Management of stress ulcers

INTRODUCTION — Stress ulcers were once a major cause of morbidity and mortality in critically ill patients. However, with improvements in resuscitation and critical care, surgical intervention is only necessary for a small number of patients with life-threatening hemorrhage or perforation from stress ulcers [1].

The nonsurgical management, indications for surgery, and surgical management of patients with stress ulcers are reviewed here. The epidemiology, pathogenesis, clinical manifestations, and prophylaxis of stress ulcers, as well as the nonsurgical treatments of upper gastrointestinal bleeding, are discussed elsewhere. (See "Stress ulcers in the intensive care unit: Diagnosis, management, and prevention" and "Approach to acute upper gastrointestinal bleeding in adults".)

The surgical treatment of peptic ulcer disease (not stress ulcer disease) is presented separately. (See "Surgical management of peptic ulcer disease".)

CLASSIFICATION — Stress gastritis may be referred to as diffuse mucosal injury, stress-related mucosal disease, stress ulceration, hemorrhagic gastritis, erosive gastritis, Curling's ulcer, and Cushing's ulcer. Stress-related erosive syndrome was first described in 1971 [2]. A commonality to all is the presence of multiple superficial erosions of the gastric mucosa, beginning in the proximal acid-secreting portion of the stomach and progressing distally. Cushing's ulcers develop following central nervous system injury. Morphologically, Cushing's ulcers tend to be single and deep and may involve the esophagus, stomach, or duodenum [3]. Curling's ulcers occur following burns involving greater than 30 percent total body surface area. Curling's ulcers can occur in the stomach or duodenum [4]. Stress gastritis erosions occur after physical trauma, shock, hemorrhage, and sepsis. Thus, stress gastritis represents end-organ failure of the stomach in critical illness.

Stress gastritis erosions can be identified within hours following injury and occur nearly universally (in the absence of prophylaxis) following severe shock [5]. These erosions appear as wedge-shaped mucosal hemorrhages with necrosis of the superficial mucosal cells. If these erosions continue to progress and extend into the submucosa, significant and life-threatening bleeding may arise. The pathogenesis of stress gastritis is presented elsewhere. (See "Stress ulcers in the intensive care unit: Diagnosis, management, and prevention", section on 'Pathophysiology'.)

INITIAL MANAGEMENT — Despite almost universal use of ulcer prophylaxis, some critically ill patients still develop stress ulcers, and a small number of them may develop clinically significant bleeding. The clinical manifestations and diagnosis of stress ulcers are discussed elsewhere. (See "Stress ulcers in the intensive care unit: Diagnosis, management, and prevention".)

When patients are diagnosed with bleeding stress ulcers, they should be promptly resuscitated with intravenous fluid or blood products. Any coagulopathy is corrected. A nasogastric tube should be inserted to remove gastric blood and irritants such as acid, bile, or pancreatic secretions, which may cause further injury to the gastric mucosa. An intravenous proton pump inhibitor should be administered, and broad-spectrum antibiotics should be given to septic patients. Underlying sepsis is an important cause of stress ulcers. Thus, in patients with sepsis, appropriate antibiotic coverage and source control are required for adequate ulcer healing. (See "Evaluation and management of suspected sepsis and septic shock in adults".)

Endoscopy is usually the first-line therapy for patients with bleeding stress ulcer disease, both for diagnosis and treatment. Depending upon local expertise, angiographic interventions can also stop bleeding from stress ulcers.

Resuscitation — Fluid resuscitation usually begins with crystalloid infusion. Maintenance of normothermia through utilization of fluid warmers is mandatory as administration of large volumes of room-temperature crystalloid may cause dilutional and hypothermic coagulopathy. Once available, blood products including packed red blood cells, fresh frozen plasma (FFP), and platelets should be used in a balanced ratio as early as possible in place of intravenous fluid. (See "Maintenance and replacement fluid therapy in adults".)

Correction of coagulopathy — Coagulopathy is an independent risk factor for developing clinically significant bleeding from stress gastritis [6]. Patients with overt gastrointestinal bleeding and prolonged prothrombin time with international normalized ratio (INR) greater than 1.5 or platelet count less than 50,000 per microliter or an abnormal thromboelastogram should be given FFP or platelet transfusion, respectively. Platelet transfusions should also be given to patients with normal platelet count but who have received antiplatelet agents such as aspirin or clopidogrel [7].

Data from mixed trauma patients with massive transfusion requirements indicate that patients with acute traumatic coagulopathy appear to benefit from receiving transfusions of packed red blood cells, FFP or similar products, and platelets in ratios approaching 1:1:1 [8,9]. These data may be applicable to patients with life-threatening bleeding from stress gastritis.  

Other hemostatic agents (recombinant human factor VIIa, prothrombin complex concentrate, tranexamic acid, desmopressin) have been tested for use in trauma patients, but no data exist for their use in hemorrhagic stress gastritis patients. (See "Etiology and diagnosis of coagulopathy in trauma patients" and "Ongoing assessment, monitoring, and resuscitation of the severely injured patient", section on 'Other agents'.)

Nasogastric tube placement — Placement of a nasogastric tube is a simple yet critical intervention in the initial treatment of hemorrhagic stress gastritis. Lavage through the nasogastric tube can remove retained blood and clot, and suction decompresses the stomach to prevent gastric distension (which increases gastrin production) and removes luminal irritants [10]. Historically, gastric cooling with iced saline was also done through a nasogastric tube as a physical means of hemostasis; however, the overall hypothermic effects likely negate any benefits from vascular constriction. (See "Inpatient placement and management of nasogastric and nasoenteric tubes in adults".)

Antisecretory agents — The administration of intravenous antisecretory agents, preferably proton pump inhibitors, is warranted if the patient develops bleeding from stress ulcers. Either a proton pump inhibitor or an H2-receptor antagonist can satisfactorily inhibit acid secretion, which promotes healing of erosions and ulcerations. However, proton pump inhibitors have been shown to be more efficacious than H2-receptor antagonists in the resolution of gastric bleeding [11]; although these data come from patients with peptic ulcer disease, the findings are likely to be applicable to patients with stress ulcers [12-15].

Endoscopy — Endoscopic therapy is usually the first-line intervention for upper gastrointestinal hemorrhage, including that from stress ulcers. Endoscopy aids in both diagnosis and potential treatment of the bleeding source. Unfortunately, in stress ulcers bleeding is frequently diffuse throughout the stomach without a dominant bleeding source that would be amenable to intervention. Despite this, initial endoscopic control of bleeding is often successful with either injection or coagulation therapy. However, the rebleed rates can be high. (See "Overview of the treatment of bleeding peptic ulcers", section on 'Endoscopic therapy'.)

Angiography — In facilities with the requisite expertise, angiographic intervention may be used to treat bleeding stress ulcers as well. (See "Angiographic control of nonvariceal gastrointestinal bleeding in adults".)

When a discrete bleeding vessel is identified on angiography, it can be subsequently embolized to stop bleeding. When no discrete bleeding source is found on angiography, an attempt at vasopressin infusion can be made into the left gastric artery, which typically supplies the bleeding site. Although catheter-directed vasopressin infusion can successfully halt bleeding initially, some patients rebleed after discontinuation of vasopressin. Thus, if vasopressin infusion is initially successful in bleeding control, the left gastric artery should then be embolized to prevent rebleed. In patients with diffuse bleeding, complete gastric devascularization can be accomplished angiographically by embolizing both the left and right gastric arteries and the left and right gastroepiploic arteries. Due to the extensive collateral circulation of the stomach, in patients without a history of previous foregut surgery, the stomach usually survives such a procedure without ischemia. (See 'Blood supply' below.)

Vasopressin has to be used with extreme caution in patients with a history of ischemic heart disease as it may precipitate acute coronary events. (See "Angiographic control of nonvariceal gastrointestinal bleeding in adults".)

INDICATIONS FOR SURGERY — Although most of the bleeding from stress ulcers can be treated nonoperatively, there remains a small subset of patients who either do not respond to nonsurgical management, rebleed after repeated nonsurgical interventions, or develop a perforation. Alternatively, patients may be too unstable to undergo nonsurgical interventions. For those patients, prompt surgical intervention is indicated because it provides the only chance of survival.

Refractory bleeding — Surgical intervention may be indicated in two different clinical scenarios involving bleeding from stress ulcers.

Bleeding causing hemodynamic instability — Surgical control of bleeding is a life-saving intervention in hemodynamically unstable patients with stress ulcers. These patients frequently present with blood loss in excess of 8 units of packed red cells, and hemostasis is unlikely to occur without surgery.

Stable patients with persistent blood loss complicating comorbid conditions — Surgical control of bleeding is sometimes warranted in patients with persistent, refractory bleeding from stress ulcers who are showing signs of clinical deterioration [16]. These patients are hemodynamically stable but have ongoing transfusion requirements. Continuation of blood product replacement therapy could lead to immunologic and inflammatory complications and also depletes resources.

Gastrointestinal perforation — Compared with patients who have superficial ulcers from trauma, shock, or sepsis, patients with Cushing's and Curling's ulcers are more susceptible to gastrointestinal perforations as these two types of stress ulcers tend to be deep and cause extensive necrosis [3,17].

Patients who develop free gastrointestinal perforation require immediate surgical intervention. Closure of the perforation is necessary to achieve source control in order to manage associated sepsis. Mortality without surgical intervention approaches 100 percent in these patients. (See "Overview of gastrointestinal tract perforation", section on 'Stomach and duodenum'.)

Because Cushing's or Curling's ulcers can cause extensive necrosis of the gastric wall before perforation occurs, more extensive gastric resection (like a subtotal gastrectomy, with a delayed anastomosis until the patient has stabilized) may be required to treat a gastric perforation caused by stress ulcers than a gastric perforation caused by type 1 gastric peptic ulcers. (See 'Gastric resection procedures' below and "Surgical management of peptic ulcer disease", section on 'Type I gastric ulcer'.)

PREOPERATIVE PREPARATION — Patients who are referred for surgery because of complicated stress ulcer disease (refractory bleeding or gastric perforation) are typically gravely ill. Thus, thorough preoperative preparations are important to ensure the best surgical outcomes. Many of these procedures are also performed urgently in the operating room, often during after-hours when only limited staff is available. Thus, cooperation among surgical, anesthesia, and nursing staff is essential to ensure a smooth operation.

The following preparations should be made prior to the operation:

●Establish two large-bore (14 or 16 gauge) peripheral intravenous lines for volume infusion. In addition, an arterial line and a central venous catheter may be placed for hemodynamic monitoring and vasopressor administration.

●Heat the operating room to an appropriate temperature (usually 85 degrees Fahrenheit); cold operating room air temperatures can exacerbate hypothermia and therefore coagulopathy.

●Ensure that blood products (typed and cross-matched packed red blood cells, fresh frozen plasma, and platelets) are readily available.

●Have adequate numbers of fluid warmers and rapid infusers readily available.

●Use pneumatic compression devices for prophylaxis against venous thromboembolism. (See "Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients", section on 'Low VTE risk: Mechanical methods'.)

●Give antibiotic prophylaxis prior to incision in patients who are not already receiving antibiotics. (See "Antimicrobial prophylaxis for prevention of surgical site infection in adults".)

SURGICAL ANATOMY — The stomach resides in the left upper quadrant of the abdomen. Anteriorly, it is contained by the chest and abdominal walls, and usually a large portion is covered by the left lateral segment of the liver. Superiorly and posteriorly, it is confined by the diaphragm. The spleen occupies its position superiorly and laterally to the greater curvature. The pancreas resides in the lesser sac, posterior to the stomach. Inferiorly, the stomach is bordered by the transverse colon. The stomach is fixed at the gastroesophageal junction and the pylorus (figure 1). However, between these two points the stomach is mobile, which assists in its ability to distend.

The most proximal portion of the stomach that attaches to the intra-abdominal esophagus is the cardia. Between the esophagus and the cardia is the lower esophageal sphincter. The highly distensible fundus is distal to the cardia and is bordered by the angle of His, which forms between the left edge of the esophagus and the fundus, the diaphragm superiorly, and the spleen laterally. Continuing distally is the body of the stomach. This is the largest portion of the stomach and contains the majority of the parietal cells. The body is defined from the antrum by the angularis incisura, at which point the lesser curvature of the stomach acutely angles toward the right. The pylorus then lies between the antrum of the stomach and the first portion of the duodenum.

Blood supply — Most of the blood supply to the stomach arises from the celiac artery (figure 2). Four vessels supply the majority of the stomach. The left and right gastric arteries supply the lesser curvature. The left and right gastroepiploic arteries supply the greater curvature. The largest artery to the stomach is the left gastric artery. In 15 to 20 percent of patients, an aberrant left hepatic artery originates from the left gastric artery. This is of special surgical significance because if the left gastric artery is ligated or embolized proximally to the takeoff of an aberrant left hepatic artery, it may lead to ischemia of the left lobe of the liver.

The stomach also has a rich collateral circulation. A substantial amount of the circulation to the proximal stomach can be provided by the inferior phrenic arteries. The short gastric arteries arising from the splenic circulation can supply much of the greater curvature. This rich collateral circulation is what allows the stomach to survive if gastric devascularization is attempted to control catastrophic bleeding.

The venous drainage from the lesser curvature is through the left gastric vein (also known as the coronary vein) and the right gastric vein, which both drain into the portal vein. The left gastroepiploic vein drains into the splenic vein, and the right gastroepiploic vein drains into the superior mesenteric vein.

Vagal innervation — The sympathetic innervation of the stomach is from the celiac plexus. The parasympathetic innervation of the stomach is from the vagus nerve (figure 3). The vagus nerve arises in the vagal nucleus in the brain, travels through the carotid sheath in the neck, and then enters the mediastinum where it divides into numerous branches around the esophagus. At the level of the diaphragmatic hiatus, those vagal branches then coalesce into the left (anterior) and right (posterior) vagus nerves. The left vagus nerve branches to give off the hepatic branch and the anterior nerve of Latarjet, which courses down the lesser curvature of the stomach. The first branch off the right vagus nerve is the criminal nerve of Grassi. The criminal nerve of Grassi is of particular interest because if it is not divided, recurrent ulcers can develop. The right vagus nerve continues to travel down the lesser curvature of the stomach, giving off branches to the celiac plexus along the way.

In order to perform a truncal vagotomy, both left and right vagus nerves are divided above the hepatic and celiac branches. A selective vagotomy divides below these branches, which preserves the hepatic and pyloric branches.

SURGICAL APPROACH — Surgery for stress ulcer disease can be challenging because patients are often ill from both their underlying disease processes (eg, sepsis) as well as acute hemorrhagic shock. For bleeding patients who are acidotic, hypothermic, or coagulopathic, a staged surgical approach appears safer [18].

The initial stage of the operation is usually done with the primary goal of bleeding control [19,20]. Once that is achieved, the second stage of the operation needs to be tailored to each individual patient based on their hemodynamic stability. Stable patients go on to have a vagotomy and pyloroplasty before abdominal closure, while unstable patients are sent back to the intensive care unit for further resuscitation with an open abdomen. More elaborate procedures such as gastrectomy or gastric devascularization are now rarely used because of the high morbidity and mortality associated with them.

Abdominal incision and exploration — A long midline incision is recommended for its versatility and expediency. The entire abdomen is then quickly but systematically explored to exclude any pathology, including bleeding, perforation, infection, obstruction, or tumor. The focus of the surgeon is then directed toward the stomach.

Anterior gastrotomy and oversewing of bleeders — The simplest and most straightforward operation is a long anterior gastrotomy with oversewing of all potential bleeding sources. As discussed earlier, due to the diffuse nature of stress gastritis, there is rarely a singular source of bleeding in those patients.

In stress gastritis, the bleeding sources often reside high along the lesser curvature close to the esophagogastric junction [21]. Therefore, the initial gastrotomy needs to be made high enough to allow for eversion and close inspection of the flattened rugal folds of the upper stomach (figure 4) [22]. A counterincision in the form of a longitudinal gastroduodenostomy can be made across the pylorus after a Kocher maneuver to mobilize the duodenum. This would allow for inspection of the distal stomach, pyloric channel, and proximal duodenum.

Subsequent approach based upon hemodynamic stability

Stable patients — In patients who are hemodynamically stable after incision, exploration, and oversewing of bleeders, a vagotomy and pyloroplasty can be added, followed by closure of the abdomen.

Vagotomy and drainage procedure — Some forms of vagotomy, usually in combination with a drainage procedure, have a long-standing history in the treatment of peptic ulcer disease (see "Vagotomy"). Not surprisingly, vagotomy has been used in conjunction with other procedures in the treatment of stress gastritis. Vagotomy reduces luminal acid production and has some efficacy in the treatment of stress gastritis in those patients requiring surgery [23,24]. Vagotomy and pyloroplasty (or other drainage procedure) can be performed in this setting, although ligation of actively bleeding ulcers must be accomplished first.

Closure — The anterior gastrotomy is closed in two layers. If a gastroduodenostomy is made separately, its closure can be incorporated into a standard Heineke-Mikulicz pyloroplasty.

Unstable patients — In patients who are hemodynamically unstable after incision, exploration, oversewing of bleeders, and closure of the gastrotomy, the abdomen should be left open using a negative pressure dressing or some other temporary closure method to prevent abdominal compartment syndrome and expedite a second-look procedure. Leaving the abdomen open also decreases operative time and allows the patient to return to the intensive care unit for further resuscitative efforts as soon as possible.

Patients may be returned to the operating room when hemodynamically stable for vagotomy and pyloroplasty (or other drainage procedure), followed by abdominal closure (usually within 24 to 48 hours) [18].

Rarely performed procedures — Gastric resectional procedures and total gastric devascularization had been used to treat patients with bleeding stress ulcers. However, these procedures are rarely used because of their high morbidity and mortality.

Gastric resection procedures — Most authors advocate for reserving resectional procedures for reoperations if a patient develops rebleeding after the initial operation [25-28]. Before proton pump inhibitors were widely used, gastric resection was sometimes carried out as the index operation because of rebleeding rates achieved with simple vagotomy and pyloroplasty [29,30].

Partial gastrectomy — A partial gastrectomy can be performed if the bleeding is confined to a portion of the stomach (for example, the antrum). However, this is rarely the case with stress ulcers, which tend to be multifocal. In addition, antrectomy is of limited benefit because stress ulcers usually start in the fundus [31].

Alternatively, a sleeve gastrectomy can be performed in combination with vagotomy and pyloroplasty in patients whose bleeding is confined to the body of the stomach. This would control bleeding by eliminating a majority of the fundus and body and have the added benefit of the acid suppression from vagotomy.

Specific techniques of partial gastrectomy are also discussed elsewhere. (See "Partial gastrectomy and gastrointestinal reconstruction".)

Subtotal or total gastrectomy — Subtotal and total gastrectomy are rarely performed now that proton pump inhibitors are in widespread use. However, in the past, a subtotal gastrectomy or even total gastrectomy was performed in dire circumstances to control bleeding. Unfortunately, patients requiring a subtotal gastrectomy had a mortality approaching 80 to 100 percent [29,32]. If performed, most surgeons would advocate for a delayed anastomosis after the gastrectomy, allowing the patient to be resuscitated out of shock before performing a definitive anastomosis 24 to 48 hours later, analogous to damage control laparotomies in trauma patients.

During gastrectomy, leaving a cuff of proximal stomach on the esophagus may be desirable because an esophageal-jejunal anastomosis is associated with a higher leak rate than a gastro-jejunal anastomosis. Before using any mechanical stapling device, the surgeon must remember to call for removal of the nasogastric tube to avoid the disastrous complication of entangling the tube by the staple line. A more detailed discussion on total gastrectomy and reconstruction is contained elsewhere. (See "Total gastrectomy and gastrointestinal reconstruction".)

Gastric devascularization — In lieu of resectional procedures, complete gastric devascularization can be performed for long-lasting hemostasis. After oversewing any visible bleeding through a gastrotomy, the left and right gastric arteries and the left and right gastroepiploic arteries are ligated. Although the stomach may initially appear ischemic following ligation, it frequently does not progress to full-thickness necrosis, given its rich collateral circulation [33]. (See 'Blood supply' above.)

POSTOPERATIVE CARE — Survival of patients with severe stress ulcers is largely dependent upon the ability to reverse the patient's underlying condition. However, if the patient survives the initial operation with successful control of bleeding, valuable time is gained for further resuscitation and correction of any organ dysfunction.

Following operative intervention, the patient is returned to the intensive care unit to continue resuscitation and medical management:

●Treatment with intravenous proton pump inhibitors is continued if any part of the stomach remains.

●Antibiotics and antifungal medications are continued.

●Normothermia needs to be maintained.

●Coagulopathy needs to be controlled.

●As noted above, the initially unstable patient may be returned to the operating room in 24 to 48 hours if hemodynamically stable for definitive procedure, anatomical restoration, and abdominal closure. (See 'Unstable patients' above.)

●Enteral feeding can commence when the patient is weaned down on vasopressors, provided that a feeding tube is placed distal to an anastomosis.

●A water-soluble contrast upper gastrointestinal series should be performed to rule out a leak in those patients undergoing gastrectomy prior to starting oral intake.

FOLLOW-UP CARE — Patients who have bleeding control by simple oversewing of the ulcerations, endoscopic therapy, or angiographic intervention only will likely require proton pump inhibitors for several months. During this period, the gastric mucosa remains friable and may take a significant amount of time to heal completely. However, those patients who also underwent vagotomy do not require antisecretory therapy, because vagotomy substantially reduces gastric acid secretion.

Long-term continuation of the proton pump inhibitor after ulcer healing is complete is controversial. Once acute shock has resolved and patients recover from their underlying illness, the nidus for stress ulceration has been removed, as has the need for long-term antisecretory therapy.

Patients who have had gastric resection and reconstruction can develop complications, including osteoporosis, iron deficiency anemia, pernicious anemia, and malnutrition. These issues are discussed elsewhere in detail. (See "Bariatric surgery: Postoperative nutritional management".)

MORBIDITY AND MORTALITY — Surgical intervention acts as a temporizing measure to halt bleeding, the most acute threat to life, and thereby allows more time to reverse the shock state. The efficacy of such interventions is therefore directly linked to the successful resolution of the underlying shock condition and control of any associated sepsis. Without resolution of the underlying disease process, any surgical intervention is destined to fail.

Thus, it is not surprising that patients who develop overt bleeding from stress ulcers continue to have a poor prognosis, with mortality rates ranging from 30 to 70 percent. Those who require surgical intervention have mortality rates in excess of 50 percent [29]. Rebleeding rates following surgical interventions vary depending on the series examined, ranging from 20 to 40 percent [29].

Surgical intervention also carries the additional risks of anastomotic leak, surgical site infections, and abdominal wall hernia.

SUMMARY AND RECOMMENDATIONS

●Etiology – Superficial stress ulcers can occur after physical trauma, shock, hemorrhage, and sepsis. They can cause major morbidity and mortality in critically ill patients because of the risk of bleeding. In addition, patients with two other forms of stress ulcers, Cushing's ulcer (following head trauma or brain surgery) and Curling's ulcer (following significant burn), are also susceptible to gastrointestinal perforations. (See 'Introduction' above.)

●Initial management – For patients diagnosed with bleeding stress ulcers, resuscitative efforts start with intravenous proton pump inhibitors, volume repletion, and correction of coagulopathy. Antibiotics are given to patients with underlying sepsis. A nasogastric tube is inserted for gastric lavage and decompression. Endoscopy or angiography can be used as first-line therapy to localize the bleeding sources and stop them if possible. (See 'Initial management' above.)

●Indications for surgery – Surgical consultation is indicated for severe bleeding causing hemodynamic instability, free gastrointestinal perforation, or refractory bleeding compromising comorbid medical conditions. (See 'Indications for surgery' above.)

●Surgical approaches – For patients with a bleeding stress ulcer, the goal of the surgery is to control bleeding. We typically make a long gastrotomy high on the anterior wall of the stomach in order to identify and oversew all bleeders. A truncal vagotomy with pyloroplasty can be added if the patient's condition permits. Gastric resection and devascularization procedures are rarely performed and are usually reserved for reoperations for stress ulcer bleeding or for patients who present with a gastric perforation. (See 'Surgical approach' above.)

●Postoperative care – After bleeding control, the abdomen can be left open to expedite the surgery and to prevent abdominal compartment syndrome in unstable patients. These patients are promptly returned to the intensive care unit for further resuscitative efforts before being brought back in 24 to 48 hours for second look, anatomical restoration, and abdominal closure. (See 'Postoperative care' above.)

●Follow-up care – Following surgical intervention, patients frequently require continued proton pump inhibitors for acid suppression and/or nutritional supplements dictated by the specific procedure they undergo. (See 'Follow-up care' above.)

●Outcomes – Patients who develop overt bleeding or perforation from stress ulcers continue to have a poor prognosis, with mortality rates ranging from 30 to 70 percent. Those who require surgical intervention have mortality rates in excess of 50 percent. Much of the morbidity and mortality are attributed to the patient's underlying disease processes. (See 'Morbidity and mortality' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges David W Mercer, MD, who contributed to earlier versions of this topic review.