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 Table of Contents  
Year : 2018  |  Volume : 4  |  Issue : 2  |  Page : 105-111

Stress ulcer prophylaxis upon discharge from intensive care units in an academic medical center

1 The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
2 The Ohio State University Wexner Medical Center; Department of Pharmacy, The Ohio State University, Columbus, Ohio, USA

Date of Submission27-Jun-2017
Date of Acceptance01-Oct-2017
Date of Web Publication30-Aug-2018

Correspondence Address:
Dr. Anthony T Gerlach
The Ohio State University Wexner Medical Center, 368 Doan Hall, 410 West Tenth Avenue, Columbus, Ohio 43210
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJAM.IJAM_64_17

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Context: Stress ulcer prophylaxis (SUP) has become the standard of care in the intensive care unit (ICU) but is often continued inappropriately at discharge.
Aims: The primary aim was to evaluate the impact of granting clinical privileges to assess appropriate discontinuation of SUP in the ICU.
Settings and Design: This study was a single-center, retrospective, observational study.
Materials and Methods: Patients admitted to medical or surgical ICUs in January 2015 (pregroup) were compared to January 2016 (postgroup).
Statistical Analysis Used: Continuous parametric data were analyzed with Student's t-test, continuous nonparametric data were analyzed with Mann–Whitney U-test, and dichotomous variables were analyzed with Fisher's exact method.
Results: One hundred and sixty patients were included (80 per group). Over 50% of patients had documented home acid suppression therapy use (52.5% pregroup vs. 58.8% postgroup, P = 0.53) and approximately 30% had gastroesophageal reflux disease documented as a problem in their medical record (27.5% pregroup vs. 31.3% postgroup, P = 0.73). The rate of inappropriate continuation of acid suppression therapy was not different between groups (15.4% vs. 14.9%, P = 0.999). The major reason for appropriate continuation of acid suppressive therapy was the presence of a chronic condition that provided a reasonable indication for therapy (46.1% vs. 60.0%, P = 0.228).
Conclusions: Overall we found no difference in continuation of SUP at ICU discharge, but this was confounded by a high rate of reported home acid suppression. Targets for education and improvement have been identified, especially the need for attention to documentation and medication reconciliation across the spectrum of patient care to allow for acid suppression therapy deprescribing.
The following core competencies are addressed in this article: Patient care, Systems-based practice

Keywords: Intensive care unit, pharmacist credentialing and privileging, stress ulcer prophylaxis

How to cite this article:
Liput SA, Ryder LP, Jordan TA, Gerlach AT. Stress ulcer prophylaxis upon discharge from intensive care units in an academic medical center. Int J Acad Med 2018;4:105-11

How to cite this URL:
Liput SA, Ryder LP, Jordan TA, Gerlach AT. Stress ulcer prophylaxis upon discharge from intensive care units in an academic medical center. Int J Acad Med [serial online] 2018 [cited 2022 Aug 17];4:105-11. Available from: https://www.ijam-web.org/text.asp?2018/4/2/105/240141

  Introduction Top

Prevention of stress-related mucosal damage and gastrointestinal (GI) bleeding in the intensive care unit (ICU) with histamine 2 receptor antagonists (H2RAs) or proton pump inhibitors (PPI) is the standard of care.[1] However, it has been demonstrated that the main risk factors for bleeding from stress ulceration are mechanical ventilation for a minimum of 48 h and coagulopathy, with the greatest risk being when both of these are present simultaneously.[1],[2] While it is appropriate to initiate acid suppression in the ICU when a risk factor is present, it is estimated that between 25%–40% of patients are discharged on one of these agents despite a lack of indication for ongoing use.[1],[3]

Although acid suppression medications have generally been considered safe, recently many adverse effects have been linked to chronic acid suppression. Increased risk of bacterial overgrowth, Clostridium difficile infection, and pneumonia are among the most well-documented concerns that have recently arisen in association with prolonged acid suppression therapy.[1],[4],[5] Recently, even more serious negative outcomes including osteoporosis, stroke, and myocardial infarction have been attributed to acid suppression therapy, especially with PPI utilization.[6],[7],[8] It must also be considered that these medications are associated with increased patient costs when continued upon discharge of the hospital.[1],[9]

Credentialing pharmacists and elevating their status of that of a nonphysician provider have been implemented at our medical center to enable pharmacists to practice at the top of their license, improve efficiency for physicians and pharmacists, and to improve patient care.[10] The privileges granted to each pharmacist depend on his or her area of practice, postgraduate training, demonstrated competency, and leadership approval.[10] In 2015, ICU pharmacy specialists were granted privileges to independently discontinue medications for SUP when no longer indicated. A protocol was developed and disseminated to guide practice and establish consistency. Major risk factors for stress ulceration outlined in this protocol are coagulopathy and mechanical ventilation, which is consistent with current evidence. Minor risk factors delineated in the guideline are high-dose prolonged glucocorticoid administration and dual antiplatelet therapy with therapeutic anticoagulation. The following conditions also are also listed in the guideline as appropriate indications for PPI use: esophageal varices, history of GI bleed, Barrett's esophagitis, Zollinger-Ellison syndrome, Helicobacter pylori, and transplant with the use of prolonged glucocorticoids. The implementation of pharmacist management of SUP in hospitalized patients has been demonstrated to be successful at other institutions.[11],[12] We aimed to evaluate the impact of the implementation of this practice at our institution to decrease rate of inappropriate SUP upon ICU discharge.

  Materials and Methods Top

The University Institutional Review Board in accordance with the ethical standards set forth in the Helsinki Declaration of 1975 approved this retrospective, observational study of patients admitted to the surgical ICUs or medical ICUs in an academic medical center with computerized prescriber order entry (EPIC, Verona, WI, USA). Patients admitted to the ICUs in January 2015 served as the pregroup and patients admitted to the same ICUs in January 2016 following the implementation of a stress ulcer prophylaxis (SUP) protocol were the postgroup. Patients were identified by an electronic medical record report of admissions to the ICU in the specified date range. Patients were included for assessment if they received a PPI or H2RA during their admission to the ICU. Patients were excluded if they had presented with GI bleed during their hospital admission, received only Sucralfate, were <18 years of age, pregnant, incarcerated, expired during admission, or were discharged to hospice.

Demographic data collected included patient age, gender, height, body mass index, and admission weight. The type of ICU to which the patient was admitted was noted. Relevant past medical history, treatment with dual antiplatelet therapy with therapeutic anticoagulation during ICU stay, use of high-dose steroids (>60 mg of prednisone equivalents per day), ICU length of stay, duration of mechanical ventilation, presence of coagulopathy (platelet count <50,000/mcL, international normalized ratio >1.5 not on warfarin or partial thromboplastin >2 times the upper limit of normal not on anticoagulation) after extubation, PPI or H2RA use before, during, and after ICU stay, total hospital length of stay, diagnosis of pneumonia, and C. difficile-associated diarrhea.

Continuation of acid suppression therapy was considered appropriate if the patient remained coagulopathic, mechanically ventilated, on treatment with dual antiplatelet therapy with therapeutic anticoagulation, or on high-dose steroids. Continuation of acid suppressive therapy upon discharge from the ICU was also determined to be appropriate if the patient had presented on home acid suppressive therapy with a H2RA or PPI or was diagnosed with one of the following chronic conditions: history of a GI bleed, Barrett's esophagitis, H. pylori-positive status, esophageal varices, active peptic ulcer disease, recent transplant with the use of high-dose steroids, Zollinger-Ellison's disease, or gastroesophageal reflux disease (GERD).

A sample size calculation determined that approximately eighty patients in each group were needed to achieve 80% power with an alpha of 0.05 to detect a 15% absolute reduction in inappropriate SUP assuming a baseline incidence of 25%. Data were analyzed using Statistical Package for the Social Sciences for Windows (IBM Version 21, Armonk, NY, USA). Continuous parametric data were analyzed using the Student's t-test whereas continuous nonparametric data were analyzed using Mann–Whitney U-test. Dichotomous variables were analyzed using Fisher's exact method.

  Results Top

In January 2015, 203 unique patients were admitted to an ICU through direct admission or transfer from another unit within the hospital. Patients were assessed for inclusion in random order until eighty patients met inclusion criteria. Of the 148 patients from this group that were randomly assessed for inclusion, 68 were excluded from the study [Figure 1]. In the postgroup in January 2016, 255 patients were admitted to an ICU in university hospital and were randomly assessed for inclusion until eighty patients met inclusion criteria. Of the 168 patients who were reviewed for inclusion, 88 patients were excluded from the study [Figure 1]. There were no differences in reasons for exclusions between groups with no acid suppression therapy administered in the ICU and expiration in the ICU being the most common.
Figure 1: Patient inclusion and exclusion assessment. ICU = Intensive Care Unit, GI = Gastrointestinal, H2RA = Histamine receptor antagonist, PPI = Proton pump inhibitor

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The baseline demographics for the study population were well matched in the pre- and post-groups with included patients having a mean age of 52.8 years and were 48.8% male. No significant differences were observed with regard to ICU or hospital length of stay [Table 1]. Overall, the documented rate of GERD was almost 30% and did not differ between groups (27.5% pregroup vs. 31.1% postgroup, P = 0.73) [Table 2]. No differences were identified between the pre- and post-groups in relation to indications for SUP during ICU admission. Mechanical ventilation was the most common indication for SUP with relatively few patients experiencing a coagulopathy, receiving dual antiplatelet therapy with concomitant therapeutic anticoagulation, or high-dose steroids [Table 3].
Table 1: Demographic characteristics of study group

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Table 2: Relevant medical history of study group

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Table 3: Indications for acid suppression therapy

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Home use of acid suppressive therapy was pronounced in over 50% of patients and not different in the pre- and post-group. PPIs were reported most frequently in approximately 40%, but the use of H2RAs was substantial as well as in approximately 15% of patients [Figure 2]. Analysis of the primary outcome, inappropriate continuation of acid suppression therapy upon discharge from the ICU, demonstrated an insignificant difference between groups. Overall, the rate of inappropriate continuation of acid suppression therapy was low and not different between groups (15.4% vs. 14.9%, P = 0.999). Furthermore, the major reason for appropriate continuation of acid suppressive therapy was the documentation of a chronic condition that provided a reasonable indication for therapy (46.1% vs. 60.0%, P = 0.228). While a significant portion of patients in both the pre- and post-group were discharged from the ICU on acid suppressive therapy, few patients were continued on therapy for the indication of SUP [Figure 3].
Figure 2: Home acid suppression therapy. H2RA = Histamine receptor antagonist, PPI = Proton pump inhibitor

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Figure 3: Discharge on acid suppression therapy. H2RA = Histamine receptor antagonist, PPI = Proton pump inhibitor

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When comparing the use of H2RAs versus PPIs in the ICU setting, H2RAs were found to be the predominant drug therapy used for acid suppression. Whereas this is consistent with the protocol which was disseminated, there was no significant difference in the pre- and post-groups in terms of the distribution of the type of acid suppression therapy used in the ICU (38.8% vs. 37.5%, P = 0.735 for PPI use and 27.5% vs. 22.5%, P = 0.527 for H2RA use). The duration of acid suppression therapy in the ICU was also compared between the pre- and post-groups. Although the median for both groups was 0.0 days of inappropriate acid suppression, the range was narrower in the postgroup ([0.0–16.0] vs. [0.0–9.0], P = 0.016). Upon discharge from the hospital, acid suppression therapy remained prevalent in both the pre- and post-groups with no differences seen in terms of distribution of type of acid suppression therapy (38.8% vs. 38.8%, P > 0.999 for PPI and 16.3% vs. 17.5%, P = 0.584 for H2RA) [Figure 3].

  Discussion Top

Overall, we found no difference in continuation of SUP at ICU discharge, but this was confounded by a high rate of reported home acid suppression before admission. Over 50% of patients were reported to be taking a PPI, H2RA, or both before admission. The most common indication was GERD in almost 30% of included patients. As patients are often admitted to the ICU for an acute illness or injury, the adjustment of outpatient prescriptions, such as acid suppression therapy, is not often performed due to concerns regarding appropriate follow-up. This is especially true in relation to the ICU pharmacists utilizing their privileges to discontinue SUP as this would then require the pharmacist to determine that the baseline indication for chronic acid suppression has been resolved. The privileged activity specifically addresses SUP not chronic acid suppression therapy. This demonstrates the need for proper medication reconciliation whenever the patient comes in contact with the medical system and the ICU may not be an optimal place to perform this important task. Moreover, this result establishes the need for patient education regarding the appropriate duration and indications for acid suppression therapy, especially given the associated risks.

Dyspepsia and GERD are common conditions that occur in 10%–20% of the Western World with a slightly lower rate in Asia.[13],[14] Clinically, troublesome heartburn is estimated in 6% of the population.[15] Clinical practice guidelines by American College of Gastroenterology recommend, in most cases, 4–8 weeks of therapy of acid suppression with H2RAs or PPIs, but these medications should not be continued lifelong.[14],[15] Studies have demonstrated that between 40%–65% of patients in the United States, Australia, and the United Kingdom have a lack of documentation for ongoing acid suppression.[9],[14],[16],[17],[18],[19],[20] We reported a diagnosis of GERD in approximately 30% of our patients and it is unknown if this was an active problem or not despite being documented on the patient's problem list. More importantly, guidelines for deprescribing PPIs have recently been published out of Canada and recommend to decrease PPI dosage or discontinue for adults 18 years and greater that received at least 4 weeks of treatment for GERD and who have resolution of symptoms.[20]

PPIs are some of the most common medications prescribed and are generally considered safe.[21],[22] They are available both as prescription and over-the-counter medications. As hospitals are trying to decrease C. difficile infections, the use of PPIs has come under increasing scrutiny. The use of PPIs is associated with increased risk of initial and recurrent C. difficile diarrhea.[4] However, this is not the only infectious complication associated with PPIs. Recently, the use of chronic PPIs has been associated with an increased risk of listeriosis and carriage of extended-spectrum beta-lactamase-Producing Enterobacteriaceae.[23],[24] Granting ICU pharmacists, the clinical privilege to discontinue acid suppression for SUP was conceived for concerns to decrease C. difficile diarrhea at our institution.

Additional risks that have recently come to light that are associated with PPI use are also extremely concerning when considering the high prevalence of inappropriate home use in the ambulatory care setting.[17] For example, in a propensity score matching analysis, PPI users were demonstrated to have a 1.58-fold greater risk of myocardial infarction than non-PPI users within a 120-day follow-up period following an acute coronary syndrome.[25] Furthermore, a recent retrospective propensity score-matched analysis found an association between PPI use and cerebrovascular risk. The association was demonstrated to be the highest when PPIs were utilized within 30 days before the ischemic stroke (adjusted odds ratio: 1.77 [95% confidence interval: 1.45–2.18, P < 0.001]).[26] These recent data compound concern with infectious risk regarding the inappropriate use of PPIs.

Our institution had a low rate of inappropriate continuation of acid suppression therapy. One reason for this finding may be the way, in which appropriate continuation of acid suppression therapy was defined. Patients with a chronic condition noted in their electronic medical record that would make acid suppression therapy a reasonable therapeutic modality were considered appropriately continued on therapy. However, this did not consider if the patient was currently experiencing symptoms as it can be hard to get reliable information from critically ill patients. Furthermore, chronic conditions were often listed from an encounter months to years in the past but continued to be carried forward in the problem list on each subsequent encounter. This was especially true in the case of GERD where the documented rate of GERD was approximately 30% higher than the reported rate of 10%–20% in published literature.[13],[14] Finally, some patients who were admitted with an acid suppression therapy on their home medication list may have been assumed to have GERD and this diagnosis was then added to the problem list. Due to the retrospective nature of this study, these aspects were difficult to control.

The findings of this investigation are somewhat surprising given the positive impact of pharmacist-led initiatives regarding SUP that have been previously published.[11],[12],[27],[28] Interventions described in the literature include protocol development, independent pharmacist direction over SUP, and pharmacist-delivered education. Our intervention encompassed all three of these aspects but focused solely on critically ill patients. Buckley et al. conducted their successful intervention in both critically ill and ward patients and demonstrated the biggest effect in the ward patients.[11] Furthermore, their sample size included a much larger patient population over a longer span of time. They also excluded patients with a history of GI disease including GERD or taking home acid suppression. In addition, the primary outcome in these studies looked at days of inappropriate SUP rather than inappropriate continuation. Although our study also showed a trend toward improvement in more efficient discontinuation of inappropriate acid suppression therapy, this was not our primary outcome. Assuming a rate of 15% inappropriate continuation in the baseline group, we would need 540 patients per group to demonstrate a significant difference of 10% in the study group and this may not be clinically significant. Regardless, education and changes to how we document home acid suppression are currently being assessed at our institution.

In addition to the need for a significantly larger sample, our study had several other limitations. First, this was a retrospective study of critically ill patients and as a result it is impossible to adequately capture home acid suppression use. Likewise, there may have been a lack of accurate documentation in the medical record of efforts to confirm home medication use. We did not include patients outside of the ICU setting when it may be more appropriate to address maintenance medication issues after the patient is no longer critically ill. Over-the-counter medication use is also difficult to identify during the critically ill period and may not be appropriately accounted for in this study. The retrospective nature of this study made it difficult to ascertain definitive reasons for acid suppression therapy and required reliance on documented problem lists which may not accurately represent active issues. It was also necessary to assume medication lists on admission medication lists and discharge summaries were accurate. Finally, pharmacy specialists were active in SUP stewardship through verbal recommendation on rounds before being granted clinical privileges to independently perform the task of discontinuation. The presence of the pharmacist on the multidisciplinary rounding team can facilitate medication management such as acid suppression therapy stewardship during active patient care. Therefore, the low baseline rate of inappropriate acid suppression may have already been reflective of the impact of pharmacist intervention.

  Conclusions Top

Based on the results of this analysis, we are unable to conclude that granting ICU pharmacists, the clinical privilege to discontinue acid suppression significantly improved inappropriate continuation SUP upon discharge from the ICU. However, numerous confounding variables and a small sample size were likely contributory to the negative results. The high use of home acid suppression therapy of patients admitted to the ICU is an alarming finding given the risks attributed to chronic acid suppression and demonstrates the need for patient education and medication reconciliation at both admission and discharge from the hospital.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Barletta JF, Bruno JJ, Buckley MS, Cook DJ. Stress ulcer prophylaxis. Crit Care Med 2016;44:1395-405.  Back to cited text no. 1
Cook DJ, Fuller HD, Guyatt GH, Marshall JC, Leasa D, Hall R, et al. Risk factors for gastrointestinal bleeding in critically ill patients. Canadian critical care trials group. N Engl J Med 1994;330:377-81.  Back to cited text no. 2
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Howell MD, Novack V, Grgurich P, Soulliard D, Novack L, Pencina M, et al. Iatrogenic gastric acid suppression and the risk of nosocomial clostridium difficile infection. Arch Intern Med 2010;170:784-90.  Back to cited text no. 4
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Huizinga P, van den Bergh MK, van Rijen M, Willemsen I, van't Veer N, Kluytmans J, et al. Proton pump inhibitor use is associated with extended-spectrum β-lactamase-producing enterobacteriaceae rectal carriage at hospital admission: A Cross-sectional study. Clin Infect Dis 2017;64:361-3.  Back to cited text no. 24
Shih CJ, Chen YT, Ou SM, Li SY, Chen TJ, Wang SJ, et al. Proton pump inhibitor use represents an independent risk factor for myocardial infarction. Int J Cardiol 2014;177:292-7.  Back to cited text no. 25
Wang YF, Chen YT, Luo JC, Chen TJ, Wu JC, Wang SJ, et al. Proton-pump inhibitor use and the risk of first-time ischemic stroke in the general population: A Nationwide population-based study. Am J Gastroenterol 2017;112:1084-93.  Back to cited text no. 26
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Khalili H, Dashti-Khavidaki S, Hossein Talasaz AH, Tabeefar H, Hendoiee N. Descriptive analysis of a clinical pharmacy intervention to improve the appropriate use of stress ulcer prophylaxis in a hospital infectious disease ward. J Manag Care Pharm 2010;16:114-21.  Back to cited text no. 28


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2], [Table 3]

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