Categories
Veterinary Medicine

Bradycardia

Symptomatic bradycardia results from problems of impulse generation in the sinus node and / or its conduction from the atria to the ventricles. Both of these processes are influenced by the autonomic nervous system with the parasympathetic system slowing and the sympathetic system accelerating impulse generation and conduction.

Non-cardiac causes of bradycardia

Sinus bradycardia is often a normal finding in athletic dogs (50 bpm or below) and is rarely associated with clinical signs. Even in dogs showing signs of vague illness, such as lethargy, which demonstrate mild sinus bradycardia, use of drugs which increase the heart rate (for example atropine) does not usually improve their behaviour. Profound symptomatic bradycardia may be caused by a number of factors which do not involve organic cardiac disease, some of which are shown in site. In many cases It is an alteration in the balance between parasympithetic and sympathetic tone to the heart which results in bradycardia so that therapy with antimuscarinic drugs (particularly where vagal tone is raised) or beta-adrenoceptor agonists is indicated to increase heart rate together with supportive therapy such as intravenous fluids and warmth. It is important to consider the underlying cause before using such symptomatic therapy as it may not always be indicated. For example, use of atropine to control bradycardia following the administration of an alpha2-adrenoceptor agonist may potentiate the transient hypertension which results after administration of such drugs to dogs and cats. Administration of beta-adrenoceptor agonists to increase the heart rate in a dog with bradycardia due to digoxin toxicity would increase the potential for ventricular tachycardia to develop. Thus, where possible, specific therapy should be administered based on the diagnosis of the underlying cause. These extrinsic factors should be considered before diagnosing the cause of symptomatic bradycardia as being due to organic disease of the sinoatrial node or of the conducting pathways in the heart.

Symptomatic bradycardia associated with organic cardiac disease

Sick sinus syndrome

This term is used to describe idiopathic disorders of the sinoatrial node, where the animals show signs of intermittent sinus arrest, sinoatrial block or sinus bradycardia. The subsidiary pacemakers fail to generate adequate escape rhythms. Some cases also show intermittent supraventricular tachyarrhythmias which may contribute to the clinical signs. This is a heterogeneous and imprecisely defined group of conditions rather than a single disease. Miniature schnauzers, pugs and dachshunds have been reported as presenting with this syndrome but it has also been seen in mixed breed dogs. In the management of this condition, it is important to manage the bradycardia first before treatment of the tachycardic episodes can be undertaken safely.

Persistent atrial standstill (silent atrium)

In persistent atrial standstill the sinus node fails to generate electrical impulses and the heart rate is governed by supraventricular, functional or ventricular escape beats. This condition is rare in dogs and cats and should be distinguished from the potentially reversible sinoventricular rhythm which accompanies severe and life-threatening hyperkalaemia.

Atrioventricular block

Failure or delay in the conduction of the sinoatrial impulse may be classified as first, second (Mobitz type I and II) or third degree atrioventricular block. In some cases, heart block can be intermittent and therefore more difficult to diagnose without the use of a continuous ambulatory ECG. First degree atrioventricular block and Mobitz type 1 seconddegree atrioventricular block are common in the dog and rarely signify intrinsic disease of the conducting system. They are easily abolished following exercise or atropine administration (0,02-0.04 mg kg-1 i.m. or i.v.). Atropine may cause an initial increase in the severity of the block (by a central action) but within 10-15 min sinus rhythm results. By contrast, in the cat even low-grade heart block is an abnormal finding and warrants further investigation.

Idiopathic persistent high-grade second-degree and complete (third degree) atrioventricular block occur in middle-aged or older dogs and are often associated with clinical signs. These may consist of weakness, exercise intolerance and syncope. Idiopathic third degree atrioventricular black has been reported in the dog in association with acquired myasthenia gravis. If obvious organic heart disease can be identified, the prognosis is much worse than for idiopathic cases where no obvious pathological process can be detected. Drug toxicity (calcium channel blockers, digoxin, beta-adrenoceptor antagonists) or electrolyte disturbances (hyperkalaemia) should be ruled out as possible causes of atrioventricular block.

Medical management of symptomatic bradycardia due to organic heart disease

Pacemaker implantation is the only long-term solution to animals exhibiting high-grade second-degree or complete atrioventricular block, persistent atrial standstill, and many cases of sick sinus syndrome. In an emergency, heart rate can be best increased by using beta-adrenoceptor agonists such as isoprenaline (10 ng kg-1 mm-1) or dopamine (2-10 μg kg-1 min-1), given by continuous intravenous infusion. An oral dose rare of isoprenaline has been described (5-10 mg three to four times daily) but there is less scope for the clinician to control the effects of the drug. Dopamine is the preferred choice since it lacks the profound peripheral vasodilatation in skeletal muscle which occurs following isoprenalinc administration. Although these drugs can be life-saving in severe cases before pacemaker implantation, their use can be associated with the occurrence of ventricular tachyarrhythmias. These should be controlled by stopping the infusion of the drug and not by the administration of drugs which suppress ventricular arrhythmias (for example lignocaine) since such drugs will suppress the escape rhythms which maintain some cardiac output in these animals.

Antimuscarinic drugs often fail to increase the heart rate in animals with heart block and atrial standstill since high vagal tone is not involved in the pathogenesis of these arrhythmias- Junctional escape rhythms may sometimes increase in rate when antimuscarinic drugs are used and some dogs with sick-sinus syndrome can be managed chronically with such drugs. Test doses of atropine will demonstrate those cases where such therapy may be worth trying. Oral preparations of antimuscarinic agents include propantheline bromide (7.5-15 mg three times daily for dogs). In dogs with both bradycardia and tachycardia, administration of antimuscarinic drugs may worsen the episodes of Tachycardia as these drugs increase conduction through the atrioventricular node. In these cases, the bradycardia should be managed by the use of a pacemaker and drugs which suppress the supraventricular tachycardia can then be safely employed. The use of pacemakers to treat symptomatic bradycardias has been extensively covered by others.

Categories
Drugs

Aminopentamide Hydrogen Sulfate (Centrine)

Anticholinergic/Antispasmodic

Highlights Of Prescribing Information

Anticholinergic/antispasmodicfor GI indications in small animals

Typical adverse effect profile (“dry, hot, red”); potentially could cause tachycardia

Contraindicated in glaucoma; relatively contraindicated in tachycardias, heart disease, GI obstruction, etc.

What Is Aminopentamide Hydrogen Sulfate Used For?

The manufacturer states that the drug is indicated “in the treatment of acute abdominal visceral spasm, pylorospasm or hypertrophic gastritis and associated nausea, vomiting and/or diarrhea” for use in dogs and cats.

Pharmacology/Actions

Aminopentamide is an anticholinergic agent that when compared to atropine has been described as having a greater effect on reducing colonic contractions and less mydriatic and salivary effects. It reportedly may also reduce gastric acid secretion.

Pharmacokinetics

No information was located.

Before you take Aminopentamide Hydrogen Sulfate

Contraindications / Precautions / Warnings

The manufacturer lists glaucoma as an absolute contraindication to therapy and to use the drug cautiously, if at all, in patients with pyloric obstruction. Additionally, aminopentamide should not be used if the patient has a history of hypersensitivity to anticholinergic drugs, tachycardias secondary to thyrotoxicosis or cardiac insufficiency, myocardial ischemia, unstable cardiac status during acute hemorrhage, GI obstructive disease, paralytic ileus, severe ulcerative colitis, obstructive uropathy or myasthenia gravis (unless used to reverse adverse muscarinic effects secondary to therapy).

Antimuscarinic agents should be used with extreme caution in patients with known or suspected GI infections, or with autonomic neuropathy. Atropine or other antimuscarinic agents can decrease GI motility and prolong retention of the causative agent(s) or toxin(s) resulting in prolonged clinical signs.

Antimuscarinic agents should be used with caution in patients with hepatic disease, renal disease, hyperthyroidism, hypertension, CHF, tachyarrhythmias, prostatic hypertrophy, esophageal reflux, and in geriatric or pediatric patients.

Adverse Effects

Adverse effects resulting from aminopentamide therapy may include dry mouth, dry eyes, blurred vision, and urinary hesitancy. Urinary retention is a symptom of too high a dose and the drug should be withdrawn until resolved.

Overdosage / Acute Toxicity

No specific information was located regarding acute overdosage clinical signs or treatment for this agent. The following discussion is from the Atropine monograph that could be used as a guideline for treating overdoses:

If a recent oral ingestion, emptying of gut contents and administration of activated charcoal and saline cathartics may be warranted. Treat clinical signs supportively and symptomatically. Do not use phenothiazines as they may contribute to the anticholinergic effects. Fluid therapy and standard treatments for shock may be instituted.

The use of physostigmine is controversial and should probably be reserved for cases where the patient exhibits either extreme agitation and is at risk for injuring themselves or others, or for cases where supraventricular tachycardias and sinus tachycardias are severe or life threatening. The usual dose for physostigmine (human) is: 2 mg IV slowly (for average sized adult), if no response, may repeat every 20 minutes until reversal of toxic antimuscarinic effects or cholinergic effects takes place. The human pediatric dose is 0.02 mg/kg slow IV (repeat q10 minutes as above) and may be a reasonable choice for treatment of small animals. Physostigmine adverse effects (bronchoconstriction, bradycardia, seizures) may be treated with small doses of IV atropine.

How to use Aminopentamide Hydrogen Sulfate

Aminopentamide Hydrogen Sulfate dosage for dogs:

a) May be administered every 8-12 hours via IM, SC or oral routes. If the desired effect is not attained, the dosage maybe gradually increased up to 5 times those listed below: Animals weighing: 10 lbs or less: 0.1 mg; 11-20 lbs: 0.2 mg; 21-50 lbs: 0.3 mg; 51 -100 lbs: 0.4 mg; over 100 lbs: 0.5 mg (Package Insert; Centrine — Fort Dodge)

b) To decrease tenesmus in malabsorption/maldigestion syndromes: 0.1-0.4 mg SC, or IM twice daily-three times daily ()

c) As an antiemetic: 0.1-0.4 mg SC, or IM two to three times daily ()

Aminopentamide Hydrogen Sulfate dosage for cats:

a) As in “a” above in dogs

b) As an antiemetic: 0.1-0.4 mg SC, or IM two to three times daily ()

c) As second-line adjunctive therapy for refractory IBD: 0.1-0.4 mg/kg SC two to three times daily ()

Client Information

■ Contact veterinarian if animal has difficulty urinating or if animal is bothered by dry eyes or mouth

Chemistry / Synonyms

An antispasmodic, anticholinergic agent, aminopentamide hydrogen sulfate has a chemical name of 4-(dimethylamino)-2,2-diphenylvaleramide.

Aminopentamide hydrogen sulfate may also be known as dimevamid or Centrine.

Storage / Stability

Store aminopentamide tablets and injection at controlled room temperature (15-30°C; 59-86°F).

Dosage Forms / Regulatory Status

Veterinary-Labeled Products:

Aminopentamide Hydrogen Sulfate Tablets: 0.2 mg; Centrine (Fort Dodge); (Rx). Approved for use in dogs and cats only.

Aminopentamide Hydrogen Sulfate Injection: 0.5 mg/mL in 10 mL vials; Centrine (Fort Dodge); (Rx). Approved for use in dogs and cats only.

Human-Labeled Products: None

Categories
Drugs

Alfentanil HCL (Alfenta)

Opiate Anesthetic Adjunct

Highlights Of Prescribing Information

Injectable, potent opiate that may be useful for adjunctive anesthesia, particularly in cats

Marginal veterinary experience & little published data available to draw conclusions on appropriate usage in veterinary species

Dose-related respiratory & CNS depression are the most likely adverse effects seen

Dose may need adjustment in geriatric patients & those with liver disease

Class-ll controlled substance; relatively expensive

What Is Alfentanil HCL Used For?

An opioid analgesic, alfentanil may be useful for anesthesia, analgesia, or sedation similar to fentanyl; fentanyl is generally preferred because of the additional experience with its use in veterinary patients and cost. Alfentanil may be particularly useful in cats as adjunctive therapy during anesthesia to reduce other anesthetic (i.e., propofol or isoflurane) concentrations.

Pharmacology/Actions

Alfentanil is a potent mu opioid with the expected sedative, analgesic, and anesthetic properties. When comparing analgesic potencies after IM injection, 0.4-0.8 mg of alfentanil is equivalent to 0.1-0.2 mg of fentanyl and approximately 10 mg of morphine.

Pharmacokinetics

The pharmacokinetics of alfentanil have been studied in the dog. The drug’s steady state volume of distribution is about 0.56 L/kg, clearance is approximately 30 mL/kg/minute, and the terminal half-life is approximately 20 minutes.

In humans, onset of anesthetic action occurs within 2 minutes after intravenous dosing, and within 5 minutes of intramuscular injection. Peak effects occur approximately 15 minutes after IM injection. The drug has a volume of distribution of 0.4-1 L/kg. About 90% of the drug is bound to plasma proteins. Alfentanil is primarily metabolized in the liver to inactive metabolites that are excreted by the kidneys into the urine; only about 1% of the drug is excreted unchanged into the urine. Total body clearance in humans ranges from 1.6-17.6 mL/minute/kg. Clearance is decreased by about 50% in patients with alcoholic cirrhosis or in those that are obese. Clearance is reduced by approximately 30% in geriatric patients. Elimination half-life in humans is about 100 minutes.

Before you take Alfentanil HCL

Contraindications / Precautions / Warnings

Alfentanil is contraindicated in patients hypersensitive to opioids. Because of the drug’s potency and potential for significant adverse effects, it should only be used in situations where patient vital signs can be continuously monitored. Initial dosage reduction may be required in geriatric or debilitated patients, particularly those with diminished cardiopulmonary function.

Adverse Effects

Adverse effects are generally dose related and consistent with other opiate agonists. Respiratory depression, and CNS depression are most likely to be encountered. In humans, bradycardia that is usually responsive to anticholinergic agents can occur. Dose-related skeletal muscle rigidity is not uncommon and neuromuscular blockers are routinely used. Alfentanil has rarely been associated with asystole, hypercarbia and hypersensitivity reactions.

Respiratory or CNS depression maybe exacerbated if alfentanil is given with other drugs that can cause those effects.

Reproductive / Nursing Safety

In humans, the FDA categorizes alfentanil as a category C drug 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). If alfentanil is administered systemically to the mother close to giving birth, offspring may show behavioral alterations (hypotonia, depression) associated with opioids. Although high dosages given for 10-30 days to laboratory animals have been associated with embryotoxicity, it is unclear if this is a result of direct effects of the drug or as a result of maternal toxicity secondary to reduced food and water intake.

The effects of alfentanil on lactation or its safety for nursing offspring is not well defined, but it is unlikely to cause significant effects when used during anesthetic procedures in the mother.

Overdosage / Acute Toxicity

Intravenous, severe overdosages may cause circulatory collapse, pulmonary edema, seizures, cardiac arrest and death. Less severe overdoses may cause CNS and respiratory depression, coma, hypotension, muscle flaccidity and miosis. Treatment is a combination of supportive therapy, as necessary, and the administration of an opiate antagonist such as naloxone. Although alfentanil has a relatively rapid half-life, multiple doses of naloxone may be necessary. Because of the drug’s potency, the use of a tuberculin syringe to measure dosages less than 1 mL with a dosage calculation and measurement double-check system, are recommended.

How to use Alfentanil HCL

(Note: in very obese patients, figure dosages based upon lean body weight.)

Alfentanil HCL dosage for dogs:

As a premed:

a) 5 mcg/kg alfentanil with 0.3-0.6 mg of atropine IV 30 seconds before injecting propofol can reduce the dose of propofol needed to induce anesthesia to 2 mg/kg, but apnea may still occur. ()

As an analgesic supplement to anesthesia:

a) 2-5 mcg/kg IV q20 minutes. ()

b) For intra-operative analgesia in patients with intracranial disease: 0.2 mcg/kg/minute ()

Monitoring

■ Anesthetic and/or analgesic efficacy

■ Cardiac and respiratory rate

■ Pulse oximetry or other methods to measure blood oxygenation when used for anesthesia

Client Information

■ Alfentanil is a potent opiate that should only be used by professionals in a setting where adequate patient monitoring is available

Chemistry / Synonyms

A phenylpiperidine opioid anesthetic-analgesic related to fentanyl, alfentanil HCL occurs as a white to almost white powder. It is freely soluble in alcohol, water, chloroform or methanol. The commercially available injection has a pH of 4-6 and contains sodium chloride for isotonicity. Alfentanil is more lipid soluble than morphine, but less so than fentanyl.

Alfentanil may also be known as: alfentanyl, Alfenta, Fanaxal, Fentalim, Limifen, or Rapifen.

Storage / Stability/Compatibility

Alfentanil injection should be stored protected from light at room temperature. In concentrations of up to 80 mcg/mL, alfentanil injection has been shown to be compatible with Normal Saline, D5 in Normal Saline, D5W, and Lactated Ringers.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products: None

The ARCI (Racing Commissioners International) has designated this drug as a class 1 substance. See the appendix for more information.

Human-Labeled Products:

Alfentanil HCL for injection: 500 mcg/mL in 2 mL, 5 mL, 10 mL, and 20 mL amps; preservative free; Alfenta (Akorn); Alfentanil HCL (Abbott); (Rx, C-II).

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

Treatment Modalities

Aerosolized drugs can be used to provide both quick relief of respiratory difficulty and long-term treatment (Table Recommended Dosages for Aerosolized Medications in Horses). Quick relief can be provided by short-acting β2-adrenergic agonists or anticholinergic drugs. Long-term therapy is provided by use of antiinflammatory drugs and perhaps long-acting β2-adrenoceptor agonists.

Table Recommended Dosages for Aerosolized Medications in Horses

Class Active Ingredient Formulation Dosage Manufacturer / Brand Name Frequency
Corticosteroids fluticasone propionate 44, 110, or 220 μg/ puff 2200 μg Glaxo Wellcome / Flovent 220 Once to twice daily
beclomethasone dipropionate HFA 40-80 μg/puff 500-1500 μg 3M Pharmaceuticals / QVAR Once to twice daily
chlorofluorocarbon 42-84 M-g/puff 1500 M-g Claxo Wellcome / Beclovent Once to twice daily
Short-acting β2-agonists albuterol (Salbutamol) 90 μg/puff 450-900 μg Schering Corporation / Proventil prn; not to exceed 4x/week unless in conjunction with corticosteroid
fenoterol 0.1 mg/puff 1-3 mg Boehringer Ingelheim / Berotec prn; not to exceed 4x/week unless in conjunction with corticosteroid
Long-acting β2-agonists salmeterol 25μg 210 μg Glaxo Wellcome / Serevent Once to twice daily in conjunction with corticosteroid therapy
Mast cell stabilizers sodium cromoglycate 800 μg 8-12 mg Aventis Pharmaceuticals / Intal Once to twice daily
nedocromil sodium 1.75 mg 17.5 mg Aventis Pharmaceuticals / Tileade Once to twice daily
Parasympatholytics ipratropium bromide 20n.g 90-180 μg 3M Pharmaceuticals / Atrovent 2-4 x daily

prn, As needed.

Short-Acting Bronchodilator Drugs

β2-Adrenoceptor Agonists

Short-acting p2-adrenoceptor agonists such as albuterol and fenoterol are vitally important in treatment of acute exacerbations of RAO. The horse that is laboring to breathe and has paroxysmal coughing will experience rapid relief with the use of β2-agonists. However, these are correctly termed rescue drugs and should not be used on a regular basis. Remembering that the inflammatory condition will persist despite apparent improvement because of transient bronchodilation and that the disease may worsen if other therapy is not administered concurrently is important. Regular use of p2-agonists in the absence of antiinflammatory medication may mask clinical signs that would otherwise indicate progressive worsening of the disease — in particular, further airway obstruction with mucus.

Short-acting p2-agonists are not performance-enhancing in humans, and increasing evidence supports this finding in horses. Nonetheless, albuterol and similar drugs remain proscribed by all equine sporting events, and due care should be taken to stop drug administration before competition. Short-acting β2-agonists can be useful in horses with inflammatory airway disease and underlying airway obstruction to improve the return to training. Administration of albuterol may also increase the peripheral lung deposition of other concurrently used drugs such as corticosteroids. Short-acting bronchodilators are also useful during lung function testing to assess the reversibility of airway obstruction in horses with RAO. Most horses bronchodilate in response to 450 μg of albuterol, irrespective of the delivery device (see “Aerosolized Drug Delivery Devices”).

Although aerosolized β2-agonists have a relatively low incidence of side effects, excessive use, or even standard use in sensitive individuals may result in systemic effects such as trembling, anxiety, and cardiac arrhythmias. This author has noted these signs in individuals treated with 900 μg of albuterol, whereas other individuals tolerate a higher dose. Repeated use of the drug tends to decrease side effects as the body down-regulates receptors. Very occasionally, horses may exhibit signs of bronchoconstriction with β2-agonists. This paradoxic response is transient — probably caused by the effects of the drug vehicle on airways.

Anticholinergic Drugs

In horses, bronchoconstriction is vagally mediated; thus parasympatholytic drugs are effective in mitigating bronchospasm. Ipratropium bromide is a quaternary derivative of atropine, and this formulation results in little systemic uptake. It antagonizes the acetylcholine receptor on bronchial smooth muscle, reduces release of calcium from intracellular stores, and causes airway smooth muscle relaxation. As with any parasympatholytic drug, potential for tachycardia, thickened mucus, decreased ciliary beat frequency, and decreased mucociliary clearance exists; however, studies in horses have showed no such side effects with doses up to 1200 micrograms. The index of safety is considerably greater than systemically administered atropine. Ipratropium has a slower onset of action than does albuterol, and its actions seem to be confined primarily to the central (larger) airways rather than bronchioles. Studies in horses suggest that pulmonary function begins to improve 15 minutes after administration. Although duration of action has only been verified through 1 hour, clinical evidence suggests that horses experience relief for up to 4 to 6 hours. Although ipratropium may act as a useful adjunct to p2-agonists for a rescue treatment during exacerbations of RAO, it is not the primary treatment of choice because of its slower onset of action. In horses with adverse responses to p2-agonists, ipratropium bromide may be preferred.

Long-Term Control

Inhaled Corticosteroids

Corticosteroids remain the cornerstone of successful treatment for both inflammatory airway disease and RAO. Inhaled corticosteroids have truly revolutionized the treatment of recurrent airway obstruction and inflammatory airway disease. Although initial systemic tapered corticosteroid therapy is often necessary with all but very mild inflammatory airway disease, regular inhaled therapy is essential for long-term success in most cases. Inflammation underlies remodeling of the airways with accompanying airway hyperreactivity — or increased twitchiness of the airways — and consequent coughing and expiratory dyspnea. Bronchodilator drugs will help to relieve acute, debilitating bronchospasm, but only consistent anti-inflammatory therapy, in conjunction with avoidance of environmental triggers, will break the cycle of inflammation, airway hyperreactivity, and bronchoconstriction. This philosophy reflects the view that both inflammatory airway disease and recurrent airway obstruction are chronic diseases; although they are clinically episodic, the underlying pathology persists even when the disease appears to be quiescent. Hence consistent vigilance in countering airway inflammation is necessary. The most important factor in limiting regular use of inhaled corticosteroids is cost; drugs such as fluticasone and beclomethasone are very expensive.

The antiinflammatory effect of corticosteroids in both recurrent airway obstruction and inflammatory airway disease is impressive. Corticosteroids activate gluco-corticoid receptors, thus putting into motion a profound inhibition of the arachidonic acid cascade and limiting production of leukotrienes and other inflammatory molecules. Corticosteroids alter the transcription of genes such as inflammatory cytokines and enzymes, directly inhibit inflammatory cells, and decrease goblet cell hyperplasia. Thus they inhibit airway reactivity both by decreasing the mediators available to initiate bronchoconstriction and by preventing the development of airway thickening that geometrically enhances airway hyperreactivity. It has been shown in humans and animals that the efficacy of corticosteroids is limited with high levels of inflammation because transcription factors bind to glucocorticoid receptors, thus blocking the steroid interaction. Response to steroids can vary considerably from horse to horse.

Despite the success of systemic glucocorticoids in limiting airway inflammation, clinicians must aim to limit their use, as their side effects are both considerable and clinically important. Fluticasone propionate (FP) and beclomethasone dipropionate (BDP) are the two most potent, best studied, and most commonly used inhaled corticosteroids in both the horse and in man. They are considered second-generation drugs in that they have greater affinity for the glucocorticoid receptor, and their increased lipophilicity results in longer duration of action and less systemic absorption. In all, this greatly decreases the potential for systemic side effects and allows chronic use of these drugs. Studies in humans have shown that the longer the use of corticosteroids is delayed both in adults and in children, the worse subsequent lung function becomes. Indeed, regular use of inhaled corticosteroids in humans has been shown to be associated with a greatly reduced risk of death from acute exacerbations of asthma. As there are similarities in the nature of inflammation in horse (RAO) and human (asthma), many concepts in humans that pertain to steroid effects are worth noting.

RAO horses treated with beclomethasone dipropionate have shown both objective and subjective evidence of decreased airway obstruction as well as decreased pulmonary neutrophilia within 24 hours of initiation of therapy. Doses range from 500 micrograms to 1200 micrograms with the hydrofluoroalkane (hydrofluoroalkane-134a) formulation, which is approximately half the recommended dose when using the chlorofluorocarbon formulation (see “Aerosolized Drug Delivery Devices”). Newer formulations of beclomethasone dipropionate that incorporate hypothalamic-pituitary axis (HPA) as the propellant have more uniform particle size, are more uniformly mixed, and require little to no agitation or waiting before actuation of the inhaler. Although evidence of adrenal/hypopituitary axis (HPA) suppression (i.e., reduced serum cortisol levels) with all doses more than 500 mg exists, this does not appear to pose a risk of chronic HPA suppression or rebound Addisonian crisis. Fluticasone propionate decreases pulmonary neutrophilia, improves pulmonary function, and reduces airway hyperreactivity in RAO-affected horses. Fluticasone propionate is the most potent of the inhaled corticosteroids, has the longest pulmonary residence time, and causes the least adrenal suppression.

The general strategy pursued at the pulmonary clinic at Tufts University School of Veterinary Medicine in Med-ford, Mass., is to treat in a stepwise manner, starting with a high dose given frequently and gradually reducing therapy until the lowest effective dose can be found. If owners are vigilant in environmental control and are compliant with treatment recommendations, many horses can eventually be treated successfully on an every-other-day basis to prevent recurrences. Some owners have been successful in documenting seasonal exacerbations; in this case we recommend beginning treatment with inhaled corticosteroids — and, occasionally, mast cell inhibitors — at least two weeks before the anticipated allergen season. It is important to remember, however, that unless all stimuli for pulmonary inflammation are removed, the effect of inhaled corticosteroids is transient, and signs will return when the horse is exposed to organic dust and other allergens. Corticosteroids should not be used for quick relief or for rescue therapy because the onset of action is at least 24 hours, and several months of regular use may be necessary for optimal results. With severe inflammation, systemic corticosteroids are usually necessary to achieve breakthrough before inhaled therapy is initiated. Most horses with recurrent airway obstruction and inflammatory airway disease will require loading doses for 2 to 4 weeks of systemic steroids before reliance on aerosol medications, although trials to demonstrate the effective preventive dose are lacking.

Mast Cell Inhibitors

Mast cells are important mediators of inflammation in horses with inflammatory airway disease or RAO, with studies linking mast cells with airway reactivity, environment, and levels of inflammatory mediators in lavage (bronchoalveolar lavage) fluid. Sodium cromoglycate has had the most extensive use in horses and is one of the few aerosolized medications that has been examined in the horse. More recently, nedocromil sodium, which has a longer duration of action and appears to be more potent in humans, has been used clinically in horses. These drugs, which most likely work by inhibiting chloride channels, act to stabilize the mast cell membrane, thus blocking degranulation and inhibiting the allergic response at an early stage. Early workers showed that clinical signs were greatly attenuated and that lung function was mildly improved in horses with recurrent airway obstruction that were given sodium cromoglycate before challenge. Other studies indicate that disodium cromoglycate can decrease the amount of histamine in mast cells that are seen in the bronchoalveolar lavage of a subset of horses with inflammatory airway disease. In our hands, disodium cromoglycate and nedocromil sodium appear to be beneficial in some horses with airway hyperreactivity and increased percentages of mast cells. These drugs have a tendency to cause cough, and horses do not like them, perhaps because of a bad taste. Anecdotal evidence suggests that pretreatment with albuterol may attenuate some of the cough response.

The greatest therapeutic effect is seen when this class of drug is given as a long-term therapy and before exposure to allergens — such as before allergy season or before transporting a horse to a new environment. Understandably, this involves less customer satisfaction and consequently poorer compliance with drugs that do not have a visibly dramatic effect, such as the β2-agonists and even the potent corticosteroids.

Long-Acting β2-Agonists

Shifting paradigms about nonseptic airway disease in the horse that emphasize inflammation have also led to new approaches to treatment. Initially, this meant that β2-agonists were relegated strictly to treatment of acute exacerbations or for initial bronchodilation while systemic and inhaled steroids were taking effect. This author tended to counsel against regular use of β2-agonist drugs except in moderate to severe RAO. However, following the asthma model, the author has begun to treat selected cases of recurrent airway obstruction and moderate inflammatory airway disease with long-acting p2-agonist therapy in addition to inhaled corticosteroids, with the initial impression of enhanced performance and quality of life. It cannot be emphasized enough, however, that regular use of long-acting β2-agonists must be accompanied with regular use of inhaled corticosteroids.

Although the most obvious and important effect of β2-agonist agents is bronchodilation, they have a host of other actions that may, in conjunction with antiinflammatory therapy, actually benefit the animal with inflammation-associated airway dysfunction. β2-agonists have been found — in humans and animals — to inhibit smooth muscle proliferation; increase the force of contraction of the diaphragm and intercostals muscles; act as mild anti-inflammatories by decreasing neutrophil numbers, activity, and ability to release cytokines; protect the epithelium against microorganisms by maintaining cyclic adenosine monophosphate (cAMP) levels; improve mucociliary clearance by increasing ciliary beat frequency; and even enhance surfactant secretion. Studies in asthmatics and humans with chronic obstructive pulmonary disease indicate that the addition of long-acting β2-agonists, in conjunction with corticosteroid therapy, allow a decrease in the corticosteroid dose (which can decrease cost of treatment considerably), decrease frequency and severity of asthma exacerbations, and improve pulmonary function parameters. When long-acting B2-agonists were used regularly in asthmatic children in the absence of corticosteroid therapy, airway hyperreactivity was not reduced, and symptoms were not adequately controlled.

The most commonly used long-acting B2-agonists are salmeterol and formoterol, whose basic mechanism of action is the familiar cAMP pathway. Salmeterol has specific binding to the B2-adrenoreceptor because of its molecular modifications and repeatedly stimulates the receptor. In this way it has a long, concentration-independent duration of action. Its Iipophilicity results in slow onset of action; thus it should not be used when rapid bronchodilation is desired. Its duration of action in horses is 6 to 8 hours. Formoterol — although also lipophilic — achieves its long life by being retained as a depot and is thus concentration-dependent. Formoterol has the property of being able to reach the receptor by the aqueous phase and thus has a much more rapid onset of action than salmeterol in humans; formoterol pharmacokinetics have not been studied in horses. Although the duration of action in humans appears to be at least 12 hours, horses appear to experience maximum relief for only 6 hours.

Categories
Horses

Bronchodilators Recommended for the Treatment of Heaves

Bronchodilators are used in heaves-affected horses to relieve the obstruction of the small airways caused by airway smooth muscle contraction (see Table Medications Recommended for the Treatment of Heaves). Bronchodilator administration should be combined with strict environmental dust control and corticosteroid administration because inflammation of the lower airways may progress despite the improvement of clinical signs observed with drugs. Because of their rapid onset of action, bronchodilators are particularly helpful when immediate relief of clinical signs is required. The administration of bronchodilators to heavey horses may worsen hypoxemia, before an elevation in PaO2 values is observed. Although this rarely appears to lead to clinical problems, combining inhaled bronchodilators with intranasal O2 insufflation in horses with respiratory distress may be advisable. The agents most commonly used for bronchodilation in horses are β2-adrenergic agonists and xanthine derivatives.

Clenbuterol (Ventipulmin), a β2-adrenergic agonist, has bronchodilator effects and increases mucociliary transport. Side effects such as tachycardia and sweating rarely are seen with lower oral doses but are more frequent with intravenous administration. The clinical efficacy of clenbuterol at the lower recommended dosage (0.8 μg/kg q12h) in horses with heaves is inconsistent, if exposure to dusty hay and bedding is maintained. With higher dosages (up to 3.2 fig/kg) the efficacy of clenbuterol improves, but so does the frequency and severity of the side effects. Fenoterol, albuterol, pirbuterol, and salmeterol are other p2-agonist agents with potent bronchodilator effects that can be administered by inhalation. With inhaled β2-agonist agents, bronchodilation is rapid and side effects are minimal but, with the exception of salmeterol, beneficial effects are short lived and therefore require frequent drug administration.

Because of their potentially severe side effects, anti-cholinergic drugs generally are not administered systemically for the treatment of heaves. Ipratropium bromide can be administered safely by aerosol, but its effects are short lived. The use of sympathomimetic agents such as ephedrine, which stimulate both a and p receptors, has decreased because of the availability of more specific β2-adrenergic agonists.

Aminophylline (Cyanamid) and pentoxifylline are methylxanthine derivatives with nonspecific phosphodiesterase inhibitory properties. Phosphodiesterase (PDE) is a family of enzymes that catalyzes the hydrolysis of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) and thereby terminates their role as second messengers in mediating cellular responses to various hormones and neurotransmitters. Activation of cAMP PDE may be a common mechanism to facilitate proinflammatory effects of cytokines and other proliferative agents. Aminophylline is used primarily as a bronchodilator in horses, but it also enhances mucociliary clearance, respiratory drive, and contractility of the diaphragm and modulates immune function. Side effects such as excitability, tachycardia, muscular tremors, and sweating are commonly observed. Because of their low therapeutic index, the use of aminophylline and other salts of theophylline are commonly preferred.

Pentoxifylline currently is approved in some countries for the treatment for navicular disease in horses. It also has bronchodilating properties, inhibits neutrophil recruitment to inflammatory sites, and at high concentration is a potent inhibitor of tumor necrosis factor (TNF)-α production. High dosage of pentoxifylline (16 g/horse, q12h) has been shown to be as beneficial as atropine for the relief of airway obstruction. However, oral absorption is variable and the efficacy of more practical lower dosages should be assessed.

Selective PDE inhibitors, particularly of the PDE4 subtypes, have been studied for the treatment of lower inflammatory airway diseases in people owing to the expression of PDE4 in airway smooth muscle, pulmonary nerves, and almost all inflammatory and immune cells relevant to the pathogenesis of asthma. A selective PDE4 inhibitor is effective at inhibiting the ex vivo production of inflammatory mediators by equine leukocytes but fails to be effective for the treatment of horses affected with heaves.

Of the various mediators known to be involved in lung inflammatory diseases, leukotrienes are considered to be among the most important. Leukotrienes are metabolites of the arachidonic acid produced via the 5-lipoxygenase (5-LO) enzyme and its essential cofactor, the 5 lipoxygen-ase-activating-proteins (FLAP). Cysteinyl leukotrienes (LTC4, LTD4, LTE4) are potent bronchoconstrictors that also increase the airway vascular permeability and mucus production. However, inhibition of leukotriene synthesis or antagonists of LTD4 receptors is not effective for the treatment of heaves.

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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.

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Diseases

Positive Inotropes

Agents capable of increasing cardiac contractility can improve a patient’s strength and exercise capacity, thereby potentially enhancing the pet’s quality of life. Ideally, these compounds would concurrently promote mortality benefits by improving cardiac efficiency and limiting the activation of endogenous compensatory mechanisms (with their detrimental long-term consequences). Unfortunately, to date most of the potent agents available to augment systolic function act by means of “upstream,” cAMP-dependent mechanisms that have shown negative effects on survival.

Membrane-associated adenylate cyclase is the enzyme responsible for cyclic adenosine monophosphate production, and phosphodiesterase III is responsible for its degradation. Therefore mechanisms to increase cyclic adenosine monophosphate concentrations may take one of two pathways: beta agonists increase production of cAMP, and phosphodiesterase inhibitors increase cytosolic cyclic adenosine monophosphate by inhibiting its breakdown. Acting through protein kinase A, cyclic adenosine monophosphate promotes phosphorylation of the L-type calcium channel to increase calcium release from the sarcoplasmic reticulum (SR). The increased systolic Ca2+ concentration (1) deinhibits the troponin complex to promote actin and myosin interaction and (2) increases the activity of myosin ATPase. These mechanisms serve to increase both the total force developed and the rate at which the force is developed. Protein kinase A also exerts beneficial lusitropic effects by promoting phosphorylation of (1) the regulatory SR membrane phosphoprotein, phospholamban, to enhance diastolic calcium uptake and (2) troponin I, to increase the rate of cross-bridge detachment and relaxation. Paradoxically, despite these beneficial properties, long-term administration of agents capable of increasing cyclic adenosine monophosphate has been linked to increased mortality rates in patients with heart failure. The increased Ca2+ concentrations are believed to contribute to the development of arrhythmias and to increase myocardial energy consumption and oxygen demand, thereby worsening the outcome. These findings lend support to the premise that downregulation and uncoupling of beta receptors, along with upregulation of adenylate cyclase inhibitory proteins, serve as compensatory protective mechanisms rather than primary biochemical abnormalities. Current investigations are evaluating agents capable of enhancing systolic performance “downstream” from cytosolic Ca2+ in the hopes of avoiding excessive mortality.

Digitalis glycosides The digitalis glycosides are the only readily available class of inotropic agents that act independendy of the cyclic adenosine monophosphate second-messenger system. This characteristic imparts a degree of safety to the glycosides, with regard to their neutral effect on mortality, but simultaneously limits their inotropic potency. Because of digoxin’s potential positive inotropic effects and rate-controlling properties for atrial fibrillation, there is litde debate that it is indicated in the treatment of dilated cardiomyopathy; however, there is substantial debate over its role in the management of mitral valve insufficiency. The authors’ rationale for the use of digoxin (0.003 mg/kg given orally twice daily) in dogs with mitral valve insufficiency is primarily its neurohormonal antagonism effect rather than pump support. Inhibition of the Na+/K+ ATPase pump in the vagal afferents sensitizes the baroreceptors to the prevailing blood pressure, which may decrease sympathetic outflow and renin-angiotensin activity. Although the findings are purely anecdotal, the authors have had and continue to have cases in which the addition of digoxin to background therapy of furosemide and enalapril has produced clear symptomatic improvement.

The cardiac glycosides inhibit the action of the Na+/K+ ATPase pump by competitively binding to the extracellular potassium site. This antagonism promotes an increase in the intracellular sodium concentration, with its subsequent exchange for calcium via the reversible Na+/Ca2+ pump. The net result is an increase in cytosolic calcium levels and enhanced cardiac contractility. Inhibition of the Na+/K+ ATPase pump further sensitizes the baroreceptors (blunting sympathetic discharge), inhibits renal tubular resorption of sodium (promoting mild diuresis), and increases the delivery of sodium to the distal tubules (inhibiting renin release).

Despite these theoretical benefits, digitalis has been unable to alter the natural course of heart failure. The Digitalis Investigation Group (DIG) enrolled 6800 human patients in a placebo-controlled study to evaluate whether digoxin administration affected mortality or morbidity. Digoxin did not reduce overall mortality but did reduce the rate of hospitalization for worsening heart failure (26.8% versus 34.7%, P < 0.001). Subgroup analysis revealed that patients in class III or class IV heart failure showed the greatest benefit from digoxin administration. Compared with results from agents not related to glycosides, including dobutamine and milrinone, the findings of this investigation did not demonstrate excess mortality. It is unlikely that a similar study evaluating the efficacy of digoxin will ever be performed in dogs because of the extreme sample size needed to detect these small differences. One study reported that four of 10 dogs with dilated cardiomyopathy showed echocardiographically identifiable improvements in cardiac contractility after treatment with digoxin. Whether the 7% increase in fractional shortening was a true increase in contractility or merely occurred subsequent to rate control (250 beats per minute (bpm] pretreatment versus 145 bpm post-treatment) is uncertain, but digoxin appears to be a relatively weak inotropic agent in dogs with heart failure. Nonetheless, it is the only oral inotropic agent that is readily available in the United States.

Therapeutic levels of digitalis increase parasympathetic tone, while blunting sympathetic activation, to promote slowing of the sinus node and increased atrioventricular (AV) node refractoriness with decreased conduction velocity. This property makes them useful in the management of dilated cardiomyopathy complicated by atrial fibrillation, because the other negative chronotropes (e.g., beta blockers, Ca2+ channel Mockers) acutely depress systolic function. Digitalis is further indicated for the management of symptomatic dilated cardiomyopathy with sinus rhythm or left to right shunting lesions complicated by myocardial failure. Although digoxin is not always considered a mainstay of therapy for the management of mitral insufficiency, the authors continue to use it in cases of heart failure subsequent to chronic degenerative valve disease (CDVD). Although some of these mitral insufficiency patients fail to attain symptomatic benefit from digoxin therapy, the drug’s low cost and safety when used appropriately continue to make it a useful agent. Digoxin is an inappropriate agent to use for rate control in cases of hyper-trophic cardiomyopathy in which the primary abnormality is diastolic rather than systolic dysfunction. Any positive inotropic response predisposes HCM patients to the development or worsening of systolic anterior motion of the mitral valve.

Digoxin Digoxin is the digitalis glycoside most commonly used in dogs, and it appears to be the most suitable glycoside for cats with systolic dysfunction. The bioavailability of digoxin after oral administration of the tablet form is approximately 60%. The digoxin elixir shows better bioavailability after oral administration (about 75%) and is easier to dose appropriately for small dogs. After absorption, digoxin has a relatively long and variable serum half-life in dogs, with reports ranging from 23 to 39 hours. In cats the duration is even more uncertain, with reports of mean half-lives ranging from 33.5 hours to 57.8 hours, with even longer half-lives during prolonged administration. Because approximately five half-lives are required to attain steady-state concentrations of a drug, digoxin cannot be expected to produce rapid symptomatic or rate-controlling benefits. Digoxin predominately undergoes renal excretion, although a small amount (approximately 15%) is metabolized by the liver. Renal failure significantly reduces the clearance of digoxin and profoundly increases the serum concentration, often to the point of intoxication. Patients with renal failure that require a cardiac glycoside should be given digitoxin because it undergoes hepatic elimination.

Determining the appropriate dose of digoxin to attain therapeutic levels yet avoid digitalis intoxication can be a frustrating endeavor. Traditionally, small dogs (less than 20 kg) have been treated with 0.005 to 0.008 mg/kg given orally twice daily, and larger dogs have been treated based on body surface area, with 0.22 mg/m given orally twice daily. The intent with these doses was to attain a therapeutic digoxin level of 1 to 2 µg/mL. The DIG trial found that human mortality varied direcdy with serum digoxin levels, even within this “therapeutic” range. A new trend has emerged from that data whereby the human medical profession has aimed to keep trough levels of digoxin at 0.5 to 1 µg/ml. Whether these recommendations hold true for dogs is uncertain, but aiming for the low end of the reference range appears to be appropriate. The authors currently institute digoxin therapy at a dosage of 0.003 mg/kg given orally twice daily. If the digoxin level is subtherapeutic 5 to 7 days after initiation of therapy, the dosage is increased by 25%, and the serum level is rechecked a week later. This regimen is continued until therapeutic levels have been attained.

A number of factors may influence the distribution of digoxin, creating a need for special consideration and monitoring. The principal reservoir for digoxin is skeletal muscle, therefore dosing recommendations should be based on lean body mass. Obese dogs require lower doses of digoxin than thin dogs, and the dosing requirement for dogs that experience marked muscle loss tends to decline. Patients with right-sided heart failure and large volumes of ascites need dosage reductions because digoxin does not distribute into free abdominal fluid. After institution of digoxin therapy, it is most appropriate to alter the dosing scheme based on the serum digoxin level, the response to therapy, and evidence of intoxication.

A number of drug interactions also are possible with digoxin. The best recognized interaction is between digoxin and the class la antiarrhythmic quinidine. When these drugs are combined, serum digoxin levels increase because quinidine displaces digoxin from the Na+/K+ ATPase pump and reduces its renal clearance through inhibition of P-glycoprotein.The binding of digoxin with myocardial Na+/K+ ATPase is “tighter” than that with skeletal muscle, therefore the net effect of this drug combination is an increase in the likelihood of digitalis intoxication. It is recommended that these agents not be used together. Fortunately, no interactions have been reported between digoxin and the more frequently used class I anti-arrhythmics procainamide and mexiletine. Most of the other reported drug interactions, with amiodarone, verapamil, nifedipine, propafenone and, to a lesser extent diltiazem, occur because of inhibition of P-glycoprotein. Any agent that alters renal blood flow or hepatic microsomal enzymes has the potential to disturb digoxin’s pharmacokinetics.

Similar to quinidine, the extracellular potassium concentration can influence digoxin binding to the Na+/K+ ATPase pump. The hypokalemia often associated with anorexia or large doses of a diuretic leaves more receptors exposed for digoxin attachment, thereby increasing the likelihood of digitalis intoxication. With hyperkalemia, more receptors are bound, and digoxin is displaced from the Na+/K+ ATPase. Hypercalcemia and hypernatremia promote digoxin’s inotropic and toxic properties, whereas decreased calcium and sodium concentrations have the opposite effects.

Since it was recognized that taurine deficiency was responsible for most cases of feline DCM, the number of cats receiving digoxin has declined over the past decade. The authors still encounter an infrequent case of dilated cardiomyopathy unrelated to taurine deficiency, and some cases of restrictive cardiomyopathy have such poor systolic function that digoxin is indicated. Cats appear to tolerate the tablet form of digoxin better than the alcohol-based elixir. The recommended dose is one fourth of a 0.125 mg tablet given orally. Dosing intervals are as follows: (1) cats weighing 3 kg or less: every 48 hours; (2) cats weighing 4 to 5 kg: every 24 to 48 hours; (3) cats weighing 6 kg or greater: every 24 hours. Because of the variable half-life of digoxin in cats, the authors typically monitor serum levels 7 to 10 days after initiation of therapy.

Digitalis toxicity Without a doubt, digoxin is a toxic substance when excessive amounts accumulate. This narrow therapeutic index highlights the need for careful client and veterinary attention when digoxin is part of a treatment regimen. In the authors’ experience, when digoxin therapy is instituted at a dosage of 0.003 mg/kg given orally twice daily, with uptitration based on serum digoxin concentrations, the incidence of digitalis toxicity is low both clinically and biochemically.

Clients should be informed of the most common manifestations of digoxin intoxication and given concise instructions on what to do if clinical signs develop. Continuing drug administration and waiting until the next recheck is not an appropriate step; the authors recommend discontinuation of all drugs followed by an immediate veterinary evaluation. It should be emphasized that the three regions frequently affected by excessive digoxin accumulation are the myocardial, gastrointestinal, and central nervous systems. Gastrointestinal manifestations, which often precede central nervous system (CNS) and myocardial toxicity, commonly include anorexia and vomiting, presumably from a direct chemoreceptor triggering effect exerted by digoxin. The serum concentration at which gastrointestinal signs develop is extremely variable. Some dogs have digoxin-associated anorexia at subtherapeutic drug concentrations, whereas others do not show any evidence of toxicity even with serum concentrations well above the therapeutic range. It can be difficult to determine whether the anorexia is associated with digoxin administration, azotemia secondary to a decreased glomerular filtration rate or renal insufficiency, poor diet palatability, or worsening heart failure. A biochemical profile, serum digoxin determination, and thoracic radiographs should be obtained in any digoxin-treated dog with heart failure that suddenly develops anorexia. In the absence of complicating factors such as azotemia or pulmonary edema, the authors temporarily discontinue digoxin administration even if the serum level is within the therapeutic range. If the pet’s appetite returns (suggesting digoxin-associated anorexia), a lower digoxin dose may be instituted or the drug may be discontinued all together. Digoxin does not provide enough mortality benefit or positive inotropic response to warrant administration in the face of profound anorexia or other complications.

Although the myocardial complications may be more difficult for owners to recognize, they often are the most serious. Digoxin toxicity may induce almost every known cardiac arrhythmia, including both bradyarrhythmias and tachyarrhythmias. First- and second-degree AV block, sinus bradycardia, and sinus arrest are presumably influenced by digoxin’s parasympathomimetic properties. Life-threatening ventricular tachyarrhythmias may develop as a consequence of cellular calcium overload. Excessive calcium precipitates late afterdepolarizations, whereby oscillations within the diastolic membrane potential periodically reach threshold and produce a premature complex. The slowed conduction and altered refractory period may then precipitate re-entry, yielding ventricular tachycardia. Obviously, determining whether the ventricular arrhythmia is associated with digoxin administration or is a manifestation of the underlying disease process may be difficult, but in general, discontinuation of digitalis is indicated.

The central nervous system alterations mediated by digoxin toxicity may include depression, disorientation, or delirium. Again, determining whether such clinical signs are attributable to digitalis intoxication or progression of the underlying disease process often is difficult. These patients should be evaluated for hypotension, in addition to having their serum digoxin levels measured.

Treatment of digitalis toxicity The aggressiveness with which digoxin toxicity is treated depends on the manifestation of intoxication rather than the serum digoxin level. Gastrointestinal disturbances can frequendy be managed by discontinuation of the drug. Dogs with bradyarrhythmias are often asymptomatic, and withdrawal of digoxin is the only therapeutic alteration required. In the rare case of symptomatic patients, short-term administration of atropine may be required while the toxic digoxin concentrations expire. The most aggressively managed complication of digitalis intoxication is ventricular tachyarrhythmias.

The class Ib antiarrhythmic drug lidocaine is the first-choice agent for acute management of digitalis-induced ventricular tachycardia. It is effective at targeting late afterdepolarizations without substantially affecting the sinus rate or AV nodal conduction. An initial bolus of 2 to 4 mg/kg is administered intravenously over 1 to 2 minutes, followed by a constant-rate infusion to suppress the arrhythmias. Lidocaine should be administered conservatively to cats because they are more sensitive to the neurotoxic side effects. Although infrequently used, phenytoin also appears efficacious for the treatment of digoxin-induced arrhythmias.

Because hypokalemia may precipitate digoxin toxicity and limit the efficacy of antiarrhythmic agents, it is important to evaluate the serum potassium concentration and to correct underlying deficits. Because of its ability to bind competitively the Na+/K+ ATPase pump, potassium can displace digoxin from the myocardium, thereby decreasing the likelihood of toxicity.

The development of a specific antibody fragment for cardiac glycosides has enabled production of an “antidote” for severe digoxin intoxication. Digibind® (GlaxoSmith Kline, Durham NC) complexes with the digoxin molecule and inhibits binding to the Na+/K+ ATPase pump, quickly resolving drug intoxication. Unfortunately, this drug is expensive, and its use in clinical practice therefore is limited.

Categories
Veterinary Medicine

Aspects Of Chemical Restraint

Chemical restraint is often necessary in reptile medicine to facilitate procedures from simply extracting the head of a leopard tortoise or box turtle, to enable a jugular blood sample to be performed, to coeliotomy procedures such as surgical correction of egg-binding.

Before any anesthetic / sedative is administered, an assessment of the reptile patient’s health is necessary. Is sedation / anesthesia necessary for the procedure required? Is the reptile suffering from respiratory disease or septicaemia, i.e. is the reptile’s health likely to be made worse by sedation / anesthesia?

Before any attempt to administer chemical restraint the reptilian respiratory system should be understood.

Overview of reptilian anatomy and physiology relevant to anesthesia

The reptilian patient has a number of variations from the basic mammalian anatomical and physiological systems. Starting rostrally:

(1) Reduced larynx: The reptile patient does have a glottis similar to the avian patient, which lies at the base of the tongue, more rostrally in snakes and lizards and more caudally in Chelonia. At rest the glottis is permanently closed, opening briefly during inspiration and expiration. In crocodiles the glottis is obscured by the basihyal valve which is a fold of the epiglottis that has to be deflected before they can be intubated.

(2) The trachea varies between orders: The Chelonia and Crocodylia have complete cartilaginous rings similar to the avian patient, with the Chelonia patient having a very short trachea, bifurcating into two bronchi in the neck in some species. Serpentes and Sauria have incomplete rings such as is found in the cat and dog, with Serpentes species having a very long trachea. Many Serpentes species have a tracheal lung – an outpouching from the trachea as a form of air sac.

(3) The lungs of Serpentes and saurian species are simple and elastic in nature. The left lung of most Serpentes species is absent or vestigial but may be present in the case of members of the Boid family (boa constrictors etc.). The right lung of Serpentes species ends in an air sac. Chelonia species have a more complicated lung structure, and the paired lungs sit dorsally inside the carapace of the shell. Crocodylia have lungs not dissimilar to mammalian ones and they are paired.

(4) No reptile has a diaphragm: Crocodylia species have a pseudodiaphragm, which changes position with the movements of the liver and gut, so pushing air in and out of the lungs.

(5) Most reptiles use intercostal muscles to move the ribcage in and out, as with birds: The exception being the Chelonia. These species require movement of their limbs and head into and out of the shell in order to bring air into and out of the lungs. This is important when they are anesthetised as such movements, and therefore breathing, cease.

(6) Some species can survive in oxygen-deprived atmospheres for prolonged periods: Chelonia species may survive for 24 hours or more and even green iguanas may survive for 4-5 hours, making inhalation induction of anesthesia almost impossible in these animals.

(7) Reptiles have a renal portal blood circulation system: This means that the blood from the caudal half of the body can pass through the kidney structure before passing into the caudal major veins and entering the heart. Therefore, if drugs that are excreted by the kidneys are injected into the caudal half of the body, then they may be excreted before they have a chance to work systemically (e.g. ketamine). In addition, if a drug is nephrotoxic (e.g. the aminoglycosides) then injection into the caudal half of the body may increase the risk of renal damage.

Pre-anesthetic preparation

Blood testing

It is useful to test biochemical and haemocytological parameters prior to administering chemical immobilising drugs. Blood samples may be taken from the jugular vein or dorsal tail vein in Chelonia, the ventral tail vein, palatine vein or by cardiac puncture in Serpentes and the ventral tail vein in Crocodylia and Sauria. Minimal testing advised is a haematocrit, blood calcium levels, blood total protein levels, aspartate transaminase (AST) levels for hepatic function and uric acid levels for renal function.

Fasting

This is necessary prior to anesthesia in Serpentes (for a period of 2 days in small snakes up to 1-2 weeks for the larger pythons) to prevent regurgitation and pressure on the lungs / heart. Chelonia rarely regurgitate and do not need prolonged fasting. It is important not to feed live prey to insectivores (e.g. leopard geckos) within 24 hours of anesthesia as the prey may still be alive when the reptile is anesthetised!

Pre-anesthetic medications

Antimuscarinic drugs

Atropine (0.01-0.04mg / kg intramuscularly (IM)) or glycopyrrolate (0.01 mg / kg IM) can reduce oral secretions and prevent bradycardia. However, these problems are rarely of concern in reptiles.

Benzodiazepines

Midazolam has been used in red-eared terrapins at 1.5 mg / kg as a premedicant and produced adequate sedation to allow minor procedures and induction of anesthesia.

Tranquillisers

Acepromazine (0.1-0.5 mg / kg intramuscularly (IM)) may be given 1 hour before induction of anesthesia to reduce the dose of induction agent required. Diazepam (0.22-0.62mg / kg IM in alligators) and midazolam (2mg / kg IM in turtles) are also useful.

Alpha-2 adrenoceptor agonists

Xylazine can be used 30 minutes prior to ketamine at 1 mg / kg in Crocodylia to reduce the dose of ketamine required. Medetomidine may be used at doses of 100-150 μ.g / kg, also reducing the required dose of ketamine in Chelonia, and it has the advantage of being reversible with atipamezole at 500-750 µg / kg.

Opioids

Butorphanol (0.4mg / kg intramuscularly (IM)), can be administered 20 minutes before anesthesia, providing analgesia and reducing the dose of induction agent required. It may be combined with midazolam at 2mg / kg.

Induction of Anesthesia

Maintenance of anesthesia with injectable agents

Ketamine

This may be used on its own for anesthesia at doses of 55-88 mg / kg intramuscularly (IM). As the dose increases, so the recovery time also increases, in some instances to several days; doses above 110 mg / kg will cause respiratory arrest and bradycardia.

Ketamine may be combined with other injectable agents to provide surgical anesthesia.

Suitable agents include: midazolam at 2 mg / kg intramuscularly (IM) with 40 mg / kg ketamine in turtles; xylazine at 1 mg / kg IM, given 30min prior to 20mg / kg ketamine in large crocodiles and medetomidine at 0.1mg / kg IM with 50mg / kg ketamine in king snakes.

Ketamine at 5mg / kg has been combined with medetomidine at 0.1mg / kg intravenously (IV) to produce a short period of anesthesia in gopher tortoises although some hypoxia was observed and supplemental oxygen is advised.

Propofol

Propofol may be used to give 20-30 min of anesthesia, which may allow minor procedures. It may be topped up at 1 mg / kg / min IV or intraosseously. Apnoea is extremely common and intubation and ventilation with 100% oxygen are advised.

Maintenance of anesthesia with inhalational agents

Maintaining Anesthesia

Categories
Veterinary Medicine

Esophageal Disorders

1. What is the most common clinical sign of an esophageal disorder?

Regurgitation.

2. What is the difference between regurgitation and reflux?

Regurgitation refers to passive, retrograde movement of ingested material to a level proximal to the upper esophageal sphincter; usually this material has not reached the stomach. In most cases, regurgitation results from abnormal esophageal peristalsis, esophageal obstruction, or asynchronous function of the gastroesophageal junction.

Reflux refers to the movement of gastric and duodenal contents into the esophagus without associated eructation or vomiting.

3. List the causes of regurgitation.

1. Megaesophagus

• Idiopathic

• Secondary

  • Myasthenia gravis
  • Polyneuropathy
  • Systemic lupus erythematosus
  • Polymyositis
  • Toxicosis (lead, thallium)
  • Hypothyroidism
  • Hypoadrenocorticism

2. Esophageal foreign body

3. Esophageal stricture

• Intraluminal stricture

• Extraluminal stricture due to compression

  • Abscess
  • Cranial mediastinal mass
  • Thoracic hilar lymphadenopathy

4. Vascular ring anomaly

5. Neoplasia (primary or metastatic)

6. Granuloma (e.g., Spirocerca lupi)

7. Hiatal hernia

8. Esophageal diverticula

4. What is megaesophagus?

Megaesophagus is a specific syndrome characterized by a dilated, hypoperistaltic esophagus.

5. What is the most common complication of megaesophagus?

Aspiration pneumonitis.

6. Does esophageal dilatation on thoracic radiographs confirm an esophageal disorder?

No. The following conditions often produce transient dilatation of the esophagus:

• Aerophagia

• Anxiety

• Respiratory distress (dyspnea)

• Anesthesia

• Vomiting

7. How is esophageal motility evaluated?

Thoracic radiography initially evaluates for evidence of an esophageal foreign body, esophageal dilatation, or thoracic mass. Ideally a barium esophagogram with fluoroscopy should be performed. It is best to mix food with the barium to observe for decreased contractility.

8. What is myasthenia gravis?

Myasthenia gravis is an immune-mediated disorder, either acquired or congenital (familial), resulting from the action of autoantibodies against nicotinic acetylcholine receptors at the neuro-muscular junctions.

9. What are the most common clinical signs of myasthenia gravis?

• Premature fatigue with exercise

• Spastic pelvic limb gait

• Tetraparesis

• Collapse

• Tachypnea

• Respiratory distress

• Sialosis

• Regurgitation

• Dysphagia

• Weakness of facial muscles

• Decreased palpebral reflex

10. What is the test of choice for myasthenia gravis?

Acetylcholine receptor antibody titers (> 0/6 nM/L) in dogs. Antibodies are detectable in 80-90% of dogs with acquired disease.

11. What other tests can be used for myasthenia gravis?

• Edrophonium response test. Edrophonium (0.1-0.2 mg/kg IV) results in dramatic improvement in gait for 1-2 minutes in many but not all animals. Pretreatment with atropine (0.02 mg/kg IV) decreases salivation, defecation, urination, bronchosecretion, and bronchoconstriction. Oxygen and an endotracheal tube should be readily available.

• Ten percent or greater decremental response to the fourth or fifth compound action potential recorded from the interosseous muscle after repetitive stimulation of the tibia or ulnar nerve at 3 Hz.

• Increase in jitter on single-fiber electromyography.

• Intercostal muscle biopsy identifying acetylcholine receptor antibodies at the neuromuscular junction.

12. Describe the typical profile of a dog with myasthenia gravis.

• Breeds most commonly affected: golden retriever, German shepherd

• Bimodal age of onset: 2-4 years and 9-13 years

13. How is myasthenia gravis treated?

1. Anticholinesterase drugs — neostigmine

• Injectable (Prostigmin [Roche]): 0.02 mg/lb IM every 6 hr

• Oral (Mestinon [Roche]): 0.25-0.45 mg/lb every 8-12 hr

2. Corticosteroids

14. Describe the principles for management of megaesophagus.

1. Remove the cause if possible.

2. Minimize chances for aspiration of esophageal contents. (Feed the animal in an upright position so that the upper body is elevated to at least 45° above the lower body. Maintain this position for at least 10 minutes after eating and before bedtime.)

3. Maximize nutrient intake to the GI tract (if possible, feed 2-4 times/day).

15. What is an alternative means of feeding dogs with megaesophagus?

Gastrostomy tube.

16. What is the prognosis for a dog with megaesophagus?

Guarded to poor.

17. List causes of esophageal stricture in dogs.

• Esophagitis

• Reflux of gastric acid during general anesthesia (on a tilted operating table)

• Ingestion of a strong acid or alkali material

• Esophageal foreign bodies

• Thermal burns

• Hairballs (cats)

18. How is esophageal stricture diagnosed?

Esophageal stricture is diagnosed by barium esophagogram and esophageal endoscopy.

19. List the treatment options for esophageal stricture and the success rate for each.

• Surgery (esophagotomy, patch grafting, resection and anastomosis): < 50% success

• Esophageal bougienage: 50-70% success

• Balloon catheter dilatation: > 50-70% success (treatment of choice, ideally done under fluoroscopy)

20. What are the most common areas of the esophagus in which foreign bodies lodge?

• Thoracic inlet

• Hiatus of the diaphragm

• Base of the heart

21. How do you manage dogs with an esophageal foreign body?

Esophageal foreign bodies are considered an emergency. The following steps are recommended:

1. Endoscopic removal of the foreign body is usually successful. Either extract the foreign body or carefully push it into the stomach. If the foreign body is a bone, it is often best to push it into the stomach. Gastrostomy is not usually required for removal of the bone, but serial radiography should be done to ensure digestion or passage of the bone.

2. If esophagoscopy is unsuccessful, surgical removal is required.

3. Assess the esophageal mucosa for hemorrhage, erosions, lacerations, or perforations.

4. Withhold food and water for 24-48 hours, and give crystalloid fluids and parenteral antibiotics.

22. What treatments are available for esophageal reflux?

Metoclopramide (Reglan) increases gastroesophageal sphincter tone and decreases gastric reflux into the stomach.

H2 receptor-blocking agents (e.g., cimetidine or ranitidine) reduce the acidity of refluxed gastric contents.

Sucralfate suspension is an aluminum salt that selectively binds to injured gastroesophageal mucosa and acts as an effective barrier against the damaging actions of gastric acid, pepsin, and bile acids associated with reflux esophagitis.