RESUMEN
BACKGROUND: Halothane more so than isoflurane potentiates an alpha1-adrenoceptor (alpha1-AR)-mediated action of epinephrine that abnormally slows conduction in Purkinje fibers and may facilitate reentrant arrhythmias. This adverse drug interaction was further evaluated by examining conduction responses to epinephrine in combination with thiopental and propofol, which "sensitize" or reduce the dose of epinephrine required to induce arrhythmias in the heart, and with etomidate, which does not, and responses to epinephrine with verapamil, lidocaine, and l-palmitoyl carnitine, a potential ischemic metabolite. METHODS: Action potentials and conduction times were measured in vitro using two microelectrodes in groups of canine Purkinje fibers stimulated at 150 pulses/min. Conduction was evaluated each minute after exposure to 5 microm epinephrine (or phenylephrine) alone or with the test drugs. Changes in the rate of phase 0 depolarization (Vmax) and the electrotonic spread of intracellular current were measured during exposure to epinephrine with octanol to evaluate the role of inhibition of active and passive (intercellular coupling) membrane properties in the transient depression of conduction velocity. RESULTS: Lidocaine (20 microm) and octanol (0.2 mm) potentiated alpha1-AR-induced conduction depression like halothane (0.4 mm), with maximum depression at 3-5 min of agonist exposure, no decrease of Vmax, and little accentuation at a rapid (250 vs. 150 pulses/min) stimulation rate. Thiopental (95 microm), propofol (50 microm), and verapamil (2 microm) similarly potentiated epinephrine responses, whereas etomidate (10 microm) did not. Between groups, the decrease of velocity induced by epinephrine in the presence of (10 microm) l-palmitoyl carnitine (-18%) was significantly greater than that resulting from epinephrine alone (-6%; 0.05
Asunto(s)
Anestésicos/farmacología , Corazón/inervación , Conducción Nerviosa/efectos de los fármacos , Ramos Subendocárdicos/efectos de los fármacos , Receptores Adrenérgicos alfa 1/efectos de los fármacos , Potenciales de Acción , Agonistas alfa-Adrenérgicos/efectos adversos , Agonistas alfa-Adrenérgicos/farmacología , Anestésicos/efectos adversos , Animales , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/fisiopatología , Perros , Sinergismo Farmacológico , Epinefrina/efectos adversos , Epinefrina/farmacología , Etomidato/efectos adversos , Etomidato/farmacología , Ácidos Grasos/metabolismo , Halotano/efectos adversos , Halotano/farmacología , Técnicas In Vitro , Lidocaína/efectos adversos , Lidocaína/farmacología , Conducción Nerviosa/fisiología , Octanoles/efectos adversos , Octanoles/farmacología , Palmitoilcarnitina/farmacología , Propofol/efectos adversos , Propofol/farmacología , Ramos Subendocárdicos/fisiología , Receptores Adrenérgicos alfa 1/fisiología , Tiopental/efectos adversos , Tiopental/farmacología , Verapamilo/efectos adversos , Verapamilo/farmacologíaRESUMEN
UNLABELLED: Perioperative malignant ventricular tachyarrhythmias pose an imminent clinical danger by potentially precipitating myocardial ischemia and severely compromising hemodynamics. Thus, immediate and effective therapy is required, which is not always provided by currently recommended IV drug regimens, indicating a need for more effective drugs. We examined antiarrhythmic effects of the new benzofurane compound E 047/1 on spontaneous ventricular tachyarrhythmia in a conscious dog model. One day after experimental myocardial infarction, 40 dogs exhibiting tachyarrhythmia randomly received (bolus plus 1-h infusion) E 047/1 6 mg/kg plus 6 mg x kg(-1) x h(-1), lidocaine 1 mg/kg plus 4.8 mg x kg(-1) x h(-1), flecainide 1 mg/kg plus 0.05 mg x kg(-1) x h(-1), amiodarone 10 mg/kg plus 1.8 mg x kg(-1) x h(-1), or bretylium 10 mg/kg plus 20 mg x kg(-1) x h(-1). Electrocardiogram was evaluated for number of premature ventricular contractions (PVC), normally conducted beats originating from the sinoatrial node, and episodes of ventricular tachycardia. Immediately after the bolus, E 047/1 reduced PVCs by 46% and increased sinoatrial beats from 4 to 61 bpm. The ratio of PVCs to total beats decreased from 98% to 58%. Amiodarone and flecainide exhibited antiarrhythmic effects with delayed onset. Lidocaine did not suppress PVCs significantly, and bretylium was proarrhythmic. The antiarrhythmic E 047/1 has desirable features, suppressing ischemia-induced ventricular tachyarrhythmia quickly and efficiently, and may be a useful addition to current therapeutic regimens. IMPLICATIONS: Life-threatening arrhythmias of the heart after myocardial infarction or ischemia may be treated quickly and efficiently by the new drug E 047/1.
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Antiarrítmicos/farmacología , Arritmias Cardíacas/tratamiento farmacológico , Benzofuranos/farmacología , Isquemia Miocárdica/complicaciones , Animales , Antiarrítmicos/sangre , Antiarrítmicos/farmacocinética , Arritmias Cardíacas/sangre , Arritmias Cardíacas/etiología , Benzofuranos/sangre , Benzofuranos/farmacocinética , Presión Sanguínea/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Vasos Coronarios/cirugía , Perros , Excipientes/administración & dosificación , Frecuencia Cardíaca/efectos de los fármacos , Infusiones Intravenosas , Ligadura , Isquemia Miocárdica/sangre , Isquemia Miocárdica/etiología , Proyectos Piloto , Polisorbatos/administración & dosificaciónRESUMEN
BACKGROUND: Although desflurane (DES) and sevoflurane (SEV) have desirable features for use in patients with coronary artery disease, their effects on ventricular dysrhythmias following infarction are less known. We therefore examined the effects of DES and SEV upon spontaneous postinfarction ventricular dysrhythmias in dogs, and compared those effects to the well-established antidysrhythmic effects of halothane (HAL) in this model. METHODS: After institutional approval, the left anterior descending coronary artery was ligated in 16 adult mongrel dogs during isoflurane anesthesia. All dogs developed acute myocardial infarction and severe ventricular tachydysrhythmias. Twenty-two hours after infarction, dogs were anesthetized at 1.5 MAC with desflurane (10.8%) followed by sevoflurane (3.5%) in the treatment group (n = 10), or halothane (1.3%) in the other group (n = 6). Anesthetic gases were allowed to equilibrate for at least 20 min at each end-tidal concentration. At this time, the ECG was recorded for 9 min and evaluated for the number of ventricular ectopic and sinoatrial beats and summed duration of ventricular tachycardia. RESULTS: DES and SEV reduced the average rate of total ventricular ectopic beats by 40 +/- 4% and 42 +/- 4%, respectively. HAL decreased total ventricular ectopic rate by 59 +/- 6% and 62 +/- 5% after durations of anesthesia comparable to DES and SEV, respectively. Decreases in dysrhythmia in the presence of DES and SEV were significantly smaller than those produced by HAL after a comparable total duration of anesthesia. CONCLUSION: DES and SEV inhibit spontaneous postinfarction ventricular dysrhythmias, although attenuation of dysrhythmias was smaller than the inhibition during comparable doses of HAL.
Asunto(s)
Anestésicos por Inhalación/farmacología , Arritmias Cardíacas/fisiopatología , Halotano/farmacología , Isoflurano/análogos & derivados , Éteres Metílicos/farmacología , Infarto del Miocardio/complicaciones , Anestesia por Inhalación , Animales , Arritmias Cardíacas/etiología , Desflurano , Perros , Electrocardiografía , Frecuencia Cardíaca/efectos de los fármacos , Isoflurano/farmacología , SevofluranoRESUMEN
BACKGROUND AND OBJECTIVES: Sympathetic neural activity contributes to the genesis of ventricular ectopic activity, particularly in the setting of myocardial ischemia and infarction, so thoracic epidural anesthesia should diminish ventricular ectopy by blocking sympathetic innervation of the heart. However, the possible antidysrhythmic effect of epidural anesthesia has been studied only in the presence of general anesthesia. We therefore examined changes in spontaneous postinfarction ventricular dysrhythmia during thoracic epidural anesthesia in awake dogs. METHODS: A survivable myocardial infarction was created by two-stage ligation of the left anterior descending coronary artery. The following day, multifocal idioventricular tachycardia was the predominant cardiac rhythm. Lidocaine was administered either by thoracic epidural catheter to achieve block of at least the first five thoracic segments or intravenously as a control for direct effects, without concurrent general anesthesia or sedation. Electrocardiographic recordings were analyzed for the number of ventricular ectopic and sinoatrial depolarizations. RESULTS: Epidural and intravenous administration both produced plasma lidocaine concentrations of about 2 mg/mL. There was no change in rhythm following intravenous lidocaine. During epidural anesthesia, total ectopic beats per minute decreased from 167 +/- 8 to 135 +/- 14 (mean +/- SE, P < .05), and the dysrhythmic ratio (ventricular beats/total beats) decreased from 0.93 +/- 0.03 to 0.81 +/- 0.08 (P < .05). However, ventricular tachydysrhythmia remained the predominant rhythm. CONCLUSIONS: Epidural block modestly reduces spontaneous ventricular dysrhythmia in a perioperative setting in dogs following a large myocardial infarction. These findings do not support the choice of thoracic epidural anesthesia for the purpose of preventing or decreasing severe ventricular dysrhythmia.
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Anestesia Epidural , Arritmias Cardíacas/prevención & control , Animales , Perros , Electrocardiografía , Infarto del Miocardio/complicacionesRESUMEN
OBJECTIVE: Trifluoromethane and CO are produced simultaneously during the breakdown of isoflurane and desflurane by dry CO2 absorbents. Trifluoromethane interferes with anesthetic agent monitoring, and the interference can be used as a marker to indicate anesthetic breakdown with CO production. This study tests representative types of gas monitors to determine their ability to provide a clinically useful warning of CO production in circle breathing systems. METHODS: Isoflurane and desflurane were reacted with dry Baralyme at 45 degrees C. Standardized samples of breakdown products were created from mixtures of reacted and unreacted gases to simulate the partial degrees of reaction which might result during clinical episodes of anesthetic breakdown using 1% or 2% isoflurane and 6% or 12% desflurane. These mixtures were measured by the monitors tested, and the indication of the wrong agent or a mixture of agents due to the presence of trifluoromethane was recorded and related to the CO concentration in the gas mixtures. RESULTS: When presented with trifluoromethane from anesthetic breakdown, monochromatic infrared monitors displayed inappropriately large amounts of isoflurane or desflurane. Agent identifying infrared and Raman scattering monitors varied in their sensitivity to trifluoromethane. Mass spectrometers measuring enflurane at mass to charge = 69 were most sensitive to trifluoromethane. CONCLUSION: Monochromatic infrared monitors were unable to indicate anesthetic breakdown via interference by trifluoromethane, but did indicate falsely elevated anesthetic concentrations. Agent identifying infrared and Raman monitors provided warning of desflurane breakdown via the interference of trifluoromethane by displaying the wrong agent or mixed agents, but may not be sensitive enough to warn of isoflurane breakdown Some mass spectrometers provided the most sensitive warnings to anesthetic breakdown via trifluoromethane, but additional data processing by some patients monitor units reduced their overall effectiveness.
Asunto(s)
Contaminantes Ocupacionales del Aire/análisis , Anestésicos por Inhalación , Monóxido de Carbono/análisis , Clorofluorocarburos de Metano , Monitoreo del Ambiente/instrumentación , Desflurano , Humanos , Isoflurano/análogos & derivados , Espectrometría de Masas , Espectrofotometría Infrarroja , Espectrometría RamanRESUMEN
Since bupivacaine and epinephrine may both precipitate dysrhythmias, circulating bupivacaine during regional anesthesia could potentiate dysrhythmogenic effects of epinephrine. We therefore examined whether bupivacaine alters the dysrhythmogenicity of subsequent administration of epinephrine in conscious, healthy dogs and in anesthetized dogs with myocardial infarction. Forty-one conscious dogs received 10 micrograms.kg-1.min-1 epinephrine. Seventeen animals responded with ventricular tachycardia (VT) within 3 min. After 3 h, these responders randomly received 1 or 2 mg/kg bupivacaine or saline over 5 min, followed by 10 micrograms.kg-1.min-1 epinephrine. In the bupivacaine groups, epinephrine caused fewer prodysrhythmic effects than without bupivacaine. VT appeared in fewer dogs and at a later time, and there were more sinoatrial beats and less ectopies. Epinephrine shortened QT less after bupivacaine than in control animals. One day after experimental myocardial infarction, six additional halothane-anesthetized dogs received 4 micrograms.kg-1.min-1 epinephrine until VT appeared. After 45 min, 1 mg/kg bupivacaine was injected over 5 min, again followed by 4 micrograms.kg-1.min-1 epinephrine. In these dogs, the prodysrhythmic response to epinephrine was also mitigated by preceding bupivacaine. Bupivacaine antagonizes epinephrine dysrhythmogenicity in conscious dogs susceptible to VT and in anesthetized dogs with spontaneous postinfarct dysrhythmias. There is no evidence that systemic subtoxic bupivacaine administration enhances the dysrhythmogenicity of subsequent epinephrine.
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Anestésicos Locales/toxicidad , Bupivacaína/toxicidad , Epinefrina/toxicidad , Taquicardia Ventricular/inducido químicamente , Animales , Perros , ElectrocardiografíaRESUMEN
BACKGROUND: The chemical breakdown of isoflurane, enflurane, or desflurane in dried carbon dioxide absorbents may produce carbon monoxide. Some mass spectrometers can give false indications of enflurane during anesthetic breakdown. METHODS: During clinical anesthesia with isoflurane or desflurane, the presence of carbon monoxide in respiratory gas was confirmed when enflurane was inappropriately indicated by a clinical mass spectrometer that identified enflurane at mass to charge ratio = 69. In vitro, isoflurane, enflurane, or desflurane in oxygen was passed through dried carbon dioxide absorbents at 35, 45, and 55 degrees C. Gases were analyzed by gas chromatography and by mass spectrometry. RESULTS: Mass spectrometry identified several clinical incidents in which 30-410 ppm carbon monoxide was measured in respiratory gas. Trifluoromethane was produced during in vitro breakdown of isoflurane or desflurane. Although these inappropriately indicated quantities of "enflurane" correlated (r2 > 0.95) to carbon monoxide concentrations under a variety of conditions, this ratio varied with temperature, anesthetic agent, absorbent type, and water content. CONCLUSIONS: Trifluoromethane causes the inappropriate indication of enflurane by mass spectrometry, and indicates isoflurane and desflurane breakdown. Because the ratio of carbon monoxide to trifluoromethane varies with conditions, this technique cannot be used to quantitatively determine the amount of carbon monoxide to which a patient is exposed. If any warning of anesthetic breakdown results from this technique then remedial steps should be taken immediately to stop patient exposure to carbon monoxide. No warning can be provided for the breakdown of enflurane by this technique.
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Anestésicos por Inhalación/metabolismo , Monóxido de Carbono/análisis , Clorofluorocarburos de Metano/metabolismo , Enflurano/metabolismo , Isoflurano/análogos & derivados , Isoflurano/metabolismo , Desflurano , Humanos , Espectrometría de MasasRESUMEN
The spread and intensity of lumbar epidural anaesthesia are unpredictable. Moreover, segments L5 and S1 are frequently missed. In this study the effect of 30 degrees trunk elevation on the spread and intensity of lumbar epidural sensory and motor blockade and on the cardiovascular system were studied. METHODS. After oral premedication with 7.5 mg midazolam, 30 patients 20 to 40 years of age, ASA 1-2, were randomly allocated to one of two groups according to their body position during injection of 20 ml 2% lidocaine (3 + 8 + 9 ml) into a lumbar epidural catheter (L2/3 or L3/4) and during the following 30 min: supine horizontal position or supine 30 degrees trunk elevation with 30 degrees leg elevation (hammock position). The patients received 500 ml Ringer solution before the epidural injection, followed by more Ringer solution. Systolic and diastolic blood pressures and heart rate were monitored noninvasively every 5 min; 30 min after the epidural injection the spread of analgesia (dullness of pinprick) and anaesthesia (no sensation of pinprick) as well as motor block according to Bromage were tested. A spread of anaesthetic segments including T12 to L3 was considered adequate for hip surgery, L3 to L5 for knee surgery, and L3 to S2 for foot surgery. Student's t-test, ANOVA, chi-square (Wilcoxon), and Mann-Whitney tests were used for statistical analysis. P < 0.05 was considered statistically significant. RESULTS. The median cephalad level of analgesia was lower in patients with the hammock position than those with the horizontal position (L1 vs T10; P < 0.05). There was no significant difference in the cranial level of anaesthesia (L2 vs L1) (Table 2). No significant difference was seen in the number of patients having adequate anaesthesia for hip surgery. Anaesthesia in the segments L5 and S1 was seen in 2/15 patients in the horizontal position and 8/15 patients in the hammock position (P < 0.05). The hammock position resulted in a higher percentage of patients having adequate anaesthesia for knee surgery (60% vs 13%; P < 0.05) and foot surgery (53% vs 13%; P < 0.05) (Table 3). Motor block was more profound in patients in the hammock position (Table 4). Blood pressure and heart rate did not change significantly in patients in the horizontal position (Fig. 1); there was a decrease in both systolic (7 mmHg) and diastolic (5 mmHg) blood pressures in patients in the hammock position. Heart rate did not change significantly (Fig. 2). No patient needed vasopressor support; the body position could be maintained in all patients during the observation period. One or two epidural reinjections according to the spread of anaesthesia 30 min after the first injection and to the scheduled operation resulted in adequate anaesthesia in every patient. DISCUSSION. More patients in the hammock position developed adequate anaesthesia in the relevant segments for knee and foot operations than patients in the horizontal position. These included the frequently missed segments L5 and S1. Patients in the hammock position had a clinically insignificant drop in systolic and diastolic blood pressure. In contrast to the young and healthy patients in this study, more severe cardiovascular changes might result in geriatric and/or ill patients subjected to a hammock position. For this reason, use of the technique in geriatric and/or ill patients requires special attention.
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Anestesia Epidural , Pierna/cirugía , Región Lumbosacra , Postura , Adulto , Femenino , Humanos , MasculinoRESUMEN
Conventional therapies with recombinant human erythropoietin (rHuEPO) to sustain preoperative autologous blood collection entail high doses of the drug at short intervals. To evaluate the efficacy of a single weekly dose of rHuEPO for autologous blood collection, we randomly assigned 24 male patients scheduled for coronary artery bypass surgery to receive 400 IU/kg rHuEPO subcutaneously once a week or iron only. Patients were examined weekly and a total of up to 4 units of autologous blood were obtained if the hemoglobin level exceeded 12 g/dL. Patients receiving rHuEPO had consistently higher hemoglobin values than those receiving iron only (P < 0.001). Consequently, more autologous red cells were obtained from this group (776 +/- 49 mL vs 682 +/- 91 mL; P < 0.05). One patient receiving rHuEPO and eight in the control group required homologous blood at surgery (P < 0.01). These results suggest that 400 IU/kg rHuEPO administered subcutaneously once a week efficiently stimulates erythropoiesis and compensates the hemoglobin decrease after autologous blood donation.