The History of IV Therapy

Intravenous (IV) therapy is a ubiquitous part of modern medicine, with the familiar IV machine readily available and widely used throughout hospitals. Behind this technology are hundreds of years of research and discoveries by medical professionals and scientists. Our current ability to provide IV therapy to replenish various fluids and nutrients is built upon this knowledge, much of which was standardized only in the 20th century. In fact, there are still many questions surrounding the best methodology and IV solutions to use, including the incongruity between what research indicates is effective and the actual methods currently used with patients, making this a vital area of research to this day.

The idea of inducing effects via IV transfusion only arose in the 1600s, after English physician William Harvey first hypothesized and then proved that blood circulates through the body. Inspired by Harvey’s book on the circulation of blood, Christopher Wren experimented with intravenous injections. Still, he ceased his work after an experiment using an emetic on a prisoner caused the prisoner to faint. Experiments using intravenous methods continued for the next two hundred years, but the first major therapeutic application was during a cholera pandemic in England. 

British physician Thomas Latta successfully treated cholera patients with severe dehydration by administering intravenous saline solution in 1832. However, the improvements in their condition were often short-lived, as the patients frequently fell back to the old state of health or died if more infusions were not performed. In addition, because of a lack of understanding of microbiology, fatal sepsis often occurred after IV injections of unsterile solutions. Despite the rocky start, Latta developed four different solutions for intravenous administration, the last of which is still used today.

Latta then died in 1833, and it took 50 years for another breakthrough in fluid therapy to come about. British clinician Sidney Ringer and Dutch physiological chemist Hartog Jacob Hamburger independently concluded that inorganic salts were essential to human blood composition and could be administered intravenously. This began the development of crystalloids, which are medications that contain electrolyte and sugar solutions to help maintain the body’s fluid balance. The ideal choice of crystalloids for fluid resuscitation remains a matter of controversy today. In addition, by 1892, it became common to sterilize IV solutions by boiling, a significant improvement for future IV treatment endeavors.

In the first half of the 20th century, IV therapy became more standardized as researchers discovered how to deliver specific nutrients and electrolytes. World War II also prompted several innovations related to shock and acute blood loss. Since injuries to soldiers often involved a significant loss of blood, saline solution alone proved ineffective. Healthcare professionals realized that some substance needed to be injected intravenously to bridge the time until the wounded soldiers could arrive at a place where blood transfusions were available. Thus began the search for an appropriate colloid, an intravenous fluid that is gelatinous and expands plasma volume. Gum arabic was used and later discontinued in 1937 due to toxicity, leading to the production of the first commercial synthetic colloid in 1939. During this time, it was discovered that coconut water from an intact nut is both sterile and compatible with human plasma, making it suitable for use as a blood substitute in emergencies.

The search for a synthetic blood substitute for treating shock continued. Gelatin was first mentioned in 1942 as a possible blood substitute due to its similar viscosity. To this day, there is an increasing interest in using gelatin preparations for critically ill patients with sepsis or kidney disease, despite a lack of sufficient evidence for their use, and gelatin having the highest rate of anaphylactic reactions of all colloids. 

Blood fractionation, the separation of blood into its individual components, led to the use of human albumin for intravenous fluid therapy. However, it is expensive to obtain and not widely available. Albumin and saline were compared in a large trial involving nearly 7,000 patients and showed little difference in mortality or organ dysfunction. However, upon further inspection, albumin improved survival in those with severe sepsis, while it decreased survival for those with a traumatic brain injury. This study demonstrates the possibility that tailoring IV solutions to specific disease treatments could reduce mortality rates, if a suitable solution can be identified, as well as the importance of understanding which types of solutions could exacerbate a particular condition.

Modern IV research still faces uncertainty on fundamental topics, such as the optimal timing, type, dose, and duration of fluid therapy. Unlike the early pioneers of fluid therapy, we now have far more advanced methods of diagnosis and delivery of IV solutions. However, we still know little about the “when, what, and how,” especially for critically ill patients. For example, evidence shows that the most commonly used fluid worldwide, 0.9% saline, has no advantage over balanced solutions and increases the risk of acute kidney injury, suggesting that it should be abandoned. It remains unclear which endpoints (targetable and measurable outcomes) would be best to use for fluid therapy, with the Surviving Sepsis Campaign Guidelines naming central venous pressure (CVP) as a target for fluid resuscitation, despite several studies proving CVP to be an unreliable marker of volume status. 

What makes this research challenging is the delicate nature of fluid resuscitation in critically ill patients. It has been found that the same fluid may help a specific patient in what is called the “golden hours,” but can then harm the patient only hours later. Therefore, at this time, comparing the efficacy of two different fluids against each other is not particularly feasible, given our still unclear understanding of the timing. Those in the field currently recommend that future IV therapy research focus on when to start, proper dosing, and when to stop IV transfusions. 

Despite hundreds of years of research, compared to some areas of medical research that currently feel like we are reaching into the future and grasping science fiction, our understanding of fluid therapy appears fragile and, in many ways, very human. The ongoing research on IV therapy is a vital effort to enhance our knowledge of the blood, our bodies, and our ability to supplement and sustain ourselves in our most critical hours of need.

Thank you for reading, 

Ashby Glover

Sources

Domenico Ribatti. “William Harvey and the discovery of the circulation of the blood.” Journal of Angiogenesis Research 1, no. 3 (September 2009). doi: 10.1186/2040-2384-1-3

Tim Kampmeier, Sebastian Rehberg, and Christian Ertmer. “Evolution of fluid therapy.” Best Practice & Research Clinical Anaesthesiology 28, no. 3 (September 2014): 207-216. doi: 10.1016/j.bpa.2014.06.001

David R. Nalin. “The History of Intravenous and Oral Rehydration and Maintenance Therapy of Cholera and Non-Cholera Dehydrating Diarrheas: A Deconstruction of Translational Medicine: From Bench to Bedside?” Tropical Medicine and Infectious Disease 7, no. 3 (March 2022): 50. doi: 10.3390/tropicalmed7030050

Jaime Fernández-Sarmiento, Carolina Casas-Certain, Sarah Ferro-Jackaman, Fabian H. Solano-Vargas, Jesús Ángel Domínguez-Rojas, and Francisco Javier Pilar-Orive. “A brief history of crystalloids: the origin of the controversy.” Frontiers in Pediatrics 11 (July 2023). doi: 10.3389/fped.2023.1202805