The Effects of the Timing of Diuretic Administration and Other Covariates on Urine Volume in Hospitalized Patients

''What time should I take my medicine?'' is an increasingly important question. Current knowledge of time - of - day effects for specific medications in hospitalized patients with cardiovascular disease is very limited. In such patients, increased medication efficiency could potentially reduce dose use and/or the length of time in the Intensive Care Unit (ICU) and/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 a patient is given a diuretic affects urine volume response. In this observational study, data were from 7,704 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. We used machine learning (ML) techniques to analyze the data. The ML technique identified factors that were expected to predict urine volume response to the diuretic: sex, age, medication dose and time, creatinine concentration, diagnosis, and hospital unit. The ML technique also identified medication administration time 00:00 - 06:00 as a predictor of higher urine volume response. Randomized controlled trials should be conducted to quantify the relative effect of modifiable factors, such as time of medication administration.

[1]  S. Redline,et al.  Toward Precision Medicine: Circadian Rhythm of Blood Pressure and Chronotherapy for Hypertension - 2021 NHLBI Workshop Report. , 2022, Hypertension.

[2]  K. Hopcia,et al.  Identifying Modifiable Predictors of COVID-19 Vaccine Side Effects: A Machine Learning Approach , 2022, Vaccines.

[3]  Wei Wang,et al.  Sleep Restriction and Recurrent Circadian Disruption Differentially Affects Blood Pressure, Sodium Retention, and Aldosterone Secretion , 2022, Frontiers in Physiology.

[4]  R. Foster,et al.  The circadian system, sleep, and the health/disease balance: a conceptual review , 2022, Journal of sleep research.

[5]  A. Kramer,et al.  Foundations of circadian medicine , 2022, PLoS biology.

[6]  Y. Ilan,et al.  Improving Diuretic Response in Heart Failure by Implementing a Patient-Tailored Variability and Chronotherapy-Guided Algorithm , 2021, Frontiers in Cardiovascular Medicine.

[7]  Gijs Geleijnse,et al.  Explainable machine learning can outperform Cox regression predictions and provide insights in breast cancer survival , 2021, Scientific Reports.

[8]  S. Verstockt,et al.  Machine Learning-Based Identification of the Strongest Predictive Variables of Winning and Losing in Belgian Professional Soccer , 2021, Applied Sciences.

[9]  Cátia M. Salgado,et al.  Circadian rhythm in critically ill patients: Insights from the eICU Database , 2021, Cardiovascular digital health journal.

[10]  R. Allada,et al.  Circadian Mechanisms in Medicine. , 2021, The New England journal of medicine.

[11]  Liangyuan Hu,et al.  Tree‐Based Machine Learning to Identify and Understand Major Determinants for Stroke at the Neighborhood Level , 2020, Journal of the American Heart Association.

[12]  Amy S. Shah,et al.  A large-scale study reveals 24-h operational rhythms in hospital treatment , 2019, Proceedings of the National Academy of Sciences.

[13]  L. Tarassenko,et al.  Circadian Blood Pressure Variations Computed From 1.7 Million Measurements in an Acute Hospital Setting , 2019, American journal of hypertension.

[14]  Steven A. Brown,et al.  Medicine in the Fourth Dimension. , 2019, Cell metabolism.

[15]  K. Ho,et al.  Machine learning for the prediction of volume responsiveness in patients with oliguric acute kidney injury in critical care , 2019, Critical Care.

[16]  J. Hogenesch,et al.  Dosing time matters , 2019, Science.

[17]  Scott M. Lundberg,et al.  Explainable machine-learning predictions for the prevention of hypoxaemia during surgery , 2018, Nature Biomedical Engineering.

[18]  D. Firsov,et al.  Circadian rhythms and the kidney , 2018, Nature Reviews Nephrology.

[19]  Jenna Wiens,et al.  Machine Learning for Healthcare: On the Verge of a Major Shift in Healthcare Epidemiology , 2018, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[20]  Johannes Gehrke,et al.  Intelligible Models for HealthCare: Predicting Pneumonia Risk and Hospital 30-day Readmission , 2015, KDD.

[21]  Michelle L. Gumz,et al.  The circadian clock in the kidney. , 2011, Journal of the American Society of Nephrology : JASN.

[22]  D. Firsov,et al.  Circadian regulation of renal function. , 2010, Kidney international.

[23]  F. Lévi,et al.  Chronotherapy and the molecular clock: Clinical implications in oncology. , 2010, Advanced drug delivery reviews.

[24]  S. Ohdo Chronotherapeutic strategy: Rhythm monitoring, manipulation and disruption. , 2010, Advanced drug delivery reviews.

[25]  F. Buttgereit,et al.  Targeting pathophysiological rhythms: prednisone chronotherapy shows sustained efficacy in rheumatoid arthritis , 2010, Annals of the rheumatic diseases.

[26]  R. Hermida,et al.  Chronotherapy With the Angiotensin-Converting Enzyme Inhibitor Ramipril in Essential Hypertension: Improved Blood Pressure Control With Bedtime Dosing , 2009, Hypertension.

[27]  F. Portaluppi,et al.  Chronobiology and chronotherapy of ischemic heart disease. , 2007, Advanced drug delivery reviews.

[28]  Michael H Smolensky,et al.  Chronobiology and chronotherapy of allergic rhinitis and bronchial asthma. , 2007, Advanced drug delivery reviews.

[29]  Ariel Miller,et al.  Chronotherapy using corticosteroids for multiple sclerosis relapses , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[30]  G. V. van Montfrans,et al.  Circadian rhythms in systemic hemodynamics and renal function in healthy subjects and patients with nephrotic syndrome. , 2001, Kidney international.

[31]  E. Brown,et al.  The parathyroid hormone circadian rhythm is truly endogenous--a general clinical research center study. , 1997, The Journal of clinical endocrinology and metabolism.

[32]  A. Vagnucci,et al.  Effects of upright posture on renal electrolyte cycles. , 1969, Journal of applied physiology.

[33]  E. Flink,et al.  Circadian variations in renal excretion of magnesium, calcium, phosphorus, sodium, and potassium during frequent feeding and fasting. , 1966, Federation proceedings.