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Biomedical subjects

B R Kuhnert

Publications and source records attributed to B R Kuhnert.

At least 37 records · Page 2Linked to original sources
PubMed1987

2-Chloroprocaine for local perineal infiltration.

Lidocaine was recently found to rapidly cross the placenta and result in considerable fetal exposure after local infiltration of the perineum for episiotomy. For this reason, a more appropriate agent for local perineal infiltration might be a drug with rapid metabolism and inactive metabolites. 2-Chloroprocaine, an ester-linked local anesthetic agent, is available but is not commonly used for this procedure. The purpose of this study was to evaluate the placental transfer of 2-chloroprocaine after local perineal infiltration. The drug was administered to 17 normal term pregnant women for episiotomy. After local perineal infiltration, the levels of 2-chloroprocaine and/or its metabolite, chloroaminobenzoic acid, were quantitated in maternal and neonatal plasma or urine. The pharmacologic data indicated that 2-chloroprocaine was nondetectable at delivery in maternal and umbilical cord vein; one patient had trace levels in the cord. Chloroprocaine was not detectable in neonatal plasma, but chloroaminobenzoic acid was detectable in both maternal and cord vein plasma. Mean levels of chloroaminobenzoic acid in maternal plasma at delivery were 1.04 +/- 0.32 micrograms/ml, and mean levels in cord vein were 0.35 +/- 0.54 micrograms/ml. Clinically, 2-chloroprocaine provided good analgesia. These results indicate that very little, if any pharmacologically active drug, reaches the fetus after local perineal infiltration with 2-chloroprocaine. Therefore 2-chloroprocaine appears to be preferable to lidocaine when used for local perineal infiltration.

Adult↗
PubMed1987

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.

Anesthesia, Obstetrical↗
PubMed1987

Neonatal manifestations of maternal phencyclidine exposure.

The purpose of this study was to determine the effects of maternal phencyclidine use on the fetus. Ninety-four neonates with maternal phencyclidine exposure were compared with 94 controls. Maternal phencyclidine use was assessed by questionnaire and repeated urine testing. Mothers of study and control patients were matched for demographic characteristics. Infants were assessed between 24-72 hours postnatally by a single examiner blind to the maternal history. The results showed that study infants had a mean of 5.02 +/- 2.93 abnormalities while controls had a mean of 4.13 +/- 2.65 abnormalities (p less than 0.01). Furthermore, study infants were more likely than controls to have poor attention, hypertonia, and depressed neonatal reflexes (p less than 0.05). The contribution of seven drug classes to the total number of abnormalities was assessed using stepwise multiple regression. Only phencyclidine accounted for a significant proportion of the variance (f = 4.38; p less than 0.05). The results of this study suggest that maternal phencyclidine use may lead to abnormal neonatal neurologic findings and behavior.

Abnormalities, Drug-Induced↗
PubMed1987

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.

Adult↗
PubMed1986

Measurement of the amino acid metabolite of phencyclidine by selected ion monitoring.

A technique is described for the extraction and quantitation of the pentanoic acid metabolite of phencyclidine by gas chromatography/mass spectrometry. This compound was measured in urine samples from asymptomatic pregnant patients who used phencyclidine (PCP) and their neonates. The technique is sensitive to 25 ng ml-1 urine and standard curves were linear at 25-2000 ng ml-1. Levels in samples from asymptomatic patients were 27-1388 ng ml-1. Results suggest that the pentanoic acid metabolite could be considered as a screening marker for occasional PCP use.

Amino Acids↗
PubMed1986

Measurement of meperidine and normeperidine in human breast milk by selected ion monitoring.

A technique is described for extraction and quantitation of meperidine and normeperidine from breast milk by gas chromatography/mass spectrometry. Both compounds were measured in breast milk from parturients who received the drug for postpartum pain relief. The technique is sensitive to 1 ng ml-1 and standard curves were linear at 1.5-2000 ng ml-1. Levels in breast milk samples were 36.2-314 ng ml-1 and 0-333 ng ml-1 for meperidine and normeperidine, respectively. Preliminary results suggest that postpartum pain medication with meperidine results in considerable levels of both meperidine and its active metabolite, normeperidine, in breast milk.

Female↗
PubMed1986

Ritodrine pharmacokinetics.

The purpose of this study was to add to the limited information available regarding the pharmacology of ritodrine in the peripartum period when treatment fails and labor is not inhibited. Plasma or urine samples from eight parturients and 13 infants were studied; in addition plasma samples at delivery were obtained from a total of 26 mothers and infants. All the mothers received ritodrine in the 24 hours before delivery. Plasma and urine ritodrine (free and conjugated) were determined with HPLC by electrochemical detection. In maternal plasma, an apparent rapid distribution phase with a t1/2 of 32 +/- 21 minutes was followed by a prolonged equilibrium phase with a t1/2 of 17 +/- 10 hours. Seventy-six percent of the ritodrine excreted by the mother was in the form of a conjugate. Ninety percent of the ritodrine excreted by the neonate was also excreted in the form of a conjugate.

Blood Proteins↗
PubMed1986

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.

Adult↗
PubMed1986

The half-life of 2-chloroprocaine.

The purpose of this study was to examine the discrepancy between the reported in vitro half-life of chloroprocaine and the slower observed disappearance of the drug in maternal plasma. The study had two aims. The first was to redetermine the in vitro half-life of 2-chloroprocaine in maternal and fetal plasma. The second was to determine the apparent half-life of 2-chloroprocaine in vivo after intrapartum epidural anesthesia in obstetric patients. Gas chromatography or gas chromatography/mass spectrometry techniques were used to measure 2-chloroprocaine in maternal or fetal plasma. Mean in vitro half-lives of 11.2 +/- 2.8 and 15.4 +/- 5.2 sec were found for maternal and fetal plasma from nine patients, respectively. The maternal half-life was significantly shorter than the fetal half-life (P less than 0.05). The mean apparent in vivo half-life in maternal plasma was found to be 3.1 +/- 1.6 min. The results of this study show that the half-life in vitro is correctly measured in seconds. However, the apparent half-life in vivo after epidural anesthesia is 3.1 +/- 1.6 min and ranges from 1.5 to 6.4 min. The differences in the magnitude of the two findings is probably due to continuous uptake of the drug from the epidural space.

Adult↗
PubMed1985

Fetal acidosis, 2-chloroprocaine, and epidural anesthesia for cesarean section.

Amide-linked local anesthetic agents, such as lidocaine and bupivacaine, can become "trapped" in their ionized forms on the fetal side of the placenta, and therefore their net transfer across the placenta is increased. An ester-linked local anesthetic agent, 2-chloroprocaine, is rapidly metabolized, and placental transfer is limited. Since the metabolism of 2-chloroprocaine by fetal plasma is slower than in maternal plasma, the potential for ion trapping exists. The purpose of this study was to determine the disposition of 2-chloroprocaine and its metabolite, chloroaminobenzoic acid, in relation to the umbilical cord vein pH at delivery, and specifically, to determine whether ion trapping exists. Epidural anesthesia with 2-chloroprocaine was administered to 44 women at term prior to cesarean section. At delivery the levels of 2-chloroprocaine and chloroaminobenzoic acid in maternal plasma and umbilical cord vein were quantitated. Neonates were divided into two groups based on the umbilical cord vein pH at delivery. Ten of the 44 patients delivered neonates with a pH less than or equal to 7.25 (acidotic group) while 34 delivered neonates with a pH greater than 7.25 (nonacidotic group). The mean umbilical cord vein pH in the acidotic and nonacidotic groups was 7.22 +/- 0.03 and 7.32 +/- 0.03, respectively (p less than 0.001). There were also no differences between the groups in maternal and neonatal clinical characteristics or in the total dose of 2-chloroprocaine administered or the drug-to-delivery interval. The pharmacologic results did not demonstrate a statistical difference in the concentration of 2-chloroprocaine or chloroaminobenzoic acid in the maternal vein or umbilical cord vein at delivery between the two groups. Thus the results of this study demonstrate that placental transfer of 2-chloroprocaine is not influenced by fetal acidosis. Therefore these data suggest that 2-chloroprocaine may be the drug of choice when fetal acidosis or distress is anticipated.

Acidosis↗
PubMed1985

Disposition of meperidine and normeperidine following multiple doses during labor. I. Mother.

Normeperidine, the active meperidine metabolite, has been implicated in adverse neonatal effects that may occur following administration of meperidine to parturients. However, recent studies have suggested that normeperidine levels are not high enough to have adverse effects following single low doses of meperidine. It is not clear what occurs following multiple injections. Therefore the purpose of this study was to quantitate plasma levels of meperidine and normeperidine in the mother following multiple doses of meperidine over long time periods and to determine the half-life of normeperidine. Twelve mothers who received multiple intravenous doses of meperidine were studied. The results show that both meperidine and normeperidine accumulate in maternal plasma following multiple injections and that the half-life of normeperidine averages 20.6 hours. The data suggest that maximum exposure of the fetus to both meperidine and normeperidine would result from multiple doses to the mother because of a continued diffusion gradient from mother to fetus.

Adolescent↗
PubMed1985

Disposition of meperidine and normeperidine following multiple doses during labor. II. Fetus and neonate.

It has been suggested that continued diffusion gradients from mother to fetus would exist and that both meperidine and normeperidine would accumulate in the fetus following multiple doses of meperidine to the mother during labor. However, no pharmacokinetic data are available. Therefore, the purpose of this study was to document the disposition of meperidine and normeperidine in the fetus and neonate following multiple doses of meperidine to the mother over long time periods. Twelve infants were studied. The results show surprisingly high concentrations of both meperidine and normeperidine in fetal blood at delivery. In addition, the amount of normeperidine increased with time in umbilical cord blood, the ratio of normeperidine to meperidine increased with time, and the umbilical artery-to-vein ratio of meperidine (but not normeperidine) was greater than one following long drug-to-delivery intervals. The data also suggest that with long drug-to-delivery intervals the levels of normeperidine may become clinically important and that the elimination of both compounds by the neonate is prolonged. The study suggests that multiple doses to the mother over long time periods result in maximum accumulation of both meperidine and normeperidine in fetal tissues.

Female↗
PubMed1985

Obstetric medication and neonatal behavior. Current controversies.

This article reviews the work on the neonatal effects of low drug doses published in the last five years. At the same time, there will be a focus on new developments in perinatal pharmacology and on current controversies in this area. The article includes discussions about neurobehavioral outcome measures and statistics, as well as recommendations for future studies.

Analgesics↗
PubMed1985

Effects of low doses of meperidine on neonatal behavior.

After meperidine administration during labor, meperidine reaches its highest level in fetal tissues within 2-3 hr. The highest levels of normeperidine, the active metabolite of meperidine, are, on the other hand, determined in fetal tissues by the time between administration of meperidine to the mother and delivery: the greater the drug-to-delivery interval (DDI), the higher the fetal levels of normeperidine. Because of the different times to peak fetal levels of meperidine and normeperidine, it may be possible to partially separate the effects of meperidine and its metabolite on the neonate using the DDI. The purpose of this study was to determine whether low doses of meperidine affected performance on the Brazelton Neonatal Behavioral Assessment Scale (BNBAS), and whether this performance is related to the DDI or to levels of meperidine or to normeperidine. Sixteen control neonates whose mothers received no meperidine and 41 study infants whose mothers received 25-100 mg meperidine intravenously (mean 39 +/- 19 mg) were studied. Comparisons of BNBAS scores of control and study infants measured at less than 12 hr, again at 3 days of age, and the effect of DDI were made using repeated measures analyses of variance (ANOVA). Correlation techniques were used to examine relationships between BNBAS performance and clinical and pharmacological variables related to drug administration. The BNBAS cluster scores representing regulation of state and number of abnormal reflexes were significantly different in study neonates from control neonates. Performance depended upon test day. Further analysis showed that longer DDIs resulted in less optimal BNBAS performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Maternal and fetal plasma concentrations of ritodrine.

Previous studies using other beta-adrenergic drugs for tocolysis suggest that if treatment fails and the patient delivers shortly after the therapy is discontinued, there is a direct correlation between neonatal drug concentration and major neonatal complications. In the present study, the disposition of ritodrine was studied in 28 maternal-infant pairs in whom intravenous ritodrine had been administered for clinical indications. The fetal to maternal ratio of ritodrine was 1.17 +/- 0.48. The concentration of ritodrine in both maternal and umbilical vein was found to vary inversely with the length of time the drug was discontinued before delivery. A stepwise multilinear regression revealed that the maternal ritodrine dose in the 24 hours before delivery and the drug discontinuance to delivery interval were both independently related to umbilical vein ritodrine concentrations. When combined, the two variables explained 52% of the variance in umbilical vein ritodrine levels. The frequency of respiratory distress syndrome was increased in the neonates in whom umbilical vein ritodrine was greater than 10 ng/mL, compared with the groups with umbilical vein levels ranging from 3.0 to 10.0 ng/mL. However, neonates with the highest ritodrine concentration were also of lower gestational age (29.4 versus 33.5 weeks, P less than .05) and thus, had greater inherent risk of prematurity-related complications.

Chromatography, High Pressure Liquid↗