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BACKGROUND: The obstetric airway is a significant cause of maternal morbidity and mortality. Endotracheal intubation is considered the standard of care but the laryngeal mask airway (LMA) has gained acceptance as a rescue airway and has been incorporated into the obstetric airway management guidelines. In this randomized controlled equivalence trial, we compared the Supreme LMA (SLMA) with endotracheal intubation (ETT) in managing the obstetric airway during cesarean section. METHODS: Parturients who underwent elective cesarean section under general anesthesia were randomized to receive either an SLMA or ETT as their airway device. Our primary outcome was first-attempt insertion success. Successful insertion was defined as adequate bilateral air entry with auscultation and the presence of end-tidal carbon dioxide on the capnogram. The first-attempt insertion success rate was compared using the Chi-Square test. Secondary outcomes included time-to-ventilation, seal pressure, ventilation/hemodynamic parameters, occurrence of clinical aspiration, fetal outcomes, and maternal side effects associated with the airway device. RESULTS: We recruited 920 parturients (460 SLMA, 460 ETT) who underwent elective cesarean section under general anesthesia. Patient characteristics were similar between the groups. First attempt success was similar (Odds Ratio--ORSLMA/ETT: 1.00 (95%CI: 0.25, 4.02), p = 1.0000). SLMA was associated with reduced time to effective ventilation (Mean Difference--MD -22.96; 95%CI: - 23.71, - 22.21 s) compared to ETT group (p < 0.0001). Ventilation parameters, maternal and fetal outcomes were similar between the groups, and there was no aspiration. CONCLUSIONS: SLMA could be an alternative airway management technique for a carefully selected low-risk obstetric population, with similar insertion success rates, reduced time to ventilation and less hemodynamic changes compared with ETT. Our findings are consistent with the airway guidelines in recommending the second-line use of LMA in the management of the obstetric airway. TRIAL REGISTRATION: The study was registered at http://www.clinicaltrials.gov , identifier: NCT01858467 , retrospectively registered. Date of registration: May 21, 2013.
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Anestesia Geral , Cesárea , Intubação Intratraqueal , Máscaras Laríngeas , Adulto , Manuseio das Vias Aéreas , Pressão Sanguínea , Feminino , Frequência Cardíaca , Humanos , Medidas de Volume Pulmonar , Gravidez , Respiração , SístoleRESUMO
BACKGROUND: Obstetric dfficult airway is a leading cause of maternal morbidity and mortality. The laryngeal mask airway (LMA) is often used as a rescue airway device after failed intubation, however, little is known about predictors of difficult LMA insertion, particularly in obstetrics. Since Mallampati scores of III/IV has been associated with difficult tracheal intubation, our present study aims to investigate if Mallampati score (MP) could predict airway outcomes for LMA use in obstetrics. METHODS: This prospective cohort study was performed at a single-center: Quanzhou Women's and Children's Hospital, Fujian Province, China. Five hundred and eighty-four parturients undergoing elective cesarean section under general anesthesia were recruited. The primary outcome was time to effective ventilation, and secondary outcomes included first attempt insertion success, seal pressure, ventilation and hemodynamic parameters, occurrence of clinical aspiration, and maternal and fetal outcomes. RESULTS: The parturients were classified into two groups based on MP of III/IV (High MP: 61) versus I/II (Low MP: 523). BMI was higher in the High MP group than in the Low MP group (mean (SD) 29.3 (7.0) vs 26.8 (3.1), p < 0.0001). There was no difference in maternal age, ASA status and gestational age. There was similar time to effective ventilation (mean (SD) High MP: 14.9 (4.5) vs Low MP: 15.7 (4.4) seconds, p = 0.2172), and first attempt success rate, seal pressure, and peak airway pressure. No clinical aspiration was noted. The incidence of blood on SLMA was higher in the High MP group than in Low MP (4 (6.6%) vs 4 (0.8%), p = 0.001). There was no difference in sore throat, voice hoarseness, maternal satisfaction and fetal outcomes. CONCLUSION: High MP was not associated with reduced SLMA airway outcomes in cesarean section under general anesthesia, but may increase the risk of blood found on SLMA upon removal. TRIAL REGISTRATION: This study was registered at http://www.clinicaltrials.gov , identifier: NCT02026882 , retrospectively registered. Date of registration: December 31, 2013.
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Anestesia Geral , Anestesia Obstétrica , Cesárea , Máscaras Laríngeas , Adulto , Manuseio das Vias Aéreas , Sangue , Pressão Sanguínea , Estudos de Coortes , Contaminação de Equipamentos , Feminino , Humanos , Idade Materna , Análise Multivariada , GravidezRESUMO
BACKGROUND: Childbirth may cause the most severe pain some women experience in their lifetime. Epidural analgesia is an effective form of pain relief during labour and is considered to be the reference standard. Traditionally epidural analgesia has been delivered as a continuous infusion via a catheter in the epidural space, with or without the ability for the patient to supplement the analgesia received by activating a programmable pump to deliver additional top-up doses, known as patient-controlled epidural analgesia (PCEA). There has been interest in delivering maintenance analgesic medication via bolus dosing (automated mandatory bolus - AMB) instead of the traditional continuous basal infusion (BI); recent randomized controlled trials (RCTs) have shown that the AMB technique leads to improved analgesia and maternal satisfaction. OBJECTIVES: To assess the effects of automated mandatory bolus versus basal infusion for maintaining epidural analgesia in labour. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the World Health Organization International Clinial Trials Registry Platform (WHO-ICTRP) and ClinicalTrials.gov on 16 January 2018. We screened the reference lists of all eligible trials and reviews. We also contacted authors of included studies in this field in order to identify unpublished research and trials still underway, and we screened the reference lists of the included articles for potentially relevant articles. SELECTION CRITERIA: We included all RCTs that compared the use of bolus dosing AMB with continuous BI for providing pain relief during epidural analgesia for labour in women. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were: risk of breakthrough pain with the need for anaesthetic intervention; risk of caesarean delivery; risk of instrumental delivery. Secondary outcomes included: duration of labour; local anaesthetic consumption. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included 12 studies with a total of 1121 women. Ten studies enrolled healthy nulliparous women only and two studies enrolled healthy parous women at term as well. All studies excluded women with complicated pregnancies. There were variations in the technique of initiation of epidural analgesia. Seven studies utilized the combined spinal epidural (CSE) technique, and the other five studies only placed an epidural catheter without any intrathecal injection. Seven studies utilized ropivacaine: six with fentanyl and one with sufentanil. Two studies used levobupivacaine: one with sufentanil and one with fentanyl. Three used bupivacaine with or without fentanyl. The overall risk of bias of the studies was low.AMB probably reduces the risk of breakthrough pain compared with BI for maintaining epidural analgesia for labour (from 33% to 20%; risk ratio (RR) 0.60; 95% confidence interval (CI) 0.39 to 0.92, 10 studies, 797 women, moderate-certainty evidence). AMB may make little or no difference to the risk of caesarean delivery compared to BI (15% and 16% respectively; RR 0.92; 95% CI 0.70 to 1.21, 11 studies, 1079 women, low-certainty evidence).AMB may make little or no difference in the risk of instrumental delivery compared to BI (12% and 9% respectively; RR 0.75; 95% CI 0.54 to 1.06, 11 studies, 1079 women, low-certainty evidence). There is probably little or no difference in the mean duration of labour with AMB compared to BI (mean difference (MD) -10.38 min; 95% CI -26.73 to 5.96, 11 studies, 1079 women, moderate-certainty evidence). There is probably a reduction in the hourly consumption of local anaesthetic with AMB compared to BI for maintaining epidural analgesia during labour (MD -1.08 mg/h; 95% CI -1.78 to -0.38, 12 studies, 1121 women, moderate-certainty evidence). Five out of seven studies reported an increase in maternal satisfaction with AMB compared to BI for maintaining epidural analgesia for labour; however, we did not pool these data due to their ordinal nature. Seven studies reported Apgar scores, though there was significant heterogeneity in reporting. None of the studies showed any significant difference between Apgar scores between groups. AUTHORS' CONCLUSIONS: There is predominantly moderate-certainty evidence that AMB is similar to BI for maintaining epidural analgesia for labour for all measured outcomes and may have the benefit of decreasing the risk of breakthrough pain and improving maternal satisfaction while decreasing the amount of local anaesthetic needed.
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Analgesia Epidural/métodos , Analgesia Obstétrica/métodos , Analgesia Controlada pelo Paciente/métodos , Dor do Parto/tratamento farmacológico , Trabalho de Parto , Automação , Feminino , Humanos , Gravidez , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Chronic pain has major adverse effects on health-related quality of life and contributes to significant socioeconomic burden. Hysterectomy is a very common gynecological surgery, resulting in chronic post-hysterectomy pain (CPHP), an important pain syndrome. We conducted a prospective cohort study in 216 Asian women who underwent abdominal or laparoscopic hysterectomy for benign conditions. Demographic, psychological, and perioperative data were recorded. Postoperative 4- and 6-month phone surveys were conducted to assess the presence of CPHP and functional impairment. The incidence rates of CPHP at 4 and 6 months were 32% (56/175) and 15.7% (25/159), respectively. Women with CPHP at 4 and 6 months had pain that interfered with their activities of daily living. Independent association factors for CPHP at 4 months were higher mechanical temporal summation score, higher intraoperative morphine consumption, higher pain score in the recovery room, higher pain score during coughing and itching at 24 hours postoperatively, and preoperative pain in the lower abdominal region. Independent association factors for CPHP at 6 months were preoperative pain during sexual intercourse, higher mechanical temporal summation score, and higher morphine consumption during postoperative 24 and 48 hours. In a majority of cases, CPHP resolved with time, but may have significant impact on activities of daily living.
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BACKGROUND: Hypotension is a common side effect of spinal anaesthesia during caesarean delivery and is associated with maternal and foetal adverse effects. We developed an updated double intravenous vasopressor automated (DIVA) system that administers phenylephrine or ephedrine based on continuous noninvasive haemodynamic monitoring using the Nexfin device. OBJECTIVE: The aim of our present study is to compare the performance and reliability of the DIVA system against Manual Vasopressor Bolus administration. DESIGN: A randomised, double-blind controlled trial. SETTING: Single-centre, KK Women's and Children's Hospital, Singapore. PATIENTS: Two hundred and thirty-six healthy women undergoing elective caesarean delivery under spinal anaesthesia. MAIN OUTCOME MEASURES: The primary outcome was the incidence of maternal hypotension. The secondary outcome measures were reactive hypertension, total vasopressor requirement and maternal and neonatal outcomes. RESULTS: The DIVA group had a significantly lower incidence of maternal hypotension, with 39.3% (46 of 117) patients having any SBP reading less than 80% of baseline compared with 57.5% (65 of 113) in the manual vasopressor bolus group (Pâ=â0.008). The DIVA group also had fewer hypotensive episodes than the manual vasopressor bolus group (4.67 versus 7.77%; Pâ<â0.0001). There was no difference in the incidence of reactive hypertension or the total vasopressor requirement. The DIVA group had less wobble in system performance. Maternal and neonatal outcomes were similar. CONCLUSION: The DIVA system achieved better control of maternal blood pressure after spinal anaesthesia than manual vasopressor bolus administration. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02277730.
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Anestesia Obstétrica/métodos , Raquianestesia/métodos , Cesárea/métodos , Hemodinâmica/efeitos dos fármacos , Vasoconstritores/administração & dosagem , Vasoconstritores/uso terapêutico , Adulto , Algoritmos , Automação , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Cuidados Intraoperatórios , Pessoa de Meia-Idade , Gravidez , Reprodutibilidade dos Testes , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: Uterine fibroids are the most common type of gynaecologic benign tumours, occurring in 25% to 50% of women during their reproductive lives. About half of the affected women have clinically significant symptoms, including abnormal bleeding, menstrual pain, frequent urination, constipation and abdominal distension. Magnetic resonance-guided focused ultrasound surgery (MRgFUS) has been used to treat patients with benign lesions and a variety of malignancies. The objective of this study is to evaluate symptom relief before and after MR-guided ultrasound ablation of fibroids. MATERIALS AND METHODS: A total of 37 patients with symptomatic uterine fibroids were treated in this study. RESULTS: MRgFUS treatment led to a significant, time-dependent decrease in not only Symptom Severity Scores (SSS), but also the mean fibroid volume. The average reductions in volume were 41.6% and 52.6% at 6 months and 12 months respectively (P <0.05). The mean SSS of the 37 patients was 41.7 ± 2.8 before treatment whereas the average SSS was 26.9 ± 3.6, 20.7 ± 3.4, 18.5 ± 3.6, 16.5 ± 7.1, 9.8 ± 3.6 at 3 months, 6 months, 1 year, 2 years, and 3 to 4 years respectively. The decrease in scores was significant at all time points up to 3 to 4 years (P <0.05 and P <0.001). CONCLUSION: MRgFUS is a safe and effective non-invasive treatment for patients with symptomatic fibroids.
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Leiomioma/diagnóstico , Leiomioma/cirurgia , Imageamento por Ressonância Magnética , Cirurgia Assistida por Computador , Ultrassonografia de Intervenção , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/cirurgia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Singapura , Resultado do TratamentoRESUMO
Neurogranin (Ng), a neuronal protein implicated in learning and memory, contains a TATA-less promoter. Analysis of 5'-deletion mutations and site-directed mutations of the mouse Ng promoter revealed that a 258bp 5'-flanking sequence (+3 to +260) conferred the basal transcription activity, and that the GC-rich sequence (+22 to +33) served as an important determinant of the promoter activity. Transient transfection of the Sp1 expression plasmid transactivated the reporter activity in neuroblastoma N2A cells while knocking down of endogenous Sp1 expression resulted in a 2.5-fold reduction of the reporter activity in HEK 293 cells. Exogenous expression of Sp3 in HEK 293 cells, however, repressed the reporter activity by 50%. Nevertheless, by gel shift assays, Sp1 and Sp3 were not found to be responsible for the protein-DNA complexes formed by the GC-rich sequence. Moreover, a nuclear factor from the mouse brain tissues was discovered to bind to multiple AT-rich regions in Ng promoter.
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Composição de Bases/genética , Neurogranina/genética , Fator de Transcrição Sp1/genética , Fator de Transcrição Sp3/genética , Ativação Transcricional/genética , Sequência de Bases , Sítios de Ligação , Linhagem Celular , Humanos , Dados de Sequência Molecular , Ligação ProteicaRESUMO
The modulatory effects of nitric oxide (NO) on voltage-dependent K+ channels are intricate. In our present study, the augmentation and reduction of K+ currents by NO donor S-nitro-N-acetylpenicillamine (SNAP) and pure dissolved NO was observed in dissociated neurons from mice neocortex with both whole cell and cell-attached patch clamp. By using a specific electrochemical sensor, the critical concentrations of NO that increased or reduced the channel activities were accurately quantified. Low concentrations of SNAP (20 microM) or NO solution (0.1 microM) enhanced whole cell delayed rectifier K+ -current (IK) and left the fast inactivating A current (IA) unchanged. However, high concentrations of SNAP (100 microM) and NO (0.5 microM) reduced both IK and IA currents. In cell-attached experiments, a significant increase in channel open probability (NP0) was observed when using low concentrations of SNAP or NO. High concentrations of SNAP or NO dramatically decreased NP0. The increase in channel activities by low concentrations of SNAP was abolished in the presence of either inhibitors of soluble guaylate cyclase or inhibitors of cGMP-dependent protein kinase G, suggesting a link to the NO-cGMP signaling cascade. The reduction of channel activities by high concentrations of SNAP was reversed by the reducing agent dithiothreitol, implying a redox reaction mechanism. Thus both NO-cGMP signaling and a redox mechanism are involved in the modulation of IK channel activity for neuron excitability.
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Canais de Potássio de Retificação Tardia/efeitos dos fármacos , Neocórtex/fisiologia , Neurônios/fisiologia , Óxido Nítrico/farmacologia , Animais , GMP Cíclico/antagonistas & inibidores , GMP Cíclico/fisiologia , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Canais de Potássio de Retificação Tardia/fisiologia , Ditiotreitol/farmacologia , Relação Dose-Resposta a Droga , Eletrofisiologia , Camundongos , Camundongos Endogâmicos , Neocórtex/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Óxido Nítrico/fisiologia , Doadores de Óxido Nítrico/farmacologia , Oxirredução , Técnicas de Patch-Clamp , Potássio/metabolismo , S-Nitroso-N-Acetilpenicilamina/farmacologia , Transdução de Sinais , Superóxidos/farmacologiaRESUMO
In the ionotropic glutamate receptor, the global conformational changes induced by partial agonists are smaller than those induced by full agonists. However, in the pentameric ligand-gated ion channel receptor family, the structural basis of partial agonism is not understood. This study investigated whether full and partial agonists induce different conformation changes in the glycine receptor chloride channel (GlyR). A substituted cysteine accessibility analysis demonstrated previously that glycine binding induced an increase in surface accessibility of all residues from Arg(271) to Lys(276) in the M2-M3 domain of the homomeric alpha1 GlyR. Here we compare the surface accessibility changes induced by the full agonist, glycine, and the partial agonist, taurine. In GlyRs incorporating the A272C, S273C, L274C, or P275C mutation, the reaction rate of the cysteine-specific compound, methanethiosulfonate ethyltrimethylammonium, depended on how strongly the receptors were activated but was agonist-independent. Reaction rates could not be compared in the R271C and K276C mutant GlyRs because methanethiosulfonate ethyltrimethylammonium did not modify the extremely small currents induced by saturating taurine or equivalent low glycine concentrations. The results indicate that bound taurine and glycine molecules impose identical conformational changes to the M2-M3 domain. We therefore conclude that the higher efficacy of glycine is due to an increased ability to stabilize a common activated configuration.