Effect of ranitidine on bupivacaine disposition.

This study was undertaken to determine the effect, if any, of ranitidine on bupivacaine disposition in 28 women undergoing cesarean section. Before epidural anesthesia, ranitidine (50 mg IM) or sodium citrate (30 mL orally) was administered to groups of 14 parturients each. Ranitidine was administered 2 h before epidural anesthesia and sodium citrate was administered 10 min before the epidural. Maternal plasma samples were collected after epidural anesthesia with bupivacaine. A total of 15 maternal plasma samples were taken from the time of administration of epidural anesthesia up to 180 min. Postpartum plasma and urine samples were also collected from both mothers and neonates. Plasma samples were collected up to 48 h postpartum at intervals of 12, 24, and 48 h. Urine samples were collected at six 6-h intervals up to 36 h postpartum. A two-way analysis of variance with repeated measures demonstrated that there was no significant difference in bupivacaine levels between the maternal plasma curves of the ranitidine and the control groups. At the time of delivery, plasma levels of bupivacaine and its N-dealkylated metabolite PPX (2,6-pipecolylxylidine) were no different in the mothers or neonates of either group. There was no significant difference in plasma protein binding of bupivacaine in the presence of ranitidine. The excretion rates of bupivacaine and PPX were not measurably influenced by ranitidine. The amount of bupivacaine excreted, the amount of metabolite excreted, and the percentage of drug excreted as metabolite in maternal urine were not significantly different. These data indicate that there is no measurable effect of ranitidine on the disposition of bupivacaine in parturients.

Neonatal resuscitation in community hospitals. A regional-based, team-oriented training program coordinated by the tertiary center.

Neonatal resuscitation in community hospitals is problematic because of the lack of on-site personnel with adequate training and experience. Even when efforts are made to transport high-risk mothers to tertiary care centers, the most complex resuscitations must occasionally be performed in all obstetric services. This dilemma can result in increased neonatal morbidity and mortality, and is reflected in the obstetric malpractice crisis. We present an approach to the problem in which a tertiary center actively intervenes to assist regional community hospitals to develop and implement resuscitation team capabilities. Key aspects of the system are training and implementation of hospital shift "Code Pink" teams composed of nonphysician professionals, a regional neonatal resuscitation protocol used by all participants, "mock code" resuscitation drills to maintain skills, and extensive quality assurance both at the local hospital and regional levels.

Lack of influence of cimetidine on bupivacaine levels during parturition.

The concurrent use of cimetidine as a prophylactic antacid and bupivacaine as a local anesthetic for epidural anesthesia for cesarean section has been promoted. However, cimetidine is known to inhibit clearance of many drugs by reducing hepatic blood flow and by inhibiting cytochrome P-450 enzymes. The purpose of this study was to determine whether cimetidine during epidural anesthesia alters the metabolism, disposition, protein binding, or placental transfer of bupivacaine. Thirty-six patients undergoing cesarean section with 0.5% bupivacaine for epidural anesthesia were studied. Sixteen patients received cimetidine (300 mg IM) 1-4 hr before cesarean section and 20 control patients received sodium citrate (30 ml PO) 10 min preoperatively. Bupivacaine and its inactive metabolite, 2,6-pipecolylxylidine (PPX) were quantitated by gas chromatography/mass spectrometry. Maternal plasma concentration time curves, fetal/maternal ratios at delivery, cord vein/cord artery ratios. PPX/bupivacaine ratios, and maternal and neonatal urinary excretion were compared between the two groups. No significant differences could be found between the groups in any of the outcome variables. However, in the presence of cimetidine, the percentage of unbound bupivacaine significantly increased from 1.36 +/- 0.63 to 1.66 +/- 0.78%. The results suggest that a single 300-mg IM dose of cimetidine does not significantly affect bupivacaine disposition or metabolism in parturients when given 1-4 hr before anesthesia.

Bupivacaine disposition in mother, fetus, and neonate after spinal anesthesia for cesarean section.

Uptake of bupivacaine from the subarachnoid space and its placental transfer were measured in six patients undergoing elective cesarean section. Maternal plasma levels (59 +/- 32 ng/ml) were only about 5% of those found in a comparable previous study of epidural anesthesia. Mean plasma umbilical venous bupivacaine levels (20.2 +/- 21 ng/ml) were 7% of those found after epidural anesthesia. Mean umbilical venous/maternal venous bupivacaine ratios were 0.34 +/- 0.12 and mean umbilical arterial/umbilical venous ratios were 0.81 +/- 0.30. No bupivacaine was detectable in neonatal plasma 24 hr after delivery. Neonatal urine had measurable levels of both bupivacaine and its inactive metabolite, 2,6-pipecolylxylidine (PPX), for at least 36 hr after delivery. The results demonstrate that bupivacaine crosses the placenta and reaches the fetus, but in very low amounts. This transplacental passage occurs despite injection of only small doses of a very highly protein bound drug into the subarachnoid space.

Lidocaine disposition in mother, fetus, and neonate after spinal anesthesia.

Although it is generally believed that concentrations of local anesthetic in maternal plasma do not reach levels that affect the fetus after spinal anesthesia, there are few studies that have measured drug levels in either maternal or neonatal plasma after spinal anesthesia. The purpose of this study was to document the disposition of lidocaine in mother, fetus, and neonate after spinal anesthesia using gas chromatographic/mass spectrometric measurement of lidocaine and two metabolites of lidocaine. Plasma concentration time curves, fetal/maternal ratios, cord artery/cord vein ratios, and neonatal urine levels were determined in ten patients. The results document that lidocaine is present in maternal and neonatal plasma. Mean (+/- SD) maternal plasma levels (0.65 +/- 0.52 micrograms/ml) were significantly lower than those previously reported after epidural anesthesia (2.09 +/- 1.31 micrograms/ml). Fetal/maternal plasma concentration ratios averaged 0.37 +/- 0.2 and mean cord arterial/cord venous ratios 0.5 +/- 6.7. Lidocaine and its metabolites were present in neonatal urine for longer than 36 hr. This study demonstrates that spinal anesthesia with lidocaine results in neonatal exposure to lidocaine.

Thermogenic alterations in the woman. II. Basal body, afternoon, and bedtime temperatures.

PIP: 19 female college students aged 17-20 years volunteered to participate in an experiment whereby they took their temperatures on 1st rising, at 5 p.m., and at bedtime for a minimum of 1 complete ovulation cycle. 3 parallel curves were found with the afternoon temperature being .7 degrees Farenheit higher than the basal and .3 degrees higher than the bedtime temperature. Several graphs illustrate the curve patterns. It is concluded that either the afternoon or the evening temperature can be used instead of the rising (or basal body) temperature, with an adjustment of the correct amount.^ieng