In acute pancreatitis, should systemic corticosteroids and non‑steroidal anti‑inflammatory drugs be avoided?

Should Steroids and NSAIDs Be Avoided in Acute Pancreatitis?

NSAIDs should generally be avoided in established acute pancreatitis due to concerns about worsening outcomes, while systemic corticosteroids are reserved only for specific immune-mediated pancreatic toxicity (such as checkpoint inhibitor-induced pancreatitis) and should be avoided in routine acute pancreatitis management.

NSAIDs in Acute Pancreatitis

Evidence Against Routine Use

The American Gastroenterological Association guidelines on diverticulitis (which shares inflammatory pathophysiology) suggest advising patients with a history of diverticulitis to avoid nonaspirin NSAIDs due to moderately increased risk of occurrence and complicated disease 1. This principle extends to pancreatitis management, where avoiding NSAIDs is prudent once acute inflammation is established.

Avoid NSAIDs if there is any evidence of acute kidney injury, as recommended for acute pancreatitis management 2. This is critical because:

• Acute pancreatitis frequently causes hypovolemia and renal hypoperfusion
• NSAIDs can precipitate or worsen acute kidney injury in this setting
• The combination significantly increases morbidity

Conflicting Research Evidence

Interestingly, some observational data suggests NSAIDs may have protective effects:

• Patients already taking NSAIDs chronically experienced less pancreatic necrosis (p=0.019) and lower pseudocyst formation rates (p=0.010) 3
• Systematic reviews of animal studies show NSAIDs reduced inflammation, amylase/lipase levels, and histopathological damage 4
• NO-donating NSAIDs in experimental models decreased inflammatory markers and tissue injury when given prophylactically 5

However, these studies evaluated prophylactic or chronic NSAID use, not therapeutic administration after acute pancreatitis onset 3, 4. The clinical context differs fundamentally—chronic NSAID users may have anti-inflammatory preconditioning, whereas introducing NSAIDs during established acute pancreatitis risks renal toxicity without proven benefit 2.

Clinical Recommendation for NSAIDs

In practice, avoid NSAIDs once acute pancreatitis is diagnosed, particularly in the first 48-72 hours when:

• Hypovolemia and renal hypoperfusion are most severe
• Fluid resuscitation is ongoing
• Renal function may be compromised

The only exception is post-ERCP pancreatitis prevention, where prophylactic rectal indomethacin or diclofenac has established benefit 6. This is a distinct clinical scenario from treating established acute pancreatitis.

Systemic Corticosteroids in Acute Pancreatitis

Standard Acute Pancreatitis

There is no proven specific drug therapy for the treatment of acute pancreatitis; management focuses on supportive care with fluid resuscitation being the cornerstone 7, 8. Systemic corticosteroids have no role in routine acute pancreatitis management and should be avoided 8, 2.

Immune-Mediated Pancreatitis Exception

The only indication for corticosteroids in pancreatic inflammation is immune checkpoint inhibitor-induced pancreatitis:

• For moderate acute pancreatitis from immunotherapy, hold the checkpoint inhibitor and initiate high-dose steroids with a planned 6-week taper 1
• For severe cases, permanently discontinue immunotherapy and treat with steroids 1
• This represents drug-induced autoimmune pancreatitis, not typical acute pancreatitis

Pain Management Algorithm Without NSAIDs

Since NSAIDs should be avoided, use this multimodal approach 2:

1. First-line: Hydromorphone (Dilaudid) is preferred over morphine or fentanyl in non-intubated patients 2
2. Adjunctive: Consider epidural analgesia as part of multimodal approach for severe pain 2
3. Avoid: Morphine theoretically increases sphincter of Oddi pressure, though clinical significance is debated

Common Pitfalls

• Do not use NSAIDs for pain control in acute pancreatitis, especially with any renal impairment 2
• Do not administer systemic corticosteroids for routine acute pancreatitis—they have no proven benefit and may increase infection risk 8
• Do not confuse prophylactic NSAID use (post-ERCP prevention) with therapeutic use in established disease—these are entirely different clinical scenarios 6
• Monitor for asymptomatic lipase/amylase elevations in patients on checkpoint inhibitors, but do not withhold immunotherapy for isolated elevations without clinical pancreatitis 1