PPI use ups mortality risk in ICU patients

Use of proton pump inhibitors (PPIs) for the prevention of stress ulceration appears to elevate the risk of mortality in patients admitted to the intensive care unit (ICU), reveals a study.

A team of investigators conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and cohort studies with trial sequential analysis, Bayesian sensitivity analysis, and fragility index analysis. Thirty-one studies including a total of 78,009 critically ill adults receiving PPIs vs any comparator met the eligibility criteria.

PPI use was significantly associated with increased mortality risk in all studies (PPI vs comparator: 19.6 percent vs 17.5 percent; relative risk [RR], 1.10, 95 percent confidence interval [CI], 1.02‒1.20; p=0.01) and in the subgroup of RCTs (19.4 percent vs 18.7 percent; RR, 1.05, 95 percent CI, 1.0‒1.09; p=0.04), but not cohort studies (19.9 percent vs 16.7 percent; RR, 1.12, 95 percent CI, 0.98‒1.28; p=0.09).

These findings persisted in the Bayesian sensitivity analysis (RR, 1.13, 95 percent credible interval, 1.035‒1.227) and the fragility index analysis, but not in the sequential analysis (p=0.16).

RCTs with a higher baseline severity of illness showed the highest risk of mortality with PPI use (PPI vs comparator: 32.1 percent vs 29.4 percent; RR, 1.09, 95 percent CI, 1.04‒1.14; p<0.001).

Notably, PPI use reduced clinically important bleeding in RCTs (PPI vs comparator: 1.4 percent vs 2.1 percent; RR, 0.67, 95 percent CI, 0.5‒0.9; p=0.009) but increased bleeding in cohort studies (2.7 percent vs 1.2 percent; RR, 2.05, 95 percent CI, 1.2‒3.52; p=0.009). When compared with histamine-2 receptor antagonists, PPI use did not correlate with a lower incidence of clinically important bleeding (1.3 percent vs 1.9 percent; RR, 0.59, 95 percent CI, 0.28‒1.25; p=0.09).