Stress ulceration

BASIC Instructor & Provider Course, October 2008, Sydney. Registration deadline 27th September.
Click here for details

Gavin Joynt

Prevention and management of stress ulcers in the ICU

Keypoints

• Prevention of overt and clinically important bleeding in ICU patients can be achieved with H2 receptor antagonists

• Patients who are not mechanically ventilated, are not coagulopathic, are enterally fed and have no major organ failure may not require prophylaxis

• Proton pump inhibitors are currently reserved for treatment of bleeding or prevention of rebleeding

Introduction

• Mucosal erosions, which may sometimes extend deeper into the submucosa, of the upper gastrointestinal tract. Usually multiple.

• Commonly found in the fundus or acid secreting parts of the stomach. 

• Associated experimentally with different types of stress

  • Cold

  • Starvation

  • Haemorrhage/hypotension

  • Burns

  • Increased acidity

  • Endotoxin

  • CNS induced stress

Pathophysiology

The upper GIT is a digestive organ. In particular, H⁺ ions play a central role in the digestion of proteins, both by a direct action and by facilitating the role of Pepsin. H⁺ ions are secreted by parietal cells in the gastric mucosa as a result of stimulation of acetylcholine, gastrin and histamine receptors (Fig 1). Autodigestion is prevented by a series of defense mechanisms. These include the production of a mucous gel layer by mucous secreting cells in the gastric mucosa, secretion of bicarbonate ions into the gel and maintenance of an “unstirred” relatively pH neutral layer of protection for gastric mucosal cells. Mucosal cells are rapidly replaced in the crypts by proliferation and migrate to damaged surfaces by the process of restitution. Prostaglandins play an important role in maintaining these defenses. Good regional blood supply and perfusion is needed to support the intense metabolic activity required to maintain these processes.

Fig 1.

Gastric mucosal circulation

• Disproportionate vasoconstrictor response to stress/shock

  • Neural nor-adrenaline and circulationg adrenaline have similar effects on vasoconstriction in gastric mucosal and systemic vascular beds

  • Renin-angiotensin system and to a lesser degree vasopressin are responsible for the disproportionate response.

    • Angiotensin II receptors in this region have a 5 fold affinity compared with other systemic vascular beds.

    • Ablation of the renin-angiotensin system in animals prevents disproportionate response

Animal studies demonstrate that the severity of stress ulceration is associated with the degree of stress induced decrease in gastric blood flow. Prevention of decreases in gastric blood flow with agents such as NO donors can protect experimental animals from stress ulceration.

Role of gastric acid and mucosal injury

• In animals exposed to ischaemia-reperfusion ranitidine and omeprazole decrease gastric erosion size and number and there is less progression to deeper ulceration. Addition of HCl restores progression.

Interventions to reduce & treat stress ulceration

Based on pathophysiology, the following preventive measures and treatments are used clinically.

• General measures

  • Maintenance of haemodynamic stability

  • Systemic and/or regional stability of perfusion pressure and flow.

  • Good sedation, analgesia, communication

• Medical therapies

  • Suppression of gastric acid secretion

    • Antacids

    • H2-receptor antagonists. Proven to be effective in reducing overt and clinically important bleeding.

    • Proton pump inhibitors. Indicated for the treatment of bleeding or the prevention of re-bleeding

  • Cyto-protective and promotion agents

    • Sucralfate

    • Prostaglandins (few studies suggest benefit but rarely used in clinical practice

Clinical questions

Can preventive medical therapies decrease morbidity and mortality from stress ulcers?

• Evidence suggests that bleeding, but not mortality can be reduced.

What are the best medical preventive therapies?

• Evidence suggests that H2 receptor antagonists are most efficient in reducing overt and clinically important bleeding in ICU patients, and do NOT increase the risk of nosocomial pneumonia when compared with sucralfate. Mortality is not changed by any agent.

• Proton pump inhibitors

  • more efficient at maintaining an alkaline gastric luminal environment than H2 receptor antagonists

  • may also have beneficial effects on gastric mucosal blood flow and demonstrate anti-oxident effects

  • Despite being the agent of choice to decrease rebleeding after ulcer haemorrhage there is still no good evidence to support routine use (instead of H2 antagonists) for stress ulcer prophylaxis

Does every ICU patient require preventive therapy?

• Incidence of stress ulceration is low and decreasing with time and routinely using prophylaxis in all patients is probably not cost effective.

  • Overt bleeding rate

    • 25% in 1980s

    • 5% in 1990s

  • Clinically important bleeding

    • Current rate probably 0.6-3%

• Direct mortality from stress ulcer bleeding is probably very low (< 0.1%)

Which patients need stress ulcer prophylaxis?

• Evidence suggests that patients who are not mechanically ventilated, are not coagulopathic, are enterally fed and have no major organ failure probably do not require prophylaxis

Treatment for bleeding stress ulcer

• Overt bleeding requires investigation by endoscopy

• Endoscopy (with or without intervention is the current accepted standard)

  • Use of heat probe or adrenaline injection may control bleeding

Prevention of rebleeding

• Treat coagulopathy

• Gastric acid suppression

Gastric acid suppression and rebleeding

• Maintain pH >6 for at least 3 to 4 days in patients with acute GI bleed. At this pH the effects of acid on platelet function and clot digestion are minimized

• Proton pump inhibitors (eg omeprazole) reduce recurrence of acute bleeding in high risk ulcers and re-bleeding rate following successful endoscopically treated ulcers. However no mortality advantage. A similar strategy is probably useful for stress ulcers

• Half-life of PPIs is short and proton pumps are continuously being synthesized

• Inactivate the actively secreting pumps with a bolus dose

• Then prevent pH lowering by newly synthesized pumps with a continuous infusion

• dose of omeprazole or pantoprazole is 80 mg intravenous bolus followed by continuous infusion of 8 mg/h

• H2 receptor antagonists are unable to consistently achieve gastric pH >6 and tachyphylaxis occurs after 24 h. There is no good evidence that they decrease the rebleeding rate. 

Salvage therapy

• if bleeding can’t be controlled: surgery – gastrectomy etc.

©Gavin Joynt, September 2003

©Charles Gomersall, September, 2008 unless otherwise stated. The author, editor and The Chinese University of Hong Kong take no responsibility for any adverse event resulting from the use of this webpage.
Copyright policy    Contributors