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Should we routinely give gastroprotectants to dogs and cats prescribed glucocorticoids?

My observation is that, amongst UK veterinary practices and institutions, there is considerable variation in protocols on when to give prophylactic PPIs to dogs (and to a lesser extent) cats who are prescribed glucocorticoids.

The mechanisms through which glucocorticoids might promote ulcer formation have been proposed to include inhibition of gastric mucus synthesis, enhancement of gastrin and parietal cell hyperplasia with increased gastric acid secretion, suppression of prostaglandin synthetase and delayed ulcer healing.

As ever, the small animal literature is very limited.  It does seem that, under some circumstances, corticosteroids can cause gastric haemorrhage in dogs:

Am J Vet Res. 1999 Aug;60(8):977-81.
Gastric hemorrhage in dogs given high doses of methylprednisolone sodium succinate.
Rohrer CR1, Hill RC, Fischer A, Fox LE, Schaer M, Ginn PE, Casanova JM, Burrows CF.

https://www.ncbi.nlm.nih.gov/pubmed/10451208

We have to go to the human research for meaningful numbers.  Even in human medicine, a lot of earlier studies examining the possible association between glucocorticoid therapy and the risk for gastric ulceration were meta-analyses or case–control studies and resulted in inconsistent findings.  Better controlled work includes:

Aliment Pharmacol Ther. 2015 Sep;42(5):599-606
Short-term use of glucocorticoids and risk of peptic ulcer bleeding: a nationwide population-based case-crossover study.
Tseng CL1,2, Chen YT1,3, Huang CJ1,4, Luo JC1,2, Peng YL1,2, Huang DF1,5, Hou MC1,2,6, Lin HC1,2, Lee FY1,2.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.13298

Their conclusion:

‘Short-term (7–28 days) exposure to glucocorticoids is significantly associated with peptic ulcer bleeding; this risk seems dose-dependent and is higher when nonselective NSAIDs or aspirin are used concurrently.’

(to be clear, it wasn’t that they found long-term use to be safe: the study only looked at short-term use)

Even more recently:

Drug Saf. 2018 Jul;41(7):725-730. 
Glucocorticoids and the Risk of Peptic Ulcer Bleeding: Case-Control Analysis Based on Swiss Claims Data.
Reinau D1,2, Schwenkglenks M3, Früh M4, Signorell A4, Blozik E4, Meier CR

https://link.springer.com/article/10.1007%2Fs40264-018-0645-3

Conclusion:

‘The use of NSAIDs with or without GC was associated with a markedly higher risk of bleeding peptic ulcer compared with GC monotherapy. Use of GC alone was associated with a moderately increased risk of bleeding peptic ulcer, which might be causal or attributed to confounding by indication.’

To cloud things slightly, we have:

BMJ Open. 2014 May 15;4(5):e004587. doi: 10.1136/bmjopen-2013-004587. Review.

Corticosteroids and risk of gastrointestinal bleeding: a systematic review and meta-analysis.

Narum S, Westergren T, Klemp M.

https://bmjopen.bmj.com/content/4/5/e004587

Conclusions:

Corticosteroid use was associated with increased risk of gastrointestinal bleeding and perforation. The increased risk was statistically significant for hospitalised patients only. For patients in ambulatory care, the total occurrence of bleeding or perforation was very low, and the increased risk was not statistically significant.

So, should we routinely give gastroprotectants to dogs and cats receiving glucocorticoids? Or only under some circumstances? Or not at all?

The case for ‘no’ is represented here:

https://www.pharmacist.com/article/inappropriate-prescription-ppis-setting-steroid-use

Which is to say that corticosteroid-associated GI bleeding is rare and does not justify the routine prophylactic use of PPIs which are not without potential adverse effects themselves.

I would argue that the same is potentially true for our veterinary patients.  We have no published statistics on incidence of gastroduodenal ulceration in corticosteroid-treated animals.  Personally, I don’t give prophylactic PPIs in such circumstances unless there is some other case-specific factor and I’m not aware of having induced any clinically-significant ulceration in years of battling pemphigus and IMHA.  I have a suspicion that some spinal cases which receive steroids and then vomit might be explained by the recently-uncovered phenomenon of spinal disease-associated pancreatitis.

J Small Anim Pract. 2018 May;59(5):305-310. doi: 10.1111/jsap.12818. Epub 2018 Jan 22.
Canine pancreatic lipase immunoreactivity concentrations associated with intervertebral disc disease in 84 dogs.
Schueler RO1, White G2, Schueler RL1, Steiner JM3, Wassef A2.

https://www.ncbi.nlm.nih.gov/pubmed/29355958

Also a well-documented phenomenon in people.

In summary:

• glucocorticoids alone probably do exert some pro-ulcer effect in most species
• we don’t have any good information on how common this might be in cats and dogs or what doses or specific agents might represent particular risk
• concurrent or recent use of NSAIDs markedly increases risk in people and, in addition to anecdotal reports from cats and dogs, this is good reason to give prophylactic gastroprotectants where this scenario arises for whatever reason.
• the prophylactic use of gastroprotectants (e.g. PPIs) might be defensible in other circumstances of high-dose glucocorticoid treatment but that depends on a rather theoretical risk-benefit analysis.  In today’s evidence-based world I’d say it’s arguably better not to.

Let me know what you think!