Use of hydroxyethyl starch (HES) products increases the risk of mortality, kidney injury, and coagulopathy.
Do not use HES products (ie, hetastarch) unless adequate alternative treatment is unavailable.
Note: With severe dehydration, administer crystalloid first. Dose and rate of infusion are dependent on amount of blood lost, on maintenance or restoration of hemodynamics, and on amount of hemodilution. Titrate to individual colloid needs, hemodynamics, and hydration status. Do not use in critically ill patients, those undergoing open heart surgery with cardiopulmonary bypass, or those with preexisting kidney dysfunction. Critical Care Medicine societies (ACCM, SCCM) recommend against the use of hydroxyethyl starch (HES) solutions for fluid resuscitation of sepsis and septic shock in neonatal and pediatric patients (Ref).
Volume expansion: Very limited data available: IV infusion: Children ≥1 year and Adolescents: 10 mL/kg/dose; dosing based on a small randomized, double-blinded study of 38 patients (age range: 1 to 15.5 years) that compared hetastarch (n=20) and albumin (n=18) as a postoperative volume expander in the first 24 hours after congenital heart surgery; no differences in safety compared to albumin were found at hetastarch daily doses ≤20 mL/kg/day; patients receiving doses of 20 to 30 mL/kg/day were noted to have an increased PT; however, there was no difference in clinical bleeding; doses >30 mL/kg have not been studied (Ref).
There are no pediatric-specific recommendation available; based on experience in adults, avoid use in patients with pre-existing renal dysfunction; use is contraindicated in renal failure with oliguria or anuria (not related to hypovolemia) and use should be discontinued at the first sign of renal injury.
There are no dosage adjustments provided in manufacturer's labeling; based on experience in adult patients, use with caution.
(For additional information see "Hetastarch (Hydroxyethyl starch; Hespan, Hextend): Drug information")
Granulocyte yield increase (Hespan) (adjunctive agent): 250 to 700 mL; Note: Citrate anticoagulant is added before use and then the mixture is administered to the input line of the centrifuge apparatus.
Plasma volume expansion: Note: Discontinue use at the first sign of kidney injury. Do not use in the critically ill, those with sepsis or septic shock, those undergoing open heart surgery and cardiopulmonary bypass, or those with preexisting kidney impairment (Ref).
IV: 500 to 1,000 mL once; may repeat as needed based on assessment of intravascular volume status. Doses of more than 1,500 mL/day (~20 mL/kg) are usually not required.
Avoid use in patients with preexisting kidney impairment. Discontinue use at the first sign of kidney injury. Not eliminated by hemodialysis.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined.
Cardiovascular: Increased plasma volume
Endocrine & metabolic: Hypervolemia, increased amylase (transient), metabolic acidosis
Hematologic & oncologic: Disorder of hemostatic components of blood (including Factor VIII deficiency, acquired von Willebrand's-like syndrome, dilutional coagulopathy), hemorrhage
Hepatic: Increased indirect serum bilirubin
Hypersensitivity: Hypersensitivity reaction (including anaphylaxis, angioedema, chest pain, erythema multiforme, fever, nonimmune anaphylaxis, severe hypotension, ventricular fibrillation)
Postmarketing:
Cardiovascular: Heart failure, lower extremity edema
Dermatologic: Pruritus
Gastrointestinal: Parotid gland enlargement, submaxillary gland enlargement, vomiting
Hematologic & oncologic: Anemia, disseminated intravascular coagulopathy (rare), hemolysis (rare), prolonged bleeding time
Nervous system: Headache, intracranial hemorrhage
Neuromuscular & skeletal: Myalgia
Renal: Acute kidney injury (Lagny 2016, Zarychanski 2013)
Respiratory: Flu-like symptoms, pulmonary edema
In patients when adequate alternative treatment is available.
Concerns related to adverse effects:
• Anaphylactoid reactions: Life-threatening anaphylactic/anaphylactoid reactions, including death, have been reported (rarely); discontinue use immediately with signs of hypersensitivity and administer appropriate therapy. Patients allergic to corn may be allergic to hetastarch.
• Bleeding/coagulopathy: Discontinue use of hydroxyethyl starch (HES) at the first sign of coagulopathy. Not recommended for use as a cardiac bypass pump prime, while the patient is on cardiopulmonary bypass, or in the period immediately afterward. HES solutions have been associated with excess bleeding in these patients. Monitor the coagulation status in patients undergoing open heart surgery in association with cardiopulmonary bypass. May cause coagulation abnormalities in conjunction with a reversible, acquired von Willebrand-like syndrome and/or factor VIII deficiency when used over a period of days. Consider replacement therapy if a severe factor VIII deficiency is detected. Coagulopathies may take several days to resolve. When used to prevent cerebral vasospasm in patients with subarachnoid hemorrhage (off-label use), significant clinical bleeding, intracranial bleeding, and death have been reported. Monitor the coagulation status of surgery patients due to excess bleeding with the administration of HES in this population.
• Fluid overload: Administration may cause fluid overload; use with caution in patients at risk from overexpansion of blood volume (eg, very young, older patients).
• Hematologic: Large volumes of hetastarch may cause a reduction in hemoglobin concentration, coagulation factors, and other plasma proteins due to hemodilution; when used for leukapheresis, frequent clinical evaluation and complete blood counts (CBC) are recommended. If leukapheresis frequency is greater than whole blood donation guidelines, consider monitoring total leukocyte and platelet counts, leukocyte differential, PT, and PTT as well. Coagulation may be impaired (eg, prolonged PT, PTT, and clotting times) and a transient prolongation of bleeding time may be observed.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Kidney impairment: Avoid use in patients with preexisting kidney impairment; monitor fluid status, urine output, and infusion rate; discontinue use at the first sign of kidney injury. Larger hetastarch molecules may leak into urine in patients with glomerular damage; may elevate urine specific gravity. Since the need for renal replacement therapy has been reported up to 90 days after HES administration, continue to monitor kidney function in all patients for at least 90 days.
• Thrombocytopenia: Use with caution in patients with thrombocytopenia; large volumes may interfere with platelet function and transiently prolong bleeding time. Observe for bleeding.
Special populations:
• Critically ill patients: Avoid use in critically ill adult patients, including those with sepsis and those admitted to the ICU. HES solutions have been associated with an increased risk of mortality in the critically ill (Brunkhorst 2008; Perel 2012; Perner 2012; SSC [Evans 2021]). Crystalloids (eg, sodium chloride and balanced solutions) are recommended as the fluid of choice for initial resuscitation and ongoing resuscitation (SSC [Evans 2021]. Avoid use in patients with preexisting kidney impairment and discontinue use at the first sign of kidney injury. Since the need for renal replacement therapy has been reported up to 90 days after HES administration, continue to monitor kidney function in all patients for at least 90 days.
Dosage form specific issues:
• Hextend: Contains calcium, lactate and potassium; use with caution in situations where electrolyte and/or acid-base disturbances may be exacerbated (kidney impairment, respiratory alkalosis, metabolic alkalosis). Do not use in leukapheresis.
Other warnings/precautions:
• Appropriate use: Not a substitute for red blood cells or coagulation factors.
Hetastarch use has been associated with acute kidney injury in pediatric patients (Reinhart 2012).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Hespan: 6% (500 mL)
Hextend: 6% (500 mL)
Generic: 6% (500 mL)
Yes
Solution (Hespan Intravenous)
6-0.9% (per mL): $0.06
Solution (Hetastarch-NaCl Intravenous)
6-0.9% (per mL): $0.05
Solution (Hextend Intravenous)
6% (per mL): $0.23
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Hetastarch is a synthetic polymer derived from a waxy starch composed of amylopectin, average molecular weight of Hespan is 600,000 kDa (range: 450,000 to 800,000 kDa), average molecular weight of Hextend is 670,000 kDa (range: 450,000 to 800,000 kDa); each liter of Hespan provides 154 mEq sodium chloride; each liter of Hextend contains the following electrolytes: Sodium 143 mEq, chloride 124 mEq, lactate 28 mEq, calcium 5 mEq, magnesium 0.9 mEq, potassium 3 mEq, and dextrose 0.99 g
Parenteral: Volume expansion: IV: Administer IV only; may be administered via infusion pump or pressure infusion; if administered by pressure infusion, air should be withdrawn or expelled from bag prior to infusion to prevent air embolus. Administration rates vary depending upon the extent of blood loss, age, and clinical condition of patient but, in general, should not exceed 1.2 g/kg/hour (20 mL/kg/hour) in adults. Change IV tubing or flush copiously with normal saline before administering blood through the same line. Do not administer Hextend with blood through the same administration set. Change IV tubing at least every 24 hours. Anaphylactoid reactions can occur; have epinephrine and resuscitative equipment available. Do not use if crystalline precipitate forms or is turbid deep brown.
IV: Plasma volume expansion: Administer IV only; may be administered via infusion pump or pressure infusion. Administration rates vary depending upon the extent of blood loss, age, and clinical condition of patient but, in general, should not exceed 1.2 g/kg/hour (20 mL/kg/hour); however, rates up to 1,000 mL over 7 to 8 minutes via pressure infusion have been studied in otherwise healthy subjects (Ref). Anaphylactoid reactions can occur, have epinephrine and resuscitative equipment available. If administered by pressure infusion, air should be withdrawn or expelled from bag prior to infusion to prevent air embolus. Do not administer Hextend with blood through the same administration set. Change IV tubing or flush copiously with normal saline before administering blood through the same line. Change IV tubing at least every 24 hours. Do not use if crystalline precipitate forms or is turbid deep brown.
Granulocyte yield increase: Mix Hespan and citrate well. Administer to the input line of the centrifuge apparatus at a ratio of 1:8 to 1:13 to venous whole blood.
Store at 25°C (77°F); avoid excessive heat; do not freeze. Brief exposure up to 40°C (104°F) does not adversely affect the product. Do not use if crystalline precipitate forms or is turbid deep brown.
Hespan: In leukapheresis, admixtures of 500 to 560 mL of hetastarch with citrate concentrations up to 2.5% are compatible for 24 hours.
Treatment of hypovolemia as a blood volume expander (Hespan, Hextend: FDA approved in adults); adjunctive use during leukapheresis to improve granulocyte harvesting and increase the yield of granulocytes by centrifugation (Hespan: FDA approved in adults). Note: Critical Care Medicine societies (ACCM, SCCM) recommend against the use of hydroxyethyl starch (HES) solutions for fluid resuscitation of sepsis and septic shock in neonatal, pediatric, and adult patients (ACCM [Davis 2017]; SCCM [Dellinger 2013]; SCCM [Rhodes 2017]; Schlapbach 2024).
Hespan may be confused with heparin
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Arbekacin: Hetastarch may enhance the nephrotoxic effect of Arbekacin. Risk X: Avoid combination
Adverse events have been observed in some animal reproduction studies.
Volume expansion: At baseline and periodically with therapy, measure the following (some parameters may require continuous monitoring): Blood pressure, capillary refill time, CVP, RAP, MAP, urine output, heart rate, if pulmonary artery catheter in place, monitor cardiac index, PWCP, SVR, and PVR; hemoglobin, hematocrit, platelets, serum electrolytes, renal function (continue to monitor for at least 90 days after administration), acid-base balance, liver function, coagulation parameters.
Leukapheresis, CBC, total leukocyte and platelet counts, leukocyte differential count, hemoglobin, hematocrit, prothrombin time, and partial thromboplastin time
Produces plasma volume expansion by virtue of its highly colloidal starch structure
Duration: 3 to 36 hours
Excretion: Urine (~33% within 24 hours); smaller molecular weight molecules (<50,000 daltons) rapidly excreted.
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