PRACTICE MANAGEMENT GUIDELINES FOR STRESS ULCER PROPHYLAXIS
EAST Practice Management Guidelines Committee
Oscar D. Guillamondegui, MD; Oliver L. Gunter, Jr., MD; John A. Bonadies, MD; Jay E. Coates, DO; Stanley J. Kurek, DO; Marc A. De Moya, MD; Ronald F. Sing, DO; Alan J. Sori MD
Chairman
Oscar D. Guillamondegui, M.D.
Vanderbilt University Medical Center
Nashville, Tennessee
oscar.guillamondegui@vanderbilt.edu
Vice-Chair
Oliver L. Gunter Jr., M.D.
Washington University, St. Louis
St. Louis, Missouri
Committee members
John A. Bonadies, M.D.
Hospital of Saint Raphael
New Haven, Connecticut
Jay E. Coates, D.O.
University of Nevada, Las Vegas
Las Vegas, Nevada
Stanley J. Kurek, D.O.
University of Tennessee
Knoxville, Tennessee
Marc A. De Moya, M.D.
Massachusetts General Hospital
Boston, Massachusetts
Ronald F. Sing, D.O.
Carolinas Medical Center
Charlotte, North Carolina
Alan J. Sori, M.D.
St. Joseph Medical Center
Patterson, New Jersey
Statement of the Problem
Stress ulcer prophylaxis has historically been a disease process with a high degree of prevalence in the setting of burns and trauma. Multiple protocols exist for prophylaxis of stress ulcer, but there are no universally accepted regiments. This has led to nationwide disorganization in current practice a stress ulcer prophylaxis. There also remains no universal determination of need for stress ulcer prophylaxis in the trauma population.
The development of clinically significant gastrointestinal hemorrhage has been associated with significant increase of morbidity and mortality. Increase of mortality may be increased as high as 50%.
Process
A MEDLINE search was performed from the years 1990 to present with the following subject words: Gastrointestinal prophylaxis, gastrointestinal hemorrhage, intensive care unit, stress ulcer prophylaxis, trauma, and critical care. All articles pertaining to the critically ill patient were reviewed by 8 trauma intensivists for adequacy and pertinence to the subject.
Quality of the references
The initial literature review identified 119 articles. Of these, 73 were removed secondary to inadequate or inappropriate data. A table of evidence was constructed using the 46 references that were identified. See table 1. (1-46)
The article was entered into a review data sheet that summarized the main conclusions of the study and identified any deficiencies. Reviewers classified each references Class I, Class II or Class III data.
The references were classified using methodology established by the Agency for Health Care Policy and Research (AHCPR) of the U. S. Department of Health and Human Services. Additional criteria and specifications were used for Class I articles from a tool described by Oxman et al. (47)
Articles were categorized as Class I, Class II or Class III data according to the following definitions:
Class I: A prospective randomized clinical trial.
Class II: A prospective non-comparative clinical study or a retrospective analysis based on reliable data.
Class III: A retrospective case series or database review.
The 46 references that met criteria were classified as follows: 27 Class I, 9 Class II, and 10 Class III.
Recommendations from the practice management guideline committee were made on the basis of studies that were included in the evidentiary table. The quality assessment instrument applied to references was that developed by the Brain Trauma Foundation and subsequently adopted by the EAST Practice Management Guidelines Committee. (48) Recommendations were categorized based on the class of data from which they were derived.
Recommendations
What are the risk factors for stress ulcer development and which patients require prophylaxis?
1. Level 1 recommendations
i. Prophylaxis is recommended for all patients with:
1. Mechanical ventilation
2. Coagulopathy
3. Traumatic brain injury
4. Major burn injury
2. Level 2 recommendations
i. Prophylaxis is recommended for all ICU patients with:
1. Multi-trauma
2. Sepsis
3. Acute renal failure
3. Level 3 recommendations
i. Prophylaxis is recommended for all ICU patients with:
1. ISS>15
2. Requirement of high-dose steroids (>250 mg hydrocortisone or equivalent per day)
ii. In selected populations, no prophylaxis is necessary
Is there a preferred agent for stress ulcer prophylaxis? If so, which?
1. Level 1 recommendations
i. There is no difference between H2 antagonists, cytoprotective agents, and some proton pump inhibitors
ii. Antacids should not be used as stress ulcer prophylaxis.
2. Level 2 recommendations
i. Aluminum containing compounds should not be used in patients on dialysis
3. Level 3 recommendations
i. Enteral feeding alone may be insufficient stress ulcer prophylaxis
ii.
i.In selected
populations, no prophylaxis is necessary
What is the duration of prophylaxis?
1. Level 1 recommendations
i. There were no level 1 recommendations
2. Level 2 recommendations
i. During mechanical ventilation or intensive care unit stay
3. Level 3 recommendations
i. Until able to tolerate enteral nutrition
Scientific Foundation
Historical
Stress ulcer prophylaxis has been an important part of the care for critical illness for over 20 years. Maynard et al. demonstrated alterations in splanchnic blood flow during acute illness. (49) The physiology of critical illness is frequently complicated with multiple systemic inflammatory abnormalities as well as alterations in hemodynamic status. Systemic hypoperfusion with associated catecholamine search, decreased cardiac output, hypovolemia, vasoconstriction, and inflammatory cytokine release is associated with splanchnic hypoperfusion. In comparison to normal patients, critically ill patients may have disturbances in their mucous and bicarbonate protective layer, owing to alterations in mucosal microcirculation. (26)
Overall, the rate of clinically important upper gastrointestinal hemorrhage is low, and is currently rarely seen as a complication of critical illness owing to several potential factors, including strict regimens of prophylaxis. Clinical importance has classically been described as obvious physiologic decline, the requirement of operative for endoscopic intervention, and transfusion requirement. Use of protective agents has historically led to at least a 50% decrease in clinically significant hemorrhage. (50)
Risk Factors
Multiple studies have identified a myriad of risk factors for the development of stress ulceration, although this has not been studied in recent years. Based on the current literature review, the most universally accepted risk factors for stress ulceration are prolonged mechanical ventilation and coagulopathy. (4, 22, 28, 30, 38) Other identified risk factors include multiple injuries, spinal cord injury, injury severity score greater than 15, acute renal failure, and requirement of high-dose steroids. (3, 6, 16, 26, 33, 34)
Timing and duration
If stress ulcer prophylaxis is to
be initiated, it should be done so that
the onset of risk factors. Based on the current literature review, it is
unclear when prophylaxis should be discontinued. Although it has been
recommended that prophylaxis be continued for at least 7 days, this has failed
to show a difference in outcomes of mortality or GI bleeding. Most studies
recommend the continuation of stress ulcer prophylaxis throughout the duration
of critical illness or intensive care unit stay. (29, 38, 41) This strategy would be individually individualized
based on patient physiology. (27, 43)
Medication Choice
There are multiple pharmacologic options for the prophylaxis of stress ulceration.
Histamine-2 receptor antagonists
As a measure efficacy, gastric pH should be greater than 4. Tolerance to these medications has been seen, requiring increased dosing based upon gastric pH measurements. (51-53) Several studies have evaluated histamine receptor antagonists in comparison to cytoprotective agents, proton pump inhibitors, placebo, and various routes and dosages of administration with mixed results.
Proton pump inhibitors
All studies have shown them to be equivocal to histamine receptor antagonists. Tolerance has not been demonstrated to these medications, however. There currently are no large studies that prove superiority of proton pump inhibitors to histamine receptor antagonists for stress ulcer prophylaxis. (2, 54) Omeprazole suspension has been shown to be effective by any enteral route, and is superior to placebo in the prevention of stress ulceration. (34, 35)
Cytoprotective agents
Sucralfate has been the best studied and the most widely used agent in this category. Its use has not been associated with an increase in stress ulceration. Sucralfate has been shown to alter intraluminal pH levels which may affect the portion of further orally administered pharmacologic agents. (24, 46) Numerous studies have shown that the impact on gastric pH is less than that associated with histamine receptor antagonists or proton pump inhibitors which may impact gastric colonization. (4, 5, 8, 9, 14, 22, 27, 38, 43) One study showed increased potential of aluminum toxicity using sucralfate in patients with renal impairment. (55)
Antacids
Use of antacids has been associated with a potential increase in the risk of hemorrhage. These agents also have been implicated in an increase in mortality, and are currently not recommended for use. (43)
Enteral feeding
Currently, there is limited data supporting the use of enteral nutrition as the sole means of stress ulcer prophylaxis. There is controversy with regard to enteral nutrition administration in the setting of hemodynamic instability requiring pressor agents. Enteral feeding also has failed to show significant increases in gastric pH. There is controversy regarding protective effects of enteral nutrition and whether it is enough to warrant discontinuation of stress ulcer prophylaxis. (8, 19, 46)
No prophylaxis
There have been some retrospective studies that have evaluated the need for prophylaxis at all. These studies have been in a mixed ICU population primarily composed of medical patients, as opposed to trauma patients alone. (12, 17, 44, 45) Adequate prospective data is lacking to warrant recommending cessation of prophylaxis.
Summary
All critically ill patients with associated risk factors should receive chemical prophylaxis for stress ulceration. All agents (with the exception of antacids) appear equally adequate for prophylaxis against stress ulceration. The agent of choice should be based upon cost-effective arrangements between vendors and individual hospitals. The duration of treatment is ill-defined, but should be maintained while risk factors are present, the patient is admitted to the intensive care unit, or for a least one week after onset of critical illness. There is currently insufficient evidence to warrant cessation of prophylaxis in the setting of enteral nutrition if other risk factors exist, or to eliminate stress ulcer prophylaxis entirely.
References
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