Hydroxyethyl starch (HES) is a type of colloid solution used in medicine for fluid resuscitation and volume expansion. It is commonly used in intravenous (IV) fluids to help increase blood volume in patients who have lost fluids due to surgery, trauma, or other medical conditions.

HES is derived from starch and is modified by adding hydroxyethyl groups. This modification reduces the tendency of the starch to be broken down by amylase enzymes, prolonging its presence in the bloodstream. The idea is that by increasing blood volume, HES can help improve circulation and tissue perfusion.

Two commonly used formulations of hydroxyethyl starch are Hespan and Hextend. These products have different concentrations and are used for various medical purposes. However, it's important to note that the use of HES has been a topic of debate and research in recent years.

Some concerns have been raised about the safety of HES, particularly in certain patient populations. The use of HES has been associated with an increased risk of kidney injury and coagulation issues in some studies. Due to these concerns, some medical guidelines and institutions have restricted the use of HES, especially in patients with sepsis, kidney problems, or coagulation disorders.

Hetastarch (Hydroxyethyl Starch) is a starch derivative that is used as a volume expander in patients with hypovolemia, hypotension, and shock. It should be avoided in patients with liver and kidney disease and those who are critically ill.

Hetastarch (Hydroxyethyl Starch) Uses:

• Granulocyte yield increase (Hespan only):
  • It is indicated as an adjunct in leukapheresis. It improves harvesting and increases granulocytes yield by centrifugation.
• Plasma volume expansion:
  • It is indicated as volume expander in case of hypovolemia.

Hetastarch (Hydroxyethyl Starch) Dose in Adults

Granulocyte yield increase (Hespan):

• Using Hespan can help increase the yield of granulocytes in the range of 250 to 700 milliliters.

Note: Before using Hespan, a substance called citrate anticoagulant is added. Then, the mixture is given through the input line of the centrifuge machine. This process is a way to improve the amount of granulocytes obtained.

Plasma volume expansion:

• When expanding plasma volume (the liquid part of blood) using Hespan through an intravenous (IV) method, the typical dosage is 500 to 1,000 milliliters, or roughly 20 milliliters per kilogram, given once.
• If necessary, this can be repeated based on individual needs, blood flow dynamics, and hydration status.
• However, caution is advised because of the risk of Hespan accumulation in the body.
• The maximum daily doses should not exceed 33 to 50 milliliters per kilogram per day, as recommended by studies (Myburgh 2012; Myburgh 2013; Perner 2012).

Note:

• It's important to note that Hespan should not be used in certain conditions, including in critically ill patients, those with sepsis or septic shock, individuals undergoing open heart surgery with cardiopulmonary bypass, or those with existing kidney problems.
• These precautions are in place to ensure the safe and appropriate use of Hespan and to avoid potential complications in specific patient groups.

Hetastarch (Hydroxyethyl Starch) Dose in Childrens

Note:

• When dealing with severe dehydration, it's advised to first use crystalloid fluids.
• The amount and speed of infusion depend on factors like the extent of blood loss, maintaining or restoring proper blood circulation, and the degree of dilution in the blood.
• It's important to adjust the dosage based on the specific needs of the individual, their blood flow dynamics, and hydration status.
• However, avoid using hydroxyethyl starch (HES) solutions in critically ill patients, those undergoing open heart surgery with cardiopulmonary bypass, or individuals with preexisting kidney issues.
• Notably, professional medical societies discourage the use of HES for fluid resuscitation in severe sepsis and septic shock in newborns and pediatric patients.

Volume expansion: Very limited data available: IV infusion:

In children aged 1 year and older, as well as adolescents.

• The suggested dose is 10 milliliters per kilogram per dose.
• This recommendation comes from a small study involving 38 patients (ages 1 to 15.5 years) who had congenital heart surgery.
• In the study, Hespan was compared to albumin as a volume expander in the first 24 hours after surgery.
• The study found no safety differences between Hespan and albumin when daily doses of Hespan were kept at or below 20 milliliters per kilogram.
• However, higher doses (20 to 30 mL/kg/day) were associated with increased PT (a blood clotting test), though there was no difference in clinical bleeding.

Pregnancy Risk Factor C

• In studies with animals, there were some negative effects or problems noticed during the process of reproduction.

Hetastarch use during breastfeeding:

• It's uncertain whether hetastarch is found in breast milk.
• The company that makes hetastarch suggests being careful when giving it to breastfeeding women.

Dose in Kidney Disease:

• Don't use hetastarch in patients with existing kidney problems.
• It's especially not allowed in cases of kidney disease where there's little or no urine production (oliguria or anuria) unrelated to low fluid levels in the body.

Dose in Liver disease:

• For individuals with mild to moderate kidney problems, there are no specific changes to the recommended dosage according to the manufacturer's instructions, but it's advised to be cautious.

• For those with severe kidney impairment, using hetastarch is not allowed (contraindicated).

Side effects of Hetastarch (Hydroxyethyl Starch):

• Cardiovascular:
  • Bradycardia
  • Cardiac Failure
  • Increased Plasma Volume
  • Peripheral Edema
  • Tachycardia
• Central Nervous System:
  • Chills
  • Headache
  • Intracranial Hemorrhage
• Dermatologic:
  • Pruritus (Dose-Dependent; May Be Delayed)
  • Skin Rash
• Endocrine & Metabolic:
  • Hypervolemia
  • Increased Amylase (Transient)
  • Metabolic Acidosis (Hyperchloremic)
• Gastrointestinal:
  • Parotid Gland Enlargement
  • Vomiting
• Hematologic & Oncologic:
  • Anemia
  • Blood Coagulation Disorder (Factor VIII Deficiency, Acquired Von Willebrand's Like Syndrome, Dilutional Coagulopathy)
  • Disseminated Intravascular Coagulopathy (Rare)
  • Hemolysis (Rare)
  • Hemorrhage
  • Prolonged Bleeding Time
  • Prolonged Partial Thromboplastin Time
  • Prolonged Prothrombin Time
  • Thrombocytopenia
  • Wound Hemorrhage
• Hepatic:
  • Increased Serum Bilirubin (Indirect)
• Hypersensitivity:
  • Anaphylactoid Reaction
  • Hypersensitivity
• Neuromuscular & Skeletal:
  • Myalgia
• Respiratory:
  • Bronchospasm
  • Flu-Like Symptoms (Mild)
  • Non-Cardiogenic Pulmonary Edema
• Miscellaneous:
  • Fever

Contraindications to Hetastarch (Hydroxyethyl Starch):

• Hetastarch should not be used in individuals who have a hypersensitivity or allergic reaction to hetastarch, hydroxyethyl starch (HES), or any component of the formulation.
• It is also contraindicated in critically ill adults, including those with sepsis or severe liver disease.
• Individuals with renal disease characterized by little or no urine production (oliguria or anuria) not related to low fluid levels, and those with any condition of fluid overload such as pulmonary edema or heart failure, should avoid hetastarch.
• Additionally, individuals with preexisting coagulation or bleeding disorders should not use hetastarch.

• For the specific formulation Hextend, there are additional contraindications.

• It should not be used for treating lactic acidosis or during leukapheresis (a medical procedure that involves separating and collecting white blood cells).

Warnings and precautions

Anaphylactoid reactions

• Serious allergic reactions, called anaphylactoid reactions, which can be life-threatening and even result in death, have been reported very rarely with hetastarch.
• If there are signs of an allergic reaction, it's crucial to stop using hetastarch right away and provide the necessary treatment.
• It's worth noting that individuals allergic to corn might also be allergic to hetastarch.

Bleeding

• Avoid using hetastarch for certain situations related to heart surgery.
• It's not recommended for use as a pump prime in cardiac bypass procedures, while the patient is on cardiopulmonary bypass, or right after.
• HES solutions, including hetastarch, have been linked to increased bleeding in these situations.
• Keep a close eye on the blood's clotting ability (coagulation status) in patients undergoing open heart surgery with cardiopulmonary bypass, and stop using hetastarch if any clotting issues arise.
• Prolonged use of hetastarch over several days may lead to coagulation problems, resembling a reversible condition similar to von Willebrand disease and/or a deficiency in factor VIII.
• If a severe factor VIII deficiency is found, replacement therapy should be considered.
• It's important to note that coagulation issues may take several days to improve.
• Additionally, when hetastarch is used to prevent blood vessel spasms in the brain for patients with subarachnoid hemorrhage (an off-label use), there have been reports of significant bleeding, bleeding within the skull, and even death.

Fluid overload:

• Using hetastarch can lead to an excess of fluids in the body, which is known as fluid overload.
• It's important to be cautious when giving hetastarch to patients who are at risk of having too much blood volume, like very young or elderly patients.
• Importantly, hetastarch should not be used in individuals with heart failure or any preexisting condition where having too much fluid in the body could be a problem.

Hematologic:

• Using large amounts of hetastarch can dilute the concentration of hemoglobin, coagulation factors, and other proteins in the blood, a process known as hemodilution.
• This effect is especially relevant when hetastarch is used for leukapheresis, a medical procedure involving the separation and collection of white blood cells.
• Regular clinical assessments and complete blood counts (CBC) are recommended during leukapheresis.
• If the frequency of leukapheresis exceeds standard blood donation guidelines, monitoring total leukocyte and platelet counts, leukocyte differential, prothrombin time (PT), and partial thromboplastin time (PTT) is also advised.
• The coagulation process may be affected, leading to prolonged PT, PTT, and clotting times, and there may be a temporary increase in bleeding time.

Hepatic impairment

• Be careful when using hetastarch in individuals with mild to moderate liver problems.
• Regularly check liver function at the beginning of treatment and at intervals throughout.
• However, in cases of severe liver impairment, using hetastarch is not allowed (contraindicated).
•  Always monitor and assess liver function to ensure the safe use of hetastarch in individuals with hepatic (liver) conditions.

Renal impairment

• Do not use hetastarch in individuals with existing kidney problems, and be vigilant in monitoring fluid status, urine output, and the rate of infusion in patients who receive hetastarch.
• If there are any signs of kidney injury, stop using hetastarch immediately. In patients with damaged kidney filters (glomerular damage), larger hetastarch molecules might leak into the urine, potentially raising urine specific gravity.
• Furthermore, using hetastarch is not allowed in cases of kidney disease where there is little or no urine production (oliguria or anuria) not due to low fluid levels (contraindicated).
• Always exercise caution and follow appropriate guidelines to prevent kidney-related issues when using hetastarch.

Thrombocytopenia:

• Exercise caution when using hetastarch in patients with low platelet counts (thrombocytopenia).
• Large amounts of hetastarch may interfere with platelet function and temporarily extend the time it takes for blood to clot.
• Keep a close eye for signs of bleeding in patients with thrombocytopenia who are receiving hetastarch.
• Regular monitoring and careful observation can help manage potential complications related to platelet function and bleeding time.

Hetastarch (Hydroxyethyl starch; Hespan, Hextend): Drug Interaction

Monitoring parameters:

Plasma Volume Expansion:

• Vital Signs: Monitor blood pressure, heart rate, and capillary refill time.
• Central Venous Pressure (CVP) and Right Atrial Pressure (RAP): Check these indicators of blood flow within the heart.
• Mean Arterial Pressure (MAP) and Urine Output: Monitor blood pressure and kidney function.
• Cardiac Monitoring (if applicable): For patients with a pulmonary artery catheter, observe cardiac index, pulmonary capillary wedge pressure (PCWP), systemic vascular resistance (SVR), and pulmonary vascular resistance (PVR).
• Blood Composition: Regularly assess hemoglobin, hematocrit, serum electrolytes, and renal function. Continue monitoring for at least 90 days after hetastarch administration.
• Coagulation and Liver Function: Keep an eye on coagulation parameters and liver function tests.

Granulocyte Yield Increase:

• Complete Blood Count (CBC): Monitor overall blood composition.
• Leukocyte and Platelet Counts: Track total leukocyte and platelet counts to assess cell levels.
• Leukocyte Differential Count: Observe the distribution of different types of white blood cells.
• Hemoglobin and Hematocrit: Measure levels of these blood components.
• Prothrombin Time (PT) and Partial Thromboplastin Time (PTT): Evaluate blood clotting time.

How to administer Hetastarch (Hydroxyethyl Starch)?

IV: Plasma Volume Expansion:

• Administration Route: Administer intravenously (IV) only.
• Infusion Method: May be given using an infusion pump or through pressure infusion.
• Administration Rates: Rates should be adjusted based on factors such as blood loss, patient age, and clinical condition, generally not exceeding 1.2 grams per kilogram per hour (20 mL/kg/hour). In specific cases, rates up to 1,000 mL over 7 to 8 minutes via pressure infusion have been studied in otherwise healthy subjects (McIlroy 2003).
• Caution for Anaphylactoid Reactions: Anaphylactoid reactions are possible; have epinephrine and resuscitative equipment readily available.
• Pressure Infusion Precautions: If administered by pressure infusion, remove air from the bag before infusion to prevent air embolus.
• Compatibility with Blood Administration: Do not administer Hextend with blood through the same administration set. Change IV tubing or flush thoroughly with normal saline before giving blood through the same line. Change IV tubing at least every 24 hours.
• Visual Inspection: Do not use if a crystalline precipitate forms or if the solution appears turbid and deep brown.

Granulocyte Yield Increase:

• Preparation: Mix Hespan and citrate thoroughly.
• Administration: Administer the mixture to the input line of the centrifuge apparatus at a ratio of 1:8 to 1:13 to venous whole blood.

Mechanism of action of Hetastarch (Hydroxyethyl Starch):

• Hetastarch works by creating an increase in the volume of plasma in the blood.
• It does this because of its special structure made from starch, which forms a highly colloidal (gel-like) substance.
• This colloidal structure helps to expand the plasma volume, contributing to better blood circulation and overall fluid balance in the body.

Duration of Action:

• Time Frame: The effects of hetastarch can last from 3 to 36 hours, providing an extended period of action.

Excretion:

• Pathway: The body eliminates hetastarch primarily through urine, with approximately 33% excreted within the first 24 hours.
• Molecular Weight Influence: Smaller molecules with a weight less than 50,000 daltons are excreted more rapidly, contributing to the removal of hetastarch from the body.

International Brand Names of Hetastarch:

• Hespan
• Hextend
• Elohaes
• Elohaest
• Farhes
• Haes Steril
• HAES-steril
• Haes-Steril
• Hemohes
• Hespander
• Hestar-200
• Hydroksyetyloskrobia
• Hyper HAES
• HyperHAES
• Hyperhes
• Infukoll HES
• Plasmasteril
• StarQuin
• Temo
• Widahes
• Widahes-130

Hetastarch  Brand Names in Pakistan: