Use of acetazolamide in volume overload: start at the beginning

The treatment of volume overload has vexed physicians for centuries. References to herbal remedies for the treatment of fluid retention date as far back as 1550 BC in the Ebers Papyrus from Ancient Egypt [1]. The term edema originates from the Greek "to swell," and the Greek hero Oedipus, meaning "swollen foot," was so named due to the swelling of his feet from injuries inflicted by his mother to prevent the fulfillment of a prophecy. There are several references to edema in the writings of Hippocrates, with various proposed treatments, ranging from herbal remedies, purgatives, phlebotomy, and cranial decompression. The word dropsy, from the Greek word for water, originated in the Middle English period and came to describe conditions associated with an accumulation of fluid in body tissue, preceding more sophisticated knowledge of distinctive disease states. Physicians often prescribed treatments such as bloodletting, purgatives, leeches, and Southey tubes, which were invented in 1877 by English physician Reginald Southey. These were small cannulas placed in a patient's swollen extremities to relieve edema, used until the 1960s [2]. It was not until the serendipitous discovery of the diuretic properties of the mercurial agent Novasurol by Alfred Vogl, while working as a medical student at the Wenckebach clinic in Vienna, used to treat a young patient with congenital syphilis [3], that spurred the interest in synthetic diuretic agents. Despite being the first agent synthesized, acetazolamide became the "forgotten diuretic" until a recent resurgence has reinvigorated interest in its utility in patients with acute decompensated heart failure. This review will describe the background, clinical trials, and proposed utility of acetazolamide in states of volume overload.