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Table 2 Changes to guidance on HES products from the FDA and EMA between 2012 and 2016

From: Comparison of hydroxyethyl starch regulatory summaries from the Food and Drug Administration and the European Medicines Agency

Variable FDA EMA
Dosage 6% Hetastarch
Adults
Administer 500 to 1000 mL.
Doses of more than 1500 mL/day for the typical 70 kg patient (approx. 20 mL/kg) are usually not required although doses of isotonic solutions containing 6% hetastarch up to 1500 mL have been used during major surgery. Volumes in excess of 1500 mL/day have been used where severe blood loss has occurred.
Newborns and children
Adequate, well controlled clinical trials to establish the safety and effectiveness of HEXTEND in paediatric patients have not been conducted.
6% Hetastarch
Identical to FDA
  6% Tetrastarches
Adults
Administer up to 30 mL/kg/day. This dose is equivalent to 2100 mL for a 70 kg patient.
Give initial 10–20 mL by slow infusion and monitor for adverse effects.
Newborns and children
Limited data on the use of 130/0.4 HES in children is available - if used individualised dose taking into account disease and haemodynamic status should be employed.
6% Tetrastarches
Identical to FDA
  No change to adult dosage guidelines in 2012
Extra information to Voluven label in 2012
<2 years: Mean dose of 16 mL/kg IV
2–12 years: Mean dose of 36 mL/kg IV
No change to adult dosage guidelines in 2012
Extra information to Voluven label in 2012
<2 years: Mean dose of 16 mL/kg IV
2–12 years: Mean dose of 36 mL/kg IV
Indications Hetastarches indicated for treatment of hypovolaemia when plasma volume expansion is desired.
It is not a substitute for blood or plasma.
Treatment of imminent or manifest hypovolaemia and shock.
  No changes to indication text in 2012 Change to indication text in 2013
In case of hypovolaemia a crystalloid solution should first be given.
HES is indicated for the treatment of hypovolaemia if patient does not respond to crystalloid solution.
Contra-indications Renal failure (with oliguria or anuria)
Hypersensitivity
Congestive cardiac failure
Treatment of lactic acidosis
Patients on dialysis
Clinical conditions with volume overload
Renal failure (with oliguria or anuria)
Hypersensitivity
Congestive cardiac failure
Hyperhydration states including pulmonary edema
Intracranial bleeding
Severely impaired hepatic function
Hyperkalaemia
Severe hypernatremia or hyperchloremia
Clinical conditions with volume overload
  Additional contraindications in 2013
Critically ill adult patients, including patients with sepsis, and those admitted to the ICU
Pre-existing renal function
Severe liver disease
Patients with pre-existing coagulation and bleeding disorders
Additional contraindications in 2013
Critically ill patients, including patients with sepsis
Burn injuries
Renal impairment or renal replacement therapy patients
Severe coagulopathy
Organ transplant patients
Adverse Effects Additions to adverse effects in 2013
Increased mortality in severe sepsis and other conditions requiring ICU admission
Increased need for RRT in severe sepsis and other conditions requiring ICU admission
Additions to adverse effects in 2013
Renal injury
Hepatic injury
Warnings and Precautions Black box warning added to label in 2013
Avoid use in patients with pre-existing renal dysfunction
Discontinue use of HES at the first sign of renal injury
Avoid fluid overload; adjust dosage with cardiac or renal dysfunction
In cases of severe dehydration, a crystalloid solution should be given first
Restriction on patient population added to label in 2013
Only use HES during the first 24 hours of fluid resuscitation treatment
Trauma and surgery: carefully weigh the expected benefit of treatment against the uncertainty of the long term safety of treatment. Consider other available treatment options
Stop HES treatment at the first sign of impaired blood clotting or renal injury
Not recommended for patients undergoing open heart surgery
Patient Monitoring Monitor fluid balance, serum electrolytes, renal and hepatic function, acid–base balance, and coagulation parameters during prolonged parenteral therapy or when warranted Because of the risk of allergic (anaphylactoid) reactions, the patient should be monitored closely and the infusion instituted at a low rate
Monitor fluid balance, serum electrolytes, renal and hepatic function. Particular caution in patients with renal impairment and elderly patients
Elevated serum amylase levels may be observed and can interfere with the diagnosis of pancreatitis
  Additions to guidance in 2013
Monitor renal function in hospitalized patients for at least 90 days as use of renal replacement therapy has been reported up to 90 days after administration of HES products
Monitor the coagulation status of patients undergoing open heart surgery in association with cardiopulmonary bypass as excess bleeding has been reported with HES solutions in this population. Discontinue use of HES at the first sign of coagulopathy
Monitor liver function in patients receiving HES products
Additions to guidance in 2013
Monitor kidney function in patients receiving HES for at least 90 days and stop HES treatment at the first sign of renal injury
Blood coagulation parameters should be monitored carefully in case of repeated administration
HES solutions should be used at the lowest effective dose for the shortest period of time
Treatment should be guided by continuous haemodynamic monitoring so that the infusion is stopped as soon as appropriate haemodynamic goals have been achieved