1. INTRODUCTION

Stress ulcers are defined as single or multiple defects on the gastrointestinal mucosa that can lead to various clinical manifestations, scaled from mild to severe ulceration, or may cause life-threatening bleeding [1]. Clinically, the risk of stress ulcers increases in hepatized patients, particularly if the patient is admitted to intensive care settings [1]. Reports indicated that 75–100% of critically ill patients in the Intensive Care Unit (ICU) had endoscopic evidence of Stress-related Mucosal Disease (SRMD) [2]. Although such mucosal erosions may cause mild clinical manifestations owing to the rapid healing process, they should be managed to avoid the risk of bleeding [3]. Many etiological factors may be related to development of SRMD including reduction in mucosal blood flow, or interruption of normal mucosal defense mechanisms combined with the harmful effects of acid on the gastrointestinal mucosa [4]. As acid is clearly associated with the pathogenesis of these mucosal erosions, acid-suppressive medications have therefore a potential role in SRMD prevention [2,5].

In the literature, several consensus guidelines for Stress Ulcer Prophylaxis (SUP) have been documented [6–8]. According to the American Society of Health-System Pharmacists (ASHP) guidelines, SUP is not recommended in noncritically ill patients or those with fewer than two risk factors for clinically significant bleeding. Meanwhile, for ICU patients, SUP is recommended if the patient has coagulopathy; has a history of gastrointestinal ulceration; is bleeding within 1 year prior to admission; requires mechanical ventilation for more than 48 h; or has at least two of the following risk factors: more than 1 week stay in the ICU, sepsis, occult bleeding lasting 6 days or more, and high-dose corticosteroids usage [7,9]. Recently, Acid-Suppressive Therapy (AST) has been largely prescribed in hospitalized patients [10,11]. Histamine-2 Receptor Antagonists (H₂RAs) and Proton Pump Inhibitors (PPIs) are the common AST agents that have been prescribed prophylactically to prevent complications in the gastrointestinal tract [12,13]. However, inappropriate prescription and overutilization of AST agents may cause a set of risks and long-term complications including pneumonia and Clostridium difficile infection [14,15]. Several published studies have revealed that inappropriate or overused prescriptions of AST agents in the hospital setting may consequently result in substantial cost expenditures without beneficial impact on care quality [16–20].

According to the ASHP guidelines, SUP is not recommended for general medical and surgical patients in non-ICU settings with no major risk factor or fewer than two minor risk factors. However, it is observed that in Sudanese hospitals there is improper prescription and overutilization of AST agents. Hence, this study aimed to evaluate the current practice of SUP in Soba University Hospital.

2. MATERIALS AND METHODS

2.3. Inclusion and Exclusion Criteria

Records of patients admitted to the medicine unit at Soba University Hospital during the study period were included in the study. However, all records of patients diagnosed with an active gastrointestinal bleeding, active peptic, gastric ulcer, or duodenal ulcer at the time of admission or during their hospital stay, and all records of patients who received acid-suppressing therapy as treatment were excluded (Figure 1).

Figure 1

Flowchart showing recruitment of participants into the study. GI, gastrointestinal.

3. RESULTS

Overall, 22.4% of the study population (n = 317) was between 61 and 70 years old, and the mean patient age was 53 ± 16.8 years. Moreover, 170 (53.6%) of patients were females. Regarding the length of hospital stay, the median length of stay was 8 (interquartile range, 5–13) days, and 29% of the participants stayed in the hospital for 4–6 days (Table 1). The records also showed that 116 (36.6%) had cardiovascular diseases, and 60 patients were diagnosed with ischemic stroke (Table 1).

Regarding SUP regimens, the study showed that among 317 patients 314 (99%) received pantoprazole 40 mg single dose per day (OD) and only three (1%) patients received ranitidine 150 mg twice/daily which in Latin means twice a day, and there was no use of other agents for SUP (Table 2). All doses used by patients in this study were corrected according to ASHP guidelines and recommendations. The appropriateness of the administration route was determined according to the oral intake of the patients; if a patient can tolerate oral medications, then that person should take AST by oral route [7]. Thus, among 317 patients who received AST, 122 (38.5%) received medications by the oral route and 195 (61.5%) by the parenteral route. Moreover, records also showed that 315 (99.4%) patients were taking medications during hospitalization, and two (0.6%) patients were discharged with acid-suppressing therapy (Table 2).

After determination of risk factors for each patient, the SUP indication was classified as either appropriate or inappropriate according to the ASHP guidelines. Among 317 patients who received AST, 233 (73.5%) did not have an indication for SUP according to ASHP guidelines; this total included 149 (47.2%) noncritically ill patients and 84 (26.4%) patients who had one minor risk factor. By contrast, 84 (26.5%) patients had risk factors that make them appropriate for indication: 75 (23.7%) patients had one major risk factor (coagulopathy was the most frequent, at 57.5%) and nine (2.8%) patients had two minor risk factors (Table 3).

Chi-square test was used to analyze the practice pattern of SUP with each component of the AST (drug class, dose, route, and duration). There was a statistically significant association (p = 0.005) between sex and indication, in that 42.9% of patients with appropriate indications were females. Furthermore, the administration route was significantly associated with the indication’s appropriateness; in parenteral, the indication was more appropriate than the oral form (p = 0.001). Moreover, a significant association was also detected between final diagnosis and indication results (p = 0.001), in that the percentage of inappropriate indication was higher in patients with cardiovascular disease (26.8%) and infectious disease (17%).

When an independent sample t-test was performed to compare the mean age among risk factors for ulcer (critically and noncritically ill patients), we found that there was no significant association between mean age among the two groups (p = 0.259). Furthermore, the Mann–Whitney U-test showed that the mean rank of hospital stay among critically ill patients was higher compared with that of noncritically ill ones (p = 0.029). When a Chi-square test was performed to determine the association between risk factors (critically ill patients and noncritically ill patients), we found that sex, route of administration, and indication had a statistically significant association with risk factors among participants (p = 0.014, p = 0.044, and p < 0.001), respectively.

When a logistic regression test was performed to determine the predictors for patients’ risk factors, as shown in Table 4, we found that females were more likely to be critically ill than males by two times [p = 0.025; 95% Confidence Interval (CI), 1.09–3.763]. Logically, the parenteral route of administration was more likely to be used than the oral route in critically ill patients by 1.6 times (Table 4). Interestingly, patients with hepatic disease were more likely to be critically ill than patients with renal diseases by eight times [p = 0.002; odds ratio (OR) = 8.4; 95% CI, 2.220–31.650) (Table 5).

4. DISCUSSION

This study evaluated the real ulcer prophylaxis (SUP) practice in 317 patients in the medicine unit of Soba University Hospital. According to ASHP guidelines for SUP, only 26% of admitted patients received the appropriate prophylaxis, whereas 74% received inappropriate acid-suppressive medications. In effect, 47.2% of the inappropriate indications were for noncritically ill medical and surgical patients. The role of SUP in noncritically ill patients at the non-ICU setting was previously reported in an American tertiary care center, which revealed the needless use of prophylactic AST in hospitalized patients [18]. Moreover, another study reported the economic cost of such practices, indicating that they increased the cost expenditures without enhancing the quality of care [20]. Thus, our findings further support the recommendations for constructing clear risk factors in the non-ICU setting to use SUP.

Proton pump inhibitors and H₂RAs drugs are still unnecessarily prescribed and overused in hospitals to prevent stress ulcers in healthcare settings [22–25]. In the current study, 314 (99.1%) of patients received pantoprazole (PPI), whereas only three (0.9%) patients received ranitidine. These findings are in contrast to another study in which H₂RAs are the most commonly used drugs for SUP [26]. However, in recent years PPIs have become clinicians’ first choice for SUP [27], as PPIs provided clinically better outcome in preventing gastrointestinal bleeding when compared with H₂RAs without increasing the risk of pneumonia [28]. Nevertheless, use of PPIs in hospitalized patients significantly increased the risk of SUP-related C. difficile infections compared with H₂RAs [13,29]. Furthermore, Buendgens et al. [30] revealed that no differences were observed in prevention of gastrointestinal hemorrhage despite the use of PPIs or H₂RAs. Similarly, other reports found no statistically significant difference in the incidence of upper gastrointestinal bleeding between these agents [27,31].

Regarding the route of administration of AST, it was inappropriately prescribed in the majority of patients. Owing to the physician’s misconception about the superior effectiveness of parenteral dosage form, in this study 36.5% of patients who could tolerate the oral dosage form received parenteral ones. Therefore, our study also recommends using only the parenteral dosage form for patients who cannot tolerate oral drugs. Consequently, reduction of potential side effects and excessive costs will be achieved [32]. However, the mean hospital stay was 10 days, and AST agents were used throughout the hospitalization period even upon removal of risk factors. This practice is also inadequate, as ASHP guidelines recommend stopping AST medications upon removal of risk factors or discharge from the hospital [7], because long-term use of AST drugs may be associated with adverse effects and increase in cost [33].

In the assessment of duration of SUP therapy in critically ill patients, a previous report showed that 357 critically ill ICU patients received AST to treat SUP. Following transfer from ICU, 80% of these patients continued on AST. However, 60% of the therapy was inappropriate, and 24.4% was attributed to an inappropriate prescription after discharge from the hospital [34].

This study is not without limitations. Because it was conducted at a single unit in Soba University Hospital, the result cannot be generalized to all hospital units or other hospitals. Therefore, these findings need be validated by a large study across Sudanese hospitals. Missing data are another limitation in this study. Despite this limitation, however, the findings of this study are interesting and new because it is the first of its kind to be conducted in Sudan. In addition, it sheds light on the current practice of SUP in Sudanese hospitals and highlights the need for the implementation of guidelines for SUP.

5. CONCLUSION

Stress ulcer prophylaxis was administered to noncritically ill hospitalized patients who had no or few risk factors for gastrointestinal bleeding. PPIs were the overwhelming choice among practitioners. Collectively, the study showed low adherence to guidelines when prescribing AST outside the critical care setting.

CONFLICTS OF INTEREST

The authors declare they have no conflicts of interest.

AUTHORS’ CONTRIBUTION

AAE developed the design and definition of the intellectual content, performed the data collection and acquisition. SB performed the analytic calculations and performed the data analysis. AAE and SB contributed to the final version of the manuscript. BAY supervised the project, designed the study, determined the concept, prepared and edited the final manuscript.