Table 2 Changes to guidance on HES products from the FDA and EMA between 2012 and 2016
Variable | FDA | EMA |
|---|---|---|
Dosage | 6% Hetastarch Adults Administer 500 to 1000Â mL. Doses of more than 1500Â mL/day for the typical 70Â kg patient (approx. 20Â mL/kg) are usually not required although doses of isotonic solutions containing 6% hetastarch up to 1500Â mL have been used during major surgery. Volumes in excess of 1500Â 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. |
| Â | 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 |
| Â | 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 24Â 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 |
| Â | Additions to guidance in 2013 Monitor renal function in hospitalized patients for at least 90Â days as use of renal replacement therapy has been reported up to 90Â 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 90Â 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 |