Diseases of the Nose and Nasal Sinuses

Functional Considerations

Functional Anatomy

The nose has four main functions: (1) to provide a portal through which air can flow to reach the alveoli, (2) to modify or regulate the flow of air, (3) to facilitate water and heat exchange (e.g. to condition the inspired air), and (4) to pass inspired air over the olfactory epithelium — the sheet of neurons and supporting cells that lines the nasal cavities. Speculation exists regarding the functions of the nasal sinuses. It seems plausible that the frontal sinuses protect the rostral portions of the brain from frontal trauma.

The apical portion of the nose, consisting of hairless integument and the nostrils, is called the nasal plane. It is supported by cartilage, which also supports the portion of the nose between the nasal plane and the bony portion.The levator nasolabial and levator labii superior muscles can move the cartilaginous parts. Dilation of the nostrils changes the pattern of flow of inspired air. The nostrils are dilated when increased airflow is needed, as in dyspnea, and to aid sampling of interesting odors.

The bony case of the nose is the facial portion of the respiratory passageway. The nasal cavity, comprised of bony and cartilaginous parts, extends from the nostrils to the choanae, being divided into right and left halves by the nasal septum. Each half of the nasal cavity has a respiratory and an olfactory region. The nasal conchae — slighdy ossified scrolls covered by nasal mucosa — fill the nasal cavities. Together with the nasal glands, the nasal mucosa has a role in conditioning the inspired air. During normal inspiration, the respiratory and olfactory air currents are concurrent. When the dog or cat wants to sample environmental odors, the nostrils are dilated and forced inspiration occurs in which a greater volume of inspired air takes a more dorsal course around the ethmoturbinates, where the olfactory receptors are most numerous.

Regulation and Conditioning of the Inspiratory and Expiratory Airflow

The respiratory airflow through the nasal cavity is regulated by the ventilatory control systems. The nose represents an important part of the resistance of the airway and thereby influences gas exchange in the alveoli. The resistance has to be overcome by greater negative pressure in the thorax during inspiration, which leads to better expanding and filling of the alveoli by the inspired air and a greater venous blood flow in the lungs. In humans, a prolonged increase in nasal resistance due to severe obstruction can lead to cor pulmonale, cardiomegaly, and pulmonary edema. In dogs, pulmonary edema is known to develop in laryngeal obstruction. Pulmonary edema may occur by a similar mechanism when severe obstruction of nasal airflow exists. The most common consequence of increased resistance is, however, mouth breathing.

Heating, or cooling of inspired and expired air as it passes through the nose is largely accomplished by radiation from the mucosal blood vessels. The flow of blood is from posterior to anterior, opposite to the flow of the inspired air. Humidification occurs by evaporation from the blanket of mucus covering the mucosa and the serous fluid from the nasal glands. Trie nasal blood flow and the activity of the nasal glands are regulated by the autonomic nervous system. The autonomic innerva-tion of the nose consists of parasympathetic and sympathetic nerve fibers, joined together in the vidian nerve. The conditioning of the inspired air by the nose is an important function for protection of the alveoli. Even under extremely dry or cold conditions, the bronchi receive air warmed to body temperature with a humidity of around 98%.

Mucosal Cleaning

The pseudostratified respiratory mucosa in the nose consists of ciliated, intermediate, basal, and goblet cells. They rest on a well-defined basement membrane supported by a deep, loose lamina propria containing small blood vessels, venous plexus, and ducts of mucous and serous glands, sensory nerves, and blood cells. The tall ciliated cell is the predominant type, and it extends from the basement membrane to the luminal surface, where cilia admixed with microvilli are found. The cilia actively move the overlying blanket of mucus by a to-and-fro movement, called the ciliary beat. A more forceful forward movement and a less forceful recovery beat occurs. The forward movement transports the mucus blanket toward the pharyngeal end of the esophagus. The two-layer mucous blanket is sticky, tenacious, and adhesive. The outer layer is more viscid than the deeper, periciliary layer. Insoluble particles, allergens, and bacteria caught on the outer layer are thus carried to the esophagus. Soluble material reaches the periciliary layer and is absorbed. Sneezing starts with a rapid inspiration followed by an involuntary, sudden, violent, and audible expulsion of air through the nose and mouth. The reflex occurs after stimulation of sensory receptors in the nasal mucosa. It is the ultimate cleaning procedure for the nasal cavity in dogs and cats.


Three sensory systems are dedicated to the detection of chemicals in the environment: (1) olfaction, (2) taste, and (3) the trigeminal chemosensory system. Olfactory information can influence feeding behavior, social interaction, and reproduction. A dog’s sense of smell, together with its personality and intelligence, functions as a nose for humans in many circumstances.

The transduction of olfactory information occurs in the nasal olfactory epithelium, the sheet of neurons and supporting cells that lines the caudolateral wall, the ethmoidal conchae, and the dorsal part of the nasal septum. The olfactory receptor neuron is a bipolar neuron that gives rise on its basal surface to an unmyelinated axon that carries the olfactory information to the brain. At its apex the receptor neuron has a single process that expands into a knoblike protrusion from which several microvilli, or olfactory cilia, extend into the thick layer of mucus that lines the nasal cavity and controls the ionic milieu of the olfactory cilia.

Generation of receptor potentials in response to odors takes place in the cilia of receptor neurons. The axons of the olfactory receptor cells form the olfactory nerves that pass through the cribriform plate directiy to the olfactory bulb, on the anteroventral aspect of the ipsilateral forebrain. Olfactory informatiori is passed to the amygdala and primary olfactory cortex. Further pathways for processing olfactory information include the thalamus, hypothalamus, entorhinal cortex, and hippocampus.

History, Clinical Signs, And Physical Examination

History and Clinical Signs

The medical history in nasal disease often includes clear statements of specific problems, because the signs of nasal disease — discharge, sneezing, bleeding — are obvious to the owner. Additional questions should be asked about the animal’s general condition, appetite, drinking, activity, and endurance, and about changes in its habits. These questions and a general clinical examination are indicated because some systemic diseases cause nasal discharge (distemper, viral rhinotracheitis) or epistaxis (bleeding disorders), whereas some nasal diseases (such as advanced aspergillosis) can cause general malaise, and dyspnea can occur in obstructive nasal disease.

If nasal discharge is the predominant sign, the following questions should help determine whether it is from the left, the right, or both nostrils. If a nasal discharge is present, it should be characterized (watery, mucoid, pus, blood) and its frequency noted. Discharge occurring only during sneezing indicates a less productive mucosal disease than does continuous discharge. Occasional nasal bleeding is less alarming than frequent and profuse nasal bleeding, which can be fatal.

Sneezing, like coughing, is a reflex associated with protection of the mucosa. Particles, foreign bodies, inflammation of the mucosa, or abnormal turbulence in the nasal cavity associated with local drying of the mucosa can stimulate the sensory receptors in the mucosa. Continuous sneezing can cause irritation of the mucosa, leading to more sneezing and sometimes epistaxis.

Pain in the nose may only become obvious when the animal begins to react adversely to the owner’s customary petting. A dog with pain in the nose may object to having a collar or the loop of a leash drawn over its head, even though this is usually associated with the pleasure of a walk. Questions to obtain information about nasal pain should be adapted to the living conditions of the dog or cat.

A nasal stridor is a soft, rustling or sniffing sound that is synchronous with inspiration, expiration, or both. Narrowing of the nasal passageway, which increases the velocity of the airflow, causes the sound.

Dyspnea may be caused by nasal obstruction in cats and dogs, both of which tend to avoid mouth breathing even in this situation, almost to the point of suffocation. Apparently, avoiding the consequent bypassing of the nasal function of air cleansing and conditioning has a high priority.

Physical Examination

After the shape of the nose as a whole is evaluated, the clinician should listen to the animal’s respiration for nasal stridor. Under quiet conditions, the clinician should listen close to the dog’s (and especially the cat’s) nose while gently closing its mouth. If stridor is noted and the clinician suspects it is caused by nostrils that are too narrow, moving the nasal alae laterally can change the tone of the stridor. Symmetry of the airstream can be examined by watching the movement of a small fluff of cotton held in front of each nostril. At the same time, the odor of the expired air can be noted. The area around the nostrils should be inspected for nasal discharge or crusts and the nasal plane for epithelial crusts (which could be caused by pathologic dryness), epithelial lesions, and depigmentation. The ventral wall of the nasal passages, which also forms the roof of the mouth, should be inspected through the opened mouth. The teeth, especially the canine teeth, should be inspected at the same time, because dental abnormalities can cause disorders of the nose. More in-depth inspections belong to special diagnostic procedures and require anesthesia.

Diseases of the Nose and Nasal Sinuses: Special Diagnostic Procedures

Congenital Diseases

Congenital malformation of the nasal plane is a common finding in brachycephalic breeds. The cartilage supporting the nasal plane is soft; thus the alae collapse, closing the nares. Corrective surgery is a simple procedure and consists of removing a cone-shaped piece of the ala and suturing the sides of the incision together in such a way that the nasal opening is enlarged.

In dogs and cats, variable congenital lesions of the nasal plane or more extensive clefts can be repaired surgically. The success of surgery is largely dependant on the available tissue around the cleft. Oronasal and oropharyngeal clefts cause rhinitis and should be considered for surgical repair. Euthanasia may be justified if repair is not possible and nasal discharge and dysphagia are causing recurrent fever and pain. Nasal dermoid sinus cysts have been reported in dogs. This cyst is recognized as a fistula in the midline of the bridge of the nose, producing intermittent discharge. Exploration of the fistula may reveal skin and hair as far down as the nasal septum. This abnormally located tissue must be completely removed before the skin incision is closed. A congenital cerebrospinal fluid (CSF) fistula, causing rhinorrhea, was reported in a cat. It was closed successfully.

The frontal sinuses are variable in size and sometimes even absent. Their absence is not associated with clinical signs. Congenital ciliary dysfunction has been documented in dogs of various breeds. Primary ciliary dyskinesia is a disorder in which ciliary function is ineffective and uncoordinated, resulting in rhinitis, bronchitis, bronchiectasis, and bronchopneumonia. When associated with situs inversus, the clinical syndrome is known as Kartagener’s syndrome. The initial signs (nasal discharge and coughing) usually begin at an early age, from days to 5 weeks of age. However, some dogs have remained asymptomatic for months. Complications are caused by colonization of the mucosa and the conchae by Pasteurella tnultocida and Bordetella bronchiseptica, which can cause hypoplastic conchae via bone resorption.

Mucociliary clearance in the dog’s nasal cavity can be measured by placing a small drop of BBTc macroaggregated albumin deep in the cavity, via a catheter, beyond the non-ciliated rostral half. The velocity of mucus clearance ranges from 7 to 20 mm/min. The test is not affected by anesthesia. However, not all normal dogs have a clearance rate within the reference range, and inflammation can change the velocity of the ciliary beat. To avoid spurious values, the test should be repeated and performed bilaterally.

Functional analysis of cilia in vitro is performed by examining transverse sections in electron micrographs after glutaraldehyde-osmium fixation. Major ultrastructural lesions in cilia of dogs with primary ciliary dyskinesia include lack of outer dynein arms, an abnormal microtubular pattern, and an electron-dense core in the basal body. The prognosis is guarded.

Affected dogs that develop severe recurrent bronchopneumo-nia usually die of sepsis. Continuous treatment with broad-spectrum antibiotics may enable such dogs to survive longer. Therefore cultures should be repeated to maintain correct antibiotic treatment based on sensitivity testing. A worthwhile review of treatment and long-term survival in dogs is available.

Inflammatory Diseases

Tumors Of The Nasal Plane, Nasal Cavity, And Frontal Sinus

Trauma To The Frontal Sinus And The Nose

Trauma to the Frontal Sinus

Blunt or sharp objects can cause traumatic injury to the frontal sinus. The frontal bone in dogs and cats is relatively thick and provides good protection, so a fracture of it implies that a heavy blow to the head has occurred. The pet should therefore be given a thorough clinical examination for (1) signs of shock such as tachycardia, hypotension (prolonged capillary refill time, weak pulse), rapid respiration, dilation of the pupils, hypothermia, muscle weakness, restlessness, and depression or even coma and (2) other fractures or wounds. Frontal bone fractures do not require immediate attention unless brain damage is suspected. In the absence of signs of brain damage, and when other traumatic injuries have been attended to, the nature and extent of the frontal bone fracture should be examined by radiography, CT, or both. Prolonged anesthesia is needed; thus these procedures are usually delayed for 24 hours or more.

When bone fragments are seen to be present in the frontal sinus they should be removed. Like any foreign body, small bone fragments are likely to become sequestered. Surgery should be performed with full attention to aseptic procedures. Before attempting reconstruction of the frontal bone, it is important to examine the patency of the nasofrontal duct and to relieve any obstruction. Airtight suturing of the sub-cutis, including periosteum, followed by routine skin closure prevents the development of subcutaneous emphysema. Administration of broad-spectrum antibiotics for 3 weeks and strict limitation of activity during this period (keeping a cat confined to the house) will prevent complications.

Trauma to the Nose

Trauma to the nose is characterized by massive bleeding, which adds to the other effects of the impact in promoting shock. A thorough examination for signs of this is indicated (see Trauma to the Frontal Sinus). Fractures and wounds should be noted, but priority must usually be given to the treatment of hypovolemic shock.

When the dog or cat is sufficiendy stable, the larger vessels should be ligated and skin sutures should be placed as needed. Skin sutures, sometimes supported by subcutaneous sutures, may be sufficient to remodel the outer form of the nose. Fractures of the choanae are best left alone, because they are unlikely to ever result in obstruction. Severe traumatic damage to the nose almost always causes temporary obstruction, making tracheotomy necessary. Adequate oxygenation aids in avoiding general malaise and loss of appetite. Liquid or soft food facilitates eating. In dogs the tracheal cannula is often left in place for 10 days or longer. In cats that have difficulties with long-term tracheostomy, a small intranasal catheter may be placed and connected to the oxygen supply. Use of this method, however, depends on the pathway through the wounded nose. In the author’s experience, the nose is functionally adequate in 2 to 3 weeks. If needed, more corrective surgery could be attempted after 6 weeks.


Epistaxis (i.e. nasal bleeding) is often spontaneous and transient, and it is apparendy due to a local cause. When it is recurrent or profuse, with considerable loss of blood, diagnostic investigation is indicated. The several causes of epistaxis should be considered in planning diagnostic procedures. Recurring epistaxis occurs in both dogs and cats, but profuse nasal bleeding occurs mosdy in dogs. Recurring epistaxis in dogs and cats can be caused by ulcerative rhinitis, mycotic rhinitis, and tumor in the nasal cavity. Profuse nasal bleeding in dogs is most often caused by aspergillosis in the nasal cavity or frontal sinus, or it is caused by tumor in the nasal cavity and frontal sinus. Epistaxis can also be the sole sign of defects in primary hemostasis (platelet plug formation) or secondary hemostasis (coagulation cascade). Lesions in the nasal mucosa leading to epistaxis can also occur with systemic diseases such as leishmaniasis and amyloidosis.

Epistaxis caused by local disease in the nasal cavity or frontal sinus is approached (as are all nasal diseases) by a general and specific examination for nasal disease, as described earlier in this post. When the bleeding has occurred recendy, radiographic examination should preferably be delayed for at least 48 hours because clotted blood can be misinterpreted as a mass in the nasal cavity. Rhinoscopy should also be delayed for at least 48 hours after the bleeding has stopped, because the presence of blood clots hinders inspection and could lead to misinterpretation of findings.

In the meantime, profuse nasal bleeding should be stopped. It is best to sedate the animal (phenobarbital (2 mg/kg] is advised, because it does not affect blood pressure). After considerable blood loss, sedation that causes hypotension could lead to shock in association with hypovolemia and should therefore be avoided. Sedation will help stop bleeding.

Nasal tamponade is only acceptable for a short period and under anesthesia. For less profuse bleeding, nasal drops of 0.1% adrenaline are helpful. The use of adrenaline should, however, be restricted. Overdose could cause death due to vasoconstric-tion of the arteries supplying the brain. The administration of three drops in one of the nasal cavities in dogs and one drop in cats, repeated up to three times per 24 hours, is acceptable and effective when used during the bleeding. It should not be used in an attempt to prevent nasal bleeding. When examination of the nasal cavity and the frontal sinus reveals no cause for the bleeding, further investigation of primary diseases causing hemostasis is indicated.


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.


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).


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. ()


■ 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)


Amikacin Sulfate (Amikin, Amiglyde-V)

Aminoglycoside Antibiotic

Highlights Of Prescribing Information

Parenteral aminoglycoside antibiotic that has good activity against a variety of bacteria, predominantly gram-negative aerobic bacilli

Adverse Effects: Nephrotoxicity, ototoxicity, neuromuscu-lar blockade

Cats may be more sensitive to toxic effects

Risk factors for toxicity: Preexisting renal disease, age (both neonatal & geriatric), fever, sepsis & dehydration

Now usually dosed once daily when used systemically

What Is Amikacin Sulfate Used For?

While parenteral use is only approved in dogs, amikacin is used clinically to treat serious gram-negative infections in most species. It is often used in settings where gentamicin-resistant bacteria are a clinical problem. The inherent toxicity of the aminoglycosides limit their systemic use to serious infections when there is either a documented lack of susceptibility to other, less toxic antibiotics or when the clinical situation dictates immediate treatment of a presumed gram-negative infection before culture and susceptibility results are reported.

Amikacin is also approved for intrauterine infusion in mares. It is used with intra-articular injection in foals to treat gram-negative septic arthritis.


Amikacin, like the other aminoglycoside antibiotics, act on susceptible bacteria presumably by irreversibly binding to the 30S ribosomal subunit thereby inhibiting protein synthesis. It is considered a bactericidal concentration-dependent antibiotic.

Amikacin’s spectrum of activity includes: coverage against many aerobic gram-negative and some aerobic gram-positive bacteria, including most species of E. coli, Klebsiella, Proteus, Pseudomonas, Salmonella, Enterobacter, Serratia, and Shigella, Mycoplasma, and Staphylococcus. Several strains of Pseudomonas aeruginosa, Proteus, and Serratia that are resistant to gentamicin will still be killed by amikacin.

Antimicrobial activity of the aminoglycosides is enhanced in an alkaline environment.

The aminoglycoside antibiotics are inactive against fungi, viruses and most anaerobic bacteria.


Amikacin, like the other aminoglycosides is not appreciably absorbed after oral or intrauterine administration, but is absorbed from topical administration (not from skin or the urinary bladder) when used in irrigations during surgical procedures. Patients receiving oral aminoglycosides with hemorrhagic or necrotic enteritises may absorb appreciable quantities of the drug. After IM administration to dogs and cats, peak levels occur from ½1 hour later. Subcutaneous injection results in slightly delayed peak levels and with more variability than after IM injection. Bio availability from extravascular injection (IM or SC) is greater than 90%.

After absorption, aminoglycosides are distributed primarily in the extracellular fluid. They are found in ascitic, pleural, pericardial, peritoneal, synovial and abscess fluids; high levels are found in sputum, bronchial secretions and bile. Aminoglycosides are minimally protein bound (<20%, streptomycin 35%) to plasma proteins. Aminoglycosides do not readily cross the blood-brain barrier nor penetrate ocular tissue. CSF levels are unpredictable and range from 0-50% of those found in the serum. Therapeutic levels are found in bone, heart, gallbladder and lung tissues after parenteral dosing. Aminoglycosides tend to accumulate in certain tissues such as the inner ear and kidneys, which may help explain their toxicity. Volumes of distribution have been reported to be 0.15-0.3 L/kg in adult cats and dogs, and 0.26-0.58 L/kg in horses. Volumes of distribution may be significantly larger in neonates and juvenile animals due to their higher extracellular fluid fractions. Aminoglycosides cross the placenta; fetal concentrations range from 15-50% of those found in maternal serum.

Elimination of aminoglycosides after parenteral administration occurs almost entirely by glomerular filtration. The approximate elimination half-lives for amikacin have been reported to be 5 hours in foals, 1.14-2.3 hours in adult horses, 2.2-2.7 hours in calves, 1-3 hours in cows, 1.5 hours in sheep, and 0.5-2 hours in dogs and cats. Patients with decreased renal function can have significantly prolonged half-lives. In humans with normal renal function, elimination rates can be highly variable with the aminoglycoside antibiotics.

Before you take Amikacin Sulfate

Contraindications / Precautions / Warnings

Aminoglycosides are contraindicated in patients who are hypersensitive to them. Because these drugs are often the only effective agents in severe gram-negative infections, there are no other absolute contraindications to their use. However, they should be used with extreme caution in patients with preexisting renal disease with concomitant monitoring and dosage interval adjustments made. Other risk factors for the development of toxicity include age (both neonatal and geriatric patients), fever, sepsis and dehydration.

Because aminoglycosides can cause irreversible ototoxicity, they should be used with caution in “working” dogs (e.g., “seeing-eye,” herding, dogs for the hearing impaired, etc.).

Aminoglycosides should be used with caution in patients with neuromuscular disorders (e.g., myasthenia gravis) due to their neuromuscular blocking activity.

Because aminoglycosides are eliminated primarily through renal mechanisms, they should be used cautiously, preferably with serum monitoring and dosage adjustment in neonatal or geriatric animals.

Aminoglycosides are generally considered contraindicated in rabbits/hares as they adversely affect the GI flora balance in these animals.

Adverse Effects

The aminoglycosides are infamous for their nephrotoxic and ototox-ic effects. The nephrotoxic (tubular necrosis) mechanisms of these drugs are not completely understood, but are probably related to interference with phospholipid metabolism in the lysosomes of proximal renal tubular cells, resulting in leakage of proteolytic enzymes into the cytoplasm. Nephrotoxicity is usually manifested by: increases in BUN, creatinine, nonprotein nitrogen in the serum, and decreases in urine specific gravity and creatinine clearance. Proteinuria and cells or casts may be seen in the urine. Nephrotoxicity is usually reversible once the drug is discontinued. While gentamicin may be more nephrotoxic than the other aminoglycosides, the incidences of nephrotoxicity with all of these agents require equal caution and monitoring.

Ototoxicity (8th cranial nerve toxicity) of the aminoglycosides can manifest by either auditory and/or vestibular clinical signs and may be irreversible. Vestibular clinical signs are more frequent with streptomycin, gentamicin, or tobramycin. Auditory clinical signs are more frequent with amikacin, neomycin, or kanamycin, but either form can occur with any of these drugs. Cats are apparently very sensitive to the vestibular effects of the aminoglycosides.

The aminoglycosides can also cause neuromuscular blockade, facial edema, pain/inflammation at injection site, peripheral neuropathy and hypersensitivity reactions. Rarely, GI clinical signs, hematologic and hepatic effects have been reported.

Reproductive / Nursing Safety

Aminoglycosides can cross the placenta and while rare, may cause 8th cranial nerve toxicity or nephrotoxicity in fetuses. Because the drug should only be used in serious infections, the benefits of therapy may exceed the potential risks. 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.) In a separate system evaluating the safety of drugs in canine and feline pregnancy (), this drug is categorized as in class: C (These drugs may have potential risks. Studies in people or laboratory animals have uncovered risks, and these drugs should he used cautiously as a last resort when the benefit of therapy clearly outweighs the risks.)

Aminoglycosides are excreted in milk. While potentially, amikacin ingested with milk could alter GI flora and cause diarrhea, amikacin in milk is unlikely to be of significant concern after the first few days of life (colostrum period).

Overdosage / Acute Toxicity

Should an inadvertent overdosage be administered, three treatments have been recommended. Hemodialysis is very effective in reducing serum levels of the drug but is not a viable option for most veterinary patients. Peritoneal dialysis also will reduce serum levels but is much less efficacious. Complexation of drug with either carbenicillin or ticarcillin (12-20 g/day in humans) is reportedly nearly as effective as hemodialysis. Since amikacin is less affected by this effect than either tobramycin or gentamicin, it is assumed that reduction in serum levels will also be minimized using this procedure.

How to use Amikacin Sulfate

Note: Most infectious disease clinicians now agree that aminoglycosides should be dosed once a day in most patients (mammals). This dosing regimen yields higher peak levels with resultant greater bacterial kill, and as aminoglycosides exhibit a “post-antibiotic effect”, surviving susceptible bacteria generally do not replicate as rapidly even when antibiotic concentrations are below MIC. Periods where levels are low may also decrease the “adaptive resistance” (bacteria take up less drug in the presence of continuous exposure) that can occur. Once daily dosing may decrease the toxicity of aminoglycosides as lower urinary concentrations may mean less uptake into renal tubular cells. However, patients who are neutropenic (or otherwise immunosuppressed) may benefit from more frequent dosing (q8h). Patients with significantly diminished renal function who must receive aminoglycosides may need to be dosed at longer intervals than once daily. Clinical drug monitoring is strongly suggested for these patients.

Amikacin Sulfate dosage for dogs:

For susceptible infections:

a) Sepsis: 20 mg/kg once daily IV ()

b) 15 mg/kg (route not specified) once daily (q24h). Neutropenic or immunocompromised patients may still need to be dosed q8h (dose divided). ()

c) 15-30 mg/kg IV, IM or SC once daily (q24h) ()

Amikacin Sulfate dosage for cats:

For susceptible infections:

a) Sepsis: 20 mg/kg once daily IV ()

b) 15 mg/kg (route not specified) once daily (q24h). Neutropenic or immunocompromised patients may still need to be dosed q8h (dose divided). ()

c) 10-15 mg/kg IV, IM or SC once daily (q24h) ()

Amikacin Sulfate dosage for ferrets:

For susceptible infections:

a) 8-16 mg/kg IM or IV once daily ()

b) 8-16 mg/kg/day SC, IM, IV divided q8-24h ()

Amikacin Sulfate dosage for rabbits, rodents, and small mammals:

a) Rabbits: 8-16 mg/kg daily dose (may divide into q8h-q24h) SC, IM or IV Increased efficacy and decreased toxicity if given once daily. If given IV, dilute into 4 mL/kg of saline and give over 20 minutes. ()

b) Rabbits: 5-10 mg/kg SC, IM, IV divided q8-24h Guinea pigs: 10-15 mg/kg SC, IM, IV divided q8-24h Chinchillas: 10-15 mg/kg SC, IM, IV divided q8-24h Hamster, rats, mice: 10 mg/kg SC, IM q12h Prairie Dogs: 5 mg/kg SC, IM q12h ()

c) Chinchillas: 2-5 mg/kg SC, IM q8- 12h ()

Amikacin Sulfate dosage for cattle:

For susceptible infections:

a) 10 mg/kg IM q8h or 25 mg/kg q12h ()

b) 22 mg/kg/day IM divided three times daily ()

Amikacin Sulfate dosage for horses:

For susceptible infections:

a) 21 mg/kg IV or IM once daily (q24h) ()

b) In neonatal foals: 21 mg/kg IV once daily ()

c) In neonatal foals: Initial dose of 25 mg/kg IV once daily; strongly recommend to individualize dosage based upon therapeutic drug monitoring. ()

d) Adults: 10 mg/kg IM or IV once daily (q24h)

Foals (<30 days old): 20-25 mg/kg IV or IM once daily (q24h).

For uterine infusion:

a) 2 grams mixed with 200 mL sterile normal saline (0.9% sodium chloride for injection) and aseptically infused into uterus daily for 3 consecutive days (Package insert; Amiglyde-V — Fort Dodge)

b) 1-2 grams IU ()

For intra-articular injection as adjunctive treatment of septic arthritis in foals:

a) If a single joint is involved, inject 250 mg daily or 500 mg every other day; frequency is dependent upon how often joint lavage is performed. Use cautiously in multiple joints as toxicity may result (particularly if systemic therapy is also given). ()

For regional intravenous limb perfusion (RILP) administration in standing horses:

a) Usual dosages range from 500 mg-2 grams; dosage must be greater than 250 mg when a cephalic vein is used for perfusion and careful placement of tourniquets must be performed. ()

Amikacin Sulfate dosage for birds:

For susceptible infections:

a) For sunken eyes/sinusitis in macaws caused by susceptible bacteria: 40 mg/kg IM once or twice daily. Must also flush sinuses with saline mixed with appropriate antibiotic (10-30 mL per nostril). May require 2 weeks of treatment. ()

b) 15 mg/kg IM or SC q12h ()

c) For gram-negative infections resistant to gentamicin: Dilute commercial solution and administer 15-20 mg/kg (0.015 mg/g) IM once a day or twice a day ()

d) Ratites: 7.6-11 mg/kg IM twice daily; air cell: 10-25 mg/egg; egg dip: 2000 mg/gallon of distilled water pH of 6 ()

Amikacin Sulfate dosage for reptiles:

For susceptible infections:

a) For snakes: 5 mg/kg IM (forebody) loading dose, then 2.5 mg/kg q72h for 7-9 treatments. Commonly used in respiratory infections. Use a lower dose for Python curtus. ()

b) Study done in gopher snakes: 5 mg/kg IM loading dose, then 2.5 mg/kg q72h. House snakes at high end of their preferred optimum ambient temperature. ()

c) For bacterial shell diseases in turtles: 10 mg/kg daily in water turtles, every other day in land turtles and tortoises for 7-10 days. Used commonly with a beta-lactam antibiotic. Recommended to begin therapy with 20 mL/kg fluid injection. Maintain hydration and monitor uric acid levels when possible. ()

d) For Crocodilians: 2.25 mg/kg IM q 72-96h ()

e) For gram-negative respiratory disease: 3.5 mg/kg IM, SC or via lung catheter every 3-10 days for 30 days. ()

Amikacin Sulfate dosage for fish:

For susceptible infections:

a) 5 mg/kg IM loading dose, then 2.5 mg/kg every 72 hours for 5 treatments. ()


■ Efficacy (cultures, clinical signs, WBC’s and clinical signs associated with infection). Therapeutic drug monitoring is highly recommended when using this drug systemically. Attempt to draw samples at 1,2, and 4 hours post dose. Peak level should be at least 40 mcg/mL and the 4-hour sample less than 10 mcg/mL.

■ Adverse effect monitoring is essential. Pre-therapy renal function tests and urinalysis (repeated during therapy) are recommended. Casts in the urine are often the initial sign of impending nephrotoxicity.

■ Gross monitoring of vestibular or auditory toxicity is recommended.

Client Information

■ With appropriate training, owners may give subcutaneous injections at home, but routine monitoring of therapy for efficacy and toxicity must still be done

■ Clients should also understand that the potential exists for severe toxicity (nephrotoxicity, ototoxicity) developing from this medication

■ Use in food producing animals is controversial as drug residues may persist for long periods

Chemistry / Synonyms

A semi-synthetic aminoglycoside derived from kanamycin, amikacin occurs as a white, crystalline powder that is sparingly soluble in water. The sulfate salt is formed during the manufacturing process. 1.3 grams of amikacin sulfate is equivalent to 1 gram of amikacin. Amikacin may also be expressed in terms of units. 50,600 Units are equal to 50.9 mg of base. The commercial injection is a clear to straw-colored solution and the pH is adjusted to 3.5-5.5 with sulfuric acid.

Amikacin sulfate may also be known as: amikacin sulphate, amikacini sulfas, or BB-K8; many trade names are available.

Storage / Stability/Compatibility

Amikacin sulfate for injection should be stored at room temperature (15 – 30°C); freezing or temperatures above 40°C should be avoided. Solutions may become very pale yellow with time but this does not indicate a loss of potency.

Amikacin is stable for at least 2 years at room temperature. Autoclaving commercially available solutions at 15 pounds of pressure at 120°C for 60 minutes did not result in any loss of potency.

Note: When given intravenously, amikacin should be diluted into suitable IV diluent etc. normal saline, D5W or LRS) and administered over at least 30 minutes.

Amikacin sulfate is reportedly compatible and stable in all commonly used intravenous solutions and with the following drugs: amobarbital sodium, ascorbic acid injection, bleomycin sulfate, calcium chloride/gluconate, cefoxitin sodium, chloramphenicol sodium succinate, chlorpheniramine maleate, cimetidine HCl, clindamycin phosphate, colistimethate sodium, dimenhydrinate, diphenhydramine HCl, epinephrine HCl, ergonovine maleate, hyaluronidase, hydrocortisone sodium phosphate/succinate, lincomycin HCl, metaraminol bitartrate, metronidazole (with or without sodium bicarbonate), norepinephrine bitartrate, pentobarbital sodium, phenobarbital sodium, phytonadione, polymyxin B sulfate, prochlorperazine edisylate, promethazine HCL, secobarbital sodium, sodium bicarbonate, succinylcholine chloride, vancomycin HCL and verapamil HCL.

The following drugs or solutions are reportedly incompatible or only compatible in specific situations with amikacin: aminophylline, amphotericin B, ampicillin sodium, carbenicillin disodium, cefazolin sodium, cephalothin sodium, cephapirin sodium, chlorothiazide sodium, dexamethasone sodium phosphate, erythromycin gluceptate, heparin sodium, methicillin sodium, nitrofurantoin sodium, oxacillin sodium, oxytetracycline HCL, penicillin G potassium, phenytoin sodium, potassium chloride (in dextran 6% in sodium chloride 0.9%; stable with potassium chloride in “standard” solutions), tetracycline HCL, thiopental sodium, vitamin B-complex with C and warfarin sodium. Compatibility is dependent upon factors such as pH, concentration, temperature and diluent used; consult specialized references or a hospital pharmacist for more specific information.

In vitro inactivation of aminoglycoside antibiotics by beta-lac-tam antibiotics is well documented. While amikacin is less susceptible to this effect, it is usually recommended to avoid mixing these compounds together in the same syringe or IV bag unless administration occurs promptly. See also the information in the Amikacin Sulfate Interaction and Amikacin Sulfate/Lab Interaction sections.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products:

Amikacin Sulfate Injection: 50 mg (of amikacin base) per mL in 50 mL vials; Amiglyde-V (Fort Dodge), AmijectD (Butler), Amikacin K-9 (RXV), Amikacin C (Phoenix), Amtech Amimax C (IVX), Caniglide (Vedco); generic (VetTek); (Rx); Approved for use in dogs.

Amikacin Sulfate Intrauterine Solution: 250 mg (of amikacin base) per mL in 48 mL vials; Amifuse E (Butler), Amiglyde-V (Fort Dodge), Amikacin E (Phoenix), Amikacin E (RXV), Amtech Amimax E (IVX), Equi-phar Equiglide (Vedco); (Rx); Approved for use in horses not intended for food.

WARNING: Amikacin is not approved for use in cattle or other food-producing animals in the USA. Amikacin Sulfate residues may persist for long periods, particularly in renal tissue. For guidance with determining use and withdrawal times, contact FARAD (see Phone Numbers & Websites in the appendix for contact information).

Human-Labeled Products:

Amikacin Injection: 50 mg/mL and 250 mg/mL in 2 mL and 4 mL vials and 2 mL syringes; Amikin (Apothecon); generic; (Rx)


Fractured Ribs

Fractured ribs most commonly are observed in neonates in conjunction with birth trauma. Rib fractures in older individuals most often result from collisions or kicks or falls. Birth trauma is the most common cause of rib fracture, and most neonates with fractures do not require medical or surgical intervention. However, rib fracture can cause life-threatening compromise to the integrity of the cardiopulmonary system and diaphragmatic hernia. Death can be due to hemorrhage into the thorax, pericardium, or abdomen, or shock, or a traumatic contact of the rib with the epicardium or myocardium that causes cardiac arrest.

Clinical Signs of Fractured Ribs

The clinical signs of fractured ribs are variable. Crepitus cannot be palpated consistently over the damaged area of the thoracic wall. In foals, simultaneous observation and palpation of the thoracic cage may reveal asymmetry of the thorax, especially at or near the costochondral junctions. Crepitation or “clicking” over a rib, heard with or without a stethoscope, is pathognomonic for the injury. Some patients reveal moderate thoracic edema ventral to the fracture sites. A stilted gait can indicate thoracic pain or the patient may “grunt” when manipulated or maneuvered. In severe cases, involving fractures in multiple consecutive ribs, the patient is in respiratory distress and presents with a flail thorax. The latter can be recognized when inspiratory effort results in collapse of the thoracic wall inward rather than the expected normal outward movement. If the patient has simultaneous pallor of the mucous membranes, internal hemorrhage should be suspected and promptly pursued in the diagnostic evaluation. Internal hemorrhage, including hemothorax, hemopericardium, and abdominal hemorrhage, may indicate that the diaphragm has been lacerated. Pneumothorax is an uncommon finding with fractured ribs in neonates but may be more likely in older individuals with fractures secondary to blunt trauma.

The location of the rib fractures is an important determinant of prognosis. Fractures in the cranioventral portion of the thorax, in proximity to the heart, can cause cardiac laceration and sudden death. Midthoracic rib fractures more frequently cause pulmonary laceration and hemothorax, occasionally with pneumothorax. Fractures in the mid-to-caudal thorax are capable of lacerating the diaphragm and causing secondary lung or abdominal visceral lesions.

Diagnosis of Fractured Ribs

The diagnosis of fractured ribs may be obvious when palpable crepitus is associated with an underlying rib. Ancillary diagnostic procedures include ultrasound evaluation and thoracic radiography. In most cases, use of ultrasound can reveal both rib fracture and displacement. Ultrasound is better than radiography for detecting the site of injury and also detects hemothorax, hemopericardium, pneumothorax, or diaphragmatic hernia. A single radiographic view provides an overall assessment of the thorax but ultrasound provides a detailed map.

Treatment of Fractured Ribs

The treatment of choice for fractured ribs is rest and confinement for 1 to 3 weeks. This conservative treatment is successful in nearly all cases of uncomplicated rib fracture. Supportive care is indicated for foals in pain, and manual assistance in helping foals to rise and nurse should be provided in a manner that avoids direct compression of either the fracture sites or the sternum. Affected foals may be assisted safely by lifting them from sternal recumbency by the elbows. Sedation may be required to prevent flailing or harmful struggling of some patients, and oxygen supplementation via nasal insufflation is indicated for obvious hypoxemia. If severe hypoxemia is present concurrently with a flail thorax, longer-term phenobarbital sedation may be required to maintain the foal in lateral recumbency. In these cases, the intact thoracic wall should be uppermost and occasionally the foal should be allowed to rest on its sternum. Foals that turn over can compress the underlying damaged lung. If the patient is allowed to be ambulatory, the primary concern is cardiac laceration and arrest if cranioventral fractures are further displaced by overactivity.

Surgical treatment of rib fractures is uncommon, but in these authors’ practice stabilization has been provided by use of dynamic compression plates. The long-term outcome of this procedure currently is being investigated. In cases where rib fractures are responsible for diaphragmatic hernia, surgical repair is essential to a favorable prognosis.

Veterinary Medicine

Portosystemic Shunts

1. What is a portosystemic shunt?

A portosystemic shunt is an abnormal vessel that connects the portal vein to a systemic vein. The most common locations for portosystemic shunts are a patent ductus venosus or a connection between the portal vein and caudal vena cava or azygous vein. Single extraheptic shunts are most common in small-breed dogs and cats, whereas single intrahepatic shunts are most common in large-breed dogs.

2. What is the difference between congenital and acquired portosystemic shunts?

Most acquired shunts are multiple and extrahepatic. Acquired shunts develop because of sustained portal hypertension from chronic liver disease and cirrhosis. Congenital portosystemic shunts are usually single and may be intra- or extrahepatic. The most common intrahepatic portosystemic shunt is a patent ductus venosus.

3. Are certain breeds associated with portosystemic shunts?

Congenital portosystemic shunts may occur in any breed of dog but are common in miniature schnauzers, miniature poodles, Yorkshire terriers, dachshunds, Doberman pinschers, golden retrievers, Labrador retrievers, and Irish setters. There are affected lines in miniature schnauzers, Irish wolfhounds, Old English sheepdogs, and Cairn terriers. Mixed breed cats are more commonly affected than purebred cats, but Himalayans and Persians seem to overrepresented as purebreds. Acquired portosystemic shunts are secondary to chronic hepatic disease and so may occur in any breed.

4. Where are most portosystemic shunts located?

Single extrahepatic shunts most commonly connect the portal vein (or the left gastric or splenic vein) with the caudal vena cava cranial to the phrenicoabdominal vein. Single intrahepatic shunts can be a communication of the portal vein to the caudal vena cava which is a failure of the ductus venosus to close. Shunts in the right medial or lateral liver lobes occur with an unknown pathogenesis.

5. Why do patients with portosystemic shunts have decreased liver function?

Portal venous blood is important because it brings hepatotropic growth factors and insulin to the liver. If insulin bypasses the liver in a shunt, significant quantities are utilized by other organs and the liver receives less benefit. Portal venous blood flow is important for normal liver development as well as glycogen storage, hypertrophy, hyperplasia, and regeneration. Congenital portosystemic shunts are often associated with hepatic atrophy, hypoplasia, and dysfunction.

6. What are the most common clinical signs of portosystemic shunts?

Failure to thrive and failure to gain weight are appropriately common. Most clinical signs are referable to hepatic encephalopathy, which is defined as clinical signs of neurologic dysfunction secondary to hepatic disease. Signs include ataxia, stupor, lethargy, unusual behavior, disorientation, blindness, and seizures. Some animals display anorexia, vomiting, and diarrhea. Polyuria and polydipsia may be present. Some animals have ammonium biurate urolithiasis, which may result in pollakiuria, hematuria, stranguria, or obstruction. Increased production of saliva (ptyalism) and abdominal distention due to ascites occur in some animals. Ptyalism is more common in cats.

7. What causes hepatic encephalopathy associated with portosystemic shunts?

Products of bacterial metabolism in the intestine, such as ammonia, short-chain fatty acids (SCFAs), mercaptans, gamma-aminobutyric acid (GABA), and endogenous benzodiazepines have been suggested as mediators of hepatic encephalopathy. In addition, the ratio of aromatic amino acids to branched-chain amino acids is often increased in patients with portosystemic shunts. The aromatic amino acids may act as false neurotransmitters. Phenylalanine and tyrosine may act as weak neurotransmitters in the presynaptic neurons of the CNS. Tryptophan causes increased production of serotonin, which is a potent inhibitory neurotransmitter. The GABA receptor has binding sites for barbiturates, benzodiazepines, and substances with similar chemical structure to benzodiazepines. These agents may be responsible for depression of the CNS in hepatic encephalopathy.

8. What factors may precipitate an hepatic encephalopathy crisis?

A protein rich meal, gastrointestinal bleeding associated with parastites, ulcers or drug therapy; administration of methionine- containing urinary acidifiers; or lipotropic agents may precipitate a crisis. Blood transfusions with stored blood may also contribute to a crisis as the ammonia levels can be high in the stored blood.

9. How is hepatic encephalopathy treated?

The animal should be evaluated for hypoglycemia immediately and treated appropriately if it is present. Appropriate fluid therapy based on acid-base and electrolyte status (see chapter 81) should be initiated to correct abnormalities. LRS should be avoided. Hypoglycemia, alkalosis, hypokalemia, and gastrointestinal bleeding should be identified and corrected. Ammonia concentration and production should be decreased by administering lactulose and neomycin (10-20 mg/kg orally every 6 hr) if a swallow response is present. Oral metronidazole may be used at a dose of 10 mg/kg every 8 hr in place of neomycin. If the animal is comatose, 20-30 ml/kg of lactulose diluted 1:2 with water or a 1:10 dilution of povidone-iodine solution may be given as an enema. Seizures may be treated initially with elimination of ammonia by enemas as listed above. Oral loading doses of potassium bromide may be useful. If seizures cannot be controlled, IV propofol as a constant rate infusion may be necessary, but respiratory support may be needed. Some animals with hepatic encephalopathy have difficulty in metabolizing benzodiazepines such as diazepam, which should be avoided. If these drugs do not control seizures, intravenous phenobarbital may be titrated slowly to effect. Patients often have decreased clearance of barbiturates.

10. What routine blood work and urinalysis abnormalities suggest portosystemic shunts?

Microcytosis is a consistent abnormality of complete blood cell count in animals with portosystemic shunts. Some animals manifest acid-base, electrolyte, and glucose disturbances (hypoglycemia). Because of vomiting and dehydration, prerenal azotemia may be present. There is no consistent finding with regard to alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum alkaline phosphatase (ALP); activities of these enzymes may be elevated, decreased, or normal in patients with portosystemic shunts. Hypoalbuminemia is common, as are coagulopathies. Some animals have isothenuric urine due to medullary wash-out; ammonium biurate crystals may be identified on microscopic examination of urine sediment.

11. What are the best ways to diagnose a portosystemic shunt?

Elevated serum pre- and postprandial bile acids in a young animal with signs of hepatic encephalopathy and stunted growth are consistent with but not diagnostic for portosystemic shunts. A nuclear medicine scan using transcolonic sodium pertechnetate Tc99m demonstrates radioactivity in the heart before the liver in an animal with portosystemic shunt. Nuclear medicine is rapid, noninvasive, and safe to the animal. The disadvantages are that the animal is radioactive for 24 hours, studies can be performed only by specially trained personnel, exact location of the shunt cannot be determined, and cases of hepatic microvascular dysplasia, which have shunting within the liver (as in Cairn terriers), may give false-negative results. When nuclear medicine facilities are unavailable, positive contrast portography may demonstrate the anomalous vessel. Portography, however, is technically demanding and invasive. Furthermore, a second surgical procedure is required to repair the shunt because of an otherwise dangerously long period of anesthesia. The major advantage of positive contrast portography is that it definitively locates the shunt.

12. What is the best way to manage a patient with portosystemic shunt?

Although medical management may be beneficial, surgical ligation of the shunt is optimal. In one study, animals that receive total ligation, even if it had to be done in two or more surgeries, showed more clinical improvement than patients with incomplete shunt ligation. In general, cats do not do as well with medical therapy.

13. Describe the preoperative management of a patient with portosystemic shunt.

In animals displaying hepatic encephalopathy, it is important to correct acid-base and electrolyte disturbances before surgery. Measures to control hepatic encephalopathy also should be performed before surgery, including a low protein diet, oral lactulose, and neomycin or metronidazole. A moderately protein-restricted diet with the bulk of calories coming from carbohydrates and fat is optimal. Vegetable and dairy proteins are better tolerated than meat and egg proteins. With each patient, the protein level should be increased to the maximum tolerated. Psyllium at 1-3 teaspoons per day has been advocated to help tolerance of proteins. Some have recommended supplementation with vitamins A, B, C, E, and K. Medical stabilization for 1-2 weeks before surgery is recommended for all patients with portosystemic shunts. A preoperative coagulation screen should be performed, and crossmatched fresh whole blood should be available. Fresh frozen plasma transfusions may be necessary for hypoalbuminemic patients. Most surgeons administer a broad-spectrum antibiotic (e.g., first-generation cephalosporin) intravenously before and during surgery.

14. What considerations must be given to drug therapy and anesthetic use in patients with portosystemic shunts?

Because liver function decreases in patients with portosystemic shunts, drugs that are potentially hepatotoxic should be avoided. In addition, hepatic clearance of drugs and anesthetic agents may be delayed.

15. What parameters should be monitored postoperatively in patients with portosystemic shunts?

After surgery, many patients with portosystemic shunts are hypoglycemic, hypothermic, and hypoalbuminemic. A postoperative database should include body weight, temperature, packed cell volume, total solids, and glucose. Additional useful information is provided by electrolytes and albumin. Maintaining hydration status and perfusion with a balanced electrolyte solution is important. Mucous membrane color, capillary refill time, pulse rate and quality, and temperature should be assessed, and the patient should be monitored for seizures. In addition, serial measurement of abdominal circumference is helpful because a number of patients develop portal hypertension and ascites postoperatively.

16. What are common postsurgical complications?

Sepsis, seizures, and portal hypertension are the most critical complications that may develop postoperatively, although pancreatitis and intussusceptions have been reported. Gastrointestinal hemorrhage also may result, which can precipitate a hepatic encephalopathy crisis. Animals with seizures should be treated with appropriate measures to normalize acid-base and electrolyte balance. Sepsis should be treated aggressively.

17. What are common signs of postoperative portal hypertension?

Portal hypertension most commonly results in abdominal distention secondary to ascites. In some cases, portal hypertension is subclinical and ascites resolves in several days. Some patients develop abdominal distention, pain, and hypovolemia; others have abdominal distention with severe pain, hypovolemia, cardiovascular collapse, hemorrhagic diarrhea, and septic or endotoxic shock.

18. How should postoperative portal hypertension be treated?

If the animal develops abdominal distention with no clinical signs of pain or discomfort, continued medical therapy is indicated. Most animals with pain and abdominal distention stabilize with colloid fluid therapy. Patients with severe pain, abdominal distention, bloody diarrhea, and cardiovascular shock should be treated for shock with fluids, stabilized as much as possible, and taken for exploratory surgery to remove the ligature or thrombus that has probably developed in a partially attenuated portosystemic shunt.

19. Why may a patient with portosystemic shunt become septic postoperatively?

A patient with portosystemic shunt may develop septic peritonitis postoperatively because of bacteremia in the portal vein. The monocyte-phagocyte system in the liver may not be fully functional. Sepsis may develop as a result of inadequate filtering of portal blood by the liver before the blood reaches the systemic circulation.

20. What is hepatic microvascular dysplasia?

Hepatic microvascular dysplasia is a congenital disorder with histologic vascular abnormalities that resemble those seen in portosystemic shunts.

21. Are there breed predispositions for hepatic microvascular dysplasia?

Cairn and Yorkshire terriers are most commonly affected with hepatic microvascular dysplasia. However, many other breeds, including dachshund, poodle, Shih Tzu, Lhasa Apso, cocker spaniel, and West Highland White terrier may be affected.

22. What are the clinical signs of hepatic microvascular dysplasia?

Clinical signs are not consistently seen, but in severe cases they are quite similar to those seen with portosystemic shunts. Hyperammonemia and ammonium biurate cystalluria rarely develop. A dog may have hepatic microvascular dysplasia with elevated bile acids but be sick for another cause.

23. When should hepatic microvascular dysplasia be considered as a differential diagnosis?

Hepatic microvascular dysplasia should be considered in a patient with clinical signs consistent with a portosystemic shunt, increased bile acid concentration, and consistent liver biopsy results. Scintigraphy is consistently normal.

24. What is the treatment for hepatic microvascular dysplasia?

Treatment should not be done if the patient is subclinical. If signs of hepatic encephalopathy are present, treatment is indicated as for patients with portosystemic shunts. It is unknown at this time whether subclinical patients will develop signs of disease.

Veterinary Drugs



An ethanolamine derivative antihistamine, dimenhydrinate contains approximately 54% diphenhydramine and 46% 8-chlorotheophylline. It occurs as an odorless, bitter and numbing-tasting, white crystalline powder with a melting range of 102°-107°C. Dimenhydrinate is slightly soluble in water and is freely soluble in propylene glycol or alcohol. The pH of the commercially available injection ranges from 6.4 to 7.2.

Storage – Stability – Compatibility

Dimenhydrinate products should be stored at room temperature; avoid freezing the oral solution and injectable products. The oral solution should be stored in tight containers and tablets stored in well-closed containers.

Dimenhydrinate injection is reportedly compatible with all commonly used intravenous replenishment solutions and the following drugs: amikacin sulfate, atropine sulfate, calcium gluconate, chloramphenicol sodium succinate, corticotropin, ditrizoate meglumine and sodium, diphenhydramine HCl, droperidol, fentanyl citrate, heparin sodium, iothalamate meglumine and sodium, meperidine HCl, methicillin sodium, metoclopramide, morphine sulfate, norepinephrine bitartrate, oxytetracycline HCl, penicillin G potassium, pentazocine lactate, perphenazine, phenobarbital sodium, potassium chloride, scopolamine HBr, vancomycin HCl and vitamin B-complex w/ vitamin C.

The following drugs are either incompatible or compatible only in certain concentrations with dimenhydrinate: aminophylline, ammonium chloride, amobarbital sodium, butorphanol tartrate, glycopyrrolate, hydrocortisone sodium succinate, hydroxyzine, iodipamide meglumine, pentobarbital sodium, prochlorperazine edisylate, promazine HCl, promethazine HCl, tetracycline HCl, and thiopental sodium. Compatibility is dependent upon factors such as pH, concentration, temperature, and diluents used and it is suggested to consult specialized references for more specific information.

Dimenhydrinate: Pharmacology

Dimenhydrinate has antihistaminic, antiemetic, anticholinergic, CNS depressant and local anesthetic effects. These principle pharmacologic actions are thought to be a result of only the diphenhydramine moiety. Used most commonly for its antiemetic/motion sickness effects, dimenhydrinate’s exact mechanism of action for this indication is unknown, but the drug does inhibit vestibular stimulation. The anticholinergic actions of dimenhydrinate may play a role in blocking acetylcholine stimulation of the vestibular and reticular systems. Tolerance to the CNS depressant effects can ensue after a few days of therapy and antiemetic effectiveness also may diminish with prolonged use.

Dimenhydrinate: Uses – Indications

In veterinary medicine, dimenhydrinate is used primarily for its antiemetic effects in the prophylactic treatment of motion sickness in dogs and cats.


The pharmacokinetics of this agent have apparently not been studied in veterinary species. In humans, the drug is well absorbed after oral administration with antiemetic effects occurring within 30 minutes of administration. Antiemetic effects occur almost immediately after IV injection. The duration of effect is usually 3-6 hours.

Diphenhydramine is metabolized in the liver, and the majority of the drug is excreted as metabolites into the urine. The terminal elimination half-life in adult humans ranges from 2.4 – 9.3 hours.


Dimenhydrinate is contraindicated in patients who are hypersensitive to it or to other antihistamines in its class. Because of their anticholinergic activity, an-tihistamines should be used with caution in patients with angle closure glaucoma, prostatic hypertrophy, pyloroduodenal or bladder neck obstruction, and COPD if mucosal secretions are a problem. Additionally, they should be used with caution in patients with hyperthyroidism, seizure disorders, cardiovascular disease or hypertension. It may mask the symptoms of ototoxicity and should therefore be used with this knowledge when concomitantly administering with ototoxic drugs.

Dimenhydrinate: Adverse Effects – Warnings

Most common adverse reactions seen are CNS depression (lethargy, somnolence) and anticholinergic effects (dry mouth, urinary retention). GI effects (diarrhea, vomiting, anorexia) are less common, but have been noted.

The sedative effects of antihistamines, may adversely affect the performance of working dogs. The sedative effects of antihistamines may diminish with time.

Dimenhydrinate: Overdosage

Overdosage may cause CNS stimulation (excitement to seizures) or depression (lethargy to coma), anticholinergic effects, respiratory depression and death. Treatment consists of emptying the gut if the ingestion was oral. Induce emesis if the patient is alert and CNS status is stable. Administration of a saline cathartic and/or activated charcoal may be given after emesis or gastric lavage. Treatment of other symptoms should be performed using symptomatic and supportive therapies. Phenytoin (IV) is recommended in the treatment of seizures caused by antihistamine overdose in humans; use of barbiturates and diazepam are avoided.

Dimenhydrinate: Drug Interactions

Increased sedation can occur if dimenhydrinate (diphenhydramine) is combined with other CNS depressant drugs. Antihistamines may partially counteract the anticoagulation effects of heparin or warfarin. Diphenhydramine may enhance the effects of epinephrine. Dimenhydrinate may potentiate the anticholinergic effects of other anticholinergic drugs. Dimenhydrinate has been demonstrated to induce hepatic microsomal enzymes in animals (species not specified); the clinical implications of this effect are unclear.

Laboratory Interactions – Antihistamines can decrease the wheal and flare response to antigen skin testing. In humans, it is suggested that antihistamines be discontinued at least 4 days before testing.

Dimenhydrinate: Doses

Doses for dogs:

For prevention and treatment of motion sickness:

a) 8 mg/kg PO q8h

b) 25 – 50 mg PO once to 3 times a day

c) 4 – 8 mg/kg PO q8h

Doses for cats:

For prevention and treatment of motion sickness:

a) 12.5 mg (total dose) PO q8h

b) 12.5 mg PO once to 3 times a day

c) 8 mg/kg PO q8h

d) 4 – 8 mg/kg PO q8h

Monitoring Parameters

1) Clinical efficacy and adverse effects (sedation, anticholinergic signs, etc.)

Dosage Forms – Preparations – FDA Approval Status – Withholding Times

Veterinary-Approved Products:


Human-Approved Products:

Dimenhydrinate Tablets or capsules 50 mg; Commonly known as Dramamine® (Upjohn) (OTC); Many other OTC products also available

Dimenhydrinate Oral Liquid 12.5 mg/4 ml, 12.5 mg/5 ml and 15.62 mg/5 ml; in pints and gallons and in 90 ml, 120 ml and 480 ml bottles Children’s Dramamine® (Upjohn) (OTC); generic (OTC)

Dimenhydrinate Injection 50 mg/ml; in 1 ml amps and vials, 5 & 10 ml vials; Dramamine® (Upjohn); Generic; (Rx)

Veterinary Drugs



A synthetic nonsteroidal estrogen agent, diethylstilbestrol occurs as an odorless, white, crystalline powder with a melting range of 169°-175°C. It is practically insoluble in water; soluble in alcohol or fatty oils. Diethylstilbestrol is also known as DES or Stilbestrol.

Storage – Stability – Compatibility

All commercially available Diethylstilbestrol tablets (plain tablets, enteric-coated tablets) should be stored at room temperature (15-30°C) in well-closed containers.

Diethylstilbestrol: Pharmacology

Estrogens are necessary for the normal growth and development of the female sex organs and in some species contribute to the development and maintenance of secondary female sex characteristics. Estrogens cause increased cell height and secretions of the cervical mucosa, thickening of the vaginal mucosa, endometrial proliferation and increased uterine tone.

Estrogens have effects on the skeletal system. They increase calcium deposition, accelerate epi-physeal closure and increase bone formation. Estrogens have a slight anabolic effect and can increase sodium and water retention.

Estrogens affect the release of gonadotropins from the pituitary gland, which can cause inhibition of lactation, inhibition of ovulation and inhibition of androgen secretion.

Excessive estrogen will delay the transport of the ovum and prevent it from reaching the uterus at the appropriate time for implantation. Diethylstilbestrol also possess antineoplastic activity against some types of neoplasias (perianal gland adenoma and prostatic hyperplasia). It affects mRNA and protein synthesis in the cell nucleus and is cell cycle nonspecific.

Diethylstilbestrol: Uses – Indications

Diethylstilbestrol has been used in estrogen responsive incontinence in spayed female dogs and in the prevention of pregnancy after mismating in female dogs and cats. Its use alone for prevention of mismating is controversial as its efficacy is in doubt.

Diethylstilbestrol is used in canine medicine for the treatment of certain estrogen-responsive neoplasias (see Pharmacology and Doses below). The use of DES for these conditions is controversial because of the risks associated with therapy.

One author states that in small animals, “because of the alternatives and its possible side effects, estrogen is only indicated for treating mismating”. Another, states that in dogs, “owners should be routinely discouraged from having their bitches undergo abortion with estrogens.”


Diethylstilbestrol is well absorbed from the GI tract of monogastric animals. It is slowly metabolized by the liver, primarily to a glucuronide form and then excreted in the urine and feces.


Diethylstilbestrol is contraindicated during pregnancy, as it has been demonstrated to cause fetal malformations of the genitourinary system.

Estrogens have been documented to be carcinogenic at low levels in some laboratory animals. Because of the potential for danger to the public health, Diethylstilbestrol must not be used in animals to be used for human consumption.

Adverse Effects – Warnings

In cats and dogs estrogens are considered to be toxic to the bone marrow and can cause blood dyscrasias. Blood dyscrasias are more prevalent in older animals and if higher dosages are used. Initially, a thrombocytosis and/or leukocytosis may be noted, but thrombocytopenia/leukopenias will gradually develop. Changes in a peripheral blood smear may be apparent within two weeks after estrogen administration. Chronic estrogen toxicity may be characterized by a normochromic, normocytic anemia, thrombocytopenia and neutropenia. Bone marrow depression may be transient and begin to resolve within 30 – 40 days or may persist or progress to a fatal aplastic anemia. Doses of 2.2 mg/kg per day have caused death in cats secondary to bone marrow toxicity.

In cats, daily administration of Diethylstilbestrol has resulted in pancreatic, hepatic and cardiac lesions.

Estrogens may cause cystic endometrial hyperplasia and pyometra. After therapy is initiated, an open-cervix pyometra may be noted 1-6 weeks after therapy.

When used chronically in male animals, feminization may occur. In females, signs of estrus may occur and persist for 7-10 days.

Experimental administration of Diethylstilbestrol to female dogs as young as 8 months, of age have induced malignant ovarian adenocarcinomas. Doses ranging from 60 to 495 mg given over 1 month to 4 years were implicated in causing these tumors.

Diethylstilbestrol: Overdosage

Acute overdosage in humans with estrogens has resulted in nausea, vomiting and withdrawal bleeding in females. No information was located regarding acute overdose in veterinary patients, however, the reader is referred to the warnings and adverse effects listed above.

Diethylstilbestrol: Drug Interactions

Rifampin may decrease estrogen activity if administered concomitantly. This is presumably due to microsmal enzyme induction with resultant increase in estrogen metabolism. Other known enzyme inducers (e.g., phenobarbital, phenylbutazone, etc.), may have a similar effect, but clinical significance is unclear.

Enhanced glucocorticoid effects may result if estrogens are used concomitantly with corticosteroid agents. It has been postulated that estrogens may either alter the protein binding of corticosteroids and/or decrease their metabolism. Corticosteroid dosage adjustment may be necessary when estrogen therapy is either started or discontinued.

Oral anticoagulant activity may be decreased if estrogens are administered concurrently. Increases in anticoagulant dosage may be necessary if adding estrogens.

Drug/Laboratory Interactions

Estrogens in combination with progestins (e.g., oral contraceptives) have been demonstrated in humans to increase thyroxine-binding globulin (TBG) with resultant increases in total circulating thyroid hormone. Decreased T3 resin uptake also occurs, but free T4 levels are unaltered.

Diethylstilbestrol: Doses

Doses for dogs:

For pregnancy avoidance after mismating:

a) 0.1-1 mg PO for 5 days if animal is presented 24-48 hours after coitus. If animal is presented later than 5 days post-coitus: 1 – 2 mg PO for 5 days after ECP therapy (0.044 mg/kg (ECP) IM once during 3-5 days of standing heat or within 72 hours of mismating)

For treatment of perianal gland adenomas and prostatic hyperplasias:

a) 0.1 – 1 mg PO q24-48h

b) 1 mg PO q72h; or 1.1 mg/kg once. Do not administer more than 25 mg.

For treatment of estrogen-responsive incontinence:

a) Initially 0.1-1 mg PO daily for 3-5 days, followed by maintenance therapy of approximately 1 mg PO per week. Some animals may require much higher initial dosages to obtain a response. Maximum initial doses of 0.1 – 0.3 mg/kg once daily for 7 days, then reduce to once weekly. All maintenance doses should be gradually reduced to the lowest effective dose.

b) 0.1-1 mg PO per day for 3-5 days, then 1 mg once weekly

c) 0.1-1 mg PO for 3-5 days followed by 1 mg every week or less often. Some animals may require more than 1 mg weekly to maintain.

Monitoring Parameters

When therapy is either at high dosages or chronic; see Adverse effects for more information.

Done at least monthly:

1) Packed Cell Volumes (PCV)

2) White blood cell counts (CBC)

3) Platelet counts

Baseline, one month after therapy, and repeated 2 months after cessation of therapy if abnormal:

1) Liver function tests

Client Information

Contact veterinarian if signs and symptoms of lethargy, diarrhea, vomiting, abnormal discharge from vulva, excessive water consumption and urination or abnormal bleeding occur.

Dosage Forms – Preparations – FDA Approval Status – Withholding Times

Veterinary-Approved Products:


Human-Approved Products:

At the time of writing, no commercially available regular oral Diethylstilbestrol products are available in the USA, however compounded preparations may be available from a variety of compounding pharmacies.

Diethylstilbestrol Diphosphate Injection 50 mg/ml in 5 ml amps: .i.Stilphostrol;® (Miles) (Rx)

Diethylstilbestrol Diphosphate 50 mg Tablets; Stilphostrol® (Miles) (Rx)

Veterinary Medicine


1. Define coma. How is it different from stupor or obtundation?

Coma is a disorder of consciousness defined by absence of awareness. The comatose animal appears asleep but is unable to respond to external stimuli or physiologic needs except by reflex activity. Stupor implies a state of depressed consciousness responsive to some stimuli, even though it may lapse back into unconsciousness when the stimulus is withdrawn. An animal is considered obtunded when it is not alert, when it is disinterested in its environment, or when it has a less than normal response to external stimuli.

2. What parts of the brain must be affected to produce coma?

Consciousness is maintained by sensory stimuli passing through the ascending reticular activating system (ARAS) from the rostral brainstem to the cerebral cortex. Decreased consciousness results from global lesions of both central hemispheres or a lesion affecting the ARAS.

3. How does coma change emergency management?

With any emergency, ensuring a patent airway, providing adequate ventilation, and restoring circulating blood volume are necessary to prevent irreversible organ damage. The danger with animals suffering coma from increased intracranial pressure is that any therapeutic maneuver or drugs that increase brain blood volume may lead to irreversible brainstem herniation. In administering fluids and analgesics and in handling such patients, care must be taken to prevent iatrogenic increases in intracranial pressure.

4. Describe the initial treatment of comatose patients.

1. Check for a patent airway and ensure that ventilation is adequate. The partial pressure of carbon dioxide in arterial blood (PaCO2) should be kept below 35 mmHg to reduce cerebral blood flow and minimize cerebral edema.

2. Ensure adequate perfusion and cardiovascular function. Fluid therapy should be individualized because supernormal blood volume and pressure contribute to increased intracranial pressure.

3. Elevate the head and avoid compressing the jugular veins with catheters, bandages, or positioning.

4. Maintain body temperature between 99°F and 102°F.

5. Control seizures with diazepam and, if necessary, phenobarbital.

6. Supply glucose as needed to maintain blood levels between 100 and 200 mg / dl.

7. Supplemental oxygen is important to ensure that the partial pressure of oxygen in arterial blood (PaO2) is above 60 mmHg. To avoid handling the animal’s head, an oxygen cage is preferable to face mask or nasal insufflation. Supplemental oxygen is not a substitute for ventilatory support and does not prevent hypercarbia. If the animal becomes hypercarbic, ventilatory support may be necessary to prevent increased intracranial pressure.

5. How does a history of trauma affect emergency management of coma?

Trauma causes structural damage to the brain through contusion, laceration, and hemorrhage. The presence of hemorrhage within the calvarium complicates therapy because aggressive fluid administration and oncotic agents such as mannitol may worsen intracranial hemorrhage. Patients with head trauma should be evaluated carefully for signs of focal neurologic deficits, which may indicate a space-occupying hemorrhage. The therapeutic goals in cases of head trauma include normalizing blood pressure by carefully titrating crystalloid fluid therapy; and maintaining tissue oxygenation through supplemental oxygen. Hyperventilation of head trauma patients is no longer recommended as the reduced blood flow may worsen ischemic injury.

6. When should mannitol be used in patients with increased intracranial pressure? What are the contraindications?

Mannitol, an osmotic diuretic, dehydrates tissues and is effective in reducing brain tissue volume. In the presence of diffuse cerebral edema, it is the most effective agent to decrease intracranial hypertension. Its effects depend on an intact blood-brain barrier. Mannitol may cause a dramatic elevation in intracranial pressure before it exerts its action and reduces tissue volume. Mannitol is contraindicated in patients with hypovolemic shock, active bleeding, or cardiovascular compromise. It may lead to volume overload and continued hemorrhage. If mannitol leaks into tissues, it may draw excessive fluids with it. This is a major concern with space-occupying intracranial hemorrhage. Mannitol may leak into the hematoma, bringing with it more fluid and further compressing the cerebrum.

7. What are the general pathophysiologic categories of coma?

• Bilateral, diffuse cerebral disease

• Compression of the rostral brainstem (midbrain, pons)

• Destructive lesions of the rostral brainstem

• Metabolic or toxic encephalopathies

8. Describe the diagnostic approach to comatose patients.

Potential brain disease first should be classified according to location of the lesion and clinical course over time. History, physical examination, and serial neurologic examinations are the most useful tools. The clinician should assume increased intracranial pressure (ICP) in any animal with altered consciousness. Care should be taken to avoid anything that would further increase intracranial pressure. Neurologic examination of the comatose patient should determine whether the lesion is focal, multifocal, or diffuse. The examination should be repeated frequently to determine whether the patient is improving, unchanged, or worsening. Primary central nervous system (CNS) disease causing coma and stupor should be considered when lateralizing signs or cranial nerve deficits are noted. Generalized disease of the cortex, cerebellum, or brainstem suggests a primary process outside the central nervous system. Diagnostic tests to look for evidence of toxic or metabolic disease or organ dysfunction help to differentiate primary CNS disease from other causes.

9. What initial laboratory evaluations should be performed in comatose patients?

Acute coma without a history of trauma suggests a toxic or metabolic disorder. Owners should be questioned about access to various drugs and poisons, including antidepressants, tranquilizers, alcohol, and ethylene glycol. Blood should be drawn immediately for serum chemistries, looking for evidence of organ dysfunction. Blood glucose can be tested easily on admission. Hypoglycemia may be treated quickly while its cause is investigated. A complete blood count may reveal signs of systemic infectious disease or thrombocytopenia. Urinalysis may reveal calcium oxalate crystals in cases of ethylene glycol intoxication, ammonium biurate crystals with hepatic insufficiency or casts and isosthenuria with acute renal failure. Activated clotting time (ACT) can be tested quickly to assess the intrinsic and common coagulation pathways; ACT is markedly prolonged in patients with acquired coagulopathies. Once the results of the screening tests have ruled out organ dysfunction and metabolic disease, cerebral spinal fluid analysis and either computed tomography or magnetic resonance imaging should be performed.

10. What are the major causes of coma?

Trauma Metabolic diseases
Intracranial mass lesions Diabetic mellitus
Abscess Hypoglycemia
Granuloma Hepatic encephalopathy
Neoplasia Myxedema coma
Uremic encephalopathy
Hemorrhage Drugs
Vascular disease Barbiturates
Coagulopathy Opiates
Hypertension Alcohol
Embolism Tranquilizers
Inflammatory diseases Bromides
Canine distemper Toxins
Granulomatous meningoencephalitis Ethylene glycol
Bacterial and fungal meningitis Lead
Protozoal infections Carbon monoxide

11. Describe changes in pupil size, position, and reaction to light that help to determine location and severity of disease.

Symmetric pupils with normal direct and consensual response to light require a functional ventrorostral brainstem, optic chiasm, optic nerves, and retinas. Increased intracranial pressure and hemiation of the cerebellum under the tentorium cerebelli stimulate the nuclei of the oculomotor (third cranial) nerve, causing brief miosis of both pupils. As the pressure increases and the nuclei are irreversibly damaged, the pupils become fixed and dilated.

Anisocoria suggests primary CNS disease. If the pupils are unequal at rest but both respond normally to light and darkness, a unilateral cerebrocortical lesion contralateral to the larger pupil is likely. If the dilated pupil does not respond to light or darkness, a unilateral oculomotor nerve III lesion is present.

Metabolic diseases may cause symmetric miosis, whereas increased sympathetic tone may cause symmetric mydriasis. However, both respond normally to light and darkness. Symmetric miosis with no response to light or darkness is seen with damage to the pons, iridospasm, or bilateral sympathetic denervation (Homer’s syndrome).

12. What abnormal breathing patterns may be seen in comatose patients?

Lesions of the medulla may damage the basic rhythmic control of inspiration and expiration. Functional transection of the brainstem cranial to the medulla allows ventilation to continue but in gasps rather than smooth inspiration and expiration. Damage to the midpons cranial to the apneustic area results in apneustic respiration, characterized by prolonged inspiration and short expiration. Cheyne-Stokes respiration is characterized by deep breathing followed by periods of apnea or shallow respirations and indicates that normal feedback mechanisms no longer function. With normal control of ventilation impaired, the deep breathing causes a drop in CO2 of arterial blood. This drop is detected by the respiratory center in the brainstem, and respiration is inhibited. Progressive deterioration or compression of the brainstem often causes a slowing of respirations associated with rapid progression toward death.

13. What is the oculovestibular reflex? How can it be used to assess comatose patients?

Infusion of cold water into an ear canal normally induces horizontal nystagmus with the fast phase opposite the direction of the infused ear. Infusion of warm water induces horizontal nystagmus with the fast phase toward the infused ear. This caloric test of the oculovestibular reflex requires integrity of the brainstem, medial longitudinal fasciculus, and cranial nerves III, IV, VI, and VIII.

14. What is hepatic encephalopathy?

Hepatic encephalopathy is a clinical syndrome characterized by abnormal mentation, altered consciousness, and impaired neurologic function in patients with advanced liver disease and severe portosystemic vascular shunts. Hepatic encephalopathy results when the liver fails to remove toxic products of gut metabolism from the portal blood. Ammonia, mercaptans, short-chain fatty acids, and gamma-aminobutyric acid (GABA) agonists have been implicated in the pathogenesis of hepatic encephalopathy.

15. How is hepatic encephalopathy diagnosed?

Hepatic encephalopathy is suspected in patients with bizarre behavior after eating or with altered mentation and elevated liver enzymes. With hepatocellular damage both alanine transferase (ALT) and aspartate transferase (AST) are elevated. With congenital portosystemic shunts or end-stage liver failure, ALT and AST may be normal. Chemical parameters that suggest poor liver function include low blood urea nitrogen, low blood glucose, low albumin, lower serum cholesterol, and elevated serum bilirubin. Fasting and postprandial serum bile acids are markedly abnormal. Blood ammonia levels may be normal or elevated. Nuclear scintigraphy may be used to quantitate blood flow around the liver with portosystemic shunts.

16. What treatments are available for patients with hepatic encephalopathy?

Withdrawal of dietary protein is necessary to prevent production of intestinal ammonia. A 10% povidone iodine enema solution rapidly suppresses colonic bacteria and impairs ammonia production. Lactulose (1-4-beta-galactosidofructose; Cephulac, Merrell-Dow) is hydrolyzed by intestinal bacteria to lactic, acetic, and formic acid. With the lower intestinal pH, ammonia (NH3) accepts an additional H+ proton to form the less diffusible ammonium ion (NH4), effectively trapping ammonium within the colon. Lactulose is an unabsorbed solute and also causes an osmotic diarrhea, decreasing intestinal transit time and absorption. Lactulose may be given orally but should be given rectally in patients with altered mentation. Patients with chronic intractable portosystemic encephalopathies may benefit from the benzodiazepine antagonist flumazenil.

Veterinary Medicine


1. What is a seizure?

A seizure is a paroxysmal, transitory disturbance of brain function that has sudden onset, ceases spontaneously, and is likely to recur. Although most veterinarians call the resulting effects (e.g., jerky movements, staring) a “seizure,” the seizure is the neuronal event itself. The observable manifestation is called “seizure activity.”

2. Why are seizures an important emergency?

Something is interfering with normal functioning of a group of neurons. The hyperactivity of the neurons causes a build-up of metabolic byproducts, resulting in a harmful effect on the neurons. Neurons depend on aerobic metabolism. When the need for oxygen outstrips the availability, the neuron is injured. If this situation is prolonged, cell death results.

3. Describe the general pathophysiology of seizures.

Seizures are the result of disturbances in normal electrical activity in the brain. Anything that alters neuronal function may lead to a lower threshold of excitability and spontaneous depolarization. If the depolarization wave spreads to other areas of the brain or the entire nervous system, seizures result. The basic pathophysiologic processes that result in seizures are excessive cellular excitation and loss of cellular inhibition.

4. How are seizures classified?

In a study of nonreferral seizures, 53 etiologic diagnoses were found. The seizures were classified as follows:

Primary epileptic seizure (idiopathic or without a definable cause) – 44%

Secondary epileptic seizure (identifiable intracranial cause) – 46%

5. What is the difference between focal and generalized seizures?

Focal seizures remain localized to one body region. They may become generalized and are more often associated with structural brain disease.

Generalized seizures affect the entire body simultaneously.

6. What is the most common seizure in animals?

Generalized, tonic-clonic seizures.

7. Define status epilepticus.

Status epilepticus is a condition characterized by an epileptic seizure that is so frequent or so prolonged as to create a fixed or lasting condition. In veterinary medicine, status epilepticus traditionally has been defined as a seizure lasting 30 minutes or longer. This does not mean that one waits 30 minutes to institute therapy! A practical, operational definition for veterinarians for status epilepticus is either continuous seizure activity lasting at least 5 minutes or 2 or more seizures with poor or incomplete recovery between seizures.

8. Give examples of bizarre behaviors that may be manifestations of seizure disorders in animals.

• Fly-biting

• Tail-biting

• Flank-sucking

9. What are the common causes of seizures?

1. Idiopathic epilepsy
2. Metabolic disease

• Hypoglycemia

• Hypoxia

• Hypocalcemia

• Renal or hepatic disease

• Hyperkalemia

3. Infection

• Feline infectious peritonitis

• Rabies

• Canine distemper

• Other fungal or bacterial causes

• Toxoplasmosis

4. Inflammation (noninfectious)

• Trauma

• Granulomatous meningoencephalitis

5. Neoplasia
6. Malformation

• Hydrocephalus

• Lissencephaly

• Lysosomal storage disorders

7. Toxicities

10. How can the signalment aid in the initial diagnosis of seizures?

1. Age

• < 1 year

Congenital: hydrocephalus, lissencephaly

Inflammatory: meningitis

Metabolic: portosystemic shunts

Toxic: lead, ethylene glycol, organophosphates

• 1-5 years: primary epilepsy

• > 5 years Neoplasia

Metabolic: hepatic or renal dysfunction, hyperadrenocorticism, hypoadrenocorticism

2. Breed

• Beagle, German shepherd, Keeshond, collie, Belgian Tervuren: genetic or inherited primary epilepsy

• Miniature/toy breeds: hypoglycemia

• Yorkshire terrier, schnauzer: portosystemic shunts

3. Sex: epilepsy affects males more often than females.

11. Is a neurologic examination helpful in animals with seizures?

Certainly. You need to examine carefully the cranial nerves, comparing right with left and completing the examination with assessment of motor function and reflexes of the extremities. Idiopathic seizures are not commonly associated with interictal neurologic deficits. The caveat is that some dogs may have neurologic deficits in the postictal period that last for days after the seizure. Metabolic causes of seizures may be associated with persistent neurologic deficits, which are most commonly symmetrical.

12. What diagnostic testing should be done to localize the lesion?

• Laboratory studies: complete blood count, serum biochemical profile, urinalysis, and heart-worm or FELV/FIV testing

• Electrocardiogram

• Specialized testing: blood lead, ethylene glycol

• Radiography: thoracic, abdominal

• Computed tomography and magnetic resonance imaging

13. How should status epilepticus be treated initially?

Status epilepticus is a true emergency and must be managed quickly. The ABCs (airway, breathing, circulation) must be attended to immediately. Supplemental oxygen should be supplied. If the airway and breathing are compromised, an endotracheal tube is inserted and ventilation is assisted. Venous access should be established and crystalloid fluids administered. If the severity of the seizure or the size of the animal prevents quick venous access, diazepam may be administered rectally at 0.5-2 mg/kg. Intravenous diazepam is delivered to effect (up to 2 mg/kg). If diazepam is not effective, phenobarbital is administered intravenously up to to 16 mg/kg. You may not see an effect with phenobarbital for 20 minutes if the animal has not taken the drug previously. Constant-rate infusions of phenobarbital may be given at 2-4 mg/kg/hr. Body temperature may be quite high if the patient has been seizing for more than 10 minutes. Seizure control and intravenous fluids are usually adequate to correct hyperthermia. Use caution if cold water bathing is necessary (temperature > 105°F after 10 min); hypothermia is frequently a problem in patients requiring long-term sedation.

14. What are the advantages of using per rectum diazepam to control seizures at home?

Advantages include the ability to reduce the number of cluster seizure events, improved overall success in therapeutic control of idiopathic epilepsy, and fostering of a better home environment for the epileptic dog and its owner through the reduction of total seizure activity, yearly emergency clinic costs, and owner anxiety.

15. How are seizures treated pharmacologically?

Drug Half-Life Metabolism Dosage Interactions Side Effects, Toxicity
Diazepam 3.2 hr Hepatic 0.5-2 mg/kg IV or rectally CNS depression
Phenobarbital 47-74 hr (dogs) 34-43 hr (cats) Renal excretion Up to 16 mg/kg IV; 2-4 mg/kg orally 2 times/ day CNS depression / excitability; polyuria, polydipsia, polyphagia
Primidone 10-14 hr Hepatic 15-30 mg/kg/day divided into 3 doses Sedation, polyuria, polydipsia, nystagmus, anorexia, hepatotoxicity, dermatitis
Phenytoin 4hr Hepatic 35-50 mg/kg 3 times/ day Sedation, polyuria, polydipsia, nystagmus, tachycardia, hepatopathy, coagulation defects; toxic to cats
Clonazepam 1.4 hr Hepatic 0.5 mg/kg orally 2 or 3 times/day Sedation: after prolonged treatment may see withdrawal signs
Cloazepate 41 hr (humans) 2 mg/kg orally 2 times/ day ?
Potassium bromide 25 days Renal excretion Loading dose = 400-600 mg/kg orally over 30-60 min; 20-60 mg/kg/ day orally or divided inti 2 doses Vomiting, sedation, diarrhea, constipation

CNS = central nervous system.

16. What is a toxic blood level of phenobarbital?

40 mg/ml.

17. What are the complications of status epilepticus?

Hyperthermia, neurologic deficits (inability to walk normally, central blindness, and tremors), hypoglycemia, rhabdomyolysis, acidosis, hypertension, cardiac dysrhythmias, and death.

18. Which causes of seizure activity result in the poorest prognosis for dogs?

Granulomatous meningoencephalitis, loss of seizure control after 6 hours of hospitalization, or the development of partial status epilepticus.

19. Other than intravenous and intrarectal, what other route may be used for administration of diazepam during seizure?

Diazepam is absorbed rapidly and efficiently following intranasal administration. Plasma concentrations match or exceed the therapeutic concentration (300 ug/L). This technique may be useful when seizures in dogs are treated by owners or when IV access is not readily available. Be careful! You can receive a severe bite wound from the dog during this procedure.

Complementary Medicine

Granulamatous Meningoencephalitis

GME – Granulamatous Meningoencephalitis
/ Peripheral Neuropathies

Definition and cause

Peripheral neuropathies may represent numerous specific diagnoses. Many are inherited and have no successful treatment. When diagnosing such conditions it is helpful to divide them into categories of disease, including degenerative, genetic, idiopathic, inflammatory-noninfectious, inflammatory-infectious, metabolic, neoplasia, trauma, and vascular. Each particular case has a pathophysiology responsible for neurological dysfunction, and this identification may be immensely helpful in selecting proper biological therapy.

Often, the pathophysiology of many of these cases is never fully elucidated and clinicians may be forced to select therapy without a full understanding of the true condition. Common causes are immune-mediated, infectious, secondary to degenerative diseases such as diabetes or cancer, or secondary to a toxic reaction to chemotherapeutics or chemical toxins.

Establishing a complete diagnosis is well worth the effort. It may be very helpful to cooperate with internists and neurologists to determine successful treatment plans for patients suffering from neuropathies. Clients need to be counseled early on that these conditions may not respond and may even continue to deteriorate, even if the correct causation is determined.

Medical therapy rationale, drug(s) of choice, and nutritional recommendations

Medical therapy depends upon the underlying cause. If properly diagnosed and treated, the hope is that the neuropathy will resolve. Immune-mediated neoplasia most often require ongoing immunosuppressing therapies such as corticosteroids and chemotherapeutics.

Anticipated prognosis

The prognosis depends upon determining the underlying cause. Generally, a response is seen 1 to 3 months after initiating the therapy. The prognosis is poor to guarded if there is no response to the initial medical therapy.

Integrated veterinary medicine

The underlying process is inflammation of the central nervous system. While the specific cause is not reported, inflammation and immune-mediated processes most often necessitate the selection of corticosteroids as the primary therapy. The integrative approach, therefore, is to use nutrients, nutraceuticals, medicinal herbs, and combination homeopathics that have anti-inflammatory properties and can help to balance the immune system and reduce an exaggerated response. Clinicians should use any appropriate therapy in these cases; integrative therapy using conventional medicine, nutrition, and biological agents may speed recovery and improve patient comfort.


General considerations / rationale

While medical therapy is focused locally upon inflammation, the nutritional approach adds glandular support for the organs of the immune system as well as nutrients to help improve brain and nerve function.

Note: Because granulamatous meningoencephalitis and its symptoms can range from local to systemic, it is recommended that blood be analyzed both medically and physiologically to determine concurrent disease. This helps clinicians to formulate therapeutic nutritional protocols that address the central nervous system as well as other organ systems (see site, Nutritional Blood Testing, for additional information).

Appropriate nutrients

Nutritional / gland therapy: Glandular brain, nerve, adrenal, and thymus supply the intrinsic nutrients that help to reduce cellular inflammation and improve nerve and immune function. This helps to spare the brain and nerve from ongoing immune attack and helps slow degeneration and loss of function (see Gland Therapy in site for a more detailed explanation).

Phospholipids found in glandular brain are a source of unsaturated omega-3 fatty acids, which are now thought to play a vital role in the development and maintenance of the central nervous system. High concentrations of phosphatidyl choline and serine are found in brain tissue. Horrocks (1986) reported on the potential clinical use of these nutrients in chronic neurological conditions.

Phosphatidyl serine: Phosphatidyl serine is a phospholipid that is essential for the integrity of cell membranes, particularly those of nerve and brain cells. It has been studied extensively in people with impaired mental functioning and degeneration with positive results.

Lecithin / phosphatidyl choline: Phosphatidyl choline is a phospholipid that is integral to cellular membranes, particularly those of nerve and brain cells. It helps to move fats into the cells and is involved in acetylcholine uptake, neurotransmission, and cellular integrity. As part of the cell membranes, lecithin is an essential nutrient required by all of the body’s cells for general health and wellness.

Magnesium: Physiologically, magnesium activates adenosine triphosphatase, which is required for the proper functioning of the nerve cell membranes and fuels the sodium potassium pump. Magnesium is associated with neuromuscular function and conditions such as muscle cramping, weakness, and neuromuscular dysfunction. Magnesium is recommended for therapy for epilepsy and weakening muscle function.

Sterols: Plant-derived sterols such as betasitosterol show anti-inflammatory properties that appear to be similar to corticosteroids. A cortisone-like effect without the associated immune suppressing effects is beneficial in any inflammatory process in the central nervous system. Bouic reports on the immune enhancing and balancing effect of plant sterols that are also beneficial to animals with immune-mediated diseases.

Essential fatty acids: Research also confirms the benefits of essential fatty acids’ calming effect on the central nervous system.

Chinese herbal medicine / acupuncture

General considerations / rationale

Granulamatous meningoencephalitis is a combination of External Wind, Heat, and Toxin invading the Ying and Blood, which affects Wei and Qi at the same time. This leads to Heart and Pericardium disturbances.

Peripheral neuropathy may be a result of trauma or it may be due to Cold and Wind invasion, leading to Qi and Blood stagnation in the Meridians.

In granulamatous meningoencephalitis, the Wind blows the pathogenic influence into the body. Heat and Toxins then invade the Ying and Blood layers of the body. The Heat refers to fever and inflammation. Toxins are the substances that cause the inflammation. Wei is the immune system, so there is a disruption of immunoregulation, which is in agreement with the Western understanding of an immune basis to this disease. Neurological signs appear when the Ying level is affected. At the Xue level, the Heart and Pericardium, which house and protect the mind, are disturbed. When this occurs, the patient does not react properly to the environment. This can explain the seizures with the attendant loss of consciousness.

Treatment is aimed at decreasing the inflammation, fever, and pain, and normalizing the neurological function.

In peripheral neuropathy the ancient Chinese physicians were well aware of the ability of trauma to damage nerves. When they could not point to trauma as a cause, they theorized that Wind blew Cold into the body. Cold was able to slow the transit of Blood and Qi in the Meridians. Without a normal flow of Blood and Qi, the limbs could not function properly. Treatment is aimed at normalizing limb function.

Appropriate Chinese herbs for granulamatous meningoencephalitis

Achyranthes (Niu xi): Has shown analgesic effects. In mice it was shown to decrease pain reactions to body torsion and hot plates. It also demonstrated anti-inflammatory effects.

Arctium Niu bang zi: Has anti-inflammatory and antipyretic effects.

Buffalo horn shaving (Niu jiao): A strong pain reliever that also decreases edema.

Coix (Yi yi ren): Can help control pain and inflammation. It helps prevent carrageenin-induced foot swelling and dimethylbenzene-induced ear swelling in mice. A study involving 26 women with severe dysmenorrhea found that coix significantly decreased pain by more than 90%.

Forsythia (Lian qiao): Has anti-inflammatory, analgesic, and anti-pyretic effects and can prevent edema.

Gastrodia (Tian ma): Can help decrease pain. It decreases the level of dopamine in the brain, and this may be responsible for the analgesic effect (Huang 1993). It was shown to decrease agar-induced swelling in mice and carrageenin- and 5-HT-induced swelling in the feet of rats. This anti-inflammatory action may be useful in treating granulamatous meningoencephalitis.

Grass-leaf sweet-flag root (Shi chang pu): Contains alpha-asarone, which demonstrated an efficacy of approximately 85% in treating seizures in a group of 90 people. It may help decrease seizures in patients with granulamatous meningoencephalitis.

Honeysuckle (Jin yin hua): An anti-inflammatory and antipyretic herb.

Isatis (Da qing ye): Has anti-inflammatory effects.

Licorice (Gan cao): Contains glycyrrhizin and glycyrrhetinic acid, which have anti-inflammatory effects. They have approximately 10% of the corticosteroid activity of cortisone. They decrease edema and decrease the formulation of granulomas.

Lophatherum (Dan zhu ye): An antipyretic herb.

Mint (Bo he): Decreases fever and inflammation.

Platycodon (Jie geng): Contains platycodin, which has antipyretic effects. It also has anti-inflammatory effects via its ability to increase corticosterone secretion.

Pueraria (Ge gen): Reduces fevers (Modern traditional Chinese medicine Pharmacology 1997).

Schizonepeta (Jing jie): Has analgesic properties.

Scutellaria (Huang qin): Contains baicalin and biacalein, which have been shown to suppress inflammation in mice. It also can lower fever.

Silkworm (Jiang can): Has been shown to be effective in stopping experimentally induced seizures in mice. In one trial, 77% of humans with epilepsy who were treated with Jiang responded well. This suggests that it may help reduce seizure activity in patients with granulamatous meningoencephalitis.

Uncaria (Gou teng): Has been proven to prevent seizures in animals.

Acupuncture for granulamatous meningoencephalitis

The World Health Organization recognizes the efficacy of acupuncture for the treatment of headache (World Health Organization 2006). In addition, acupuncture has been shown to be better than phenobarbital at stopping fever-induced seizures in children. This may have a dual effect of addressing both the seizure and fever aspects of granulamatous meningoencephalitis.

Appropriate Chinese herbs for forelimb neuropathies

Angelica root (Dang gui): Increases phagocytic activity of macrophages, which may help patients with infectious peripheral neuropathies. It also decreases inflammation, which may make it beneficial in inflammatory etiologies.

Astragalus (Huang qi): Can improve humoral and cellular immune functions, which may help in the case of bacterial or viral neuropathies.

Centipede (Wu gong): Has antibiotic properties. It inhibits cancer cells in vitro, which indicates that it may be useful for neuropathies secondary to these causes.

Cinnamon twig (Gui zhi): Inhibits some bacteria and viruses.

Earthworm (Di long): Has anti-neoplastic effects. The mechanism is not yet elucidated, but it may be due to enhanced immunity and scavenging of free radicals. This may help in some forms of neoplastic neuropathy.

Jujube fruit (Da zao): Can inhibit dimethylbenzene-induced ear swelling in mice, and egg white-induced toe swelling in rats. It may also ameliorate inflammatory neuritis.

Licorice (Gan cao): Inhibits bacteria and viruses. It may be efficacious in viral and bacteria-mediated neuropathies.

Milettia (Ji xue teng): Has antiviral effects. It has been shown to inhibit herpes virus I (simplex), a virus known to be neurotropic. In addition, it has demonstrated activity against cancers via increased NK activity in mice.

Rehmannia / cooked (Shu di huang): May help improve the conditions of nerves. One trial examined the results of an herbal supplement containing rehmannia with Rou cong rong, Lu han cao, Gu sui bu, Yin yang huo, Ji xue teng, and Lai fu zi in 1,100 patients with myelitis. 73% had significant improvement, and another 13% had moderate improvement in clinical signs.

Tumeric (Jiang huang): May decrease neuronal inflammation. It inhibits MIP-2 (macrophage inflammatory protein-2) production. This chemical has been implicated in traumatic brain injury, which strongly suggests applicability in patients with neuropathy.

White peony (Bai shao): Contains paeoniflorin, which is a strong anti-inflammatory. In addition, it seems to have a neurotropic effect. It contains gallotannin, which prevents neuron damage in mice with cobalt-induced seizures (Sunaga 2004). This may make it a powerful herb for decreasing neuronal inflammation.

Wild ginger (Xi xin): Inhibits carrageenin-induced foot swelling. It may prevent inflammation in the nervous system, thereby treating inflammatory neuropathies.

Appropriate Chinese herbs for hindlimb neuropathies

Achyranthes (Niu xi): Decreases egg-white-induced foot swelling in rats. It may help decrease inflammation in the nervous system.

Alpinia (Yi zhi ren): Has demonstrated some anti-neoplastic activity.

Antler powder (Lu jiao jiao): Enhances the phagocytic function of macrophages and can be used as an adjuvant in cancer treatment.

Astragalus (Huang qi): See forelimb paralysis, above.

Cornus (Shan zhu yu): Can inhibit carrageenin-induced toe swelling in rats and mice. This suggests that it may be useful in cases of inflammatory etiologies.

Dioscorea (Shan yao): Stimulates both the humoral and cellular immune system. It may help with infectious causes of neuropathy.

Eucommia (Du zhong): Contains chlorogenic acid, which has antibacterial effects. It stimulates cellular immunity, which may make it useful when the neuropathy is due to infectious etiologies.

Ophiopogon (Mai men dong): Effective against Staphylococcus albus, Bacillus subtilis, E. coli, and Salmonella typhi.

Papaya (Mu gua): Has inhibitory effects on tumors.

Poria (Fu ling): Has antibiotic effects. It also stimulates cellular immunity. Finally, it has demonstrated anti-neoplastic activity.

Rehmannia / cooked (Shu di huang): See forelimb paralysis, above.

White atractylodes (Bai zhu): Has demonstrated anti-neoplastic efficacy.

Appropriate Chinese herbs for facial neuropathies

Angelica root (Dang gui): See forelimb neuropathies, above.

Centipede (Wu gong): See forelimb neuropathies, above.

Cnidium (Chuang xiong): Increases the phagocytic function of macrophages. It may be helpful in infectious neuropathies.

Gastrodia (Tian ma): Decreases nerve pain from toxins and vascular causes.

Ginseng (Ren shen): Prevents the decrease in plasma T3 and T4 levels as laboratory animals age. It may be useful in hypothyroid-induced neuropathies.

Siler (Fang feng): Has antibiotic properties. It is also anti-neoplastic.

Silkworm (Jiang can): Can inhibit some bacteria.

White aconite (Bai fu zi): May help with facial nerve disorders. In one study, 90% of 418 people with facial numbness recovered completely when an herbal formula containing typhonium (Bai fu zi), angelica root (Dang gui), scorpion (Quan xie), sick silkworm (Jiang can), and centipede(Wu gong) was injected into acupoints.


General considerations / rationale

Granulamatous meningoencephalitis is an intracranial proliferative inflammatory process involving mesenchymal cells, which may present in a generalized inflammatory form or a mass form. The cause is unknown. Lymphocytes and macrophages are the primary inflammatory cells that are present (Bagley 2005).

There is no published material on this condition in any homotoxicology references, which makes the material that follows an academic discussion. Goldstein (2006) has successfully used the protocol below in combination with other integrative modalities discussed in this section.

Because connective tissue elements function in an abnormal and deleterious manner, this condition represents a disease to the right of the Biological Divide, most likely the Impregnation and Degeneration phases. There may be Dedifferentiation Phase factors involved. Examination of such cases for chemical or viral agents may prove interesting in researching the cause. Antihomotoxic agents discussed in the encephalitis / meningitis section are applicable. Phase remedies and deep detoxification with support of energy-producing enzyme systems represent a logical clinical approach to this condition. The expected prognosis is guarded. The use of drugs such as corticosteroids and immunosuppressants are warranted to preserve patient comfort and ability. As with all neurological problems, use of a qualified neurologist may be helpful in establishing the correct diagnosis and most current treatment options.

Selecting symptom remedies and detoxification protocols is extremely important in neurology cases. Many homeopathic and herbal agents have affinity for neural tissue in specific body regions (neck, face, lumbar spine, extremities), and the integrative clinician should always be sure to consider the anatomical region is designing proper treatment programs. In traumatic cases, the use of simple single antihomotoxic formulas such as Traumeel S may give immediate improvement. Most cases of peripheral neuropathies presented to veterinarians represent deeper homotoxicoses and require combinations of therapy and careful monitoring of progress. Always remember that the goal of therapy is regressive vicariation and that signs of inflammation and discharge may well represent the beginning of healing in a patient. Inherited conditions generally carry a guarded prognosis, but may improve or stabilize with biological therapies integrated with conventional medical handlings, and it is beneficial to have a basic understanding of these approaches when faced with a nonresponsive or difficult case.

The development of acutely painful conditions similar to shingles in humans may represent the movement of homotoxins from chronic Impregnation and Degeneration phases to the Inflammation Phase, and should be welcomed as a potentially good sign. Other neurological signs may occur during these regressive vicariations (i.e., altered awareness, personality changes, tics, and seizures) and may require experienced handling as the patient moves from right to left of the Six-Phase Table of Homotoxicology.

Appropriate homotoxicology formulas

Aesculus compositum: Useful in improving circulation following stroke or reduced cerebral circulation (Aesculus hippocastanum and Secale cornutum). Areteria suis supports the arteries. Solanum nigrum further supports cerebral function, particularly in cases with confusion, epileptic seizures, or disorientation. Several other agents support homotoxin removal and improve vessel stability.

Apis homaccord: Generally useful in edema, but also in cerebral sensitivity. May assist cardiac-induced cerebral weakness through Scilla, Apisinum, and Apis mellifica. The main symptoms of Apis may be summed up as follows for quick reference: sensitivity to touch and jarring; irritation of the meninges, especially from suppressed eruptions; diseases of the serosa, joints, and meninges; infiltration of the cellular tissues; and serous meningitis. Apis is also found in Aesculus compositum, Cerebrum compositum, Blacenta compositum, and Tonsilla compositum.

Arsuraneel: Used for patients not responding to initial therapy; this formula may move them into a recovery phase through stimulation of the general defenses. Useful in cases with seizures, anxiety, feeling worse at night, paresis, and muscular disability.

Belladonna homaccord: Belladonna, which has an affinity for the central nervous system, is useful in patients manifesting seizures and who scream out at night. Violent delirium is characteristic of Belladonna, above all in fever. Belladonna’s typical action on the eyes is also well-known, with cramps in the muscles of the eyes and eyelids, enlargement of the pupils and, in particular, an inflammatory or irritative condition of the conjunctiva with marked photophobia, lachrymation, and pain. Belladonna is indicated in incipient boils, tonsillitis, and surface inflammations such as erysipelas, conjunctivitis, scarlet fever, otitis, cholangitis, meningitis, and other inflammatory affections. A delirious state occurs with a violent rise in temperature with considerably raised sensitivity of all the senses and a disproportionate sensitivity to touch, noises, light, cold air — especially draughts and jarring — as can be the case in meningitis. Along with nasal catarrhs, there may be catarrhs of the larynx and trachea, with slight mucus, accompanied a typical cough, which is dry, rough, and barking, with hoarseness. In the digestive organs, Belladonna affects acute gastric catarrhs. Belladonna is also common to Traumeel, Spigelon, Viburcol, BHI-Inflammation, BHI-Neuralgia, and BHI-Recovery formulas.

BHI-Inflammation: Contains Rhus toxicodendron for cases of weakness and paresis. Cases may be aggravated after lying in wet grass. Patients that benefit may have pustular, pruritic skin conditions; joint pain; myelitis; vertigo / dizziness; intercostal pain; and other types of neuralgia. Commonly used in combination with other antihomotoxic agents.

Bryaconeel: Used for neuralgia, serous membrane inflammation such as meningitis (Bryonia cretica), acute feverish conditions, and influenza-like signs. Contains Phosphorus to support parenchymatous organs such as the lung and liver. Moderates severe or overaggressive vicariations. Used in meningitis in cases not responsive to primary therapy.

Cerebrum compositum: Supports cerebral tissue, stem cells, and vessels (Cerebrum suis, Placenta suis, Arnica montana). Treats memory loss and forgetfulness and improving memory (Selenium, Thuja occidentalis, Acidum phosphoricum, Manganum phospohoricum, Semecarpus anacardium, Ambra grisea, Conium maculatum, Medorrhinum-Nosode). Supports cerebral function and vascular structures (Kalium phophoricum). Treats vertigo, stupor, headache, and weakness (Gelsemium sempervirens, Kalium bichromicum, Ruta graveolens) anxiety (Aconitum napellus), and exhaustion (China, Amarita cocculus). Supports capillary and other circulation, as well as lymph (Aesculus hippocastanum) and enzyme systems and difficulty sleeping (Hyoscyamus niger).

Coenzytne compositum: Supports energy production through enzyme induction and repair, and is useful in repairing damage to enzyme systems of metabolism and following administration of drugs injurious to metabolism. Sulfhydral groups in Cysteinum assist in repairing therapeutic damage and in cases of forelimb weakness. Phase remedy in Degeneration and Dedifferentiation phases.

Cruroheel: Has strong connective tissue effects and is useful in difficult cases or those with strong vicariations.

Discus compositum: Clears the deep matrix and supports connective tissue repair, and treats irritation originating in the spinal column. Contain a number of useful remedies that particularly benefit musculoskeletal function, including Funiculus umbicalis suis (also contained in Cutis compositum, Blacenta compositum, Tbyroidea compositum, Tonsilla compositum, and Zeel) for debility. Treats arteriosclerosis, cervical spondylosis, collagen diseases, scleroderma, fibromas, vascular pathology, geriatric indications of all kinds, dystonia of the autonomic nervous system, autoimmune diseases, damage from antibiotics and other drugs, general iatrogenic damage, multiple sclerosis, and muscular atrophy. Also contains Niconitamidum, which is used to activate the energy metabolism in insufficiencies of the respiratory chain. The substance, which occurs naturally in the body, is an important component of NAD and NADP. Treats deficiencies of Nicotinamidum that lead to mental and neurological disturbances. It is common to the remedies Coenzytne compositum, Discus compositum, Ginseng compositum, Ubichinon compositum, Zeel, and BHI-Enzyme.

Echinacea compositum: Contains Aconitum, which is indicated for catarrhs, neuralgic symptoms with paresthesia, hyperthermia, and encephalitis with very high temperatures (e.g. post-vaccinial encephalitis or meningo-encephalitis, which may be activated by the implantation of living cells). Low potencies are normally given in pyrexia and organic complaints. The component Aconitum is common to several useful remedies, including Barijodeel, Bryanconeel, Cerebrum compositum, Gripp-Heel, and Traumeel. Baptisia is included for meningitis and encephalitis, serious feverish infections, general blood poisoning, and states of confusion. Aesculus compositum, Arnica-Heel, and other complexes are also included.

Engystol N: Has antiviral effects through immunostimulation.

Galium-Heel: Phase remedy in the matrix and cellular phases. Provides powerful support of the immune system (Echinacea augustifolia). Assists in drainage of cell and matrix, supports renal tubular function, and decreases swelling and edema (Apis mellifica, Galium aparine, and Galium mollugo). It is a critical component in the deep detoxification formula. Doses should be administered with regard to clinical condition and response, with the dose reduced if strong reactions are noted.

Gelsemium homaccord: Treats neuralgia and nerve pain, headache, and posterior weakness. Commonly required in aging large-breed dogs. This is a major antihomotoxic agent used in many neuropathy cases. Think of this agent in trembling pets because Gelsemium is known as the “trembling” remedy.

Ginseng compositum: Treats eyelid weakness and exhaustion.

Glyoxal compositum: Provides mitochondrial repair of damaged enzyme systems in Degeneration and Dedifferentiation phase disorders.

Listeriosis nosode: This remedy is not available in any of the homotoxicology combinations, but could be useful as a single remedy. The zoonotic organism Listeria monocytogenes causes a disease characterized by granulomatous meningoencephalitis in small animals.

Lymphomyosot: Used after cortisone therapy and for mesenchymal purging in chronic disease states.

Neuralgo-Rheum-Injeel: The components Causticum Hahnemanni and Rhus toxicodenron are powerful neurological remedies that cover a wide variety of chronic rheumatic-arthritic complaints, skin conditions, and intercostalsciatic neuralgias.

Placenta compositum: Supports hypophysis after cortisone therapy. Contains sulfur to support enzyme and metabolic repair. Regenerative of hypophyseal-adrenal axis, and repairs vascular structures. Used intermittently in endocrine disorders.

Psorinonheel: Useful in deep, constitutional / genetic homotoxicoses. Consider in experimental application in inherited conditions. This remedy contains Cicuta, which is indicated for meningitis with hypersensitivity. It is a complementary remedy in tuberculous meningitis.

Solidago compositum: Deposition Phase remedy needed to remove debris from the matrix after regressive vicariation begins. In Traditional Chinese Medicine, the Kidney Chi governs the Brain, and as such, neurological issues may benefit from support of the Kidney and related tissues. Part of the deep detoxification formula. An interesting indication in this remedy is for Coxsackie virus nosode, which is used for abacterial meningitis and encephalitis.

Spigelon: Helpful for symptoms of headache, cerebral conditions with inflammation, and weakness of connective tissues.

Thyroidea compositum: Used for matrix drainage and autoregulation repair. Contains low levels of thyroid, pineal, spleen, bone marrow, umbilical cord, and liver to support glandular function and repair. Galium aparine drains the matrix and cellular components. Cortisonum aceticum in low potency assists in repairing damage from excess levels of cortisone. Precursors and Krebs cycle constituents promote energy metabolism through the Michae-lis-Menten law of enzyme activity. Pulsatilla and Sulfur assist in regulation rigidity-type situations. Part of the deep detoxification formula.

Tonsilla compositum: Main antihomotoxic drug for chronic diseases involving endocrine disorders. Supports a wide number of tissues including tonsil, lymph node, bone marrow, umbilical cord (stem cell precursors), spleen, hypothalamus, liver, embryo, and adrenal cortex. Contains Cortisonum aceticum and thyroid hormone in nanodilutions. Also contains Psorinum for deep constitutional, lack of reaction cases. Degeneration Phase agent.

Ubichinon compositum: Provides mitochondrial repair of energy production mechanisms. Used in chronic diseases and iatrogenic injury to mitochondria from antibiotic therapy, and is part of the deep detoxification formula. Parabenzochinon, a critical component in this regard, is indicated for autoimmune issues, and has been recommended for a state of paresis occurring after poliomyelitis, encephalitis or vaccinations, disturbance in neuromuscular coordination, conditions such as multiple sclerosis and tumors in the spinal area with pains and paresis, and brain tumors. In many cases of meningeal irritation, parabenzoquinone deals with the terrible pains better than an opiate.

Authors’ suggested protocols


Brain / nerve and immune support formulas: 1 tablet for each 25 pounds of body weight BID.

Phosphatidyl serine: 25 mgs for each 25 pounds of body weight BID.

Lecithin / phosphatidyl choline: One-fourth teaspoon for each 25 pounds of body weight BID.

Betathyme: 1 capsule for each 35 pounds of body weight BID (maximum, 2 capsules BID).

Essential fats: One-half teaspoon for every 35 pounds of body weight with food.

Magnesium: 10 mgs for every 10 pounds of body weight SID.

Chinese herbal medicine / acupuncture

For granulamatous meningoencephalitis, the patent formula is Yin Qiao San. It contains arctium (Niu bang zi), forsythia (Lian qiao), honeysuckle (Jin yin hua), licorice (Can cao), lophatherum (Dan zhu ye), mint (Bo he), phragmites root (Lu gen), platycodon (Jie geng), schizonepeta (Jing jie), and soybean (Dan dou chi). It is dosed according to the manufacturer’s recommendation. Yin Qiao San has been shown experimentally to decrease inflammation. It inhibited dimethlybenzine-induced increase in skin capillary permeability. It also has antipyretic effects similar to aspirin. In addition it has been shown to have antibacterial and antiviral efficacy (Shanghai Health and Epidemic Prevention Station 1960). Finally, it has analgesic properties as demonstrated using hot plate and acetic torsion experiments in mice. It was used to treat encephalitis B in 37 people with good response. In another study on people with encephalitis (nonspecified origin), 74 of 81 people recovered completely, 2 did not respond completely and 5 people died.

An alternative herbal supplement is H25 granulamatous meningoencephalitis Disorder at a dose of 1 capsule per 10 to 20 pounds twice daily. In addition to the herbs in Yin Qiao San, H25 granulamatous meningoencephalitis also contains achyranthes (Niu xi), buffalo horn shavings (Niu jiao), chrysanthemum (ju hua), coix (Yi yi ren), gastrodia (Tian ma), grass-leaf sweet-flag root (Shi chang pu), hoelen spirit (Fu shen), isatis leaf (Da qing ye), isatis root (Ban Ian gen), papaya (Mu gua), phellodendron (Huang bai), pueraria (Ge gen), scutellaria (Huang qin), silkworm (Jiang can), and uncaria (Gou teng).

These formulas can be combined with conventional drugs, but often are only needed for a short period of time.

The author uses the following acupuncture points for granulamatous meningoencephalitis: ST36, GV14, CV17 and GB20.

For forelimb neuropathies, the authors recommend H41 Forelimb Paralysis at a dose of 1 capsule per 10 to 20 pounds twice daily. In addition to the herbs discussed above, H41 Forelimb Paralysis contains codonopsis (Dang shen) and scorpion (Quan xie), which increase the efficacy of the formula.

The author recommends the following acupuncture points: LIU, SI9, TH6, LI10, ST36, and Bai Hui.

For hindlimb neuropathies the authors recommend H 72 Hindlimb Paralysis / Incontinence at a dose of 1 capsule per 10 to 20 pounds twice daily. In addition to the herbs mentioned above, H72 Hindlimb Paralysis / Incontinence contains American ginseng (Xi yang shen), ciborium (Gou ji), cynomorium (Suo yang), fossil bones / raw (Long gu), lindera (Wu yao), mantis egg case (Sang piao xiao), polygonatum (Yu zhu), and tortoise plastron (Gui ban). These herbs enhance the function of the herbal supplement.

The author uses the following acupuncture points: ST36, UB60, BL30, and Bai Hui.

For facial neuropathies the authors use H 73 Facial Nerve Paralysis at a dose of 1 capsule per 10 to 20 pounds twice daily. In addition to the herbs listed above, H 73 Facial Nerve Paralysis contains scorpion (Quan xie) to improve the efficacy of the formula.

The author recommends the following acupuncture points: ST4, ST6,ST7, and SI9.


Deep detoxification may assist noninherited conditions, and support of energy metabolism through the use of catalysts should be considered. Use of antihomotoxic agents that match the patient’s symptoms may be helpful. Treatment must be individualized to the specific patient’s needs. Any clinician successfully treating either inherited or acquired polyneuropathies should report their findings for publication.

GME (granulamatous meningoencephalitis)

Symptom formula: Two protocols exist.

1. Administer Echinacea compositum IV and Solidago compositum and Galium-Heel as an autosanguis, and dispense anoral cocktail consisting of Traumeel, Psorinoheel, and Aesculus compositum BID to TID. Use Ubichinon compositum orally BID. Administer Spigelon for pain and inflammation associated with the illness, and consider Listeria nosode, obtained from a single remedy company, or Heel-Germany.

2. Administer Gelsemium homaccord, BHI-Inflammation, Spigelon, and Traumeel S mixed together and given PO BID for 3 weeks, then alternate with Pulsatilla compositum in an attempt to shift regulation rigidity. Give Cerebrum compositum 1 to 3 times weekly. Consider autosanguis therapy.

Deep detoxification formula: Galium-Heel, Lymphomyosot, Hepar compositum, Solidago compositum, Thyroidea compositum (alternated with Tonsilla compositum in inflammatory conditions), Coenzyme compositum, and Ubichinon compositum combined and given orally twice weekly. Consider giving these and the above symptom formula agents as autosanguis therapy.

Acquired peripheral neuropathies

In nearly all cases it would be appropriate to administer Neuralgo-Rheum and Discus compositum 2 to 3 times weekly by injection.

Deep detoxification formula: Galium-Heel, Lymphomyosot, Hepar compositum, Solidago compositum, Thyroidea compositum (alternated with Tonsilla compositum in inflammatory conditions), Coenzyme compositum, and Ubichinon compositum combined and given orally twice weekly. Consider giving these agents as autosanguis therapy.

Diabetic polyneuropathy

Lymphomyosot, Syzygium compositum, and Mucosa compositum given orally in conjunction with alpha-lipoic acid. (See also Diabetes mellitus protocol).

Hypothyroid polyneuropathy

Administer in addition to proper thyroid hormone replacement therapy. Thyroidea compositum given twice weekly alone or as part of the deep detoxification formula if the condition is stable.

Iatrogenic pharmaceutical injury (vincristine, vinblastine, and colchicines)

Deep detoxification formula, IV fluid support, and avoidance of the offending drug until it can be cleared.


Deep detoxification formula, and also consider BHI-Body Pure for 1 to 3 months.

Immune-mediated (autoimmune such as systemic lupis erythmatosis)

See autoimmune protocols.

Infectious (Neospora caninum and FeLV)

Use clindimycin for Neospora. See the FeLV protocol section. Tonsilla compositum given twice weekly and Echinacea compositum daily by injection during acute involvement. Engystol may improve immune function given daily. Traumeel S if acute inflammation or swelling is involved.

Toxic injury (metals, solvents such ascarbon tetracycline, organophosphate, insecticides)

Deep detoxification formula in conjunction with appropriate antidote, plus supportive and chelation therapy.

Product sources


Brain / nerve and immune support formulas: Animal Nutrition Technologies. Alternatives: Immune System Support — Standard Process Veterinary Formulas; Immuno Support — Rx Vitamins for Pets; Immugen — Thorne Veterinary Products.

Phosphatidyl serine: Integrative Therapuetics.

Lecithin / phosphatidyl choline: Designs for Health.

Betathyme: Best for Your Pet. Alternative: Moducare Thorne Veterinary Products.

Beyond essential fats: Natura Health Products. Alternatives: Flax oil — Barlean’s Organic Oils; Hemp oil — Nature’s Perfect Oil; Ultra EFA — Rx Vitamins; Omega- 3,6,9 — Vetri Science.

Magnesium: Over the counter.

Chinese herbal medicine

Yin Qiao San: Mayway Corp.

Formulas H25 granulamatous meningoencephalitis, H41 Forelimb Paralysis, H72 Hindlimb Paralysis / Incontinence, and H73 Facial Nerve

Paralysis: Natural Solutions, Inc.


BHI / Heel Corporation