Timing of diuretic administration effects on urine volume in hospitalized patients

Importance: Some medications have effects that depend on the time of day they are given. Current knowledge of the time-of-day effects of specific medications in hospitalized patients with cardiovascular disease is very limited. In hospitalized patients, increased medication efficiency might reduce dose (and associated side effects) and/or the length of time in the Intensive Care Unit (ICU) or hospital-potentially improving patient outcomes and patient and family quality of life and reducing financial costs. We studied whether the time of day or night patients in Cardiac or Intensive Care Units receive a diuretic affects urine volume. Methods: In this observational study, data were collected from 7,685 patients (63% male, 18 to 98 years old) admitted to one hospital's Acute Care Cardiac units, Cardiac ICUs, Cardiac Surgery ICUs, and/or Non-cardiac ICUs who received intravenous furosemide (a diuretic), had measurements of urine volume, were hospitalized for ≥3 days between January 2016 to July 2021 and were older than 18 years. The outcomes of interest were urine volume normalized by the most recent (not older than 24 h) weight or body mass index (BMI), (i) in the hour after the time of diuretic administration, and (ii) when no diuretics were administered for the previous 3 h. Results: We identified diuretic medication administration time 23:00-04:59 as a predictor of higher urine volume response. For patients without recent diuretic medication, higher urine volume was predicted 11:00-16:59 and 17:00-22:59. Other factors that affected urine volume response to the diuretic were sex, age, medication dose, creatinine concentration, diagnoses, and hospital unit. Discussion: Time-of-day of medication administration may be a factor associated with increased medication efficiency. Randomized controlled trials should be conducted to quantify the relative effect of modifiable factors, such as time of medication administration, that may affect short- and longer-term outcomes.