Therapeutics

Acute Management and Stabilization

Acutely nonambulatory patients are often best managed with hospitalization. The emo­tional distress of the owner and the need to prevent further declines generally makes this the best approach.

Chronic Therapeutic Options

If owners confront a condition that is likely to be progressive, it is important to have early and extensive conversations regarding their goals, treatment philosophies, financial or logistical limitations, as well as the point at which they feel that mobility could impair their animal's quality of life. The latter is dif­ficult to raise when an animal's condition is stable and mild, but such documented con­versations serve as important reference points for future decisions about care and end-of-life.

Therapeutic interventions are best offered and administered in a stepwise fashion in order to better assess a patient's response to a particular intervention, especially given that the chronic management of most patients will be multimodal. Owners are over­whelmed by the diversity of options and the relative merits if presented at an initial evaluation.

Pharmacologic Interventions

Mobility disorders without an inflammatory component or pain generally fail to respond to pharmacologic interventions.

If a patient has reduced mobility due to an inflammatory condition such as osteoarthri­tis, the following drugs may be of benefit.

• Prednisone (0.5-1 mg/kg/day), predniso­lone (same dose, cats) or equivalent steroid: Animals which respond should be tapered to the lowest effect dose. Many dogs can demonstrate a response at 0.25mg∕kg every other day, which is consistent with ‘physiologic' dosing but which appears to still ameliorate clinical signs in some patients. Steroids are not recommended by the author as a first-line in the manage­ment of intervertebral disc disease.

• Carprofen (2.2mg∕kg BID) or equivalent non-steroidal anti-inflammatory drug in dogs: Carprofen remains the most well- studied of all the NSAIDs in dogs and is effective in the management of mobility reductions secondary to degenerative joint disease. Many geriatric dogs benefit from lower doses at the same frequency, espe­cially in combination with analgesics when appropriate.

• NSAID use in cats: A number of NSAIDs are now labeled for use in cats, but their use should still be approached with caution and with the dose titrated to the lowest effective dose. Meloxicam and robenacoxib are labeled for use in cats, but only short-term. The American Association of Feline Practitioners main­tains guidelines for the use of NSAIDs in cats which should be reviewed prior to their use.

Pain may have primary or secondary effects on mobility, and in either case should be treated aggressively. Adjunctive agents are often necessary even when administering a glucocorticoid or NSAID. The following therapeutic options are available.

• Tramadol: 5mg∕kg q6-12h dogs, 2mg∕kg q12-24h cats. Tramadol is extremely well tolerated in both species with minimal risk of a meaningful overdose.

• Amantadine: 3-5mg∕kg q12-24h. This drug works on the NMDA receptor but without the dissociative effects associated with ketamine. It has been shown to be well-tolerated in dogs, especially in combi­nation with an NSAID. Experience in cats is limited, and once daily dosing at the low end of the dose range is prudent.

• Buprenorphine: 5-20 ug/kg q8h sublin­gually (cats). This opioid can be used chronically as needed but may be difficult to administer to some cats and has the disadvantage of needing to be dosed more frequently than other options.

• Gabapentin: 5-10mg∕kg q12h starting dose. Gabapentin has been suggested for chronic and neuropathic pain although its efficacy has been variable depending on the condition for which it was adminis­tered. It is recommended an adjunctive agent for that reason.

• Amitriptyline: 0.25-2 mg/kg q12-24 h. This tricyclic antidepressant may have effects on chronic pain through central mediation of pain. Caution should be used with other tricyclic drugs, selective serotonin reuptake inhibitors (SSRIs), and monoamine oxidase inhibitors (MAOIs).

• Fentanyl patch: 2-5ug∕kg∕h, to a maxi­mum of a 100 ug∕h patch for large dogs, rounded to the nearest size patch and 25 ug∕h for cats. Fentanyl patches provide analgesic support for at least 72 hours, but potentially for up to a week in some patients. Onset may be delayed 4-24 hours after application, and animals should be monitored so as to not remove or ingest the patch.

• Topical lidocaine patches: Patches are cut to size and deliver drug to the area deep to the patch. Effects will be limited to the site of contact and by duration of drug delivery, which is about 12-24 hours.

Intra-articular Injections

Degenerative joint disease may be managed with a combination of local and systemic therapies. Intra-articular injections are a valuable adjunct if isolated joints are a significant source of lameness or pain.

1) Triamcinolone: A glucocorticoid with documented efficacy at reducing inflam­mation. The recommended dose is not well established, but doses of 3mg for small joints or feline injections have been recommended. Doses of 6mg for larger canine joints are often used. If multiple joints are to be injected, a total dose not to exceed 1mg∕kg has been used by the author. Systemic absorption will occur, and there will be some suppression of the adrenocortical axis but side effects are typically mild. Theoretical contraindica­tions on cartilage growth exist, but some literature suggests that the inflammatory environment of the joint is more hostile to cartilage repair than is a glucocorticoid injection. Animals typically respond within 5-7 days, and effects may be sus­tained for 1-2 months.

2) Morphine: Intra-articular (IA) morphine has been shown to have postoperative analgesic effects in animals and sustained effects in human osteoarthritic patients. Doses of 0.1-0.5 mg/kg have been reported, with the author dosing on the high end. The duration of IA morphine is unknown, but is likely effective at least for several days. Given the uncertainty about dosing, the author typically mixes with another IA agent.

3) Local anesthetic: Bupivicaine or mepiv- acaine (0.5% solution) can be adminis­tered concurrently with other agents to reduce postinjection discomfort resultant from the capsular distension associated with an IA injection. Doses of 0.5 mg/kg have been used postoperatively for anal­gesia, but the volume may be determined by the practical volume limits if other agents are given.

4) Regenerative therapies: Platelets and stem cells are discussed in greater detail later but are equipped to provide growth fac­tors and stimulate tissue repair. It remains unclear as to whether IA stem cell injec­tions cause differentiation of cells into chondrocytes or if the stem cells have other indirect effects on reducing joint inflammation and inducing tissue repair.

5) Prolotherapy: Prolotherapy, or the injec­tion of irritants, in the joint remains uncommon in veterinary medicine but it has attracted significant attention in human medicine. IA concentrated dex­trose solutions produced equivalent effects to IA steroids in some human studies. However, a study of osteoarthritic dogs found no benefit to IA injections of 5 mL of 25% dextrose.

Nutrition and Supplements

Dogs and cats with impaired mobility require evaluation of dietary intake. The three major considerations are as follows:

1) Caloric intake. If animals are less active than expected, caloric expenditure is likely to decrease. Most pet dogs require no more than 95 ? (ideal body weight in kg)⁰'⁷⁵ kcal per day. Paralyzed humans dis­play a reduction in caloric intake of about 1/3 although this may be mediated by a reduction in muscle mass. Pet foods vary widely in caloric content and therefore owners should be given specific instruc­tions on what and how to feed. These recommendations are consistent with current AAHA guidelines that all patients receive a nutritional recommendation.

2) Protein content. Most dogs with impaired mobility should be fed diets with elevated amounts of protein. Higher protein diets are shown to preserve lean body mass in aging animals and those with reduced activity. A diet with more than 75 grams of protein per 1000 calories fed should be administered. The protein content of a diet can be determined from the guaran­teed analysis with the following formula:

a) Add 1.5% to the minimum protein content listed on the bag.

b) Divide the value by the caloric density of the food (kcal/kg) divided by 10,000.

c) For example, consider a diet with 21.5% min. protein and 4,000kcal∕kg. An estimate of the number of protein grams per 1000 calories would be 57.5. This was calculated as follows: ((21.5 + 1.5)/(4000/10,000)).

3) Omega 3 fatty acids. In patients with inflammatory conditions, the omega 3 fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) pro­duce less inflammatory prostaglandins and leukotrienes than omega 6 fatty acids.

Table 3.1 is a suggested macronutrient profile (expressed as grams per 1000 kcal) for dogs of normal body condition with mobility impairment.

Therapeutic diets should be critically eval­uated as to whether they meet therapeutic goals for nutritional intake. Consider the comparison of diets labeled for degenerative joint disease shown in Table 3.2.

Dietary supplements may be of value in patients with altered mobility secondary to

Table 3.1 Suggested macronutrient profile (grams per 1000 kcal) for dogs of normal body condition with mobility impairment.

Protein Fat Carbohydrate EPA + DHA

75 >35 1 osteoarthritis. Table 3.3 is an abbreviated list of available therapeutic options.

Supplements may influence lean body mass, oxidative balance, and other possible biologic processes, and therefore be effective for both orthopedic and neurologic causes of mobility impairment (Table 3.4).

Weight Management

Calorie restriction must be initiated in over­weight animals to achieve a slow rate of weight loss of 0.5% to 2% weekly. Higher rates may be associated with a greater risk of lean body mass loss. Diets high in protein appear superior to those with moderate amounts of protein, and the energy density of the diet is often decreased by: limiting the fat content (fat is more than two times more energy dense than protein and carbohydrate), increasing the moisture content, or by add­ing dietary fiber.

Table 3.5 shows the macronutrient compo­sition in grams per 1000 calories recom­mended for weight-loss diets in animals with mobility challenges.

The caloric intake required for weight loss can be estimated in animals by reducing food intake by 1/3 from the known current weight­stable calorie intake. If an animal is actively gaining weight on a fixed number of calories it is more difficult to determine the amount of restriction required. Moreover, the diet history is often unknown or unclear because owners may be unaware of how much they are feeding

Table 3.2 Diets labeled for degenerative joint disease.

NR = not reported.

Table 3.3 Therapeutic supplements.

Table 3.4 Nutritional Supplements.

Table 3.5 Recommended macronutrient composition (grams per 1000 calories) for weight-loss diets in animals with mobility challenges.

Hydrotherapy

Mobility impairments in small animals are often due to an inability to support weight normally during a full gait cycle. Therefore, animals may display improved ambulation when load-bearing is reduced. Animals recovering from intervertebral disc protru­sions will often ambulate first when body weight is supported. Hydrotherapy remains one of the more common methods of achiev­ing this effect in dogs and occasionally in cats. The principles of aquatic therapy relate to the effects of the water on buoyancy and resistance. Underwater treadmill therapy reduces concussive forces on joints and pro­motes increased joint flexion and full active extension. It may also improve muscular conditioning due to the increased work required to move against the density of the water. It has been used for both weight loss protocols and for postoperative rehabilita­tion of dogs following cruciate repair. Hydrotherapy techniques include swimming and underwater treadmill therapy. Animals in an underwater treadmill tend to use their hindlimbs more reliably than when swim­ming. The underwater treadmill will result in increased joint loading as compared to swim­ming and this is related to the height of the water (Table 3.7).

Swimming is often used rather than under­water treadmill when trying to manipulate an active range of motion; hip, stifle, and hock flexion were all increased in a pool as com­pared to a ground treadmill. However, hip and stifle extension angles are reduced. Severely osteoarthritic dogs are typically exercised more comfortably in a pool because they are completely non-weight bearing.

Underwater treadmill may be better for proprioceptive training and dynamic balance than swimming since neither is required with complete buoyancy. Additional data are required to better inform the optimal time for starting hydrotherapy but many authors advocate early use after acute loss of mobility and early initiation of any program for chronic mobility impairment.

Laser Therapy

Several classes of therapeutic lasers are availa­ble to veterinarians and are marketed for pain, inflammation, and wound healing. The most common are class IIIb lasers with a power of 0.5 Watts, and class IV lasers which generally offer a variable power of 0.5-15 Watts. Laser is an acronym for light amplification by stimu­lated emission of radiation. Light in the visible red and infrared spectra (600-1000 nm) exerts the biologic effects of photobiomodulation, which include:

Table 3.7 Weight loading as a result of water height.

1) Increased adenosine triphosphate (ATP) production through activity on mito­chondrial cytochrome C oxidase

2) Induction of cellular antioxidant produc­tion due to a sublethal increase of free oxygen radicals

3) Vasodilation as a result of nitric oxide release from proteins.

The effects of laser on mobility have been theorized as a reduction in inflammatory mediators in osteoarthritic joints and on a reduction of inflammation. A neuroregenera- tive effect has been proposed, and a single clinical veterinary study reported a significant reduction in the time of ambulation following decompressive hemilaminectomy in dogs.

Animals with impaired mobility will likely require frequent and chronic treatments, with twice daily administration not uncom­mon among laser therapy protocols. Ten treatment sessions are likely necessary over a one month period to fully evaluate the clini­cal utility in a patient. The area to be dosed is generally roughly measured to estimate numerical area in cm². Approximately 5 Joules of laser energy per cm² is required in the affected tissue to achieve the effects of photobiomodulation. The power of a laser in Watts is equivalent to the number of Joules delivered per second. Animals should ideally be shaved before administration because melanin in pigment, and the air in the inter­face between laser and patient, may signifi­cantly reduce laser penetration. The depth of the tissue also influences the amount of pho­tons absorbed by intervening tissue, and dosing should be increased 50% for lesions greater than 1cm in depth and 100% more for lesions greater than 2.5 cm in depth. Photons emitted from a laser are unlikely to penetrate bone in sufficient amounts to achieve clinical effects, which should be con­sidered when treating spinal lesions.

As an example of laser dosing, a 40 kg lab­rador has a circumferential area of 150cm² around the stifle. The stifle joint is located deep to overlying tissue, and consequently an increase of 50% is elected. A Class IV laser is set to 10 W of power. The desired dose is (150 cm² ? 5 JZcm²?1.5J), or 1125 Joules. A 10 W laser will provide 10 JZsec and therefore the treatment time is just under two minutes. A Class IIIb laser with a power of 0.5 W would take 40 minutes to treat the same area.

Shockwave Therapy

Extracorporeal shockwave therapy utilizes high energy sound or pressure waves to transfer energy to biologic tissues. More specifically, energy causes cavitation and microstresses in tissues and cells with high impedance. The resulting stress in the tissue stimulates an acute response which may stimulate a compensatory endogenous repar­ative phase of healing. Additional analgesic effects may be provided through modulation of serotonin. The modality may have particu­lar utility in animals with impaired mobility secondary to chronic tendinopathy; increased collagen deposition and increased neovascularization have been reported fol­lowing the therapy. Clinical utility may also exist for osteoarthritic patients as benefits have been shown in clinical studies of dogs, likely mediated by a reduction in nitric oxide and preservation of chondrocytes. The modality requires access to a shockwave unit and trode, and dogs should be sedated for the procedure. Doses of between 400-800 shocks are used per site, and treatments may be repeated every 1-3 weeks for acute inju­ries affecting mobility and on a patient-spe­cific regular schedule for chronic diseases like osteoarthritis. Clinical responses and dosing frequencies appear to be patient- and condition-dependent, and further research is needed to inform optimal treatment protocols.

Therapeutic Ultrasound

Therapeutic ultrasound provides energy in the form of sound, which is absorbed by tissues of high protein content such as skele­tal muscle, thereby providing deep heating to target tissues. Short-term (muscles of dogs following ultrasound with powers of between 1 and 1.5W∕cm². This short-term thermal effect of ultrasound may facilitate improved stretching and is most beneficial when followed by range of motion exercises. As an example, calcaneal tendon extensibility and tarsal flexion increased for 5 minutes following ultrasound application in dogs. Repeated and frequent administration may produce faster rates of healing in tendons and in other tissues. A therapeutic ultrasound unit typically has several settings (Table 3.8) which must be selected by the user.

Acupuncture

Acupuncture remains a source of significant controversy in veterinary medicine largely due to debates surrounding the antiquity of acupuncture, and available evidence suggests that modern veterinary acupuncture is a recent invention. A dated systematic review found there was insufficient evidence to rec­ommend acupuncture in small animal patients, and studies have been conflicting; most studies of osteoarthritis failed to docu­ment an immediate benefit although long­term studies have not been performed. However, several studies of intervertebral disc disease suggest a benefit on return or improvement of ambulation. Research has

Table 3.8 Ultrasound settings.