No abstract

Repeated administration of HES 130/0.42 shows no accumulation and fewer tendencies to time-dependent changes in pharmacokinetic parameters than HES 200/0.5. The improved reproducibility may improve drug safety, particularly as the accumulation of residual starch with HES 200/0.5 does not contribute to the colloid's volume effect, but may rather increase the risk of undesired reactions.

Background: For the purpose of haemodilution different medium substituted hydroxyethyl starches (HES) are available. These plasma substitutes can be further characterized by their average molecular weight (Mw) into medium Mw (HES 200/0.5) and low Mw (HES 70/0.5) starches. Patients and Methods: Pharmacokinetic data were collected in a trial with a design similar to clinical use. 8 healthy volunteers were given 50 g HES on 5 consecutive days (=250 g) to estimate the in vivo changes of the chemical structures of HES (70/0.5). Results: Calculated half-life of serum elimination were 6–10 h which was representative for medium substituted HES and the chosen infusion scheme. The mild accumulation of HES (70/0.5) should be without clinical relevance. The in vivo Mw is equivalent to the in vitro Mw of the infused HES (70/0.5). The in vivo Mw is about 60,000 Dalton for most medium substituted HES. Nevertheless, regarding molar substitution and pattern of substitution (C2:C6) there are some differences between applied HES (70/0.5) and HES recovered in urine. These changes also indicate a shift in the chemical properties of infused HES in the organism. Only 60% of infused HES were recovered in urine. The destination of the remaining 40% (∼100 g in this clinical trial) is still unexplained. A fractional amount might be stored in the reticuloendothelial system. Concerning the measured data of medium substituted HES (70/0.5) it stands to reason that differences in the approximate substituted HES (200/0.5) with a higher molecular weight are without clinical relevance. Conclusion: The in vivo Mw is independent of the in vitro Mw of the applied HES. Pharmacokinetic data suggest that HES (70/0.5) is a good option for the purpose of haemodilution.

Groups were comparable regarding age, weight and time of gestation. Total bupivacaine doses and injection to delivery times were similar in both groups. Figure 1 shows that there were 40% more pain-free (VAS = 0) patients in the B+F group during uterine eventration and wound closure (P < 0.05). Mean postoperative duration of analgesia was significantly longer in the B+F group (382 vs 236 min). The rate of nausea and mild itching was significantly higher in the B+F group. Respiratory depression was never detected in patients or newborns. Small group differences in blood pressure or respiratory rate were inconstant and clinically irrelevant, as were differences in umbilical venous pCO2. One hundred and twenty-five blood samples were analysed for fentanyl concentrations. The mean fentanyl concentration before epidural injection was not zero, but 0.25 ng/mg (range 0.02-0.32). Maternal concentrations at 20 and 40 min after injection were 0.55 ng/ml (0.12-1.14) and 0.52 ng/ ml (0.26-1.04) (Fig. 3). At delivery, mean maternal fentanyl concentration was 0.58 ng/ml (0.14-1.18); mean umbilical arterial and venous concentrations were 0.51 ng/ml (0.04-1.8) and 0.41 ng/ml (0.18- 1.2), respectively. Rare results of fentanyl concentrations > 1.0 ng/ml correlated neither with sedation, maternal respiratory rate and side effects, nor with Apgar scores and umbilical blood gas values. No Apgar score at 5 min was below 9, and no umbilical pH was below 7.20. (ABSTRACT TRUNCATED)