RESUMO
BACKGROUND: Intravenous (IV) infusions of volatile anesthetics in lipid emulsion may increase blood lipid concentration, potentially altering the anesthetic agent's blood solubility and blood-gas partition coefficient (BGPC). We examined the influence of a low-lipid concentration 20% sevoflurane emulsion on BGPC, and the anesthetic potency of this emulsion using dogs. METHODS: We compared BGPC and anesthetic characteristics in 6 dogs between the IV anesthesia of emulsion and the sevoflurane inhalation anesthesia in a randomized crossover substudy. Minimum alveolar concentrations (MACs) were determined by tail-clamp stimulation by using the up-and-down method. Blood sevoflurane concentration and partial pressure were measured by gas chromatography; end-tidal sevoflurane concentration was measured using a gas monitor. The primary outcome was BGPC at the end of IV anesthesia and inhalation anesthesia. Secondary outcomes were time to loss/recovery of palpebral reflex, finish intubation and awakening, MAC, blood concentration/partial pressure at MAC and awakening, correlation between blood partial pressure and gas monitor, and the safety of emulsions. RESULTS: BGPC showed no difference between IV and inhaled anesthesia (0.859 [0.850-0.887] vs 0.813 [0.791-0.901]; P = .313). Induction and emergence from anesthesia were more rapid in IV anesthesia of emulsion than inhalation anesthesia. MAC of emulsion (1.33% [1.11-1.45]) was lower than that of inhalation (2.40% [2.33-2.48]; P = .031), although there was no significant difference in blood concentration. End-tidal sevoflurane concentration could be estimated using gas monitor during IV anesthesia of emulsion. No major complications were observed. CONCLUSIONS: IV anesthesia with emulsion did not increase the BGCP significantly compared to inhalation anesthesia. It was suggested that the anesthetic potency of this emulsion may be equal to or more than that of inhalation.
Assuntos
Anestésicos Inalatórios/administração & dosagem , Anestésicos Intravenosos/administração & dosagem , Emulsões Gordurosas Intravenosas/administração & dosagem , Sevoflurano/administração & dosagem , Administração por Inalação , Anestésicos Inalatórios/sangue , Anestésicos Intravenosos/sangue , Animais , Estado de Consciência/efeitos dos fármacos , Estudos Cross-Over , Cães , Composição de Medicamentos , Emulsões Gordurosas Intravenosas/metabolismo , Infusões Intravenosas , Limiar da Dor/efeitos dos fármacos , Distribuição Aleatória , Sevoflurano/sangue , Equivalência TerapêuticaRESUMO
BACKGROUND: The influence of preoperative rehydration on the action of rocuronium has not yet been investigated. OBJECTIVE: The objective is to evaluate the hypothesis that preoperative rehydration lowers arterial rocuronium plasma concentrations and changes its associated neuromuscular blocking effects during induction of anaesthesia. DESIGN: Randomised, single-blinded study. SETTING: A secondary hospital from October 2013 to July 2014. PATIENTS: In total, 46 men undergoing elective surgery were eligible to participate and were randomly allocated into two groups. Exclusion criteria were severe hepatic, renal or cardiovascular disorder; neuromuscular disease; history of allergy to rocuronium; BMI more than 30âkgâm; receiving medication known to influence neuromuscular function. INTERVENTION: Participants received 1500âml of oral rehydration solution (rehydration group) or none (control group) until 2 hours before anaesthesia. Arterial blood samples were obtained 60, 90 and 120âs and 30âmin after rocuronium (0.6âmgâkg) administration during total intravenous anaesthesia. Responses to 0.1-Hz twitch stimuli were measured at the adductor pollicis muscle using acceleromyography. MAIN OUTCOME MEASURES: Arterial plasma rocuronium concentrations. RESULTS: Arterial plasma rocuronium concentrations at 60, 90 and 120âs in the rehydration and control groups were 9.9 and 13.7, 6.8 and 9.5 and 6.2 and 8.1âµgâml, respectively (Pâ=â0.02, 0.003 and 0.02, respectively); the onset times in the rehydration and control groups were 92.0 and 69.5âs (Pâ=â0.01), and the times to twitch re-appearance were 25.3 and 30.4âmin (Pâ=â0.004), respectively. CONCLUSION: Preoperative rehydration significantly reduces arterial plasma rocuronium concentrations in the first 2 minutes after administration, prolonging the onset time and shortening the duration of effect. A higher dose or earlier administration should be considered for patients who receive preoperative rehydration. TRIAL REGISTRATION: Umin identifier: UMIN000011981.
Assuntos
Androstanóis/sangue , Anestesia Intravenosa/efeitos adversos , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Hidratação/efeitos adversos , Fármacos Neuromusculares não Despolarizantes/sangue , Adulto , Androstanóis/administração & dosagem , Período de Recuperação da Anestesia , Anestesia Intravenosa/métodos , Desidratação/etiologia , Desidratação/terapia , Jejum/efeitos adversos , Humanos , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Período Pré-Operatório , Rocurônio , Método Simples-Cego , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Rapid fluid infusion resulting in increased hepatic blood flow may decrease the propofol plasma concentration (Cp) because propofol is a high hepatic extraction drug. The authors investigated the effects of rapid colloid and crystalloid infusions on the propofol Cp during target-controlled infusion. METHODS: Thirty-six patients were randomly assigned to 1 of 3 interventions (12 patients per group). At least 30 min after the start of propofol infusion, patients received either a 6% hydroxyethyl starch (HES) solution at 24 ml·kg·h or acetated Ringer's solution at 24 or 2 ml·kg·h during the first 20 min. In all groups, acetated Ringer's solution was infused at 2 ml·kg·h during the next 20 min. The propofol Cp was measured every 2.5 min as the primary outcome. Cardiac output, blood volume, and indocyanine green disappearance rate were determined using a pulse dye densitogram analyzer before and after the start of fluid administration. Effective hepatic blood flow was calculated as the blood volume multiplied by the indocyanine green disappearance rate. RESULTS: The rapid HES infusion significantly decreased the propofol Cp by 22 to 37%, compared to the Cp at 0 min, whereas the rapid or maintenance infusion of acetate Ringer's solution did not decrease the propofol Cp. Rapid HES infusion, but not acetate Ringer's solution infusion, increased the effective hepatic blood flow. CONCLUSIONS: Rapid HES infusion increased the effective hepatic blood flow, resulting in a decreased propofol Cp during target-controlled infusion. Rapid HES infusion should be used cautiously as it may decrease the depth of anesthesia.
Assuntos
Derivados de Hidroxietil Amido/administração & dosagem , Derivados de Hidroxietil Amido/farmacologia , Hipnóticos e Sedativos/sangue , Soluções Isotônicas/administração & dosagem , Soluções Isotônicas/farmacologia , Propofol/sangue , Adulto , Idoso , Volume Sanguíneo/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Soluções Cristaloides , Sistemas de Liberação de Medicamentos , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Infusões Intravenosas , Circulação Hepática/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Substitutos do Plasma/administração & dosagem , Solução de Ringer , Resultado do TratamentoRESUMO
BACKGROUND: Circulatory factors modify the onset time of neuromuscular-blocking drugs. Therefore, we hypothesized that infusion of a saline flush immediately after rocuronium administration would shorten the onset time without influencing the duration of the rocuronium effect. METHODS: Forty-eight patients were randomly allocated to the control or saline flush group. Anesthesia was induced and maintained with propofol and remifentanil, and all patients received 0.6 mg/kg rocuronium in 10 mL of normal saline. In the saline flush group, 20 mL normal saline was immediately infused after rocuronium administration. Neuromuscular blockade was assessed using acceleromyography at the adductor pollicis muscle with train-of-four (TOF) stimulation. The neuromuscular indices for rocuronium were calculated as follows: the latent onset time, defined as the time from the start of rocuronium infusion until first occurrence of depression of the first twitch of the TOF (T1) ≥5%; onset time, defined as the time from the start of rocuronium infusion until first occurrence of depression of the T1 ≥95%; clinical duration, defined as the time from the start of rocuronium administration until T1 recovered to 25% of the final T1 value; recovery index, defined as the time for recovery of T1 from 25% to 75% of the final T1 value; and the total recovery time, defined as the time from the start of rocuronium administration until reaching a TOF ratio of 0.9. Significance was designated at P <0.05. RESULTS: The measured latent onset time and onset time were significantly shorter in the saline flush group than the control group by 15 seconds (95.2% confidence interval, 0-15, P = 0.007) and 15 seconds (0-30, P = 0.018), respectively. Saline flush significantly depressed the T1 height at 30, 45, and 60 seconds after the rocuronium bolus by 17%, 24%, and 14%, respectively. In addition, the recovery phase was significantly prolonged in the saline flush group. The mean clinical duration (5th-95th percentile range) in the saline flush group and control group was 35 minutes (27-63 minutes) and 31 minutes (19-48 minutes; P = 0.032), respectively; the recovery index was 13 minutes (8-25 minutes) and 10 minutes (7-19 minutes; P = 0.019), respectively; and the total recovery time was 61 minutes (44-108 minutes) and 50 minutes (35-93 minutes; P = 0.048), respectively. CONCLUSIONS: Administering a 20-mL saline flush immediately after infusion of 0.6 mg/kg rocuronium in 10 mL normal saline shortened the onset time and prolonged the recovery phase of neuromuscular blockade.
Assuntos
Androstanóis , Bloqueio Neuromuscular/métodos , Fármacos Neuromusculares não Despolarizantes , Cloreto de Sódio , Adulto , Idoso , Idoso de 80 Anos ou mais , Androstanóis/administração & dosagem , Período de Recuperação da Anestesia , Anestésicos Intravenosos , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Miografia , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Propofol , Rocurônio , Método Simples-Cego , Adulto JovemRESUMO
BACKGROUND: Under emergent conditions, endotracheal drug administration may be an effective method of delivering emergency drugs. A common technique is to administer these drugs using a nonatomized spray. Atomized drug delivery may be an attractive alternative to nonatomized delivery because atomized particles are small, cover a large surface area, and may better adhere to endotracheal membrane resulting in more effective drug absorption. In this study, we compared the pharmacokinetic profile of lidocaine administered into the trachea using an atomized or a nonatomized technique. METHODS: Twenty patients were anesthetized using propofol and remifentanil. Ten minutes after rocuronium was administered, patients received 4% lidocaine (2 mg/kg) intratracheally over 2 seconds before tracheal intubation. Ten patients received atomized lidocaine using a mucosal atomization device, and the other 10 patients received nonatomized lidocaine using a traditional spray tube. Arterial lidocaine plasma concentrations were measured before; at 1, 3, 5, 7, 10, 15, 20, 30, 45, and 60 minutes; and then every 60 minutes after the administration of lidocaine until the end of the operation. We developed a pharmacokinetic model to examine whether bioavailability or absorption rate was different between atomized versus nonatomized lidocaine administration. The total body clearance was fixed at a published value to determine the bioavailability. RESULTS: Peak plasma concentrations were larger using the mucosal atomization device (median [range]: 1.9 [1.4-3.2] µg/mL) than the spray tube (1.1 [0.6-2.0] µg/mL; P = 0.0021). Our pharmacokinetic model estimated a difference of bioavailability between the atomized and the nonatomized lidocaine (0.801 and 0.559 respectively, P = 0.0005), whereas our model estimated no difference in the absorption rate constant (0.00688/min). CONCLUSIONS: Our results suggest that when using atomized delivery of lidocaine, less drug is required to achieve a near equivalent plasma lidocaine concentration. Atomized drug administration may be a more efficient method for endotracheal drug administration.
Assuntos
Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacocinética , Lidocaína/administração & dosagem , Lidocaína/farmacocinética , Traqueia/metabolismo , Administração por Inalação , Aerossóis , Idoso , Anestesia Geral , Anestesia Intravenosa , Anestésicos Locais/efeitos adversos , Anestésicos Locais/sangue , Disponibilidade Biológica , Feminino , Humanos , Japão , Lidocaína/efeitos adversos , Lidocaína/sangue , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Modelos Biológicos , Nebulizadores e Vaporizadores , Mucosa Respiratória/metabolismo , Absorção pelo Trato RespiratórioRESUMO
BACKGROUND: Halogenated volatile anesthetics can be safely and rapidly administered to animals and humans using emulsion formulations. However, they must be administered simultaneously with a high dose of lipids. Increasing the concentration of volatile anesthetics may solve this clinical issue. Moreover, careful observation is needed when the emulsion is injected because anaphylactic reactions have been reported. METHODS: We prepared a 20% sevoflurane lipid emulsion and administered it to 69 male Sprague-Dawley rats via the tail vein. The median effective dose (ED50) for the loss of righting reflex and the median lethal dose (LD50) were determined. ED50 and LD50 values were calculated using nonlinear regression, and data were fitted with a cumulative Gaussian model using GraphPad Prism. Measurements of vital signs and evaluation of the presence of adverse effects associated with continuous infusion of emulsions were verified. Stability of the emulsion was assessed by measuring particle size at 365 days and sevoflurane concentrations after opening the vial at 180 minutes. RESULTS: The ED50 and LD50 were 0.47 mL/kg (95% confidence interval [CI], 0.46-0.48) and 1.13 mL/kg (95% CI, 1.07-1.18), respectively. The therapeutic index (LD50/ED50) was 2.41 (95 CI%, 2.23-2.59), which compares favorably with therapeutic index of a fluoropolymer-based emulsion of sevoflurane, propofol, and thiopental. There were no adverse effects associated with the continuous infusion of emulsions. Particle size of the emulsion at 365 days after preparation was 78.9 ± 3.8 nm (±SD), and sevoflurane concentration at 180 minutes after opening the vial was 19.0% ± 0.6% (±SD). CONCLUSIONS: We prepared a 20% sevoflurane lipid emulsion using caprylic triglyceride (i.e., medium-chain triglyceride). In rats, this emulsion was an effective anesthetic and was not associated with adverse events. The emulsion was stable after consecutive evaluation for 365 days and for 180 minutes after the vial was opened.
Assuntos
Anestésicos Intravenosos/química , Anestésicos Intravenosos/farmacologia , Éteres Metílicos/química , Éteres Metílicos/farmacologia , Anafilaxia/fisiopatologia , Anestesia Intravenosa , Anestésicos Intravenosos/administração & dosagem , Animais , Química Farmacêutica , Relação Dose-Resposta a Droga , Hipersensibilidade a Drogas/fisiopatologia , Estabilidade de Medicamentos , Emulsões Gordurosas Intravenosas , Dose Letal Mediana , Masculino , Éteres Metílicos/administração & dosagem , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Sevoflurano , Triglicerídeos/químicaRESUMO
PURPOSE: Rocuronium concentration prediction using pharmacokinetic (PK) models would be useful for controlling rocuronium effects because neuromuscular monitoring throughout anesthesia can be difficult. This study assessed whether six different compartmental PK models developed from data obtained after bolus administration only could predict the measured plasma concentration (Cp) values of rocuronium delivered by bolus followed by continuous infusion. METHODS: Rocuronium Cp values from 19 healthy subjects who received a bolus dose followed by continuous infusion in a phase III multicenter trial in Japan were used retrospectively as evaluation datasets. Six different compartmental PK models of rocuronium were used to simulate rocuronium Cp time course values, which were compared with measured Cp values. Prediction error (PE) derivatives of median absolute PE (MDAPE), median PE (MDPE), wobble, divergence absolute PE, and divergence PE were used to assess inaccuracy, bias, intra-individual variability, and time-related trends in APE and PE values. RESULTS: MDAPE and MDPE values were acceptable only for the Magorian and Kleijn models. The divergence PE value for the Kleijn model was lower than -10 %/h, indicating unstable prediction over time. The Szenohradszky model had the lowest divergence PE (-2.7 %/h) and wobble (5.4 %) values with negative bias (MDPE = -25.9 %). These three models were developed using the mixed-effects modeling approach. The Magorian model showed the best PE derivatives among the models assessed. CONCLUSIONS: A PK model developed from data obtained after single-bolus dosing can predict Cp values during bolus and continuous infusion. Thus, a mixed-effects modeling approach may be preferable in extrapolating such data.
Assuntos
Androstanóis/farmacocinética , Anestesia/métodos , Modelos Biológicos , Adulto , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Infusões Intravenosas , Japão , Masculino , Pessoa de Meia-Idade , Monitoração Neuromuscular , Estudos Retrospectivos , Rocurônio , Adulto JovemRESUMO
Langerhans cell histiocytosis is a rare disease, associated with histiocyte increases, and granuloma, in various organs. About 160 patients are reported in Japan. A pregnant patient with a pulmonary Langerhans cell histiocytosis underwent cesarean section under spinal anesthesia. She had repeated pneumothorax with bilateral pulmonary cysts rapidly becoming worse during pregnancy. She was treated with continuous oxygen after 28 weeks of the pregnancy. On 34 weeks of the pregnancy, spinal anesthesia with 0.5% hyperbaric bupivacaine (2 ml) and fentanyl (25 µg) for cesarean section was performed, and provided excellent analgesia without any side-effects.
Assuntos
Anestesia Obstétrica/métodos , Cesárea , Histiocitose de Células de Langerhans , Complicações na Gravidez , Anestésicos Locais , Feminino , Histiocitose de Células de Langerhans/diagnóstico por imagem , Humanos , Gravidez , Complicações na Gravidez/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
BACKGROUND: In animal models, exposure to general anesthetics induces widespread increases in neuronal apoptosis in the developing brain. Subsequently, abnormalities in brain functioning are found in adulthood, long after the anesthetic exposure. These abnormalities include not only reduced learning abilities but also impaired social behaviors, suggesting pervasive deficits in brain functioning. But the underlying features of these deficits are still largely unknown. METHODS: Six-day-old C57BL/6 female mice were exposed to 3% sevoflurane for 6 h with or without hydrogen (1.3%) as part of the carrier gas mixture. At 7-9 weeks of age, they were mated with healthy males. The first day after parturition, the maternal behaviors of dams were evaluated. The survival rate of newborn pups was recorded for 6 days after birth. RESULTS: Female mice that received neonatal exposure to sevoflurane could mate normally and deliver healthy pups similar to controls. But these dams often left the pups scattered in the cage and nurtured them very little, so that about half of the pups died within a couple of days. Yet, these dams did not show any deficits in olfactory or exploratory behaviors. Notably, pups born to sevoflurane-treated dams were successfully fostered when nursed by control dams. Mice coadministered of hydrogen gas with sevoflurane did not exhibit the deficits of maternal behaviors. CONCLUSION: In an animal model, sevoflurane exposure in the developing brain caused serious impairment of maternal behaviors when fostering their pups, suggesting pervasive impairment of brain functions including innate behavior essential to species survival.
Assuntos
Anestésicos Inalatórios/efeitos adversos , Animais Recém-Nascidos/fisiologia , Comportamento Materno/efeitos dos fármacos , Éteres Metílicos/efeitos adversos , Animais , Antioxidantes/farmacologia , Ensaio de Imunoadsorção Enzimática , Feminino , Hidrogênio/farmacologia , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Ocitocina/sangue , Paridade , Comportamento Paterno/efeitos dos fármacos , Gravidez , Área Pré-Óptica/fisiologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Sevoflurano , Olfato/efeitos dos fármacos , Sobrevida , Vasopressinas/sangueRESUMO
Although sevoflurane is one of the most commonly used inhalational anesthetic agents, the popularity of desflurane is increasing to a level similar to that of sevoflurane. Inhalational anesthesia generally activates and represses the expression of genes related to xenobiotic metabolism and immune response, respectively. However, there has been no comprehensive comparison of the effects of sevoflurane and desflurane on the expression of these genes. Thus, we used a next-generation sequencing method to compare alterations in the global gene expression profiles in the livers of rats subjected to inhalational anesthesia by sevoflurane or desflurane. Our bioinformatics analyses revealed that sevoflurane and, to a greater extent, desflurane significantly activated genes related to xenobiotic metabolism. Our analyses also revealed that both anesthetic agents, especially sevoflurane, downregulated many genes related to immune response.
Assuntos
Anestésicos Inalatórios , Isoflurano , Éteres Metílicos , Animais , Ratos , Sevoflurano/farmacologia , Desflurano , Isoflurano/farmacologia , Éteres Metílicos/farmacologia , Transcriptoma , Xenobióticos , Anestésicos Inalatórios/farmacologia , Anestesia por InalaçãoRESUMO
BACKGROUND: In animal models, several anesthetics induce widespread increases in neuronal apoptosis in the developing brain with subsequent neurologic deficits. Although the mechanisms are largely unknown, the neurotoxicity may, at least in part, be due to elevated oxidative stress caused by mitochondrial dysfunction. In an investigation of potential therapies that could protect against this type of damage, we studied the effects of molecular hydrogen on anesthetic-induced neurotoxicity in the developing mouse brain. METHODS: Six-day-old C57BL/6 mice were exposed to 3% sevoflurane for 6 h with or without hydrogen (< 1.3%) as part of the carrier gas mixture. Apoptosis was evaluated by immunohistochemical staining for cleaved caspase-3 (n = 8-10/group). Western blot analysis for cleaved poly-(adenosine diphosphate-ribose) polymerase was also performed to examine apoptosis (n = 3-6/group). Oxidative stress was assessed by immunohistochemical staining for 4-hydroxy-2-nonenal (n = 8/group). Long-term memory and social behavior were examined using the fear conditioning test and the sociability test, respectively (n = 18-20/group). RESULTS: Western blot analysis showed that coadministration of 1.3% hydrogen gas significantly (P < 0.001) reduced the level of neuronal apoptosis to approximately 40% compared with sevoflurane exposure alone. Immunohistochemical analysis showed that hydrogen reduced oxidative stress induced by neonatal sevoflurane exposure. Although neonatal sevoflurane exposure caused impairment in long-term memory and abnormal social behaviors in adulthood, mice coadministered hydrogen gas with sevoflurane did not exhibit these deficits. CONCLUSIONS: Inhalation of hydrogen gas robustly decreased neuronal apoptosis and subsequent cognitive impairments caused by neonatal exposure to sevoflurane.
Assuntos
Apoptose/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Hidrogênio/farmacologia , Transtornos da Memória/induzido quimicamente , Éteres Metílicos/efeitos adversos , Neurônios/efeitos dos fármacos , Anestésicos Inalatórios/efeitos adversos , Animais , Animais Recém-Nascidos , Western Blotting , Encéfalo/efeitos dos fármacos , Modelos Animais de Doenças , Transtornos da Memória/prevenção & controle , Memória de Longo Prazo/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Sevoflurano , Comportamento SocialRESUMO
BACKGROUND: Measuring cardiac output accurately during anesthesia is thought to be helpful for safely controlling hemodynamics. Several minimally invasive methods to measure cardiac output have been developed as alternatives to thermodilution with pulmonary artery catheterization. We evaluated the reliability of a novel pulse wave transit time method of cardiac output assessment to trend with thermodilution cardiac output in patients undergoing partial hepatectomy. METHODS: Thirty-one patients (ASA physical status II or III) undergoing partial hepatectomy under general anesthesia were evaluated. Cardiac output measurements by pulse wave transit time method and by thermodilution were recorded after induction of anesthesia, after a change in body positioning to 20° head up, after a change to 20° head down, after volume challenge with 10 mL·kg hydroxyethyl starch 6%, during the Pringle maneuver, and immediately after Pringle maneuver release. Trending was assessed using Bland-Altman analysis and concordance analysis. RESULTS: The direction of change between consecutive pulse wave transit time measurements and the corresponding thermodilution measurements showed a concordance rate of 96.0% (lower 95% confidence interval = 64%), with limits of agreement -1.51 and 1.61 L·min. CONCLUSIONS: The pulse wave transit time method had good concordance but fairly wide limits of agreement with regard to trending in patients with changes in preload and systemic vascular resistance. There are potential inaccuracies when vasopressors are used to treat hypotension associated with decreased systemic vascular resistance. The study limitations are that the cardiac output data were collected in a nonblinded fashion, and an existing intraarterial catheter was used, although the system requires only routine, noninvasive cardiovascular monitors. This is a promising technique that currently has limitations and will require further improvements and clinical assessment.
Assuntos
Débito Cardíaco , Hepatectomia/métodos , Monitorização Intraoperatória/métodos , Análise de Onda de Pulso , Termodiluição , Idoso , Idoso de 80 Anos ou mais , Anestesia Geral , Pressão Arterial , Feminino , Frequência Cardíaca , Hepatectomia/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/instrumentação , Posicionamento do Paciente , Valor Preditivo dos Testes , Análise de Onda de Pulso/instrumentação , Reprodutibilidade dos Testes , Fatores de Tempo , Resistência VascularRESUMO
PURPOSE: Intravenous solutions are often administered to the mother on the day of a cesarean delivery to minimize the effect of preoperative fasting or to stabilize the hemodynamics. Different intravenous solutions contain varying amounts of glucose, and rapid administration may lead to hypoglycemia in the neonate. We conducted a study to compare blood glucose levels of the mother and the fetus/neonate after they were rapidly given a Ringer's solution containing 0, 1, or 5 % glucose. The effect of the glucose load that these intravenous solutions impose during cesarean delivery has not been fully reported. Therefore, we compared the effect of 0 % (Group I, n = 15), 1 % (Group II, n = 15), and 5 % (Group III, n = 15) glucose acetated Ringer's solutions on maternal and umbilical blood glucose levels to determine the optimal glucose concentration. METHODS: Once the patients were in the operating room, the intravenous solutions were administered before delivery. The primary endpoint was changes in umbilical blood glucose levels and minimum neonatal blood glucose levels, and the secondary endpoint was the proportion of neonates who received a glucose infusion. RESULTS: Maternal blood glucose levels before and after intravenous infusion were 79.2 ± 12.2 and 74.6 ± 4.6 in Group I, 81.2 ± 12.9 and 103.3 ± 11.2 in Group II (P < 0.001), and 82.3 ± 8.7 and 252.5 ± 41.8 in Group III (P < 0.001). Umbilical blood glucose levels were 53.9 ± 10.2 in Group I, 80.8 ± 13.7 in Group II, and 181.8 ± 22.2 in Group III (P < 0.01: Group I vs. Group II and P < 0.01: Group II vs. Group III) (P < 0.001: Group I vs. Group III). Minimum neonatal blood glucose levels measured up to 8 h after birth were 35.7 ± 9.6 in Group I, 49.8 ± 10.8 in Group II, and 29.2 ± 7.5 in Group III. Neonatal hypoglycemia requiring glucose before the first milk feeding occurred in 6 neonates whose mothers were in Group I, 3 in Group II, and 9 in Group III, indicating a trend towards less neonatal hypoglycemia in Group II. CONCLUSIONS: The use of 1 % glucose acetated Ringer's solution did not induce hyperglycemia in the mother and it was able to maintain appropriate blood glucose levels in the fetus.
Assuntos
Cesárea , Glucose/farmacologia , Adulto , Análise de Variância , Anestesia Obstétrica , Glicemia/metabolismo , Feminino , Sangue Fetal/química , Feto/metabolismo , Glucose/administração & dosagem , Humanos , Recém-Nascido , Infusões Intravenosas , Soluções Isotônicas , Gravidez , Solução de Ringer , SoluçõesRESUMO
Intracellular signaling through extracellular signal-regulated kinase (ERK) is important in regulating cellular functions in a variety of tissues including the CNS. Although ERK1 and ERK2 have a very similar substrate profile and amino acid sequences, there are strikingly different phenotypes between Erk1- and Erk2-deficient mice. Thus, the question arose as to whether these two proteins are functional homologs that compensate for each other, or whether they have distinct functions. Here, we generated double knock-out mice deficient for Erk2 in the CNS, with ubiquitous homozygous deletion of Erk1, and compared the phenotypes of these mice with those of monogenic Erk2-deficient mice. Although we did obtain double knock-out newborn pups, they survived for not >1 d. These pups appeared normal just after parturition. However, they had no milk in their stomachs even 6-7 h after birth. Intracerebral hemorrhages with varying location and severity were observed. The ventricular zones and corpus callosum of the double knock-out pups did not develop adequately. Neuronal size and nuclear morphology in some brain regions were markedly aberrant in the double knock-out pups compared with controls, while deficiency in Erk2 only caused a mild phenotype. These results suggest that total ERK1/2 activity governs cellular behaviors to ensure proper brain development.
Assuntos
Agenesia do Corpo Caloso , Córtex Cerebral/anormalidades , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Neurogênese/fisiologia , Animais , Apoptose/fisiologia , Western Blotting , Contagem de Células , Proliferação de Células , Córtex Cerebral/metabolismo , Corpo Caloso/metabolismo , Genes Letais , Marcação In Situ das Extremidades Cortadas , Camundongos , Camundongos Knockout , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/genéticaRESUMO
Signaling through extracellular signal-regulated kinase (ERK) is important in multiple signal transduction networks in the CNS. However, the specific role of ERK2 in in vivo brain functions is not fully understood. Here we show that ERK2 play a critical role in regulating social behaviors as well as cognitive and emotional behaviors in mice. To study the brain function of ERK2, we used a conditional, region-specific, genetic approach to target Erk2 using the Cre/loxP strategy with a nestin promoter-driven cre transgenic mouse line to induce recombination in the CNS. The resulting Erk2 conditional knock-out (CKO) mice, in which Erk2 was abrogated specifically in the CNS, were viable and fertile with a normal appearance. These mice, however, exhibited marked anomalies in multiple aspects of social behaviors related to facets of autism-spectrum disorders: elevated aggressive behaviors, deficits in maternal nurturing, poor nest-building, and lower levels of social familiarity and social interaction. Erk2 CKO mice also exhibited decreased anxiety-related behaviors and impaired long-term memory. Pharmacological inhibition of ERK1 phosphorylation in Erk2 CKO mice did not affect the impairments in social behaviors and learning disabilities, indicating that ERK2, but not ERK1 plays a critical role in these behaviors. Our findings suggest that ERK2 has complex and multiple roles in the CNS, with important implications for human psychiatric disorders characterized by deficits in social behaviors.
Assuntos
Proteína Quinase 1 Ativada por Mitógeno/fisiologia , Atividade Motora/fisiologia , Comportamento Social , Animais , Regulação para Baixo/genética , Feminino , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Proteína Quinase 1 Ativada por Mitógeno/genética , Atividade Motora/genética , GravidezRESUMO
The central vein catheter-related infection and thrombosis are comparatively frequent and may cause a serious complication. AVA3Xi was taken into custody to the internal jugular vein, and the patient suffured from thrombophlebitis on the seventh day after the operation. A 73-year-old woman 151 cm tall and weighing 50 kg was scheduled for pancreatoduodenectomy under propofol-remifentanil anesthesia combined with epidural anesthesia (operating time 9 hours and 21 minutes, anesthetizing time 12 hours and 1 minute). The past history of the thrombosis was not present, and it was especially unquestionable for the trap including the preoperative testing and the central venous catheter insertion. The time course after the operation was also good. But the patient claimed the stiffness of the cervix on the postoperative seventh day; fever and shivering were also accompanied. S. epidermidis was identified by the blood culture. Thrombophlebitis was diagnosed with CT. It is necessary to choose an appropriate catheter and endeavor for the prevention and early detection of the blood clot formation to prevent catheter-related infection and thrombosis with cooperation with the surgeon.
Assuntos
Cateterismo Venoso Central/efeitos adversos , Tromboflebite/etiologia , Idoso , Infecções Relacionadas a Cateter , Feminino , Humanos , Veias JugularesRESUMO
BACKGROUND: esCCO (estimated continuous cardiac output, Nihon Kohden, esCCO) is a new cardiac output measurement system which uses pulse wave transit time to calculate cardiac output continuously and non-invasively. One of the most commonly used methods to monitor cardiac output is continuous cardiac output CCO (Edwards Lifesciences) which has an accuracy equivalent to that of thermodilution method. METHODS: We compared esCCO to CCO in 67 operating room patients and 128 intensive care unit patients. CCO and esCCO were measured simultaneously in patients with a pulmonary artery catheter inserted after admission to the operating room or intensive care unit. RESULTS: CCO and esCCO showed a high correlation with a correlation coefficient of 0.84 in 496 total data points, and 95% limits of agreement between these two methods were -2.49 to 2.35 l x min(-1). CONCLUSIONS: This result suggests that esCCO could be used to measure cardiac output accurately and non-invasively in different cases.
Assuntos
Débito Cardíaco , Monitorização Intraoperatória/instrumentação , Monitorização Fisiológica/instrumentação , Análise de Onda de Pulso , Difusão Térmica , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Salas Cirúrgicas , Sensibilidade e Especificidade , Fatores de TempoRESUMO
BACKGROUND: In animal models, neonatal exposure to volatile anesthetics induces neuroapoptosis, leading to memory deficits in adulthood. However, effects of neonatal exposure to desflurane are largely unknown. METHODS: Six-day-old C57BL/6 mice were exposed to equivalent doses of desflurane, sevoflurane, or isoflurane for 3 or 6 h. Minimum alveolar concentration was determined by the tail-clamp method as a function of anesthesia duration. Apoptosis was evaluated by immunohistochemical staining for activated caspase-3, and by TUNEL. Western blot analysis for cleaved poly-(adenosine diphosphate-ribose) polymerase was performed to examine apoptosis comparatively. The open-field, elevated plus-maze, Y-maze, and fear conditioning tests were performed to evaluate general activity, anxiety-related behavior, working memory, and long-term memory, respectively. RESULTS: Minimum alveolar concentrations at 1 h were determined to be 11.5% for desflurane, 3.8% for sevoflurane, and 2.7% for isoflurane in 6-day-old mice. Neonatal exposure to desflurane (8%) induced neuroapoptosis with an anatomic pattern similar to that of sevoflurane or isoflurane; however, desflurane induced significantly greater levels of neuroapoptosis than almost equivalent doses of sevoflurane (3%) or isoflurane (2%). In adulthood, mice treated with these anesthetics had impaired long-term memory, whereas no significant anomalies were detected in the open-field and the elevated plus-maze tests. Although performance in a working memory task was normal in mice exposed neonatally to sevoflurane or isoflurane, mice exposed to desflurane had significantly impaired working memory. CONCLUSIONS: In an animal model, neonatal desflurane exposure induced more neuroapoptosis than did sevoflurane or isoflurane and impaired working memory, suggesting that desflurane is more neurotoxic than sevoflurane or isoflurane.
Assuntos
Anestésicos Inalatórios/toxicidade , Apoptose/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Animais , Desflurano , Marcação In Situ das Extremidades Cortadas , Isoflurano/análogos & derivados , Isoflurano/toxicidade , Éteres Metílicos/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Oxigênio/sangue , SevofluranoRESUMO
BACKGROUND: JM-1232(-) {(-)-3-[2-(4-methyl-1-piperazinyl)-2-oxoethyl]-2-phenyl-3,5,6,7-tetrahydrocyclopenta[f]isoindol-1(2H)-one} is a new water-soluble sedative-hypnotic drug with affinity for the benzodiazepine binding site on γ-aminobutyric acid A receptors. The effects of JM-1232(-) on synaptic transmission in the brain are not known. In the present study, we investigated the effects of JM-1232(-) on synaptic transmission, synaptic plasticity (i.e., long-term potentiation [LTP] and paired-pulse facilitation), and excitatory/inhibitory postsynaptic currents (EPSCs/IPSCs) of pyramidal neurons in the CA1 region of mouse hippocampal slices. METHODS: We recorded Schaffer collateral-evoked field excitatory postsynaptic potentials and EPSCs and IPSCs of pyramidal neurons using whole-cell patch-clamp techniques in the CA1 region of mouse hippocampal slices. RESULTS: JM-1232(-) had no significant effect on the field excitatory postsynaptic potentials. Application of JM-1232(-) for 20 minutes before theta-burst stimulation dose dependently impaired LTP. JM-1232(-) impaired paired-pulse facilitation. The benzodiazepine antagonist flumazenil abolished the inhibitory effect of JM-1232(-) on LTP and paired-pulse facilitation. JM-1232(-) had no effect on Schaffer collateral stimulation-evoked EPSCs, whereas it potentiated the amplitude and prolonged the decay of evoked IPSCs in CA1 pyramidal neurons. Flumazenil blocked the effect of JM-1232(-) on the amplitude and decay of evoked IPSCs. JM-1232(-) suppressed the action potential discharge in the CA1 pyramidal neurons during theta-burst stimulation, which was reversed by flumazenil. CONCLUSION: JM-1232(-) enhances synaptic inhibition and impairs LTP and paired-pulse facilitation in area CA1 of the mouse hippocampus. These effects were mediated by benzodiazepine binding sites on γ-aminobutyric acid A receptors.
Assuntos
Região CA1 Hipocampal/efeitos dos fármacos , Hipnóticos e Sedativos/farmacologia , Isoindóis/farmacologia , Potenciação de Longa Duração/efeitos dos fármacos , Piperazinas/farmacologia , Animais , Estimulação Elétrica , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Inibidores/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Técnicas de Patch-Clamp , Células Piramidais/efeitos dos fármacos , Receptores de GABA-A/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Ritmo TetaRESUMO
In animal models, neonatal exposure of general anaesthetics significantly increases apoptosis in the brain, resulting in persistent behavioural deficits later in adulthood. Consequently, there is growing concern about the use of general anaesthetics in obstetric and paediatric practice. JM-1232(-) has been developed as a novel intravenous anaesthetic, but the effects of JM-1232(-) on the developing brain are not understood. Here we show that neonatal administration of JM-1232(-) does not lead to detectable behavioural deficits in adulthood, contrarily to other widely-used intravenous anaesthetics. At postnatal day 6 (P6), mice were injected intraperitoneally with a sedative-equivalent dose of JM-1232(-), propofol, or midazolam. Western blot analysis of forebrain extracts using cleaved poly-(adenosine diphosphate-ribose) polymerase antibody showed that JM-1232(-) is accompanied by slight but measurable apoptosis 6 h after administration, but it was relatively small compared to those of propofol and midazolam. Behavioural studies were performed in adulthood, long after the neonatal anaesthesia, to evaluate the long-term effects on cognitive, social, and affective functions. P6 administration to JM-1232(-) was not accompanied by detectable long-term behavioural deficits in adulthood. However, animals receiving propofol or midazolam had impaired social and/or cognitive functions. These data suggest that JM-1232(-) has prospects for use in obstetric and paediatric practice.