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

Background: Several clinical studies have shown that hydroxyethyl starch (HES) may be as effective and safe as, but less expensive than, albumin when used for perioperative plasma volume replacement (PVR) in children. The new third generation HES 130/0.42 solution was designed to reduce adverse drug reactions (ADRs) and improve safety while maintaining efficacy. Therefore, the objective of this prospective multicenter observational postauthorization safety study (PASS) was to evaluate the perioperative use of HES 130/0.42 in 1000 children with a particular focus on possible ADRs. Methods: Approximately 300 of 1000 pediatric patients aged up to 12 years with ASA risk scores of I-III receiving perioperative HES 130/0.42 (Venofundin 6%; Braun, Melsungen, Germany) should be enrolled for interims analysis in the first year. The statistical sample size calculation showed that this number of patients would be sufficient to detect a 1% incidence of ADRs. Following approval by local ethics committee, patient demographics, data relating to HES 130/0.42 use, the procedures performed, anesthesia, and ADRs were documented with a particular focus on cardiovascular stability, hemodilution, acid-base balance, renal function, blood coagulation, and hypersensitivity. Results: Three hundred and sixteen children (ASA I-III, age 3 +/- 3.4 [range, day of birth-12 years], body weight 13 +/- 10.5 [range, 1.1-60 kg]) were studied at five centers in Germany, Austria, and Italy from May 2006 until August 2007. Forty-five percent of the patients underwent abdominal surgery, 12.4% urologic procedures, 11.4% thoracic surgery, 7.6% orthopedic procedures, and 7% cardiovascular surgery. The mean volume of infused HES 130/0.42 was 11 +/- 4.8 ml.kg(-1) (range, 5-42). Cardiovascular stability was maintained in all cases. After HES infusion, hemoglobin (11.5 vs 10.25 g.dl(-1)), base excess (-2 vs -2.7 mmol.l(-1)), anion gap (12.9 vs 11.2 mmol.l(-1)), and strong ion difference (34.3 vs 31.4 mmol.L-1) decreased, and chloride (105.7 vs 107.8 mmol.l(-1)) increased significantly (P < 0.05). No serious ADRs (i.e., anaphylactoid reaction, renal failure, clotting disorders) were observed. Conclusion: Moderate doses of HES 130/0.42 help to maintain cardiovascular stability and lead to only moderate changes in hemoglobin concentration and acid-base balance in children. The probability of serious ADRs is lower than 1%. Therefore, HES 130/0.42 for PVR seems to be safe and effective even in neonates and small infants with normal renal function and coagulation.