Stress-related Mucosal Disease Research Articles

Analysis of inappropriate prophylactic use of proton pump inhibitors during the perioperative period: an observational study

BackgroundThe prevalence and characteristics of inappropriate use of proton pump inhibitors (PPIs) to prevent stress-related mucosal disease (SRMD) during the perioperative period and its associated factors are rarely reported. This study aimed to investigate the prevalence and characteristics of inappropriate prophylactic use of proton pump inhibitors (PPIs) during the perioperative period and identify its associated factors in a tertiary care and academic teaching hospital in China and to provide evidence for regulation authorities and pharmacists to take targeted measures to promote rational drug use.MethodsInpatients who underwent surgical operations and received prophylactic use of PPIs from June 2022 to November 2022 were included in this retrospective study. The appropriateness of perioperative prophylactic use of PPIs was evaluated by clinical pharmacists. Associated factors with inappropriate perioperative prophylactic use of PPIs were analyzed by univariable and multivariable logistic regression.ResultsFour-hundred seventy-two patients were finally included in this study, of which 131 (27.75%) patients had at least one problem with inappropriate perioperative prophylactic use of PPIs. The three most common problems were drug use without indication (52.0%), inappropriate usage and dosage (34.6%), and inappropriate duration of medication (6.7%). Multiple logistic regression analysis showed that oral dosage form of PPIs [OR = 18.301, 95% CI (7.497, 44.671), p < 0.001], discharge medication of PPIs [OR = 11.739, 95% CI (1.289, 106.886), p = 0.029], and junior doctors [OR = 9.167, 95% CI (3.459, 24.299), p < 0.001] were associated with more inappropriate prophylactic use of PPIs. Antithrombotics [OR = 0.313, 95% CI (0.136, 0.721), p = 0.006] and prolonged postoperative hospital stay (longer than 15 days) [OR = 0.262, 95% CI (0.072, 0.951), p = 0.042] were associated with less inappropriate prophylactic use of PPIs.ConclusionsThe inappropriate prophylactic use of PPIs during the perioperative period is common. Regulation authorities and pharmacists should take more targeted measures to promote the rational prophylactic use of PPIs during the perioperative period.

Rationality of Use and Effectiveness of Stress Ulcer Prophylaxis in Critically Ill Patients: An Experience from A Tertiary Intensive Care Unit

Background: Stress-related mucosal disease (SRMD) frequently develops in critically ill patients, increasing mortality and length of intensive care unit (ICU) stay. There is limited data on stress ulcer prophylaxis (SUP) on critically ill patients in Indonesia.Objective:Methods: This is a retrospective cohort study of patients admitted to the ICU from January 1, 2015, to December 31, 2017. The subjects were all ICU patients who used proton pump inhibitor (PPI) and histamine-2 receptor antagonist (H2RA) as SUP therapy.Results: A total of 315 patients were included, and mean age was 48 years. Approximately 55.2% were women, and 62.8% of patients were admitted to ICU following high-risk surgery. PPI was given to 187 patients (59.4%) and H2RA to 128 patients (40.6%), with an average usage for 5 days. The incidence of SRMD was 15.9% (n = 50), and mean length of stay in the ICU was 6 days. Gender, age, duration of SUP, and ICU length of stay of the PPI and H2RA groups were not statistically different (p &gt; 0.05) and did not affect the GI event (p &gt; 0.05). The use of rational SUP was 98.4%. Major American Society of Health-System Pharmacists (ASHP) risk factor criterion was ventilator use (86.8%), while the minor ASHP criterion was anticoagulant therapy (22.2%). The incidence of GI event was significantly lower in PPI groups than H2RA groups (p &lt; 0.05).Conclusions: The use of SUP is rational with an average use of 5 days. PPI are superior to H2RA for SRMD prophylaxis.

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.

Upper Gastrointestinal Bleeding in Critically Ill Patient: Literature Review

Critically ill patients are at risk for stress ulcers in the upper digestive tract. Various risk factors have been associated with this condition. Patients who are critically ill are at risk of bleeding due to stress related mucosal disease (SRMD). Upper gastrointestinal tract problems usually occur as a result of severe physiological stress. Patients may develop gastric erosion and develop stress ulcers with severe gastrointestinal bleeding which can be fatal. Routine pharmacological use of stress ulcer prophylaxis (SUP) does not reduce overall mortality in intensive care patients. This increases the risk of infectious complications, particularly nosocomial pneumonia and Clostridium difficile-associated diarrhea. Early enteral nutrition has been shown to be effective in preventing stress ulceration of the upper gastrointestinal tract in critically ill patients. Routine use of stress ulcer prophylaxis in all critically ill patients may be dangerous and does not appear to be cost-effective. SUP administration must follow an algorithm that clearly balances risks and benefits.

Pantoprazole-induced Thrombocytopenia: Unresponsive to Corticosteroid and Thrombocyte Concentrate Transfusion

Introduction: Pantoprazole is a proton pump inhibitor (PPI) class drug that is widely used in the treatment of SRMD (stress-related mucosal disease in critical ill patients. PPI are one class of drugs used commonly both for treatment and prophylactic therapy for stress ulcers in intensive care unit (ICU). Case: We report a case of a 51-year old male who was referred to PKU Hospital. He was admitted to ICU with diagnosis of Hyperosmolar Hyperglymic State and bronchopneumonia. Thrombocytopenia was noted in admission. There was more than 70% decrease in platelet count after initiation of pantoprazole. Patient received Thrombocyte Concentrate (TC) transfusion and corticosteroid iv for several days, but only had minor increase in platelet count. The platelets recovered after stopping pantoprazole. Discussion: In the present case report, another exposures to parenteral pantoprazole in a dose of 40 mg once daily reproduced the same adverse drug reaction. In comparison to lansoprazole, thrombocytopenia from pantoprazole is more severe that necessitate TC transfusion and corticosteroid trial. However, in the present case, TC transfusion and corticosteroid fail to escalate platelet count. This finding suggests probability of non-immune mechanism of pantoprazole-induced thrombocytopenia. Conclusion: Pantoprazole may induce thrombocytopenia with new features that were immediately developed, resulting a decrease in platelet count >70%. The mechanism found in this case may be non-immune. Drug-induced thrombocytopenia is one of the rare complications that has to be kept in mind with the use of pantoprazole.

Risk Stratification in Acute Upper Gastrointestinal Bleeding Occurring in Hospitalized Patients: Comparison of Clinical Risk Scoring Systems and Clinically Significant Bleeding Criteria

Background: Upper gastrointestinal bleeding (UGIB) while being hospitalized is common, resulting in increased disability and mortality. Using the clinical risk scoring system to assess these patients is, therefore, important in assessing the necessity for endoscopic intervention, predicting rebleeding rate, and 30-day mortality rate. Objective: To assess the effectiveness of the clinical risk scoring system in terms of predicting the need of endoscopic intervention, rebleeding rate, and 30-day mortality in in-hospital UGIB patients. Materials and Methods: The patients with in-hospital UGIB who were admitted during August 2014 to August 2018 and underwent esophagogastroduodenoscopy within 72 hours after bleeding onset were included. The data were retrospectively collected. A comparison of the effectiveness of the clinically significant bleeding criteria, Glasgow-Blatchford score, and AIMS65 score was done. Results: One hundred and sixteen patients were included into the study. The main cause of UGIB was stress-related mucosal disease (SRMD) (88.8%). The effective system of predicting the necessity for endoscopic intervention was the clinically significant bleeding criteria (sensitivity 84%, specificity 74%). The effective scoring system for predicting rebleeding rate and 30-day mortality was the AIMS65 score (sensitivity 83%, specificity 59%). Conclusion: In-hospital UGIB is a common condition, mostly associated with SRMD. Patients with clinically significant bleeding would benefit from endoscopic intervention. Keywords: Upper gastrointestinal bleeding, In-hospital UGIB, Clinically significant bleeding, GBS, AIMS65

Oxidative stress is important in the pathogenesis of stress-related mucosal disease.

Stress-related mucosal disease (SRMD) is a common complication in patients in the intensive care unit (ICU). The aim of the present study was to investigate the possible mechanisms for the pathogenesis of SRMD. In total, 38 patients with SRMD were enrolled from an ICU, as well as 15 healthy volunteers. The disease severity of patients in ICU was evaluated using the Acute Physiology and Chronic Health Evaluation (APACHE) II score. Gastric mucosa with the most severe lesions were biopsied for hematoxylin and eosin staining and then assessed by pathological damage scoring. The serum levels of malondialdehyde (MDA), superoxide dismutase (SOD) and ischemic modified albumin (IMA) were also detected. In addition, claudin-3 and inducible nitric oxide (NO) synthase (iNOS) in the gastric mucosa were assessed by western blotting and immunohistochemistry. The average APACHE II score of the patients with SRMD was significantly higher compared with the controls. Moreover, the levels of MDA (4.74±2.89 nmol/ml) and IMA (93.61±10.78 U/ml) in patients with SRMD were significantly higher compared with the controls (P<0.001), while those of SOD (89.66±12.85 U/ml) in the patients with SRMD were significantly lower compared with the controls (P<0.001). Furthermore, compared with the control, iNOS expression was significantly higher (P=0.034), while the expression of claudin-3 was significantly lower in patients with SRMD (P<0.001). The results indicated that APACHE II score was positively correlated with pathological damage score (r=0.639, P<0.001) and levels of MDA (r=0.743, P<0.001), but negatively correlated with the level of SOD (r=-0.392, P=0.015). In addition, MDA was positively correlated with IMA (r=0.380, P=0.018), but negatively correlated with claudin-3 (r=-0.377, P=0.020). Therefore, it was speculated that oxidative stress may play an important role in the pathogenesis of SRMD, and NO levels and cell membrane permeability are altered during this process.

Evaluation of the Role of Clinical Pharmacist in Optimizing Stress-Related Mucosal Disease Prophylaxis in Patients Admitted to Nephrology Ward: A Quasi-Experimental Study

Evaluation of the Role of Clinical Pharmacist in Optimizing Stress-Related Mucosal Disease Prophylaxis in Patients Admitted to Nephrology Ward: A Quasi-Experimental Study

Dolichos lablab L. extracts as pharmanutrient for stress-related mucosal disease in rat stomach.

Gastric stress-related mucosal disease (SRMD) presented from superficial gastritis to deep ulceration consequent to insufficient perfusion, ischemia, and oxidative stress. Though pharmacologic interventions to optimize tissue perfusion or to enhance defensive mechanism are essential, limited clinical outcome necessitates strong acid suppressors or natural agents. Under the hypothesis that Dolichos lablab L. (NKM 23-1) can enhance defense against SRMD, water immersion restraint stress (WIRS) were imposed to rats and additional groups pretreated with differing doses of NKM 23-1 were monitored. On gross and microscopic evaluation, they significantly rescued SRMD (p<0.01). The levels of inflammatory mediators such as IL-18, IL-1β, IL-8, iNOS, TNF-α, caspase-1, NOXs as well as MMPs accompanied with NF-κB p50 activation were all significantly increased in WIRS, but their levels were significantly decreased in Groups pretreated with NKM 23-1. WIRS significantly increased apoptosis, but significantly decreased with NKM 23-1 accompanied with significantly increased levels of cyclin D/E and HSP70/HSP27. Gastric mucin was significantly preserved in Groups pretreated with NKM 23-1, while depleted in WIRS, accompanied with increased expressions of Muc5A. Gastric levels of HO-1 and NQO1 were significantly increased in Group treated with NKM 23-1 with transcriptional activation of Nrf2. Conclusively, preemptive intake of NKM 23-1 significantly rescued SRMD.

603 Incidence of Non-Variceal Upper Gastrointestinal Bleeding Worsens Outcomes With Acute Coronary Syndrome: Result of a National Cohort

INTRODUCTION: Upper gastrointestinal bleeding (UGIB) is a feared complication of acute coronary syndromes (ACS) and has been shown to increase morbidity and mortality. UGIB may occur due to stress-related mucosal disease as well as from standard therapy with antiplatelet and anticoagulant medications. Our aim was to assess the incidence of non-variceal UGIB in patients with ACS in a national cohort and its impact on in-hospital mortality, length of stay (LOS), and cost of hospitalization. METHODS: This was a retrospective cohort study using the 2016 Nationwide Inpatient Sample (NIS) utilizing ICD 10 CM codes. Principal discharge diagnoses of ACS (STEMI, NSTEMI and UA) in patients over 18 years of age were included. Non-variceal UGIB with interventions including endoscopy, angiography and embolization were also evaluated using ICD 10 CM. Primary outcome was national incidence of concomitant non-variceal UGIB in the setting of ACS. Secondary outcomes included impact on in-hospital mortality, LOS and cost of stay. Proportions were compared using Fisher's exact test and continuous variables using Student t-test. Multivariable and Poisson regression were performed. RESULTS: A total of 661,324 discharges with principal discharge diagnosis of ACS in 2016 were included. Patient demographics are listed in Table 1. Of this cohort, 0.65% (n = 4289) were complicated with non-variceal UGIB with increased frequency in older patients (OR 1.04, 95% CI 1.04-1.05; P = 0.001). Despite endoscopic evaluation, 17.35% (n = 744) underwent angiography whereas embolization was required in 0.5% (n = 21) of these cases. After adjustment of confounders (see Table 2), inpatient mortality was significantly higher in patients with UGIB (OR 1.49, 95% CI 1.10-2.03; P = 0.01). Non-variceal UGIB also led to significantly longer LOS (10.21 days vs 4.38 days; P = 0.001) and total cost of stay ($177,000 vs $88,592, P &lt; 0.0001) (Table 3 and Table 4). CONCLUSION: We performed a retrospective cohort study which showed that the national incidence of non-variceal UGIB complicating ACS is low (less than 1%). However, as expected, its occurrence in ACS patients resulted in significantly higher inpatient mortality, LOS, and hospitalization charges. Limitations of the study include lack of information on antiplatelet or anticoagulant therapy which could affect outcomes. Further studies are needed to determine the safety and efficacy of endoscopy in patients on dual antiplatelet agents or anticoagulation.

Dietary threonine prevented stress-related mucosal diseases in rats.

Stress-related mucosal disease (SRMD), or stress ulceration, is a group of conditions ranging from stress-related superficial gastric mucosal damage to deep gastric ulcers that are primarily correlated with mucosal ischemia, and pharmacologic interventions that optimize tissue perfusion or preserve defensive mucus aim to decrease the occurrence of conditions, such as gastric acidity, or enhance gastric defenses. However, the identification of multifactorial pathogenesis may be effective in preventing SMRD, and the use of stress prophylaxis is generally preferred. Since threonine is a component in the polymerization and synthesis of gastric mucin and possibly enhanced defense actions and lignin may provide structural support for defense and antioxidative function, we hypothesized that dietary intake of threonine and/or lignin can enhance defense against SRMD. The water immersion-restraint stress (WIRS) was used in rats and additional groups were pretreated with threonine alone or the combination of threonine and lignin. Based on gross and microscopic evaluations, threonine alone or the combination of threonine and lignin, a natural antioxidant, significantly reduced the development of SRMD (P < 0.05). According to molecular explorations, the levels of inflammatory mediators, such as interleukin (IL)-8, IL-6, IL-1β, inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ), all of which are mediators that play a significant role in controlling WIRS, significantly decreased in the groups pretreated with either threonine alone or the combination of threonine and lignin (P < 0.01). WIRS significantly increased apoptosis in the stomach. However, the apoptotic index significantly decreased with threonine pretreatment. According to periodic acid Schiff staining results, the expression of gastric mucin was significantly preserved in groups pretreated with threonine but remarkedly decreased in the WIRS group. The gastric heme oxygenase-1 levels significantly increased in the group treated with threonine. In conclusion, the dietary intake of threonine or the combination of threonine and lignin is effective in preventing SRMD.

Bacteriologic Evaluation of Ventilator-Associated Pneumonia According to Stress Related Mucosal Disease Prophylaxis in the Intensive Care Unit

Background: Ventilator associated pneumonia is one of the most important nosocomial infections with often poor outcomes and heavy economic burdens on health care systems. Objectives: Several studies have been done for evaluating the effect of different types of stress related mucosal disease (SRMD) prophylaxis on nosocomial pneumonia, as among factors participating in its establishment, gastrointestinal tract is believed to play an important role especially in ventilator-associated pneumonia. Methods: In this cross-sectional study, 150 patients who were admitted to intensive care unit (ICU) and developed documented culture positive VAP, were evaluated for the study inclusion criteria. The patients with clinical pulmonary infection score (CPIS) ≥ 6 were included and some others with conditions affecting comparability excluded. The patients with Acute Physiology and chronic health evaluation II (APACHEII) scores between 10 and 24, within the first 24 hours of ICU stay, were included. Finally, 100 patients who fulfilled all criteria were evaluated for the responsible organisms and type of SRMD prophylaxis they had received. The patients included were either on intravenous pantoprazole (49 patients) or intravenous ranitidine (51 patients). The goal of this study was to evaluate the organisms, which have been isolated from the sputum of ICU patients with ventilator-associated pneumonia, according to their SRMD prophylaxis regimen. Results: There were 59 men (59) and 41 women (41) ranging from 19 to 82 years old. The mean ages were not significantly different between the two groups (P = 0.586). APACHEII score was ranging between 15 and 21 with the mean of 17.57 in pantoprazole and 16.80 in ranitidine group (P = 0.006), there was a statistical but not clinical difference. With P-value of 0.001, there was significant difference in ICU stay days. The mean mortality rates were 18.4 and 1.8 for pantoprazole and ranitidine group, respectively. The difference was statistically significant (P < 0.001). Multi-drug resistant pathogens were significantly higher in the pantoprazole group (0.001). The organisms, which have been obtained from each group were different. Acinetobacter and Pseudomonas aeruginosa were highly cultivated in the pantoprazole group, while Staphylococcus aureus and Proteus were more in patients who had received ranitidine. Conclusions: It can be suggested that each bacterium has a unique propensity to grow in specific gastric pH and other systemic changes made by various agents used for SRMD prophylaxis. More studies are needed to evaluate large number of patients receiving SRMD prophylaxis, with perspective of VAP incidence, the responsible organisms, hospital and ICU stay days, and mortality rate in order to prevent poor outcomes caused by specific organisms. © 2018, Archives of Clinical Infectious Diseases.

Use of Enteral Nutrition for Gastrointestinal Bleeding Prophylaxis in the Critically Ill: Review of Current Literature.

This review provides a comprehensive overview of the etiology of stress-related mucosal disease, current acid suppression therapy recommendations, and the role enteral nutrition may play in disease prevention. Recent literature indicates enteral nutrition may prevent complications of stress-related mucosal disease by increasing splanchnic blood flow, enhancing gastrointestinal motility, and promoting cellular immunity and integrity through local nutrient delivery. Stress-related mucosal disease is a common complication of hospitalization in the critically ill which may lead to overt gastrointestinal bleeding and enhanced mortality. High-risk patients have historically been prescribed acid suppression therapy, though enteral nutrition may also have a role in disease mitigation.

Evaluation of Stress Ulcer Prophylaxis Benefits and Outcomes: A Simple Literature Review

Background: One of the commonest complications in critically ill patients is stress related mucosal disease (SRMD). It can be associated with increase in the risk of development of overt gastrointestinal bleeding. As a result, a lot of literatures have been done to evaluate the pathogenesis that stands behind its development, and assessment of the measures that can be used to lower the risk of its 'occurrence. Aim of the Work: In this review we aimed at discussing the pathogenesis that stands behind stress ulcer development, Also, discussing the role of anta- acid as a prophylaxis against harms and benefits. In addition to providing an intensive study that analyzed the recent literatures considered this field of study. Methodology: A comprehensive search was done using biomedical databases; Medline, and Pubmed, for studies concerned with assessment of stress ulcer prophylaxis. Keywords used in our search through the databases were as; “stress ulcer”, “stress ulcer prophylaxis”, “stress ulcer in ICU patients”. Conclusion: Stress related mucosal disease is associated with increase in the risk of clinically overt gastrointestinal bleeding. As a result, patients who require mechanically ventilation for more than 48 h and those with a manifest of coagulopathy are highly recommended for having stress ulcer prophylaxis (SUP). Anta- acid such as Proton Pump Inhibitors (PPIs) and histamine 2 receptor antagonists (H2RA) help in prevention of gastrointestinal bleeding, but did not have any effect on mortality risk reduction. Still further prospective randomizes trials needs to be done to evaluate our scientific research survey to guide the physicians in making a decision about the use of SUP in ICU patients.

Evaluation of Stress Ulcer Prophylaxis Benefits and Outcomes: A Simple Literature Review

Background: One of the commonest complications in critically ill patients is stress related mucosal disease (SRMD). It can be associated with increase in the risk of development of overt gastrointestinal bleeding. As a result, a lot of literatures have been done to evaluate the pathogenesis that stands behind its development, and assessment of the measures that can be used to lower the risk of its 'occurrence. Aim of the Work: In this review we aimed at discussing the pathogenesis that stands behind stress ulcer development, Also, discussing the role of anta- acid as a prophylaxis against harms and benefits. In addition to providing an intensive study that analyzed the recent literatures considered this field of study. Methodology: A comprehensive search was done using biomedical databases; Medline, and Pubmed, for studies concerned with assessment of stress ulcer prophylaxis. Keywords used in our search through the databases were as; “stress ulcer”, “stress ulcer prophylaxis”, “stress ulcer in ICU patients”. Conclusion: Stress related mucosal disease is associated with increase in the risk of clinically overt gastrointestinal bleeding. As a result, patients who require mechanically ventilation for more than 48 h and those with a manifest of coagulopathy are highly recommended for having stress ulcer prophylaxis (SUP). Anta- acid such as Proton Pump Inhibitors (PPIs) and histamine 2 receptor antagonists (H2RA) help in prevention of gastrointestinal bleeding, but did not have any effect on mortality risk reduction. Still further prospective randomizes trials needs to be done to evaluate our scientific research survey to guide the physicians in making a decision about the use of SUP in ICU patients.

Stress-related upper gastrointestinal bleeding in adult neurocritical care patients: a Chinese multicenter, retrospective study

Objective: China has limited data on stress-related gastrointestinal ulcers in patients admitted for neurosurgical care. This study evaluated the incidence of upper gastrointestinal bleeding (UGIB) and use of stress ulcer prophylaxis (SUP) in Chinese neurocritical care patients (Glasgow Coma Scale [GCS] score ≤10).Methods: This multicenter, retrospective study was performed from January 2015 to July 2015. Medical records of 1468 patients hospitalized during 2014 were reviewed. An estimated UGIB incidence rate of 4.4% was considered for precision of 1.3% for estimation of UGIB. The primary endpoint was evaluation of overall incidence of any overt UGIB in ≤14 days after cerebral lesion. Secondary endpoints included incidence of UGIB with or and without clinically significant complications, time to UGIB, associated risk factors and SUP used.Results: We analyzed 1416 patients (mean age: 53.7 ± 14.00 years; males: 62.4%) with cerebral lesions. Overall incidence rate of UGIB ≤14 days was 12.9% (95% CI: 11.2%–14.7%), 0.76% with and 12.1% without significant clinical complications. Average time and duration of bleeding were 2.9 ± 3.37 days and 4.2 ± 8.4 days, respectively. The most significant risk factors for UGIB were mechanical ventilation for >48 hours (p < .0001), UGIB history (p = .0026) and use of anticoagulants (p < .0001). Acid-suppression drugs were administered for SUP in 79.0% of the patients, whereas 40.5% received hemostatic drugs.Conclusions: The rate of UGIB incidence was higher than the estimated rate in neurocritical care patients in China, suggesting the need for better management and treatment for stress-related mucosal disease in China. History of UGIB, mechanical ventilation and/or anticoagulants significantly affected UGIB.ClinicalTrials registry number: NCT02316990.

Effect of sucralfate on gastric permeability in an ex vivo model of stress-related mucosal disease in dogs.

BackgroundSucralfate is a gastroprotectant with no known systemic effects. The efficacy of sucralfate for prevention and treatment of stress‐related mucosal diseases (SRMD) in dogs is unknown.Hypothesis/ObjectivesTo develop a canine ex vivo model of SRMD and to determine the effect of sucralfate on mucosal barrier function in this model.AnimalsGastric antral mucosa was collected immediately postmortem from 29 random‐source apparently healthy dogs euthanized at a local animal control facility.MethodsRandomized experimental trial. Sucralfate (100 mg/mL) was applied to ex vivo canine gastric mucosa concurrent with and after acid injury. Barrier function was assessed by measurement of transepithelial electrical resistance (TER) and radiolabeled mannitol flux.ResultsApplication of acidified Ringers solution to the mucosal side of gastric antrum caused a reduction in gastric barrier function, and washout of acidified Ringers solution allowed recovery of barrier function (TER: 34.0 ± 2.8% of control at maximum injury, 71.3 ± 5.5% at recovery, P < .001). Sucralfate application at the time of injury or after injury significantly hastened recovery of barrier function (TER: 118.0 ± 15.2% of control at maximum injury, P < .001 and 111.0 ± 15.5% at recovery, P = .35).Conclusions and Clinical ImportanceSucralfate appeared effective at restoring defects in gastric barrier function induced by acid and accelerating repair of tissues subjected to acid in this model, suggesting that sucralfate could have utility for the treatment and prevention of SRMD in dogs.

Effectifity and Cost Analysis of Omeprazole and Pantoprazole for Stress Related Mucosal Disease Prophylaxis in ICU

Currently, the most effective therapeutic agent as a Stress Related Mucosal Disease (SRMD) prophylaxis therapy is the group of Proton Pump Inhibitor (PPI). In Indonesia, PPI agent most commonly used is pantoprazole and omeprazole, for they are already available in the form of injection and also available in generic product. This study aimed to determine the effectiveness and the therapy cost of omeprazole and pantoprazole used as a prophylaxis agent of SRMD. This study used observational analytic method using a retrospective cohort study. The subjects were patients in ICU of Bethesda Hospital in Yogyakarta with age ≥ 18 year old who received the therapy of omeprazole or pantoprazole as a prophylaxis of SRMD during January 2012 – September 2016 who meet the inclusion and exclusion criteria. The effectivity of therapy was seen by the bleeding events. The cost was calculated based on the amount of fee required by the patient, both the use of the medicine as a prophylaxis therapy of SRMD and for the bleeding therapy of SRMD. The value of Expected Monetary Value (EMV) was then calculated using the method of Decision Tree. Subject in this study were 152 patients, in which there were 76 patients on each group therapy of pantoprazole and omeprazole. The comparison between the number of patients who did not experience bleeding between group of pantoprazole and group of omeprazole is 85.5%: 81.6% (p = 0.512). The value of EMV in the pantoprazole group is Rp. 431.490,76, while the omeprazole group is Rp. 382.042,57. There is no difference in the effectivity between pantoprazole and omeprazole as a prophylaxis of SRMD, and the cost for SRMD prophylaxis is cheaper in the omeprazole therapy than in the pantoprazole therapy.

Acute mental stress induces mitochondrial bioenergetic crisis and hyper-fission along with aberrant mitophagy in the gut mucosa in rodent model of stress-related mucosal disease

Psychological stress, depression and anxiety lead to multiple organ dysfunctions wherein stress-related mucosal disease (SRMD) is common to people experiencing stress and also occur as a side effect in patients admitted to intensive care units; however the underlying molecular aetiology is still obscure. We report that in rat-SRMD model, cold restraint-stress severely damaged gut mitochondrial functions to generate superoxide anion (O2•-), depleted ATP and shifted mitochondrial fission-fusion dynamics towards enhanced fission to induce mucosal injury. Activation of mitophagy to clear damaged and fragmented mitochondria was evident from mitochondrial translocation of Parkin and PINK1 along with enhanced mitochondrial proteome ubiquitination, depletion of mitochondrial DNA copy number and TOM 20. However, excess and sustained accumulation of O2•--generating defective mitochondria overpowered the mitophagic machinery, ultimately triggering Bax-dependent apoptosis and NF-κB-intervened pro-inflammatory mucosal injury. We further observed that stress-induced enhanced serum corticosterone stimulated mitochondrial recruitment of glucocorticoid receptor (GR), which contributed to gut mitochondrial dysfunctions as documented from reduced ETC complex 1 activity, mitochondrial O2•− accumulation, depolarization and hyper-fission. GR-antagonism by RU486 or specific scavenging of mitochondrial O2•− by a mitochondrially targeted antioxidant mitoTEMPO ameliorated stress-induced mucosal damage. Gut mitopathology and mucosal injury were also averted when the perception of mental stress was blocked by pre-treatment with a sedative or antipsychotic. Altogether, we suggest the role of mitochondrial GR-O2•−-fission cohort in brain-mitochondria cross-talk during acute mental stress and advocate the utilization of this pathway as a potential target to prevent mitochondrial unrest and gastropathy bypassing central nervous system.

Continuation of acid suppression therapy on intensive care discharge: a clinical audit

It is standard practice in intensive care to commence patients at risk of stress-related mucosal disease (SRMD) on acid suppression therapy (AST).[1][1] The aim of this audit was to determine the proportion of patients inappropriately continued on AST at the point of critical care discharge, and to