To evaluate the efficacy of intravenous pantoprazole as a stress ulcer prophylaxis in sick children to prevent gastrointestinal (GI) bleeding.

A randomized controlled trial included children aged one-month to 18 years requiring intensive care. Participants were randomly assigned to receive intravenous pantoprazole or a placebo (normal saline) daily. The primary outcome was the incidence of GI bleeding (clinically significant or overt). Secondary outcomes were the median time of onset of GI bleeding, incidence of ventilator-associated pneumonia (VAP), duration of hospitalization, organ dysfunction scores, and all-cause mortality.

A total of 151 and 150 children were allocated to group A (pantoprazole) and group B (placebo), respectively. No significant difference was observed in the incidence of GI bleeding between the groups (group A: 21/151 vs group B: 19/150 [RR (95% CI) 1.03 (0.18, 5.82), P = 0.985]. Comparable results were observed for clinically significant GI bleeding (1.3% vs 0.6%; RR (95% CI) 0.54 (0.21, 1.28); P = 0.653 and overt GI bleeding [12.6% vs 12%; RR (95% CI) 0.98 (0.39, 2.23); P value = 0.313]. On multivariate analysis, there was a reduced incidence of GI bleeding in children with coagulopathy in pantoprazole group (n = 29) as compared to placebo (n = 25) [RR (95%CI) 0.52 (0.32, 0.87); P = 0.022].

Among critically ill children, pantoprazole prophylaxis did not reduce the incidence of gastrointestinal bleeding, although, a notable decrease in gastrointestinal bleeding was observed in children with coagulopathy.

Clinical Trials Registry of India, Ref no: CTRI/2021/08/035785, Date of registration:18th August 2021.

Gastric perforation is a serious yet rare complication in critically ill patients on mechanical ventilation and GI prophylaxis. This report highlights an unexpected gastric perforation in a patient with a negative barium swallow study while receiving GI prophylaxis during intubation. A 65-year-old male with COPD and tobacco use disorder was treated with Oseltamivir for Influenza A infection, intubated for acute respiratory failure, and received IV pantoprazole for GI prophylaxis. After extubation and an unremarkable barium swallow study, he developed abdominal pain and tachycardia. Imaging showed free air under the diaphragm, and a CT scan indicated gastrointestinal perforation. Emergency surgery confirmed an anterior gastric ulcer perforation with purulent peritonitis. He was successfully treated with a washout and antibiotics and was discharged in stable condition. This case underscores the necessity of vigilance for abdominal symptoms and the potential for gastric perforation in critically ill patients despite GI prophylaxis, highlighting the importance of recognizing early signs of pneumoperitoneum.

Serotonin reuptake inhibitor (SRI) antidepressants have known antiplatelet properties. Patients with hematologic malignancies (HMs) are at an increased risk of bleeding complications due to their malignancy and treatment-induced thrombocytopenia.

The purpose of this study was to evaluate the risk of clinically significant bleeding (CSB) in patients with HM and thrombocytopenia who are prescribed SRIs.

This retrospective cohort study included adult patients admitted to the hospital with HM and thrombocytopenia. Patients were stratified into SRI-exposed and SRI-unexposed groups. Patients were followed up until resolution of thrombocytopenia, hospital discharge, death, or SRI therapy interruption. The primary outcome was the incidence of CSB.

A total of the 324 patients were included in the study (119 SRI exposed vs 205 SRI unexposed). The median baseline platelet value was 35 × 109/L and 31 × 109/L, respectively. The median platelet nadir was 6 × 109/L, and the median duration of study inclusion was 12 days in both groups. No difference was seen in the incidence of CSB between groups (16% vs 13%, P = 0.487). Hospital length of stay (LOS) (20 vs 19 days, P = 0.227) and intensive care unit (ICU) LOS (3.9 vs 3.9 days, P = 0.996) were similar between groups. On multivariable analysis, SRI exposure was not independently associated with CSB (adjusted odds ratio [aOR] = 1.46, 95% confidence interval [CI] 0.75-2.86).

In patients with HM and thrombocytopenia, SRI exposure was not associated with an increased risk of CSB. Given the small study size, assessment of patient-specific risks versus benefits should still be considered when prescribing SRI therapy in this patient population.

This study aimed to evaluate the effectiveness of a pharmacist-led intervention in decreasing the overuse of stress ulcer prophylaxis (SUP) compared with the usual care for adult patients in Chinese ICUs.

Pragmatic, multicenter, stepped-wedge, cluster-randomized controlled trial.

Twenty-six ICUs in China from October 2022 to March 2023.

We enrolled 2199 patients 18 years old or older who were newly admitted to the participating ICUs.

Using the Medical Research Council framework for developing and evaluating complex intervention measures, a multidisciplinary team (Scenarios, Improving and Refining Interventions, Constructing, Refining and Testing Research Theories, Incorporating Stakeholders, Identifying Important Uncertainties, and Economics Considerations) designed a multifaceted intervention.

The primary outcomes were the proportion of patients receiving SUP and that with overt gastrointestinal bleeding. We conducted intention-to-treat analyses using generalized linear mixed models to adjust for potential confounders (age, sex, and acute physiology and chronic health evaluation II score) with random effects for the site. The proportion of patients receiving SUP in the intervention group was lower than that in the control group (45.5% vs. 49.5%; odds ratio [OR], 0.81; 95% CI, 0.68-0.96; p = 0.017). The proportion of patients with overt gastrointestinal bleeding was similar (3.7% vs. 4.0%; OR, 1.05; 95% CI, 0.65-2.85; p = 0.81).

The pharmacist-led intervention reduced the proportion of patients receiving SUP in the ICUs, without significantly affecting the proportion of patients with overt gastrointestinal bleeding. These findings will help guide ICU medical decision-making.

Increasing healthcare costs, particularly in Low- and Middle-Income Countries (LMICs) like Egypt, highlight the need for rational economic strategies. Clinical pharmacy interventions offer potential benefits by reducing drug therapy problems and associated costs, thereby supporting healthcare system sustainability.

This study evaluates the economic impact and clinical benefits of clinical pharmacy interventions in four tertiary hospitals in Egypt by implementing an innovative tool for medication management, focusing on cost avoidance and return on investment (ROI), while accounting for case severity and drug therapy problem (DTP) resolution.

Utilizing a digital tool, cost avoidance was assessed by considering the severity of patient cases and the effectiveness of clinical pharmacists' interventions in resolving identified DTPs. Additionally, ROI was calculated by incorporating both full-time equivalent (FTE) and non-FTE costs to evaluate the overall economic impact of clinical pharmacy services over a six-year period across four tertiary care hospitals in Egypt.

Over six years, a total of 492,612 patients were reviewed, leading to 19,240 comprehensive clinical pharmacy interventions. These interventions achieved an 88.63% resolution of DTPs, significantly reducing patient risk by preventing adverse DTP consequences, resulting in a total cost avoidance of EGP 265.32 million (USD 8.60 million) and an average ROI of 7.6 (760%). This underscores the substantial economic impact of clinical pharmacy services, particularly in LMICs and countries transitioning to universal health insurance coverage, where cost efficiency and patient safety are critical.

This study underscores the importance of clinical pharmacy interventions in improving healthcare outcomes and generating significant economic benefits, particularly in low- and middle-income countries. By accounting for case severity and the level of DTP consequences, along with the efficiency of clinical pharmacist-led interventions in resolving DTPs, the economic impact of these services can be more accurately evaluated. These findings are essential for informing policy decisions, highlighting the critical role of clinical pharmacy services in supporting healthcare systems facing economic constraints.

Proton pump inhibitors (PPIs) are widely known drugs that are used quite frequently and indicated in both the short and long terms, in numerous acid-related diseases. Our aim was to produce an expert review that establishes recommendations for the adequate prescription and deprescription of PPIs.

A group of experts in PPI use that are members of the Asociación Mexicana de Gastroenterología (AMG), after extensively reviewing the published literature and discussing each recommendation at a face-to-face meeting, prepared the present document of good clinical practice recommendations. This document is not intended to be a clinical practice guideline or utilize the methodology said format requires.

Eighteen experts on PPI use developed 22 good clinical practice recommendations for prescribing short-term, long-term, and on-demand PPIs, recognizing adverse events, and lastly, deprescribing PPIs, in acid-related diseases.

At present, there is scientific evidence on PPI use in numerous diseases, some in the short term (4-8 weeks), others on-demand (for short periods until symptoms improve), or in the long term (without suspending). Numerous adverse effects have been attributed to PPIs, but the majority have no well-established causal association. Nevertheless, PPIs should be suspended when there is no clear indication for their use. These recommendations aim to aid general physicians and specialists, with respect to PPI prescription and deprescription.

Renal replacement therapy (RRT) may affect coagulation and platelet function in critically ill patients. However, the mechanism and the difference in the impact on coagulation between intermittent hemodialysis (iHD) and continuous renal replacement therapy (CRRT) remains unclear. This study aimed to investigate and compare the impact of iHD and CRRT on coagulation and platelet function.

Critically ill patients undergoing RRT were classified into the iHD group or the CRRT group. After the first blood sampling, patients underwent either a single session of hemodialysis or 48 h of CRRT, then a second blood sample was taken. Rotational thromboelastometry (ROTEM), platelet aggregometry and conventional coagulation tests were performed. The primary outcome was a change in extrinsically activated ROTEM (EXTEM) clotting time (CT).

60 dialysis sessions from 56 patients were finally included, with 30 dialysis sessions per group. EXTEM CT was prolonged significantly after dialysis in the iHD group (90 [74, 128] vs. 74 [61, 91], p < 0.001), but did not change in the CRRT group (94.4 ± 29.4 vs. 91.6 ± 22.9, p = 0.986). The platelet aggregation did not change after both iHD and CRRT. A change in EXTEM CT was significantly greater in the iHD group compared to the CRRT group (p = 0.006). The difference in the incidence of bleeding events was insignificant between the two groups (p = 0.301).

EXTEM CT was significantly prolonged after iHD, but this change was not shown after CRRT. Platelet function was not affected by both dialysis modalities.

Patients in the intensive care unit (ICU) may need bedside endoscopy for gastrointestinal (GI) emergencies. Conducting endoscopy in the ICU for critically ill patients needs special consideration. This mini review focuses on indications for bedside endoscopes, including GI bleeding, volvulus, and bowel obstruction. It explains the risks associated with urgent endoscopies in critical patients and outcomes. Hemodynamic instability, coagulopathy, and impaired mucosal visualization are important considerations before bedside endoscopy. It also discusses the anesthesia considerations for non-operating room anesthesia. Multidisciplinary collaboration, meticulous patient selection, and procedural optimization help mitigate risks and maximize procedural success.

Acute kidney injury (AKI) is a severe postoperative complication in patients undergoing major surgery. Proton pump inhibitors (PPIs) are used preoperatively as prophylaxis for postoperative gastrointestinal bleeding. Whether preoperative PPI use is associated with an increased risk of postoperative AKI remains uncertain.

This retrospective cohort study used electronic medical records from the clinical data warehouse of Peking University First Hospital to screen all adult hospitalizations undergoing major surgery between 1 January 2018 and 31 December 2020. Exposure was preoperative PPI use, defined as PPI use within 7 days before major surgery. The primary outcome was postoperative AKI, defined as AKI occurring within 7 days after major surgery; secondary outcomes included in-hospital AKI and in-hospital mortality.

A total of 21,533 patients were included in the study (mean [SD] age, 57.8 [15.0] years; 51.2% male), of which 944 (4.4%) were prescribed PPI within 7 days before major surgery (PPI users). Overall, 72 PPI users (7.6%) and 356 non-users (1.7%) developed postoperative AKI. After adjustment, preoperative PPI use was associated with an increased risk of postoperative AKI (adjusted OR, 1.47; 95% CI, 1.04-2.07) and in-hospital AKI (adjusted OR, 1.41; 95% CI, 1.03-1.94). Moreover, subgroup analyses showed that the risk of PPI on postoperative AKI was amplified by the concomitant use of non-steroidal anti-inflammatory drugs or diuretics. No significant difference was observed between preoperative PPI use and in-hospital mortality in the fully adjusted model (adjusted OR 1.63; 95% CI, 0.55-4.85).

Preoperative PPI use was associated with an increased risk of AKI in patients undergoing major surgery. This risk may be enhanced by the concomitant use of other nephrotoxic drugs. Clinicians should weigh the pros and cons before initiating PPI prophylaxis.

Antithrombotic medications include both antiplatelet and anticoagulants and are used for a wide variety of cardiovascular conditions. A common complication of antithrombotic use is gastrointestinal bleeding. As a result, gastrointestinal prophylaxis is a common consideration for patients on a single or combination antithrombotic regimen. Prophylaxis is typically achieved through use of either proton pump inhibitors or histamine 2 receptor antagonists. Current recommendations for use of gastrointestinal prophylaxis with concomitant use of antithrombotic medications are scarce. In this systematic review, we explore the current evidence and recommendations regarding gastrointestinal prophylaxis for patients on antiplatelet or anticoagulant therapy as well as combination regimens.

To verify whether the bleeding risk assessment guidelines from the 9th American College of Chest Physicians (ACCP) are prognostic for respiratory intensive care unit (RICU) patients and to explore risk factors for hemorrhages, we conducted a secondary data analysis based on our previously published cohort study of venous thromboembolism.

We performed a secondary data analysis on the single-center prospective cohort from our previous study. Patients admitted to the RICU at Beijing Chao-Yang Hospital from August 1, 2014 to December 31, 2020 were included and followed up until discharge.

The study enrolled 931 patients, of which 715 (76.8%) were at high risk of bleeding, while the remaining were at low risk. Of the total, 9.2% (86/931) suffered major bleeding, and no significant difference was found between the two risk groups (p = 0.601). High-risk patients had poor outcomes, including higher mortality and longer stays. Independent risk factors for major bleeding were APACHE II score ≥ 15; invasive pulmonary aspergillosis; therapeutic dose of anticoagulants; extracorporeal membrane oxygenation; and continuous renal replacement therapy. Blood transfusion not related to bleeding appeared to be an independent protective factor for major bleeding (OR 0.099, 95% CI 0.045-0.218, p < 0.001).

Bleeding risk assessment models from the 9th ACCP guidelines may not be suitable for patients in RICU. Building a bleeding risk assessment model that is suitable for patients in all RICUs remains a challenge. Trial registration ClinicalTrials.gov: NCT02213978.

Intensive care unit (ICU) patients frequently require and benefit from stress ulcer prophylaxis (SUP) using proton pump inhibitors (PPIs). Despite recognized benefits, PPIs are overutilized in patients who do not have high-risk factors predisposing them to clinically significant gastrointestinal bleeding (CSGIB), including mechanical ventilation and coagulopathy. This overuse increases the risk of adverse effects associated with PPIs. Several urban healthcare systems have created educational initiatives aimed at reducing PPI usage in patients who do not meet recommendations or who are outside the period for serious risk of CSGIB. However, there was no available literature exploring PPI use or educational trends in rural hospitals. This situation presents an opportunity to investigate the disparities in PPI use between rural and urban healthcare settings. This narrative review aimed to assess current data on PPI usage in both urban and rural critical care environments, and to appraise existing practices, ultimately identifying gaps in current literature and informing future guidelines. With these evaluations, this review intended to provide a comprehensive overview of current PPI prescribing practices in the ICU and improve patient care across diverse healthcare settings.

Patients in the intensive care unit (ICU) commonly receive stress ulcer prophylaxis drugs, either proton pump inhibitors (PPIs) or histamine-2 receptor blockers (H2RBs). The goal of this research was to evaluate the impact of these drugs on mortality among ICU patients hospitalized for major adverse cardiovascular and cerebrovascular events (MACCEs).

ICU patients hospitalized for MACCEs were sourced from the Medical Information Mart for Intensive Care-III database. We performed a propensity score matching analysis to match patients treated with PPIs to those treated with H2RBs for stress ulcer prophylaxis. The outcome was 90-day mortality. We used multivariable Cox regression analyses to compare the effect. Hazard ratio (HR), 95% CIs, and P values were reported from the model.

From 2001 to 2012, a total of 3577 patients hospitalized for MACCEs (1997 received PPIs and 1580 received H2RBs) were admitted. The 90-day mortality was 23.7% (848/3577); it was 27% (540/1997) and 19.5% (308/1580) for PPIs and H2RBs users, respectively. The PPI group exhibited a greater 90‑day mortality in comparison to the H2RBs group (relative risk = 1.17; P = 0.036), after conditioning on potential confounder. The results remained robust in propensity score matching, sensitivity analyses, and subgroup analyses.

PPIs for stress ulcer prophylaxis were linked to an increased risk of in-hospital mortality than H2RBs in patients hospitalized for MACCEs. Further investigation of this association and validation of its clinical significance is needed.

Current guidelines recommend four weeks of stress ulcer prophylaxis following traumatic spinal cord injury.

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.

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.

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.

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.

Critically ill adults can develop stress-related mucosal damage from gastrointestinal hypoperfusion and reperfusion injury, predisposing them to clinically important stress-related upper gastrointestinal bleeding (UGIB).

The objective of this guideline was to develop evidence-based recommendations for the prevention of UGIB in adults in the ICU.

A multiprofessional panel of 18 international experts from dietetics, critical care medicine, nursing, and pharmacy, and two methodologists developed evidence-based recommendations in alignment with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Conflict-of-interest policies were strictly followed during all phases of guideline development including task force selection and voting.

The panel members identified and formulated 13 Population, Intervention, Comparison, and Outcome questions. We conducted a systematic review for each question to identify the best available evidence, statistically analyzed the evidence, and then assessed the certainty of the evidence using the GRADE approach. We used the evidence-to-decision framework to formulate the recommendations. Good practice statements were included to provide additional guidance.

The panel generated nine conditional recommendations and made four good practice statements. Factors that likely increase the risk for clinically important stress-related UGIB in critically ill adults include coagulopathy, shock, and chronic liver disease. There is no firm evidence for mechanical ventilation alone being a risk factor. Enteral nutrition probably reduces UGIB risk. All critically ill adults with factors that likely increase the risk for stress-related UGIB should receive either proton pump inhibitors or histamine-2 receptor antagonists, at low dosage regimens, to prevent UGIB. Prophylaxis should be discontinued when critical illness is no longer evident or the risk factor(s) is no longer present despite ongoing critical illness. Discontinuation of stress ulcer prophylaxis before transfer out of the ICU is necessary to prevent inappropriate prescribing.

The guideline panel achieved consensus regarding the recommendations for the prevention of stress-related UGIB. These recommendations are intended for consideration along with the patient's existing clinical status.

Annual prevalence estimates of peptic ulcer disease range between 0·12% and 1·5%. Peptic ulcer disease is usually attributable to Helicobacter pylori infection, intake of some medications (such as aspirin and non-steroidal anti-inflammatory medications), or being critically ill (stress-related), or it can be idiopathic. The clinical presentation is usually uncomplicated, with peptic ulcer disease management based on eradicating H pylori if present, the use of acid-suppressing medications-most often proton pump inhibitors (PPIs)-or addressing complications, such as with early endoscopy and high-dose PPIs for peptic ulcer bleeding. Special considerations apply to patients on antiplatelet and antithrombotic agents. H pylori treatment has evolved, with the choice of regimen dictated by local antibiotic resistance patterns. Indications for primary and secondary prophylaxis vary across societies; most suggest PPIs for patients at highest risk of developing a peptic ulcer, its complications, or its recurrence. Additional research areas include the use of potassium-competitive acid blockers and H pylori vaccination; the optimal approach for patients at risk of stress ulcer bleeding requires more robust determinations of optimal patient selection and treatment selection, if any. Appropriate continuation of PPI use outweighs most possible side-effects if given for approved indications, while de-prescribing should be trialled when a definitive indication is no longer present.

Stroke-associated pneumonia (SAP) and gastrointestinal bleeding (GIB) are common medical complications after stroke. The previous study suggested a strong association between SAP and GIB after stroke. However, little is known about the time sequence of SAP and GIB. In the present study, we aimed to verify the association and clarify the temporal sequence of SAP and GIB after ischemic stroke.

Patients with ischemic stroke from in-hospital Medical Complication after Acute Stroke study were analyzed. Data on occurrences of SAP and GIB during hospitalization and the intervals from stroke onset to diagnosis of SAP and GIB were collected. Multiple logistic regression was used to evaluate the association between SAP and GIB. Kruskal-Wallis test was used to compare the time intervals from stroke onset to diagnosis of SAP and GIB.

A total of 1129 patients with ischemic stroke were included. The median length of hospitalization was 14 days. Overall, 86 patients (7.6%; 95% CI, 6.1-9.2%) developed SAP and 47 patients (4.3%; 95% CI, 3.0-5.3%) developed GIB during hospitalization. After adjusting potential confounders, SAP was significantly associated with the development of GIB after ischemic stroke (OR = 5.13; 95% CI, 2.02-13.00; P < 0.001). The median time from stroke onset to diagnosis of SAP was shorter than that of GIB after ischemic stroke (4 days vs. 5 days; P = 0.039).

SAP was associated with GIB after ischemic stroke, and the onset time of SAP was earlier than that of GIB. It is imperative to take precautions to prevent GIB in stroke patients with SAP.

Whether proton-pump inhibitors are beneficial or harmful for stress ulcer prophylaxis in critically ill patients undergoing invasive ventilation is unclear.

In this international, randomized trial, we assigned critically ill adults who were undergoing invasive ventilation to receive intravenous pantoprazole (at a dose of 40 mg daily) or matching placebo. The primary efficacy outcome was clinically important upper gastrointestinal bleeding in the intensive care unit (ICU) at 90 days, and the primary safety outcome was death from any cause at 90 days. Multiplicity-adjusted secondary outcomes included ventilator-associated pneumonia, Clostridioides difficile infection, and patient-important bleeding.

A total of 4821 patients underwent randomization in 68 ICUs. Clinically important upper gastrointestinal bleeding occurred in 25 of 2385 patients (1.0%) receiving pantoprazole and in 84 of 2377 patients (3.5%) receiving placebo (hazard ratio, 0.30; 95% confidence interval [CI], 0.19 to 0.47; P<0.001). At 90 days, death was reported in 696 of 2390 patients (29.1%) in the pantoprazole group and in 734 of 2379 patients (30.9%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.85 to 1.04; P = 0.25). Patient-important bleeding was reduced with pantoprazole; all other secondary outcomes were similar in the two groups.

Among patients undergoing invasive ventilation, pantoprazole resulted in a significantly lower risk of clinically important upper gastrointestinal bleeding than placebo, with no significant effect on mortality. (Funded by the Canadian Institutes of Health Research and others; REVISE ClinicalTrials.gov number, NCT03374800.).

Patients on veno-arterial extracorporeal membrane oxygenation (V-A ECMO) support are at a high risk of hemorrhagic complications, including upper gastrointestinal bleeding (UGIB). The objective of this study was to evaluate the incidence and impact of this complication in V-A ECMO patients.

A retrospective single-center study (2013-2017) was conducted on V-A ECMO patients, excluding those who died within 24 h. All patients with suspected UGIB underwent esophagogastroduodenoscopy (EGD) and were analyzed and compared to the remainder of the cohort, from the initiation of ECMO until 5 days after explantation.

A total of 150 V-A ECMO cases (65 after cardiac surgery and 85 due to medical etiology) were included. 90% of the patients received prophylactic proton pump inhibitor therapy and enteral nutrition. Thirty-one patients underwent EGD for suspected UGIB, with 16 confirmed cases of UGIB. The incidence was 10.7%, with a median occurrence at 10 [7-17] days. There were no significant differences in clinical or biological characteristics on the day of EGD. However, patients with UGIB had significant increases in packed red blood cells and fresh frozen plasma needs, mechanical ventilation duration and V-A ECMO duration, as well as in length of intensive care unit and hospital stays. There was no significant difference in mortality. The only independent risk factor of UGIB was a history of peptic ulcer (OR = 7.32; 95% CI [1.07-50.01], p = 0.042).

UGIB occurred in at least 1 out of 10 cases of V-A ECMO patients, with significant consequences on healthcare resources. Enteral nutrition and proton pump inhibitor prophylaxis did not appear to protect V-A ECMO patients. Further studies should assess their real benefits in these patients with high risk of hemorrhage.

The objective of this study was to create a definition of patient-important upper gastrointestinal bleeding during critical illness as an outcome for a randomized trial.

This was a sequential mixed-methods qualitative-dominant multi-center study with an instrument-building aim. In semi-structured individual interviews or focus groups we elicited views from survivors of critical illness and family members of patients in the intensive care unit (ICU) regarding which features indicate important gastrointestinal bleeding. Quantitative demographic characteristics were collected. We analyzed qualitative data using inductive content analysis to develop a definition for patient-important upper gastrointestinal bleeding.

Canada and the United States.

51 ICU survivors and family members of ICU patients.

Participants considered gastrointestinal bleeding to be important if it resulted in death, disability, or prolonged hospitalization. The following also signaled patient-important upper gastrointestinal bleeding: blood transfusion, vasopressors, endoscopy, CT-angiography, or surgery. Whether an intervention evinced concern depended on its effectiveness, side-effects, invasiveness and accessibility; contextual influences included participant familiarity and knowledge of interventions and trust in the clinical team.

Survivors of critical illness and family members described patient-important upper gastrointestinal bleeding differently than current definitions of clinically-important upper gastrointestinal bleeding.

After encountering a unique patient case, we revisit the updated literature on stress ulcer prophylaxis with more updated studies. A 47-year-old male came to the hospital and was found to have acute cholecystitis. After undergoing urgent cholecystectomy, the patient developed melena and a 6 mg/dL drop from 12.5 g/dL to 6.5 g/dL in hemoglobin. He was found to have a gastric ulcer and was started on a proton pump inhibitor, which posed the question of whether or not stress ulcer prophylaxis was indicated. Therefore, the pathophysiology of stress ulcer prophylaxis is refreshed, discussing the various mechanisms through which stress ulcers form in a clinical context. Then, the main risk factors and indications for stress ulcer prophylaxis are defined based on current literature, further investigating whether or not stress ulcer prophylaxis has shown benefit and protection in various patient groups. Additionally, this review discusses the adverse effects of stress ulcer prophylaxis, including dysbiosis, community-acquired pneumonia, nutritional deficiencies, drug interactions, and fractures. Finally, inappropriate stress ulcer prophylaxis and contributing factors to overutilization are discussed, and alternative approaches to prevent stress ulcer formation are covered, including early enteral nutrition. Overall, there are mixed conclusions on the effectiveness of stress ulcer prophylaxis in noncritical patients. There are many adverse effects and unnecessary costs associated with inappropriate administration, and many studies have found that it should be reserved for specific clinical indications.

Suspected upper gastrointestinal bleeding (SUGIB) is a common issue during ICU stay. In the absence of specific guidelines on the indication and timing of esophagogastroduodenoscopy (EGD), there is substantial variability in EGD indication depending on accessibility and clinical presentation. This study aimed to investigate factors associated with the need for per-EGD hemostatic therapy and to create a score predicting therapeutic benefit of emergency bedside EGD in ICU patients with SUGIB.

We conducted a retrospective study in our ICU to identify factors associated with the need for hemostatic procedure during EGD performed for SUGIB. From this observational cohort, we derived a score predicting the need for hemostasis during EGD, the SUGIBI score. This score was subsequently validated in a retrospective multicenter cohort.

Two hundred fifty-five patients not primarily admitted for GI bleeding who underwent a bedside EGD for SUGIB during their ICU stay were analyzed. The preeminent EGD indication were anemia (79%), melena (19%), shock (14%), and hematemesis (13%). EGD was normal in 24.7% of cases, while primary lesions reported were ulcers (23.1%), esophagitis (18.8%), and gastritis (12.5%). Only 12.9% of patients underwent hemostatic endotherapy during EGD. A SUGIBI score < 4 had a negative predictive value of 95% (91-99) for hemostatic endotherapy [AUC of 0.81; 0.75-0.91 (p < 0.0001)]. The SUGIBI score for predicting the need for an EGD-guided hemostatic procedure was next validated in a multicenter cohort with an AUC of 0.75 (0.66-0.85) (p < 0.0001), a score < 4 having a negative predictive value of 95% (92-97).

Our study shows that the therapeutic usefulness of bedside emergency EGD for SUGIB in critically ill patients is limited to a minority of patients. The SUGIBI score should help clinicians stratify the probability of a therapeutic EGD.

Proton pump inhibitors (PPIs) are among the drugs most commonly used in critically ill patients. Although mainly applied temporarily for stress ulcer prophylaxis, their application is frequently not terminated. Potential adverse effects of PPI treatment could impact the outcome in case of unnecessary and, therefore, avoidable long-term continuation. We tested the hypotheses that nonindicated PPI therapy continued beyond hospital discharge is associated with increased morbidity, rehospitalization rate, and mortality.

Nationwide retrospective cohort study considering critically ill patients treated on German ICUs between January, 2017, and December, 2018 with a 2-year follow-up.

A total of 591,207 patient datasets of a German healthcare insurer were screened.

We identified 11,576 ICU patients who received PPI therapy for the first time during their index ICU stay without having an indication for its continuation.

The cohort was stratified into two groups: 1) patients without further PPI therapy and 2) patients with continuation of PPI therapy beyond 8 weeks after hospital discharge.

Frequency of predescribed adverse events associated with PPI therapy, 1-year rehospitalization rate, and 2-year mortality were determined. The proportion of patients with continued PPI therapy without an objectifiable indication was 41.7% (4,825 of 11,576 patients). These patients had a 27% greater risk of pneumonia (odds ratio [OR] 1.27; 95% CI, 1.15-1.39; p < 0.001) and a 17% greater risk of cardiovascular events (OR 1.17; 95% CI, 1.08-1.26; p < 0.001). Continued PPI therapy was associated with a 34% greater risk of rehospitalization (OR 1.34; 95% CI, 1.23-1.47) and a nearly 20% greater 2-year mortality risk (hazard ratio 1.17; 95% CI, 1.08-1.27; p = 0.006).

These data demonstrate that an unnecessary continuation of PPI therapy after hospital discharge may significantly impact morbidity and mortality. To avoid potentially harmful overuse of a PPIs, intensivists should ensure timely cessation of a temporarily indicated PPI therapy.

The REVISE (Re-Evaluating the Inhibition of Stress Erosions in the ICU) trial will evaluate the impact of the proton pump inhibitor pantoprazole compared to placebo in invasively ventilated critically ill patients.

To outline the statistical analysis plan for the REVISE trial.

REVISE is a randomized clinical trial ongoing in intensive care units (ICUs) internationally. Patients ≥ 18 years old, receiving invasive mechanical ventilation, and expected to remain ventilated beyond the calendar day after randomization are allocated to either 40 mg pantoprazole intravenously or placebo while mechanically ventilated.

The primary efficacy outcome is clinically important upper GI bleeding; the primary safety outcome is 90-day mortality. Secondary outcomes are ventilator-associated pneumonia, Clostridioides difficile infection, new renal replacement therapy, ICU and hospital mortality, and patient-important GI bleeding. Tertiary outcomes are total red blood cells transfused, peak serum creatinine concentration, and duration of mechanical ventilation, ICU, and hospital length of stay. Following an interim analysis of results from 2400 patients (50% of 4800 target sample size), the data monitoring committee recommended continuing enrolment.

This statistical analysis plan outlines the statistical analyses of all outcomes, sensitivity analyses, and subgroup analyses. REVISE will inform clinical practice and guidelines worldwide.

www.

gov NCT03374800. November 21, 2017.

The Re-Evaluating the Inhibition of Stress Erosions (REVISE) Trial aims to determine the impact of the proton pump inhibitor pantoprazole compared with placebo on clinically important upper gastrointestinal (GI) bleeding in the intensive care unit (ICU), 90-day mortality and other endpoints in critically ill adults. The objective of this report is to describe the rationale, methodology, ethics and management of REVISE.

REVISE is an international, randomised, concealed, stratified, blinded parallel-group individual patient trial being conducted in ICUs in Canada, Australia, Saudi Arabia, UK, US, Kuwait, Pakistan and Brazil. Patients≥18 years old expected to remain invasively mechanically ventilated beyond the calendar day after enrolment are being randomised to either 40 mg pantoprazole intravenously or an identical placebo daily while mechanically ventilated in the ICU. The primary efficacy outcome is clinically important upper GI bleeding within 90 days of randomisation. The primary safety outcome is 90-day all-cause mortality. Secondary outcomes include rates of ventilator-associated pneumonia, Clostridioides difficile infection, new renal replacement therapy, ICU and hospital mortality, and patient-important GI bleeding. Tertiary outcomes are total red blood cells transfused, peak serum creatinine level in the ICU, and duration of mechanical ventilation, ICU and hospital stay. The sample size is 4800 patients; one interim analysis was conducted after 2400 patients had complete 90-day follow-up; the Data Monitoring Committee recommended continuing the trial.

All participating centres receive research ethics approval before initiation by hospital, region or country, including, but not limited to - Australia: Northern Sydney Local Health District Human Research Ethics Committee and Mater Misericordiae Ltd Human Research Ethics Committee; Brazil: Comissão Nacional de Ética em Pesquisa; Canada: Hamilton Integrated Research Ethics Board; Kuwait: Ministry of Health Standing Committee for Coordination of Health and Medical Research; Pakistan: Maroof Institutional Review Board; Saudi Arabia: Ministry of National Guard Health Affairs Institutional Review Board: United Kingdom: Hampshire B Research Ethics Committee; United States: Institutional Review Board of the Nebraska Medical Centre. The results of this trial will inform clinical practice and guidelines worldwide.

NCT03374800.

Proton pump inhibitors (PPIs) have been available for over three decades and are among the most commonly prescribed medications. They are effective in treating a variety of gastric acid-related disorders. They are freely available and based on current evidence, use of PPIs for inappropriate indications and duration appears to be common. Over the years, concerns have been raised on the safety of PPIs as they have been associated with several adverse effects. Hence, there is a need for PPI stewardship to promote the use of PPIs for appropriate indication and duration. With this objective, the Indian Society of Gastroenterology has formulated guidelines on the rational use of PPIs. The guidelines were developed using a modified Delphi process. This paper presents these guidelines in detail, including the statements, review of literature, level of evidence and recommendations. This would help the clinicians in optimizing the use of PPIs in their practice and promote PPI stewardship.

Gastrointestinal bleeding (GIB) is a common condition in clinical practice, and predictive models for patients with GIB have been developed. However, assessments of in-hospital mortality due to GIB in the intensive care unit (ICU), especially in critically ill patients, are still lacking. This study was designed to screen out independent predictive factors affecting in-hospital mortality and thus establish a predictive model for clinical use.

This retrospective study included 1,442 patients with GIB who had been admitted to the ICU. They were selected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) 1.0 database and divided into a training group and a validation group in a ratio of 7:3. The main outcome measure was in-hospital mortality. Least absolute shrinkage and section operator (LASSO) regression was used to screen out independent predictors and create a nomogram.

LASSO regression picked out nine independent predictors: heart rate (HR), activated partial thromboplastin time (aPTT), acute physiology score III (APSIII), sequential organ failure assessment (SOFA), cerebrovascular disease, acute kidney injury (AKI), norepinephrine, vasopressin, and dopamine. Our model proved to have excellent predictive value with regard to in-hospital mortality (the area under the receiver operating characteristic curve was 0.906 and 0.881 in the training and validation groups, respectively), as well as a good outcome on a decision curve analysis to assess net benefit.

Our model effectively predicts in-hospital mortality in patients with GIB, indicating that it may prove to be a valuable tool in future clinical practice.