Gut microbiota dysbiosis contributes to depression-like behaviors via hippocampal NLRP3-mediated neuroinflammation in a postpartum depression mouse model.

Postpartum depression (PPD) is a severe mental disorder that affects approximately 10---20% of women after childbirth. The precise mechanism underlying PPD pathogenesis remains elusive, thus limiting the development of therapeutics. Gut microbiota dysbiosis is considered to contribute to major depressive disorder. However, the associations between gut microbiota and PPD remain unanswered. Here, we established a mouse PPD model by sudden ovarian steroid withdrawal after hormone-simulated pseudopregnancy-human (HSP-H) in ovariectomy (OVX) mouse. Ovarian hormone withdrawal induced depression-like and anxiety-like behaviors and an altered gut microbiota composition. Fecal microbiota transplantation (FMT) from PPD mice to antibiotic cocktail-treated mice induced depression-like and anxiety-like behaviors and neuropathological changes in the hippocampus of the recipient mice. FMT from healthy mice to PPD mice attenuated the depression-like and anxiety-like behaviors as well as the inflammation mediated by the NOD-like receptor protein (NLRP)-3/caspase-1 signaling pathway both in the gut and the hippocampus, increased fecal short-chain fatty acids (SCFAs) levels and alleviated gut dysbiosis with increased SCFA-producing bacteria and reduced Akkermansia in the PPD mice. Also, downregulation of NLRP3 in the hippocampus mitigated depression-like behaviors in PPD mice and overexpression of NLRP3 in the hippocampal dentate gyrus induced depression-like behaviors in naïve female mice. Intriguingly, FMT from healthy mice failed to alleviate depression-like behaviors in PPD mice with NLRP3 overexpression in the hippocampus. Our results highlighted the NLRP3 inflammasome as a key component within the microbiota-gut-brain axis, suggesting that targeting the gut microbiota may be a therapeutic strategy for PPD.

Ncf1 knockout in SMCs exacerbates angiotensin II-induced aortic aneurysm and dissection by activating the STING pathway.

AIMS: Aortic aneurysm and dissection (AAD) is caused by the progressive loss of aortic smooth muscle cells (SMCs) and is associated with a high mortality rate. Identifying the mechanisms underlying SMC apoptosis is crucial for preventing AAD. Neutrophil cytoplasmic factor 1 (Ncf1) is essential in reactive oxygen species (ROS) production and SMC apoptosis; Ncf1 absence leads to autoimmune diseases and chronic inflammation. Here, the role of Ncf1 in angiotensin II (Ang II)-induced AAD was investigated. METHODS AND RESULTS: Ncf1 expression increased in injured SMCs. Bioinformatics analysis identified Ncf1 as a mediator of AAD-associated SMC damage. Ncf1 expression is positively correlated with DNA replication and repair in SMCs of AAD aortas. AAD incidence increased in Ang II-challenged Sm22CreNcf1fl mice. Transcriptomics showed that Ncf1 knockout activated the stimulator of interferon genes (STING) and cell death pathways. The effects of Ncf1 on SMC death and the STING pathway in vitro were examined. Ncf1 regulated the hydrogen peroxide-mediated activation of the STING pathway and inhibited SMC apoptosis. Mechanistically, Ncf1 knockout promoted the ubiquitination of nuclear factor erythroid 2-related factor 2 (NRF2), thereby inhibiting the negative regulatory effect of NRF2 on the stability of STING mRNA and ultimately promoting STING expression. Additionally, the pharmacological inhibition of STING activation prevented AAD progression. CONCLUSIONS: Ncf1 deficiency in SMCs exacerbated Ang II-induced AAD by promoting NRF2 ubiquitination and degradation and activating the STING pathway. These data suggest that Ncf1 may be a potential therapeutic target for AAD treatment.

Tunable Phonon Polariton Hybridization in a van der Waals Hetero-Bicrystal.

Phonon polaritons, the hybrid quasiparticles resulting from the coupling of photons and lattice vibrations, have gained significant attention in the field of layered van der Waals heterostructures. Particular interest has been paid to hetero-bicrystals composed of molybdenum oxide (MoO3) and hexagonal boron nitride (hBN), which feature polariton dispersion tailorable via avoided polariton mode crossings. In this work, we systematically study the polariton eigenmodes in MoO3-hBN hetero-bicrystals self-assembled on ultrasmooth gold using synchrotron infrared nanospectroscopy. We experimentally demonstrate that the spectral gap in bicrystal dispersion and corresponding regimes of negative refraction can be tuned by material layer thickness, and we quantitatively match these results with a simple analytic model. We also investigate polaritonic cavity modes and polariton propagation along "forbidden" directions in our microscale bicrystals, which arise from the finite in-plane dimension of the synthesized MoO3 micro-ribbons. Our findings shed light on the unique dispersion properties of polaritons in van der Waals heterostructures and pave the way for applications leveraging deeply sub-wavelength mid-infrared light matter interactions. This article is protected by copyright. All rights reserved.

Optimal flow of high-flow nasal cannula oxygenation to prevent desaturation during sedation for bronchoscopy: a randomized controlled study.

BACKGROUND: Although high-flow nasal cannula (HFNC) oxygenation is currently recommended to prevent desaturation during sedation for bronchoscopy, there is no consensus on an optimal flow rate. OBJECTIVE: To determine the optimal oxygen flow rate for HFNC to effectively prevent desaturation during sedation for bronchoscopy. DESIGN: Prospective, randomized, and controlled study. METHODS: Patients (n = 240) scheduled for bronchoscopy were randomized to receive HFNC with propofol sedation (fraction of inspired oxygen, 100%) at one of six flow rates of 10, 20, 30, 40, 50, and 60 L/min, designated as groups 1-6, respectively. RESULTS: The incidence of desaturation significantly decreased by increasing the oxygen flow rate (42.5%, 17.5%, 15%, 10%, 2.5%, and 0% for groups 1-6, respectively, p < 0.0001). The optimal oxygen flow rate for HFNC determined by probit regression to effectively prevent desaturation in 95% of patients was 43.20 (95% confidence interval, 36.43-55.96) L/min. The requirement for airway intervention was significantly decreased by increasing the oxygen flow rate. CONCLUSION: An HFNC flow rate of 50-60 L/min is recommended to prevent desaturation during sedation for bronchoscopy. REGISTRATION: NCT05298319 at ClinicalTrials.gov.

High-flow nasal cannula oxygenation during bronchoscopyMany patients undergo a special test to check their airways for problems. Sometimes, doctors need to take out a small part of the area that's causing trouble to find out what's wrong. But during this test, some patients can struggle to get enough oxygen, which can even be life-threatening. To help with this, there's a device called a high-flow nasal cannula (HFNC). It gives patients adjustable amounts of oxygen, like a gentle breeze into their nose. But doctors weren't sure how much oxygen was best during this test. So, we studied 240 patients using HFNC at different oxygen levels­like slow, medium, and fast flows. We found that the higher the oxygen flow, the less likely patients were to have oxygen problems. For example, at the lowest flow (10 liters per minute), about 42.5% of patients had oxygen trouble, but at the highest flow (60 liters per minute), none did. And we figured out that a flow rate around 43.2 liters per minute would prevent 95% patients from having oxygen problems. So, we recommend using a flow rate between 50 and 60 liters per minute during this test to keep patients safe from oxygen issues.

Effect of Remimazolam Supplementation on Propofol Requirements During Hysteroscopy: A Double-Blind, Dose-Response Study.

BACKGROUND: Propofol is commonly used for procedural sedation but may increase side effects in a dose-dependent manner. Remimazolam, an ultrashort-acting benzodiazepine, has been approved for procedural sedation but may delay awakening. This study tested the hypothesis that remimazolam as a supplement reduces effect-site propofol concentration (Ceprop) required to suppress response to cervical dilation in patients undergoing hysteroscopy. METHODS: One hundred and fifty patients who were scheduled for hysteroscopy were randomized to receive 0, 0.05, 0.1, 0.15, or 0.2 mg·kg-1 intravenous remimazolam, followed by a bolus of sufentanil 0.15 µg⋅kg-1, and a target-controlled propofol infusion. The initial target Ceprop was 3.5 µg·mL-1 and was increased or decreased in subsequent patients by steps of 0.5 µg·mL-1 according to whether there was loss of response to cervical dilation in the previous patient. We used up-down sequential analysis to determine values of Ceprop that suppressed response to cervical dilation in 50% of patients (EC50). RESULTS: The EC50 of propofol for suppressing response to cervical dilation was lower in patients given 0.1 mg·kg-1 (2.08 [95% confidence interval, CI, 1.88-2.28] µg·mL-1), 0.15 mg⋅kg-1 (1.83 [1.56-2.10] µg·mL-1), and 0.2 mg⋅kg-1 (1.43 [1.27-1.58] µg·mL-1) remimazolam than those given 0 mg⋅kg-1 (3.67 [3.49-3.86] µg·mL-1) or 0.05 mg⋅kg-1 (3.47 [3.28-3.67] µg·mL-1) remimazolam (all were P < .005). Remimazolam at doses of 0.1, 0.15, and 0.2 mg·kg-1 decreased EC50 of propofol by 43.3% (95% CI, 41.3%-45.5%), 50.3% (48.0%-52.8%), and 61.2% (58.7%-63.8%), respectively, from baseline (remimazolam 0 mg⋅kg-1). Propofol consumption was lower in patients given 0.1 mg⋅kg-1 (4.15 [3.51-5.44] mg·kg-1), 0.15 mg⋅kg-1 (3.54 [3.16-4.46] mg·kg-1), and 0.2 mg⋅kg-1 (2.74 [1.73-4.01] mg·kg-1) remimazolam than those given 0 mg⋅kg-1 (6.09 [4.99-7.35] mg·kg-1) remimazolam (all were P < .005). Time to anesthesia emergence did not differ significantly among the 5 groups. CONCLUSIONS: For women undergoing hysteroscopic procedures, remimazolam at doses from 0.1 to 0.2 mg·kg-1 reduced the EC50 of propofol inhibiting response to cervical dilation and the total propofol requirement. Whether the combination could improve perioperative outcomes deserves further investigation.

Off-pump versus on-pump coronary artery bypass grafting in elderly patients at 30 days: a propensity score matching study.

BACKGROUND: Elderly patients are at increased risk of perioperative morbidity and mortality after conventional on-pump coronary artery bypass grafting (ONCABG). This study was to determine whether such high-risk population would benefit from off-pump coronary artery bypass grafting (OPCABG). METHODS: A retrospective analysis was performed on patients aged 65 years or older who underwent isolated coronary artery bypass grafting for the first time in Wuhan Union Hospital from January 2015 to January 2021. We used propensity score matching to adjust for differences in baseline characteristics between the ONCABG and OPCABG groups. Morbidity and mortality within 30 days after surgery were compared between the two groups. All operations were performed by experienced cardiac surgeons. RESULTS: A total of 511 patients (ONCABG 202, OPCABG 309) were included. After 1:1 matching, the baseline characteristics of the two groups were comparable (ONCABG 173, OPCABG 173). The OPCABG group had higher rate of incomplete revascularization (13.9% vs. 6.9%; P = .035) than the ONCABG group. However, OPCABG reduced the risk of postoperative renal insufficiency (15.0% vs. 30.1%; P = .001) and reoperation for bleeding (0.0% vs. 3.5%; P = .030). There were no significant differences in early postoperative mortality, myocardial infarction, stroke, and other outcomes between the two groups. CONCLUSIONS: OPCABG is an alternative revascularization method for elderly patients. It reduces the risk of early postoperative renal insufficiency and reoperation for bleeding.

Accelerated Nano-Optical Imaging through Sparse Sampling.

The integration time and signal-to-noise ratio are inextricably linked when performing scanning probe microscopy based on raster scanning. This often yields a large lower bound on the measurement time, for example, in nano-optical imaging experiments performed using a scanning near-field optical microscope (SNOM). Here, we utilize sparse scanning augmented with Gaussian process regression to bypass the time constraint. We apply this approach to image charge-transfer polaritons in graphene residing on ruthenium trichloride (α-RuCl3) and obtain key features such as polariton damping and dispersion. Critically, nano-optical SNOM imaging data obtained via sparse sampling are in good agreement with those extracted from traditional raster scans but require 11 times fewer sampled points. As a result, Gaussian process-aided sparse spiral scans offer a major decrease in scanning time.

Neuron-derived exosomes mediate sevoflurane-induced neurotoxicity in neonatal mice via transferring lncRNA Gas5 and promoting M1 polarization of microglia.

Sevoflurane exposure during rapid brain development induces neuronal apoptosis and causes memory and cognitive deficits in neonatal mice. Exosomes that transfer genetic materials including long non-coding RNAs (lncRNAs) between cells play a critical role in intercellular communication. However, the lncRNAs found in exosomes derived from neurons treated with sevoflurane and their potential role in promoting neurotoxicity remain unknown. In this study, we investigated the role of cross-talk of newborn mouse neurons with microglial cells in sevoflurane-induced neurotoxicity. Mouse hippocampal neuronal HT22 cells were exposed to sevoflurane, and then co-cultured with BV2 microglial cells. We showed that sevoflurane treatment markedly increased the expression of the lncRNA growth arrest-specific 5 (Gas5) in neuron-derived extracellular vesicles, which inhibited neuronal proliferation and induced neuronal apoptosis by promoting M1 polarization of microglia and the release of inflammatory cytokines. We further revealed that the exosomal lncRNA Gas5 significantly upregulated Foxo3 as a competitive endogenous RNA of miR-212-3p in BV2 cells, and activated the NF-κB pathway to promote M1 microglial polarization and the secretion of inflammatory cytokines, thereby exacerbating neuronal damage. In neonatal mice, intracranial injection of the exosomes derived from sevoflurane-treated neurons into the bilateral hippocampi significantly increased the proportion of M1 microglia, inhibited neuronal proliferation and promoted apoptosis, ultimately leading to neurotoxicity. Similar results were observed in vitro in BV2 cells treated with the CM from HT22 cells after sevoflurane exposure. We conclude that sevoflurane induces the transfer of lncRNA Gas5-containing exosomes from neurons, which in turn regulates the M1 polarization of microglia and contributes to neurotoxicity. Thus, modulating the expression of lncRNA Gas5 or the secretion of exosomes could be a strategy for addressing sevoflurane-induced neurotoxicity.

Propofol EC50 for inducing loss of consciousness in patients under combined epidural-general anesthesia or general anesthesia alone: a randomized double-blind study.

Background: Combined epidural-general anesthesia (GA + EA) has been recommended as a preferred technique for both thoracic and abdominal surgery. The epidural anesthesia on the general anesthetic (GA) requirements has not been well investigated. Therefore, we conducted the present study to explore the predicted effect-site concentration of propofol (Ceprop) required for achieving the loss of consciousness (LOC) in 50% of patients (EC50) with or without epidural anesthesia. Methods: Sixty patients scheduled for gastrectomy were randomized into the GA + EA group or GA alone group to receive general anesthesia alone. Ropivacaine 0.375% was used for epidural anesthesia to achieve a sensory level of T4 or above prior to the induction of general anesthesia. The EC50 of predicted Ceprop for LOC was determined by the up-down sequential method. The consumption of anesthetics, emergence time from anesthesia, and postoperative outcomes were also recorded and compared. Results: The EC50 of predicted Ceprop for LOC was lower in the GA + EA group than in the GA alone group [2.97 (95% CI: 2.63-3.31) vs. 3.36 (95% CI: 3.19-3.53) µg mL-1, (p = 0.036)]. The consumption of anesthetics was lower in the GA + EA group than in the GA alone group (propofol: 0.11 ± 0.02 vs. 0.13 ± 0.02 mg kg-1 min-1, p = 0.014; remifentanil: 0.08 ± 0.03 vs. 0.14 ± 0.04 µg kg-1 min-1, p < 0.001). The emergence time was shorter in the GA + EA group than in the GA alone group (16.0 vs. 20.5 min, p = 0.013). Conclusion: Concomitant epidural anesthesia reduced by 15% the EC50 of predicted Ceprop for LOC, decreased the consumptions of propofol and remifentanil during maintenance of anesthesia, and fastened recovery from anesthesia. Clinical trial registration: ClinicalTrials.gov, identifier: NCT05124704.

Visualizing moiré ferroelectricity via plasmons and nano-photocurrent in graphene/twisted-WSe2 structures.

Ferroelectricity, a spontaneous and reversible electric polarization, is found in certain classes of van der Waals (vdW) materials. The discovery of ferroelectricity in twisted vdW layers provides new opportunities to engineer spatially dependent electric and optical properties associated with the configuration of moiré superlattice domains and the network of domain walls. Here, we employ near-field infrared nano-imaging and nano-photocurrent measurements to study ferroelectricity in minimally twisted WSe2. The ferroelectric domains are visualized through the imaging of the plasmonic response in a graphene monolayer adjacent to the moiré WSe2 bilayers. Specifically, we find that the ferroelectric polarization in moiré domains is imprinted on the plasmonic response of the graphene. Complementary nano-photocurrent measurements demonstrate that the optoelectronic properties of graphene are also modulated by the proximal ferroelectric domains. Our approach represents an alternative strategy for studying moiré ferroelectricity at native length scales and opens promising prospects for (opto)electronic devices.

Infrared nano-imaging of Dirac magnetoexcitons in graphene.

Magnetic fields can have profound effects on the motion of electrons in quantum materials. Two-dimensional electron systems subject to strong magnetic fields are expected to exhibit quantized Hall conductivity, chiral edge currents and distinctive collective modes referred to as magnetoplasmons and magnetoexcitons. Generating these propagating collective modes in charge-neutral samples and imaging them at their native nanometre length scales have thus far been experimentally elusive. Here we visualize propagating magnetoexciton polaritons at their native length scales and report their magnetic-field-tunable dispersion in near-charge-neutral graphene. Imaging these collective modes and their associated nano-electro-optical responses allows us to identify polariton-modulated optical and photo-thermal electric effects at the sample edges, which are the most pronounced near charge neutrality. Our work is enabled by innovations in cryogenic near-field optical microscopy techniques that allow for the nano-imaging of the near-field responses of two-dimensional materials under magnetic fields up to 7 T. This nano-magneto-optics approach allows us to explore and manipulate magnetopolaritons in specimens with low carrier doping via harnessing high magnetic fields.

Comparison of Dural Puncture Epidural, Epidural and Combined Spinal-Epidural Anesthesia for Cesarean Delivery: A Randomized Controlled Trial.

Purpose: Catheter-based techniques such as combined spinal-epidural (CSE) anesthesia which are sometimes indicated for obstetric anesthesia have a complex mechanism of action. The application of the dural puncture epidural (DPE) anesthesia for cesarean section (CS) has not been well investigated. The present study compared the relatively novel DPE technique with epidural (EA) and CSE anesthesia. Patients and Methods: We randomly assigned 150 parturients who underwent elective CS to receive DPE, EA or CSE anesthesia. The primary outcome was the onset of sensory anesthesia to the T5 dermatome assessed using the Cox proportional hazards model. Secondary outcomes included median time to sensory block, quality of block, patient and surgeon satisfaction, APGAR scores and other side effects. Results: For DPE anesthesia versus EA anesthesia, the onset of anesthesia was faster (hazard ratio 2.47 [95% CI 1.56 to 3.90], adjusted P < 0.001) and the median time to surgical level was shorter (16 [IQR 14-18] min versus 19 [15.5-21] min, adjusted P < 0.001); the incidence of intraoperative pain was lower (7/48 versus 17/47, adjusted P = 0.046) and the median patient satisfaction score was higher (9 [IQR 9-10] versus 8 [8-9.5], adjusted P = 0.004). In the CSE group, the onset of anesthesia was faster than in the other two but the incidence of hypotension was higher (P < 0.001) and the phenylephrine requirement was greater (P < 0.001). Conclusion: DPE anesthesia had a faster onset and better quality of block than EA anesthesia and provided less influence to maternal hemodynamic parameters than CSE anesthesia for CS. These results suggest that the dural puncture plays a significant role in enhancing the effectiveness of epidural top-ups during CSE anesthesia and indicates enlightenment that contributes to the satisfaction of anesthetic effect in DPE technique labor analgesia transferred to CS.

Development and validation of an artificial neural network prediction model for postpartum hemorrhage with placenta previa.

BACKGROUND: Postpartum hemorrhage (PPH) is a leading cause of maternal morbidity worldwide and placenta previa is one of the major risk factors for PPH in overall population. However, the clinical prediction of PPH remains challenging. This study aimed to investigate an ideal machine learning-based prediction model for PPH in placenta previa parturients with cesarean section. METHODS: The clinical data of 223 placenta previa parturients who underwent cesarean delivery in our hospital from 2016 to 2019 were retrospectively collected for analysis. An artificial neural network model was designed to predict PPH, defined as blood loss exceeding 1000 mL with 24h after delivery. Twenty clinical variables were selected as predictors. We also applied six conventional machine learning methods as reference models, including support vector machine, decision tree, random forest, gradient boosting decision tree, adaboost and logistic regression. All the models were validated using 5-fold cross-validation. The area under the receiver operating characteristic curve (AUC), precision, recall and the prediction accuracy of each model were reported. RESULTS: A total of 223 pregnant women were enrolled in this study, including 101 cases (45.29%) experienced PPH. The proposed model achieved superior prediction performance with an AUC of 0.917, an accuracy of 0.851, a precision score of 0.829 and a recall score of 0.851, which outperformed other six conventional machine learning methods. CONCLUSIONS: Compared to the conventional machine learning approaches, artificial neural network model shows discriminative ability in identifying women's risk of PPH with placenta previa during cesarean section.

Determination of the 50% and 95% Effective Dose of Remimazolam Combined with Propofol for Intravenous Sedation During Day-Surgery Hysteroscopy.

Purpose: Remimazolam has demonstrated the potential as a valuable medication for procedural sedation. However, there were some shortcomings for higher doses of remimazolam during hysteroscopy in spite of less frequent adverse events. The aim of this study was to find the 50% and 95% effective dose (ED50 and ED95) of remimazolam when combined with propofol for intravenous sedation during day-surgery hysteroscopy. Patients and Methods: Patients were randomly assigned evenly (20 per group) to one of five different dosage of remimazolam: group A (0.05mg/kg), group B (0.075mg/kg), group C (0.1mg/kg), group D (0.125mg/kg) or group E (0.15mg/kg). Intravenous injection of sufentanil 0.1µg/kg was administered before sedative medication. Intravenous anesthesia was commenced with remimazolam. Subsequently, propofol was administered at 1mg/kg and maintained at 6mg/kg/h. Success was defined when the patient did not move during cervical dilation, had sufficient sedation as judged by SE <60 and no requirement for rescue doses. The success rate, induce and average dosage of propofol, the induction time, total surgery time, recovery time, and adverse events were recorded. Estimate of ED50 and ED95 with 95% confidence interval (CI) was performed by probit regression. Results: The mean (95% CI) values for ED50 and ED95 of remimazolam in patients were 0.09 (0.08-0.11) mg/kg and 0.21 (0.16-0.35) mg/kg, respectively. There was no difference in the induction time, total surgery time, and recovery time among groups. No serious adverse events occurred in all patients. Conclusion: The dose-response effects of remimazolam were evaluated for intravenous sedation during hysteroscopy. A combination of remimazolam and propofol was recommended to produce stabler sedation, reduce the total dosage and have less effect on cardiovascular and respiratory depression.

Distinguishing preeclampsia using the falling scaled slope (FSS) --- a novel photoplethysmographic morphological parameter.

BACKGROUND: Preeclampsia (PE) presence could lead to hemodynamic changes. Previous research suggested that morphological parameters based on photoplethysmographic pulse waves (PPGW) could help diagnose PE. AIM: To investigate the performance of a novel PPGPW-based parameter, falling scaled slope (FSS), in distinguishing PE. To investigate the advantages of the machine learning algorithm over the conventional statistical methods in the analysis. METHODS: Eighty-one pieces of PPGPW data were acquired for the study (PE, n = 44; normotensive, n = 37). The FSS values were calculated and used to construct a PE classifier using the K-nearest neighbors (KNN) algorithm. A predicted PE state varying from 0 to 1 was also calculated. The classifier's performance in distinguishing PE was evaluated using the ROC and AUC. A comparison was conducted with previously published PPGPW-based models. RESULT: Compared to the previous PPGPW-based parameters, FSS showed a better performance in distinguishing PE with an AUC value of 0.924, the best threshold of 0.498 could predict PE with a sensitivity of 84.1% and a specificity of 89.2%. As for the analysis method, training a classifier using the KNN algorithm had an advantage over the conventional statistical methods with the AUC values of 0.878 and 0.749, respectively. CONCLUSION: The result indicated that FSS might be an effective tool for identifying PE. Moreover, the machine learning algorithm could further help the data analysis and improve performance. [Figure: see text].

Determination of the Optimal Volume of Programmed Intermittent Epidural Bolus When Combined With the Dural Puncture Epidural Technique for Labor Analgesia: A Random-Allocation Graded Dose-Response Study.

BACKGROUND: The dural puncture epidural (DPE) and the programmed intermittent epidural bolus (PIEB) techniques are recent innovations for labor analgesia. The optimal volume of PIEB during traditional epidural analgesia has been investigated previously but it is unknown whether these findings are applicable to DPE. This study aimed to determine the optimal volume of PIEB for effective labor analgesia after initiation of analgesia using DPE. METHODS: Parturients requesting labor analgesia received dural puncture with a 25-gauge Whitacre spinal needle and then had analgesia initiated with 15 mL of ropivacaine 0.1% with sufentanil 0.5 µg/mL. Analgesia was maintained using the same solution delivered by PIEB with boluses given at a fixed interval of 40 minutes starting 1 hour after the completion of the initial epidural dose. Parturients were randomized to 1 of 4 PIEB volume groups: 6, 8, 10, or 12 mL. Effective analgesia was defined as no requirement for a patient-controlled or manual epidural bolus for 6 hours after the completion of the initial epidural dose or until full cervical dilation. The PIEB volumes for effective analgesia in 50% of parturients (EV50) and 90% of parturients (EV90) were determined using probit regression. RESULTS: The proportions of parturients with effective labor analgesia were 32%, 64%, 76%, and 96% in the 6-, 8-, 10-, and 12-mL groups, respectively. The estimated values for EV50 and EV90 were 7.1 (95% confidence interval [CI], 5.9-7.9) mL and 11.3 (95% CI, 9.9-15.2) mL, respectively. There were no differences in side effects, including hypotension, nausea and vomiting, and fetal heart rate (FHR) abnormalities among groups. CONCLUSION: Under the conditions of the study, after initiation of analgesia using DPE, the EV90 of PIEB for effective labor analgesia using ropivacaine 0.1% with sufentanil 0.5 µg/mL was approximately 11.3 mL.

Efficacy and Safety of Esketamine for Supplemental Analgesia During Elective Cesarean Delivery: A Randomized Clinical Trial.

Importance: Epidural anesthesia is a primary choice for cesarean delivery, but supplemental analgesics are often required to relieve pain during uterine traction. Objective: To investigate the sedative and analgesic effects of intravenous esketamine administered before childbirth via cesarean delivery with the patient under epidural anesthesia. Design, Setting, and Participants: This multicenter, double-blind randomized clinical trial assessed 903 women 18 years or older who had full-term single pregnancy and were scheduled for elective cesarean delivery with epidural anesthesia in 5 medical centers in China from September 18, 2021, to September 20, 2022. Intervention: Patients were randomized to receive intravenous injection of 0.25 mg/kg of esketamine or placebo before incision. Main Outcomes and Measures: The coprimary outcomes included scores on the numeric rating scale of pain (an 11-point scale, with 0 indicating no pain and 10 indicating the worst pain; a difference of ≥1.65 points was clinically meaningful) and Ramsay Sedation Scale (a 6-point scale, with 1 indicating restlessness and 6 indicating deep sleep without response; a difference of ≥2 points was clinically meaningful) immediately after fetal delivery. Secondary outcomes included neonatal Apgar score assessed at 1 and 5 minutes after birth. Results: A total of 600 women (mean [SD] age, 30.7 [4.3] years) were enrolled and randomized; all were included in the intention-to-treat analysis. Immediately after fetal delivery, the score on the numeric rating scale of pain was lower with esketamine (median [IQR], 0 [0-1]) than with placebo (median [IQR], 0 [0-2]; median difference, 0; 95% CI, 0-0; P = .001), but the difference was not clinically important. The Ramsay Sedation Scale scores were higher (sedation deeper) with esketamine (median [IQR], 4 [3-4]) than with placebo (median [IQR], 2 [2-2]; median difference, 2; 95% CI, 2-2; P < .001). The neonatal Apgar scores did not differ between the 2 groups at 1 minute (median difference, 0; 95% CI, 0-0; P = .98) and at 5 minutes (median difference, 0; 95% CI, 0-0; P = .27). Transient neurologic or mental symptoms were more common in patients given esketamine (97.7% [293 of 300]) than in those given placebo (4.7% [14 of 300]; P < .001). Conclusions and Relevance: For women undergoing cesarean delivery under epidural anesthesia, a subanesthetic dose of esketamine administered before incision produced transient analgesia and sedation but did not induce significant neonatal depression. Mental symptoms and nystagmus were common but transient. Indications and the optimal dose of esketamine in this patient population need further clarification, but study should be limited to those who require supplemental analgesia. Trial Registration: ClinicalTrials.gov Identifier: NCT04548973.