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Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU
Mette Krag1, Søren Marker1, Anders Perner1
1From the Department of Intensive Care (M.K., S.M., A.P., I.-L.J., J.O.W., B.B., M.B.M., L.Q., K.J.T., A.M., J. Wiis, A.G., C.T.A., T.S.M, P.B.H., M.H.M.), Copenhagen Trial Unit, Center for Clinical Intervention Research (J. Wetterslev, J.E.), and the Department of Neurointensive Care (R.D.N, C.S.), Rigshospitalet, Bispebjerg and Frederiksberg Hospital (D.F.P.), and the Section of Biostatistics (T.L.), University of Copenhagen, Copenhagen, Center for Research in Intensive Care (M.K., S.M., A.P., J. Wetterslev, B.S.R., T.L., B.A.-L., M.H.M.), Aalborg University Hospital, Aalborg University, Aalborg (B.S.R., S.R.A., J.B.A., C.A.S., P.H., J. Hauge), Randers Hospital, Randers (H.B., M.L.V., K.B.P., K.L.D.A.), Aarhus University Hospital, Nørrebrogade (T.E., J.F.), and Aarhus University Hospital, Skejby (O.B.) - both in Aarhus, Zealand University Hospital, Køge (J.V.J., C.K.W.K.), Viborg Hospital, Viborg (L.L., C.G.S.), Nordsjællands Hospital, University of Copenhagen, Hillerød (M.H.B.), Holbæk Hospital, Holbæk (J.M.E.), Zealand University Hospital, Roskilde (A.W.), Herning Hospital, Herning (R.W.), and Slagelse Hospital, Slagelse (S.I.) - all in Denmark; the Center for Statistical Science, Peking University, Beijing (T.L.); University Hospital of Wales, Cardiff (M.P.W., M.P.G.M.), and Oxford University Hospitals NHS Foundation Trust, Oxford (M. Borthwick) - both in the United Kingdom; Inselspital, Bern University Hospital, University of Bern, Bern (J.C.S., J.T., S.M.J.), and Basel University Hospital, Basel (M.S., A.H., J.S., D.T., T.V.) - both in Switzerland; University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (F.K., I.C.C.H., W.D.); Haukeland University Hospital, University of Bergen, Bergen (A.B.G., B.S.), and Oslo University Hospital (J.H.L.) and Akershus University Hospital (P.M.B.), Oslo - all in Norway; and Kuopio University Hospital, Kuopio (S.B., J.K.), Helsinki University Hospital, Helsinki (M. Bäcklund), and Turku University Hospital, Turku (J.G.) - all in Finland.
Proton-pump inhibitor pantoprazole did not reduce 90-day mortality in intensive care unit (ICU) patients at risk for gastrointestinal bleeding. This study found similar outcomes for pantoprazole and placebo groups, including clinically important events.
Area of Science:
- Critical Care Medicine
- Gastroenterology
- Pharmacology
Background:
- Prophylaxis for gastrointestinal stress ulceration is common in intensive care units (ICUs).
- The risks and benefits of this prophylaxis remain unclear.
- This study investigated the efficacy of pantoprazole for preventing gastrointestinal bleeding in ICU patients.
Purpose of the Study:
- To evaluate the effect of intravenous pantoprazole compared to placebo on 90-day mortality in critically ill patients.
- To assess the incidence of clinically important events, including gastrointestinal bleeding, pneumonia, Clostridium difficile infection, and myocardial ischemia.
Main Methods:
- A European, multicenter, parallel-group, blinded trial.
- Adult ICU patients at risk for gastrointestinal bleeding were randomized to receive 40 mg of intravenous pantoprazole or placebo daily.
- The primary outcome was death by 90 days after randomization.
Main Results:
- 3298 patients were enrolled; 1645 received pantoprazole and 1653 received placebo.
- At 90 days, mortality was 31.1% in the pantoprazole group and 30.4% in the placebo group (relative risk, 1.02; 95% CI, 0.91 to 1.13).
- Clinically important events occurred in 21.9% of the pantoprazole group and 22.6% of the placebo group. Gastrointestinal bleeding occurred in 2.5% vs. 4.2% respectively.
Conclusions:
- Pantoprazole did not significantly reduce 90-day mortality in ICU patients at risk for gastrointestinal bleeding.
- Mortality and the incidence of clinically important events were similar between the pantoprazole and placebo groups.
- The findings suggest that the routine use of pantoprazole for stress ulcer prophylaxis in this population may not be beneficial.
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