cardiomegaly, and an abnormally wide vascular pedicle on chest x-ray. The diffuse, bilateral infiltrates of ARDS are generally more peripheral. Focal infiltrates are typically caused by lobar pneumonia, atelectasis, or lung contusion. Although echocardiography may show left ventricular dysfunction, implying a cardiac origin, this finding is not specific because sepsis can also reduce myocardial contractility.
When ARDS is diagnosed but the cause is not obvious (eg, trauma, sepsis, severe pulmonary infection, pancreatitis), a review of drugs and recent diagnostic tests, procedures, and treatments may suggest an unrecognized cause, such as use of a radiographic contrast agent, air embolism, or transfusion. When no predisposing cause can be uncovered, some experts recommend doing bronchoscopy with bronchoalveolar lavage to exclude alveolar hemorrhage and eosinophilic pneumonia and, if this procedure is not revealing, a lung biopsy to exclude other disorders (eg, extrinsic allergic alveolitis, acute interstitial pneumonitis).
Prognosis is highly variable and depends on a variety of factors, including etiology of respiratory failure, severity of disease, age, and chronic health status. Overall, mortality in ARDS was very high (40 to 60%) but has declined in recent years to 25 to 40%, probably because of improvements in mechanical ventilation and in treatment of sepsis. However, mortality remains very high (> 40%) for patients with severe ARDS (ie, those with a PaO2:FIO2< 100 mm Hg). Most often, death is not caused by respiratory dysfunction but by sepsis and multiorgan failure. Persistence of neutrophils and high cytokine levels in bronchoalveolar lavage fluid predict a poor prognosis. Mortality otherwise increases with age, presence of sepsis, and severity of preexisting organ insufficiency or coexisting organ dysfunction. Pulmonary function returns to close to normal in 6 to 12 mo in most ARDS patients who survive; however, patients with a protracted clinical course or severe disease may have residual pulmonary symptoms, and many have persistent neuromuscular weakness.
Underlying conditions must be addressed as discussed elsewhere in The Manual. AHRF is initially treated with high flows of 70 to 100% O2 by a nonrebreather face mask. If O2 saturation > 90% is not obtained, mechanical ventilation probably should be instituted. Specific management varies by condition.
Mechanical ventilation benefits the failing left ventricle in several ways. Positive inspiratory pressure reduces left and right ventricular preload and left ventricular afterload and reduces the work of breathing. Reducing the work of breathing may allow redistribution of a limited cardiac output away from overworked respiratory muscles. Expiratory pressure (expiratory positive airway pressure [EPAP] or PEEP) redistributes pulmonary edema from alveoli to the interstitium, allowing more alveoli to participate in gas exchange.
Noninvasive positive pressure ventilation (NIPPV), whether continuous positive pressure ventilation or bilevel ventilation, is useful in averting endotracheal intubation in many patients because drug therapy often leads to rapid improvement. Typical settings are inspiratory positive airway pressure (IPAP) of 10 to 15 cm H2O and EPAP of 5 to 8 cm H2O (see Overview of Mechanical Ventilation : Noninvasive positive pressure ventilation (NIPPV)).
Conventional mechanical ventilation can use several ventilator modes. Most often, assist-control (A/C) is used in the acute setting, when full ventilatory support is desired. Initial settings are tidal volume of 6 to 8 mL/kg ideal body weight, respiratory rate of 25/min, Fio2 of 1.0, and PEEP of 5 to 8 cm H2O. PEEP may then be titrated upward in 2.5-cm H2O increments while the Fio2 is decreased to nontoxic levels. Pressure support ventilation can also be used (with similar levels of PEEP). The initial pressure delivered should be sufficient to fully rest the respiratory muscles as judged by subjective patient assessment, respiratory rate, and accessory muscle use. Typically, a pressure support level of 10 to 20 cm H2O over PEEP is required.
Nearly all patients require mechanical ventilation, which, in addition to improving oxygenation, reduces O2 demand by resting respiratory muscles. Targets include
PEEP should be high enough to maintain open alveoli and minimize FIO2 until a plateau pressure of 28 to 30 cm H2O is reached. Patients with moderate to severe ARDS are the most likely to have mortality reduced by use of higher PEEP.
NIPPV is occasionally useful with ARDS. However, compared with treatment of cardiogenic pulmonary edema, higher levels of support for a longer duration are often required, and EPAP of 8 to 12 cm H2O is often necessary to maintain adequate oxygenation. Achieving this expiratory pressure requires inspiratory pressures > 18 to 20 cm H2O, which are poorly tolerated; maintaining an adequate seal becomes difficult, the mask becomes more uncomfortable, and skin necrosis and gastric insufflation may occur. Also, NIPPV-treated patients who subsequently need intubation have generally progressed to a more advanced condition than if they had been intubated earlier; thus, critical desaturation is possible at the time of intubation. Intensive monitoring and careful selection of patients (see Noninvasive positive pressure ventilation (NIPPV)) are required.
Conventional mechanical ventilation in ARDS previously focused on normalizing ABG values. It is now clear that ventilating with lower tidal volumes reduces mortality. Accordingly, in most patients, tidal volume should be set at 6 mL/kg ideal body weight (see Initial Ventilator Management in ARDS for Equation). This setting necessitates an increase in respiratory rate, even up to 35/min, to produce sufficient alveolar ventilation to allow for adequate CO2 removal. On occasion, however, respiratory acidosis develops, some degree of which is accepted for the greater good of limiting ventilator-associated lung injury and is generally well tolerated, particularly when pH is ≥ 7.15. If pH drops below 7.15, bicarbonate infusion or tromethamine may be helpful. Because hypercapnia may cause dyspnea and cause the patient to breathe in a fashion that is not coordinated with the ventilator, analgesics (fentanyl or morphine) and sedatives may be needed (eg, propofol initiated at 5 mcg/kg/min and increasing to effect up to 50 mcg/kg/min; because of the risk of hypertriglyceridemia, triglyceride levels should be checked every 48 h). Sedation is preferred to neuromuscular blockade because blockade still requires sedation and may cause residual weakness.
PEEP improves oxygenation in ARDS by increasing the volume of aerated lung through alveolar recruitment, permitting the use of a lower Fio2. The optimal level of PEEP and the way to identify it have been debated. Many clinicians simply use the least amount of PEEP that results in an adequate arterial O2 saturation on a nontoxic Fio2. In most patients, this level is a PEEP of 8 to 15 cm H2O, although, occasionally,patients with severe ARDS require levels > 20 cm H2O. In these cases, close attention must be paid to other means of optimizing O2 delivery and minimizing O2 consumption (see Ventilator settings).
The best indicator of alveolar overdistention is measurement of a plateau pressure through an end-inspiratory hold maneuver (see Acute Hypoxemic Respiratory Failure (AHRF, ARDS) : Mechanical ventilation in ARDS); it should be checked every 4 h and after each change in PEEP or tidal volume. The target plateau pressure is < 30 cm H2O. If the plateau pressure exceeds this value and there is no problem with the chest wall that could be contributing (eg, ascites, pleural effusion, acute abdomen, chest trauma), the physician should reduce the tidal volume in 0.5- to 1.0-mL/kg increments as tolerated to a minimum of 4 mL/kg, raising the respiratory rate to compensate for the reduction in minute ventilation and inspecting the ventilator waveform display to ensure that full exhalation occurs. The respiratory rate may often be raised as high as 35/min before overt gas trapping due to incomplete exhalation results. If plateau pressure is < 25 cm H2O and tidal volume is < 6 mL/kg, tidal volume may be increased to 6 mL/kg or until plateau pressure is > 25 cm H2O. Some investigators believe pressure control ventilation protects the lungs better, but supportive data are lacking, and it is the peak pressure rather than the plateau pressure that is being controlled. With pressure control ventilation, because the tidal volume will vary as the patient's lung compliance evolves, it is necessary to continually monitor the tidal volume and adjust the inspiratory pressure to ensure that the patient is not receiving too high or too low a tidal volume.
Prone positioning (see Overview of Mechanical Ventilation : Patient positioning) improves oxygenation in some patients by allowing recruitment of nonventilating lung regions. A recent study suggests this positioning may improve survival.
Optimal fluid management of patients with ARDS balances the requirement for an adequate circulating volume to preserve end-organ perfusion with the goal of lowering preload and thereby limiting transudation of fluid in the lungs. Recently, a large multicenter trial has shown that a conservative approach to fluid management, in which less fluid is given, shortens the duration of mechanical ventilation and ICU length of stay when compared with a more liberal strategy. However, there was no difference in survival between the 2 approaches, and use of a pulmonary artery catheter also did not improve outcome. Patients not in shock are candidates for such an approach but should be monitored closely for evidence of decreased end-organ perfusion, such as hypotension, oliguria, thready pulses, or cool extremities (see Shock).
A definitive pharmacologic treatment for ARDS that reduces morbidity and mortality remains elusive. Inhaled nitric oxide, surfactant replacement, activated protein C (drotrecogin alfa) and many other agents directed at modulating the inflammatory response have been studied and found not to reduce morbidity or mortality. Some small studies suggest that systemic corticosteroids may be beneficial in late-stage ARDS, but a larger, prospective, randomized trial found no reduction in mortality. Corticosteroids may be deleterious when given early in the course of the condition.