THIS is the third and final article in a series discussing recognition and quantification (article 1) and pharmacotherapy (article 2) of chronic pain in dogs. The articles have focused on the use of non-steroidal anti-inflammatory drugs (NSAIDs) for chronic pain management in dogs and this article will make recommendations for monitoring dogs receiving NSAIDs, including assessment of drug efficacy and requirement for additional analgesia. There are currently no published, evidence-based, recommendations about monitoring of dogs receiving chronic NSAID therapy. However, the International Society of Feline Medicine (ISFM) and the American Association of Feline Practitioners (AAFP) have published consensus guidelines on the long-term use of NSAIDs in cats (Sparkes et al, 2010) and where appropriate, these recommendations for cats have been extrapolated to dogs in this article.
What should you monitor following the start of NSAID therapy?
Following commencement of longterm NSAID therapy, it is important to monitor both drug efficacy and the health status of the patient. With respect to health status, pay particular attention to the body systems in which adverse effects are most likely (i.e. gastrointestinal, renal, hepatic and cardiovascular systems); however, do not neglect to monitor the progress of any underlying disease conditions that may be the cause of chronic pain or any concurrent disease processes. Changes in health status caused by concurrent diseases may increase the risk of NSAID-related toxicities and progression of a disease causing chronic pain may change the requirement for ongoing analgesia.
How frequently should you monitor dogs on NSAID therapy?
Most NSAID-related adverse events in dogs occur between 14 and 30 days after starting therapy (Hampshire et al, 2004); however, the time course of adverse events varies greatly in individual animals. The timing of adverse events also depends on the body system involved. Acute renal failure can manifest two to three days after starting therapy, while deteriorations in hepatic function may only manifest after a few months. Gastrointestinal side effects frequently occur in the first two weeks after starting therapy. An important factor that should never be overlooked is the importance of owner compliance and education. The owners play a crucial role in recognising NSAID toxicity early and should be made aware of potential sideeffects associated with NSAID
administration. Ensure that clients have a clear understanding of the potential complications of NSAIDs, along with an understanding of all the ways that NSAIDs can benefit their pet.
Reassessment of NSAID efficacy and any signs of side effects is recommended in all dogs 7-10 days after starting NSAID therapy
It is prudent to instruct owners to stop NSAID administration and contact you should any signs develop earlier in the course of treatment. A useful guideline is to advise owners not to give a
NSAID dose if their dog has stopped eating or drinking, experiences vomiting or significant diarrhoea or becomes lethargic. Inappetence is a common sign of NSAID-related side effects. Vomiting can also be an early presenting sign of gastrointestinal perforation (Lascelles et al, 2005). If inappetence and/or vomiting is caused by unrelated concurrent disease, discontinuation of the medication also prevents NSAID administration to dogs at risk of dehydration and hypotension, which would predispose to renal compromise. Treatment can be resumed if gastro-intestinal signs abate, but further evaluation is necessary if signs continue or re-present when NSAIDs are restarted. After 7-10 days it is practical to assess analgesia provided by NSAIDs, and this is a good time point to make a decision about whether adjunctive analgesic drugs are required.
Remember that nonpharmacological therapies for osteoarthritis can take longer to be effective (e.g. weight loss, dietary changes such as feeding prescription diets enriched with nutraceuticals);
therefore requirement for adjunctive analgesic agents may change later in the course of NSAID therapy for pain associated with osteoarthritis. Following an initial recheck appointment, the frequency of reassessment will vary depending on the health
status of the dog and the underlying condition that is the cause of pain. More frequent monitoring is indicated in dogs at a higher risk of developing NSAIDrelated side effects. Young, healthy dogs are at a low risk of NSAIDrelated adverse events, but this patient
population rarely requires NSAID therapy for chronic pain. Older dogs are at a higher risk of adverse events, although it is difficult to define when a dog is aged. Consider whether a dog is clinically
geriatric (taking into account age, breed and health status) rather than relying on chronological age alone to classify age status. Since side effects occur more commonly in middle-aged to older dogs, every effort should be made to prescreen these patients
before instituting NSAID therapy. Not only does this approach help in early detection of organ disorders, it also establishes a complete baseline for the sake of comparison in the event that problems do occur as a result of drug administration. In dogs that are at a high risk of NSAIDrelated adverse effects, regular monitoring at 1-2 monthly intervals is recommended. Frequent
monitoring is also recommended in dogs with a progressive or unstable underlying disease condition, particularly with respect to requirement for analgesia and administration of adjunctive analgesic agents. Less frequent monitoring (for example at three months and then every six months) is acceptable for dogs at a low risk of NSAID adverse events.
Monitoring of analgesic efficacy
As discussed in article 1, owners must be involved in the assessment of analgesic efficacy during ongoing NSAID therapy and it can be useful to adopt Client Specific Outcome Measures (CSOM) to objectively monitor changes in specific activities following the start of treatment. Use of CSOM provides an assessment tool that is directly relevant to each specific patient and is therefore more sensitive at detecting improvements or deterioration in analgesia provided by NSAID therapy. As well as assessing activity and mobility, it is important to question the owner about the dog’s overall quality of life (QoL), particularly if the dog has concurrent disease conditions that may affect QoL, for example significant cardiovascular disease. Asking the owner to keep a diary about their dog’s activity level, specific behaviours (e.g. willingness to get up to greet the owner when he or she arrives home, changes in temperament, sleep-related behaviour and restlessness) can be very helpful to determine changes in QoL over time. Together with the owner, it is important to determine QoL criteria for the individual patient that may indicate requirement for further intervention. Interventions may involve administration of adjunctive analgesic drugs [for example, the addition of amantadine to NSAID therapy (Lascelles et al, 2008)], or for some animals it may be appropriate to consider euthanasia. These intervention criteria can also help the owner determine whether a follow-up appointment is required earlier than the next planned assessment consultation.
Health monitoring during NSAID therapy
Dogs receiving NSAIDs for the management of chronic pain are commonly geriatric and have concurrent systemic disease, therefore it is very difficult to make general recommendations for
health monitoring. Each monitoring plan must be tailored to the individual requirements’ of the patient. Target body systems
most likely to be associated with NSAIDrelated side effects are the
gastrointestinal, renal, hepatic and cardiovascular systems and require particular attention, but that is not to say that all of these systems must be evaluated with specific clinical and biochemical tests at each evaluation. Although it is not unexpected that dogs with pre-existing disease in one target organ might be more susceptible to NSAID-related side effects in that organ, it is worth remembering that interactions occur between body systems. For example, dogs with cardiac disease requiring diuretics or ACE
inhibitors will also be at an increased risk of renal dysfunction while receiving NSAID therapy. This type of scenario would benefit
from an increased frequency of monitoring, and this should be discussed with the owners to explain why their dog might benefit from monitoring at a particular frequency with defined tests.
If cost is a limiting factor for on-going monitoring, then ensure that the owners are fully aware of signs indicative of deteriorations in organ function and carry out reexamination when
possible, but at least at six monthly intervals.
Interventions when changes in target organ function are detected
If an acute deterioration in renal or liver function is detected or signs indicative of gastrointestinal ulceration are detected, stop NSAID therapy and instigate appropriate supportive measures. Usually organ function will improve again with treatment and cessation of NSAID therapy. Report adverse events to the appropriate pharmaceutical company and regulatory board to support pharmacovigilance. Provide alternative analgesia for dogs that have stopped NSAID therapy, and consider very carefully whether to restart NSAID therapy once the dog has recovered from the episode. This will depend on the severity of the event, the capability to manage pain with other classes of analgesic drugs and the outcome of discussions with the owner. If NSAID therapy is reinitiated, do so cautiously, switch to a different NSAID drug and start therapy at the lowest recommended dose. Frequent monitoring of these patients is required, at least for the first six months after starting therapy. Frequently, decision making about what to do when abnormalities are detected on re-examination is difficult because changes in function are often subtle and deterioration is gradual. There are also no specific criteria for when changes in serum biochemistry indicate that NSAID administration should be stopped. If possible, interpret monitored parameters with respect to baseline values measured before the start of NSAID therapy, or with respect to historical data when dogs have been monitored over time. Remember to consider the complete clinical picture rather than changes in
single parameters in isolation. Be prepared to change the frequency of monitoring dependent on changes in organ function and the underlying disease condition. If mild signs of changes in organ function are detected, it is sensible to reduce the NSAID dose to the lowest effective dose and repeat the evaluation one to two months later.
Conclusions
Monitoring NSAID efficacy and organ function are integral to the safe and effective use of NSAIDs for chronic pain management.
It is important to tailor monitoring to the requirements of the individual patient and the owner. More frequent and intensive monitoring is required in dogs that are at a higher risk of NSAID-related side effects.
References
Hampshire et al (2004) J Am Vet Med Assoc 22: 533-536.
Lascelles et al (2008) J Vet Intern Med 22: 53-59.
Lascelles et al (2005) J Am Vet Med Assoc 227: 1,112-1,117.
Sparkes et al (2010) J Feline Med Surg 12: 521- 538.
