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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.
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BACKGROUND: Dexmedetomidine has sympatholytic effects. We investigated whether dexmedetomidine could attenuate stress responses in patients undergoing endoscopic transnasal transseptal transsphenoidal surgery. METHODS: Forty-six patients were randomized to receive a continuous infusion of 0.9% saline (n = 23) or dexmedetomidine (n = 23). Immediately after general anesthesia induction, the dexmedetomidine group received a loading dose of 1 mcg/kg dexmedetomidine over 10 min, followed by a maintenance dose of 0.2-0.7 mcg/kg/h and the control group received 0.9% saline at the same volume until 30 min before the end of surgery. Serum levels of epinephrine, norepinephrine, and glucose were assessed before surgery (T1) and the end of drug infusion (T2). The primary outcome was the change in norepinephrine levels between the two time points. RESULTS: Changes (T2-T1 values) in perioperative serum norepinephrine levels were significantly greater in the dexmedetomidine group than in the control group (median difference, 56.9 pg/dL; 95% confidence interval, 20.7 to 83.8 pg/dL; P = 0.002). However, epinephrine level changes did not show significant intergroup differences (P = 0.208). Significantly fewer patients in the dexmedetomidine group than in the control group required rescue analgesics at the recovery area (4.3% vs. 30.4%, P = 0.047). CONCLUSIONS: Intraoperative dexmedetomidine administration reduced norepinephrine release and rescue analgesic requirement. Dexmedetomidine might be used as an anesthetic adjuvant in patients undergoing transnasal transseptal transsphenoidal surgery. TRIAL REGISTRATION: Clinical Trial Registry of Korea, identifier: KCT0003366; registration date: 21/11/2018; presenting author: Ji Seon Jeong.
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Dexmedetomidina/farmacologia , Norepinefrina/sangue , Neoplasias Hipofisárias/cirurgia , Seio Esfenoidal/cirurgia , Estresse Psicológico/prevenção & controle , Adulto , Glicemia/análise , Método Duplo-Cego , Epinefrina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/sangue , Estudos ProspectivosRESUMO
In this in vivo and in vitro study, we aimed to investigate whether isoflurane preconditioning-induced neuronal protection is mediated by reactive oxygen species (ROS) signaling at the reperfusion stage. In the in vivo study, Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) and in the in vitro study, rat pheochromocytoma (PC12) cells were subjected to oxygen glucose deprivation (OGD). Isoflurane preconditioning was carried out prior to MCAO or OGD and the ROS scavenger, N-2-mercaptopropiopylglycine (2-MPG), was administered at the start of reperfusion. Infarct volume, neurological severity score, and TUNEL staining were analyzed in the in vivo study and cell viability, Bcl-2/Bax ratio, cleaved caspase 3/caspase 3 ratio, and ROS fluorescence intensity were measured in the in vitro study. In the in vivo study, infarct volume, neurological severity score, and TUNEL-positive cell count were significantly decreased with preconditioning but were abrogated by administration of 2-MPG. In the in vitro study, cell viability and Bcl-2/Bax ratio were significantly increased with preconditioning, and cleaved caspase-3/caspase-3 ratio and ROS fluorescence intensity were significantly decreased. Administration of 2-MPG for 10â¯min abrogated this preconditioning effect, but it did not abolish the protection when administered for 60â¯min of reperfusion. Isoflurane preconditioning-induced protection was abolished by ROS scavengers at the start of reperfusion, indicating that ROS signaling can mediate the isoflurane preconditioning effect, which suggests that the time window can be important.
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Isoflurano/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Anestésicos Inalatórios/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Infarto da Artéria Cerebral Média , Isoflurano/metabolismo , Masculino , Neuroproteção/efeitos dos fármacos , Neuroproteção/fisiologia , Fármacos Neuroprotetores/farmacologia , Células PC12 , Ratos , Ratos Sprague-Dawley , Reperfusão/métodos , Traumatismo por Reperfusão , Transdução de Sinais/efeitos dos fármacosRESUMO
Intraoperative hypothermia occurs frequently, but hyperthermia is relatively rare during general anesthesia. We experienced a case of hyperthermia during living donor liver transplantation that appeared to be significantly associated with biliary obstruction. A 65-year-old male patient was diagnosed with intrahepatic cholangiocarcinoma, and living donor liver transplantation was planned after confirmation of no metastasis via intraoperative frozen biopsy. Following resection of a segment of common bile duct for frozen biopsy, the surgeon clamped the common bile duct, and the patient's body temperature increased gradually to 39.5°C. As the congested bile was drained, the body temperature decreased to the normal range. This case report suggests that when a patient develops unexplained hyperthermia during hepatobiliary surgery or in a chance of biliary obstruction, clinicians should consider bile congestion as a possible reason for hyperthermia.
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INTRODUCTION: This prospective observational study compared the postoperative analgesic effectiveness of intrathecal morphine (ITM) and surgical-site infusion (SSI) of ropivacaine as adjuncts to intravenous (IV) patient-controlled analgesia (PCA) (fentanyl) in living-donor kidney transplant recipients. METHODS: Patients undergoing living-donor kidney transplantation who received ITM or SSI in addition to IV PCA were included. Rescue analgesia was achieved with IV meperidine as required. The primary outcome, measured using the Numeric Pain Rating Scale (NRS), was pain at rest and when coughing. Patients were assessed for 48 hours after surgery. RESULTS: A total of 53 patients (32 ITM, 21 SSI) were included in the study. The ITM group showed significantly lower NRS scores, at rest and when coughing, for up to 12 and eight hours. NRS scores were comparable between the groups at other times. The ITM group had significantly less postoperative systemic opioid requirement in the first 24 hours, but there was no significant difference between the systemic opioid consumption of the groups on postoperative Day 2. In the ITM group, 3 (9.4%) patients presented with bradypnoea and 1 (3.1%) with excessive sedation in the first 12 postoperative hours. More patients in the ITM group developed pruritus requiring treatment during the first 24 hours. There were no differences between the groups in other outcomes (e.g. nausea/vomiting, change in pulmonary or kidney functions). CONCLUSION: Compared with SSI, ITM reduced immediate postoperative pain and IV opioid consumption on postoperative Day 1 after living-donor kidney transplantation, but at the cost of increased pruritus and respiratory depression.
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Amidas/administração & dosagem , Analgesia Controlada pelo Paciente , Fentanila/administração & dosagem , Falência Renal Crônica/cirurgia , Transplante de Rim , Morfina/administração & dosagem , Adulto , Idoso , Analgésicos Opioides/uso terapêutico , Feminino , Humanos , Infusões Intravenosas , Injeções Espinhais , Doadores Vivos , Masculino , Meperidina/uso terapêutico , Pessoa de Meia-Idade , Manejo da Dor , Medição da Dor , Dor Pós-Operatória , Período Pós-Operatório , Prurido/etiologia , Insuficiência Respiratória/etiologia , Ropivacaina , Fatores de Tempo , Resultado do TratamentoRESUMO
We retrospectively evaluated the effects of 6% hydroxyethyl starch (HES) 130/0.4 on postoperative blood loss and acute kidney injury (AKI) in patients undergoing off-pump coronary artery bypass grafting (OPCAB).Electronic medical records of 771 patients who underwent OPCAB in our hospital between July 2012 and July 2014 were reviewed, and 249 patients without intraoperative HES-exposure (group NoHES) were matched 1:N with intraoperative HES-exposed 413 patients (group HES) based on propensity score. The effects of intraoperative HES on postoperative cumulative blood loss within the first 24âhours, need for bleeding-related reoperation, and occurrence of postoperative AKI (determined by KDIGO and RIFLE criteria) were analyzed.In our propensity score matched cohort, there were no significant differences between groups for median postoperative 24âhours blood loss (525âmL in group HES vs. 540âmL in group NoHES, Pâ=â.203) or need for bleeding-related reoperation (OR, 2.44; 95% confidence interval [CI], 0.64-9.34, Pâ=â.19). However, postoperative AKI (assessed by 2 criteria) occurred more frequently in group HES than in group NoHES (by KDIGO criteria: 10.7% vs. 3.6%; OR 3.43 [95% CI, 1.67-7.04]; Pâ<â.001 and by RIFLE criteria: 9.6% vs. 2%; OR 3.32 [95% CI, 1.34-8.24]; Pâ=â.01). The median volume of infused HES per patient weight was 16âmL/kg in group HES.In the patients undergoing OPCAB, intraoperative 6% HES 130/0.4 did not increase postoperative bleeding. However, renal safety remains a concern. Intraoperative use of HES should be determined cautiously during OPCAB.
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Injúria Renal Aguda/etiologia , Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Derivados de Hidroxietil Amido/administração & dosagem , Substitutos do Plasma/administração & dosagem , Hemorragia Pós-Operatória/etiologia , Idoso , Feminino , Humanos , Derivados de Hidroxietil Amido/efeitos adversos , Incidência , Masculino , Pessoa de Meia-Idade , Substitutos do Plasma/efeitos adversos , Pontuação de Propensão , Reoperação , Estudos Retrospectivos , Risco , Resultado do TratamentoRESUMO
BACKGROUND: Hemodialysis via the internal jugular vein (IJV) has been widely used for patients with end stage renal disease (ESRD) patients, as they have a higher risk of arterial diseases. We investigated the ultrasonographic findings of the IJV and carotid artery (CA) in recipients of kidney transplantation (KT) and identified factors influencing IJV/CA abnormalities. METHODS: We enrolled 120 adult KT recipients. Patients in group A (n = 57) had a history of IJV hemodialysis, while those in group B (n = 63) were not yet on dialysis or undergoing dialysis methods not involving the IJV. The day before surgery, we evaluated the state of the IJV and CA using ultrasonography. We followed patients with IJV stenosis for six months after KT. RESULTS: Ultrasonography revealed that four patients (7%) in group A had IJV abnormalities, while no patients in group B had abnormalities (P = 0.118). Of the four patients with abnormalities, one with 57.4% stenosis normalized during follow- up. However, another patient with 90.1% stenosis progressed to occlusion, while the two patients with total occlusion remained the same. Twenty patients in group A (n = 11) and B (n = 9) had several CA abnormalities (P = 0.462). Upon multivariate analysis with stepwise selection, height and age were significantly correlated with IJV stenosis (P = 0.043, odds ratio = 0.9) and CA abnormality (P = 0.012, odds ratio = 1.1), respectively. CONCLUSIONS: IJV abnormalities (especially with a history of IJV hemodialysis) and CA abnormalities may be present in ESRD patients. Therefore, we recommend ultrasonographic evaluation before catheterization.
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Isoflurane has either neuroprotective or neurotoxic effects. High-dose oxygen is frequently used throughout the perioperative period. We hypothesized that hyperoxia will affect cell viability of rat pheochromocytoma (PC12) cells that were exposed to isoflurane and reactive oxygen species (ROS) may be involved. PC12 cells were exposed to 1.2% or 2.4% isoflurane for 6 or 24h respectively, and cell viability was evaluated. To investigate the effects of hyperoxia, PC12 cells were treated with 21%, 50%, or 95% oxygen and 2.4% isoflurane for 6h, and cell viability, TUNEL staining, ROS production, and expression of B-cell lymphoma 2 (BCL-2), BCL2-associated X protein (BAX), caspase-3 and beta-site APP cleaving enzyme (BACE) were measured. ROS involvement was evaluated using the ROS scavenger 2-mercaptopropiopylglycine (MPG). The viability of cells exposed to 2.4% isoflurane was lower than that of cells exposed to 1.2% isoflurane. Prolonged exposure (6h vs. 24h) to 2.4% isoflurane resulted in a profound reduction in cell viability. Treatment with 95% (but not 50%) oxygen enhanced the decrease in cell viability induced by 2.4% isoflurane alone. Levels of ROS, Bax, caspase-3 and BACE were increased, whereas expression of Bcl-2 was decreased, in cells treated with 95% oxygen plus 2.4% isoflurane compared with the control and 2.4% isoflurane plus air groups. MPG attenuated the effects of oxygen and isoflurane. In conclusion, isoflurane affects cell viability in a dose- and time-dependent manner. This effect is augmented by hyperoxia and may involve ROS, the mitochondrial apoptotic signaling pathway, and ß-amyloid protein.
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Anestésicos Inalatórios/farmacologia , Apoptose/efeitos dos fármacos , Hiperóxia/metabolismo , Isoflurano/farmacologia , Mitocôndrias/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Marcação In Situ das Extremidades Cortadas , Células PC12 , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Estatísticas não Paramétricas , Fatores de Tempo , Proteína X Associada a bcl-2/metabolismoRESUMO
The objective of this study is to investigate the degree of serum sodium changes and its association with patient outcomes in pediatrics undergoing heart surgery with cardiopulmonary bypass (CPB). We reviewed the medical records of 275 pediatric patients who underwent heart surgery with CPB. Prior to CPB, hyponatremia (≤135 mmol/L) was observed in 21 of 275 patients. After initiation of CPB, serum sodium decreased significantly and severe hyponatermia (≤130 mmol/L) subsequently developed in 32 patients. At the end of CPB, however, hypernatremia (≥145 mmol/L) developed in 86 patients. The degree of acute serum sodium change during CPB was not associated with patient outcomes. However, the patients with preoperative hyponatremia and those with hypernatremia at the conclusion of CPB had longer hospital stays and higher postoperative complication rates. Lower serum sodium prior to CPB and higher serum sodium at the end of CPB, along with age and duration of the operation, were independently associated with worse in-hospital outcomes. Acute and transient hyponatremia occurred frequently after initiation of CPB, and then serum sodium immediately increased above preoperative levels at the end of CPB. Caution is required to avoid serum sodium overcorrection on the conclusion of CPB.
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OBJECTIVE: We evaluated the effect of partial neuromuscular blockade (NMB) and no NMB on successful intraoperative monitoring of the lateral spread response (LSR) during microvascular decompression (MVD) surgery. METHODS: Patients were randomly allocated into one of three groups: the TOF group, the NMB was targeted to maintain two counts of train-of-four (TOF); the T1 group, maintain the T1/Tc (T1: amplitude of first twitch, Tc: amplitude of baseline twitch) ratio at 50%; and the N group, no relaxants after tracheal intubation. Successful LSR monitoring was defined as effective baseline establishment and maintenance of the LSR until dural opening. RESULTS: The success rate of LSR monitoring was significantly lower in the TOF group. But, there was no significant difference between T1 and N. The detection rate of spontaneous free-run electromyography (EMG) activity was significantly higher in the N group compared with the TOF and T1 groups. CONCLUSIONS: Partial NMB with a target of T1/Tc ratio at 50% allows good recording of LSR with same outcome as surgery without NMB, and reduced spontaneous EMG activity. SIGNIFICANCE: We suggested the availability of partial NMB for intraoperative LSR monitoring.
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Espasmo Hemifacial/cirurgia , Cirurgia de Descompressão Microvascular/métodos , Monitorização Intraoperatória/métodos , Bloqueio Neuromuscular/métodos , Monitoração Neuromuscular/métodos , Adulto , Idoso , Eletromiografia , Músculos Faciais/inervação , Músculos Faciais/cirurgia , Nervo Facial/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Although anesthetic-induced inhibition of lipopolysaccharide (LPS)-induced lung injury has been recognized, the underlying mechanism is obscure. Some studies suggest that reactive oxygen species (ROS) by isoflurane play a crucial role for anesthetic-induced protective effects on the brain or the heart; however, it still remains controversial. In this study, we examined the role of isoflurane-derived ROS in isoflurane-induced inhibition of lung injury and nuclear factor κB (NFκB) activation in LPS-challenged rat lungs. METHODS: Male Sprague-Dawley rats were subjected to inhalation of 1.0 minimum alveolar concentration of isoflurane for 60 minutes, and intratracheal LPS 0.1 mg was administered 60 minutes later. In some cases, ROS scavenger, 2-mercaptopropinyl glycine or N-acetylcysteine was given 30 minutes before isoflurane. ROS generation was measured by fluorometer before LPS challenge and 4 hours after. Isoflurane's preconditioning effect was assessed by histologic examination, protein content, neutrophil recruitment, and determination of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 levels in bronchoalveolar lavage fluid and lung tissue. Western blotting measured phosphorylation of inhibitory κB α (ser 32/36), NFκB p65, and inducible nitric oxide synthase (iNOS). TNF-α and IL-6 mRNA expression and immunofluorescence staining for iNOS were also assessed. RESULTS: Isoflurane preconditioning reduced inflammatory lung injury and TNF-α, IL-1ß, and IL-6 release in the lung. Isoflurane upregulated ROS generation before LPS but inhibited a ROS burst after LPS challenge. ROS scavenger administration before isoflurane abolished the isoflurane preconditioning effect as well as isoflurane-induced inhibition of phosphorylation of inhibitory κBα, NFκB p65, iNOS activation, and mRNA expression of TNF-α and IL-6 in acute LPS-challenged lungs. CONCLUSIONS: This study suggests a crucial role of upregulated ROS generation by isoflurane for modification of inflammatory pathways by isoflurane preconditioning in acute inflammation of the lung.
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Anestésicos Inalatórios/farmacologia , Isoflurano/farmacologia , Lipopolissacarídeos , NF-kappa B/antagonistas & inibidores , Pneumonia/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Western Blotting , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Núcleo Celular/metabolismo , Citocinas/biossíntese , Citosol/metabolismo , Imunofluorescência , Interleucina-6/metabolismo , Masculino , Infiltração de Neutrófilos/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/biossíntese , Fenótipo , Pneumonia/induzido quimicamente , Pneumonia/patologia , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Perioperative lidocaine infusion improves postoperative outcomes, mostly after abdominal and urologic surgeries. Knowledge of the effect of lidocaine on peripheral surgeries is limited. Presently, we investigated whether intraoperative lidocaine infusion reduced anesthetic consumption, duration of ileus, pain intensity, analgesic consumption and hospital stay after breast plastic surgeries. METHODS: Sixty female patients, aged 20-60 years, enrolled in this prospective study were randomly and equally divided to two groups. One group (n = 30) received a 1.5 mg/kg bolus of lidocaine approximately 30 min before incision followed by continuous infusion of lidocaine (1.5 mg/kg/h) until skin closure (lidocaine group). The other group (n = 30) was untreated (control group). Balanced inhalation (sevoflurane) anesthesia and multimodal postoperative analgesia were standardized. End tidal sevoflurane concentration during surgery, time to the first flatus and defecation, visual analog pain scale (0-10), analgesic consumption and associated side effects at 24, 48, and 72 h after surgery, hospital stay, and patient's general satisfaction were assessed. RESULTS: Compared to the control group, intraoperative lidocaine infusion reduced by 5% the amount of sevoflurane required at similar bispectral index (P = 0.014). However, there were no significant effects of lidocaine regarding the return of bowel function, postoperative pain intensity, analgesic sparing and side effects at all time points, hospital stay, and level of patient's satisfaction for pain control. CONCLUSIONS: Low dose intraoperative lidocaine infusion offered no beneficial effects on return of bowel function, opioid sparing, pain intensity and hospital stay after various breast plastic surgeries.
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OBJECTIVE: An inhalation anesthetic-induced attenuation effect on the inflammatory reaction during one-lung ventilation (OLV) has been reported. Pulmonary inflammation is a substantive prognostic factor for Ivor Lewis operations. Blood inflammatory parameters and postoperative pulmonary complications between sevoflurane and propofol-remifentanil anesthesia in patients undergoing Ivor Lewis operations were compared. DESIGN: A prospective, randomized study. SETTING: A medical university. PARTICIPANTS: Forty-eight patients undergoing Ivor Lewis operation allocated randomly into 2 groups. INTERVENTIONS: Patients received sevoflurane or total intravenous anesthesia using propofol and remifentanil (n = 24 per group). MEASUREMENTS AND MAIN RESULTS: Blood interleukin-6 (IL-6), malondialdehyde (MDA), oxygenation, abnormalities on a chest radiograph (CXR), extubation, intensive care unit (ICU) stay, length of hospitalization, and postoperative complications were compared between the 2 anesthetic techniques. The level of IL-6 at the end of surgery was lower for sevoflurane (69.5 [35.9-121.0] pg/mL) than propofol-remifentanil (128.2 [92.8-163.8] pg/mL, p = 0.03), but this difference was not maintained 24 hours after surgery. Frequencies of abnormalities measured by a CXR, PaO(2)/F(I)O(2)<300, and PaCO(2) <50 mmHg until discharge, the postoperative highest C-reactive protein level, white blood cells, and MDA did not differ between the 2 anesthetics. No differences in the extubation time, ICU stay, discharge day, or the incidence of hospital complications between sevoflurane and propofol-remifentanil anesthesia techniques were observed. CONCLUSIONS: Sevoflurane anesthesia attenuated an increase in blood IL-6 at the end of surgery but did not provide any advantages over propofol remifentanil in terms of postoperative pulmonary complications in Ivor Lewis operations.
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Esofagoscopia/efeitos adversos , Pneumopatias/epidemiologia , Éteres Metílicos/administração & dosagem , Piperidinas/administração & dosagem , Complicações Pós-Operatórias/epidemiologia , Propofol/administração & dosagem , Idoso , Anestesia por Inalação/métodos , Feminino , Humanos , Pneumopatias/etiologia , Pneumopatias/prevenção & controle , Masculino , Pessoa de Meia-Idade , Morbidade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Remifentanil , SevofluranoRESUMO
Two cases were reported in which severe postoperative laryngeal edema were developed after the operation of diffuse idiopathic skeletal hyperostosis (DISH) of cervical spine. In the first case, sudden airway obstruction was developed in the general ward 6 hour after uneventful decompression surgery for osteophyte. In the second patient, an elective preoperative tracheostomy was performed before surgery but the tube could not be removed for 2 months because of laryngeal edema and decreased vocal cord mobility. It should be emphasized that this airway problem can develop during the postoperative as well as the preoperative period, especially in the case of anterior cervical spine surgery.
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BACKGROUND: The effect of opioids on inflammation and immune responses is an important subject of investigation because immunoregulatory cytokines are produced in the central nervous system and opioid receptors are widespread in these cells. OBJECTIVES: The aim of this study was to evaluate the immunomodulatory effect of morphine on the C3 expression (both constitutive and proinflammatory cytokine-induced C3 expression) in primary rat astrocytes. METHODS: Primary rat astrocytes were untreated or treated with morphine in different concentrations (10(-6) to 10(-2) M) before incubation without or with 5 U/mL tumor necrosis factor-α (TNF-α), and C3 protein and mRNA expressions were measured. Similarly, astrocytes were treated with 10(-3) M morphine and stimulated with other proinflammatory cytokines, including 10 ng/mL interleukin-8 (IL-8) and 5 U/mL IL-1ß. Astrocytes were exposed to 10(-5) M naloxone for 2 hours before adding morphine, and TNF-α and C3 protein was measured. Tumor growth factor-ß (TGF-ß) was measured from the supernatants of each proinflammatory cytokine. RESULTS: All results are expressed as mean percentages of C3 production by normalizing C3 without morphine or any cytokine treatment as 100%. Constitutive C3 protein production was decreased at morphine 10(-3) M (57.2%) and 10(-2) M (30.1%). Pretreatment with morphine suppressed induction of C3 expression at both the protein and mRNA levels in astrocytes stimulated with TNF-α, IL-8, and IL-1ß (P < 0.05) in a dose-dependent manner. The inhibition of C3 protein production by morphine (10(-3) M; 33%) was partially attenuated by naloxone (52.0%) (P < 0.05). The pretreatment of astrocytes with morphine (10(-3) M) before stimulation with TNF-α, IL-8, and IL-1ß increased by 33% (P < 0.05), decreased by 15.2% (P < 0.05), and did not change the production of TGF-ß protein, respectively. CONCLUSIONS: Morphine downregulated both constitutive and proinflammatory cytokine-induced C3 expression of astrocytes at the transcriptional level, but not in a cytokine-specific manner.
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BACKGROUND: Leukemic cells originate from hypoxic bone marrow, which protects them from anti-cancer drugs. Although many factors that cause drug resistance in leukemic cells have been studied, the effect of hypoxia on drug-induced apoptosis is still poorly understood. METHODS: In this study, we examined the effect of hypoxia on anti-leukemic drug resistance in leukemic cell lines treated with cobalt chloride (CoCl(2)), a hypoxia-mimetic agent. Cellular proliferation was evaluated using the methyl thiazolyl tetrazolium (MTT) assay. Flow cytometry analysis and western blots were performed to investigate apoptosis-related proteins. RESULTS: Unlike its previously known apoptotic effect, the expression of HIF-1α increased the survival rate of human promyelocytic leukemia HL-60 cells when these cells were exposed to anti-leukemic drugs; these effects were mediated by heat-shock protein HSP70 and the pro-apoptotic protein Bax. CONCLUSION: These findings may provide new insights for understanding the mechanisms underlying hypoxia and for designing new therapeutic strategies for acute myeloid leukemia.
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OBJECT: Stable hemodynamics, normocapnia, and adequate pain relief are considered important factors in the reduction of neurological complications in pediatric patients undergoing encephaloduroarteriomyosynangiosis (EDAMS) operations for the treatment of moyamoya disease. A preoperative skull block may reduce hemodynamic fluctuations and hypo- or hyperventilation due to emergence delirium or oversedation and provide adequate pain relief, thereby reducing postoperative morbidity. METHODS: Pediatric patients (age 3-13 years) undergoing EDAMS surgery for moyamoya disease were randomly divided into a nerve block (NB) group (18 cases) or control group (21 cases). The treatment group patients received a preoperative NB (0.25% 5-8 ml bupivacaine mixed with 20-40 mg methylprednisolone) targeting the supraorbital, supratrochlear, auriculotemporal, and posterior auricular nerves. Patients in the control group did not receive NB. General anesthesia with sevoflurane was induced in both groups. RESULTS: In the NB group, stable hemodynamic parameters were obtained with a lower sevoflurane concentration than in the control group. For delirious awakening, the odds ratio in the control group was 4.9 compared with the NB group. Pain and analgesic requirement were higher in the control patients than in the NB-treated patients during the postanesthesia care unit stay. However, the arterial CO(2) tension in the postanesthesia care unit did not differ between the 2 groups. The odds ratio in the control group for the rate of morbidity (cerebral infarction and reversible ischemic neurological deficits) during the first 24 hours following the operation was 3.2 compared with the NB group. CONCLUSIONS: The use of skull block during EDAMS surgery provided easy hemodynamic control, calm awakening, and better pain relief and may be related to the reduced postoperative morbidity.
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Doença de Moyamoya/cirurgia , Bloqueio Nervoso/métodos , Crânio/inervação , Adolescente , Anestésicos Inalatórios , Bupivacaína/administração & dosagem , Dióxido de Carbono/sangue , Circulação Cerebrovascular/efeitos dos fármacos , Criança , Pré-Escolar , Delírio/prevenção & controle , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Éteres Metílicos , Metilprednisolona/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , SevofluranoRESUMO
BACKGROUND: Preexposure of brain to isoflurane, a commonly used anesthetic, induces ischemic tolerance. This phenomenon is called isoflurane preconditioning. However, it is not known whether isoflurane application after ischemia provides neuroprotection. METHODS: Corticostriatal slices (400 microm) freshly prepared from adult male Sprague-Dawley rats were subjected to a 15-min oxygen-glucose deprivation (OGD; to simulate ischemia in vitro). Isoflurane was applied after OGD. Brain slices were harvested 2 h after OGD for measuring 2,3,5-triphenyltetrazolium chloride (TTC) conversion to quantify cell injury. Adult male Sprague-Dawley rats were also subjected to middle cerebral arterial occlusion for 90 min and then treated with or without 2% isoflurane for 60 min started at the onset of reperfusion. The infarct volumes, neurologic deficit scores, and performance on rotarod were evaluated at 24 h after the onset of reperfusion. RESULTS: Isoflurane applied immediately after the 15-min OGD for 30 min dose-dependently reversed the OGD-induced decrease of TTC conversion. The TTC conversion was 34 +/- 16% and 58 +/- 28% of the control, respectively, for OGD alone and OGD plus 2% isoflurane (P < 0.05, n = 12). Application of 2% isoflurane for 30 min started at 10 min after the OGD also reduced the OGD-decreased TTC conversion. The presence of 0.3 microm glibenclamide, a general adenosine 5'-triphosphate-sensitive potassium channel blocker, or 500 microm 5-hydroxydecanoic acid, a mitochondrial adenosine 5'-triphosphate-sensitive potassium channel blocker, during the application of 2% isoflurane abolished the isoflurane preservation of TTC conversion. Application of isoflurane during reperfusion also improved neurologic outcome after brain ischemia. CONCLUSIONS: The results suggest that isoflurane administrated after OGD or brain ischemia provides neuroprotection. Mitochondrial adenosine 5'-triphosphate-sensitive potassium channels may be involved in this protection.
Assuntos
Anestésicos Inalatórios/farmacologia , Encéfalo/irrigação sanguínea , Hipóxia-Isquemia Encefálica/prevenção & controle , Isoflurano/farmacologia , Fármacos Neuroprotetores/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Ácidos Decanoicos/farmacologia , Relação Dose-Resposta a Droga , Glibureto/farmacologia , Hidroxiácidos/farmacologia , Hipóxia-Isquemia Encefálica/etiologia , Hipóxia-Isquemia Encefálica/patologia , Infarto da Artéria Cerebral Média/complicações , Masculino , Artéria Cerebral Média/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Bloqueadores dos Canais de Potássio/farmacologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/prevenção & controle , Sais de Tetrazólio/metabolismo , Sais de Tetrazólio/farmacocinéticaRESUMO
Live Salmonella vaccines are limited in use by the inherent toxicity of the lipopolysaccharide. The waaN gene encodes a myristyl transferase required for the secondary acylation of lipid A in lipopolysaccharide. A waaN mutant exhibits reduced induction of the inflammatory cytokines associated with lipopolysaccharide toxicity. Here the characteristics of a Salmonella enterica serovar Typhimurium aroA waaN mutant (SK100) in vitro and in vivo compared with its parent aroA strain (SL3261) were described. Phenotypic analysis of purified lipopolysaccharide obtained from SK100 confirmed that the physical and biological activities of the lipopolysaccharide had been altered. Nevertheless both strains had similar patterns of colonization and persistence in mice and significantly the aroA waaN mutant was equally as effective as the parent at protecting against challenge with wild-type S. Typhimurium. Furthermore, a SK100 strain was constructed expressing both tetanus toxin fragment C and the circumsporozoite protein of a malaria parasite. In marked contrast to its isogenic parent, the new attenuated strain induces significantly enhanced immune responses against the circumsporozoite protein. The waaN mutation enhances the ability of this strain to elicit immune responses towards guest antigens. This study provides important insights into the development of safe and effective multivalent Salmonella vaccines.
Assuntos
Vacinas Antimaláricas/imunologia , Vacinas contra Salmonella/imunologia , Salmonella typhimurium/genética , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Antiprotozoários/sangue , Proteínas de Bactérias/genética , Linhagem Celular , Contagem de Colônia Microbiana , Feminino , Lipopolissacarídeos/isolamento & purificação , Lipopolissacarídeos/toxicidade , Fígado/microbiologia , Macrófagos/microbiologia , Vacinas Antimaláricas/genética , Camundongos , Camundongos Endogâmicos BALB C , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/imunologia , Polissacarídeos Bacterianos/isolamento & purificação , Polissacarídeos Bacterianos/toxicidade , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Infecções por Salmonella/imunologia , Infecções por Salmonella/prevenção & controle , Vacinas contra Salmonella/genética , Salmonella typhimurium/imunologia , Salmonella typhimurium/patogenicidade , Baço/microbiologia , Toxina Tetânica/genética , Toxina Tetânica/imunologia , Fator de Necrose Tumoral alfa/biossíntese , Vacinas Tíficas-Paratíficas/genética , Vacinas Atenuadas/genética , Vacinas Atenuadas/imunologiaRESUMO
PURPOSE: Arrhythmias after an esophagectomy (most commonly atrial fibrillation) are a significant contributing factor to patient morbidity. However, the significance of an intraoperative arrhythmia is not completely understood. The aim of this retrospective study was to determine the occurrence and risk factors for developing intraoperative arrhythmias in patients undergoing an esophagectomy. MATERIALS AND METHODS: We reviewed the records of 427 patients who underwent a transthoracic esophagectomy between 2001 and 2005. Variables such as age, sex, hypertension, diabetes, cardiac disease, preoperative pulmonary function test (PFT) results, cancer level, combined radiochemotherapy, intrathoracic cavity adhesions and anastomosis site, hemoglobin, central venous pressure (CVP), fluid balance, serum potassium level, dose of vasopressors, temperature, and combined general and epidural anesthesia were analyzed as risk factors for the occurrence of an arrhythmia. We defined this arrhythmia as one not originating from the sinus node. RESULTS: The incidence of intraoperative arrhythmia in this subset of patients was 17.1%, with a 37.2% reoccurrence rate during the first three postoperative days. Univariate and multivariate analysis revealed the presence of heart disease, poor PFTs, cervical anastomosis, elevated CVP, and higher ephedrine doses to be independent predictors of the development of an intraoperative arrhythmia. CONCLUSION: The incidence of intraoperative arrhythmia during esophagectomy was 17.1% with a 37.2% of reoccurrence rate.