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.

Investigation of factors influencing biogas production in a large-scale thermophilic municipal biogas plant.

A continuously operated, thermophilic, municipal biogas plant was observed over 26 months (sampling twice per month) in regard to a number of physicochemical parameters and the biogas production. Biogas yields were put in correlation to parameters such as the volatile fatty acid concentration, the pH and the ammonium concentration. When the residing microbiota was classified via analysis of the 16S rRNA genes, most bacterial sequences matched with unidentified or uncultured bacteria from similar habitats. Of the archaeal sequences, 78.4% were identified as belonging to the genus Methanoculleus, which has not previously been reported for biogas plants, but is known to efficiently use H(2) and CO(2) produced by the degradation of fatty acids by syntrophic microorganisms. In order to further investigate the influence of varied amounts of ammonia (2-8 g/L) and volatile fatty acids on biogas production and composition (methane/CO(2)), laboratory scale satellite experiments were performed in parallel to the technical plant. Finally, ammonia stripping of the process water of the technical plant was accomplished, a measure through which the ammonia entering the biogas reactor via the mash could be nearly halved, which increased the energy output of the biogas plant by almost 20%.

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 x kg(-1) (range, 5-42). Cardiovascular stability was maintained in all cases. After HES infusion, hemoglobin (11.5 vs 10.25 g x dl(-1)), base excess (-2 vs -2.7 mmol x l(-1)), anion gap (12.9 vs 11.2 mmol x l(-1)), and strong ion difference (34.3 vs 31.4 mmol x L(-1)) decreased, and chloride (105.7 vs 107.8 mmol x 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.