***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Objectives : Pantoprazole is frequently administered to critically ill patients for prophylaxis against gastrointestinal bleeding . However , comparison to placebo has been inadequately evaluated , and pantoprazole has the potential to cause harm . Our objective was to evaluate benefit or harm associated with pantoprazole administration . Design : Prospect i ve r and omized double-blind parallel-group study . Setting : University-affiliated mixed medical-surgical ICU . Patients : Mechanically ventilated critically ill patients suitable for enteral nutrition . Interventions : We r and omly assigned patients to receive either daily IV placebo or pantoprazole . Measurements and Main Results : Major outcomes were clinical ly significant gastrointestinal bleeding , infective ventilator-associated complication or pneumonia , and Clostridium difficile infection ; minor outcomes included overt bleeding , hemoglobin concentration profiles , and mortality . None of the 214 patients r and omized had an episode of clinical ly significant gastrointestinal bleeding  , three patients met the criteria for either an infective ventilator-associated complication or pneumonia ( placebo : 1 vs pantoprazole : 2 ) , and one patient was diagnosed with Clostridium difficile infection ( 0 vs 1 ) . Administration of pantoprazole was not associated with any difference in rates of overt bleeding ( 6 vs 3 ; p = 0.50 ) or daily hemoglobin concentrations when adjusted for transfusion rates of packed red cells ( p = 0.66 ) . 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 : We found no evidence of benefit or harm with the prophylactic administration of pantoprazole to mechanically ventilated critically ill patients anticipated to receive enteral nutrition . The practice of routine administration of acid-suppressive drugs to critically ill patients for stress ulcer prophylaxis warrants further evaluation The efficacy of cimetidine in the prevention of  gastrointestinal haemorrhage  in a general intensive care unit was evaluated in 221 patients by a placebo controlled double blind r and omised study . Criteria for bleeding were ( i ) haematemesis or gastric aspirate greater than 50 ml fresh blood , ( ii ) melaena or fresh blood per rectum with an upper source verified by endoscopy if the gastric aspirate was clear , ( iii ) a fall in haemoglobin level greater than 2 g/dl in a 24 hour period associated with either 4 + occult blood in stools , or coffee ground gastric drainage of at least 100 ml . The drug and placebo groups were similar for age , sex , duration of study and risk factors . One hundred and fourteen received cimetidine and 107 placebo . Only 8 % of the patients bled with no significant difference between the two groups ( 6/114 cimetidine , 11/107 placebo ; p = 0.16 ) . There was no correlation between the frequency of bleeding and either the number of risk factors per patient or the duration of intensive care unit stay . Thirteen patients died in each study group , result ing in overall mortality of 12 % . The low incidence of haemorrhage , the lack of statistical benefit from cimetidine and the similar mortality all argue against the routine use of this drug in intensive care unit patients Objective To estimate the mortality and length of stay in the intensive care unit ( ICU ) attributable to clinical ly important gastrointestinal bleeding in mechanically ventilated critically ill patients . Design Three strategies were used to estimate the mortality attributable to bleeding in two multicentre data bases . The first method matched  patients who bled with those who did not  (  matched cohort ) , using duration of ICU stay prior to the bleed , each of six domains of the Multiple Organ Dysfunction Score ( MODS ) measured 3 days prior to the bleed , APACHE II score , age , admitting diagnosis , and duration of mechanical ventilation . The second approach employed Cox proportional hazards regression to match bleeding and non-bleeding patients ( model-based matched cohort ) . The third method , instead of matching , derived estimates based on regression modelling using the entire population ( regression method ) . Three parallel analyses were conducted for the length of ICU stay attributable to clinical ly important bleeding . Setting Sixteen Canadian university-affiliated ICUs . Patients A total of 1666 critically ill patients receiving mechanical ventilation for at least 48 hours . Measurements We prospect ively collected data on patient demographics , APACHE II score , admitting diagnosis , daily MODS , clinical ly important bleeding , length of ICU stay , and mortality . Independent adjudicators determined the occurrence of clinical ly important gastrointestinal bleeding , defined as overt bleeding in association with haemodynamic compromise or blood transfusion . Results Of 1666 patients , 59 developed clinical ly important gastrointestinal bleeding . The mean APACHE II score was 22.9 ± 8.6 among bleeding patients and 23.3 ± 7.7 among non-bleeding patients . The risk of death was increased in patients with bleeding using all three analytic approaches ( matched cohort method : relative risk [RR]= 2.9 , 95 % confidence interval (CI)= 1.6–5.5 ; model-based matched cohort method : RR = 1.8 , 95 % CI = 1.1–2.9 ; and the regression method : RR = 4.1 , 95 % CI = 2.6–6.5 ) . However , this was not significant for the adjusted regression method ( RR = 1.0 , 95 % CI = 0.6–1.7 ) . The median length of ICU stay attributable to clinical ly important bleeding for these three methods , respectively , was 3.8 days ( 95 % CI = -0.01 to 7.6 days ) , 6.7 days ( 95 % CI = 2.7–10.7 days ) , and 7.9 days ( 95 % CI = 1.4–14.4 days ) . Conclusions Clinical ly important upper gastrointestinal bleeding has an important attributable morbidity and mortality , associated with a RR of death of 1–4 and an excess length of ICU stay of approximately 4–8 days Purpose : We investigated whether early enteral nutrition alone may be sufficient prophylaxis against stress‐related gastrointestinal ( GI ) bleeding in mechanically ventilated patients . Material s and methods : Prospect i ve , double blind , r and omized , placebo‐controlled , exploratory study that included mechanically ventilated patients in medical ICUs of two academic hospitals .  Intravenous pantoprazole and early enteral nutrition were compared to placebo and early enteral nutrition as stress‐ulcer prophylaxis . The incidences of clinical ly significant and overt GI bleeding were compared in the two groups . Results : 124 patients were enrolled in the study . After exclusion of 22 patients , 102 patients were included in analysis : 55 patients in the treatment group and 47 patients in the  placebo group . Two patients ( one from each group ) showed signs of overt GI bleeding ( overall incidence 1.96 % ) , and both patients experienced a drop of > 3 points in hematocrit in a 24‐hour period indicating a clinical ly significant GI bleed . There was no statistical significant difference in the incidence of overt or significant GI bleeding between groups ( p = 0.99 ) . Conclusion : We found no benefit when pantoprazole is added to early enteral nutrition in mechanically ventilated critically ill patients . The routine prescription of acid‐suppressive therapy in critically ill patients who tolerate early enteral nutrition warrants further evaluation . Highlights : GI bleeding has low incidence in the critically ill mechanically ventilated patients .Adding PPI to enteral nutrition may not offer an added prophylaxis against stress‐related GI bleeding . Our study supports the protective role of enteral nutrition in ICU BACKGROUND / AIMS Critically ill patients especially who require mechanical ventilation or have coagulopathy are at increased risk for stress-related gastrointestinal hemorrhage . There are conflicting data on the efficacy and complication rates of various prophylactic regimens . METHODOLOGY Our single-center r and omized , placebo-controlled study included 287 patients with high risk for stress-related upper gastrointestinal hemorrhage ( > 48 h mechanical ventilation , coagulopathy ) . We compared 3 prophylactic regimens ( proton pump inhibitor -- omeprazole 40 mg i.v . once daily , n=72 ; H2 antagonists -- famotidine 40 mg twice a day , n=71 ; and sucralfate 1 g every 6 hours , n=69 ) with placebo ( n=75 ) in patients with trauma or after major surgery . RESULTS Of 287 assessable patients , clinical ly significant stress-related upper gastrointestinal bleeding was observed in 1 % , 3 % , 4 % , and 1 % of patients assigned to receive omeprazole , famotidine , sucralfate , and placebo , respectively ( p>0.28 ) . Bleeding developed significantly more often in patients with coagulopathy compared with the others ( 10 % vs. 2 % ; p=0.006 ) . The gastric pH ( p>0.001 ) and gastric colonization ( p<0.05 ) was significantly higher in the patients who received pH increasing substances when compared with the other 2 groups . Nosocomial pneumonia occurred in 11 % of patients receiving omeprazole , in 10 % of famotidine patients , in 9 % of sucralfate patients and in 7 % of controls ( p>0.34 ) . No statistically significant differences were found for days on ventilator , length of ICU stay , or mortality among all the 4 groups . CONCLUSIONS We could not show that omeprazole , famotidine , or sucralfate prophylaxis can affect already very low incidence of clinical ly important stress-related bleeding in high-risk surgical intensive care unit patients . Furthermore , our data suggested that especially gastric pH increasing medication could increase the risk for nosocomial pneumonia . Routine prophylaxis for stress-related bleeding even in high-risk patients seems not to be justified Objectives To determine whether a continuous iv infusion of cimetidine , a histamine-2 ( H2 ) receptor antagonist , is needed to prevent upper gastrointestinal ( GI ) hemorrhage when compared with placebo and if that usage is associated with an increased risk of nosocomial pneumonia . Due to the importance of this latter issue , data were collected to examine the occurrence rate of nosocomial pneumonia under the conditions of this study . Design A multicenter , double-blind , placebocontrolled study . Interventions Patients were r and omized to receive cimetidine ( n = 65 ) as an iv infusion of 50 to 100 mg/hr or placebo  ( n = 66 ) . Setting Intensive care units in 20 institutions . Patients Critically ill patients ( n = 131 ) , all of whom had at least one acute stress condition that previously had been associated with the development of upper GI hemorrhage . Measurements and Main Results Sample s of gastric fluid from nasogastric aspirates were collected every 2 hrs for measurement of pH and were examined for the presence of blood . Upper GI hemorrhage was defined as bright red blood or persistent ( continuing for > 8 hrs ) “ coffee ground material ” in the nasogastric aspirate . Baseline chest radiographs were performed and sputum specimens were collected from all patients , and those patients without clear signs of pneumonia ( positive chest radiograph , positive cough , fever ) at baseline were followed prospec-tively for the development of pneumonia while receiving the study medication . Cimetidine-infused patients experienced significantly ( p = .009 ) less upper GI hemorrhage than placebo-infused patients : nine ( 14 % ) of 65 cimetidine vs. 22 ( 33 % ) of 66 placebo patients . Cimetidine patients demonstrated significantly ( p = .0001 ) higher mean intragastric pH ( 5.7 vs. 3.9 ) , and had intragastric pH values at > 4.0 for a significantly ( p = .0001 ) higher mean percentage of time ( 82 % vs. 41 % ) than placebo patients . Differences in pH variables were not found between patients who had upper GI hemorrhage and those patients who did not , although there was no patient in the cimetidine group who bled with a pH < 3.5 compared with 11 such patients in the placebo group . Also , the upper GI hemorrhage rate in patients with one risk factor ( 23 % ) was similar to that rate in patients with two or more risk factors ( 25 % ) . Of the 56 cimetidine-infused patients and 61 placebo-infused patients who did not have pneumonia at baseline , no cimeti-dine-infused patient developed pneumonia while four ( 7 % ) placebo-infused patients developed pneumonia . Conclusions The continuous iv infusion of cimetidine was highly effective in Background Critically ill patients in the intensive care unit ( ICU ) are at risk of clinical ly important gastrointestinal bleeding , and acid suppressants are frequently used prophylactically . However , stress ulcer prophylaxis may increase the risk of serious adverse events and , additionally , the quantity and quality of evidence supporting the use of stress ulcer prophylaxis is low . The aim of the SUP-ICU trial is to assess the benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in adult patients 
    Output:
    
This meta- analysis demonstrated that SUP use was associated with significant reductions in bleeding but not mortality .