Lau and Leow have indicated that perforated peptic ulcer was clinically recognized by 1799, but the first successful surgical management of gastric ulcer was by Ludwig Heusner in Germany in 1892. In 1894, Henry Percy Dean from London was the first surgeon to report successful repair of a perforated duodenal ulcer.
Partial gastrectomy, although performed for perforated gastric ulcer as early as 1892, did not become a popular treatment until the 1940s. This was carried out as a result of the perceived high recurrence rate of ulcer symptoms after simple repair. The physiologic effects of truncal vagotomy on acid secretion had been known since the early 19th century, and this approach was introduced to the treatment of chronic duodenal ulcer in the 1940s. The next development in the management of peptic ulcer disease was the introduction of high selective vagotomy in the late 1960s. However, neither of these approaches proved to be useful, and several postoperative complications, including high rates of ulcer recurrence, have limited their use. Currently, in patients with gastric perforation, simple closure of perforated ulcers is more commonly performed than is gastric resection.
During World War I, the mortality rate following isolated injuries of the small intestine and colon was approximately 66% and 59%, respectively. The possible reasons for the high mortality and morbidity rates at that time may have been related to the following factors:
Knowledge in the area of bowel injuries and the pathophysiologic changes triggered by such injuries was inadequate.
Clinical skills and diagnostic techniques that allow early detection of such injuries were lacking.
Intravenous saline solutions or blood transfusions were not used in the management of hypovolemia and hemodynamic changes of these patients.
No antibiotics were available.
Laparotomy was not recommended in abdominal injuries.
The technical maneuvers to assess bowel injuries and to mobilize ascending and descending colon were generally not recommended.
During the early years of World War II, Ogilvie, a leading surgeon in the British Army, recommended colostomy for management of all colonic injuries. This notion was supported by a publication from the office of the Surgeon General of the United States. However, the data presented in Ogilvie's series were not convincing. He reported a mortality rate of 53% for colonic injuries treated with colostomy, a rate similar to that observed during World War I.
According to Ogilvie, colostomy apparently failed to improve the mortality rate in World War II because primary repairs were used to treat less-severe injuries during World War I. Many patients in World War I were treated expectantly and were not included in the mortality data. On the other hand, Ogilvie's data included all patients with bowel injuries. These apparent differences in the methodology used convinced surgeons to continue using colostomies in such injuries after World War II.
Several reports clearly indicated that surgeons used colostomy during the Korean and Vietnam wars, particularly in the management of left colonic injuries. However, in civilian injuries, it has been reported that primary repair can be successfully used. By the end of 1980s, primary repair was considered to the management strategy of choice, and it has replaced the use of colostomies in the treatment of civilian patients in most hospitals in the United States, the United Kingdom, Europe, and Australia. At present, primary repairs are widely used for such bowel injuries.
Upper bowel perforation can be described as either free or contained. Free perforation occurs when bowel contents spill freely into the abdominal cavity, causing diffuse peritonitis (eg, duodenal or gastric perforation). Contained perforation occurs when a full-thickness hole is created by an ulcer, but free spillage is prevented because contiguous organs wall off the area (as occurs, for example, when a duodenal ulcer penetrates into the pancreas).
Lower bowel perforation (eg, in patients with acute diverticulitis or acute appendicitis) results in free intraperitoneal contamination.
In children, small bowel injuries following blunt abdominal trauma are infrequent, with an incidence of 1-7%. Evidence shows, however, that the incidence of these injuries is increasing.
In adults, perforations of peptic ulcer disease were a common cause of morbidity and mortality with acute abdomen until the latter half of the 20th century. The rate has fallen in parallel with the general decline in the prevalence of peptic ulcer disease. Duodenal ulcer perforations are 2-3 times more common than are gastric ulcer perforations. About a third of gastric perforations are due to gastric carcinoma.
Approximately 10-15% of patients with acute diverticulitis develop free perforation. Although most episodes of perforated diverticulum are confined to the peridiverticular region or pelvis, patients occasionally present with signs of generalized peritonitis. The overall mortality rate is relatively high (~20-40%), largely because of complications, such as septic shock and multiorgan failure.
In elderly patients, acute appendicitis has a mortality rate of 35% and a morbidity rate of 50%. A major contributing factor to morbidity and mortality in these patients is the presence of 1 or more severe medical conditions coexisting with, but predating, the appendicitis.
Endoscopy-associated bowel injuries are not a common cause of perforation. For example, perforations related to endoscopic retrograde cholangiopancreatography (ERCP) occur in about 1% of patients.
Causes of intestinal perforation include the following:
Penetrating injury to the lower chest or abdomen (eg, knife injuries) - In cases of penetrating trauma, the small bowel is the most commonly injured intra-abdominal viscus, because it is coiled in the abdomen and occupies most of the area of the peritoneal cavity. In addition, the small bowel is attached to a mesentery and is highly mobile.
Blunt abdominal trauma to the stomach - Such injuries are more common in children than they are in adults and include vehicle-related trauma, bicycle handlebar injuries, and seatbelt syndrome.
Ingestion of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and steroids - Intestinal perforation from such causes is particularly observed in elderly patients. Prescribing NSAIDs to patients with diverticular disease carries an increased risk of colonic perforation.
Presence of a predisposing condition - Predisposing conditions include peptic ulcer disease, acute appendicitis, acute diverticulitis, and inflamed Meckel diverticulum. Indeed, acute appendicitis is still one of the common causes of bowel perforation in elderly patients and is associated with relatively poor outcomes.
Bowel injuries associated with endoscopy - Injuries can occur with ERCP and colonoscopy.[3, 6, 7, 8]
Endoscopic biliary stent - Dislocation and migration of biliary stents to the intestine may cause bowel perforation.
Intestinal puncture as a complication of laparoscopy - Factors that may predispose patients to this complication are obesity, pregnancy, acute and chronic bowel inflammation, and bowel obstruction.
Bacterial infections - Bacterial infections (eg, typhoid fever) may be complicated by intestinal perforation in about 5% of patients. Perforation in these patients may unexpectedly occur after their condition has started to improve.
Inflammatory bowel disease - Bowel perforation may occur in patients with acute ulcerative colitis, and perforation of the terminal ileum may occur in patients with Crohn disease (CD); the CD-associated gene SLCO3A1 has been shown to mediate inflammatory processes in intestinal epithelial cells and thereby result in a higher incidence of bowel perforation in CD patients
Perforation secondary to intestinal ischemia (eg, ischemic colitis)
Bowel perforation by intra-abdominal malignancy, lymphoma, or metastatic renal carcinoma - Even benign tumours, such as desmoid tumours (eg, those originating from the fibrous tissues of the mesentery), may cause bowel perforation.
Radiotherapy of cervical carcinoma and other intra-abdominal malignancies - This may be associated with late complications, including bowel obstruction and bowel perforation.
Necrotizing vasculitis - Wegener’s granulomatosis affecting the viscera, although uncommon, may cause bowel ulcerations and perforations.
Kidney transplantation - Following kidney transplantation, gastrointestinal perforations may occur as a complication. In these cases, the perforation is usually related to the use of high doses of immunosuppressive medications, a treatment employed in the early postoperative period and in the management of acute rejection episodes.
Ingestion of caustic substances - Accidental or intentional ingestion of caustic substances may result in acute intestinal perforation and peritonitis. Delayed perforation may occur up to 4 days after acid exposure.
Foreign bodies (eg, toothpicks) - These may cause perforation of the esophagus, stomach, or small intestine, with intra-abdominal infection, peritonitis, and sepsis.
Normally, the stomach is relatively free of bacteria and other microorganisms because of its high intraluminal acidity. Most persons who experience abdominal trauma have normal gastric functions and are not at risk of bacterial contamination following gastric perforation. However, those who have a preexisting gastric problem are at risk of peritoneal contamination with gastric perforation. Leakage of acidic gastric juice into the peritoneal cavity often results in profound chemical peritonitis. If the leakage is not closed and food particles reach the peritoneal cavity, chemical peritonitis is succeeded by gradual development of bacterial peritonitis. Patients may be free of symptoms for several hours between the initial chemical peritonitis and the later occurrence of bacterial peritonitis.
The microbiology of the small bowel changes from its proximal to its distal part. Few bacteria populate the proximal part of the small bowel, whereas the distal part of the small bowel (the jejunum and ileum) contains aerobic organisms (eg, Escherichia coli) and a higher percentage of anaerobic organisms (eg, Bacteroides fragilis). Thus, the likelihood of intra-abdominal or wound infection is increased with perforation of the distal bowel.
The presence of bacteria in the peritoneal cavity stimulates an influx of acute inflammatory cells. The omentum and viscera tend to localize the site of inflammation, producing a phlegmon. (This usually occurs in perforation of the large bowel.) The resulting hypoxia in the area facilitates growth of anaerobes and produces impairment of bactericidal activity of granulocytes, which leads to increased phagocytic activity of granulocytes, degradation of cells, hypertonicity of fluid forming the abscess, osmotic effects, shift of more fluids into the abscess area, and enlargement of the abdominal abscess. If untreated, bacteremia, generalized sepsis, multiorgan failure, and shock may occur.
A careful medical history often suggests the source of the problem, which is subsequently confirmed by clinical examination and radiologic study findings. Possible etiologies include the following:
Penetrating injury or blunt trauma to the lower chest or abdomen
Aspirin, NSAIDs, or steroid intake, particularly in elderly patients
Treatment for peptic ulcer disease or ulcerative colitis; perforation due to acute ulcerative colitis (usually identified by the history of the primary disease and the results of past investigations)
Ask patients about the time of onset of pain, the duration and location of pain, the characteristics of pain, relieving and aggravating factors, and other symptoms associated with abdominal pain. A history of similar attacks may also suggest the etiology.
Sharp, severe, sudden-onset epigastric pain that awakens the patient from sleep often suggests perforated peptic ulcer. Differentiate this from conditions such as cholecystitis and pancreatitis. Painless perforation of a peptic ulcer can occur with steroid use. The presence of shoulder pain suggests involvement of the parietal peritoneum of the diaphragm.
In elderly patients, consider the possibility of perforated diverticulitis or ruptured acute appendicitis if the pain is located in the lower abdomen. Approximately 30-40% of elderly patients with acute appendicitis present more than 48 hours after the onset of abdominal pain. (Delayed presentation is usually associated with increased risk of perforation.) Elderly patients may have minimal pain.
In young adults with pain in the lower abdominal quadrant, consider perforated appendicitis as a possible diagnosis. Acute appendicitis with sudden perforation is usually associated with illness of several hours. The pain is typically localized in the right lower quadrant of the abdomen, unless the disease process has progressed to generalized peritonitis. In young women, also consider ruptured ovarian cyst and ruptured tuboovarian abscess in the differential diagnosis.
Vomiting - This occurs, albeit uncommonly, in patients with a perforated ulcer. Vomiting is, however, frequently noted in patients with acute cholecystitis. In patients with appendicitis, pain almost always precedes vomiting by 3-4 hours. The converse is true in gastroenteritis.
Hiccup - This is a common late symptom in patients with a perforated peptic ulcer.
History of travel to or of residing in tropical areas, with symptoms suggestive of typhoid fever (eg, fever, abdominal pain, abdominal distension, constipation, bilious vomiting)
History of endoscopic procedures, such as colonoscopy[3, 6, 7, 8]
History of chronic disease, such as ulcerative colitis
General appearance and vital signs - Take vital signs and assess for any hemodynamic changes. (Take pulse and blood pressure measurements with the patient lying in bed and sitting, and note any postural changes.)
Examine the abdomen for any external signs of injury, abrasion, and/or ecchymosis. Observe patients' breathing patterns and abdominal movements with breathing, and note any abdominal distension or discoloration. (In perforated peptic ulcer disease, patients lie immobile, occasionally with knees flexed, and the abdomen is described as boardlike.)
Carefully palpate the entire abdomen, noting any masses or tenderness. Tachycardia, fever, and generalized abdominal tenderness may suggest peritonitis. Abdominal fullness and doughy consistency may indicate intra-abdominal hemorrhage.
Tenderness on percussion may suggest peritoneal inflammation.
Bowel sounds are usually absent in generalized peritonitis.
Rectal and bimanual vaginal and pelvic examination - These examinations may help in assessing conditions such as acute appendicitis, ruptured tuboovarian abscess, and perforated acute diverticulitis.
The peritoneal cavity is lined with a single layer of mesothelial cells, connective tissue (including collagen), elastic tissues, macrophages, and fat cells. The parietal peritoneum covers the abdominal cavity (ie, abdominal wall, diaphragm, pelvis); the visceral peritoneum covers all of the intra-abdominal viscera, forming a cavity that is completely enclosed except at the open ends of the fallopian tubes.
The peritoneal cavity is divided by the transverse mesocolon. The greater omentum extends from the transverse mesocolon and from the lower pole of the stomach to line the lower peritoneal cavity. Abdominal organs, such as the pancreas, duodenum, and ascending and descending colon, are located in the anterior retroperitoneal space; the kidneys, ureters, and adrenal glands are found in the posterior retroperitoneal space. Other abdominal organs, the liver, stomach, gallbladder, spleen, jejunum, ileum, transverse colon, sigmoid colon, cecum, and appendix are found within the peritoneal cavity.
A small amount of fluid sufficient to allow movement of organs is usually present in the peritoneal space. This fluid is normally serous (protein content of < 30 g/L, < 300 WBCs/µL). In the presence of infection, the amount of this fluid increases, its protein content climbs to more than 30 g/L, and the white blood cell (WBC) count increases to more than 500 WBCs/µL; in other words, the fluid becomes an exudate.
Erect radiographs of the chest are recognized as the most appropriate first-line investigation when a perforated peptic ulcer is considered likely. However, in approximately 30% of patients, no free gas can be identified. Thus, an erect posteroanterior chest radiograph is not sufficiently sensitive to rule out pneumoperitoneum in patients presenting with upper abdominal pain.
Plain supine and erect radiographs of the abdomen are the most common first steps in the diagnostic imaging evaluation of patients presenting with medical history and/or clinical signs suggestive of bowel perforation. Findings suggestive of perforation include the following:
Free air trapped in the subdiaphragmatic locations - If the quantity of free air is great enough, its presence can be visualized on the supine radiograph of the abdomen, allowing clear definition of the inner and outer surface of the wall of the bowel.
Visible falciform ligament - The ligament may appear as an oblique structure extending from the right upper quadrant toward the umbilicus, particularly when large quantities of gas are present on either side of the ligament.
Air-fluid level - This is indicated by the presence of hydropneumoperitoneum or pyopneumoperitoneum on erect radiographs of the abdomen.
Water-soluble radiologic contrast media administered orally or through a nasogastric tube can be used as an adjunct diagnostic tool to detect any intraperitoneal leak.
The perforation has sealed at presentation in approximately 50% of patients. For those who favor a nonoperative approach, contrast radiology is routine in the management of these patients.
Ultrasonograms of the abdomen
Localized gas collection related to bowel perforation may be detectable, particularly if it is associated with other ultrasonographic abnormalities (eg, thickened bowel loop).
The site of bowel perforation can be detected by ultrasonography (eg, gastric vs duodenal perforation, perforated appendicitis vs perforated diverticulitis).
Ultrasonograms of the abdomen can also provide rapid evaluation of the liver, spleen, pancreas, kidneys, ovaries, adrenals, and uterus.
Computed tomography (CT) scans of the abdomen - This modality can be a valuable investigative tool, providing differential morphologic information not obtainable with plain radiography or ultrasonography.
CT scans may provide evidence of localized perforation (eg, perforated duodenal ulcer) with leakage in the area of the gallbladder and right flank with or without free air being apparent.
CT scans may show inflammatory changes in the pericolonic soft tissues and focal abscess due to diverticulitis (may mimic perforated colonic carcinoma).
CT scans may not provide definitive radiographic evidence of perforated Meckel diverticulitis.
Peritoneal diagnostic tap may be useful in determining the presence of intra-abdominal blood, fluid, and pus.
Peritoneal lavage is more valuable in the presence of a history of blunt abdominal trauma.
The presence of blood or purulent material or the detection of bacteria on Gram stain suggests the need for early surgical exploration.
Alkaline phosphatase concentration in the peritoneal lavage is a helpful and sensitive test that may be used to detect occult blunt intestinal injuries. A concentration greater than 10 IU/L has been shown to be a sensitive and reliable test in the detection of occult small bowel injuries.
Fine-catheter peritoneal cytology
This procedure involves the insertion of a venous cannula into the peritoneal cavity, through which a fine umbilical catheter is inserted while the patient is under local anesthesia.
Peritoneal fluid is aspirated, placed on a slide, and stained for examination under a light microscope for percentage of polymorphonuclear cells.
A value greater than 50% suggests a significant underlying inflammatory process.
This test, however, provides no clue as to the exact cause of inflammation.
The mainstay of treatment for intestinal perforation is surgery. Emergency medical care includes the following steps:
Establish intravenous access, and initiate crystalloid therapy in patients with clinical signs of dehydration or septicemia.
Do not give anything by mouth.
Start intravenous administration of antibiotics to patients with signs of septicemia. Antibiotics should cover aerobic and anaerobic organisms. The goals of antibiotic treatment are to eradicate infection and to minimize related postoperative complications.
However, if symptoms and signs of generalized peritonitis are absent, a nonoperative policy may be used with antibiotic therapy directed against gram-negative and anaerobic bacteria.[18, 19]
Antibiotics have proven effective in decreasing the rate of postoperative wound infection and in improving outcome in patients with intraperitoneal infection and septicemia.
Metronidazole (Flagyl) is typically used in combination with an aminoglycoside to provide broad gram-negative and anaerobic coverage. It is reduced to a product that interacts with deoxyribonucleic acid (DNA) to cause a loss of helical DNA structure and strand breakage, resulting in inhibition of protein synthesis and cell death in susceptible organisms. Adult dosing is 7.5 mg/kg IV before surgery. Pediatric dosing is 15-30 mg/kg/d IV divided bid/tid for 7 d. It is a pregnancy category B drug.
Gentamicin (Garamycin, Genoptic, Gentacidin) is an aminoglycoside antibiotic with gram-negative coverage. It is used in combination with both an agent against gram-positive organisms and one that covers anaerobes. Although it is not the DOC, consider gentamicin if penicillins or other less-toxic drugs are contraindicated, when clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms. Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of distribution. It may be given IV/IM. In adults, the loading dose before surgery is 2 mg/kg IV; thereafter, dosing is 3-5 mg/kg/d divided tid/qid. In infants, dosing is 7.5 mg/kg/d IV divided tid. In children, dosing is 6-7.5 mg/kg/d IV divided tid. It is a pregnancy category C drug.
Cefotetan (Cefotan) is a second-generation cephalosporin that inhibits bacterial cell wall synthesis by binding to 1 or more of the penicillin-binding proteins. It inhibits the final transpeptidation step of peptidoglycan synthesis, resulting in cell wall death. Adult dosing is 2 g IV once before surgery. In children < 3 months, dosing is not established. In those >3 months, dosing is 30-40 mg/kg IV once before surgery. It is a pregnancy category B drug.
Cefoxitin (Mefoxin) is also a second-generation cephalosporin that inhibits bacterial cell wall synthesis by binding to 1 or more of the penicillin-binding proteins. It inhibits the final transpeptidation step of peptidoglycan synthesis, resulting in cell wall death. Adult dosing is 2 g IV once before surgery, followed by 4 doses of 2 g IV q4-6h. In children < 3 months, dosing is not established. In those >3 months, dosing is 30-40 mg/kg IV before surgery, followed by 3 doses of 2 g IV q4-6h for 24 h. It is a pregnancy category B drug.
Cefoperazone sodium (Cefobid) is a third-generation cephalosporin that inhibits bacterial cell wall synthesis by binding to 1 or more of the penicillin-binding proteins. It inhibits the final transpeptidation step of peptidoglycan synthesis, resulting in cell wall death. Adult dosing is 2-4 g/d IV divided q12h. Pediatric dosing is 100-150 mg/kg/d IV divided q8-12h, not to exceed 12 g/d. It is a pregnancy category B drug.
Operative management depends on the cause of perforation. Perform urgent surgery either on patients not responding to resuscitation or following stabilization and maintenance of adequate urine output. All necrotic material and contaminated fluid should be removed and accompanied by lavage with antibiotics (tetracycline 1 mg/mL). Decompress distended bowel via a nasogastric tube.
Laparoscopic or laparoscopic-assisted (minilaparotomy) surgery is also being increasingly used with outcomes comparable with conventional laparotomy. Experience and the advancement in accessories have enabled endoscopic repair of a significant number of intestinal perforations, such as iatrogenic perforation. Management of such cases needs to be individualized to the patient.
In a study involving 934 patients with sigmoid diverticulitis, Ritz et al found that the risk of free perforation in acute sigmoid diverticulitis decreases with the increases in the number of previous episodes of sigmoid diverticulitis. They concluded that the first episode has the highest risk for a free perforation. Therefore, the indication for colectomy should not be made based on the potential risk of free perforation.
Wound infection rates correlate with the bacterial load in the bowel, so this complication occurs more often with colonic perforation (eg, perforated diverticulitis).
The judicious use of prophylactic antibiotics has been demonstrated to reduce the incidence of wound infection in contaminated and potentially contaminated wounds.
Wound failure (partial or total disruption of any or all layers of the operative wound) may occur early (ie, wound dehiscence) or late (ie, incisional hernia).
The following factors are associated with wound failure:
Hematoma (with or without infection)
Localized abdominal abscess
Multiorgan failure and septic shock
Septicemia is defined as proliferation of bacteria in the bloodstream resulting in systemic manifestations such as rigors, fever, hypothermia (in gram-negative septicemia with endotoxemia), leukocytosis or leukopenia (in profound septicemia), tachycardia, and circulatory collapse.
Septic shock is associated with a combination of the following:
Loss of vasomotor tone
Increased capillary permeability
Consumption of WBCs and platelets
Dissemination of powerful vasoactive substances, such as histamine, serotonin, and prostaglandins, resulting in capillary permeability
Complement activation and damage of capillary endothelium
Gram-negative infections are associated with a much worse prognosis than gram-positive infections, possibly because of associated endotoxemia.
Renal failure and fluid, electrolyte, and pH imbalance
Gastrointestinal mucosal hemorrhage: This complication is usually associated with failure of multiple organ systems and is probably related to a defect in the protective gastric mucosa.
Mechanical intestinal obstruction: Mechanical obstruction of the intestine is most often caused by postoperative adhesions.
Postoperative delirium: The following factors may cause a predisposition to postoperative delirium:
Samy A Azer, MD, PhD, MPH, Professor of Medical Education and Head of Curriculum Development Unit, King Saud University, Riyadh, Saudi Arabia; Visiting Professor of Medical Education, Faculty of Medicine, University of Toyama, Japan; former Professor of Medical Education, Chair of Medical Education Research and Development Unit, Faculty of Medicine, Universiti Teknologi MARA, Malaysia; former Consultant to the Victorian Postgraduate Medical Foundation, Melbourne, Australia; former Senior Lecturer in Medical Education, Faculty Education Unit, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne and University of Sydney, Australia
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
Michael A Grosso, MD, Consulting Staff, Department of Cardiothoracic Surgery, St Francis Hospital
Disclosure: Nothing to disclose.
Paolo Zamboni, MD, Professor of Surgery, Chief of Day Surgery Unit, Chair of Vascular Diseases Center, University of Ferrara, Italy
Disclosure: Nothing to disclose.
John Geibel, MD, DSc, MSc, MA, Vice Chair and Professor, Department of Surgery, Section of Gastrointestinal Medicine, and Department of Cellular and Molecular Physiology, Yale University School of Medicine; Director, Surgical Research, Department of Surgery, Yale-New Haven Hospital