Introduction

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are two clinical diseases that result from an inflammatory state somewhere in the body, which leads to abnormal lung function and respiratory distress.

History and Clinical Signs

Given ALI and ARDS occur secondary to an inflammatory disease process anywhere in the body, animals may initially present with historical findings and clinical signs reflective of the primary inflammatory process, and not develop clinical signs of respiratory distress until several days after the primary insult.

For example, a dog may present with multiple long bone fractures following motor vehicle trauma and later develop signs of respiratory distress (ARDS) while in hospital. In this example an inflammatory process distant from the lungs (long bone fractures) creates inflammation that subsequently results in ALI/ARDS. In other cases, the animal may present with a primary lung problem (i.e., aspiration pneumonia), which fails to improve or deteriorates while hospitalized, which may indicate the onset of ALI/ARDS.

Once ALI/ARDS is present, the most frequently reported clinical signs include tachypnea, dyspnea (increased effort, often pronounced), cyanosis, and hypoxemia. A cough may also be noted, and is often paroxysmal on tracheal palpation. On physical examination, increased breath sounds/crackles may be ausculted. The patient may also display abdominal breathing, open mouth breathing, and/or frothy pink exudate coming from the respiratory tract.

It should be noted that not all patients that develop respiratory distress while hospitalized have ALI or ARDS. The most common causes for the hospital-acquired respiratory distress include ALI and ARDS, aspiration or bacterial pneumonia, congestive heart failure (CHF) secondary to fluid overload, and pulmonary thromboembolism.

Diagnosis

In 2007, a panel of veterinary experts published a set of five criteria to accurately diagnose ALI/ARDS in veterinary patients. Four of these criteria are required for a diagnosis, and the fifth is optional.

Criteria 1 - Acute Onset

The patient must be dyspneic at rest and the onset of dyspnea should have developed in less than 72 hours. The time of onset should be determined based on the patient's history.

Criteria 2 - Risk Factors

For a diagnosis of ALI/ARDS the patient must have a primary underlying disease process that causes enough inflammation to set up a reaction in the lungs. To determine if the patient has an underlying risk factor present, a thorough history and diagnostic testing is performed and is usually sufficient to detect the underlying inflammatory state (complete blood count, serum chemistry profile, urinalysis, imaging). See Table 1 for common risk factors for ALI/ARDS. Note that this list is general and is not all-inclusive (any disease process that can lead to a systemic inflammatory response syndrome [SIRS] can cause ALI/ARDS).

Table 1. Risk factors for ALI/ARDS in veterinary patients

 Inflammation

 Infection

 Sepsis

 Systemic inflammatory response syndrome (SIRS)

 Severe trauma

 Long bone fracture

 Head injury

 Pulmonary contusion

 Multiple transfusions

 Smoke inhalation

 Near-drowning

 Aspiration of stomach contents

 Drugs and toxins

Criteria 3 - Evidence of Pulmonary Capillary Leak Without Evidence of Increased Hydrostatic Pressures

Any one of the following 4 criteria: 1) bilateral/diffuse infiltrates on thoracic radiographs (more than 1 quadrant), 2) proteinaceous fluid within the conducting airways, 3) bilateral dependent density gradient on CT, 4) increased extravascular lung water.

This criteria is designed to rule out heart failure as the cause of abnormal lung function. Congestive heart failure produces low protein content edema via increased hydrostatic pressures, while acute lung injury and ARDS produce a high protein content edema through increased vascular permeability. Proteinaceous fluid within the conducting airways is consistent with ARDS.

In people, historically, a pulmonary capillary wedge pressure was used to rule out increased hydrostatic pressure. However, this is invasive and not practical in veterinary medicine. Therefore, heart disease/failure should be ruled out with ultrasound in place of a capillary wedge pressure. In addition, imaging of the lungs is required to document pulmonary changes consistent with ALI/ARDS. See below.

Imaging

The typical fluid distribution in acute lung injury and ARDS results in a bilateral or diffuse pattern of infiltrate on thoracic radiographs that involves more than one quadrant or lobe. These changes can be quite variable, however, and may range from increased interstitial and peribronchial patterns to diffuse, bilateral alveolar infiltrates. The pulmonary vasculature should appear normal (there should not be evidence of venous congestion/distension which would suggest CHF and increased hydrostatic pressures).

Cardiac Function Assessment

If pulmonary infiltrates are seen, the next step is to rule out edema resulting from congestive heart failure. Echocardiography evaluates left atrial size and systolic function quickly and accurately. A lack of left atrial enlargement or systolic dysfunction supports the finding of noncardiogenic pulmonary edema associated with ALI and ARDS.

Criteria 4 - Evidence of Inefficient Gas Exchange

Any one or more of the following: 1) hypoxemia defined by PaO₂/FiO₂ ratios, 2) increased alveolar-arterial oxygen gradient, 3) venous admixture (noncardiac shunt).

Inefficient gas exchange is confirmed by the presence of hypoxemia, which may be defined by arterial oxygen pressures or arterial hemoglobin oxygen saturation.

PaO₂

The PaO₂ should be about 80 to 110 mm Hg in patients' breathing room air at sea level. If the patient is receiving oxygen supplementation, the PaO₂ should be about five times the percentage of oxygen being supplemented.

SpO₂

Pulse oximetry is a widely available noninvasive tool that can be used to provide a quick assessment of oxygenation by indirectly measuring the oxygen saturation of hemoglobin (SpO₂). This tool may be useful when blood gas analysis is not available, but it has several disadvantages. SpO₂ measurement can be difficult to perform in animals with a thick coat, pigmented skin, or poor perfusion. SpO₂ may underestimate the true oxygen saturation in those circumstances. The best way to ensure accurate readings include minimizing movement of the patient, using the probe on thin skin that is adequately perfused, comparing the measured heart rate to the actual heart rate of the patient, ensuring a proper waveform (on machines that record wave forms), and taking several consistent SpO₂ readings. Finally, SpO₂ cannot differentiate PaO₂ values > 100 mm Hg; the results will all be 97% to 100% regardless of the PaO₂ value once it is > than 100 mm Hg. Therefore, animals receiving oxygen supplementation that have significant lung dysfunction may still have a SpO₂ of 99% to 100% as long as their PaO₂ remains above 100 mm Hg.

PaO₂/FiO₂ Ratio

Arterial blood gas results can be further analyzed to determine the ratio of PaO₂ to the fraction of inspired oxygen (FiO₂). The PaO₂/FiO₂ ratio is used to determine the severity of respiratory compromise and is the one factor that distinguishes acute lung injury from ARDS. A ratio of < 300 indicates acute lung injury, and a ratio < 200 is diagnostic of ARDS. A recent consensus statement in the human literature (the Berlin definition) suggests categorizing ARDS by severity in the following manner: mild: PaO₂/FiO₂ < 300, moderate: PaO₂/FiO₂ < 200, severe: PaO₂/FiO₂ < 100. The PaO₂/FiO₂ ratio also allows accurate comparison between different arterial samples taken when different levels of oxygen (FiO₂) were being supplemented to the patient.

Criteria 5 - Evidence of Pulmonary Inflammation

The last criterion for diagnosing acute lung injury or ARDS, and the only criterion that is optional, is evidence of pulmonary inflammation. Transtracheal wash or bronchoalveolar lavage samples taken from animals with acute lung injury or ARDS demonstrate the presence of inflammation in the lavage fluid. Cytologic examination of lavage fluid reveals predominantly neutrophils (suppurative inflammation but not necessarily septic inflammation). When these diagnostic samples are tested for inflammatory cytokines such as tumor necrosis factor alpha and interleukin-1, these substances are increased from normal values. However, it should be noted that these tests may be contraindicated because of the risks associated with anesthesia or the procedure itself.

Prognosis

The mortality of ARDS in human patients varies between references of 30% to 60% depending on the study and severity of ARDS. The presence of more than one risk factor significantly enhances the likelihood of developing ARDS. Genetics as well as environmental factors (smoking) play a role. The most common risk factors reported in the human literature include aspiration pneumonia, pancreatitis, pulmonary contusion, traumatic injury, fat embolism, ischemia/reperfusion, and sepsis. A study in dogs showed similar results. ARDS is often complicated by the development of non-pulmonary organ failure, which results in higher mortality.

Treatment

A variety of treatment strategies have been tried, but supportive therapy and addressing the underlying cause are the mainstay of therapy. It should be noted that patients that progress to ARDS carry a very guarded prognosis, are labor intensive and can be very expensive to treat. They often require referral to a 24-hour facility to allow proper care. Patients with ALI carry a better prognosis and response to therapy will often provide a more accurate prognosis to help guide therapeutic decisions. The underlying disorder (risk factor) should be fully evaluated and treated aggressively and specifically, if possible.

Fluid Therapy

Supportive care should include maintaining organ perfusion with appropriate fluid therapy. Some clinicians advocate the conservative use of fluids since the lung vasculature is already more permeable than normal and it might be easy to cause fluid overload in these patients. If a conservative approach to fluid therapy is implemented, the blood pressure needs to be closely monitored to make sure the patient does not become hypotensive, which occurs frequently in septic patients. If the patient has been sufficiently volume-loaded and hypotension is still present, use of vasopressors such as dobutamine, dopamine, vasopressin, or norepinephrine may help to stabilize the patient.

Oxygen Therapy

Oxygen therapy is also a vital part of treatment for these patients. Animals can tolerate 100% oxygen for up to 24 hours, and then up to 60% oxygen thereafter without concern for oxygen toxicosis (prolonged exposure of the alveoli of the lung to high oxygen concentrations can lead to oxygen free radical production in the lung and subsequent cell injury). High oxygen concentrations may be difficult to obtain unless a tightly sealed oxygen cage is available. Closely monitor the patient for response, and consider obtaining samples for serial blood gas analysis to check for hypoxemia and response to therapy. If a patient remains persistently hypoxemic with a PaO₂ < 60 mm Hg, a PaCO₂ > 60 mm Hg, or increased respiratory effort despite receiving oxygen therapy, consider ventilator therapy.

Other Therapies

Other supportive care measures that have been attempted in people include antibiotic therapy, gastric ulcer prophylaxis, nitric oxide administration, surfactant replacement, specific cytokine therapy, glucocorticoid therapy, and nutritional management. No strong evidence supports or negates these treatment options, and further studies are required before such therapies can be implemented in veterinary patients.

Ventilator Therapy

Almost all people with ARDS require ventilation for respiratory support. ARDS reduces lung compliance, so over time respiratory effort increases, which eventually causes respiratory muscle fatigue. Ventilator therapy helps decrease fatigue by performing the work required for breathing. Therefore, any animal with excessively labored respirations may be a candidate for mechanical ventilation. Additionally, ventilator therapy allows the delivery of higher oxygen concentrations than can be obtained through routine methods, may recruit alveoli that were collapsed and may help keep patients alive until the underlying cause can be reversed. If an animal cannot maintain a PaO₂ of at least 60 mm Hg with oxygen therapy, mechanical ventilation should be considered.

Conclusion

Acute lung injury and ARDS are secondary disorders caused by a severe inflammatory reaction, the origin of which may be the lung or a site distant to the lung. A diagnosis is based on the presence of four main criteria. The most important and practical diagnostic tests include a thorough history, thoracic radiography, echocardiography, and arterial blood gas analysis. Treatment usually involves addressing the primary disease and providing supportive therapy and, possibly, mechanical ventilation. Acute lung injury and ARDS are important disorders for all small-animal practitioners to understand and to be able to diagnose so treatment can be instituted early and aggressively, with referral to a critical care facility if necessary. However, by the time acute lung injury or ARDS is diagnosed, safe referral may be difficult unless a critical care facility is only a short distance away or veterinary care can be provided during transport. Diagnosing acute lung injury or ARDS provides important prognostic information for clients.

References

1.  Matthay M, Ware LB, Zimmerman GA. The acute respiratory distress syndrome. J Clin Invest. 2012;122(8):2731–2749.

2.  Barbas CS, Matos GFJ, Amato MBP, Carvalho CRR. Goal-oriented respiratory management for critically ill patients with acute respiratory distress syndrome. Crit Care Res Pract. 2012. Article ID 952168. 13 pages.

3.  Wilkins, Otto, Baumgardner, et al. Acute lung injury and acute respiratory distress syndromes in veterinary medicine: consensus definitions: the Dorothy Russell Havemeyer Working Group on ALI and ARDS in Veterinary Medicine. J Vet Emerg Crit Care. 2007;17(4):333–339.