Hydroxyethyl Starch (HES): Clinical Applications and Safety Concerns
Hydroxyethyl starch (HES) is a synthetic colloid solution that has been used for fluid resuscitation but is now contraindicated in critically ill patients, especially those with sepsis, due to increased risk of mortality and renal failure. 1
Definition and Composition
- HES is a synthetic colloid derived from waxy starch composed almost entirely of amylopectin, with hydroxyethyl ether groups introduced into the glucose units 2
- It is classified according to its molecular weight (high: 450-480 kDa, medium: 200 kDa, low: 70 kDa) and degree of hydroxyethyl substitution (ranging from 0.4 to 0.7) 3
- The 6% HES formulation typically contains 6g of hetastarch per 100mL, often in 0.9% sodium chloride solution 2
- HES solutions are pharmacologically classified as plasma volume expanders 2
Clinical Applications
- HES has been used as a colloidal volume-expanding solution for fluid resuscitation in hypovolemic states 1
- In endoscopic procedures, HES can be used as a relatively inexpensive submucosal lifting agent that produces longer-lasting lift compared to normal saline for endoscopic mucosal resection 1
- For endoscopic procedures, HES requires less volume to maintain adequate lift and fewer injections compared to normal saline 1
Safety Concerns and Contraindications
- HES is contraindicated in critically ill adult patients, including those with sepsis, due to increased risk of mortality and renal replacement therapy 1, 2
- Multiple large randomized controlled trials have demonstrated increased mortality and acute kidney injury with HES use in sepsis 1, 4, 5
- The European Medicines Agency (EMA) recommended in 2013 that HES no longer be used for volume resuscitation, particularly in sepsis patients 1, 4
- Additional contraindications include 2:
- Severe liver disease
- Known hypersensitivity to hydroxyethyl starch
- Clinical conditions where volume overload is a potential problem (congestive heart failure, renal disease with anuria or oliguria not related to hypovolemia)
- Pre-existing coagulation or bleeding disorders
Evidence Against HES Use in Critical Care
- The 6S trial demonstrated that patients with severe sepsis assigned to HES 130/0.42 had a 51% mortality rate at 90 days compared to 43% with Ringer's acetate (relative risk 1.17, p=0.03) 5
- Patients receiving HES required more renal replacement therapy (22% vs 16%, relative risk 1.35, p=0.04) 5
- A Cochrane review found that all HES products increase the risk of acute kidney injury and need for renal replacement therapy in all patient populations 6
- The CHEST study reported increased incidence of renal replacement therapy in the HES group compared to isotonic crystalloids 1
Current Recommendations for Fluid Resuscitation
- Crystalloids are recommended as the initial fluid of choice in resuscitation of patients with severe sepsis and septic shock (Grade 1B) 1
- Balanced crystalloids should be used in preference to 0.9% normal saline for resuscitation and to maintain intravascular volume 1
- For emergency laparotomy, the use of HES solutions is not recommended due to the increased risk of kidney failure and mortality 1
- In trauma patients, if colloids are administered, they should be used within the prescribed limits for each solution (Grade 1B) 1
Alternative Fluid Options
- Balanced crystalloid solutions are preferred for most resuscitation scenarios 1, 7
- For patients requiring substantial amounts of crystalloids, albumin may be considered in the fluid resuscitation of severe sepsis and septic shock (Grade 2C) 1
- Isotonic crystalloids are the preferred initial fluid for resuscitation in most clinical scenarios 8
HES products have fallen out of favor in critical care medicine due to the substantial evidence of harm, particularly regarding mortality and renal function. While they may still have limited applications in specific clinical scenarios like endoscopic procedures, their use for fluid resuscitation should be avoided, especially in critically ill patients.