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This month, Dr. Townes Hillier, a small animal surgery resident at the University of Georgia, tells us more about her latest study in the Journal of the American Veterinary Medical Association. This retrospective study looks at the medical records of 33 dogs with gastrointestinal ulcerations that received NSAIDs and/or corticosteroids within 30 days of their diagnosis. Ulceration was diagnosed by endoscopy, surgery, or necropsy. Clinical data collected included dose and reason for NSAID or corticosteroid administration.
Among the important takeaways: NSAIDs and steroids can cause GI ulceration, even when administered at the recommended dose. Dr. Hillier spoke about the study and the practical applications uncovered for practitioners.
Did the study’s findings align with your hypothesis based on your clinical experience, or were you surprised by the results?
Dr. Hillier: The study’s findings align with our hypothesis and previous research, which indicate that administering NSAIDs above recommended doses or combining them with a second NSAID or steroid often leads to severe gastrointestinal (GI) ulceration. However, we were surprised by the incidence of ulceration associated with carprofen, which occurred in 9 out of 22 dogs given a single NSAID. Additionally, 11 dogs receiving a single NSAID at an appropriate dose developed ulcerations. Of those 11 dogs, 7 were administered carprofen at the recommended dose of 2.2 mg/kg PO q12h. Although previous studies have documented subclinical ulceration with NSAIDs at the recommended doses, this is the first study to report clinical ulceration in dogs given carprofen, including 5 cases with perforating ulcers.
Since this study, have your recommendations on NSAID and/or corticosteroid administration changed?
Dr. Hillier: Despite carprofen being the NSAID most associated with GI ulceration in this study, I will continue to prescribe it to my patients. The higher incidence of ulceration in our study is likely due to its more frequent use overall and may not reflect an inherently higher risk profile. (Carprofen has previously been associated with less severe subclinical GI ulceration compared to other NSAIDs.) I am now more inclined to stay as close to the recommended dose as possible without exceeding it or choose a different NSAID if a therapeutic dose cannot be safely achieved for a dog of a particular size. Additionally, I prefer to calculate the dose based on an animal’s lean body weight rather than its actual weight. This study had limitations of a retrospective design, which meant we did not know the body condition scores (BCS) of the included dogs. Further research is needed to evaluate the effect of BCS on NSAID dose, especially given the rising rate of canine obesity.
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Along those same lines, do you have any pointers, or cautionary words, for primary care veterinarians on how they prescribe NSAIDs and/or corticosteroids?
Dr. Hillier: NSAID dosing should likely be based on lean body weight, and it’s essential to remember that GI ulceration can occur even at recommended doses. A slight increase over the recommended dose can elevate the risk of fatal complications. Additionally, GI ulceration may develop with short-term and chronic NSAID use. When transitioning from one NSAID to another, from a steroid to an NSAID, or an NSAID to a steroid, a washout period should be employed between 2 drugs. The ideal period between drugs is not well defined, but at least 3 to 4 times the half-life of the drug being discontinued is generally recommended.
Careful attention to patient history is critical—double- or even triple-check for any history of NSAID or steroid use. Owners often have difficulty recalling these medications, so I specifically ask them about any past NSAID or steroid use by naming the drugs. In our study, we found that all 5 dogs receiving 2 NSAIDs concurrently suffered full-thickness perforations. NSAIDs should be avoided in dogs with comorbidities known to increase the risk of GI ulceration, such as mast cell tumors.
Educating owners is crucial. They should be instructed to follow label instructions closely and discontinue NSAID use if their dog becomes inappetent. They should watch for vague clinical signs such as vomiting, diarrhea, and lethargy and seek prompt veterinary evaluation if any occur. GI ulceration is often underdiagnosed due to its subtle clinical signs and inconclusive blood work findings. Thus, if a dog exhibits any abnormal behaviors, NSAID treatment is ideally paused until further evaluation.
What is the most important takeaway from this study for private practice veterinarians?
Dr. Hillier: NSAIDs and steroids can be dangerous even at recommended doses. Careful monitoring by veterinarian and owner is essential with these medications, regardless of the duration of administration.
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Is there anything you would like our readers to learn or know from this study (that has not been mentioned)?
Dr. Hillier: It’s important to remember that the most common location for perforation from NSAIDs and steroids is the pylorus and proximal duodenum. Diagnosing proximal GI perforation can be challenging due to low bacterial loads and/or potential reduction of bacteria by therapeutic interventions like antibiotics. In our study, intracellular bacteria were identified in only 4 samples from the 13 dogs that underwent perioperative abdominocentesis despite 7 of those dogs having full-thickness perforations. We should avoid relying on intracellular bacteria to confirm septic peritonitis in cases where perforation secondary to an upper GI ulcer is suspected.
The Study:
Dogs receiving cyclooxygenase-2-sparing nonsteroidal anti-inflammatory drugs and/or nonphysiologic steroids are at risk of severe gastrointestinal ulceration.
Hillier TN, Watt MM, Grimes JA, Berg AN, Heinz JA, Dickerson VM. JAVMA. doi:10.2460/javma.24.06.0430