Categories
Veterinary Medicine

Arterial thromboembolism in the cat

Cats with any form of cardiomyopathy have a predilection to form intracardiac thrombi in the left atrium; the incidence is highest in cats with hypertrophic cardiomyopathy. These thrombi often become lodged at the bifurcation of the iliac arteries; less frequently they may occlude the brachia!, coeliac or renal arteries.

Pathophysiology

Altered blood flow and vascular stasis predispose to thrombus formation. Localized release of vasoactive substances such as serotonin and thromboxane at the site of vascular occlusion result in vasoconstriction of the collateral blood supply adjacent to the occluded vessel. Moreover, the release of serotonin induces platelets to aggregate which further potentiates clot formation. Occlusion at the iliac bifurcation (a so called *saddle* thrombus) results in ischaemic damage to the muscles and nerves of both hind limbs (ischaemic neuromyopathy).

Clinical signs

Iliac thrombosis is characterized by the sudden onset of crying and hindlimb paresis which results in dragging of one or both hind limbs (occlusion of a brachial artery may cause similar signs in a fore limb). The cat may present with acute dyspnoea and mouth breathing and the mucous membranes may appear cyanotic (particularly if a pulmonary artery is thrombosed). The affected muscles become firm and painful to touch after 24 hours. One or both femoral pulses may be absent and the paws and distal limbs are hypothermic (pink pads may appear pale).

Diagnosis

Diagnosis is usually based on the history and clinical signs. Since most cases of iliac thrombosis are associated with cardiomyopathy echocardiography should be performed as soon as the cat is stabilized. Non-selective angiocardiography may be helpful to determine the extent of the thrombosis and also the integrity of the collateral blood supply. Acute muscle damage results in increased plasma concentrations of aspartate aminotransferase (AST) and creatine kinase (CK). Urea and creatinine concentrations may increase after embolization of a renal artery.

Since the clinical signs of iliac thrombosis resemble those of lower motor neurone paralysis, spinal cord lesions, for example, acute spinal cord trauma, intervertebral discprotrusion (rarein the cat) or haemorrhage, and intravertebral tumours (lymphosarcoma) should be considered as differential diagnoses.

Arterial thromboembolism: Treatment

Treatment should he directed at alleviating signs associated with the thrombus as well as the underlying cardiac disorder responsible for its formation. Aspirin (25 mg kg-1 body weight per os every 72 h) should be given to inhibit platelet function. One study showed that the administration of aspirin resulted in significant preservation of collateral blood supply in eats after experimental induction of iliac thrombosis and a shortening of the recovery period. However, there is evidence to suggest that aspirin is not effective in preventing further embolic episodes. The use of acepromazine (0,2-0.4 mg kg-1 bodyweight subcutaneously three times daily) has been advocated for its vasodilator properties. Heparin may be given to prevent further activation of the coagulation process (an initial intravenous dose of 1000 USP followed 3 h later by 50 USP units kg-1 body weight subcutancously and thereafter 50 USP units kg-1 bodyweight every 6-8 b). Regular daily monitoring of activated partial thromboplastin lime (APTT) is advised so that the APTT is not prolonged by more than 1.5-2,0 times the preheparin baseline values. Morphine (0.1 mg kg-1 bodyweight) can be given as an analgesic for the first 24-48 h.

The use of the serotonin antagonist, cyproheptadine, and thrombolvtic agents such as streptokinase, urokinase and tissue plasminogen activator (t-PA) have yet to be fully evaluated and to date the results have been equivocal.

Prognosis

The prognosis is at best guarded. Many animals fail to respond to medical management or succumb to the underlying cardiomyopathy. Recurrence is common. Spontaneous recanalization of the clot may occur with or without drug therapy after 2-4 days. Many cats are left with signs of residual peripheral nerve damage. Full recovery may take up to 4-6 weeks.

Categories
Diseases

Diseases of the Throat: Diagnosis

Diagnostic Imaging

Lateral and ventrodorsal radiographic views of both the skull and cervical areas are indicated. Radiopaque foreign bodies can be identified that may be missed on laryngoscopy and pharyngoscopy (e.g. sewing needle embedded in soft tissues). Radiographs are also useful in identifying bony changes associated with chronic inflammation or neoplasia, identifying clues of unreported trauma (e.g. subcutaneous emphysema), and occasionally soft tissue masses. Suggestion of a soft tissue mass is confirmed by direct visualization and histopathology. Thoracic radiographs are also indicated. Symptoms of lower respiratory disease may be masked when a patient has concurrent, and more severe, upper respiratory symptoms. Evaluation for aspiration pneumonia, metastases, or suggestion of a motility disorder (i.e. megaesophagus) is possible.

Ultrasonography and computed tomography (CT) are noninvasive modalities to evaluate the pharynx and larynx. Ultrasonography can identify soft tissue masses, help guide fine needle aspiration, and evaluate laryngeal function. The presence of air in these areas can limit the usefulness of this modality in establishing a definitive diagnosis. CT may be used to fully evaluate involvement of neoplasia or middle-ear disease if a nasopharyngeal polyp is suspected.

Videofluoroscopy is essential for any case of dysphagia. A barium swallow allows the act of swallowing to be recorded and studied for abnormalities. The patient should be recorded attempting to swallow barium to mimic liquids and then should be given a meal (canned food mixed with barium) to be recorded. Videofluoroscopy is superior to radiography because it allows all phases of deglutition to be evaluated instead of recording one moment (intermittent moments) of the event. Unfortunately videofluoroscopy is limited to referral centers only.

Pharyngoscopy and Laryngoscopy

Laryngoscopy and pharyngoscopy allow assessment of both structural abnormalities and function of the larynx. A flexible endoscope is used for these procedures because visualization of the nasopharynx requires retroflexion. Occasionally a foreign body will be found just caudal to the larynx and may be retrieved endoscopically. The patient is placed in sternal recumbency and anesthetized with either propofol or sodium thiopental. Once anesthetized, gauze is passed under the maxilla behind the canine teeth. The gauze is used to elevate the head, so external compression of the neck is avoided. Flexible endoscopy is ideal to evaluate the nasopharynx. If that is not possible, the caudal pharynx can be evaluated using a dental mirror and a snook hook. This will be sufficient in evaluating most nasopharyngeal polyps, masses, or caudal foreign bodies. It will not allow diagnosis of more rostral diseases such as nasopharyngeal stenosis. Laryngeal function is usually evaluated first by assessing the motion of the arytenoid cartilages. The traditional approach involves titrating anesthesia that allows both visualization of the arytenoid cartilages and deep spontaneous breaths to occur. In a normal animal the arytenoid cartilages will abduct symmetrically with each inspiration and close on expiration. The frustration with this technique is multiple. Maintaining the correct level of anesthesia is difficult (i.e. the animal is too awake to allow adequate visualization of the arytenoid cartilages or anesthetized so that the patient will not spontaneously breathe); shallow breathing can limit adequate assessment; and concerns about the effect of anesthesia on laryngeal function are legitimate concerns when performing the traditional laryngeal examination. The recently introduced technique attempts to eliminate the effects of anesthesia from the examination. Patients are premedicated with acepromazine maleate and butorphanol tartrate and induced with propofol. Doxapram hydrochloride (2.2 mg/kg intravenously) is used to increase laryngeal motion and minimize or eliminate the effects of anesthesia,

Miscellaneous

Hematology and biochemical profiles should be performed on patients with pharyngeal and laryngeal dysfunction, but they will rarely confirm the definitive diagnosis. Occasionally virus isolation (feline calicivirus (FCV)) and PCR (feline herpes-1 virus (FHV-1), Chlantydia spp. and Mycoplasma spp.) are indicated in the diagnostic workup. Culture and sensitivity of tissue or secretions can provide valuable information during the diagnostic workup. Cytology and histopathology are also essential for critically evaluating infiltrative disease or mass lesions.

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

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

Hypertrophic Cardiomyopathy: Acute Therapy

Just as with dilated cardiomyopathy, cats that have respiratory distress suspected of having heart failure secondary to hypertrophic cardiomyopathy may need to be placed in an oxygen-enriched environment as soon as possible. If possible the cat should be initially evaluated by doing a cursory physical examination, taking care not to stress the patient during this or any other procedure, because stress exacerbates dyspnea and arrhythmias and often leads to death. Most, but not all, cats with severe hypertrophic cardiomyopathy that are in heart failure will have a heart murmur and gallop rhythm. A butterfly catheter should be used to perform thoracentesis on both sides of the chest to look for pleural effusion as soon as possible. Generally this should be done with the cat in a sternal position so that it does not become stressed during the procedure. Clipping of the hair is not needed. If fluid is identified, it should be removed. Most cats that arc dyspneic due to pleural effusion have 150 to 250 mL of fluid in their pleural space. If none is identified, a lateral thoracic radiograph to identify pulmonary edema may be taken with the veterinarian present to ensure that the cat is not stressed (e.g., the clinician should make sure no one stretches the cat out or in any way interferes with its ability to breathe). If the patient struggles or appears to be stressed or fractious during or before radiographic examination, the procedure should be canceled and the patient placed into an oxygen-enriched environment. A preferable alternative to blind tapping is to perform a superficial ultrasonographic examination to identify and locate fluid accumulation.

Furosemide

Furosemide should initially be administered intravenously or intramuscularly to the cat in severe respiratory distress. The route of administration depends on the stress level of the patient. Furosemide should bo administered intramuscularly to cats that are very distressed and cannot tolerate restraint for an intravenous injection. Cats that can tolerate an intravenous injection may benefit from the more rapid onset of action (within 5 minutes of an intravenous injection versus 30 minutes for an intramuscular injection).The initial rurosemide dose to a cat in distress should generally be in the 1 to 2 mg/lb range, intramuscularly or intravenously. This dose may be repeated within 1 hour to 2 hours ().

High-dose parenteral furosemide therapy commonly produces electrolyte disturbances and dehydration in cats. Cats with severe heart failure that require intensive therapy are often precarious. They may be presented dehydrated and electrolyte-depleted because of anorexia. They may remain anorexic and consequently dehydrated and depleted of electrolytes once the edema, the effusion, or both are lessened. Judicious intravenous or subcutaneous fluid administration may be required to improve these cats clinically. Overzealous fluid administration will result in the return of congestive heart failure. If fluid administration is required, the furosemide administration must be discontinued for that time.

Nitroprusside

Anecdotally, nitroprusside may be beneficial in cats with severe pulmonary edema due to hypertrophic cardiomyopathy. As with dilated cardiomyopathy, it may be administered empirically at 2 ug/lb/min or titrated, using blood pressure measurement to document efficacy, starting at a dose of 1 to 2 pg/lb/min. Nitroprusside has a very short half-life. Consequently, if clinically significant systemic-hypotension is produced (e.g., weakness, collapse, poor capillary refill time) cessation of the infusion will result in the systemic blood pressure returning to normal within several minutes.

Nitroglycerin

Nitroglycerin cream may be beneficial in cats with severe edema formation secondary to feline cardiomy-opathy. However, no studies have examined effects or efficacy. Nitroglycerin is safe and some benefit may occur with its administration in some cats. Consequently, one-eighth inch to one-fourth inch of a 2% cream may be administered to the inside of an ear every 4 to 6 hours for the first 24 hours as long as furosemide is being administered concomitandy. Nitroglycerin is not a primary drug. Tolerance develops rapidly in other species, and prolonged administration is probably of even lesser benefit.

Once drug administration is complete, the cat should be left to rest quietly in an oxygen-enriched environment. Care should be taken not to distress the cat. A baseline measurement of the respiratory rate and assessment of respiratory character should be taken when the cat is resting. This should be followed at 30-minute intervals and furosemide administration continued until the respiratory rate starts to decrease (a consistent decrease of the respiratory rate from 70 to 90 breaths per minute into the 50 to 60 breaths per minute range is a general guide), the character of the cat’s respiratory effort improves, or both occur. When this happens, the furosemide dose and dose frequency should be curtailed sharply.

Sedation or Anesthesia

In some cats, sedation with acepromazine (0.02 to 0.5 mg/lb intramuscularly or intravenously) may help by producing anxiolysis. Oxymorphone (0.02 to 0.04 mg/lb every 6 hours intramuscularly, intravenously, or sub-cutaneously) or butorphanol tartrate (0.04 mg/lb intravenously or 0.18 mg/lb every 4 hours subcutaneously) may also be used but are secondary choices because they can produce respiratory depression. Oxymorphone may produce excitement in some cats.

In some cats with fulminant heart failure, anesthesia, intubation, and ventilation are required to control the respiratory failure. Although this method is not preferred for most severely dyspneic cats, it can be life saving in some. This procedure has the advantage of being able to administer 100% oxygen and to be able to drain or suction fluid from the large airways in a controlled environment. The disadvantage is the administration of anesthetic agents to a cat that has cardiovascular compromise.

Categories
Diseases

Treatment of Systemic Arterial Thromboembolism

Euthanasia In cats that are in acute pain that have a poor prognosis due to severe cardiomyopathy, euthanasia is a humane means of dealing with the problem. Systemic throm-boembolism is often a horrible complication of cardiomyopathy, the treatment options are all relatively poor, and rethrombosis is common. Consequently, although one should not automatically give up on a patient, one should not give false hope either.

Pain Control Cats that present in pain must be treated appropriately for their pain. Appropriate drugs include a fentanyl patch, oxymorphone (intramuscularly, intravenously, or subcutaneously) and butorphanol tartrate (subcutaneously). Aspirin does not produce adequate pain control. Oxymorphone may produce excitement in some cats. The analgesic properties of butorphanol are five times that of morphine, and it remains a nonscheduled drug by the Food and Drug Administration. Its respiratory depressant effects equal that of morphine. Consequently, one must be careful when administering this drug to a patient with dyspnea. Acepromazine may be administered intravenously in addition as an anxiolytic agent to cats that still appear distressed after the administration of the analgesic or to cats that become agitated after oxymorphone administration. The pain abates with time (usually hours) as sensory nerves undergo necrosis.

Palliative Therapy Beyond pain control, many cats with systemic arterial thromboembolism receive only supportive care or the administration of drugs with no proven benefit. The primary outcome of arterial occlusion depends upon the extent of occlusion and the time to spontaneous reperfusion. Poor prognostic factors for short-term survival include worsening azotemia, moderate to severe pulmonary edema or pleural effusion, malignant arrhythmias, severe hypothermia, disseminated intravascular coagulation, and evidence of multiorgan embolization. Long-term, cats may lose an affected leg because of ischemic necrosis, die of toxemia, remain paralyzed from peripheral nerve damage, or regain full or partial function of their legs. About 50% of cats that are not treated definitively will regain all or most caudal limb motor function within 1 to 6 weeks. Return of function presumably is due to the cat’s own thrombolytic system (e.g., plasmin) disrupting the thromboembolus. The degree and rapidity of the dissolution depend on the activity of a particular cat’s thrombolytic system and the size and quality of the thromboembolus. Usually, cats that have some evidence of caudal limb flow recover more rapidly than do cats with no evidence of flow. Presumably this is because the size of the thromboembolus in cats with some flow is smaller. With total occlusion, some cats recanalize within days (others never recanalize).This extreme variability makes it very difficult to render a prognosis for a particular patient at presentation.

Palliative therapy may be only cage rest and pain control or can include administering drugs such as heparin, aspirin, or arteriolar dilators along with the cage rest. No drugs administered for palliation have any proven benefit over cage rest alone.

Heparin is commonly administered in the hopes of preventing new thrombus formation on top of the existing thromboembolus or in the hope of preventing a new thrombus from forming in the left atrium. However, no evidence indicates that heparin is of benefit in cats with STE. Heparin does not aid in thrombolysis. Heparin can be administered at an initial dose of 100 U/lb intravenously followed by a maintenance dose of 30 to 100 U/lb subcutaneously every 6 hours. The dose should be tailored to each individual cat to increase the activated partial thromboplastin time (aPTT) to at least 1.5 times baseline.

Indomethacin is effective at preventing vasoconstriction distal to the thromboembolus when administered to experimental cats prior to creating an aortic thrombus. Theoretically aspirin could do the same thing. However, no evidence indicates that it improves collateral blood flow.

The administration of drugs that dilate systemic arterioles (e.g., hydralazine, acepromazine) has been advocated. These drugs act by relaxing the smooth muscle in systemic arterioles. The exact anatomy of collateral vessels is not well described, but they are probably larger vessels than arterioles. They contain smooth muscle, because they can open and close. The ability of arteriolar dilators to counteract serotonin and thromboxane A2-induced vasoconstriction is unknown.

Definitive Therapy Definitive treatments for systemic arterial thromboembolism in cats include administration of exogenous fibrinolytic agents, balloon embolectomy, rheolytic thrombectomy, and surgery. All definitive procedures are associated with high mortality and common recurrence of the thromboembolus days to months after the initial removal.

Surgery Surgical removal of systemic thromboemboli is generally thought to be associated with high mortality and is not frequently performed. Cats with systemic arterial thromboembolism commonly have underlying cardiac disease, and many are in heart failure. They are poor anesthetic risks, and reperfusion syndrome may be produced. In reperfusion syndrome the muscles of the legs prior to removal of the systemic arterial thromboembolism undergo necrosis, cellular breakdown, and the release of potassium and hydrogen ions from the cells into the interstitial spaces. Sudden reperfusion carries these ions into the systemic circulation, causing acute and often severe hyperkalemia and metabolic acidosis. Surgical intervention may be a viable option if careful monitoring and treatment for reperfusion syndrome with insulin and glucose, sodium bicarbonate, or calcium (or a combination of these therapies) can be initiated immediately if it occurs.

Balloon embolectomy The procedure of choice in human medicine is balloon embolectomy. The author has had limited experience with balloon embolectomy. In this procedure the femoral arteries are isolated and a small balloon embolec-tomy catheter is passed from one femoral artery into the aorta. The femoral arteries are not extremely difficult to isolate. The catheter is pushed past the thromboembolus, and the balloon is then inflated and the catheter withdrawn, along with throm-boembolic material. The catheter is passed sequentially, first in one artery and then in the other. Usually this sequence must be repeated several times. Reperfusion syndrome may occur with balloon embolectomy.

Thrombolytic therapy Thrombolytic therapy is a possible means of dealing with cats with systemic arterial thromboembolism using fibrinolytic agents. Thromboemboli in cats are composed of red cells, strands of fibrin, and possibly platelets. Fibrinolytic agents cleave plas-minogen to plasmin. Plasmin hydrolyzes fibrin, resulting in thrombolysis. Different agents vary in their ability to bind specifically to fibrin-bound plasminogen and in their half-lives. Efficacy and complication rates appear to be very similar in humans. Complications consist primarily of hemorrhage due to fibrinolysis and rethrombosis. Fibrinolytic agents can be very effective at lysing systemic thromboemboli. However, the author and colleagues currently treat few cats with systemic arterial thromboembolism with these agents because reperfusion syndrome and rethrombosis are common.

Tissue plasminogen activator (t-PA) and streptokinase have been used in cats. Tissue plasminogen activator is an intrinsic protein present in all mammals. Numerous reports exist of the use of t-PA for the lysis of thrombi as therapy for acute myocardial infarction, pulmonary thromboembolism, and peripheral vascular obstruction in humans and experimental animals. The activity of genetically engineered t-PA in feline plasma is 90% to 100% of that seen in human plasma. The half-life of t-PA is quite short. Heparin must be administered concomitandy to prevent acute rethrombosis but does not need to be administered with streptokinase because it has a longer half-life. A clinical trial with t-PA in cats with aortic thromboemboli has shown acute thrombolytic efficacy (shortened time to reperfusion and ambulation) associated with the administration of t-PA at a rate of 0.1 mg to 0.4 mg/lb/hr for a total dose of 0.4 to 4 mg/lb intravenously. Forty three percent of cats treated survived therapy and were walking within 48 hours of presentation. Post-t-PA angiograms demonstrated resolution of the primary vascular occlusion. Thus acutely, t-PA effectively decreases the time to reperfusion and return to function in cats with aortic thromboemboli. However, 50% of the cats died during therapy in this clinical trial, which raises extreme concerns regarding acute thrombolysis. Fatalities resulted from reperfusion syndrome (70%), congestive heart failure (15%), and sudden arrhythmic death, presumably the result of embolization of a small thrombus to a coronary artery (15%). Severe hemorrhage into the region distal to the systemic arterial thromboembolism causing anemia was also a common complication. The cats that successfully completed t-PA therapy exhibited signs of increasing neuromuscular function and ambulatory ability within 2 days of presentation. This contrasts with 1 to 6 weeks before seeing similar signs of improvement in most cats exhibiting spontaneous resolution.

Mortality due to reperfusion syndrome can be reduced if the patient can be observed continuously by an individual trained to identify clinical and electrocardiographic evidence of hyperkalemia, if intensive monitoring of electrolytes and blood pH can be performed, and if aggressive medical therapy for hyperkalemia and metabolic acidosis can be initiated very quickly. This means dedicated care 24 hours a day until the thromboembolus is lysed. Thrombolysis may occur within 3 hours or take as long as 48 hours.

If reperfusion syndrome was the only major complicating factor in cats treated with thrombolytic agents, continued use in selected patients might be warranted. However, 90% of the cats that were successfully treated in the aforementioned clinical trial

had another systemic arterial thromboembolism within 1 to 3 months. Rethromboembolism occurred despite aspirin, warfarin, or heparin administration. In addition, t-PA is expensive. Consequently, the author does not currently use t-PA for systemic arterial thromboembolism in cats.

Streptokinase has clinical efficacy very similar to t-PA in human patients with coronary artery thrombosis. Streptokinase is less expensive. No controlled clinical trials of streptokinase use for systemic arterial thromboembolism in cats are available, and the author’s clinical experience with the drug has been generally negative. There has been one small experimental study in which throm-bin was injected between two ligatures placed at the terminal aorta to create a soft thrombus, followed by removal of the ligatures. Streptokinase was administered as a loading dose at 90,000 III followed by 45,000 IU/hr for 3 hours. This dose produced evidence of systemic fibrinolysis in a separate group of normal cats but without evidence of severe fibrinolysis or bleeding. In most cats there was no angiographic change and no improvement in limb temperature. There was a tendency for the thrombus weight to be lower in the treated cats when compared with control cats at postmortem examination. However, lysis of a fresh thrombus created with thrombin is probably much different from trying to lyse an established thromboembolus. Streptokinase is usually unsuccessful, may hasten the death of some cats through bleeding complications, and should not be routinely used.

Rheolytic thrombectomy Rheolytic thrombectomy is an experimental catheter-based system used for the dissolution of the thromboembolus using a high-velocity water jet at the end of the catheter that breaks up the thromboembolus and sucks it back into the system using the Venturi effect. Anesthesia is required and blood transfusion is almost always needed. The catheter is passed from the carotid artery to the region of the thromboembolus. The author and colleagues have used it in six cats. The procedure successfully removed the thromboembolus in five cats but only three left the hospital. Time from onset of clinical signs to thrombectomy was several hours to 8 days. The cat that had the procedure 8 days after the event had residual neurologic deficits but was the longest survivor. Interestingly, reperfusion syndrome has not been a common complication.

Adjunctive therapy Cats with systemic arterial thromboembolism are commonly in heart failure at the time of presentation. Medical therapy with furosemide and an angiotensin-converting enzyme inhibitor is often indicated. Cats that are in pain usually do not eat or drink. Fluid therapy is warranted but must not aggravate or produce heart failure

Cats that take a long time to recover caudal limb function or that only attain partial function may develop regions of skin and muscle necrosis, especially on the distal limbs. These regions may need to be debrided surgically. Cats that lose the function of only one leg or that do not regain function of one leg benefit from amputating that leg. Cats that have perma-nendy lost muscle function distal to the hock may benefit from arthrodesis.

Prognosis The short-term prognosis for life is guarded in cats without heart failure. Cats with a rectal temperature lower than 98.9° F had a worse prognosis in one study. Ifi The long-term prognosis is highly variable and depends on the ability to control the heart failure and the events surrounding the STE. One of the most common causes of death within the first 24 hours is euthanasia. In one study, cats lived between 3 and 30 months after the initial episode. The average survival time was about 10 to 12 months. In another study, MST for cats that recovered and were discharged from the hospital was approximately 4 months but was only about 2.5 months in cats that were also being treated for heart failure. The long-term prognosis for limb function depends on the ability of the cat to lyse its own clot or on the success of intervention. Many biologic variables determine whether or not reperfusion will spontaneously occur. A significant percentage of cats will develop a new thromboembolus, days to months after recovery.

Prophylaxis Feline patients with myocardial disease, especially those with an enlarged left atrium, should be considered at risk for developing intracardiac thrombi and signs of peripheral arterial thromboembolism, although the incidence appears to be low. Preventing peripheral thrombosis is, in theory, one of the most important therapeutic objectives for the veterinarian managing cats with severe myocardial disease. The ideal means of preventing thrombosis is resolution of the underlying myocardial disease. This is usually only possible in a cat with dilated cardiomyopathy secondary to taurine deficiency.

At-present, the only option available is to manipulate the patient’s coagulation system in an attempt to alter the delicate balance between the pathways that promote clotting and those that inhibit thrombus formation to reduce the patient’s thrombogenic potential. At this time, antiplatclet and anticoagulant therapies are the only means of preventing thrombus formation in cats with myocardial disease. Unfortunately, they are often ineffective and, in the case of warfarin, can produce serious side effects. Experience is similar in human medicine.

Antiplatelet therapy Prostaglandins enhance platelet aggregation via activation of cyclic adenosine monophosphate (cAMP). Aspirin (acetylsalicylic acid) acetylates platelet cyclooxygenase, preventing the formation of thromboxane A2, a potent prostaglandin-like platelet aggregating substance. The inhibition of platelet cyclooxygenase is irreversible, and bleeding time is restored to normal only after the production of new platelets. The inhibition of endothelial cyclooxygenase is reversible. The dose of aspirin recommended in cats is 10 mg/lb every third day. Whether or not this dose allows endothelial cyclooxygenase to recover or not in cats is undetermined. At this dose, aspirin has a half-life of 45 hours in the cat. In humans, doses as low as 20 to 100 mg/day inhibit platelet cyclooxygenase; however, no evidence suggests that this low dose has any more benefit than conventional daily doses of 625 to 1250 mg. In one study in cats, no difference was seen in thromboembolus recurrence between cats on low dose (5 mg/cat every 72 hours) and high dose (greater than or equal to 40 mg/cat every 72 hours). No evidence indicates that any dose of aspirin is effective at preventing the formation of an intracardiac thrombus in cats with myocardial disease. Clinical impression of aspirin’s efficacy varies between clinicians. Cats that have already experienced one systemic arterial thromboembolism are the only appropriate population in which to study the efficacy of an agent meant to prevent STE. Aspirin does not prevent recurrence of peripheral thromboembolism in this population.

Glycoprotein IIb and IIIa, an integrin present on platelet surfaces, is a receptor for fibrinogen, fibronectin, and von Willebrand factor. It mediates aggregation, adhesion, and spreading of platelets. The binding of prothrombin to glycoprotein IIb and IIIa also enhances the conversion of prothrombin to thrombin. Glycoprotein IIb and IIIa antagonists have been developed, and one (abciximab) increased mucosal bleeding time and reduced thrombus area when combined with aspirin (when compared with aspirin and placebo).

Anticoagulant therapy Available anticoagulants include heparin, the low molecular weight heparins, and warfarin. Heparin binds to a lysine site on AT, producing a conformational change at the arginine-reactive site that converts AT from a slow, progressive thrombin inhibitor to a very rapid inhibitor of thrombin and factor Xa. AT binds covalently to the active serine centers of coagulation enzymes. Factor Xa bound to platelets and thrombin bound to fibrin are protected from activation by the heparin-antithrombin III complex. Heparin may be administered intravenously or subcutaneously. Repeated intramuscular injection is discouraged because local hemorrhage may result. Some owners can administer heparin subcutaneously at home but the method is not ideal. The author and colleagues have noted rethrombosis with heparin therapy in some cats with cardiac disease. The dose of heparin for preventing thrombosis in cats is unknown.

Low molecular weight heparins include nadroparin calcium, enoxaparin sodium, dalteparin, ardeparin, tinzaparin, reviparin, and danaparoid sodium. The low molecular weight heparins have fewer bleeding complications in experimental animals, improved pharmacokinetics over heparin, are administered subcutaneously, and do not require monitoring in most situations. Although heparin does not reduce red cell aggregation in slow-moving blood, heparin and low molecular weight heparins are effective at preventing deep vein thrombosis in humans. Consequently, they may be beneficial in preventing intracardiac thrombus formation in cats with cardiomyopathy. No controlled studies are available. The author empirically uses enoxaparin sodium at a dose of 2.2 mg/lb every 12 hours subcutaneously in cats that have recovered from an systemic arterial thromboembolism or that have a severely enlarged left atrium and SEC.

Warfarin sodium is an oral anticoagulant (). Warfarin exerts no anticoagulant effect in vitro. In vivo, inhibitory effects on synthesis of clotting factors begin immediately. However, clotting is unaffected until already existing clotting factors decline. Therefore a delay occurs between initial administration and effect on the prothrombin time (FT). Historically, oral warfarin therapy has been monitored with the PT.This test measures the activity of factors II, VII, and X. The factor depressed most quickly and profoundly (usually factor VII) determines the FT during the initial days of therapy. The FT is performed by measuring the clotting time of platelet-poor plasma after the addition of thromboplastin and calcium, a combination of tissue factor and phospholipid. Intra- and interlaboratory variation in the FT was a significant problem for laboratories in the past, when crude extracts of human placenta or rabbit brain were the only source of thromboplastin. The international normalized ratio (INR), developed by the WHO in the early 1980s, is designed to eliminate problems in oral anticoagulant therapy caused by variability in the sensitivity of different commercial sources and different lots of thromboplastin. The INR is used worldwide by most laboratories performing oral anticoagulation monitoring and is routinely incorporated into dose planning for human patients receiving warfarin. When the anticoagulant effect is excessive, it can be counteracted by administering vitamin K,. However, once synthesis of factors 11, VII, IX, and X is reinstituted, time must elapse before factors achieve concentrations in the plasma that will adequately reverse the bleeding tendency. If serious bleeding occurs during therapy with warfarin, it may be stopped immediately by administering fresh blood or plasma that contains the missing clotting factors. Other drugs can modify the anticoagulant actions of warfarin by altering the bioavailability of vitamin K by altering the absorption, distribution, or elimination of the coumarins; by affecting synthesis or degradation of clotting factors; or by altering protein binding of the warfarin. The maintenance dose should be evaluated daily during the initial titration (3 days), then every other day (twice), and then weekly until a safe and stable dose regimen is determined. The therapeutic effect should be reevaluated periodically (at least once per month). The recommended initial dose is 0.1 to 0.2 mg per cat every 24 hours orally to a 6 to 10 lb/cat. The dose may then be increased to maintain an INR of 2.0 to 3.0. It can take up to 1 week for new steady state conditions to be achieved. The efficacy of warfarin at preventing recurrent thrombosis in cats with cardiac disease has been reported. M-s In one report, out of 23 cats examined retrospectively, 10 experienced a new thromboembolic episode while being administered warfarin. Two of these cats had at least two new episodes. In the other report, eight of 18 cats on warfarin experienced a new thromboembolic episode. This may be some improvement over the 75% recurrence rate reported for aspirin alone after t-PA therapy, but these results are still disappointing.i:,h In the first report, four cases also died suddenly (which could have been caused by thromboembolLsm). Three of these cats did not have postmortem examinations. The one cat that did have a postmortem examination had a thrombus present in its left atrium. One cat also died of a renal infarct that produced renal failure. Four cats appeared to have bleeding complications. In the second report, one cat died of a hemoabdomen and one was suspected to have an acute intracranial hemorrhage resulting in death. Consequendy, it appears that warfarin therapy can produce fatal complications. However, it should be noted that these studies were performed without using the INR for monitoring.

Categories
Drugs

Acepromazine Maleate (PromAce, Aceproject)

Phenothiazine Sedative / Tranquilizer

Highlights Of Prescribing Information

Negligible analgesic effects

Dosage may need to be reduced in debilitated or geriatric animals, those with hepatic or cardiac disease, or when combined with other agents

Inject IV slowly; do not inject into arteries

Certain dog breeds (e.g., giant breeds, sight hounds) may be overly sensitive to effects

May cause significant hypotension, cardiac rate abnormalities, hypo- or hyperthermia

May cause penis protrusion in large animals (esp. horses)

What Is Acepromazine Used For?

Acepromazine is approved for use in dogs, cats, and horses. Labeled indications for dogs and cats include: “… as an aid in controlling intractable animals… alleviate itching as a result of skin irritation; as an antiemetic to control vomiting associated with motion sickness” and as a preanesthetic agent. The use of acepromazine as a sedative/tranquilizer in the treatment of adverse behaviors in dogs or cats has largely been supplanted by newer, effective agents that have fewer adverse effects. Its use for sedation during travel is controversial and many no longer recommend drug therapy for this purpose.

In horses, acepromazine is labeled “… as an aid in controlling fractious animals,” and in conjunction with local anesthesia for various procedures and treatments. It is also commonly used in horses as a pre-anesthetic agent at very small doses to help control behavior.

Although not approved, it is used as a tranquilizer (see doses) in other species such as swine, cattle, rabbits, sheep and goats. Acepromazine has also been shown to reduce the incidence of halothane-induced malignant hyperthermia in susceptible pigs.

Before you take Acepromazine

Contraindications / Precautions / Warnings

Animals may require lower dosages of general anesthetics following acepromazine. Use cautiously and in smaller doses in animals with hepatic dysfunction, cardiac disease, or general debilitation. Because of its hypotensive effects, acepromazine is relatively contraindicated in patients with hypovolemia or shock. Phenothiazines are relatively contraindicated in patients with tetanus or strychnine intoxication due to effects on the extrapyramidal system.

Intravenous injections should be made slowly. Do not administer intraarterially in horses since it may cause severe CNS excitement/depression, seizures and death. Because of its effects on thermoregulation, use cautiously in very young or debilitated animals.

Acepromazine has no analgesic effects; treat animals with appropriate analgesics to control pain. The tranquilization effects of acepromazine can be overridden and it cannot always be counted upon when used as a restraining agent. Do not administer to racing animals within 4 days of a race.

In dogs, acepromazine’s effects may be individually variable and breed dependent. Dogs with MDR1 mutations (many Collies, Australian shepherds, etc.) may develop a more pronounced sedation that persists longer than normal. It may be prudent to reduce initial doses by 25% to determine the reaction of a patient identified or suspected of having this mutation.

Acepromazine should be used very cautiously as a restraining agent in aggressive dogs as it may make the animal more prone to startle and react to noises or other sensory inputs. In geriatric patients, very low doses have been associated with prolonged effects of the drug. Giant breeds and greyhounds may be extremely sensitive to the drug while terrier breeds are somewhat resistant to its effects. Atropine may be used with acepromazine to help negate its bradycardic effects.

In addition to the legal aspects (not approved) of using acepromazine in cattle, the drug may cause regurgitation of ruminal contents when inducing general anesthesia.

Adverse Effects

Acepromazine’s effect on blood pressure (hypotension) is well described and an important consideration in therapy. This effect is thought to be mediated by both central mechanisms and through the alpha-adrenergic actions of the drug. Cardiovascular collapse (secondary to bradycardia and hypotension) has been described in all major species. Dogs may be more sensitive to these effects than other animals.

In male large animals acepromazine may cause protrusion of the penis; in horses, this effect may last 2 hours. Stallions should be given acepromazine with caution as injury to the penis can occur with resultant swelling and permanent paralysis of the penis retractor muscle. Other clinical signs that have been reported in horses include excitement, restlessness, sweating, trembling, tachypnea, tachycardia and, rarely, seizures and recumbency.

Its effects of causing penis extension in horses, and prolapse of the membrana nictitans in horses and dogs, may make its use unsuitable for show animals. There are also ethical considerations regarding the use of tranquilizers prior to showing an animal or having the animal examined before sale.

Occasionally an animal may develop the contradictory clinical signs of aggressiveness and generalized CNS stimulation after receiving acepromazine. IM injections may cause transient pain at the injection site.

Overdosage / Acute Toxicity

The LD50 in mice is 61 mg/kg after IV dosage and 257 mg/kg after oral dose. Dogs receiving 20-40 mg/kg over 6 weeks apparently demonstrated no adverse effects. Dogs gradually receiving up to 220 mg/kg orally exhibited signs of pulmonary edema and hyperemia of internal organs, but no fatalities were noted.

There were 128 exposures to acepromazine maleate reported to the ASPCA Animal Poison Control Center (APCC; www.apcc.aspca.org) during 2005-2006. In these cases, 89 were dogs with 37 showing clinical signs and the remaining 39 reported cases were cats with 12 cats showing clinical signs. Common findings in dogs recorded in decreasing frequency included ataxia, lethargy, sedation, depression, and recumbency. Common findings in cats recorded in decreasing frequency included lethargy, hypothermia, ataxia, protrusion of the third eyelid, and anorexia.

Because of the apparent relatively low toxicity of acepromazine, most overdoses can be handled by monitoring the animal and treating clinical signs as they occur; massive oral overdoses should definitely be treated by emptying the gut if possible. Hypotension should not be treated with epinephrine; use either phenylephrine or norepinephrine (levarterenol). Seizures may be controlled with barbiturates or diazepam. Doxapram has been suggested as an antagonist to the CNS depressant effects of acepromazine.

How to use Acepromazine

Note: The manufacturer’s dose of 0.5-2.2 mg/kg for dogs and cats is considered by many clinicians to be 10 times greater than is necessary for most indications. Give IV doses slowly; allow at least 15 minutes for onset of action.

Acepromazine dosage for dogs:

a) Premedication: 0.03-0.05 mg/kg IM or 1-3 mg/kg PO at least one hour prior to surgery (not as reliable) ()

b) Restraint/sedation: 0.025-0.2 mg/kg IV; maximum of 3 mg or 0.1-0.25 mg/kg IM; Preanesthetic: 0.1-0.2 mg/kg IV or IM; maximum of 3 mg; 0.05-1 mg/kg IV, IM or SC ()

c) To reduce anxiety in the painful patient (not a substitute for analgesia): 0.05 mg/kg IM, IV or SC; do not exceed 1 mg total dose ()

d) 0.55-2.2 mg/kg PO or 0.55-1.1 mg/kg IV, IM or SC (Package Insert; PromAce — Fort Dodge)

e) As a premedicant with morphine: acepromazine 0.05 mg/kg IM; morphine 0.5 mg/kg IM ()

Acepromazine dosage for cats:

a) Restraint/sedation: 0.05-0.1 mg/kg IV, maximum of 1 mg ()

b) To reduce anxiety in the painful patient (not a substitute for analgesia): 0.05 mg/kg IM, IV or SC; do not exceed 1 mg total dose ()

c) 1.1-2.2 mg/kg PO, IV, IM or SC (Package Insert; PromAce — Fort Dodge)

d) 0.11 mg/kg with atropine (0.045-0.067 mg/kg) 15-20 minutes prior to ketamine (22 mg/kg IM). ()

Acepromazine dosage for ferrets:

a) As a tranquilizer: 0.25-0.75 mg/kg IM or SC; has been used safely in pregnant jills, use with caution in dehydrated animals. ()

b) 0.1-0.25 mg/kg IM or SC; may cause hypotension/hypothermia ()

Acepromazine dosage for rabbits, rodents, and small mammals:

a) Rabbits: As a tranquilizer: 1 mg/kg IM, effect should begin in 10 minutes and last for 1-2 hours ()

b) Rabbits: As a premed: 0.1-0.5 mg/kg SC; 0.25-2 mg/kg IV, IM, SC 15 minutes prior to induction. No analgesia; may cause hypotension/hypothermia. ()

c) Mice, Rats, Hamsters, Guinea pigs, Chinchillas: 0.5 mg/kg IM. Do not use in Gerbils. ()

Acepromazine dosage for cattle:

a) Sedation: 0.01-0.02 mg/kg IV or 0.03-0.1 mg/kg IM ()

b) 0.05 -0.1 mg/kg IV, IM or SC ()

c) Sedative one hour prior to local anesthesia: 0.1 mg/kg IM ()

Acepromazine dosage for horses:

(Note: ARCI UCGFS Class 3 Acepromazine)

a) For mild sedation: 0.01-0.05 mg/kg IV or IM. Onset of action is about 15 minutes for IV; 30 minutes for IM ()

b) 0.044-0.088 mg/kg (2-4 mg/100 lbs. body weight) IV, IM or SC (Package Insert; PromAce — Fort Dodge)

c) 0.02-0.05 mg/kg IM or IV as a preanesthetic ()

d) Neuroleptanalgesia: 0.02 mg/kg given with buprenorphine (0.004 mg/kg IV) or xylazine (0.6 mg/kg IV) ()

e) For adjunctive treatment of laminitis (developmental phase): 0.066-0.1 mg/kg 4-6 times per day ()

Acepromazine dosage for swine:

a) 0.1-0.2 mg/kg IV, IM, or SC ()

b) 0.03-0.1 mg/kg ()

c) For brief periods of immobilization: acepromazine 0.5 mg/ kg IM followed in 30 minutes by ketamine 15 mg/kg IM. Atropine (0.044 mg/kg IM) will reduce salivation and bronchial secretions. ()

Acepromazine dosage for sheep and goats:

a) 0.05-0.1 mg/kg IM ()

Monitoring

■ Cardiac rate/rhythm/blood pressure if indicated and possible to measure

■ Degree of tranquilization

■ Male horses should be checked to make sure penis retracts and is not injured

■ Body temperature (especially if ambient temperature is very hot or cold)

Client Information

■ May discolor the urine to a pink or red-brown color; this is not abnormal

■ Acepromazine is approved for use in dogs, cats, and horses not intended for food

Chemistry / Synonyms

Acepromazine maleate (formerly acetylpromazine) is a phenothiazine derivative that occurs as a yellow, odorless, bitter tasting powder. One gram is soluble in 27 mL of water, 13 mL of alcohol, and 3 mL of chloroform.

Acepromazine Maleate may also be known as: acetylpromazine maleate, “ACE”, ACP, Aceproject, Aceprotabs, PromAce, Plegicil, Notensil, and Atravet.

Storage / Stability/Compatibility

Store protected from light. Tablets should be stored in tight containers. Acepromazine injection should be kept from freezing.

Although controlled studies have not documented the compatibility of these combinations, acepromazine has been mixed with atropine, buprenorphine, chloral hydrate, ketamine, meperidine, oxymorphone, and xylazine. Both glycopyrrolate and diazepam have been reported to be physically incompatible with phenothiazines, however, glycopyrrolate has been demonstrated to be compatible with promazine HC1 for injection.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products:

Acepromazine Maleate for Injection: 10 mg/mL for injection in 50 mL vials; Aceproject (Butler), PromAce (Fort Dodge); generic; (Rx). Approved forms available for use in dogs, cats and horses not intended for food.

Acepromazine Maleate Tablets: 5, 10 & 25 mg in bottles of 100 and 500 tablets; PromAce (Fort Dodge); Aceprotabs (Butler) generic; (Rx). Approved forms available for use in dogs, cats and horses not intended for food.

When used in an extra-label manner in food animals, it is recommended to use the withdrawal periods used in Canada: Meat: 7 days; Milk: 48 hours. Contact FARAD (see appendix) for further guidance.

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

Human-Labeled Products: None

Categories
Horses

Management of Stallions for Artificial Breeding

The management of stallions used in an artificial insemination program must be tailored to the individual stallion and to the facilities and personnel at the breeding farm. The stallion owner, farm manager, and veterinarian should develop a coordinated plan to optimize the stallion’s health for his athletic and breeding careers, to coordinate the housing and movement of all horses on the farm, to utilize farm personnel efficiently, to achieve a high level of fertility in an efficient manner, and to minimize risks to the stallion, personnel, and individual mares. A unique plan must be developed for a stallion being used in a breeding program but which is still actively competing in his athletic discipline. The health and breeding program must address the needs of the stallion based on his age, existing disease conditions such as orthopedic problems, location and number of mares to be bred, semen quality, and the innate fertility of the stallion.

General Health Considerations

The nutritional needs of the stallion used in an artificial insemination (AI) program are not unique. The goal of the feeding program should be to maintain the stallion at an ideal weight and fitness. Pasture, good quality grass or grass-alfalfa mixed hay, and water should be available at all times. Grain supplementation may be necessary to provide adequate vitamin and mineral consumption not supplied by hay. If the stallion is fed a balanced ration, it is unlikely that additional supplementation of the ration will increase fertility or daily sperm production. The stallion’s feeding program should be associated with an exercise program to keep the horse alert, athletic, and content.

A stallion needs daily exercise in a paddock or small pasture. If the stallion does not exercise freely during turnout time, it may be necessary to ride, drive, hand walk, or lunge the horse daily to maintain the stallion’s athleticism and body condition. A stallion needs exercise even during inclement weather. Many objectionable stallion behaviors are associated with a poorly implemented nutrition and exercise program.

Breeding stallions should be dewormed at regular intervals along with all the other horses on a farm. Fecal exams can be performed periodically to ensure the effectiveness of the parasite control program. To this author’s knowledge, reproductive performance of stallions has not been altered by regular use of commonly available de-worming compounds.

Yearly dental examinations should be performed to maintain normal mastication. Dental procedures should be carried out as needed. However, if tranquilization is required, promazine tranquilizers should not be used because of the risk of penile paralysis.

The farrier should evaluate the stallion’s feet at regular intervals of 6 to 8 weeks. Stallions receiving adequate turn out, frequently require minimal hoof trimming. Problems such as prior athletic injury, laminitis, hoof-wall cracks, flat soles, and underrun heels may require evaluation and treatment by the farrier and veterinarian to maintain hoof health and stallion longevity.

In general, stallions should be vaccinated against tetanus, eastern and western encephalomyelitis, and rabies. Many other vaccines are available and may be appropriate for use in individual stallions, based on age, horse farm population density, current farm disease status, and other factors. The vaccination program should be designed for the individual farm and stallion. Vaccinations against upper respiratory tract infections also should be considered for most active, breeding stallions. Maintaining immunity against influenza, rhinopneumonitis, and strangles may prevent infections with these viruses and bacteria and minimize the adverse effect of elevated body temperature on spermatogenesis and semen quality. Special effort should be made to use vaccines containing the most current serovars of influenza and rhinopneumonitis viruses. Other vaccines that should be considered based on disease prevalence at the farm include botulism and Potomac horse fever (Neorickettsia risticii).

Currently, a provisional license has been granted for the production of a vaccine against equine protozoal myeloencephalitis (Sarcocystis neurona) and West Nile virus encephalitis. Data are not available, at this time, to fully support the efficacy of these vaccines and potential adverse effects on breeding stallions. Consideration of the use of these vaccines in endemic regions of the country may be necessary.

Equine arteritis virus (EAV) can be spread from stallions to mares via respiratory tract secretions but, more commonly, through semen. Approximately 30% of stallions seropositive for EAV shed virus in their semen. Virus may be shed in the semen of an infected stallion for a short period of time or a lifetime. This virus can cause upper respiratory infections and abortion. All stallions used in an AI program should be tested serologically for EAV antibodies. A serologically negative stallion can be used to breed seropositive or seronegative mares without risk. If the stallion is seropositive for EAV antibodies, an aliquot of semen from one or more ejaculates should be submitted to the diagnostic laboratory for virus isolation. If the stallion is actively shedding virus in his semen, he should be used to inseminate only naturally exposed or vaccinated seropositive mares. Equine arteritis virus can infect mares inseminated with fresh, cooled, or frozen semen.

The use of the polymerase chain reaction (PCR) testing of semen for EAV is not accurate in determining the presence of virus in semen. If a stallion is determined to be serologically negative for EAV antibodies, vaccination against EAV should be strongly considered. Vaccination of the seronegative stallion prevents development of the carrier state if the stallion is exposed to field strain virus. However, vaccination apparently does not alter the carrier state once infection has been established. Vaccination of stallions against EAV should occur at least 30 days before the onset of the breeding season. The seropositive stallion that does not shed virus in his semen can be used safely in an AI program using fresh, cooled, or frozen semen. All stallions used for breeding should be tested annually for equine infectious anemia.

The economic value and importance of the stallion to a breeding program may be substantial. Many stallion owners elect to insure the stallion with mortality and/or fertility policies. These policies are not necessarily standardized but may include physical examination of the stallion and historical fertility data. A breeding soundness evaluation usually is not required.

Breeding Soundness Evaluation

A thorough breeding soundness evaluation should be performed on stallions entering an AI program. This evaluation should be done before purchase and before the onset of each breeding season. The purpose of the evaluation is to assess any physical limitations to breeding. The stallion’s willingness and manner of mounting an estrous mare or phantom should be assessed. Seminal quality should be determined. Specifically, the number of sperm ejaculated, percentage and type of sperm motility, morphologic analysis of sperm, bacteriologic and, possibly, viral status of the semen are determined. The longevity and type of sperm motility in semen extenders also should be determined. Any evidence of physical abnormalities or lesions of the external and internal genitalia should be noted.

The evaluation of semen quality may require the collection of numerous ejaculates of semen. The seminal quality of initial ejaculates from sexually rested stallions may not be representative of the stallion’s seminal quality while in routine use. The semen from sexually rested stallions frequently has markedly elevated sperm numbers, reduced sperm motility, poor longevity of sperm motility under shipped, cooled semen conditions, and an increased incidence of sperm morphologic abnormalities.

The semen quality of most sexually rested stallions stabilizes after three to six ejaculations over a period of 3 to 7 days. If the stallion’s semen quality has not stabilized, the practitioner may reach erroneous conclusions concerning the longevity of sperm motility in a shipped, cooled semen program, the acceptability of different semen extenders or antibiotics that are added to the extender, or the number of mares that may be bred using a single ejaculate.

The goals of the breeding soundness evaluation before the onset of the breeding season are to determine any limitations on the size of the stallion’s book; to identify any physical ailments that may have become apparent since the last breeding season; and to determine the suitability of the particular stallion for use in an on-farm or shipped, cooled semen breeding program. Selection of a good quality semen extender to maintain sperm motility for 24 to 72 hours or longer and control pathogenic bacteria in semen is made at this time. Semen quality and bacterial status of extended semen are evaluated periodically throughout the breeding season, in case adjustments are necessary. A final goal of the breeding soundness evaluation should be to establish the presence or absence of pathogens in equine semen, such as EAV, contagious equine metritis (CEM; Taylorella equigenitalis), Pseudomonas sp., Klebsiella sp., and Streptococcus zooepidemkus.

Semen Collection

Management Of Breeding-Related Problems Using Semen Collection And Artificial Insemination

Categories
Horses

Twins

The diffuse microcotyledonary placentation of the mare makes it highly unlikely that a twin pregnancy will be carried to term. If the twin pregnancy is maintained until the latter part of gestation the placenta cannot meet the nutrient demands of the rapidly growing fetuses. Death of one or both fetuses is followed by abortion, with the characteristic avillous areas on the fetal membranes confirming the amount of placental disruption (). Twin abortions in the last few months of gestation are likely to cause a dystocia. The live birth of twin foals is extremely uncommon, and many of these neonates do not survive. The mares are prone to fetal membrane retention and may be difficult to rebreed. Thus it is not surprising that the equine breeding industry has always tried to avoid twin pregnancies. This chapter will review the management options that are currently available.

Monitoring Follicular Development And Ovulation

A high incidence of twin ovulations occurs in some breeds, such as Thoroughbreds and warmbloods, and mares that tend to double ovulate can be expected to do this repeatedly. Thus a mare with a tendency to double-ovulate should have this information noted prominently on her breeding record. Most twin pregnancies arise from such double ovulations. Owners need to appreciate that these double ovulations are generally asynchronous and may be separated by a couple of days. If a fertile stallion was used to breed the mare on the first ovulation, it is possible that viable sperm will still be present in the reproductive tract when the second oocyte arrives. This possibility must be remembered when scanning mares for pregnancy at 14 to 16 days. At that time, it is good practice to scan the ovaries for evidence of luteal tissue from a second ovulation.

In the past, one strategy that was employed when a veterinarian palpated two large (>30 mm) follicles was to wait to breed until the next cycle. This approach wasted valuable days in the breeding season, and many of these mares would repeat the same follicular process during the next cycle. An alternate approach was to hope that the second follicle would continue to develop for 10 to 12 hours after the first detected ovulation. Because the ovulated oocyte is unlikely to be viable at this time, a delayed breeding could be performed in anticipation of the second ovulation. Today the preferred strategy is to breed all eligible mares — irrespective of the number of preovulatory follicles. The widespread adoption of early ultrasonographic pregnancy examinations has permitted the focus to be placed on embryonic vesicle reduction once the presence of a twin pregnancy has been confirmed.

Manual Reduction

The increasing size of the embryonic vesicle, coupled with the increasing tone of the early pregnant uterus, tends to fix the conceptus at the base of one uterine horn by day 16. It is essential that the ultrasound scan of the uterus be thorough, with a complete examination of the length of both horns plus the uterine body as far back as the cervix. This is especially important before day 16 because the vesicle moves freely within the lumen of both horns and the uterine body. The advantage of these early scans is that if twin vesicles are detected it will be easier to manually separate them before day 16. Successful elimination of one vesicle is more likely at that time because the uterine walls are thin, and minimal pressure is required to crush a vesicle. A definite “pop” can be felt when the vesicle ruptures, but success should always be confirmed by ultrasound.

The downside to this approach is that an early embryonic vesicle can easily be confused with an endometrial cyst. The embryo itself does not become readily identifiable until the fourth week of pregnancy. Thus it is good practice to note the size and location of any cysts at the time the mare is being examined for breeding. However, it is not an uncommon occurrence that the veterinarian doing the early (14-16 days) pregnancy scan will be examining the mare for the first time. If no record of cyst size and location exists, it is virtually impossible to differentiate twin vesicles from a singleton and a cyst with a single examination. This is especially true because asynchronous ovulations are likely to result in considerable size discrepancy between the two vesicles. Under these circumstances it may be best to measure each suspect vesicle and note its location. A second scan in 1 to 2 days should note a size increase in any normally growing vesicle (~4 mm/day). Only then can a confident decision be made about attempting to “pinch” one of the growing vesicles. Unfortunately this delay may make separation of unilaterally fixed vesicles more difficult because of their ongoing growth and the increased uterine tone.

Manual reduction of bilaterally fixed vesicles requires less manipulation than with unilateral twins. It is a relatively easy procedure, and success rates exceeding 90% are not uncommon if the vesicle is crushed before day 16. If the vesicles are unilaterally fixed, the clinician should attempt to move the more proximal vesicle away towards the tip of the uterine horn. At this location the manual reduction procedure is less likely to disrupt the remaining vesicle. The vesicle can be crushed by pinching it between the thumb and fingers. Alternately, the vesicle is squeezed against the mare’s pelvis until it ruptures. If the twins can be separated before crushing, the success rate may be similar to that for reduction of bilateral twins. If the unilateral twins cannot be separated or are greater than 20 days’ gestation, the success rate is lower. The extra pressure used to eliminate a twin vesicle after fixation is the reason many clinicians will accompany reduction with antiinflammatory medications and progestin therapy. The likelihood of success improves with experience, and some clinicians develop a reputation for being especially adept at the procedure. Obviously the nature of the mare is an important factor, and those that strain excessively can make the procedure extremely difficult. If the unilateral vesicles are not detected until after day 20, manipulations can easily result in the disruption of both vesicles. The best option in these cases may be to wait and see whether natural reduction occurs.

Natural Reduction

Almost three quarters (70%) of twin embryonic vesicles become fixed unilaterally; only 30% of twin vesicles become fixed bilaterally. The advantage of this probability is that natural reduction to a single pregnancy is far more likely with unilaterally fixed vesicles. Over 80% of unilaterally fixed twins are likely to naturally reduce to a singleton, with over half of these occurring between days 16 and 20. On the other hand, the majority of bilaterally fixed vesicles will continue to develop. Late in the season these odds play an important part in any informed discussion about management options. Early in the season most veterinarians will opt to attempt reduction, knowing that if both vesicles are lost that it will still be possible to rebreed the mare. Close to the end of the season an unsuccessful attempt at reduction may preclude the mare from being rebred. If natural reduction does not occur by day 30, the advent of transvaginal reduction has opened a window for later attempts at reduction. If this fails, owners may opt to put the mare under lights and breed her early next season rather than be locked into a pattern of late foals.

Pregnancy Termination With Prostaglandin

If natural reduction does not occur, terminating the pregnancy with a prostaglandin injection is always possible. This will cause lysis of the corpora lutea that resulted from the double ovulation, and the precipitous decline in progesterone will bring the mare back into estrus. However, this treatment must be given before day 35. Once the endometrial cups form it may take repeated injections to terminate the pregnancy, and the mare is unlikely to return to estrus until the cups are sloughed. The endometrial cups originate from specialized fetal trophoblast cells. They secrete equine chorionic gonadotropin (eCG), a hormone that causes the development of accessory corpora lutea and thus augments the progesterone level in support of the early pregnancy.

Transvaginal Ultrasound-Guided Allantocentesis

Although the advent of transrectal ultrasonography has dramatically improved the ability of veterinarians to make an early diagnosis of twin pregnancies, diagnostic errors still occur. This could be due to an early pregnancy diagnosis when the second vesicle was too small to detect, incomplete examination of the entire uterus, poor image quality, or an inability of the clinician to differentiate two embryonic vesicles that are closely apposed to each other. If natural reduction does not occur or the diagnosis of twins is not confirmed until after 30 days, transvaginal aspiration of one vesicle is an option. The results are best if the procedure is performed before day 35. Although spontaneous reduction of twin pregnancies can occur even after day 40, the probability is low. Natural twin reduction is more likely to occur if an obvious size discrepancy is present between the two vesicles at this time.

If a transvaginal reduction is to be attempted, the mare should be treated with flunixin meglumine. Many clinicians will also administer oral altrenogest. Because sedation causes significant uterine relaxation, most clinicians use a lidocaine enema to reduce straining. The transvaginal aspiration technique employs a 5.0- or 7.5-MHz endovaginal curvilinear transducer. The transducer and casing should be cold-disinfected or sterilized before use. The assembled unit is then placed in a sterile transducer cover that has been filled with sterile lubricating gel. The transducer is advanced aseptically until it is seated lateral to the cervix. The clinician then grasps the pregnancy per rectum and advances a sterile 60-cm, 18-gauge spinal needle with an echogenic tip along the needle guide in the transducer casing. A dotted line on the ultrasound screen can be used to select a path for the needle entry into the embryonic vesicle. A sharp jab of the needle penetrates the vaginal wall, peritoneal lining, uterus, and ultimately the allantoic or yolk sac. A 60-ml syringe is attached to the needle, and the embryonic fluid aspirated. Aspiration should be stopped when danger of damaging the adjacent vesicle of unilateral twins arises. If a bilateral twin is being eliminated, the needle can be moved within the vesicle until all detectable fluid has been aspirated. The success rate is better for bilateral twin reductions. Death of the remaining twin is most likely to occur within 2 weeks of the procedure. Although reports are scarce, preliminary data suggest that experienced operators may achieve a live singleton birth in about one third of cases.

Transabdominal Ultrasound-Guided Fetal Cardiac Puncture

In advanced twin pregnancies, attempting reduction by a transabdominal approach is possible. Fetal intracardiac injection of potassium chloride is effective but requires accurate placement of the KC1 into the fetal heart. Best results are obtained when the pregnancy is between 115 and 130 days. At this stage experienced operators can achieve a 50% success rate. Procaine penicillin G can cause fetal death when injected into either the fetal thorax or abdomen, but the effect is not instantaneous. The advantage of the latter treatment is that it does not require precise placement of the injection into the fetal heart. Mares should be started on oral altrenogest, systemic antibiotics, and flunixin meglumine on the day of the procedure. The antibiotic coverage and antiinflammatory medication should be continued for 3 days.

A 3.0-MHz transducer can be used to image the 90- to 130-day fetus in the caudal abdomen, just cranial to the udder (Figure 5.9-2). Once the mare has been sedated, the uterus will relax, and the location of the fetuses will shift cranially. A sedative/analgesic combination that works well for this procedure is acepromazine (10 mg), xylazine (100 mg), and butorphanol (10 mg). The smallest and/or most easily accessible fetus is selected for reduction. The ventral abdomen should be surgically prepared, and local anesthetic infiltrated at the puncture site. Some clinicians are adept at a “free-hand” injection technique, whereby the fetus is injected by merely observing the ultrasound image. Others prefer to use an ultrasound transducer that is fitted with a biopsy guide. An 18-gauge, 6- to 8-inch spinal needle with stylet can be used for most fetal injections. The distance from the skin surface to the fetus determines the length of the needle that is required. Specialized needles with echogenic tips are available to provide better visualization via ultrasound. Once the location of the selected twin’s thorax is confirmed, the needle is introduced through the prepared skin, abdominal wall, and uterus. If procaine penicillin G is to be injected, the needle may puncture either the fetal thorax or abdomen. Up to 20 ml is typically injected into the fetus. Fetal death should be confirmed the following day.

Although the benefits of supplemental progestin therapy are debatable, many clinicians suggest that the mare be medicated for at least 2 weeks if the initial twin reduction has been successful. It is essential that fetal viability be checked regularly because supplemental progestin therapy may prevent elimination of the dead fetuses if both die. Most abortions will occur within 1 to 2 months after the reduction procedure. Survival of the remaining twin seems to depend somewhat on the amount of endometrial surface that was its domain before the reduction. If the operator is experienced in the technique, between 30% and 60% of cases can be expected to deliver a singleton foal, although the ultimate size and viability may be suboptimal. The eliminated twin in these cases can be seen as a mummified remnant contained within an invaginated pouch that protrudes into the allantoic space of the viable foal’s fetal membranes.

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Horses

Complications Of Burns

Infection is a serious and frequent complication of burns and must be addressed at an early stage. For the most part, normal skin commensal organisms such as Streptococcus equi var. zooepidemicus, Staphylococcus aureus, and Pseudomonas aeruginosa are encountered with some complicated by other gram-negative species, such as E. coli and Clostridia spp., and yeasts can be found. Silver sulfadiazine (Silvadene) is a useful broad antibacterial that has little or no harmful effects on wound healing.

Some horses suffer from renal shutdown after sustaining a severe burn and renal function must be encouraged and repeatedly checked. Diuretics such as furosemide are often indicated but should be used with considerable care.

Smoke inhalation or internal burns can cause serious pulmonary edema and thus must be controlled. Oxygen supplied directly to the trachea or nasally may be helpful. A single intravenous dose of dexamethasone (0.5 mg/kg) may assist. Intravenous administration of dimethyl sulfoxide (DMSO) at 1 g/kg over the first 2 days may be helpful in reducing the pulmonary edema. All cases in which smoke inhalation has occurred must have systemic antibiotic therapy because the respiratory tract is particularly susceptible to serious infection after inhalation damage. Obtaining a transtracheal aspirate for culture if the chosen antibiotics do not appear to be helping is justifiable. Fungal infections pose a particularly serious threat that may be untreatable.

Cornea] and eyelid damage is particularly dangerous because of the delicate nature of the tissue and their intolerance to injury. In cases in which the face has been involved in the burn (to any extent at all) the corneas should be medicated carefully with artificial tears. In all cases the cornea should be stained with fluorescein to check for ulceration and necrotic tissue. All necrotic tissue should be gently removed with a saline-soaked cotton swab. Under no circumstances should corticosteroids or any strong chemicals such as chlorhexidine or povidone iodine be applied to the eye. Topical antibiotics (e.g., triple antibiotic or gentamicin) should be applied with atropine to control any reflex uveitis. If the eyelids are involved or are suspected to be involved, then particular care must be taken to protect the corneas with artificial tears (applied every hour), and, if necessary, a third eyelid flap can be drawn over the eye to afford sustained protection.

Healing of burn sites is reported to be slower than other types of wounds. This is possibly because the full extent of the injury is not apparent from the outset; furthermore, the damaged tissue is usually slow to separate from the healthy underlying structures. Scarring is inevitable and can be either functionally limiting (e.g., the eyelids or over joints), cosmetically unacceptable, or both. Most serious burn cases have degrees of immunosuppression, which renders them liable to infection and delayed wound healing.

Healing burn sites are often pruritic, and self-inflicted damage can be severe. Suitable sedation may be required (usually acepromazine is effective) to prevent self-inflicted trauma. Cross-tying, neck cradles, or muzzles can also be useful. These measures will require extra nursing observation.

Other complications from burns include colic (usually an impaction) or laminitis. Inappetence or failure to drink are serious potential complications and must be managed early. Fresh green grass is usually a good stimulant to appetite and also provides significant water intake. Caustic burns can result in absorption of the caustic material; thus serious systemic effects may occur.