Management of peptic ulcer disease

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Management of Peptic Ulcer Disease (PUD)

Peptic ulcer disease (PUD) refers to mucosal defects in the stomach or duodenum caused primarily by Helicobacter pylori infection and/or NSAID use. The final common pathway is acid-peptic injury of the gastroduodenal mucosal barrier, and consequently all management strategies target acid suppression, eradication of causative factors, and prevention of complications.

1. General Principles

The mainstays of treatment are:

Gastric acid suppression (PPI or H2-receptor antagonist)
H. pylori eradication (when present)
NSAID cessation or gastroprotection (when causative)
Management of complications (bleeding, perforation, obstruction)

"Gastric antisecretory agents and H. pylori eradication therapy are the mainstays of treatment, and elective surgery is very rarely performed." - Bailey and Love's Short Practice of Surgery, 28th ed.

2. Acid Suppression

Proton Pump Inhibitors (PPIs)

PPIs are the cornerstone of acid suppression. They render patients virtually achlorhydric and can heal nearly all peptic ulcers. Standard doses include omeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg, or esomeprazole 20-40 mg, taken 30-60 min before a meal.

Duodenal ulcers: 4-week PPI course
Gastric ulcers: 8-week PPI course (longer needed; also confirm non-malignant at follow-up endoscopy)

H2-Receptor Antagonists (H2RAs)

Ranitidine (now withdrawn in many markets due to NDMA contamination), famotidine, and cimetidine are second-line agents. Less potent than PPIs. Largely superseded for active ulcer healing but may be used for maintenance.

3. Helicobacter pylori Eradication

Indications (Established)

Per the American College of Gastroenterology (ACG) guidelines:

Active PUD (gastric or duodenal)
Confirmed history of PUD not previously treated for H. pylori
Gastric MALT lymphoma (low grade)
After endoscopic resection of early gastric cancer
Uninvestigated dyspepsia (in regions where prevalence >20%)
Unexplained iron-deficiency anemia or ITP

Eradication should be offered regardless of time of presentation, severity, or whether the ulcer is in remission. H. pylori treatment dramatically decreases ulcer recurrence - from ~80% to <5% over 12 months for both duodenal and gastric ulcers.

(Schwartz's Principles of Surgery, 11th ed., pp. 1148-1152)

First-Line Eradication Regimens (10-14 days)

All combination therapies are used because no single agent is effective alone. 14-day courses provide the greatest eradication rates:

Regimen	Drugs
Clarithromycin triple therapy	PPI (standard or double dose) BD + clarithromycin 500 mg BD + amoxicillin 1 g BD (or metronidazole 500 mg TDS)
Metronidazole triple therapy	PPI BD + metronidazole 500 mg BD + amoxicillin 1 g BD
Levofloxacin triple therapy	PPI BD + amoxicillin 1 g BD + levofloxacin 500 mg daily
Sequential therapy	PPI + amoxicillin 1 g BD for 5-7 days, THEN PPI + clarithromycin 500 mg BD + metronidazole 500 mg BD for 5-7 days

Second-Line / Salvage: Bismuth Quadruple Therapy

Used when first-line regimens fail or when local clarithromycin/metronidazole resistance is high:

PPI BD + bismuth subsalicylate 300 mg QDS + tetracycline 500 mg QDS + metronidazole 250 mg QDS

(Schwartz's Principles of Surgery, 11th ed., Table 26-10)

Antibiotic Resistance Considerations

The steady rise in H. pylori resistance to clarithromycin and metronidazole significantly impacts treatment choice. Per Harrison's Principles of Internal Medicine 22nd ed. (2025):

"The steady increase in H. pylori resistance to antibiotics, in particular clarithromycin and metronidazole, has significantly impacted the approach to eradication... increasing resistance has led to a higher incidence of infections refractory to first-line therapies."

Where clarithromycin resistance is known to be high, bismuth quadruple therapy or levofloxacin-based regimens should be chosen as first-line. Rifabutin-based triple therapy (RHB-105) is an emerging option for refractory infection.

Test of Cure

Confirm eradication at least 4 weeks after completing antibiotics (and 2 weeks after stopping PPIs) using:

Urea breath test (preferred non-invasive)
Stool H. pylori antigen test
Endoscopic biopsy (if follow-up endoscopy is needed anyway, e.g., gastric ulcer)

4. NSAID-Induced Ulcers

Management

Discontinue NSAID if clinically feasible
Heal the ulcer with PPI (8 weeks for gastric, 4 weeks for duodenal)
Test and treat H. pylori - eradication alone does not fully eliminate risk if NSAIDs are continued, but decreases NSAID-induced GI bleeding

Prophylaxis for Patients Who Must Continue NSAIDs

Concomitant acid suppression is needed if any of the following risk factors are present (Schwartz's, Table 26-7):

Age >60 years
History of acid/peptic disease
Concurrent corticosteroid use
Concurrent anticoagulant use
High-dose or chronic NSAID use
High-dose or chronic aspirin use (>325 mg/day)

Options for prophylaxis:

PPI co-prescription (preferred, most effective)
Misoprostol 200 mcg QDS (prostaglandin analogue; reduces ulcer risk but side effects of diarrhea/cramping limit tolerance)
Consider switching to a selective COX-2 inhibitor (celecoxib), which carries lower GI risk (though cardiovascular risk persists)

(Rosen's Emergency Medicine; Schwartz's Principles of Surgery)

5. Special Situations

Zollinger-Ellison Syndrome (ZES)

Caused by gastrinoma secreting excess gastrin → massive acid hypersecretion
Treat with high-dose PPI (omeprazole 60-120 mg/day or equivalent)
Surgical resection of the gastrinoma if localized and resectable
Exclude MEN-1 syndrome (parathyroid, pituitary, and pancreatic tumors)

Stress Ulcers (ICU patients)

Prophylaxis with IV PPI or H2RA for mechanically ventilated patients or those with coagulopathy
Sucralfate (1 g QDS) is an alternative that coats the ulcer bed

Refractory Ulcers

Ensure compliance with treatment
Confirm H. pylori eradication failure and treat with salvage regimen
Rule out ZES (serum gastrin), Crohn's disease, or malignancy
Consider maintenance PPI therapy

6. Management of Complications

A. Bleeding Peptic Ulcer

The most common and most lethal complication. Most PUD deaths in the US are due to bleeding.

Risk Stratification:

Rockall Score (pre- and post-endoscopy): predicts rebleeding and mortality. Score ≥5 is high risk (rebleeding ~24-44%, mortality ~11-41%).
AIMS65 Score: albumin <3, INR >1.5, mental status alteration, SBP ≤90, age ≥65. Score 0 = negligible mortality; score 5 = ~30% in-hospital mortality.

Resuscitation:

IV access, fluid resuscitation, blood transfusion (restrictive strategy: target Hb ≥7-8 g/dL)
Correct coagulopathy, hold anticoagulants temporarily

Initial pharmacotherapy:

IV PPI bolus + infusion (e.g., omeprazole 80 mg IV bolus then 8 mg/hr infusion) before and after endoscopy - raises intragastric pH >6, stabilizes clot

Endoscopic therapy (within 24 hours, within 12 hours for high-risk features):

Endoscopic hemostasis for Forrest Ia/Ib (active bleeding) and IIa/IIb (visible vessel, adherent clot)
Methods: injection therapy (dilute epinephrine), thermal coagulation (heater probe, argon plasma), mechanical clips
Forrest IIc (flat pigmented spot) and III (clean base) can be managed medically

Forrest Classification:

Class	Lesion	Rebleeding Risk
Ia	Spurting hemorrhage	~90%
Ib	Oozing hemorrhage	~50%
IIa	Non-bleeding visible vessel	~50%
IIb	Adherent clot	~30%
IIc	Flat pigmented spot	~8%
III	Clean ulcer base	~2%

Second-look endoscopy is not routinely recommended but may be considered in high-risk cases.

Interventional radiology:

Transcatheter arterial embolization (TAE) for failed endoscopic hemostasis, especially in high-risk surgical candidates

Surgical treatment (when endoscopy and IR fail, or in hemodynamic instability unresponsive to resuscitation):

Oversewing of the bleeding vessel (most common)
± Vagotomy (truncal or highly selective) to reduce acid secretion

B. Perforated Peptic Ulcer

Classic presentation: sudden onset severe epigastric pain, rigid abdomen, pneumoperitoneum on erect CXR or CT
Initial management: nil by mouth, IV fluids, NG tube decompression, IV antibiotics, IV PPI
Definitive treatment: surgery
- Omental patch repair (Graham patch) for the perforation - this is the most common procedure performed today
- ± Vagotomy (increasingly uncommon due to reliance on postoperative PPIs)
- Laparoscopic approach is preferred in stable patients
Post-operatively: test and treat for H. pylori, continue PPI

C. Gastric Outlet Obstruction (GOO)

Usually from pyloric or duodenal scarring from chronic/recurrent ulcers
Presents with vomiting of undigested food, succussion splash, metabolic alkalosis (hypochloremic, hypokalemic)
Acute management: NG decompression, IV fluid + electrolyte correction (saline + KCl), IV PPI
Endoscopic balloon dilatation may relieve obstruction
Surgical treatment: truncal vagotomy + gastrojejunostomy (bypass), or truncal vagotomy + antrectomy (Billroth I or II reconstruction) - needed for fibrotic, non-dilatable obstruction
Always exclude malignancy as a cause of GOO

7. Elective Surgical Treatment

Elective surgery for PUD is now very rarely performed given the effectiveness of PPI + H. pylori eradication. Indications include intractability (failure of medical therapy), non-healing ulcer, or concern for malignancy.

Surgical Options for Duodenal Ulcer

Procedure	Operative Mortality	Ulcer Recurrence	Dumping (severe)	Diarrhea (severe)
Parietal cell (highly selective) vagotomy (HSV)	0%	5-15%	0%	0%
Truncal vagotomy + pyloroplasty (V+P)	<1%	5-15%	1%	2%
Truncal vagotomy + antrectomy	~1%	<2%	1-2%	1-2%

HSV (preserves pyloric innervation, no drainage procedure required) has the best side-effect profile but the highest recurrence. Truncal vagotomy + antrectomy has the lowest recurrence but greatest morbidity.

(Schwartz's Principles of Surgery, 11th ed., Table 26-11)

Surgical Options for Gastric Ulcer

Distal gastrectomy including the ulcer (Billroth I preferred if feasible)
Ulcer biopsy is mandatory to exclude malignancy

8. Lifestyle and Supportive Measures

Stop smoking - smoking impairs ulcer healing and increases recurrence
Avoid alcohol - directly toxic to gastric mucosa
Dietary modification - no specific diet has proven benefit, but avoiding foods that worsen symptoms is reasonable
Stress reduction - stress does not cause ulcers per se but may worsen symptoms

9. Follow-Up

Duodenal ulcers: confirm H. pylori eradication with breath or stool test; repeat endoscopy not routinely needed unless symptoms persist
Gastric ulcers: repeat endoscopy at 6-8 weeks is mandatory to confirm healing and exclude malignancy (biopsies at least 6-8 samples from ulcer margin)
If the ulcer fails to heal after 8-12 weeks of optimal therapy, reconsider malignancy, ZES, or NSAID non-compliance

Recent Evidence Update

A 2024-2025 meta-analysis (PMID 38818853) found that endoscopic therapy is superior to medical management alone for peptic ulcers with adherent clots in terms of rebleeding rates. A 2025 systematic review (PMID 40132025) highlighted that pharmacist-led interventions significantly improve adherence and outcomes in PUD management. A 2026 systematic review in Gastroenterology (PMID 41236450) quantified substantial additional benefits of mass H. pylori eradication beyond gastric cancer prevention, including reduced PUD burden.

Sources: Schwartz's Principles of Surgery 11th ed. | Harrison's Principles of Internal Medicine 22nd ed. (2025) | Bailey and Love's Short Practice of Surgery 28th ed. | Sleisenger and Fordtran's Gastrointestinal and Liver Disease | Yamada's Textbook of Gastroenterology 7th ed.

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