Acute lung injury and acute respiratory distress syndrome (ARDS) are challenging and frequently lethal respiratory disorders encountered in veterinary medicine. These disorders have been recognized since the late 1960s in human medicine1 but have only recently been defined in the veterinary community.2 While you may not commonly encounter these conditions in general practice, it is important to be familiar with them as complications of critical illness. Early recognition of acute lung injury and ARDS is essential in helping you make the best treatment decisions, which may include early referral, since affected animals usually require 24-hour critical care.
Acute lung injury and ARDS are severe disturbances in respiration that result in hypoxemia, tachypnea, dyspnea, and death in about 50% of affected people.3 ARDS is the more severe form of acute lung injury; it has a specific and more severe level of hypoxemia.
The primary insult that results in acute lung injury and ARDS produces systemic and respiratory tissue inflammation with ensuing release of macrophages, neutrophils, and inflammatory cytokines. These cells and cytokines directly damage the epithelial integrity of type I pneumocytes, which are the primary cell type that line alveoli and are involved in gas exchange. The endothelial lining of blood capillaries in the lung tissue is also directly damaged, allowing for increased permeability.3,6,7 The damage to these two cell layers and subsequent increased permeability result in extravasation of a high-protein fluid (edema) into lung parenchyma and alveolar spaces. Pulmonary edema causes poor oxygen exchange in the lungs, decreased lung compliance, and increased ventilation-perfusion (V/Q) mismatch; in acute lung injury and ARDS, this edema is considered noncardiogenic.3,6,7
PRESENTING HISTORY AND CLINICAL SIGNS
Since acute lung injury and ARDS are secondary disease processes, animals may have a variety of historical findings and clinical signs based on the primary disease. Animals will usually be hospitalized for the primary disease before acute lung injury or ARDS becomes apparent. It often takes one to four days for acute lung injury or ARDS to develop after the onset of the initial inflammation, so patients may originally be presented without marked respiratory signs and develop these complications later. If respiratory disease was a patient's admitting complaint, a failure to improve or a decline in respiratory status may indicate acute lung injury or ARDS.
Tachypnea, respiratory distress, cyanosis, hypoxemia, and, potentially, coughing are some of the more common clinical signs.6 On physical examination increased respiratory noises may be heard, including loud bronchovesicular sounds or crackles. The patient may also display abdominal breathing, orthopnea, or foamy pink exudate coming from the respiratory tract.4,6,7 The key clinical sign is respiratory distress.
A typical scenario of acute lung injury or ARDS would be a dog that initially presented for one of the disorders listed in Table 1. This patient may have no evidence of respiratory disease on initial presentation. After a few (one to four) days, the patient's respiratory rate would begin to elevate, followed by the patient exhibiting increased respiratory effort and, finally, severe respiratory distress. If the patient had already been managed at another hospital for a few days before referral, it may have already had time to develop acute lung injury or ARDS and may present in respiratory distress as a complication of one of those disorders.
Hospital-acquired respiratory distress occurs in animals that have been hospitalized for an unspecified length of time and develop signs of respiratory distress while in the hospital. It may arise as an acute onset of respiratory signs in an animal that previously was determined to have a normal respiratory status, or it may be a worsening of clinical signs in an animal that already had respiratory compromise. The most common differential diagnoses for hospital-acquired respiratory distress include acute lung injury and ARDS, aspiration or bacterial pneumonia, congestive heart failure (CHF) secondary to fluid overload, and pulmonary thromboembolism.
No. 1—Acute onset
The rate of onset of tachypnea and dyspnea at rest should be < 72 hours and is easily determined based on a patient's history.
No. 2—Risk factors
Evaluating for risk factors involves establishing whether the patient has a severe primary disease that might have resulted in acute lung injury or ARDS. This risk factor assessment is easily accomplished by obtaining a thorough history and performing basic diagnostic tests (complete blood count, serum chemistry profile, urinalysis, imaging) that evaluate the patient for an underlying disease listed in Table 1.
No. 3—Evidence of pulmonary capillary leak with normal pulmonary capillary pressure
This criterion requires that the patient have fluid in the lungs that does not appear to have been caused by left-sided CHF.2 Acute lung injury, ARDS, and left-sided CHF all cause pulmonary edema. The principal difference is that CHF produces edema that has a low protein content because of high pressure within the lung vasculature (increased hydrostatic pressure), while acute lung injury and ARDS produce edema that has a high protein content because of inflamed and permeable vessels and alveolar epithelial lining.3 To properly evaluate a patient for this criterion, thoracic radiography and a cardiac function evaluation must be performed to determine whether left-sided heart failure is present.
No. 4—Evidence of inefficient gas exchange
Inefficient gas exchange is confirmed by the presence of hypoxemia and, occasionally, hypercapnia. The best way to determine whether a patient has hypoxemia is to obtain an arterial blood gas sample for analysis (see sidebar titled "How to obtain arterial samples for blood gas analysis"). Many bench-top and point-of-care analyzers are reliable sources of blood gas information. The partial pressure of oxygen in arterial blood (PaO2) provides information about blood oxygenation. A normal PaO2 should be about 80 to 110 mm Hg if the patient is breathing room air.9 If the patient is receiving oxygen supplementation, the PaO2 should be about five times the percentage of oxygen being supplemented. For example, a patient receiving 40% oxygen in an oxygen cage should be expected to have a PaO2 around 200 mm Hg (40 x 5), while an anesthetized patient receiving 100% oxygen should have a PaO2 near 500 mm Hg (100 x 5).
If blood gas analysis is not available in a practice, pulse oximetry measurement can be performed to get a general idea of blood oxygenation. However, blood gas analysis is necessary for true diagnosis of acute lung injury or ARDS; it is also necessary to distinguish between these two conditions.
PaCO 2 and SaO 2 . Other parameters that may help define a patient's respiratory status include the partial pressure of carbon dioxide in arterial blood (PaCO2) and the percent of hemoglobin that is saturated with oxygen (SaO2). The PaCO2 provides information about carbon dioxide production and elimination. Normal values are between 32 and 43 mm Hg in dogs and 26 and 36 mm Hg in cats.9 Elevation in PaCO2 represents hypoventilation, while values below normal suggest hyperventilation. The SaO2 should be near 100% when a patient has a PaO2 of 100 mm Hg or more. An SaO2 of 96% corresponds to a PaO2 of 80 mm Hg or above, while an SaO2 of 91% corresponds to a PaO2 of 60 mm Hg.9 SaO2 is not as effective of a measurement of arterial oxygenation as PaO2 is when a patient is receiving oxygen supplementation because of the small change in percentage once PaO2 exceeds 100 mm Hg.9
SpO2. Pulse oximetry is a widely available noninvasive tool that can also 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 results may also be inaccurately low in these circumstances. The best ways 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, and taking several consistent SpO2 readings. Finally, SpO2 cannot differentiate PaO2 values > 100 mm Hg; the results will all be 99% to 100%. 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). FiO2 is equal to 21% (or 0.21) when the patient is breathing room air. Most oxygen cages supplement up to at least 40% oxygen, so the FiO2 is 40%, or 0.4.10 Oxygen (100%) delivered through bilateral nasal cannulas can supplement an FiO2 of 50% if the patient is not panting.10 An anesthetized patient is receiving 100% oxygen, barring any leak in the system, so the FiO2 is 100%, or 1. However, in nonventilated dogs it can be difficult to determine FiO2 because of wide variation in the character of respiration demonstrated by the patient.
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.2 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. The ratio is calculated by dividing the PaO2 by the FiO2 percentage (expressed as a decimal). A normal animal should have a value > 400. For example, an animal breathing room air with a PaO2 of 60 mm Hg would have a PaO2/FiO2 ratio of 60/0.21, which = 285 and is consistent with acute lung injury when other criteria that indicate acute lung injury are present.
Because ARDS is a more severe form of acute lung injury, distinguishing between these two respiratory disorders might indicate the severity of the disease and provide prognostic information for the owner.
No. 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 characteristic types of inflammation. Cytologic examination of respiratory fluid reveals a predominance of neutrophils (suppurative inflammation).2 When these diagnostic samples are tested for inflammatory cytokines such as tumor necrosis factor alpha and interleukin-beta, these substances are also increased from normal values.2,6 However, performing these diagnostic tests in a dyspneic animal may be contraindicated because of the risks associated with anesthesia or the procedure itself. So while these diagnostic procedures may provide useful information, they are not currently a requirement in diagnosing acute lung injury or ARDS. These tests might be more practical if a dog is already being ventilated or if samples are necessary for diagnosis and treatment of pneumonia.
A variety of treatment strategies have been attempted, but strong clinical evidence for the best approach to these patients is lacking. In general, managing acute lung injury and ARDS should focus on early recognition with treatment of the underlying disease and supportive care for the respiratory system. The underlying disorder (risk factor) should be fully evaluated and treated aggressively and specifically, if possible. In patients that require transfusions, use blood products cautiously because, in people, transfusion-related acute lung injury is another cause of noncardiogenic pulmonary edema.
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. Additionally, the hope is that mild dehydration may help pull some of the interstitial lung fluid back into the vasculature.3,4,7 But if you use this conservative approach to fluid therapy, monitor blood pressure closely to make sure the patient does not become hypotensive, which is especially likely in septic patients. If the patient has been sufficiently volume-loaded and hypotension is still present, use vasopressors such as dobutamine, dopamine, vasopressin, or norepinephrine to stabilize systemic blood pressure and achieve adequate organ perfusion. Other clinicians advocate aggressive fluid management to maximize oxygen delivery and organ perfusion as a more appropriate approach, but no consensus has been reached at this time.
A recent study in people evaluated these two philosophies of fluid therapy, placing patients in either a conservative or liberal fluid management group. No difference in 60-day mortality was seen between the groups, but patients in the conservative fluid group had significantly more days alive, ventilator-free, and spent outside of the intensive care unit.11 These findings suggest that providing as small a fluid volume as possible while maintaining organ perfusion may be the most appropriate fluid plan for patients with acute lung injury or ARDS. Colloid therapy may help improve systemic blood pressure by increasing the volume of fluid in circulation, but it should generally be avoided in patients with suspected pulmonary capillary leaks. The colloid may leak from the capillary into the pulmonary interstitium, worsening the existing pulmonary edema.12
Oxygen therapy. Oxygen therapy is also a vital part of treatment for these patients. Oxygen may be provided by intranasal cannulas or nasal prongs, an enclosed hood, or an oxygen cage (Figure 2). Animals can tolerate up to 60% oxygen without concern for oxygen toxicosis,4 but high 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. If a patient persistently has a PaO2 < 60 mm Hg, a PaCO2 > 60 mm Hg, or increased respiratory effort despite receiving oxygen therapy, consider ventilator therapy.9
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.13,14 While no strong evidence supports or negates some of these treatment options, we do know that early nutritional interventions are important in human critical care and are probably equally important in our veterinary patients.15 Nutrition can be provided either enterally or parenterally. Most patients with dyspnea will be unwilling to eat on their own, so parenteral therapy may be necessary. If the patient must be anesthetized, consider placing a feeding tube to provide enteral nutrition since early enteral nutrition improves gastrointestinal mucosal barrier function and may decrease the incidence of bacterial translocation.16
Almost all people with ARDS require ventilation for respiratory support.3 ARDS reduces lung compliance, so, over time, respiration 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. If an animal cannot maintain a PaO2 of at least 60 mm Hg with oxygen therapy, mechanical ventilation should be considered.
Ventilators use positive pressure ventilation, often with positive end-expiratory pressure (PEEP), which keeps airway pressure above atmospheric pressures during exhalation. This helps to keep small airways and alveoli open even during exhalation, facilitates a more uniform distribution of tidal volume, recruits collapsed lung units, and may help reduce lung inflammation from repeated opening and closing of small airways and alveoli.3,14,17 In people, ventilator therapy with lower tidal volumes than traditional ventilator therapy also reduces lung inflammation, resulting in a lower mortality rate and an increased number of ventilator-free days.17
The benefits of ventilator therapy for ARDS are tremendous and often necessary for survival, but there can be serious side effects. Ventilator therapy can result in decreased venous return or ventilator-associated pneumonia or pneumothorax, which may cause more respiratory compromise. Another downside in small-animal patients is the requirement for anesthesia to allow constant intubation of the patient or the need for a tracheostomy. Anesthesia and the critical care monitoring to properly manage these cases necessitate 24-hour patient care. Thus, ventilator therapy is extremely labor- and time-intensive and can only be performed at 24-hour clinics with ventilator equipment, proper monitors, and trained staff. This level of care results in substantial cost for the client that may be financially impossible in many cases. Regardless of these downsides, the ventilator can be a life-saving device in patients with acute lung injury or ARDS.
Acute lung injury and ARDS are secondary disorders caused by a severe primary respiratory or systemic disease. To properly make a diagnosis, four criteria must be met. 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. Much remains to be learned about these disorders, but for now they continue to carry an extremely high mortality rate and a grave prognosis.
Katherine Snyder, DVM, DACVIM
Department of Small Animal Clinical Sciences
College of Veterinary Medicine
Texas A&M University
College Station, TX 77843
1. Ashbaugh DG, Bigelow DB, Petty TL, et al. Acute respiratory distress in adults. Lancet 1967;2(7511):319-323.
2. Wilkins PA, Otto CM, Baumgardner JE, 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.
3. Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med 2000;342(18):1334-1349.
4. Parent C, King LG, Van Winkle TJ, et al. Respiratory function and treatment in dogs with acute respiratory distress syndrome: 19 cases (1985-1993). J Am Vet Med Assoc 1996;208(9):1428-1433.
5. Brady CA, Otto CM, Van Winkle TJ, et al. Severe sepsis in cats: 29 cases (1986-1998). J Am Vet Med Assoc 2000;217(4):531-535.
6. DeClue AE, Cohn LA. Acute respiratory distress syndrome in dogs and cats: a review of clinical findings and pathophysiology. J Vet Emerg Crit Care 2007;17(4):340-347.
7. Chan DL, Rozanski EA. Acute lung injury and acute respiratory distress syndrome. In: Respiratory diseases in dogs and cats. 1st ed. St. Louis, Mo: Saunders, 2004;504-507.
8. Walker T, Tidwell AS, Rozanski EA, et al. Imaging diagnosis: acute lung injury following massive bee envenomation in a dog. Vet Radiol Ultrasound 2005;46(4):300-303.
9. Haskins SC. Interpretation of blood gas measurements. In: Respiratory diseases in dogs and cats. 1st ed. St. Louis, Mo: Saunders, 2004;181-193.
10. Dunphy ED, Mann FA, Dodam JR, et al. Comparison of unilateral versus bilateral nasal catheters for oxygen administration in dogs. J Vet Emerg Crit Care 2002;12(4):245-251.
11. Wiedemann HP, Wheeler AP, Bernard GR, et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 2006;354(24):2564-2575.
12. Hughes D, Boag AK. Fluid therapy with macromolecular plasma volume expanders. In: Fluid, electrolyte, and acid-base disorders in small animal practice. 3rd ed. St. Louis, Mo: Saunders, 2006;621-634.
13. Miao CH, Sun B, Jiang H, et al. Pharmacodynamics and pharmacokinetics of inhaled nitric oxide in dogs with septic acute respiratory distress syndrome. Acta Pharmacol Sin 2002;23(3):278-284.
14. Brower RG, Ware LB, Berthiaume Y, et al. Treatment of ARDS. Chest 2001;120(4):1347-1367.
15. Chan DL, Freeman LM. Nutrition in critical illness. Vet Clin North Am Small Anim Pract 2006;36(6):1225-1241.
16. Mohr AJ, Leisewitz AL, Jacobson LS, et al. Effect of early enteral nutrition on intestinal permeability, intestinal protein loss, and outcome in dogs with severe parvoviral enteritis. J Vet Intern Med 2003;17(6):791-798.
17. The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000;342(18):1301-1308.