Low Dextrans

Usage

Low molecular weight dextran (LMWD), also known as Dextran 40, is primarily indicated for the prevention and treatment of hypovolemic shock and to improve blood flow in peripheral vascular disease. It is also used as a prophylactic measure against thromboembolic events, particularly post-surgery. It belongs to the pharmacological class of plasma volume expanders. LMWD works by expanding plasma volume, thereby increasing blood volume and improving tissue perfusion. This is achieved through its colloid osmotic effects.

Alternate Names

Dextran 40 is also known as low molecular weight dextran, Rheomacrodex, and LMD. Gentran 40 is a brand name under which it’s marketed.

How It Works

Pharmacodynamics: LMWD exerts its effect by drawing fluid from the interstitial space into the intravascular compartment, which leads to an increase in plasma volume. This effect is attributed to its high molecular weight and colloid osmotic pressure. The increased plasma volume leads to improved blood flow and tissue perfusion.

Pharmacokinetics:

• Absorption: Administered intravenously, therefore, 100% bioavailability.
• Metabolism: LMWD undergoes hydrolysis by dextranases present in the body to smaller dextrans and eventually glucose.
• Elimination: Primarily renal excretion, with about 75% eliminated within 24 hours. Smaller amounts may be excreted in feces.

Dosage

Standard Dosage

Adults:

For shock: Initial dose of 10-20 mL/kg IV (maximum 20 mL/kg in the first 24 hours); followed by 10 mL/kg/day thereafter. Therapy shouldn’t exceed 5 days. For prophylaxis of thromboembolism: 500-1000 mL (approximately 10 mL/kg) IV on the day of surgery, followed by 500 mL daily for 2-3 days, then 500 mL every other day for up to two weeks.

Children:

Infants: 5 mL/kg IV. Children: 10 mL/kg IV.

Special Cases:

• Elderly Patients: Start with lower doses and adjust cautiously due to potential for fluid overload and compromised organ function.
• Patients with Renal Impairment: Use with extreme caution. Monitor urine output. Dose adjustment might be needed.
• Patients with Hepatic Dysfunction: Use cautiously. Dose adjustment may be required.
• Patients with Comorbid Conditions: Careful monitoring is crucial, especially for patients with cardiac failure. Adjust fluid management accordingly.

Clinical Use Cases

• Intubation: Not specifically indicated.
• Surgical Procedures: Prophylactically against thromboembolism.
• Mechanical Ventilation: Not typically used.
• Intensive Care Unit (ICU) Use: For shock and fluid resuscitation.
• Emergency Situations: Hypovolemic shock.

Dosage Adjustments

Dosage adjustments are needed based on patient specific factors such as renal/hepatic impairment, and comorbidities. Careful monitoring of hydration status and fluid balance is crucial, especially for patients with compromised organ function.

Side Effects

Common Side Effects

Mild itching, rash, fever, arthralgias, nausea, vomiting, and headache.

Rare but Serious Side Effects

Anaphylactoid reactions (hypotension, bronchospasm, angioedema), bleeding complications (especially if pre-existing coagulopathies are present), acute renal failure (especially in patients with pre-existing renal insufficiency), pulmonary edema, and circulatory overload.

Long-Term Effects

No specific long-term effects directly attributable to LMWD, but prolonged use might increase the risk of bleeding complications and renal dysfunction.

Contraindications

Absolute contraindications include known hypersensitivity to dextran, severe bleeding disorders, severe cardiac decompensation, and renal failure with anuria or severe oliguria.

Drug Interactions

LMWD can enhance the anticoagulant effects of heparin, warfarin, and other antiplatelet agents, increasing the risk of bleeding. It can also interfere with certain laboratory tests (e.g., blood glucose, bilirubin, and coagulation studies). Concurrent use with drugs with nephrotoxic potential should be avoided.

Pregnancy and Breastfeeding

Pregnancy Safety Category: C (US FDA - Old System). Animal reproduction studies haven’t been conducted. Use during pregnancy only if the potential benefit outweighs the risk. It is not known whether it is excreted in human milk. Caution advised during breastfeeding.

Drug Profile Summary

• Mechanism of Action: Plasma volume expansion via colloid osmotic effects.
• Side Effects: Itching, rash, fever, nausea, vomiting, anaphylaxis, bleeding.
• Contraindications: Hypersensitivity, severe bleeding disorders, cardiac decompensation, renal failure.
• Drug Interactions: Enhances anticoagulant effects, interferes with some lab tests.
• Pregnancy & Breastfeeding: Category C (US FDA - Old System); caution advised.
• Dosage: Shock: 10-20 mL/kg IV initially, followed by 10 mL/kg/day. Thromboembolism prophylaxis: 500-1000 mL IV on day of surgery, then 500 mL daily for 2-3 days, then every other day for up to two weeks.
• Monitoring Parameters: Urine output, blood pressure, signs of bleeding and allergic reactions, hematocrit, hemoglobin, and coagulation studies.

Popular Combinations

Often used alone. In some settings, it may be used in combination with crystalloid solutions for fluid resuscitation.

Precautions

Closely monitor renal function, fluid balance, and coagulation parameters. Pre-hydration is essential before administration in patients with dehydration. Administer a small test dose before infusion to check for hypersensitivity reactions. Monitor for anaphylactic reactions.

FAQs

Q1: What is the recommended dosage for Low Dextrans?

A: For shock: 10-20 mL/kg IV initially, then 10 mL/kg/day. For prophylaxis of thromboembolism: 500-1000 mL IV on day of surgery, then 500 mL/day for 2-3 days, followed by 500 mL every other day for up to two weeks.

Q2: What are the major side effects of Low Dextrans?

A: Common side effects include itching, rash, fever, nausea, and vomiting. Serious side effects are anaphylaxis, bleeding, and renal failure.

Q3: Can Low Dextrans be used in patients with renal impairment?

A: Use with extreme caution in patients with renal impairment. Dose adjustment and close monitoring of renal function are necessary.

Q4: What is the mechanism of action of Low Dextrans?

A: It expands plasma volume by exerting colloid osmotic pressure, drawing fluid into the intravascular compartment, which enhances tissue perfusion and improves blood flow.

Q5: What are the contraindications to using Low Dextrans?

A: Contraindications include hypersensitivity to dextran, severe bleeding disorders, severe cardiac decompensation, and renal failure with anuria or severe oliguria.

Q6: How is Low Dextrans administered?

A: Administered intravenously.

Q7: Can Low Dextrans be used during pregnancy?

A: Use during pregnancy only if the potential benefits clearly outweigh the potential risks. FDA Pregnancy Category C (Old System).

Q8: Are there any drug interactions I should be aware of when prescribing Low Dextrans?

A: LMWD enhances the effects of anticoagulants and antiplatelet drugs. It can also interfere with some laboratory tests. Concurrent use with nephrotoxic drugs should be avoided.

Q9: What monitoring parameters are important when a patient is receiving Low Dextrans?

A: Monitor renal function (urine output), blood pressure, signs of bleeding, and allergic reactions, hematocrit, hemoglobin, and coagulation parameters.

Q10: What precautions should be taken when administering Low Dextrans?

A: Pre-hydration in dehydrated patients is essential. Administer a test dose before full infusion to assess for hypersensitivity. Closely monitor patients for any signs of anaphylaxis. Careful fluid management in patients at risk of overload.