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Background: The rotational thromboelastogram (ROTEM) has been used in the management of massive bleeding and transfusion strategy. This study investigated ROTEM parameters measured during Cesarean section as predictors for the progression of persistent postpartum hemorrhage (PPH) in parturients with placenta previa. Methods: This prospective observational study recruited 100 women scheduled for elective Cesarean section after being diagnosed with placenta previa. Recruited women were divided into two groups according to the amount of estimated blood loss: the PPH group (PPH > 1500 ml) vs. the non-PPH group. ROTEM with laboratory tests was performed three times, preoperative, intraoperative, and postoperative time, which were compared between the two groups. Results: The PPH and non-PPH groups included 57 and 41 women, respectively. The area under the receiver-operating characteristic curve of postoperative FIBTEM A5 to detect PPH was 0.76 (95% CI = 0.64 to 0.87; P < 0.001). When postoperative FIBTEM A5 was 9.5, the sensitivity and specificity were 0.74 (95% CI = 0.55 to 0.88) and 0.73 (95% CI = 0.57 to 0.86), respectively. When subgrouping the PPH group based on the postoperative FIBTEM A5 value of 9.5, intraoperative cEBL was similar between the two subgroups; however, postoperative RBC was transfused more in the subgroup with FIBTEM A5 < 9.5 than the subgroup with FIBTEM A5 ≥ 9.5 (7.4 ± 3.0 vs 5.1 ± 2.3 units, respectively; P = 0.003). Conclusion: Postoperative FIBTEM A5, with appropriate selection of the cut-off value, can be a biomarker for more prolonged PPH and massive transfusion following Cesarean section by placenta previa.
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BACKGROUND: Acute postoperative pain and chronic discomfort are reported after robotic or endoscopic thyroidectomy. The purpose of this prospective, randomized, and double-blinded clinical trial was to investigate whether intraoperative infusion of nefopam decreases acute postoperative pain and chronic discomfort following either a robotic or endoscopic thyroidectomy via the bilateral axillo-breast approach (BABA). METHODS: Patients were randomized into two groups: The control group (n = 29) or the nefopam group (n = 29). Patients in each group were infused with the same volume of saline or nefopam (0.2 mg/kg bolus, 120 µg/kg/h continuous infusion) during surgery. Acute postoperative pain, the need for rescue analgesics, and other postoperative adverse effects were assessed at 1, 6, 24, and 48 h postoperatively. Chronic pain and discomfort was recorded at 3 months after surgery. RESULTS: Patients in the nefopam group reported lower pain scores in the neck, as well as the axilla and anterior chest areas at 1, 6, 24, and 48 h postoperatively, when compared with the control group (P < 0.05 at each time points). Rescue analgesics were required less in the nefopam group than in the control group (1.4 [1] vs. 2.3 [1.5]; P = 0.001). The degree of chronic pain and discomfort were relatively lower in the nefopam group (P < 0.05). CONCLUSION: We report that intravenous nefopam infusion during surgery decreased acute postoperative pain and the need for rescue analgesics, as well as chronic discomfort, following BABA robotic or endoscopic thyroidectomy without adverse events.
Assuntos
Analgésicos não Narcóticos/uso terapêutico , Endoscopia/métodos , Nefopam/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Tireoidectomia/efeitos adversos , Adulto , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Some short procedures require deep neuromuscular blockade, which needs to be reversed at the end of the procedure. Forty-four patients undergoing elective laryngeal micro-surgery were randomly allocated into two groups: rocuronium 0.45 mg.kg-1 with neostigmine (50 µg.kg-1 with glycopyrrolate 10 µg.kg-1 ) reversal (moderate block group) vs. rocuronium 0.90 mg.kg-1 with sugammadex (4 mg.kg-1 ) reversal (deep block group). The primary outcome was the intubating conditions during laryngoscopy secondary outcomes included recovery of neuromuscular block; conditions for tracheal intubation; satisfaction score as determined by the surgeon; onset of neuromuscular block; and postoperative sore throat. The onset of neuromuscular block was more rapid, and intubation conditions and ease of intra-operative laryngoscopy were more favourable, and the satisfaction score was lower in the moderate block group compared with the deep block group. No difference was found in the incidence of postoperative sore throat. In laryngeal micro-surgery, the use of rocuronium 0.9 mg.kg-1 with sugammadex for reversal was associated with better surgical conditions and a shorter recovery time than rocuronium 0.45 mg.kg-1 with neostigmine.
Assuntos
Neostigmina/farmacologia , Bloqueio Neuromuscular/métodos , Fármacos Neuromusculares não Despolarizantes/antagonistas & inibidores , Rocurônio/antagonistas & inibidores , Sugammadex/farmacologia , Adulto , Idoso , Período de Recuperação da Anestesia , Anestesia Geral/métodos , Atitude do Pessoal de Saúde , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Intubação Intratraqueal/efeitos adversos , Intubação Intratraqueal/métodos , Laringoscopia/efeitos adversos , Laringoscopia/métodos , Laringe/cirurgia , Masculino , Microcirurgia , Pessoa de Meia-Idade , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Faringite/etiologia , Complicações Pós-Operatórias , Rocurônio/administração & dosagemRESUMO
In clinical practice, both a thin-walled introducer needle and catheter-over-needle technique can be used to allow insertion of a guidewire during central venous catheterisation using the Seldinger technique. We compared the incidence of catheterisation-related complications (arterial puncture, haemothorax, pneumothorax, haematoma and catheter tip malposition) and insertion success rate for these two techniques in patients requiring right-sided subclavian central venous catheterisation. A total of 414 patients requiring infraclavicular subclavian venous catheterisation were randomly allocated to either a thin-walled introducer needle (needle group, n = 208) or catheter-over-needle technique (catheter group, n = 206). The catheterisation-related complication rate was lower in the needle group compared with the catheter group (5.8% vs. 15.5%; p = 0.001). Overall insertion success rates were similar (97.1% and 92.7% in the needle and catheter groups respectively; p = 0.046), although the first-pass success rate was higher in the needle group (62.0% vs. 35.4%; p < 0.001). We recommend the use of a thin-walled introducer needle technique for right-sided infraclavicular subclavian venous catheterisation.
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Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/métodos , Hemorragia/epidemiologia , Erros Médicos/estatística & dados numéricos , Pneumotórax/epidemiologia , Veia Subclávia , Cateterismo Venoso Central/instrumentação , Catéteres , Feminino , Hematoma/epidemiologia , Hemotórax/epidemiologia , Humanos , Incidência , Pessoa de Meia-Idade , Agulhas , Estudos Prospectivos , Método Simples-CegoRESUMO
Activation of the extensive cross-talk among the receptor tyrosine kinases (RTKs), particularly ErbB family-Met cross-talk, has emerged as a likely source of drug resistance. Notwithstanding brilliant successes were attained while using small-molecule inhibitors or antibody therapeutics against specific RTKs in multiple cancers over recent decades, a high recurrence rate remains unsolved in patients treated with these targeted inhibitors. It is well aligned with multifaceted properties of cancer and cross-talk and convergence of signaling pathways of RTKs. Thereby many therapeutic interventions have been actively developed to overcome inherent or acquired resistance. To date, no bispecific antibody (BsAb) showed complete depletion of dual RTKs from the plasma membrane and efficient dual degradation. In this manuscript, we report the first findings of a target-specific dual internalization and degradation of membrane RTKs induced by designed BsAbs based on the internalizing monoclonal antibodies and the therapeutic values of these BsAbs. Leveraging the anti-Met mAb able to internalize and degrade by a unique mechanism, we generated the BsAbs for Met/epidermal growth factor receptor (EGFR) and Met/HER2 to induce an efficient EGFR or HER2 internalization and degradation in the presence of Met that is frequently overexpressed in the invasive tumors and involved in the resistance against EGFR- or HER2-targeted therapies. We found that Met/EGFR BsAb ME22S induces dissociation of the Met-EGFR complex from Hsp90, followed by significant degradation of Met and EGFR. By employing patient-derived tumor models we demonstrate therapeutic potential of the BsAb-mediated dual degradation in various cancers.
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Anticorpos Biespecíficos/uso terapêutico , Receptores ErbB/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Receptor ErbB-2/antagonistas & inibidores , Animais , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/metabolismo , Feminino , Humanos , Camundongos , Neoplasias/patologia , Proteínas Proto-Oncogênicas c-met/metabolismo , Receptor ErbB-2/metabolismo , Transdução de SinaisRESUMO
After elective ear surgery with cisatracurium neuromuscular blockade, 48 adults were randomly assigned to receive neostigmine: (a) at appearance of the fourth twitch of a 'train-of-four'; (b) at loss of fade to train-of-four; or (c) at loss of fade to double-burst stimulation, all monitored using a TOF-Watch SX® on one arm. For each of these conditions, the recovery from train-of-four (TOF) ratio was measured in parallel objectively using a TOF-Watch SX placed on the contralateral arm. The median (IQR [range]) time from administration of reversal to a train-of-four ratio ≥ 0.9 was 11 (9-15.5 [2-28]) min, 8 (4-13.5 [1-25]) min and 7 (4-10 [2-15]) min in the three groups, respectively. This recovery time was significantly shorter when reversal was given at loss of fade to double-burst stimulation (c), than when given at the appearance of the fourth twitch (a), p = 0.046. However, the total time to extubation may be unaffected as it takes longer for fade to be lost after double-burst stimulation than for four twitches subjectively to appear.
Assuntos
Período de Recuperação da Anestesia , Atracúrio/análogos & derivados , Estimulação Elétrica , Neostigmina/administração & dosagem , Bloqueio Neuromuscular/métodos , Inibidores da Colinesterase/administração & dosagem , Esquema de Medicação , Orelha/inervação , Orelha/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Bloqueadores Neuromusculares , Junção Neuromuscular/efeitos dos fármacos , Fatores de TempoRESUMO
We investigated the effects of magnesium sulphate on blood coagulation profiles using rotational thromboelastometry in patients undergoing laparoscopic colorectal cancer surgery. Patients were randomly allocated to the magnesium group (n = 22) or control group (n = 22). The magnesium group received intravenous magnesium sulphate (50 mg.kg(-1) followed by a continuous infusion of 15 mg.kg(-1) .h(-1) ), whereas the control group received the same volume of isotonic saline. Mean (SD) postoperative serum magnesium levels were 1.60 (0.13) mmol.l(-1) in the magnesium group compared with 0.98 (0.06) mmol.l(-1) in the control group (p < 0.001). All maximum clot firmness values of ROTEM analysis were significantly lower on the third postoperative day in the magnesium group compared with the control group (p < 0.05). We conclude that ROTEM analysis demonstrated that intra-operative administration of intravenous magnesium sulphate reduces blood hypercoagulability in patients undergoing laparoscopic colorectal cancer surgery.
Assuntos
Neoplasias Colorretais/cirurgia , Laparoscopia , Sulfato de Magnésio/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Tromboelastografia/métodos , Trombofilia/prevenção & controle , Idoso , Método Duplo-Cego , Feminino , Humanos , Magnésio/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The oblique subcostal transversus abdominis plane (OSTAP) block has been described as an effective analgesic method for upper abdominal surgery. We evaluated the postoperative analgesia of the OSTAP block and compared it with that of the transversus abdominis plane (TAP) block in patients undergoing laparoscopic cholecystectomy (LC). METHODS: Patients scheduled for elective LC were randomized to receive either standard care or to undergo an OSTAP or TAP block. All blocks were performed with ultrasound guidance, and 20 mL of 0.375% ropivacaine was injected bilaterally. The postoperative pain score and consumption of rescue analgesics were evaluated. RESULTS: The OSTAP block reduced postoperative verbal numerical rating scale pain scores (median [Interquartile range, IQR]) compared to standard care at 10 min (2 [1-4] vs. 7 [5-8]), 30 min (2 [1-5] vs. 6 [5-8]), 1 h (2 [1-3] vs. 5 [4-6]), and 3 h (2 [2-3] vs. 4 [3-5]). Pain scores were also lower in the OSTAP group than in the TAP group at 10 min (2 [1-4] vs. 4 [2-6]), 1 h (2 [1-3] vs. 3 [3-4]), 3 h (2 [2-3] vs. 3 [3-4]), 6 h (2 [2-3] vs. 3 [3-5]), and 24 h (1 [1-2] vs. 2 [2-3]) postoperatively. The total fentanyl requirement was reduced in the OSTAP group (p = 0.005). CONCLUSION: The OSTAP block can provide better analgesia than the TAP block or standard care during the postoperative 24 h period in patients undergoing LC.
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Músculos Abdominais , Colecistectomia Laparoscópica/métodos , Bloqueio Nervoso/métodos , Dor Pós-Operatória/tratamento farmacológico , Ultrassonografia de Intervenção/métodos , Adulto , Analgésicos/administração & dosagem , Analgésicos/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The present study was conducted to investigate the influence of different operating table heights on the quality of laryngeal view and the discomfort of the anaesthetist during enodotracheal intubation. METHODS: Eight anaesthetists participated, to each of whom 20 patients were allocated. Before induction of anaesthesia, the height of the operating table was adjusted to place the patient's forehead at one of four landmarks on the anaesthetist's body (the order being determined by block randomization with eight blocks): umbilicus (Group U), lowest rib margin (Group R), xiphoid process (Group X), and nipple (Group N). Next, the anaesthetist began the laryngoscopy and evaluated the grade of laryngeal view. For this 'initial posture', the anaesthetist was not allowed to adjust his or her posture (flexion or extension of the neck, lower back, knee, and ankle). This laryngeal view was then re-graded after these constraints were relaxed. At each posture, the anaesthetist's joint movements and discomfort during mask ventilation or intubation were evaluated. RESULTS: The laryngeal view before postural changes was better in Group N than in Group U (P=0.003). The objective and subjective measurements of neck or lower back flexion during intubation were higher in Group U than in Groups X and N (P<0.01 for each). The improvement of laryngeal view resulting from postural changes correlated with the anaesthetist's discomfort score before the postural change (P<0.01). CONCLUSIONS: Higher operating tables (at the xiphoid process and nipple level of the anaesthetist) can provide better laryngeal views with less discomfort during tracheal intubation. TRIAL REGISTRY NUMBER: NCT01649973 (clinicaltrials.gov).
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Ergonomia/métodos , Intubação Intratraqueal/métodos , Laringe , Mesas Cirúrgicas , Adulto , Idoso , Desenho de Equipamento , Feminino , Humanos , Laringoscopia/métodos , Masculino , Pessoa de Meia-Idade , Saúde Ocupacional , Posicionamento do Paciente/métodos , PosturaRESUMO
This study compared the predicted effect-site concentration of propofol at loss and recovery of consciousness when using target-controlled infusion devices with the same pharmacokinetic model (Marsh) but a different plasma effect-site equilibration rate constant (ke0 ), the Diprifusor(TM) (ke0 0.26 min(-1) ) and Base Primea™ (ke0 1.21 min(-1) ). We studied 60 female patients undergoing minor gynaecological surgery under general anaesthesia. Although the total dose of propofol and time until loss of consciousness were comparable, the effect-site concentration at loss of consciousness was significantly lower with the Diprifusor than with the Base Primea (1.2 (0.3) µg.ml(-1) vs 4.5 (0.9) µg.ml(-1) , respectively, p < 0.001). The effect-site concentration at recovery of consciousness was significantly higher with the Diprifusor than with the Base Primea (1.8 (0.4) µg.ml(-1) vs 1.5 (0.2) µg.ml(-1) , respectively, p = 0.01). In conclusion, the effect-site concentration of propofol differs depending on the ke0 , despite the use of the same pharmacokinetic model. Therefore, the ke0 should be considered when predicting loss and recovery of consciousness based on the effect-site concentration of propofol.
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Período de Recuperação da Anestesia , Anestésicos Intravenosos/farmacocinética , Estado de Consciência/efeitos dos fármacos , Propofol/farmacocinética , Adulto , Idoso , Algoritmos , Anestesia Geral/métodos , Anestésicos Intravenosos/sangue , Relação Dose-Resposta a Droga , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Infusões Intravenosas/instrumentação , Infusões Intravenosas/métodos , Pessoa de Meia-Idade , Modelos Biológicos , Propofol/sangue , Adulto JovemRESUMO
BACKGROUND: Catheter-related bladder discomfort (CRBD) secondary to intraoperative catheterization of urinary bladder is one of the most distressing symptoms during recovery from anaesthesia. Butylscopolamine, a peripheral antimuscarinic agent, is effective for relieving the pain, which is because of smooth muscle contraction. The aim of this study was to assess the efficacy and safety profiles of butylscopolamine in treating CRBD after urological surgeries. METHODS: Adult male patients undergoing urological surgery requiring urinary bladder catheterization intraoperatively were enrolled. Induction and maintenance of anaesthesia were standardized. Patients were randomized into two groups after complaining of CRBD in the post-anaesthesia care unit. The control group (n=29) received normal saline and the butylscopolamine group (n=28) was administered butylscopolamine 20 mg i.v. The severity of CRBD, postoperative pain, and adverse effects were assessed at baseline, 20 min, 1, 2, and 6 h after administration of the study drug. RESULTS: The severity of CRBD observed in the butylscopolamine group was significantly lower than that of the control group at 1, 2, and 6 h after administration of the study drug [59 (12), 50 (16), 40 (21) in the control group vs 41 (22), 32 (25), 23 (18) in the butylscopolamine group, P<0.01]. Rescue analgesics were required less in the butylscopolamine group than in the control group (P=0.001). Adverse events were comparable between the two groups. CONCLUSION: Butylscopolamine 20 mg administered i.v. after complaining CRBD during recovery reduced both the severity of CRBD and the need for rescue analgesics without adverse effects in patients undergoing urologic surgeries.
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Brometo de Butilescopolamônio/uso terapêutico , Disuria/tratamento farmacológico , Antagonistas Muscarínicos/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Cateterismo Urinário/efeitos adversos , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Brometo de Butilescopolamônio/efeitos adversos , Método Duplo-Cego , Disuria/etiologia , Frequência Cardíaca/efeitos dos fármacos , Humanos , Cuidados Intraoperatórios/efeitos adversos , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/efeitos adversos , Medição da Dor/métodos , Dor Pós-Operatória/etiologia , Cuidados Pós-Operatórios/métodos , Estudos Prospectivos , Resultado do Tratamento , Procedimentos Cirúrgicos Urológicos Masculinos/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: The purpose of this study was to investigate whether combined administration of celecoxib and sevoflurane after ischaemia produces additive neuroprotection against transient global cerebral ischaemia in rats. METHODS: Cerebral ischaemia was induced by bilateral common carotid artery occlusion with haemorrhagic hypotension for 8 min. After ischaemia, no drugs were administered in the sham (n=4) and control (n=10) groups. In the celecoxib group (n=10), celecoxib 2 mg kg(-1) was administered after reperfusion. In the sevoflurane group (n=10), after reperfusion, sevoflurane 2.4% was inhaled two times for 5 min each at an interval of 10 min to achieve postconditioning. In the celecoxib+sevoflurane group (n=10), administration of celecoxib 2 mg kg(-1) and the sevoflurane postconditioning were performed simultaneously. Necrotic or apoptotic cells were examined in the hippocampus 7 days after ischaemia. Serum levels of proinflammatory cytokines including tumour necrosis factor-α and interleukin-1ß were measured 2 h, and 3 and 7 days after ischaemia. RESULTS: Necrotic or apoptotic cells were observed more frequently in the control group than in the celecoxib or sevoflurane groups 7 days after ischaemia (P<0.05). Cytokine levels were higher in the control group when compared with the celecoxib or sevoflurane groups 2 h after ischaemia (P<0.05). However, the histological outcomes and cytokine levels were similar in all three groups treated with celecoxib or sevoflurane. CONCLUSIONS: Combined treatment with celecoxib and sevoflurane after global cerebral ischaemia has no additive neuroprotective effects in rats.
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Anestésicos Inalatórios/administração & dosagem , Isquemia Encefálica/tratamento farmacológico , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Éteres Metílicos/administração & dosagem , Fármacos Neuroprotetores/farmacologia , Pirazóis/administração & dosagem , Sulfonamidas/administração & dosagem , Animais , Celecoxib , Sinergismo Farmacológico , Interleucina-1beta/sangue , Masculino , Éteres Metílicos/farmacologia , Pirazóis/farmacologia , Ratos , Ratos Sprague-Dawley , Sevoflurano , Sulfonamidas/farmacologia , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUND: Sevoflurane is widely used in paediatric anaesthesia but frequently causes emergence agitation (EA). This study evaluated whether limiting the sevoflurane concentration by combining remifentanil with sevoflurane reduced the incidence of EA. METHODS: Eighty-four preschool children scheduled for adenotonsillectomy were randomly assigned to either the remifentanil or sevoflurane group. In the remifentanil group, anaesthesia was induced with thiopental, rocuronium, and 1% sevoflurane. It was maintained with 1% sevoflurane, 60% nitrous oxide in oxygen, and a continuous infusion of remifentanil. For the sevoflurane group, anaesthesia was induced with thiopental, rocuronium, and 8% sevoflurane, and was maintained with 2-3% sevoflurane. Both groups received ketorolac 1 mg/kg and dexamethasone 0.15 mg/kg. EA was measured using the paediatric anaesthesia emergence delirium (PAED) scale and a four-point EA scale in the post-anaesthesia care unit. RESULTS: The scores on the PAED scales were significantly lower in the remifentanil group than in the sevoflurane group [median (interquartile range); 6 (4.25-10.25) vs. 11 (7.75-14.0), P = 0.007], and the proportion of patients with PAED scores ≥ 10 was significantly lower in the remifentanil group than in the sevoflurane group [15 (35.7%) vs. 27 (64.2%), P = 0.009]. The incidence of EA evaluated using the four-point scale was also lower in the remifentanil group [11 (26.1%) vs. 21 (50%), respectively, P = 0.025]. CONCLUSION: The incidence of EA was lower in children undergoing adenotonsillectomy who received a lower concentration of sevoflurane combined with remifentanil than in those given a higher concentration of sevoflurane without remifentanil.
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Adenoidectomia/efeitos adversos , Período de Recuperação da Anestesia , Anestésicos Inalatórios/efeitos adversos , Anestésicos Intravenosos/efeitos adversos , Éteres Metílicos/efeitos adversos , Piperidinas/efeitos adversos , Agitação Psicomotora/epidemiologia , Tonsilectomia/efeitos adversos , Pré-Escolar , Delírio/psicologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/psicologia , Agitação Psicomotora/psicologia , Remifentanil , SevofluranoRESUMO
The progression and exacerbations of chronic obstructive pulmonary disease (COPD) are intimately associated with tobacco smoke/biomass fuel-induced oxidative and aldehyde/carbonyl stress. Alterations in redox signaling proinflammatory kinases and transcription factors, steroid resistance, unfolded protein response, mucus hypersecretion, extracellular matrix remodeling, autophagy/apoptosis, epigenetic changes, cellular senescence/aging, endothelial dysfunction, autoimmunity, and skeletal muscle dysfunction are some of the pathological hallmarks of COPD. In light of the above it would be prudent to target systemic and local oxidative stress with agents that can modulate the antioxidants/ redox system or by boosting the endogenous levels of antioxidants for the treatment and management of COPD. Identification of various antioxidant agents, such as thiol molecules (glutathione and mucolytic drugs, such as N-acetyl-L-cysteine, N-acystelyn, erdosteine, fudosteine, ergothioneine, and carbocysteine lysine salt), dietary natural product-derived polyphenols and other compounds (curcumin, resveratrol, green tea catechins, quercetin sulforaphane, lycopene, acai, alpha-lipoic acid, tocotrienols, and apocynin) have made it possible to modulate various biochemical aspects of COPD. Various researches and clinical trials have revealed that these antioxidants can detoxify free radicals and oxidants, control expression of redox and glutathione biosynthesis genes, chromatin remodeling, and ultimately inflammatory gene expression. In addition, modulation of cigarette smoke-induced oxidative stress and related cellular changes have also been reported to be effected by synthetic molecules. This includes specific spin traps like α-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a superoxide dismutase mimetic M40419, lipid peroxidation and protein carbonylation blockers/inhibitors, such as edaravone and lazaroids/tirilazad, myeloperoxidase inhibitors, as well as specialized pro-resolving mediators/inflammatory resolving lipid mediators, omega-3 fatty acids, vitamin D, and hydrogen sulfide. According to various studies it appears that the administration of multiple antioxidants could be a more effective mode used in the treatment of COPD. In this review, various pharmacological and dietary approaches to enhance lung antioxidant levels and beneficial effects of antioxidant therapeutics in treating or intervening the progression of COPD have been discussed.
Assuntos
Antioxidantes/uso terapêutico , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/metabolismo , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Radicais Livres/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Pulmão/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Carbonilação Proteica/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fumaça/efeitos adversos , Nicotiana/efeitos adversosRESUMO
BACKGROUND: Polymeric modification of islet surface is highly effective in preventing transplanted islets against host immune reactions. However, grafted islets are eventually rejected by the host immune reaction. Thus, repetitive islet transplantation is needed to treat type 1 diabetic patients experiencing graft rejection. We explored whether using poly(ethylene glycol) (PEG) as surface camouflage of islets (PEGylation) can be an affordable immunoprotective remedy for repeated islet transplantation. METHODS: The surface coverage of PEG was evaluated in vitro. The viability of PEGylated islets cocultured with sensitized or nonsensitized splenocytes was evaluated using lactate dehydrogenase assay. In addition, the effect of surface modification on immunoprotection for repetitively transplanted islets was evaluated in a sensitized rat model. RESULTS: Unmodified islets transplanted in combination with Cyclosporine (CsA) and anti-CD4 monoclonal antibody (OX-38) into the sensitized recipients did not maintain a normal level of blood glucose over 20 days. Interestingly, however, three of the five recipients became normoglycemic up to 30 days when PEGylated islets were transplanted in combination with CsA and OX-38. CONCLUSION: These results demonstrated that PEGylation alone was not an affordable immunoprotective method, but the combination of CsA and OX-38 along with PEGylation showed a highly improved a synergic effects on the inhibition of sensitized host immune reactions.
Assuntos
Anticorpos Monoclonais/farmacologia , Ciclosporina/farmacologia , Diabetes Mellitus Experimental/cirurgia , Imunossupressores/farmacologia , Transplante das Ilhotas Pancreáticas/imunologia , Ilhotas Pancreáticas/efeitos dos fármacos , Polietilenoglicóis/farmacologia , Animais , Biomarcadores/metabolismo , Glicemia/metabolismo , Técnicas de Cocultura , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Sinergismo Farmacológico , Quimioterapia Combinada , Imuno-Histoquímica , Ilhotas Pancreáticas/imunologia , Ilhotas Pancreáticas/metabolismo , L-Lactato Desidrogenase/metabolismo , Masculino , Ratos , Ratos Endogâmicos F344 , Ratos Sprague-Dawley , Baço/citologia , Baço/imunologia , Fatores de Tempo , Técnicas de Cultura de TecidosRESUMO
BACKGROUND: Many anti-epileptics cause resistance to non-depolarizing neuromuscular blocking agents, but this has not been reported for valproic acid (VPA). We hypothesized that VPA would increase the rocuronium requirement and that magnesium sulphate (MgSO(4)) may reduce this increase. METHODS: Fifty-five patients undergoing cerebrovascular surgeries were studied. Subjects were allocated into three groups at a 1:1:1 ratio: Groups VM, VC, and C. Groups VM and VC were given VPA premedication; Group C was not. A rocuronium injection (0.6 mg kg(-1) i.v.) was administered to Group VM, followed by MgSO(4) as a 50 mg kg(-1) i.v. bolus and 15 mg kg(-1) h(-1) infusion. The same volume of 0.9% saline was administered to the other groups. Supplementary rocuronium (0.15 mg kg(-1)) was given whenever the train-of-four count reached 2. Rocuronium requirements (primary outcome), mean arterial pressure (MAP), heart rate (HR), nausea, vomiting, shivering, and use of anti-emetics and nicardipine were compared. RESULTS: Group VC showed the highest rocuronium requirement [mg kg(-1) h(-1): 0.47 (0.08) vs 0.33 (0.12) (Group C), 0.31 (0.07) (Group VM); P<0.001]. MAP, intraoperative HR, nausea, vomiting, shivering, and use of anti-emetics and nicardipine were not significantly different among the groups. Postoperative HR was lower in Group VM than in Group VC. CONCLUSIONS: VPA increased the rocuronium requirement, and MgSO(4) infusion attenuated this increase.
Assuntos
Androstanóis/administração & dosagem , Anticonvulsivantes/farmacologia , Transtornos Cerebrovasculares/cirurgia , Sulfato de Magnésio/farmacologia , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Ácido Valproico/farmacologia , Adolescente , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Craniotomia , Método Duplo-Cego , Interações Medicamentosas , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , RocurônioRESUMO
We investigated the effects of magnesium sulphate on blood coagulation profiles using rotational thromboelastometry in gynaecological patients undergoing pelviscopic surgery. Patients were randomly allocated to the magnesium group (n = 20) or control group (n = 20). The magnesium group received magnesium sulphate (50 mg.kg(-1) followed by continuous infusion of 15 mg.kg(-1).h(-1)), whereas the control group received the same volume of isotonic saline according to the same methods. Mean (SD) postoperative serum magnesium levels were 1.58 (0.17) mmol.l(-1) in the magnesium group compared with 0.98 (0.06) mmol.l(-1) in the control group (p < 0.001). Postoperative clotting time, clot formation time, α-angle and maximum clot firmness of INTEM, and clot formation time, α-angle, and maximum clot firmness of EXTEM were significantly different between the two groups (p < 0.05). Intra-operative infusion of magnesium sulphate seems to attenuate postoperative hypercoagulability by maintaining magnesium levels at the upper limit of the normal range.
Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Sulfato de Magnésio/farmacologia , Complicações Pós-Operatórias/prevenção & controle , Tromboelastografia/métodos , Trombofilia/prevenção & controle , Adulto , Método Duplo-Cego , HumanosRESUMO
BACKGROUND: Remifentanil is known to cause bradycardia and hypotension, as well as the decreases of cardiac output (CO). We hypothesized that hemodynamic suppression by remifentanil would affect the onset time of rocuronium. This study investigated whether the onset of rocuronium was influenced by the drug-administration sequence during induction of anesthesia with target-controlled infusion of propofol and remifentanil. METHODS: Healthy adult patients (n = 126) undergoing elective surgery under general anesthesia were randomized into two groups according to drug-administration sequence. In Remi-Pro-Rocu group (n = 62), remifentanil was infused first, followed by propofol. Then, rocuronium was administered lastly. In Pro-Rocu-Remi group (n = 64), propofol, rocuronium, and remifentanil were given in that order. As a primary outcome, the onset time of rocuronium was measured. Mean arterial pressure (MAP), heart rate (HR), CO, and stroke volume were recorded before anesthesia (T1), at injection of rocuronium (T2), immediately before and after intubation (T3 and T4). RESULTS: In Remi-Pro-Roc group, the onset of rocuronium was delayed significantly compared with Pro-Rocu-Remi group [median (interquartile range); 130 (105-150) vs. 90 (71-100) s, P < 0.001]. At the time of rocuronium injection (T2), MAP, HR, and CO were significantly lower in Remi-Pro-Rocu group than Pro-Rocu-Remi group (P < 0.001). CONCLUSION: The onset time of rocuronium is prolonged significantly by early administration of remifentanil during target-controlled infusion of propofol and remifentanil, and it may be due to the decreased CO caused by remifentanil.
Assuntos
Androstanóis , Anestésicos Intravenosos/administração & dosagem , Fármacos Neuromusculares não Despolarizantes , Piperidinas/administração & dosagem , Propofol/administração & dosagem , Adulto , Anestésicos Intravenosos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Método Duplo-Cego , Interações Medicamentosas , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Junção Neuromuscular/efeitos dos fármacos , Dor Pós-Operatória/epidemiologia , Piperidinas/efeitos adversos , Propofol/efeitos adversos , Remifentanil , Rocurônio , Tamanho da Amostra , Volume Sistólico/efeitos dos fármacos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: In this prospective, randomized, double-blind study, we evaluated and compared the incidence of postoperative nausea and vomiting (PONV) after paediatric strabismus surgery with two different anaesthetic methods, sevoflurane or remifentanil-sevoflurane. METHODS: In total, 78 paediatric patients (aged 6-11 yr) undergoing strabismus surgery were enrolled and randomly assigned to two groups, sevoflurane (Group S) and remifentanil-sevoflurane (Group R). Anaesthesia was maintained with 2-3% sevoflurane in Group S (n=39) or with a continuous infusion of remifentanil combined with 1% sevoflurane in Group R (n=39), both using 50% N(2)O/O(2). Arterial pressure and heart rate before induction, after tracheal intubation, after skin incision, and at the end of surgery were recorded. The incidence of PONV in the post-anaesthesia care unit, the day surgery care unit, and at home 24 h after surgery was recorded. RESULTS: Arterial pressure and heart rate were stable throughout the surgery, but were significantly lower in Group R than in Group S after tracheal intubation and skin incision. The incidence of PONV and postoperative vomiting was 17.9%/17.9% and 12.8%/10.2% (Group S/Group R) at the respective time points; values were comparable between the groups. CONCLUSIONS: The incidence of PONV after paediatric strabismus surgery under sevoflurane anaesthesia was relatively low, and combining remifentanil with sevoflurane did not further increase the incidence.