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Biomedical subjects

J W Downing

Publications and source records attributed to J W Downing.

At least 19 recordsLinked to original sources
PubMed2000

Transfer of methohexital across the perfused human placenta.

STUDY OBJECTIVES: To evaluate the transfer properties of methohexital and the influence of protein binding using the in vitro human placental perfusion model. DESIGN: Fresh term human placentae from healthy parturients were perfused bidirectionally via a cannulated fetal chorionic artery and vein and needles placed into the maternal intervillous space. Maternal-to-fetal (M-->F) and fetal-to-maternal (F-->M) transfer and ultimate distribution of methohexital was investigated using a closed (recirculating) placental perfusion model. SETTING: Obstetric anesthesia laboratories of two university medical centers. PATIENTS: No patient participation occurred as placentae were obtained after delivery. INTERVENTION: M-->F and F-->M transfer of methohexital was compared in vitro in perfusates with equal protein concentrations (2 g/100 mL in both perfusates) or albumin-simulated physiologic protein binding concentrations (maternal 8 g/100 mL; fetal 4 g/100 mL). MEASUREMENTS AND MAIN RESULTS: Data obtained consisted of measurements of methohexital and antipyrine concentrations by high-performance liquid chromatography. Glucose and lactate concentrations and perfusate loss were measured to assess placental viability. Methohexital protein binding was assessed at 2, 4, and 8 g/100 mL of albumin by equilibrium dialysis. The transfer index of 0.83 +/- 0.11 for the M-->F perfusions was significantly greater (p < or = 0.05) than in the F-->M direction (0.61 +/- 0.04) when albumin concentration was equal in both perfusates. This transfer asymmetry disappeared when albumin concentrations simulating maternal (8 g/100 mL) versus fetal (4 g/100 mL) protein concentrations in the perfusate were used (M-->F 0.87 +/- 0.12 and F-->M 0.95 +/- 0.11). CONCLUSION: Methohexital readily crosses the placenta in both directions. Protein binding has significant effects on the degree of transfer of methohexital at any time when compared with antipyrine and its ultimate fetal/maternal distribution.

Adolescent↗
PubMed1999

A comparison of the placental transfer of ropivacaine versus bupivacaine.

UNLABELLED: This study compares the placental transfer of ropivacaine and bupivacaine using the dual perfused, single cotyledon human placental model. We studied the effects of maternal/fetal protein binding, maternal ropivacaine concentration, and fetal pH on ropivacaine transfer. At a clinically relevant maternal concentration (1 microg/mL), the calculated transfer ratios (local anesthetic percent transfer/antipyrine percent transfer) of ropivacaine (0.82 +/- 0.03) and bupivacaine (0.74 +/- 0.01) were comparable at the completion of the perfusion experiment (120 min). When the perfusates were modified to simulate actual in vivo plasma protein binding values, the maternal-to-fetal transfer of ropivacaine and bupivacaine decreased significantly (P < 0.05) as indicated by transfer ratios of 0.42% +/- 0.07% and 0.40% +/- 0.03%, respectively. No saturation of the transfer process was observed for either drug at the maternal concentrations investigated. The placental transfer of both local anesthetic agents increased significantly as the fetal pH decreased. This investigation shows that ropivacaine and bupivacaine cross the human placenta at a similar rate, despite their differences in lipophilicity and stereochemistry. Placental transfer of both compounds is highly influenced by maternal and fetal protein concentration and the fetal pH. IMPLICATIONS: The placental transfer of ropivacaine was shown to be similar to that of bupivacaine, and is thus highly influenced by the degree of maternal and fetal protein binding and fetal pH.

Adult↗
PubMed1997

The pharmacokinetics of epidural lidocaine and bupivacaine during cesarean section.

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.

Adolescent↗
PubMed1997

The placental transfer of sufentanil: effects of fetal pH, protein binding, and sufentanil concentration.

This study investigated factors that influence the placental transfer of sufentanil using the dual-perfused, single-cotyledon human placental model. Placentas were collected from healthy women. Experiments were designed to elucidate the effects of maternal protein binding, changing maternal sufentanil concentration (1, 10, 20, and 100 ng/mL) and decreasing fetal pH (fetal acidemia 7.2, 7.0, 6.8) on the placental transfer of sufentanil. Sufentanil crossed the placenta rapidly at a rate two-thirds that of the transfer marker, antipyrine. Sufentanil transfer increased linearly with the maternal concentration (r = 0.999). Sufentanil/antipyrine maternal to fetal (M-->F) transfer ratios were significantly reduced (0.66 +/- 0.05 vs 0.40 +/- 0.04, P < 0.05) when fresh frozen plasma was added to the maternal circuit to enhance protein binding. Fetal pH and sufentanil transfer were related because sufentanil M-->F clearance increased significantly as the fetal pH decreased (r = 0.973, P < 0.05). Sufentanil appears to cross the placenta by passive diffusion but is modulated by the degree of maternal protein binding. Sufentanil M-->F transfer is enhanced by fetal acidemia.

Adult↗
PubMed1996

Effects of fetal pH on local anesthetic transfer across the human placenta.

BACKGROUND: Fetal acidemia increases umbilical venous bupivacaine concentrations in the in situ rabbit model. The authors studied the effects of decreasing fetal pH on the rate of maternal to fetal (M-->F) clearances of lidocaine, bupivacaine, 2-chloroprocaine, and antipyrine (a nonionic marker of placental transfer) across the isolated, dual perfused, human placental cotyledon. METHODS: Maternal to fetal clearances of bupivacaine, lidocaine, 2-chloroprocaine, and antipyrine were determined at fetal pH (7.4), during progressive fetal acidemia (pH 7.2-->7.0-->6.8), and after recovery to fetal pH 7.4 in experiments with both low protein state and in those with in vivo maternal and fetal protein-binding potentials. RESULTS: Placental transfer of all three agents increased linearly as the fetal pH decreased. Antipyrine transfer was unaffected. Clearance of lidocaine and bupivacaine, but not 2-chloroprocaine, returned to baseline when fetal pH was restored to 7.4. When maternal and fetal protein-binding potentials were increased, clearance at fetal pH 7.4 of bupivacaine, but not lidocaine, decreased significantly. During fetal acidemia, the transfer of both agents increased, but to a lesser extent than in the low protein concentration experiments. CONCLUSIONS: Increasing the pH difference between maternal and fetal perfusates promotes M-->F passage of unionized lidocaine, bupivacaine, and 2-chloroprocaine. This likely results from an increased proportion of ionized local anesthetic in the acidemic fetal perfusate and consequent widening of the M-->F concentration gradient of the unionized form. Transfer of lidocaine and bupivacaine was limited by the maternal protein binding.

Anesthetics, Local↗
PubMed1995

Bupivacaine transfer across the human term placenta. A study using the dual perfused human placental model.

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.

Antipyrine↗
PubMed1993

The transfer of cocaine and its metabolites across the term human placenta.

This study defines human placental transport of cocaine and its two minor, but pharmacologically active, metabolites--norcocaine and cocaethylene. The experimental system was the single, isolated perfused cotyledon of a normal term human placenta, and antipyrine served as a freely diffusible marker. Cocaine was transferred rapidly by the placenta at a rate about 80% that of antipyrine. The transfer had characteristics of passive transport consistent with the high lipid solubility of the drug. We found no evidence of significant placental metabolism of cocaine during its rapid placental transfer. Ethanol did not alter the cocaine transfer rate. Norcocaine and cocaethylene were equally as rapidly transferred. Thus the placenta is no barrier to the transfer of cocaine and its derivatives to the fetus.

Biological Transport↗
PubMed1989

Incidence of venous air embolism during cesarean section is unchanged by the use of a 5 to 10 degree head-up tilt.

One hundred healthy parturients were divided at random into two demographically similar groups and were positioned for cesarean section either horizontally or flexed 5 to 10 degrees head up, with a 15 degrees lateral tilt. A Doppler ultrasound transducer was positioned over the fourth intercostal space parasternally. Initially, two patients received spinal, three general, and 95 epidural anesthesia. Two patients subsequently needed general for failed epidural anesthesia. Changes in Doppler heart tones (greater than 15 sec duration) indicative of venous air embolism (VAE) were identified 15 times in 11 patients--seven in supine and four in head-up patients (no statistically significant difference). Six awake patients (three horizontal, three head-up) developed chest tightness or pain during surgery, but only one episode correlated with VAE. No patient developed breathlessness. Moderate hypotension (greater than 10% decrease in systolic arterial pressure [SAP]) occurred in seven of 11 (63.6%) patients with, and in 26 (29.2%) of 89 patients without, VAE (P less than 0.001). More severe hypotension (SAP less than 90 mm Hg) due to bleeding occurred once. We conclude that a modest (5-10 degrees) head-up position does not influence the occurrence of VAE in patients having cesarean section. An 11% incidence of clinically insignificant VAE, although low, is still worrisome, as even small air bubbles in the circulation are potentially harmful, especially if the foramen ovale is patent. VAE during cesarean section should be anticipated and the anesthetic management planned accordingly.

Adult↗
PubMed1987

Intravenous cannula fixing and dressing--comparison between the use of transparent polyurethane dressing and conventional technique.

A sterile, disposable, polyurethane intravenous catheter dressing (OpSite; Smith & Nephew), was compared with a conventional dressing for both convenience and cost. Despite lack of familiarity, the use of OpSite proved as easy and acceptable as the traditional non-sterile control method. OpSite was also as durable and would appear, on calculation, to be cheaper when intravenous therapy lasts longer than a day. OpSite is therefore recommended as the intravenous dressing of choice. Its use, or that of a similar sterile disposable product, should be considered mandatory for paediatric and other patients in whom sterility is vital, and in situations where intravenous infusion will continue for more than 24 hours.

Antisepsis↗
PubMed1987

Maternal deaths from neurological complications of hypertensive crises in pregnancy.

Fourteen maternal deaths from eclampsia or severe pre-eclampsia where disturbed cerebral function, as evidenced by prolonged unconsciousness, was given as the main cause of death are reviewed. Prolonged duration of seizures, hypotensive/hypoxic episodes, cerebral oedema and intracranial haematomas were most frequently identified as causative agents in the development of cerebral dysfunction. Failure to maintain an airway and iatrogenically induced hypotension were the two most important contributory factors to the patients' deaths. Management recommendations to prevent this type of maternal death are given.

Adult↗