Dextran 40 (Monograph)

Brand name: LMD
Drug class: Replacement Preparations
VA class: BL800
CAS number: 9004-54-0

Introduction

Plasma volume expander; nonprotein colloid.

Uses for Dextran 40

Shock

Early fluid replacement and plasma volume expansion in the adjunctive treatment of certain types of shock or impending shock (e.g., burns, surgery, hemorrhage, or other trauma in which a circulating volume deficit is present) when whole blood or blood products are not available, or when the need for haste precludes the necessary cross-matching of blood.

Minimizes sludging of blood as a result of microcirculation effects.

Not a replacement for other forms of therapy; complementary to fluids and electrolytes.

Extracorporeal Circulation

Priming fluid (alone or as an additive to other priming fluids) in pump oxygenators for perfusion during extracorporeal circulation.

Prophylaxis of Thromboembolic Disorders

Prophylaxis of venous thrombosis and pulmonary embolism for surgical procedures associated with a high risk of thromboembolic complications (e.g., hip surgery).

May be beneficial in patients undergoing hip surgery; however, 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 as sole method of thromboprophylaxis in elective hip arthroplasty.

Dextran 40 Dosage and Administration

Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion. Preservative-free, single-use container; discard unused portion.

Administer 20 mL dextran 1 before administration of dextran 40. (See Sensitivity Reactions under Cautions.)

When infusing concentrated dextran 40, use an administration set with a filter. An administration set is provided with commercially available preparation; consult the manufacturer’s instructions for proper use.

Prophylaxis of Thromboembolic Disorders

Generally, initiate dextran 40 therapy during the surgical procedure.

Rate of Administration

Shock

Infusion rate is dependent on patient-specific requirements (e.g., amount of fluid loss, resultant hemoconcentration). May infuse the first 500 mL (10 mL/kg) of solution rapidly if closely monitoring central venous pressure; however, infuse the remainder of the dose slowly. (See Circulatory and/or Volume Overload in Warnings.)

If not monitoring central venous pressure, infuse drug more slowly; closely observe patient for signs of circulatory overload.

Dosage

Pediatric Patients

Shock

IV

Adjust dosage and rate of infusion based on individual patient requirements, amount of fluid loss and resultant hemoconcentration. (See Rate of Administration under Administration.)

Infants: 0.5 g/kg (5 mL/kg).

Children: 1 g/kg (10 mL/kg).

Adolescents: Maximum total dosage (first 24 hours) of 2 g/kg (20 mL/kg); thereafter, maximum dosage of 1 g/kg (10 mL/kg) daily for up to 5 days.

Extracorporeal Circulation

IV

Infants: 0.5 g/kg (5 mL/kg).

Children: 1 g/kg (10 mL/kg).

Prophylaxis of Thromboembolic Disorders

IV

Infants: 0.5 g/kg (5 mL/kg).

Children: 1 g/kg (10 mL/kg).

Adolescents: Select dosage according to the risk of thromboembolic complications (e.g., type of surgery, duration of immobilization). Generally, the day of surgery, 50–100 g (500–1000 mL [approximately 10 mL/kg]). Then, 50 g (500 mL) daily for an additional 2–3 days. Thereafter, may give 50 g (500 mL) every 2–3 days for up to 2 weeks, according to the risk of thromboembolic complications.

Adults

Shock

IV

Adjust dosage and rate of infusion based on individual patient requirements, amount of fluid loss, and resultant hemoconcentration. (See Rate of Administration under Administration.)

Maximum total dosage (first 24 hours): 2 g/kg (20 mL/kg); thereafter, maximum dosage of 1 g/kg (10 mL/kg) daily for up to 5 days.

Extracorporeal Circulation

IV

Usual dose: 1–2 g/kg (10–20 mL/kg); maximum 2 g/kg (20 mL/kg). The amount of solution used varies with the volume of the pump oxygenator.

Prophylaxis of Thromboembolic Disorders

IV

Select dosage according to the risk of thromboembolic complications (e.g., type of surgery, duration of immobilization).

Generally, the day of surgery, 50–100 g (500–1000 mL [approximately 10 mL/kg]). Then, 50 g (500 mL) daily for an additional 2–3 days. Thereafter, may give 50 g (500 mL) every 2–3 days for up to 2 weeks, according to the risk of thromboembolic complications.

Prescribing Limits

Pediatric Patients

Shock

IV

Adolescents (first 24 hours): Maximum of 2 g/kg (20 mL/kg). Thereafter, maximum of 1 g/kg (10 mL/kg) daily. Maximum duration: 5 days.

Adults

Shock

IV

First 24 hours: Maximum of 2 g/kg (20 mL/kg). Thereafter, maximum of 1g/kg ( 10 mL/kg daily).

Maximum duration: 5 days.

Extracorporeal Circulation

IV

Total dosage: Maximum 2 g/kg (20 mL/kg).

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time. (See Hepatic Effects under Cautions.)

Renal Impairment

In advanced renal disease, do not exceed maximum recommended dosages. (See Renal Effects, Sodium Content, and Renal Impairment under Cautions.)

Geriatric Patients

No specific dosage recommendations at this time except those related to renal impairment.

Cautions for Dextran 40

Contraindications

• Known hypersensitivity to dextran or any ingredient in the formulation.

• Marked cardiac decompensation.

• Renal disease with severe oliguria or anuria.

• Marked hemostatic defects of all types (e.g., thrombocytopenia, hypofibrinogenemia), including those caused by drugs (e.g., heparin, warfarin).

• Some clinicians consider extreme dehydration a contraindication to dextran 40 therapy. (See Renal Effects under Cautions.)

Warnings/Precautions

Warnings

Circulatory and/or Volume Overload

Dextran 40 is a hypertonic colloidal solution; vascular overload may occur with large doses of dextran 40. Monitor central venous pressure closely when drug is administered by rapid infusion and in patients with poor hydration status needing additional fluid therapy.

Immediately discontinue drug if precipitous rise in central venous pressure or any clinical signs of circulatory overloading occur.

May cause fluid and/or solute overloading (especially when using large doses) resulting in dilution of serum electrolytes, overhydration, congested states, or pulmonary edema. Do not administer to patients with pulmonary edema; use with caution in cardiac decompensation and CHF. (See Sodium Content under Cautions.)

Risk of dilutional states is inversely proportional to the solution’s electrolyte concentration. Risk of solute overloading, resulting in congestion with peripheral and pulmonary edema, is directly proportional to the solution’s electrolyte concentration.

Renal Effects

Increases viscosity and specific gravity of urine, especially in patients with decreased urine flow. Typically, specific gravity increases only slightly in adequately hydrated patients with normal renal function; however, tubular stasis and blocking reported even in adequately hydrated patients. Low specific gravity of urine during dextran therapy may indicate a failure of renal dextran clearance; discontinue dextran.

Assess hydration before administration of dextran. Administer additional fluid if signs of dehydration are present. (See Contraindications under Cautions.)

If decreased urinary output is secondary to shock, may use dextran 40 so long as urinary output improves after administration of the drug.

Monitor urinary flow rates during administration; discontinue therapy if oliguria or anuria occurs and administer an osmotic diuretic to minimize vascular overloading.

Renal failure reported, particularly in extremely dehydrated patients. May be precipitated by excessive doses in patients with advanced renal disease; do not exceed dosage recommendations. (See Contraindications under Cautions.)

Tubular vacuolization (osmotic nephrosis) reported; possibly reversible. However, clinical importance not fully known.

Abnormal renal function test results reported, generally in patients who have undergone surgery or cardiac catheterization. Specific effect of dextran 40 on renal function not yet determined.

Hepatic Effects

Abnormal hepatic function test results (increased AST and ALT) reported, generally in patients who have undergone surgery or cardiac catheterization. Specific effect of dextran 40 on hepatic function not yet determined.

Metabolic Effects

Mild to moderate acidosis (usually transient) may develop during perfusion with any priming fluid in pump oxygenators; is not altered by dextran 40 administration; may require an alkalinizing agent.

Excessive Doses

Avoid exceeding the recommended dose; possible dose-related increase of wound hematoma, wound seroma, wound bleeding (hematuria and melena), and pulmonary edema.

Hematologic Effects

May interfere with platelet function; use with caution in thrombocytopenia.

Transient prolongation of bleeding time possible in patients receiving >1 L of 10% dextran 40 solution; slight increase in bleeding tendency may also occur.

Dextran 40 causes marked factor VIII decrease and a greater decrease in factors V and IX than expected from the effects of hemodilution alone. Usually occurs at doses near 1.5 g/kg (15 mL/kg). Observe trauma and major surgery patients for early signs of bleeding complications. Slightly increased blood loss possible in postoperative patients.

Additional blood loss may occur in patients with active hemorrhage because of the increase in perfusion pressure and improved blood flow.

Determine hematocrit after administration of dextran 40; avoid depressing below 30% by volume.

May cause increased rouleaux formation; draw blood samples for typing and cross-matching prior to dextran infusion. Reserve samples for subsequent use, if necessary. (See Specific Drugs and Laboratory Tests under Interactions.)

Administration of large volumes of dextran solution results in lowered plasma protein concentrations.

Sodium Content

Each 500 mL of the commercially available 10% dextran 40 in 0.9% sodium chloride injection provides 77 mEq sodium. (See Specific Drugs and Laboratory Tests under Interactions.)

Use products with sodium ions with caution in CHF, severe renal insufficiency, and edema with sodium retention. (See Renal Impairment, Renal Effects, and Circulatory and/or Volume Overload under Cautions.)

Observe the usual precautions and contraindications associated with sodium in patients receiving 10% dextran 40 in 0.9% sodium chloride injection.

Sensitivity Reactions

Mild urticarial reactions reported.

Dextran-induced Anaphylactoid Reactions

Severe dextran-induced anaphylactoid reactions (e.g., generalized urticaria, tightness of the chest, wheezing, hypotension, nausea, vomiting, severe hypotension, shock, cardiac and respiratory arrest, death) reported rarely. Typically occur early in the infusion period in patients with no previous exposure to dextran 40, even with doses as small as 0.5 g (5 mL). Closely monitor patients with no previous exposure to dextran, especially during the first minutes of infusion.

Administration of 20 mL of dextran 1 prior to dextran 40 infusion decreases the likelihood of anaphylactoid reactions; however, serious reactions may still occur.

Discontinue dextran at first sign of allergic reaction so long as circulation can be maintained by other means. Immediate medical intervention (e.g., parenteral epinephrine, antihistamines, and other supportive therapy) may relieve symptoms. If circulatory collapse due to anaphylaxis occurs after discontinuing dextran, begin rapid volume substitutions with another agent.

Keep resuscitative measures readily available during dextran use.

General Precautions

Local Injection Site Reactions

Adverse local reactions caused by IV administration of dextran 40 include febrile response, infection at the injection site, venous thrombosis or phlebitis extending from the injection site, extravasation, and hypervolemia. If such reactions occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic countermeasures, and save the remainder of the solution for examination if deemed necessary.

Diabetes Mellitus

Use with caution in patients with diabetes mellitus (subclinical or overt). (See Specific Drugs and Laboratory Tests under Interactions.)

Observe the usual precautions and contraindications associated with dextrose in patients receiving 10% dextran 40 in 5% dextrose injection.

Cardiac Patients

Dextran 40 is hazardous to heart failure patients because of the plasma volume expanding effect, especially when administered in sodium chloride. (See Sodium Content under Cautions.)

Specific Populations

Pregnancy

Category C.

Lactation

Not know whether dextran 40 is distributed into milk. Caution if used in nursing women.

Pediatric Use

Safety and efficacy not established in neonates.

Renal Impairment

Use with caution in patients with impaired renal clearance of dextran; circulatory overload possible. Risk of sodium retention in patients with renal insufficiency. (See Circulatory and/or Volume Overload, Renal Effects, and Sodium Content under Cautions.)

Drug Interactions

Rouleaux Formation

Dextran may increase the formation of rouleaux; draw blood samples for typing and cross-matching prior to dextran infusion. Reserve sample for subsequent use, if necessary.

Turbidity

Dextran in the blood may cause turbidity; turbidity may interfere with some assays.

Specific Drugs and Laboratory Tests

Dextran 40 Pharmacokinetics

Absorption

Onset

Maximum plasma volume reached within several minutes after the end of the infusion.

Duration

Extent and duration of the expansion in plasma volume vary with the volume infused, preadministration plasma volume, and the rate of renal clearance.

Plasma Concentrations

Plasma concentration depends on the rate of infusion, the total amount of drug administered, and the rate of disappearance of the drug from plasma.

In normal renal function, plasma concentration falls rapidly during the first hour following infusion and more slowly thereafter.

Distribution

Extent

Evenly distributed in the vascular system.

Not known whether dextran 40 is distributed into milk.

Elimination

Metabolism

Large, unexcreted molecules (molecular weight ≥50,000) slowly degraded by dextranase enzyme to glucose which is metabolized to carbon dioxide and water.

Elimination Route

In normovolemic patients, principally excreted unchanged in urine (approximately 75%) within 24 hours; small amounts eliminated in feces.

Stability

Storage

Parenteral

Injection for IV Infusion

Constant temperature, preferably 25°C (may be exposed to ≤40°C). Protect from freezing and excessive heat.

Dextran flakes may form in solution when stored for long periods or if storage temperature varies greatly. Dissolve flakes by heating solution in a water bath at 100°C until clear, or by autoclaving at 110°C for 15 minutes.

Compatibility

Parenteral

Drug Compatibility

Actions

• Low molecular weight polymer of glucose.

• Plasma volume expansion results from a colloidal osmotic effect in drawing fluid from the interstitial to the intravascular spaces; plasma volume expansion is slightly greater than the volume of dextran infused.

• Plasma volume expansion is accompanied by an increase in central venous pressure, cardiac output, stroke volume, BP, urinary output, capillary perfusion, and pulse pressure, and by a decrease in heart rate, peripheral resistance, blood viscosity, and mean transit time.

• Enhances blood flow through correction of hypovolemia and improved microcirculation.

• May coat erythrocytes and other formed elements, reducing bonding forces and maintaining the erythrocytes in a state of electronegativity and mutual repellency. May decrease erythrocyte rigidity, facilitating passage through small blood vessels.

• Dextrose provides calories, restores blood glucose concentrations, has a protein-sparing effect; may help minimize liver glycogen depletion.

Advice to Patients

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., renal insufficiency, diabetes mellitus, CHF).

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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