What is the most likely diagnosis and recommended urgent work‑up and management for a patient presenting with epigastric pain, vomiting, leukocytosis, and glucosuria?

Acute Pancreatitis: Most Likely Diagnosis

The constellation of epigastric pain, vomiting, leukocytosis, and glucosuria strongly suggests acute pancreatitis, which requires immediate confirmation with serum lipase (≥2× upper limit of normal) or amylase (≥4× normal), followed by urgent contrast-enhanced CT abdomen to assess for necrosis and complications. 1, 2, 3

Immediate Diagnostic Workup

Laboratory Confirmation

• Measure serum lipase immediately (preferred over amylase as it remains elevated longer and has higher specificity of 80-90%), with diagnostic threshold ≥2× the upper limit of normal 1, 3
• Serum amylase ≥4× normal is diagnostic when lipase is unavailable, though it has more non-pancreatic sources 1, 4
• Order complete blood count, C-reactive protein, serum lactate, liver and renal function tests, and serum electrolytes 2
• Check procalcitonin level as the most sensitive test for detecting pancreatic infection, with low values strongly predicting absence of infected necrosis 5
• Obtain cardiac troponins at 0 and 6 hours to exclude myocardial infarction, which can present with isolated epigastric pain and carries 10-20% mortality if missed 6

Critical Imaging

• Obtain contrast-enhanced CT abdomen and pelvis immediately to confirm pancreatitis, assess for necrosis (which increases mortality from 0-11% to 40%), detect complications, and exclude surgical emergencies like perforated viscus or leaking aortic aneurysm 1, 5, 3
• CT shows extraluminal gas in 97% of perforations, fluid/fat stranding in 89%, and focal wall defects in 84% 2, 6
• Obtain right upper quadrant ultrasound within 48 hours to identify gallstones (the leading cause of acute pancreatitis) and guide need for ERCP or cholecystectomy 3, 7
• Chest and abdominal plain x-rays should be performed to exclude perforated viscus and intestinal obstruction 1

Vital Sign Assessment

• Check for tachycardia ≥110 bpm, fever ≥38°C, or hypotension, which predict sepsis, perforation, or anastomotic leak with high specificity 2
• Monitor for organ failure criteria including persistent hypotension, respiratory failure, or renal dysfunction to classify severity 5

Life-Threatening Differentials to Exclude Immediately

Cardiac Causes

• Obtain ECG within 10 minutes to exclude acute coronary syndrome, especially in women, diabetics, and elderly patients who present atypically with epigastric pain 6
• Myocardial infarction presenting as epigastric pain has 10-20% mortality if missed 2, 6

Surgical Emergencies

• Perforated peptic ulcer presents with sudden severe epigastric pain, fever, abdominal rigidity, and 30% mortality if treatment is delayed 6
• Mesenteric ischemia must be excluded in elderly patients with vascular risk factors and pain out of proportion to examination 2
• Leaking abdominal aortic aneurysm must be excluded in patients over 50 years with vascular risk factors 2, 6

Immediate Management

Resuscitation and Supportive Care

• Initiate aggressive IV fluid resuscitation targeting urine output >0.5 mL/kg/hr, though recent data suggest more cautious resuscitation in the first 24 hours may be appropriate for some patients 5, 3
• Maintain NPO status until surgical emergency is excluded 6
• Provide IV opiates judiciously for pain control, as they are generally safe when used appropriately 3

Antiemetic Therapy

• Administer ondansetron 8 mg sublingual every 4-6 hours, promethazine 12.5-25 mg orally/rectally every 4-6 hours, or prochlorperazine 5-10 mg every 6-8 hours 2
• Obtain baseline ECG before administering ondansetron due to QTc prolongation risk 2

Empirical Acid Suppression

• Start high-dose PPI therapy (omeprazole 20-40 mg once daily before meals) while awaiting diagnostic workup, as peptic ulcer disease remains in the differential 2, 6

Biliary Intervention

• Perform urgent ERCP if cholestatic liver injury with fever is present, as this suggests ascending cholangitis requiring immediate biliary drainage 5
• Defer elective biliary interventions until the acute inflammatory phase resolves 5

Severity Assessment and Prognosis

• Overall mortality for acute pancreatitis is <10%, but reaches 30-40% in necrotizing pancreatitis 1, 2, 6
• Sterile necrosis carries 0-11% mortality, while infected necrosis averages 40% and may exceed 70% 1
• Use Ranson criteria or Bedside Index of Severity in Acute Pancreatitis (BISAP) score to facilitate disposition decisions 3

Critical Pitfalls to Avoid

• Never dismiss cardiac causes in patients with "atypical" epigastric pain regardless of age or presentation, as myocardial infarction can present with isolated epigastric symptoms 6
• Do not delay ERCP when cholestatic injury with fever is present, as this may represent cholangitis requiring urgent drainage 5
• Avoid performing complex interventional procedures during the acute inflammatory phase due to increased complication risk 5
• Persistent vomiting is a red-flag sign that excludes functional dyspepsia and mandates investigation for structural disease 2
• Glucosuria in this context may reflect stress hyperglycemia from acute pancreatitis or underlying diabetes, both of which worsen prognosis 2, 8