Development and study of alternative fluid therapy. Clinical search and development of better ways to manage sepsis, third spacing, Adult respiratory Distress Syndrome (ARDS) and Multiorgan Failure (MOF). Study and development of larger and functional albumin molecule that would be retained in the intravascular space.

Third spacing of fluids occurs rapidly with traditional crystalloid solutions. Normal saline used as a bolus will come to total body equilibration 38 minutes and multiple doses are therefore required. Standard human serum albumin also equilibrates somewhat slower but also contributes to third spacing complications.

Third spacing and fluid overload are major clinical complications in current medical therapy.

Fluid overload negatively impacts the respiratory, cardiac, liver, gastrointestinal, central nervous system, and wound recovery.

Fluid overload and traditional fluid therapy damages and diminishes the glycocalyx. Loss of or damage to the glycocalyx exposes the endothelial cells surface and inflammation causing cytokine release.    Icam1, Vcam1, Il-6, TNFalfa, H-hscp, P-E1F2alfa, AtF6 protein are some of the known sites.    

Excessive strain on the respiratory system manifests with pulmonary edema, altered pulmonary chest wall compliance, and increased extravascular lung water, resulting in decreased effective lung volume requiring prolonged ventilation and difficult weaning from ventilator support.

Liver effects from hepatic congestion results in impaired synthetic function, increased: Cholestasis, decreased cytochrome P4 50 activity, and hepatic compartment syndrome.

Visceral and gastrointestinal effects are ascites formation, gut edema, problems of malabsorption, ileus, increased bowel contractility, increased intestinal permeability and increased bacterial translocation and possible decrease of micro-circulatory flow.

Central nervous system develops cerebral edema with impaired cognition, delirium, and increased intracranial pressure.

Cardiovascular effects are myocardial edema, conduction disturbance, impaired myocardial contractility, diastolic dysfunction resulting in an increase in holiness pressure, and decrease venous return, pericardial effusions, leading to increased stroke volume and decreased cardiac output.

Renal effects of fluid overload are renal interstitial edema, increased renal venous pressure, decreased renal blood flow, increased interstitial pressure, salt and water retention contribute to decreased malarial filtration rate and acute kidney injury.

Wound effects are for wound healing good increased edema, increased wound infections, increased pressure ulcers and generally decreased tissue compliance.

Thus the altered physiology due to fluid overload continues to be a major component of medical illness.

In 1886 Ernest Starling published the Starling Principal of the capillary which essentially stated the increased oncotic pressure within the vascular space is a process to bring fluids from the extracellular space into the intravascular circulating volume.  During all the subsequent years no product has been able to clinically repeat the effect of the Starling Principal.  Clinical use, indicates that TNS, with a larger molecular volume, is able to bring the Starling Principal into effect.

The study of fluids as therapy is generally recognized to have begun in 1831 when William Brooke O’Shaughnessy identify the need for fluids in the Blue Cholera epidemic. Thomas Latta reported, “The First Use of Intravenous Saline for The Treatment of Disease,” In The Journal Lancet In 1832. Although lives were saved with the use of IV fluids, the of standardization and preparation resulted in this therapy being abandoned at that time.

In the Netherlands in 1896, Hartog Jacob Hamburger introduce 0.9% saline [normal saline] the same product used today. During the 1880s while working on electrolyte solutions he inadvertently substituted well water for distilled water and noted that this fluid resulted in the heart beating longer. He noted the benefit of additional chemicals and this product eventually became “Ringers Solution.”

In the 1930’s Alexis Hartman modified Ringers Solution with the addition of lactate and the “Hartman Solution” is generally accepted as the preferred crystalloid solution today.

In 1941, the needs for blood replacement led to a major effort to find a product or use with war casualties. Human serum albumin was separated from whole blood.  Since the time that Human Serum Albumin was separated from whole blood in the 1940’s only the techniques of separation and purification have been applied.

No major developments were made with the use of Human Serum Albumin and standard fluid therapy is woefully inadequate. Systemedical has been studying the use of alternate fluid therapy and has developed a compound of human serum albumin and amino acids which have been used in a clinical setting. For more information see our Hypotheses and Literature page.