RESUMO
The management of neurological disorders heavily relies on neurotherapeutic drugs, but notable concerns exist regarding their possible negative effects on reproductive health. Traditional preclinical models often fail to accurately predict reprotoxicity, highlighting the need for more physiologically relevant systems. Organoid models represent a promising approach for concurrently studying neurotoxicity and reprotoxicity, providing insights into the complex interplay between neurotherapeutic drugs and reproductive systems. Herein, we have examined the molecular mechanisms underlying neurotherapeutic drug-induced reprotoxicity and discussed experimental findings from case studies. Additionally, we explore the utility of organoid models in elucidating the reproductive complications of neurodrug exposure. Have discussed the principles of organoid models, highlighting their ability to recapitulate neurodevelopmental processes and simulate drug-induced toxicity in a controlled environment. Challenges and future perspectives in the field have been addressed with a focus on advancing organoid technologies to improve reprotoxicity assessment and enhance drug safety screening. This review underscores the importance of organoid models in unraveling the complex relationship between neurotherapeutic drugs and reproductive health.
RESUMO
Bisphenol A (BPA), a widespread environmental contaminant, poses concerns due to its disruptive effects on physiological functions of the uterine endometrium. In contrast, melatonin (MT) and Resveratrol (RSV) are under scrutiny for their potential protective roles against BPA-induced damage. For the efficacy and ethical concerns in the animal test, endometrial organoids, three-dimensional models mimicking endometrium, serve as crucial tools for unraveling the impact of environmental factors on reproductive health. This study aimed to comprehensively characterize the morphological, molecular and metabolic responses of porcine endometrial organoids to BPA and assess the potential protective effects of MT and RSV. Porcine uteri were prepared, digested with collagenase, mixed with Matrigel, and incubated at 38°C with 5â¯% CO2. Passaging involved dissociation through trypsin-EDTA treatment and subculturing. The culture medium was refreshed every 2-3 days. To investigate the environmental impact on reproductive health, endometrial organoids were treated with BPA (0.5⯵M), MT (with/without BPA at 0.1⯵M), and/or RSV (10⯵M). Various molecular screening using gene expression, western blotting, immunofluorescence staining, and metabolites profiling were assessed the effects of BPA, MT, and RSV in terms of cell viability, morphology, reproductivity, and metabolism alteration in the endometrial organoids. As expected, BPA induced structural and molecular disruptions in organoids, affecting cytoskeletal proteins, Wnt/ß-catenin signaling, and epithelial/mesenchymal markers. It triggered oxidative stress and apoptotic pathways, altered miRNA expression, and disrupted the endocannabinoid system. The level of glucose, galactose, and essential amino acids were increased or decreased by approximately 1.5-3â¯times in BPA-treated groups compared to the control groups (p-value < 0.05), indicating metabolic changes. Moreover, MT and RSV treated groups exhibited protective effects, mitigating BPA-induced disruptions across multiple pathways. For the first time, our study models endometrial organoids, advancing understanding of environmental impacts on reproductive health.
RESUMO
BACKGROUND: Remimazolam is a short-acting benzodiazepine newly approved for the induction and maintenance of general anesthesia. Remimazolam emerges as an ideal drug for the neurosurgical population due to its rapid emergence, enabling early neurological assessment, and its ability to maintain perfusion pressure, which is crucial for preventing cerebral ischemia. However, the use of benzodiazepine has been associated with an increased risk of postoperative delirium (POD). There is currently limited evidence about the relationship between remimazolam-based total intravenous anesthesia (TIVA) and POD. METHODS: In this double-blind, randomized, non-inferiority trial, we plan to include 696 adult patients with American Society of Anesthesiologists physical status class I to III, undergoing elective neurovascular surgery under general anesthesia. After informed consent, the patients will be randomized to receive either remimazolam or propofol-based TIVA with a 1:1 ratio. The primary outcome is the incidence of POD within 5 days after surgery. Secondary outcomes include subtypes, number of positive assessments and severity of POD, emergence agitation, intraoperative awareness and undesirable patient movement, intraoperative hypotension, and postoperative cognitive function. The data will be analyzed in modified intention to treat. DISCUSSION: This trial will evaluate the effect of remimazolam on the development of POD compared to propofol anesthesia. The results of this trial will provide evidence regarding the choice of optimal anesthetics to minimize the risk of POD in neurosurgical patients. TRIAL REGISTRATION: The study protocol was prospectively registered at the Clinical trials ( https://clinicaltrials.gov , NCT06115031, principal investigator: Jiseon Jeong; date of first registration: November 2, 2023, before the recruitment of the first participant.
RESUMO
Dried Blood Spots (DBS) revolutionize therapeutic drug monitoring using LC-MS for the precise quantification of cardiovascular drugs (CDs), enabling personalized treatment adapted to patient-specific pharmacokinetics with minimal invasiveness. This study aims to achieve simultaneous quantification of eight CDs in DBS, overcoming physicochemical challenges. A two-step protein precipitation method was used for simple and precise sample preparation. The drugs were analyzed using LC-MS/MS in ESI positive-ion mode, showing high sensitivity and linearity, with a correlation coefficient (r2) exceeding 0.999, after being separated on a reversed-phase chromatography by gradient elution of DW-acetonitrile containing 0.1 % formic acid + 2 mM ammonium formate. The validation results indicate good selectivity, with no observed matrix effect and carry-over. The intra- and inter-day accuracy and precision were within 6 % for most drugs, except for digoxin and deslanoside at low therapeutic levels where the variation was within 20 %. Stability tests confirmed suitable DBS handling and storage conditions, indicating drug stability for at least 30 days at room temperature. The analysis of whole spot has demonstrated remarkable precision and reliability in all target drugs. The analysis of 3 mm internal diameter discs, punched in and out of DBS, presumed to contain 3 µL of blood, showed acceptable accuracy for most drugs, with less polar drugs like digoxin and deslanoside showing lower accuracy, indicating a need for further correction due to non-uniform drug distribution. Consequently, the developed LC-MS/MS method enables the quantification of multiple CDs in a single DBS analysis, while suggesting the potential for accuracy-based analysis.
Assuntos
Fármacos Cardiovasculares , Teste em Amostras de Sangue Seco , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Teste em Amostras de Sangue Seco/métodos , Humanos , Reprodutibilidade dos Testes , Modelos Lineares , Cromatografia Líquida/métodos , Fármacos Cardiovasculares/sangue , Fármacos Cardiovasculares/farmacocinética , Limite de Detecção , Monitoramento de Medicamentos/métodosRESUMO
This study aims to establish an LC-MS/MS method to simultaneously analyze 11 antiepileptic drugs with a particular focus on maintaining accuracy while reducing the number of isotope-labeled internal standards employed for cost-effectiveness. By applying a water/acetonitrile gradient elution containing 0.1â¯% formic acid and 2â¯mM ammonium formate as the mobile phase, optimal sensitivity for the target drugs could be obtained in positive ESI mode in LC-MS/MS. After optimizing various extraction techniques, extraction with 70â¯% acetonitrile was selected as it provided good recoveries (>93â¯%) for all targets without matrix effects. Accuracies within 3â¯% were achieved from the combination of six internal standards, while accuracies of 5â¯% and 10â¯% were obtained by reducing the number of internal standards to four and two, respectively, for more economical analysis. The accuracy of the established method was maintained in hyperglycemia, hyperlipidemia, and hyperalbuminemia sera, suggesting that it can be successfully applied to individual serum samples with various properties.
Assuntos
Anticonvulsivantes , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Anticonvulsivantes/sangue , Anticonvulsivantes/análise , Humanos , Reprodutibilidade dos Testes , Cromatografia Líquida/métodos , Modelos Lineares , Limite de Detecção , Marcação por Isótopo/métodos , Espectrometria de Massa com Cromatografia LíquidaRESUMO
Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc_1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc_1409 promoted E-cadherin/ß-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/ß-catenin signaling. Our results demonstrate that Amuc_1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health.
Assuntos
Verrucomicrobia , beta Catenina , Masculino , Camundongos , Animais , beta Catenina/metabolismo , Verrucomicrobia/metabolismo , Intestinos , Caderinas/metabolismo , AkkermansiaRESUMO
STUDY OBJECTIVE: To investigate the analgesic efficacy of erector spinae plane block (ESPB) in major gynecologic surgery, expressed as cumulative opioid consumption 24 h after surgery. DESIGN: A single-center, patient-assessor blinded, randomized controlled study. SETTING: Samsung medical center (tertiary university hospital), between February 2022 to January 2023. PATIENTS: Eighty-eight females undergoing major surgery with long midline incision for gynecologic malignancy. INTERVENTIONS: Patients were randomly assigned to receive standard systemic analgesia (Control group) or ESPB (ESPB group). ESPB was performed bilaterally at the level of the 9th thoracic vertebra with a mixture of 20 mL of 0.5% ropivacaine and 100 µg of epinephrine. MEASUREMENTS: The primary outcome was cumulative opioid consumption at 24 h postoperatively. Secondary outcomes included opioid consumption and pain severity during the 72 h after surgery. The variables regarding postoperative recovery and patient-centered outcomes were compared. MAIN RESULTS: The mean cumulative opioid consumption 24 h after surgery was 35.8 mg in the ESPB group, which was not significantly different from 41.4 mg in the control group (mean difference, 5.5 mg; 95% CI -1.7 to 12.8 mg; P = 0.128). However, patient satisfaction regarding analgesia was significantly higher in the ESPB group compared with the control group at 24 h postoperative (median difference, -1; 95% CI -3 to 0; P = 0.038). There were no significant differences in the variables associated with postoperative recovery. CONCLUSION: ESPB did not reduce opioid consumption during the 24 h postoperative but attenuated pain intensity during the early period after surgery.
Assuntos
Analgésicos Opioides , Bloqueio Nervoso , Humanos , Feminino , Analgésicos , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Hospitais Universitários , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Ultrassonografia de IntervençãoRESUMO
In brief: Porcine endometrial organoids (EOs) were isolated and characterized, revealing distinctive features such as unique extracellular matrix formation, fusion into uterine bud-like structures, and facilitation of embryo elongation. The yield of EOs was significantly enhanced by cryopreservation medium supplemented with the rock inhibitor (Y-27632), resulting in reduced expression of apoptotic mRNAs and microRNAs. Abstract: Endometrial organoids (EOs) are acceptable models for understanding maternal-embryonic cross talk. This study was conducted to generate EOs and optimize their cryopreservation and provide coculture modeling with embryos. The endometrial tissues were used for culturing the organoids inside domes of Matrigel®. To improve the long-term storage of EOs, 10 µM ROCK inhibitor (RI) was added to the cryopreservation medium. Day 7 parthenogenetically activated embryos were cocultured with EOs or EO outgrowths, and embryonic cell numbers and embryo attachment were monitored. Spherical EOs 100-300 µm in size can be retrieved on day 7 of culture, and larger EOs, approximately 1.5 mm in diameter, can be maintained in the Matrigel® dome for 21 days. The nuclear expression of Ki67 indicates that more than 80% of EOs nuclei were proliferative. EOs exhibit unique novel characters such as formation of extracellular matrix and ability for fusion. RI increased the yield and quality of organoids after freezing or thawing. The cell number of cocultured embryos increased five-fold, and the proportion of trophoblast outgrowths increased seven-fold compared with those of control embryos. The embryos cultured with EO-conditioned medium showed a better attachment rate than the other models, and - for the first time - we report embryonic elongation. Immunofluorescence staining of the attached embryos showed CDX2 in the periphery of EOs outgrowths. The 3D assembly and cryopreservation of EOs was optimized, and EO coculture supported embryo attachment, trophoblast outgrowth, and elongation, which would provide a valuable tool for studying the intricate processes involved in porcine embryo implantation.
Assuntos
Implantação do Embrião , Quinases Associadas a rho , Animais , Suínos , Trofoblastos , Embrião de Mamíferos , Técnicas de CoculturaRESUMO
We describe the simultaneous quantification of six antiviral drugs in serum based on high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The target drugs-hydroxychloroquine, chloroquine, favipiravir, umifenovir, ritonavir, and lopinavir-were extracted and purified from serum with 75 % v/v methanol as the precipitant reagent. The six analytes were clearly separated within 15 min using gradient elution and mixed-mode stationary phase. The measurement accuracy and precision were assured by adopting isotopes as internal standards. The optimized measurement procedure was strictly validated in linearity, sensitivity, accuracy, and precision. To confirm the robustness of the method in matrix, the method was additionally applied to various types of serum, namely hyperlipidemic and hyperglycemic serum. The method was then applied to assess the stability of the drugs in serum in order to set sample handling and storage guides for laboratory testing. Lastly, the method was implemented in different LC-MS systems to confirm its applicability across similar equipment commonly used in clinical testing laboratories. The overall results show that the optimized protocol is suitable for the accurate, simultaneous quantification of the six antiviral drugs in serum, and it is anticipated to satisfactorily serve as a reference protocol for the analysis of a wide range of other antiviral drugs for drug monitoring with various purposes.
Assuntos
Antivirais , Espectrometria de Massas em Tandem , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Isótopos , Reprodutibilidade dos TestesRESUMO
Oral and laryngeal epithelial lesions are currently diagnosed using histological criteria based on the World Health Organization (WHO) classification, which can cause interobserver variability. An integrated diagnostic approach based on immunohistochemistry (IHC) would aid in the interpretation of ambiguous histological findings of epithelial lesions. In the present study, IHC was used to evaluate the expression of p53 and Ki-67 in 114 cases of oral and laryngeal epithelial lesions in 104 patients. Logistic regression analysis and decision tree algorithm were employed to develop a scoring system and predictive model for differentiating the epithelial lesions. Cohen's kappa coefficient was used to evaluate interobserver variability, and next-generation sequencing (NGS) and IHC were used to compare TP53 mutation and p53 expression patterns. Two expression patterns for p53, namely, diffuse expression type (pattern HI) and null type (pattern LS), and the pattern HI for Ki-67 were significantly associated with high-grade dysplasia (HGD) or squamous cell carcinoma (SqCC). With an accuracy and area under the receiver operating characteristic curve (AUC) of 84.6% and 0.85, respectively, the scoring system based on p53 and Ki-67 expression patterns classified epithelial lesions into two types: non-dysplasia (ND) or low-grade dysplasia (LGD) and SqCC or HGD. The decision tree model constructed using the p53 and Ki-67 expression patterns classified epithelial lesions into ND, LGD, and group 2, including HGD or SqCC, with an accuracy and AUC of 75% and 0.87, respectively. The integrated diagnosis had a better correlation with near perfect agreement (weighted kappa 0.92, unweighted kappa 0.88). The patterns HI and LS for p53 were confirmed to be correlated with missense mutations and nonsense/frameshift mutations, respectively. A predictive model for diagnosis was developed based on the correlation between TP53 mutation and p53 expression patterns. These results indicate that the scoring system based on p53 and Ki-67 expression patterns can differentiate epithelial lesions, especially in cases when the morphological features are ambiguous.
Assuntos
Carcinoma de Células Escamosas , Lesões Pré-Cancerosas , Humanos , Antígeno Ki-67/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/patologia , Carcinoma de Células Escamosas/diagnóstico , HiperplasiaRESUMO
The scalp nerve block, created by injecting local anesthetics around the scalp nerves, is reported to effectively reduce pain after surgery. In this study, we evaluated the efficacy of scalp nerve block in patients with hemifacial spasm (HFS) undergoing microvascular decompression (MVD). Seventy-four patients who underwent MVD for HFS were enrolled. The block group received scalp nerve block with 0.5% ropivacaine before surgery. The primary outcome was cumulative dose of rescue analgesics 24 h postoperatively. The secondary outcomes were included pain scores, postoperative antiemetic consumption, and Quality of Recovery-15 scale. The cumulative dose of rescue analgesics at 24 h postoperatively was not significantly different between the two groups (4.80 ± 3.64 mg vs. 5.92 ± 3.95 mg, p = 0.633). However, the pain score was significantly reduced in the block group at 6, 12, and 24 h postoperatively. Postoperative antiemetic consumption was lower in the block group than the control group at 12 h. There were no significant differences between the two groups for other secondary outcomes. In MVD for HFS, a preoperative scalp nerve block might reduce postoperative pain in the early postoperative period, but a larger study using a multimodal approach is needed to confirm the efficacy of a scalp block.
RESUMO
BACKGROUND: Primary cardiac sarcomas are rare and their clinicopathologic features are heterogeneous. Among them, particularly intimal sarcoma is a diagnostic challenge due to nonspecific histologic features. Recently, MDM2 amplification reported to be a characteristic genetic event in the intimal sarcoma. In this study, we aimed to identify the types and incidence of primary cardiac sarcomas that occurred over 25 years in tertiary medical institutions, and to find clinicopatholgical significance through reclassification of diagnoses using additional immunohistochemistry (IHC). METHODS: We reviewed the primary cardiac sarcoma cases between January 1993 and June 2018 at Asan Medical Center, South Korea, with their clinicopathologic findings, and reclassified the subtypes, especially using IHC for MDM2 and then, analyzed the significance of prognosis. RESULTS: Forty-eight (6.8%) cases of a primary cardiac sarcoma were retrieved. The tumors most frequently involved the right atrium (n = 25, 52.1%), and the most frequent tumor subtype was angiosarcoma (n = 23, 47.9%). Seven cases (53.8%) were newly reclassified as an intimal sarcoma by IHC for MDM2. Twenty-nine (60.4%) patients died of disease (mean, 19.8 months). Four patients underwent a heart transplantation and had a median survival of 26.8 months. This transplantation group tended to show good clinical outcomes in the earlier stages, but this was not statistically significant (p = 0.318). MDM2 positive intimal sarcoma showed the better overall survival (p = 0.003) than undifferentiated pleomorphic sarcoma. Adjuvant treatment is beneficial for patient survival (p < 0.001), particularly in angiosarcoma (p < 0.001), but not in intimal sarcoma (p = 0.154). CONCLUSION: Our study supports the use of adjuvant treatment in primary cardiac sarcoma, as it was associated with a significantly better overall survival rate. Further consideration of tumor histology may be important in determining the optimal use of adjuvant treatment for different types of sarcomas. Therefore, accurate diagnosis by MDM2 test is important condsidering patient's prognosis and treatment.
Assuntos
Neoplasias Cardíacas , Hemangiossarcoma , Sarcoma , Humanos , Terapia Combinada , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/genética , Neoplasias Cardíacas/terapia , Hemangiossarcoma/genética , Hemangiossarcoma/terapia , Prognóstico , Proteínas Proto-Oncogênicas c-mdm2/genética , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma/terapiaRESUMO
BACKGROUND: Dexmedetomidine, one of the sedatives, has an analgesic effect. We aimed to investigate postoperative analgesia with dexmedetomidine as adjuvants for procedural sedation using perfusion index (PI). METHODS: In this prospective, randomized, case-control, observational study, 72 adult patients, 19-70 years, who were scheduled for chemoport insertion under monitored anesthesia care were performed. According to the group assignment, remifentanil or dexmedetomidine was simultaneously infused with propofol. The primary outcome was PI 30 min after admission to the post anesthesia care unit (PACU). And, pain severity using numerical rating scale (NRS) score and the relationship between NRS score and PI were investigated. RESULTS: During PACU staying, PI values were significantly different between the two groups PI values at 30 min after admission to the PACU were 1.3 (0.9-2.0) in the remifentanil group and 4.5 (2.9-6.8) in the dexmedetomidine group (median difference, 3; 95% CI, 2.1 to 4.2; P < 0.001). The NRS scores at 30 min after admission to the PACU were significantly lower in the dexmedetomidine group (P = 0.002). However, there was a weak positive correlation between NRS score and PI in the PACU (correlation coefficient, 0.188; P = 0.01). CONCLUSION: We could not find a significant correlation between PI and NRS score for postoperative pain control. Using PI as a single indicator of pain is insufficient. TRIAL REGISTRATION: Clinical Trial Registry of Korea, https://cris.nih.go.kr : KCT0003501, the date of registration: 13/02/2019.
Assuntos
Anestesia , Dexmedetomidina , Propofol , Adulto , Humanos , Remifentanil , Estudos Prospectivos , Índice de Perfusão , Estudos de Casos e ControlesRESUMO
BACKGROUND: Compared with open surgery, laparoscopic liver resection is a minimally invasive surgical technique. However, a number of patients experience moderate-to-severe postoperative pain after laparoscopic liver resection. This study aims to compare the postoperative analgesic effects of erector spinae plane block (ESPB) and quadratus lumborum block (QLB) in patients undergoing laparoscopic liver resection. METHODS: One hundred and fourteen patients undergoing laparoscopic liver resection will be randomly allocated to three groups (control, ESPB, or QLB) in a 1:1:1 ratio. In the control group, participants will receive systemic analgesia consisting of regular NSAIDs and fentanyl-based patient-controlled analgesia (PCA) according to the institutional postoperative analgesia protocol. In the two experimental groups (ESPB or QLB group), the participants will receive preoperative bilateral ESPB or bilateral QLB in addition to systemic analgesia according to the institutional protocol. ESPB will be performed at the 8th thoracic vertebra level with ultrasound guidance before surgery. QLB will be performed in the supine position on the posterior plane of the quadratus lumborum with ultrasound guidance before surgery. The primary outcome is cumulative opioid consumption 24 h after surgery. Secondary outcomes are cumulative opioid consumption, pain severity, opioid-related adverse events, and block-related adverse events at predetermined time points (24, 48, and 72 h after surgery). Differences in plasma ropivacaine concentrations in the ESPB and QLB groups would be investigated, and the quality of postoperative recovery among the groups will be compared. DISCUSSION: This study will reveal the usefulness of ESPB and QLB in terms of postoperative analgesic efficacy and safety in patients undergoing laparoscopic liver resection. Additionally, the study results will provide information on the analgesic superiority of ESPB versus QLB in the same population. TRIAL REGISTRATION: Prospectively registered with the Clinical Research Information Service on August 3, 2022; KCT0007599.
Assuntos
Laparoscopia , Bloqueio Nervoso , Humanos , Analgésicos Opioides/efeitos adversos , Bloqueio Nervoso/efeitos adversos , Bloqueio Nervoso/métodos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Analgesia Controlada pelo Paciente , Fígado , Ultrassonografia de Intervenção/métodos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Few studies have investigated the changes in patient state index (PSI) and bispectral index (BIS) in response to abrupt increase in electromyographic (EMG) activity. These were performed using intravenous anesthetics or reversal agents for neuromuscular blockade (NMB) other than sugammadex. We compared the changes in BIS and PSI values caused by the sugammadex reversal of NMB during steady-state sevoflurane anesthesia. We enrolled 50 patients with American Society of Anesthesiologists physical status 1 and 2. At the end of the surgery, we administered 2 mg kg-1 sugammadex while maintaining sevoflurane for a 10-min study period. The changes in BIS and PSI from baseline (T0) to train of four ratio of 90% were not significantly different (median difference 0; 95% CI - 3 to 2; P = 0.83), neither were the changes in BIS and PSI values from T0 to their maximum values (median difference 1; 95% CI - 1 to 4; P = 0.53). Maximum BIS and PSI were significantly higher than their baseline values (median difference 6; 95% CI 4-9; P < 0.001 and median difference 5; 95% CI 3-6; P < 0.001, respectively). We found weak positive correlations between BIS and BIS-EMG (r = 0.12, P = 0.01), as well as PSI and PSI-EMG (r = 0.25, P < 0.001). Both PSI and BIS were affected to some extent by EMG artifacts after sugammadex administration.
Assuntos
Anestesia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sevoflurano , Bloqueio Neuromuscular , SugammadexRESUMO
BACKGROUND: Surgery for gynecologic malignancy via midline-laparotomy leads to severe postoperative pain. Adequate pain control while sparing opioid consumption does offer benefits in postoperative complications and recovery. Intrathecal morphine (ITM) provides simple and effective analgesia. In this randomized trial, we compared postoperative opioid consumption in patients who received either ITM or a sham procedure. METHODS: We enrolled 68 adult patients undergoing open gynecologic oncology surgery from June 2021 to November 2021. They were randomly allocated to the ITM group (ITM; 200 µg injection) or sham group (sham procedure) to achieve a final 1:1 ratio between groups. We compared opioid consumption and pain severity during 72 hours after surgery. The variables regarding postoperative recovery and patient-centered outcomes were collected. The primary outcome is cumulative intravenous (IV) opioid consumption 24 hours after surgery. RESULTS: The median (interquartile range) cumulative IV opioid consumption during 24 hours after surgery was 18 mg (12-29) in the ITM group and 36 mg (27-42) in the sham group (median difference, 13; 95% confidence interval, 7.2-20.7; P < .001). Patient satisfaction regarding pain control was statistically significantly higher in the ITM group than in the sham group at postoperative 24 and 48 hours ( P < .001 and P = .005, respectively). There were no significant differences in the variables associated with postoperative recovery and frequency of complications requiring treatment. CONCLUSIONS: ITM is a safe and effective analgesic method after curative intent laparotomy for gynecologic malignancy. ITM provides better pain relief, reduces opioid consumption, and improves patient satisfaction without additional evident adverse events.
Assuntos
Analgésicos Opioides , Neoplasias dos Genitais Femininos , Adulto , Humanos , Feminino , Morfina , Neoplasias dos Genitais Femininos/cirurgia , Neoplasias dos Genitais Femininos/induzido quimicamente , Neoplasias dos Genitais Femininos/tratamento farmacológico , Injeções Espinhais , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologiaRESUMO
PURPOSE: Remimazolam, an ultra-short-acting benzodiazepine, was recently approved in numerous jurisdictions as an induction drug for general anesthesia. We aimed to determine the doses of remimazolam that would allow placement of a supraglottic airway device (SGD) in 50% and 95% of nonparalyzed patients (ED50 and ED95). METHODS: In this prospective study, 30 American Society of Anesthesiology Physical Status I-II grade female patients scheduled for hysteroscopic surgery were enrolled. Anesthesia was induced with 1 µg·kg-1 of fentanyl and continuous infusion of remimazolam without neuromuscular blockade. An i-gel® SGD was inserted 2.5 min after the start of remimazolam infusion. We used Dixon's up-and-down method and isotonic regression to determine the ED50 and ED95 of remimazolam for insertion of an SGD. RESULTS: Twenty-eight patients were included in the final analysis. The ED50 and ED95 of remimazolam required for successful i-gel insertion were 8.8 mg·kg-1·hr-1 (95% confidence interval [CI], 6.3 to 10.6) and 10.7 mg·kg-1·hr-1 (95% CI, 10.6 to 11.7), respectively. A nonfully relaxed jaw was found in 7/13 patients (54%) in the success group and 14/15 patients (93%) in the failure group (difference in proportions, 40%; 95% CI, 7 to 65; P = 0.02). Bucking or other movements during SGD insertion only occurred in the failure group (11/15, 73%). CONCLUSION: In 95% of nonparalyzed female patients undergoing hysteroscopy, 10.7 mg·kg-1·hr-1 of remimazolam with 1 µg·kg-1 of fentanyl facilitates i-gel insertion. Remimazolam showed a high incidence of poor jaw relaxation and bucking or other movements during SGD insertion. STUDY REGISTRATION: Clinical Trial Registry of the Republic of Korea (KCT0006527, https://cris.nih.go.kr ; registered 1 September 2021; principal investigator: Ji Seon Jeong).
RéSUMé: OBJECTIF: Le remimazolam, une benzodiazépine à action ultra-brève, a récemment été approuvé dans de nombreuses juridictions comme agent d'induction pour l'anesthésie générale. Notre objectif était de déterminer les doses de remimazolam qui permettraient l'insertion d'un dispositif supraglottique (DSG) chez 50 % et 95 % des patients non paralysés (DE50 et DE95). MéTHODE: Dans cette étude prospective, 30 patientes de statut physique I-II selon l'American Society of Anesthesiology devant bénéficier d'une chirurgie hystéroscopique ont été recrutées. L'anesthésie a été induite avec 1 µg·kg−1 de fentanyl et une perfusion continue de remimazolam sans bloc neuromusculaire. Un DSG i-gel® a été inséré 2,5 minutes après l'amorce de la perfusion de remimazolam. Nous avons utilisé la méthode de l'escalier de Dixon et la régression isotonique pour déterminer la DE50 et DE95 de remimazolam pour l'insertion d'un DSG. RéSULTATS: Vingt-huit patientes ont été incluses dans l'analyse. Les DE50 et DE95 du remimazolam requises pour une insertion réussie de l'i-gel était de 8,8 mg·kg−1·h−1 (intervalle de confiance [IC] à 95 %, 6,3 à 10,6) et 10,7 mg·kg−1·h−1 (IC 95 %, 10,6 à 11,7), respectivement. Une mâchoire non complètement détendue a été observée chez 7 patientes sur 13 (54 %) dans le groupe d'intubation réussie et chez 14/15 patientes (93 %) dans le groupe d'échec d'intubation (différence de proportions, 40 %; IC 95 %, 7 à 65; P = 0,02). Le fléchissement ou d'autres mouvements pendant l'insertion du DSG ne se sont produits que dans le groupe d'échec de l'induction (11/15, 73 %). CONCLUSION: Chez 95 % des patientes non paralysées bénéficiant d'une hystéroscopie, 10,7 mg·kg−1·h−1 de remimazolam avec 1 µg·kg−1 de fentanyl ont facilité l'insertion d'un dispositif i-gel. Le remimazolam a montré une incidence élevée de mauvaise relaxation de la mâchoire et de fléchissement ou d'autres mouvements lors de l'insertion du DSG. ENREGISTREMENT DE L'éTUDE: Registre des essais cliniques de la République de Corée (KCT0006527, https://cris.nih.go.kr ; enregistrée le 1er septembre 2021; chercheur principal : Ji Seon Jeong).