Stress Ulcer Prophylaxis In The ICU. Scott W. Wolf Anesthesiology Critical Care Medicine
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1 Stress Ulcer Prophylaxis In The ICU Scott W. Wolf Anesthesiology Critical Care Medicine
2 Some history Stress Ulceration described in ICU patients as long as 45 years ago Patients had a constellation of problems but primarily included respiratory failure, hypotension, and sepsis Subsequent studies using H2 receptor antagonists showed a decreased risk of bleeding, and stress ulcer prophylaxis (SUP) became a standard of care
3 More history Proton pump inhibitors (PPI) have also become commonly prescribed for SUP although evidence showing superiority to H2RAs is lacking Some presumed risks exist Colonization of the UGI tract leading to HAP Increased risk of C-difficile infection Drug side effects and drug-drug interactions (H2 blockers and low plt, PPI and statins)
4 Past and present Most recommendations were based on trials that existed during a different era of critical care Before goal-directed resucitation Before early enteral nutrition Before ventilator bundles
5 Revisiting some old questions Is there a role for stress ulcer prophylaxis in the ICU? Is there any added benefit in patients receiving enteral nutrition? Is there any risk associated with the practice of giving stress ulcer prophylaxis? Is there any benefit to H2 blockers vs PPIs?
6
7 SUP vs placebo or no prophylaxis Systematic review using meta-analysis Included randomized clinical trials comparing H2 blockers or PPI s to placebo or no prophylaxis Adult patients admitted to the ICU Patients were considered to have received enteral nutrition if they used any volume of enteral nutrition Primary outcomes included mortality Secondary outcomes were GI bleeding and PNA
8 SUP vs placebo or no prophylaxis Ultimately included 20 trials of 393 screened 16 were single-centered 12 used placebo 7 where patients were fed enterally 8 used SICU patients 5 used MICU patients 20 trials used H2 blockers and 2 used PPIs also 19 trials the route was IV Dosing and duration varied Total of 1971 patients enrolled
9 SUP vs placebo or no prophylaxis All-cause mortality: NO significant difference No increased intervention effect with PPIs GI Bleeding Conventional meta-analysis showed a statistically significant difference in those treated with SUP primarily with H2 blockers Trial sequential analysis (adjusting for the significance of data sizes) did not show a statistically significant difference, suggesting a high risk of bias HAP NO significant difference with either H2 blockers or PPI s compared to placebo or no prophylaxis CONCLUSION: the quality and quantity of evidence for using SUP in adult ICU patients is low
10 Crit Care Med 2010 Vol 38 No. 11
11 SUP: A review of risks and benefits and the effect of enteral nutrition Authors postulated that SUP has no added benefit in ICU patients receiving enteral nutrition and may actually have increased risk Meta analysis to look at the effect of SUP on the risk of bleeding and grouped the studies by whether or not they used enteral nutrition
12 SUP: A review of risks and benefits and the effect of enteral nutrition Randomized placebo controlled clinical trials that evaluated the role of H2 blockers For trials that included PPI or sucralfate only the patients that got H2 blockers were included Incidence of clinical bleeding or bleeding by endoscopy Other endpoints included HAP and mortality
13 SUP: A review of risks and benefits and the effect of enteral nutrition Meta analysis included 17 studies 1836 patients Clinically significant bleeding was reported in 16 studies and one study reported bleeding according to endoscopy
14 SUP: A review of risks and benefits and the effect of enteral nutrition Results: SUP with H2 blockers decreased the risk of GIB Benefit was only seen in those patients that did not receive enteral nutrition In studies where patients received enteral nutrition there was no benefit to SUP 9 studies looked at the incidence of HAP H2 blockers did NOT increase the risk however it was increased in the group receiving enteral nutrition 14 studies looked at mortality SUP did NOT effect mortality overall, however It DID increase mortality in patients getting an H2 blocker AND receiving enteral nutrition ** Likely an effect of increased ph and gastric colonization - A major limitation is that patients only received adequate enteral nutrition in 3 studies - No clinical trial has adquately prospectively studied the effect of enteral nutrition on the risk of SUP
15 What about H2 blockers vs PPI s?? Critical Care Medicine March 2013 Vol 41 No 3
16 H2 Blockers vs PPI s Three prior meta-anlysises comparing H2 blockers to PPI s have been published 2009 Pongprasobchai included 569 pts from 3 trials and showed a lower incidence of GIB with PPIs 2010 Lin included 936 pts from 7 trials and it showed no difference 2012 Barkun included 1587 pts from 13 trials and showed a lower incidence of GIB with PPI s Goal was to provide an updated meta-analysis comparing H2 blockers to PPIs
17 H2 Blockers vs PPI s Adult critically ill patients in MICU or SICU Control group: pts receiving H2 blockers Intervention group: pts receiving PPIs Primary outcome: clinically important bleeding or overt UGI bleeding Secondary outcome: PNA, mortality, ICU LOS
18 H2 Blockers vs PPI s 14 randomized trials were included 1720 patients total 3 trials at low risk of bias 6 trials at high risk of bias
19 H2 Blockers vs PPI s Clinically important bleeding 12 trials included PPIs were associated with a lower risk of bleeding Overt bleeding 14 trials included (coffee ground emesis, hematemesis, hematochezia) PPIs were associated with a lower risk of bleeding PNA 8 trials included NO difference noted Mortality 8 trials included NO difference in mortality ICU LOS 5 trials included NO difference noted
20 H2 Blockers vs PPI s Was noted that higher quality trials were associated with a smaller treatment effect NO major difference between IV vs PO NO major difference in frequency of dosing NO major difference in SICU vs MICU This meta analysis did not stratify patients according to nutritional strategies Overall number of events was very small
21 Summary There is not rigorous prospective evidence to support the use of stress ulcer prophylaxis with any pharmacologic agent It probably makes sense to use an H2 blocker in those patients that are not receiving enteral nutrition although there may be a reduced incidence of clinically important GI bleeding with the use of a PPI There may be an advantage of PPI s to H2 blockers in terms of bleeding but this might not be significant compared to placebo or no prophylaxis SUP should be stopped once a patient is taking a regular diet or receiving enteral nutrition to avoid increasing the risk of HAP and mortality
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