Stress ulcer prophylaxis (SUP) is generally given to critically ill patients and treated in the intensive care unit (ICU)1. Appropriate use of SUP is defined when proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are administered to patients with at least one risk factor (coagulopathy, mechanical ventilation ≥48 hours, and gastrointestinal bleeding or ulceration within a year) before hospitalization) or with some minor risk factors (sepsis, multiple organ failure, liver failure, renal insufficiency, inpatient ICU ≥7 days, hypotension or shock, organ transplant, multiple trauma, burns of more than 25-30% of body surface area, major surgery, hidden gastrointestinal bleeding ≥6 days, and use of anticoagulants, corticosteroids, or nonsteroidal anti-inflammatory drugs (NSAIDs))2. The American Society of Health-System (ASHP) in 1999 published guidelines for the use of SUP in medical, surgical, respiratory and pediatric patients in the ICU3. Research related to inappropriate prescribing of acid-suppressing therapy due to a low-risk factor for bleeding in the use of SUP based on the stress ulcer-related gastrointestinal bleeding (SURGIB) criteria was developed by Herzig et al.4 of 88.5% and an estimated cost savings of inpatient medication hospitalization of $114,622 (approximately Rp. 1,396,095,960) in the 253 studied patients5.

Long-term use of acid-suppressing therapy is of particular concern as complications (Clostridium difficile: diarrhea, osteoporosis, and pneumonia) are associated, mainly when PPIs are used for long durations at high doses6. Several studies7,8 reported that C. difficile infection increased three times from prolonged use of SUP. If SUP is not used based on the indications of the disease in the patient, it will lead to unexpected side effects such as diarrhea due to C. difficile, the incidence of pneumonia, and increased unnecessary costs9. Therefore, evaluating SUP can be an evaluation for health workers in providing therapy to patients and obtaining optimal therapeutic effectiveness. The researcher is interested in conducting a study regarding the utilization of SUP in patients hospitalized in the internal medicine ward of Sleman Regional Public Hospital due to the completeness of medical record documentation reaching 85% out of 100% based on the patient safety and quality improvement program.

Materials

The research instruments included medical records of patients hospitalized in the internal medicine ward of Sleman Regional Public Hospital, Special Region of Yogyakarta, Indonesia, in 2020. ASHP Therapeutic Guidelines on Stress Ulcer Prophylaxis 19993 and Stress Ulcer Prophylaxis Clinical Guidelines from Stanford Hospital and Clinics 201510 were used as therapeutic references. Sample recording was adjusted according to the inclusion criteria such as gender, patient age, length of hospitalization, drug name, drug class, drug dose, rules of use, and duration of drug use. This research has obtained research ethics approval from the Health Research Ethics Committee, Sleman Regional Public Hospital with number 180/4126.

Methods

Research design and participants

The study took medical record data of inpatients at the Sleman Regional Public Hospital and the costs of using SUP from January to December 2020. Patient characteristics and therapy data were obtained from medical records, while therapy costs were obtained from the hospital's finance department. The sample in this study was all inpatients in the internal medicine ward who used SUP and met the inclusion criteria at the Sleman Regional Public Hospital for January to December 2020. The inclusion criteria were that patients hospitalized in the internal medicine ward were given SUP during treatment with data, and the medical records were complete and legible. The exclusion criteria were patients who entered and experienced bleeding in the gastrointestinal tract, which was marked by the occurrence of hematemesis, melena, and blackish-red NG fluid; Patients with a diagnosis of gastrointestinal disorders; and a history of peptic ulcers or gastrointestinal bleeding within one year before admission.

Sample size calculation

The sample was calculated using the proportion estimation formula as shown in Equation 1, taking the following assumptions: the proportion of appropriate use of SUP = 0.5, a margin of error = 5%, and a 95% confidence interval11. The correction formula was used since the population was less than 10,000 (total patient population in a year (N) = 3000), which could represent the study sample. The corrected number of samples was then calculated, as shown in Equation 2. Then, 340 samples were selected with a random sampling technique.

[1]

[2]

Criteria establishment

Based on published evidence-based guidelines and previous literature on SUP clinical practices, we established the criteria to evaluate the appropriateness of SUP medication. Stress ulcer prophylaxis medication was considered appropriate if an inpatient in the internal medicine department had one major or at least two minor risk factors3,10 in Table I.

TableI. Risk factor for stress ulcer.

Outcome measurement

Our primary outcome variable was the appropriateness evaluation of SUP prescribing patterns for inpatients in the Internal Medicine Department and the cost of using SUP, both the total cost and average cost per patient of appropriate and inappropriate indicated prophylactic use.

Data analysis

Data analysis in this study was in the form of descriptive analysis to describe the characteristics of patients based on gender, age, length of hospitalization, and risk factors to determine the profile of SUP used by inpatients in the internal medicine ward of Sleman Regional Public Hospital based on the class of drugs used, to determine the accuracy and inaccuracy of the indications for the use of SUP for inpatients in the internal medicine ward, as well as identifying the costs calculated by multiplying the total number of appropriate and inappropriate therapeutic doses given during hospitalization with the price of the drug used.

Based on the data obtained from 340 samples in Table II, there are more male (55%) than female patients (45%). Patient characteristics by gender are dominated by males, with a higher prevalence of male smokers (62.9%). Based on Indonesian Basic Health Research 2018 (Riset Kesehatan Dasar, Riskesdas)12, regularly consuming coffee could increase the risk of stress ulcers. Coffee containing caffeine can stimulate the hormone gastrin, which stimulates and accelerates the production of stomach acid, resulting in gastric ulceration13. In addition, regularly drinking coffee can increase the risk of 3.57 times experiencing gastritis. If left untreated, it will worsen, and the stomach acid can cause ulcers14.

Inpatients in the internal medicine ward who receive SUP are given at >65 years old who have entered older people. The increasing age can cause a decrease in gastric mucosal function, reduced secretory function, and loss of nutritional factors in the gastric mucosa, so the stomach is prone to bleeding15. Age does not affect the incidence of stress ulcers as it is not included as a risk factor for gastrointestinal bleeding. However, a study revealed that older age becomes one factor in the administration of excessive gastric acid-suppressing drugs9.

Furthermore, the maximum length of hospitalization was <7 days with a percentage of 93.24% and >7 days with a percentage of 6.76%. Farsaei et al.9 explained that patients who required longer hospitalization and more medical services could unconsciously encourage doctors to provide SUP, preventing more gastrointestinal bleeding complications. Elderly patients and longer hospitalization were shown to be significant overuse predictors of SUP. In addition, Issa et al.16 have similarly identified factors contributing to the overuse of SUP. They revealed that the length of hospitalization is one of the factors in which SUP is frequently used.

In this study, the major risk factor was the incidence of coagulopathy (12.35%), in which most patients were dengue fever patients. Therefore, according to Huang et al.17, it is necessary to give anti-ulcer to prevent stress ulcers. Meanwhile, the minor risk factor is the use of antiplatelets (10.59%), which can inhibit the production of prostaglandins by the gastric mucosa associated with gastric epithelial damage18. Our previous study19 revealed that there were 52 patients receiving antiplatelets, where the use of antiplatelets significantly affected the incidence of bleeding.

TableII. Patients characteristics.

The profile of SUP in inpatients in the internal medicine ward at the Sleman Regional Public Hospital in 2020 was primarily the PPIs group of 45.8% (Table III). Acid suppressive therapy (AST), including PPIs and H2RAs as SUP, is one of the most common medical practices in inpatients5. The PPIs are more potent in increasing gastric pH than H2RAs and maintain gastric pH between 3.5 and 5.0, which can minimize the risk of gastric mucosal injury. Of the four meta-analyses comparing PPIs with H2RAs, three suggested that PPIs are superior to H2RAs20.

TableIII. Stress ulcer prophylaxis use profile.

Evaluation of the use of SUP revealed that patients prescribed acid-suppressing drugs were 40 patients or 11.76%. One indication had a major risk factor; 17 patients, or 5%, had at least two or more indications of a minor risk factor as SUP, and 283 patients, or 83.24%, received acid-suppressing drugs without appropriate indications (Table IV). This is similar to several studies conducted abroad regarding the high prescription of gastric acid suppressant drugs that are not appropriate to treatment guidelines5,21-23. In recent years, SUP has become commonplace in patients with general treatment and little or no supporting evidence24. Inappropriate use of indications for SUP can increase the incidence of unexpected drug reactions, drug interactions, problems in polypharmacy, and unnecessary drug costs25.

TableIV. The use of SUP.

A cost analysis was performed to assess the economic impact of SUP during therapy without incorrect indications. The cost of prophylaxis is calculated based on the total oral administration or injection of acid-suppressing drugs given during hospitalization, looking at the smallest unit of drug price from the hospital. The biggest expenditure on SUP was the inappropriate of the drug, which was Rp. 19,933,582 (Table V). It indicated that the hospital could save on that cost if the drug is not used Rp. 19,933,582. Moreover, there were limitations in identifying the patient's direct costs, so the cost calculation is only from the drug's price.

TableV. Drug expenses for the use of SUP.

Researchers have not been able to explain the factors that influence the high prevalence of inappropriate prescribing, but there is a similar study that observed the factors that influence the inappropriate prescribing of prophylactic stress ulcers; a study stated that the reasons why clinicians prescribed SUP inappropriately were multifactorial. First, the fear of the development of SUP in non-ICU patients who were not on SUP therapy. Second, Due to the tense relationship between doctors and patients in China, doctors had to prescribe SUP therapy for low-risk inpatients to protect themselves from litigation. Third, the incidence of an adverse reaction related to acid suppression medicines has not been high. For this reason, doctors have believed PPIs to be safe26. One study27 reported that several adverse effects (specified in C. difficile infections, respiratory infections, hypomagnesemia, adverse skeletal muscle effects, and psychiatric symptoms) after reducing inappropriate proton pump inhibitor use for SUP decreased significantly (35% control group versus 8% intervention group)28. The inappropriate use of SUP therapy can also have economic implications for patients and the healthcare system.

Associated with those factors, the researcher indicated that clinicians needed to provide more information about the rationality and efficiency of their prescribing practices. Clinical pharmacists should execute effective intervention strategies to reduce improper SUP medication. The ASHP Therapeutic Guidelines on Stress Ulcer Prophylaxis 19993 and Stress Ulcer Prophylaxis Clinical Guidelines from Stanford Hospital and Clinics 201510 can be implemented in clinical practice to prevent unnecessary acid-suppressing therapy in patients due to the low risk of stress ulcer bleeding. Computerized ordering systems can reduce unnecessary use of acid suppression therapy, lower patient prescribing costs, and limit side effects25,28.

The profile of the use of SUP drugs in patients hospitalized in the internal medicine ward at Sleman Regional Public Hospital in 2020 included PPIs of 45.8%, H2RAs of 42.6%, sucralfate of 7.4%, and antacid of 4.2%. The use of SUP in the patients described 57 patients (16.8%) with correct indications and 283 patients (83.2%) with incorrect indications. Expenditure on the use of SUP drugs in a correct indication was Rp 6,240,384 with an average of Rp 109,480 for 57 patients and Rp 19,933,582 for an incorrect indication with an average of Rp 70,436 for 283 patients.

We want to thank the Research and Innovation Institute (LRI) Universitas Muhammadiyah Yogyakarta for providing support in completing this research. We greatly appreciate all participants in the study. This manuscript has been presented at the 3rd International Conference on Pharmaceutical Updates (ICPU 2022), Universitas Muhammadiyah Yogyakarta, Indonesia, 20-21 July 2022.

Conceptualization: Mega Octavia, Nurul Maziyyah

Data curation: Rima Nurul Fauziyah

Formal analysis: Mega Octavia, Nurul Maziyyah, Rima Nurul Fauziyah

Funding acquisition: -

Investigation: Rima Nurul Fauziyah

Methodology: Mega Octavia, Nurul Maziyyah

Project administration: Mega Octavia, Nurul Maziyyah

Resources: Mega Octavia, Nurul Maziyyah

Software: -

Supervision: Mega Octavia, Nurul Maziyyah, Rima Nurul Fauziyah

Validation: Mega Octavia, Nurul Maziyyah

Visualization: -

Writing - original draft: Rima Nurul Fauziyah

Writing - review & editing: Mega Octavia, Nurul Maziyyah

None.

The authors declare there is no conflict of interest.

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