Hetastarch (Monograph)

Brand names: Hespan, Hextend
Drug class: Replacement Preparations
VA class: BL800
CAS number: 9005-27-0

Medically reviewed by Drugs.com on Apr 19, 2024. Written by ASHP.

Introduction

Plasma volume expander; a nonprotein synthetic colloid.

Uses for Hetastarch

Hypovolemia

Used for plasma volume expansion in the treatment of hypovolemia associated with elective surgery. Not a substitute for whole blood or plasma.

Comparable to albumin human 5% solution as a plasma volume expander.

Leukapheresis

6% Hetastarch in 0.9% sodium chloride injection: Adjunct in leukapheresis to enhance the yield of granulocytes by centrifugal means.

Hetastarch Dosage and Administration

Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion.

6% Hetastarch in lactated electrolyte injection (Hextend): Do not administer simultaneously with blood through the same administration set. Hextend contains calcium; risk of coagulation.

Preparations contain no preservatives and are intended for single use only; discard partially used containers.

Rate of Administration

Determine rate of infusion based on amount of blood or plasma lost, resultant hemoconcentration, and patient’s age, weight, and clinical condition.

Dosage

Adults

Hypovolemia

IV

Determine dosage based on amount of blood or plasma lost, resultant hemoconcentration, and patient’s age, weight, and clinical condition.

Usually, 500–1000 mL (30–60 g). Doses up to 1500 mL (90 g) have been used during major surgery, generally without need for blood or blood products.

Leukapheresis

IV

Add citrate anticoagulant to 250–700 mL of 6% hetastarch in 0.9% sodium chloride injection and mix thoroughly; add to the input line of the centrifugation apparatus in a hetastarch-to-venous whole blood ratio of 1:8 to 1:13.

Prescribing Limits

Adults

Hypovolemia

IV

Total daily dose >20 mL/kg (1.2 g/kg) or >1500 mL (90 g) for a typical 70-kg patient usually not needed.

Dosages >1500 mL daily have been used in postoperative and trauma patients with severe blood loss, generally in conjunction with blood and blood products.

Special Populations

Geriatric Patients

Select dosage with caution. (See Geriatric Use and also see Renal Impairment under Cautions.)

Cautions for Hetastarch

Contraindications

• Critically ill adult patients, including those with sepsis. (See Increased Mortality and Severe Renal Injury under Cautions.)

• Severe liver disease.

• Preexisting coagulation or bleeding disorders.

• CHF, renal disease with oliguria or anuria not related to hypovolemia, or other clinical conditions exacerbated by volume overload.

• Known hypersensitivity to hydroxyethyl starch (HES) or any ingredient in the formulation.

• 6% Hetastarch in lactated electrolyte injection: Lactic acidosis.

Warnings/Precautions

Warnings

Increased Mortality and Severe Renal Injury

Increased mortality and/or severe renal injury requiring renal replacement therapy reported in critically ill adults, including those with sepsis, receiving various HES preparations. Increased mortality and/or severe renal injury occurred within the recommended dosage range for HES (500–1500 mL [30–90 g] daily). Considered by FDA to be class effects of HES.

HES solutions are contraindicated in critically ill adults, including those with sepsis. Avoid use in patients with preexisting renal dysfunction. Discontinue use at first sign of renal injury. Monitor renal function for ≥90 days in hospitalized patients receiving HES. (See Advice to Patients.)

Sensitivity Reactions

Hypersensitivity Reactions

Death, life-threatening anaphylactic/anaphylactoid reactions (e.g., rash, erythema multiforme, urticaria, pruritus, angioedema, facial and periorbital edema, chills, flushing, severe hypotension, tachycardia, bradycardia, ventricular fibrillation, cardiac arrest, wheezing, shortness of breath, stridor, tachypnea, cough, chest pain, noncardiac pulmonary edema, laryngeal edema, bronchospasm, restlessness, fever, sneezing) reported rarely. Hypersensitivity reactions can occur even after therapy is discontinued.

Possible hypersensitivity reaction in patients allergic to corn; use with caution in such patients.

If a hypersensitivity reaction occurs, discontinue therapy immediately; institute and continue appropriate treatment and supportive measures until symptoms have resolved.

Other Warnings and Precautions

Therapy Limitations

Hypovolemia: Safety established only for treatment of hypovolemia in elective surgery.

Do not use as a cardiac bypass pump prime, while patient is on cardiopulmonary bypass, or in the immediate period after the pump has been discontinued.

6% Hetastarch in lactated electrolyte injection (Hextend): Not indicated for use in leukapheresis or for treatment of lactic acidosis.

Hemodilution and Circulatory Overload

Risk of excessive hemodilution (e.g., decreased hematocrit and plasma protein concentrations) following administration of volumes >25% of blood volume in <24 hours. Modest decreases in platelet counts and hemoglobin concentrations reported in donors undergoing repeated leukapheresis procedures; hemoglobin concentration returns to normal within 24 hours.

Risk of circulatory overload largely dependent on clinical circumstances; however, use of doses >20 mL/kg (1.2 g/kg) within 24 hours may substantially increase risk.

Avoid excessive hemodilution and circulatory overload, particularly in patients at risk of CHF or pulmonary edema. Consider administering packed red cells, platelets, or fresh frozen plasma if excessive hemodilution occurs.

Hematologic Effects and Coagulopathy

In patients with hypovolemia, risk of altered coagulation and bleeding (due to hemodilution and direct inhibition of factor VIII); increased risk with higher dosages. Transient prolongation of PT, aPTT, clotting time, and bleeding time may occur. Bleeding, anemia, and coagulopathy (including rare cases of disseminated intravascular coagulation and hemolysis) reported. (See Therapy Limitations and also see Patient Evaluation and Laboratory Monitoring under Cautions.)

Safety of prolonged use (i.e., over several days) not established in situations other than leukapheresis. Prolonged use associated with coagulation abnormalities, von Willebrand-like syndrome, and/or factor VIII deficiency; intracranial bleeding resulting in death reported. Consider replacement therapy if severe factor VIII deficiency or von Willebrand disease occurs. Coagulopathy may take several days to resolve.

Increased bleeding reported in patients undergoing open heart surgery with cardiopulmonary bypass receiving HES. Excess bleeding occurred irrespective of molecular weight or molar substitution of the HES preparation and, therefore, is considered by FDA to be a class effect of HES. Monitor the coagulation status of patients undergoing open heart surgery in association with cardiopulmonary bypass. Do not use 6% hetastarch in 0.9% sodium chloride injection (Hespan) as a cardiac bypass pump prime, during cardiopulmonary bypass, or in the immediate period after discontinuance of the pump. Discontinue HES at first sign of coagulopathy.

Hepatic Effects

Elevated indirect bilirubin concentration reported following multiple infusions; concentrations return to normal 96 hours after final infusion; total bilirubin concentrations remained within normal limits. Importance of these elevations not known; use with caution in patients with history of liver disease.

Monitor liver function in patients receiving HES preparations, including hetastarch.

Contraindicated in patients with severe liver disease.

Pancreatic Effects

Transient elevation of serum amylase concentration may occur; may persist for longer periods in patients with renal impairment. No association between increased amylase concentration and pancreatitis, but this effect limits use of serum amylase concentrations as an aid in the diagnosis of pancreatitis for up to 3–5 days after hetastarch administration.

Electrolyte and Other Components of Hetastarch Preparations

6% Hetastarch in 0.9% sodium chloride injection contains sodium; use with caution in patients receiving concomitant therapy with drugs affecting electrolyte balance (e.g., corticosteroids, corticotropin). Use with extreme caution, if at all, in patients with edema with sodium retention.

6% Hetastarch in lactated electrolyte injection contains dextrose and various electrolytes (e.g., lactate, potassium, sodium). Use with caution in patients with known subclinical or overt diabetes mellitus, patients with cardiac disease (particularly in those receiving digoxin), and patients receiving concomitant therapy with drugs affecting electrolyte balance (e.g., corticosteroids, corticotropin). Use with extreme caution in patients with metabolic or respiratory alkalosis and in patients with conditions that result in increased concentrations or impaired utilization of lactate ions (e.g., severe hepatic impairment). Use with extreme caution, if at all, in patients with hyperkalemia, potassium retention, or edema with sodium retention.

Patient Evaluation and Laboratory Monitoring

Hypovolemia: Closely monitor vital signs, fluid balance, electrolyte concentrations, acid-base balance, hemoglobin, hematocrit, platelet count, PT, and aPTT.

Leukapheresis: Perform clinical evaluation regularly. Monitor CBC. If frequency of leukapheresis exceeds guidelines for whole blood donation, consider monitoring total leukocyte and platelet counts, leukocyte differential count, hemoglobin and hematocrit, PT, and aPTT.

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether hetastarch is distributed into human milk. Use with caution.

Pediatric Use

Safety and efficacy not established.

In a limited number of pediatric patients (1–15.5 years of age) receiving 6% hetastarch in 0.9% sodium chloride injection at dosages ≤20 mL/kg, no differences in coagulation parameters or in amount of required replacement fluid reported compared with pediatric patients receiving albumin; increased PT reported in those receiving hetastarch dosages >20 mL/kg.

Geriatric Use

No substantial differences in efficacy relative to younger adults, but increased sensitivity cannot be ruled out.

Substantially eliminated by kidneys; because geriatric patients are more likely to have decreased renal function, select dosage with caution and monitor renal function for ≥90 days in hospitalized patients. (See Increased Mortality and Severe Renal Injury and also see Renal Impairment under Cautions.)

Hepatic Impairment

Use with caution in patients with history of liver disease. Monitor liver function in patients receiving HES preparations, including hetastarch. (See Hepatic Effects under Cautions.)

Contraindicated in patients with severe liver disease.

6% Hetastarch in lactated electrolyte injection: Because of lactate component, use with extreme caution in patients with severe hepatic impairment. (See Electrolyte and Other Components of Hetastarch Preparations under Cautions.)

Renal Impairment

Avoid use in patients with preexisting renal impairment. (See Increased Mortality and Severe Renal Injury under Cautions.)

Patients with renal glomerular damage: Possible leakage of larger hetastarch molecules into urine, resulting in an elevated specific gravity, which can obscure diagnosis of renal failure.

Common Adverse Effects

Hypersensitivity reactions, coagulopathy, hemodilution, circulatory overload, metabolic acidosis, CHF, pulmonary edema, bleeding, vomiting, peripheral edema, submaxillary and parotid glandular enlargement, mild influenza-like symptoms, headache, muscle pain.

Drug Interactions

Drugs Affecting Coagulation

Caution in patients receiving drugs that affect the coagulation system.

Drugs Affecting Electrolyte Balance

Because of the electrolyte components in various preparations, use with caution in patients receiving concomitant therapy with drugs that affect electrolyte balance.

Specific Drugs

Hetastarch Pharmacokinetics

Absorption

Onset

Maximum plasma volume expansion in hypovolemic patients reached within several minutes after the end of IV infusion.

Duration

Plasma volume expansion diminishes over 24–36 hours following IV infusion.

Elimination

Metabolism

Hydroxyethylated glucose units not completely metabolized and are excreted intact; substantial quantities of glucose are not produced.

Elimination Route

Primarily excreted by the kidneys. Hetastarch molecules with molecular weight <50,000 are excreted rapidly in urine; approximately 33% of a single 500-mL (30-g) dose is excreted in urine within 24 hours. Molecules with molecular weight ≥50,000 are retained for varying periods depending on their size and ease of breakdown.

Intravascular concentration of the drug is <10% of the total dose after 2 weeks.

Biliary excretion accounts for <1% of total dose.

Not removed by hemodialysis. Not known if removed by other extracorporeal elimination techniques.

Stability

Storage

Parenteral

Injection

25°C (up to 40°C). Do not freeze; protect from excessive heat.

Compatibility

Hespan

Drug Compatibility

Compatible with citrate concentrations up to 2.5% for 24 hours at room temperature.

Hextend

Solution Compatibility

Do not administer simultaneously with blood through the same administration set; risk of coagulation due to calcium in Hextend.

Drug Compatibility

Actions

• Synthetic colloid derived from a waxy starch composed mainly of amylopectin. Approximately 75% of glucose units of the starch are hydroxyethylated to form polymers resembling glycogen; average molecular weight is approximately 600–670 (range: 450–800).

• Exhibits colloidal oncotic effect. Retains intravascular fluid, resulting in plasma volume expansion.

• Causes temporary increase in arterial and venous pressures, cardiac index, stroke work index, and pulmonary wedge pressure in hypovolemic patients.

• Increases erythrocyte sedimentation rate when added to whole blood; improves granulocyte collection by centrifugal leukapheresis.

Advice to Patients

• Risk of severe kidney damage. Importance of immediately reporting signs and symptoms suggestive of kidney damage (e.g., change in frequency, volume, or color of urine; blood in urine; difficulty in urinating; swelling of the legs, ankles, feet, face, or hands; unusual weakness or fatigue; nausea and vomiting; shortness of breath).

• Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., CHF, liver disease, renal impairment).

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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