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Critical illness can disrupt the many functions of the gastrointestinal (GI) system and signs of gut failure are a clear marker of critical illness severity. Prevention and management of GI dysfunction aims to improve outcomes for the critically ill patient. Early enteral nutrition is protective on the gut and encourages GI motility. A careful balance must be struck to deliver sufficient calories and protein while avoiding overfeeding with its associated complications. Gut dysmotility at any level of the GI tract is a common barrier to nutrient delivery in the critically ill. The microbiome is central to gut health and critical illness has an invariably harmful effect on its composition and function. Gut-derived sepsis is one possible consequence that carries high mortality. GI bleeding, intra-abdominal hypertension and bowel ischaemia represent severe manifestations of gut dysfunction. Management of all these complications in the ICU should involve prevention strategies, detection through regular and thorough assessment, and systematic approach to treatment. [ABSTRACT FROM AUTHOR]

Abstract Background During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies. Objective To describe the conduct of an international randomized trial of stress ulcer prophylaxis (Re-Evaluating the Inhibition of Stress Erosions in the ICU [REVISE]) during the pandemic, addressing enrolment patterns, center engagement, informed consent processes, data collection, a COVID-specific substudy, patient transfers, and data monitoring. Methods REVISE is a randomized trial among mechanically ventilated patients, comparing pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important upper gastrointestinal bleeding and the primary safety outcome of 90-day mortality. We documented protocol implementation status from March 11th 2020-August 30th 2022. Results The Steering Committee did not change the scientific protocol. From the first enrolment on July 9th 2019 to March 10th 2020 (8 months preceding the pandemic), 267 patients were enrolled in 18 centers. From March 11th 2020-August 30th 2022 (30 months thereafter), 41 new centers joined; 59 were participating by August 30th 2022 which enrolled 2961 patients. During a total of 1235 enrolment-months in the pandemic phase, enrolment paused for 106 (8.6%) months in aggregate (median 3 months, interquartile range 2;6). Protocol implementation involved a shift from the a priori consent model pre-pandemic (188, 58.8%) to the consent to continue model (1615, 54.1%, p

Background: During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies. Objective: To describe the conduct of an international randomized trial of stress ulcer prophylaxis (Re-Evaluating the Inhibition of Stress Erosions in the ICU [REVISE]) during the pandemic, addressing enrolment patterns, center engagement, informed consent processes, data collection, a COVID-specific substudy, patient transfers, and data monitoring. Methods: REVISE is a randomized trial among mechanically ventilated patients, comparing pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important upper gastrointestinal bleeding and the primary safety outcome of 90-day mortality. We documented protocol implementation status from March 11th 2020-August 30th 2022. Results: The Steering Committee did not change the scientific protocol. From the first enrolment on July 9th 2019 to March 10th 2020 (8 months preceding the pandemic), 267 patients were enrolled in 18 centers. From March 11th 2020-August 30th 2022 (30 months thereafter), 41 new centers joined; 59 were participating by August 30th 2022 which enrolled 2961 patients. During a total of 1235 enrolment-months in the pandemic phase, enrolment paused for 106 (8.6%) months in aggregate (median 3 months, interquartile range 2;6). Protocol implementation involved a shift from the a priori consent model pre-pandemic (188, 58.8%) to the consent to continue model (1615, 54.1%, p < 0.01). In one new center, an opt-out model was approved. The informed consent rate increased slightly (80.7% to 85.0%, p = 0.05). Telephone consent encounters increased (16.6% to 68.2%, p < 0.001). Surge capacity necessitated intra-institutional transfers; receiving centers continued protocol implementation whenever possible. We developed a nested COVID-19 substudy. The Methods Centers continued central statistical monitoring of trial metrics. Site monitoring was initially remote, then in-person when restrictions lifted. Conclusion: Protocol implementation adaptations during the pandemic included a shift in the consent model, a sustained high consent rate, and launch of a COVID-19 substudy. Recruitment increased as new centers joined, patient transfers were optimized, and monitoring methods were adapted. [ABSTRACT FROM AUTHOR]

Abstract Background 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. Objective To outline the statistical analysis plan for the REVISE trial. Methods 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. Results 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. Conclusions This statistical analysis plan outlines the statistical analyses of all outcomes, sensitivity analyses, and subgroup analyses. REVISE will inform clinical practice and guidelines worldwide. Trial registration www.ClinicalTrials.gov NCT03374800. November 21, 2017.

Background: 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. Objective: To outline the statistical analysis plan for the REVISE trial. Methods: 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. Results: 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. Conclusions: This statistical analysis plan outlines the statistical analyses of all outcomes, sensitivity analyses, and subgroup analyses. REVISE will inform clinical practice and guidelines worldwide. Trial registration: www.ClinicalTrials.gov NCT03374800. November 21, 2017. [ABSTRACT FROM AUTHOR]

Abstract Background Critically ill patients commonly receive proton pump inhibitors (PPIs) to prevent gastrointestinal (GI) bleeding from stress-induced ulceration. Despite widespread use in the intensive care unit (ICU), observational data suggest that PPIs may be associated with adverse outcomes in patients with COVID-19 infection. This preplanned study is nested within a large randomized trial evaluating pantoprazole versus placebo in invasively ventilated patients. The 3 objectives are as follows: (1) to describe the characteristics of patients with COVID-19 in terms of demographics, biomarkers, venous thromboembolism, tracheostomy incidence and timing, and other clinical outcomes; (2) to evaluate the impact of COVID-19 infection on clinically important GI bleeding, 90-day mortality, and other outcomes compared to a propensity-matched non-infected cohort; and (3) to explore whether pantoprazole has a differential treatment effect on clinically important GI bleeding, 90-day mortality, and other outcomes in patients with and without COVID-19 infection. Methods The ongoing trial Re-EValuating the Inhibition of Stress Erosions (REVISE) compares pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important GI bleeding and the primary safety outcome of 90-day mortality. The protocol described in this report is for a substudy focused on patients with COVID-19 infection that was not in the original pre-pandemic trial protocol. We developed a one-page case report form to characterize these patients including data related to biomarkers, venous thromboembolism, COVID-19 therapies, tracheostomy incidence and timing, duration of mechanical ventilation, and ICU and hospital stay. Our analysis will describe the trajectory of patients with COVID-19 infection, a propensity-matched analysis of infected and non-infected patients, and an extended subgroup analysis comparing the effect of PPI among patients with and without COVID-19 infection. Discussion Prophylactic acid suppression in invasively ventilated critically ill patients with COVID-19 infection has unknown consequences. The results of these investigations will inform practice, guidelines, and future research. Trial registration REVISE Trial [NCT03374800 December 15, 2017], COVID-19 Cohort Study [NCT05715567 February 8, 2023].

Background: Critically ill patients commonly receive proton pump inhibitors (PPIs) to prevent gastrointestinal (GI) bleeding from stress-induced ulceration. Despite widespread use in the intensive care unit (ICU), observational data suggest that PPIs may be associated with adverse outcomes in patients with COVID-19 infection. This preplanned study is nested within a large randomized trial evaluating pantoprazole versus placebo in invasively ventilated patients. The 3 objectives are as follows: (1) to describe the characteristics of patients with COVID-19 in terms of demographics, biomarkers, venous thromboembolism, tracheostomy incidence and timing, and other clinical outcomes; (2) to evaluate the impact of COVID-19 infection on clinically important GI bleeding, 90-day mortality, and other outcomes compared to a propensity-matched non-infected cohort; and (3) to explore whether pantoprazole has a differential treatment effect on clinically important GI bleeding, 90-day mortality, and other outcomes in patients with and without COVID-19 infection. Methods: The ongoing trial Re-EValuating the Inhibition of Stress Erosions (REVISE) compares pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important GI bleeding and the primary safety outcome of 90-day mortality. The protocol described in this report is for a substudy focused on patients with COVID-19 infection that was not in the original pre-pandemic trial protocol. We developed a one-page case report form to characterize these patients including data related to biomarkers, venous thromboembolism, COVID-19 therapies, tracheostomy incidence and timing, duration of mechanical ventilation, and ICU and hospital stay. Our analysis will describe the trajectory of patients with COVID-19 infection, a propensity-matched analysis of infected and non-infected patients, and an extended subgroup analysis comparing the effect of PPI among patients with and without COVID-19 infection. Discussion: Prophylactic acid suppression in invasively ventilated critically ill patients with COVID-19 infection has unknown consequences. The results of these investigations will inform practice, guidelines, and future research. Trial registration: REVISE Trial [NCT03374800 December 15, 2017], COVID-19 Cohort Study [NCT05715567 February 8, 2023]. [ABSTRACT FROM AUTHOR]

Critical illness can disrupt the many functions of the gastrointestinal (GI) system and signs of gut failure are a clear marker of critical illness severity. Prevention and management of GI dysfunction aims to improve outcomes for the critically ill patient. Early enteral nutrition is protective on the gut and encourages GI motility. A careful balance must be struck to deliver sufficient calories and protein while avoiding overfeeding with its associated complications. Gut dysmotility at any level of the GI tract is a common barrier to nutrient delivery in the critically ill. The microbiome is central to gut health and critical illness has an invariably harmful effect on its composition and function. Gut-derived sepsis is one possible consequence that carries high mortality. GI bleeding, intra-abdominal hypertension and bowel ischaemia represent severe manifestations of gut dysfunction. Management of all these complications in the ICU should involve prevention strategies, detection through regular and thorough assessment, and systematic approach to treatment. [ABSTRACT FROM AUTHOR]

Background: The long-term effects of stress ulcer prophylaxis with pantoprazole are unknown in ICU patients. We report 1-year mortality outcome in the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial.Methods: In the SUP-ICU trial, acutely admitted adult ICU patients at risk of gastrointestinal bleeding were randomised to intravenous pantoprazole 40 mg vs placebo (saline) once daily during their ICU stay. We assessed mortality at 1 year and did sensitivity analyses according to the trial protocol and statistical analysis plan.Results: A total of 3261 of the 3291 patients with available data (99.1%) were followed up at 1 year after randomisation; 1635 were allocated to pantoprazole and 1626 to placebo. At 1 year after randomisation, 610 of 1635 patients (37.3%) had died in the pantoprazole group as compared with 601 of 1626 (37.0%) in the placebo group (relative risk, 1.01; 95% confidence interval 0.92-1.10). The results were consistent in the sensitivity analysis adjusted for baseline risk factors and in those of the per-protocol population. We did not observe heterogeneity in the effect of pantoprazole vs placebo on 1-year mortality in the predefined subgroups, that is, patients with and without shock, mechanical ventilation, liver disease, coagulopathy, high disease severity (SAPS II > 53) or in medical vs surgical ICU patients.Conclusion: We did not observe a difference in 1-year mortality among acutely admitted adult ICU patients with risk factors for gastrointestinal bleeding allocated to stress ulcer prophylaxis with pantoprazole or placebo during the ICU stay. (The SUP-ICU trial was funded by Innovation Fund Denmark and others; ClinicalTrials.gov number, NCT02467621). [ABSTRACT FROM AUTHOR]

Purpose: In the subgroup of patients with Simplified Acute Physiology Score (SAPS) II > 53 in the Stress Ulcer Prophylaxis in Intensive Care Unit (SUP-ICU) trial, there was interaction (P = 0.049) suggesting increased mortality in patients allocated to pantoprazole as compared with placebo. We aimed to explore this further.Methods: The SUP-ICU trial allocated acutely admitted adults at risk of gastrointestinal bleeding to pantoprazole vs placebo. In this post hoc study, we repeated all the preplanned analyses of SUP-ICU in patients with baseline SAPS II > 53.Results: A total of 1140 patients had a complete SAPS II > 53 and were included. At 90 days, 272/579 patients (47%) assigned to pantoprazole had died, as compared with 229/558 patients (41%) assigned to placebo [relative risk 1.13; 95% confidence interval (CI) 1.00-1.29]. This was supported by sensitivity analyses adjusted for risk factors and those in the per-protocol population. When accounting for patients with incomplete SAPS II in two additional analyses, the relative risk was 1.08; 95% CI 0.96-1.22 and 1.10; 95% CI 0.97-1.25. This was also observed for the secondary outcome days alive without life support. There were no differences between the intervention groups in the other secondary outcomes.Conclusions: In this post hoc analysis of patients with high disease severity included in the SUP-ICU trial, we observed higher 90-day mortality and fewer days alive without life support with pantoprazole vs placebo. Some of this may have been explained by missing SAPS II data, but further research is needed to draw firm conclusions. CLINICALTRIALS.GOV: ClinicalTrials.gov No. NCT02467621. [ABSTRACT FROM AUTHOR]

Objective: The occurrence of digestive complications especially upper gastrointestinal bleeding (UGIB) has increased after cardiac surgery. The aim of this study was to determine the incidence of UGIB and identify the independent risk factors. Materials and Methods: We retrospectively analyzed data of 1077 patients undergoing cardiopulmonary bypass (CPB) from 1994 to 2012 The group of patients with UGIB (n 1 = 20) was compared with the population group (n 2 = 1057). Demographic characteristics, therapeutic management, endoscopic findings, and outcomes were analyzed. Through a regression analysis we identified independent risk factors of UGIB. Results: The mean age of the group n 1 was 58.2 ± 12.4 years and 50.18 ± 13.5 years in the group n 2. UGIB occurred about 13 ± 5.5 days after cardiac surgery. Gastroduodenal ulcer was the most common etiology of hemorrhage (n = 13, 65%). Renal insufficiency, previous gastric ulcer, increased lactate concentration during CPB, prolonged mechanical ventilation, use of vasopressor drug and pulmonary infection was likely contributing factors in UGIB. Conclusion: UGIB following open cardiac surgery is most frequently secondary to gastroduodenal ulceration. Many determinant factors of bleeding are incriminated. Surgeons must be aware of these factors to avoid fatal complications.

Objective: Stress ulcers occur frequently in neurosurgical intensive care patients and can pose serious risks. We summarized the clinical experience of the combined application of nasointestinal tubes for early restoration of enteral nutrition and of nasogastric (NG) tubes for stress ulceration treatment in patients hospitalized in a neurosurgical intensive care unit. Methods: From January 2011 to June 2011, a series of 67 patients with stress ulceration hospitalized in a neurosurgical intensive care unit were randomized to two groups. The control group (33 patients) received treatment with NG tube decompression and drainage according to international guidelines, and parenteral nutrition was changed to enteral feeding until there was no grossly visible blood in the NG tube. The nasointestinal tube group (34 patients) received treatment combining application of NG tubes and nasointestinal tubes. Drainage was performed with NG tubes as in the control group, with concurrent placement of nasointestinal tubes. Duration until resolution of stress ulceration and days until start of enteral nutrition were compared between the two groups. Results: Duration until resolution of stress ulceration was 4.5 days in the control group and 4.3 days in the nasointestinal tube group. There was no difference between the two groups ( P > 0.05). Duration until start of enteral nutrition was 4.5 days in the control group and 1 day in the nasointestinal tube group. There was an obvious difference between the two groups ( P < 0.01). Conclusions: The combined application of NG tubes and nasointestinal tubes in neurosurgical intensive care patients with stress ulceration is an effective means of treating stress ulceration and restoring early enteral nutrition. [ABSTRACT FROM AUTHOR]

Gastrointestinal dysfunction is common in critically ill patients and it is important to prevent or manage its manifestations. In this article we discuss the aetiology, management and prevention of: stress ulceration, ileus, bacterial translocation, intra-abdominal hypertension, abdominal compartment syndrome, diarrhoea and constipation in the context of critically ill patients. We also discuss feeding strategies for intensive care patients who cannot be fed normally. [ABSTRACT FROM AUTHOR]

Purpose: To assess the effects of stress ulcer prophylaxis (SUP) versus placebo or no prophylaxis on all-cause mortality, gastrointestinal (GI) bleeding and hospital-acquired pneumonia in adult critically ill patients in the intensive care unit (ICU). Methods: We performed a systematic review using meta-analysis and trial sequential analysis (TSA). Eligible trials were randomised clinical trials comparing proton pump inhibitors or histamine 2 receptor antagonists with either placebo or no prophylaxis. Two reviewers independently assessed studies for inclusion and extracted data. The Cochrane Collaboration methodology was used. Risk ratios/relative risks (RR) with 95 % confidence intervals (CI) were estimated. The predefined outcome measures were all-cause mortality, GI bleeding, and hospital-acquired pneumonia. Results: Twenty trials ( n = 1,971) were included; all were judged as having a high risk of bias. There was no statistically significant difference in mortality (fixed effect: RR 1.00, 95 % CI 0.84–1.20; P = 0.87; I2 = 0 %) or hospital-acquired pneumonia (random effects: RR 1.23, 95 % CI 0.86–1.78; P = 0.28; I2 = 19 %) between SUP patients and the no prophylaxis/placebo patients. These findings were confirmed in the TSA. With respect to GI bleeding, a statistically significant difference was found in the conventional meta-analysis (random effects: RR 0.44, 95 % CI 0.28–0.68; P = 0.01; I2 = 48 %); however, TSA (TSA adjusted 95 % CI 0.18–1.11) and subgroup analyses could not confirm this finding. Conclusions: This systematic review using meta-analysis and TSA demonstrated that both the quality and the quantity of evidence supporting the use of SUP in adult ICU patients is low. Consequently, large randomised clinical trials are warranted. [ABSTRACT FROM AUTHOR]

Abstract: Gastrointestinal dysfunction is common in critically ill patients and it is important to try to prevent or manage its manifestations. In this article we discuss the aetiology, management and prevention of: stress ulceration, ileus, bacterial translocation, intra-abdominal hypertension, abdominal compartment syndrome, diarrhoea and constipation in the context of critically ill patients. We also discuss feeding strategies for intensive care patients who cannot be fed normally. [Copyright &y& Elsevier]

The author reflects on stress ulcer prophylaxis de-adoption. Topics discussed include stress ulceration, respiratory failure, hypotension, and sepsis. Also being discussed are the demonstration of multiple superficial ulcers through pathologic examination, critically ill intensive care unit (ICU) patients, and gastrointestinal bleeding.

Abstract: Gastrointestinal dysfunction in the critically ill surgical patient is common and associated with increased morbidity and mortality. Manifestations such as stress ulceration, ileus, breakdown in barrier function and hypermotility are often difficult to assess. Clinically significant ulceration is now rarely seen because of routine antacid prophylaxis and improved resuscitation. Routine antacid prophylaxis, however, increases the risk ventilator associated pneumonia. Ileus, secondary to neurogenic or inflammatory mechanisms, is common in critically ill surgical patients. Prevention or limitation is preferable to managing fully developed ileus. Minimally invasive surgical techniques, avoidance of opiates and optimizing fluid regimens all have an important role. Prokinetics and opioid antagonists may be of use. Barrier function describes the gastrointestinal tract''s role in preventing translocation of bacteria and toxins from the lumen to the systemic circulation. Ensuring adequate oxygen delivery, early instigation of enteral nutrition and glutamine supplementation best protects it. There is also increasing evidence and support for selective decontamination of the digestive tract. Hypermotility, frequently caused by drugs, such as antibiotics, is a frequent problem. Pseudomembranous colitis associated with Clostridium difficile toxin is potentially very serious and invariably associated with antibiotic use. Probiotics may be helpful in simple diarrhoea associated with antibiotic use. [Copyright &y& Elsevier]

Study Objective. To determine the frequency with which patients who begin to receive stress ulcer prophylaxis in the surgical intensive care unit (SICU) are discharged receiving inappropriate acid suppressive therapy (AST). Design. Prospective, observational evaluation. Setting. Level 1 trauma center and academic tertiary care hospital. Patients. A total of 248 consecutive adult patients admitted to the SICU during a 6-month period who began to receive AST with a proton pump inhibitor or histamine2-receptor antagonist. Measurements and Main Results. In most patients (237 [95.6%] of 248), initiation of AST was associated with one or more risk factors for gastrointestinal bleeding. Continuation of AST during hospitalization outside the SICU occurred in 215 patients (86.7%). Sixty patients (24.2%) were discharged from the hospital receiving AST: 52 patients (21.0%) went to skilled nursing facilities or rehabilitation centers, and eight (3.2%) were discharged home. Compared with those whose AST was discontinued in the hospital, patients who continued to receive AST after hospital discharge required extended mechanical ventilation (p=0.001), had twice as many risk factors for gastrointestinal bleeding (p<0.001), were frequently discharged with anticoagulant therapy (p<0.001), exhibited longer hospital arid SICU stays (p<0.001), and more frequently demonstrated Glasgow Coma Scale scores of 8 or lower and/or had head injury (p<0.001), hepatic failure (p=0.004), and major trauma (p=0.049). Evaluation of continuation of AST during hospitalization revealed that only 7.4% (16/215) of patients at SICU transfer and 5.0% (3/60) of patients at hospital discharge had a compelling risk factor to continue AST as demonstrated by a coagulopathy at discharge; no patients required mechanical ventilation at hospital discharge. Conclusion. Most patients inappropriately continued to receive stress ulcer prophylaxis during post-SICU hospitalization. Presence of risk factors for stress ulcer-related gastrointestinal bleeding at SICU admission appears to influence continuation of AST after discharge from the hospital. A low percentage (3.2%) of patients was discharged home receiving inappropriate AST, yet overall, few study patients demonstrated a compelling risk factor for continuation of AST. [ABSTRACT FROM AUTHOR]

Rationale Doctors frequently give non-critically ill patients unjustified stress ulcer prophylaxis (SUP). It is unknown if this practice also occurs during residency training. Objective To evaluate the pattern of SUP given to non-critically ill medical patients on the teaching service of an internal medicine residency programme. Methods This was a retrospective cohort study of non-critically ill adults admitted to the internal medicine teaching service of a community hospital from August 2003 to July 2004. We assessed receipt of SUP, association of SUP with risk factors for stress ulcer bleeding; appropriateness of SUP according to evidence-based criteria; and incidence of stress ulcer bleeding. Results Of the 774 patient records reviewed, 545 were included in the study. The average age was 55.4 years. Patients were more likely to receive SUP if they had more risk factors for stress ulcer bleeding ( P < 0.001). Overall, 54.9% (299 of 545) of patients received SUP. Of these 299 patients, at least 58.5% did not warrant SUP, depending on the criteria used. Of the entire cohort of 545 non-critically ill patients, 32.1% to 54.9% received unjustified SUP, depending on the criteria applied. There were no cases of stress ulcer bleeding. Conclusions Many non-critically ill patients on the teaching service received unjustified SUP, suggesting the need for institutional protocols and educational interventions to promote evidence-based practice during residency training. [ABSTRACT FROM AUTHOR]

Background. Restraint stress produces gastric hypercontractility and acidity leading to stress ulceration. Intracerebroventricular (ICV) salmon calcitonin (sCT) decreases restraint injury and acidity, but its effects on restraint-induced hypercontractility are unknown.Methods. Using stereotactic guidance, ICV catheters were placed into the lateral ventricle of adult male rats and calibrated gastric strain gauge transducers were implanted 5 days prior to restraint stress. sCT rats (n = 8) were pretreated with 5 μg of calcitonin ICV (10 μl volume), while controls (n = 10) received 10 μl of ICV saline prior to restraint for 2 h at 20°C followed by 2 h at 4°C. Gastric motility data were collected with AT-CODAS and analyzed with ADVANCED CODAS. Gastric volume, pH, and lesions were recorded following the stress.Results. ICV calcitonin prevented gastric mucosal injury in all animals (0% vs 100%, P < .01) and elevated pH slightly (2.5 ± .3 vs 1.6 ± .1, P < .05). Stress caused the force of contractions to increase from 0.35 ± .1 to 1.38 ± .4 g in controls (P < .01), while treated animal’s force fell from .42 ± .1 to 0.2 ± .05 g (P < .01 vs control). Stress did not affect contractions/min (3.4 + .6 vs 3.5 + .3), but sCT increased frequency (2.5 + .4 to 5.0 + .2, P < .01). Stress prolonged contraction duration (11.5 + 1 to 16.5 + 1.7 s, P < .01), but stress’s effect was prevented by sCT (11.0 + .5 to 11.2 + .3, P < .01 vs control).Conclusions. Pretreatment with 5 μg central sCT prevents the increased amplitude and duration of gastric contractions produced by restraint stress for 2 h, in association with gastroprotection. [Copyright &y& Elsevier]

Objective: To determine the role of Helicobacter pylori infection in critically ill patients admitted to the intensive care unit in the formation of gastric and duodenal mucosal injury in these patients.Design and Setting: Prospective cohort analysis in an 18-bed mixed medical and surgical closed format ICU in a teaching hospital.Patients: Fifty consecutive patients admitted to the intensive care unit for emergency reasons and requiring mechanical ventilation were included.Interventions: H. pylori infection was detected by the laser-assisted ratio analyzer [13C]urea breath test (UBT). Gastric and duodenal mucosal lesions were assessed by upper gastrointestinal endoscopy and classified as minor (up to five erosions or submucosal hemorrhages) or major (more than five erosions or submucosal hemorrhages) mucosal injury.Measurements and Main Results: Six patients were not eligible because the UBT could not be processed. Of the 44 eligible patients 22 were H. pylori positive by UBT and 22 H. pylori negative. Either minor or major gastric mucosal injury was found on endoscopy in 66 %. Of the 29 patients with minor mucosal injury 10 (34.5 %) were infected with H. pylori as indicated by positive LARA 13C-UBT. In contrast, of the 15 patients with major mucosal injury 12 (80%) were infected with H. pylori (p = 0.004). H. pylori was the only risk factor significantly associated with major mucosal injury in a multiple regression analysis (p = 0.019).Conclusion: The severity of gastric and duodenal mucosal injury in critically ill patients during mechanical ventilation is significantly correlated with the presence of H. pylori infection. [ABSTRACT FROM AUTHOR]

Objective: To study the incidence of stress-ulcer related bleeding in ICU patients receiving prolonged (> 2 days) mechanical ventilation without any stress ulceration prophylaxis.Design: A prospective cohort study in 183 patients.Interventions: All patients received clinical treatment including maintenance of adequate tissue perfusion (with low dose inotropes and vasodilators), infection prevention (by selective decontamination of the digestive tract) throughout ICU stay and suppression of generalized inflammatory reaction (by steroids).Setting: Medical/surgical ICU of a major teaching hospital in Amsterdam (Onze Lieve Vrouwe Gasthuis).Measurements and Results: 167 patients were evaluated during 2182 treatment days in the ICU and during 1753 days on mechanical ventilation without stress ulceration prophylaxis. The mean total risk score for stress ulceration related bleeding was 38 (Tryba score). Stress ulceration related bleeding developed in 1 patient (0.6%).Conclusions: The incidence of SURB was less then 1% in this cohort of ICU patients receiving longterm mechanical ventilation with a high risk for SURB (mean total risk score 38). All patients received agressive shock resuscitation, infection prevention with selective decontamination of the digestive tract (SDD) and suppression of inflammatory response with steroids. Further studies are needed to evaluate the contribution of each of these elements of the integral approach. [ABSTRACT FROM AUTHOR]

We have studied the mechanisms of the increased dosage requirements of the H-receptor antagonist cimetidine in paediatric burned patients in a pharmacokinetic and pharmacodynamic study. Cimetidine (10-15 mg·kg) was given to 21 burned children and multiple blood samples were obtained for determination of plasma cimetidine concentrations and pharmacokinetic analysis. The relation of gastric pH to plasma cimetidine concentrations was studied in five of these children who had nasogastric tubes. In an additional four patients the effects of cimetidine on gastric pH were studied during a continuous infusion of cimetidine, which maintained steady-state plasma cimetidine concentrations above 0.5 µg·ml. The mean (SEM) clearance of cimetidine in burned children was 16.22 ml·kg and cimetidine half-life was 1.06 h. The cimetidine clearance and half-life values were significantly higher in burned children compared with our previously reported values for normal adult patients, 8.2 ml·min·kg and 2.21 h respectively. Endogenous creatinine clearance normalized to 70 kg in burned children was 190 ml·min. In burned children 41% of the dose of intact cimetidine was excreted during 8 h of the study compared with 45% excretion during 24 h in healthy adult controls previously reported. The correlation coefficient between creatinine and cimetidine clearances was 0.93 ( r=0.85). The plasma concentration of cimetidine needed to increase gastric pH to ≥4.0 was ≥1.0 µg·ml, which contrasts with the value of >0.5 µg·ml required for adult burned patients. These findings support the hypothesis that the higher dosage requirements of cimetidine in burned children is due both to enhanced elimination kinetics and to alterations in target organ sensitivity, requiring higher than normal plasma concentrations for the desired effect. In burned children Cimetidine should be given in higher doses and/or more frequently. [ABSTRACT FROM AUTHOR]

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Unlike hemorrhage from peptic ulcer, surgical management for hemorrhage from stress ulcer is not necessarily successful on many occasions. Thus, the most important thing one can try is to prevent the development of this condition. Forty eight patients admitted to the Shock and Trauma Unit, Hahnemann Medical College and Hospital, who had a primary diagnosis of shock were divided into three groups: group 1 received the standard shock regimen plus large dose steroid therapy repeated every four hours for 36 hours; group 2 received the standard shock regimen plus small dose steroid therapy repeated every four hours for 96 hours; group 3 received the standard shock regimen without the addition of steroids. There was a 57.9 per cent incidence of acute gastric ulceration in those shock patients not treated with steroids (group 3) compared with 33.3 per cent incidence of gastric ulceration in group 2 and 5.9 per cent incidence in group 1. The use of pharmacologic doses of steroids early in the shock state for period of less than 36 hours seems to reduce the incidence of gastric ulceration and hemorrhage in low flow states associated with septic, cardiogenic and hemorrhagic shock. [ABSTRACT FROM AUTHOR]

Abstract: Gastrointestinal dysfunction in critically ill patients is common and associated with delayed recovery and increased morbidity and mortality. Common problems include failure to absorb enteral feed, diarrhoea, stress ulceration and sepsis. The principal functions of the gut are nutrient absorption and protection against bacteria and toxins within the lumen. Normal function depends upon neuronal and neurohumoral signalling pathways, an adequate blood supply and a competent immune system. Gut motility is affected by many factors including surgery, trauma, drug therapy and shock. The loss of barrier function may allow bacterial translocation and potentially result in systemic sepsis or multi-organ dysfunction. Strategies to reduce gastrointestinal dysfunction include minimally invasive surgical techniques, epidural analgesia and fluid therapy. Gut perfusion must be maintained and nutrition provided. Prokinetic drugs are commonly used to enhance gut motility, and histamine antagonists or proton pump inhibitors are prescribed for prophylaxis against stress ulcers. Other therapies include selective decontamination of the digestive tract to reduce infection caused by translocation. [Copyright &y& Elsevier]

pH-Dependent bactericidal activity on four gram-negative bacilli that are mainly responsible for gastric to airway colonisation has been investigated. Organisms studied were Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae and Serratia marcescens. At pH of the medium adjusted to 2.7 or lower all four organisms were killed in 1.5 h. At pH 3.1 or greater, no reduction in viable bacterial number was noted over 2 h. Even when pH of the medium was adjusted to 6.8, no increase in bacterial count was observed in 4 h. Relevance of these findings in relation to airway colonisation and prophylaxis of acid aspiration and stress ulcer syndromes is discussed. It is suggested to maintain pH of the gastric contents above 4.0 by H2 antagonists and prevent growth of gram-negative organisms in the stomach by keeping it empty. [ABSTRACT FROM AUTHOR]