Stress ulcer
Encyclopedia
Stress ulcers are single or multiple mucosal defects which can become complicated by upper gastrointestinal bleeding
during the physiologic stress
of serious illness. Ordinary peptic ulcers are found commonly in the gastric antrum and the duodenum
whereas stress ulcers are found commonly in fundic mucosa and can be located anywhere within the stomach
and proximal duodenum
.
Stress ulcer can be diagnosed after the initial management of gastrointestinal bleeding, the diagnosis can be confirmed by upper GI endoscopy.
Generally, there are multiple lesions located mainly in the stomach and occasionally in the duodenum. They range in depth from mere shedding of the superficial epithelium (erosion) to deeper lesions that involve the entire mucosal thickness (ulceration).
The pathogenesis of stress ulcer is unclear but probably is related to a reduction in mucosal blood flow or a breakdown in other normal mucosal defense mechanisms in conjunction with the injurious effects of acid and pepsin on the gastroduodenal mucosa.
for more than 48 hours and coagulopathy
(OR 15.6 and 4.3, respectively).
, proton pump inhibitors (PPIs), prostaglandin analogs, and nutrition
.
, patients were given an oral suspension by mouth followed by nasogastric tube and there were no episodes of bleeding or signs of toxicity. Similar results were reproduced in another study.
has not been shown to effectively decrease the incidence of stress ulcer formation. This was demonstrated in a large randomized, double-blinded, control trial of 1200 patients and compared sucralfate
to the H2-receptor blocker, ranitidine
.
and the likes. Significant side effects including diarrhea, drug interactions, lack of overall efficacy and availability of much better alternatives preclude its use in current medical practice.
Endoscopic means of treating stress ulceration may be ineffective and operation required. It is believed that shunting of blood away from the mucosa makes the mucous membrane ischaemic and more susceptible to injury.
Treatment of stress ulceration usually begins with prevention. Careful attention to respiratory status, acid-base balance, and treatment of other illnesses helps prevent the conditions under which stress ulcers occur. Patients who develop stress ulcers typically do not secrete large quantities of gastric acid; however, acid does appear to be involved in the pathogenesis of the lesions. Thus it is reasonable either to neutralize acid or to inhibit its secretion in patients at high risk.
In case of severe hemorrhagic or erosive gastritis and stress ulcers, a combination of antacids and H2-blockers may stop active bleeding and prevent re bleeding. In selected patients, either endoscopic therapy or selective infusion of vasopressin into the left gastric artery may help control the hemorrhage.
Upper gastrointestinal bleeding
Upper gastrointestinal bleeding refers to hemorrhage in the upper gastrointestinal tract. The anatomic cut-off for upper GI bleeding is the ligament of Treitz, which connects the fourth portion of the duodenum to the diaphragm near the splenic flexure of the colon.Upper GI bleeds are considered...
during the physiologic stress
Stress (biology)
Stress is a term in psychology and biology, borrowed from physics and engineering and first used in the biological context in the 1930s, which has in more recent decades become commonly used in popular parlance...
of serious illness. Ordinary peptic ulcers are found commonly in the gastric antrum and the duodenum
Duodenum
The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum...
whereas stress ulcers are found commonly in fundic mucosa and can be located anywhere within the stomach
Stomach
The stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...
and proximal duodenum
Duodenum
The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum...
.
Incidence/Significance
Stress ulcers, as defined by overt bleeding and hemodynamic instability, decreased hemoglobin, and/or need for transfusion, was seen in 1.5% of patients in the 2252 patients in the Canadian Critical Care Trials group study. Patients with stress ulcers have a longer ICU length of stay (up to 8 days) and a higher mortality (up to 4 fold) than compared to patients who do not have stress ulceration and bleeding. While the bleeding and transfusions associated with the stress ulcerations contribute to the increased mortality, the contribution of factors like hypotension, sepsis and respiratory failure to the mortality independently of the stress ulceration cannot be ignored...Risk Factors
Risk factors for stress ulcer formation that have been identified are numerous and varied. However, two landmark studies and one position paper exist that addresses the topic of risk factors for stress ulcer formation:- Non-critically ill medical patients with 2 or more of the following: respiratory failureRespiratory failureThe term respiratory failure, in medicine, is used to describe inadequate gas exchange by the respiratory system, with the result that arterial oxygen and/or carbon dioxide levels cannot be maintained within their normal ranges. A drop in blood oxygenation is known as hypoxemia; a rise in arterial...
, sepsisSepsisSepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...
, heart failure, hepatic encephalopathyHepatic encephalopathyHepatic encephalopathy is the occurrence of confusion, altered level of consciousness and coma as a result of liver failure. In the advanced stages it is called hepatic coma or coma hepaticum...
, jaundiceJaundiceJaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
, renal failureRenal failureRenal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
, strokeStrokeA stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
, hypertensionHypertensionHypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, previous gastrointestinal disease and treatment with corticosteroids, NSAIDS, heparinHeparinHeparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...
, or warfarinWarfarinWarfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
. - In surgical critically ill patients, only those patients who are on a mechanical ventilator for more than 48 hours and/or those with a coagulopathyCoagulopathyCoagulopathy is a condition in which the blood’s ability to clot is impaired. This condition can cause prolonged or excessive bleeding, which may occur spontaneously or following an injury or medical and dental procedures.The normal clotting process depends on the interplay of various proteins in...
. - The American Society of Health-System Pharmacists guideline recommends against the practice of stress ulcer prophylaxis in non-critically ill patients.
Diagnosis
Stress ulcer is suspected when there is upper gastrointestinal bleeding in the appropriate clinical setting, for example, when there is upper gastrointestinal bleeding in elderly patients in a surgical intensive care unit (ICU) with heart and lung disease, or when there is upper gastrointestinal bleeding in patients in a medical ICU who require respirators.Stress ulcer can be diagnosed after the initial management of gastrointestinal bleeding, the diagnosis can be confirmed by upper GI endoscopy.
The site of ulcerations
The ulcerations may be superficial and confined to the mucosa, in which case they are more appropriately called erosions, or they may penetrate deeper into the submucosa. The former may cause diffuse mucosal oozing of blood, whereas the latter may erode into a submucosal vessel and produce frank hemorrhage.Lesion of stress ulcers
The characteristic lesions may be multiple, superficial mucosal erosions similar to erosive gastroduodenitis. Occasionally, there may be a large acute ulcer in the duodenum (Curling’s ulcer).Generally, there are multiple lesions located mainly in the stomach and occasionally in the duodenum. They range in depth from mere shedding of the superficial epithelium (erosion) to deeper lesions that involve the entire mucosal thickness (ulceration).
Stress Ulcer formation
The pathogenic mechanisms are similar to those of erosive gastritis.”The pathogenesis of stress ulcer is unclear but probably is related to a reduction in mucosal blood flow or a breakdown in other normal mucosal defense mechanisms in conjunction with the injurious effects of acid and pepsin on the gastroduodenal mucosa.
Stress Ulcer Prophylaxis (SUP)
Prevention of this condition is far better than trying to treat it once it occurs. Significant bleeding associated with the ulcers and bleeding is associated with increased morbidity and mortality.Who should be on stress ulcer prophylaxis?
Not every patient who enters the hospital needs SUP. Cook et al. demonstrated that in surgical critically ill patients the only risk factors associated with clinically significant bleeding from stress ulcers were mechanical ventilationMechanical ventilation
In medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing. This may involve a machine called a ventilator or the breathing may be assisted by a physician, respiratory therapist or other suitable person compressing a bag or set of bellows...
for more than 48 hours and coagulopathy
Coagulopathy
Coagulopathy is a condition in which the blood’s ability to clot is impaired. This condition can cause prolonged or excessive bleeding, which may occur spontaneously or following an injury or medical and dental procedures.The normal clotting process depends on the interplay of various proteins in...
(OR 15.6 and 4.3, respectively).
Drug classes and options available
Prophylactic agents include antacids, H2-receptor blockers, sucralfateSucralfate
Sucralfate is a cytoprotective agent, an oral gastrointestinal medication primarily indicated for the treatment of active duodenal ulcers. Brand names include Sucramal in Italy; Carafate in U.S.A.; Pepsigard, Sucral, Sucrafil, Hapifate in India; Sutra or Musin in parts of South-East Asia; Sulcrate...
, proton pump inhibitors (PPIs), prostaglandin analogs, and nutrition
Nutrition
Nutrition is the provision, to cells and organisms, of the materials necessary to support life. Many common health problems can be prevented or alleviated with a healthy diet....
.
Proton pump inhibitors
PPIs are also widely used in SUP. "Data regarding the efficacy and potential adverse effects of these drugs in the prevention of stress ulceration are less extensive than for antacids, H2 blockers, or sucralfate." In one study looking at omeprazoleOmeprazole
Omeprazole is a proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease , gastroesophageal reflux disease , laryngopharyngeal reflux and Zollinger–Ellison syndrome...
, patients were given an oral suspension by mouth followed by nasogastric tube and there were no episodes of bleeding or signs of toxicity. Similar results were reproduced in another study.
H2 Receptor antagonists
In contrast, H2-receptor blockers are widely used in SUP. Most trials, but not all, have demonstrated their effectiveness in preventing stress ulcer formation.Sucralfate
SucralfateSucralfate
Sucralfate is a cytoprotective agent, an oral gastrointestinal medication primarily indicated for the treatment of active duodenal ulcers. Brand names include Sucramal in Italy; Carafate in U.S.A.; Pepsigard, Sucral, Sucrafil, Hapifate in India; Sutra or Musin in parts of South-East Asia; Sulcrate...
has not been shown to effectively decrease the incidence of stress ulcer formation. This was demonstrated in a large randomized, double-blinded, control trial of 1200 patients and compared sucralfate
Sucralfate
Sucralfate is a cytoprotective agent, an oral gastrointestinal medication primarily indicated for the treatment of active duodenal ulcers. Brand names include Sucramal in Italy; Carafate in U.S.A.; Pepsigard, Sucral, Sucrafil, Hapifate in India; Sutra or Musin in parts of South-East Asia; Sulcrate...
to the H2-receptor blocker, ranitidine
Ranitidine
Ranitidine is a histamine H2-receptor antagonist that inhibits stomach acid production. It is commonly used in treatment of peptic ulcer disease and gastroesophageal reflux disease . Ranitidine is also used alongside fexofenadine and other antihistamines for the treatment of skin conditions...
.
Prostaglandin analogues
This class includes MisoprostolMisoprostol
Misoprostol is a drug that is used for the prevention of non steroidal anti inflammatory drug induced gastric ulcers, for early abortion, to treat missed miscarriage, and to induce labor. The latter use is controversial in the United States. Misoprostol was invented and marketed by G.D...
and the likes. Significant side effects including diarrhea, drug interactions, lack of overall efficacy and availability of much better alternatives preclude its use in current medical practice.
Antacids
Antacids are not effective treatment for SUP. It is not recommended that antacids be used due to increased risk of hemorrhage and mortality.Treatment
The principles of management are the same as for the chronic ulcer. The steps of management are similar as in erosive gastritis.Endoscopic means of treating stress ulceration may be ineffective and operation required. It is believed that shunting of blood away from the mucosa makes the mucous membrane ischaemic and more susceptible to injury.
Treatment of stress ulceration usually begins with prevention. Careful attention to respiratory status, acid-base balance, and treatment of other illnesses helps prevent the conditions under which stress ulcers occur. Patients who develop stress ulcers typically do not secrete large quantities of gastric acid; however, acid does appear to be involved in the pathogenesis of the lesions. Thus it is reasonable either to neutralize acid or to inhibit its secretion in patients at high risk.
In case of severe hemorrhagic or erosive gastritis and stress ulcers, a combination of antacids and H2-blockers may stop active bleeding and prevent re bleeding. In selected patients, either endoscopic therapy or selective infusion of vasopressin into the left gastric artery may help control the hemorrhage.
Footnote
Selected Readings
- Cheung, L. Y. Pathogenesis, prophylaxis and treatment of stress gastritis. Am. J. Surg. 156:437, 1988.
- Craven, D. E., et al. Risk factors for pneumonia and fatality in patients receiving continuous mechanical ventilation. Am. Rev. Respir. Dis. 133:792, 1986.
- Driks, M. R., et al. Nosocomial pneumonia in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers. N. Engl. J. Med. 317:1376, 1987.
- DuMoulin, G. C., et al. Aspiration of gastric bacteria in antacid-treated patients: A frequent cause of postoperative colonisation of the airway. Lancet 1:242, 1982.
- Lamothe, P. H., et al. Comparative efficacy of cimetidine, famotidine, ranitidine, and Mylanta in postoperative stress ulcers: Gastric pH control and ulcer prevention in patients undergoing coronary artery bypass graft surgery. Gastroenterology 100:1515, 1991.
- Priebe, H. J., et al. Antacid versus cimetidine in preventing acute gastrointestinal bleeding: A randomized trial in 75 ill patients. N. Engl. J. Med. 302:426, 1980.
- Shuman, R. B., Schuster, D. P., and Zuckerman, G. R. Prophylactic therapy for stress ulcer bleeding: A reappraisal. Ann Intern. Med. 106:562, 1987.
- Tryba, M. Stress bleeding prophylaxis with sucralfate: Pathophysiologic basis and clinical use. Scand. J. Gastroenterol. [Suppl. 173] 25:22, 1990.