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November - 2018

   

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Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU

Mette Krag, M.D., Ph.D., Søren Marker, M.D., Anders Perner, for the SUP-ICU Trial Group New Eng J Med, 2018, Online first

Comment

The administration of proton-pump-inhibitors or H2 antagonists to prevent stress ulcers in mechanically ventilated patients has been a source of ongoing debate in critical care. PPIs are the most commonly used SUP agents, although there are concerns about efficacy, and side effects including c.difficile, pneumonia, and myocardial events.

The Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial evaluated the effects of and adverse events associated with the prophylactic use of pantoprazole in adult ICU patients at risk for gastrointestinal bleeding. This European, multicenter, parallel-group, blinded trial, randomly assigned;

  • 3298 adults admitted to ICU for an acute condition (unplanned admission) and at risk for gastrointestinal bleeding to receive 40 mg IV pantoprazole or placebo daily during the ICU stay. 
  • Exclusion criteria included already receiving PPI, GI haemorrhage during index hospital admission, endoscopically identified ulcer. Patients with liver disease or receiving glucocorticoids were included.
  • Baseline similar, median ICU LOS 6 days
  • Primary outcome was death by 90 days after randomization, occurring in 31.1% pantoprazole vs 30.4% of placebo (RR, 1.02; 95% CI, 0.91 to 1.13; P=0.76).
  • There was no heterogeneity in the effect of pantoprazole vs placebo on 90d mortality in following groups - history of liver disease, history of or ongoing coagulopathy, shock, or mechanical ventilation, or between patients with different types of ICU admission
  • There was heterogeneity in the estimate of the intervention effect among patients with higher as compared with lower baseline severity of disease (defined as a SAPS II of >53 and ≤53, respectively) , suggesting increased mortality in higher severity patients receiving pantoprazole.
  • At least one clinically important event (a composite of clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection, or myocardial ischemia) occurred in 21.9% of patients assigned to pantoprazole and 22.6% of those assigned to placebo (RR, 0.96; 95% CI, 0.83 to 1.11). 
  • GIT bleeding occurred in 2.5% pantoprazole vs  4.2% placebo (RR 0.58, 95% CI 0.40-0.86) - no p-value supplied because of lack of adjustment for multiple comparisons.
  • There was no difference in infections or serious adverse reactions, percentage of days alive without life support within 90 days.

 The routine administration of pantoprazole to adult ICU patients at risk for gastrointestinal bleeding was not assoicated with a difference in mortality at 90 days, or composite clinically important events, when compared to placebo. There was a possible difference in clinically important gastrointestinal bleeding, although this was no able to be analysed. 

Therefore we can consider two conclusions. The first is PPI SUP offers no benefit compared to placebo. The second is PPI SUP may decrease GI bleeding from 42 to 25 per 1000 ICU patients, without improving recovery, and at the expense of 6000 doses of pantoprazole in the same population.

 

Abstract

BACKGROUND

Prophylaxis for gastrointestinal stress ulceration is frequently given to patients in the intensive care unit (ICU), but its risks and benefits are unclear.

METHODS

In this European, multicenter, parallel-group, blinded trial, we randomly assigned adults who had been admitted to the ICU for an acute condition (i.e., an unplanned admission) and who were at risk for gastrointestinal bleeding to receive 40 mg of intravenous pantoprazole (a proton-pump inhibitor) or placebo daily during the ICU stay. The primary outcome was death by 90 days after randomization.

RESULTS

A total of 3298 patients were enrolled; 1645 were randomly assigned to the pan- toprazole group and 1653 to the placebo group. Data on the primary outcome were available for 3282 patients (99.5%). At 90 days, 510 patients (31.1%) in the panto- prazole group and 499 (30.4%) in the placebo group had died (relative risk, 1.02; 95% confidence interval [CI], 0.91 to 1.13; P=0.76). During the ICU stay, at least one clinically important event (a composite of clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection, or myocardial ischemia) had occurred in 21.9% of patients assigned to pantoprazole and 22.6% of those as- signed to placebo (relative risk, 0.96; 95% CI, 0.83 to 1.11). In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, as compared with 4.2% in the placebo group. The number of patients with infections or serious adverse reactions and the percentage of days alive without life support within 90 days were similar in the two groups.

CONCLUSIONS

Among adult patients in the ICU who were at risk for gastrointestinal bleeding, mortality at 90 days and the number of clinically important events were similar in those assigned to pantoprazole and those assigned to placebo.

November


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