Cushing Ulcer

A stress ulcer (single or multiple, often deep, in the oesophagus, stomach or duodenum) associated with raised intracranial pressure from traumatic brain injury, intracranial surgery, intracerebral haemorrhage, stroke or brain tumour.

• Occurs in about 5 to 20% of severe brain injury patients without prophylaxis; the ulcers tend to be deeper than other stress ulcers, with a higher risk of perforation and massive bleeding; onset is usually in the first week.
• Risk factors: Glasgow Coma Scale of 8 or less, raised intracranial pressure, mechanical ventilation for more than 48 hours, coagulopathy, corticosteroid use, sepsis, and previous ulcer disease.
• Mechanism: raised intracranial pressure and brainstem injury cause vagal overactivity with increased gastrin and acid secretion (hypersecretion), combined with ischaemia from stress and impaired mucosal defence.

Usually silent until bleeding: coffee-ground nasogastric aspirate, haematemesis, melaena, falling haemoglobin, haemodynamic instability.

• Perforation: sudden abdominal distension, peritonitis, free air; signs are masked in coma.
• Differential diagnosis: peptic ulcer (pre-existing), Curling ulcer, Mallory-Weiss tear, oesophagitis, erosive gastritis, varices, Dieulafoy lesion, coagulopathy-related bleeding, nasogastric tube trauma.
• Complications: massive haemorrhage, perforation, transfusion requirement, aspiration, longer stay in intensive care, and death (mainly from the brain injury).

Clinical when bleeding occurs in a patient with a recent brain injury or neurosurgery: coffee-ground aspirate of more than 100 mL, haemoglobin fall of 20 g/L or more, or melaena.

• Upper endoscopy when stable: ulcers (often larger and deeper) and erosions in the oesophagus, stomach and duodenum; assess for a bleeding vessel.
• Blood tests: full blood count, clotting profile, fibrinogen, urea, creatinine, electrolytes (sodium, with hypertonic therapy), liver tests, glucose, group and crossmatch.
• Erect chest X-ray or CT abdomen for perforation; CT angiography or angiography for massive bleeding.
• Intracranial pressure monitoring and brain imaging as clinically required.

Control the brain injury: head of bed at 30 degrees, normocapnia (PaCO2 4.5 to 5.0 kPa), sedation, osmotherapy (mannitol 0.25 to 1 g/kg IV over 15 to 20 minutes, or 3% sodium chloride 2 to 5 mL/kg, or 23.4% sodium chloride 30 mL via central line), cerebral perfusion pressure of 60 to 70 mmHg, treatment of seizures and fever, and decompressive surgery when indicated.

• Prophylaxis for patients with severe brain injury (Glasgow Coma Scale of 8 or less, ventilation for more than 48 hours, coagulopathy):
  • Pantoprazole 40 mg IV once daily (or omeprazole 40 mg IV or enterally once daily; some units use 40 mg twice daily when intracranial pressure is raised) until the patient is awake, feeding and off ventilation.
  • Famotidine 20 mg IV twice daily (10 mg twice daily if creatinine clearance is under 50 mL/min) is an alternative.
  • Sucralfate 1 g four times daily by nasogastric tube is an alternative (avoid in renal failure).
  • Early enteral feeding within 24 to 48 hours (25 to 30 kcal/kg/day).
• Treatment of bleeding:
  • Resuscitation, transfusion at 70 g/L (80 g/L in cardiovascular disease), avoiding hypotension (which worsens cerebral perfusion), correction of coagulopathy (platelets to 50 x 10^9/L, or 100 x 10^9/L in intracranial haemorrhage; vitamin K 10 mg IV; prothrombin complex concentrate 25 to 50 units/kg for warfarin).
  • Omeprazole 80 mg IV bolus then 8 mg/hour for 72 hours.
  • Endoscopy within 24 hours when stable: adrenaline 1 in 10,000 injection (up to 10 mL) with thermal therapy or haemoclip; large deep ulcers often need clips plus embolisation.
  • Angiographic embolisation or surgery (oversewing, vagotomy and pyloroplasty, resection) for failed endoscopic control.
  • Tranexamic acid is not helpful.
• Perforation: laparotomy, repair or omental patch, antibiotics (piperacillin-tazobactam 4.5 g IV every 6 hours).
• Avoid ulcerogenic drugs (NSAIDs, high-dose corticosteroids unless essential); thromboprophylaxis with enoxaparin 40 mg SC daily once the neurosurgical team allows.
• Helicobacter pylori testing after recovery, with eradication when positive (omeprazole 20 mg twice daily, amoxicillin 1 g twice daily and clarithromycin 500 mg twice daily for 14 days).
• Special groups: children (omeprazole 1 mg/kg once daily, maximum 40 mg, or famotidine 0.25 mg/kg IV every 12 hours, maximum 20 mg); pregnancy (omeprazole 20 to 40 mg daily, fetal monitoring, multidisciplinary neurocritical care); elderly (famotidine dose reduction, delirium risk); renal impairment (reduce famotidine, avoid sucralfate and aluminium antacids); anticoagulated patients (reverse and discuss restart with neurosurgery).
• Red flags: haematemesis, haemoglobin fall of 20 g/L or more, shock, rigid abdomen, free air, coagulopathy, rapidly rising intracranial pressure.
• Follow-up: stop prophylaxis when the patient is feeding enterally, awake and off ventilation; omeprazole 20 to 40 mg daily for 4 to 8 weeks after a bleed; check haemoglobin and ferritin at discharge and at 4 to 8 weeks; repeat endoscopy at 6 to 8 weeks for gastric ulcers.