Respiratory Difficulty

Hb, Hemoglobin; MCHC, mean corpuscular hemoglobin concentration; MCV mean corpuscular volume; PCV, packed cell volume; RBC, red blood cells; TP, total protein; WBC, white blood cells.

excitement, pain, stress, respiratory disease, hypoxia (cardiac disease, pulmonary disease, shock), dehydration, shock, toxemia, or metabolic acidosis. Periodic apnea and abnormally slow respirations are often the result of metabolic disturbances (hypoglycemia, hypocalcemia), hypothermia, prematurity, or hypoxia-induced suppression of the respiratory center.

Abnormal posture of the head and neck are exhibited by neonates with respiratory difficulty, particularly upper airway obstruction, but meningoencephalitis, otitis media, hyperna­tremia, polioencephalomalacia, congenital defects of the CNS, and lasalocid toxicity should be considered.

Conditions causing occlusion of the upper airway, such as choanal atresia, necrotic laryngitis, and pharyngeal swelling or edema, often induce pronounced inspiratory dyspnea, stridor, and/or open-mouth breathing. Expiratory stridor and increased and prolonged expiratory effort are usually associated with lower airway disease. A malodorous breath may be present with necrotic pharyngeal injuries, necrotic laryngitis, cleft palate, or aspiration pneumonia. Inspiratory stridor is often a feature of extrathoracic airway obstruction, and increased abdominal effort on expiration is often an indication of pul­monary disease causing reduced lung compliance.

Lung disease in the newborn is usually diffuse and is the result of infection acquired in utero or postpartum and/or lung atelectasis associated with immaturity, recumbency, or surfactant dysfunction. Signs of lung disease include increased work of breathing characterized by nostril flare, rib retractions, and increased abdominal effort. A cough and nasal discharge, salient features of respiratory disease in older neonates, are infrequent findings in newborns with lung disease. Animals with few or no audible thoracic abnormalities may have severe respiratory disease.

Respiratory Condition Diagnostic Testing

A complete blood cell count, a serum chemistry profile, electro­lyte concentrations, arterial or venous blood gas concentrations, and a test of immune transfer status provide useful information to the clinician concerned about a respiratory condition in a neonatal ruminant.

Knowing whether there is anemia, evidence of infection, endotoxemia, organ dysfunction, metabolic abnormalities, hypercarbia, hypoxemia, or FPT of immunity may distinguish upper airway problems from lower airway disease or pulmonary disease from a nonpulmonary cause of respiratory difficulty.

Arterial blood gas concentrations provide a useful measure of respiratory function. Optimal sites for collection of arterial blood samples from neonatal calves are the brachial artery proximomedial to the elbow⁶¹ or the caudal auricular artery.⁶² Normal arterial blood gas values for neonates of different postnatal and gestational ages are presented in Table 20.5.

Several factors can interfere with accurate interpretation of blood gases in the neonate. First, significant inaccuracies can occur if the blood sample is collected, handled, or measured improperly. The most common artifact is the introduction of room air into the sample, resulting in an artificially increased PaO₂, decreased PaCO₂, and more alkaline pH. The position of the patient and amount of struggling during sample collection may also potentially cause transient changes in all blood gas values. The inspired oxygen concentration should always be considered when analyzing arterial blood gas values. With supplemental oxygen, PaO₂ is increased variably, depending on the inspired oxygen concentration (FiO₂), the amount of pathology present (particularly the extent of right-to-left shunting), and the respiratory rate and tidal volume. Hypoxemia due to hypoventilation is usually addressed by increasing inspired PO₂ via a face mask or intranasal oxygen.

Common patterns of arterial blood gas derangement in the neonatal ruminant include hypoxemia (PaO₂ 50 mm Hg). If hypercapnia and resulting respiratory acidosis exist, ventilation is inadequate or there is ventilation-perfusion

■ TABLE 20.5

Normal Arterial Blood Gas Values for Calves

inequality.

Interpretation of venous blood gas can be deceptive and should be limited to evaluation of metabolic conditions such as metabolic acidosis but not considered adequate for assessment of pulmonary gas exchange. To avoid problems associated with regional blood sampling, peripheral venous blood should be taken from a free-flowing jugular vein, since the metabolic status of the head is usually stable.

Plasma lactate measurement may provide prognostic value for calves with acute bronchopneumonia.⁶³ Acute phase proteins such as haptoglobin, fibrinogen, serum amyloid A, and lipopolysaccharide-binding protein have also been evaluated for diagnostic and prognostic value in bovine respiratory disease (BRD), but they are not specific for BRD, vary with etiology and stage of infection, and do not offer a clear distinction between normal and abnormal animals.

Thoracic radiographs are helpful in diagnosing the presence, type, and extent of respiratory disease in neonatal ruminants. Shortly after birth the smaller vessels posterior to the heart and in the caudodorsal lung fields should be clear. The heart, posterior vena cava, and aorta should be clearly defined. When the radiographic appearance of the lung fields is evaluated, the type of infiltrate (interstitial, nodular, alveolar, mixed), severity, and location (diffuse, cranioventral, caudodorsal) should be noted. Other soft tissue structures (including the heart, vessels, and diaphragm) and bones (ribs, vertebrae, long bones of the forelimb) should also be evaluated. Thoracic radiographs are routinely taken in the standing or lateral recumbent position in calves. Cranioventral consolidation is a common radiographic finding of infectious bronchopneumonia in calves.

Ultrasonographic evaluation of the neonatal ruminant thorax is useful for identification of aspiration of amniotic fluid, atelectasis, pleural effusion, nonventilated lung, pleuritis, and chest wall abscesses, and for detecting congenital heart defects. It appears most suitable for detecting pathologic processes close to the pleura.⁶⁴

Respiratory endoscopy can be used for evaluation of the nasal cavity and septum, oropharynx and nasopharynx, epiglottis, larynx, and trachea. It is particularly useful for diagnostic evaluation of neonatal ruminants with respiratory stridor, stertorous breathing, malodorous breath or nasal discharge, inspiratory dyspnea, or related clinical signs indicative of upper airway problems.

Airway sampling is useful to determine presence, type, and etiology of respiratory inflammation and infection of neonatal ruminants. Deep pharyngeal swabs with a guarded catheter, transtracheal fluid aspirate, tracheobronchial lavage fluid, or bronchoalveolar lavage fluid analyses and cultures have been described. Techniques, sample handling, and interpretation are described in Chapter 31. For a neonate in respiratory distress, airway sampling may not be indicated until the patient is stabilized. Selection of the appropriate airway sampling method will depend on the patient condition and demeanor, supplies and equipment, test cost, technical assistance, clinician preference, anticipated etiology, sample handling, processing, and interpretation expertise. Specific airway sample, culture, polymerase chain reaction (PCR), ELISA, and other available tests for respiratory bacterial, Mycoplasma, Chlamydia, and viral pathogens are discussed in Chapter 31. Test positive and negative predictive values may be improved when used for herd-level testing rather than for individual animal test interpretation.

Postmortem examination is a useful diagnostic tool for evaluation of respiratory conditions of neonatal ruminants. In addition to the examination of the upper and lower respiratory tract, brain, heart, GI tract, immunologic sites, navel, other mucosal surfaces, and cavity fluids can provide information pertinent to a diagnosis. Lung culture, pathology, and immu­nohistochemistry (IHC) results can be particularly useful.

Upper Respiratory Tract Disorders

Conditions of the upper airway of neonatal ruminants are not common, but choanal atresia, stenotic nares, congenital cysts, cleft palate, pharyngeal trauma, pharyngeal and laryngeal edema, pharyngeal dysfunction, necrotic laryngitis, and tracheal collapse have been described. With the exception of necrotic laryngitis, most upper respiratory conditions of neonatal ruminants are present within the first week of life but may become progressive with age. Upper airway conditions, particularly those affecting pharyngeal and laryngeal function, predispose to aspiration pneumonia.

Diagnosis of most upper airway disorders can usually be made with a careful physical examination in combination with arterial blood gas concentrations, radiography, and/or endoscopy. Clinical signs of upper airway conditions include inspiratory effort, dyspnea, upper respiratory noise, stridor, malodorous nasal discharge, and cough. Dysphagia, poor appetite, milk reflux from the nostril, and aspiration pneumonia may be noted. Dyspnea is likely to result in failure to thrive and malnourishment.

Impaired pharyngeal and laryngeal function may result from physical deformation or neuromuscular disorders. Sporadic outbreaks of pharyngeal and laryngeal injuries are often associ­ated with improper application or use of damaged feeding tubes and oral medication equipment. Compression of the larynx by a retropharyngeal abscess or mass tends to cause inspiratory dyspnea. Edema and necrosis of the larynx may be observed with infectious bovine rhinotracheitis virus infections in neonatal calves.^65,66 Fusobacterium necrophorum typically causes necrotic laryngitis in weaned calves but sporadically infects neonates following pharyngeal trauma.⁶⁷ Necrotic laryngitis is frequently detected only when clinical signs of dyspnea with stridor are evident. By this stage the disease tends to be chronic, and the response to systemic antimicrobial and antiinflammatory treatment is generally poor.⁶⁸ Partial occlusion of the upper airway induces turbulent airflow and subsequent mucosal edema. Placement of a tracheostomy tube provides an alternate, sometimes life-saving airway and rests the inflamed mucosa. Surgical intervention may be required; tracheotomy, trache­ostomy, laryngotomy, laryngostomy, and tracheolaryngostomy have been described, with variable outcomes.^67-69

Nutritional myodegeneration and botulism may induce laryngeal paresis. Dysphagia and subsequent aspiration pneu­monia are common sequelae. Collapsed trachea is a rare congenital or acquired condition. In this condition, there is a dynamic dorsoventral collapse of the trachea during inspiration, but no stenosis is present. The caudal cervical and cranial thoracic sections of the trachea in the area of the thoracic inlet are most frequently affected. Acquired tracheal collapse is commonly associated with fractured ribs and compression of the trachea at the thoracic inlet by the bony callus that develops with healing. Clinical signs include an intermittent honking cough, stridor, and dyspnea with mild exercise. Treatment of collapsed trachea in the calf by surgical reconstruction has been attempted, but the prognosis is poor.^70-73

Respiratory Infection

A number of respiratory disease syndromes may be observed in neonatal calves. Pneumonia in calves younger than 5 days of age is most likely hematogenous in origin, a consequence of neonatal septicemia or aspiration pneumonia from inhalation of fetal fluid, meconium, colostrum, or milk as a complication of recumbency, obtunded mentation, large volume forced feeding, large holes in teat nipples, poor esophageal tubing technique, or pharyngeal dysfunction (white muscle disease). Fever, cough, and nasal discharge are not consistently present in the early stages of pneumonia in the neonate. With hematog­enous pneumonia, evidence of infection in other organs, includ­ing omphalophlebitis, meningitis, enteritis, and polyarthritis, is frequently present. Without early and aggressive treatment, sepsis can progress to shock, multiple organ dysfunction, and death relatively rapidly. E. coli or other gram-negative bacterial organisms are the most common culprits. With aspiration pneumonia, a mixture of gram-positive, gram-negative, and anaerobic bacteria can be cultured from the lungs, inciting a severe inflammatory response, toxemia, and occasionally sepsis. For hematogenous and aspiration pneumonia, broad­spectrum antimicrobial coverage must be instituted early and accompanied by antiinflammatory drug therapy, fluid therapy, nutritional supplementation, and supportive care. Long-term treatment is frequently necessary, and prognosis for survival is guarded.

Bacterial pneumonia of dairy calves, frequently described as affecting calves 2 to 6 months of age, may occur as early as 2 weeks of age and frequently peaks in incidence at 5 to 6 weeks of age. In bacterial pneumonia of calves, inhaled patho­gens first colonize the bronchoalveolar junction, overcome host defenses, incite inflammation at that site, and go on to spread through the contiguous airways or through adjacent lung tissue. Pneumonia occurs as an endemic problem on many farms but can also occur as an outbreak. Frequently the problem is multifactorial, including bacterial organisms, individual and farm, or environmental risk factors.

Clinical signs of bacterial pneumonia in young calves usually include a combination of the following: fever, nasal discharge, lacrimation or ocular discharge, cough (spontaneous or inducible by tracheal compression), depression, reduced appetite, rough hair coat, expiratory effort, and abdominal breathing effort. Concurrent signs of otitis may be noted. Subjective parameters like attitude, appetite, appearance, activity level, or respiratory character that are used to detect pneumonia on farms can be insensitive and delay the pneumonia diagnosis and treatment. Remote recording devices that monitor objective parameters such as core body temperature, activity levels and behavior, and frequency and volume of milk consumption are becoming more common and will improve farm pneumonia detection. Automatic or computerized calf feeding is gaining popularity, providing opportunities to monitor calf feeding behavior. Parameters commonly measured include milk volume consumed, drinking speed, rewarded visits to the feeder (calf is fed), and unrewarded visits to the feeder (calf is not fed, as the interval from the last feed is too short). Calves with respiratory disease have been observed to have reduced milk intake and a reduced number of unrewarded visits. The changes in calf behavior were detectable 3 days prior to clinical recognition of disease and persisted for 7 days following identification of respiratory disease.⁷⁴ Similar changes have been reported by others, includ­ing reductions in drinking speed, milk volume consumed, and rewarded and unrewarded visits. However, these behavioral changes were found to be less sensitive at detecting calves with respiratory disease compared to calves with diarrhea.⁷⁵

Bacterial agents are frequently the primary pathogens in calf pneumonia. Alone or in combination, Mannheimia hae- molytica, Pasteurella multocida, Mycoplasma bovis, or Mycoplasma dispar are the most common bacterial isolates cultured from airway samples early in the infection. Histophilus somni or T. pyogenes is found in more advanced pneumonia cases. While any Salmonella species can cause pneumonia, Salmonella dublin can be the cause of fulminating pneumonia in 1- to 8-month-old calves. Outbreaks of respiratory disease in this age-group may be associated with mixed bacterial infections, including M. bovis, or with primary or concurrent viral infection with bovine respiratory syncytial virus (BRSV), bovine coronavirus (BCV), or bovine viral diarrhea virus (BVDV) infection. Viral infections increase the risk of opportunistic bacterial infections by their immunosuppressive effects and damage to the respiratory epithelium and pulmonary clearance mechanisms. Pleuritis is an uncommon feature of most neonatal respiratory infections but may be a manifestation of a generalized polyserositis with specific pathogens such as Mycoplasma infections of ruminant neonates⁷⁶ and occasionally Pasteurella infections in lambs.⁷⁷

FPT of immunity is one of the most important risk factors for the development of calf pneumonia in individual animals and in herds. Calves with FPT had 1.6 times greater odds of being treated for respiratory disease.⁷⁸ In this study the preva­lence of FPT was 32%, and the attributable fraction of BRD associated with FPT was 21%, suggesting that 1 in 5 cases of respiratory disease could have been avoided among calves with FPT if they had had adequate passive transfer.⁷⁸

Poor nutrition is another risk factor for pneumonia in dairy calves that are limit-fed milk or milk replacer. A number of pathogens capable of causing respiratory disease are shed in milk. These include Mycoplasma spp.,^76,79,80 CAEV,^81,82 and S. dublin. The practice of feeding unpasteurized mastitic milk or nonsaleable milk to neonates increases the risk of disease transmission, including S. dublin, an invasive host-adapted Salmonella serotype, to cattle, Mycoplasma spp. infections to goat kids and calves, and CAEV to goat kids. CAEV produces a number of disease syndromes in goats, including mastitis, arthritis, encephalitis, and pneumonia. Encephalitis and subclini- cal respiratory disease typically occurs in kids 2 to 4 months 8183 of age and occasionally in kids as young as 1 month of age.⁸¹,⁸³ Goat kids infected with Mycoplasma mycoides subsp. mycoides (large colony type) are often in a lot of pain, febrile, and reluctant to stand, and have multiple hot, swollen joints from acute polyserositis. Approximately 50% of kids develop pneumonia or pleuropneumonia manifested by an increase in respiratory rate and auscultable lung sounds.⁷⁶ Outbreaks of Mycoplasma pneumonia in calves are usually caused by feeding waste milk contaminated with M. bovis.^84,85 Clinical signs include an increased rate and effort of breathing associated with pneumonia, joint and tendon sheath distention reflecting arthritis, polyserositis, tenosynovitis, auricular discharge, and a head tilt reflecting otitis media or interna^79,85; decubital abscesses are a less common manifestation.⁸⁶ Clinical signs associated with Mycoplasma otitis include cranial nerve 7 and 8 deficits, unilateral or bilateral ear droop, ptosis, epiphora, head tilt, and recumbency in severely affected calves. Pasteuriza­tion of milk fed to goat kids and calves is recommended.

Additional environmental risk factors for pneumonia include extremes of temperature, poor ventilation, dust, ammonia, and overcrowding. Overcrowding, especially with commingled age-groups of calves, creates a high risk for pneumonia. Housing factors associated with reduced respiratory disease prevalence in naturally ventilated dairy calf barns are solid panels between calves that prevent contact, deep bedding, and low airborne bacterial counts.⁸⁷ A minimum space requirement of 2.2 to 3 m² per calf is associated with low airborne bacterial counts and less respiratory disease for calves in individual and group pens. Increased time between successive occupants of individual or group calf pens reduces the environmental exposure to disease organisms. An all in-all out housing system on farms reduces the chance for endemic pneumonia problems. Other risk factors for pneumonia include poor-quality feed, limited availability of water, stress, inappropriate medications, overvac­cinating, parasitism, and concurrent infection.

Herd-based pneumonia problem solving is needed where respiratory disease in calves is endemic. Routine calf care, herd vaccinations, navel care, colostrum feeding, feed types, amounts, times, and additives are important. Learn the pneumonia definition, screening method, and treatment protocols. Review records to find seasonal trends, relationship to passive transfer of immunity, age at first diagnosis, and related management factors. Survival curves and incidence calculations can be useful. Observe people and procedures, and examine animals. Deter­mine how many current cases have been detected and treated. Successful management of endemic pneumonia problems requires early detection, effective treatment, and resolution of the most important risk factors.

For treatment consideration, many antibiotics are labeled for BRD. Treatment plans for individual animals or farm pro­tocols should be based on valid diagnostic information, recent examinations, and responsible use of antibiotics. Compliance with prescribed dose, route, and frequency of administration is factored into antibiotic selection. For one-dose respiratory treat­ment protocols, enrofloxacin, tulathromycin, ceftiofur, florfenicol, gamithromycin, or tildipirosin may be considered. For antibiotics like spectinomycin, enrofloxacin, ceftiofur, and florfenicol, multiple­dose treatment protocols are also effective for BRD.

Mycoplasma spp. are susceptible to antimicrobial agents that affect DNA, RNA, protein synthesis, or the integrity of the cell membrane. Mycoplasma spp. are not susceptible to agents that interfere with synthesis of folic acid or that act on the cell wall. Tylosin, tetracyclines, erythromycin, tilmicosin, tulathromycin, gamithromycin, florfenicol, aminoglycosides, and fluoroquinolones have been shown to have activity against one or more Mycoplasma spp.⁸⁸ However, the efficacy of antimicrobial therapy to eliminate the organism is limited, and while animals may recover, chronic infections may persist.⁸⁹

Prevention of neonatal ruminant respiratory conditions includes appropriate vaccination programs, frequent observation of adults and neonates, uncomplicated births, adequate colos­trum, navel care, optimal nutrition, and housing that is clean, dry, and draft free.

Neonatal Apnea and Irregular Breathing Patterns

Periods of apnea in the neonate are commonly associated with nonrespiratory factors, including infection, CNS disorders, hypothermia, and metabolic causes such as hypoglycemia. Seizure activity may be expressed by changes in breathing rate and pattern, and neonatal asphyxia may induce respiratory depression, whether or not cerebral lesions are present.⁹⁰ Neonatal respiratory distress may also cause apnea resulting from respiratory center depression or diaphragmatic fatigue. There are two mechanisms of apnea: central apnea, resulting from cessation of diaphragmatic activity; and obstructive apnea, resulting from obstruction of the airway, usually at the pha­ryngeal level.