RESUMEN
BACKGROUND: Acetate-containing colloid infusion solutions are recommended to recover normovolemia during pediatric anesthesia. Until now, no studies investigating the compatibility with common anesthetic drugs were available. AIMS: This in vitro study was conducted to reveal possible incompatibilities between common anesthetic drugs and the acetate-containing colloid infusion solutions 6% hydroxyethyl starch and 4% gelatin with normal saline as control. METHODS: The colloid infusion solutions were mixed 1:1 with 29 common intravenous drugs in concentrations used in daily clinical practice. Macroscopically visible changes as well as electrical conductivity, pH, and turbidimetric light diffusion at 405 nm were measured immediately after mixing and subsequently 30 and 60 minutes later. All experiments were conducted in triplicate. RESULTS: Fifty-nine of the 87 colloid infusion-drug mixtures showed no significant changes in pH, electrical conductivity, turbidimetrically detectable light diffusion, or macroscopic appearance after mixing with hydroxyethyl starch, gelatin, and NaCl 0.9%. Fifteen mixtures showed equivocal reactions, and 13 mixtures showed incompatibility reactions. CONCLUSION: Most of the tested drugs did not show observable incompatibility reactions. However, some common drugs are highly incompatible with colloid infusion solutions: gelatin (cefazolin, diazepam, midazolam, phenytoin, vancomycin), hydroxyethyl starch (diazepam, midazolam, phenytoin, thiopental), and NaCl 0.9% (diazepam, ketamine (S), phenytoin, thiopental). These combinations should be avoided in clinical practice in case there are fewer intravenous lines available than needed.
Asunto(s)
Anestésicos Intravenosos/farmacología , Incompatibilidad de Medicamentos , Interacciones Farmacológicas , Gelatina/farmacología , Derivados de Hidroxietil Almidón/farmacología , Sustitutos del Plasma/farmacología , Técnicas In VitroRESUMEN
BACKGROUND: Volatile anaesthetics are a potential hazard during occupational exposure, pregnancy or in individuals with existing disposition to malignant hyperthermia. Anaesthetic waste gas concentration in postanaesthesia care units (PACU) has rarely been investigated. OBJECTIVE(S): The current study aims to assess concentrations of volatile anaesthetics in relation to room size, number of patients and ventilator settings in different PACUs. DESIGN: A prospective observational study. SETTING: Two different PACUs of the Hannover Medical School (Hannover, Germany) were evaluated in this study. The rooms differed in dimensions, patient numbers and room ventilation settings. PATIENTS: During the observation period, sevoflurane anaesthesia was performed in 65 of 140 patients monitored in postanaesthesia unit one and in 42 of 70 patients monitored in postanaesthesia unit two. MAIN OUTCOME MEASURES: Absolute trace gas room concentrations of sevoflurane measured with a compact, closed gas loop high-resolution ion mobility spectrometer. RESULTS: Traces of sevoflurane could be detected in 805 out of 970 samples. Maximum concentrations were 0.96â±â0.20âppm in postanaesthesia unit one, 0.82â±â0.07âppm in postanaesthesia unit two. Median concentration was 0.12 (0.34)âppm in postanaesthesia unit one and 0.11 (0.28)âppm in postanaesthesia unit two. CONCLUSION: Low trace amounts of sevoflurane were detected in both PACUs equipped with controlled air exchange systems. Occupational exposure limits were not exceeded.
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Contaminantes Ocupacionales del Aire/análisis , Contaminación del Aire Interior/análisis , Anestésicos por Inhalación/análisis , Exposición Profesional/estadística & datos numéricos , Sala de Recuperación/estadística & datos numéricos , Contaminantes Ocupacionales del Aire/efectos adversos , Contaminación del Aire Interior/estadística & datos numéricos , Anestésicos por Inhalación/efectos adversos , Alemania , Humanos , Exposición Profesional/efectos adversos , Exposición Profesional/prevención & control , Estudios Prospectivos , Sevoflurano/efectos adversos , Sevoflurano/análisis , Análisis Espectral/instrumentación , Análisis Espectral/métodosAsunto(s)
Anestesiología , Anestesiología/educación , Competencia Clínica , Curriculum , Manejo del DolorRESUMEN
OBJECTIVE: After surgical procedures, anesthesia itself may affect pain perception. Particularly, there is increasing evidence that opioids not only have analgesic effects but also provoke pronociceptive changes, that is, opioid-induced hyperalgesia. We investigated the effect of different anesthetic regimens on pain processing in volunteers using a transdermal electrical pain model. In this model, stimulation of epidermal nerve fibers representing mainly peptidergic C-nociceptors leads to secondary hyperalgesia and habituation to the stimulus. METHODS: Forty-eight healthy volunteers underwent conditioning noxious stimulation (CS) over 5 days. On day 2, the volunteers were randomized into 4 groups: control group (no anesthesia) and 3 groups receiving anesthesia before CS in anesthetic doses: propofol (P), propofol/remifentanil (PR), and propofol/remifentanil/S-ketamine (PRK). Quantitative sensory testing was performed on days 1 through 5 and on day 22. RESULTS: In every group, CS was associated with short- and long-term habituation to the electrical stimulus. Repetitive CS resulted in unmodified short-term sensitization with stable areas of hyperalgesia. Although the PR group showed a trend toward increased areas of hyperalgesia on day 2, no significant differences were detectable between the groups. In contrast, anesthesia resulted in decreased intensity of the electrically evoked pain on day 2. Finally, the mechanical pain threshold before CS on day 5 was increased in all groups and remained elevated 3 weeks after the first CS, consistent with a long-term antinociceptive effect after CS. CONCLUSIONS: The results suggest a short-term analgesic effect of general anesthesia. Furthermore, the conditioning stimulation over several days induced differential modulation of pro- and antinociceptive systems.
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Anestésicos/farmacología , Hiperalgesia/inducido químicamente , Umbral del Dolor/efectos de los fármacos , Adulto , Analgésicos Opioides/farmacología , Femenino , Humanos , Hiperalgesia/fisiopatología , Ketamina/farmacología , Masculino , Dolor/tratamiento farmacológico , Dimensión del Dolor/efectos de los fármacos , Piperidinas/farmacología , Propofol/farmacología , Remifentanilo , Adulto JovenRESUMEN
Part-time work concepts are requested for different reasons from an increasing number of employees. Despite this fact there are no systematic part-time work concepts published in the German literature, especially for physicians working in hospitals. This article describes background and circumstances of a part-time work concept which was established two years ago in a department of anaesthesiology at a university hospital in Germany. This concept considers needs of young families as well as older employees. We are convinced that a transparent part-time work concept is a good argument for job-seeking physicians when deciding for an employer. The benefit for the already employed colleagues has at least the same value.
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Servicio de Anestesia en Hospital/organización & administración , Empleo/organización & administración , Hospitales Universitarios/organización & administración , Selección de Personal/organización & administración , Admisión y Programación de Personal/organización & administración , Carga de Trabajo , Alemania , Satisfacción en el Trabajo , Modelos OrganizacionalesRESUMEN
The surveillance of acid-base homeostasis is concerted by diverse mechanisms, including an activation of sensory afferents. Proton-evoked activation of rodent sensory neurons is mainly mediated by the capsaicin receptor TRPV1 and acid-sensing ion channels. In this study, we demonstrate that extracellular acidosis activates and sensitizes the human irritant receptor TRPA1 (hTRPA1). Proton-evoked membrane currents and calcium influx through hTRPA1 occurred at physiological acidic pH values, were concentration-dependent, and were blocked by the selective TRPA1 antagonist HC030031. Both rodent and rhesus monkey TRPA1 failed to respond to extracellular acidosis, and protons even inhibited rodent TRPA1. Accordingly, mouse dorsal root ganglion neurons lacking TRPV1 only responded to protons when hTRPA1 was expressed heterologously. This species-specific activation of hTRPA1 by protons was reversed in both mouse and rhesus monkey TRPA1 by exchange of distinct residues within transmembrane domains 5 and 6. Furthermore, protons seem to interact with an extracellular interaction site to gate TRPA1 and not via a modification of intracellular N-terminal cysteines known as important interaction sites for electrophilic TRPA1 agonists. Our data suggest that hTRPA1 acts as a sensor for extracellular acidosis in human sensory neurons and should thus be taken into account as a yet unrecognized transduction molecule for proton-evoked pain and inflammation. The species specificity of this property is unique among known endogenous TRPA1 agonists, possibly indicating that evolutionary pressure enforced TRPA1 to inherit the role as an acid sensor in human sensory neurons.
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Canales de Calcio/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Protones , Canales de Potencial de Receptor Transitorio/metabolismo , Animales , Sitios de Unión/genética , Calcio/metabolismo , Canales de Calcio/genética , Capsaicina/farmacología , Células Cultivadas , Cimenos , Ganglios Espinales/citología , Ganglios Espinales/metabolismo , Células HEK293 , Humanos , Concentración de Iones de Hidrógeno , Ionomicina/farmacología , Macaca mulatta , Potenciales de la Membrana/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Monoterpenos/farmacología , Mutación , Proteínas del Tejido Nervioso/genética , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/fisiología , Potasio/farmacología , Ratas , Especificidad de la Especie , Canal Catiónico TRPA1 , Canales de Potencial de Receptor Transitorio/genéticaRESUMEN
BACKGROUND: Systemic administration of lipid emulsions is an established treatment for local anesthetic intoxication. However, it is unclear by which mechanisms lipids achieve this function. The high cardiac toxicity of the lipophilic local anesthetic bupivacaine probably results from a long-lasting inhibition of the cardiac Na channel Nav1.5. In this study, we sought to determine whether lipid emulsions functionally interact with Nav1.5 or counteract inhibition by bupivacaine. METHODS: Human embryonic kidney cells expressing human Nav1.5 were investigated by whole-cell patch clamp. The effects of Intralipid® and Lipofundin® were explored on functional properties and on bupivacaine-induced inhibition. RESULTS: Intralipid and Lipofundin did not affect the voltage dependency of activation, but induced a small hyperpolarizing shift of the steady-state fast inactivation and impaired the recovery from fast inactivation. Lipofundin, but not Intralipid, induced a concentration-dependent but voltage-independent tonic block (42% ± 4% by 3% Lipofundin). The half-maximal inhibitory concentration (IC50) values for tonic block by bupivacaine (50 ± 4 µM) were significantly increased when lipids were coapplied (5% Intralipid: 196 ± 22 µM and 5% Lipofundin: 103 ± 8 µM). Use-dependent block by bupivacaine at 10 Hz was also reduced by both lipid emulsions. Moreover, the recovery of inactivated channels from bupivacaine-induced block was faster in the presence of lipids. CONCLUSIONS: Our data indicate that lipid emulsions reduce rather than increase availability of Nav1.5. However, both Intralipid and Lipofundin partly relieve Nav1.5 from block by bupivacaine. These effects are likely to involve not only a direct interaction of lipids with Nav1.5 but also the ability of lipid emulsions to absorb bupivacaine and thus reduce its effective concentration.
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Anestésicos Locales/efectos adversos , Anestésicos Locales/farmacología , Bupivacaína/efectos adversos , Emulsiones Grasas Intravenosas/farmacología , Canal de Sodio Activado por Voltaje NAV1.5/efectos de los fármacos , Fosfolípidos/farmacología , Sorbitol/farmacología , Aceite de Soja/farmacología , Absorción , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Electrofisiología , Emulsiones/farmacología , Células HEK293 , Humanos , Concentración 50 Inhibidora , Riñón/efectos de los fármacos , Lípidos/química , Técnicas de Placa-Clamp , Bloqueadores de los Canales de Sodio/farmacologíaRESUMEN
In the Helsinki Declaration terms and conditions are demanded to control problems in airway management in perioperative care situations. A differentiated airway management can reduce morbidity and mortality. This includes staff- and structure-adjusted standard operating procedures (SOP), which take into account different patient groups, situations of treatment and current guidelines. Along with these SOPs continuing education, sytematic screening of patients and the use of algorithms and checklists are recommended. In this regard paediatric care requires special consideration. Furthermore the fibreoptic as the gold standard for the difficult airway as well as surgical airway management are essential and must be available at all times, whereas videolaryngoscopy takes on increasing evidence as an additional technique.
Asunto(s)
Manejo de la Vía Aérea/normas , Anestesiología/normas , Declaración de Helsinki , Guías de Práctica Clínica como Asunto , Neumología/normas , Humanos , Seguridad del PacienteRESUMEN
BACKGROUND: Opioids induce analgesia mainly by inhibiting synaptic transmission via G protein-coupled opioid receptors. In addition to analgesia, buprenorphine induces a pronounced antihyperalgesia and is an effective adjuvant to local anesthetics. These properties only partially apply to other opioids, and thus targets other than opioid receptors are likely to be employed. Here we asked if buprenorphine inhibits voltage-gated Na(+) channels. METHODS: Na(+) currents were examined by whole cell patch clamp recordings on different recombinant Na(+) channel α-subunits. The effect of buprenorphine on unmyelinated mouse C-fibers was examined with the skin-nerve preparation. Data are presented as mean ± SEM. RESULTS: Buprenorphine induced a concentration-dependent tonic (IC(50) 33 ± 2 µM) and use-dependent block of endogenous Na(+) channels in ND7/23 cells. This block was state-dependent and displayed slow on and off characteristics. The effect of buprenorphine was reduced on local anesthetic insensitive Nav1.4-mutant constructs and was more pronounced on the inactivation-deficient Nav1.4-WCW mutant. Neuronal (Nav1.3, Nav1.7, and Nav1.8), cardiac (Nav1.5), and skeletal muscle (Nav1.4) α-subunits displayed small differences in tonic block, but similar degrees of use-dependent block. According to our patch clamp data, buprenorphine blocked electrically evoked action potentials in C-fiber nerve terminals. Buprenorphine was more potent than other opioids, including morphine (IC(50) 378 ± 20 µM), fentanyl (IC(50) 95 ± 5 µM), sufentanil (IC(50) 111 ± 6 µM), remifenatil (IC(50) 612 ± 17 µM), and tramadol (IC(50) 194 ± 9 µM). CONCLUSIONS: Buprenorphine is a potent local anesthetic and blocks voltage-gated Na(+) channels via the local anesthetic binding site. This property is likely to be relevant when buprenorphine is used for pain treatment and for local anesthesia.
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Anestésicos Locales/farmacología , Buprenorfina/farmacología , Narcóticos/farmacología , Receptores Opioides mu/agonistas , Bloqueadores de los Canales de Sodio , Canales de Sodio/efectos de los fármacos , Potenciales de Acción/efectos de los fármacos , Animales , Línea Celular , Interpretación Estadística de Datos , Ganglios Espinales/citología , Humanos , Lidocaína/farmacología , Ratones , Ratones Endogámicos C57BL , Canal de Sodio Activado por Voltaje NAV1.4 , Fibras Nerviosas/efectos de los fármacos , Fibras Nerviosas Amielínicas/efectos de los fármacos , Técnicas de Placa-Clamp , Piel/inervación , Canales de Sodio/genética , Canales de Sodio/fisiología , Tetrodotoxina/farmacologíaAsunto(s)
Hipotensión/diagnóstico , Hipotensión/prevención & control , Complicaciones Intraoperatorias/diagnóstico , Complicaciones Intraoperatorias/prevención & control , Monitoreo Intraoperatorio/métodos , Anestesia/efectos adversos , Determinación de la Presión Sanguínea/métodos , Medicina Basada en la Evidencia , Humanos , Hipotensión/etiología , Complicaciones Intraoperatorias/etiología , Oximetría/métodos , Resultado del TratamientoRESUMEN
Sodium channel blockers are known for reducing pain and hyperalgesia. In the present study we investigated changes in cerebral processing of secondary mechanical hyperalgesia induced by pharmacological modulation with systemic lidocaine. An experimental electrical pain model was used in combination with functional magnetic resonance imaging. After induction of pin-prick hyperalgesia lidocaine or placebo was administered systemically using a double-blinded design. A 2 x 2 factorial analysis was performed. The factors were (1) sensitization to pain (levels: pin-prick hyperalgesia and normal pin-prick pain) and (2) pharmacological modulation (levels: lidocaine and placebo). A main effect of (1) sensitization was found in bilateral secondary somatosensory cortex (S2), insula, anterior cingulate gyrus (ACC), medial prefrontal cortex (mPFC), dorsolateral prefrontal cortex (dlPFC), parietal association cortex (PA), thalamus and contralateral midbrain. A main effect of (2) pharmacological modulation was found in bilateral S2, insula, ACC, mPFC, dlPFC, PA, midbrain and contralateral primary motor cortex, and thalamus. Interaction of pharmacological modulation and sensitization to pin-prick pain with activity increase during hyperalgesia and placebo was found in mPFC, posterior cingulate gyrus and thalamus. However, only activity in mPFC was inversely correlated to area of hyperalgesia during placebo and antihyperalgesic treatment effect. Furthermore, the difference of mPFC activity during hyperalgesia and placebo versus hyperalgesia and lidocaine correlated inversely with the change of the weighted hyperalgesic area (as a factor of area and rated pain intensity). We conclude that activity in mPFC correlates inversely with individual extent of central hyperalgesia and predicts individual pharmacological antihyperalgesic treatment response.
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Anestésicos Locales/farmacología , Hiperalgesia/fisiopatología , Lidocaína/farmacología , Dolor/fisiopatología , Corteza Prefrontal/fisiología , Adulto , Encéfalo/efectos de los fármacos , Encéfalo/fisiología , Mapeo Encefálico , Estudios Cruzados , Método Doble Ciego , Estimulación Eléctrica , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Dimensión del Dolor , Estimulación Física , Corteza Prefrontal/efectos de los fármacosRESUMEN
BACKGROUND: Propofol (Disoprivan, AstraZeneca AG, Zug, Switzerland) has long been considered to be nonanalgesic. However, accumulating evidence shows that propofol possesses modulatory action on pain processing and perception. In this study, the authors investigated the modulatory effects of propofol and a formulation similar to the solvent of propofol (10% Intralipid; Fresenius Kabi, Stans, Switzerland) on pain perception and central sensitization in healthy volunteers. METHODS: Fourteen healthy volunteers were included in this randomized, double-blind, placebo-controlled, crossover study. Intracutaneous electrical stimulation (48.8 +/- 25.8 mA) induced spontaneous acute pain (Numeric Rating Scale, 6 of 10) and stable areas of hyperalgesia and allodynia. Pain intensities and areas of hyperalgesia were assessed regularly before, during, and after a 45-min target-controlled infusion (2 microg/ml) of propofol, the solvent 10% Intralipid, and saline. RESULTS: During administration, propofol significantly decreased pain scores and areas of hyperalgesia and allodynia compared with both 10% Intralipid and saline (placebo-corrected mean Numerical Rating Scale score reduction by propofol: 38 +/- 28%). This difference disappeared shortly after cessation of the infusion. Thereafter, no significant group differences were observed in the Numerical Rating Scale score and the areas of hyperalgesia or allodynia. However, there was a trend to reduced hyperalgesia and allodynia after propofol treatment. Pharmacodynamic modeling regarding the analgesic effect of propofol showed an EC50 (half-maximum effect site concentration) of 3.19 +/- 0.37 microg/ml. Ten percent Intralipid was free of pain-modulatory effects in the authors' experiments. CONCLUSIONS: Propofol showed short-lasting analgesic properties during its administration, whereas the solvent-like formulation 10% Intralipid had no effect on pain perception.
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Analgésicos/farmacología , Hiperalgesia/tratamiento farmacológico , Dimensión del Dolor/efectos de los fármacos , Dolor/tratamiento farmacológico , Propofol/farmacología , Adulto , Analgésicos/uso terapéutico , Estudios Cruzados , Método Doble Ciego , Estimulación Eléctrica/efectos adversos , Emulsiones Grasas Intravenosas/farmacología , Emulsiones Grasas Intravenosas/uso terapéutico , Humanos , Hiperalgesia/etiología , Masculino , Dolor/etiología , Dimensión del Dolor/métodos , Propofol/uso terapéutico , Adulto JovenRESUMEN
Tumor necrosis factor (TNF)-alpha has been identified as a pathogenic factor in many immunologically based diseases and complex regional pain syndrome (CRPS). In this case series, we used radiolabeled technetium anti-TNF-alpha antibody to scintigraphically image TNF-alpha in 3 patients with type 1 CRPS. The results show that TNF-alpha was localized only in affected hands of patients with early-stage CRPS. No uptake was seen in clinically unaffected hands and late-stage CRPS. Our findings support the growing evidence for neuroimmune disturbance in patients with CRPS and may have important further implications for specific anticytokine treatment in patients with CRPS.
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Anticuerpos Monoclonales , Radiofármacos , Distrofia Simpática Refleja/sangre , Factor de Necrosis Tumoral alfa/metabolismo , Adulto , Anticuerpos Monoclonales/farmacocinética , Femenino , Mano/diagnóstico por imagen , Humanos , Procesamiento de Imagen Asistido por Computador , Infliximab , Marcaje Isotópico , Masculino , Persona de Mediana Edad , Proyectos Piloto , Cintigrafía , Radiofármacos/farmacocinética , Medronato de Tecnecio Tc 99m , Distribución Tisular , Recuento Corporal Total , Adulto JovenRESUMEN
Platelet dysfunction is an important cause of bleeding early after cardiac surgery. Whole-blood multiple electrode aggregometry (MEA), investigating the adhesion and aggregation of activated platelets onto metal electrodes, has shown correlations with platelet concentrates transfusion in this setting. Platelet activity in vivo is dependent on shear stress, an aspect that cannot be investigated with MEA, but with the cone and plate(let) analyzer (CPA) Impact-R that measures the interaction of platelets and von Willebrand factor (vWF) in whole blood under shear. We hypothesized that preoperative CPA may show better correlation with platelet concentrates transfusion post-cardiac surgery than MEA, since it is dependent on both platelet activity and platelet interaction with vWF multimers. Blood was obtained preoperatively from 30 patients undergoing aorto-coronary bypass (ACB) and 20 patients with aortic valve (AV) surgery. MEA was performed in hirudin-anticoagulated blood. The Impact-R analyses were performed in blood anticoagulated with hirudin, heparin or the standard anticoagulant citrate. For the light microscopy images obtained, the parameter surface coverage (SC) was calculated. Preoperative Impact-R results were abnormally decreased in AV patients and significantly lower than in ACB patients. For the Impact-R analysis performed in citrated blood, no correlation with platelet concentrates transfusion was observed. In contrast, MEA was comparable between the groups and correlated significantly with intraoperative platelet concentrates transfusion in both groups (rho between -0.47 and -0.62, p < 0.05). Multiple electrode aggregometry appeared more useful and easier to apply than CPA for preoperatively identifying patients with platelet concentrates transfusion in cardiac surgery.