Although approximately 70% of patients with peptic ulcer disease may initially be asymptomatic, most patients with a perforated peptic ulcer will present with symptoms. Special populations such as the extremes of age (young or elderly), immunocompromised and those with altered level of consciousness may prove to be more challenging in obtaining a reliable history. When an honest account is obtainable, a detailed history may identify other symptoms that may have been present before ulcer perforation. The most common symptom in patients with peptic ulcer disease is dyspepsia or upper abdominal pain. This pain may be vague upper abdominal discomfort or it may be localized to either right upper quadrant, left upper quadrant, or epigastrium. Gastric ulcers may be worsened by food whereas pain from a duodenal ulcer may be delayed 2-5 hours after eating. Patients who are experiencing bleeding from a peptic ulcer may complain of nausea, hematemesis or melanotic stools. Some patients may report bright red blood per rectum or maroon-colored stool if the upper gi bleeding is brisk. 

Patients with peptic ulcer perforation typically will complain of sudden and severe epigastric pain. Pain while initially localized, quickly becomes more generalized in location. Patients may present with symptoms of lightheadedness or syncope secondary to hypotension from blood loss or SIRS (systemic inflammatory response syndrome)/sepsis. After several hours, abdominal pain may temporarily improve though it is still reproducible by movement. If there is a delay in seeking medical attention and the perforation is not walled off, patients are likely to experience increasing abdominal distension along with clinical manifestations of SIRS/ sepsis.[5][11]

A thorough physical examination should be done on all patients complaining of abdominal pain. Those with a perforated peptic ulcer are likely to have diffuse abdominal tenderness that progresses to guarding and rigidity. Rectal examination may demonstrate positive guaiac stools. Patients are likely to be tachycardic and may be hypotensive. They may be febrile and have mental status changes if there has been a delay in presentation.[5]

The evaluation of a patient in whom perforated peptic ulcer is suspected should be done quickly as the morbidity and mortality increase significantly with time. Even if a perforated peptic ulcer is suspected due to history and physical examination, diagnostic studies should be obtained to confirm the diagnosis and to rule out other possible etiologies. Typical workup includes labs and imaging studies. Standard labs should include complete blood count (CBC), chemistry panel, liver function tests, coagulation profile, and lipase levels (to rule out pancreatitis). Blood type and screening should be done as well. A set of blood cultures and lactic acid should be done on patients meeting the systemic inflammatory response syndrome (SIRS) criteria. Lactic acid will help elucidate coexistent ischemia. A urinalysis can be done in patients with similar pain or those with urinary symptoms.

Imaging studies should be obtained once the patient is stabilized. While plain abdominal films or chest x-ray may demonstrate free air, a computed tomogram (CT) scan of the abdomen and pelvis will have the highest yield diagnostically. Intravenous (IV) or oral contrast is not required to illustrate pneumoperitoneum, but IV contrast may be used in patients with undifferentiated abdominal pain/peritonitis. 

Perforated peptic ulcers are life-threatening conditions with a mortality rate that approaches 30%. Early surgery and aggressive management of sepsis are mainstays of therapy.[7]  An initial emergent surgery consultation is required in all patients with peritonitis even before definitive diagnosis. Patients should be resuscitated with crystalloids, antibiotics, and analgesics. Administration of early IV antibiotics should be considered, especially to patients presenting with SIRS criteria. Once the diagnosis of peptic ulcer perforation is made, a nasogastric tube should be placed, IV proton pump inhibitor should be administered, IV antibiotics should be given, and a surgical evaluation must be done. Then the decision can be made regarding whether the patient will require surgery. 

Sepsis accounts for approximately half of all mortalities in the setting of perforated peptic ulcers.[7] Given the high prevalence of sepsis and its associated mortality, antibiotics should be administered to all in patients with a perforated peptic ulcer. Antibiotics should be broad-spectrum and cover gram-negative rods and anaerobes. A combination of a third-generation cephalosporin and metronidazole is a reasonable choice as is monotherapy with a combination beta-lactam/beta-lactamase inhibitor (i.e., ampicillin-sulbactam, piperacillin-tazobactam).[12]

Intravenous proton pump inhibitors (PPI) help bleeding cessation and facilitate healing, but efficacy in perforated ulcers has not been established. That said, intravenous PPI administration should be given to create a neutral pH environment that aids in maintaining platelet aggregation and hence should promote rapid sealing of perforated ulcers.[1][13]

The mainstay treatment for a perforated peptic ulcer is early operative intervention as mortality significantly increases with surgical delay.[14] Surgery will typically consist of a peritoneal lavage of 5-10 liters of saline followed by an interrupted sutured closure of the perforated ulcer followed by an omental patch (Roseo-Graham patch). A drain is placed in the dependent areas and the abdomen is closed. The surgical drain is removed on postoperative day 3-5. This procedure can be done by an open approach or laparoscopically as there have been no significant differences in terms of mortality or clinically significant outcomes when comparing the two methods. A select number of patients may be chosen to forego surgery in favor of medical treatment alone. This option is a decision that would be made by the surgical consultant and would be limited to patients < 70 years old with early presentation (<24 hours), mild/localized symptoms, and in stable condition. In such patients, perforated peptic ulcer is managed by iv fluids, antibiotics, Ryle's tube aspiration, constant monitoring of urine output and electrolytes. This is referred to as the Hermen-Taylor regimen.[7][13] After 12 weeks follow up gastroscopy must be done.

Differential diagnosis includes but is not limited to the following:

• Abdominal aortic aneurysm (AAA)
• Acute coronary syndrome
• Aortic dissection
• Appendicitis
• Boerhaave's syndrome
• Cholecystitis
• Cholelithiasis 
• Choledocholithiasis
• Diverticulitis
• Duodenitis
• Esophagitis
• Foreign body ingestion
• Gastritis
• Hepatitis
• Hernia
• Mesenteric ischemia
• Neoplasm
• Nephrolithiasis
• Pyelonephritis
• Small bowel obstruction
• Ureterolithiasis
• Volvulus

Gastric ulcers are premalignant and hence biopsy of the ulcer or perforation margins are indicated in such patients. If found positive for neoplasia, thorough staging using endoscopy and imaging is used to stage and grade the disease, followed by resection and/or a combination of chemotherapy and surgery is recommended.

The mortality rate of perforated peptic ulcer is 10 times higher than that seen with acute appendicitis or cholecystitis. Though bleeding is a more common complication than perforation (6:1), the mortality rate is 5-fold higher with a perforated peptic ulcer compared with bleeding peptic ulcer.[7] The estimated 30-day mortality rate with perforation is 24%.[6] Patients with comorbidities or those older than 65 have a worse prognosis. Similarly, patients who have a delayed presentation or have a shock on initial presentation also have increased mortality.[6]

Complications of untreated peptic ulcer perforation are severe and will eventually lead to patient demise. Short term complications include hypovolemia, shock, sepsis, and gastrocolic fistula formation.

Patients with peptic ulcer disease should be warned about the possible complication of perforation. They should be counseled on medication compliance to ensure adequate healing of the ulcer occurs. Smoking cessation should be emphasized and other aggravating agents should be avoided as much as possible. These include nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, and caffeinated beverages. 

Managing a patient with a perforated peptic ulcer can be challenging given the morbidity and mortality associated with the disease. Hence it requires an interprofessional approach to maximize the chances of a favorable outcome. Diagnosis relies on suspicion of the underlying disorder. This treatment begins with the nurse triaging the patient and continues with the emergency medicine provider. Once suspected, resuscitative measures must be initiated while diagnostic studies are being obtained. This takes a coordinated effort between the ED provider and staff members of nursing, pharmacy, and radiology departments. Once the diagnosis is made, further communication is required between the ED provider and the on-call surgeon. Interprofessional communication is central to an expedited workup and treatment with the ultimate goal of getting the appropriate patient to the operating room promptly as surgical delay has been related to mortality.