Hextend(R) is used intravenously as a colloidal plasma volume expander. It has no oxygen-carrying capacity. Hextend(R) produces increases in circulating blood volume that are comparable to that of albumin, dextran or Hespan(R). Hetastarch has fewer antigenic properties than dextran. Although Hespan(R) has been used clinically as an adjunct in the management or prevention of shock caused by hemorrhage, burns, surgery, or trauma; Hextend is currently only indicated in the treatment of hypovolemia during surgery. Hextend(R) contains 6% hetastarch, dextrose, normal physiological concentrations of sodium and calcium, and slightly lower than normal physiological levels of potassium and magnesium. Lactate is included for buffering capacity. 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. Hextend(R) was approved by the FDA on 3/31/99.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
Intravenous Administration:
-Hetastarch with dextrose and electrolytes is administered by IV infusion.
-Use only if solution is clear and container and seals are intact. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. If leaks are found, discard the solution.
-Discard any unused portions (single dose containers).
-Solutions containing calcium should not be administered simultaneously with blood through the same administration set because of the likelihood of coagulation.
-Do not use plastic container in series connection.
-If administration is by pressure infusion, all air should be withdrawn or expelled from the bag through the medication port prior to infusion.
-If administration is controlled by a pumping device, care must be taken to discontinue pumping action before the container runs dry or air embolism may result.
In small clinical trials comparing the plasma volume expanding properties of Hextend with those of hetastarch injection (Hespan) or albumin, there were no significant differences in the number of adverse events including blood loss.
Of the total number of patients in clinical trials of Hextend, 30% were 65 or older while 12% were 70 or older. Other reported experience with hetastarch injection has not identified differences in responses between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Hetastarch 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). Hydroxyethyl starch-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.
Do not use Hextend in patients undergoing leukapheresis.
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. 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 the first sign of coagulopathy.
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. Use Hextend with caution, if at all, in patients with hyperkalemia and severe renal failure and in situations where potassium retention is present.
Hextend contains dextrose and should be used with caution in patients with known subclinical or overt diabetes mellitus.
Hextend contains lactate and is contraindicated in lactic acidosis. The administration of lactate solutions should be used with caution in conditions associated with increased serum lactate or impaired utilization of lactate, such as lactic acidosis or severe hepatic insufficiency. Solutions containing lactate ions should be used with caution in respiratory alkalosis or metabolic alkalosis; excess lactate administration may cause metabolic alkalosis.
Hextend contains calcium (5 mEq/L) and should be used with caution in hypercalcemia.
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; Dextrose; Electrolytes solution is classified as FDA pregnancy risk category C. There are no adequate and well controlled studies in pregnant women. Hextend should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
According to the manufacturer, it is not known whether hetastarch is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Hextend is administered to breast-feeding women. 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 administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.
The safety and effectiveness of Hextend in pediatric patients have not been established; however, hetastarch 6% in 0.9% saline has been studied in children.
For use as a plasma expander in hypovolemia during surgery:
NOTE: Hextend contains hetastarch, dextrose, and electrolytes. Hextend is not a substitute for blood or plasma.
Intravenous infusion:
Adults: Initially, 500-1000 mL IV infusion. Maximum dosage recommended by the manufacturer is 1500 mL/day IV (or approximately 20 mL/kg/day). The manufacturer does not provide specific guidelines for the rate of infusion; however, a rate up to 20 mL/kg/hour of hetastarch 6% solutions without electrolytes (see Hespan) has been used to treat acute hemorrhagic shock. Doses of isotonic solutions containing 6% hetastarch up to 1500 mL have been used during major surgery usually without a need to administer blood or blood products. Volumes in excess of 1500 mL per day have been used where severe blood loss has occurred, although generally only as an adjunct to the use of blood and blood products. Dosage and infusion rate depend on amount of fluid loss and must be individualized considering the amount of blood or plasma lost, the degree of hemoconcentration, age, weight, and clinical condition of the patient. During prolonged parenteral therapy, the patient should be monitored for fluid and electrolyte balance, acid-base balance, and coagulation status.
Geriatric: See adult dosage. No specific dosage recommendations are available; associated renal dysfunction in elderly patients may reduce hetastarch clearance.
Adolescents, Children, Infants, and Neonates: Safety and efficacy have not been established.
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
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-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
No recommendations are available; Hextend is contraindicated in renal failure with anuria or oliguria (except when caused by hypovolemia). Hetastarch is eliminated renally.
*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.
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.
Pharmacokinetics:
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.
Elimination of the electrolyte and dextose components of Hextend are by normal physiologic mechanisms. Approximately 80% of body calcium is excreted in the feces as insoluble salts; urinary excretion accounts for the remaining 20%. The distribution and excretion of sodium (Na+) and chloride (Cl-) are primarily regulated by renal mechanisms. About 80 to 90% of administered potassium is excreted in the urine; the remainder is excreted in the feces and skin. Dextrose injected parenterally undergoes oxidation to carbon dioxide and water. In the liver, the lactate is metabolized by glycogen, which is converted to carbon dioxide and water by oxidative metabolism. When oxidative activity is intact, one to two hours is required for metabolism of lactate; some shock states with acidosis may impair lactate metabolism.
-Special Populations
Renal Impairment
Hetastarch is not eliminated by hemodialysis.