Clinical Pharmacology of Loop Diuretics in Critical Care.

Jacopo Fumagalli, Fiorenza Ferrari, Manfredi Tesauro, Antonio Voza, Giacomo Grasselli, Christian Zanza, Yaroslava Longhitano, Raymond Planinsic, Vittorio Scaravilli

Journal: Clinical pharmacokinetics 2025;64(7):987-997

PMID: 40445471

Abstract

Loop diuretics are a cornerstone in the management of fluid overload in critically ill patients; however, their use is often complicated by variable pharmacokinetics and the phenomenon of diuretic resistance. This narrative review comprehensively examines the pharmacokinetic properties of loop diuretics and discusses the implications of altered pharmacokinetics due to factors such as organ dysfunction, fluid shifts, and concomitant medications, highlighting the challenges in achieving therapeutic targets. Furthermore, we explore the adverse events associated with loop diuretic administration, including electrolyte imbalances and ototoxicity. The review delves into the concept of diuretic resistance, exploring its multifactorial origins, including altered pharmacodynamics and increased compensatory mechanisms. Various strategies to overcome diuretic resistance are presented, including combination therapy with other diuretics, optimizing dosing regimens, and utilizing novel pharmacological agents. Given the complexity of loop diuretic therapy in critically ill patients, a tailored approach is crucial for optimizing fluid management and mitigating adverse effects. This review aims to inform clinicians about the nuances of loop diuretic use in critical care settings, providing insights into pharmacological strategies and clinical considerations essential for enhancing patient outcomes.

© 2025. The Author(s).

Address: International Renal Research Institute of Vicenza (IRRIV), Department of Nephrology, Dialysis and Transplantation, San Bortolo Hospital, Azienda ULSS 8 Berica, Vicenza, Italy.; Department of Anaesthesia, Critical Care and Emergency, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.; Geriatric Medicine Residency Program, University of Rome "Tor Vergata", Rome, Italy. [email protected].; Geriatric Medicine Residency Program, University of Rome "Tor Vergata", Rome, Italy.; Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy.; Department of Anaesthesiology and Perioperative Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.; Department of Emergency Medicine-Emergency Medicine Residency Program, Humanitas University-Research Hospital, Rozzano, Italy.; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, Milan, Italy.; Department of Anaesthesia, Critical Care and Emergency, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.

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