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Nowadays, ultrasound-guidance is commonly used in regional anaesthesia (USGRA) and to locate the spinal anatomy in neuraxial analgesia. The aim of this second guideline on the PERi-operative uSE of UltraSound (PERSEUS-RA) is to provide evidence as to which areas of regional anaesthesia the use of ultrasound guidance should be considered a gold standard or beneficial to the patient. The PERSEUS Taskforce members were asked to define relevant outcomes and rank the relative importance of outcomes following the GRADE process. Whenever the literature was not able to provide enough evidence, we decided to use the RAND method with a modified Delphi process. Whenever compared with alternative techniques, the use of USGRA is considered well tolerated and effective for some nerve blocks but there are certain areas, such as truncal blocks, where a lack of robust data precludes useful comparison. The new frontiers for further research are represented by the application of USG during epidural analgesia or spinal anaesthesia as, in these cases, the evidence for the value of the use of ultrasound is limited to the preprocedure identification of the anatomy, providing the operator with a better idea of the depth and angle of the epidural or spinal space. USGRA can be considered an essential part of the curriculum of the anaesthesiologist with a defined training and certification path. Our recommendations will require considerable changes to some training programmes, and it will be necessary for these to be phased in before compliance becomes mandatory.
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Anestesia de Conducción , Anestesia Raquidea , Anestesiología , Cuidados Críticos , Humanos , Nervios Periféricos/diagnóstico por imagenRESUMEN
BACKGROUND: The effect of dexmedetomidine on Nociception Level Index-guided (Medasense, Israel) antinociception to reduce intra-operative opioid requirements has not been previously investigated. OBJECTIVE: We aimed to determine if low-dose dexmedetomidine would reduce remifentanil requirements during Nociception Level Index-guided antinociception without increasing complications associated with dexmedetomidine. DESIGN: Double-blind randomised controlled trial. SETTING: Two university teaching hospitals in Brussels, Belgium. PATIENTS: American Society of Anesthesiologists 1 and 2 patients (nâ=â58) undergoing maxillofacial or cervicofacial surgery under propofol--remifentanil target-controlled infusion anaesthesia. INTERVENTIONS: A 30âmin infusion of dexmedetomidine, or equal volume of 0.9% NaCl, was infused at 1.2âµgâkg-1âh-1 immediately preceding induction and then decreased to 0.6âµgâkg-1âh-1 until 30âmin before ending surgery. Nociception Level Index and frontal electroencephalogram guided the remifentanil and propofol infusions, respectively. MAIN OUTCOMES: The primary outcome was the remifentanil requirement. Other outcomes included the propofol requirement, cardiovascular status and postoperative outcome. RESULTS: Meanâ±âSD remifentanil (3.96â±â1.95 vs. 4.42â±â2.04ângâml-1; Pâ=â0.0024) and propofol (2.78â±â1.36 vs. 3.06â±â1.29âµgâml-1; Pâ=â0.0046) TCI effect site concentrations were lower in the dexmedetomidine group at 30âmin postincision and remained lower throughout surgery. When remifentanil (0.133â±â0.085 vs. 0.198â±â0.086âµgâkg-1âmin-1; Pâ=â0.0074) and propofol (5.7â±â2.72 vs. 7.4â±â2.80âmgâkg-1âh-1; Pâ=â0.0228) requirements are represented as infusion rates, this effect became statistically significant at 2âh postincision. CONCLUSION: In ASA 1 and 2 patients receiving Nociception Level Index-guided antinociception, dexmedetomidine decreases intra-operative remifentanil requirements. Combined frontal electroencephalogram and Nociception Level Index monitoring can measure dexmedetomidine's hypnotic and opioid-sparing effects during remifentanil-propofol target-controlled infusion anaesthesia. TRIAL REGISTRATIONS: Clinicaltrials.gov: NCT03912740, EudraCT: 2018-004512-22.
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Dexmedetomidina , Propofol , Anestésicos Intravenosos , Bélgica , Humanos , Nocicepción , RemifentaniloRESUMEN
BACKGROUND: Opioid-free anesthesia (OFA) is a new method of anesthesia based on a paradigm shift. Under general anesthesia, the physiology and/or the pathophysiological variations clinically observed are more a reflection of a systemic reaction to the stress (surgical and anesthesia stresses) than a true reflection of pain. OBJECTIVE: To report the results of a large monocenter, retrospective, non-interventional observational study of all consecutive patients who received a total intravenous (IV)-OFA protocol for the surgical management of major open abdominal and urological surgery. PATIENTS AND METHODS: We retrospectively extracted the anesthesia files of 311 consecutive patients (regional anesthesia excluded). No opioids were administered to any of these patients during the surgery. IV morphine administered in the recovery room was the primary endpoint of the study. The secondary endpoints included the amount of opioid required during the first two postoperative days, as well as the maximum pain intensity. RESULTS: Only very small doses of IV morphine were administered. The mean total morphine titration was 2 mg (1.9 ± 2.9 mg), corresponding to control of the maximal level of pain to 2.1 ± 2.6 as evaluated with a numerical scale in the postoperative care unit. Similarly, we observed a very low level of morphine consumption during the first two postoperative days. CONCLUSIONS: These results highlight the safety and the feasibility of our total IV-OFA protocol, thus confirming this new paradigm. Under general anesthesia, the cardiovascular and inflammatory response to the stress could be reliably managed through a multimodal approach without a need for opioids. In the postoperative period, very low doses of opioids were required.
RESUMEN
BACKGROUND: Opioid-free anesthesia decreases the incidence of opioid adverse events, but its optimal antinociceptive depth has not been clearly defined. Personalizing intraoperative opioid-free infusions with a nociception monitor may be the solution. CASE REPORT: We describe the feasibility and potential limitations of titrating opioid-free antinociception during major abdominal surgery using the Analgesia Nociception Index (Mdoloris, Lille, France) in an obese patient. After stabilizing the patient's nociception-antinociception balance intraoperatively we quickly reversed anesthesia and the patient did not require postoperative opioids. CONCLUSION: Personalizing opioid-free antinociception with a nociception monitor is feasible. It may optimize intraoperative antinociception and improve postoperative comfort.
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Anestesia por Inhalación , Anestesia Intravenosa , Nocicepción , Medicina de Precisión/métodos , Incontinencia Urinaria/cirugía , Fístula Vesicovaginal/cirugía , Analgesia/instrumentación , Analgesia/métodos , Analgésicos Opioides/efectos adversos , Electroencefalografía , Femenino , Humanos , Persona de Mediana Edad , Obesidad Mórbida/complicaciones , Incontinencia Urinaria/etiología , Fístula Vesicovaginal/complicacionesRESUMEN
Abstract Background: Opioid-free anesthesia decreases the incidence of opioid adverse events, but its optimal antinociceptive depth has not been clearly defined. Personalizing intraoperative opioid-free infusions with a nociception monitor may be the solution. Case report: We describe the feasibility and potential limitations of titrating opioid-free antinociception during major abdominal surgery using the Analgesia Nociception Index (Mdoloris, Lille, France) in an obese patient. After stabilizing the patient's nociception-antinociception balance intraoperatively we quickly reversed anesthesia and the patient did not require postoperative opioids. Conclusion: Personalizing opioid-free antinociception with a nociception monitor is feasible. It may optimize intraoperative antinociception and improve postoperative comfort.
Resumo Introdução A anestesia sem opioides diminui a incidência de eventos adversos associados aos opioides, mas a profundidade antinociceptiva ideal dessa abordagem não está claramente definida. Personalizar a infusão intraoperatória sem opioides com o uso de monitor de nocicepção pode ser a solução. Relato de caso Descrevemos a viabilidade e as eventuais limitações da titulação da antinocicepção sem opioides por meio do uso do Índice de Analgesia/Nocicepção (Mdoloris, Lille, França) durante cirurgia abdominal de grande porte em paciente com obesidade. Depois de estabilizar o equilíbrio nocicepção-antinocicepção da paciente no intraoperatório, revertemos rapidamente a anestesia e a paciente não precisou de opioides no pós-operatório. Conclusão A personalização da antinocicepção sem opioides por meio do emprego de monitor de nocicepção é factível. A abordagem pode otimizar a antinocicepção intraoperatória e melhorar o conforto pós-operatório.
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Humanos , Femenino , Incontinencia Urinaria/cirugía , Fístula Vesicovaginal/cirugía , Medicina de Precisión/métodos , Nocicepción , Anestesia por Inhalación , Anestesia Intravenosa , Incontinencia Urinaria/etiología , Obesidad Mórbida/complicaciones , Fístula Vesicovaginal/complicaciones , Electroencefalografía , Analgesia/instrumentación , Analgesia/métodos , Analgésicos Opioides/efectos adversos , Persona de Mediana EdadRESUMEN
: Ultrasound for diagnostic and procedural purposes is becoming a standard in daily clinical practice including anaesthesiology and peri-operative medicine. The project of European Society of Anaesthesiology (ESA) Task Force for the development of clinical guidelines on the PERioperative uSE of Ultra-Sound (PERSEUS) project has focused on the use of ultrasound in two areas that account for the majority of procedures performed routinely in the operating room: vascular access and regional anaesthesia. Given the extensive literature available in these two areas, this paper will focus on the use of ultrasound-guidance for vascular access. A second part will be dedicated to peripheral nerve/neuraxial blocks. The Taskforce identified three main domains of application in ultrasound-guided vascular cannulation: adults, children and training. The literature search were performed by a professional librarian from the Cochrane Anaesthesia and Critical and Emergency Care Group in collaboration with the ESA Taskforce. The Grading of Recommendation Assessment (GRADE) system for assessing levels of evidence and grade of recommendations were used. For the use of ultrasound-guided cannulation of the internal jugular vein, femoral vein and arterial access, the level evidence was classified 1B. For other accesses, the evidence remains limited. For training in ultrasound guidance, there were no studies. The importance of proper training for achieving competency and full proficiency before performing any ultrasound-guided vascular procedure must be emphasised.
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Anestesia , Anestesiología/normas , Cateterismo Venoso Central/normas , Guías de Práctica Clínica como Asunto , Adulto , Cateterismo , Humanos , Sociedades Médicas , Ultrasonografía IntervencionalRESUMEN
OBJECTIVE: To evaluate the feasibility of routine outpatient management after robotic-assisted radical prostatectomy (RARP). Prostate cancer is indeed the second most common cancer in men. Surgical technics have evolved from open surgery to robot-assisted surgery with a reduction of postoperative complications. Such technical improvements associated with modern anesthesia allow outpatient surgery in various types of procedures. MATERIAL AND METHODS: After approval of the IRB, this observational prospective and monocentric study was performed in the urology unit at Rennes University Hospital between December 2015 and October 2017. All patients scheduled for RARP performed by one experienced surgeon were consecutively included. The possibility of discharge was evaluated using the Post Anesthesia Discharge Scoring System (PADSS) score until patients had a score of 9 or higher allowing their discharge. Risk factors of delayed discharge were secondarily assessed RESULTS: Ninety-seven patients scheduled for RARP performed by one experienced surgeon were consecutively included. Only 1 patient had a PADSS score ≥ 9 the day of the surgery (day 0). Seventy-four percent of the patients achieved discharge criteria 1 day after surgery whereas, 33% and 66% of the population was effectively discharged on day 2 and day 3, respectively. Patients with a PADSS score ≥ 9 at day 1 experienced significantly less postoperative nausea and vomiting than patients with a PADSS score ≥ 9 at day 2 or 3 (7% vs 28%, Pâ¯=â¯.01). CONCLUSION: Outpatient RARP was not feasible in most patients. However, routine discharge at day 1 seems conceivable. Improving the management of postoperative nausea and vomiting may even allow outpatient management. This progress remains to be confirmed by further studies.
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Procedimientos Quirúrgicos Ambulatorios/métodos , Pacientes Ambulatorios , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Procedimientos Quirúrgicos Robotizados/métodos , Estudios de Factibilidad , Francia/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Estudios ProspectivosRESUMEN
PURPOSE OF REVIEW: In the past two decades, opioids have been prescribed increasingly for the treatment of various chronic pain conditions and during the perioperative period. Perioperative opioid administration is associated with well known adverse effects and recently to long-term use and poor surgical outcomes. In this context, the anesthesiologists have to face their responsibilities. The review discusses the neurophysiological basis of opioid-free anesthesia (OFA), the rational supporting its use in perioperative medicine as well as barriers and future challenges in the field. RECENT FINDINGS: OFA has gained in popularity as a way to enhance early recovery and to spare opioids for the postoperative period. Whether it is possible to deliver safe and stable anesthesia without intraoperative opioids to many patients undergoing various surgical procedures, OFA still raises questions. Accurate monitoring to measure intraoperative nociception and guide the use of adjuvants are not available. There is a need for the development of procedure-specific strategies as well as indications and contraindications to the technique. Finally, objective assessment of OFA use on patient outcomes should be recorded in large multicenter studies. SUMMARY: OFA stands as a new paradigm, which questions anesthesiology practice and might help to rationalize perioperative opioids use.
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Analgésicos Opioides , Anestesia/métodos , Atención Perioperativa/métodos , Analgésicos Opioides/efectos adversos , Dolor Crónico/tratamiento farmacológico , Humanos , Dolor Postoperatorio/tratamiento farmacológicoRESUMEN
BACKGROUND: Polyamines have been identified as pain agonists and interact with N-methyl-D-aspartate receptors. A prospective, randomized, multicenter, and blinded phase II clinical trial was conducted to evaluate a polyamine-deficient diet for the treatment of perioperative pain in patients during spinal surgery. METHODS: All analyses followed the intention-to-treat principle. The trial was designed to evaluate the dose-ranging effect of a low polyamine diet with respect to a total (group 1) or partial (group 2) polyamine diet on perioperative pain (7 d before and 5 d after surgery). Pain (numerical scale at rest and motion), quality of life questionnaires (Brief Pain Inventory, EIFEL questionnaire, and Short Form-12 acute questionnaire), and tolerance of and compliance with the nutritional program were measured. RESULTS: Compliance (preoperatively: 100% in group 1 and 83% in group 2; postoperatively: 83% in group 1 and 71% in group 2) and tolerance were good. After 7 d following the diet before surgery, decreased pain was observed in group 1 whereas no effect was observed in group 2 (P = 0.144). This analgesic effect became significant in group 1 in the subgroup of patients with initial high levels of pain (NS ≥ 4) at rest (P = 0.03) and during motion (P = 0.011). Quality of life was significantly improved in group 1 (P = 0.0465). In the postoperative period, pain was significantly decreased in group 1 compared to group 2 at rest (P = 0.022) and during motion (P = 0.029). The effect was significantly better on patients with higher initial pain both at rest (P = 0.013) and during motion (P = 0.005) in group 1 compared to group 2. CONCLUSION: Suppression of polyamines from the diet offers a nutrition-based treatment option for perioperative pain reduction independent of and complementary to typical analgesic approaches.
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Dieta , Dolor/dietoterapia , Atención Perioperativa , Poliaminas/administración & dosificación , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cooperación del Paciente , Estudios Prospectivos , Calidad de Vida , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Regarding nerves as simple cables and electrical conduits is a gross error that does not allow us to understand the anomalies and disorders observed postoperatively. Instead, nerves should be seen as a living tissue of which physiological regulation is as complex as that of the blood-brain barrier. This review describes the basic structure and functions of this blood-nerve barrier and highlights the mechanisms of its breakdown and the resultant disorders. For clinical practice, it is important to note that the diffusion of molecules from the perineurium or from the blood is very limited, and so the blood-nerve barrier is a major pharmacologic barrier. Any stress upon neural physiological balance, particularly the terminal vascular blood supply, will induce the classic inflammatory cascade. Due to the complexity of the vascular system, nerve ischaemia will occur more quickly when the terminal blood supply is compromised. This blood supply can adapt in a variety of ways but when these possibilities of adaptation are exceeded, tissue ischaemia may be more extensive. Also, even after the initial injury has subsided, inflammation can cause a secondary insult. This could be particularly important in some patients with subclinical neuropathy.
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Barrera Hematoencefálica/fisiología , Barrera Hematoencefálica/fisiopatología , Traumatismos de los Nervios Periféricos/fisiopatología , Nervios Periféricos/fisiología , Nervios Periféricos/fisiopatología , Animales , Barrera Hematoencefálica/diagnóstico por imagen , Humanos , Inflamación/diagnóstico por imagen , Inflamación/fisiopatología , Traumatismos de los Nervios Periféricos/diagnóstico por imagen , Nervios Periféricos/diagnóstico por imagenRESUMEN
Lidocaine has analgesic effect and antihyperalgesic and anti-inflammatory properties, which enable its use as a general anesthetic adjuvant. Lidocaine can reduce nociception and/or cardiovascular responses to surgical stress, postoperative pain, and/or analgesic requirements. However, its mechanisms of action remain unclear, despite its different known properties. Although the exact mechanism of action remains uncertain, initial bolus followed by a continuous lidocaine infusion has clear analgesic benefits. Lidocaine is one of the major drugs for opioid-reduced anesthesia or opioid-free anesthesia procedures. It clearly improves the postoperative outcomes with increased patient satisfaction. Such procedures should be included wisely in the enhanced recovery after surgery protocols. By using the recommended protocols, a high safety and efficacy of lidocaine can be achieved.
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Anestésicos Locales/administración & dosificación , Lidocaína/administración & dosificación , Dimensión del Dolor/efectos de los fármacos , Dolor Postoperatorio/prevención & control , Analgésicos Opioides/efectos adversos , Animales , Humanos , Infusiones Intravenosas , Dimensión del Dolor/métodos , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/fisiopatologíaRESUMEN
BACKGROUND: Amitriptyline (AMI) is a lipophilic, tricyclic antidepressant with analgesic properties that could potentially be used for epidural (EPI) analgesia. However, no pharmacokinetic data are available for AMI in spinal spaces. The objective of this study was to evaluate the spinal disposition and intrathecal (IT) bioavailability of AMI after IT and EPI administration. METHODS: Six Lacaune ewes received 3 consecutive administrations of AMI. They initially received 10 mg of AMI administered intravenously, then 5 mg of AMI administered intrathecally, and 50 mg of AMI injected into the EPI space. Consecutive administrations were separated by intervals of 2 hours. A simultaneous microdialysis technique was used to determine the EPI and IT concentrations of AMI. Population analysis with S-ADAPT software was used to evaluate the pharmacokinetic parameters. RESULTS: Following intravenous administration, the clearance and central compartment (Vc) in plasma were 1.32 L/min and 147 L, respectively. Concentration-time profiles for the IT and EPI compartments were highly variable after transmeningeal diffusion. The IT Vc after IT administration and the EPI Vc after EPI administration were 2.4 and 48.9 mL, respectively. Less AMI transferred from the EPI to the IT space than from the IT to the EPI compartment, with bioavailabilities of 1.3% and 55%, respectively. CONCLUSIONS: Simultaneous population analysis for AMI demonstrated differences in EPI and IT pharmacokinetics following the EPI and IT administration of this drug. The IT bioavailability of AMI after EPI administration is relatively low.
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Amitriptilina/administración & dosificación , Amitriptilina/farmacocinética , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/farmacocinética , Espacio Epidural/metabolismo , Administración Intravenosa , Analgesia Epidural/métodos , Animales , Espacio Epidural/efectos de los fármacos , Femenino , Inyecciones Epidurales , Inyecciones Espinales , OvinosRESUMEN
The pneumatic tourniquet is frequently used for upper and lower limb surgery to reduce bleeding, improve visualisation of important structures and expedite surgical procedures. Despite advances in technology, localised tissue damage secondary to cuff compression, ischaemia-reperfusion injuries and systemic complications still occur. The combination of these problems may affect outcome and contribute to prolonged hospitalisation. Use of the correct pneumatic tourniquet cuff size and a patient-specific cuff pressure with careful control of the duration of inflation may help reduce the incidence of these injuries. The efficacy of ischaemic preconditioning or postconditioning, and experimental treatments such as free radical scavenging, and use of nitric oxide synthetase inhibitors on endothelial dysfunction, systemic neutrophil activation and coagulation reactions needs to be established.
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Daño por Reperfusión/etiología , Torniquetes/efectos adversos , Animales , Coagulación Sanguínea , Vasos Sanguíneos/patología , Endotelio Vascular/patología , Inhibidores Enzimáticos/farmacología , Diseño de Equipo , Hemostasis , Humanos , Isquemia/patología , Extremidad Inferior/patología , Neutrófilos/metabolismo , Óxido Nítrico Sintasa/antagonistas & inhibidores , Piel/patología , Extremidad Superior/patologíaRESUMEN
Following epidural administration, cerebrospinal fluid bioavailability of local anesthetics is low, one major limiting factor being diffusion across the arachnoid mater barrier. The aim of this study was to evaluate the influence of absorption enhancers on the meningeal permeability of epidurally administered ropivacaine. Five enhancers known for their ability to increase drug permeability via transcellular and/or paracellular pathways, i.e. palmitoyl carnitine, ethylenediaminetetraacetic acid, sodium caprate, dodecylphosphocholine and pentylglycerol, were tested ex vivo on fresh specimen of meninges removed from cervical to lumbar level of rabbit spine following laminectomy and placed in diffusion chambers. Among them, sodium caprate lead to the best permeability improvement for both marker and drug (440% and 112% for mannitol and ropivacaine, respectively) and was therefore selected for in vivo study in a sheep model using microdialysis technique to evaluate epidural and intrathecal ropivacaine concentrations following epidural administration. Resulting dialysate and plasma concentrations were used to calculate pharmacokinetic parameters. Following sodium caprate pre-treatment, ropivacaine intrathecal maximal concentration (Cmax) was 1.6 times higher (78 ± 16 µg ml(-1) vs 129 ± 26 µg ml(-1), p<0.05) but the influence of the absorption enhancer was only effective the first 30 min following ropivacaine injection, as seen with the significantly increase of intrathecal AUC(0-30 min) (1629 ± 437 µg min ml(-1) vs 2477 ± 559 µg min ml(-1), p<0.05) resulting in a bioavailable fraction 130% higher 30 min after ropivavaine administration. Co-administration of local anesthetics with sodium caprate seems to allow a transient and reversible improvement of transmeningeal passage into intrathecal space.
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Amidas/farmacocinética , Anestésicos Locales/farmacocinética , Ácidos Decanoicos/farmacología , Meninges/efectos de los fármacos , Absorción , Amidas/administración & dosificación , Amidas/sangre , Amidas/líquido cefalorraquídeo , Amidas/química , Anestésicos Locales/administración & dosificación , Anestésicos Locales/sangre , Anestésicos Locales/líquido cefalorraquídeo , Anestésicos Locales/química , Animales , Disponibilidad Biológica , Química Farmacéutica , Ácidos Decanoicos/administración & dosificación , Difusión , Composición de Medicamentos , Ácido Edético/farmacología , Glicerol/análogos & derivados , Glicerol/farmacología , Inyecciones Epidurales , Meninges/metabolismo , Microdiálisis , Palmitoilcarnitina/farmacología , Permeabilidad , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacología , Conejos , Ropivacaína , OvinosRESUMEN
Many pro-inflammatory cytokines are involved in the process of inflammatory pain. Bi directional axonal transport of Tumor Necrosis Factor-alpha (TNF-alpha) occurs in case of neuropathic pain induced by nerve ligation. We used an in vivo preparation with injection of carrageenan and fluorescent TNF-alpha in the territory of the saphenous nerve of rats to study this transport. We have shown that retrograde transport of TNF-alpha occurs after an inflammatory insult caused by the injection of carrageenan. This transport was likely mediated by the TNF receptor 1. A nerve block with bupivacaine totally abolishes the expression of the receptor in the dorsal root ganglion and the retrograde transport of TNF-alpha. In addition, bupivacaine at low concentrations (1-10 microM) was able to stop the axonal transport ex vivo. Tetrodotoxin was less efficacious for inhibiting the TNF-alpha transport and the rise in receptor expression and for inhibiting the axonal transport ex vivo. This may partly explain the efficacy of nerve blocks with bupivacaine to decrease the neurogenic inflammation and in a lower extent the long-term inhibition of hyperalgesic phenomenon observed in animals and in humans.
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Anestésicos Locales/administración & dosificación , Transporte Axonal/inmunología , Bupivacaína/farmacología , Bloqueo Nervioso , Inflamación Neurogénica/inmunología , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Transporte Axonal/efectos de los fármacos , Carragenina , Modelos Animales de Enfermedad , Edema/inmunología , Nervio Femoral/efectos de los fármacos , Fluorescencia , Pie/patología , Ganglios Espinales/inmunología , Ganglios Espinales/metabolismo , Inyecciones Subcutáneas , Masculino , Bloqueo Nervioso/métodos , Inflamación Neurogénica/tratamiento farmacológico , Inflamación Neurogénica/metabolismo , Reacción en Cadena de la Polimerasa , Polisacáridos , Ratas , Ratas Sprague-Dawley , Receptores Tipo I de Factores de Necrosis Tumoral/genética , Tetrodotoxina/administración & dosificación , Factor de Necrosis Tumoral alfa/administración & dosificaciónRESUMEN
BACKGROUND AND OBJECTIVES: Neural blockade techniques are associated with a risk of acute cardiac toxicity after accidental intravenous (IV) injection of local anesthetics. The aim of this study was to compare electrocardiographic (ECG) and hemodynamic (HEM) effects induced by IV infusion of local anesthetics in an anesthetized ewe model. METHODS: Thirty-two anesthetized ewes received IV bupivacaine (BUPI), ropivacaine (ROPI), or levobupivacaine (S-BUPI) at an equimolar dose, or lidocaine (LIDO) at a 3-fold higher rate (n = 8 in each group). RR, PR, QRS, and QT intervals (QTc), changes (Delta) in systolic and diastolic arterial pressure (SAP and DAP), and in myocardial contractility (dP/dt), were assessed every 30 seconds for 7 minutes. From main ECG variables (RR, PR, QRS, QT), we proposed to use multiple correspondence analysis and hierarchical ascending classification to explore the structure of statistical dependencies among those measurements, and to determine the different patterns of ECG and HEM changes induced by infusion of BUPI, ROPI, S-BUPI, and LIDO. RESULTS: Graphic representation of multiple correspondence analysis associated BUPI with the most pronounced modifications in ECG and HEM variables, followed by in decreasing order ROPI, S-BUPI, and LIDO. Comparisons of clusters identified by hierarchical ascending classification confirmed this classification for ECG variables. Ventricular tachycardia occurred only in the BUPI group. CONCLUSIONS: In our anesthetized ewe model, high dose IV infusion of BUPI induced the most marked changes in RR, PR, QRS, QT, QTc intervals, DeltaSAP, and DeltadP/dt. ROPI altered ECG variables less than BUPI but more than S-BUPI. LIDO was associated with the smallest changes.
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Amidas/administración & dosificación , Anestésicos Locales/administración & dosificación , Electrocardiografía , Frecuencia Cardíaca/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Lidocaína/administración & dosificación , Amidas/sangre , Amidas/toxicidad , Anestesia General , Anestésicos Locales/sangre , Anestésicos Locales/toxicidad , Animales , Presión Sanguínea/efectos de los fármacos , Bupivacaína/administración & dosificación , Bupivacaína/análogos & derivados , Bupivacaína/sangre , Bupivacaína/toxicidad , Análisis por Conglomerados , Femenino , Infusiones Intravenosas , Levobupivacaína , Lidocaína/sangre , Lidocaína/toxicidad , Modelos Estadísticos , Contracción Miocárdica/efectos de los fármacos , Análisis de Componente Principal , Ropivacaína , Ovinos , Taquicardia Ventricular/inducido químicamente , Taquicardia Ventricular/fisiopatología , Factores de TiempoRESUMEN
BACKGROUND: Microparticulate local anesthetics-loaded delivery systems are known to provide a controlled release of drug and to reduce systemic toxicity resulting from transient high plasma concentrations. The aim of this study was to evaluate epidural, intrathecal and plasma pharmacokinetics of ropivacaine following epidural administrations of repeated boluses or infusions and to compare them with the epidural administration of polylactide-co-glycolide ropivacaine-loaded microspheres. METHODS: In the first step, the epidural and intrathecal pharmacokinetics was evaluated in 3 Lacaunes ewes, receiving epidural continuous infusion of ropivacaine with increasing doses (20, 50 and 100mg/h). Then, six animals received an epidural administration of ropivacaine-loaded microspheres (500 mg), three others received ropivacaine in epidural bolus (30 mg) followed by infusion (2mg/ml during 6h), and the last three animals received three successive epidural boluses of ropivacaine (50mg) at 2h interval. A simultaneous microdialysis technique was used to measure epidural and intrathecal concentrations of ropivacaine. RESULTS: After epidural administration of ropivacaine-loaded microspheres, Cmax in plasma was around 100 ng/ml while epidural and intrathecal Cmax of ropivacaine were close to 600 and 150 microg/ml, respectively. The ratios of intrathecal to epidural AUC (AUCit/AUCepi) for bolus administration, bolus+infusion administration, and for microspheres were 13.4+/-2.4; 14.1+/-6.1 and 33.9+/-22.6%, respectively. This suggested that administration of ropivacaine as microspheres increased the transmeningeal passage of ropivacaine in comparison to other administration regimens. CONCLUSIONS: Epidural administration of ropivacaine-loaded microspheres led to the sustained levels of ropivacaine in the intrathecal space compared to the boluses of ropivacaine solution. Moreover, epidural administration of microspheres resulted in the highest efficiency in intrathecal uptake of ropivacaine compared to administration in solution.
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Amidas/administración & dosificación , Analgesia Epidural/métodos , Ácido Láctico/química , Microesferas , Ácido Poliglicólico/química , Amidas/líquido cefalorraquídeo , Anestésicos Locales/administración & dosificación , Animales , Área Bajo la Curva , Disponibilidad Biológica , Química Farmacéutica/métodos , Relación Dosis-Respuesta a Droga , Sistemas de Liberación de Medicamentos , Meninges/efectos de los fármacos , Microscopía Electrónica de Rastreo/métodos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Polímeros/química , Ropivacaína , OvinosRESUMEN
JUSTIFICATIVA E OBJETIVOS: As microesferas podem ser utilizadas como um sistema de liberação controlada para prolongar a ação de anestésicos locais. Esse estudo teve como objetivo a preparação, caracterização e análise da liberação in vitro de microesferas de bupivacaína em excesso enantiomérico de 50 por cento (S75-R25). MÉTODO: As micropartículas foram preparadas utilizando o co-polímero de ácido poliláctico-co-glicólico contendo bupivacaína em excesso enantiomérico de 50 por cento pelo método spray-dryed. RESULTADOS: A caracterização das microesferas em relação ao seu tamanho e conteúdo foram similares aos valores teóricos. A liberação in vitro apresentou um padrão bifásico. CONCLUSÕES: O processo de fabricação de microesferas contendo bupivacaína em excesso enantiomérico de 50 por cento pelo método spray-dryed é factível de ser realizado, com resultados semelhantes aos encontrados com microesferas de bupivacaína.
BACKGROUND AND OBJECTIVES: Microspheres can be used as a controlled delivery system to prolong the duration of action of local anesthetics. The objective of this study was the preparation, characterization and analysis of the in vitro release of 50 percent enantiomeric excess bupivacaine (S75-R25)-loaded microspheres. METHODS: Microspheres were prepared using the copolymer of polylactide-co-glycolic acid by the spray-dryed method. RESULTS: Characterization of microspheres regarding their size and content were similar to the theoretical values. The in vitro release demonstrated a biphasic pattern. CONCLUSIONS: Manufacturing of 50 percent enantiomeric excess bupivacaine-loaded microspheres by the spray-dryed method with results similar to bupivacaine-loaded microspheres can be done.
JUSTIFICATIVA Y OBJETIVOS: Las micro esferas pueden ser utilizadas como un sistema de liberación controlada para prolongar la acción de anestésicos locales. Este estudio tuvo como objetivo la preparación, caracterización y el análisis de la liberación in vitro de micro esferas de bupivacaina en exceso enantiomérico de 50 por ciento (S75-R25). MÉTODO: Las micro partículas fueron preparadas utilizando el copolímero de ácido poliláctico-co-glicólico con bupivacaina en exceso enantiomérico de un 50 por ciento por el método spray-dryed. RESULTADOS: La caracterización de las micro esferas con relación a su tamaño y contenido fueron similares a los valores teóricos. La liberación in vitro presentó un estándar bifásico. CONCLUSIONES: El proceso de fabricación de micro esferas con bupivacaina en exceso enantiomérico de 50 por ciento por el método spray-dryed se puede realizar con resultados semejantes a los encontrados con micro esferas de bupivacaina.
Asunto(s)
Anestésicos Locales , Bupivacaína , Microesferas , Anestésicos Locales/administración & dosificación , Bupivacaína/administración & dosificación , Tecnología FarmacéuticaRESUMEN
BACKGROUND AND OBJECTIVES: Microspheres can be used as a controlled delivery system to prolong the duration of action of local anesthetics. The objective of this study was the preparation, characterization and analysis of the in vitro release of 50% enantiomeric excess bupivacaine (S75-R25)-loaded microspheres. METHODS: Microspheres were prepared using the copolymer of polylactide-co-glycolic acid by the spray-dryed method. RESULTS: Characterization of microspheres regarding their size and content were similar to the theoretical values. The in vitro release demonstrated a biphasic pattern. CONCLUSIONS: Manufacturing of 50% enantiomeric excess bupivacaine-loaded microspheres by the spray-dryed method with results similar to bupivacaine-loaded microspheres can be done.