VA Class:BL800

AHFS Class:

• Replacement Preparations 40:12

Generic Name(s):

• Dextran 40

Dextran 40, a nonprotein colloid, is a plasma volume expander.

Dextran 40 is a nonprotein colloid used for early fluid replacement and for plasma volume expansion in the adjunctive treatment of certain types of shock or impending shock when whole blood or blood products are not available, or when the need for haste precludes the necessary cross-matching of blood. Dextran 40 differs from dextran 70 and 75 in molecular weight and adverse effects. In addition to producing plasma volume expansion, dextran 40 appears to minimize sludging of blood as a result of its effects on microcirculation. Types of shock for which dextran 40 may be used include those resulting from burns, surgery, hemorrhage, or other trauma in which a circulating volume deficit is present. Dextran 40 does not replace other forms of therapy but is complementary to fluids and electrolytes. For additional information, see Uses in Albumin Human 16:00.

Extracorporeal Circulation

Dextran 40 is also used as a priming fluid, either alone or as an additive to other priming fluids, in pump oxygenators for perfusion during extracorporeal circulation.

Thromboembolic Disorders

Dextran 40 may also be used for prophylaxis of venous thrombosis and pulmonary embolism in patients undergoing surgical procedures associated with a high risk of thromboembolic complications (e.g., hip surgery). Although dextran 40 appears to be beneficial in patients undergoing hip surgery, the drug has not been shown to be more effective than oral anticoagulants or heparin in patients undergoing general surgery. The American College of Chest Physicians (ACCP) does not recommend the use of dextran as the sole method of thromboprophylaxis in patients undergoing elective hip arthroplasty.200

Other Uses

Dextran 40 has been used to improve circulation in a number of other conditions†, including sickle cell crisis. The drug has also been administered for the prevention of nephrotoxicity associated with radiographic contrast media†, for the treatment of various vascular diseases†, for use in transplantation and graft procedures†, and for use in exchange transfusions for treatment of polycythemia secondary to hypoxic lung disease†.

Administration

Dextran 40 is administered in 10% solution by IV infusion. Because dextran 40 injections do not contain preservatives, partially used containers should be discarded.

Dosage

Shock

When dextran 40 is used as an adjunct to other forms of shock therapy, dosage and the rate of infusion depend upon the amount of fluid loss and the resultant hemoconcentration and must be determined according to the requirements of the patient. Total dosage of the 10% solution during the first 24 hours should not exceed 2 g/kg (20 mL/kg); if therapy is continued beyond 24 hours, dosage should not exceed 1 g/kg (10 mL/kg) daily. Therapy should not be continued for longer than 5 days. The first 500 mL of dextran 40 solution may be infused rapidly while central venous pressure is closely monitored. (See Cautions: Precautions and Contraindications.) The remaining dose should be infused slowly. If central venous pressure is not monitored, infusion of the drug should be slower and the patient should be closely observed for signs of circulatory overload.

Priming Pump Oxygenators

Dextran 40 can be used as the only priming fluid or as an additive to other primers in pump oxygenators. The amount of solution used varies with the volume of the pump oxygenator. Generally, dextran 40 is added to the perfusion circuit as the 10% solution in a dose of 1-2 g/kg (10-20 mL/kg); total dose should not exceed 2 g/kg (20 mL/kg).

Prophylaxis of Venous Thrombosis and Pulmonary Embolism

For prophylaxis of venous thrombosis and pulmonary embolism, dextran 40 therapy should generally be initiated during the surgical procedure. On the day of surgery, dextran 40 is given as the 10% solution in a dose of 50-100 g (500-1000 mL or approximately 10 mL/kg). Treatment is continued for an additional 2-3 days with a dosage of 50 g (500 mL) daily. Thereafter, according to the risk of thromboembolic complications, 50 g (500 mL) may be given every second or third day during the period of risk, for up to 2 weeks.

Adverse Effects

Adverse effects resulting from the antigenic properties of dextran 40, including mild urticarial reactions, have been reported. Rarely, severe anaphylactoid reactions manifested by generalized urticaria, tightness of the chest, wheezing, hypotension, nausea and vomiting, and occasionally resulting in fatalities, have occurred after administration of as little as 5 mL of dextran 40 solution. Anaphylactoid symptoms may be relieved by parenteral administration of epinephrine; antihistamines and other supportive therapy may also be used.

Because it is so rapidly excreted, dextran 40 increases the viscosity and specific gravity of urine, especially in patients with decreased urine flow. In adequately hydrated patients with normal renal function, the specific gravity of urine following administration of dextran 40 rises only slightly; however, tubular stasis and blocking, including one fatality, have been reported even in patients with adequate hydration. Tubular vacuolization (osmotic nephrosis), which appears to be reversible, has also been reported, probably as a result of high concentrations of the drug in the urine.

Increased serum AST (SGOT) and ALT (SGPT) concentrations have been reported after dextran 40 administration, but the specific effect of the drug on hepatic function has not been determined. The development of mild to moderate acidosis may occur during perfusion with any priming fluid in pump oxygenators and is not altered by dextran 40 administration. Acidosis, if it occurs, is usually transient; however, the administration of an alkalinizing agent may be necessary.

Precautions and Contraindications

Because dextran 40 can cause severe anaphylactoid reactions, patients should be closely observed during the first minutes of infusion, and other means of maintaining circulation should be available so that dextran therapy can be stopped at the first signs of allergic reactions. Resuscitative measures should also be readily available. Dextran 40 is contraindicated in patients who are hypersensitive to dextrans.

Prior to dextran 40 administration, the patient's state of hydration should be assessed. If there are signs of dehydration, additional fluid should be administered. Some clinicians consider extreme dehydration a contraindication to dextran 40 therapy, since renal failure has occurred following administration of the drug in extremely dehydrated patients. Low specific gravity of urine during dextran 40 therapy may indicate a failure of renal dextran clearance and is an indication for discontinuing the drug. It is necessary to monitor urinary flow rates during the administration of dextran 40. If oliguria or anuria occurs, dextran 40 infusion should be discontinued and an osmotic diuretic such as mannitol should be administered to minimize vascular overloading. Dextran 40 is contraindicated in patients with renal disease who have severe oliguria or anuria; the drug may be used in patients with decreased urinary output secondary to shock if there is improvement in urinary output after the drug is given.

When dextran 40 is administered by rapid infusion, central venous pressure should be closely monitored. Dextran 40 should be immediately discontinued if there is a precipitous rise in central venous pressure or if there are any clinical signs of circulatory overloading. Because of its plasma volume expanding effect, dextran 40 is hazardous when administered to patients with heart failure, especially when the drug is administered in sodium chloride solution. In those patients for whom restriction of sodium is indicated, it must be noted that 500 mL of 10% dextran 40 in 0.9% sodium chloride contains 77 mEq of both sodium and chloride. Large doses which result in overloading of the vascular system may cause pulmonary edema. Dextran 40 should not be administered to patients with pulmonary edema and should be given with caution to patients with cardiac decompensation.

The patient's hematocrit should be determined after administration of dextran 40, and care should be taken to avoid depressing it below 30% by volume. When large volumes of dextran are administered, plasma protein concentrations will be decreased. Dextran 40 does not appear to affect blood coagulation substantially at recommended dosage, but higher dosage may result in a prolongation of bleeding time. Dextran 40 should be administered with caution to patients with active hemorrhage because the increased perfusion pressure and improved microcirculatory flow may result in additional blood loss; the possibility of slightly increased blood loss in post-operative patients must also be considered. Dextran 40 is contraindicated in patients with marked thrombocytopenia or hypofibrinogenemia. One manufacturer cites defects of the clotting mechanism and bleeding disorders as contraindications.

Pregnancy and Lactation

Pregnancy

Animal reproduction studies have not been performed with dextran 40; and it is also not known whether the drug can cause fetal harm when administered to pregnant women. Dextran 40 should be used during pregnancy only when clearly needed.

Lactation

It is not known whether dextran 40 is excreted in human milk. Because of the potential for serious adverse reactions to dextran 40 in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

Laboratory Test Interferences

Although the use of dextran 40 solutions does not interfere with blood-typing and cross-matching when these tests are carried out by saline agglutination and indirect-antiglobulin methods, difficulties may be encountered when proteolytic enzyme techniques are used to cross-match blood. Blood glucose determinations that involve sulfuric acid or acetic acid hydrolysis may give high values in patients receiving dextran 40. The presence of dextran in the blood may result in development of turbidity which may interfere with bilirubin assays in which alcohol is used and in total protein assays using biuret reagent. To avoid misleading results when these tests are indicated, blood samples should be drawn before initiating dextran therapy.

Pharmacology

The principal effect of dextran 40 following IV administration is plasma volume expansion, resulting from the drug's colloidal osmotic effect in drawing fluid from the interstitial to the intravascular spaces. Dextran 40 produces a plasma volume expansion slightly greater than the volume of dextran 40 solution infused. Maximum plasma volume is reached within several minutes after the end of infusion; the extent and duration of the expansion in plasma volume vary with the volume of dextran 40 solution infused and depend on the preadministration plasma volume and the rate of renal clearance of dextran. Plasma volume expansion is accompanied by an increase in central venous pressure, cardiac output, stroke volume, blood pressure, urinary output, capillary perfusion, and pulse pressure, and by a decrease in heart rate, peripheral resistance, blood viscosity, and mean transit time.

Dextran 40 also enhances blood flow through correction of hypovolemia and improved microcirculation. It has been postulated that dextran 40 improves microcirculation mainly by preventing, diminishing, or reversing erythrocyte aggregation and/or by decreasing blood viscosity, but the precise mechanism of action is not known. Dextran 40 may coat erythrocytes, thus reducing bonding forces and maintaining the erythrocytes in a state of electronegativity and mutual repellancy; dextran 40 may also coat other formed elements. In addition, the drug may decrease erythrocyte rigidity, thereby facilitating passage of erythrocytes through small blood vessels.

Pharmacokinetics

The plasma concentration of dextran 40 depends on the rate of infusion, the total amount of drug administered, and the rate of disappearance of the drug from plasma. In patients with normal renal function, the plasma concentration of the drug falls rapidly during the first hour following infusion and more slowly thereafter. Dextran molecules of molecular weight 15,000 or less are rapidly excreted through the kidneys; therefore, the plasma distribution of dextran, according to molecular weight, shifts toward the higher molecular weight polymers. About 70% of a dose of dextran 40 is excreted unchanged in urine within 24 hours after administration. Dextran molecules of molecular weight 50,000 or greater are not excreted by the kidneys but are slowly degraded to glucose which is metabolized to carbon dioxide and water. A small amount of the infused dextran is also excreted into the GI tract and eliminated in the feces.

Chemistry and Stability

Chemistry

Dextran 40 is a low molecular weight polymer of glucose with an average molecular weight of approximately 40,000 and a molecular weight range of approximately 10,000-90,000. Linkages in the polymers are principally of the 1,6-glucosidic type.

Dextran 40 occurs as a white, amorphous powder and is soluble in water and insoluble in alcohol. Each 500 mL of the commercially available, colloidal solution containing 10% dextran 40 in 0.9% sodium chloride provides 77 mEq of sodium; the pH is 3.5-7. A colloidal solution of 10% dextran 40 in 5% dextrose has a pH of 3-7.

Stability

Dextran 40 solution should not be administered unless it is clear. If dextran solution is stored for long periods or if storage temperature varies greatly, dextran flakes may form in the solution. These flakes can be dissolved by heating the solution in a water bath at 100°C until it becomes clear, or by autoclaving at 110°C for 15 minutes. Dextran 40 solution should be stored at a constant temperature, preferably 25°C.

Only references cited for selected revisions after 1984 are available electronically.

200. Geerts WH, Pineo GF, Heit JA et al. Prevention of venous thromboembolism The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest . 2004; 126(Suppl):338S-400S. [PubMed 15383478]