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Current acute pain intensity assessment tools are mainly based on self-reporting by patients, which is impractical for non-communicative, sedated or critically ill patients. In previous studies, various physiological signals have been observed qualitatively as a potential pain intensity index. On the basis of that, this study aims at developing a continuous pain monitoring method with the classification of multiple physiological parameters. Heart rate (HR), breath rate (BR), galvanic skin response (GSR) and facial surface electromyogram were collected from 30 healthy volunteers under thermal and electrical pain stimuli. The collected samples were labelled as no pain, mild pain or moderate/severe pain based on a self-reported visual analogue scale. The patterns of these three classes were first observed from the distribution of the 13 processed physiological parameters. Then, artificial neural network classifiers were trained, validated and tested with the physiological parameters. The average classification accuracy was 70.6%. The same method was applied to the medians of each class in each test and accuracy was improved to 83.3%. With facial electromyogram, the adaptivity of this method to a new subject was improved as the recognition accuracy of moderate/severe pain in leave-one-subject-out cross-validation was promoted from 74.9 ± 21.0 to 76.3 ± 18.1%. Among healthy volunteers, GSR, HR and BR were better correlated to pain intensity variations than facial muscle activities. The classification of multiple accessible physiological parameters can potentially provide a way to differentiate among no, mild and moderate/severe acute experimental pain.
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Dolor Agudo/diagnóstico , Enfermedad Crítica , Frecuencia Cardíaca , Monitoreo Fisiológico/métodos , Redes Neurales de la Computación , Dimensión del Dolor/métodos , Adulto , Área Bajo la Curva , Electromiografía , Femenino , Respuesta Galvánica de la Piel , Voluntarios Sanos , Calor , Humanos , Masculino , Curva ROC , Reproducibilidad de los Resultados , Respiración , Adulto JovenRESUMEN
AIM: To describe and compare shift leaders' important information needs by profession, unit, time of day and type of hospital. BACKGROUND: Professionals responsible for care provision in hospital units make ad hoc decisions about available resources to meet patient care needs but, currently, much effort is needed to obtain the necessary information to support decision making. METHODS: This survey was carried out in nine randomly chosen hospitals in Finland. Nurses and physicians responsible for day-to-day operations were eligible to participate (N = 873). The response rate was 65% (n = 570, including 453 nurses and 111 physicians). Data were collected in 2015-2016 using the Hospital Shift Leaders' Information Needs Questionnaire with 114 information need items. RESULTS: Shift leaders reported many real-time information needs. Nurses' important information needs concerned patients, personnel, and materials, and physicians' needs focused on patient care. Large mean differences existed in the needs between nurses and physicians, and imaging units when compared to other units. CONCLUSION: Real-time information systems for shift leaders should consider the needs of different users to support shared situational awareness and operational intelligence. IMPLICATIONS FOR NURSING MANAGEMENT: The important information-need items identified here may be used in designing and developing information systems that better support shift leaders' work in hospitals.
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Conducta en la Búsqueda de Información , Enfermeras Administradoras/psicología , Estudios Transversales , Finlandia , Humanos , Enfermeras Administradoras/tendencias , Habitaciones de Pacientes/organización & administración , Psicometría/instrumentación , Psicometría/métodos , Encuestas y CuestionariosRESUMEN
AIMS: The aims were (1) to evaluate the modified version of the Intensive Care Unit Information Need Questionnaire for the broader hospital setting, and (2) to describe the differences in respondents' managerial activities and information needs according to the position held by the respondent and the type of hospital unit. BACKGROUND: Information systems do not support managerial decision-making sufficiently and information needed in the day-to-day operations management in hospital units is unknown. METHODS: An existing questionnaire was modified and evaluated. Shift leaders, that is, the nurses and physicians responsible for the day-to-day operations management in hospital units were reached using purposive sampling (n = 258). RESULTS: The questionnaire ascertained the importance of information. Cronbach's α ranged from .85-.96 for the subscales. Item - total correlations showed good explanatory power. Managerial activities and information needs differed between respondents in different positions, although all shared about one-third of important information needs. The response rate was 26% (n = 67). CONCLUSIONS: The validity and reliability of the questionnaire were good. Attention should be paid to the positions of shift leaders when developing information systems. IMPLICATIONS FOR NURSING MANAGEMENT: The questionnaire can be used to determine important information when developing information systems to support day-to-day operations management in hospitals.
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Continuidad de la Atención al Paciente/normas , Enfermeras Administradoras/tendencias , Encuestas y Cuestionarios/normas , Adulto , Continuidad de la Atención al Paciente/tendencias , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Necesidades/normas , Reproducibilidad de los ResultadosRESUMEN
AIMS: Dexmedetomidine (dexdor®) is approved in the European Union (EU) for sedation of adults in the intensive care unit (ICU). The present observational, retrospective study was requested by the European Medicines Agency to investigate dexmedetomidine use in clinical practice, with a particular focus on off-label use, including the paediatric population. METHODS: Study countries and sites were chosen from those with highest dexmedetomidine use, based on sales. Site selection (blind) was conducted by a multispecialist, independent group. Anonymized data on demographics, treatment indication, dexmedetomidine dosing, concomitant medications and treatment effectiveness were collected retrospectively from records of all dexmedetomidine-treated patients at the site during the enrolment period. Informed consent was waived, to avoid influencing the prescribing of dexmedetomidine. Recruitment was completed within 18 months of first site initiation. RESULTS: Data from 2000 patients were collected from 16 hospitals in four EU countries (Finland 750, Poland 505, Germany 470, Austria 275). The median age was 62 years, with more males (70.2%) than females. Dexmedetomidine was primarily used in the adult ICU (86.0%) for ICU sedation (78.6%) and mostly dosed according the product label. The intended sedative effect was obtained in 84.9% of administrations. Paediatric use (5.9% of patients, mostly in Austria and Finland) occurred mainly in the adult or paediatric ICU (75.6%) for sedation (67.2%). CONCLUSIONS: Overall, most patients were treated with dexmedetomidine according to the product labelling. Use in children was limited but significant and similar in scope to that in adults. Administrations not fully according to the product labelling usually occurred in an ICU environment and reflected extensively investigated clinical uses of dexmedetomidine.
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Dexmedetomidina/uso terapéutico , Utilización de Medicamentos/estadística & datos numéricos , Uso Fuera de lo Indicado/estadística & datos numéricos , Distribución por Edad , Austria , Femenino , Finlandia , Alemania , Humanos , Hipnóticos y Sedantes/uso terapéutico , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Polonia , Estudios RetrospectivosRESUMEN
BACKGROUND: There is no comprehensive data in our country on the prevalence of life-supporting prolonged invasive ventilation support. The objective of the survey was to clarify in all hospital districts of continental Finland the prevalence of patients who were dependent on invasive ventilation support, and the disease leading to the treatment. PATIENTS AND METHODS: The KOTIVEHNO 2015 survey was carried out as population-based cross-sectional study by sending a questionnaire to all doctors in charge of prolonged invasive ventilation support. The questionnaires were used to collect data on the patients within care on 1st January, 2017. RESULTS: The prevalence of life-supporting prolonged invasive ventilation support in Finland among the population aged over 16 years or more was 2/4 patients/100,000 habitants. Altogether 107 patients were within the care. There was variation in the prevalence among the hospital districts. Of the patients, 24% were affected with a motoneuron disease, in 18% the cause was spinal cord injury, 15% suffered from Duchenne's muscular dystrophy, and the rest had some other rare neurological disease. CONCLUSIONS: Life-supporting prolonged invasive ventilation support is rare in Finland. The treatment is associated with neuromuscular diseases causing respiratory insufficiency, and with spinal cord injuries.
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Cuidados para Prolongación de la Vida , Enfermedades Neuromusculares/fisiopatología , Enfermedades Neuromusculares/terapia , Respiración Artificial/métodos , Insuficiencia Respiratoria/fisiopatología , Insuficiencia Respiratoria/terapia , Adolescente , Adulto , Anciano , Estudios Transversales , Femenino , Finlandia , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Encuestas y CuestionariosRESUMEN
An increase in cardiac output during pregnancy increases the risk of arrhythmias for the expectant mother. Supraventricular tachycardia (SVT) underlies the sensations of arrhythmia in a pregnant woman in as many as one sixth of the cases. Vagal nerve (n. vagus) stimulation and adenosine serve as first-line treatment, but electrical cardioversion is likely to be a safe alternative as well. We describe a case in which the SVT of a woman in the third trimester of pregnancy was unresponsive to vagal nerve stimulation and pharmacological treatments. Electrical cardioversion was successfully performed after having a cesarean section procedure.
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Cardioversión Eléctrica , Complicaciones Cardiovasculares del Embarazo/terapia , Taquicardia Supraventricular/terapia , Adulto , Cesárea , Femenino , Humanos , Embarazo , Complicaciones Cardiovasculares del Embarazo/diagnóstico , Tercer Trimestre del Embarazo , Taquicardia Supraventricular/diagnósticoRESUMEN
PURPOSE: Dexmedetomidine is an α2-adrenoceptor agonist used for perioperative and intensive care sedation. This study develops mechanism-based population pharmacokinetic-pharmacodynamic models for the cardiovascular and central nervous system (CNS) effects of intravenously (IV) and intranasally (IN) administered dexmedetomidine in healthy subjects. METHOD: Single doses of 84 µg of dexmedetomidine were given once IV and once IN to six healthy men. Plasma dexmedetomidine concentrations were measured for 10 h along with plasma concentrations of norepinephrine (NE) and epinephrine (E). Blood pressure, heart rate, and CNS drug effects (three visual analog scales and bispectral index) were monitored to assess the pharmacological effects of dexmedetomidine. PK-PD modeling was performed for recently published data (Eur J Clin Pharmacol 67: 825, 2011). RESULTS: Pharmacokinetic profiles for both IV and IN doses of dexmedetomidine were well fitted using a two-compartment PK model. Intranasal bioavailability was 82%. Dexmedetomidine inhibited the release of NE and E to induce their decline in blood. This decrease in NE was captured with an indirect response model. The concentrations of the mediator NE served via a biophase/transduction step and nonlinear pharmacologic functions to produce reductions in blood pressure and heart rate, while a direct effect model was used for the CNS effects. CONCLUSION: The comprehensive panel of two biomarkers and seven response measures were well captured by the population PK/PD models. The subjects were more sensitive to the CNS (lower EC 50 values) than cardiovascular effects of dexmedetomidine.
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Dexmedetomidina/farmacología , Hipnóticos y Sedantes/farmacología , Administración Intranasal , Disponibilidad Biológica , Presión Sanguínea , Estudios Cruzados , Dexmedetomidina/sangre , Dexmedetomidina/farmacocinética , Relación Dosis-Respuesta a Droga , Epinefrina/metabolismo , Frecuencia Cardíaca , Humanos , Hipnóticos y Sedantes/sangre , Hipnóticos y Sedantes/farmacocinética , Infusiones Intravenosas , Masculino , Tasa de Depuración Metabólica , Norepinefrina/metabolismo , Escala Visual Analógica , Adulto JovenRESUMEN
Amyotrophic lateral sclerosis (ALS) is a disease causing degeneration of motor neurons, without any curative treatment. The most common cause of death is respiratory arrest due to atrophy of the respiratory musculature. ALS-associated respiratory insufficiency differs in mechanism from the more common causes of dyspnea, such as diseases of pulmonary or cardiac origin. Recognizing the respiratory insufficiency can be challenging for a clinician. It should be possible to predict the development of respiratory insufficiency in order to avoid leaving the treatment decisions concerning respiratory insufficiency to emergency services. Noninvasive ventilatory support can be used to alleviate the patient's dyspnea. It is actually recommended as the first-line treatment of ALS-associated respiratory insufficiency.
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Esclerosis Amiotrófica Lateral/complicaciones , Ventilación no Invasiva , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapia , HumanosRESUMEN
AIM: The purpose of this study was to culturally validate three pain measurement instruments [Behavioral Pain Scale (BPS), the Critical-Care Pain Observation Tool (CPOT) and the Nonverbal Adult Pain Assessment Scale (NVPS)] for sedated intensive care patients and in doing so to prepare the tools for psychometric testing in the Finnish intensive care environment. BACKGROUND: Most patients feel pain during their stay in an intensive care unit. Pain recognition and assessment is the first step towards effective pain management. The BPS, CPOT and NVPS are the most valid and reliable pain assessment instruments developed to objectively assess pain in sedated intensive care patients. METHOD: The translation and cultural adaptation of the instruments were done according to the guidelines of the International Society for Pharmacoeconomics and Outcomes (ISPOR). The process included 10 phases aiming to produce semantically correct Finnish versions of the pain assessment instruments. This translation process was chosen due to its rigorousness and systematic approach. RESULTS: The 10-step translation and cultural validation process were successfully conducted, although it was complex and time-consuming. The resulting Finnish versions of the three pain assessment instruments showed good evidence of content and conceptual equivalence. Although further work is needed to test these instruments in the Finnish intensive care context, the current Finnish versions are potential instruments for clinicians to use. CONCLUSION: Deciding when this high-quality process is needed requires thorough consideration. However, it is worthwhile to use it when implementing new instruments at a national level. We need a valid, reliable and feasible instrument for pain assessment in sedated intensive care patients in Finland. The next step in our process is conducting psychometric testing of these three instruments to choose the tool with the best properties to be implemented in clinical practice.
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Unidades de Cuidados Intensivos , Dimensión del Dolor , Finlandia , HumanosRESUMEN
One of the greatest challenges of modern neuroscience is to discover the neural mechanisms of consciousness and to explain how they produce the conscious state. We sought the underlying neural substrate of human consciousness by manipulating the level of consciousness in volunteers with anesthetic agents and visualizing the resultant changes in brain activity using regional cerebral blood flow imaging with positron emission tomography. Study design and methodology were chosen to dissociate the state-related changes in consciousness from the effects of the anesthetic drugs. We found the emergence of consciousness, as assessed with a motor response to a spoken command, to be associated with the activation of a core network involving subcortical and limbic regions that become functionally coupled with parts of frontal and inferior parietal cortices upon awakening from unconsciousness. The neural core of consciousness thus involves forebrain arousal acting to link motor intentions originating in posterior sensory integration regions with motor action control arising in more anterior brain regions. These findings reveal the clearest picture yet of the minimal neural correlates required for a conscious state to emerge.
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Estado de Conciencia/fisiología , Lóbulo Frontal/fisiología , Red Nerviosa/fisiología , Neuronas/fisiología , Lóbulo Parietal/fisiología , Vigilia/fisiología , Adulto , Anestesia General/métodos , Encéfalo/citología , Encéfalo/fisiología , Mapeo Encefálico/métodos , Lóbulo Frontal/citología , Humanos , Masculino , Red Nerviosa/citología , Lóbulo Parietal/citología , Adulto JovenRESUMEN
BACKGROUND: Hypoventilation due to respiratory muscle atrophy is the most common cause of death as a result of amyotrophic lateral sclerosis (ALS). Patients aged over 65 years and presenting bulbar symptoms are likely to have a poorer prognosis. The aim of the study was to assess the possible impact of age and treatment with non-invasive ventilation (NIV) on survival in ALS. Based on evidence from earlier studies, it was hypothesized that NIV increases rates of survival regardless of age. METHODS: Eighty-four patients diagnosed with ALS were followed up on from January 2001 to June 2012. These patients were retrospectively divided into two groups according to their age at the time of diagnosis: Group 1 comprised patients aged ≤ 65 years while Group 2 comprised those aged > 65 years. Each group included 42 patients. NIV was tolerated by 23 patients in Group 1 and 18 patients in Group 2. Survival was measured in months from the date of diagnosis. RESULTS: The median age in Group 1 was 59 years (range 49 - 65) and 76 years in Group 2 (range 66 - 85). Among patients in Group 1 there was no difference in probability of survival between the NIV users and non-users (Hazard Ratio = 0.88, 95% CI 0.44 - 1.77, p = 0.7). NIV users in Group 2 survived longer than those following conventional treatment (Hazard Ratio = 0.25, CI 95% 0.11 - 0.55, p <0.001). ALS patients in Group 2 who did not use NIV had a 4-fold higher risk for death compared with NIV users. CONCLUSIONS: This retrospective study found that NIV use was associated with improved survival outcomes in ALS patients older than 65 years. Further studies in larger patient populations are warranted to determine which factors modify survival outcomes in ALS.
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PURPOSE: The purpose of our study was to compare the effectiveness of subacromial bupivacaine infusion and a transdermal fentanyl patch in the treatment of postoperative pain after arthroscopic shoulder surgery. METHODS: Sixty patients with rotator cuff disease scheduled for elective arthroscopic shoulder surgery were enrolled in the study. For the treatment of postoperative pain, 30 patients constituted group F and received a 12.0-µg/h fentanyl patch for 72 hours and saline solution infusion in a subacromial manner at the rate of 4 mL/h. The remaining 30 patients constituted group B and received a placebo patch and an infusion of 2.5-mg/mL bupivacaine in a subacromial manner for 72 hours. The primary outcome measure was the postoperative numerical rating scale pain score. The consumption of opioids, ibuprofen, and acetaminophen was also recorded. The Constant scores and general recovery were followed up until the 90th postoperative day. RESULTS: There was no statistically significant difference in the numerical rating scale scores (P = .60) between the groups. No differences in the use of rescue analgesic were observed except that the patients receiving bupivacaine used more ibuprofen (median, 1,200 mg v 600 mg) during the day of surgery (P = .042). No difference was found in general recovery between the groups. CONCLUSIONS: A fentanyl patch delivering 12-µg/h fentanyl offers an easy and safe treatment option as a part of multimodal analgesia with few adverse effects in the treatment of postoperative pain in a carefully selected patient group after arthroscopic shoulder surgery. LEVEL OF EVIDENCE: Level I, randomized controlled trial.
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Analgésicos Opioides/administración & dosificación , Anestésicos Locales/administración & dosificación , Artroscopía/efectos adversos , Bupivacaína/administración & dosificación , Fentanilo/administración & dosificación , Dolor Postoperatorio/tratamiento farmacológico , Manguito de los Rotadores/cirugía , Acetaminofén/administración & dosificación , Analgésicos no Narcóticos/administración & dosificación , Método Doble Ciego , Procedimientos Quirúrgicos Electivos/efectos adversos , Femenino , Humanos , Ibuprofeno/administración & dosificación , Inyecciones Intraarticulares , Masculino , Persona de Mediana Edad , Oxicodona/administración & dosificación , Dimensión del Dolor , Hombro/cirugía , Parche TransdérmicoRESUMEN
BACKGROUND: Hypoventilation due to respiratory insufficiency is the most common cause of death in amyotrophic lateral sclerosis (ALS) and non-invasive ventilation (NIV) can be used as a palliative treatment. The current guidelines recommend performing spirometry, and recording nocturnal oxyhemoglobin saturation and arterial blood gas analysis to assess the severity of the hypoventilation. We examined whether the respiratory rate and thoracic movement were reliable preliminary clinical signs in the development of respiratory insufficiency in patients with ALS. METHODS: We measured the respiratory rate and thoracic movement, performed respiratory function tests and blood gas analysis, and recorded subjective hypoventilation symptoms in 42 ALS patients over a 7-year period. We recommended NIV if the patient presented with hypoventilation matching the current guidelines. We divided patients retrospectively into two groups: those to whom NIV was recommended within 6 months of the diagnosis (Group 1) and those to whom NIV was recommended 6 months after the diagnosis (Group 2). We used the Mann Whitney U test for comparisons between the two groups. RESULTS: The mean partial pressure of arterial carbon dioxide in the morning in Group 1 was 6.3 (95% confidence interval 5.6-6.9) kPa and in Group 2 5.3 (5.0-5.6) kPa (p = 0.007). The mean respiratory rate at the time of diagnosis in Group 1 was 21 (18-24) breaths per minute and 16 (14-18) breaths per minute in Group 2 (p = 0.005). The mean thoracic movement was 2.9 (2.2-3.6) cm in Group 1 and 4.0 (3.4-4.8) cm in Group 2 (p = 0.01). We observed no other differences between the groups. CONCLUSIONS: Patients who received NIV within six months of the diagnosis of ALS had higher respiratory rates and smaller thoracic movement compared with patients who received NIV later. Further studies with larger numbers of patients are needed to establish if these measurements can be used as a marker of hypoventilation in ALS.
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The aim of this validation study was to assess the reliability of gas exchange measurement with indirect calorimetry among subjects who undergo non-invasive ventilation (NIV). Oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured in twelve healthy volunteers. Respiratory quotient (RQ) and resting energy expenditure (REE) were then calculated from the measured VO2 and VCO2 values. During the measurement period the subjects were breathing spontaneously and ventilated using NIV. Two different sampling air flow values 40 and 80 l/min were used. The gas leakage from the measurement setup was assessed with a separate capnograph. The mean weight of the subjects was 93 kg. Their mean body mass index was 29 (range 22-40) kg/m2. There was no statistically significant difference in the measured values for VO2, VCO2, RQ and REE during NIV-supported breathing and spontaneous breathing. The change of sampling air flow had no statistically significant effect on any of the above parameters. We found that REE can be accurately measured with an indirect calorimeter also during NIV-supported breathing and the change of sampling air flow does not distort the gas exchange measurement. A higher sampling air flow in indirect calorimetry decreases the possibility for air leakages in the measurement system and increases the reliability of REE measurement.
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Calorimetría Indirecta , Metabolismo Energético , Respiración Artificial , Adulto , Dióxido de Carbono/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Consumo de Oxígeno , Intercambio Gaseoso Pulmonar , Valores de Referencia , Adulto JovenRESUMEN
INTRODUCTION: Only limited information exists on the pharmacokinetics of prolonged (> 24 hours) and high-dose dexmedetomidine infusions in critically ill patients. The aim of this study was to characterize the pharmacokinetics of long dexmedetomidine infusions and to assess the dose linearity of high doses. Additionally, we wanted to quantify for the first time in humans the concentrations of H-3, a practically inactive metabolite of dexmedetomidine. METHODS: Thirteen intensive care patients with mean age of 57 years and Simplified Acute Physiology Score (SAPS) II score of 45 were included in the study. Dexmedetomidine infusion was commenced by using a constant infusion rate for the first 12 hours. After the first 12 hours, the infusion rate of dexmedetomidine was titrated between 0.1 and 2.5 µg/kg/h by using predefined dose levels to maintain sedation in the range of 0 to -3 on the Richmond Agitation-Sedation Scale. Dexmedetomidine was continued as long as required to a maximum of 14 days. Plasma dexmedetomidine and H-3 metabolite concentrations were measured, and pharmacokinetic variables were calculated with standard noncompartmental methods. Safety and tolerability were assessed by adverse events, cardiovascular signs, and laboratory tests. RESULTS: The following geometric mean values (coefficient of variation) were calculated: length of infusion, 92 hours (117%); dexmedetomidine clearance, 39.7 L/h (41%); elimination half-life, 3.7 hours (38%); and volume of distribution during the elimination phase, 223 L (35%). Altogether, 116 steady-state concentrations were found in 12 subjects. The geometric mean value for clearance at steady state was 53.1 L/h (55%). A statistically significant linear relation (r2 = 0.95; P < 0.001) was found between the areas under the dexmedetomidine plasma concentration-time curves and cumulative doses of dexmedetomidine. The elimination half-life of H-3 was 9.1 hours (37%). The ratio of AUC0-∞ of H-3 metabolite to that of dexmedetomidine was 1.47 (105%), ranging from 0.29 to 4.4. The ratio was not statistically significantly related to the total dose of dexmedetomidine or the duration of the infusion. CONCLUSIONS: The results suggest linear pharmacokinetics of dexmedetomidine up to the dose of 2.5 µg/kg/h. Despite the high dose and prolonged infusions, safety findings were as expected for dexmedetomidine and the patient population. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00747721.
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Enfermedad Crítica , Dexmedetomidina/farmacocinética , Hipnóticos y Sedantes/farmacocinética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Dexmedetomidina/administración & dosificación , Dexmedetomidina/efectos adversos , Relación Dosis-Respuesta a Droga , Semivida , Humanos , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/efectos adversos , Infusiones Intravenosas , Tasa de Depuración Metabólica , Persona de Mediana EdadRESUMEN
PURPOSE: The aim of this proof-of-concept study was to characterize the pharmacokinetics and pharmacodynamics of intranasal dexmedetomidine compared with its intravenous administration in a small number of healthy volunteers. METHODS: Single doses of 84 µg of dexmedetomidine were given once intravenously and once intranasally to seven healthy men. Plasma dexmedetomidine concentrations were measured for 10 h, and pharmacokinetic variables were calculated with standard noncompartmental methods. Heart rate, blood pressure, concentrations of adrenaline and noradrenaline in plasma, and central nervous system drug effects (with the Maddox wing, Bispectral Index, and three visual analog scales) were monitored to assess the pharmacological effects of dexmedetomidine. RESULTS: Six individuals were included in the analyses. Following intranasal administration, peak plasma concentrations of dexmedetomidine were reached in 38 (15-60) min and its absolute bioavailability was 65% (35-93%) (medians and ranges). Pharmacological effects were similar with both routes of administration, but their onset was more rapid after intravenous administration. CONCLUSIONS: Dexmedetomidine is rather rapidly and efficiently absorbed after intranasal administration. Compared with intravenous administration, intranasal administration may be a feasible alternative in patients requiring light sedation.
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Agonistas de Receptores Adrenérgicos alfa 2/administración & dosificación , Agonistas de Receptores Adrenérgicos alfa 2/farmacocinética , Sedación Consciente/métodos , Dexmedetomidina/administración & dosificación , Dexmedetomidina/farmacocinética , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/farmacocinética , Administración Intranasal , Agonistas de Receptores Adrenérgicos alfa 2/sangre , Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Adulto , Disponibilidad Biológica , Presión Sanguínea/efectos de los fármacos , Estado de Conciencia/efectos de los fármacos , Estudios Cruzados , Dexmedetomidina/sangre , Dexmedetomidina/farmacología , Epinefrina/sangre , Semivida , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hipnóticos y Sedantes/sangre , Hipnóticos y Sedantes/farmacología , Inyecciones Intravenosas , Masculino , Tasa de Depuración Metabólica , Mucosa Nasal/efectos de los fármacos , Norepinefrina/sangre , Fases del Sueño/efectos de los fármacosRESUMEN
Anesthetic-induced changes in the neural activity of the brain have been recently utilized as a research model to investigate the neural mechanisms of phenomenal consciousness. However, the anesthesiologic definition of consciousness as "responsiveness to the environment" seems to sidestep the possibility that an unresponsive individual may have subjective experiences. The aim of the present study was to analyze subjective reports in sessions where sedation and the loss of responsiveness were induced by dexmedetomidine, propofol, sevoflurane or xenon in a nonsurgical experimental setting. After regaining responsiveness, participants recalled subjective experiences in almost 60% of sessions. During dexmedetomidine sessions, subjective experiences were associated with shallower "depth of sedation" as measured by an electroencephalography-derived anesthesia depth monitor. Results confirm that subjective experiences may occur during clinically defined unresponsiveness, and that studies aiming to investigate phenomenal consciousness under sedative and anesthetic effects should control the subjective state of unresponsive participants with post-recovery interviews.
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Anestésicos/farmacología , Estado de Conciencia/efectos de los fármacos , Dexmedetomidina/farmacología , Hipnóticos y Sedantes/farmacología , Éteres Metílicos/farmacología , Propofol/farmacología , Xenón/farmacología , Adolescente , Adulto , Encéfalo/efectos de los fármacos , Electroencefalografía , Humanos , Masculino , SevofluranoRESUMEN
BACKGROUND: Dexmedetomidine, an alpha2-adrenoceptor agonist, has been evaluated as an adjunct to anesthesia and for the delivery of sedation and perioperative hemodynamic stability. It provokes dose-dependent and centrally-mediated sympatholysis. Coronary artery bypass grafting (CABG) with extracorporeal circulation is a stressful procedure increasing sympathetic nervous system activity which could attenuate renal function due the interrelation of sympathetic nervous system, hemodynamics and renal function. We tested the hypothesis that dexmetomidine would improve kidney function in patients undergoing elective CABG during the first two postoperative days. METHODS: This was a double-blind, randomized, parallel-group study. Patients with normal renal function and scheduled for elective CABG were randomized to placebo or to infusion of dexmedetomidine to achieve a pseudo steady-state plasma concentration of 0.60 ng/ml. The infusion was started after anesthesia induction and continued until 4 h after surgery. The primary endpoint was creatinine clearance. Other variables included urinary creatinine and output, fractional sodium and potassium excretion, urinary potassium, sodium and glucose, serum and urinary osmolality and plasma catecholamine concentrations. The data were analyzed with repeated-measures ANOVA or Cochran-Mantel-Haenszel test. RESULTS: Sixty-six of 87 randomized patients were evaluable for analysis. No significant between-group differences were recorded for any indices of renal function except for a mean 74% increase in urinary output with dexmedetomidine in the first 4 h after insertion of a urinary catheter (p < 0.001). Confidence interval examination revealed that the sample size was large enough for the no-difference statement for creatinine clearance. CONCLUSIONS: Use of intravenous dexmedetomidine did not alter renal function in this cohort of relatively low-risk elective CABG patients but was associated with an increase in urinary output.This study was carried out in 1994-1997 and was thus not registered.
RESUMEN
BACKGROUND: General anesthetics can alter the relationship between regional cerebral glucose metabolism (rCMR(glc)) and blood flow (rCBF). In this positron emission tomography study, our aim was to assess both rCMR(glc) and rCBF in the same individuals during xenon anesthesia. METHODS: (18)F-labeled fluorodeoxyglucose and (15)O-labeled water were used to determine rCMR(glc) and rCBF, respectively, in five healthy male subjects at baseline (awake) and during 1 minimum alveolar anesthetic concentration of xenon. Anesthesia was based solely on xenon. Changes in rCMR(glc) and rCBF were quantified using region-of-interest and voxel-based analyses. RESULTS: The mean (sd) xenon concentration during anesthesia was 67.2 (0.8)%. Xenon anesthesia induced a uniform reduction in rCMR(glc), whereas rCBF decreased in 7 of 13 brain regions. The mean decreases in the gray matter were 32.4 (4.0)% (P < 0.001) and 14.8 (5.9)% (P = 0.007) for rCMR(glc) and rCBF, respectively. rCMR(glc) decreased by 10.9 (6.4)% in the white matter (P = 0.030), whereas rCBF increased by 9.2 (7.3)% (P = 0.049). The rCBF/rCMR(glc) ratio was especially increased in the insula, anterior and posterior cingulate, and in the somatosensory cortex. CONCLUSIONS: In general, the magnitude of the decreases in rCMR(glc) during 1 minimum alveolar anesthetic concentration xenon anesthesia exceeded the reductions in rCBF. As a result, the ratio between rCMR(glc) and rCBF was shifted to a higher level. Interestingly, xenon-induced changes in cerebral metabolism and blood flow resemble those induced by volatile anesthetics.
Asunto(s)
Anestesia por Inhalación , Anestésicos por Inhalación , Química Encefálica/efectos de los fármacos , Encéfalo/diagnóstico por imagen , Circulación Cerebrovascular/efectos de los fármacos , Glucosa/metabolismo , Xenón , Adulto , Anestesia por Circuito Cerrado , Glucemia/metabolismo , Fluorodesoxiglucosa F18 , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Tomografía de Emisión de Positrones , Radiofármacos , Respiración Artificial , Adulto JovenRESUMEN
AIM: This paper is a report of a systematic review describing instruments developed for pain assessment in unconscious or sedated intensive care patients. BACKGROUND: Intensive care patients who are unconscious or sedated are unable to communicate and therefore recognition and assessment of the pain is difficult. To assess these patients' pain, it is important to use a valid and reliable pain assessment tool. DATA SOURCES: A systematic bibliographical review was conducted, based on seven databases, covering the period from January 1987 to February 2007. A total of 1,586 abstracts was identified and reviewed, 58 papers were selected for full-text review and nine papers were included in the review. METHODS: Two researchers independently reviewed the abstracts and three reviewers extracted the papers. The included papers were evaluated using a quality assessment instrument previously developed to evaluate pain assessment tools. RESULTS: Five different pain assessment tools were identified that had been used with unconscious or sedated intensive care patients. All five instruments included behavioural indicators and three included physiological indicators. Their psychometric properties varied and it was not possible to deduce their clinical utility. CONCLUSION: All instruments were reasonably new. In most of them psychometric testing was in an early stage or even absent. Before any of the reported instruments can be chosen in preference to others, it is essential to test their validity, reliability and feasibility further.