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1.
J Anesth ; 38(1): 65-76, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38019351

RESUMO

PURPOSE: Midline approach of spinal anesthesia has been widely used for patients undergoing surgical procedures. However, it might not be effective for obstetric patients and elderly with degenerative spine changes. Primary objective was to examine the success rate at the first attempt between the paramedian and midline spinal anesthesia in adults undergoing surgery. METHODS: Databases of MEDLINE, EMBASE, and CENTRAL were searched from their starting date until February 2023. Randomized clinical trials (RCTs) comparing the paramedian versus midline approach of spinal anesthesia were included. The primary outcome was the success rate at the first attempt of spinal anesthesia. RESULTS: Our review included 36 RCTs (n = 5379). Compared to the midline approach, paramedian approach may increase success rate at the first attempt but the evidence is very uncertain (OR: 0.47, 95% CI 0.27-0.82, ρ = 0.007, level of evidence:very low). Our pooled data indicates that the paramedian approach likely reduced incidence of post-spinal headache (OR: 2.07, 95% CI 1.51-2.84, ρ < 0.00001, level of evidence:moderate). The evidence suggests that the paramedian approach may result in a reduction in the occurrence of paresthesia (OR: 1.61, 95% CI 1.06-2.45, ρ = 0.03, level of evidence:low). CONCLUSIONS: Our meta-analysis of 36 RCTs showed that paramedian approach may result in little to no difference in success rate at the first attempt owing to its very low level of evidence. However, given the low level of evidence and studies with small sample sizes, these findings need to be interpreted with caveat. CLINICAL TRIAL REGISTRATION NUMBER: CRD42023397781.


Assuntos
Raquianestesia , Cefaleia Pós-Punção Dural , Adulto , Feminino , Gravidez , Humanos , Idoso , Raquianestesia/métodos , Incidência , Bases de Dados Factuais
2.
J Cardiothorac Vasc Anesth ; 36(12): 4449-4459, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36038444

RESUMO

OBJECTIVE: To examine the effect of bispectral index (BIS)-guided anesthesia on the incidence of postoperative delirium (POD) in elderly patients undergoing surgery. DESIGN: A systematic review, meta-analysis, and trial sequential analysis (TSA). SETTING: In the operating room, postoperative anesthesia care units (PACU), and ward. PARTICIPANTS: Elderly patients (>60 years old) undergoing surgery. INTERVENTIONS: The EMBASE, MEDLINE, and CENTRAL databases were searched systematically from their inception until December 2020 for randomized controlled trials comparing BIS and usual care or blinded BIS. MEASUREMENTS AND MAIN RESULTS: Ten trials (N = 3,891) were included for quantitative meta-analysis. In comparison to the control group, there was no significant difference in the incidence of POD in elderly patients randomized to BIS-guided anesthesia (odds ratio [OR] 0.71, 95% CI 0.47-1.08, I2 = 76%, p = 0.11, level of evidence = very low, TSA = inconclusive). The authors' review demonstrated that elderly patients with BIS-guided anesthesia were significantly associated with a lower incidence of postoperative cognitive dysfunction (POCD) (OR 0.64, 95% CI 0.46-0.88, p = 0.006), extubation time (mean difference [MD] -3.38 minutes, 95% CI -4.38 to -2.39, p < 0.00001), time to eye opening (MD -2.17 minutes, 95% CI -4.21 to -0.14, p = 0.04), and time to discharge from the PACU (MD -10.77 minutes, 95% CI -11.31 to - 10.23, p < 0.00001). CONCLUSION: The authors' meta-analysis demonstrated that BIS-guided anesthesia was not associated with a reduced incidence of POD, but it was associated with a reduced incidence of POCD and improved recovery parameters.


Assuntos
Anestesia , Anestesiologia , Delírio , Complicações Cognitivas Pós-Operatórias , Idoso , Humanos , Pessoa de Meia-Idade , Anestesia/efeitos adversos , Delírio/diagnóstico , Delírio/epidemiologia , Delírio/etiologia , Complicações Cognitivas Pós-Operatórias/diagnóstico , Complicações Cognitivas Pós-Operatórias/epidemiologia , Complicações Cognitivas Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Br J Anaesth ; 127(2): 316-323, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34127252

RESUMO

BACKGROUND: Residual neuromuscular block is associated with an increased risk of postoperative pulmonary complications in retrospective studies. The aim of our study was to investigate prospectively the incidence of postoperative pulmonary complications after reversal with either sugammadex (SUG) or neostigmine (NEO) in high-risk older patients. METHODS: We randomly allocated 180 older patients with significant morbidity (ASA physical status 3) ≥75 yr old to reversal of rocuronium with either SUG or NEO. Adverse events in the recovery room and pulmonary complications (defined by a 5-point [0-4; 0=best to 4=worst] outcome score) on postoperative Days 1, 3, and 7 were compared between groups. RESULTS: Data from 168 patients aged 80 (4) yr were analysed; SUG vs NEO resulted in a reduced probability (0.052 vs 0.122) of increased pulmonary outcome score (impaired outcome) on postoperative Day 7, but not on Days 1 and 3. More patients in the NEO group were diagnosed with radiographically confirmed pneumonia (9.6% vs 2.4%; P=0.046). The NEO group showed a non-significant trend towards longer hospital length of stay across all individual centres (combined 9 vs 7.5 days), with a significant difference in Malaysia (6 vs 4 days; P=0.011). CONCLUSIONS: Reversal of rocuronium neuromuscular block with SUG resulted in a small, but possibly clinically relevant improvement in pulmonary outcome in a select cohort of high-risk older patients. CLINICAL TRIAL REGISTRATION: ACTRN12614000108617.


Assuntos
Avaliação Geriátrica/métodos , Neostigmina/farmacologia , Bloqueio Neuromuscular/métodos , Complicações Pós-Operatórias/epidemiologia , Insuficiência Respiratória/epidemiologia , Sugammadex/farmacologia , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Inibidores da Colinesterase/farmacologia , Método Duplo-Cego , Feminino , Humanos , Incidência , Masculino , Estudos Prospectivos , Risco , Resultado do Tratamento
4.
BMC Anesthesiol ; 21(1): 20, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33451283

RESUMO

BACKGROUND: The Revised American Pain Society Patient Outcome Questionnaire (APS-POQ-R) evaluates the patient-reported quality of pain management in adults. A validated APS-POQ-R is pivotal to guide effective pain management with better patient satisfaction. Previous studies revealed that subscales of "patients' perception of pain management" were unstable cross-culturally. This study aims to evaluate the construct validity of the APS-POQ-R in gynecological postoperative patients with a multi-cultural background using confirmatory factor analysis to allow comparisons among different a priori models at the latent factor level. METHODS: Patients aged 18 years old or above and who were scheduled for gynecology surgery were selected. Three different models with a combination of latent factors were based on a priori hypotheses from previous studies. The root-mean-squared error of approximation, comparative fit index, Tucker-Lewis Index, Chi-squared test, and change in Chi-squared statistic given a change in degrees of freedom between models were used to assess the model fit to the present data. RESULTS: A total of 302 patients completed the questionnaire. The five-factor model which was based on Gordon's study has an acceptable fit for the data and was superior when compared to the one-factor baseline model. Although the four-factor model, which originated from Botti's study, also demonstrates a good model fit, the "perception of care" construct was excluded in this model. The "perception of care" construct is conceptually important as patient-centered care has become the focus of quality improvement of pain service. CONCLUSIONS: The APS-POQ-R is easy to administer and is useful for quality evaluation in postoperative pain management. The present study demonstrates that a five-factor structure of the APS-POQ-R is the best fitting model in our patient sample. The results of this study provide further evidence to support the use of APS-POQ-R as a measurement tool for pain management evaluation in acute postoperative patients with a multi-cultural background.


Assuntos
Doenças dos Genitais Femininos/cirurgia , Avaliação de Resultados em Cuidados de Saúde/métodos , Dor Pós-Operatória/tratamento farmacológico , Satisfação do Paciente/estatística & dados numéricos , Inquéritos e Questionários/normas , Analgesia/métodos , Estudos Transversais , Diversidade Cultural , Análise Fatorial , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Malásia , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/normas , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Manejo da Dor/métodos , Reprodutibilidade dos Testes
5.
BMC Anesthesiol ; 20(1): 184, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32736516

RESUMO

BACKGROUND: The 4th National Audit Project of The Royal College of Anaesthetists and The Difficult Airway Society (NAP4) reported a higher incidence of supraglottic airway device (SAD) related pulmonary aspiration in obese patients especially with the first-generation SADs. The latest single-use SAD, the Protector™ provides a functional separation of the respiratory and digestive tracts and its laryngeal cuff with two ports allowing additional suction in tandem with the insertion of a gastric tube. The laryngeal cuff of LMA Protector™ allows a large catchment reservoir in the event of gastric content aspiration. METHODS: We evaluated the performance characteristics of the LMA Protector™ in 30 unparalysed, moderately obese patients. First attempt insertion rate, time for insertion, oropharyngeal leak pressure (OLP), and incidence of complications were recorded. RESULTS: We found high first and second attempt insertion rates of 28(93%) and 1(33%) respectively, with one failed attempt where no capnography trace could be detected, presumably from a downfolded device tip. The LMA Protector™ was inserted rapidly in 21.0(4.0) seconds and demonstrated high OLP of 31.8(5.4) cmH2O. Fibreoptic assessment showed a clear view of vocal cords in 93%. The incidence of blood staining on removal of device was 48%, postoperative sore throat 27%, dysphagia 10% and dysphonia 20% (all self-limiting, resolving a few hours postoperatively). CONCLUSIONS: We conclude that the LMA Protector™ was associated with easy, expedient first attempt insertion success, demonstrating high oropharyngeal pressures and good anatomical position in the moderately obese population, with relatively low postoperative airway morbidity. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12617001152314 . Registered 7 August 2017.


Assuntos
Intubação Intratraqueal/métodos , Máscaras Laríngeas , Obesidade/complicações , Adulto , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Disfonia/epidemiologia , Disfonia/etiologia , Desenho de Equipamento , Feminino , Tecnologia de Fibra Óptica , Humanos , Intubação Intratraqueal/instrumentação , Masculino , Pessoa de Meia-Idade , Faringite/epidemiologia , Faringite/etiologia
6.
Eur J Drug Metab Pharmacokinet ; 48(1): 11-21, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36207565

RESUMO

BACKGROUND AND OBJECTIVE: Oxycodone, a semisynthetic thebaine derivative µ-opioid (MOP) receptor agonist, is effective for treating moderate and severe pain in different clinical conditions. The pharmacokinetics of intravenous oxycodone in the obese population has not been studied. This study aims to characterize the pharmacokinetic profile of oxycodone after intravenous administration and to simulate an appropriate dosage for analgesic efficacy in obese patients. METHODS: We recruited 33 (age range from 21 to 72 years) adult patients with a body mass index of 30 kg/m2 and above, who were scheduled for non-cardiac surgeries. Intravenous oxycodone was administered after induction of general anesthesia and blood samples were collected up to 24 h after oxycodone administration. Plasma concentrations of oxycodone were assayed using liquid chromatography-tandem mass spectrometry and 253 concentration-time points were used for pharmacokinetic analysis using nonlinear mixed-effects modeling. RESULTS: Intravenous oxycodone pharmacokinetics were well described by a two-compartment open model. The estimated total clearance and central volume of distribution of oxycodone are 28.5 l/h per 70 kg and 56.4 l per 70 kg, respectively. Total body weight was identified as a significant covariate of the clearance and central volume of distribution. Dosing simulations based on the final model demonstrate that a starting dose of 0.10 mg/kg of intravenous oxycodone is adequate to achieve a target plasma concentration and repeated doses of 0.02 mg/kg may be administered at 1.5-h intervals to maintain a plasma concentration within an effective analgesic range. CONCLUSIONS: A population pharmacokinetic model using total body weight as a covariate supports the administration of 0.10 mg/kg of intravenous oxycodone as a starting dose and repeated doses of 0.02 mg/kg at 1.5-h intervals to maintain targeted plasma concentrations for analgesia in the obese adult population.


Assuntos
Analgésicos Opioides , Oxicodona , Humanos , Adulto , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Oxicodona/farmacologia , Oxicodona/uso terapêutico , Analgésicos Opioides/farmacocinética , Administração Intravenosa , Dor/tratamento farmacológico , Analgésicos/uso terapêutico , Obesidade/tratamento farmacológico
7.
Indian J Anaesth ; 66(7): 523-529, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36111094

RESUMO

Background and Aims: Postoperative sore throat (POST) is an undesirable event reported in up to 62% of patients receiving general anaesthesia (GA). The incidence of POST following GA using a supraglottic airway device (SAD) is approximately 50%, with symptoms persisting up to 48 h. We examined the role of preoperative lozenges containing amylmetacresol and dichlorobenzyl alcohol (AMC/DCBA) with lignocaine (Strepsils® Max Plus) in reducing the incidence and intensity of POST following GA using SAD. Methods: We conducted a prospective, double-blinded, randomised, placebo-controlled trial involving 88 adults receiving GA for elective surgery using SAD not exceeding 2 h. Patients received either Strepsils Max Plus (Strepsils-LA group) or a placebo before induction of GA. The incidence and intensity of sore throat, dysphagia and dysphonia was measured using the Verbal Rating Scale at 30 min (early) and at 24 h (late) after removal of SAD. Results: Overall POST incidence was lower in the Strepsils-LA group (27.7% versus 56.8%, P = 0.007). Patients in the Strepsils-LA group reported a significantly lower incidence of early POST (14.9% versus 37.8%, P = 0.016) with a lower mean ± standard deviation intensity score (0.17 ± 0.43 versus 0.49 ± 0.69, P = 0.016). Although the overall incidence of dysphagia was lower (23.4% versus 48.6%, P = 0.016), more patients experienced dysphonia in the Strepsils-LA group. AMC/DCBA with lignocaine lozenges showed a relative risk reduction of 50% and a number needed to treat of 4 in reducing POST. Conclusion: AMC/DCBA with lignocaine lozenges administered before GA using SAD is a simple and safe method to reduce the incidence and severity of POST.

8.
Asian J Anesthesiol ; 59(1): 7-21, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33504143

RESUMO

Dexmedetomidine is a highly selective α2-adrenoceptor agonist, which is off-labelled use for pediatric sedation. However, the hemodynamic responses of dexmedetomidine remain unclear in the pediatric population. The primary objectives of this systematic review and meta-analysis were to examine the hemodynamic effects of high-dose and low-dose dexmedetomidine in pediatric patients undergoing surgery. EMBASE, MEDLINE, and CENTRAL were systematically searched from its inception until April 2019. All randomized clinical trials comparing high-dose (> 0.5 mcg/kg) and low-dose (≤ 0.5 mcg/ kg) dexmedetomidine in pediatric surgical patients were included, regardless of the types of surgeries. Observational studies, case series, and case reports were excluded. Four trials (n = 473) were included in this review. Our review demonstrated that high-dose dexmedetomidine was associated with lower heart rate than low-dose dexmedetomidine after intravenous bolus of dexmedetomidine (studies, 3; n = 274; mean difference [MD], -5 [-6 to -4]; P < 0.0001) and during surgical stimulant (studies, 2; n = 153; MD, -11 [-13 to -9]; P < 0.0001). In comparison to the low-dose dexmedetomidine, high-dose dexmedetomidine was also associated with a significant longer recovery time (studies, 3; n = 257; MD, 5.90 [1.56 to 10.23]; P = 0.008) but a lower incidence of emergence agitation (studies, 2; n = 153; odds ratio, 0.17 [0.03 to 0.95]; P = 0.040). In this meta-analysis, low-dose dexmedetomidine demonstrated better hemodynamic stability with shorter recovery time than high-dose dexmedetomidine. However, these findings need to be interpreted with caution due to limited published studies, a small sample size, and a high degree of heterogeneity.


Assuntos
Dexmedetomidina , Delírio do Despertar , Anestesia Geral , Criança , Hemodinâmica , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Obes Surg ; 31(10): 4305-4315, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34282569

RESUMO

BACKGROUND: Transversus abdominis plane (TAP) block and intraperitoneal local anesthetics (IPLA) are widely investigated techniques that potentially improve analgesia after bariatric surgery. The analgesic efficacy of TAP block has been shown in previous studies, but the performance of TAP block can be difficult in patients with obesity. We performed a systematic review and meta-analysis to compare the analgesic efficacy of TAP block and IPLA. An alternative technique is useful in clinical setting when TAP block is not feasible. METHODS: We searched PubMed, Embase, and CENTRAL from inception until August 2020 for randomized controlled trials comparing both techniques. The primary outcome was cumulative morphine consumption at 24 h. Secondary pain-related outcomes included pain score at rest and on movement at 2, 6, 12, and 24 h; postoperative nausea and vomiting; and length of hospital stay. RESULTS: We included 23 studies with a total of 2,178 patients. TAP block is superior to control in reducing opioid consumption at 24 h, improving pain scores at all the time points and postoperative nausea and vomiting. The cumulative opioid consumption at 24 h for IPLA is less than control, while the indirect comparison between IPLA with PSI and control showed a significant reduction in pain scores at rest, at 2 h, and on movement at 12 h, and 24 h postoperatively. CONCLUSIONS: Transversus abdominis plane block is effective for reducing pain intensity and has superior opioid-sparing effect compared to control. Current evidence is insufficient to show an equivalent analgesic benefit of IPLA to TAP block.


Assuntos
Cirurgia Bariátrica , Obesidade Mórbida , Músculos Abdominais , Analgésicos Opioides , Anestésicos Locais , Humanos , Metanálise em Rede , Obesidade Mórbida/cirurgia , Dor Pós-Operatória/tratamento farmacológico
10.
Int J Surg ; 82: 192-199, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32871271

RESUMO

BACKGROUND: Studies have reported that general anesthesia (GA), especially volatile agents were associated with higher cancer recurrence rate after cancer resection surgery. However, the effect of supplementary regional anesthesia (RA) in reducing the use of anesthetic agents on oncological outcomes remains unclear. The primary aim of this meta-analysis was to examine the effect of adjunctive use of RA on the cancer recurrence rate in adults undergoing cancer resection surgery. METHODS: MEDLINE, EMBASE and CENTRAL were systematically searched for randomized control trials (RCTs) from its inception until April 2020. RESULTS: Six RCTs (n = 3139 patients) were included. In comparison to the GA alone, our meta-analysis demonstrated no significant difference in the cancer recurrence rate in patients who received the adjunctive use of RA in the routine care of GA (3 studies, n = 2380 patients; odds ratio 0.93, 95%CI 0.63-1.39, ρ = 0.73, certainty of evidence = very low). Our review also showed no significant difference in cancer-related mortality (2 studies, n = 545; odds ratio 1.20, 95%CI 0.83-1.74, ρ = 0.33, certainty of evidence = low), all-cause mortality (3 studies, n = 2653; odds ratio 0.98, 95%CI 0.69-1.39, ρ = 0.89, certainty of evidence = low) and duration of cancer-free survival (2 studies, n = 659; mean difference 0.00 years, 95%CI -0.25-0.25, ρ = 1.00, certainty of evidence = high). CONCLUSION: This meta-analysis concluded that the adjunctive use of RA in the routine care of GA did not reduce cancer recurrence rate in cancer resection surgery. However, this finding needs to be interpreted with caution due to low level of evidence, substantial heterogeneity and potential risk of bias across the included studies. STUDY REGISTRATION NUMBER: CRD42020171368.


Assuntos
Anestesia por Condução , Anestesia Geral/efeitos adversos , Recidiva Local de Neoplasia/epidemiologia , Neoplasias/cirurgia , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Neoplasias/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Korean J Anesthesiol ; 72(6): 606-609, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31304693

RESUMO

BACKGROUND: The laryngeal mask airway (LMAⓇ) ProtectorTM (Teleflex Medical Co., Ireland) is the latest innovation in the second generation of LMA devices. One distinguishing feature of this device is its integrated, color-coded cuff pressure indicator (Cuff PilotTM technology) which enables continuous cuff pressure monitoring and allows adjustments when necessary; this ensures patient safety due to better monitoring. CASE: We report a case of postoperative unilateral hypoglossal nerve palsy after uncomplicated use of the LMA Protector. To the best of our knowledge, this could be the second reported case. CONCLUSIONS: This case demonstrates that anesthetists need to routinely measure cuff pressure and that the Cuff PilotTM technology is not a panacea for potential cranial nerve injury after airway manipulation.


Assuntos
Doenças do Nervo Hipoglosso/etiologia , Máscaras Laríngeas/efeitos adversos , Complicações Pós-Operatórias/etiologia , Idoso , Desenho de Equipamento , Hérnia Inguinal/cirurgia , Herniorrafia , Humanos , Masculino
12.
Expert Rev Med Devices ; 15(8): 597-603, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30095289

RESUMO

BACKGROUND: The Baska functional endoscopic sinus surgery (FESS) mask is a new supraglottic airway designed for head and neck procedures. This prospective, randomized controlled trial compared the oropharyngeal leak pressure (OLP) of the Baska FESS mask with the laryngeal mask airway (LMA) Supreme in different head and neck positions. METHODS: One hundred patients undergoing elective surgery were recruited. OLP was compared in supine position, 45° lateral rotation, 45° neck extension, and 30° neck flexion. Glottic view, insertion time, ease of insertion, number of attempts, ease and time of insertion of gastric tube, and complications were also compared. RESULTS: The OLP of the Baska FESS was higher than the LMA Supreme in all head and neck positions studied (p < 0.001). Glottic views were better in the Baska FESS in supine and lateral rotation. LMA Supreme was easier (p = 0.046) and faster (p < 0.001) to insert. First attempt insertion success rates were 91.8% for Baska FESS and 98% for LMA Supreme. Gastric drain was easier and faster to insert (p < 0.001) in the LMA Supreme. CONCLUSIONS: The Baska FESS provides a superior airway seal with higher mean OLP than the LMA Supreme in all head and neck positions studied. However, LMA Supreme was superior in terms of ease and speed of insertion.


Assuntos
Endoscopia , Cabeça/fisiopatologia , Máscaras Laríngeas , Pescoço/fisiopatologia , Seios Paranasais/cirurgia , Postura , Adulto , Desenho de Equipamento , Feminino , Glote/cirurgia , Hemodinâmica , Humanos , Masculino , Orofaringe/fisiopatologia , Orofaringe/cirurgia , Pressão , Estudos Prospectivos
13.
BMJ Case Rep ; 20142014 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-24862427

RESUMO

Care of an acutely ill parturient is particularly difficult when we have to balance the needs of both mother and the fetus to survive. The literature suggests there should be emphasis on stabilising the mother's condition. In dealing with metabolic acidosis, however, we believe delivering the baby early might not only relieve the threat of the acidosis on the mother, it may be the only way to deliver a live baby. We report two parturient women with severe metabolic acidosis which was considerably reduced very soon after the delivery and how our timely delivery resulted in the birth of two neurologically intact babies.


Assuntos
Cesárea , Cetoacidose Diabética/terapia , Complicações na Gravidez/terapia , Acidose/etiologia , Acidose/terapia , Adulto , Colecistite Aguda/etiologia , Colelitíase/complicações , Feminino , Humanos , Pancreatite/etiologia , Gravidez , Índice de Gravidade de Doença
14.
Shock ; 42(2): 154-60, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24667629

RESUMO

Excessive free radical production by immune cells has been linked to cell death and tissue injury during sepsis. Peroxynitrite is a short-lived oxidant and a potent inducer of cell death that has been identified in several pathological conditions. Caffeic acid phenethyl ester (CAPE) is an active component of honeybee products and exhibits antioxidant, anti-inflammatory, and immunomodulatory activities. The present study examined the ability of CAPE to scavenge peroxynitrite in RAW 264.7 murine macrophages stimulated with lipopolysaccharide/interferon-γ that was used as an in vitro model. Conversion of 123-dihydrorhodamine to its oxidation product 123-rhodamine was used to measure peroxynitrite production. Two mouse models of sepsis (endotoxemia and cecal ligation and puncture) were used as in vivo models. The level of serum 3-nitrotyrosine was used as an in vivo marker of peroxynitrite. The results demonstrated that CAPE significantly improved the viability of lipopolysaccharide/interferon-γ-treated RAW 264.7 cells and significantly inhibited nitric oxide production, with effects similar to those observed with an inhibitor of inducible nitric oxide synthase (1400W). In addition, CAPE exclusively inhibited the synthesis of peroxynitrite from the artificial substrate SIN-1 and directly prevented the peroxynitrite-mediated conversion of dihydrorhodamine-123 to its fluorescent oxidation product rhodamine-123. In both sepsis models, CAPE inhibited cellular peroxynitrite synthesis, as evidenced by the absence of serum 3-nitrotyrosine, an in vivo marker of peroxynitrite. Thus, CAPE attenuates the inflammatory responses that lead to cell damage and, potentially, cell death through suppression of the production of cytotoxic molecules such as nitric oxide and peroxynitrite. These observations provide evidence of the therapeutic potential of CAPE treatment for a wide range of inflammatory disorders.


Assuntos
Ácidos Cafeicos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Macrófagos/efeitos dos fármacos , Ácido Peroxinitroso/antagonistas & inibidores , Álcool Feniletílico/análogos & derivados , Sepse/tratamento farmacológico , Animais , Ácidos Cafeicos/administração & dosagem , Ácidos Cafeicos/uso terapêutico , Células Cultivadas , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Sequestradores de Radicais Livres/administração & dosagem , Sequestradores de Radicais Livres/uso terapêutico , Interferon gama/imunologia , Lipopolissacarídeos/imunologia , Ativação de Macrófagos/efeitos dos fármacos , Ativação de Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Óxido Nítrico/biossíntese , Ácido Peroxinitroso/biossíntese , Álcool Feniletílico/administração & dosagem , Álcool Feniletílico/farmacologia , Álcool Feniletílico/uso terapêutico , Sepse/sangue , Tirosina/análogos & derivados , Tirosina/sangue
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