Categories
Veterinary Procedures

Oral Administration: Liquids

Without a Stomach Tube

Patient Preparation

None required. Technique is appropriate for owners to perform at home.

Technique

Small amounts of liquid medicine can be given successfully to dogs and cats by pulling the commissure of the lip out to form a pocket (). Deposit the liquid medication into the “cheek pouch,” where it subsequently flows between the teeth as the head is held slightly upward. Patience and gentleness, along with a reasonably flavored medication, contribute to the success.

Spoons are ineffective, as fluids are easily spilled. A disposable syringe can be used to measure and administer liquids orally. Depending on the liquid administered, disposable syringes can be reused several times, assuming they are rinsed after each administration. In addition, disposable syringes can be dispensed legally to clients for home administration of liquid medication. Mixing of medications in the same syringe is not recommended. However, dispensing of a separate, clearly marked syringe for each type of liquid medication prescribed for home administration is recommended.

Special Considerations

Compounding pharmacies are also available and can mix many medications into palatable flavors to help facilitate the oral administration of medications.

Dogs with swallowing disorders should not be treated at home with liquid medications because this could cause complications associated with aspiration.

With an Administration Tube

Patient Preparation

None required.

Note: This procedure is reserved for in-hospital use only. The technique should be performed only by individuals trained to perform this procedure.

Technique

Administration of medications, contrast material, and rehydrating fluids can be accomplished with the use of a well lubricated feeding tube passed through the nostrils into the stomach or distal esophagus. When a feeding tube is placed for long-term use (multiple days) and repeated use (described under Gastrointestinal Procedures later), it is generally recommended to avoid passing the tip of the tube beyond the distal esophagus. The reason for recommending nasoesophageal intubation over nasogastric intubation is based on the fact that reflex peristalsis of the esophagus against a tube passing through the cardia can result in significant mucosal ulceration within 72 hours. This is not a factor in patients receiving a single dose of medication or contrast material.

TABLE The French Catheter Scale Equivalents*

  Size
Scale Millimeters Inches
3 1 0.039
4 1.35 0.053
5 1.67 0.066
6 2 0.079
7 2.3 0.092
8 2.7 0.105
9 3 0.118
10 3.3 0.131
11 3.7 0.144
12 4 0.158
13 4.3 0.170
14 4.7 0.184
15 5 0.197
16 5.3 0.210
17 5.7 0.223
18 6 0.236
19 6.3 0.249
20 6.7 0.263
22 7.3 0.288
24 8 0.315
26 8.7 0.341
28 9.3 0.367
30 10 0.393
32 10.7 0.419
34 11.3 0.445

*Multiple types of pediatric polyurethane nasogastric feeding tubes are available in sizes ranging from 8F to 12F that easily accommodate administration of liquids medications and fluids to kittens, cats, and small dogs.

The narrow lumen of tubes passed through the nostril of small dogs and cats limits the viscosity of solutions that can be administered through a tube directly into the gastrointestinal tract. Nasoesophageal intubation can be done with a variety of tube types and sizes (Table The French Catheter Scale Equivalents). Newer polyurethane tubes, when coated with a lidocaine lubricating jelly, are nonirritating and may be left in place with the tip at the level of the distal esophagus. When placing the nasogastric tube, instill 4 to 5 drops of 0.5% proparacaine in the nostril of the cat or small dog; 0.5 to 1.0 mL of 2% lidocaine instilled into the nostril of a larger-breed dog may be required to achieve the level of topical anesthesia needed to pass a tube through the nostril. With the head elevated, direct the tube dorsomedially toward the alar fold (). Pushing dorsally on the nasal philtrum and pushing the nostril from lateral to medially will help facilitate passage of the tube into the ventrome-dial nasal meatus.

Caution: The tip of the feeding tube can be inadvertently introduced through the glottis and into the trachea. Topical anesthetic instilled into the nose can anesthetize the arytenoid cartilages, thereby blocking a cough or gag reflex.

After inserting the tip 1 to 2 cm into the nostril, continue to advance the tube until it reaches the desired length. If the turbinates obstruct the passage of the tube, withdraw the tube by a few centimeters. Then readvance the tube, taking care to direct the tube ventrally through the nasal cavity. Occasionally it will be necessary to withdraw the tube completely from the nostril and repeat the procedure. In particularly small patients or patients with obstructive lesions (e.g., tumor) in the nasal cavity, it may not be possible to pass a tube. Do not force the tube against significant resistance through the nostril.

Gavage, or gastric lavage and feeding, in puppies and kittens can be accomplished by passing a soft rubber catheter or feeding tube into the mouth, tilting the puppy’s or kittens head, and watching it swallow the tube. Most puppies or kittens will struggle and vocalize. They usually will not vocalize if the tube has been placed into the trachea. A 12F catheter is of an adequate diameter to pass freely, but it is too large for dogs and cats less than 2 to 3 weeks of age. Mark the tube with tape or a pen at a point equal to the distance from the mouth to the last rib. Merely push the tube into the pharynx and down the esophagus to the caudal thoracic level (into the stomach). Verify the placement of the tube using the same dry syringe aspiration technique to ensure that the tube is positioned in the esophagus or stomach rather than the trachea. Attach a syringe to the flared end, and slowly inject medication or food.

Depending on the feeding tube type, the end of the tube may or may not accommodate a syringe. For example, soft, rubber urinary catheters are excellent tubes for single administration use. However, the flared end may not accommodate a syringe. To affix a syringe to the outside end of a tapered feeding tube or catheter, insert a plastic adapter () into the open end of the tube.

Special Considerations

Esophageal (versus intratracheal) placement of the feeding tube can be verified with a dry, empty syringe. Attach the empty syringe to the end of the feeding tube. Rather than injecting air or water in an attempt to auscultate borborygmus over the abdomen, attempt simply to aspirate air from the feeding tube. If there is no resistance during aspiration and air fills the syringe, the tube likely has been placed in the trachea. Completely remove the tube and repeat the procedure. However, if repeated attempts to aspirate are met with immediate resistance and no air enters the syringe, the tube tip is positioned properly within the esophagus. If there is any question regarding placement, a lateral survey radiograph is indicated.

Definitive confirmation of proper tube placement can be made by diluting 1 to 2 ml of an iodinated contrast agent with sterile saline, instilling the liquid into the tube, then taking a lateral thoracoabdominal radiograph to confirm entry of the contrast material into the stomach.

Categories
Veterinary Procedures

Urine Collection Techniques

Urine can be removed from the bladder by one of four methods: (1) voided (the “free catch”), (2) manual compression of the urinary bladder (expressing the bladder), (3) catheterization, or (4) cystocentesis.

Voiding

For routine urinalysis, collection of urine by voiding (micturition) is satisfactory. The major disadvantage is risk of contamination of the sample with cells, bacteria, and other debris located in the genital tract and the perineal hair coat. The first portion of the stream is discarded, as it is most likely to contain debris. Voided urine samples are not recommended when bacterial cystitis is suspected.

Manual Compression of the Bladder

Compressing the urinary bladder is occasionally used to collect urine samples from dogs and cats. Critical: Do not use excessive pressure; if moderate digital pressure does not induce micturition, discontinue the technique. Excessive pressure can culminate in forcing contaminated urine (bladder) into the kidneys, or, worse, in patients with a urethral obstruction the urinary bladder can rupture. The technique is most difficult to accomplish in male dogs and male cats.

Urinary Catheterization

Several types of urinary catheters are currently available for use in dogs and cats. The catheter types most often used today are made of rubber, polypropylene, and latex-free silicone. Stainless steel catheters are occasionally used but unless placed with care these can cause damage to the urethra and/or urinary bladder. Generally, urinary catheters serve one of four purposes:

  1. 1. To relieve urinary retention
  2. 2. To test for residual urine
  3. 3. To obtain urine directly from the bladder for diagnostic purposes
  4. 4. To perform bladder lavage and instillation of medication or contrast material

The size of catheters (diameter) usually is calibrated in the French scale; each French unit is equivalent to roughly 0.33 mm. The openings adjacent to the catheter tips are called “eyes.” Human urethral catheters are used routinely in male and female dogs; 4F to 10F catheters are satisfactory for most dogs (Table Recommended Urethral Catheter Sizes for Routine Use in Dogs and Cats). Polypropylene catheters should be individually packaged and sterilized by ethylene oxide gas.

TABLE Recommended Urethral Catheter Sizes for Routine Use in Dogs and Cats

Animal Urethral Catheter Type Size (French Units*)
Cat Flexible vinyl, red rubber, or Tom Cat catheter (polyethylene) 3.5
Male dog (<25 lb) Flexible vinyl, red rubber, or polyethylene 3.5 or 5
Male dog (>25 lb) Flexible vinyl, red rubber, or polyethylene 8
Male dog (>75 lb) Flexible vinyl, red rubber, or polyethylene 10 or 12
Female dog (<10 lb)) Flexible vinyl, red rubber, or polyethylene 5
Female dog (10-50 lb) Flexible vinyl, red rubber, or polyethylene 8
Female dog (>50 lb) Flexible vinyl, red rubber, or polyethylene 10, 12, or 14

*The diameter of urinary catheters is measured on the French (F) scale. One French unit equals roughly 0.33 mm.

Catheterization of the Male Dog

Patient Preparation

Equipment needed to catheterize a male dog includes a sterile catheter (4F to 10F, 18 inches long, with one end adapted to fit a syringe), sterile lubricating jelly, povidone-iodine soap or chlorhexidine, sterile rubber gloves or a sterile hemostat, a 20-mL sterile syringe, and an appropriate receptacle for the collection of urine.

Proper catheterization of the male dog requires two persons. Place the dog in lateral recumbency on either side. Pull the rear leg that is on top forward, and then flex it (). Alternatively, long-legged dogs can be catheterized easily in a standing position.

Before catheter placement, retract the sheath of the penis and cleanse the glans penis with a solution of povidone-iodine 1% or chlorhexidine. Lubricate the distal 2 to 3 cm of the appropriate-size catheter with sterile lubricating jelly. Never entirely remove the catheter from its container while it is being passed because the container enables one to hold the catheter without contaminating it.

Technique

The catheter may be passed with sterile gloved hands or by using a sterile hemostat to grasp the catheter and pass it into the urethra. Alternatively, cut a 2-inch “butterfly” section from the end of the thin plastic catheter container. This section can be used as a cover for the sterile catheter, and the clinician can use the cover to grasp and advance the catheter without using gloves.

If the catheter cannot be passed into the bladder, the tip of the catheter may be caught in a mucosal fold of the urethra or there may be a stricture or block in the urethra. In small-breed dogs, the size of the groove in the os penis may limit the size of the catheter that can be passed. One also may experience difficulty in passing the catheter through the urethra where the urethra curves around the ischial arch. Occasionally a catheter of small diameter may kink and bend on being passed into the urethra. When the catheter cannot be passed on the first try, reevaluate the size of the catheter and gently rotate the catheter while passing it a second time. Never force the catheter through the urethral orifice.

Special Considerations

Effective catheterization is indicated by the flow of urine at the end of the catheter, and a sterile 20-mL syringe is used to aspirate the urine from the bladder. Walk the dog immediately after catheterization to encourage urination.

Catheterization of the Female Dog

Patient Preparation

Equipment needed to catheterize a female dog includes flexible urethral catheters identical to those used in the male dog. The following materials also should be on hand: a small nasal speculum, a 20-mL sterile syringe, lidocaine 0.5%, sterile lubricating jelly, a focal source of light, appropriate receptacles for urine collection, and 5 mL of povidone-iodine or a dilute chlorhexidine solution.

Use strict asepsis. Cleanse the vulva with a solution of povidone-iodine or dilute chlorhexidine. Instillation of lidocaine 0.5% into the vaginal vault helps to relieve the discomfort of catheterization. The external urethral orifice is 3 to 5 cm cranial to the ventral commissure of the vulva. In many instances the female dog may be catheterized in the standing position by passing the female catheter into the vaginal vault, despite the fact that the urethral papilla is not visualized directly.

Technique

In the spayed female dog, in which blind catheterization may be difficult, the use of a sterilized otoscope speculum andlight source (), vaginal speculum, or anal speculum with a light source will help to visualize the urethral tubercle on the floor of the vagina. In difficult catheterizations it may be helpful to place the animal in dorsal recumbency (). Insertion of a speculum into the vagina almost always permits visualization of the urethral papilla and facilitates passage of the catheter. Take care to avoid attempts to pass the catheter into the fossa of the clitoris because this is a blind, possibly contaminated cul-de-sac.

Catheterization of the Male Cat

Patient Preparation

Before attempting urinary bladder catheterization of the male cat, administer a short-term anesthetic (e.g., ketamine, 25 mg/kg IM), but only after a careful assessment of the cats physical, acid-base, and electrolyte status (see treatment of hyperkalemia).

In some cases, drugs to treat hyperkalemia may be required before anesthetic induction. Once the patient’s electrolyte status has been evaluated and hyperkalemia, if present, addressed appropriately, anesthesia can be induced with a combination of propofol (4 to 7 mg/kg intravenously [IV]) and diazepam (0.1 mg/kg IV); then the patient is intubated and maintained on gas anesthesia.

Technique

Place the anesthetized patient in dorsal recumbency. Gently grasp the ventral aspect of the prepuce and move it caudally in such a manner that the penis is extruded. Withdraw the penis from the sheath and gently pull the penis backward. Keeping sterile catheters in a freezer will help them become more rigid to facilitate passage into the urethra. Pass a sterile, flexible plastic or polyethylene (PE 60 to 90) catheter or 3- to 5-inch, 3.5F urethral catheter into the urethral orifice and gently into the bladder, keeping the catheter parallel to the vertebral column of the cat.

Caution: Never force the catheter through the urethra. The presence of debris within the urethral lumen may require the injection of 3 to 5 mL of sterile saline to back-flush urinary “sand” or concretions so that the catheter can be passed. In some instances the presence of cystic and urethral calculi will prevent the passage of a catheter into the urethra. For this reason a lateral radiograph of the penis, with the patients hindlimbs pulled caudally, may help document the presence of a urethral stone.

Catheterization of the Female Cat

Patient Preparation

Urinary bladder catheterization of the female cat is not a simple procedure. When indicated, and after a preanesthetic examination has been performed, attempt the technique only in the anesthetized cat. Urinary bladder catheterization can be accomplished with the use of a rubber or plastic, side-hole (blunt-ended) urinary catheter. The same catheter type used in male cats is effective in female cats. Instilling lidocaine 0.5% has been recommended as a means of decreasing sensitivity to catheter insertion in sedated (not recommended) cats. Cleanse the vulva with an appropriate antiseptic.

Technique

Catheterization can be accomplished with the cat in dorsal or ventral recumbency.

Experience and size of the cat dictate which technique works best.

After cleansing of the perineum and vaginal vault, place the patient in sternal recumbency, and gently pass the catheter along the ventral floor of the vaginal vault. Conversely, if the patient is placed in dorsal recumbency, direct the catheter dorsally along the ventral vaginal floor. If a catheter cannot be placed blindly, a small otoscopic speculum can be placed into the vagina, and the catheter pushed into the urethral papilla once it is visualized directly.

Indwelling Urethral Catheter

Patient Preparation

For continuous urine drainage in the awake, ambulatory patient, use a closed collection system to help prevent urinary tract infection. A soft urethral or Foley catheter can be used, and polyvinyl chloride tubing should be connected to the catheter and to the collection bag outside the cage. The collection bag should be below the level of the animal’s urinary bladder. Place an Elizabethan collar on the animal to discourage chewing on the catheter and associated tubing.

Technique

The urinary bladder is catheterized as described previously. Despite the quality of care of the catheter, urinary tract infection still may develop in any patient fitted with an indwelling urinary catheter. Ideally, remove the catheter as soon as it is no longer necessary, or if there are clinical signs of a urinary tract infection or previously undiagnosed fever. A urinary catheter is generally changed after it has been in place for more than 48 hours.

Special Considerations

Observe the patient for development of fever, discomfort, pyuria, or other evidence of urinary tract infection. If infection is suspected, remove the catheter and submit urine for culture and sensitivity or determination of minimum inhibitory concentration (MIC). Previously, culture of the catheter tip was recommended to diagnose a catheter-induced infection. However, culture of the catheter tip is no longer recommended, as it may not accurately reflect the type of microorganisms in a urinary tract infection. The empiric use of antibiotics to help prevent catheter-induced infection is not recommended, as their use can allow colonization of resistant nosocomial bacteria in the patient’s urinary tract.

Cystocentesis

Patient Preparation

Cystocentesis is a common clinical technique used to obtain a sample of urine directly from the urinary bladder of dogs and cats when collecting a voided, or free-catch, aliquot is not preferred. The procedure is indicated when necessary to obtain bladder urine for culture purposes. Urine that is collected by free catch has passed through the urethra and may be contaminated with bacteria, thereby making interpretation of the culture results difficult. Cystocentesis also is performed as a convenience when it is desirable to obtain a small sample of urine but the patient is not ready or cooperative.

Cystocentesis involves insertion of a needle, with a 6- or 12-mL syringe attached, through the abdominal wall and bladder wall to obtain urine samples for urinalysis or bacterial culture. The technique prevents contamination of urine by urethra, genital tract, or skin and reduces the risk of obtaining a contaminated sample. Cystocentesis also may be needed to decompress a severely overdistended bladder temporarily in an animal with urethral obstruction. In these cases, cystocentesis should be performed only if urethral catheterization is impossible. Warning: Penetration of a distended (obstructed) urinary bladder with a needle could result in rupture of the bladder.

Technique

To perform cystocentesis, palpate the ventral abdomen just cranial to the junction of the bladder with the urethra, and trap the urinary bladder between the fingers and the palm of the hand. Use one hand to hold the bladder steady within the peritoneal cavity while the other guides the needle. Next, insert the needle through the ventral abdominal wall into the bladder at a 45-degree angle (). Although this procedure is relatively safe, the bladder must have a reasonable volume of urine, and the procedure should not be performed without first identifying and immobilizing the bladder. For the procedure to be performed safely and quickly, the patient must be cooperative. If collection of a urine sample by cystocentesis is absolutely necessary, sedation may be indicated to restrain the patient adequately for the procedure.

Special Considerations

Generally, cystocentesis is a safe procedure, assuming the patient is cooperative and the bladder can be identified and stabilized throughout the procedure. However, injury and adverse reactions can occur. In addition to laceration of the bladder with the inserted needle (patient moves abruptly), the needle can be passed completely through the bladder and into the colon, causing bacterial contamination of the bladder or peritoneal cavity. There is also risk of penetrating a major abdominal bloodvessel, resulting in significant hemorrhage.

Categories
Diseases

Atherosclerosis

Atherosclerosis denotes inner arterial wall thickening in association with lipid deposition. Affected large coronary arteries often appear grossly thickened, yellow-white, and may have narrowed lumina. Histologically, deposits of plaque containing cholesterol, lipoid material, focal calcification, and lipophages thicken the inner sections of arterial wall (intima and inner media). There can be widespread involvement of arteries from many organs. Unlike the disease in humans, canine atherosclerosis is uncommonly associated with extensive plaque formation, arterial calcification, or thrombosis. Atherosclerosis has not been described in cats.

Atheromas are lipoid arterial plaques and they are rare features of canine atherosclerosis. Atheromas are sometimes referred to as xanthomatosis. Atherothrombosis results when a localized atheroma forms on an atherosclerotic plaque, resulting in disruption of blood flow and subsequent ischemia, infarction, or both. Atherothrombosis is most severe in both extramural and intramural coronary arteries, carotid arteries, and renal arteries.

Atherosclerosis has been detected in older dogs as a consequence of the hypercholesterolemia and lipidemia associated with thyroid atrophy. A predisposition for spontaneous atherosclerosis was reported in old, obese dogs with atrophied thyroid glands and hypothyroidism. This observation is in accordance with experiments in which atherosclerosis could be induced in thyroidectomized dogs fed large quantities of cholesterol or cholic acids. The spontaneous disease mainly affects male and spayed female dogs. An increased prevalence in miniature schnauzers, Doberman pinchers, and Labrador retrievers has been reported. The distribution and severity of arterial lesions and thyroid atrophy are typically associated with clinical signs of lethargy, anorexia, weakness, dyspnea, collapse, heart failure, vomiting, disorientation, blindness, circling, and coma. Recorded ECG abnormalities included atrial fibrillation, notched QRS complexes, and ST segment elevation. Laboratory abnormalities included hypercholesterolemia, lipidemia, low serum triiodothyronine (T3) and thyroxine (T4) concentrations, elevated blood urea nitrogen (BUM) (often associated with renal infarction) and liver enzyme concentrations, and high alpha2 and beta fractions in the protein electrophoresis.

Clinical diagnosis of atherosclerosis is difficult, and the prognosis for dogs with clinical signs related to stenosing atherosclerosis is poor. Potential treatments include thyroid replacement drugs, antihypertensive medication, blood cholesterol-reducing agents, or a low-cholesterol diet. Treatment strategies have not been tested in dogs, and severe lesions are essentially irreversible. Not all dogs with hypothyroidism develop atherosclerosis. Only those with increased levels of very low-density beta lipoproteins tend to be prone to develop atherosclerosis and plaques. Blood levels of low-density lipoproteins may be increased in these dogs because lipoprotein receptors are reduced and lipoid removal by the tissues is decreased. The elevated lipoprotein concentrations account for arterial lipoid deposits.

Atherosclerosis is strongly suspected as being an inflammatory disease developing in response to injury in the vessel wall in humans. Infiltration of the mononuclear lymphocytes into the intima, local expansion of vascular smooth muscle cells, and accumulation of extracellular matrix is believed to be the pathogenesis of the inflammation. Previously determined risk factors including hyperlipidemia and hypercholesterolemia are believed to enhance leukocyte adhesion to damaged endothelium and reduce local immune response. The role of inflammation in the development of canine atherosclerosis has yet to be determined.

Arteriovenous Fistulas (Arteriovenous Malformations)

Traumatic and Functional Arterial Disease

Trauma from direct accidental injury or iatrogenic trauma (e.g. surgery or vascular interventional procedures) is a common cause of vascular disease. Direct trauma may result in direct vascular wounds, or it can result in mural contusions leading to delayed thrombosis, necrosis, late hemorrhage, and false aneurysm formation. Vascular wounds can also occur from fractures because adjacent vessels are relatively fixed and vulnerable. Clinical features of traumatic arterial injuries may include diminished or absent pulse, enlarging hematoma, pulsatile arterial bleeding, symptoms of ischemia distal to the wound, injury of anatomically related nerves, and hypotension with major hemorrhage. Compressive forces from local tissue trauma (compartment syndrome) and vascular stenosis may delay or inhibit return to normal function of the affected area. Accurate diagnosis and extent of traumatic vascular injuries can be accomplished by direct examination, arteriography, ultrasound, and magnetic resonance imaging (MRI).

Vasospasm refers to reversible localized or diffuse vasocon-striction of arteries or small blood vessels. If short lived, the ischemia is reversible and permanent damage does not result. However, prolonged vasospasm with ischemia may lead to tissue damage and ulceration. Vasospasm is a common response to blunt and perforating vascular trauma and may also result from perivascular injection of irritating substances. When this occurs, tissue injury and vasospasm can be minimized by local infiltration with procaine hydrochloride or lidocaine. Uncommonly, vasospasm occurs in association with spontaneous arterial rupture (e.g. ruptured cerebral aneurysm, stroke). Angiography is usually required for confirmation. Vasospasm may be elicited by exotoxins. The best-known example is ergotism that produces intense vasospasm of the digits and large vessels by stimulation of the alpha-adrenoceptor. The differential diagnosis of vasospasm includes polycythemia, cold agglutinins, thrombosis, arteriosclerosis, and vasculitis.

Diseases of Veins

Diseases of the Peripheral Lymphatics

Categories
Diseases

Diseases of the Ear: General Principles Of Management

The therapeutic plan for otitis externa requires identification of the primary disease process and perpetuating factors. Ideally management is aimed at thoroughly cleaning and drying the ear canal, removing or managing the primary factors, controlling perpetuating factors, administering appropriate topical or systemic therapy (or both), and evaluating response to therapy.

Ear Cleaning

Ear cleaning serves several functions: (1) it removes material that supports or perpetuates infection; (2) it removes bacterial toxins, white blood cells (WBCs), and free fatty acids that stimulate inflammation; (3) it allows complete evaluation of the external ear canal and tympanum; (4) it allows topical therapy to contact all portions of the ear canal; and (5) it removes material that may inactivate topical medications. Significandy painful ears may benefit from initial anti-inflammatory therapy to decrease pain and swelling of the ear canal prior to cleaning. Severe cases of otitis externa often require general anesthesia to facilitate complete cleaning and evaluation of the external and middle ear.

Many different solutions are available for removing cerumen, exudate, and debris from the ear canal (Table Otic Cleaning Solutions). If the tympanic membrane cannot be visualized, only physiologic saline solution or water should be used, because many topical cleaning agents are ototoxic or incite inflammation of the middle ear. An operating otoscope, ear loops, and alligator forceps facilitate manual removal of large amounts of cerumen or debris. Debris is carefully removed under direct visualization, and care is taken deeper in the ear canal (close to the tympanic membrane). Aggressive hair removal is not advised, because inflammation and damage to the epithelium can result in secondary bacterial colonization and infection. Flushing may be performed after large accumulations of cerumen and debris are mechanically removed from the ear canal.

Otic Cleaning Solutions

Trade Name Acetic Acid Boric Acid Salicylic Acid Isopropyl Alcohol Propylene Clycol Dss Other
Ace-Otic Cleanser 2%   0.1%       Lactic acid 2.7%
Adams Pan-Otic         X X Parachlorometaxylenol, tris EDTA, methylparaben, diazolidinyl urea, popylparaben, octoxynol
Alocetic Ear Rinse X     X     Nonoxynol-12, methylparaben, alovera gel
Cerulytic Ear Ceruminolytic         X   Benzyl alcohol, butylated hydroxytoluene
Cerumene             25% Isopropyl myristate
DermaPet Ear/Skin Cleanser for Pets X X          
Docusate Solution         X X  
Earmed Boracetic Flush X X         Aloe
Earmed Cleansing Solution & Wash         X   50A 40B alcohol, cocamidopropyl phosphatidyl and PE dimonium chloride
Earoxide Ear Cleanser             Carbamide peroxide 6.5%
Epi-Otic Ear Cleanser     X   X X Lactic acid, chitosanide
Fresh-Ear X X X X X   Lidocaine hydrochloride, glycerin, sodium docusate, lanolin oil
OtiCalm     X       Benzoic acid, malic acid, oil of eucalyptus
Otic Clear X X X X X   Glycerin, lidocaine hydrochloride
Oticlean-A Ear Cleaning Lotion X X X 35% X   Lanolin oil, glycerin
Oti-Clens     X   X   Malic acid, benzoic acid
Otipan Cleansing Solution         X   Hydroxypropyl cellulose, octoxynol
Otocetic Solution 2% 2%          
Wax-O-Sol 25%             Hexamethyltetracosane

Flushing and evacuation of solution is done under direct visualization through an operating otoscope. A bulb syringe and red rubber catheter system may be used to both flush and evacuate solutions and accumulations from the ear canal. The operator, avoiding drastic pressure changes within the external ear canal that could damage the tympanum, should carefully control suction and manual evacuation of the contents of the bulb syringe from the ear canal. Other alternatives include tomcat catheters (3.5 F) or flexible, intravenous catheters (14 gauge, Teflon); stiff, narrow catheters should be used cautiously and under direct visualization deep in the external ear canal. Other reservoir systems for delivery or evacuation of solutions include a 12 mL syringe or suction tubing attached to in-house vacuum systems. In-house vacuum systems should be used cautiously and under direct visualization. Care should be taken to avoid trauma to the tympanic membrane until its integrity can be assessed. Initial flushes should be done with physiologic saline solution or water until the integrity of the tympanic membrane is established.

Other solutions may aid in the removal of wax in the ear canal. Ceruminolytics are emulsifiers and surfactants that break down ceruminocellular aggregates by causing lysis of squamous cells. A ceruminolytic agent in an alkaline pH may more effectively lyse squamous cells via cell surface protein disruption. Oil-based products soften and loosen debris to aid in their removal but do not cause cell lysis. Water-based ceruminolytics are easier to remove and dry more quickly than oil-based solutions, which are occlusive if they remain in the ear canal. Water-based products include dioctyl sodium sulfosuccinate, calcium sulfosuccinate, and carbamate peroxide, which has a foaming action with the release of urea and oxygen. Oil-based products include squalene, triethanolamine polypeptide, hexamethyltetracosane, oleate condensate, propylene glycol, glycerin, and mineral oil. In a recent study only the combination of squalene and isopropyl myristate in a liquid petrolatum base had no adverse effects on hearing, the vestibular system, and histopathologic examination. Other agents tested contained glycerin, dioctyl sodium sulfosuccinate (2% or 6.5%), parachlorometaxylenol, carbamide peroxide (6%), propylene glycol, triethanolamine polypeptide oleate condensate (10%), and chlorobutanol (0.5%).

Alcohol-based drying agents added to ceruminolytics include boric acid, benzoic acid, and salicylic acid, which decrease the pH of the ear canal, cause keratolysis, and have a mild antimicrobial effect. Drying the ear canal is important to combat increased humidity, which potentiates infection.

If the tympanum is intact, the ear canal is filled with a ceruminolytic agent for at least 2 minutes and the pinna is cleaned at the same time. The solution is flushed twice with warm water, and the canal inspected. The procedure is repeated until cleaning is complete. Other solutions commonly advocated for ear flushing include dilute chlorhexidine solution (0.05%), dilute povidone-iodine, and acetic acid (2.5%). The first two agents are potentially ototoxic or induce inflammation and should not be used if the tympanum is ruptured. A combination of propylene glycol malic, benzoic, or salicylic acid; 2% acetic acid; or dilute povidone-iodine have been suggested for use in dogs with a ruptured tympanum.

Owners may clean the ears at home with mild preparations of ceruminolytics and drying agents if mild otitis is present without severe accumulation of cerumen or exudate. Aqueous solutions are usually recommended because they are less occlusive and easier to clean from the ear, dog, and home environment.

The ear should be filled with the solution, then massaged for 40 to 60 seconds. The pet should be allowed to shake its head to remove the majority of the solution, and the excess should be wiped from the ear canal and pinna with a tissue. Daily flushing is usually recommended, followed by every other day, weekly, then as needed, depending on the solution. Ear swabs are not recommended for home use, because cerumen and debris may be forced into the horizontal ear canal and impact against the tympanic membrane

Topical Therapy

Erythematous ceruminous otitis externa is diagnosed 2.7 times more often than acute suppurative otitis according to one report. Yeast ± cocci were identified in those cases, with cocci or rods identified in suppurative otitis. Topical therapy should be based on the cytologic examination to diminish the incidence of inappropriate treatment (Table Topical Medications Used in the Treatment of Ear Disease). Many preparations combine anti-inflammatories and antimicrobials in an attempt to decrease the inflammation and combat bacterial or yeast overgrowth. All topical medications should be considered supportive, and specific treatment should be aimed at controlling the primary disease process.

Topical Medications Used in the Treatment of Ear Disease

Generic Name Trade Name Dose Frequency Description
Fluocinolone 0.01% DMSO 60% Synotic 4-6 drops; total dose<17mL q12h initially. q48-72h maintenance Potent corticosteroid anti-inflammatory
Hydrocortisone 1.0% HB101,

Burrows H,

2-12 drops, depending on ear size q12h initially. q24-48h maintenance Mild corticosteroid anti-inflammatory
Hydrocortisone 1.0%, lactic acid Epiotic HC 5-10 drops q12h for 5 days Mild corticosteroid anti-inflammatory, drying agent
Hydrocortisone 0.5%, sulfur 2%. acetic acid 2.5% Clear X Ear Treatment 2-12 drops, depending on ear size q12-24h initially. q24-48h maintenance Mild corticosteroid anti-inflammatory, astringent, germicidal
DSS 6.5%. urea (carbamide peroxide 6%) Clear X Ear Cleansing Solution 1-2 mL per ear Once per week to as necessary Ceruminolytic, lubricating agent
Chlorhexidine 2% Nolvasan Dilute 1:40 in water As necessary Antibacterial & antifungal activity
Chlorhexidine 1.5% Nolvasan Dilute 2% in

propylene glycol

q12h Antibacterial & antifungal activity
Povidone-iodine 10% Betadine solution Dilute 1:10-1:50 in water As necessary Antibacterial activity
Polyhydroxidine iodine 0.5% Xenodyne Dilute 1:1-1:5 in water As necessary, q12h, once weekly Antibacterial activity
Acetic acid 5% White vinegar Dilute 1:1-1:3 in water As necessary; q12-24h for Pseudomonas Antibacterial activity, lowers ear canal pH
Neomycin 0.25%, triamcinolone 0.1%, thiabendazole 4% Tresaderm 2-12 drops depending on ear size q12h up to 7 days Antibacterial & antifungal activity, parasiticide (mites), moderate corticosteroid anti-inflammatory
Neomycin 0.25%, triamcinolone 0.1%, nystatin 100,000 U/mL Panalog 2-12 drops depending on ear size q12h to once weekly Antibacterial & antifungal activity, moderate corticosteroid anti-inflammatory
Chloramphenicol 0.42%. prednisone 0.17%, tetracaine 2%, squalene Liquachlor, Chlora-Otic 2-12 drops depending on ear size q12h up to 7 days Antibacterial activity, mild corticosteroid anti-inflammatory
Neomycin 1.75 & polymyxin B 5000 lU/mL, penicillin C procaine 10,000 lU/mL Forte Topical 2-12 drops depending on ear size q12h Antibacterial activity
Centamicin 0.3%, betamethasone valerate 0.1% Centocin Otic Solution, Betagen Otic Solution 2-12 drops depending on ear size q12h for 7 to 14 days Antibacterial activity, potent corticosteroid anti-inflammatory
Centamicin 0.3%, betamethasone 0.1%, clotrimazole 0.1% Otomax, Obibiotic Ointment 2-12 drops depending on ear size q12h for 7 days Antibacterial & antifungal activity, potent corticosteroid anti-inflammatory
Centamicin 0.3%, betamethasone valerate 0.1%, acetic acid 2.5% Centaved Otic Solution 2-12 drops, depending on ear size q12h for 7 to 14 days Antibacterial activity, potent corticosteroid anti-inflammatory
Polymixin B 10,000 lU/mL, hydrocortisone 0.5% Otobiotic 2-12 drops, depending on ear size q12h Antibacterial activity, mild corticosteroid anti-inflammatory
Enrofloxacin 0.5%, silver sulfadiazine 1% Baytril Otic 2-12 drops, depending on ear size q12h for up to 14 days Antibacterial activity
Carbaryl 0.5%, neomycin 0.5%, tetracaine Mitox Liquid 2-12 drops, depending on ear size   Antibacterial activity, parasiticide (mites)
Pyrethrins 0.06%, piperonyl butoxide 0.6% Ear Mite and Tick Control 5 drops q12h Parasiticide (mites)
Pyrethrins 0.05%, squalene 25% Cerumite 2-12 drops, depending on ear size q24h for 7 to 10 days Parasiticide (mites), ceruminolytic
Isopropyl alcohol 90%, boric acid 2% Panodry Fill ear canal As necessary Drying agent
Acetic acid 2%, aluminum acetate Otic Domeboro Fill ear canal q12-48h Drying agent, antibacterial activity, lowers ear canal pH
Silver sulfadiazine Silvadene Dilute 1:1 with water, 1 g powder in 100 mL water q12h for 14 days Antibacterial & antifungal activity
Tris EDTA±

gentamicin 0.03%

  2-12 drops, depending on ear size q12h for 14 days 1 L distilled water, 1.2g Tris EDTA, 1 mL glacial acetic acid; antibacterial activity
Silver nitrate   Use sparingly As necessary Cauterization of

ulcerative otitis externa

Miconazole 1%; ± topical glucocorticoid (7.5 mL of dexamethasone phosphate (4 mg/mL] to10mLof1% miconazole) Conofite 2-12 drops, depending on ear size q12-24h Antifungal activity
Ivermectin 0.01% Acarexx 0.5 mL per ear Once Parasiticide (mites)
Pyrethrins 0.15%, piperonyl butoxide 1.5% Many 2-12 drops, depending on ear size Twice at 7-day interval Parasiticide (mites)
Pyrethrins 0.05%, piperonyl butoxide 0.5%, squalene 25% Cerumite 2-12 drops, depending on ear size q24h for 7 days Parasiticide (mites), ceruminolytic
Pyrethrins 0.04%, piperonyl butoxide 0.49%, DSS 1.952%, benzocaine 1.952% Aurimite 10 drops q12h  
Rotenone 0.12%, cube resins 0.16% Many 2-12 drops, depending on ear size Every other day Parasiticide (mites)

Topical glucocorticoids benefit most cases of otitis externa by decreasing pruritus, exudation, swelling, and proliferative changes of the ear canal. The most potent glucocorticoids available in topical preparations are betamethasone valerate and fluocinolone acetonide. Less potent corticosteroids include triamcinolone acetonide and dexamethasone; the least potent is hydrocortisone. Most dogs benefit from short-term therapy with topical corticosteroids at the initiation of therapy, with concurrent therapy aimed at the primary and other perpetuating factors. Long-term therapy with topical corticosteroids can be deleterious because of systemic absorption of drug. Increased serum liver enzymes and depressed adrenal responsiveness may occur; with prolonged use iatrogenic hyperadreno-corticism is possible. Glucocorticoids alone may be of benefit for short-term therapy in cases of allergic or erythematous ceruminous otitis.

Antimicrobials are important for controlling secondary bacterial or yeast overgrowth or infection. Antimicrobials are indicated in any case with cytologic evidence of bacterial overgrowth or infection, with attention paid to the morphology and gram-staining characteristics of the bacteria. Otic preparations commonly contain aminoglycoside antibiotics. Neomycin is effective against typical otitis bacteria such as Staphylococcus intermedium. Gentamicin and polymyxin B are also appropriate initial topical treatments for gram-negative bacterial otitis externa.The significant risk of bone marrow toxicity in people limits the use of chloramphenicol for treating otitis in dogs and cats despite its antibacterial spectrum and availability.

Due to the frequency of resistant gram-negative bacteria such as Pseudomonas, other topical preparations have been developed. Enrofloxacin, ophthalmic tobramycin, and topical application of injectable ticarcillin have been used to treat otitis in dogs.< Their use should be limited to cases of resistant bacteria, and culture and susceptibility testing should be performed prior to application. Other topical agents may be used to supplement treatment of resistant Pseudomonas, such as silver sulfadiazine solution and tris EDTA. Tris EDTA can render Pseudomonas susceptible to enrofloxacin or cephalosporins by enhancing membrane permeability and altering ribosome stability. Frequent ear cleaning may also assist in the treatment of resistant bacterial otitis; ceruminolytics have antimicrobial properties, and their use in clinical cases has been evaluated. Acetic acid in combination with boric acid is effective against both Pseudomonas and Staphylococcus, depending on concentration and duration of exposure. Ear cleaning removes proinflammatory products, cells, and substances that diminish the effectiveness of topical antibiotics.

Many topical preparations control yeast organisms, which may complicate erythematous ceruminous otitis and suppurative otitis. Common active ingredients include miconazole, clotrimazole, nystatin, and thiabendazole. Preparations containing climbazole, econazole, and ketoconazole have also been evaluated. Eighty percent of yeast were susceptible to miconazole and econazole, intermediately resistant to ketoconazole, and 90% were resistant to nystatin and amphotericin B in one in vitro study. Topical ear cleaning agents have some efficacy against Malassezia organisms. Other preparations (e.g. chlorhexidine, povidone-iodine, acetic acid) are also effective in the treatment of secondary yeast overgrowth.

Response to topical therapy should be gauged by re-evaluation of physical, cytologic, and otoscopic examinations every 10 to 14 days after the initiation of therapy. Any changes in the results of these examinations should be recorded. Most cases of otitis can be managed topically; failure to respond to therapy should prompt re-evaluation of the diagnosis and treatment.

Systemic Therapy

Systemic glucocorticoid administration may be beneficial in cases of severe, acute inflammation of the ear canal, chronic proliferative changes of the ear canal, and allergic otitis. Anti-inflammatory doses should be limited to 7 to 10 days. Cases of significant thickening or proliferative changes in the external ear canal benefit from systemic antimicrobial therapy. Systemic therapy should be considered if concurrent dermatologic changes of the surrounding skin, pinna, or other regions of the body are present. Long-term administration of appropriate antimicrobials based on culture and susceptibility is required in all cases of otitis media. Systemic therapy for yeast is rarely recommended in animals with otitis alone. One study evaluated oral itraconazole therapy, and in ear samples evaluated on cytology and culture, no change in cytology score was found.

 

Categories
Drugs

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based (Abelcet, Fungizone)

Antifungal

Highlights Of Prescribing Information

Systemic antifungal used for serious mycotic infections

Must be administered IV

Nephrotoxicity is biggest concern, particularly with the deoxycholate form; newer lipid based products are less nephrotoxic & penetrate into tissues better, but are more expensive

Renal function monitoring essential

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based interactions

What Is Amphotericin B Desoxycholate, Amphotericin B Lipid-Based Used For?

Because the potential exists for severe toxicity associated with this drug, it should only be used for progressive, potentially fatal fungal infections. Veterinary use of amphotericin has been primarily in dogs, but other species have been treated successfully. For further information on fungal diseases treated, see the Pharmacology and Dosage sections.

The liposomal form of amphotericin B can be used to treat Leishmaniasis.

Pharmacology / Actions

Amphotericin B is usually fungistatic, but can be fungicidal against some organisms depending on drug concentration. It acts by binding to sterols (primarily ergosterol) in the cell membrane and alters the permeability of the membrane allowing intracellular potassium and other cellular constituents to “leak out.” Because bacteria and rickettsia do not contain sterols, amphotericin B has no activity against those organisms. Mammalian cell membranes do contain sterols (primarily cholesterol) and the drug’s toxicity may be a result of a similar mechanism of action, although amphotericin binds less strongly to cholesterol than ergosterol.

Amphotericin B has in vitro activity against a variety of fungal organisms, including Blastomyces, Aspergillus, Paracoccidioides, Coccidioides, Histoplasma, Cryptococcus, Mucor, and Sporothrix. Zygomycetes is reportedly variable in its response to amphotericin. Aspergillosis in dogs and cats does not tend to respond satisfactorily to amphotericin therapy. Additionally, amphotericin B has in vivo activity against some protozoa species, including Leishmania spp. and Naegleria spp.

It has been reported that amphotericin B has immunoadjuvant properties but further work is necessary to confirm the clinical significance of this effect.

Pharmacokinetics

Pharmacokinetic data on veterinary species is apparently unavailable. In humans (and presumably animals), amphotericin B is poorly absorbed from the GI tract and must be given parenterally to achieve sufficient concentrations to treat systemic fungal infections. After intravenous injection, the drug reportedly penetrates well into most tissues but does not penetrate well into the pancreas, muscle, bone, aqueous humor, or pleural, pericardial, synovial, and peritoneal fluids. The drug does enter the pleural cavity and joints when inflamed. CSF levels are approximately 3% of those found in the serum. Approximately 90-95% of amphotericin in the vascular compartment is bound to serum proteins. The newer “lipid” forms of amphotericin B have higher penetration into the lungs, liver and spleen than the conventional form.

The metabolic pathways of amphotericin are not known, but it exhibits biphasic elimination. An initial serum half-life of 24-48 hours, and a longer terminal half-life of about 15 days have been described. Seven weeks after therapy has stopped, amphotericin can still be detected in the urine. Approximately 2-5% of the drug is recovered in the urine in unchanged (biologically active) form.

Before you take Amphotericin B Desoxycholate, Amphotericin B Lipid-Based

Contraindications / Precautions / Warnings

Amphotericin is contraindicated in patients who are hypersensitive to it, unless the infection is life-threatening and no other alternative therapies are available.

Because of the serious nature of the diseases treated with systemic amphotericin, it is not contraindicated in patients with renal disease, but it should be used cautiously with adequate monitoring.

Adverse Effects

Amphotericin B is notorious for its nephrotoxic effects; most canine patients will show some degree of renal toxicity after receiving the drug. The proposed mechanism of nephrotoxicity is via renal vasoconstriction with a subsequent reduction in glomerular filtration rate. The drug may directly act as a toxin to renal epithelial cells. Renal damage may be more common, irreversible and severe in patients who receive higher individual doses or have preexisting renal disease. Usually, renal function will return to normal after treatment is halted, but may require several months to do so.

Newer forms of lipid-complexed and liposome-encapsulated amphotericin B significantly reduce the nephrotoxic qualities of the drug. Because higher dosages may be used, these forms may also have enhanced effectiveness. A study in dogs showed that amphotericin B lipid complex was 8-10 times less nephrotoxic than the conventional form.

The patient’s renal function should be aggressively monitored during therapy. A pre-treatment serum creatinine, BUN (serum urea nitrogen/SUN), serum electrolytes (including magnesium if possible), total plasma protein (TPP), packed cell volume (PCV), body weight, and urinalysis should be done prior to starting therapy. BUN, creatinine, PCV, TPP, and body weight are rechecked before each dose is administered. Electrolytes and urinalysis should be monitored at least weekly during the course of treatment. Several different recommendations regarding the stoppage of therapy when a certain BUN is reached have been made. Most clinicians recommend stopping, at least temporarily, amphotericin treatment if the BUN reaches 30-40 mg/dL, serum creatinine >3 mg/dL or if other clinical signs of systemic toxicity develop such as serious depression or vomiting.

At least two regimens have been used in the attempt to reduce nephrotoxicity in dogs treated with amphotericin desoxycholate. Mannitol (12.5 grams or 0.5-1 g/kg) given concurrently with amphotericin B (slow IV infusion) to dogs may reduce nephrotoxicity, but may also reduce the efficacy of the therapy, particularly in blasto-mycosis. Mannitol treatment also increases the total cost of therapy. Sodium loading prior to treating has garnered considerable support in recent years. A tubuloglomerular feedback mechanism that induces vasoconstriction and decreased GFR has been postulated for amphotericin B toxicity; increased sodium load at the glomerulus may help prevent that feedback. One clinician (Foil 1986), uses 5 mL/kg of normal saline given in two portions, before and after amphotericin B dosing and states that is has been “… helpful in averting renal insufficiency….”

Cats are apparently more sensitive to the nephrotoxic aspects of amphotericin B, and many clinicians recommend using reduced dosages in this species (see Dosage section).

Adverse effects reported in horses include: tachycardia, tachyp-nea, lethargy, fever, restlessness, anorexia, anemia, phlebitis, polyuria and collapse.

Other adverse effects that have been reported with amphotericin B include: anorexia, vomiting, hypokalemia, distal renal tubular aci-dosis, hypomagnesemia, phlebitis, cardiac arrhythmias, non-regenerative anemia and fever (may be reduced with pretreatment with NSAIDs or a low dosage of steroids). Calcinosis cutis has been reported in dogs treated with amphotericin B. Amphotericin B can increase creatine kinase levels.

Reproductive / Nursing Safety

The safety of amphotericin B during pregnancy has not been established, but there are apparently no reports of teratogenicity associated with the drug. The risks of therapy should be weighed against the potential benefits. In humans, the FDA categorizes this drug as category B for use during pregnancy (Animal studies have not yet demonstrated risk to the fetus, hut there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, hut adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters.) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: A (Prohahly safe. Although specific studies may not have proved the safety of all drugs in dogs and cats, there are no reports of adverse effects in laboratory animals or women.)

Overdosage / Acute Toxicity

No case reports were located regarding acute intravenous overdose of amphotericin B. Because of the toxicity of the drug, dosage calculations and solution preparation procedures should be double-checked. If an accidental overdose is administered, renal toxicity maybe minimized by administering fluids and mannitol as outlined above in the Adverse Effects section.

How to use Amphotericin B Desoxycholate, Amphotericin B Lipid-Based

All dosages are for amphotericin B desoxycholate (regular amphotericin B) unless specifically noted for the lipid-based products.

Note: Some clinicians have recommended administering a 1 mg test dose (less in small dogs or cats) IV over anywhere from 20 minutes to 4 hours and monitoring pulse, respiration rates, temperature, and if possible, blood pressure. If a febrile reaction occurs some clinicians recommend adding a glucocorticoid to the IV infusion solution or using an antipyretic prior to treating, but these practices are controversial.

A published study () demonstrated less renal impairment and systemic adverse effects in dogs who received amphotericin BIV slowly over 5 hours in 1 L of D5W than in dogs who received the drug IV in 25 mL of D5W over 3 minutes.

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based dosage for dogs:

For treatment of susceptible systemic fungal infections:

a) Two regimens can be used; after diluting vial (as outlined below in preparation of solution section), either:

1) Rapid-Infusion Technique: Dilute quantity of stock solution to equal 0.25 mg/kg in 30 mL of 5% dextrose. Using butterfly catheter, flush with 10 mL of D5W. Infuse amphotericin B solution IV over 5 minutes. Flush catheter with 10 mL of D5W and remove catheter. Repeat above steps using 0.5 mg/kg 3 times a week until 9-12 mg/kg accumulated dosage is given.

2) Slow IV Infusion Technique: Dilute quantity of stock solution to equal 0.25 mg/kg in 250-500 mL of D5W. Place indwelling catheter in peripheral vein and give total volume over 4-6 hours. Flush catheter with 10 mL of D5W and remove catheter. Repeat above steps using 0.5 mg/kg 3 times a week until 9-12 mg/kg accumulated dosage is given. ()

b) In dehydrated, sodium-depleted animals, must rehydrate before administration. Dosage is 0.5 mg/kg diluted in D5W. In dogs with normal renal function, may dilute in 60-120 mL of D5W and give by slow IV over 15 minutes. In dogs with compromised renal function, dilute in 500 mL or 1 liter of D5W and give over slowly IV over 3-6 hours. Re-administer every other day if BUN remains below 50 mg/dl. If BUN exceeds 50 mg/dl, discontinue until BUN decreases to at least 35 mg/dl. Cumulative dose of 8 -10 mg/kg is required to cure blastomycosis or histoplasmosis. Coccidioidomycosis, aspergillosis and other fungal diseases require a greater cumulative dosage. ()

c) For treating systemic mycoses using the lipid-based products: AmBisome, Amphocil or Abelcet Give test dose of 0.5 mg/ kg; then 1-2.5 mg/kg IV q48h (or Monday, Wednesday, Friday) for 4 weeks or until the total cumulative dose is reached. Use 1 mg/kg dose for susceptible yeast and dimorphic fungi until a cumulative dose of 12 mg/kg is reached; for more resistant filamentous fungal infections (e.g., pythiosis) use the higher dose 2-2.5 mg/kg until a cumulative dose of 24-30 mg/kg is reached. ()

d) For treating systemic mycoses using the amphotericin B lipid complex (ABLC; Abelcet) product: 2-3 mg/kg IV three days per week for a total of 9-12 treatments (cumulative dose of 24-27 mg). Dilute to a concentration of 1 mg/mL in dextrose 5% (D5W) and infuse over 1-2 hours ()

e) For systemic mycoses using amphotericin B lipid complex (Abelcet): Dilute in 5% dextrose to a final concentration of 1 mg/mL and administer at a dosage of 2-3 mg/kg three times per week for 9-12 treatments or a cumulative dosage of 24-27 mg/kg ()

For blastomycosis (see general dosage guidelines above):

a) Amphotericin B 0.5 mg/kg 3 times weekly until a total dose of 6 mg/kg is given, with ketoconazole at 10-20 mg/kg (30 mg/kg for CNS, bone or eye involvement) divided for 3-6 months ()

b) Amphotericin B 0.15-0.5 mg/kg IV 3 times a week with ketoconazole 20 mg/day PO once daily or divided twice daily; 40 mg/kg divided twice daily for ocular or CNS involvement (for at least 2-3 months or until remission then start maintenance). When a total dose of amphotericin B reaches 4-6 mg/kg start maintenance dosage of amphotericin B at 0.15-0.25 mg/kg IV once a month or use ketoconazole at 10 mg/kg PO either once daily, divided twice daily or ketoconazole at 2.5-5 mg/kg PO once daily. If CNS/ocular involvement use ketoconazole at 20-40 mg/kg PO divided twice daily ()

c) For severe cases, using amphotericin B lipid complex (Abelcet): 1-2 mg/kg IV three times a week (or every other day) to a cumulative dose of 12-24 mg/kg ()

For cryptococcosis (see general dosage guidelines above):

a) Amphotericin B 0.5 – 0.8 mg/kg SC 2 – 3 times per week. Dose is diluted in 0.45% NaCl with 2.5% dextrose (400 mL for cats, 500 mL for dogs less than 20 kg and 1000 mL for dogs greater than 20 kg). Concentrations greater than 20 mg/L result in local irritation and sterile abscess formation. May combine with flucytosine or the azole antifungals. ()

For histoplasmosis (see general dosage guidelines above):

a) Amphotericin B 0.15 – 0.5 mg/kg IV 3 times a week with ketoconazole 10-20 mg/day PO once daily or divided twice daily (for at least 2-3 months or until remission then start maintenance). When a total dose of amphotericin B reaches 2-4 mg/kg, start maintenance dosage of amphotericin B at 0.15-0.25 mg/kg IV once a month or use ketoconazole at 10 mg/kg PO either once daily, divided twice daily or at 2.5-5 mg/kg PO once daily ()

b) As an alternative to ketoconazole treatment: 0.5 mg/kg IV given over 6-8 hours. If dose is tolerated, increase to 1 mg/ kg given on alternate days until total dose of 7.5-8.5 mg/kg cumulative dose is achieved ()

For Leishmaniasis:

a) Using the liposomal form of Amphotericin B: 3-3.3 mg/kg IV 3 times weekly for 3-5 treatments)

b) Using AmBisome (lipid-based product): Give initial test dose of 0.5 mg/kg, then 3-3.3 mg/kg IV every 72-96 hours until a cumulative dose of 15 mg/kg is reached. May be possible to give the same cumulative dose with a lower level every 48 hours. ()

For gastrointestinal pythiosis:

a) Resect lesions that are surgically removable to obtain 5 – 6 cm margins. Follow-up medical therapy using the amphotericin B lipid complex (ABLC; Abelcet) product: 1-2 mg/kg IV three times weekly for 4 weeks (cumulative dose 12-24 mg). May alternatively use itraconazole at 10 mg/kg PO once daily for 4-6 months. ()

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based dosage for cats:

For treatment of susceptible systemic fungal infections: a) Rapid-Infusion Technique: After diluting vial (as outlined below in preparation of solution section), dilute quantity of stock solution to equal 0.25 mg/kg in 30 mL of 5% dextrose. Using butterfly catheter, flush with 10 mL of D5W Infuse amphotericin B solution IV over 5 minutes. Flush catheter with 10 mL of D5W and remove catheter. Repeat above steps using 0.25 mg/kg 3 times a week until 9-12 mg/kg accumulated dosage is given. ()

For cryptococcosis (see general dosage guidelines above):

a) As an alternative therapy to ketoconazole: Amphotericin B: 0.25 mg/kg in 30 mL D5WIV over 15 minutes q48h with flucytosine at 200 mg/kg/day divided q6h PO. Continue therapy for 3-4 weeks after clinical signs have resolved or until BUN >50 mg/dl. (Legendre 1989)

b) Amphotericin B 0.15-0.4 mg/kg IV 3 times a week with flucytosine 125-250 mg/day PO divided two to four times a day. When a total dose of amphotericin B reaches 4-6 mg/ kg, start maintenance dosage of amphotericin B at 0.15-0.25 mg/kg IV once a month with flucytosine at dosage above or with ketoconazole at 10 mg/kg PO once daily or divided twice daily ()

c) Amphotericin B 0.5-0.8 mg/kg SC 2-3 times per week. Dose is diluted in 0.45% NaCl with 2.5% dextrose (400 mL for cats, 500 mL for dogs less than 20 kg and 1000 mL for dogs greater than 20 kg). Concentrations greater than 20 mg/L result in local irritation and sterile abscess formation. May combine with flucytosine or the azole antifungals. ()

d) For treating systemic mycoses using the amphotericin B lipid complex (ABLC; Abelcet) product: 1 mg/kg IV three days per week for a total of 12 treatments (cumulative dose of 12 mg). Dilute to a concentration of 1 mg/mL in dextrose 5% (D5W) and infuse over 1-2 hours ()

For histoplasmosis (see general dosage guidelines above):

a) Amphotericin B: 0.25 mg/kg in 30 mL D5WIV over 15 minutes q48h with ketoconazole at 10 mg/kg q12h PO. Continue therapy for 4-8 weeks or until BUN >50 mg/dl. If BUN increases greater than 50 mg/dl, continue ketoconazole alone. Ketoconazole is used long-term (at least 6 months of duration. ()

b) Amphotericin B 0.15-0.5 mg/kg IV 3 times a week with ketoconazole 10 mg/day PO once daily or divided twice daily (for at least 2-3 months or until remission, then start maintenance). When a total dose of amphotericin B reaches 2-4 mg/ kg, start maintenance dosage of amphotericin B at 0.15-0.25 mg/kg IV once a month or use ketoconazole at 10 mg/kg PO either once daily, divided twice daily or at 2.5-5 mg/kg PO once daily ()

For blastomycosis (see general dosage guidelines above):

a) Amphotericin B: 0.25 mg/kg in 30 mL D5WIV over 15 minutes q48h with ketoconazole: 10 mg/kg q12h PO (for at least 60 days). Continue amphotericin B therapy until a cumulative dose of 4 mg/kg is given or until BUN >50 mg/dl. If renal toxicity does not develop, may increase dose to 0.5 mg/ kg of amphotericin B. ()

b) Amphotericin B 0.15-0.5 mg/kg IV 3 times a week with ketoconazole 10 mg/day PO once daily or divided twice daily (for at least 2-3 months or until remission then start maintenance). When a total dose of amphotericin B reaches 4-6 mg/ kg start maintenance dosage of amphotericin B at 0.15-0.25 mg/kg IV once a month or use ketoconazole at 10 mg/kg PO either once daily, divided twice daily or ketoconazole at 2.5 – 5 mg/kg PO once daily. If CNS/ocular involvement, use ketoconazole at 20-40 mg/kg PO divided twice daily. ()

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based dosage for rabbits, rodents, and small mammals:

a) Rabbits: 1 mg/kg/day IV ()

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based dosage for horses:

For treatment of susceptible systemic fungal infections:

a) For fungal pneumonia: Day 1: 0.3 mg/kg IV; Day 2: 0.4 mg/kg IV; Day 3: 0.6 mg/kg IV; days 4-7: no treatment; then every other day until a total cumulative dose of 6.75 mg/kg has been administered ()

b) For phycomycoses and pulmonary mycoses: After reconstitution (see below) transfer appropriate amount of drug to 1L of D5W and administer using a 16 g needle IV at a rate of 1 L/ hr. Dosage schedule follows: Day 1: 0.3 mg/kg IV; Day 2: 0.45 mg/kg IV; Day 3: 0.6 mg/kg IV; then every other day for 3 days per week (MWF or TTHSa) until clinical signs of either improvement or toxicity occur. If toxicity occurs, a dose may be skipped, dosage reduced or dosage interval lengthened. Administration may extend from 10-80 days. ()

For intrauterine infusion: 200-250 mg. Little science is available for recommending doses, volume infused, frequency, diluents, etc. Most intrauterine treatments are commonly performed every day or every other day for 3-7 days. ()

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based dosage for Llamas:

For treatment of susceptible systemic fungal infections: a) A single case report. Llama received 1 mg test dose, then initially at 0.3 mg/kg IV over 4 hours, followed by 3 L of LRS with 1.5 mL of B-Complex and 20 mEq of KC1 added. Subsequent doses were increased by 10 mg and given every 48 hours until reaching 1 mg/kg q48h IV for 6 weeks. Animal tolerated therapy well, but treatment was ultimately unsuccessful (Coccidioidomycosis). ()

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based dosage for birds:

For treatment of susceptible systemic fungal infections:

a) For raptors and psittacines with aspergillosis: 1.5 mg/kg IV three times daily for 3 days with flucytosine or follow with flucytosine. May also use intratracheally at 1 mg/kg diluted in sterile water once to 3 times daily for 3 days in conjunction with flucytosine or nebulized (1 mg/mL of saline) for 15 minutes twice daily. Potentially nephrotoxic and may cause bone marrow suppression. ()

b) 1.5 mg/kg IV q12h for 3-5 days; topically in the trachea at 1 mg/kg q12h; 0.3-1 mg/mL nebulized for 15 minutes 2-4 times daily ()

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based dosage for reptiles:

For susceptible fungal respiratory infections: a) For most species: 1 mg/kg diluted in saline and given intratracheally once daily for 14-28 treatments ()

Client Information

■ Clients should be informed of the potential seriousness of toxic effects that can occur with amphotericin B therapy

■ The costs associated with therapy

Chemistry / Synonyms

A polyene macrolide antifungal agent produced by Streptomyces nodosus, amphotericin B occurs as a yellow to orange, odorless or practically odorless powder. It is insoluble in water and anhydrous alcohol. Amphotericin B is amphoteric and can form salts in acidic or basic media. These salts are more water soluble but possess less antifungal activity than the parent compound. Each mg of amphotericin B must contain not less than 750 micrograms of anhydrous drug. Amphotericin A may be found as a contaminant in concentrations not exceeding 5%. The commercially available powder for injection contains sodium desoxycholate as a solubilizing agent.

Newer lipid-based amphotericin B products are available that have less toxicity than the conventional desoxycholate form. These include amphotericin B cholesteryl sulfate complex (amphotericin B colloidal dispersion, ABCD, Amphotec), amphotericin B lipid complex (ABLC, Abelcet), and amphotericin B liposomal (ABL, L-AMB, Ambisome).

Amphotericin B may also be known as: amphotericin; amphotericin B cholesteryl sulfate complex, amphotericin B lipid complex, amphotericin B liposome, amphotericin B phospholipid complex, amphotericin B-Sodium cholesteryl sulfate complex, anfotericina B, or liposomal amphotericin B; many trade names are available.

Storage / Stability / Compatibility

Vials of amphotericin B powder for injection should be stored in the refrigerator (2-8°C), protected from light and moisture. Reconstitution of the powder must be done with sterile water for injection (no preservatives — see directions for preparation in the Dosage Form section below).

After reconstitution, if protected from light, the solution is stable for 24 hours at room temperature and for 1 week if kept refrigerated. After diluting with D5W (must have pH >4.3) for IV use, the manufacturer recommends continuing to protect the solution from light during administration. Additional studies however, have shown that potency remains largely unaffected if the solution is exposed to light for 8-24 hours.

Amphotericin B deoxycholate is reportedly compatible with the following solutions and drugs: D5W, D5W in sodium chloride 0.2%, heparin sodium, heparin sodium with hydrocortisone sodium phosphate, hydrocortisone sodium phosphate/succinate and sodium bicarbonate.

Amphotericin B deoxycholate is reportedly incompatible with the following solutions and drugs: normal saline, lactated Ringer’s, D5-normal saline, Ds-lactated Ringer’s, amino acids 4.25%-dextrose 25%, amikacin, calcium chloride/gluconate, carbenicillin disodium, chlorpromazine HCL, cimetidine HCL, diphenhydramine HCL, dopamine HCL, edetate calcium disodium (Ca EDTA), gentamicin sulfate, kanamycin sulfate, lidocaine HCL, metaraminol bitartrate, methyldopate HCL, nitrofurantoin sodium, oxytetracycline HCL, penicillin G potassium/sodium, polymyxin B sulfate, potassium chloride, prochlorperazine mesylate, streptomycin sulfate, tetracycline HCL, and verapamil HCL. Compatibility is dependent upon factors such as pH, concentration, temperature and diluent used; consult specialized references or a hospital pharmacist for more specific information.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products: None

Human-Labeled Products:

Amphotericin B Desoxycholate Powder for Injection: 50 mg in vials; Amphocin (Gensia Sicor); Fungizone Intravenous (Apothecon); generic (Pharma-Tek); (Rx)

Directions for reconstitution/administration: Using strict aseptic technique and a 20 gauge or larger needle, rapidly inject 10 mL of sterile water for injection (without a bacteriostatic agent) directly into the lyophilized cake; immediately shake well until solution is clear. A 5 mg/mL colloidal solution results. Further dilute (1:50) for administration to a concentration of 0.1 mg/mL with 5% dextrose in water (pH >4.2). An in-line filter may be used during administration, but must have a pore diameter >1 micron.

Amphotericin B Lipid-Based Suspension for Injection: 100 mg/20 mL (as lipid complex) in 10 mL & 20 mL vials with 5 micron filter needles: Abelcet (Enzon); (Rx)

Amphotericin B Lipid-Based Powder for Injection: 50 mg/vial (as cholesteryl) in 20 mL vials; 100 mg (as cholesteryl) in 50 mL vials; Amphotec (Sequus Pharmaceuticals); 50 mg (as liposomal) in single-dose vials with 5-micron filter; AmBisome (Fujisawa; (Rx)

Amphotericin B is also available in topical formulations: Fungizone (Apothecon); (Rx)

Categories
Drugs

Amiodarone HCL (Cordarone, Pacerone)

Class III Antiarrhythmic

Highlights Of Prescribing Information

Antidysrhythmic agent that can be used in dogs for arrhythmias associated with left ventricular dysfunction or to convert atrial fib into sinus rhythm; very limited experience warrants cautious use

May be useful in horses to convert atrial fib or V tach into sinus rhythm

Contraindicated in 2nd, 3rd degree heart block, bradyarrhythmias

In DOGS: GI disturbances (vomiting, anorexia) most likely adverse effect, but neutropenia, thrombocytopenia, bradycardia, hepatotoxicity, positive Coombs’ test reported

In HORSES: Limited use, accurate adverse effect profile to be determined; Hind limb weakness, increased bilirubin reported when used IV to convert atrial fib

Many drug interactions

What Is Amiodarone HCL Used For?

Because of its potential toxicity and lack of experience with use in canine and equine patients, amiodarone is usually used when other less toxic or commonly used drugs are ineffective. It may be useful in dogs and horses to convert atrial fib into sinus rhythm and in dogs for arrhythmias associated with left ventricular dysfunction. In horses, one horse with Ventricular tachycardia was converted into sinus rhythm using amiodarone.

As the risk of sudden death is high in Doberman pinschers exhibiting rapid, wide-complex ventricular tachycardia or syncope with recurrent VPC’s, amiodarone maybe useful when other drug therapies are ineffective.

Pharmacology/Actions

Amiodarone’s mechanism of action is not fully understood; it apparently is a potassium channel blocker that possesses unique pharmacology from other antiarrhythmic agents. It can be best classified a Class III antiarrhythmic agent that also blocks sodium and calcium channels, and beta-adrenergic receptors. Major properties include prolongation of myocardial cell action-potential duration and refractory period.

Pharmacokinetics

Amiodarone may be administered parenterally or orally. Amiodarone is widely distributed throughout the body and can accumulate in adipose tissue. Amiodarone is metabolized by the liver into the active metabolite desethylamiodarone. After oral administration of a single dose in normal dogs, amiodarone’s plasma half-life averaged 7.5 hours, but repeated dosing increased its half-life from 11 hours to 3.2 days.

In horses, amiodarone has a low oral bioavailability (range from 6-34%) and peak levels of amiodarone and desethylamiodarone occur about 7-8 hours after an oral dose. After IV administration amiodarone is rapidly distributed with a high apparent volume of distribution of 31 L/kg. In horses, amiodarone is relatively highly bound to plasma proteins (96%). Clearance was 0.35 L/kg/hr and median elimination half-lives for amiodarone and desethylamiodarone were approximately 51 and 75 hours, respectively ().

In humans, oral absorption is slow and variable, with bioavailabilities ranging from 22-86%. Elimination half-lives for amiodarone and desethylamiodarone range from 2.5-10 days after a single dose, but with chronic dosing, average 53 days and 60 days, respectively.

Before you take Amiodarone HCL

Contraindications / Precautions / Warnings

Amiodarone is considered contraindicated in patients (humans) hypersensitive to it, having severe sinus-node dysfunction with severe sinus bradycardia, 2nd or 3rd degree heart block, or bradycardial syncope.

Clinical experience in veterinary patients is limited. Consider use only when other less toxic and more commonly used drugs are ineffective.

Adverse Effects

Gastrointestinal effects (e.g., anorexia, vomiting) are apparently the most likely adverse effects seen in the limited number of canine patients treated. Hepatopathy (bilirubinemia, increased hepatic enzymes) has been reported in dogs on amiodarone. Because hepatic effects can occur before clinical signs are noted, routine serial evaluation of liver enzymes and bilirubin is recommended. Other adverse effects reported in dogs include bradycardia, neutropenia, thrombocytopenia, or positive Coombs’ test. During IV infusion, pain at injection site, and facial pruritus and hyperemia have been noted. Corneal deposits may be seen in dogs treated with amiodarone, but this affect apparently occurs less frequently in dogs than in humans.

In human patients, adverse effects are very common while on amiodarone therapy. Those that most commonly cause discontinuation of the drug include: pulmonary infiltrates or pulmonary fi-brosis (sometimes fatal), liver enzyme elevations, congestive heart failure, paroxysmal ventricular tachycardia, and thyroid dysfunction (hypo- or hyperthyroidism). An odd effect seen in some individuals is a bluish cast to their skin. Reversible corneal deposits are seen in a majority of humans treated with amiodarone.

Clinical experience in dogs is limited; the adverse effect profile of this drug in people warrants its use in veterinary patients only when other less toxic agents are ineffective and treatment is deemed necessary.

Reproductive / Nursing Safety

In laboratory animals, amiodarone has been embryotoxic at high doses and congenital thyroid abnormalities have been detected in offspring. Use during pregnancy only when the potential benefits outweigh the risks of the drug. In humans, the FDA categorizes this drug as category D for use during pregnancy (There is evidence of human fetal risk, hut the potential benefits from the use of the drug in pregnant women may he acceptable despite its potential risks.)

Overdosage / Acute Toxicity

Clinical overdosage experience is limited; most likely adverse effects seen are hypotension, bradycardia, cardiogenic shock, AV block, and hepatotoxicity. Treatment is supportive. Bradycardia may be managed with a pacemaker or beta-1 agonists (e.g., isoproterenol); hypotension managed with positive inotropic agents or vasopressors. Neither amiodarone nor its active metabolite are dialyzable.

How to use Amiodarone HCL

Note: Some human references state that because of the potential for drug interactions with previous drug therapies, the life-threatening nature of the arrhythmias being treated, and the unpredictability of response from amiodarone, the drug should be initially given (loaded) over several days in an inpatient setting where adequate monitoring can occur.

Amiodarone HCL dosage for dogs:

For conversion of atrial fibrillation:

a) At the time of writing (2007) one case report () and one retrospective evaluation () have been published using amiodarone to convert atrial fibrillation in dogs. Dosage recommendations are yet to be fully defined; monitor the current literature for further recommendations.

For recurrent ventricular tachycardia not controlled with other less toxic drugs:

a) 10-25 mg/kg PO twice daily for 7 days, followed by 5-7.5 mg/kg PO twice daily for 14 days, followed by 7.5 mg/kg PO once daily ()

b) For ventricular arrhythmias secondary to occult cardiomyopathy in Doberman pinschers: 10 mg/kg PO twice daily for one week and then 8 mg/kg PO once daily. For severe V-Tach, mexiletine is added at 5-8 mg/kg three times daily for one week. Once efficacy confirmed, patient weaned off mexiletine. ()

c) Amiodarone as above in “b”, but after 6 months may be reduced to 5 mg/kg once daily. ()

d) 10-20 mg/kg PO q12h ()

Amiodarone HCL dosage for horses:

For conversion of atrial fibrillation or ventricular tachycardia: a) 5 mg/kg/hr for one hour, followed by 0.83 mg/kg/hr for 23 hours and then 1.9 mg/kg/hour for the following 30 hours. In the study (A fib), infusion was discontinued when conversion occurred or when any side effects were noted. 4 of 6 horses converted from A fib; one horse from V tach. In order to increase success rate and decrease adverse effects, regimen should be further adapted based upon PK/PD studies in horses. ()

Monitoring

■ Efficacy (ECG)

■ Toxicity (GI effects; CBC, serial liver enzymes; thyroid function tests; blood pressure; pulmonary radiographs if clinical signs such as dyspnea/cough occur)

Client Information

■ Because of the “experimental” nature (relatively few canine/equine patients have received this agent) and the toxicity dangers associated with its use, clients should give informed consent before the drug is prescribed.

Chemistry / Synonyms

An iodinated benzofuran, amiodarone is unique structurally and pharmacologically from other antiarrhythmic agents. It occurs as a white to cream colored lipophilic powder having a pKa of approximately 6.6. Amiodarone 200 mg tablets each contain approximately 75 mg of iodine.

Amiodarone HCL may also be known as: amiodaroni hydrochloridum, L-3428, 51087N, or SKF-33134-A; many trade names are available.

Storage / Stability/Compatibility

Tablets should be stored in tight containers, at room temperature and protected from light. A 3-year expiration date is assigned from the date of manufacture.

Injection should be stored at room temperature and protected from light or excessive heat. While administering, light protection is not necessary. Use D5W as the IV diluent. Amiodarone is reportedly compatible with dobutamine, lidocaine, potassium chloride, procainamide, propafenone, and verapamil. Variable compatibility is reported with furosemide and quinidine gluconate.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products: None

The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information.

Human-Labeled Products:

Amiodarone Oral Tablets: 100 mg, 200 mg & 400 mg; Cordarone (Wyeth-Ayerst); Pacerone (Upsher Smith); generic; (Rx)

Amiodarone Concentrate for Injection (for IV Infusion): 50 mg/mL in 3 mL amps & vials; Cordarone (Wyeth-Ayerst); generic; (Rx)

Categories
Drugs

Aminophylline Theophylline

Phosphodiesterase Inhibitor Bronchodilator

Highlights Of Prescribing Information

Bronchodilator drug with diuretic activity; used for bronchospasm & cardiogenic pulmonary edema

Narrow therapeutic index in humans, but dogs appear to be less susceptible to toxic effects at higher plasma levels

Therapeutic drug monitoring recommended

Many drug interactions

What Is Aminophylline Theophylline Used For?

The theophyllines are used primarily for their broncho dilatory effects, often in patients with myocardial failure and/or pulmonary edema. While they are still routinely used, the methylxanthines must be used cautiously due to their adverse effects and toxicity.

Pharmacology/Actions

The theophyllines competitively inhibit phosphodiesterase thereby increasing amounts of cyclic AMP which then increase the release of endogenous epinephrine. The elevated levels of cAMP may also inhibit the release of histamine and slow reacting substance of anaphylaxis (SRS-A). The myocardial and neuromuscular transmission effects that the theophyllines possess maybe a result of translocating intracellular ionized calcium.

The theophyllines directly relax smooth muscles in the bronchi and pulmonary vasculature, induce diuresis, increase gastric acid secretion and inhibit uterine contractions. They have weak chronotropic and inotropic action, stimulate the CNS and can cause respiratory stimulation (centrally-mediated).

Pharmacokinetics

The pharmacokinetics of theophylline have been studied in several domestic species. After oral administration, the rate of absorption of the theophyllines is limited primarily by the dissolution of the dosage form in the gut. In studies in cats, dogs, and horses, bioavail-abilities after oral administration are nearly 100% when non-sustained release products are used. One study in dogs that compared various sustained-release products (), found bioavailabilities ranging from approximately 30-76% depending on the product used.

Theophylline is distributed throughout the extracellular fluids and body tissues. It crosses the placenta and is distributed into milk (70% of serum levels). In dogs, at therapeutic serum levels only about 7-14% is bound to plasma proteins. The volume of distribution of theophylline for dogs has been reported to be 0.82 L/kg. The volume of distribution in cats is reported to be 0.46 L/kg, and in horses, 0.85-1.02 L/kg. Because of the low volumes of distribution and theophylline’s low lipid solubility, obese patients should be dosed on a lean body weight basis.

Theophylline is metabolized primarily in the liver (in humans) to 3-methylxanthine which has weakbronchodilitory activity. Renal clearance contributes only about 10% to the overall plasma clearance of theophylline. The reported elimination half-lives (mean values) in various species are: dogs = 5.7 hours; cats = 7.8 hours, pigs = 11 hours; and horses = 11.9 to 17 hours. In humans, there are very wide interpatient variations in serum half-lives and resultant serum levels. It could be expected that similar variability exists in veterinary patients, particularly those with concurrent illnesses.

Before you take Aminophylline Theophylline

Contraindications / Precautions / Warnings

The theophyllines are contraindicated in patients who are hypersensitive to any of the xanthines, including theobromine or caffeine. Patients who are hypersensitive to ethylenediamine should not take aminophylline.

The theophyllines should be administered with caution in patients with severe cardiac disease, seizure disorders, gastric ulcers, hyperthyroidism, renal or hepatic disease, severe hypoxia, or severe hypertension. Because it may cause or worsen preexisting arrhythmias, patients with cardiac arrhythmias should receive theophylline only with caution and enhanced monitoring. Neonatal and geriatric patients may have decreased clearances of theophylline and be more sensitive to its toxic effects. Patients with CHF may have prolonged serum half-lives of theophylline.

Adverse Effects

The theophyllines can produce CNS stimulation and gastrointestinal irritation after administration by any route. Most adverse effects are related to the serum level of the drug and may be symptomatic of toxic blood levels; dogs appear to tolerate levels that may be very toxic to humans. Some mild CNS excitement and GI disturbances are not uncommon when starting therapy and generally resolve with chronic administration in conjunction with monitoring and dosage adjustments.

Dogs and cats can exhibit clinical signs of nausea and vomiting, insomnia, increased gastric acid secretion, diarrhea, polyphagia, polydipsia, and polyuria. Side effects in horses are generally dose related and may include: nervousness, excitability (auditory, tactile, and visual), tremors, diaphoresis, tachycardia, and ataxia. Seizures or cardiac dysrhythmias may occur in severe intoxications.

Reproductive / Nursing Safety

In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, hut there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans.)

Overdosage / Acute Toxicity

Clinical signs of toxicity (see above) are usually associated with levels greater than 20 mcg/mL in humans and become more severe as the serum level exceeds that value. Tachycardias, arrhythmias, and CNS effects (seizures, hyperthermia) are considered the most life-threatening aspects of toxicity. Dogs appear to tolerate serum levels higher than 20 mcg/mL.

Treatment of theophylline toxicity is supportive. After an oral ingestion, the gut should be emptied, charcoal and a cathartic administered using the standardized methods and cautions associated with these practices. Patients suffering from seizures should have an adequate airway maintained and treated with IV diazepam. The patient should be constantly monitored for cardiac arrhythmias and tachycardia. Fluid and electrolytes should be monitored and corrected as necessary. Hyperthermia may be treated with phenothiazines and tachycardia treated with propranolol if either condition is considered life threatening.

How to use Aminophylline Theophylline

Note: Theophyllines have a low therapeutic index; determine dosage carefully. Because of aminophylline/theophylline’s pharmacokinet-ic characteristics, it should be dosed on a lean body weight basis in obese patients. Dosage conversions between aminophylline and theophylline can be easily performed using the information found in the Chemistry section below. Aminophylline causes intense local pain when administered IM and is rarely used or recommended via this route.

Aminophylline Theophylline dosage for dogs:

a) Using Theochron Extended-Release Tablets or Theo-Cap Extended-Release Capsules: Give 10 mg/kg PO every 12 hours initially, if no adverse effects are observed and the desired clinical effect is not achieved, give 15 mg/kg PO q12h while monitoring for adverse effects. ()

b) For adjunctive medical therapy for mild clinical signs associated with tracheal collapse (<50% collapse): aminophylline: 11 mg/kg PO, IM or IV three times daily. ()

c) For adjunctive therapy of severe, acute pulmonary edema and bronchoconstriction: Aminophylline 4-8 mg/kg IV or IM, or 6-10 mg/kg PO every 8 hours. Long-term use is not recommended. ()

d) For cough: Aminophylline: 10 mg/kg PO, IV three times daily ()

e) As a broncho dilator tor collapsing trachea: 11 mg/kg PO or IV q6- 12h ()

Aminophylline Theophylline dosage for cats:

a) Using Theo-Dur 20 mg/kg PO once daily in the PM; using Slo-Bid 25 mg/kg PO once daily in the PM (Johnson 2000) [Note: The products Theo-Dur and Slo-Bid mentioned in this reference are no longer available in the USA. Although hard data is not presently available to support their use in cats, a reasonable alternative would be to cautiously use the dog dose and products mentioned above in the reference by Bach et al — Plumb]

b) Using aminophylline tablets: 6.6. mg/kg PO twice daily; using sustained release tablets (Theo-Dur): 25-50 mg (total dose) per cat PO in the evening ()

c) For adjunctive medical therapy for mild clinical signs associated with tracheal collapse (<50% collapse): aminophylline: 5 mg/kg PO, two times daily. ()

d) For adjunctive therapy for bronchoconstriction associated with fulminant CHF: Aminophylline 4-8 mg/kg SC, IM, IV q8-12h. ()

e) For cough: Aminophylline: 5 mg/kg PO twice daily ()

Aminophylline Theophylline dosage for ferrets:

a) 4.25 mg/kg PO 2-3 times a day ()

Aminophylline Theophylline dosage for horses:

(Note: ARCI UCGFS Class 3 Aminophylline Theophylline)

NOTE: Intravenous aminophylline should be diluted in at least 100 mL of D5W or normal saline and administered slowly (not >25 mg/min). For adjunctive treatment of pulmonary edema:

a) Aminophylline 2-7 mg/kg IV q6- 12h; Theophylline 5-15 mg/kg PO q12h ()

b) 11 mg/kg PO or IV q8-12h. To “load” may either double the initial dose or give both the oral and IV dose at the same time. IV infusion should be in approximately 1 liter of IV fluids and given over 20-60 minutes. Recommend monitoring serum levels. ()

For adjunctive treatment for heaves (RAO):

a) Aminophylline: 5-10 mg/kg PO or IV twice daily. ()

b) Aminophylline: 4-6 mg/kg PO three times a day. ()

Monitoring

■ Therapeutic efficacy and clinical signs of toxicity

■ Serum levels at steady state. The therapeutic serum levels of theophylline in humans are generally described to be between 10-20 micrograms/mL. In small animals, one recommendation for monitoring serum levels is to measure trough concentration; level should be at least above 8-10 mcg/mL (Note: Some recommend not exceeding 15 micrograms/mL in horses).

Client Information

■ Give dosage as prescribed by veterinarian to maximize the drug’s benefit

Chemistry / Synonyms

Xanthine derivatives, aminophylline and theophylline are considered to be respiratory smooth muscle relaxants but, they also have other pharmacologic actions. Aminophylline differs from theophylline only by the addition of ethylenediamine to its structure and may have different amounts of molecules of water of hydration. 100 mg of aminophylline (hydrous) contains approximately 79 mg of theophylline (anhydrous); 100 mg of aminophylline (anhydrous) contains approximately 86 mg theophylline (anhydrous). Conversely, 100 mg of theophylline (anhydrous) is equivalent to 116 mg of aminophylline (anhydrous) and 127 mg aminophylline (hydrous).

Aminophylline occurs as bitter-tasting, white or slightly yellow granules or powder with a slight ammoniacal odor and a pKa of 5. Aminophylline is soluble in water and insoluble in alcohol.

Theophylline occurs as bitter-tasting, odorless, white, crystalline powder with a melting point between 270-274°C. It is sparingly soluble in alcohol and only slightly soluble in water at a pH of 7, but solubility increases with increasing pH.

Aminophylline may also be known as: aminofilina, aminophyllinum, euphyllinum, metaphyllin, theophyllaminum, theophylline and ethylenediamine, theophylline ethylenediamine compound, or theophyllinum ethylenediaminum; many trade names are available.

Theophylline may also be known as: anhydrous theophylline, teofillina, or theophyllinum; many trade names are available.

Storage / Stability/Compatibility

Unless otherwise specified by the manufacturer, store aminophylline and theophylline oral products in tight, light-resistant containers at room temperature. Do not crush or split sustained-release oral products unless label states it is permissible.

Aminophylline for injection should be stored in single-use containers in which carbon dioxide has been removed. It should also be stored at temperatures below 30°C and protected from freezing and light. Upon exposure to air (carbon dioxide), aminophylline will absorb carbon dioxide, lose ethylenediamine and liberate free theophylline that can precipitate out of solution. Do not inject aminophylline solutions that contain either a precipitate or visible crystals.

Aminophylline for injection is reportedly compatible when mixed with all commonly used IV solutions, but may be incompatible with 10% fructose or invert sugar solutions.

Aminophylline is reportedly compatible when mixed with the following drugs: amobarbital sodium, bretylium tosylate, calcium gluconate, chloramphenicol sodium succinate, dexamethasone sodium phosphate, dopamine HCL, erythromycin lactobionate, heparin sodium, hydro cortisone sodium succinate, lidocaine HCL, mephentermine sulfate, methicillin sodium, methyldopate HCL, metronidazole with sodium bicarbonate, pentobarbital sodium, phenobarbital sodium, potassium chloride, secobarbital sodium, sodium bicarbonate, sodium iodide, terbutaline sulfate, thiopental sodium, and verapamil HCL

Aminophylline is reportedly incompatible (or data conflicts) with the following drugs: amikacin sulfate, ascorbic acid injection, bleomycin sulfate, cephalothin sodium, cephapirin sodium, clindamycin phosphate, codeine phosphate, corticotropin, dimenhydrinate, dobutamine HCL, doxorubicin HCL, epinephrine HCL, erythromycin gluceptate, hydralazine HCL, hydroxyzine HCL, insulin (regular), isoproterenol HCL, levorphanol bitartrate, meperidine HCL, methadone HCL, methylprednisolone sodium succinate, morphine sulfate, nafcillin sodium, norepinephrine bitartrate, oxytetracycline, penicillin G potassium, pentazocine lactate, procaine HCL, prochlorperazine edisylate or mesylate, promazine HCL, promethazine HCL, sulfisoxazole diolamine, tetracycline HCL, vancomycin HCL, and vitamin B complex with C. Compatibility is dependent upon factors such as pH, concentration, temperature, and diluent used and it is suggested to consult specialized references for more specific information.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products: None

The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information.

Human-Labeled Products:

The listing below is a sampling of products and sizes available; consult specialized references for a more complete listing.

Aminophylline Tablets: 100 mg (79 mg theophylline) & 200 mg (158 mg theophylline); generic; (Rx)

Aminophylline Injection: 250 mg (equiv. to 197 mg theophylline) mL in 10 mL & 20 mL vials, amps and syringes; generic; (Rx)

Theophylline Time Released Capsules and Tablets: 100 mg, 125 mg 200 mg, 300 mg, 400 mg, 450 mg, & 600 mg. (Note: Different products have different claimed release rates which may or may not correspond to actual times in veterinary patients; Theophylline Extended-Release (Dey); Theo-24 (UCB Pharma); Theophylline SR (various); Theochron (Forest, various); Theophylline (Able); Theocron (Inwood); Uniphyl (Purdue Frederick); generic; (Rx)

Theophylline Tablets and Capsules: 100 mg, 200 mg, & 300 mg; Bronkodyl (Winthrop); Elixophyllin (Forest); generic; (Rx)

Theophylline Elixir: 80 mg/15 mL (26.7 mg/5 mL) in pt, gal, UD 15 and 30 mL, Asmalix (Century); Elixophyllin (Forest); Lanophyllin (Lannett); generic; (Rx)

Theophylline & Dextrose Injection: 200 mg/container in 50 mL (4 mg/mL) & 100 mL (2 mg/mL); 400 mg/container in 100 mL (4 mg/ mL), 250 mL (1.6 mg/mL), 500 mL (0.8 mg/mL) & 1000 mL (0.4 mg/mL); 800 mg/container in 250 mL (3.2 mg/mL), 500 mL (1.6 mg/mL) & 1000 mL (0.8 mg/mL); Theophylline & 5% Dextrose (Abbott & Baxter); (Rx)

Categories
Diseases

Arrhythmocenic Right Ventricular Cardiomyopathy

ARVC is a recendy reported and rare form of feline cardiomyopathy. It has been identified in humans, dogs (boxer dogs), and cats. It is characterized by fibrofatty or fatty infiltration of primarily the right ventricular free wall. The right ventricular wall is commonly thinned in humans and cats with the disease. Ventricular tachyarrhythmias are common in all three species, and sudden death is a common feature of the disease in humans and boxer dogs. The disease is also commonly known as arrhythmogenic right ventricular dysplasia (ARVD).

Cause of Arrhythmocenic Right Ventricular Cardiomyopathy

The cause of arrhythmogenic right ventricular cardiomyopathy is unknown in cats. In humans at least six forms of the disease (ARVD 1 to 6) are inherited as an auto-somal dominant trait, and one (Naxos syndrome) is inherited as an autosomal recessive trait.Iu The cause of ARVD 2 has been recently identified as several mutations in the gene that encodes for the calcium release channel (also known as the ryanodine receptor) on the myocardial sarcoplasmic reticulum. Ryanodine receptor dysfunction has been identified in boxer dogs with ARVC.

Pathophysiology of Arrhythmocenic Right Ventricular Cardiomyopathy

In cats, arrhythmogenic right ventricular cardiomyopathy most commonly (8 of 12 cats in the one study reported to date) produces right heart failure, presumably through the destruction of right ventricular myocardium resulting in right ventricular systolic and, possibly, diastolic dysfunction along with secondary tricuspid regurgitation. The changes in the right ventricular free wall also commonly produce ventricular tachyarrhythmias (9 of 12 cats) and supraven-tricular tachyarrhythmias (5 of 12 cats). Tumor necrosis factor (TNF) is commonly increased in cats with right heart failure, which may contribute to the systemic effects of the disease.

Pathology of Arrhythmocenic Right Ventricular Cardiomyopathy

The right ventricular and atrial chambers are markedly enlarged in cats that die of the disease.IH Thinning of the right ventricular free wall is a consistent feature of the disease and may be focal or diffuse. Aneurysms of the wall may occur, especially at the apex of the right ventricle (RV). The wall is often so thin that light can be seen through it. Histopathologically either fibre-fatty or fatty replacement of myocardium exists. Inflammatory cells are commonly present, especially in regions of fibrofatty replacement. Although most prominent in the right ventricular free wall, these changes are also commonly present in the left ventricular and occasionally identified in the left atrium. Apoptosis is common.

Clinical Manifestations

Evidence of right heart failure, including ascites, pleural and pericardia! effusions, and jugular vein distension, is common. The pleural effusion may be severe enough to cause tachypnea and dyspnea. A heart murmur secondary to tricuspid regurgi-tation is common. Arrhythmias are also commonly heard on auscultation, and ECG evidence of a ventricular arrhythmia may be one clue that one is dealing with arrhythmogenic right ventricular cardiomyopathy and not tricuspid valve dysplasia. Supraventricular tachyarrhythmias, including atrial fibrillation, may also occur. In the severe stage, echocardiography reveals marked enlargement of the right ventricular and right atrial chambers. The right ventricular chamber enlargement may be segmental. Tricuspid regurgitation is usually present on color flow Doppler. Careful echocardiographic interrogation may reveal localized regions of right ventricular wall thinning or regions of aneurysmal dilation. The right ventricular trabeculae may appear abnormal, especially at the apex. The disease may not be confined to the right heart, which means the left atrial and ventricular chambers may also be enlarged. Syncope due to ventricular tachycardia may be present.

Differential Diagnosis

Cats with severe arrhythmogenic right ventricular cardiomyopathy are commonly misdiagnosed as having tricuspid valve dysplasia because tricuspid regurgitation is a common sequel to the disease. Cats from 1 to 20 years of age have been diagnosed with the disease.

Therapy of Arrhythmocenic Right Ventricular Cardiomyopathy

Right heart failure is treated with furosemide and an angiotensin-converting enzyme inhibitor. Digoxin combined with either diltiazem or atenolol may be used to control supraventricular tachycardia or the ventricular rate in cats with atrial fibrillation. Malignant ventricular tachycardia or ventricular tachycardia that causes clinical signs (eg., syncope) can be managed acutely with lidocaine (5 to 20 µg/lb/min) and chronically with sotalol (1 to 2 mg/lb every 12 hours orally).

Categories
Horses

Bronchoalveolar Lavage

Today the use of fiberoptic bronchoscopy is a common and standard diagnostic procedure, which allows direct observation of the upper and lower conducting airways. During passage of the endoscope through the nasopharynx, trachea, and large bronchi, the quantity of mucous secretions can be assessed readily in addition to the degree of mucosal edema and bronchospasm. In addition to examination of the airway lumen, one of the greatest advantages and rewards from bronchoscopy is the ability to sample the large and small airways and the alveoli. The specimens collected are then analyzed for their cellular and noncellular constituents.

In recent years, bronchoalveolar lavage (bronchoalveolar lavage) using either an endoscope or specialized tubing has gained some popularity over more traditional sampling methods such as tracheal aspiration for most cases in which a diffuse inflammatory disorder is suspected. For many years, it has been assumed that sampling the lower trachea provides a representative impression of the alveoli and small airways because airway free cells from the peripheral lung eventually were swept toward the trachea for clearance.

However, a large clinical case survey of young athletic horses presented with poor performance attributable to the lower respiratory system has shown that the cytologic and bacteriologic results are correlated poorly between samples obtained from the tracheal aspirate versus those from bronchoalveolar lavage. The study demonstrated that tracheal aspirate and bronchoalveolar lavage cytologic cell differential counts differed greatly within the same horse, which suggests that samples from the tracheal puddle may not reflect accurately the population of cells and secretions present within the small airways and alveoli. This is relevant insofar as exercise intolerance, airway injury resulting from inflammation, and airway hyperreactivity are associated with disease in the small airways, reflected best by bronchoalveolar lavage cytology. In addition, a higher rate of positive bacterial cultures was obtained from tracheal aspirate samples versus bronchoalveolar lavage samples performed on the same occasion. Thus the lower trachea apparently harbors a normal bacterial flora that may not be present within the small airways and alveoli. For these reasons, bronchoalveolar lavage is becoming a more popular tool to assess distal (small) airway inflammation rather than the tracheal aspirate method of sampling.

To validate the relevance of bronchoalveolar lavage differential cell counts as a complementary diagnostic tool in the assessment of the respiratory system, other quantitative measurements are necessary beyond the routine clinical examination. In the last two decades, the syndrome of heaves has been studied extensively, and several research laboratories throughout the world have clearly demonstrated a high correlation between the bronchoalveolar lavage cell differential and results of pulmonary function testing and histamine bronchoprovocation in heaves-affected horses. In recent years, similarly characterized lung function in young athletic horses with noninfectious inflammatory airway disease (IAD) has paralleled these findings with respect to the diagnostic usefulness of bronchoalveolar lavage.

The purpose of this chapter is to discuss the use of the bronchoalveolar lavage technique as a tool to identify and characterize pulmonary inflammation in horses that suffer from diffuse lung pathology such as inflammatory airway disease in the young athletic horse and the heaves syndrome in mature horses. In addition viral and bacterial pulmonary conditions are discussed briefly with respect to their diagnosis by bronchoalveolar lavage.

Indications For Bronchoalveolar Lavage

Bronchoalveolar Lavage Procedure

bronchoalveolar lavage can be performed on most conscious horses with mild sedation (xylazine 0.3-0.5 mg/kg IV or romifidine 0.03-0.05 mg/kg IV) and airway desensitization by a local anesthetic (lidocaine solution 0.4% w/v, without epinephrine). The procedure can be conducted using either a bronchoscope 1.8 to 2 m in length or a specialized bronchoalveolar lavage tube (Bivona Medical Technologies, Gary, Ind.). Once the bronchoscope or bronchoalveolar lavage tube is in the trachea, reaching the tracheal bifurcation (carina) usually induces coughing. Infusing 60 to 100 ml of prewarmed lidocaine solution (0.4%, without epinephrine) is therefore beneficial at this point to desensitize cough receptors located at the carina. After this infusion step the endoscope or bronchoalveolar lavage tube is gently but securely wedged, as detected by resistance to further advancement. Prewarmed sterile saline (200-300 ml) is infused rapidly into the lung and is subsequently aspirated.

The total amount of saline should be divided into two separate boluses for infusion, with attempts to retrieve as much fluid as possible between each bolus. In general, retrieval of 40% to 60% of the total amount of infusate indicates a satisfactory bronchoalveolar lavage. In horses with advanced disease, lower volumes are recovered and a tendency exists for less foam (surfactant) to be present. The bronchoalveolar lavage fluid samples are then pooled and kept on ice if processing is not possible within 1 hour after collection. Gross examination of the fluid should be performed to detect any flocculent debris or discoloration. One or two serum or ethylenediaminetetraacetic acid (EDTA) tubes of bronchoalveolar lavage fluid are centrifuged (1500 X g for 10 min) and air-dried smears are made from the sample pellet after removal of the supernatant. In preparation of the smears, the slides must be air dried rapidly using a small bench-top fan to preserve good cellular morphology. Smears thus prepared can be kept at room temperature for up to 8 to 10 months with little cellular alterations. The air-dried smears can be stained with Diff-Quik, Wright-Giemsa, May Gruenwald, Leishman’s, or Gram’s stain for cellular and noncellular constituent interpretation. The cellular profile and morphology may serve as a guide to the nature of airway injury, inflammation, and the pulmonary immunologic response to infections or foreign antigens.

Differential Cell Counts And Their Interpretation

Conclusion

bronchoalveolar lavage is undoubtedly becoming a powerful ancillary diagnostic tool to assist in the diagnosis of clinical and sub-clinical lower airway respiratory conditions such as non-infectious inflammatory airway disease in the young athletic horse and recurrent airway obstruction, or heaves, in older horses. Using recognized, standardized procedures, the bronchoalveolar lavage differential cell count is fairly consistent for normal horses and any alteration in the cytologic profiles from normal values identifies a wide range of nonseptic inflammatory processes. Although at present, clinicians are recommending specific treatment according to cytologic findings of the bronchoalveolar lavage cell differential, a more in-depth knowledge of the various disorders in the future may allow equine practitioners to provide more accurate prognostic information to members of the horse industry with respect to respiratory diseases in athletic horses. More so, the majority of young and mature athletic horses with an excess amount of white mucopus within the airways and markedly elevated neutrophil percentage on the cell differential do not represent a septic process. Rather, these cases demonstrate nonseptic inflammatory airway disease.

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Horses

Permanent Tracheostomy in Standing Horses

Diseases of the upper airway such as laryngeal hemiplegia, arytenoid chondritis, subepiglottic cysts, aryepiglottic fold entrapment, and dorsal displacement of the soft palate are commonly encountered in horses. In all of these conditions some abnormality of the upper airway compromises the cross-sectional area of the airway and causes decreased airflow; the condition usually becomes clinically significant only at exercise. In the majority of these cases, surgical correction specifically addresses the area of compromise and corrects the abnormality.

Certain conditions exist, however, in which the lesion causes such severe stenosis of the upper airway that surgical correction of the lesion is met with a guarded or poor long-term prognosis. In this author’s experience and based on literature review, the most common conditions in which less invasive procedures have failed are related to the problem of nasopharyngeal cicatrix. In this syndrome, a circular web of tissue forms in the pharynx, first ventrally over the floor of the pharynx and then dorsally, in which position it extends above the pharyngeal openings of the guttural pouches. Arytenoid chondritis is commonly associated with this generalized inflammatory process. Resection of the diseased cartilage does not seem to be curative because the generalized inflammatory process continues with the subsequent pharyngeal/laryngeal swelling that leads to obstruction of the airway. In these cases, permanent tracheostomy can provide an effective alternative approach by bypassing the obstruction. Other indications for a permanent tracheostomy are neoplasia of the upper airway and severe deformity of the nasal passages.

Surgical Technique

Although permanent tracheostomy can be performed with the horse under general anesthesia, the technique described here can be readily performed in the standing horse. This provides some advantages because the surgical structures are in a more normal anatomic orientation and create less tension on the tracheostomy closure during the healing period. This position also avoids complications associated with general anesthesia and recovery and reduces the expense of the procedure.

Perioperative antibiotics (procaine penicillin G, 20,000 IU/kg q12h, IM) and antiinflammatories (flunixin meglumine, 1.1 mg/kg IV) should be administered. The horse is restrained in the stocks and cross-tied so that it is positioned forward in the stocks with its head extended in front of the side poles of the stocks. With this restraint, the surgeon has easy access to the surgical area. Maintenance of this position is easier if the horse’s head is suspended from a bar that extends from the top of the stocks over the head. The head is suspended by means of the halter that is placed upside down so that the throat-latch strap is over the horse’s forehead (between the eyes and ears) and not under the throat adjacent to the surgical site. Padding should be placed between the halter and the mandible to prevent facial nerve paralysis. Placement of the horse’s head in a stand similar to a crutch may also help in maintaining the head and neck in an extended position. Sedation and analgesia is provided by administration of detomidine (0.02 mg/kg, half administered IV and half IM) and butorphanol (0.011 to 0.022 mg/kg IV).

The incision is positioned over the second to sixth tracheal rings. Local anesthesia is infiltrated subcutaneously in an inverted U pattern dorsal and lateral to the second through sixth tracheal rings. Starting approximately 3 cm distal to the cricoid cartilage and centered over midline, the surgeon removes a 3-cm wide x 6-cm long rectangular section of skin. The surgeon then continues the incision on midline, separating the paired sternothyrohyoideus muscles to expose the tracheal rings. Dissection is performed laterally around the abaxial borders of the paired sternothyrohyoideus muscle. The muscle bellies are isolated and clamped (Ferguson Angiotribe Forceps; Miltex, Lake Success, N.Y.) at their proximal and distal exposure in the incision. After clamping for several minutes to crush the vessels, the muscle bellies are transected. This author also recommends removal of a section of the omohyoid muscle in a similar fashion. The fascia covering the tracheal rings is carefully removed. A ventral midline incision and two paramedian incisions, approximately 15 mm on either side of the midline incision, are made through the tracheal ring cartilage without penetrating the tracheal mucosa. The tracheal cartilage segments are carefully dissected free from the tracheal submucosa, leaving the submucosa and mucosa intact. Although this may appear very difficult, the mucosa is thick and separates easily from the rings with patient dissection.

Most commonly a total of five tracheal rings (two through six) are removed although removal of four rings is often adequate. To alleviate dead space, subcutaneous tissue is sutured to the tracheal fascia with 0-polydioxane (PDS; Ethicon Inc, Somerville, NJ.) with use of a simple interrupted pattern. In some horses this author inserts a 23-gauge, 2.5-cm needle into the lumen of the trachea and injects 30 ml of 25% lidocaine HCl proximal to the incision to desensitize the tracheal mucosa. The tracheal mucosa is incised in what has been described as a double Y pattern. In this pattern, a central midline incision is made that ends approximately one tracheal ring width before the rostral and caudal ends of exposed tracheal mucosa. The midline incision is extended as a V with each leg connecting to the corners of one end of the exposed rectangular section of tracheal mucosa. In this way, a double Y pattern is formed. The surgeon sutures the tracheal mucosa and submucosa to the skin with simple interrupted sutures of 0-polydioxone, starting at the ends and then suturing along the lateral borders.

Permanent Tracheostomy in Standing Horses: Aftercare

Because the proximal trachea is not a sterile environment, antibiotics should be administered for 5 to 7 days postoperatively. Nonsteroidal antiinflammatory drugs should be continued for 5 to 7 days depending on the amount of postoperative swelling. The stoma should be cleaned once or twice daily until the sutures are removed 10 to 14 days after surgery. The stoma needs to be cleaned daily for the first month after surgery, but usually by 1 to 2 months postoperatively the discharge will decrease and make daily cleaning unnecessary. In the majority of this author’s long-term postoperative cases, cleaning has been necessary only once or twice a week.

In this author’s experience, postoperative swelling with or without partial dehiscence is the most commonly encountered complication. Incisions that develop partial dehiscence can heal satisfactorily by second intention. In some cases the areas of partial dehiscence have had to be surgically repaired, a method that usually involves removing more of the adjacent muscle and resuturing the mucosa and submucosa to the skin. In a small percentage of cases that had insufficient stoma size repairs were made by removing sections of the omohyoid muscle. Because of this experience, this author now routinely removes a portion of the omohyoid when performing a tracheostomy.

Permanent Tracheostomy in Standing Horses: Prognosis

In this author’s experience the long-term prognosis after tracheostomy is good, and more than 90% of owners say that they are pleased with the outcome. Tracheostomy has been performed on many broodmares without causing problems during foaling, although close observation of the mare around the foaling period is still recommended. In some horses the tracheostomies were performed more than 10 years ago and the stoma is still patent and causes no problems. This procedure does not prevent the horse from being used for athletic purposes; some of the aforementioned horses are used for pleasure riding and some used as Western performance horses. Although the tracheostomy bypasses a component of the pulmonary defense mechanism that acts to moderate temperature and humidity and filter inspired air, these horses have not appeared to be predisposed to airway infections. Approximately one fourth cough occasionally during exercise, most likely because of irritation of the trachea from dust particles. Consequently maintenance of the horses in an environment that is as dust-free as possible is recommended.