Managing pulmonary parenchymal diseases (Proceedings)

Parenchymal pulmonary diseases usually restrict expansion of the lungs leading to dyspnea, and may be occasionally with soft cough. The most commonly encountered parenchymal diseases in dogs and cats are pulmonary edema and pneumonia. Pulmonary fibrosis is an important cause of parenchymal lung disease in dogs.

Pulmonary Edema

Pulmonary edema is the accumulation of fluids in the interstitium and alveoli of the lung. There are two main basic mechanisms for edema development: increased hydrostatic pressure in the lung capillaries ("high-pressure edema") and increase vascular permeability ("low-pressure edema). This classification helps understand the basic pathophysiological differences between the two types of pulmonary edema, but has limitations. Disruption of some or all layers of the alveolar-capillary unit occurs during elevated capillary hydrostatic pressures, a phenomenon termed "pulmonary capillary stress failure". Pulmonary capillary stress failure represents a process that blurs the distinction between high-pressure and low-pressure pulmonary edema, as the disruption of the alveolar-capillary membrane by high hydrostatic pressures may render it more permeable to fluid and proteins. The resulting edema fluid has a higher concentration of protein than would be expected in conventional high-pressure pulmonary edema. These observations may explain some features seem in high-altitude pulmonary edema and neurogenic pulmonary edema.

High-pressure edema is usually secondary to left-sided congestive heart failure and many times called "cardiogenic pulmonary edema", whereas low-pressure pulmonary edema are termed "noncardiogenic". Fluid in noncardiogenic pulmonary has a higher concentration of proteins and the edema occurs with normal capillary wedge pressure. The increased vascular permeability can occur with a wide variety of pulmonary and systemic disorders including vasculitis, acute respiratory distress syndrome, electric shock, neurogenic edema and uremic pneumonitis. Patients with pulmonary edema are usually presented with expiratory or mixed dyspnea with normal to increased lung sounds and presence of abnormal sounds (e.g.; crackles). Radiographs are helpful in the diagnosis and differentiation between cardiogenic and noncardiogenic edema based on the distribution of the edema.

The initial goals of therapy in cardiogenic pulmonary edema include increasing arterial PO2, reducing oxygen demand, establishing a diuresis, and unloading the ventricles while supporting blood pressure, tissue perfusion and renal function. Supplemental oxygen therapy and sedation are used as needed to reduce distress or air hunger. Pulmonary edema sufficient to cause respiratory failure and respiratory muscle fatigue is an indication for artificial ventilation. Diuresis is established with furosemide at an initial IV bolus of 2–5 mg/kg that can be followed by serial IV or IM boluses of 1-4 mg/kg every 6 to 8 hours or more frequently when necessitated by insufficient clinical response. The use of constant rate infusion (CRI) of furosemide also may be used to treat dogs and cats with life-threatening pulmonary edema. In healthy dogs and in human patients with CHF, furosemide CRI increases urine output and minimizes electrolyte disturbances when compared to repeated bolus injections. After the initial IV bolus of furosemide, the furosemide dosage required for the next 24 hours is estimated, and then infused by syringe pump. Supplemental boluses also can be given if required during the CRI. Nitroglycerin ointment can be used to decrease preload, whereas nitroprusside can be used to decrease afterload in dogs with florid pulmonary edema. Two percent nitroglycerin ointment (¼ to 1 inch of the 2% ointment, topically q12h) acts primarily as a systemic venodilator, and this treatment is well-tolerated by both dogs and cats. Although some question exists about the efficacy of topically-administered nitroglycerin, the anticipated venodilation should work in concert with furosemide to lower venous and capillary hydrostatic pressures. The need for arteriolar dilators in the hospital setting depends on the cause and severity of CHF. Although vasodilator therapy has the potential to induce systemic hypotension, such treatment generally is safe in dogs when baseline ABP exceeds 95 mm Hg. For dogs with severe CHF, sodium nitroprusside (1–5 μg/kg/min IV by constant rate infusion), enalapril (0.5 mg/kg PO q12h), and hydralazine (1–2 mg/kg PO q12h) are effective vasodilators in the hospital setting. Each drug can increase stroke volume and reduce pulmonary edema. Afterload reduction is particularly useful in the treatment of severe mitral regurgitation arising from canine endocardiosis or when left ventricular dysfunction is evident, as in dogs with dilated cardiomyopathy.

Cardiac output, arterial blood pressure, and tissue perfusion are supported when necessary by providing inotropic support. In dogs or cats with severe systemic hypotension (ABP <80 mm Hg), inotropic support with dobutamine (2.5–10 μg/kg/min) or dopamine (2–10 μg/kg/min) is indicated. Catecholamines most often are administered to dogs in CHF caused by dilated cardiomyopathy. Occasionally, this approach is used in patients with severe mitral regurgitation or pulmonary embolism. Cats with any form of cardiomyopathy may develop cardiogenic shock characterized by bradycardia, hypothermia, and hypotension. Treatment with dobutamine can be life-saving in affected cats. Infusions should be titrated to a systolic ABP of 90 to 120 mm Hg and can be combined with slow external warming in an oxygen incubator. When treatment with catecholamines is impractical, oral administration of the calcium sensitizer pimobendan should be considered once this drug is available for general use.

There is no specific pharmacological treatment for noncardiogenic pulmonary edema. Diuretics are often ineffective and, despite widespread use, there is no evidence that corticosteroids are helpful. Support therapies include: controlling the causative factor, ventilatory support and maintaining the patient well hydrated.

Bacterial Pneumonia

Bacterial pneumonia is the inflammation developed in response to the presence of virulent bacteria in the pulmonary parenchyma. It is usually secondary to aspiration or systemic infection (hematogenous pneumonia). Bacterial pneumonia is more common in dogs than cats. Affected dogs are predominantly young males of large breeds. Clinical signs in dogs with pneumonia can change from mild signs related to infection until severe depression and evidence of systemic inflammatory response syndrome. Some dogs may have purulent nasal discharge, dyspnea and fever. Crackels may be heard on auscultation, especially in the cranio-ventral lung fields. Cough, if present, is usually soft.

In dogs, Bordetella bronchiseptica and Streptococcus zooepidemicus are primary pathogens leading to pneumonia. In most cases, however, the bacteria are opportunistic invaders. Gram-negative aerobes: Escherichia coli, Pasteurella multocida, Klebsiella pneumoniae, and Pseudomonas aeruginosa are most commonly isolated from dogs with pneumonia. Staphylococcus spp, Streptococcus spp and Mycoplasma spp. Can also be isolated from dogs with bacterial pneumonia. Anaerobes are seen in patients with pulmonary abscess. Oral bacteria are more common in cats. Most pneumonia in cats are due to Moraxella spp, Pasteurella multocida, Streptococcus spp, Escherichia coli, Klebsiella pneumoniae, Bordetella bronchiseptica, Proteus miriabilis, and Mycoplasma spp.

In patients with aspiration pneumonia, radiographic examination usually reveal an alveolar pattern in the cranio-ventral lung fields or in the region of the right middle lung lobe. Cytology obtained by transtracheal wash may show a neutrophilic inflammation with degenerate neutrophils. Bacteria can be found in less than 50% of samples. Anaerobic and aerobic cultures are thus mandatory to identify the organisms and determine their antibiotic susceptibility.

Therapy of the stable patient (still eats, temperature < 104, no left shift) consists of antibiotics at home for 2 weeks, nutritional support and rest. Reasonable empiric antibiotic choices in patients with pneumonia include amoxicillin+clavulanic acid, cephalexin or trimethropin+sulfonamide. Antibiotic choice should be reevaluated based on culture and sensitivity or if there is no improvement in 72 hours. A stable patient that got worse should be hospitalized and rehydrated. A new antibiotic should be selected based on culture and sensitivity.

The unstable patient should be hospitalized, kept hydrated and receive nutritional support and IV antibiotic therapy. Dogs with complicated pneumonia usually have an aerobe gram negative, especially E. coli. The first choice of antibiotics is cefazoline: 15-25 mg/kg q6-8h or ampicillin: 20 – 40 mg/kg q6-8h + enrofloxacin: 2.5 mg/kg q12h. Unstable cats are likely to have infection caused by a gram negative organism. Cefazolin (33 mg/kg q8-12h) also is the initial drug of choice for cats while waiting for culture and sensitivity. Ampicillin + enrofloxacin can also be used in cats with complicated pneumonia.

Pulmonary Fibrosis in Dogs

Pulmonary fibrosis is a poorly characterized disease in the dog. The etiology is not known although multifocal alveolitis similar to the one associated with pulmonary fibrosis in human beings has been suggested. This is reinforced by the fact that in animal models of pulmonary fibrosis, alveolitis usually precedes development of fibrosis.

Dogs with pulmonary fibrosis are usually old, and small terrier breeds may be predisposed. There is usually a long and progressive history of shortness of breath. Cough is usually absent unless the patient also has chronic bronchitis or secondary bacterial pneumonia. Bilateral, diffuse, very-loud late-inspiratory, early-expiratory crackles are the most significant physical findings. Exercise may cause tachypnea, open-mouth breathing and cyanosis in affected dogs.

Radiographs may reveal mild cardiomegaly due to cor pulmonale or decreased lung expansion. A mild diffuse interstitial pattern is usually evident. Rounding of the peripheral lung edges and flattening of the diaphragm may also be present. Arterial blood gas usually reveal hypoxemia and hypocapnia.

Bronchoscopy and bronchoalveolar lavage may help in the diagnosis of pulmonary fibrosis. In patients with no evidence of bronchitis, alveolar fluid (obtained by bronchoalveolar lavage) containing more than 20% of neutrophils suggest the presence of alveolitis and potentially fibrosis. The diagnosis can only be achieved with certainty, however, through lung biopsy.

There is no effective treatment for pulmonary fibrosis in dogs. Obesity should be corrected and exposure to airway irritants (e.g. dust, smoke) should be minimized. Sildenafil (1mg/kg q8h) causes arterial vasodilation in the pulmonary vasculature improving blood flow. Patients with pulmonary fibrosis with moderate to severe pulmonary hypertension may greatly benefit from sildenafil. Those patients may show a great improvement in exercise tolerance increases and a decrease in associated clinical signs.