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Overuse of stress ulcer prophylaxis in the critical care setting and beyond
Journal of Critical Care (2010) 25, 214–220
Overuse of stress ulcer prophylaxis in the critical care setting and beyond Christopher P. Farrell DOa,⁎, Giancarlo Mercogliano MDb , Catherine L. Kuntz MD, MSa,c a
Department of Internal Medicine Residency Program, Annenberg Conference Center, Lankenau Hospital, Wynnewood, PA 19096, USA b Division of Gastrointestinal Medicine, Lankenau Hospital, Wynnewood, PA 19096, USA c Division of Pulmonary and Critical Care Medicine, Lankenau Hospital, Wynnewood, PA 19096, USA
Keywords: Stress ulcers; Prophylaxis; Proton pump inhibitors; Histamine 2 receptor antagonists; Coagulopathy
Abstract Background: Patients admitted to the intensive care unit (ICU) are susceptible to stress ulcers. We hypothesize that despite recommendations, stress ulcer prophylaxis (SUP) is still overused in the ICU and often continued after resolution of risk factors for bleeding. Methods: We retrospectively studied all ICU admissions for 4 months. Risk factors for stress ulcer bleeding were collected. Patients were categorized into 4 groups: (1) ≥1 major risk factor; (2) ≥1 minor risk factors; (3) no risk factors; (4) preadmission use of acid-suppressive medication. The rate of SUP was calculated by group during ICU stay, on transfer from the ICU, and at hospital discharge. Results: Two hundred ten patients were studied. Of all the ICU admissions, 87.1% received SUP. Among patients with no risk factors, 68.1% were placed on prophylaxis on ICU admission; 60.4% continued on treatment upon transfer from the ICU; 31.0% were discharged home on an agent without a new indication. Conclusions: Although judicious use of SUP in high-risk patients can decrease the incidence of gastrointestinal bleeding, inappropriate use may increase drug reactions, unnecessary hospital costs, and personal monetary burden. Our findings argue for improvement measures to reduce initial inpatient overuse of SUP and to prompt discontinuation before hospital discharge. © 2010 Elsevier Inc. All rights reserved.
1. Introduction Critically ill patients requiring admission to intensive care units (ICU) are at risk of developing gastrointestinal (GI) stress ulcers. Gastric ulcerations and erosions have been known to develop in such patients since the 1800s, and treatment with stress ulcer prophylaxis (SUP) became ⁎ Corresponding author. Tel.: +1 215 850 2575; fax: +1 610 645 8141. E-mail address: [email protected] (C.P. Farrell). 0883-9441/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.jcrc.2009.05.014
routine care in the 1980s [1]. Acid-suppressive medications (ASMs) used for this purpose include proton pump inhibitors (PPIs), histamine 2 receptor antagonists (H2 antagonists), and sucralfate, with PPIs gaining widespread use because of data suggesting superior safety and efficacy [2]. Stress ulcers have been shown to increase morbidity and mortality, with stress-related bleeding prolonging ICU stay between 4 and 8 days and increasing mortality up to 4-fold [1]. Evidence has illustrated that there is an increased risk for developing stress ulcers in patients with respiratory failure requiring mechanical ventilation for more than 48 hours
Stress ulcer prophylaxis in the critical care setting (odds ratio [OR], 15.6) and patients experiencing a coagulopathy (OR, 4.3) [1,3,4]. One multicenter observational study showed a number needed to treat 30 patients to prevent clinically important bleeding if one or both of these risk factors were present, compared with 900 patients in those considered low risk [4]. The use of SUP can lead to adverse reactions, drug-drug interactions, and increased hospital and prescription costs [5,6]. Links have been made between PPI use and Clostridium difficile infections; recent data suggest possible adverse outcomes when PPIs are used in conjunction with clopidogrel in patients with acute coronary syndrome; H2 antagonists have been linked to thrombocytopenia and nosocomial pneumonia [7,8,9,10,11]. Proton pump inhibitors and H2 antagonists interact with the cytochrome P-450 pathway and may result in important drug-drug interactions and affect absorption of various other medications by altering gastric pH [1]. Using SUP on general medical patients who have little to no risk at all for developing stress ulcers has been demonstrated in prior studies [12]. Previous analyses have attempted to delineate risk factors for stress ulcer bleeding among critically ill patients [1,4]. Standard of care regarding the use of SUP in the critical care setting is still limited by lack of universally accepted standardized guidelines for when to initiate and discontinue these medications, but knowledge of risk factors for SUP helps guide decision making. When providing ICU care, many intensivists believe patients should be risk stratified to determine whether to implement prophylaxis early enough to provide a benefit [13,14]. Our hypothesis was that SUP in our hospital's ICU is used excessively, even in the absence of clear risk factors, and, among this cohort, is often continued once risk factors have resolved. Our primary aim was to report (a) the rate of SUP use upon admission to the ICU among different risk categories, (b) the proportion of patients among different risk categories who remained on SUP upon transfer out of the ICU, and (c) the proportion of patients discharged from the hospital on SUP. Our secondary aim was to identify factors that were associated with use of SUP by physicians during ICU stay to explore reasons why decisions might be made to initiate SUP, sometimes even in the absence of clear risk factors.
2. Methods 2.1. Study population We conducted a retrospective study of all patients admitted to the ICU at a 331-bed community-based academic medical center from December 1, 2006, through March 31, 2007. Care is provided by medical and surgical residents and attending medical and surgical intensivists. The patient population includes all critically ill medical, surgical, and
215 cardiac patients within our hospital. Inclusion criteria were admission to the ICU in patients aged 16 years or older. Exclusion criteria included admission diagnoses of GI bleeding or bleeding within the first 24 hours because these diagnoses require treatment of disease rather than prophylaxis, new-onset gastroesophageal reflux disease (GERD) or esophagitis, treatment of an allergic reaction with an H2 antagonist, and withdrawal of care initiated upon admission. Subjects who were taking ASM before admission were examined separately.
2.2. Data collection Data collection was retrospective, which avoided treatment bias induced by physician awareness of the study hypothesis. Abstracted data included patient demographics, medical diagnoses, admission diagnosis, preadmission medications, and SUP treatment received in the ICU, throughout hospital stay, and upon discharge. The presence of risk factors for stress-related mucosal bleeding (Table 1) were recorded [1,4].
2.3. Statistical analysis Among our sample, we categorized patients into the following groups based on risk: (1) one or more major risk factors present; (2) no major but with one or more minor risk factors present; (3) no major or minor risk factors present; and (4) known GERD, peptic ulcer disease, Barrett's esophagus, or other conditions requiring outpatient acidsuppressive therapy (Table 2). Upon each transition of care (out of ICU to general hospital floors, from the hospital to home), patients were restratified based on risk. For our primary aim, the SUP rate was calculated for the entire cohort and for the groups stratified by risk. Rates of SUP were computed during ICU stay, upon transfer out of
Table 1
Major and minor stress ulcer risk factors
Major
Minor
Mechanical ventilation Coagulopathy b
Sepsis or severe hypotension a ARF c Hepatic failure d Severe head or spinal cord trauma History of GI bleeding Burns N35% of body surface area Major surgery N4 h High-dose corticosteroids e
Sessler, J.M., Cook, D.J., et al. a Systolic blood pressure b80 mm Hg. b International normalized ratio N1.5, partial thromboplastin time N2 times the upper limit of normal, or platelets b50 000. c Creatinine clearance b40 mL/min or serum creatinine N2.8 mg/dL. d Aspartate aminotransferase N500 U/L or total bilirubin N8.8 mg/dL. e Equivalent of N250 mg of hydrocortisone per day.
216
C.P. Farrell et al.
Table 2
Patient groups according to risk factors
Group
Major risk factors
Minor risk factors
1 2 3 4a
≥1 0 0 –
– ≥1 0 –
3. Results 3.1. Patient characteristics
a
Group 4: patients who were on a PPI, H2 antagonist, or sucralfate as an outpatient.
the ICU, and at time of discharge from the hospital and are reported with 95% confidence intervals (CIs). Discharge medications in group 4 patients who were on ASM before admission were examined upon release from the hospital to see if their discharge medication differed from their admission medication. For our secondary aim, we tested the following variables to see if they were associated with the use of SUP by physicians among patients not previously on ASM: sex, age, mechanical ventilation, coagulopathy, sepsis/shock, acute renal failure (ARF), and total number of minor risk factors present. Burns, head trauma, steroid use, and hepatic failure were not tested separately because of very small numbers in our study population. Age was not normally distributed and was tested as a categorical variable by decades. Each variable was tested to determine its association with SUP use in a univariate model. Binary and categorical variables were tested using χ2 and Fisher exact analysis. Ordered categorical variables were tested using χ2 test for trend. Continuous variables were tested using logistic regression methods. For each variable of interest, multivariable logistic regression modeling separately tested every other variable as a potential confounder of the relationship of interest. A variable was considered a confounder if adding that variable to the model changed the unadjusted OR for the variable of interest and the outcome (SUP) by 10% or more [15]. The final model included all variables with a P value of .2 or lower and all confounding variables. Statistical comparisons were performed using STATA version 8.0 (STATA Corp, College Station, Tex). This research was
Table 3 Risk stratification: during ICU admission, transfer to GMF, discharge from the hospital Group a
1 2 3 4
During ICU
Transfer ICU to GMF
Discharge from hospital
n = 210
n = 190
n = 185
n (%)
n (%)
n (%)
44 41 47 78
2 5 111 72
0 1 113 71
(21.0) (19.5) (22.4) (37.1)
(1.1) (2.6) (58.4) (37.9)
(0) (0.5) (61.1) (38.4)
Groups: 1, ≥1 major risk factor; 2, ≥1 minor risk factor; 3, no risk factors; 4, preadmission ASM. a
approved by the Institutional Review Board at the Lankenau Institute for Medical Research.
The total number of patients admitted to the ICU over the 4-month period was 241. Thirty-one patients were excluded; 27 for GI bleeding on admission or within the first 24 hours, 1 for acute esophagitis, 1 for acute GERD, 1 for angioedema/ allergic reaction, and 1 for immediate withdrawal of care. The median age of the 210 patients included was 61 years, and 51.9% were male. Stratification of groups based on risk factors is illustrated in Table 3 for patients during ICU stay, upon transfer from ICU to the general medical floor (GMF), and at discharge from the hospital. Patient characteristics are shown in Table 4.
3.2. Stress ulcer prophylaxis during ICU Of the 210 patients, 87.1% (95% CI, 81.8, 91.4) were placed on SUP during ICU stay. By risk factor groups, 95.5% of patients in group 1 (major risk factors), 82.9% of patients in group 2 (minor risk factors), 68.1% of patients in group 3 (no risk factors), and 96.2% of patients in group 4 (previous ASM use) were placed on SUP (Table 5).
3.3. Stress ulcer prophylaxis on transfer from ICU After attrition of ICU patients due to death (19) or hospital transfer (1), the total number of patients studied at the time of transfer out of ICU was 190. These patients Table 4 Characteristics of patients not previously on acidsuppressing medications before ICU admission
Age (mean) Sex, male VDRF present Coagulopathy present Sepsis/shock ARF Liver failure Head trauma History of GI bleeding Steroid use Surgery N4-h duration No. of major RF 0 1 2 RF indicates risk factors.
SUP not received
SUP received
n = 27 (12.9%)
n = 183 (87.1%)
54.5 ± 7.7 15 (62.5) 2 (8.3) 1 (4.2) 2 (8.3) 7 (29.2) 0 (0) 1 (4.2) 0 (0) 1 (4.2) 0 (0)
60.5 ± 3.8 52 (48.2) 37 (34.5) 13 (12.0) 21 (19.4) 40 (37.0) 6 (5.6) 2 (1.8) 1 (0.9) 12 (11.1) 4 (3.7)
22 (91.7) 1 (4.2) 1 (4.2)
66 (61.1) 34 (31.5) 8 (7.4)
Stress ulcer prophylaxis in the critical care setting Table 5 group Group a
Stress ulcer prophylaxis rate based on risk factor No. of prophylaxed
No. of patients total
During ICU 1 42 44 2 34 41 3 32 47 4 75 78 Total 183 210 Transfer out of the ICU 1 2 2 2 5 5 3 67 111 4 68 72 Total 142 190 Discharge from the hospital 1 0 0 2 1 1 3 35 113 4 61 71 Total 97 185
% prophylaxis (95% CI) 95.5 (84.5-99.4) 82.9 (67.9-92.8) 68.1 (52.9-80.9) 96.2 (89.2-99.2) 87.1 (81.8-91.4) 100.0 (0.96-1 b) 100.0 (0.96-1 b) 60.4 (50.6-69.5) 94.4 (86.4-98.5) 74.7 (67.9-80.7) 0.0 100.0 (0.25-1 b) 31.0 (22.6-40.4) 85.9 (75.6-93.0) 52.4 (45.0-59.8)
Patients separated by group placed on prophylaxis with a PPI, H2 antagonist, or sucralfate during ICU stay, transfer out of the ICU, and discharge from the hospital. a Groups: 1, ≥1 major risk factor; 2, ≥1 minor risk factor; 3, no risk factors; 4, preadmission ASM. b One-sided CIs.
were reevaluated in relation to their risk factors at transfer. Most risk factors for stress ulcer bleeding had resolved (Tables 3 and 5). Of the few patients with any remaining major or minor risk factors (groups 1 and 2), all were continued on SUP at transfer. Of the patients, 60.4% in Table 6
217 group 3 (no continuing risk factors) and 94.4% in group 4 were continued on medication (Table 5).
3.4. Stress ulcer prophylaxis upon hospital discharge One hundred eighty-five of 210 subjects survived to hospital discharge. At discharge, patients were again restratified based on risk factors (Tables 3 and 5). Ninetyseven (52.4%) of these 185 patients were sent home on SUP. Sixty-one of these patients discharged on medication were from group 4 and had been admitted on ASM. However, 36 patients who had not been on acid suppression at admission were sent home on ASM. Only one of these 36 had a single minor risk factor at the time of discharge (steroid dose equivalent to ≥250 mg of hydrocortisone per day). Of the patients who were not on any ASM on admission to the ICU and who possessed no risk factors at all at the time of discharge, 31.0% were discharged home on ASM. On chart review, none of these patients had developed a new indication for ASM during their hospitalization. Of the patients who came into the hospital on an ASM (group 4) and survived to hospital discharge, 85.9% were sent home on one of these medications. Of these patients, 14.1% had their medications discontinued before or at hospital discharge. Of this group, 31.3% was discharged on a different ASM than their admission medication.
3.5. Factors associated with SUP Univariate analysis was performed and is shown in Table 6. Age categorized by decades and number of minor risk factors were tested with the χ2 test for trend for ordered
Univariate analysis and multivariable logistic regression for factors associated with the use of SUP by physicians
VDRF Coagulopathy Sex (reference, male) Age Sepsis ARF Group 1 (ref 3) b (major RF vs no RF) Group 2 (ref 3) (minor RF vs no RF) Group 1 (ref 2) (major RF vs minor RF) Any major RF No. of minor RF
OR a (95% CI)
P
Adjusted OR
P
5.73 (1.28-25.72) 3.15 (0.39-25.30) 1.79 (0.72-4.45) 1.16 (0.92-1.45) 2.66 (0.58-12.19) 1.43 (0.55-3.74) 9.84 (2.10-46.17)
.023 .28 .21 .20 .21 .47 .004
5.31 (1.08-26.01) 1.30 (0.14-12.39) 1.78 (0.69-4.61) 1.16 (0.92-1.47) 1.58 (0.31-8.00) 0.90 (0.32-2.56) 9.20 (1.95-43.45)
.039 .82 .24 .21 .58 .84 .005 c
2.28 (0.82-6.31)
.11
2.09 (0.74-5.88)
.16 c
4.32 (0.84-22.18)
.08
7.00 (1.56-31.32) 1.88 (0.96-3.69)
.011 .065
5.76 (1.24-26.82) 1.40 (0.67-2.92)
.026 d .38 d
Age categorized by decades and number of minor risk factors were tested with χ2 test for trend for ordered categorical variables; P values were less than .20. RF indicates risk factors. a Odds ratios, reported from logistic regression modeling. b Group 1 in reference to group 3. c Controlled for age and sex only because other factors are collinear and define groups. d Adjusted model includes age, sex, any major risk factor, and number of minor risk factors.
218 categorical variables and by logistic regression, and ORs per increment are reported. Therefore, an OR of 1.16 for age suggests that for each 10-year increase above the age of 25 years, the odds of SUP use increased by 16% (P = .20). The only associations that achieved statistical significance for SUP use by physicians in univariate analysis were ventilatordependent respiratory failure (VDRF) or the presence of any major risk factor. All variables of interest tested were included in the multivariable model either because of a possible association with SUP use (P ≤ .2) in univariate analysis (VDRF, sex, and age) or because they were discovered to be confounders between the other variables of interest and the outcome (coagulopathy, sepsis, and ARF). Only the presence of VDRF retained a significant association with SUP use in multivariable modeling. A second model looked at risk factor groups as defined. In univariate analysis, group 1 with any major risk factor had a significantly higher odds of SUP than group 3 with no clear major or minor risk factor (OR, 9.84; P = .004); there was no significant difference in SUP use between groups 2 (minor risk factors) and 3 (no risk factors) (OR, 2.28; P = .11), nor between groups 1 (major risk factor) and 2 (minor risk factors) (OR, 4.32; P = .08). A multivariable model looked at risk factor groups adjusting for age and sex. Only group 1 had a higher odds of SUP prophylaxis (reference group 3; OR, 9.20; P = .005). A final model sought to explore whether the number of risk factors present was associated with SUP use. When adjusted for age and sex, only the presence of either major risk factor but not the number of minor risk factors was significantly associated with SUP use.
4. Discussion Current medical care is capable of decreasing the frequency of stress-related GI bleeding in the ICU. Prior studies have shown that routine use of SUP in most hospitals on non-ICU patients is often unnecessary and sometimes inappropriate [16,17]. In the ICU, SUP indications have been better defined by studies that identified high-risk patients who would benefit most. Still, current guidelines are often not definitive as to which patients without these major risk factors warrant prophylaxis. The Surviving Sepsis Campaign advocates SUP in severe sepsis, noting that many patients have a major risk factor (mechanical ventilation or coagulopathy) for stress ulcer bleeding; they acknowledge the lack of studies specific for sepsis [18]. The Eastern Association for the Surgery of Trauma recommends using SUP in traumatic brain injury, major burns, mechanical ventilation, and coagulopathy but recognizes that use for the former 2 categories is debatable [19]. The American Society of Health Systems Pharmacists created guidelines for SUP use from literature review, incorporating factors studied by Cook et al, stating that mechanical ventilation and coagulopathy are the only
C.P. Farrell et al. independent risk factors and that other conditions have not been well studied [20]. Therefore, although guidelines exist, with the exception of the 2 major risk factors, there is differing opinion as to what other risk factors, if any, should be the indications for SUP. In our hospital, the overall incidence of SUP upon admission to the ICU over this 4-month period was 87.1%. A good percentage of the treatment could be considered controversial. Postoperative patients have been shown to have a low frequency of clinically important bleeding and little improvement with prophylaxis [21]. Sepsis, shock, burns, steroid use, past episode of GI bleeding, and renal or hepatic failure have not shown enough significance in previous studies to definitively warrant prophylaxis as standard treatment, although this remains debatable [1,4]. These patients are often prophylaxed. Among our study population, 82.9% of patients with one or more of these risk factors received SUP. Furthermore, among the group with no identifiable risk factors for stress-related bleeding, 68.1% still received SUP. The potential benefit of SUP while in the ICU is felt to be substantial by some, whereas the downside is probably minor. Perhaps a greater issue arises when these medications are not discontinued later in the hospital course. In fact, 31.0% of patients not admitted on ASM were discharged on ASM despite having no new identifiable indications for use. Our study highlights the initial reaction to use particular medications under certain circumstances without recognizing the definitive indications. We go further to emphasize the downstream effect of continuation of these medications once they have been initiated. Patients who were on ASM as outpatients before admission were also studied. Of these patients, 14.1% were not sent home on ASM at all, and 31.3% of these patients were discharged home on a medication different from their admission medication. This exemplifies the importance of medicine reconciliation at discharge to avoid the use of incorrect medications or perhaps even the use of 2 ASMs, the medication on which the patient is discharged, and the medication that is waiting at home. Our study did not explore reasons why these medications changed, but most of these cases involved exchanging one PPI for another rather than crossing classes of medications. The major risk factors for the development of stress ulcers have been extensively studied in the past. Mechanical ventilation can lead to splanchnic hypoperfusion and subsequent gastric mucosal damage and ulceration; coagulopathy affects the body's ability to prevent and stop bleeding [22,23]. Therefore, we would expect that the presence of these major risk factors for stress ulceration would be associated with SUP use by our physicians. Our results show that most people (95.5%) with one or more of these 2 major risk factors received SUP during ICU stay. In our exploration of which patient variables were associated with SUP in the ICU, only the presence of either one of these 2 risk factors was significantly associated with SUP use in univariate and
Stress ulcer prophylaxis in the critical care setting in multivariable analysis. To this extent, our physicians are likely influenced by guidelines. Nevertheless, the fact that major risk factors were associated with SUP use among our physicians did not change the finding that SUP was still used in most patients without major and even without minor risk factors. Among these patients, none of the variables we examined, such as sex, age, or the total number of minor risk factors present were associated with SUP use. Because of the cross-sectional nature of our study, these are associations only and should not be interpreted as definitive predictors of physician behavior. However, one possible explanation for our findings is that simply being in the ICU alone is the factor that prompts initiation of treatment by many physicians rather than a process of risk stratification. Another possibility is that there are other variables involved in physician decision making to prophylax, which we did not capture. These medications do have downsides. Sucralfate is not systemically absorbed and has been known to decrease the absorption of other medications administered around the same time [1]. H2 antagonists can lead to ailments such as confusion, delirium, hallucinations, slurred speech, and thrombocytopenia [1,11,24]. H2 antagonists have been linked to an increase in nosocomial pneumonia while on mechanical ventilation, thought to be due to an increase in pH in the stomach allowing bacterial overgrowth and retrograde colonization of the pharynx [8,9]. Common adverse events from PPIs include diarrhea, nausea, vomiting, abdominal pain, and headaches [25]. Proton pump inhibitors have been shown to impair neutrophil activity and, hence, may affect the immune response [26]. A possible correlation between PPI use and C difficile infections has also been suggested but requires further investigation [10]. Our study did not specifically report on complications attributable to SUP because many of these reported adverse effects are common in the ICU, often resulting from illness rather than SUP use; because almost all of our population received SUP, making a comparison group very small; and because confounding by indication alone could account for more ventilator-associated pneumonia, thrombocytopenia, C difficile, and delirium in sicker patients who received SUP. Besides these medications posing health risks, there is also the issue of monetary burden on the hospital and the individual [5,6]. Cost-effective analysis in the hospital setting has shown a significant financial loss and overuse of resources [27]. For the individual after hospital discharge, depending on the drug and its class, the price for a month's supply can range from $15 to $200 for patients without a prescription plan. These examples support that these medications should not be distributed universally to all patients, can increase morbidity, and can have significant impact on cost when used in circumstances where they are not indicated. Our study has several limitations. We studied a small sample of 210 patients for just a 4-month period. Nevertheless, our results are impressive and suggest substantial
219 overuse of SUP within our hospital. A larger study over a longer period would better represent groups that were underrepresented in our population. A 4-month study period has potential to show different results depending on what period of the academic year we chose to study. We did select our 4-month study period during the latter half of the academic year to avoid reflecting the practices of new and less skilled intern and resident physicians. Furthermore, there are likely other additional factors for stress ulcer bleeding that have not been considered or proven in prior studies, which we also did not capture in our study. Among these is noninvasive ventilation with bilevel positive airway pressure as a measure of assisted ventilation, not studied in earlier analyses because of the relatively few number of patients being managed in this way. Therefore, we do not know to what extent noninvasive mechanical ventilation might affect risk for stress ulcer bleeding, and we did not explore this further. However, future studies would be extremely valuable in examining whether and to what extent noninvasive ventilation puts one at risk for stress ulcer bleeding, because this could extend the use of SUP both within and beyond the realm of intensive care. Our hospital is not a trauma center, and so our exposure to the head trauma and burn patient populations, 2 risk factors for stress ulcer bleeding [28], was limited. Furthermore, our hospital is only a kidney transplant center, limiting our exposure to patients with liver failure and chronic steroid use. The lack of exposure to these risk factors limited our ability to more adequately explore associations between these minor risk factors and SUP use in our institution. This does not, however, affect the overall results of our study. We recognize that our community-based academic medical center has several features that might not apply to other centers. First, decisions for medications such as SUP and continuation of medications within transfer orders are often written by resident and not attending physicians and, at times, are not supervised by attending staff. Second, our order system at the time of data collection was still a written and not computer-based entry system, lacking computerized prompts that might remind us about the necessity or lack of ongoing necessity of certain treatments. Therefore, our results might not be generalizable to some larger Universitybased practices or smaller nonacademic community hospitals without house staff physicians. However, our practices are feasibly reflective of other similar hospitals across the country, and our findings suggest that other hospitals should be looking closely at their practices when it comes to SUP. In conclusion, our study highlights the important issue of SUP overuse in the ICU despite evidence-based knowledge of risk. Moreover, we have shown that patients are frequently continued on prophylactic treatment upon transfer out of the ICU and even upon discharge to home when no clear indication for continuation exists. Our findings argue for instituting measures to improve physician awareness in an attempt to both reduce the initial inpatient “overuse” of these medications and to prompt the discontinuation of SUP before
220 discharge from the hospital. Education alone is often not enough to correct such issues. We would advocate for a multifaceted approach that would involve pharmacists, nurses, and doctors and would include electronic order sets that require justification for initiation of SUP, for continuation on transfer orders, and that initiate regular prompts suggesting the consideration of discontinuation. Our future aims will explore the impact of instituting such measures on SUP use.
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Overuse of stress ulcer prophylaxis in the critical care setting and beyond Christopher P. Farrell DOa,⁎, Giancarlo Mercogliano MDb , Catherine L. Kuntz MD, MSa,c a
Department of Internal Medicine Residency Program, Annenberg Conference Center, Lankenau Hospital, Wynnewood, PA 19096, USA b Division of Gastrointestinal Medicine, Lankenau Hospital, Wynnewood, PA 19096, USA c Division of Pulmonary and Critical Care Medicine, Lankenau Hospital, Wynnewood, PA 19096, USA
Keywords: Stress ulcers; Prophylaxis; Proton pump inhibitors; Histamine 2 receptor antagonists; Coagulopathy
Abstract Background: Patients admitted to the intensive care unit (ICU) are susceptible to stress ulcers. We hypothesize that despite recommendations, stress ulcer prophylaxis (SUP) is still overused in the ICU and often continued after resolution of risk factors for bleeding. Methods: We retrospectively studied all ICU admissions for 4 months. Risk factors for stress ulcer bleeding were collected. Patients were categorized into 4 groups: (1) ≥1 major risk factor; (2) ≥1 minor risk factors; (3) no risk factors; (4) preadmission use of acid-suppressive medication. The rate of SUP was calculated by group during ICU stay, on transfer from the ICU, and at hospital discharge. Results: Two hundred ten patients were studied. Of all the ICU admissions, 87.1% received SUP. Among patients with no risk factors, 68.1% were placed on prophylaxis on ICU admission; 60.4% continued on treatment upon transfer from the ICU; 31.0% were discharged home on an agent without a new indication. Conclusions: Although judicious use of SUP in high-risk patients can decrease the incidence of gastrointestinal bleeding, inappropriate use may increase drug reactions, unnecessary hospital costs, and personal monetary burden. Our findings argue for improvement measures to reduce initial inpatient overuse of SUP and to prompt discontinuation before hospital discharge. © 2010 Elsevier Inc. All rights reserved.
1. Introduction Critically ill patients requiring admission to intensive care units (ICU) are at risk of developing gastrointestinal (GI) stress ulcers. Gastric ulcerations and erosions have been known to develop in such patients since the 1800s, and treatment with stress ulcer prophylaxis (SUP) became ⁎ Corresponding author. Tel.: +1 215 850 2575; fax: +1 610 645 8141. E-mail address: [email protected] (C.P. Farrell). 0883-9441/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.jcrc.2009.05.014
routine care in the 1980s [1]. Acid-suppressive medications (ASMs) used for this purpose include proton pump inhibitors (PPIs), histamine 2 receptor antagonists (H2 antagonists), and sucralfate, with PPIs gaining widespread use because of data suggesting superior safety and efficacy [2]. Stress ulcers have been shown to increase morbidity and mortality, with stress-related bleeding prolonging ICU stay between 4 and 8 days and increasing mortality up to 4-fold [1]. Evidence has illustrated that there is an increased risk for developing stress ulcers in patients with respiratory failure requiring mechanical ventilation for more than 48 hours
Stress ulcer prophylaxis in the critical care setting (odds ratio [OR], 15.6) and patients experiencing a coagulopathy (OR, 4.3) [1,3,4]. One multicenter observational study showed a number needed to treat 30 patients to prevent clinically important bleeding if one or both of these risk factors were present, compared with 900 patients in those considered low risk [4]. The use of SUP can lead to adverse reactions, drug-drug interactions, and increased hospital and prescription costs [5,6]. Links have been made between PPI use and Clostridium difficile infections; recent data suggest possible adverse outcomes when PPIs are used in conjunction with clopidogrel in patients with acute coronary syndrome; H2 antagonists have been linked to thrombocytopenia and nosocomial pneumonia [7,8,9,10,11]. Proton pump inhibitors and H2 antagonists interact with the cytochrome P-450 pathway and may result in important drug-drug interactions and affect absorption of various other medications by altering gastric pH [1]. Using SUP on general medical patients who have little to no risk at all for developing stress ulcers has been demonstrated in prior studies [12]. Previous analyses have attempted to delineate risk factors for stress ulcer bleeding among critically ill patients [1,4]. Standard of care regarding the use of SUP in the critical care setting is still limited by lack of universally accepted standardized guidelines for when to initiate and discontinue these medications, but knowledge of risk factors for SUP helps guide decision making. When providing ICU care, many intensivists believe patients should be risk stratified to determine whether to implement prophylaxis early enough to provide a benefit [13,14]. Our hypothesis was that SUP in our hospital's ICU is used excessively, even in the absence of clear risk factors, and, among this cohort, is often continued once risk factors have resolved. Our primary aim was to report (a) the rate of SUP use upon admission to the ICU among different risk categories, (b) the proportion of patients among different risk categories who remained on SUP upon transfer out of the ICU, and (c) the proportion of patients discharged from the hospital on SUP. Our secondary aim was to identify factors that were associated with use of SUP by physicians during ICU stay to explore reasons why decisions might be made to initiate SUP, sometimes even in the absence of clear risk factors.
2. Methods 2.1. Study population We conducted a retrospective study of all patients admitted to the ICU at a 331-bed community-based academic medical center from December 1, 2006, through March 31, 2007. Care is provided by medical and surgical residents and attending medical and surgical intensivists. The patient population includes all critically ill medical, surgical, and
215 cardiac patients within our hospital. Inclusion criteria were admission to the ICU in patients aged 16 years or older. Exclusion criteria included admission diagnoses of GI bleeding or bleeding within the first 24 hours because these diagnoses require treatment of disease rather than prophylaxis, new-onset gastroesophageal reflux disease (GERD) or esophagitis, treatment of an allergic reaction with an H2 antagonist, and withdrawal of care initiated upon admission. Subjects who were taking ASM before admission were examined separately.
2.2. Data collection Data collection was retrospective, which avoided treatment bias induced by physician awareness of the study hypothesis. Abstracted data included patient demographics, medical diagnoses, admission diagnosis, preadmission medications, and SUP treatment received in the ICU, throughout hospital stay, and upon discharge. The presence of risk factors for stress-related mucosal bleeding (Table 1) were recorded [1,4].
2.3. Statistical analysis Among our sample, we categorized patients into the following groups based on risk: (1) one or more major risk factors present; (2) no major but with one or more minor risk factors present; (3) no major or minor risk factors present; and (4) known GERD, peptic ulcer disease, Barrett's esophagus, or other conditions requiring outpatient acidsuppressive therapy (Table 2). Upon each transition of care (out of ICU to general hospital floors, from the hospital to home), patients were restratified based on risk. For our primary aim, the SUP rate was calculated for the entire cohort and for the groups stratified by risk. Rates of SUP were computed during ICU stay, upon transfer out of
Table 1
Major and minor stress ulcer risk factors
Major
Minor
Mechanical ventilation Coagulopathy b
Sepsis or severe hypotension a ARF c Hepatic failure d Severe head or spinal cord trauma History of GI bleeding Burns N35% of body surface area Major surgery N4 h High-dose corticosteroids e
Sessler, J.M., Cook, D.J., et al. a Systolic blood pressure b80 mm Hg. b International normalized ratio N1.5, partial thromboplastin time N2 times the upper limit of normal, or platelets b50 000. c Creatinine clearance b40 mL/min or serum creatinine N2.8 mg/dL. d Aspartate aminotransferase N500 U/L or total bilirubin N8.8 mg/dL. e Equivalent of N250 mg of hydrocortisone per day.
216
C.P. Farrell et al.
Table 2
Patient groups according to risk factors
Group
Major risk factors
Minor risk factors
1 2 3 4a
≥1 0 0 –
– ≥1 0 –
3. Results 3.1. Patient characteristics
a
Group 4: patients who were on a PPI, H2 antagonist, or sucralfate as an outpatient.
the ICU, and at time of discharge from the hospital and are reported with 95% confidence intervals (CIs). Discharge medications in group 4 patients who were on ASM before admission were examined upon release from the hospital to see if their discharge medication differed from their admission medication. For our secondary aim, we tested the following variables to see if they were associated with the use of SUP by physicians among patients not previously on ASM: sex, age, mechanical ventilation, coagulopathy, sepsis/shock, acute renal failure (ARF), and total number of minor risk factors present. Burns, head trauma, steroid use, and hepatic failure were not tested separately because of very small numbers in our study population. Age was not normally distributed and was tested as a categorical variable by decades. Each variable was tested to determine its association with SUP use in a univariate model. Binary and categorical variables were tested using χ2 and Fisher exact analysis. Ordered categorical variables were tested using χ2 test for trend. Continuous variables were tested using logistic regression methods. For each variable of interest, multivariable logistic regression modeling separately tested every other variable as a potential confounder of the relationship of interest. A variable was considered a confounder if adding that variable to the model changed the unadjusted OR for the variable of interest and the outcome (SUP) by 10% or more [15]. The final model included all variables with a P value of .2 or lower and all confounding variables. Statistical comparisons were performed using STATA version 8.0 (STATA Corp, College Station, Tex). This research was
Table 3 Risk stratification: during ICU admission, transfer to GMF, discharge from the hospital Group a
1 2 3 4
During ICU
Transfer ICU to GMF
Discharge from hospital
n = 210
n = 190
n = 185
n (%)
n (%)
n (%)
44 41 47 78
2 5 111 72
0 1 113 71
(21.0) (19.5) (22.4) (37.1)
(1.1) (2.6) (58.4) (37.9)
(0) (0.5) (61.1) (38.4)
Groups: 1, ≥1 major risk factor; 2, ≥1 minor risk factor; 3, no risk factors; 4, preadmission ASM. a
approved by the Institutional Review Board at the Lankenau Institute for Medical Research.
The total number of patients admitted to the ICU over the 4-month period was 241. Thirty-one patients were excluded; 27 for GI bleeding on admission or within the first 24 hours, 1 for acute esophagitis, 1 for acute GERD, 1 for angioedema/ allergic reaction, and 1 for immediate withdrawal of care. The median age of the 210 patients included was 61 years, and 51.9% were male. Stratification of groups based on risk factors is illustrated in Table 3 for patients during ICU stay, upon transfer from ICU to the general medical floor (GMF), and at discharge from the hospital. Patient characteristics are shown in Table 4.
3.2. Stress ulcer prophylaxis during ICU Of the 210 patients, 87.1% (95% CI, 81.8, 91.4) were placed on SUP during ICU stay. By risk factor groups, 95.5% of patients in group 1 (major risk factors), 82.9% of patients in group 2 (minor risk factors), 68.1% of patients in group 3 (no risk factors), and 96.2% of patients in group 4 (previous ASM use) were placed on SUP (Table 5).
3.3. Stress ulcer prophylaxis on transfer from ICU After attrition of ICU patients due to death (19) or hospital transfer (1), the total number of patients studied at the time of transfer out of ICU was 190. These patients Table 4 Characteristics of patients not previously on acidsuppressing medications before ICU admission
Age (mean) Sex, male VDRF present Coagulopathy present Sepsis/shock ARF Liver failure Head trauma History of GI bleeding Steroid use Surgery N4-h duration No. of major RF 0 1 2 RF indicates risk factors.
SUP not received
SUP received
n = 27 (12.9%)
n = 183 (87.1%)
54.5 ± 7.7 15 (62.5) 2 (8.3) 1 (4.2) 2 (8.3) 7 (29.2) 0 (0) 1 (4.2) 0 (0) 1 (4.2) 0 (0)
60.5 ± 3.8 52 (48.2) 37 (34.5) 13 (12.0) 21 (19.4) 40 (37.0) 6 (5.6) 2 (1.8) 1 (0.9) 12 (11.1) 4 (3.7)
22 (91.7) 1 (4.2) 1 (4.2)
66 (61.1) 34 (31.5) 8 (7.4)
Stress ulcer prophylaxis in the critical care setting Table 5 group Group a
Stress ulcer prophylaxis rate based on risk factor No. of prophylaxed
No. of patients total
During ICU 1 42 44 2 34 41 3 32 47 4 75 78 Total 183 210 Transfer out of the ICU 1 2 2 2 5 5 3 67 111 4 68 72 Total 142 190 Discharge from the hospital 1 0 0 2 1 1 3 35 113 4 61 71 Total 97 185
% prophylaxis (95% CI) 95.5 (84.5-99.4) 82.9 (67.9-92.8) 68.1 (52.9-80.9) 96.2 (89.2-99.2) 87.1 (81.8-91.4) 100.0 (0.96-1 b) 100.0 (0.96-1 b) 60.4 (50.6-69.5) 94.4 (86.4-98.5) 74.7 (67.9-80.7) 0.0 100.0 (0.25-1 b) 31.0 (22.6-40.4) 85.9 (75.6-93.0) 52.4 (45.0-59.8)
Patients separated by group placed on prophylaxis with a PPI, H2 antagonist, or sucralfate during ICU stay, transfer out of the ICU, and discharge from the hospital. a Groups: 1, ≥1 major risk factor; 2, ≥1 minor risk factor; 3, no risk factors; 4, preadmission ASM. b One-sided CIs.
were reevaluated in relation to their risk factors at transfer. Most risk factors for stress ulcer bleeding had resolved (Tables 3 and 5). Of the few patients with any remaining major or minor risk factors (groups 1 and 2), all were continued on SUP at transfer. Of the patients, 60.4% in Table 6
217 group 3 (no continuing risk factors) and 94.4% in group 4 were continued on medication (Table 5).
3.4. Stress ulcer prophylaxis upon hospital discharge One hundred eighty-five of 210 subjects survived to hospital discharge. At discharge, patients were again restratified based on risk factors (Tables 3 and 5). Ninetyseven (52.4%) of these 185 patients were sent home on SUP. Sixty-one of these patients discharged on medication were from group 4 and had been admitted on ASM. However, 36 patients who had not been on acid suppression at admission were sent home on ASM. Only one of these 36 had a single minor risk factor at the time of discharge (steroid dose equivalent to ≥250 mg of hydrocortisone per day). Of the patients who were not on any ASM on admission to the ICU and who possessed no risk factors at all at the time of discharge, 31.0% were discharged home on ASM. On chart review, none of these patients had developed a new indication for ASM during their hospitalization. Of the patients who came into the hospital on an ASM (group 4) and survived to hospital discharge, 85.9% were sent home on one of these medications. Of these patients, 14.1% had their medications discontinued before or at hospital discharge. Of this group, 31.3% was discharged on a different ASM than their admission medication.
3.5. Factors associated with SUP Univariate analysis was performed and is shown in Table 6. Age categorized by decades and number of minor risk factors were tested with the χ2 test for trend for ordered
Univariate analysis and multivariable logistic regression for factors associated with the use of SUP by physicians
VDRF Coagulopathy Sex (reference, male) Age Sepsis ARF Group 1 (ref 3) b (major RF vs no RF) Group 2 (ref 3) (minor RF vs no RF) Group 1 (ref 2) (major RF vs minor RF) Any major RF No. of minor RF
OR a (95% CI)
P
Adjusted OR
P
5.73 (1.28-25.72) 3.15 (0.39-25.30) 1.79 (0.72-4.45) 1.16 (0.92-1.45) 2.66 (0.58-12.19) 1.43 (0.55-3.74) 9.84 (2.10-46.17)
.023 .28 .21 .20 .21 .47 .004
5.31 (1.08-26.01) 1.30 (0.14-12.39) 1.78 (0.69-4.61) 1.16 (0.92-1.47) 1.58 (0.31-8.00) 0.90 (0.32-2.56) 9.20 (1.95-43.45)
.039 .82 .24 .21 .58 .84 .005 c
2.28 (0.82-6.31)
.11
2.09 (0.74-5.88)
.16 c
4.32 (0.84-22.18)
.08
7.00 (1.56-31.32) 1.88 (0.96-3.69)
.011 .065
5.76 (1.24-26.82) 1.40 (0.67-2.92)
.026 d .38 d
Age categorized by decades and number of minor risk factors were tested with χ2 test for trend for ordered categorical variables; P values were less than .20. RF indicates risk factors. a Odds ratios, reported from logistic regression modeling. b Group 1 in reference to group 3. c Controlled for age and sex only because other factors are collinear and define groups. d Adjusted model includes age, sex, any major risk factor, and number of minor risk factors.
218 categorical variables and by logistic regression, and ORs per increment are reported. Therefore, an OR of 1.16 for age suggests that for each 10-year increase above the age of 25 years, the odds of SUP use increased by 16% (P = .20). The only associations that achieved statistical significance for SUP use by physicians in univariate analysis were ventilatordependent respiratory failure (VDRF) or the presence of any major risk factor. All variables of interest tested were included in the multivariable model either because of a possible association with SUP use (P ≤ .2) in univariate analysis (VDRF, sex, and age) or because they were discovered to be confounders between the other variables of interest and the outcome (coagulopathy, sepsis, and ARF). Only the presence of VDRF retained a significant association with SUP use in multivariable modeling. A second model looked at risk factor groups as defined. In univariate analysis, group 1 with any major risk factor had a significantly higher odds of SUP than group 3 with no clear major or minor risk factor (OR, 9.84; P = .004); there was no significant difference in SUP use between groups 2 (minor risk factors) and 3 (no risk factors) (OR, 2.28; P = .11), nor between groups 1 (major risk factor) and 2 (minor risk factors) (OR, 4.32; P = .08). A multivariable model looked at risk factor groups adjusting for age and sex. Only group 1 had a higher odds of SUP prophylaxis (reference group 3; OR, 9.20; P = .005). A final model sought to explore whether the number of risk factors present was associated with SUP use. When adjusted for age and sex, only the presence of either major risk factor but not the number of minor risk factors was significantly associated with SUP use.
4. Discussion Current medical care is capable of decreasing the frequency of stress-related GI bleeding in the ICU. Prior studies have shown that routine use of SUP in most hospitals on non-ICU patients is often unnecessary and sometimes inappropriate [16,17]. In the ICU, SUP indications have been better defined by studies that identified high-risk patients who would benefit most. Still, current guidelines are often not definitive as to which patients without these major risk factors warrant prophylaxis. The Surviving Sepsis Campaign advocates SUP in severe sepsis, noting that many patients have a major risk factor (mechanical ventilation or coagulopathy) for stress ulcer bleeding; they acknowledge the lack of studies specific for sepsis [18]. The Eastern Association for the Surgery of Trauma recommends using SUP in traumatic brain injury, major burns, mechanical ventilation, and coagulopathy but recognizes that use for the former 2 categories is debatable [19]. The American Society of Health Systems Pharmacists created guidelines for SUP use from literature review, incorporating factors studied by Cook et al, stating that mechanical ventilation and coagulopathy are the only
C.P. Farrell et al. independent risk factors and that other conditions have not been well studied [20]. Therefore, although guidelines exist, with the exception of the 2 major risk factors, there is differing opinion as to what other risk factors, if any, should be the indications for SUP. In our hospital, the overall incidence of SUP upon admission to the ICU over this 4-month period was 87.1%. A good percentage of the treatment could be considered controversial. Postoperative patients have been shown to have a low frequency of clinically important bleeding and little improvement with prophylaxis [21]. Sepsis, shock, burns, steroid use, past episode of GI bleeding, and renal or hepatic failure have not shown enough significance in previous studies to definitively warrant prophylaxis as standard treatment, although this remains debatable [1,4]. These patients are often prophylaxed. Among our study population, 82.9% of patients with one or more of these risk factors received SUP. Furthermore, among the group with no identifiable risk factors for stress-related bleeding, 68.1% still received SUP. The potential benefit of SUP while in the ICU is felt to be substantial by some, whereas the downside is probably minor. Perhaps a greater issue arises when these medications are not discontinued later in the hospital course. In fact, 31.0% of patients not admitted on ASM were discharged on ASM despite having no new identifiable indications for use. Our study highlights the initial reaction to use particular medications under certain circumstances without recognizing the definitive indications. We go further to emphasize the downstream effect of continuation of these medications once they have been initiated. Patients who were on ASM as outpatients before admission were also studied. Of these patients, 14.1% were not sent home on ASM at all, and 31.3% of these patients were discharged home on a medication different from their admission medication. This exemplifies the importance of medicine reconciliation at discharge to avoid the use of incorrect medications or perhaps even the use of 2 ASMs, the medication on which the patient is discharged, and the medication that is waiting at home. Our study did not explore reasons why these medications changed, but most of these cases involved exchanging one PPI for another rather than crossing classes of medications. The major risk factors for the development of stress ulcers have been extensively studied in the past. Mechanical ventilation can lead to splanchnic hypoperfusion and subsequent gastric mucosal damage and ulceration; coagulopathy affects the body's ability to prevent and stop bleeding [22,23]. Therefore, we would expect that the presence of these major risk factors for stress ulceration would be associated with SUP use by our physicians. Our results show that most people (95.5%) with one or more of these 2 major risk factors received SUP during ICU stay. In our exploration of which patient variables were associated with SUP in the ICU, only the presence of either one of these 2 risk factors was significantly associated with SUP use in univariate and
Stress ulcer prophylaxis in the critical care setting in multivariable analysis. To this extent, our physicians are likely influenced by guidelines. Nevertheless, the fact that major risk factors were associated with SUP use among our physicians did not change the finding that SUP was still used in most patients without major and even without minor risk factors. Among these patients, none of the variables we examined, such as sex, age, or the total number of minor risk factors present were associated with SUP use. Because of the cross-sectional nature of our study, these are associations only and should not be interpreted as definitive predictors of physician behavior. However, one possible explanation for our findings is that simply being in the ICU alone is the factor that prompts initiation of treatment by many physicians rather than a process of risk stratification. Another possibility is that there are other variables involved in physician decision making to prophylax, which we did not capture. These medications do have downsides. Sucralfate is not systemically absorbed and has been known to decrease the absorption of other medications administered around the same time [1]. H2 antagonists can lead to ailments such as confusion, delirium, hallucinations, slurred speech, and thrombocytopenia [1,11,24]. H2 antagonists have been linked to an increase in nosocomial pneumonia while on mechanical ventilation, thought to be due to an increase in pH in the stomach allowing bacterial overgrowth and retrograde colonization of the pharynx [8,9]. Common adverse events from PPIs include diarrhea, nausea, vomiting, abdominal pain, and headaches [25]. Proton pump inhibitors have been shown to impair neutrophil activity and, hence, may affect the immune response [26]. A possible correlation between PPI use and C difficile infections has also been suggested but requires further investigation [10]. Our study did not specifically report on complications attributable to SUP because many of these reported adverse effects are common in the ICU, often resulting from illness rather than SUP use; because almost all of our population received SUP, making a comparison group very small; and because confounding by indication alone could account for more ventilator-associated pneumonia, thrombocytopenia, C difficile, and delirium in sicker patients who received SUP. Besides these medications posing health risks, there is also the issue of monetary burden on the hospital and the individual [5,6]. Cost-effective analysis in the hospital setting has shown a significant financial loss and overuse of resources [27]. For the individual after hospital discharge, depending on the drug and its class, the price for a month's supply can range from $15 to $200 for patients without a prescription plan. These examples support that these medications should not be distributed universally to all patients, can increase morbidity, and can have significant impact on cost when used in circumstances where they are not indicated. Our study has several limitations. We studied a small sample of 210 patients for just a 4-month period. Nevertheless, our results are impressive and suggest substantial
219 overuse of SUP within our hospital. A larger study over a longer period would better represent groups that were underrepresented in our population. A 4-month study period has potential to show different results depending on what period of the academic year we chose to study. We did select our 4-month study period during the latter half of the academic year to avoid reflecting the practices of new and less skilled intern and resident physicians. Furthermore, there are likely other additional factors for stress ulcer bleeding that have not been considered or proven in prior studies, which we also did not capture in our study. Among these is noninvasive ventilation with bilevel positive airway pressure as a measure of assisted ventilation, not studied in earlier analyses because of the relatively few number of patients being managed in this way. Therefore, we do not know to what extent noninvasive mechanical ventilation might affect risk for stress ulcer bleeding, and we did not explore this further. However, future studies would be extremely valuable in examining whether and to what extent noninvasive ventilation puts one at risk for stress ulcer bleeding, because this could extend the use of SUP both within and beyond the realm of intensive care. Our hospital is not a trauma center, and so our exposure to the head trauma and burn patient populations, 2 risk factors for stress ulcer bleeding [28], was limited. Furthermore, our hospital is only a kidney transplant center, limiting our exposure to patients with liver failure and chronic steroid use. The lack of exposure to these risk factors limited our ability to more adequately explore associations between these minor risk factors and SUP use in our institution. This does not, however, affect the overall results of our study. We recognize that our community-based academic medical center has several features that might not apply to other centers. First, decisions for medications such as SUP and continuation of medications within transfer orders are often written by resident and not attending physicians and, at times, are not supervised by attending staff. Second, our order system at the time of data collection was still a written and not computer-based entry system, lacking computerized prompts that might remind us about the necessity or lack of ongoing necessity of certain treatments. Therefore, our results might not be generalizable to some larger Universitybased practices or smaller nonacademic community hospitals without house staff physicians. However, our practices are feasibly reflective of other similar hospitals across the country, and our findings suggest that other hospitals should be looking closely at their practices when it comes to SUP. In conclusion, our study highlights the important issue of SUP overuse in the ICU despite evidence-based knowledge of risk. Moreover, we have shown that patients are frequently continued on prophylactic treatment upon transfer out of the ICU and even upon discharge to home when no clear indication for continuation exists. Our findings argue for instituting measures to improve physician awareness in an attempt to both reduce the initial inpatient “overuse” of these medications and to prompt the discontinuation of SUP before
220 discharge from the hospital. Education alone is often not enough to correct such issues. We would advocate for a multifaceted approach that would involve pharmacists, nurses, and doctors and would include electronic order sets that require justification for initiation of SUP, for continuation on transfer orders, and that initiate regular prompts suggesting the consideration of discontinuation. Our future aims will explore the impact of instituting such measures on SUP use.
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