Synovial fluid collection.

Joint taps to obtain synovial fluid are an essential technique for obtaining information to differentiate arthropathies. Sedation or general anesthesia is recommended, especially if the animal is fractious (see p. 1037). Equipment needed includes sterile gloves, 25-gauge needles, 22-gauge needles (for shoulder, elbow, and stifle joints in larger dogs), 3-inch needles (for the hip joint), and 3-ml syringes. Only a small amount of fluid is needed to determine viscosity, estimated cell count, and differential cell count, and for culture.

Synovial fluid aspirates commonly show no bacterial growth when cultured directly on blood agar plates. More reliable results are obtained if the synovial fluid sample is incubated for 24 hours in a blood culture medium or specific enrichment broth before culturing onto blood agar plates. Select the joint or joints that are swollen for initial taps. Clip the appropriate area over the joint, and prepare the site for an aseptic procedure (Fig. 34-1, A-I). Use a gloved hand to palpate landmarks. Insert a needle attached to a syringe into the joint. Apply gentle suction to the syringe. After the fluid has been collected, release the negative pressure on the syringe and withdraw the needle. If blood appears in the syringe, withdraw the syringe immediately; contamination with blood can alter cell counts. If only a few drops of fluid are obtained (common in small dogs and cats), spray the material directly onto a slide, and examine it cytologically. Estimate viscosity as the fluid drops from the needle to the slide. Normal joint fluid is viscous and forms a long string. Place a drop of fluid on a slide and make a smear for an estimated complete cell count and a differential cell count. Culture fluid for bacterial and mycoplasmal growth: with the same needle and syringe aseptically aspirate an appropriate culture broth (e.g., trypticase soy broth from a blood culture vial). Rinse the barrel of the syringe and hub of the needle with the culture medium, and then inject this culture medium into a blood culture vial with the same medium.

Omega-3 fatty acids.

Omega-3 fatty acids are nutritional supplements added to canine diets specifically for management of joint disease. They may be added to commercial foods or the owner may supplement them. They are anti-inflammatory when given at the correct dosage and work by replacing arachidonic acid (AA) in cell walls with eicosapentaenoic acid (EPA). Replacing AA with EPA decreases pain and inflammation associated with joint injury or osteoarthritis. Omega-3 fatty acids may also help ease inflammation by blocking some of the genes that cause inflammation in osteoarthritic joints.

Studies in dogs suggest that omega-3 fatty acids can ease the pain of osteoarthritis. Recent studies have demonstrated that the use of omega-3 fatty acids can improve weight bearing (Roush et al, 2010) and decrease the need for nonsteroidal anti-inflammatory drugs (NSAIDs) in dogs with osteoarthritis (Fritsch et al, 2010). Fatty-acid supplements rarely cause gastrointestinal problems, although sometimes dog owners claim that the supplement has given their dog “fishy-smelling breath.” Omega-3 fatty acids appear to be safe.

Slow-acting, disease-modifying osteoarthritis agents.

Alternative therapies for managing osteoarthritis focus on administering chondroprotective agents to slow cartilage degradation and promote cartilage matrix synthesis. Oral chondroprotective supplements are reported to provide supraphysiologic amounts of glucosamine and chondroitin sulfate to the joints to act as precursors for synthesis of hyaline cartilage matrix. These compounds appear to be safe; they cross the gastrointestinal-blood barrier intact when administered orally and may modify pain associated with osteoarthritis. Meta-analysis demonstrates a moderate level of comfort for the efficacy of a combination of glucosamine, chondroitin, and manganese in the treatment of osteoarthritis in dogs (Aragon et al, 2007).

NSAIDs.

Medical management of DJD often includes therapy with NSAIDs. NSAIDs reduce pro-inflammatory mediators (e.g., thromboxanes, prostaglandins, prostacyclin, and oxygen radicals) by inhibiting cyclooxygenase 1 and 2 (COX-1 and COX-2) pathways. Inhibiting COX-1 inhibits normal physiologic responses in the gastrointestinal and renal systems. Uses of NSAIDs that significantly inhibit COX-1 (e.g., aspirin, ibuprofen, and phenylbutazone) have greater potential to cause gastrointestinal ulceration and/or nephrotoxicity (Fig. 34-2). Most contemporary veterinary NSAIDs (Table 34-4) preferentially inhibit COX-2. It was initially believed that these drugs would provide clinical benefit without the risk of the older NSAIDs; however, the mechanisms of action and adverse effects of these drugs are not as clear as was initially postulated. Numerous studies have reported conflicting results regarding the COX-1:COX-2 ratios of these drugs. However, the method by which an NSAID is determined to affect COX-2 versus COX-1 involves in vitro tests that may or may not accurately reflect what happens in vivo. Presently, it is probably best to say that some drugs appear to be COX-1 sparing instead of COX-2 selective, and it may be more accurate to state that these drugs are “safer” as opposed to saying that they are “safe.” There is a high level of comfort (strong evidence) for the efficacy of NSAIDs in lessening the clinical signs of osteoarthritis in dogs (Sanderson et al, 2009). Finally, some drugs (e.g., tepoxalin) significantly inhibit 5-lipoxygenase, an enzyme that is responsible for leukotriene production (another mediator of inflammation).

Side effects of the NSAIDs vary depending on the specific drug and means of reporting adverse events. Owners should be cautioned that anti-inflammatory medication may cause gastrointestinal, liver, or kidney disease (see Table 34-4). Other potential side effects include altered platelet function, extended clotting times, and keratoconjunctivitis sicca (Brainard et al, 2007; Klauss et al, 2007; Luna et al, 2007). Aspirin is commonly used in dogs, but owners should be warned of its propensity to cause gastrointestinal toxicity. Concurrent administration of misoprostol may provide some degree of protection against NSAID-induced gastric lesions (Box 34-3), if needed.

Other medical therapies.

Compounds such as polysulfated glycosaminoglycans (PSGAGs) and hyaluronic acid (HA) enhance macromolecular synthesis by chondrocytes and hyaluron synthesis by synoviocytes, inhibit degradative enzymes or inflammatory mediators, and remove or prevent the formation of fibrin, thrombi, or plaques in synovia or subchondral blood vessels. Although there are anecdotal reports of positive results with both PSGAGS and HA, no controlled studies have been performed in dogs to establish their efficacy or safety.

Pentosan polysulfate, isolated from beechwood hemicellulose, appears to provide protection against cartilage damage. When given once a week (3 mg/kg SC) it may relieve clinical signs associated with canine chronic osteoarthritis. Although not derived from animal sources, the compound preserves proteoglycan content and stimulates hyaluronic acid synthesis. Pentosan polysulfate may also increase bleeding times. One meta-analysis demonstrated a moderate level of comfort for the efficacy of Pentosan polysulfate in the treatment of osteoarthritis in dogs (Aragon et al, 2007), whereas another demonstrated only weak or no evidence to support efficacy (Sanderson et al, 2009).

Polysulfated glycosaminoglycans (PSGAGs) (Adequan) have been routinely used in the management of osteoarthritis in dogs (4 mg/kg IM intramuscular twice a week for 4 weeks). PSGAGs are injectable, highly sulfated glycosaminoglycans marketed for treatment of osteoarthritis. They have a protective effect on cartilage homeostasis in models of osteoarthritis and inconsistently have shown anabolic effects on cartilage metabolism. They have heparin-like activity and may increase bleeding times in dogs. Meta-analysis demonstrated a moderate level of comfort for the efficacy of PSGAGs in the treatment of osteoarthritis in dogs (Aragon et al, 2007).

Hyaluronan is a large glycosaminoglycan found in joint fluid and cartilage. In joint fluid, it is a major contributor to viscoelasticity, whereas in cartilage it forms the backbone that links aggrecan molecules. Hyaluronan has been administered intra-articularly to help restore viscosity of joint fluid in arthritic joints. It also has anti-inflammatory activity by interfering with oxygen-free radicals and inhibition of degradative enzymes. There is conflicting information regarding the value of hyaluronan administration in the management of canine osteoarthritis, although there is evidence that it may aid in pain relief of this condition. Two meta-analyses have shown weak or no evidence for the efficacy of hyaluronan in the treatment of arthritis in dogs (Aragon et al, 2007; Sanderson et al, 2009).

Antibiotics.

Antibiotics should be administered for infectious arthritis (see p. 1229) and prophylactically for specific surgical procedures (see Chapter 9). In general, antibiotics should be selected for treatment of bacterial septic arthritis on the basis of identification of the organism and susceptibility testing. Broad-spectrum bactericidal antibiotics should be administered until culture and susceptibility testing results are obtained and then adjusted as necessary (Table 34-5). Gram-positive bacteria are most commonly cultured from septic joints; therefore, initial treatment with first generation cephalosporins is usually indicated before culture and bacterial susceptibility reports are received. If bacterial L-forms are suspected (primarily in cats), doxycycline is the antibiotic of choice. Chloramphenicol and erythromycin might also be effective. If Borrelia spp., Ehrlichia ewingii, Neorickettsia risticii, Anaplasma phagocytophilum, or Rickettsia rickettsii is suspected, doxycycline is the antibiotic of choice. Antibiotics should be administered for 4 to 6 weeks and at least 2 weeks after the cessation of clinical signs.

Antibiotics may be administered initially when differentiation between immune-mediated and rickettsial infection has not been made; doxycycline is the antibiotic of choice (see Table 34-5). Doxycycline may be administered until tick titer results are available or as a trial to observe for resolution of clinical signs before initiating steroid therapy for presumptive nonerosive immune-mediated joint disease.

Antibiotics should be administered prophylactically to prevent surgical infections, especially in joint replacement procedures, but they are not a substitute for aseptic technique (see Chapters 1, 5, and 6). A broad-spectrum, bactericidal antibiotic, such as cefazolin (22 mg/kg given IV), should be administered after an intravenous (IV) line has been placed and anesthesia induced. This dose can be repeated every 90 minutes to 3 hours during surgery. Antibiotics can be discontinued after surgery, or they may be continued until culture results are obtained. If culture results are negative, antibiotics should be discontinued; if results are positive, antibiotics may be continued or changed according to the results of susceptibility testing.

Corticosteroids.

Corticosteroids effectively reduce synovial inflammation by inhibiting activity of phospholipase A (see Fig. 34-2), reducing production of both cyclooxygenases and lipoxygenases. Corticosteroids may also protect cartilage matrix by reducing metalloproteinase activity; however, they depress chondrocyte metabolism and alter the matrix composition by diminishing proteoglycan and collagen synthesis. Because of the adverse systemic effects of long-term corticosteroid administration and their deleterious effects on cartilage, they are seldom indicated for treatment of cartilage injury or DJD. Corticosteroids often are used to treat inflammatory noninfectious arthropathies. When used long term, dosages should be titrated to the smallest amount that achieves an effect, and short-acting steroids (e.g., prednisolone) should be administered every other day if possible to prevent suppression of the hypothalamic-pituitary-adrenal axis; however, inadequate dosage may increase resistance to effective treatment. Efficacy of steroids in the management of immune-mediated joint disease must be based on repeat joint taps and not on clinical evaluation of lameness.