Peptic ulcer disease refers to an insult to the mucosa of the upper digestive tract resulting in ulceration that extends beyond the mucosa and into the submucosal layers. Peptic ulcers most commonly occur in the stomach and duodenum though they can occasionally be found elsewhere (esophagus or Meckel's diverticulum). While the majority of peptic ulcers are initially asymptomatic, clinical manifestations range from mild dyspepsia to complications including gi bleeding, perforation, and gastric outlet obstruction. This article will provide a brief overview of peptic ulcer disease with a primary focus on the complexity of perforated peptic ulcer from an Emergency Medicine perspective.
Peptic ulcer disease was traditionally thought to be the result of increased acid production, dietary factors, and even stress. However, Helicobacter Pylori infections and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) including low-dose aspirin are now the more popular etiologies leading to the development of peptic ulcer disease. . Other factors such as smoking and alcohol may also contribute.
The lifetime prevalence of peptic ulcer disease is declining and is currently estimated to be between 5-10%. It tends to be less prevalent in developed countries. Just as there has been a downward trend in the overall incidence of peptic ulcer disease, so too has there been a decline in the overall rate of complications.  Even though the overall incidence of complications is declining, complications including bleeding, perforation, and obstruction are responsible for nearly 150,000 hospitalizations annually in the United States.  Upper GI bleeding is the most common complication of peptic ulcer disease. The next most common complication is a perforation. The annual incidence of upper gi bleeding secondary to a peptic ulcer is estimated to be between 19 to 57 cases per 100,000 individuals. In comparison, ulcer perforation is expected to be 4 to 14 cases per 100,000 individuals. Advanced age is a risk factor as 60% of patients with PUD are older than 60. Infections with Helicobacter Pylori and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) are each identified as risk factors for the development of bleeding ulcers and peptic ulcer perforation.
The ulcerogenic process occurs as a result of damage to the protective mucosal lining of the stomach and duodenum. H pylori infections and the use of NSAIDs and low dose aspirin are known to damage the mucosal lining. The cost to the mucosal lining in the setting of an H pylori infection is the result of both bacterial factors and second the host's inflammatory response. In the case of NSAID (and aspirin) use, mucosal damage is secondary to inhibition of cyclooxygenase 1 (COX-1) derived prostaglandins which are important in maintaining mucosal integrity. Once the mucosal layer is disrupted, the gastric epithelium is exposed to acid, and the ulcerative process ensues. If the process continues, the ulcer deepens reaching the serosal layer. A perforation occurs once the serosal layer is breached at which point the gastric contents are released into the abdominal cavity. 
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 pain 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/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 systemic inflammatory response syndrome (SIRS)/ sepsis.
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.
The evaluation of a patient in whom perforated peptic ulcer is suspected should be done quickly as this is a sick patient population in which mortality increases significantly with time. Even if a perforated peptic ulcer is the suspected cause 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 CBC, chemistry panel, liver function tests, coags, and lipase. Blood type and screening should be done. A set of blood cultures and lactic acid should be done on patients meeting SIRS criteria. Lactic acid should also be performed if entertaining the diagnosis of mesenteric 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, CT scan of the abdomen and pelvis will have the highest yield diagnostically. No IV or oral contrast is required to illustrate pneumoperitoneum, but IV contrast may be used in the patient 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.  An initial emergent surgery consultation is required in all patients with peritonitis even before definitive diagnosis. Patients should be resuscitated with IV fluids 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, an IV proton pump inhibitor should be administered, IV antibiotics should be given, and a stat surgical consult should be obtained. 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.  Given the high prevalence of sepsis and its associated mortality, antibiotics should be administered to all in patients with perforated peptic ulcer. Antibiotics should be broad spectrum and cover gram-negative rods and anaerobes. 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).
Intravenous Proton Pump Inhibitors help bleeding cessation and facilitate healing, but efficacy in perforated ulcers has not been established. That said, IV PPI administration should be given that a neutral pH aids in maintaining platelet aggregation and hence should promote a more rapid sealing of perforated ulcers.
The mainstay treatment for a perforated peptic ulcer is early operative intervention as mortality significantly increases with surgical delay.  Surgery will typically consist of a peritoneal lavage followed by an interrupted sutured closure of the perforated ulcer followed by an omental patch. This procedure can be done by 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.
Differential diagnosis includes but is not limited to the following:
Mortality rate 10x higher than that seen with acute appendicitis or cholecystitis. Though bleeding is more common complication than perforation (6:1), the mortality rate is 5-fold higher with a perforated peptic ulcer compared with bleeding peptic ulcer.  The estimated 30-day mortality rate with perforation is 24%. 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. 
Complications of untreated peptic ulcer perforation include hypovolemia, SIRS, sepsis, abscess formation, gastrocolic fistula formation.
Managing a patient with a perforated peptic ulcer can be challenging given the morbidity and mortality associated with the disease. Hence it requires a multidisciplinary 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.
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