Continuing Education Activity

Stress ulcers is a well-known clinical entity described as stress-induced gastritis or gastropathy where the gastric and sometimes esophageal or duodenal mucosal barrier is disrupted secondary to a severe acute illness. It may present in the form of erosive gastritis ranging from asymptomatic superficial lesions, and occult gastrointestinal (GI) bleed to overt clinically significant GI bleeding. This activity reviews the cause, pathophysiology, and presentation of Curling ulcers and highlights the role of the interprofessional team in its management.

Objectives:

• Review the etiology of Curling ulcers.
• Describe the pathophysiology of Curling ulcers.
• Summarize the treatment of Curling ulcers.
• Outline modalities to improve care coordination among interprofessional team members in order to improve outcomes for patients affected by Curling ulcers.

Introduction

Stress ulcers are stress-induced gastritis or gastropathy where the gastric and sometimes esophageal or duodenal mucosal barrier is disrupted secondary to a severe acute illness. It may present in the form of erosive gastritis ranging from asymptomatic superficial lesions, and occult gastrointestinal (GI) bleed to overt clinically significant GI bleeding. The stress ulcers secondary to systemic burns are known as Curling ulcer, stress ulcers in patients with acute traumatic brain injury are known as Cushing ulcer. The gastric body and fundus are common locations for stress ulcerations but can also be seen in antrum and duodenum.[1][2]

Etiology

The major risk factors for the development of stress ulcerations include:

• Mechanical ventilation for more than 48 hours
• Abnormal coagulation profile such as platelet count less than 50,000, INR greater than 1.5 and PTT greater than 2 times the control value
• Sepsis or septic shock
• Use of vasopressors
• Use of high dose systemic corticosteroids (more than 250 mg  or the equivalent of hydrocortisone per day)
• Hepatic failure
• Renal failure
• Multiorgan failure
• Burns of more than 30% of body surface area
• Head trauma
• Lack of sanitation during intensive care unit (ICU) stay
• History of GI bleeds within a year[3][4][5]

Epidemiology

The incidence of stress ulcer is not well known but is thought to almost always occur in severe acute illness. The most common presentation of stress ulceration is in the form of upper GI bleeding, and GI bleed secondary to stress ulcerations may range from 1.5% to 15% depending on whether or not patients received stress ulcer prophylaxis. The incidence of stress ulceration and its complications are known to be declining with the advent of active prophylaxis methods for the prevention of stress-related gastritis. Patients with GI bleeding secondary to stress ulceration have increased morbidity and mortality compared to those who do not have GI bleed. Hence stress ulcer prophylaxis has been the center of many randomized clinical trials. Very rarely (less than 1% of the times), stress ulcers can cause perforation and perforation related complications.[2]

Pathophysiology

Stress ulceration results from damage to the mucosal barrier secondary to systemic stress resulting in multiple superficial erosions of the gastric mucosa. The possible pathological changes leading to ulceration can be an impaired mucosal barrier where the mucosal glycoprotein is denuded by increased concentrations of refluxed bile salts or uremic toxins due to a critical illness. Increased secretion of gastric acid in response to higher secretion of gastrin hormone in patients is also thought to be responsible for stress ulceration. However, this is more commonly seen in patients with acute neurological trauma than other stress-related diseases. Helicobacter pylori infection has also been associated with stress ulcers though the evidence is limited. There could be a subgroup of critical care patients who may present with overt GI bleeding without stress ulceration or stress-related mucosal damage (SRMD), such as a patient with variceal bleeds, vascular anomalies, or diverticulosis. Hence these GI bleeds may not respond adequately to stress ulcer prophylaxis (SUP) or antireflux therapy with proton pump inhibitors (PPI) or antihistaminic.[6]

Patients with acute respiratory distress syndrome (ARDS) who receive positive pressure ventilation (PPV) for more than 3 days are especially susceptible to mucosal damage due to splanchnic hypo-perfusion, which is more pronounced at positive end-expiratory pressure (PEEP) levels of 15-20 cm of water (H2O).[7][8]

Histopathology

Ulcers are covered with slough and inflammatory debris. Sometimes hemorrhagic spots are seen. These are usually less than one centimeter with a brown circular base due to digested blood in it. Beneath the ulcer base, there is neutrophilic infiltration and active granulation with mononuclear infiltration. Fibrinoid necrosis may also be found. In chronic forms, lymphocytes, monocytes, and plasma cells are seen to infiltrate the mucosa and submucosa.

History and Physical

The most common mode of presentation of stress ulcers is the onset of acute upper GI bleed like hematemesis or melena in a patient with an acute critical illness. The patient may or may not have hemodynamic instability in the presence of bleeding, and most of these patients do have a drop in hemoglobin concentration requiring blood transfusions. The clinician should maintain a high index of suspicion in those patients who are in intensive care settings and are noted to have decreased hematocrit. The following signs and symptoms are present in typical cases.

• Coffee ground vomitus
• Hematemesis
• Melena
• Abdominal pain
• Nausea
• Orthostasis in severe cases

Evaluation

Before the diagnostic evaluation for stress ulceration, the stabilization of the patients should take priority. Monitor the need for fluid resuscitation and blood transfusion and reversal of coagulopathy if needed. Gastric lavage can be used to confirm whether blood is present in the upper gastrointestinal tract or not. It also helps to quantify the amount of blood if found. Esophagogastroduodenoscopy should be performed. Stress ulcers are seen as small superficial mucosal erosions or ulcerations in the gastric body and fundus. Testing for H. pylori infection like urease breath test or stool antigen test can also be undertaken for refractory stress ulceration.

Treatment / Management

Management of stress-induced gastritis includes prompt identification and prevention of complications related to stress ulceration. The management can be divided into pharmacological and non-pharmacological interventions.

The nonpharmacological interventions include early enteral feeding, NG tube placement intravenous fluid resuscitation, blood transfusion, and reversal of coagulopathy by platelets transfusion or transfusion of fresh frozen plasma or cryoprecipitate.[9][10]

The medical management of patients with stress ulcers is more or less similar to the management of peptic ulcer disease in general. The medication targeting acid peptic disease includes proton pump inhibitors, antihistaminic, and ulcer-healing drugs like sucralfate. Patients with overt GI bleeding from ulceration will require endoscopic evaluation and management of the stress ulcers. Endoscopic therapies may include epinephrine injection, electro-cauterization, or clipping of the bleeding vessels. Bleeding ulcers refractory to localized endoscopic treatment may need embolization of the culprit vessel or rarely surgical intervention as a last resort. Surgical interventions are commonly indicated for patients with refractory bleeding despite endoscopic or angiographic treatment or patients with unstable hemodynamics to undergo endoscopic or angiographic procedures. Surgeries are performed as an ultimate life-saving approach.[11] 

Sometimes the ulcers can be deep enough to cause perforation of the gastric wall leading to acute peritonitis requiring urgent laparotomy. In comparison to other forms of stress ulcerations, perforations are most likely to happen with Cushing and Curling ulcers as they tend to be deep and can cause extensive necrosis. Mortality without surgical intervention in these patients who develop free wall GI perforation is almost 100%.[6][12]

Differential Diagnosis

The following should also be considered in the differential diagnosis:

• Peptic ulcer disease
• Nonsteroidal anti-inflammatory drug (NSAID)–induced gastritis
• Alcoholic gastropathy
• Gastroesophageal reflux disease (GERD)
• Gastric or esophageal cancer
• Gastroparesis
• Pancreatic cancer
• Biliary pain
• Uremic gastropathy
• Dyspepsia

Pertinent Studies and Ongoing Trials

Proton pump inhibitors (PPIs) have traditionally been considered superior to histamine receptor-2 (H2) blockers for the prevention of stress ulceration in critically ill patients at risk. Recent studies have raised the concern of increased mortality in patients who receive PPIs for stress-ulcer prophylaxis. Large trials directly comparing the agents for stress ulcer prophylaxis are lacking, and further studies are needed to determine whether PPIs are harmful.

Staging

Forrest classification is used to stage gastric ulcers, which is largely based on endoscopic findings. 

Acute Hemorrhage

• Forrest Ia      Active spurter
• Forrest Ib      Active oozing

Signs of recent hemorrhage

• Forrest IIa     Non-bleeding visible vessel
• Forrest IIb     Adherent clot
• Forrest IIc     Flat pigmented haematin on ulcer base

Lesions without active bleeding

• Forrest III     Lesions without active bleeding

Prognosis

Patients with stress ulceration usually have poor prognosis secondary to the underlying critical illness. Moreover, GI bleeds in these patients secondary to stress-related mucosal disease is independently associated with increased morbidity and mortality.  More often, these patients are too unstable for advanced endoscopic or surgical procedures to suppress GI bleed, leading to worse outcomes. Hence, aggressive prophylactic measures for the appropriate patient population at risk of developing stress ulceration remains the cornerstone in the management of stress-induced gastropathy.[13][14]

Complications

Stress ulceration can be associated with the following complications:

• Bleeding
• Anemia
• Strictures
• Perforation
• Peritonitis
• Gastrocolic fistula
• Gastric outlet obstruction due to strictures
• Hemorrhagic shock
• Increased length of ICU stay
• Death

Consultations

Patients with stress ulceration are usually managed in intensive care units. Gastroenterology service should be consulted if there are any signs or symptoms related to ulcer development. Neurosurgery and general surgery teams should be consulted if stress ulceration arises in the setting of head injury or buns, respectively. Interprofessional teamwork improves mortality and morbidity outcomes in the setting of stress ulceration. 

Deterrence and Patient Education

Stress ulcers are sores in the digestive tract that can cause stomach upset, and that can lead to bleeding. Symptoms include upper abdominal pain, nausea, vomiting, or blood in the stool. In stressful situations, there is excess acid in the system, and the protective layer of mucus on the lining is broken down, which makes it more susceptible to damage. Prophylactic treatment in intensive care units leads to the decreased recurrence of stress ulcers. Healthcare providers are the best source of information for concerns related to stress ulcer formation. 

Pearls and Other Issues

Stress ulcer prophylaxis (SUP) has been a center of debate for various national and international societies of critical care. SUP has shown to be of benefit in preventing GI bleeding related to stress ulceration, but the guidelines regarding the indications, drug selection, and duration of SUP are not clear.[15]

Surviving sepsis campaign recommends SUP for patients on mechanical ventilation for more than 48 hours and patients with coagulopathy. The other indications for SUP include sepsis and septic shock, severe burn injuries, use of high dose steroids, and neurological trauma. Surviving sepsis campaign recommends the use of PPI over antihistamines for SUP. Even though multiple studies have challenged the superiority of one over the other, PPIs are the most common agents used in the ICU and burn unit as SUP. Sucralfate an ulcer-healing drug can also be used for SUP, it is shown to be less effective than PPI ad histamine blockers but safer regarding adverse reactions. Cytoprotective agents like prostaglandin analogs (misoprostol) can also be used for SUP. They not only suppress acid secretion via a cyclic AMP pathway but also enhance the mucosal barrier of the gastric epithelium. However, they are still under investigation and lack adequate evidence for use in SUP. The adverse effects of the frequent use of PPIs in this population, including but not limited to, Clostridium difficile-associated diarrhea, pneumonia, and adverse drug interactions.[16][8]

The duration of stress ulcer prophylaxis is usually for the period of critical illness or the duration of mechanical ventilation, and sometimes it can be continued until the patient begins to tolerate the oral diet.[17]

Enhancing Healthcare Team Outcomes

The major part of the management of stress ulcers is its prevention in the critical care population with high-risk factors as the outcomes associated with stress-induced gastritis, and the GI bleed is worse but preventable. An interprofessional team consisting of the critical care nurse and critical care specialist physician working towards minimizing the risk will provide the best patient outcomes. Pharmacists evaluate medications use for prophylaxis and check for drug-drug interactions. Nursing staff monitor patients and update the team when the patient status changes.[Level 5]