Vudozuru Neither study evaluated the role of early enteral nutrition. Patient selection for minimizing the use of SUP is a very important parameter that has prophylazis discerned throughout the years. All Published work is licensed under a Creative Commons Attribution 4. May 28, ; Published date: Tolerance of enteral nutrition may be the surrogate marker for aahp perfusion as seen in the studies discussed above. Prevalence, pathology and association with adverse outcomes. Surviving Sepsis Campaign Bundles.

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Corresponding author. Stress-related mucosal disease SRMD is an acute, erosive gastritis representing conditions ranging from stress-related injury to stress ulcers 1 , 2.

Stress-related injury is superficial mucosal damage that presents primarily as erosions, whereas stress ulcers are deep, focal mucosal damage penetrating the submucosa with high risk for gastrointestinal bleeding 2 , 3. Clinically important gastrointestinal bleeding can cause hemodynamic instability and increase the need for red blood cell transfusions 1. Significant bleeding may also increase the length of stay in the ICU and mortality 1.

The guidelines do not recommend SUP in adult patients in non-ICU settings since most clinical trials discontinued prophylaxis without evidence of clinically important bleeding upon extubation or ICU discharge 5. Thus, continuation of SUP in the general medicine setting is not necessary unless patients have at least one independent risk factor increasing the risk of clinically important bleeding 6. Gastrointestinal microcirculation and the mucus layer normally maintain the integrity of the gastric mucosa by providing nourishment; eliminating hydrogen ions, oxygen radicals, and other toxic substances; and increasing bicarbonate secretion to neutralize hydrogen ions 2 , 3 , 6.

SRMD occurs when the mucosal barrier is compromised and can no longer block the detrimental effects of hydrogen ions and oxygen radicals 3. Thus, antacids, sucralfate, histamine2-receptor antagonists H2RAs , and proton pump inhibitors PPIs are utilized to prevent mucosal damage from acid produced by gastric cells or by inhibiting acid secretion 1.

The Table provides the risk factors as provided by ASHP and a literature review noting a landmark trial by Cook et al 9. Several studies based on surgical and medical ICU patients suggest that as the number of risk factors increases, the frequency of clinically important bleeding increases 5.

Specifically, two risk factors have been found to be independent predictors of clinically important bleeding—coagulopathy and mechanical ventilation 9 —while others are potential risk factors for SRMD 1 — 3. Spinal cord injuries 2. Partial hepatectomy 6. Hepatic or renal transplantation 8.

History of gastric ulceration or bleeding during year before admission 9. The choice should consider concerns regarding administration, adverse drug reactions ADRs , and total costs 6. Antacids Antacids neutralize the acidic contents of the stomach 1. Antacids require administration every 1 to 2 hours to maintain pH levels acceptable to decrease SRMD, which is labor intensive 3. Another disadvantage associated with high doses of antacids is the increase in ADRs, such as aspiration pneumonia and toxicity due to electrolyte accumulation 1.

Sucralfate Sucralfate is composed of aluminum hydroxide sulfate salts surrounding a core of sucrose molecules. Sucralfate adheres to epithelial cells to coat the gastric mucosa and creates a thin, protective layer between the mucosa and gastric acid in the stomach lumen 1 , 3.

One advantage of sucralfate is that it does not interact with other medications in the bloodstream since it is not a systemic drug. Sucralfate can be administered through a nasogastric tube but is labor intensive, as it requires dosing every 6 hours 3. Sucralfate has the potential to decrease the absorption of medications administered concurrently such as fluoroquinolones, tetracycline, ranitidine, ketoconazole, and digoxin 3.

Thus, it is recommended to administer other medications at least 2 hours apart to minimize drug interactions. Another possible disadvantage of sucralfate is that it should be avoided in patients with significant renal dysfunction due to potential aluminum accumulation and toxicity with repeated doses and prolonged use 3. H2RAs H2RAs work by inhibiting histamine-stimulated acid secretion by reversible, competitive inhibition of H2 receptors of the parietal cells 1 , 3.

Among the available H2RAs, cimetidine is the least potent, ranitidine is in the middle, and famotidine is the most potent. H2RAs can be administered orally and intravenously by intermittent bolus administration and continuous infusions. One disadvantage is a lack of potency of H2RAs, since gastrin and acetylcholine can stimulate acid secretion at different receptor sites on the parietal cells, leading to incomplete acid suppression 3.

Other disadvantages are multiple dosing requirements due to the short duration of action of H2RAs and the development of tolerance as soon as 72 hours after H2RA administration 1 , 3.

Drug interactions can occur with H2RAs due to the inhibition of cytochrome P enzymes, with cimetidine causing more drug interactions than ranitidine 3. H2RAs have to be dose adjusted in patients with renal dysfunction 1. PPIs PPIs inhibit the hydrogen-potassium-adenosinetriphosphatase enzyme at the secretory surface of the parietal cell 1. Inhibiting the final step in acid production leads to a longer duration of acid suppression than that of H2RAs 3.

Esomeprazole, omeprazole, lansoprazole, rabeprazole, and pantoprazole are available in the USA. Esomeprazole and omeprazole may interfere with the cytochrome system, whereas rabeprazole and pantoprazole have minimal significant drug interactions. Some advantages of PPIs are that they have a rapid onset of action, longer duration of action, and a lack of observed tolerance 3. Hospitalized patients may experience delirium and thrombocytopenia when receiving an H2RA 7.

The frequency of ADRs may increase in renally impaired, elderly, and malnourished patients 5 , 7. Central nervous system disturbances caused by H2RAs and electrolyte accumulation due to antacids are seen more frequently in these patient populations 5 , 6. PPIs and H2RAs have recently been associated with an increase in risk of developing community- and hospital-acquired Clostridium difficile—associated disease 10 ; the risk increases with prolonged duration of therapy 7.

A study by Kingsley et al 11 showed a higher bleeding rate in patients receiving antacids versus cimetidine, 8. A multicenter randomized controlled trial by Cook et al 12 in enrolled patients requiring mechanical ventilation for 48 hours. Patients were assigned to receive either nasogastric sucralfate 1 g every 6 hours and intravenous placebo or intravenous ranitidine 50 mg every 8 hours. Ten 1. There was no statistically significant difference between the groups in the rate of ventilator-associated pneumonia The authors concluded that approximately 48 critically ill patients undergoing mechanical ventilation need to receive prophylaxis with ranitidine rather than sucralfate to prevent one clinically important upper gastrointestinal hemorrhage.

In contrast, an earlier randomized controlled trial by Grau et al 13 in compared the efficacy of cimetidine and sucralfate in preventing gastrointestinal bleeding in the general medicine population. A total of patients with the presence of risk factors for SRMD listed in the Table were enrolled in the study; 74 patients were randomized to receive cimetidine mg by mouth at bedtime versus sucralfate 1 g by mouth every 6 hours.

Bleeding was observed in two patients 2. Levy et al 14 compared omeprazole with ranitidine in patients with risk factors for stress ulcer—related bleeding. Thirty-five patients were randomized to receive ranitidine mg bolus followed by a mg intravenous infusion every 8 hours , and 32 patients were randomized to receive omeprazole mg capsule administered orally or nasogastrically once a day. No statistically significant difference was found in the rate of nosocomial pneumonia between groups.

One major limitation of the study is that more risk factors for SRMD were present at baseline in the ranitidine group than in the omeprazole group 2. The results of this trial independently reaffirm the findings by Levy et al, and the investigators concluded that omeprazole is superior in efficacy, safety, and cost when compared with continuous infusion intravenous ranitidine.

A subsequent trial compared the efficacy of three drugs for SUP: mg daily of continuously infused ranitidine, sucralfate 1 g every 6 hours via nasogastric tube, and omeprazole 40 mg intravenously every 12 hours in patients admitted to a general ICU with at least one risk factor for stress-related gastrointestinal bleeding Gastrointestinal bleeding occurred in The incidence of nosocomial pneumonia was not statistically significantly different between the groups Mortality was also not statistically different between the three groups.

This study suggests the superiority of omeprazole compared with ranitidine and sucralfate in preventing gastrointestinal hemorrhage; however, a statistically significant difference was not found in this small, single-center trial. Eighty-seven patients were randomly selected and followed for their entire hospital admission.

Three patients experienced C. Most of the patients who experienced one of these adverse events were also on AST prior to admission. SUP in the general medicine setting has not been proven necessary by clinical trials unless the patient has at least one independent risk factor that increases the risk of clinically important bleeding. However, the data available to support these recommendations are not strong. PPIs appear to reduce overall gastrointestinal bleeding when compared to H2RAs, antacids, and sucralfate; however, there is insufficient evidence to prove they improve survival.

The use of unnecessary AST can lead to potential ADRs as well as an increase in medication costs for the patient and health care system. Health care professionals can play an important role in minimizing the inappropriate use of AST and maintaining optimal patient care by carefully scrutinizing the need for AST once a patient has left the ICU setting. References 1. Stollman N, Metz DC. Pathophysiology and prophylaxis of stress ulcer in intensive care unit patients. J Crit Care.

Spirt MJ. Stress-related mucosal disease: risk factors and prophylactic therapy. Clin Ther. Spirt MJ, Stanley S. Update on stress ulcer prophylaxis in critically ill patients. Crit Care Nurse. Stress ulcer prophylaxis in hospitalized patients not in intensive care units. Am J Health Syst Pharm. Stevens AM, Thomas Z.

The case against stress ulcer prophylaxis in Hospital Pharmacy. Magnitude and economic impact of inappropriate use of stress ulcer prophylaxis in non-ICU hospitalized patients. Am J Gastroenterol. Frequency of inappropriate continuation of acid suppressive therapy after discharge in patients who began therapy in the surgical intensive care unit.

Risk factors for gastrointestinal bleeding in critically ill patients. N Engl J Med. Centers for Disease Control and Prevention CDC Severe Clostridium difficile—associated disease in populations previously at low risk—four states, Kingsley AN. Prophylaxis for acute stress ulcers. Antacids or cimetidine. Am Surg. Prophylaxis of gastrointestinal tract bleeding in patients admitted to a general hospital ward.

Comparative study of sucralfate and cimetidine. Scand J Gastroenterol.





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Stress ulcer prophylaxis in the intensive care unit


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