ABSTRACT
Objetivo: La anestesia regional es ampliamente utilizada en Cirugía Mayor Ambulatoria (CMA), asociando innumerables ventajas y un mejor control del dolor postoperatorio. La ropivacaína surgió como una alternativa menos tóxica a la bupivacaína, sin embargo, se han descrito casos de arritmias o parada cardiorrespiratoria tras su administración. Las alteraciones electrocardiográficas en la intoxicación por anestésicos locales afectan a la conducción ventricular, prolongando el intervalo QRS del ECG. Nuestro objetivo fue evaluar si la prolongación del intervalo QRS se correlaciona con niveles elevados en sangre de ropivacaína, lo que podría alertar al clínico de una intoxicación grave. Material y métodos: El estudio se realizó en 4 cerdos minipig premedicados con ketamina intramuscular (20 mg/kg) que fueron anestesiados con tiopental sódico (5 mg/kg) y sevoflurano. Tras la instrumentalización y monitorización continua del ECG se administraron 5 mg/kg de ropivacaína intravenosa. Se realizaron determinaciones analíticas y mediciones de parámetros electrocardiográficos basales y a los 5, 15 y 30 minutos. Se evaluó la correlación entre los niveles plasmáticos de ropivacaína y la duración del intervalo QRS. Análisis estadístico: test de correlación de Spearman. Significación estadística: p < 0,05. Resultados: La ropivacaína indujo un aumento significativo del intervalo QRS a los 5, 15 y 30 minutos. Los intervalos PR, QT y QTc también aumentaron. El porcentaje de aumento máximo del QRS fue de un 51 % a los 5 minutos. Se observó una correlación positiva entre la duración del intervalo QRS y los niveles de ropivacaína, r = 0,8 (p < 0,0001). Conclusión: Nuestro modelo experimental ha permitido relacionar la duración del intervalo QRS con los niveles sanguíneos de ropivacaína. Su ensanchamiento instantáneo puede ser un marcador útil para detectar casos de intoxicación sistémica por ropivacaína, muy utilizada en anestesia regional en CMA (AU)
Objective: Regional anaesthesia is widely used in ambulatory surgery (AS) and is associated with numerous benefits and a better control of postoperative pain. Ropivacaine emerged as a less toxic alternative to bupivacaine, however, cases of arrhythmias or cardiorespiratory arrest have been reported following accidental administration. Electrocardiographic alterations in local anaesthetic intoxication affect ventricular conduction by prolonging the QRS interval of the EKG. Our aim was to assess whether QRS interval prolongation correlates with elevated blood levels of ropivacaine, which could alert the clinician to the presence of severe intoxication. Material and methods: The study was performed in 4 minipig pigs premedicated with intramuscular ketamine (20 mg/kg) and anaesthetized with sodium thiopental (5 mg/kg) and sevoflurane. After instrumentation and continuous ECG monitoring, 5 mg/kg of intravenous ropivacaine was administered. Analytical blood gas samples determinations and measurements of electrocardiographic parameters were performed at baseline and at 5, 15 and 30 minutes. Correla tion between plasmatic levels of ropivacaine and QRS interval duration was assessed. Statistical analysis: Spearman correlation test. Statistical significance: p < 0.05. Results: Ropivacaine induced a significant increase in the QRS interval at 5, 15 and 30 minutes. The PR, QT and QTc intervals also increased. The percentage of maximum QRS increase was 51 % at 5 minutes. A positive correlation was observed between QRS interval duration and ropivacaine levels, correlation coefficient r = 0.8 (p < 0.0001). Conclusion: our experimental model has allowed us to relate QRS interval duration to ropivacaine blood levels. Its instantaneous widening could be a useful marker to detect cases of systemic intoxication by ropivacaine, widely used in regional anesthesia in AS (AU)
Subject(s)
Animals , Ambulatory Surgical Procedures , Ropivacaine/adverse effects , Anesthetics, Local/adverse effects , Anesthesia, Conduction/methods , Predictive Value of Tests , Electrocardiography , SwineABSTRACT
beta-Aminopropionitrile (beta APN), inhibits the activity of lysyl oxidase, an important enzyme for the post-translational formation of inter- and intramolecular covalent cross-linking between the connective tissue proteins, collagen and elastin. We became interested in the possible use of this compound as a therapeutic agent in the so-called human collagen diseases. beta APN's action mechanism is known, but its pharmacokinetics in rabbits have not yet been determined. The present study defined the kinetic parameters of beta APN in rabbits, after oral or intravenous (iv) administration. The HPLC technique was recently modified using OPA (ortho-phthalaldehyde) as the derivative agent. beta APN plasma concentration vs time following the iv administration of 200 mg/kg was best described by the biexponential equation C = 92.43.e(-0.0728 t) + 61.78.e(-0.0088 t) (t1/2 beta = 78.73 +/- 5.19 min; Vc = 1.29 +/- 0.04 L.kg-1). After oral administration, beta APN followed a zero-order absorption pattern (Ko = 3.02 +/- 0.34 mg.kg-1.min-1), which means that the beta APN reached the blood very quickly.
Subject(s)
Aminopropionitrile/pharmacokinetics , Administration, Oral , Aminopropionitrile/administration & dosage , Aminopropionitrile/blood , Animals , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/blood , Enzyme Inhibitors/pharmacokinetics , Half-Life , Injections, Intravenous , Intestinal Absorption , Metabolic Clearance Rate , Protein-Lysine 6-Oxidase/antagonists & inhibitors , RabbitsABSTRACT
beta-Aminopropionitrile (beta APN), a peptide found in leguminous plants, is a multifunctional aminonitrile because it has some action on collagen, elastin, and nervous cells. Due to its action on the nervous system, it is very interesting to show its inhibitory effect on cultures of neurons. In the present study, we have demonstrated that beta APN can produce progressive degeneration of neurons and that this effect is dose-dependant. Neuronal cultures were prepared from 14-day-old rat embryos with a cell density of 10(4) cells/cm2 in the control plates. Progressive concentrations of beta APN (from 10(-7) M to 10(-3) M) were added and a 50 Inhibitory Dose (ID50) of 10(-5) M was found. At concentrations of 10(-5) M of beta APN, the neurons showed a loss of synapsis and thinning of neuronal prolongations. Based on the morphological changes observed, we think that beta APN may be used as a neurodegeneration model similar to that obtained with acrylamide, carbon disulfide, beta-beta'-iminodipropionitrile, or aluminum salts.
