Hydroxyethyl starch 130/0.42/6:1 for perioperative plasma volume replacement in 1130 children: results of an European prospective multicenter observational postauthorization safety study (PASS).

INTRODUCTION Third-generation hydroxyethyl starch (HES) is now approved also for the use in children, but safety studies including large numbers of pediatric patients are still missing. Therefore, we performed an European multicentric prospective observational postauthorization safety study (PASS) to evaluate the use of HES 130/0.42/6:1 in normal saline (ns-HES) or a balanced electrolyte solution (bal-HES) in children undergoing surgery. METHODS Children aged up to 12 years with ASA risk scores of I-III receiving ns-HES (Venofundin 6%; Braun) or bal-HES (Tetraspan 6%; Braun) were followed perioperatively. Demographic data, surgical procedures performed, anesthesia, hemodynamic and laboratory data, adverse events (AE), and adverse drug reactions (ADR) were documented using a standardized case report form. RESULTS Of 1130 children studied at 11 European pediatric centers from 2006 to 2009 (ns-HES, 629 children; bal-HES, 475 children; mean age, 3.6 ± 3.8 [range, day of birth-12 years]; and body weight, 15.4 ± 13 [0.9-90 kg]), 1104 were included for analysis. The mean infused HES volume was 10.6 ± 5.8 (0.83-50) ml·kg(-1). In the 399 (36.1%) cases with blood gas analysis before and after HES infusion, hemoglobin and strong ion difference decreased significantly in both groups, whereas bicarbonate and base excess (BE before infusion: ns-HES -1.8 ± 3.1, bal-HES -1.2 ± 3.3 mm; after infusion: ns-HES -2.5 ± 2.8; bal-HES -1.1 ± 3.2 mm, P < 0.05) decreased only with ns-HES but remained stable with bal-HES. Chloride concentrations increased in both groups and were significantly higher with ns-HES (Cl before infusion: ns-HES 105.5 ± 3.6, bal-HES 104.9 ± 2.9 mm; Cl after infusion: ns-HES 107.6 ± 3.4, bal-HES 106.3 ± 2.9 mm, P < 0.05). For the AE/ADR rates, dose-response but no age relationships could be demonstrated. No serious and no severe ADR directly related to HES (i.e. anaphylactoid reaction, clotting disorders, renal failure) were observed. CONCLUSION Moderate doses of HES 130/0.42/6:1 for perioperative plasma volume replacement seem to be safe even in neonates and small infants. The probability of serious ADR is lower than 0.3%. Changes in acid-base balance may be decreased when HES is used in an acetate-containing balanced electrolyte solution instead of normal saline. Caution should be exercised in patients with renal function disturbances and those with an increased bleeding risk.