A second-generation blood substitute (perflubron emulsion) increases the blood solubility of modern volatile anesthetics in vitro.

UNLABELLED: Perfluorocarbon-based emulsions increase the blood solubility of isoflurane, enflurane, and halothane, with a maximal effect reported for the less soluble isoflurane. Current volatile anesthetics are less soluble and may be more affected by this phenomenon. Perflubron (Oxygent(TM)) is a perfluorocarbon-based emulsion in late-stage clinical testing in surgical patients for use as a temporary oxygen carrier. We tested the hypothesis that perflubron increases the solubility of isoflurane, sevoflurane, and desflurane, as reflected by their blood/gas partition coefficient (lambda(Bl:g)). Fresh whole-blood samples were drawn from eight volunteers and mixed with perflubron to obtain concentrations of 1.2%, 1.8%, and 3.6% by volume (equivalent to in vivo doses of 1.8 to 5.4 g/kg, which represent up to twice the intended clinical dose range). By using the double-extraction method, we demonstrated increased lambda(Bl:g) for isoflurane, sevoflurane, and desflurane. However, the solubility in blood does not really change, because volatile anesthetics are actually partitioning into perflubron. Increasing the amount of emulsion in the blood consequently increases the amount of gas carried, as reflected by the measured linear correlation between the lambda(Bl:g) values of all three volatile anesthetics and perflubron doses. Even though the increase ranges from 0.9 (desflurane) to 2.6 (sevoflurane) times the normal value, the apparent lack of clinical implications in current trials with perflubron may trigger further in vivo experiments. IMPLICATIONS: Perflubron increases the in vitro solubility of volatile anesthetics when present in the blood at clinically relevant concentrations. Volatile anesthetics actually partition into the emulsion, but the solubility in the blood does not change. Further studies are needed to assess whether perflubron will affect the pharmacokinetics of volatile anesthetics in vivo.

In children, the addition of epinephrine modifies the pharmacokinetics of ropivacaine injected caudally.

PURPOSE: To describe the modification of the ropivacaine (R) pharmacokinetics produced by the addition of epinephrine (E). METHODS: After Institutional Review Board approval, 18 ASA I boys received a caudal block (1 mL x kg(-1)) with either plain 0.2% R (Group E-) or with 0.2% R containing E (5 microg x mL(-1); Group E+). Venous blood samples were taken at zero, 15, 30, 60, 90, 120, 180, 240, 420, 720, 1440 min after caudal injection. Total R concentration in plasma was determined by high pressure liquid chromatography. Maximal concentration (C(max)) and time to peak concentration (T(max)) were obtained from the data, terminal half-life (T(1/2z)), clearance (Cl) and volume of distribution (Vd) were estimated by a non-compartmental approach. Subsequently, in order to determine the absorption rate (Ka) and to reduce to number of blood samples, 25 other children, receiving plain R and another group of 25 receiving the E solution were studied using a population approach (NONMEM). A one compartment model with first order absorption was used. The effect of weight, age and E on Cl, Vd and Ka was estimated. RESULTS: C(max) was significantly lower in Group E+ (0.93 mg x L(-1) +/- 0.29 vs 0.61 mg x L(-1) +/- 0.28, P = 0.05) and T(max) occurred later (124 min +/- 53 vs 47 min +/- 16, P = 0.003). Weight was a significant covariate for Cl and Vd while E significantly slowed R Ka [Group I Ka 0.025 min(-1) [coefficient of variation (CV) 21%] vs 0.078 min(-1) (CV 25%) in Group II]. CONCLUSION: The addition of E significantly modifies the pharmacokinetics of R injected caudally.