5

1 2 3 4 5 6 7 8 9 10 11

indicate that NSAIDS that spare cyclooxygenase (COX)-1 produce a lower frequency of GI lesions, although the more highly COX-2-selective inhibitors may actually produce more AEs when underlying gastric damage is already present.19,27 The leading risk factors for NSAID-associated GI perforations are incorrect dosing, concurrent use with other NSAIDs or corticosteroids, and continued use despite GI signs or anorexia.20,24 Signs of GI toxicity usually emerge within 2–4 wk but can occur at any at any point during administration.28,29 It is critical that veterinarians communicate NSAID toxicity risk factors to pet owners (e.g., providing client information that describes potential side effects, including the commercial circulars provided by drug manufacturers and instruction on when to stop medication and contact a veterinarian). This Task Force strongly encourages implementation of practice systems that ensure communication to clients of appropriate AEs and risk information for any prescribed drug, including NSAIDs. Another important side effect associated with NSAIDs is nephrotoxicity. When administered before anesthesia in healthy dogs with controlled modest hypotension, no adverse effect on renal function was detected.30,31 However, because some dogs in those studies did develop changes in renal parameters, the importance of maintaining a normotensive state during anesthesia is considered paramount when utilizing preoperative NSAIDs. Preoperative administration in dogs is superior in efficacy to postoperative use, consistent with results of multiple studies performed in humans.32 Similar studies have not been conducted in cats undergoing anesthesia, but one feline study revealed no alteration in glomerular filtration rate measured by iohexol clearance after 5 days of oral meloxicam.27 If IV access is not possible and normotension cannot be achieved with certainty, the Task Force recommends limiting the use of NSAIDs to postsurgical administration. Idiosyncratic hepatocellular necrosis has been reported with various NSAIDs but remains exceedingly rare, only 1.4 cases/10, 000 dogs (0.052%), usually occurring between 2 and 4 wk after starting treatment. Preexisting elevated liver enzymes are not a risk factor.19 Idiosyncratic hepatocellular necrosis is not a true toxicosis but rather an intrinsic, heritable reaction to the molecule being administered.20 Highly COX-2-selective NSAIDs have caused delayed bone healing in rabbit and rodent models, and one study in dogs demonstrated delayed healing of experimental tibial osteotomies following long-term NSAID use.33 The latter study may not be a clinically relevant model, and another study reported that normal tissue healing is rapidly restored once the NSAID is withdrawn.34 Further, of 299 dogs receiving deracoxib, carprofen, and firocoxib in the FDA-approval process, none were reported to have delayed fracture healing or nonunion fractures. Finally, no clinically significant bleeding dyscrasias have been reported with the use of veterinary NSAIDs.20 72 JAAHA | 51:2 Mar/Apr 2015 Local Anesthetics (LAs) This is the only class of drug that renders complete analgesia. The totality of evidence in humans and animal studies reveal the predictable analgesic and anesthetic drug-sparing effects of LAs. In addition, LAs are reported to be antimicrobial, immunomodulating, and can diminish postoperative maladaptive pain states. They do not appear to delay tissue healing.35 LAs can be administered either directly at a simple incision site or at a specific nerve to provide analgesia to a large region (or area). A discussion of the many locoregional blocks that can be utilized in dogs and cats is beyond the scope of these guidelines but can be found in several readily accessible resources, and most of those blocks can be readily learned by clinicians. LAs are considered safe, with AEs generally limited to very high doses or inadvertent IV administration (bupivacaine especially). The Task Force supports the International Veterinary Academy of Pain Management position that, because of their safety and significant benefit, LAs should be utilized, insofar as possible, with every surgical procedure. a-2 Adrenergic Agonists a-2 Adrenergic receptors are located with opioid receptors. Thus, the two drug classes used together are highly synergistic for sedation and analgesia. a-2 Agonists have a versatile dosing profile. That allows low and even micro doses in combination with opioids to be clinically useful and minimizes the cardiovascular effects. Clinicians should be mindful that cardiovascular side effects occur even with very low doses of a-2 adrenergic agonists, that lower doses will have a shorter duration of effect, and that analgesic effects have a shorter duration than the sedative effects. FIGURE 3 Nine Ways to Minimize the Risks of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 1. Obtain a complete medication history. Avoid or use extreme caution with concurrent or recent use of NSAIDs and/or corticosteroids (including some nutritional supplements that may contain aspirin or other cyclooxygenase-inhibiting mechanisms). Practitioners should observe the following additional precautions due to potential drug interactions: Avoid with furosemide and use caution with angiotensin-converting enzyme inhibitors. Avoid with potentially nephrotoxic drugs (e.g., aminoglycosides, cisplatin). Caution with use of additional multiple highly protein-bound drugs (e.g., phenobarbital, digoxin, cyclosporine, cefovecin, chemotherapy agents). 2. Be discriminating in patient selection. Be cautious or avoid NSAIDs in patients with the following existing/anticipated conditions: Low-flow states such as dehydration, hypovolemia, congestive heart failure, and hypotension. In such cases, IV fluid support and blood pressure monitoring should be available for anesthetized animals. Renal, cardiac, or hepatic dysfunction. 3. Provide verbal and written client instructions to avoid the medications described in point 1 above and to discontinue and alert the hospital at the first sign of an adverse event (see point 4). 4. Recognize the earliest signs of adverse events and withdraw NSAID treatment immediately if those events occur,