Spinal versus general anesthesia in cesarean sections: the effects on postoperative pain perception.

OBJECTIVE: To compare postoperative pain perception and analgesia requirements in patients undergoing cesarean section (CS) using general versus spinal anesthesia. STUDY DESIGN: A prospective, observational study of patients undergoing elective CS during 2009 under either general or spinal anesthesia. Postoperative pain intensity and analgesia requirements were evaluated for up to 48 h after surgery. RESULTS: A total of 153 women were enrolled; 77 received general and 76 received regional anesthesia. Postoperative meperidine requirements in the first 24 h were significantly higher in the general anesthesia group. Pain scores were mostly comparable between the groups. Nevertheless, lower pain scores were graded after 8 h in the general versus the spinal anesthesia and this reversed at 48 h. CONCLUSION: Spinal anesthesia is comparable to general anesthesia in terms of post-operative pain control. In choosing the type of anesthesia in CS, other factors such as the urgency and potential maternal and fetal hazards should be taken into account.

[Joint cartilage lesions caused by quinolones in young animals--can we generalize to children?].

A number of new generation fluoroquinolone antibiotics are currently available for use in hospital and community-based settings. This antibiotic class possesses a broad anti-bacterial spectrum of activity, can be administered orally as well as intravenously, and is, generally, well-tolerated, causing few adverse drug reactions. Lesions in articular cartilage were observed in animal studies conducted in young animals, mostly Beagle dogs and rats. For this reason the use of fluoroquinolones is contraindicated in pregnant women, infants, children and adolescents up to the age of 18 years. Nevertheless, the rate of fluoroquinolone use in children has increased over the last decade. Use of fluoroquinolones has been associated with reversible musculoskeletal events in both children and adults. The putative mechanism of fluoroquinolone damage to articular cartilage is believed to be related to their tendency to form stable complexes with magnesium ions, resulting in decreased concentrations of this ion in cartilage. Magnesium is known to play an essential role in several biochemical processes that take place in cartilage.

Nitrofurantoin transport by placental choriocarcinoma JAr cells: involvement of BCRP, OATP2B1 and other MDR transporters.

OBJECTIVE: To determine the role of BCRP in nitrofurantoin (NF) transport in JAr cells and the possible contribution of OATP2B1, P-gp and MRPs to this transport. METHODS: Cells were incubated with various BCRP, P-gp, MRPs, organic anion transporting polypeptide (OAT) and OATP2B1 inhibitors for 15 min, followed by incubation for 30 min with NF, with or without the inhibitors mentioned earlier. NF cytotoxicity was examined using neutral red (NR) assay. Intracellular NF levels were analyzed by HPLC. RESULTS: NR assay showed that incubation conditions with NF (as carried out in our experiments) were not cytotoxic. Incubation with specific inhibitors of BCRP (FTC, Chrysin and Novobiocin), showed a significant increase in NF accumulation in the cells. Inhibitors of OATP2B1 (EGCG and BSP) had no influence on NF accumulation. Specific inhibitors of P-gp and MRPs (Verapamil and Indomethacin, respectively) also had no influence on NF accumulation in JAr cells. CONCLUSIONS: NF is probably a specific substrate of BCRP, and BCRP has a major active role in NF transport in JAr cells. For the first time, we showed, that P-gp, MRPs, and the OATP2B1, probably have a negligible contribution to NF transport in JAr cells.

Carrier-mediated uptake of Levofloxacin by BeWo cells, a human trophoblast cell line.

OBJECTIVE: Placental transfer of Levofloxacin (LF), a broad spectrum fluoroquinolone antibiotic, and its inhibition was investigated in BeWo cells, a human trophoblast cell line. METHODS: The experiments of LF uptake by BeWo cells were performed after preincubation and in the presence of the P-glycoprotein inhibitors (Cyclosporin A, Verapamil and Quercetin), the organic anion/cation transporter inhibitor (Cimetidine) and the MCT substrates (lactic acid and salicylic acid). RESULTS: P-glycoprotein inhibitors increased the uptake of LF by BeWo cells. The increase in LF accumulation by Cyclosporin A, Verapamil and Quercetin was by 30, 90 and 80%, respectively. Cimetidine, the organic cation inhibitor, increased the transport of LF by 48%. Lactic acid and salicylic acid, the MCT substrates, initially decreased the accumulation of LF by 30% and subsequently increased the uptake of LF by 500 and 53%, respectively. CONCLUSIONS: The uptake of LF by human trophoblast cells is mediated by multiple transporters as well as passive diffusion.

The role of various transporters in the placental uptake of ofloxacin in an in vitro model of human villous trophoblasts.

INTRODUCTION: Six years after the US Food and Drug Administration approval of the broad-spectrum antibiotic ofloxacin (OFLX), the chiral switching of this racemic mixture resulted in a drug composed of the L-optical isomer levofloxacin (LVFX). Since both fluoroquinolones (FQs) were introduced to the pharmaceutical market, they have been widely prescribed by physicians, with careful administration during pregnancy and breastfeeding. Therefore, the role of the influx and efflux placental transporters in the concentrations of these drugs that permeate through human placental barrier model was investigated in this study. METHODS: The contribution of major carriers on the transplacental flux of OFLX and LVFX uptake into choriocarcinoma BeWo cells was evaluated in the presence vs absence of well-known inhibitors. RESULTS: Our results reveal that neither the influx transporters such as organic cation transporters, organic anion transporters, and monocarboxylate transporters nor the efflux transporters such as P-glycoprotein or breast cancer resistance protein significantly affected the transport of OFLX. In contrast, multiple transporters revealed pronounced involvement in the transfer of the levorotatory enantiomer in and out of the in vitro placental barrier. These data suggest a non-carrier-mediated mechanism of transport of the racemic mixture, while LVFX is subjected to major influx and efflux passage through the placental brush border membranes. CONCLUSION: This study provides underlying insights to elucidate the governing factors that influence the flux of these FQs through organ barriers, in view of the controversial safety profile of these drugs in pregnant population.

Transfer of ciprofloxacin, ofloxacin and levofloxacin across the perfused human placenta in vitro.

OBJECTIVE: To investigate the transfer of therapeutically important fluoroquinolones: ciprofloxacin, ofloxacin and levofloxacin, through the isolated perfused human placenta, from the maternal to the fetal compartment. STUDY DESIGN: Isolated placental cotyledons from normal human term placentae were dually perfused with M199 medium enriched with 3g/l bovine serum albumin and 1g/l glucose. Perfusion rates were 12 and 6 ml/min in the maternal and fetal circulation, respectively. Maternal and fetal closed circulation was used to evaluate steady-state concentrations and transplacental gradient formation. Eighteen placentae were used in our study: six for each experiment with ciprofloxacin, ofloxacin and levofloxacin were added to the maternal circulation. Samples were collected from the maternal and fetal compartments. Antipyrine was used as a reference drug that crosses the placenta by simple diffusion. The concentrations of ciprofloxacin, ofloxacin, levofloxacin and antipyrine were measured by specific HPLC (high performance liquid chromatography) methods. Results are presented as mean+/-S.D. RESULTS: In all the placentae, ciprofloxacin, ofloxacin, levofloxacin crossed the placenta from the maternal to the fetal compartment. The mean transplacental transfer percent of ciprofloxacin was 3.2+/-0.7% and the transplacental transfer index, the ratio of transplacental transfer between ciprofloxacin and antipyrine was 0.34+/-0.12. The mean transplacental transfer percent of ofloxacin was 3.7+/-2.4% and the transplacental transfer index was 0.33+/-0.3. The mean transplacental transfer percent of levofloxacin was 3.9+/-1.5% and the transplacental transfer index was 0.34+/-0.2. CONCLUSIONS: Only a small fraction of ciprofloxacin, ofloxacin and levofloxacin passed from the maternal to the fetal compartment. This fraction is significantly smaller compared to antipyrine. This may indicate that there is a barrier to the transport of fluoroquinolones in human placenta.

Transfer of insulin lispro across the human placenta.

Our in vitro perfusion study confirms the result of the Boskovic et al., that insulin lispo is not crossing the human placental membranes at low concentrations. In our study maternal steady state concentration reached 48 +/- microU in the maternal artery and 28 +/- 1 microU in the maternal vein, while in the fetal site insulin lispo was not detected. However, the concentration of insulin lispo in placental tissue was 1836 +/- 220 microU.

Preoperative analgesia with local lidocaine infiltration for post cesarean delivery pain management.

OBJECTIVE: To evaluate the impact of local lidocaine incision-site injection in patients undergoing cesarean deliveries (CD), on post operative pain and analgesic requirements. STUDY DESIGN: In this prospective, double-blinded, placebo-controlled study, patients undergoing elective CD were randomly assigned to receive 1% lidocaine solution or placebo to the incision site, prior to the performance of a Pfannenstiel incision. Pain intensity was evaluated for up to 48 hours after surgery and analgesic requirements of the patients were recorded. RESULTS: During the study period, 153 patients were enrolled; 77 received pre-emptive analgesia with lidocaine and 76 received a placebo. No significant differences were noted between the groups in respect to parity, previous CD, maternal age and gestational age. Pain scores or requirements of analgesia did not differ between the groups. CONCLUSION: Pre-emptive analgesia with local incision-site injection with lidocaine does not seem beneficial in reducing post cesarean pain scores and analgesic requirements.

A randomized, double-blind, placebo-controlled trial of selective digestive decontamination using oral gentamicin and oral polymyxin E for eradication of carbapenem-resistant Klebsiella pneumoniae carriage.

OBJECTIVE: To assess the effectiveness of selective digestive decontamination (SDD) for eradicating carbapenem-resistant Klebsiella pneumoniae (CRKP) oropharyngeal and gastrointestinal carriage. DESIGN: A randomized, double-blind, placebo-controlled trial with 7 weeks of follow-up per patient. SETTING: A 1,000-bed tertiary-care university hospital. PATIENTS: Adults with CRKP-positive rectal swab cultures. METHODS: Patients were blindly randomized (1 :1) over a 20-month period. The SDD arm received oral gentamicin and polymyxin E gel (0.5 g 4 times per day) and oral solutions of gentamicin (80 mg 4 times per day) and polymyxin E (1 x 10(6) units 4 times per day for 7 days). The placebo arm received oral placebo gel 4 times per day and 2 placebo oral solutions 4 times per day for 7 days. Strict contact precautions were applied. Samples obtained from the throat, groin, and urine were also cultured. RESULTS: Forty patients (mean age ± standard deviation, 71 ± 16 years; 65% male) were included. At screening, greater than or equal to 30% of oropharyngeal, greater than or equal to 60% of skin, and greater than or equal to 35% of urine cultures yielded CRKP isolates. All throat cultures became negative in the SDD arm after 3 days (P < .0001). The percentages of rectal cultures that were positive for CRKP were significantly reduced at 2 weeks. At that time, 16.1% of rectal cultures in the placebo arm and 61.1% in the SDD arm were negative (odds ratio, 0.13; 95% confidence interval, 0.02-0.74; P < .0016). A difference between the percentages in the 2 arms was still maintained at 6 weeks (33.3% vs 58.5%). Groin colonization prevalence did not change in either arm, and the prevalence of urine colonization increased in the placebo arm. CONCLUSIONS: This SDD regimen could be a suitable decolonization therapy for selected patients colonized with CRKP, such as transplant recipients or immunocompromised patients pending chemotherapy and patients who require major intestinal or oropharyngeal surgery. Moreover, in outbreaks caused by CRKP infections that are uncontrolled by routine infection control measures, SDD could provide additional infection containment.