Hetastarch

Class: Replacement Preparations
VA Class: BL800
CAS Number: 9005-27-0
Brands: Hespan, Hextend

Warning(s)

  • Increased mortality and/or severe renal injury requiring renal replacement therapy reported in critically ill adults, including patients with sepsis.100 104 106 Do not use in such patients.100 104 106 (See Contraindications and also see Increased Mortality and Severe Renal Injury under Cautions.)

Introduction

Plasma volume expander; a nonprotein synthetic colloid.100 106

Uses for Hetastarch

Hypovolemia

Used for plasma volume expansion in the treatment of hypovolemia associated with elective surgery.100 106 Not a substitute for whole blood or plasma.100 106

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Comparable to albumin human 5% solution as a plasma volume expander.100 106

Leukapheresis

6% Hetastarch in 0.9% sodium chloride injection: Adjunct in leukapheresis to enhance the yield of granulocytes by centrifugal means.100

Hetastarch Dosage and Administration

Administration

IV Administration

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

Administer by IV infusion.100 106

6% Hetastarch in lactated electrolyte injection (Hextend): Do not administer simultaneously with blood through the same administration set.106 Hextend contains calcium; risk of coagulation.106

Preparations contain no preservatives and are intended for single use only; discard partially used containers.100 106

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.100 106

Dosage

Adults

Hypovolemia
IV

Determine dosage based on amount of blood or plasma lost, resultant hemoconcentration, and patient’s age, weight, and clinical condition.100 106

Usually, 500–1000 mL (30–60 g).100 106 Doses up to 1500 mL (90 g) have been used during major surgery, generally without need for blood or blood products.106

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 1:13.100

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.100 106

Dosages >1500 mL daily have been used in postoperative and trauma patients with severe blood loss, 100 generally in conjunction with blood and blood products.106

Special Populations

Geriatric Patients

Select dosage with caution.106 (See Geriatric Use and also see Renal Impairment under Cautions.)

Cautions for Hetastarch

Contraindications

  • Critically ill adult patients, including those with sepsis.100 106 (See Increased Mortality and Severe Renal Injury under Cautions.)

  • Severe liver disease.100 106

  • Preexisting coagulation or bleeding disorders.100 106

  • CHF, renal disease with oliguria or anuria not related to hypovolemia, or other clinical conditions exacerbated by volume overload.100 106

  • Known hypersensitivity to hydroxyethyl starch (HES) or any ingredient in the formulation.100 106

  • 6% Hetastarch in lactated electrolyte injection: Lactic acidosis.106

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.100 104 106 Increased mortality and/or severe renal injury occurred within the recommended dosage range for HES (500–1500 mL [30–90 g] daily).104 Considered by FDA to be class effects of HES.104

HES solutions are contraindicated in critically ill adults, including those with sepsis.100 104 106 Avoid use in patients with preexisting renal dysfunction.100 104 106 Discontinue use at first sign of renal injury.100 104 106 Monitor renal function for ≥90 days in hospitalized patients receiving HES.100 104 106 (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.100 106 Hypersensitivity reactions can occur even after therapy is discontinued.106

Possible hypersensitivity reaction in patients allergic to corn; use with caution in such patients.100 106

If a hypersensitivity reaction occurs, discontinue therapy immediately; institute and continue appropriate treatment and supportive measures until symptoms have resolved.100 106

Other Warnings and Precautions

Therapy Limitations

Hypovolemia: Safety established only for treatment of hypovolemia in elective surgery.100 106

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.100

6% Hetastarch in lactated electrolyte injection (Hextend): Not indicated for use in leukapheresis or for treatment of lactic acidosis.106

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.100 106 Modest decreases in platelet counts and hemoglobin concentrations reported in donors undergoing repeated leukapheresis procedures; hemoglobin concentration returns to normal within 24 hours.100

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.100

Avoid excessive hemodilution and circulatory overload, particularly in patients at risk of CHF or pulmonary edema.100 106 Consider administering packed red cells, platelets, or fresh frozen plasma if excessive hemodilution occurs.100 106

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.100 106 Transient prolongation of PT, aPTT, clotting time, and bleeding time may occur.106 Bleeding, anemia, and coagulopathy (including rare cases of disseminated intravascular coagulation and hemolysis) reported.100 106 (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.100 Prolonged use associated with coagulation abnormalities, von Willebrand-like syndrome, and/or factor VIII deficiency; intracranial bleeding resulting in death reported.100 106 Consider replacement therapy if severe factor VIII deficiency or von Willebrand disease occurs.100 106 Coagulopathy may take several days to resolve.100 106

Increased bleeding reported in patients undergoing open heart surgery with cardiopulmonary bypass receiving HES.104 106 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.104 Monitor the coagulation status of patients undergoing open heart surgery in association with cardiopulmonary bypass.104 106 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.100 104 Discontinue HES at first sign of coagulopathy.100 104 106

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.100 106 Importance of these elevations not known; use with caution in patients with history of liver disease.100 106

Monitor liver function in patients receiving HES preparations, including hetastarch.100 104 106

Contraindicated in patients with severe liver disease.100 106

Pancreatic Effects

Transient elevation of serum amylase concentration may occur; may persist for longer periods in patients with renal impairment.100 106 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.100 106

Electrolyte and Other Components of Hetastarch Preparations

6% Hetastarch in 0.9% sodium chloride injection contains sodium;100 use with caution in patients receiving concomitant therapy with drugs affecting electrolyte balance (e.g., corticosteroids, corticotropin).106 Use with extreme caution, if at all, in patients with edema with sodium retention.106

6% Hetastarch in lactated electrolyte injection contains dextrose and various electrolytes (e.g., lactate, potassium, sodium).106 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).106 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).106 Use with extreme caution, if at all, in patients with hyperkalemia, potassium retention, or edema with sodium retention.106

Patient Evaluation and Laboratory Monitoring

Hypovolemia: Closely monitor vital signs, fluid balance, electrolyte concentrations, acid-base balance, hemoglobin, hematocrit, platelet count, PT, and aPTT.100 106

Leukapheresis: Perform clinical evaluation regularly.100 Monitor CBC.100 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.100

Specific Populations

Pregnancy

Category C.100 106

Lactation

Not known whether hetastarch is distributed into human milk.100 106 Use with caution.100 106

Pediatric Use

Safety and efficacy not established.100 106

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.100 106

Geriatric Use

No substantial differences in efficacy relative to younger adults, but increased sensitivity cannot be ruled out.106

Substantially eliminated by kidneys; because geriatric patients are more likely to have decreased renal function, select dosage with caution106 and monitor renal function for ≥90 days in hospitalized patients.100 104 106 (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.100 106 Monitor liver function in patients receiving HES preparations, including hetastarch.100 106 (See Hepatic Effects under Cautions.)

Contraindicated in patients with severe liver disease.100 106

6% Hetastarch in lactated electrolyte injection: Because of lactate component, use with extreme caution in patients with severe hepatic impairment.106 (See Electrolyte and Other Components of Hetastarch Preparations under Cautions.)

Renal Impairment

Avoid use in patients with preexisting renal impairment.100 104 106 (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.106

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.100 106

Interactions for Hetastarch

Drugs Affecting Coagulation

Caution in patients receiving drugs that affect the coagulation system.100 106

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.106

Specific Drugs

Drug

Interaction

Comments

Corticosteroids

Possible altered electrolyte balance106

Use concomitantly with caution106

Corticotropin

Possible altered electrolyte balance106

Use concomitantly with caution106

Hetastarch Pharmacokinetics

Absorption

Onset

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

Duration

Plasma volume expansion diminishes over 24–36 hours following IV infusion.100 106

Elimination

Metabolism

Hydroxyethylated glucose units not completely metabolized and are excreted intact; substantial quantities of glucose are not produced.100 106

Elimination Route

Primarily excreted by the kidneys.100 106 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.100 106 Molecules with molecular weight ≥50,000 are retained for varying periods depending on their size and ease of breakdown.107

Intravascular concentration of the drug is <10% of the total dose after 2 weeks.100 106

Biliary excretion accounts for <1% of total dose.100 106

Not removed by hemodialysis.100 106 Not known if removed by other extracorporeal elimination techniques.100 106

Stability

Storage

Parenteral

Injection

25°C (up to 40°C).100 106 Do not freeze; protect from excessive heat.100 106

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Hespan

Drug Compatibility

Compatible with citrate concentrations up to 2.5% for 24 hours at room temperature.100

Admixture CompatibilityHID

Compatible

Enalaprilat

Fosphenytoin sodium

Oxacillin sodium

Incompatible

Ampicillin sodium

Y-site CompatibilityHID

Compatible

Diltiazem HCl

Enalaprilat

Ertapenem sodium

Nicardipine HCl

Incompatible

Amikacin sulfate

Cefotaxime sodium

Cefoxitin sodium

Gentamicin sulfate

Theophylline

Tobramycin sulfate

Variable

Ampicillin sodium

Cefazolin sodium

Doxycycline hyclate

Ranitidine HCl

Hextend

Solution Compatibility

Do not administer simultaneously with blood through the same administration set; risk of coagulation due to calcium in Hextend.106

Drug Compatibility
Y-site CompatibilityHID

Compatible

Alfentanil HCl

Amikacin sulfate

Aminophylline

Amiodarone HCl

Ampicillin sodium

Ampicillin sodium–sulbactam sodium

Atracurium besylate

Azithromycin

Aztreonam

Bumetanide

Butorphanol tartrate

Calcium gluconate

Cefazolin sodium

Cefepime HCl

Cefotaxime sodium

Cefotetan disodium

Cefoxitin sodium

Ceftazidime

Cefuroxime sodium

Chlorpromazine HCl

Ciprofloxacin

Cisatracurium besylate

Clindamycin phosphate

Co-trimoxazole

Dexamethasone sodium phosphate

Digoxin

Diltiazem HCl

Diphenhydramine HCl

Dobutamine HCl

Dolasetron mesylate

Dopamine HCl

Doxycycline hyclate

Droperidol

Enalaprilat

Ephedrine sulfate

Epinephrine HCl

Erythromycin lactobionate

Esmolol HCl

Famotidine

Fenoldopam mesylate

Fentanyl citrate

Fluconazole

Furosemide

Gentamicin sulfate

Granisetron HCl

Haloperidol lactate

Heparin sodium

Hydrocortisone sodium succinate

Hydromorphone HCl

Hydroxyzine HCl

Isoproterenol HCl

Ketorolac tromethamine

Labetalol HCl

Levofloxacin

Lidocaine HCl

Lorazepam

Magnesium sulfate

Mannitol

Meperidine HCl

Methylprednisolone sodium succinate

Metoclopramide HCl

Metronidazole

Midazolam HCl

Milrinone lactate

Morphine sulfate

Nalbuphine HCl

Nitroglycerin

Norepinephrine bitartrate

Ondansetron HCl

Palonosetron HCl

Pancuronium bromide

Phenylephrine HCl

Piperacillin sodium–tazobactam sodium

Potassium chloride

Procainamide HCl

Prochlorperazine edisylate

Promethazine HCl

Ranitidine HCl

Rocuronium bromide

Sodium nitroprusside

Succinylcholine chloride

Sufentanil citrate

Theophylline

Ticarcillin disodium–clavulanate potassium

Tobramycin sulfate

Vancomycin HCl

Vecuronium bromide

Verapamil HCl

Incompatible

Amphotericin B

Diazepam

Sodium bicarbonate

Actions

  • Synthetic colloid derived from a waxy starch composed mainly of amylopectin.100 106 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).100 106

  • Exhibits colloidal oncotic effect.106 Retains intravascular fluid,106 resulting in plasma volume expansion.100 106

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

  • Increases erythrocyte sedimentation rate when added to whole blood; improves granulocyte collection by centrifugal leukapheresis.100

Advice to Patients

  • Risk of severe kidney damage.104 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).104

  • 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).100 106

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.100 106

  • Importance of informing patients of other important precautionary information.100 106 (See Cautions.)

Preparations

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

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

Hetastarch in Sodium Chloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV infusion only

6% Hetastarch in 0.9% Sodium Chloride*

Hespan

Braun

6% Hetastarch in 0.9% Sodium Chloride Injection

Hetastarch in Lactated Electrolyte Injection

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV infusion only

6% Hetastarch in Lactated Electrolyte Injection

Hextend

Hospira

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions April 29, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

Only references cited for selected revisions after 1984 are available electronically.

100. B. Braun Medical Inc. Hespan (6% hetastarch in 0.9% sodium chloride injection) prescribing information. Bethlehem, PA; 2013 Oct.

101. Damon L, Adams M, Stricker RB et al. Intracranial bleeding during treatment with hydroxyethyl starch. N Engl J Med. 1987; 317:964-5. [IDIS 234727] [PubMed 2442613]

102. Bianchine JR. Intracranial bleeding during treatment with hydroxyethyl starch. N Engl J Med. 1987; 317:965.

104. Food and Drug Administration. FDA Drug Safety Communication: Boxed warning on increased mortality and severe renal injury, and additional warning on risk of bleeding, for use of hydroxyethyl starch solutions in some settings. 2013 Nov 25. From FDA website. Accessed 2014 Jan 8.

106. Hospira Inc. Hextend (6% hetastarch in lactated electrolyte injection) prescribing information. Lake Forest, IL; 2013 Oct.

107. Westphal M, James MF, Kozek-Langenecker S et al. Hydroxyethyl starches: different products--different effects. Anesthesiology. 2009; 111:187-202. [PubMed 19512862]

a. AHFS drug information 13. McEvoy GK, ed. Hetastarch. Bethesda, MD: American Society of Health-System Pharmacists; 2013:2752-3.

HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2013:611-6.

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