Hetastarch for Shock: A Comprehensive Overview

Overview:

Hetastarch or hydroxyethyl starch is a synthetic plasma expander or colloid used to treat shock that results from hypovolemia (reduced volume) in the body. Such expanding agents will be used to increase blood volume and improve circulation in cases of shock or hypovolemia. In shock, there is a significant decrease in circulating blood volume, leading to reduced or inadequate tissue perfusion and organ dysfunction. Hetastarch works by expanding blood volume when administered intravenously, thereby improving hemodynamic parameters, such as blood pressure and cardiac output. Its large molecular size helps to retain fluid within the vascular compartment, effectively increasing intravascular volume. Additionally, Hetastarch possesses oncotic properties, which aid in pulling fluid from the interstitial space back into the blood vessels.

Hetastarch was approved by the U.S. Food and Drug Administration (FDA) for medical use in the United States in the 1970s. It has been used clinically for several decades, primarily as an intravenous infusion for volume expansion in situations such as surgery, trauma, and shock. However, its use has become more limited in recent years due to safety concerns and the availability of alternative fluid options.

Dosage and Route of Administration:

• Hetastarch is given only through an intravenous route to the body. The general dose of Hetastarch given is six percent in 0.9 percent saline. This means that six percent of Hetastarch is diluted in 0.9 percent saline.

• Every container of Hetastarch has 30 grams of Hetastarch mixed in 500 mL (milliliters) of 0.9 percent normal saline.

• For an adult with hypovolemia and shock, the amount required would be 500 to 1000 mL. In cases of severe blood loss following a trauma, the dose can be increased to 1500 mL.

For Patients:

What Is Hypovolemic Shock?

Several factors such as profuse bleeding internally or externally due to trauma (hemorrhage), dehydration, fluid loss from burns, or fluid shifts, such as severe vomiting or diarrhea, can cause a significant drop in the blood volume and lead to a condition called hypovolemia. Hypovolemic shock arises from excessive loss of fluid volume of more than one-fifth of the body's volume. This leads to reduced blood supply and perfusion of the tissues, resulting in a hypoxic state. In such conditions, the heart tries to combat the loss of volume but ultimately fails. This can cause severe damage and death of vital organs in the body.

Symptoms of Hypovolemic Shock:

• Rapid heartbeat.

• Blood pressure becomes low.

• Cool and clammy skin.

• Skin turns pale.

• Confusion.

• Dizziness.

• Excessive thirst.

• Anxiety.

• Nausea.

• Vomiting.

• Restlessness.

• Fatigue.

• Extremities turn cold.

When hypovolemia advances, there can be profound hypotension leading to unconsciousness and organ failure.

How Is Hypovolemic Shock Managed?

The main goal in cases of hypovolemic shock is to increase the blood volume and perfusion of the tissues. Immediate fluid replacement will be done. Blood transfusions will be done in cases of severe hemorrhage or trauma. Measures to control bleeding like the use of clotting factors will be employed and surgical intervention will be done in necessary cases.

Why Is Hetastarch Given for Hypovolemic Shock?

Hetastarch is given mainly to resuscitate the lost blood volume and improve perfusion. This improves the oxygen availability to tissues. The burden on the heart to pump and supply more blood will also be curbed after the administration of colloids like Hetastarch. Hetastarch has the ability to increase blood volume more effectively than crystalloid solutions due to its larger molecular size, which helps to retain fluid within the vascular compartment for a longer duration. Additionally, Hetastarch possesses oncotic properties, meaning it can increase the colloid osmotic pressure within blood vessels, thereby pulling fluid from the interstitial space back into the bloodstream. This dual mechanism of action makes Hetastarch an attractive option for volume resuscitation in hypovolemic shock.

How Is Hetastarch Taken?

Hetastarch (six percent hydroxyethyl starch in 0.9 percent normal saline) is a crystalloid solution that will be administered only by medical professionals through the veins of hypovolemic individuals.

What Are the Side Effects of Hetastarch?

The use of Hetastarch has been limited in recent years due to the risk of incidence of acute kidney injury and coagulopathy resulting in mortality of the patients after administration of Hetastarch.

Side Effects Noted With Hetastarch Are:

• Acute kidney injury following the administration of Hetastarch. In some cases, the acute kidney injury may be so severe that the individual may require renal replacement therapy. Surgically intervened individuals and people with pre-existing renal disorders are highly susceptible to developing acute renal injury after administration of Hetastarch. This may be due to the accumulation of Hetastarch molecules within the course of renal blood flow, thus obstructing the blood vessels and perfusion of the kidney. This exacerbates the ischemic injury to the kidneys and results in acute kidney injury.

• Another significant side effect of Hetastarch is the development of coagulopathy (impaired clot formation) after taking Hetastarch. This occurs through several mechanisms which act together to cause coagulopathy. One primary mechanism is the dilutional effect of Hetstarch on coagulation factors. As Hetastarch expands intravascular volume, it dilutes the concentration of clotting factors in the bloodstream, thus impairing the body's ability to form clots effectively. Additionally, Hetastarch can interfere with platelet function, leading to decreased platelet aggregation and adhesion, which are highly essential for hemostasis. Also, the large molecular size of Hetastarch particles can physically obstruct blood flow through small vessels, impairing the delivery of clotting factors and platelets to sites of injury. These combined effects contribute to an increased risk of bleeding and coagulopathy in patients receiving Hetastarch, especially at elevated doses or in people with pre-existing or underlying coagulation disorders or other risk factors.

• Intracranial bleeding following the administration of Hetastarch has been observed in some cases.

• Some patients have shown hypersensitive reactions to Hetastarch solution.

• Hetastarch can lead to excessive fluid accumulation in the body, causing edema (swelling) or congestive heart failure (weakened pumping action of heart), notably in individuals having dysfunctional cardiac or renal systems.

• Prolonged use of Hetastarch can result in tissue deposition of starch particles, leading to complications such as organ dysfunction or granuloma formation.

• Some people may show anemia (reduced erythrocytes) or other clotting factor deficiency following Hetastarch administration.

Minor Side Effects Noted Are:

• Vomiting.

• Muscle pain.

• Peripheral edema.

• Salivary gland enlargement.

• Headache.

• Itching.

For Doctors:

Indications:

• Hetastarch is used for the expansion of plasma volume when alternative treatment modalities fail to improve it. This is beneficial in cases of hypovolemia (hypovolemic shock), intraoperative fluid replacement and management, and albumin replacement.

• By serving as a volume expander, Hetastarch helps to maintain hemodynamic stability during leukapheresis, which involves the selective removal of leukocytes (white blood cells) from the blood. The use of Hetastarch in leukapheresis allows for the efficient collection of white blood cells while minimizing the risk of adverse hemodynamic effects associated with fluid shifts. For this purpose, the dosage given is 200 to 750 mL (7.03 to 26.4 ounces).

Contraindications:

• Patients with ongoing or active infections and septic states should not be given Hetastarch.

• Patients with an allergy to components of Hetastarch are contraindicated.

• People with existing kidney disease should be avoided for treatment with Hetastarch.

• Individuals with clotting disorders are excluded from treatment with Hetastarch.

• People with trauma to the head are generally not given Hetastarch due to the risk of internal (intracranial) bleeding.

Drug Ingredients:

Active Ingredient: Hetastarch (Hydroxyethyl starch).

Inactive Ingredients:

• Sodium chloride - 0.9 grams in 100 mL.

• Sodium hydroxide - To adjust pH to 5.5.

• Water.

Every 100 mL of Hetastarch solution contains six grams of Hetastarch diluted in 0.9 grams of sodium chloride.

Clinical Pharmacology:

Hetastarch, a synthetic colloid solution, exerts its clinical effects primarily by rapidly augmenting intravascular volume. When administered intravenously, Hetastarch molecules predominantly stay within blood vessels due to their considerable size, thus bolstering plasma volume and enhancing hemodynamic parameters like blood pressure and cardiac output. Furthermore, Hetastarch possesses oncotic properties, aiding in sustaining colloid osmotic pressure within the vasculature, thereby facilitating fluid retention and preventing its dispersion into surrounding tissues. Additionally, Hetastarch has the potential to transiently increase blood viscosity, influencing blood flow characteristics and tissue perfusion.

Half-Life:

The half-life of Hetastarch is around 17 days.

Pharmacokinetics

Absorption and Distribution:

After administration through a vein, Hetastarch is distributed throughout the intravascular space. The molecules of Hetastarch remain in the intravascular space and cause the expansion of plasma volume. While Hetastarch does not undergo absorption into tissues or systemic circulation in the same manner as orally administered drugs, its effects are exerted through its distribution within the bloodstream, where it helps to maintain colloid osmotic pressure and increase intravascular volume.

Excretion:

Small-sized molecules (molecular weight less than 50,000) are removed rapidly from the kidneys. 99 percent of the remaining molecules take around 17 days to be eliminated from the body completely through the renal route.

Pharmacodynamics:

By augmenting intravascular volume and sustaining colloid osmotic pressure, Hetastarch promotes fluid retention within the vasculature, thereby, enhancing tissue perfusion and oxygen delivery. This property is essential for treating hypovolemic shock. Six percent Hetastarch in 0.9 percent sodium chloride replaces five percent of albumin in the human body.

How Should Hetastarch Be Administered?

An intravenous route is employed to administer Hetastarch. Excessive pumping action should be avoided to prevent air embolism, distortion, and breakage of the container. The administered drug should be clear with no particulate matter. Sterile equipment should be used and the intravenous unit should be replaced every 24 hours.

Drug Storage:

Hetastarch can be stored at room temperature for one day. Temperature above 25 degrees Celcius (77 degrees Fahreinheit) can reduce the moisture content in Hetastarch.

Clinical Toxicity:

• Hetastarch can cause acute kidney damage, especially in people with a history of kidney disease. In advanced cases, people may require replacement of their kidneys due to severe kidney damage.

• Administration of Hetastarch can interfere with blood coagulation and platelet function, increasing the risk of bleeding or clotting disorders.

• Fluid or volume overload accompanies Hetastarch administration. This can cause edema of the peripheries and result in congestive heart failure.

• Rashes and itching are reported after Hetastarch administration (anaphylactoid reaction).

• Metabolic acidosis is seen in some cases after administering Hetastarch.

• Intracranial bleeding is a common occurrence.

• Hetastarch has the capacity to cause hemodilution and result in reduced properties of blood components like erythrocytes and thrombocytes.

Due to such toxic effects of Hetastarch, the rates of hospital stays and mortalities have markedly increased. Thus, Hetastarch use is very limited in today’s medical practice.

Drug Interactions:

Hetastarch may interact with blood products such as packed red blood cells or platelets if administered concurrently. Mixing Hetastarch with blood products in the same IV (intravenous) line can lead to hemolysis or clotting, and therefore, they should be administered separately or with caution. The use of other drugs with Hetastarch has not been studied yet.

Guidelines for Specific Population:

Pregnant and Nursing Mothers

There are no adequate studies to show the effectiveness or hazardous nature of Hetastarch on pregnant and lactating individuals. Hetastarch is generally avoided. If given, continuous evaluation of the mother and the child is necessary.

Geriatric Individuals

People with renal disorders, cardiovascular issues, or liver disorders are refrained from Hetastarch administration.

What Are the Precautions to Be Taken With Hetastarch Administration?

• Regularly assess renal function before and during Hetastarch administration. Hetastarch administration should be stopped immediately when the first sign of kidney injury is noted.

• Coagulation parameters like bleeding time, clotting time, and international normalized ratio should be evaluated from time-to-time to monitor any changes in the coagulation process or coagulopathy in the body.

• Hetastarch is not recommended for use as a cardiac bypass pump prime or during cardiopulmonary bypass, as well as in the immediate post-bypass period due to the risk of increasing coagulation abnormalities and bleeding.

• Patients with liver diseases should also be continuously evaluated after Hetastarch administration.

• Monitoring of renal functions should be performed for at least 90 days after Hetastarch administration as people have been given renal replacement therapy after 90 days.

Overall, Hetastarch, a synthetic colloid solution, is utilized for volume expansion in hypovolemic shock and perioperative fluid management. It increases intravascular volume rapidly, improving hemodynamic parameters. However, its use has declined due to safety concerns, including renal impairment, coagulopathy, and adverse outcomes in critically ill patients. Precautions include monitoring renal and coagulation function, avoiding use in certain settings, and considering alternative fluid options. Close monitoring and prompt action at the first signs of renal injury or coagulopathy are essential.