Association of Histamine-2 Blockers and Proton-Pump Inhibitors With Delirium Development in Critically Ill Adults: A Retrospective Cohort Study.

Histamine-2 receptor antagonists are commonly administered for stress ulcer prophylaxis in critically ill adults and may be associated with delirium development. We aimed to determine differential associations of histamine-2 receptor antagonist or proton-pump inhibitor administration with delirium development in patients admitted to a medical ICU.
Design: Retrospective observational study using a deidentified database sourced from the University of North Carolina Health Care system. Participants were identified as having delirium utilizing an International Classification of Diseases -based algorithm. Associations among histamine-2 receptor antagonist, proton-pump inhibitor, or no medication administration and delirium were identified using relative risk. Multiple logistic regression was used to control for potential confounders including mechanical ventilation and age.
Setting: Academic tertiary care medical ICU in the United States.
Patients: Adults admitted to the University of North Carolina medical ICU from January 2015 to December 2019, excluding those on concurrent histamine-2 receptor antagonists and proton-pump inhibitors in the same encounter.
Interventions: None.
Measurements and Main Results: We identified 6,645 critically ill patients, of whom 29% ( n = 1,899) received mechanical ventilation, 45% ( n = 3,022) were 65 or older, and 22% ( n = 1,487) died during their medical ICU encounter. Of the 6,645 patients, 31% ( n = 2,057) received an histamine-2 receptor antagonist and no proton-pump inhibitors, 40% ( n = 2,648) received a proton-pump inhibitor and no histamine-2 receptor antagonists, and 46% ( n = 3,076) had delirium. The histamine-2 receptor antagonist group had a greater association with delirium than the proton-pump inhibitor group compared with controls receiving neither medication, after controlling for mechanical ventilation and age (risk ratio, 1.36; 1.25-1.47; p < 0.001) and (risk ratio, 1.15; 1.07-1.24; p < 0.001, respectively).
Conclusions: Histamine-2 receptor antagonists are more strongly associated with increased delirium than proton-pump inhibitors. Prospective studies are necessary to further elucidate this association and to determine if replacement of histamine-2 receptor antagonists with proton-pump inhibitors in ICUs decreases the burden of delirium in critically ill patients.
Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest.
(Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)