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We studied the maternal pharmacokinetics of epidural lidocaine and bupivacaine in 20 healthy parturients with institutional review board approval and written, informed consent. Epidural anesthesia was induced using either 2% lidocaine with epinephrine 1:200,000, n = 10, or 0.5% plain bupivacaine, n = 10. Maternal arterial (Ma) blood was sampled at regular intervals and umbilical venous (Uv) blood at delivery. Results for lidocaine and bupivacaine, respectively, were (mean +/- SEM): age 30.4 +/- 1.5 and 24.7 +/- 1.6 yr; weight 74.0 +/- 4.2 and 74.9 +/- 4.5 kg; duration of surgery 55.5 +/- 4.3 and 53.1 +/- 3.5 min; epidural dosage 6.1 +/- 0.6 and 1.5 +/- 0.2 mg/kg; elimination half-life 113.9 +/- 5.6 and 110.4 +/- 20.4 min; plasma clearance 6.1 +/- 0.4 and 13.6 +/- 1.3 mL.kg-1.min-1; volume of distribution 0.98 +/- 0.1 and 1.67 +/- 0.3 L/kg; time to peak concentration 31 +/- 2.3 and 40.5 +/- 1.7 min; peak Ma concentration 6.4 +/- 0.65 and 0.8 +/- 0.1 microgram/mL; and Uv/Ma gradient 0.43 +/- 0.05 and 0.26 +/- 0.1. Peak Ma lidocaine concentrations in 2 of 10 patients reached potentially toxic levels without producing clinical toxicity, whereas peak bupivacaine Ma concentrations never approached levels considered unsafe. The results suggest that epidural bupivacaine reliably produces acceptable Ma concentrations below the toxic range.

Background Bupivacaine is widely used for obstetric analgesia, yet published information on the mechanism of human placental bupivacaine transfer is sparse. The dual perfused human placental model was used to elucidate the factors governing the placental transfer of bupivacaine. Methods Bupivacaine transfer was studied using the recirculating (closed) model and the single pass (open) model. Single placental cotyledons were perfused with either heparinized Krebs-Ringer's buffer (KRB) supplemented with human albumin (fetal and maternal circuits) or 100% fresh frozen plasma (maternal circuit) to control the bupivacaine protein binding in those circuits. In the open model, bupivacaine clearance was compared before and after being subjected to either increasing concentrations of bupivacaine or its structural analog, mepivacaine. Results For those studies in which the maternal and fetal protein binding was equal, the maternal to fetal (M-->F) transfer was significantly greater (P < 0.05) than that in the fetal to maternal (F-->M) direction. When the perfusates were modified to simulate actual in vivo plasma protein concentrations, bupivacaine transfer was shown to be related to the degree of protein binding found in the two circuits. In the open studies, bupivacaine transfer was similar at all concentrations investigated, unaffected by mepivacaine, and related to the pH of the fetal perfusate. A concentration effect was seen within the placental tissue at the end of the experiment. Conclusions Bupivacaine placental transfer characteristics suggest passive diffusion rather than active drug transport and appear to be influenced by the maternal and fetal plasma protein binding, fetal pH, and placental uptake.

Factors affecting lidocaine transfer across the normal term human placenta were studied using the dual perfused isolated single cotyledon. Experiments were performed using perfusates which provided equal protein binding in both the maternal and fetal circuits as well as perfusates that approached the actual in vivo maternal/fetal protein binding gradient. Additional experiments were performed to investigate the effects of increasing maternal lidocaine concentration (5, 10, 40, 80 microg/mL) on maternal to fetal (M--F) lidocaine transfer across the human placenta. Lidocaine crossed the placenta rapidly in both the M--F and fetal to maternal (F--M) directions. When protein binding was similar in the two circuits, M--F transfer ratios (lidocaine transfer/antipyrine transfer) were significantly lower than the transfer ratios seen in the F--M direction (0.59+/-0.04 versus 0.84+/-0.06, P0.05). Transfer ratios (M--F: 0.83+/-0.06, F--M: 0.96+/-0.06) were not reduced when the physiological maternal/fetal protein binding gradient was present. Lidocaine transfer was not diminished by increasing maternal concentrations and, in contrast to bupivacaine, was not significantly affected by its binding.

A therapeutic leukapheresis of a five-year-old girl with adult-type chronic granulocytic leukemia is described, with techniques for minimizing the effects of hypovolemia. The patient's unduly rapid response to chemotherapy suggested that the procedure had effected a substantial reduction in the leukocyte mass.