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Using steroids in dogs with acute pancreatitis | VETgirl Veterinary Continuing Education Podcasts

In today’s VETgirl online veterinary continuing education podcast, we will be reviewing a treatment that is often a bit controversial – steroids! In particular, we will look at the use of steroids in the treatment of acute pancreatitis in dogs. Steroids may appear attractive to use in this inflammatory disease since glucocorticoids impart anti-inflammatory affects in the body. Glucocorticoids may theoretically improve pancreatic blood flow and in critically ill patients with refractory blood pressure concerns, glucocorticoids are sometimes used to treat suspected (or confirmed) CIRCI. But with the possibility of eliciting negative side effects from steroid use, owing to their unwanted gastrointestinal tract side effects and their immunomodulatory effects, are they worth the risk in treating these patients?

So, Okanishi et al wanted to evaluate whether steroid use in acute pancreatitis was beneficial to patient recovery in a study entitled Comparison of initial treatment with and without corticosteroids for suspected acute pancreatitis in dogs. This was a non-blinded, non-randomized clinical study out of Japan. For dogs to be included in this study, they had to receive a diagnosis of acute pancreatitis with the following criteria: they had to exhibit at least two clinical signs consistent with acute pancreatitis, have either a serum Spec-cPL>400 mcg/L or plasma v-LIP>200 U/L, have supportive ultrasonographic findings consistent with pancreatic inflammation, and have a C-reactive protein concentration greater than or equal to 1 mg/dL. C-reactive protein (CRP) is an acute phase protein produced by the liver in response to inflammation. As such, it is often used as an indicator of inflammatory conditions – the rise and fall of this protein level in the body has been attributed to worsening and improvement of systemic inflammation respectively and has shown to be elevated in acute pancreatitis (Holm). In order to subjectively assess response to treatment, dogs were assigned AP scores based on the following clinical signs: lethargy, appetite, vomiting, stool condition, and abdominal pain. These categories were rated on a scale of 0 to 3 with 3 being the most severe presentation. Initial AP scores were assigned by the dogs’ owners and admitting clinicians on the first day and then assigned daily by the clinician managing daily care. It’s important to note that the clinicians ascribing the AP scores were not blinded to the dogs’ treatment groups.

Dogs in the prednisolone group received 1 mg/kg/day prednisolone as a subcutaneous injection until discharge from hospital. All dogs in both groups also received IV fluids, but the types and rates were not standardized so they received varying types, rates, and total volumes. All dogs also received 1 mg/kg/day maropitant, 1 mg/kg/day famotidine, 5 mg/kg/day enrofloxacin (although research does not support the prophylactic use of antibiotics in canine acute pancreatitis) (Mansfield), fentanyl CRI at 3-6 ug/kg/hr, and a multivitamin solution. Baseline bloodwork obtained for these patients included WBC, PCV, platelet count, BUN, creatinine, ALP, ALT, albumin, glucose, t.bili, Ca, v-LIP, and Spec-cPL.

An unknown number of included dogs had concurrent underlying systemic disease such as seizures, heart disease, gallbladder disease, tracheal disease, atopic dermatitis and prostatic disease. These are all conditions known to cause varying degrees of systemic inflammation. C-reactive protein levels have been evaluated in many canine conditions, and evidence suggests diseases such as epilepsy, asymptomatic cardiac disease (Reimann), and tracheal disease do not cause statistically significant increases in CRP. Although not specific for atopic dermatitis, severe skin disease in dogs has been shown to cause elevations in CRP (Severo). Prior research suggests that these particular canine diseases do not statistically affect CRP. It would perhaps add a level of confidence to exclude dogs with concurrent underlying disease from similar future studies, or at least to match the dogs’ diseases between groups. We also don’t know what other treatments were being used for chronic management of these underlying conditions and what influence those treatments may have had on results.

A total of 65 dogs were included in this study. For reasons not clearly described, 9 additional dogs were excluded because they received additional therapies such as dopamine, blood transfusions, or low molecular weight heparin. Aberrant clotting in acute pancreatitis is not an uncommon finding and occurs as a result of intense inflammation producing a systemically hypercoagulable state (Nielsen). It is also not uncommon to use low molecular weight heparin for prevention of aberrant clotting in intensely inflammatory conditions such as acute pancreatitis (Sharp). So it remains unclear why these critically ill patients were excluded from this study as they represent the more severe presentations of acute pancreatitis. C-reactive protein data from dogs that died within the study window were excluded from analysis, but the reasoning for this omission is unclear. Perhaps these deaths were attributed to financially driven euthanasia, and so, to avoid data bias from financial concerns, the authors chose to exclude this patient subset. But this is all speculation on the authors’ decision.

On day 3 of treatment, CRP concentrations remained significantly lower in the prednisolone group. Median time for CRP levels to fall below 2 mg/dL was 4 days in the prednisolone group compared to a median time of 8 days in the control group. These numbers sound intriguing, but must be seen in light of a heavily unbalanced number of subjects in each group. Only 16 dogs were present in the control group while 43 dogs were present in the treatment group. In addition to the large subject number disparity, the groups were also not evenly distributed according to dogs’ age, breed, or underlying disease so there are many variables that could be influencing this study’s results. As an example, dogs in the control group were overrepresented by Dachshunds and were older than dogs in the treatment group. It remains unclear how this may have affected the study results.

The authors suggest that hospitalization was shorter in the treatment group compared to the control group, but again the groups were not closely balanced in numbers or patient signalment. Only 20 dogs were present in the control group compared to 45 dogs in the treatment group. No statistically significant difference between groups was found for in-hospital mortality or for post-hospitalization recurrence rate.

This study suggests that prednisolone use in acute pancreatitis may be beneficial to patient outcomes. But with the many limiting factors in this study’s design, we should rather interpret these results as a promising suggestion, warranting further investigation with a more robust and evenly matched, blinded study. Factors to consider in future studies include blinding the clinicians to treatments, evenly distributing numbers of subjects between treatment and control groups, excluding patients with concurrent underlying systemic diseases, including CRP data from natural deaths occurring within the study window, and evenly matching the subjects between groups in regards to age, breed, gender, underlying disease, and body index. Authors also note that the v-Lip used as part of the diagnostic workup for acute pancreatitis in this study is not a pancreatic-specific enzyme and should not be used in future studies as a diagnostic criteria for acute pancreatitis.

In conclusion, the findings of this study should be interpreted very lightly. VETGirl always urges the cautious use of any medication with careful attention given to your patient’s condition. We aren’t steroid-haters! In fact, we like glucocorticoid use for many different diseases! And it is plausible that there is a real benefit to using steroids in the treatment of acute pancreatitis. But there are just too many complicating factors in this particular study’s design for VETGirl to feel comfortable with a blanket recommendation for steroid use in acute pancreatitis. Instead, we suggest that this study been seen as a good pilot study, setting the stage for a much needed larger, blinded study with evenly distributed numbers and conditions of subjects. Such a study would then provide us the unbiased data we need to determine if we should start recommending routine use of steroids as part of our medical management for acute pancreatitis.

References:
1. Holm JL, Rozanski EA, Freeman LM, et al. C‐reactive protein concentrations in canine acute pancreatitis. J Vet Emerg Crit Care 2004;14(3):183-186.
2. Mansfield C, Beths T. Management of acute pancreatitis in dogs: a critical appraisal with focus on feeding and analgesia. J Small Anim Pract 2015;56:27-39.
3. Reimann MJ, Liungvail I, Hillstrom A, et al. Increased serum C-reactive protein concentrations in dogs with congestive heart failure due to myxomatous mitral valve disease. Vet J 2016;209:113-8.
4. Severo JS, Santana AE, Aoki V, et al. Evaluation of C-reactive protein as an inflammatory marker of pemphigus foliaceus and superficial pyoderma in dogs. Vet Derm 2018;29(2):128-e51.
5. Nielsen L, Holm J, Rozanski E, et al. Multicenter investigation of hemostatic dysfunction in 15 dogs with acute pancreatitis. J Vet Emerg Crit Care 2019;29(3):264-268.
6. Sharp CR, Goggs R, Blais MC, et al. Clinical application of the American College of Veterinary Emergency and Critical Care (ACVECC) Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE) guidelines to small animal cases. J Vet Emerg Crit Care 2019;29(2):121-131.
7. Okanishi H, Nagata T, Nakane S, et al. Comparison of initial treatment with and without corticosteroids for suspected acute pancreatitis in dogs. J of Sm An Prac 2019;60:298–304.

Abbreviations:
AP: Acute pancreatitis
CIRCI: Critical illness-related corticosteroid insufficiency
CRP: C-reactive protein
V-lip: Serum lipase

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