Resuscitation Fluid

a technology of resuscitation fluid and tissue perfusion, which is applied in the direction of extracellular fluid disorder, drug composition, peptide/protein ingredient, etc., can solve the problems of many other medical emergencies, insufficient tissue perfusion rate, and life-threatening medical emergencies

Inactive Publication Date: 2010-07-01
UNIVERSITY OF SOUTH CAROLINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention is a resuscitation fluid that contains an ionic salt, a soluble protein, an intermediate energy substrate, and optionally an agent to mitigate intracellular acidosis. The fluid is effective in preventing or treating septic shock, hemorrhagic shock, hypotension, acidosis, and hypovolumia by administering it to a subject in need. The invention also provides a method for making the resuscitation fluid by intermixing the ingredients. The technical effects of the invention are improved resuscitation and recovery from shock and injury-related complications.

Problems solved by technology

Shock is a serious medical condition where the rate of tissue perfusion is insufficient to meet demand for oxygen and nutrients.
This hypoperfusion state is a life-threatening medical emergency and one of the leading causes of death for critically ill people.
Shock may also lead to many other medical emergencies, such as hypoxia and / or cardiac arrest.
The prognosis of cardiogenic shock is even worse.
Prolonged hypovolemia and hypotension does, however, carry a risk of respiratory and then cardiac arrest.
Insufficient perfusion of the brain may be the greatest danger during shock.
Since oxygen is mainly bound to hemoglobin in red blood cells, insufficient blood supply causes tissue to become hypoxic, or, if no oxygen is supplied at all, anoxic.
This can cause necrosis (i.e., cell death).
Ischemia in brain tissue, for example due to stroke or head injury, causes a process called the ischemic cascade to be unleashed, in which proteolytic enzymes, reactive oxygen species, and other chemicals that are harmful in this context can damage and may ultimately kill brain tissue.
Restoration of blood flow after a period of ischemia can actually be more damaging than the ischemia.
Reintroduction of oxygen causes a greater production of damaging free radicals, resulting in reperfusion injury.
On the other hand, large volumes of fluids are required to be administered, and cell death often occurs despite the additions of large volumes of the fluids due to cells lapsing into a regime of anaerobic metabolism from which they could not recover.
Whole blood is also used, but it is expensive, often unavailable and cross matching may delay therapy.
Such large volumes may cause peripheral and pulmonary edema.
Additionally, the large volume requirements of isotonic fluids means that there are time delays and logistic difficulties associated with vascular delivery of effective therapy.
However, there remain some important limitations / side effects.
Treatment with hypertonic saline can also lead to a hyperchloremic acidosis, possibly due to excessive chloride load.
Circulatory shock is often associated with an acidosis and, therefore, increased acidotic insult may be deleterious.
Although hypertonic saline rapidly improves both blood pressure and cardiac output, these beneficial effects may be overshadowed by deleterious effects from increased blood pressure.
Uncontrolled internal bleeding in trauma patients may be aggravated by increased pressure, leading to increased bleeding.
Return of normal blood pressure resulting in increased bleeding due to arterial pressure increase may lead to increased mortality over no treatment.
Another aspect of resuscitation fluids is their use under less than ideal (non-hospital) conditions.
Logistic restraints may severely curtail transportation of weighty or voluminous material.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

[0078]This example illustrates a method of forming an embodiment of the present resuscitation fluid.

[0079]To form a 100 mL solution, add to pyrogen free distilled water 7.5 g NaCl (Fisher), 25 g albumin bovine serum (Sigma Aldrich cGMP, ≧98.5%, non-animal source), 2 g N-acetyl cysteine (Sigma, Fraction V, ≧96% heat shock fractionate, remainder mostly globulins), and 1 mL pyruvate (Fluky Chemika, >97% by GC).

example 2

[0080]This example illustrates an additional method of forming an embodiment of the present resuscitation fluid.

[0081]50 mL of pyrogen free distilled water were added to a flask on a stir plate. While stirring, 7.5 g NaCl and 2 g N-acetyl cysteine were added to the flask. The pH was adjusted to 7.4 using 1N NaOH that was sterile filtered (0.2 micron). 1 mL pyruvate was added. After 15 minutes, the pH was adjusted to 7.4 using 1N NaOH. 20 mL water were added to the flask, followed by the addition of 10 g albumin. The composition was stirred until the albumin was dissolved, then the pH was adjusted to 7.0. An additional 5 g of albumin was added and allowed to dissolve before the pH was adjusted to 7.0. An additional 10 g of albumin was then added and allowed to dissolve while stirring, followed by addition of water to a total volume of 100 mL. The final pH of the fluid was 6.8.

example 3

[0082]This example relates to a rat test, wherein a rat was allowed to hemorrhage without treatment. A 410 g male Sprague Dawley rat was anesthetized with 0.24 mL of 50 mg / mL ketamine, 0.07 mL of 20 mg / mL xylazine, and 0.05 mL of 10 mg / mL acepromazine. The following results were observed:

Time (s)ActionMAP (mm Hg)Notes1130Catheters in place901130  4 cc hemorrhage50Initial bleed11351.5 cc hemorrhage40Rebleed11501.0 cc hemorrhage37Rebleed12251.0 cc hemorrhage4512271.0 cc hemorrhage401235death

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Abstract

The present invention relates to a resuscitation fluid which includes an ionic salt at a concentration above about 0.9%, at least one soluble protein, at least one intermediate energy substrate, and optionally an agent to mitigate intracellular acidosis. Methods of making and using the fluid are also described.

Description

BACKGROUND OF THE INVENTION[0001]The present invention relates generally to the treatment and prevention of hemorrhagic and ischemia disorders. More specifically, the present invention relates to a method and composition for treating and preventing one or more of hemorrhagic shock, septic shock, hypotension, acidosis, and / or hypovolumia.[0002]Shock is a serious medical condition where the rate of tissue perfusion is insufficient to meet demand for oxygen and nutrients. This hypoperfusion state is a life-threatening medical emergency and one of the leading causes of death for critically ill people. Shock may also lead to many other medical emergencies, such as hypoxia and / or cardiac arrest.[0003]The management of shock requires immediate intervention. Re-establishing perfusion to the organs is the primary goal and is achieved by restoring and maintaining the blood circulating volume, ensuring oxygenation and blood pressure are adequate, achieving and maintaining effective cardiac fun...

Claims

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Application Information

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Patent Type & AuthorityApplications(United States)
IPC IPC(8): A61K33/14A61P7/08A61P7/04
CPCA61K31/221A61K33/14A61K38/38A61K38/385A61K45/06A61P7/04A61P7/08
InventorFANN, STEPHANYOST, MICHAEL J.
OwnerUNIVERSITY OF SOUTH CAROLINA