Hydroxyethyl Starch (HES)

Usage

• Hydroxyethyl starch (HES) is prescribed for the treatment and prophylaxis of hypovolemia (low blood volume). It is used to expand plasma volume in situations where it’s necessary to increase the circulating blood volume, such as during surgery or after significant blood loss. It is not a substitute for red blood cells or coagulation factors.
• Pharmacological Classification: Plasma volume expander, colloid.
• Mechanism of Action: HES is a synthetic colloid that works by increasing the osmotic pressure of the blood, drawing fluid from the interstitial space into the intravascular compartment, thereby increasing blood volume.

Alternate Names

• HES (Hydroxyethyl Starch)
• Hetastarch
• Tetrastarch
• Brand Names: Voluven, Volulyte, Hespan, Hextend

How It Works

• Pharmacodynamics: HES increases the oncotic pressure within the blood vessels, leading to an expansion of plasma volume. The degree and duration of volume expansion depend on the molecular weight, molar substitution, and dosage of HES.
• Pharmacokinetics: HES is administered intravenously. It is primarily excreted by the kidneys, with the rate of excretion depending on the molecular weight and degree of substitution of the HES preparation. Some metabolism occurs, but the exact pathways and extent are not fully defined.
• Mode of Action: HES molecules are too large to cross capillary membranes, remaining within the vascular compartment and drawing fluid into the bloodstream via osmosis.
• Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: HES does not directly bind to receptors, inhibit enzymes, or modulate neurotransmitters. Its primary action is based on its physicochemical properties as a colloid.
• Elimination Pathways: Primarily renal excretion; some metabolic breakdown occurs.

Dosage

Standard Dosage

Adults:

• Up to 50 mL/kg body weight per day (equivalent to 3 g HES/kg/day).
• The maximum daily dose is 3500 mL for a 70 kg patient.
• The rate of infusion depends on the patient’s clinical status and hemodynamic response.

Children:

• Dosage should be individualized based on the patient’s colloid needs, disease state, hemodynamic status, and hydration.
• Limited clinical data is available for pediatric use. Doses used in trials:
  • Newborns and infants (< 2 years): mean dose 16 ± 9 mL/kg/day.
  • Children (2-12 years): mean dose 36 ± 11 mL/kg/day.
  • Adolescents (>12 years): same as adult dose.
• Pediatric safety regarding mortality and renal injury has not been fully evaluated.

Special Cases:

• Elderly Patients: Close monitoring of fluid status and renal function is recommended due to age-related physiological changes.
• Patients with Renal Impairment: Contraindicated in severe renal failure. Use with caution in patients with mild to moderate renal impairment, closely monitoring renal function.
• Patients with Hepatic Dysfunction: Contraindicated in severe hepatic impairment. Caution should be exercised in patients with mild to moderate hepatic impairment.
• Patients with Comorbid Conditions: Adjust dosage based on the presence of conditions like cardiac insufficiency.

Clinical Use Cases

• Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use/Emergency Situations: Dosage and infusion rate depend on blood loss, hemodynamic stability, and hemodilution. Close monitoring is crucial in these situations.

Dosage Adjustments

• Adjust dosage in patients with renal/hepatic dysfunction, cardiac insufficiency, or other relevant conditions. Closely monitor fluid and electrolyte balance.

Side Effects

Common Side Effects

• Pruritus (itching)
• Elevated serum amylase (may interfere with pancreatitis diagnosis)
• Hemodilution (can affect coagulation parameters and hematocrit)

Rare but Serious Side Effects

• Anaphylactoid/hypersensitivity reactions (e.g., bronchospasm, hypotension, angioedema)
• Coagulopathy (bleeding complications)
• Acute kidney injury
• Increased mortality (particularly in critically ill patients)

Long-Term Effects

• Chronic pruritus (rare)
• Long-term kidney dysfunction (rare)

Adverse Drug Reactions (ADR)

• Severe anaphylactoid reactions requiring immediate treatment
• Acute renal failure requiring dialysis
• Severe bleeding episodes requiring intervention

Contraindications

• Critically ill patients, including those with sepsis
• Severe liver disease
• Pre-existing renal dysfunction, especially with oliguria or anuria
• Volume overload/hyperhydration
• Bleeding disorders
• Hypersensitivity to HES
• Patients undergoing dialysis
• Severe hypernatremia or hyperchloremia
• Intracranial bleeding

Drug Interactions

• HES may interact with anticoagulants, potentially increasing the risk of bleeding.
• Compatibility issues can occur when mixing HES with certain medications (e.g., diazepam, midazolam, phenytoin, thiopental, cefazolin, vancomycin). Use separate IV lines for incompatible drugs.
• No known interactions with CYP450 enzymes.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C (US FDA). Not recommended unless the benefit outweighs the potential risk to the fetus. Animal studies suggest potential embryo-fetal toxicity.
• Breastfeeding: It’s unknown if HES is excreted in human milk. Exercise caution. Animal studies show potential adverse effects on postnatal development.

Drug Profile Summary

• Mechanism of Action: Colloid, expands plasma volume by increasing oncotic pressure.
• Side Effects: Pruritus, elevated amylase, hemodilution, anaphylactoid reactions, coagulopathy, renal injury.
• Contraindications: Critically ill patients, sepsis, severe liver/renal disease, volume overload, bleeding disorders, hypersensitivity.
• Drug Interactions: Anticoagulants, incompatibilities with certain IV medications.
• Pregnancy & Breastfeeding: Use with caution; potential fetal and neonatal risks.
• Dosage: Adults: Up to 50 mL/kg/day (max 3500 mL). Children: individualized based on clinical status.
• Monitoring Parameters: Renal function, coagulation parameters, fluid and electrolyte balance, hemodynamic status.

Popular Combinations

• HES is often used in combination with crystalloid solutions for fluid resuscitation. The specific combination and ratio depend on individual patient needs and clinical context.

Precautions

• General Precautions: Careful monitoring of fluid and electrolyte balance, renal function, and coagulation status. Avoid fluid overload.
• Specific Populations (Pregnant Women, Breastfeeding Mothers, Children, Elderly): Use with caution. Adjust dosage based on age and clinical condition. Closely monitor renal function in the elderly.
• Lifestyle Considerations: No specific lifestyle considerations related to HES administration.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Hydroxyethyl Starch?

A: Adults: Up to 50 mL/kg/day (max 3500 mL). Children: individualized dosage based on colloid needs and clinical status.

Q2: What are the major contraindications for HES?

A: Critically ill patients (including sepsis), severe liver or renal disease, bleeding disorders, hypersensitivity to HES, volume overload.

Q3: How is HES eliminated from the body?

A: Primarily through renal excretion. Some metabolic breakdown occurs.

Q4: Can HES be used in pregnant or breastfeeding women?

A: Use with caution only if clearly needed. Potential fetal/neonatal risks exist.

Q5: What are the common side effects of HES?

A: Pruritus, elevated serum amylase, hemodilution.

Q6: What are the serious side effects of HES?

A: Anaphylactoid reactions, bleeding, acute kidney injury, increased mortality (in critically ill).

Q7: How does HES affect coagulation?

A: Can cause coagulopathy and increased bleeding risk, especially at higher doses. Close monitoring of coagulation parameters is needed.

Q8: Does HES interact with other medications?

A: Can interact with anticoagulants, increasing bleeding risk. Compatibility issues can occur with certain IV drugs.

Q9: Can HES be used in patients with renal impairment?

A: Contraindicated in severe renal impairment. Use with caution in mild to moderate impairment and closely monitor renal function.

Q10: What is the role of HES in fluid management?

A: Expands plasma volume to treat or prevent hypovolemia, but it is not a substitute for red blood cells or coagulation factors.