Diuretic-associated admissions to the emergency department – too hot to handle? Results from the ADRED-study

Abstract Background Rising ambient temperatures and increasing thermal stress are major public health challenges, associated with increased emergency department (ED) visits in Europe. Frequently prescribed diuretics may exacerbate heat-related risks through mechanisms such as dehydration and electrolyte imbalance. Although many studies have shown a connection between temperature and mortality, the effect of cumulative ambient temperature on diuretic-associated adverse drug reactions (ADRs) remains underexplored. This study investigates whether higher temperatures are associated with an increase in diuretic-related ADRs in ED admissions. Methods Data from a prospective, observational study on ADRs leading to ED admission (ADRED-study) with a standardized causality assessment of documented drugs were analyzed. Linear, polynomial, and segmented regression were applied to quantify the relationship between 5-day mean temperature and the ratio of suspected diuretic-related ADRs to all diuretic uses. Results A significant relationship between higher 5-day mean temperatures and more diuretic-associated ADRs was found in linear regression analysis (β = 0·0035, 95%CI: 0·0015 − 0·0054, R²=0·188). A segmented regression model identified a critical threshold of ~ 15·7 °C (adjusted R 2 = 0·382). After the threshold at higher temperatures, the slope for diuretic-associated ADRs increased significantly (β = 0·0201, 95%CI: 0·0068–0·0333). The spline model similarly showed a high statistical fit (adjusted R 2 = 0·399), indicating a non-linear, accelerating increase in ADRs at higher temperatures. Conclusions Diuretic-associated ADRs increase non-linearly with ambient temperature, with a breakpoint at approximately 15·7 °C. Especially diuretic-medicated individuals may be vulnerable to cumulative thermal stress. Trial registration The ADRED-study was registered in the German Clinical Trials Register under DRKS00008979.