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Intensive Care Med. 2019 Feb;45(2):143-158. doi: 10.1007/s00134-019-05526-z. Epub 2019 Jan 24.

Stress ulcer prophylaxis with proton pump inhibitors or histamin-2 receptor antagonists in adult intensive care patients: a systematic review with meta-analysis and trial sequential analysis.

Author information

1
Copenhagen Trial Unit, Centre for Clinical Intervention Research, 2100, Copenhagen, Denmark. marija.barbateskovic@ctu.dk.
2
Centre for Research in Intensive Care, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. marija.barbateskovic@ctu.dk.
3
Centre for Research in Intensive Care, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
4
Department of Intensive Care, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
5
Copenhagen Trial Unit, Centre for Clinical Intervention Research, 2100, Copenhagen, Denmark.
6
Department of Cardiology, Holbaek Hospital, Holbaek, Denmark.

Abstract

PURPOSE:

Most intensive care unit (ICU) patients receive stress ulcer prophylaxis. We present updated evidence on the effects of prophylactic proton pump inhibitors (PPIs) or histamine 2 receptor antagonists (H2RAs) versus placebo/no prophylaxis on patient-important outcomes in adult ICU patients.

METHODS:

We conducted a systematic review with meta-analysis and trial sequential analysis (TSA) of randomised clinical trials assessing the effects of PPI/H2RA versus placebo/no prophylaxis on mortality, gastrointestinal (GI) bleeding, serious adverse events (SAEs), health-related quality of life (HRQoL), myocardial ischemia, pneumonia, and Clostridium (Cl.) difficile enteritis in ICU patients.

RESULTS:

We identified 42 trials randomising 6899 ICU patients; 3 had overall low risk of bias. We did not find an effect of stress ulcer prophylaxis on mortality [relative risk 1.03, 95% confidence interval (CI) 0.94-1.14; TSA-adjusted CI 0.94-1.14], but the occurrence of any GI bleeding was reduced as compared with placebo/no prophylaxis (0.60, 95% CI 0.47-0.77; TSA-adjusted CI 0.36-1.00). The conventional meta-analysis indicated that clinically important GI bleeding was reduced (RR 0.63, 95% CI 0.48-0.81), but the TSA-adjusted CI 0.35-1.13 indicated lack of firm evidence. The effects of stress ulcer prophylaxis on SAEs, HRQoL, pneumonia, myocardial ischemia and Cl. difficile enteritis are uncertain.

CONCLUSIONS:

In this updated systematic review, we were able to refute a relative change of 20% of mortality. The occurrence of GI bleeding was reduced, but we lack firm evidence for a reduction in clinically important GI bleeding. The effects on SAEs, HRQoL, pneumonia, myocardial ischemia and Cl. difficile enteritis remain inconclusive.

KEYWORDS:

Critical care; Gastrointestinal haemorrhage; Histamine-2 receptor antagonists; Meta-analysis; Peptic ulcer; Proton pump inhibitors; Stress ulcer prophylaxis

PMID:
30680444
DOI:
10.1007/s00134-019-05526-z

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