Background The dural puncture epidural technique may improve analgesia quality by confirming midline placement and increasing intrathecal translocation of epidural medications. This would be advantageous in obese parturients with increased risk of block failure. This study hypothesizes that quality of labor analgesia will be improved with dural puncture epidural compared to standard epidural technique in obese parturients. Methods Term parturients with body mass index greater than or equal to 35 kg · m–2, cervical dilation of 2 to 7 cm, and pain score of greater than 4 (where 0 indicates no pain and 10 indicates the worst pain imaginable) were randomized to dural puncture epidural (using 25-gauge Whitacre needle) or standard epidural techniques. Analgesia was initiated with 15 ml of 0.1% ropivacaine with 2 µg · ml–1 fentanyl, followed by programed intermittent boluses (6 ml every 45 min), with patient-controlled epidural analgesia. Parturients were blinded to group allocation. The data were collected by blinded investigators every 3 min for 30 min and then every 2 h until delivery. The primary outcome was a composite of (1) asymmetrical block, (2) epidural top-ups, (3) catheter adjustments, (4) catheter replacement, and (5) failed conversion to regional anesthesia for cesarean delivery. Secondary outcomes included time to a pain score of 1 or less, sensory levels at 30 min, motor block, maximum pain score, patient-controlled epidural analgesia use, epidural medication consumption, duration of second stage of labor, delivery mode, fetal heart tones changes, Apgar scores, maternal adverse events, and satisfaction with analgesia. Results Of 141 parturients randomized, 66 per group were included in the analysis. There were no statistically or clinically significant differences between the dural puncture epidural and standard epidural groups in the primary composite outcome (34 of 66, 52% vs. 32 of 66, 49%; odds ratio, 1.1 [0.5 to 2.4]; P = 0.766), its individual components, or any of the secondary outcomes. Conclusions A lack of differences in quality of labor analgesia between the two techniques in this study does not support routine use of the dural puncture epidural technique in obese parturients. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New
Estrogen promotes the proliferation and migration of vascular endothelial cells (ECs), which likely underlies its ability to accelerate re-endothelialization and reduce adverse remodeling after vascular injury. In previous studies, we have shown that the protective effects of E2 (the active endogenous form of estrogen) in vascular injury require the estrogen receptor alpha (ERα). ERα transduces the effects of estrogen via a classical DNA binding, “genomic” signaling pathway and via a more recently-described “rapid” signaling pathway that is mediated by a subset of ERα localized to the cell membrane. However, which of these pathways mediates the effects of estrogen on endothelial cells is poorly understood. Here we identify a triple point mutant version of ERα (KRR ERα) that is specifically defective in rapid signaling, but is competent to regulate transcription through the “genomic” pathway. We find that in ECs expressing wild type ERα, E2 regulates many genes involved in cell migration and proliferation, promotes EC migration and proliferation, and also blocks the adhesion of monocytes to ECs. ECs expressing KRR mutant ERα, however, lack all of these responses. These observations establish KRR ERα as a novel tool that could greatly facilitate future studies into the vascular and non-vascular functions of ERα rapid signaling. Further, they support that rapid signaling through ERα is essential for many of the transcriptional and physiological responses of ECs to E2, and that ERα rapid signaling in ECs, in vivo, may be critical for the vasculoprotective and anti-inflammatory effects of estrogen.
BACKGROUND: Chloroprocaine is a short-acting local anesthetic that has been used for spinal anesthesia in outpatient surgery. There is limited experience with spinal chloroprocaine for prophylactic cervical cerclage placement. We sought to determine the effective dose of intrathecal chloroprocaine for 90% of patients (ED90) undergoing prophylactic cervical cerclage placement. We hypothesized that the ED90 of intrathecal chloroprocaine when combined with 10-ug fentanyl would be between 33 and 54 mg. METHODS: In this prospective 2-center double-blinded study, we enrolled women undergoing prophylactic cervical cerclage placement under combined spinal-epidural anesthesia. A predetermined dose of intrathecal 3% chloroprocaine with fentanyl 10 ug was administered. The initial dose was 45-mg intrathecal chloroprocaine. Subsequent dose adjustments were determined based on the response of the previous subject using an up-down sequential allocation with a biased-coin design. A dose was considered effective if at least a T12 block was achieved, and there was no requirement for epidural activation or intraoperative analgesic supplementation during the procedure. The primary outcome was the ED90 of intrathecal chloroprocaine with fentanyl 10 ug. Secondary outcomes included duration of surgery, anesthetic side effects, time to resolution of motor and sensory block, time to achieve recovery room discharge criteria, and patient satisfaction with anesthetic care. Isotonic regression was used to estimate the ED90. RESULTS: Forty-seven patients were enrolled into the study. Two patients were excluded (1 protocol violation and 1 failed block). In total, 45 patients completed the study. The estimated ED90 (95% confidence interval) for intrathecal chloroprocaine combined with fentanyl 10 ug was 49.5 mg (45.0-50.1 mg). The median (interquartile range [IQR]) duration of surgery was 15 (10-24) minutes. Resolution of the motor (Bromage 0) and sensory block took a median time of 60 (45-90) minutes and 90 (75-105) minutes, respectively. The median time to achieve recovery room discharge criteria was 150 (139-186) minutes. Satisfaction with anesthetic management was high in all patients. There were no reports of postdural puncture headache or transient neurological symptoms postoperatively CONCLUSIONS: The ED90 of intrathecal chloroprocaine combined with fentanyl 10 ug was 49.5 mg. Intrathecal chloroprocaine was associated with rapid block recovery and high patient satisfaction, which makes it well suited for outpatient obstetric procedures. (Anesth Analg 2022;134:834-42) KEY POINTS• Question: What is the dose of intrathecal chloroprocaine with fentanyl that provides effective anesthesia in 90% of patients (ED90) for elective cervical cerclage placement? • Findings: The estimated ED90 (95% confidence interval) for intrathecal chloroprocaine combined with fentanyl 10 ug was 49.5 (45.0-50.1) mg. • Meaning: This study estimates the dose of intrathecal chloroprocaine that provides effective anesthesia in 90% of women undergoing prophylactic cerv...
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