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.

Central Amygdala Prepronociceptin-Expressing Neurons Mediate Palatable Food Consumption and Reward.

Food palatability is one of many factors that drives food consumption, and the hedonic drive to feed is a key contributor to obesity and binge eating. In this study, we identified a population of prepronociceptin-expressing cells in the central amygdala (PnocCeA) that are activated by palatable food consumption. Ablation or chemogenetic inhibition of these cells reduces palatable food consumption. Additionally, ablation of PnocCeA cells reduces high-fat-diet-driven increases in bodyweight and adiposity. PnocCeA neurons project to the ventral bed nucleus of the stria terminalis (vBNST), parabrachial nucleus (PBN), and nucleus of the solitary tract (NTS), and activation of cell bodies in the central amygdala (CeA) or axons in the vBNST, PBN, and NTS produces reward behavior but did not promote feeding of palatable food. These data suggest that the PnocCeA network is necessary for promoting the reinforcing and rewarding properties of palatable food, but activation of this network itself is not sufficient to promote feeding.