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Tu1356 Administration of Stress Ulcer Prophylaxis May Cause Harm in Critically Ill Patients: A Randomized Double Blind Exploratory Study
AGA Abstracts
0.005]. Mortality during inpatient AUGIB (33%) was significantly higher than those admitted with AUGIB (14%). Discontinuation of antithrombotic therapy post endoscopy was associated with increased thrombotic events (RR 5.5, p<0.001), reduced rebleeding (RR 0.5, p=0.35), and increased incidence of any adverse event (RR 2.1, p=0.005). Discontinuation post discharge was associated with reduced survival ( p=0.03), increased thrombotic events (p= 0.01) and any adverse event ( p=0.006). Conclusion: In our patient group, mortality from thrombotic causes following AUGIB is high. Maintenance of antithrombotic therapy, including non-aspirin regimens, appears to be associated with improved thrombotic outcomes and reduced mortality.
Tu1357 Idarucizumab for Emergent Reversal of Dabigatran-Related Anticoagulation During Severe Gastrointestinal Hemorrhage: Interim Results (N=123) From the Reverse-AdTM Study James Aisenberg, Prapti Chatterjee, Paul Reilly, Fredrik Gruenenfelder, Eva Kleine, Stephan Glund, Charles Pollack Background: Gastrointestinal bleeding (GIB) is a feared complication of anticoagulation. Idarucizumab (IDA) is a rapid-onset specific reversal agent for the direct thrombin inhibitor dabigatran. IDA should benefit management of dabigatran users experiencing severe GIB. Methods: The on-going REVERSE-ADTM study evaluates the safety and efficacy of IDA 5 grams intravenously in dabigatran users with (A) life-threatening hemorrhage or (B) requirement for emergency surgery. Here, we analyze the clinical characteristics and outcomes of REVERSE-ADTM enrollees presenting with severe GIB. Our study is performed on an interim analysis cohort of 123 patients; centralized laboratory coagulation data are available for 90/ 123 (20/27 patients with MGIB). Results: Of the 66 patients enrolled in REVERSE-ADTM due to severe bleeding, 27 (41%) bled in the GI tract. The mean age of GIB patients was 77.5 years (range, 60-93), 15 (56%) were male, and renal impairment was present in 22 of the 23 patients with creatinine clearance measurements (96%). Atrial fibrillation was the indication for anticoagulation in 93%; 74% took their most recent dabigatran dose < 24 hours before presentation. Ten patients (37%) bled from the upper GI tract, 8 (30%) from the lower GI tract, and 9 (33%) from an unknown level of the GI tract. IDA achieved immediate reversal of dabigatran-related anticoagulation, and its effect lasted for up to 24 hours in the majority of patients (Figure 1).Hospital admission was required for 25 patients (93%, median length of stay= 6.0 nights); 8 patients required > 1 day in intensive care unit (ICU) (30%, median length of ICU stay=3.5 days). In 23 subjects for whom bleeding duration is reported by the local investigator, median time to cessation of GIB after IDA administration was 4.5 hours (range 0-645 hours). Patients with lower GI bleeding had shorter time to cessation of bleeding (median 1.5 hours vs. 7.3 hours). No adverse events attributable to IDA were reported. A total of 24 patients received ‡1 unit packed red cells (mean 4.5 units); 9 received fresh frozen plasma (mean 2.6 units); 2 received platelets (mean 1.5 units); and 1 received prothrombin complex concentrate prior to IDA treatment. There were 3 deaths by 90 days, but none directly attributable to GIB. Antithrombotic therapy was resumed in 20 patients (74%) prior to study termination, within a median of 6.1 days (range 0-41 days) after IDA administration. Dabigatran was resumed in 6 patients (22%). Conclusions: The GI tract is the most common site of anticoagulant-associated hemorrhage meeting clinical criteria for emergent reversal. IDA achieves immediate reversal of dabigatran-induced anticoagulation, an effect that is sustained for up to 1 day in the majority of patients. Overall, GIB outcomes in this setting are favorable; antithrombotic therapy can be resumed promptly in most patients.
Tu1355 GI Bleeding in LVAD Patients Is Associated With Higher Levels of Circulating VEGF One Month Post LVAD Implantation Anjali S. Shah, Nathaniel Ranney, Loretta Jophlin, Andrew Brock, Meredith Brisco, Don C. Rockey Objective: It is known that individuals with left ventricular assist device (LVADs) are at increased risk of having clinically significant gastrointestinal (GI) bleeding due to the development of angioectasias in the GI tract. The association between and pathophysiology behind LVAD placement and GI bleeding due to angioectasias is incompletely understood. It is possible that angiogenic factors like vascular endothelial growth factor (VEGF) play a role in the development of luminal angioectasias that are at risk for bleeding. In this study, we hypothesized that individuals with LVADs who developed GI bleeding would have higher levels of circulating plasma VEGF than individuals who do not have GI bleeding. Methods: This is a prospective, observational study of 25 consecutive patients who underwent placement of an LVAD at the Medical University of South Carolina from April 2014 to January 2015. Plasma was obtained from each patient at the following time points: enrollment (prior to LVAD placement), within 24 hours after LVAD placement, 1 month after LVAD placement, 6 months after LVAD placement, and after cardiac transplant (when applicable). Patients were prospectively followed and any hospitalizations related to GI bleeding were captured. An additional sample of plasma was obtained during any hospitalization related to GI bleeding. A commercially available Elisa kit was used to detect VEGF levels and statistical analysis was performed using a one-tailed Mann-Whitney U test with a p value of 0.05 denoting significance. Results: 25 patients underwent LVAD placement and were followed prospectively for a mean period of 6 months. 7 patients (28%) were hospitalized with GI bleeding during this time period. Plasma levels of VEGF were similar between the population of patients who had GI bleeding versus those who did not bleed at the time of study enrollment (25.17pg/ml +/- 36 vs 36.22 pg/ml +/- 21.7, p = 0.17) and 24 hours after LVAD implantation (33.6 pg/ml +/- 33.4 vs 41.8 pg/ml +/- 24.2, p=0.13). The population of patients who eventually had a clinically relevant GI bleed had statistically significant higher levels of circulating VEGF at one month post LVAD implantation (111.5pg/ml +/-69.6 vs 62.7 pg/ml +/- 40.3, p=0.048). Conclusion: Patients with LVADs who suffer from GI bleeding have higher levels of circulating VEGF at 1 month post LVAD placement as compared to those who do not have GI bleeding.
Tu1356 Administration of Stress Ulcer Prophylaxis May Cause Harm in Critically Ill Patients: A Randomized Double Blind Exploratory Study Shane P. Selvanderan, Matthew Summers, Mark Finnis, Mark Plummer, Yasmine Ali Abdelhamid, Michael Anderson, Marianne Chapman, Chris Rayner, Adam M. Deane INTRODUCTION Acid suppressive drugs such as pantoprazole are frequently administered to mechanically ventilated critically ill patients for prophylaxis against gastrointestinal (GI) bleeding; however, these drugs have been inadequately evaluated in this group and have the potential to cause harm. STUDY OBJECTIVES To evaluate the effect of prophylactic pantoprazole administration on the rates of clinically significant GI bleeding, infective ventilator-associated complications or pneumonia, and Clostridium difficile infection in mechanically ventilated, critically ill patients suitable for enteral nutrition. Secondary outcomes included rates of overt GI bleeding, daily haemoglobin concentrations, units of packed red cells transfused and all-cause mortality by day 90. METHODS All patients anticipated to require mechanical ventilation for > 24 hours and to commence enteral nutrition within 48 hours of admission who were admitted to a single mixed medical-surgical quaternary-level adult intensive care unit between 28 January 2014 and 27 January 2015 were eligible. 214 patients were randomly assigned to receive intravenous pantoprazole (40mg) or placebo daily in a double blind fashion. Data were collected for overt GI bleeding (haematemesis, bloody gastric aspirate, melaena or haematochezia), clinically significant bleeding (overt bleeding accompanied by a drop in mean arterial pressure >20mmHg, or reduction in haemoglobin >20g/L, or need for surgical intervention), infective ventilator-associated complication or pneumonia, and C difficile infection. RESULTS There were no episodes of clinically significant GI bleeding. One patient met the criteria for an infective ventilator-associated complication (placebo: 0 vs. pantoprazole: 1) and three patients met the criteria for infective ventilatorassociated complication or pneumonia (1 vs. 2). Only one patient was diagnosed with C difficile infection (0 vs. 1). Administration of prophylactic pantoprazole was not associated with any difference in rates of overt bleeding (6 vs. 3; P=0.50), daily hemoglobin concentrations, transfusion rates of packed red cells (P=0.66) or rates of clinician-adjudicated ventilatorassociated pneumonia (8 vs. 12; P=0.35). Mortality was similar between groups (log-rank P=0.33: adjusted hazard ratio for pantoprazole: 1.68 (95% CI 0.97, 2.90); P=0.06). CONCLUSIONS In this exploratory study the prophylactic administration of pantoprazole did not reduce clinically significant GI bleeding, but point estimates indicate that this approach is associated with harm. There is an urgent need for a definitive randomized controlled trial.
AGA Abstracts
Tu1358 Mortality Associated with Peptic Ulcer Bleeding - Analysis of the National Hospital Discharge Survey David Mossad, Ronald J. Markert, Sangeeta Agrawal Introduction Patients presenting with upper gastrointestinal bleeding (UGIB) due to peptic ulcer disease (PUD) are acutely at high risk for morbidity and mortality. Multiple scoring systems stratify risk in these patients to assess the need for endoscopy, chances of rebleeding, and mortality risk. The purpose of this study was to assess the effects of patient demographics, comorbidity burden, and hospital characteristics on in-hospital mortality in patients with UGIB due to PUD. Methods We used ICD-9 diagnosis codes from the 20012010 National Hospital Discharge Survey to identify cases of UGIB due to PUD. Comparisons on demographics, number of comorbidities, hospital length of stay (LOS), and selected health system characteristics were made between those who died in-hospital and those discharged. SPSS was used for chi-square and t test analysis. Results Among 12,196 cases of UGIB due to PUD, 499 died in-hospital and 11,697 were discharged. The mortality group was older (mean age of 74.4 vs 67.5 years, p<0.001) and had a longer LOS (13.1 vs 6.2 days, p<0.001). There was no difference in mortality between genders (4.0% of males vs 4.2% of females, p=0.71) or race (Caucasians 4.5%, African Americans 4.0% and others 3.5%, p=0.06). Patients with seven or more comorbidities had a higher mortality rate (5.1%) compared to those with six or fewer comorbidities (1.4%) [p<0.001]. Neither chronic kidney
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0.005]. Mortality during inpatient AUGIB (33%) was significantly higher than those admitted with AUGIB (14%). Discontinuation of antithrombotic therapy post endoscopy was associated with increased thrombotic events (RR 5.5, p<0.001), reduced rebleeding (RR 0.5, p=0.35), and increased incidence of any adverse event (RR 2.1, p=0.005). Discontinuation post discharge was associated with reduced survival ( p=0.03), increased thrombotic events (p= 0.01) and any adverse event ( p=0.006). Conclusion: In our patient group, mortality from thrombotic causes following AUGIB is high. Maintenance of antithrombotic therapy, including non-aspirin regimens, appears to be associated with improved thrombotic outcomes and reduced mortality.
Tu1357 Idarucizumab for Emergent Reversal of Dabigatran-Related Anticoagulation During Severe Gastrointestinal Hemorrhage: Interim Results (N=123) From the Reverse-AdTM Study James Aisenberg, Prapti Chatterjee, Paul Reilly, Fredrik Gruenenfelder, Eva Kleine, Stephan Glund, Charles Pollack Background: Gastrointestinal bleeding (GIB) is a feared complication of anticoagulation. Idarucizumab (IDA) is a rapid-onset specific reversal agent for the direct thrombin inhibitor dabigatran. IDA should benefit management of dabigatran users experiencing severe GIB. Methods: The on-going REVERSE-ADTM study evaluates the safety and efficacy of IDA 5 grams intravenously in dabigatran users with (A) life-threatening hemorrhage or (B) requirement for emergency surgery. Here, we analyze the clinical characteristics and outcomes of REVERSE-ADTM enrollees presenting with severe GIB. Our study is performed on an interim analysis cohort of 123 patients; centralized laboratory coagulation data are available for 90/ 123 (20/27 patients with MGIB). Results: Of the 66 patients enrolled in REVERSE-ADTM due to severe bleeding, 27 (41%) bled in the GI tract. The mean age of GIB patients was 77.5 years (range, 60-93), 15 (56%) were male, and renal impairment was present in 22 of the 23 patients with creatinine clearance measurements (96%). Atrial fibrillation was the indication for anticoagulation in 93%; 74% took their most recent dabigatran dose < 24 hours before presentation. Ten patients (37%) bled from the upper GI tract, 8 (30%) from the lower GI tract, and 9 (33%) from an unknown level of the GI tract. IDA achieved immediate reversal of dabigatran-related anticoagulation, and its effect lasted for up to 24 hours in the majority of patients (Figure 1).Hospital admission was required for 25 patients (93%, median length of stay= 6.0 nights); 8 patients required > 1 day in intensive care unit (ICU) (30%, median length of ICU stay=3.5 days). In 23 subjects for whom bleeding duration is reported by the local investigator, median time to cessation of GIB after IDA administration was 4.5 hours (range 0-645 hours). Patients with lower GI bleeding had shorter time to cessation of bleeding (median 1.5 hours vs. 7.3 hours). No adverse events attributable to IDA were reported. A total of 24 patients received ‡1 unit packed red cells (mean 4.5 units); 9 received fresh frozen plasma (mean 2.6 units); 2 received platelets (mean 1.5 units); and 1 received prothrombin complex concentrate prior to IDA treatment. There were 3 deaths by 90 days, but none directly attributable to GIB. Antithrombotic therapy was resumed in 20 patients (74%) prior to study termination, within a median of 6.1 days (range 0-41 days) after IDA administration. Dabigatran was resumed in 6 patients (22%). Conclusions: The GI tract is the most common site of anticoagulant-associated hemorrhage meeting clinical criteria for emergent reversal. IDA achieves immediate reversal of dabigatran-induced anticoagulation, an effect that is sustained for up to 1 day in the majority of patients. Overall, GIB outcomes in this setting are favorable; antithrombotic therapy can be resumed promptly in most patients.
Tu1355 GI Bleeding in LVAD Patients Is Associated With Higher Levels of Circulating VEGF One Month Post LVAD Implantation Anjali S. Shah, Nathaniel Ranney, Loretta Jophlin, Andrew Brock, Meredith Brisco, Don C. Rockey Objective: It is known that individuals with left ventricular assist device (LVADs) are at increased risk of having clinically significant gastrointestinal (GI) bleeding due to the development of angioectasias in the GI tract. The association between and pathophysiology behind LVAD placement and GI bleeding due to angioectasias is incompletely understood. It is possible that angiogenic factors like vascular endothelial growth factor (VEGF) play a role in the development of luminal angioectasias that are at risk for bleeding. In this study, we hypothesized that individuals with LVADs who developed GI bleeding would have higher levels of circulating plasma VEGF than individuals who do not have GI bleeding. Methods: This is a prospective, observational study of 25 consecutive patients who underwent placement of an LVAD at the Medical University of South Carolina from April 2014 to January 2015. Plasma was obtained from each patient at the following time points: enrollment (prior to LVAD placement), within 24 hours after LVAD placement, 1 month after LVAD placement, 6 months after LVAD placement, and after cardiac transplant (when applicable). Patients were prospectively followed and any hospitalizations related to GI bleeding were captured. An additional sample of plasma was obtained during any hospitalization related to GI bleeding. A commercially available Elisa kit was used to detect VEGF levels and statistical analysis was performed using a one-tailed Mann-Whitney U test with a p value of 0.05 denoting significance. Results: 25 patients underwent LVAD placement and were followed prospectively for a mean period of 6 months. 7 patients (28%) were hospitalized with GI bleeding during this time period. Plasma levels of VEGF were similar between the population of patients who had GI bleeding versus those who did not bleed at the time of study enrollment (25.17pg/ml +/- 36 vs 36.22 pg/ml +/- 21.7, p = 0.17) and 24 hours after LVAD implantation (33.6 pg/ml +/- 33.4 vs 41.8 pg/ml +/- 24.2, p=0.13). The population of patients who eventually had a clinically relevant GI bleed had statistically significant higher levels of circulating VEGF at one month post LVAD implantation (111.5pg/ml +/-69.6 vs 62.7 pg/ml +/- 40.3, p=0.048). Conclusion: Patients with LVADs who suffer from GI bleeding have higher levels of circulating VEGF at 1 month post LVAD placement as compared to those who do not have GI bleeding.
Tu1356 Administration of Stress Ulcer Prophylaxis May Cause Harm in Critically Ill Patients: A Randomized Double Blind Exploratory Study Shane P. Selvanderan, Matthew Summers, Mark Finnis, Mark Plummer, Yasmine Ali Abdelhamid, Michael Anderson, Marianne Chapman, Chris Rayner, Adam M. Deane INTRODUCTION Acid suppressive drugs such as pantoprazole are frequently administered to mechanically ventilated critically ill patients for prophylaxis against gastrointestinal (GI) bleeding; however, these drugs have been inadequately evaluated in this group and have the potential to cause harm. STUDY OBJECTIVES To evaluate the effect of prophylactic pantoprazole administration on the rates of clinically significant GI bleeding, infective ventilator-associated complications or pneumonia, and Clostridium difficile infection in mechanically ventilated, critically ill patients suitable for enteral nutrition. Secondary outcomes included rates of overt GI bleeding, daily haemoglobin concentrations, units of packed red cells transfused and all-cause mortality by day 90. METHODS All patients anticipated to require mechanical ventilation for > 24 hours and to commence enteral nutrition within 48 hours of admission who were admitted to a single mixed medical-surgical quaternary-level adult intensive care unit between 28 January 2014 and 27 January 2015 were eligible. 214 patients were randomly assigned to receive intravenous pantoprazole (40mg) or placebo daily in a double blind fashion. Data were collected for overt GI bleeding (haematemesis, bloody gastric aspirate, melaena or haematochezia), clinically significant bleeding (overt bleeding accompanied by a drop in mean arterial pressure >20mmHg, or reduction in haemoglobin >20g/L, or need for surgical intervention), infective ventilator-associated complication or pneumonia, and C difficile infection. RESULTS There were no episodes of clinically significant GI bleeding. One patient met the criteria for an infective ventilator-associated complication (placebo: 0 vs. pantoprazole: 1) and three patients met the criteria for infective ventilatorassociated complication or pneumonia (1 vs. 2). Only one patient was diagnosed with C difficile infection (0 vs. 1). Administration of prophylactic pantoprazole was not associated with any difference in rates of overt bleeding (6 vs. 3; P=0.50), daily hemoglobin concentrations, transfusion rates of packed red cells (P=0.66) or rates of clinician-adjudicated ventilatorassociated pneumonia (8 vs. 12; P=0.35). Mortality was similar between groups (log-rank P=0.33: adjusted hazard ratio for pantoprazole: 1.68 (95% CI 0.97, 2.90); P=0.06). CONCLUSIONS In this exploratory study the prophylactic administration of pantoprazole did not reduce clinically significant GI bleeding, but point estimates indicate that this approach is associated with harm. There is an urgent need for a definitive randomized controlled trial.
AGA Abstracts
Tu1358 Mortality Associated with Peptic Ulcer Bleeding - Analysis of the National Hospital Discharge Survey David Mossad, Ronald J. Markert, Sangeeta Agrawal Introduction Patients presenting with upper gastrointestinal bleeding (UGIB) due to peptic ulcer disease (PUD) are acutely at high risk for morbidity and mortality. Multiple scoring systems stratify risk in these patients to assess the need for endoscopy, chances of rebleeding, and mortality risk. The purpose of this study was to assess the effects of patient demographics, comorbidity burden, and hospital characteristics on in-hospital mortality in patients with UGIB due to PUD. Methods We used ICD-9 diagnosis codes from the 20012010 National Hospital Discharge Survey to identify cases of UGIB due to PUD. Comparisons on demographics, number of comorbidities, hospital length of stay (LOS), and selected health system characteristics were made between those who died in-hospital and those discharged. SPSS was used for chi-square and t test analysis. Results Among 12,196 cases of UGIB due to PUD, 499 died in-hospital and 11,697 were discharged. The mortality group was older (mean age of 74.4 vs 67.5 years, p<0.001) and had a longer LOS (13.1 vs 6.2 days, p<0.001). There was no difference in mortality between genders (4.0% of males vs 4.2% of females, p=0.71) or race (Caucasians 4.5%, African Americans 4.0% and others 3.5%, p=0.06). Patients with seven or more comorbidities had a higher mortality rate (5.1%) compared to those with six or fewer comorbidities (1.4%) [p<0.001]. Neither chronic kidney
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