dextran 1
Promit

dextran, low-molecular-weight (dextran 40)
Gentran 40, 10% LMD, Rheomacrodex

dextran, high-molecular-weight (dextran 70, dextran 75)
Gendex 75, Gentran 70, Macrodex

Available forms
Available by prescription only
dextran 1
Injection: 150 mg/ml in 20-ml vials
low-molecular-weight dextran
Injection: 10% dextran 40 in D₅W or normal saline solution
high-molecular-weight dextran
Injection: 6% dextran 70 in normal saline solution or D₅W; 6% dextran 75 in normal saline solution or D₅W

Indications and dosages
 Prevention of severe anaphylactoid reaction caused by low- or high-molecular-weight dextran. Adults: 20 ml dextran 1 by rapid I.V. push 1 to 2 minutes before dextran infusion.
Children: 0.3 ml/kg dextran 1 by rapid I.V. push 1 to 2 minutes before dextran infusion.
 Plasma volume expansion.  Dosage depends on amount of fluid loss.
Adults: Initially, 500 ml of dextran 40 with CVP monitoring. Infuse remaining dose slowly. Total daily dose shouldn’t exceed 2 g/kg (20 ml/kg) body weight. If therapy continues past 24 hours, don’t exceed 1 g/kg (10 ml/kg) daily. Continue for no longer than 5 days.
 Usual dose of dextran 70 or 75 solution is 30 g (500 ml of 6% solution) I.V. In emergencies, may be administered at 1.2 to 2.4 g/minute (20 to 40 ml/ minute). Total dose during the first 24 hours isn’t to exceed 1.2 g/kg; actual dose depends on amount of fluid loss and resultant hemoconcentration and must be determined individually. In normovolemic patients, the administration shouldn’t exceed 240 mg/minute (4 ml/minute).
Children: Total dosage of dextran 70 or 75 shouldn’t exceed 1.2 g/kg (20 ml/kg), with the dose based on body weight or surface area. If therapy is continued, dosage shouldn’t exceed 0.6 g/kg (10 ml/kg) daily.
 Priming pump oxygenators. Adults: Dextran 40 can be used as the only priming fluid or as an additive to other primers in pump oxygenators. Dextran 40 is added to the perfusion circuit as the 10% solution in a dose of 1 to 2 g/kg (10 to 20 ml/kg); total dose shouldn’t exceed 2 g/kg (20 ml/kg).
 Prophylaxis of venous thrombosis and pulmonary embolism. Adults: Dextran 40 therapy usually should be given during the surgical procedure. On the day of surgery, dextran 40 (10% solution) is given at the dose of 50 to 100 g (500 to 1,000 ml or about 10 ml/kg). Treatment is continued for 2 to 3 days at a dose of 50 g (500 ml) daily. Then, if needed, 50 g (500 ml) may be given q 2 or 3 days for up to 2 weeks to reduce the risk of thromboembolism (deep venous thrombosis) or pulmonary embolism.

Pharmacodynamics
Plasma-expanding action: Dextran 1 is a monovalent hapten and reacts with dextran-reactive IgG without a bridge formation so there is no tendency for large immune complexes to form. Given before clinical dextran, the dextran 1 complex competitively prevents immune complexes of polyvalent dextrans from forming, thereby impeding anaphylaxis.
 Dextran 40 (10%) has an average molecular weight of 40,000, the osmotic equivalent of twice the volume of plasma, and has a duration of action of 2 to 4 hours. Dextran 70 has an average molecular weight of 70,000. I.V. infusion results in expansion of plasma volume slightly in excess of volume infused. This effect, useful in treating shock, lasts for about 12 hours. Dextran 40, 70, and 75 enhance blood flow, particularly in microcirculation.
Prophylaxis of venous thrombosis and pulmonary embolism: Dextran 40 inhibits vascular stasis and platelet adhesiveness and alters structure and lysability of fibrin clots. Dextran 40 increases cardiac output and arterial, venous, and microcirculatory flow and reduces mean transit time, mainly by expanding plasma volume and by reducing blood viscosity through hemodilution and reducing red cell aggregation.

Pharmacokinetics
Absorption: Administered I.V. Plasma level depends on rate of infusion and rate of disappearance of drug from plasma.
Distribution: Distributed throughout vascular system.
Metabolism: Dextran molecules with molecular weights above 50,000 are enzymatically degraded by dextrinase to glucose at about 70 to 90 mg/kg daily. Process is variable.
Excretion: Dextran 1 is rapidly and completely excreted by glomerular filtration. Dextran molecules with molecular weights below 50,000 are eliminated by renal excretion, with 40% of dextran 70 appearing in urine within 24 hours. About 50% of dextran 40 excreted in urine within 3 hours, 60% within 6 hours, and 75% within 24 hours. Remaining 25% is hydrolyzed partially and excreted in urine, excreted partially in feces, and partially oxidized.

Contraindications and precautions
Low-molecular-weight dextran is contraindicated in patients hypersensitive to drug and in those with marked hemostatic defects, marked cardiac decompensation, and renal disease with severe oliguria or anuria. High-molecular-weight dextran is also contraindicated in patients with hypervolemic conditions, severe congestive heart failure, pulmonary edema, or severe bleeding disorders, and when use of sodium chloride could be detrimental.
  Use low-molecular-weight dextran cautiously in patients with active hemorrhage, thrombocytopenia, or diabetes mellitus. High-molecular-weight dextran should be used cautiously in patients with active hemorrhage, thrombocytopenia, impaired renal clearance, chronic liver disease, and abdominal conditions or in those undergoing bowel surgery.

Interactions
Drug-drug. Anticoagulants, antiplatelet drugs: May cause abnormally prolonged bleeding times. Monitor patient closely.

Adverse reactions
CNS: fever.
CV: thrombophlebitis, hypotension, bradycardia.
EENT: nasal congestion (with high-molecular-weight dextran).
GI: nausea, vomiting.
GU: tubular stasis and blocking, increased urine viscosity, oliguria, anuria, increased specific gravity of urine (with high-molecular-weight dextran).
Hematologic: increased bleeding time (with higher doses of low-molecular-weight dextran), increased bleeding time and significant suppression of platelet function (with high-molecular-weight dextran in doses of 15 ml/kg body weight).
Musculoskeletal: arthralgia.
Other: hypersensitivity reactions (urticaria, anaphylaxis).

Effects on lab test results
• May increase ALT and AST levels.
• May increase bleeding time. May decrease hemoglobin and hematocrit.

Overdose and treatment
Drug is rapidly cleared by the kidneys so effects are short-lived with minimal consequences.

Special considerations
• Dehydrated patients should be rehydrated before dextran infusion.
• Dextran in saline solution is hazardous when given to patients with heart failure, severe renal failure, and clinical states in which edema exists with sodium restriction. Use D₅W solution.
• Drug works as plasma expander via colloidal osmotic effect, drawing fluid from interstitial to intravascular space. Provides plasma expansion slightly greater than volume infused. Observe for circulatory overload or rise in CVP readings.
• Dextran 1 should be given just before infusing low- or high-molecular-weight dextran. Repeat dosage of dextran 1 if more than 15 minutes elapses during infusion.
• Avoid doses that exceed recommendations because dose-related increases in wound hematoma, wound seroma, wound bleeding, occult bleeding (such as hematuria and melena), and pulmonary edema have been observed.
• Store at constant temperature of 77° F (25° C). Solution may precipitate in storage. Discard any solution that isn’t clear.
• Falsely elevated blood glucose levels may occur in patients receiving dextran 40 or 70 if test uses high levels of acid. Dextran may cause turbidity, which interferes with bilirubin assays that use alcohol, total protein levels using biuret reagent, and blood glucose levels using orthotoluidine method. Blood typing and cross-matching using enzyme techniques may give unreliable readings if samples are taken after dextran infusion.
• Monitor urine output during administration. If oliguria or anuria occurs or isn’t reversed by initial infusion (500 ml), stop administration.
• Monitor urine or serum osmolarity; urine specific gravity will be increased by urine dextran concentration.
• Monitor CVP when dextran is given by rapid I.V. infusion. A precipitous rise in CVP or other signs of fluid overload indicate need to stop infusion.
• Monitor hemoglobin and hematocrit; don’t allow to fall below 30% by volume.
• Monitor patient closely during early phase of infusion; check for infiltration, phlebitis, and anaphylactoid reactions.
Breast-feeding patients
• It isn’t known whether dextran appears in breast milk. Use cautiously in breast-feeding women.
Geriatric patients
• Use dextran cautiously in elderly patients; they may be at increased risk for fluid overload.

Patient education
• Explain use and administration of dextran to patient and family.
• Tell patient to report adverse effects.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use