Incidence, timing, and risk factors for development of gastrointestinal bleeding in acute traumatic spinal cord injury: A systematic review.

CONTEXT: Current guidelines recommend four weeks of stress ulcer prophylaxis following traumatic spinal cord injury. OBJECTIVES: Assess the current literature on the incidence, timing, and risk factors for gastrointestinal bleeding/clinically important gastrointestinal bleeding in the acute setting following a traumatic spinal cord injury and whether the use of stress ulcer prophylaxis has been shown to reduce the rates of gastrointestinal bleeding. METHODS: A systematic review was performed in PubMed, Embase, Web of Science, and Cochrane Library following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. RESULTS: A total of 24 articles met the inclusion/exclusion criteria. The average rate of gastrointestinal bleeding among all studies was 5.5% (95% CI = 5.4-5.6%; n = 26,576). The average rate of clinically important gastrointestinal bleeding was 1.8% (95% CI = 1.79-1.82%; n = 3,857). The mean time since injury to when gastrointestinal bleeding occurred ranged from 5 to 22.5 days. For clinically important gastrointestinal bleeding the average time was 16 days or less. Those with cervical injuries had a higher incidence of clinically important gastrointestinal bleeding compared to those with non-cervical injuries (2.7% vs. 0.7%). No study found any difference in the use of stress ulcer prophylaxis in participants with or without gastrointestinal bleeding. CONCLUSIONS: The overall incidence of clinically important gastrointestinal bleeding among studies was found to be low. Individuals with non-cervical injury were not found to be at high risk of clinically important gastrointestinal bleeding. There was also insufficient evidence to indicate that use of stress ulcer prophylaxis reduces the rate of gastrointestinal bleeding in those with traumatic spinal cord injury.

Stress Ulcer Prophylaxis in Mechanically Ventilated Patients With Acute Myocardial Infarction.

Background: Proton pump inhibitors (PPIs) and histamine type 2-receptor blockers (H2Bs) are commonly used for stress ulcer prophylaxis among patients requiring invasive mechanical ventilation (IMV). Recent studies suggest an increased mortality associated with PPIs compared to H2Bs, but these studies poorly represent patients with cardiovascular disease or acute myocardial infarction (AMI). Objectives: The aim of this study was to compare outcomes related to stress ulcer prophylaxis with PPIs compared to H2Bs in patients with AMI requiring IMV. Methods: We queried the Vizient Clinical Data Base for adults aged ≥18 years admitted between October 2015 and December 2019 with a primary diagnosis of AMI and requiring IMV. Using multivariable logistic regression, we assessed for the association between stress ulcer prophylaxis and in-hospital mortality. Results: Including 11,252 patients with AMI requiring IMV, 66.7% (n = 7,504) received PPIs and 33.3% (n = 3,748) received H2Bs. Age, sex, and the proportion of patients presenting with ST-segment elevation myocardial infarction or cardiogenic shock were similar between groups (all, P > 0.05). Compared to PPIs, patients receiving H2Bs had a lower mortality (41.5% vs 43.5%, P = 0.047), which was not statistically significant after multivariate adjustment (odds ratio 0.97; 95% confidence interval: 0.89-1.06, P = 0.49). In unadjusted and adjusted analyses, H2Bs use was associated with fewer ventilator days, less ventilator-associated pneumonia, and lower hospitalization cost but similar Clostridium difficile infections. Conclusions: Among patients with AMI requiring IMV in this observation cohort study, there was no difference in mortality among patients receiving H2Bs vs PPIs for stress ulcer prophylaxis despite fewer ventilator days and lower ventilator-associated pneumonia in those receiving H2Bs.

Effect of proton pump inhibitors versus histamine-2 receptor antagonists on acute kidney injury in septic patients at high risk for developing stress ulcers.

BACKGROUND: To compare the effects of proton pump inhibitor (PPI) and histamine-2 receptor antagonist (H2RA) use on the occurrence of acute kidney injury (AKI) in septic patients at high risk for developing stress ulcers. METHODS: Using the Medical Information Mart for Intensive Care IV version 2.2 database, septic patients with high-risk factors for stress ulcers (i.e., shock, coagulopathy, invasive mechanical ventilation, or chronic liver diseases) were included. Exposures included PPIs and H2RAs within 24 h of intensive care unit (ICU) admission or prior to ICU admission. The primary end point was severe sepsis-associated AKI as defined by the Kidney Disease Improving Global Outcomes criteria stage 3 (KDIGO-3). Propensity score matching (PSM) was performed to balance baseline characteristics. Multivariable Cox proportional hazards regression was used to estimate the effect size. RESULTS: 4731 PPI users and 4903 H2RA users were included. After PSM, there were 1785 pairs exposed to PPIs and H2RAs. In the PSM cohort, the cumulative incident KDIGO-3 rate was higher in the PPI group than in the H2RA group (log-rank test, p = 0.009). Regression analyses showed that PPI exposure [adjusted hazard ratio 1.32, 95% confidence interval (CI) 1.11-1.58, p = 0.002] was associated with incident KDIGO-3 compared with H2RA use. This association remained consistent in sensitivity analyses. Additionally, the PPI group had a higher need for kidney replacement therapy compared with the H2RA group (3.6% vs. 2.1%, P = 0.012). CONCLUSIONS: Among septic patients at high risk for developing stress ulcers, PPI exposure was associated with incident KDIGO-3 AKI compared with H2RA use.

Proton pump inhibitors for gastrointestinal bleeding prophylaxis in critically ill patients: A systematic review protocol.

BACKGROUND: Proton pump inhibitors (PPIs) are the most commonly prescribed drugs for preventing upper gastrointestinal bleeding in critically ill patients. However, concerns have arisen about the possible harms of using PPIs, including potentially increased risk of pneumonia, Clostridioides difficile infection, and more seriously, an increased risk of death in the most severely ill patients. Triggered by the REVISE trial, which is a forthcoming large randomized trial comparing pantoprazole to placebo in invasively mechanically ventilated patients, we will conduct this systematic review to evaluate the efficacy and safety of PPIs versus no prophylaxis for critically ill patients. METHODS: We will systematically search randomized trials that compared gastrointestinal bleeding prophylaxis with PPIs versus placebo or no prophylaxis in adults in the intensive care unit (ICU). Pairs of reviewers will independently screen the literature, and for those eligible trials, extract data and assess risk of bias. We will perform meta-analyses using a random-effects model, and calculate relative risks for dichotomous outcomes and mean differences for continuous outcomes, and the associated 95% confidence intervals. We will conduct subgroup analysis to explore whether the impact of PPIs on mortality differs in more and less severely ill patients. We will assess certainty of evidence using the GRADE approach. DISCUSSION: This systematic review will provide the most up-to-date evidence regarding the merits and limitations of stress ulcer prophylaxis with PPIs in critically ill patients in contemporary practice.

Assessment of the appropriateness of stress ulcer prophylaxis use and its determinants among admitted surgical patients at Debre Berhan University Hakim Gizaw Hospital, Ethiopia. A hospital-based cross-sectional study.

Introduction: Pharmacological stress ulcer prophylaxis (SUP) has been recommended for many years to reduce the risk of clinically significant upper gastrointestinal (GI) bleeding caused by stress ulcers (SUs). Stress-related ulcer bleeding in surgical patients significantly increases morbidity and mortality. Therefore, preventing stress-induced hemorrhage is the most appropriate measure for patients who are at increased risk. However, the inappropriate use of SUP has increased in recent years, and its use in Ethiopian surgical patients has not been well studied. Objective: The aim of this study was to assess the appropriateness of SUP use and its determinants among admitted surgical patients at Debre Berhan University Hakim Gizaw Hospital (DBUHGH), Ethiopia. Methods: We randomly selected 230 patients from the whole cross-sectional group of all surgical patients at DBUHGH from 1 February to 30 June 2023. The risk of stress ulcer (SU) development was assessed using the modified American Society of Health-System Pharmacists (ASHP) guidelines. For data analysis, we used SPSS version 25. Results: The mean age of study participants was 47.2 years (SD ± 20.4), and out of the total of 230, 130 (56.5%) were women. Approximately 66% of study participants took inappropriate SUP based on ASHP guidelines criteria. The most commonly used drug class for SUP was histamine-2 receptor blockers 115 (50%). Study participants who have a Charlson Comorbidity Index Score of moderate and GI bleeding have been significantly associated with the inappropriate use of SUP. Conclusion: In our study, inappropriate SUP use was common in the surgical ward of DBUHGH. This may be an area that requires further and more focused working together among clinical pharmacists and medical professionals in an institution-specific SUP protocol that aids clinicians in identifying appropriate candidates for SUP medication.

Assessment of adherence to the national stress ulcer prophylaxis guidelines: A cross-sectional analysis.

Background: Clinical guidelines support the use of stress ulcer prophylaxis (SUP) in patients at risk of gastrointestinal (GI) bleeding such as those with coagulopathy, renal replacement therapy, and mechanical ventilation. Despite the observed benefits of SUP, its overuse has been highly associated with serious adverse effects. Objective: To assess the adherence to the national SUP guidelines in a tertiary hospital in Saudi Arabia. Methods: A cross-sectional study was conducted using electronic health records at King Fahad Specialist Hospital (KFSH), Buraydah, Saudi Arabia. We collected the data from January 1st to December 31st, 2020. Adult patients aged 18 and older who received SUP prescriptions were included. Descriptive analysis was performed to assess the adherence to the guidelines and to explore the factors associated with SUP use in a hospital-based setting. Results: A total of 424 patients were enrolled in this study. The median age of patients was 55.2 years old. Only 54% of patients were candidates for SUP. Internal medicine and surgery wards ranked the highest in prescribing SUP at 34.2% and 30.4%, respectively. The most common major criterion to start SUP was the concomitant use of two or more of these medications (anticoagulants, aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and antidepressants) followed by using NSAIDs or corticosteroids by older adult patients aged (≥65 years) or have GI bleeding history at 43.2% and 21.5%, respectively. Conclusion: The observed overuse of anti-ulcer drugs (AUD) indicates a need for greater adherence to SUP guidelines. Areas of improvement can be implemented to ensure appropriate adherence to SUP guidelines to control the costs and avoid unnecessary anti-ulcer-related adverse effects.

Impact of a multifaceted intervention on non-guideline-recommended prescribing of acid suppressive medications for stress ulcer prophylaxis in critically ill patients.

OBJECTIVE: To promote an effective strategy to improve the non-guideline-recommended prescribing (NGRP) of acid suppressive medications for stress ulcer prophylaxis (SUP) in critically ill patients and to evaluate the impact and barriers of a multifaceted intervention on NGRP in critically ill patients. RESEARCH DESIGN AND METHODS: A retrospective, pre- post-intervention study was performed in the medical-surgical ICU. This study included pre-intervention and post-intervention period. There was no SUP guideline and intervention in the pre-intervention period. In the post-intervention period, the multifaceted intervention included five features: a practice guideline, an education campaign, medication review and recommendations, medication reconciliation, and pharmacist rounding with the ICU team. RESULTS: A total of 557 patients were studied (305 in the pre-intervention group and 252 in the post-intervention group). Patients who underwent surgery, stayed in ICU more than 7 days, or used corticosteroids experienced significantly higher rate of NGRP in the pre-intervention group. The average percentage of patient days of NGRP was significantly reduced from 44.2% to 23.5% (p < .001) by implementing the multifaceted intervention. The percentage of patients with NGRP decreased from 86.7% to 45.5% in terms of all 5 criteria (indication, dosage, IV to PO, duration, and ICU discharge; p = .003). Per-patient NGRP cost decreased from $45.1 (22.6, 93.0) to $11.3 (11.3, 45.1; p = .004). The main barrier influencing NGRP was the factors of the patient, including the concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs), the number of comorbidities, and undergoing surgery. CONCLUSION: The multifaceted intervention was effective in improving NGRP. Further studies are needed to confirm whether our strategy is cost-effective.

Overuse of Intravenous Proton Pump Inhibitors in General Medicine and Surgery Wards.

BACKGROUND: Overuse of stress ulcer prophylaxis is prevalent globally despite guidelines leading to the added cost, especially the intravenous proton pump inhibitor (IVPPI). This study aims to analyze the prevalence of such overuse and be aware of rational use which may help develop local guidelines. METHODS: This study analyzed the prospectively collected data on IVPPI use in adult patients in general wards of medicine and surgery at Patan Hospital, Patan Academy of Health Sciences, Nepal, from April-Jun 2022. Ethical approval was obtained. Variables analyzed were the patient's age, gender, history of peptic ulcer disease, risk for stress ulcer and gastrointestinal bleeding, the status of nil per os (NPO ≥12 hours), appropriate use of IVPPI, and cost. RESULTS: Prevalence of IVPPI use was 36.24% (274/756 admissions), surgery 39.45(189/479), medicine ward 30.68% (85/277). The mean age was 43.1 ±18.6 years, males 113(41.2%), surgery 189 (69%). Inappropriate overuse in 253(92.3%, significantly more in surgery-182 than medicine-7, p=0.001. Appropriate use was in 21 (7.7%, i.e., NPO-15, NPO + gastrointestinal bleed, and NPO + non steroid anti-inflammatory drugs each 3). CONCLUSIONS: Prevalence of IVPPI use was 36.24%. Inappropriate overuse of IVPPI was high (92.2%, 253/274), more in surgery. The nil per os status was the main reason for appropriate use of IVPPI.

Age-to-Glasgow Coma Scale score ratio predicts gastrointestinal bleeding in patients with primary intracerebral hemorrhage.

Objective: Recent clinical studies have demonstrated that advanced age and low initial Glasgow Coma Scale (GCS) score were independent predictors of gastrointestinal bleeding (GIB) in patients with primary intracerebral hemorrhage (ICH). However, used singly, age and GCS score have their respective shortcomings in predicting the occurrence of GIB. This study aimed to investigate the association between the age-to-initial GCS score ratio (AGR) and the risk of GIB following ICH. Methods: We conducted a single-center, retrospective observational study of consecutive patients presenting with spontaneous primary ICH at our hospital from January 2017 through January 2021. Patients who fulfilled the inclusion and exclusion criteria were categorized into GIB and non-GIB groups. Univariate and multivariate logistic regression analyses were implemented to identify the independent risk factors for the occurrence of GIB, and a multicollinearity test was performed. Furthermore, one-to-one matching was conducted to balance important patient characteristics by the groups' propensity score matching (PSM) analysis. Results: A total of 786 consecutive patients fulfilled the inclusion/exclusion criteria for the study, and 64 (8.14%) patients experienced GIB after primary ICH. Univariate analysis revealed that patients with GIB were significantly older [64.0 (55.0-71.75) years vs. 57.0 (51.0-66.0) years, p = 0.001] and had a higher AGR [7.32 (5.24-8.96) vs. 5.40 (4.31-7.11), p < 0.001] and a lower initial GCS score [9.0 (7.0-11.0) vs. 11.0 (8.0-13.0), p < 0.001]. The multicollinearity test revealed that no multicollinearity was observed in the multivariable models. Multivariate analysis showed that the AGR was a significant independent predictor of GIB [odds ratio (OR) 1.155, 95% confidence interval (CI) 1.041-1.281, p = 0.007], as well as prior anticoagulation or antiplatelet therapy (OR 0.388, 95% CI 0.160-0.940, p = 0.036) and MV used >24 h (OR 0.462, 95% CI 0.252-0.848, p = 0.013). Receiver operating curve (ROC) analysis illustrated that the optimal cutoff value for the AGR as a predictor for GIB in patients with primary ICH was 6.759 [the area under the curve (AUC) was 0.713 with a corresponding sensitivity of 60.94% and specificity of 70.5%, 95% CI 0.680-0.745, p < 0.001]. After 1:1 PSM, the matched GIB group had significantly higher AGR levels compared with the matched non-GIB group [7.47(5.38-9.32) vs. 5.24(4.24-6.40), p <0.001]. The ROC analysis indicated an AUC of 0.747 (the sensitivity was 65.62%, and the specificity was 75.0%, 95% CI 0.662-0.819, p < 0.001) for AGR levels as an independent predictor of GIB in patients with ICH. In addition, AGR levels were statistically correlated with unfunctional 90-day outcomes. Conclusion: A higher AGR was associated with an increased risk of GIB and unfunctional 90-day outcomes in patients with primary ICH.

Associations between enteral nutrition and outcomes in the SUP-ICU trial: Protocol for exploratory post hoc analyses.

Critically ill patients are at risk of gastrointestinal (GI) bleeding. Counter measures to minimise this risk include the use of pharmacological stress ulcer prophylaxis (SUP). The effect of enteral nutrition as SUP on GI bleeding event rates is unknown. There are conflicting data describing the effect of co-administration of enteral nutrition with pharmacological SUP, and there is substantial variation in practice. We aim to conduct an exploratory post hoc analysis to evaluate the association of enteral nutrition with clinically important GI bleed rates in ICU patients included in the SUP-ICU trial, and to explore any interactions between enteral nutrition and pharmacologic SUP on patient outcomes. The SUP-ICU trial dataset will be used to assess if enteral nutrition is associated with the outcomes of interest. Extended Cox models will be used considering relevant competing events, including treatment allocation (SUP or placebo) and enteral nutrition as a daily time-varying covariate, with additional adjustment for severity of illness (SAPS II). Results will be presented as adjusted hazard ratios for treatment allocation and enteral nutrition, and for treatment allocation and enteral nutrition considering potential interactions with the other variable, all with 95% confidence intervals and p-values for the tests of interaction. All results will be considered as exploratory only. This post hoc analysis may yield important insights to guide practice and inform the design of future randomised clinical trial investigating the effect of enteral nutrition on GI bleeding.

Stress ulcer prophylaxis in critically ill adult patients with sepsis at risk of gastrointestinal bleeding: a retrospective cohort study.

BACKGROUND: The Surviving Sepsis Campaign Guidelines recommend stress ulcer prophylaxis (SUP) for patients with sepsis who have gastrointestinal (GI) bleeding risks; however, the effect of SUP has not been specially studied in these patients. AIMS: To determine the effects of SUP versus no prophylaxis on patient-important outcomes in critically ill adult patients with sepsis who have risk factors for GI bleeding. METHODS: This retrospective cohort study utilised data from the Medical Information Mart for Intensive Care III database. We compared those who received SUP with proton-pump inhibitors or histamine-2 receptor antagonists for ≥3 days with those who received no prophylaxis. Propensity score matching (PSM) was conducted to make comparisons between groups with similar distributions of study variables. The primary outcome was inhospital mortality. RESULTS: A total of 7744 patients were included in the analysis, with 1088 (14.0%) in the non-SUP group and 6656 (86.0%) in the SUP group. A 1:1 PSM created 866 patients in each cohort. No significant differences were noted between the two groups with regard to inhospital mortality (22.3% vs 20.4%; P = 0.379), GI bleeding (4.7% vs 6.4%; P = 0.172), pneumonia (38.9% vs 36.6%; P = 0.346), Clostridium difficile infection (CDI) (6.4% vs 8.9%; P = 0.0.057) or intensive care unit (ICU) length of stay (LOS) (4.2 days vs 4.6 days; P = 0.394). CONCLUSIONS: Among critically ill, septic, adult patients at risk for GI bleeding, SUP showed no effect on hospital mortality, the rate of GI bleeding, pneumonia, CDI and ICU LOS.

CYP2C19 Gene Profiling as a Tool for Personalized Stress Ulcer Prophylaxis With Proton Pump Inhibitors in Critically Ill Patients - Recommendations Proposal.

To this date, there are no recommendations for personalized stress ulcer prophylaxis (SUP) in critical care that would take the patient's individual genetic predispositions into account. Of drugs used for this purpose, proton pump inhibitors (PPIs) are the first-choice drugs in intensive care unit patients. The degradation of proton pump inhibitors is mediated by cytochrome P450 (CYP) enzymes; in particular, CYP2C19 and, to a lesser extent, CYP3A4 are involved. Expression and metabolic activity of, namely in, CYP2C19 is significantly affected by single nucleotide polymorphisms, the drug metabolization rate varies greatly from ultrarapid to poor and likely influences the optimal dosage. As these CYP2C19 predictive phenotypes via CYP2C19 haplogenotypes (rs12248560/rs4244285) can be relatively easily determined using the current standard equipment of hospital laboratories, we prepared a set of recommendations for personalized PPI-based stress ulcer prophylaxis taking into account the patient's CYP2C19 predictive phenotype determined in this way. These recommendations are valid, in particular, for European, American and African populations, because these populations have the high representations of the CYP2C19*17 allele associated with the overexpression of the CYP2C19 gene and ultrarapid degradation of PPIs. We propose the CYP2C19 gene profiling as a tool for personalized SUP with PPI in critically ill patients.

Impact of Stress Ulcer Prophylaxis Discontinuation Guidance in Mechanically Ventilated, Critically Ill Patients: A Pre-Post Cohort Study.

Purpose: Recent data highlight unclear efficacy and potential negative sequelae of stress ulcer prophylaxis (SUP) in the intensive care unit (ICU). Minimizing SUP exposure has pertinent clinical and other implications. This study assessed medication use and clinical outcomes before and after implementation of a practice guideline promoting early discontinuation of SUP in mechanically ventilated ICU patients. Methods: Retrospective, single-center, pre-post cohort study within a medical ICU at a large, academic medical center. Adult patients requiring mechanical ventilation and receiving SUP via a histamine-2 receptor antagonist (H2RA) or proton pump inhibitor (PPI) were eligible for inclusion. The clinical practice guideline was implemented on January 1, 2020. The impact of implementation was assessed via percent of patient-days with inappropriate SUP. Incidence of clinically important GI bleed was the primary safety outcome. Results: A total of 137 pre-guideline and 112 post-guideline patients were included. Comorbidity burden was similar between groups. A higher prevalence of baseline vasopressor receipt (39% vs 67%, P < .01) and acute kidney injury (56% vs 69%, P = .04) was observed in post-guideline patients. Post-guideline patients experienced a significantly lower percentage of patient-days of inappropriate SUP (25% vs 50%, P < .01) as well as higher rates of SUP discontinuation before extubation (71% vs 12%, P < .01) and during ICU stay (93% vs 50%, P < .01). Post-guideline patients observed a significantly lower incidence of SUP at hospital discharge (4% vs 35%, P < .01). No differences in bleeding outcomes were observed, though post-guideline patients experienced longer durations of mechanical ventilation, ICU stay, and hospital stay. Conclusions: Implementation of an early SUP discontinuation guideline was associated with significant improvements in SUP prescribing practices. Baseline differences between groups likely explain observed differences in clinical outcomes.

Appropriateness and Associated Factors of Stress Ulcer Prophylaxis for Surgical Inpatients of Orthopedics Department in a Tertiary Hospital: A Cross-Sectional Study.

Background: Stress ulcer prophylaxis (SUP) prescribed in patients admitted to surgical wards with a low risk of stress-related mucosal disease (SRMD) accounted for a considerable proportion of improper use of proton pump inhibitors (PPIs). This study aimed to analyze the appropriateness of SUP prescribing patterns and identify its associated factors in the orthopedics department of a tertiary hospital in the Northwestern China. Methods: In this cross-sectional study, information regarding the demographic and clinical characteristics of 1,200 fracture inpatients who underwent surgical operations from January 2020 to August 2021 were collected from medical records. Established criteria were used to assess the appropriateness of the prescribing pattern for SUP, and the incidence of inappropriate SUP medication was calculated. Logistic regression analyses were used to identify factors associated with inappropriate SUP medication. Results: Approximately, 42.4% of the study population was interpreted as inappropriate prescription of SUP. A total of 397 (33.1%) patients received SUP without a proper indication (overprescription), and the incidence of inappropriate SUP medication was calculated to be 43.11 per 100 patient-days. In addition, 112 (9.3%) inpatients for whom SUP was indicated did not receive SUP (underprescription). PPIs were prescribed in 96.1% of the inpatients who used acid suppression therapy (AST), and intravenous PPIs accounted for 95.3% thereof. In a multivariate logistic regression analysis, age above 65 years and prolonged hospitalization were associated with overprescription of SUP. Increased number of drugs excluding PPIs, the concurrent use of systemic corticosteroids, comorbidity of hypertension, and unemployed or retired status in inpatients were associated with a reduced likelihood of overprescription for SUP. Conversely, prolonged hospitalization, the concurrent use of systemic corticosteroids or anticoagulants, and unemployed status in inpatients were positively associated with underprescription of SUP. Conclusion: There was a high prevalence of inappropriate SUP prescription among noncritically ill inpatients of fracture who underwent surgical operations. We delineated the associated factors with inappropriate SUP medication, which indicated that more information was required for clinicians about rationality and efficiency of their prescribing practices. Effective intervention strategies should be executed by clinical pharmacists to reduce improper SUP medication.

Prophylactic acid suppressants in patients with primary neurologic injury: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Neurocritical care patients are at risk of stress-induced gastrointestinal ulceration. We performed a systematic review and meta-analysis of stress ulcer prophylaxis (SUP) in critically ill adults admitted with a primary neurologic injury. MATERIALS AND METHODS: We included randomized controlled trials (RCTs) comparing SUP with histamine-2-receptor antagonists (H2RAs) or proton pump inhibitors (PPIs) to placebo/no prophylaxis, as well as to each other. The primary outcome was in-ICU gastrointestinal bleeding (GIB). Predefined secondary outcomes were all-cause 30-day mortality, ICU length of stay (LOS), nosocomial pneumonia, and other complications. RESULTS: We identified 14 relevant trials enrolling 1036 neurocritical care patients; 11 trials enrolling 930 patients were included in the meta-analysis. H2RAs resulted in a lower incidence of GIB as compared to placebo or no prophylaxis (Risk ratio [RR] 0.42, 95% CI 0.30-0.58; p < 0.001); PPIs with a lower risk of GIB compared to placebo/no prophylaxis (RR 0.37, 95% CI 0.23-0.59; p < 0.001). No significant difference was observed in GIB comparing PPIs with H2RAs (RR 0.53, 95% CI 0.26-1.06; p = 0.07; I2 = 0%). CONCLUSIONS: In neurocritical care patients, the overall high or unclear risk of bias of individual trials, the low event rates, and modest sample sizes preclude strong clinical inferences about the utility of SUP.

Efficacy and safety of proton pump inhibitors versus histamine-2 receptor blockers in the cardiac surgical population: insights from the PEPTIC trial.

OBJECTIVES: The comparative effectiveness and safety of proton pump inhibitors (PPIs) versus histamine-2 receptor blockers for stress ulcer prophylaxis in the cardiac surgical intensive care unit population is uncertain. Although the Proton Pump Inhibitors versus Histamine-2 Receptor Blockers for Ulcer Prophylaxis Therapy in the Intensive Care Unit (PEPTIC) trial reported a higher risk of mortality in the PPI arm with no difference in gastrointestinal bleeding, detailed information on surgical variables and clinically relevant surgical subgroups was not available. METHODS: The analysis included all Canadian cardiac surgery patients enrolled in the PEPTIC trial. Data were electronically linked using unique patient identifiers to a clinical information system. Outcomes of interest included in-hospital mortality, gastrointestinal bleeding, Clostridium difficile infections, ventilator-associated conditions and length of stay. RESULTS: We studied 823 (50.6%) randomized to PPIs and 805 (49.4%) to histamine-2-receptor blockers. In the intention-to-treat analysis, there were no differences in hospital mortality [PPI: 4.3% vs histamine-2 receptor blockers: 4.8%, adjusted odds ratio (aOR) 0.97, 95% confidence interval (CI) 0.55-1.70], gastrointestinal bleeding (3.9% vs 4.8%, aOR 1.09, 95% CI 0.66-1.81), C. difficile infections (0.9% vs 0.1%, aOR 0.18, 95% CI 0.02-1.59), ventilator-associated conditions (1.6% vs 1.7%, aOR 0.92, 95% CI 0.85-1.00) or median length of stay (9.2 vs 9.8 days, adjusted risk ratio 1.06, 85% CI 0.99-1.13). No significant treatment differences were observed among subgroups of interest or per-protocol populations. CONCLUSIONS: In a secondary analysis of cardiac surgery patients enrolled in the PEPTIC trial in Canada, no differences in effectiveness or safety were observed between use of PPIs and histamine-2 receptor blockers for stress ulcer prophylaxis. CLINICAL TRIAL REGISTRATION NUMBER: anzctr.org.au identifier: ACTRN12616000481471.

The effects of pantoprazole vs. placebo on 1-year outcomes, resource use and employment status in ICU patients at risk for gastrointestinal bleeding: a secondary analysis of the SUP-ICU trial.

PURPOSE: Patients in intensive care units (ICUs) are at risk of stress-related gastrointestinal (GI) bleeding and stress ulcer prophylaxis (SUP), including proton pump inhibitors, is widely used in the attempt to prevent this. In this secondary analysis of Stress Ulcer Prophylaxis in Intensive Care Unit (SUP-ICU) trial, we assessed 1-year outcomes in the pantoprazole vs. placebo groups. METHODS: In the SUP-ICU trial, 3298 acutely admitted ICU patients at risk of GI bleeding were randomly allocated, stratified for site, to pantoprazole or placebo. In this secondary analysis, we assessed clinically important GI bleedings in ICU and 1-year mortality, health care resource use (e.g. readmission with GI bleeding, use of home care and general practitioner), health care costs, and employment status for the Danish participants using registry data. RESULTS: Among the 2099 Danish participants, 2092 had data in the registries; 1045 allocated to pantoprazole and 1047 to placebo. The number of clinically important GI bleedings in ICU was 1.9 percentage points [95% CI 0.3-3.5] lower in the pantoprazole group vs. the placebo group, but none of the 1-year outcomes differed statistically significantly between groups, including total health care costs (€1954 [- 2992 to 6899]), readmission with GI bleeding (- 0.005 admissions [- 0.016 to 0.005]), 1-year mortality (- 0.013 percentage points [- 0.051 to 0.026]), and employment (- 0.178 weeks [- 0.390 to 0.034]). CONCLUSION: Among ICU patients at risk of GI bleeding, pantoprazole reduced clinically important GI bleeding in ICU, but this did not translate into a reduction in 1-year mortality, health care resource use or improvements in employment status.

Indications for the Use of Proton Pump Inhibitors for Stress Ulcer Prophylaxis and Peptic Ulcer Bleeding in Hospitalized Patients.

Proton pump inhibitors are widely used throughout the world for the treatment of gastrointestinal disorders that are related to acid secretion, such as peptic ulcer disease and dyspepsia. Another common indication for proton pump inhibitors is stress ulcer prophylaxis. Proton pump inhibitors have proven efficacy for the treatment of acid-related gastrointestinal disorders, but there is concern that their use may be associated with the development of significant complications, such as fractures, Clostridium difficile infection, acute kidney injury, chronic kidney disease, and hypomagnesemia. Proton pump inhibitors are overused in the hospital setting, both for stress ulcer prophylaxis and gastrointestinal bleeding, and then they are often inappropriately continued after discharge from the hospital. This narrative review article outlines the evidence surrounding appropriate proton pump inhibitor use for stress ulcer prophylaxis and peptic ulcer bleeding.

Are Proton Pump Inhibitors More Effective Than Histamine-2-Receptor Antagonists for Stress Ulcer Prophylaxis in Critically Ill Patients? A Systematic Review and Meta-Analysis of Cohort Studies.

BACKGROUND: Histamine-2-receptor antagonists (H2RAs) have been largely replaced by proton pump inhibitors (PPIs) for stress ulcer prophylaxis (SUP) despite the inconclusive evidence concerning comparative effectiveness. OBJECTIVE: To compare the effectiveness of PPIs and H2RAs on SUP in real-world setting. METHODS: PubMed, Embase, and the Cochrane Library were searched from inception to September 19, 2021. We included cohort studies comparing PPIs with H2RAs in critically ill adult patients and explicitly reporting the outcome of gastrointestinal (GI) bleeding or mortality. Newcastle-Ottawa Scale was used to assess potential risk of bias. We conducted a random-effects meta-analysis and only the studies with adjusted effect estimates were pooled. The Grading of Recommendations Assessment, Development, and Evaluation system was used to assess the overall quality of the evidence. RESULTS: Thirteen cohort studies (N = 145 149) were eligible and 11 of them available for full texts were of low to moderate risk of bias. Meta-analysis of adjusted effect estimates indicated that PPIs were associated with a significantly higher risk of GI bleeding, compared with H2RAs (8 studies, odds ratio [OR] = 1.98, 95% confidence interval [CI] = 1.30-3.01, low certainty). Post hoc pooling analysis also suggested that PPIs were associated with a slightly higher risk of mortality in comparison with H2RAs (7 studies, OR = 1.27, 95% CI = 1.13-1.42, low certainty). CONCLUSION AND RELEVANCE: The systematic review of cohort studies showed that PPIs were associated with higher risks of GI bleeding and mortality, although the certainty of evidence was low. Overall, we suggest not excluding H2RAs for SUP, while further studies are essential for elucidating the risk stratification, optimal regimen, and specific duration.