Fluids are a common tool in both the emergency and critical care setting. They are used for a wide range of diseases, including hypovolemia, electrolyte disorders, dehydration, etc. However, much like any other drugs, they do come with potential adverse effects. There are several efforts to develop newer generation fluids.

The Ideal Fluid

A significant portion of acute care research is driven by military research or military-funded research due to the unique demands of battlefield resuscitation. This is reflected by a few of the below characteristics of a hypothetical ideal fluid:

Novel Crystalloids

There are several research efforts centered around increasing the oxygen carrying capacity of crystalloids. A fluid containing nitrate and nitrite (to support nitric oxide production) and magnesium and transition metals improved tissue perfusion in a pig model of hemorrhagic shock. This approach is novel, as it does not leverage larger synthetic or naturally occurring proteins that could lead to immune complications.

Polyethylene glycol polymers have also been put in solution; those products improve microcirculation. Preclinical data in hemorrhagic shock showed that this product improved both micro- and microcirculation in various animal models of shock.

Hypertonic crystalloids are often mentioned in the veterinary literature. While their mechanism of action and clinical benefits remain debated, researchers are enhancing their properties. One such effort relies on the addition of adenosine, lidocaine, and magnesium. This approach has led to encouraging data in laboratory animals in the setting of hemorrhage and traumatic brain injury.

Novel Blood Products/Blood Product Replacement

Hemorrhage is the leading cause of death in the battlefield. Reducing death from blood losses would lead to a significant number of lives saved for the military. This fact drives a large effort to develop blood products specifically for hemorrhagic shock resuscitation in war theaters. There are also considerable civilian efforts, since hemorrhage has a significant burden in civilian environments as well. While our patients are likely to benefit from those efforts, there are also efforts specifically geared toward veterinary patients, especially dogs. Those products can be divided into red cell, platelet, and plasma replacements.

Red Blood Cells Replacement Products

Hemoglobin-based oxygen-carriers have been extensively used in veterinary medicine but are not available anymore. This is also true for our human counterparts. There is renewed interest in developing a shelf-stable product that will replicate hemoglobin function. Efforts to better the product include chemical alterations to prolong half-lives, such as polymerization or linking to non-protein molecules such as PEG or polyoxyethylene; and pairing with antioxidant molecules, such as ascorbic acid, to prevent oxidative stress. Hemoglobin can also be encapsulated alone or in combination with other agents to increase circulating half-life.

Red blood cells can also be grown in vitro. This allows production of a product similar to naturally occurring erythrocytes. Those cells are free from pathogens and can be cultured to reduce the likelihood of transfusion reaction when later administered to patients.

Finally, non-hemoglobin-based products are also under development. Perfluorocarbons are a class of drugs that can transport oxygen, albeit with a lesser affinity. They are also smaller than native erythrocytes, which may allow easier circulation through damaged microcirculation networks.

Novel Platelet Products

Platelet access is currently challenging for many veterinary practices owing to their unique and short storage requirements. A synthetic platelet product, SynthoPlate^® is made of liposomes that are "decorated" with multiple types of peptides on their surface. One peptide is a von Willebrand factor binding peptide, which facilitates adherence to circulating or tethered von Willebrand factor. Another peptide is a collagen-binding peptide allowing the liposome to adhere to exposed collagen. The third peptide is GP IIb-IIIa binding fibrinogen-mimetic peptide allowing the liposome to participate in aggregation with other platelets. SynthoPlate^® is not designed to replicate all of the capabilities of natural platelets such as degranulation, contraction, and morphologic changes. However, SynthoPlate^® can help active platelets adhere to surfaces as well as allow multiple platelets to bind to them, acting as an extender for the host platelets.

There are also ongoing efforts to develop lyophilized platelets, which have been studied in dogs.

Fresh-Frozen Plasma Replacement

The Department of Defense has invested significant resources to develop a freeze-dried plasma product. There are currently two products nearing FDA clearance. Those products can be either from a single-donor or pooled with reduced immunogenicity through removal of cells and cell debris.