How can mild acute pancreatitis present with normal serum amylase and lipase and unremarkable abdominal ultrasound or computed tomography, and what is the recommended initial management?

Mild Pancreatitis with Normal Labs and Imaging

Even when serum amylase, lipase, and initial imaging are normal, acute pancreatitis can still be present and should be diagnosed based on compatible clinical features combined with delayed contrast-enhanced CT imaging obtained after 72 hours. 1, 2

Diagnostic Approach When Enzymes Are Normal

Immediate Steps

• Measure serum lipase as the priority enzyme test because it remains elevated for 8-14 days compared to amylase's 3-7 days, providing a larger diagnostic window for patients presenting later in their disease course. 1, 3

• Obtain abdominal ultrasound immediately to detect gallstones, bile duct dilation, or free peritoneal fluid, even if initial imaging was unremarkable. 1, 2

• Recognize that enzyme elevations <3 times the upper limit of normal have low specificity and are consistent with but not diagnostic of acute pancreatitis—diagnosis requires compatible clinical features including upper abdominal pain with epigastric or diffuse abdominal tenderness. 1

When Clinical Suspicion Remains High Despite Normal Enzymes

• Perform contrast-enhanced CT scan after 72 hours of symptom onset when clinical and biochemical findings are inconclusive, as this is the gold standard for confirming diagnosis. 1, 2

• Early CT (<72 hours) underestimates pancreatic necrosis and should be avoided unless there is diagnostic uncertainty requiring immediate exclusion of other life-threatening disorders. 4, 1, 5

• Consider acute pancreatitis in unexplained multiorgan failure or systemic inflammatory response syndrome even without classic abdominal pain or enzyme elevation. 1

Critical Pitfall to Avoid

Normal serum lipase in acute pancreatitis is extremely rare but has been documented. 6, 5 In appropriate clinical settings with persistent symptoms—particularly abdominal bloating, distension, and epigastric tenderness—do not exclude pancreatitis based solely on normal enzymes. 5

Severity Stratification

Within First 24-48 Hours

• Calculate APACHE II score (cutoff of 8) to guide ICU triage decisions and predict severe disease. 1, 2

• Assess for organ failure (cardiovascular, respiratory, renal) or SIRS, which automatically indicates severe disease regardless of enzyme levels. 4, 2

• Measure hematocrit (>44% indicates risk of pancreatic necrosis) and blood urea nitrogen (>20 mg/dL predicts mortality). 4, 1

At 48-72 Hours

• Measure C-reactive protein—levels ≥150 mg/L indicate severe acute pancreatitis with approximately 80% accuracy. 4, 1, 2

• Serial CRP measurements improve accuracy as CRP peaks at 48-72 hours, so initial values may underestimate severity. 1

Initial Management

Fluid Resuscitation

• Initiate aggressive intravenous hydration within the first 12-24 hours unless there are cardiovascular or renal contraindications. 2

• Recent evidence from the WATERFALL trial indicates caution: aggressive fluid resuscitation (>10 ml/kg/hour) in non-severe pancreatitis showed threefold increased risks of fluid overload and potentially mortality compared to non-aggressive resuscitation. 4

Supportive Care

• Provide oxygen supplementation, pain control, and early nutrition regime. 7

• Encourage early oral feeding if tolerated; if not, provide liquid supplements or enteral tube feeding (preferably nasogastric) within 48 hours to prevent infectious complications in severe pancreatitis. 2, 7

Monitoring Strategy

• Use serial clinical examinations instead of enzyme levels to evaluate progression—monitor resolution of abdominal pain, tolerance to oral intake, and absence of systemic inflammatory signs. 2

• Be vigilant for complications 6-10 days after admission, including persistent organ failure or sepsis. 2

Etiologic Workup

• Obtain liver function tests (bilirubin, AST, ALT, alkaline phosphatase) to assess for biliary etiology. 1, 2

• Measure serum triglycerides—levels >1000 mg/dL (>11.3 mmol/L) indicate hypertriglyceridemia as the cause. 4, 1, 2

• Evaluate serum calcium to assess for hypercalcemia-induced pancreatitis. 1, 2

• If gallstones are detected with severe pancreatitis, consider urgent ERCP. 2

Advanced Imaging for Occult Biliary Disease

• When ultrasound does not show gallstones and liver function tests are normal, use MRCP or endoscopic ultrasound rather than diagnostic ERCP to screen for occult choledocholithiasis. 4

• MRCP has 97.98% sensitivity and 84.4% specificity for choledocholithiasis, avoiding the need for invasive imaging in most patients. 4

Key Clinical Pearls

Clinical assessment alone misclassifies approximately 50% of patients, making objective biochemical markers and delayed imaging essential when initial workup is unrevealing. 1

Patients who already exhibit clear organ failure should be escalated to intensive care management immediately, without awaiting the 48-hour CRP result or delayed CT imaging. 1, 2

Abdominal distension that cannot be explained by common causes (ascites, bowel edema, ileus) should raise suspicion for pancreatitis even with normal enzymes, prompting delayed CT imaging. 5