Treatment-related mortality and renal replacement therapy:
In critically ill adults, including patients with sepsis, use of hydroxyethyl starch (HES) products increases the risk mortality and renal replacement therapy.
Do not use HES products, including hetastarch, in critically ill adults, including patients with sepsis.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Hespan: 6% (500 mL)
Hextend: 6% (500 mL)
Generic: 6% (500 mL)
Mechanism of Action
Produces plasma volume expansion by virtue of its highly colloidal starch structure
Urine (~33% within 24 hours); smaller molecular weight molecules (<50,000 daltons) rapidly excreted
Duration of Action
24 to 36 hours
Use: Labeled Indications
Granulocyte yield increase (Hespan only): Adjunct in leukapheresis to improve harvesting and increase the yield of granulocytes by centrifugation.
Plasma volume expansion: Blood volume expander used in treatment of hypovolemia.
Hypersensitivity to hetastarch, hydroxyethyl starch (HES), or any component of the formulation; critically ill adults, including sepsis, severe liver disease; renal disease with oliguria or anuria (not related to hypovolemia); any fluid overload condition (eg, pulmonary edema, heart failure); preexisting coagulation or bleeding disorders
Hextend: Additional contraindications: Treatment of lactic acidosis; leukapheresis.
Dosage and Administration
Granulocyte yield increase (Hespan): 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: IV: 500 to 1,000 mL or ~20 mL/kg once; may repeat as needed based on individual colloid needs, hemodynamics, and hydration status. Due to the risk of accumulation, maximum daily doses should not exceed 33 to 50 mL/kg/day (Myburgh 2012; Myburgh 2013; Perner 2012). Note: 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 renal impairment.
Refer to adult dosing.
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 renal dysfunction. Critical Care Medicine societies (ACCM, SCCM) recommend against the use of hydroxyethyl starch (HES) solutions for fluid resuscitation of severe sepsis and septic shock in neonatal and pediatric patients (ACCM [Davis 2017]; SCCM [Dellinger 2013]).
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) 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 (Brutocao 1996).
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 (McIlroy 2003). 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. Avoid excessive heat. 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.
Arbekacin: Hetastarch may enhance the nephrotoxic effect of Arbekacin. Avoid combination
Serum amylase levels may be temporarily elevated following administration; could interfere with the diagnosis of pancreatitis. Do not use serum amylase levels to assess or to evaluate for pancreatitis for 3 for 5 days after administration.
Large hetastarch volumes may result in decreased coagulation factors, plasma proteins, and /or hematocrit due to dilutional effect.
Frequency not defined.
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
Postmarketing and/or case reports: Angioedema, chest pain, cough, dyspnea, erythema multiforme, facial edema, flushing, hypotension, laryngeal edema, periorbital edema, renal insufficiency, restlessness, severe hypotension, sneezing, stridor, submaxillary gland enlargement, tachypnea, urticaria, ventricular fibrillation, wheezing
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: 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. Discontinue use of HES at the first sign of coagulopathy. 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.
- Fluid overload: Administration may cause fluid overload; use with caution in patients at risk from overexpansion of blood volume (eg, very young, elderly patients); use is contraindicated in heart failure or any preexisting condition where volume overload is a potential concern.
- 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.
- Hepatic impairment: Use with caution in patients with mild to moderate hepatic impairment; use is contraindicated in patients with severe hepatic impairment. Monitor liver function at baseline and periodically during treatment.
- Renal impairment: Avoid use in patients with preexisting renal impairment; monitor fluid status, urine output, and infusion rate; discontinue use at the first sign of renal injury. Larger hetastarch molecules may leak into urine in patients with glomerular damage; may elevate urine specific gravity. Use is contraindicated in renal disease with oliguria or anuria not related to hypovolemia.
- Thrombocytopenia: Use with caution in patients with thrombocytopenia; large volumes may interfere with platelet function and transiently prolong bleeding time. Observe for bleeding.
- Critically-ill patients: [US Boxed Warning]: HES solutions have been associated with mortality and renal injury requiring renal replacement therapy in critically ill patients, including patients with sepsis; avoid use in critically ill adults, including those with sepsis. Use should also be avoided in patients admitted to the ICU (Brunkhorst 2008; Perel 2012; Perner 2012). The Society of Critical Care Medicine (SCCM) also recommends against the use of HES solutions (ie, colloids) for fluid resuscitation of severe sepsis and septic shock; crystalloids (eg, sodium chloride, Ringer's lactate) are recommended as the fluid of choice for initial resuscitation and subsequent intravascular volume replacement (Rhodes 2017). If used in patients who are not critically ill, avoid use in patients with preexisting renal impairment and discontinue use at the first sign of renal injury. Since the need for renal replacement therapy has been reported up to 90 days after HES administration, continue to monitor renal 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 (renal impairment, respiratory alkalosis, metabolic alkalosis). Do not use in leukapheresis.
- Appropriate use: Not a substitute for red blood cells or coagulation factors.
Plasma volume expansion: Blood pressure, heart rate, capillary refill time, CVP, RAP, MAP, urine output; if pulmonary artery catheter in place, monitor cardiac index, PCWP, SVR, and PVR; hemoglobin, hematocrit, serum electrolytes, renal function (continue to monitor for at least 90 days after administration), acid-base balance, coagulation parameters, liver function tests
Granulocyte yield increase: CBC, total leukocyte and platelet counts, leukocyte differential count, hemoglobin, hematocrit, PT, PTT
Pregnancy Risk Factor
Adverse events have been observed in some animal reproduction studies.
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Have patient report immediately to prescriber signs of kidney problems (unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain), signs of acidosis (confusion, fast breathing, fast heartbeat, abnormal heartbeat, severe abdominal pain, nausea, vomiting, fatigue, shortness of breath, or loss of strength and energy), shortness of breath, excessive weight gain, swelling of arms or legs, bruising, or bleeding (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.