Dextran is a branched polysaccharide used intravenously as a plasma volume expander. It is formed by a bacterium, Leuconostoc mesenteroides, which contributes to its antigenicity; however, due to improved preparation techniques, the incidence of hypersensitivity reactions is reduced. Dextran is available in various molecular weights, and these products exhibit different osmotic and pharmacologic properties. Dextran 40 contains molecules of molecular weight (MW) 40,000 daltons while dextran 70 contains molecules of 70,000 daltons. Both types of products contain molecules of varying molecular weights, some lower and some higher than the stated label. Dextran is used clinically as an adjunct in the management or prevention of shock caused by hemorrhage, burns, surgery, or trauma, and in the prophylaxis of venous thrombosis and pulmonary embolism in patients undergoing surgery that carries a high risk of thromboembolic complications (e.g., hip surgery). Dextran was first approved in 1951 as a 6% solution. Dextran 70/75 was approved by the FDA in 1953 and Dextran 40 in 1967.
Administration
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit; do not use if crystallization has occurred.
Intravenous Administration
-Administer by IV infusion.
-Dextran 40 may be administered as a 10% solution in 5% dextrose or 0.9% sodium chloride; use a filter when infusing concentrated solution.
-Dextran 70 or 75 may be administered as a 6% solution in 5% dextrose or 0.9% sodium chloride.
-Infusion rate must depend on fluid loss and individual patients hematologic requirements. In emergency, the drug may be given at a rate of 1.2-2.4 g/minute or 20-40 mL/minute IV. In normovolemic or nearly normovolemic patients, the infusion rate should not exceed 0.24 g/minute or 4 mL/minute.
Severe and fatal anaphylactoid reactions/anaphylactic shock (dextran-induced anaphylactoid reactions, DIAR), consisting of cardiac arrest and respiratory arrest, have been reported with IV dextran. Most reaction have occurred in patients not previously exposed to IV dextran during the early infusion period. Other allergic reactions consist of urticaria, nasal congestion, wheezing, tightness of the chest, and hypotension. Close observation during the first few minutes of administration is essential; discontinue therapy at the first sign of allergic reaction. Symptoms can be alleviated with administration of parenteral epinephrine, while other means of treatment for shock are instituted. Dextran 40 has less potential for causing these adverse reactions, compared to other Dextran preparations.
Renal failure (unspecified) has been reported to occur after the use of Dextran 40. Evidence of tubular vacuolization (osmotic nephrosis) has been reported. Molecular weight must be under 50,000 for excretion by the kidneys, so this reaction does not apply to dextran 70 or 75. Dextran 40 undergoes rapid urinary excretion, increasing viscosity and specific gravity of urine. Adequate hydration is essential.
Adverse gastrointestinal (GI) effects have been reported from use of dextran including nausea and vomiting.
Dextran cause prolonged bleeding time through interference with platelet function (platelet dysfunction). These effects may be dose related.
An injection site reaction has been reported with dextran administration, and could be due to the solution itself or the technique of administration. Injection site infection, venous thrombosis or phlebitis extending from the injection site, or extravasation could occur. A febrile response (fever) or hypervolemia have also been associated with administration. Joint pain may also occur.
Severe anaphylactoid reactions can occur during treatment with dextran 40, 70, or 75, indicating hypersensitivity to dextran. Close observation of the patient is required during the first few minutes of infusion and a determination made as to whether hypotension results from shock or from dextran. Alternative methods for maintaining circulation and for resuscitation should be available.
The possibility of circulatory overload is one of the major concerns for administration of dextran. These effects are variable with the different molecular weights of dextran preparations. An absolute contraindication is recommended for dextran 70 and 75 in patients with severe heart failure or severe renal failure, while caution should be exercised during use of dextran 40, 70, or 75 in patients with renal disease or cardiac failure. Dextran 40 is also contraindicated in patients with renal disease accompanied by severe oliguria or anuria, and in patients with pulmonary edema.
Dextran 70 or 75 can prolong bleeding time through interference with platelet function, and it should be used with caution in patients with thrombocytopenia and not at all in those with severe coagulopathy. Dextran 40 appears to have little effect on bleeding time at the recommended dosage, but it should be used with caution in patients with coagulopathy (e.g., hemophilia), thrombocytopenia or hypofibrinogenemia. Dextran 40 also can increase blood loss because of increased perfusion pressure and improved microcirculatory flow. When patients are dehydrated, adequate fluid intake is essential; renal failure is possible in severe dehydration because of increased urine viscosity and specific gravity.
Use dextran during pregnancy only if clearly needed. It is not known whether dextran can cause fetal harm when administered during pregnancy or can affect reproduction capacity. Animal reproduction studies have not been conducted with dextran.
It is not known whether dextran is excreted in human milk. Because many medications are excreted in human milk, use caution when administering dextran during breast-feeding.
For priming pump oxygenators:
Priming pump oxygenator (Dextran 40):
Adults: 10 to 20 mL/kg (1 to 2 g/kg) added to the perfusion circuit; amount used depends on the volume of the pump oxygenator. Usual Max: 20 mL/kg (2 g/kg). May be used as the only priming fluid or in conjunction with other primers.
Adolescents: 10 to 20 mL/kg (1 to 2 g/kg) added to the perfusion circuit; amount used depends on the volume of the pump oxygenator. Usual Max: 20 mL/kg (2 g/kg). May be used as the only priming fluid or in conjunction with other primers.
Children: 10 mL/kg (1 gm/kg) added to the perfusion circuit; amount used depends on the volume of the pump oxygenator. Usual Max: not defined in children; 20 mL/kg (2 g/kg) in adolescents. May be used as the only priming fluid or in conjunction with other primers.
Infants: 5 mL/kg (0.5 gm/kg) added to the perfusion circuit; amount used depends on the volume of the pump oxygenator. Usual Max: not defined for infants; 20 mL/kg (2 g/kg) in adolescents. May be used as the only priming fluid or in conjunction with other primers.
For adjunctive therapy in the treatment of shock due to hypovolemia caused by burns, surgery, hemorrhage or trauma:
Intravenous Infusion (Dextran 40):
Adults: 10 mL/kg infused as rapidly as necessary. Max: 20 mL/kg/day for the first 24 hours and 10 mL/kg/day thereafter. Max duration of therapy is 5 days.
Adolescents: 10 mL/kg infused as rapidly as necessary. Max: 20 mL/kg/day for the first 24 hours and 10 mL/kg/day thereafter. Max duration of therapy is 5 days.
Children: 10 mL/kg infused as rapidly as necessary. Max: not defined in children; 20 mL/kg/day for the first 24 hours and 10 mL/kg/day thereafter in adolescents. Max duration of therapy is 5 days.
Infants: 5 mL/kg infused as rapidly as necessary. Max: not defined for infants; 20 mL/kg/day for the first 24 hours and 10 mL/kg/day thereafter in adolescents. Max duration of therapy is 5 days.
Intravenous Infusion (Dextran 70):
Adults: 500 mL given at a rate of 20 to 40 mL/minute in emergency situations. Max: 20 mL/kg/day for the first 24 hours. Total dose and rate of infusion are dependent upon the magnitude of fluid loss and resultant hemoconcentration.
Children* and Adolescents*: Safety and efficacy have not been established; limited data suggests total dosage should not exceed 20 mL/kg.
For surgical deep venous thrombosis (DVT) prophylaxis and pulmonary embolism prophylaxis:
Intravenous Infusion (Dextran 40):
Adults: 500 to 1,000 mL (approximately 10 mL/kg) administered on the day of surgery. Continue treatment at a dose of 500 mL/day for an additional 2 to 3 days. Further treatment depends on the risk of thromboembolic complications; 500 mL may be given every 2 to 3 days during the risk period, for up to 2 weeks.
Adolescents: 500 to 1,000 mL (approximately 10 mL/kg) administered on the day of surgery. Continue treatment at a dose of 500 mL/day for an additional 2 to 3 days. Further treatment depends on the risk of thromboembolic complications; 500 mL may be given every 2 to 3 days during the risk period, for up to 2 weeks.
Children: 10 mL/kg administered on the day of surgery. Continue treatment (10 mL/kg/dose) for an additional 2 to 3 days. Further treatment depends on the risk of thromboembolic complications; 10 mL/kg may be given every 2 to 3 days during the risk period, for up to 2 weeks.
Infants: 5 mL/kg administered on the day of surgery. Continue treatment (5 mL/kg/dose) for an additional 2 to 3 days. Further treatment depends on the risk of thromboembolic complications; 5 mL/kg may be given every 2 to 3 days during the risk period, for up to 2 weeks.
For the treatment of frostbite*:
Intravenous dosage (Dextran 40):
Adults: 20 mL IV bolus, followed by 20 mL/hour continuous IV infusion for 3 to 7 days. Consider a test dose prior to administration due to the low risk of anaphylaxis. Guidelines recommend low molecular weight dextran if other systemic treatments, such as thrombolytic therapy, are not being given. Intravenous low molecular weight dextran improves rheology by decreasing blood viscosity by preventing red blood cell aggregation and formation of microthrombi.
Maximum Dosage Limits:
-Adults
Maximum dosage is dependent on indication for therapy and formulation used.
-Geriatric
Maximum dosage is dependent on indication for therapy and formulation used.
-Adolescents
Maximum dosage is dependent on indication for therapy and formulation used.
-Children
Maximum dosage is dependent on indication for therapy and formulation used.
-Infants
Maximum dosage is dependent on indication for therapy and formulation used.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Anticoagulants: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Antithrombin III: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Apixaban: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Argatroban: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Betrixaban: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Bivalirudin: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Dabigatran: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Dalteparin: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Edoxaban: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Enoxaparin: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Fondaparinux: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Heparin: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
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.
Pentosan: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Rivaroxaban: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
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).
Warfarin: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
The colloidal osmotic effect exerted by dextran draws fluid into the vascular system from the interstitial spaces, resulting in increased circulating blood volume. This increased volume causes an increase in central venous pressure, cardiac output, stroke volume, blood pressure, urinary output, and capillary perfusion, and a decrease in heart rate, peripheral resistance, and blood viscosity. Dextran 70 and 75 both exert osmotic and pharmacologic effects similar to those of albumin. Unlike the higher MW products, dextran 40 not only corrects hypovolemia, but also improves microcirculation independently of its volume-expanding effects. The exact mechanism of this activity is unknown, but it is believed to occur by minimizing erythrocyte aggregation and/or decreasing blood viscosity. Dextran 40 is also believed to coat erythrocytes, which maintains erythrocyte electronegativity and the ability to repel one another, and reduces erythrocyte rigidity to aid in passage through capillaries.
Pharmacokinetics:
Dextran is administered intravenously. Following a single infusion, circulating blood volume is increased maximally within a few minutes following infusion of dextran 40 and within 1 hour after dextran 70 or 75. Volume expansion can persist for 24 hours or longer. Molecules of the lowest molecular weight contained in dextran 40 are excreted rapidly via the kidney, leaving molecules with higher molecular weight. Molecules that are over molecular weight 50,000 (which includes most of those in dextran 70 and 75) are slowly converted to glucose and subsequently metabolized to carbon dioxide and water. In patients with normal renal function, 70% of a dose of dextran 40 and 50% of dextran 70 or 75 is excreted in the urine within 24 hours.