Hespan(R) injection contains hetastarch, a synthetic polymer, and is used intravenously as a colloidal plasma volume expander. It has no oxygen-carrying capacity. Hespan(R) produces increases in circulating blood volume that are comparable to that of albumin, dextran or Hextend(R). Hetastarch has fewer antigenic properties than dextran. Hextend(R) has been used clinically as an adjunct in the management or prevention of shock caused by hemorrhage, burns, surgery, or trauma. Also, it is added to whole blood to facilitate the collection of granulocytes in leukapheresis. It is commercially available as a colloidal solution. Hespan(R) contains 6% hetastarch in 0.9% sodium chloride solution. Hetastarch is derived from a waxy starch composed almost entirely of amylopectin. Due to a structural similarity to glycogen, hetastarch has hydroxyl ethers introduced into its glucose residues to retard degradation by serum amylase. About 75% of the glucose units are hydroxyethylated. The average molecular weight of hetastarch is approximately 670,000; at least 80% of the polymer units have a molecular weight between 20,000 and 2,500,000. Hetastarch was approved by the FDA in 1972.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
NOTE: Hetastarch may be administered as a 6% solution in 0.9% sodium chloride.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Do not administer solution that is cloudy or contains a precipitate. Discard any unused portions.
Intravenous Administration:
-Hetastarch is administered by intravenous infusion.
Continuous IV infusion
-Administer undiluted. Rate of administration is determined by individual patient requirements (i.e., amount of fluid loss, indication, and patient response).
Hetastarch (HES) does not have the antigenic properties seen with dextran, but serious and fatal anaphylactoid reactions have occurred. Reported hypersensitivity reactions with 6% hetastarch solutions include: life-threatening anaphylactic or anaphylactoid reactions, cardiac arrest, ventricular fibrillation, severe hypotension, non-cardiac pulmonary edema, laryngeal edema, bronchospasm, angioedema, wheezing, restlessness, tachypnea, stridor, fever, chest pain (unspecified), sinus bradycardia, sinus tachycardia, dyspnea or shortness of breath, chills, urticaria, pruritus, facial and periorbital edema, cough, sneezing, flushing, erythema multiforme, and rash (unspecified). HES-associated pruritus has also been reported in some patients with deposits of hydroxyethyl starch in peripheral nerves.
Circulatory overload may cause pulmonary edema or heart failure during therapy with hetastarch (HES) 6% solutions, especially in patients with renal disease and/or renal impairment. An increased risk of mortality and severe renal injury requiring renal replacement therapy in critically ill adult patients (e.g., patients with sepsis and those admitted to ICU) was found in an FDA analysis. Monitor patients for signs of renal failure (unspecified) and discontinue hetastarch at the first sign of renal injury. Continue to monitor renal function for at least 90 days in all patients; need for renal replacement therapy has been reported up to 90 days after HES administration.
Excessive bleeding has been reported in patients undergoing open heart surgery in association with cardiopulmonary bypass. Hetastarch should be discontinued at the first sign of coagulopathy. Large volumes of isotonic solutions containing 6% hetastarch may transiently alter the coagulation mechanism due to hemodilution and a mild direct inhibitory action on Factor VIII. Hemodilution may also result in a 24 hour decline of total protein, albumin, and fibrinogen levels and in transient prolongation of prothrombin, activated partial thromboplastin, clotting, and bleeding times. Hematocrit and plasma proteins may also be decreased by hemodilution. Administration of packed red cells, platelets, and fresh frozen plasma should be considered if excessive hemodilution occurs. Hematologic reactions to 6% hetastarch isotonic solutions include: intracranial bleeding, prolonged bleeding time, bleeding and/or anemia due to hemodilution and/or reversible clotting factor deficiency (factor VIII deficiency or acquired von Willebrand's-like syndrome), and coagulopathy including rare cases of disseminated intravascular coagulation (DIC) and hemolysis. Coagulopathies develop due a direct effect of hetastarch as well as due to hemodilution; it occurs when hetastarch solutions are used over several days. If a coagulopathy develops, it may take several days to resolve. Replacement therapy should be considered if a severe Factor VIII or von Willebrand deficiency is identified. Intracranial bleeding resulting in death has been reported with the use of hetastarch solutions, especially when used repeatedly over a period of days for the prevention of cerebral vasospasms.
Adverse effects reported with hetastarch solutions include: nausea/vomiting, peripheral edema of the lower extremities, submaxillary and parotid glandular enlargement, mild influenza-like symptoms, headache, metabolic acidosis, and muscle pain or myalgia.
Solutions containing hetastarch are contraindicated in patients with known history of hydroxyethyl cellulose hypersensitivity. Caution should be used when administering solutions containing hetastarch to patients with a corn hypersensitivity because such patients can also be allergic to hetastarch. If a hypersensitivity effect occurs, administration of the drug should be discontinued and appropriate treatment and supportive measures should be undertaken. Life threatening anaphylactic or anaphylactoid reactions have been reported with solutions containing hetastarch; death has occurred. Patients who develop severe anaphylactic or anaphylactoid reactions may need continued supportive care until symptoms have resolved. Hypersensitivity reactions can occur even after solutions containing hetastarch have been discontinued.
Excess bleeding has occurred with hetastarch use in patients undergoing surgery. Do not use hetastarch unless adequate alternative treatment is unavailable. Hetastarch is contraindicated in patients with a pre-existing coagulopathy or bleeding disorder or intracranial bleeding. Hetastarch is not recommended for use as a cardiac bypass pump prime, while the patient is on cardiopulmonary bypass, or in the immediate period after the pump has been discontinued because of the risk of increasing coagulation abnormalities and bleeding in patients whose coagulation status is already impaired. Monitor the coagulation status of patients undergoing coronary artery bypass graft surgery (CABG) as excess bleeding has been reported with hetastarch solutions in this population. Discontinue use of hetastarch at first sign of coagulopathy. Repeated administration or large volumes of hetastarch over several days has been associated with coagulation abnormalities in conjunction with an acquired, reversible acquired von Willebrand's-like syndrome and/or factor VIII deficiency. Consider replacement therapy if a severe factor VIII deficiency is identified. If a coagulopathy develops, it may take several days to resolve. Certain conditions may affect the safe use of hetastarch on a chronic basis. For example, in patients with subarachnoid hemorrhage where hetastarch is used repeatedly over a period of days for the prevention of cerebral vasospasm, significant clinical bleeding may occur.
Hetastarch is contraindicated in adults with critical illness, including patients with sepsis, due to increased risk of mortality and renal replacement therapy (RRT) as well as in patients receiving dialysis or with clinical conditions where hypervolemia is a potential problem, including congestive heart failure or renal disease with anuria or oliguria not related to hypovolemia. Avoid excessive hemodilution and circulatory overload in patients at risk for developing congestive heart failure or pulmonary edema. Blunt trauma patients are also at increased risk of mortality and RRT. Do not use hetastarch unless adequate alternative treatment is unavailable. Avoid hetastarch use in patients with pre-existing renal impairment or renal failure. Discontinue hetastarch use at the first sign of renal injury. Continue to monitor renal function in hospitalized patients for at least 90 days as use of RRT has been reported up to 90 days after administration of hetastarch. Avoid fluid overload; adjust hetastarch dosage in patients with cardiac disease or renal impairment. Assess fluid status and rate of infusion regularly during treatment, especially in patients with cardiac insufficiency or severe kidney dysfunction.
Total bilirubin remains normal in liver function tests, but indirect serum bilirubin concentrations have been reported infrequently. Indirect bilirubin levels of 8.3 mg/L (normal 0.07-7 mg/L) have been reported in 2 of 20 normal subjects who received multiple infusions of hetastarch injection. Total bilirubin was within normal limits at all times; and indirect bilirubin returned to normal by 96 hours following the final infusion. The implications of these results have not been fully evaluated, but hetastarch should be used with caution in patients with hepatic disease.
Elevated serum amylase levels may be observed temporarily following administration of solutions containing hetastarch although no association with pancreatitis has been demonstrated. Serum amylase levels cannot be used to assess or to evaluate for pancreatitis for 3-5 days after administration of solutions containing hetastarch. Elevated serum amylase levels persist for longer periods of time in patients with renal impairment. Solutions containing hetastarch have not been shown to increase serum lipase. The implications of these results have not been fully evaluated, but hetastarch should be used with caution in patients with pancreatitis.
Hetastarch solution (Hespan) is classified as FDA pregnancy category C. Hetastarch has been shown to be embryocidal in animal studies; however, there are no adequate and well controlled studies in pregnant women. Hetastarch solutions should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
It is not known whether hetastarch is excreted in human milk. According to the manufacturer, because many drugs are excreted in human milk, caution should be exercised when hetastarch is administered to breast-feeding women. However, the very large molecular weight of hetastarch most likely limits the amount of drug that is excreted into breast milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Safe and effective use of hetastarch has not been established in neonates.
For use as a plasma expander in cardiopulmonary bypass surgery and in the treatment of shock due to hypovolemia caused by hemorrhage, surgery, trauma, sepsis, or burns:
NOTE: Dosage and infusion rate depend on amount of fluid loss and must be individualized.
Intravenous infusion (Hespan solution; contains 6% hetastarch in 0.9% sodium chloride):
Adults: Initially, 30-60 g (500-1000 mL) IV infusion. Do not exceed 1.2 g/kg (20 mL/kg) or 90 g (1500 mL) per day. A rate up to 1.2 g/kg/hour (20 mL/kg/hour) may be used in acute hemorrhagic shock. A slower rate is used in septic shock or burns.
Geriatric: See adult dosage. No specific dosage recommendations are available; associated renal dysfunction in elderly patients may reduce hetastarch clearance.
Adolescents and Children: Initially, 10 mL/kg IV infusion (do not exceed 20 mL/kg/hour for hemorrhagic shock). Maximum dosage 20 mL/kg/day.
Neonates: Safety and efficacy have not been established.
For enhancement of granulocyte yield during continuous-flow centrifugation leukapheresis procedures:
Intravenous infusion (Hespan solution; contains 6% hetastarch in 0.9% sodium chloride):
Adults: 250-700 mL with added citrate anticoagulant is administered by aseptic addition to the input line of the centrifugation apparatus at a ratio of 1:8 to 1:13 to venous whole blood. Up to 2 procedures a week, and a total number of between 7 and 10 procedures have been used safely. NOTE: When stored at room temperature, hetastarch admixtures of 500-560 mL with citrate concentrations up to 2.5% are compatible for 24 hours.
Maximum Dosage Limits:
-Adults
1500 mL/day IV (or approximately 20 mL/kg/day IV).
-Geriatric
1500 mL/day IV (or approximately 20 mL/kg/day IV).
-Adolescents
20 mL/kg/day IV.
-Children
20 mL/kg/day IV.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific dosage guidelines are not available.
Patients with Renal Impairment Dosing
CrCl < 10 mL/min: The usual initial dose may be given, but subsequent doses should be reduced by about 25-50% of the usual dosage.
*non-FDA-approved indication
Dichlorphenamide: (Moderate) Use dichlorphenamide and hetastarch together with caution as both drugs can cause metabolic acidosis. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Lithium: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
Tolvaptan: (Moderate) Coadministration of tolvaptan and hypertonic saline (e.g., 3% NaCl injection solution) is not recommended. The use of hypertonic sodium chloride in combination with tolvaptan may result in a too rapid correction of hyponatremia and increase the risk of osmotic demyelination (i.e., central pontine myelinolysis).
Hetastarch produces volume expansion by increasing the oncotic pressure within the intravascular space. This mechanism is similar to both albumin and dextran. Administration of the colloidal mixture of hetastarch causes water to move from interstitial spaces into the intravascular space, thereby increasing the circulating blood volume. Intravenous infusion of hetastarch 6% solution results in expansion of plasma volume that decreases over the succeeding 24 to 36 hours. The degree of plasma volume expansion and improvement in hemodynamic state depend upon the patient's intravascular and cardiovascular status. In patients who are hypovolemic, this results in an increase in cardiac index, stroke work index, arterial and venous pressures, and pulmonary wedge pressures. Large volumes of hetastarch solution may transiently alter the coagulation mechanism due to hemodilution in addition to a mild direct inhibitory action on Factor VIII.
Hetastarch causes an increase in the erythrocyte sedimentation rate (ESR) when added to whole blood. This facilitates the collection of granulocytes by centrifugation. Compared with dextran 75, hetastarch causes a greater increase in the ESR.
Hetastarch is administered by intravenous infusion. It produces a volume expansion that is slightly greater than the administered volume, with maximum expansion occurring within minutes following cessation of infusion. Increases in plasma volume last for 24 hours or longer. Hetastarch molecules below 50,000 molecular weight are rapidly eliminated by renal excretion, about 33% of the dose is excreted in the urine within 24 hours. The hydroxyethyl groups present in hetastarch are not metabolized but are excreted intact (attached to the glucose residues). About 2 weeks after administration, the intravascular hetastarch concentration accounts for less than 10% of the total dose injected. Hetastarch is not eliminated by hemodialysis.
-Special Populations
Renal Impairment
Hetastarch is not eliminated by hemodialysis.