2016 WINTER: E-cigarettes | Canine Respiratory Distress | Regenerative Medicine for Hip Dysplasia | Hospital Happenings
The Dangers of E-cigarettes
With the increased popularity of the e-cigarette, as an alternative to the more popular and conventional cigarette, has also come an increase in the number of hospital admissions to many veterinary emergency clinics. E-cigarette ingestion/exposure poses a serious risk to pets, but unfortunately outside of the veterinary world, this information may be relatively new or unheard of to many pet owners. The primary concern with the ingestion of e-cigarettes has to do with the ingestion of its ingredient, nicotine. While the e-cigarette may seem relatively harmless, each cartridge packs a powerful punch, containing anywhere from 6 to 24 mg of nicotine; in contrast the average cigarette only contains approximately 9 mg of nicotine. Although the e-cigarette resembles the traditional cigarette, e-cigarettes work by atomizing liquid (containing nicotine) into a vapor that can be inhaled. Many people who use these products also enjoy the different flavors and varieties that these products come in, ranging from peppermint to cherry. The aroma or scent of these e-cigarette cartridges is what makes them a popular target among pets. Pets are drawn to these different scents and in many reported cases ingest the flavored nicotine liquid.
In addition to the increased nicotine content of these products, vials of liquid nicotine, called “e-juice,” are often available to refill cartridges. Moreover, pre-filled cartridges are often sold in packs containing up to 20 or more individual cartridges. This added danger makes intoxication almost guaranteed, whereby pets are likely to show severe clinical signs up to and even including death. According to Pet Poison Helpline, a 50-lb dog ingesting a single cartridge will often show clinical signs; whereas consumption of the same quantity by a 10-lb dog will often result in death. On the other hand, signs may vary with partial consumption. In addition, consumption of e-cigarettes, and or any of their parts may result in severe gastroenteritis or gastrointestinal obstruction.
The onset of clinical signs is rapid, with pets showing signs such as vomiting, diarrhea, tachycardia, tachypnea, neurologic signs like tremors, ataxia, weakness, and seizures, in as little as 15 minutes. Cardiac arrest and even death is observed as well. Delayed signs have been documented especially with cutaneous exposures. Below is a listing of clinical signs by the system affected:
- Gastrointestinal: vomiting, hypersalivation, diarrhea, abdominal pain/discomfort
- Cardiovascular: hypertension, cardiac arrhythmias
- Neurologic: ataxia, weakness, mydriasis, seizures
- Pulmonary: initial tachypnea followed by respiratory depression
The diagnosis is often made possible by a history inclusive of exposure to nicotine and is often suggested by the combination of clinical signs with their acute onset. Differential diagnoses should include other potential toxicants with similar clinical signs. Metaldehyde, bromethalin and methylxanthine products; insecticides (carbamates, organophosphates), strychnine, mycotoxins, and toxic mushrooms are among the most common. Bloodwork is often non-specific, with some pets showing hyperkalemia. More advanced laboratory analysis of blood and vomitus, such as HPLC, or mass spectrometry is possible, although often not feasible given the time it takes to send off these samples to a reference laboratory.
Although there is no specific antagonist treatment for nicotine intoxication, treatment is aimed at controlling signs of respiratory distress, cardiac arrhythmias, cardiovascular collapse, shock and general supportive care with intravenous fluids, gastroprotectants, anti-emetics and oxygen therapy. Cutaneous or ocular exposure should include decontamination of the affected surface with copious amounts of a lavage solution (ocular), or bathing with soap and water (cutaneous).
If a known ingestion occurs, immediate veterinary care is recommended. At-home care is not recommended due to the rapid onset of clinical signs and severity of symptoms. It is recommended that owners take their pets to the closest emergency clinic and or contact either, Pet Poison Helpline (800.213.6680) or the ASPCA Animal Poison Control Center (888.426.4435) for further advice.
Respiratory Distress in Dogs
Dyspnea is the sensation of “air hunger,” a somewhat anthropomorphic term for respiratory distress. Dyspnea can be a sign of life-threatening hypoxemia, and thus should prompt immediate evaluation and therapy. While definitive diagnosis of respiratory disease may require invasive or time-consuming diagnostic testing, history, physical exam and basic diagnostic aids are often sufficient to determine appropriate stabilization and emergent treatment of the dyspneic dog.
Because respiratory reserve capacity has been depleted, animals in respiratory distress are “fragile.” When dealing with these dogs, remember the axiom of “First, do no harm.” Invasive or stressful diagnostics should be postponed until the patient is deemed stable. Stabilization usually includes oxygen supplementation. This can be accomplished in a number of ways, including use of a face mask, oxygen cage, flow-by oxygen, oxygen attached to a bag placed over the head, or nasal cannula. Severely anxious animals may benefit from sedative administration. If clinical presentation and brief exam suggests a specific diagnosis, appropriate immediate lifesaving treatment is indicated. For example, animals with a history of known heart disease presenting with mixed inspiratory and expiratory dyspnea and crackles on auscultation can benefit from immediate therapy with diuretics and perhaps vasodilators such as nitroglycerin. In patients with inspiratory dyspnea and decreased lung sounds ventrally, where pleural effusion is suspected, thoracocentesis may provide immediate relief.
There are a variety of approaches to the dog with respiratory distress. In general, respiratory distress can be caused by 1) upper airway disease, 2) lower airway disease, 3) pulmonary parenchymal disease, 4) pleural space disease, 5) chest wall and/or muscular disease, or 6) non-respiratory diseases and conditions. Localization of the disease process is key to both initial management and initial diagnostic testing.
A variety of non-respiratory conditions can lead to rapid, labored or otherwise altered respiration. For instance, severe abdominal distention (e.g., gastric dilatation volvulus, severe ascites) can result in diagrammatic compression and limit inspiratory capacity. Severe anemia or hemoglobin abnormalities like methemoglobinemia cause tissue hypoxia and apparent respiratory distress. Metabolic disease (e.g., diabetic ketoacidosis) or neurologic disease can likewise result in dramatically altered respiratory patterns. Pain, hyperthermia and many other conditions may cause tachypnea in the absence of respiratory disease. Many of these conditions are readily apparent based on history, brief physical examination or very minimal basic laboratory data (e.g., packed cell volume, urine dipstick).
Respiratory distress due to chest wall disease or muscular disease is also usually easily identified and separated from other causes of respiratory distress. Flail chest usually follows trauma. Multiple broken ribs result in a segment of chest wall that is pulled inward on inspiration and pushed outward on expiration, a finding that is easily recognized on physical examination. Muscular paralysis of the diaphragm and/or intercostal muscles can result in respiratory distress. The diseases that result in this type of paralysis (e.g., botulism) usually result in generalized paralysis that is easily recognized on examination.
Pattern-Based Approach to Respiratory Distress
The remainder of this article will focus on approach to animals with respiratory distress due to disorders of the upper and lower airways, pulmonary parenchyma or pleural space.
Physical examination often allows localization of distress. While all components of the physical examination can have relevance to the dog with respiratory distress, the author finds simple observation of the distressed animal to be most useful. Simply stand back and carefully observe respiration with attention to the phase of respiration during which distress occurs. Palpation, percussion and auscultation follow observation.
Approach to the Dog with Loud Inspiratory Distress
Noisy inspiratory distress generally signals upper airway disease. Although nasal and nasopharyngeal disorders may result in stertor or other changes in respiratory pattern, they generally do not result in distress since a dog can simply breathe through his mouth. Conversely, disorders of the larynx or trachea can cause distress. Most upper airway related distress is due to airway obstruction. Obstruction can be dynamic (e.g., laryngeal paralysis, cervical tracheal collapse) or fixed (e.g., tumors, foreign bodies, granuloma). Brachycephalic airway syndrome may have both dynamic and fixed components of obstruction. The noise and effort associated with dynamic upper airway collapse is largely confined to inspiration, while fixed obstruction results in noise on both phases of respiration. Although noise occurs during both inspiration and expiration, inspiratory distress predominates with a fixed obstruction. Generally, unless the obstruction is very severe, it is easier to exhale air past a mass or foreign body than to inhale around it.
For the dog presenting with noisy inspiratory distress, history and signalment can be particularly useful in formulating differential diagnoses. For the older retriever-breed dog with inspiratory stridor and distress, laryngeal paralysis is the most likely differential, particularly if there is a history of voice change or prior episodes of exercise induced stridor. In small breed dogs of any age, tracheal collapse is the leading differential if inspiratory distress is accompanied by a history of paroxysmal cough. Foreign body is a frequent cause of acute onset of distress in a previously healthy young dog. For the older dog with evidence of fixed obstruction, tumor occluding the airway is likely.
In any case, for the severely distressed dog oxygen administration and sedation may be lifesaving. Oxygen can be administered as described; oxygen cages are not ideal if the dog will need frequent monitoring or manipulation. Dogs with upper airway obstruction may appear more “panicked” than dogs with other forms of respiratory distress, and sedation can be a key to stabilization. However, sedation is not always effective and complete airway collapse may ensue. If these therapies fail to stabilize the dog, intubation may be lifesaving and provides the opportunity to visually inspect the larynx and surrounding structures. Tracheostomy is only beneficial if the area of obstruction can be bypassed with the tracheostomy tube.
Diagnostic evaluation of the upper airways (following stabilization) will include observation of laryngeal function under sedation, cervical and thoracic radiographs, and examination of the nasopharynx, larynx, and trachea visually and/or with endoscopy. Because relief of severe upper airway obstruction can lead to non-cardiogenic pulmonary edema, thoracic radiographs are appropriate even when upper airway obstruction is confirmed as the cause of initial distress. Tracheal collapse is rarely confined to a single segment, so both inspiratory (cervical and thoracic) and expiratory (thoracic) radiographs are indicated. Other tests may be indicated in some dogs.
Approach to the Dog with Expiratory Distress
Expiratory distress is observed primarily in disease of the lower airway, with the classic example being feline asthma. Asthma is essentially a non-entity in dogs. In dogs, expiratory distress due to dynamic airway obstruction is more likely to be related to marked intrathoracic tracheal collapse or to bronchomalacia. Although most dogs with collapsing trachea present with paroxysms of cough, they occasionally present for overt respiratory distress, collapse and cyanosis. The condition occasionally causes death by asphyxiation due to complete collapse of either intra- or extrathoracic tracheal segments. For dogs presenting with this type of collapse, temporary intubation and rapid placement of tracheal stents can be life-saving. Only intraluminal stents are suitable for use in the intrathoracic trachea. Bronchomalacia, collapse of weakened cartilage on expiration, can result from severe bronchitis. Expiratory wheezes are suggestive of airway narrowing as is found in bronchomalacia. Bronchi are not amenable to stenting, and thus chronic medical therapy is the only management option; these dogs have a guarded prognosis at best. Chronic, progressive fixed obstruction of major lower airways (e.g., tumor) allows time for compensation and is unlikely to result in acute respiratory distress. Plugging of major or multiple airways by mucus or debris can and does lead to acute respiratory distress.
Diagnostic evaluation of the lower airways begins with good thoracic radiographs. Collapse of the intrathoracic trachea is best documented on expiratory films, while evaluation of the pulmonary parenchyma is best accomplished with inspiratory thoracic radiographs. Tracheal collapse is detectable radiographically ~60% of the time. Fluoroscopy can sometimes identify collapse that is missed on plain films. Often, visual examination via bronchoscopy is also indicated. Bronchoscopy is the most sensitive means of detecting and grading collapse of both trachea and bronchi and can identify bronchial foreign bodies, tumors or sites of extralumenal compression. Bronchoscopy also facilitates directed sampling of airways via bronchoalveolar lavage for both cytology and culture. Airway infection is a common cause of cough and respiratory disease, but an uncommon cause of respiratory distress unless the pulmonary parenchyma is also infected. Nevertheless, abnormal airways are more susceptible to secondary bacterial pathogens and therefore bacterial culture is often indicated.
Approach to the Dog with Mixed Inspiratory-Expiratory Distress
Mixed inspiratory and expiratory distress is most often due to pulmonary parenchymal disease. There are important exceptions to this rule; these exceptions include pulmonary fibrosis (a restrictive parenchymal disease) or the combination of diseases in multiple locations (e.g., intra and extrathoracic tracheal collapse). The pulmonary parenchyma consists of the terminal and respiratory bronchioles, interstitium, alveoli and vasculature. Diseases of these tissues are varied, but prominently include infection (i.e., bacterial, viral, fungal, protozoal, or parasitic), inflammation (e.g., acute respiratory distress syndrome, eosinophilic pulmonary infiltrates, aspiration pneumonia), neoplasia (primary or metastatic), pulmonary edema (cardiogenic or non-cardiogenic), fibrosis (reactive or idiopathic), and vascular disease (e.g., thromboembolism, vascular leakage). Signalment and history are often very useful in prioritizing differential diagnoses. For example, a young, unvaccinated puppy would be more likely to have a viral pneumonia than neoplastic lung disease, and a dog with pneumonia is usually systemically ill. Physical exam findings are also useful in sorting differential diagnoses for dogs with lung disease. For example, crackles on inspiration are suggestive of pulmonary fibrosis, pneumonia, pulmonary edema or hemorrhage. When loud, coarse crackles are heard in the absence of an alveolar radiographic pattern a diagnosis of pulmonary fibrosis is likely.
Oxygen administration is often crucial for stabilization of hypoxemic animals with respiratory distress due to pulmonary parenchymal disease. Sedation is less likely to benefit the dog with distress due to parenchymal disease than it is the dog with distress due to dynamic airway collapse but can still be useful in the very anxious patient. For dogs with a history of known heart disease or findings of a prominent heart murmur or dysrhythmia, diuretic therapy (i.e., furosemide) and vasodilation (i.e., nitroglycerine) may be administered pending further diagnostics. If respiratory arrest appears imminent, sedation, intubation and ventilation may be indicated. The variety of diseases associated with parenchymal lung disorders usually necessitates further diagnostic investigation before additional treatment is initiated.
Inspiratory thoracic radiographs using an appropriate technique (long grey scale) form the mainstay of evaluation. The entire film is evaluated, including attention to size and shape of the cardiac silhouette and pulmonary vasculature as well as the presence, location, and intensity of interstitial, bronchial and alveolar lung patterns. An alveolar pattern suggests that the small airways and alveoli are filled with fluid, water, pus or blood. A perihilar alveolar distribution suggests cardiogenic pulmonary edema, while a cranioventral distribution is suggestive of bacterial pneumonia. The right middle lung lobe or the caudal portion of the left cranial lung lobe are most often affected by aspiration. A miliary interstitial pattern is suggestive of fungal pneumonia or metastatic lung disease, while a nodular interstitial pattern is suggestive of neoplasia, abscessation, granuloma or eosinophilic infiltrate. A diffuse unstructured interstitial pattern associated with respiratory distress may be found in dogs with interstitial pneumonia, including non-infectious interstitial fibrotic conditions. When non-respiratory disease and upper airway disease are ruled out, respiratory distress in a dog with normal thoracic radiographs is suggestive of either very early disease (e.g., acute aspiration) or pulmonary thromboembolism. Other imaging techniques may be useful depending on results of thoracic radiographs. For instance, dogs with an obscured or enlarged cardiac silhouette should likely be imaged via echocardiography. Although they require some restraint, imaging techniques have the advantage of being relatively safe in the dyspneic dog while providing a wealth of information.
Often, invasive diagnostic techniques are required for dogs with lung disease. For dogs with a productive cough and suspected pneumonia, tracheal lavage can provide good samples for cytologic evaluation and culture with minimal risk. Bronchoscopically guided or blinded bronchoalveolar lavage allows sampling of the deeper airways when a definitive diagnosis is not apparent with less invasive techniques but is relatively contraindicated in the dyspneic dog; it should only be performed when potential benefit outweighs risk. Fine needle aspiration of the lungs is minimally invasive and relatively safe, but diagnostic utility is limited unless there is an identifiable mass lesion or severe infiltrative lung disease present. More invasive techniques (e.g., lung biopsy) are rarely attempted in a markedly dyspneic dog. Minimally invasive tests such as CBC, chemistry profile and urinalysis rarely provide a specific diagnosis, but they may suggest certain pulmonary disease conditions. For example, marked proteinuria and hypoalbuminemia could suggest that otherwise unexplained respiratory distress may be due to pulmonary thromboembolism. (Loss of antithrombin through the kidney predisposes to thromboembolic events.)
Approach to the Dog with Quiet Inspiratory Distress
Quiet inspiratory distress is most often due to pleural space disease. This includes pleural effusion, pneumothorax or mass effects within the pleural space. Pleural masses include tumors, granuloma, abscess or even abdominal organs in cases of diaphragmatic hernia. Often, lung sounds are muffled in these dogs, at least in some locations (e.g., ventral muffling with effusion, muffled sounds over areas of mass). Percussion may identify areas of hypo (effusion, mass) or hyper (air) resonance in the thorax. Again, signalment and history may also help order differential diagnosis; for instance, the recently traumatized dog is more likely to have pleural hemorrhage, pneumothorax or diaphragmatic hernia than a thoracic tumor.
Oxygen supplementation is certainly indicated for the dog with quiet inspiratory distress, but just as oxygen alone may not be sufficient to stabilize the dyspneic dog with airway obstruction, it may not be sufficient for the dog with pleural disease. Thoracocentesis prior to further investigation can be life-saving in these dogs by removing pleural effusion or air. When using a 20 ga butterfly catheter, the technique is relatively safe even if effusion or air are not present, so attempts at thoracocentesis are unlikely to do harm and may provide tremendous benefit in these patients. If large quantities of air are removed, immediate placement of a large bore thoracostomy tube is indicated. After attempts to stabilize with oxygen and/or thoracocentesis, thoracic radiographs again become the diagnostic mainstay for animals with pleural disease. If effusion is identified, samples should be obtained for classification and possible further evaluation (e.g., culture). Other specific diagnostic tests will be chosen based on results of these first evaluations. For example, if a bloody fluid is identified from a dog without known trauma, coagulation should be evaluated; if a transudate is identified, serum albumin should be measured.
For more information on respiratory distress or for a case consultation, contact our criticalist, Jacqueline Nobles, DVM, DACVECC at 405.749.6989.
We would like to thank our colleague at BluePearl in New York, Benjamin Davidson, BVSc, MACVSc, DACVECC, for allowing us to use this article for Companion.
Regenerative Medicine for Treatment of Canine Hip Dysplasia
C.H. “Skip” Tangner, DVM, MS, DACVS
Regenerative medicine is relatively new to veterinary medicine. Many of us have used stem cell therapy with mixed results. In human medicine use of intact or morselized acellular bioscaffold, such as MatriStem MicroMatrix® from Acell®, is being used routinely to improve wound healing, surgical reconstructions and orthopedic conditions. To give an overview of the rationale for the use of bioscaffold, I have included data from a study by veterinarians William Rose and Jeffery Wood, et al, in which they used extracellular matrix (ECM) powder to treat severe canine hip dysplasia.
Osteoarthritis (OA) in canine hip dysplasia is characterized by degeneration of the articular cartilage surface, matrix loss, fibrillation and formation of fissures that can result in complete loss of the cartilage surface and significant pain. Chondrocytes are responsible for maintaining a balance between synthesis and degradation of the extracellular matrix, which they accomplish through the secretion of macromolecular components (collagen, glycosaminoglycans, and hyaluronic acid), and through modulation of the extracellular matrix turnover. Chondrocytes secrete tissue-damaging mediators (cytokines, free radicals, proteases, and prostaglandins) and anabolic and reparative substances (growth factors, and inhibitors of catabolic cytokines), as well as inhibitors of degradative enzymes. The balance of these three processes is key in maintaining a homeostatic joint environment. In OA, there exists an overproduction of destructive and pro-inflammatory mediators relative to the inhibitors. This “negative” overproduction results in a balance in favor of catabolism rather than anabolism, leading to the progressive lysis of articular cartilage.
The field of tissue engineering and regenerative medicine involves the study of the restoration of normal structure and function to damaged or missing tissues and organs and shows promise for treating diseases such as OA. Tissue engineering therapies include cell-based approaches, scaffold-based approaches, bioactive molecular approaches, or combinations of the above. In contrast to drug therapy, regenerative medical therapy, such as using ECM as a bioscaffold for tissue reconstruction, does not rely on a single target receptor or pathway for its action. Intact ECM contains a diversity of structural proteins and associated bioactive molecules, including cytokines and growth factors that act as potent modulators of cell behavior. The growth factors contained in ECM include epidermal growth factor, transforming growth factor beta, keratinocyte growth factor, hepatocyte growth factor, and platelet-derived growth factor, among others. Other components of ECM include collagens, proteoglycans and glycoproteins.
In contrast to using growth factors alone as a recently studied therapeutic approach, using ECM in its native state as a scaffold for tissue repair allows all the attendant growth factors as well as their inhibitors to be present in the locally relevant quantities that exist in nature, and in their native three-dimensional structure. ECM exists in all tissues, yet can only be harvested for use as a scaffold from skin, urinary bladder, the submucosa of the small intestine, the pericardium, basement membrane and a few other sources. ECM scaffolds that are harvested in a manner that allows retention of the native structure, as opposed to chemical crosslinking, promote progenitor cell infiltration, rapid scaffold degradation, and deposition of host-derived neomatrix that results in tissue remodeling with minimal scar tissue formation. Porcine-derived urinary bladder extracellular matrix (UBM-ECM) represents a resorbable bioscaffold material that has been successfully used for the repair of musculotendinous structures, lower urinary tract reconstruction, dura mater replacement, repair of full and partial thickness skin wounds, and vascular and esophageal reconstruction. The remodeling process in all of these applications has been remarkably similar.
ECM bioscaffolds typically degrade in vivo within 30-90 days and are replaced by site-specific host cells that repopulate and/or augment host tissues that are missing, injured or otherwise deficient. Initially cellular infiltrate consisting of polymorphonuclear leukocytes and mononuclear cells occurs. By 72 hours, the cellular infiltrate is almost entirely mononuclear cells in appearance with early evidence for neovascularization. Between days 3 and 14, the number of mononuclear cells increases, vascularization increases, and there is a progressive degradation of the xenogeneic scaffold with associated deposition of host-derived neomatrix. Following day 14, the mononuclear cell infiltrate diminishes and there is the appearance of site-specific parenchymal cells that orient along lines of stress. These parenchymal cells consist of fibroblasts, smooth muscle cells, skeletal muscle cells and epithelial cells depending upon the site in which the scaffold has been placed. Circulating, marrow-derived progenitor cells participate in this remodeling process when ECM scaffolds are used. So injection of bioscaffold appears to have many advantages over stem cell therapies including lack of antigenic stimulation.
In their blinded study Dr. Rose, et al, injected 100mg of ECM powder in 1.5cc of saline in each arthritic hip of their treatment group (10 dogs, 20 hips) and saline in the dysplastic hips of the placebo group (10 dogs). The dogs in the placebo group did not improve and 4 were transferred to the treatment group. The study lasted for 5 months. Every owner at the 5-month study end point reported that the treatment was very effective and improved the dog’s quality of life. Measured parameters of activity level, pain and hip extension were statistically improved at 168 days. The length of time these improvements will go beyond 5 months is not known.
We have used ECM powder in elbows and knees and are pleased with the short-term results we have seen.
If you would like to discuss ECM powder or get a copy of the published study, please call Dr. Tangner at BluePearl Surgery Center, 405.751.3920.
I hope you all had a wonderful holiday season! As I mentioned in our last newsletter, we are thrilled to be moving into a new hospital in 2016! Our renderings are in the lobby if you want to come check them out!
The new hospital will be able to accommodate our CEs, allowing you to come in and partner with us “behind the scenes.” In the meantime, we are looking to change venues for our CEs to make this year a little different. We’ll be offering CEs every other month as well as bringing CEs to your door. If you have specific subjects you would like presented to your team, let us know!
We are excited about our move and our updated CE plans. And, we’re looking forward to our continued partnership with you. Thank you!