Episode 92 – When the Cause is the Remedy

Why don’t we use steroids in acute pancreatitis?

If there is one process that, day in and day out, we fight against in medicine, it’s inflammation. Everything from asthma to gout to psoriasis involves it. Mild inflammation is often treated with things most people have at home, like ibuprofen, while more severe disease can require potent agents like steroids. In episode 88 of The Curious Clinicians, we departed from our usual “why do we do __ to treat __?” when we asked why don’t we use systemic vasodilators to treat the hypoxia in COPD, which is due to pulmonary vasoconstriction. In this episode, we’re asking a similar question. Since acute pancreatitis (AP) is highly inflammatory, why don’t we use steroids to treat it?

There’s a reason it’s not called acute pancreatopathy. AP involves both local (within the pancreas) and systemic inflammation. In the BISAP calculator used to estimate mortality risk in acute pancreatitis, one of the 5 categories considered is having ≥2 Systemic Inflammatory Response Syndrome (SIRS) criteria. Approximately 62% of patients with AP meet SIRS criteria on the first day of hospitalization. And just looking at fever, 22% are attributed to pancreatitis alone and not to co-existing infection, including complications such as pancreatic necrosis.

The laboratory data backs this up. Severe AP can raise serum levels of inflammatory cytokines IL-1B, IL-6, IL-8 and IL-10, with IL-6 being especially notable as a predictor of severity and organ failure. Cytokines are typically not measured on the wards, but the inflammatory markers ESR and CRP are often elevated in AP, with one study showing that 100% of patients with AP had an elevation in one or both. Even procalcitonin (PCT), which is used more as a marker of bacterial infection, can be high, with one study actually suggesting it outperforms CRP as a predictor of organ failure when measured on admission.

So, in short, there’s good biochemical evidence that AP patients have systemic inflammation and good clinical evidence that systemic inflammation is associated with worse outcomes. However, the treatment for AP is mostly supportive care with IV fluids and diet as tolerated. Why don’t we reach for the ultimate “big gun” anti-inflammatory agent, steroids?

Physicians were asking the same question decades ago. The first case report of steroids being used in AP is from 1952. A young woman in New York was admitted with a temperature of 103.8°F and a white blood cell count of 18,200 secondary to severe hemorrhagic pancreatitis. Her fever rose to 106°F and her blood pressure plummeted. No remedy was working, so her doctor gave her 100mg of cortisone (equivalent to about 40mg of prednisone). She experienced periods of “euphoria” where she kept asking to leave the hospital. However, her symptoms did eventually improve. In 1957, Dr. Murrel Kaplan published a case report of 25 AP patients who recovered after cortisone treatment. Kaplan cautioned, however, that clinicians shouldn’t draw too many conclusions from these results.

In fact, the opposite conclusion may be true. In 1959, a report was published of acute, necrotic pancreatitis in a woman who was on chronic cortisone therapy. Recently, a 2013 case-control study showed that oral steroid therapy carried an odds ratio of 1.53 for AP, with risk highest 4-14 days after initiation. How steroids could cause pancreatitis (if they even do at all) is not clear, with some arguing that steroids alter pancreatic emptying and therefore cause accumulation of caustic enzymes.

So which is it then? Do steroids cause or treat pancreatitis? It could be both. Pneumocystis (or PJP) pneumonia is an example of a condition where steroids increase the risk of it, but are also used to treat. However, given that AP is generally treatable with supportive care, steroids are avoided because of the possible risk. Anti-inflammatory agents are still used, even if just prophylactically. As one 2012 RCT showed, rectal indomethacin reduces the risk of pancreatitis ( a well-known complication) after ERCP.

There are some recent and upcoming trials that revisit steroids as pancreatitis therapy.  One 2021 propensity-matched study from China split AP patients into steroid vs non-steroid groups. Not only did the steroid group have reduced hospital stays and costs, they were less likely to have organ failure (41% vs. 53%) and multi-organ failure (35% vs. 68%, P < 0.05). In 2027 or 2028, we should start seeing data from the Corticosteroids to Reduce Inflammation in Severe Pancreatitis (CRISP) trial. This multi-center trial is randomizing patients with severe pancreatitis to either 100 mg of IV hydrocortisone every 8 hours for 3 days or a matching placebo. Until there is more data, steroids for acute pancreatitis will most likely remain theoretically beneficial but outside of the standard of care.

Take Home Points

1. Acute pancreatitis is a highly inflammatory condition.
2. Despite early data suggesting there may be a benefit to steroids in acute pancreatitis, they have fallen out of favor and are not currently recommended.
3. Hopefully, the CRISP study will give us more clear answers.

Listen to the episode!

92 – When the Cause is the Remedy – The Curious Clinicians

Instead of "Why do we…?" this week the Curious Clinicians answer a "Why don't we?" question: why don't we use steroids in acute pancreatitis? Watch this episode on our new YouTube channel here, and read the show notes here! Click here to obtain AMA PRA Category 1 Credits™ (0.5 hours), Non-Physician Attendance (0.5 hours), or ABIM MOC Part 2 (0.5 hours). Audio edited by Clair Morgan of Nodderly.com. Medical student Giancarlo Buonomo is our producer. 

1. 92 – When the Cause is the Remedy 21:48
2. 91 – Ancient Antibiotics 24:28
3. 90 – Less Sugar, More Blood 23:10
4. 89 – Tusks & Tumor Suppressors 29:45
5. 88 – Shunting a Mismatch 23:02

Watch the episode on YouTube!

CME/MOC

Click here to obtain AMA PRA Category 1 Credits™ (0.5 hours), Non-Physician Attendance (0.5 hours), or ABIM MOC Part 2 (0.5 hours).

As of January 1, 2024, VCU Health Continuing Education will charge a CME credit claim fee of $10.00 for new episodes. This credit claim fee will help to cover the costs of operational services, electronic reporting (if applicable), and real-time customer service support. Episodes prior to January 1, 2024, will remain free. Due to system constraints, VCU Health Continuing Education cannot offer subscription services at this time but hopes to do so in the future.

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Credits & Suggested Citation

◾️Episode written by Tony Breu
◾️Show notes written by Giancarlo Buonomo and Tony Breu
◾️Audio edited by Clair Morgan of nodderly.com

Breu AC, Abrams HR, Cooper AZ, Buonomo G. When the Cause is the Remedy. The Curious Clinicians Podcast. June 26, 2024.

Image Credit: MD Anderson Cancer Center