Mechanism Of Action
The plasma volume expansion produced by HESPAN® approximates that of 5% Albumin (Human).
Intravenous infusion of HESPAN® results in expansion of plasma volume.
HESPAN® results in expansion of plasma volume that decreases over the succeeding 24 to 36 hours.
The degree of plasma volume expansion and improvement in hemodynamic state depend upon the
patient’s intravascular status.
Hetastarch molecules below 50,000 molecular weight are rapidly eliminated by renal excretion. A
single dose of approximately 500 mL of HESPAN® (approximately 30 g) results in elimination in the
urine of approximately 33% of the dose within 24 hours. This is a variable process but generally
results in an intravascular hetastarch concentration of less than 10% of the total dose injected by two
weeks. A study of the biliary excretion of HESPAN® in 10 healthy males accounted for less than 1%
of the dose over a 14 day period. The hydroxyethyl group is not cleaved by the body but remains intact
and attached to glucose units when excreted. Significant quantities of glucose are not produced as
hydroxyethylation prevents complete metabolism of the smaller polymers.
The addition of hetastarch to whole blood increases the erythrocyte sedimentation rate. Therefore,
HESPAN® is used to improve the efficiency of granulocyte collection by centrifugal means.
Surgical Patients Comparative Studies
In randomized, controlled, comparative studies of HESPAN® (6% hetastarch in 0.9% sodium chloride
injection) (n=92) and Albumin (n=85) in surgical patients, no patient in either treatment group had a
bleeding complication and no significant difference was found in the amount of blood loss between the
Pediatric Postoperative Volume Expander Study
In one small double-blind study, 47 infants, children, and adolescents (ages 1 year to 15.5 years)
scheduled for repair of congenital heart disease with moderate hypothermia were randomized to
receive either HESPAN® or Albumin as a postoperative volume expander during the first 24 hours
after surgery. Thirty-eight children required colloid replacement therapy, of which 20 children
received HESPAN®. No differences were found in the coagulation parameters or in the amount of
replacement fluids required in the children receiving 20 mL/kg or less of either colloid replacement
therapy. In children who received greater than 20 mL/kg of HESPAN®, an increase in prothrombin time
was demonstrated (p=0.006).11 There were no neonates included in this study [see Use In Specific Populations].
Adult Critically Ill Studies
Three randomized controlled trials (RCTs) followed critically ill adult patients treated with different
HES products for 90 days.
One trial (N=804) in severe sepsis patients using HES product (not approved in the U.S.) reported
increased mortality (relative risk, 1.17; 95% CI, 1.01 to 1.36; p=0.03) and RRT (relative risk, 1.35; 95%
CI, 1.01 to 1.80; p=0.04) in the HES treatment arm.4
Another trial (N=196) using different HES in severe sepsis patients reported no difference in mortality
(relative risk,1.20; 95% CI, 0.83 to 1.74; p=0.33) and a trend for RRT (relative risk, 1.83; 95% CI, 0.93
to 3.59; p=0.06) in HES patients.5
A third trial (N=7000) using different HES in a heterogeneous patient population consisting of
critically ill adult patients admitted to the ICU reported no difference in mortality (relative risk, 1.06;
95% CI, 0.96 to 1.18; p=0.26) but increased use of RRT (relative risk, 1.21; 95% CI, 1.00 to 1.45;
p=0.04) in HES patients.6
4. Perner A, et al., Hydroxyethyl starch 130/0.42 versus Ringer"s acetate in severe sepsis patients. The
New England Journal of Medicine, 2012 July 12;367(2):124-34.
5. Guidet B, et al., Assessment of hemodynamic efficacy and safety of 6% hydroxyethyl starch 130/0.4
vs 0.9% NaCl fluid replacement in patients with severe sepsis: The CRYSTMAS Study. Critical
Care, 2012 May 24;16(3):R94.
6. Myburgh JA, et al., Hydroxyethyl starch or saline for fluid resuscitation in intensive care. The New
England Journal of Medicine, 2012 November 15;367(20):1901-11.
7. Diehl J., et al., Clinical Comparison of Hetastarch and Albumin in Postoperative Cardiac Patients.
The Annals of Thoracic Surgery, 1982;34(6):674-679.
8. Gold M., et al., Comparison of Hetastarch to Albumin for Perioperative Bleeding in Patients
Undergoing Abdominal Aortic Aneurysm Surgery. Annals of Surgery, 1990;211(4):482-485.
9. Kirklin J., et al., Hydroxyethyl Starch versus Albumin for Colloid Infusion Following
Cardiopulmonary Bypass in Patients Undergoing Myocardial Revascularization. The Annals of
Thoracic Surgery, 1984;37(1):40-46.
10. Moggio RA., et al., Hemodynamic Comparison of Albumin and Hydroxyethyl Starch in
Postoperative Cardiac Surgery Patients. Critical Care Medicine, 1983;11(12):943-945.
11. Brutocao D., et al., Comparison of Hetastarch with Albumin for Postoperative Volume Expansion in
Children After Cardiopulmonary Bypass. Journal of Cardiothoracic and Vascular Anesthesia,