Analysis of the temporal regression of the QRS widening induced by bupivacaine after intralipid administration. Study in an experimental porcine model | Revista Española de Anestesiología y Reanimación (English Edition)

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"apellidos" => "Anadón" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "f" "identificador" => "aff0030" ] ] ] ] "afiliaciones" => array:6 [ 0 => array:3 [ "entidad" => "Servicio de Anestesiología, Reanimación y Terapéutica del Dolor, Hospital Universitario Gregorio Marañón, Universidad Complutense de Madrid, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Cardiología, Hospital Universitario de Getafe, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Cardiología, Hospital de Torrejón, Torrejón de Ardoz, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Unidad de Electrofisiología Cardíaca y Arritmología Clínica, Grupo HM Hospitales, Universidad CEU-San Pablo, Madrid, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Instituto Nacional de Toxicología y Ciencias Forenses, Universidad Complutense de Madrid, Madrid, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Departamento de Toxicología y Legislación Sanitaria, Universidad Complutense de Madrid, Madrid, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Análisis de la regresión temporal en el ensanchamiento del intervalo QRS inducido por bupivacaína con la administración de Intralipid. Estudio en un modelo experimental porcino" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1463 "Ancho" => 2167 "Tamanyo" => 426985 ] ] "descripcion" => array:1 [ "en" => "Example of QRS interval widening following bupivacaine administration. The baseline QRS interval of 50ms extended to 200ms following bupivacaine administration." ] ] ] "textoCompleto" => "IntroductionBupivacaine, due to its effectiveness, low cost and prolonged action, is still one of the most widely used local anaesthetics (LA).<a class="elsevierStyleCrossRef" href="#bib0005">1</a> However, it has been associated with cardiac arrest following administration, involving practically simultaneous presentation of seizures and asystole that require prolonged, fruitless, cardiopulmonary resuscitation.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>The cardiac toxicity of bupivacaine is due to the combination of acute depression of myocardial contractility and a severe decrease in ventricular conduction, which in turn causes reentrant arrhythmias.<a class="elsevierStyleCrossRefs" href="#bib0015">3,4</a> Various electrophysiological mechanisms can explain this phenomenon, one of the most relevant being sodium channel block, followed by calcium and potassium channel block to a lesser extent.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> Electrocardiographically, this sodium channel inhibition manifests as a distinct QRS widening.In recent years, laboratory studies and individual case reports have suggested that administration of lipids, such as Intralipid (IL), during LA-induced cardiac toxicity can act as an antidote to bupivacaine and potentially reduce morbidity.<a class="elsevierStyleCrossRefs" href="#bib0030">6,7</a> One of the suggested mechanisms behind this effect is the capacity of this lipid to absorb the LA. This is known as the “lipid sink” effect, and is a consequence of the lipophilicity of bupivacaine, which reduces the tissue content of the drug.Preliminary studies have suggested that IL can modify the toxic action of bupivacaine.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> However, there is scant information on the effect of IL on bupivacaine-induced cardiac conduction alterations.The aim of this study is to evaluate whether bupivacaine-induced cardiac alterations can be reversed by administration of IL at a dose that is non-lethal but capable of causing severe impairment of the cardiac conduction system.We based our study on the hypothesis that IL administration would reverse bupivacaine-induced depression of myocardial conduction velocity.Material and methodsStudy designThis is a randomized, case–control experimental study. The protocol was approved by the Animal Research Ethics Committee of the Gregorio Marañón teaching hospital (ACTA CEEA no. 1. 2013). Twelve large-white pigs of both sexes weighing between 28 and 52kg (mean 37±10kg) were used. Animals were randomized to one of the two groups using the online randomizing programme Research-randomizer. <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> shows the study design sequence.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Preparation of animalsThe animals fasted for 10h prior to the start of the study, but were given unlimited water. The animals were premedicated with 20mgkg−1 intramuscular ketamine 20min before transfer to the operating room. When the desired level of sedation had been reached, the animals were transferred to the operating room where intravenous access was obtained from a vein in the outer ear. Anaesthesia was induced with 5mgkg−1 sodium thiopental (Tiobarbital Braun, B Braun medical S.A.). Following this, the animal was intubated without the use of muscle relaxants in order to avoid drug conflict that could interfere with the study. The animal received mechanical ventilation with pure oxygen, and the minute volume was adjusted to maintain partial pressure of CO2 at around 35–40mm Hg (Respirador Dräger SA1, Dräger Medical Hispania S.A., Spain). A warming blanket was used to maintain the animal's temperature at around 38°C (Warm Touch, Patient Warming System, Mallinckrodt Medica). During the intervention, a saline solution (0.9%) was infused at a rate of between 2 and 5mLkg−1h−1. Anaesthesia was maintained with 2.6% sevoflurane, the MAC described for pigs.<a class="elsevierStyleCrossRef" href="#bib0045">9</a>An ultrasound-guided (Vivid S5 – GE Healthcare) arterial line was placed in the femoral artery and vein for invasive monitoring and intraoperative determinations.Continuous 12-lead echocardiography recordings were obtained (ECG Lab 3.0. Tecnomed 2000 S. L. Madrid), together with recording from the standard II lead (PowerLab 16/30, AD Instruments). The continuous recordings were saved to a laptop computer.Experimental protocolWhen the monitoring instruments had been placed and the animal had been stabilized, baseline measurements were taken and a preliminary dose of 4mgkg−1 bupivacaine (bupivacaine hydrochloride, Inibsacain, Inibsa), was administered over 30s. The toxic target in our animal model was the induction of cardiac toxicity, which we defined as a 150% increase in the QRS interval. If this was not achieved within 3min of bupivacaine administration, an additional dose of 1mgkg−1 was administered. If the toxic target was not achieved, further doses of 1mgkg were administered, up to a total of 6mgkg−1.An initial dose of 1mgkg was chosen because this had been shown to give a plasma level of 2000ngmL−1 in other bupivacaine-induced cardiac toxicity models. This is usually sufficient to induce severe electrophysiological alterations without causing asystole and the subsequent deterioration of the animal, thus avoiding confounding factors.<a class="elsevierStyleCrossRefs" href="#bib0040">8,10</a>When the target toxic effect had been achieved, we proceeded to administer a loading dose of 1.5mLkg−1 IL (supplied by the hospital's pharmacy) injected over 1min, followed by infusion of 0.25mLkg−1min−1. We used the IL infusion recommended in guidelines published by various anaesthesiology associations for the treatment of local anaesthetic-induced toxicity. In the control group, IL was replaced by saline solution.We took samples of venous and arterial blood to measure blood gases and bupivacaine levels at the different study time points (GEM® Premier 3000 Blood Gas analyser Model 5700).Determination of bupivacaine levelsDetermination of plasma bupivacaine levels was performed with liquid chromatography-tandem mass spectroscopy (LC–MS/MS), following the method used with other local anaesthetics. For this purpose, a 2mL sample of venous blood from the femoral vein was centrifuged a 4000rpm for 10min. All samples were stored frozen at −20°C until needed for analysis. The analysis was performed with 50μL of plasma (previously brought up to room temperature) to which mepivacaine was added as an internal standard. We used solid phase extraction (Strata-X columns [3mL/60mg]) to eliminate any matrix interference.Bupivacaine was separated from its internal standard within 1.5min and quantified using the LC–MS/MS system equipped with an electrospray ionization source in positive ionization mode. The mass spectrometry method used was MRM (multiple reaction monitoring), in which two phases for both bupivacaine (289.3>149.2 and 289.3>84.2) and its internal standard (247>98 and 247>70.1) were monitored.<a class="elsevierStyleCrossRef" href="#bib0055">11</a>Times and measurementsEchocardiographic parameters were measured at baseline, following administration of bupivacaine, and then every minute until the toxic target was reached (usually within the first 5min). After administration of IL, echocardiographic parameters were determined at 1, 5, 10 and 30min.QRS interval duration: following the standard criteria recommended by the American Heart Association, we considered global intervals in all 12 leads. QRS duration was measured in the lead of earliest onset and up to the lead of latest offset.<a class="elsevierStyleCrossRef" href="#bib0060">12</a>PR interval: measured from the beginning of the P wave to the beginning of the Q wave.QT interval: from the beginning of the QRS complex to the end of the T wave.Corrected QT interval (Qtc=QT/√RR, Bazett's formula).Statistical analysisStatistical analysis was performed using SPSS version 20.0. (SPSS Inc., Chicago, IL, USA).Results are expressed as median and interquartile range. The general study data and characteristics of study animals were analyzed descriptively.QRS values, bupivacaine levels, haemodynamic and blood gas parameters were compared between the IL and control groups using the Mann–Whitney U test for independent samples. QRS values prior to bupivacaine administration, at the moment of maximum toxicity, and following administration of IL were compared using the Wilcoxon test for related samples. Significance levels were not adjusted for multiple comparisons.Sample sizeWe estimated that mean QRS widening, on the basis of the bupivacaine dose administered, would be greater the 150% of the baseline value. We considered that a difference of over 50% in the reversal of the QRS value in the Intralipid group vs control would be clinically relevant. We estimated that 6 animals in each group would be sufficient, considering an alpha risk of 0.05 and a beta risk of 0.2.ResultsThe mean bupivacaine dose required to produce the QRS interval target was 4.33±0.81mg/kg in the IL group and 4.66±1.15mg/kg in the control (C) group, p=0.59. Haemodynamic and blood gas measurements over the study period are shown in <a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a>. No significant differences were observed between groups in either of these parameters, except for pO2 following bupivacaine administration, when this parameter was slightly lower in controls (540±8.6mm Hg IL group vs 495±28mm Hg C group).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>The evolution of bupivacaine levels over the study period is shown in <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>. Toxic levels in excess of 2000ngmL−1 were observed in all animals. Plasma levels did not differ between groups.<elsevierMultimedia ident="fig0010"></elsevierMultimedia>A significant increase in the QRS interval following administration of bupivacaine was observed. This widened from baseline values of 63±7ms and 59±11ms in the IL and C groups, respectively, to 175±29ms (Δ177%) in the IL group and 192±29ms in the C group (Δ228%); (p=0.43). <a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a> shows an example of the effect of bupivacaine on the QRS interval.<elsevierMultimedia ident="fig0015"></elsevierMultimedia>Following infusion of IL, QRS widening was reversed in the IL group, but remained the same in the C group (p<0.05), (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). At 10min after IL administration, the QRS interval decreased to 132±56% vs 15±76%, relative to the maximum bupivacaine-induced increase observed, p=0.03. The QRS interval remained significantly widened in the C group at 30min vs the IL group (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>). Other electrocardiographic changes are shows in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>. The PR interval was prolonged with administration of bupivacaine and partially corrected following IL administration. At 10min it remained significantly prolonged in the C group (135±19ms IL group vs 206±24C group, p=0.002). The QTc interval also increased following bupivacaine infusion. However, it did not return to baseline following administration of IL, and at 30min both groups showed similar values.<elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Arrhythmias were induced in 3 animals from each group. The most common type was complete AV block (1 animal in the IL group and 2 in the C group). Other arrhythmias included nonsustained ventricular tachycardia in 2 animals from the IL group, and 1 episode of sustained ventricular tachycardia in the C group. IL administration reversed the arrhythmia in all animals except for 1, which developed a high-grade AV block with severe hypotension that ended in asystole. This animal received external cardiac massage and 30μgkg−1, after which its haemodynamic and electrocardiographic parameters were recovered.DiscussionThe main finding in this study is that IL was effective in rapidly correcting bupivacaine-induced cardiac conduction toxicity, and in particular in reversing prolongation of the QRS interval.Bupivacaine-induced depression of cardiac conduction is a well-known phenomenon that manifests on ECG as a widening of the QRS interval.<a class="elsevierStyleCrossRefs" href="#bib0025">5,13</a> This widening correlates in turn with plasma bupivacaine levels, and is caused by sodium channel block.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> Reports from clinical practice have described post-local anaesthesia plasma bupivacaine levels that are high enough to trigger major electrophysiological and haemodynamic alterations. Therefore, a widening of the QRS interval observed in a patient receiving local anaesthetic should prompt clinicians to suspect anaesthetic toxicity, and to take appropriate monitoring and therapeutic measures.In an earlier study of bupivacaine toxicity in a porcine model similar to ours, the authors compared the effects of early administration of two lipid preparations vs saline solution on cardiac conduction.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> This study showed that early (30s post-bupivacaine) infusion of lipids can reverse bupivacaine-induced electrophysiological and electrocardiographic alterations. In contrast to this study, in our bupivacaine toxicity model we specifically sought to reproduce a situation of severe cardiac toxicity with a mean widening of the QRS interval of over 150% over baseline. Once this target toxicity had been achieved, we administered IL. This cardiac conduction delay impairs the electrical and mechanical activation of the left ventricle, a depolarisation that could in turn trigger reentrant arrhythmia. In our study, IL successfully restored electrical conduction after the toxic effects of bupivacaine administration had been confirmed, thus adding further evidence to support the administration of lipid solutions in the event of accidental bupivacaine intoxication. However, it is important to note that the effect of bupivacaine on the QRS interval persists 10min after IL administration. This finding, together with the persistence of other electrocardiographic alterations up to 30min after IL infusion, suggests the need for continued clinical monitoring due to the continued vulnerability of the heart.Our findings are consistent with those of earlier studies showing that IL reverses bupivacaine-induced cardiac arrest and myocardial depression.<a class="elsevierStyleCrossRefs" href="#bib0030">6,7,14,15</a> In dogs given higher toxic doses of bupivacaine that those used in our study, IL infusion associated with other cardiopulmonary resuscitation measures increased the survival rate in the treatment group vs controls not receiving lipids.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> Similarly, pre-treatment with lipids in rats receiving bupivacaine increased the dose of bupivacaine required to cause death in 50% of animals by 48%.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> Generally speaking, most authors have found that lipid administration improve both survival and the effectiveness of resuscitation measures in in vivo models, and facilitates the restoration of cardiac parameters in isolated heart models.<a class="elsevierStyleCrossRefs" href="#bib0080">16,17</a>Several reports concerning patients presenting severe LA intoxication have shown that lipid administration facilitated patient recovery, often when other resuscitation measures had failed.<a class="elsevierStyleCrossRefs" href="#bib0090">18–20</a>The protective mechanism of lipids against toxicity from long acting LA suggests they are lipophilic, and shows the excellent capacity of lipid emulsions to bind with LAs. The most widely accepted theory in this regard is Weinberg's lipid sink phenomenon, which suggests that a tissue-blood concentration gradient is established that drives the LA drug from the heart and other tissues into the newly formed ‘lipid sink. Other mechanisms suggested involve an increase in intracellular fatty acid content that overcomes the reduced ATP production caused by LA-induced blockade of fatty acid transport and oxidation.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> Despite these theories, further research is needed to definitively explain the mechanism responsible for the anti-LA toxicity action of lipid emulsions.Clinical considerationsExtraordinary progress has been made in recent years in local anaesthesia techniques in response to a growing demand from both patients and surgeons.<a class="elsevierStyleCrossRef" href="#bib0105">21</a> Despite their proven efficacy, however, the risk of systemic toxicity has been a recurring problem since LAs were first introduced into clinical practice. The findings of our study support those of earlier authors who showed that IL reverses the cardiac conduction alternations induced by bupivacaine toxicity. We also found that cardiac toxicity persists for at least 10min after IL infusion, suggesting that patients should remain under observation until they are stabilized and out of danger. It is essential to take precaution to avoid adverse events when administering local anaesthesia. However, should cardiac toxicity occur, administration of a lipid emulsion should be considered to reverse the toxic effects of bupivacaine on cardiac electrical conduction.LimitationsIn our study, we did not evaluate the mechanism of action of Intralipid, and therefore we cannot specifically confirm the action of this emulsion. However, the existence of a control group in which cardiac toxicity was not reversed would corroborate the effectiveness of the antidote. Likewise, we cannot be sure whether cardiac recovery can be extrapolated to a model with a higher dose of bupivacaine and higher level of cardiac toxicity. However, the electrocardiographic parameters obtained showed that the levels obtained in this study were sufficiently toxic, and this in our opinion justifies our conclusions.ConclusionsThis study has shown that administration of Intralipid effectively reverses the cardiac toxicity induced by non-lethal doses of bupivacaine. These findings justify the use of Intralipid in situations of bupivacaine toxicity, and supports the recommendations made in toxicity management guidelines. This does not rule out, however, the need for concomitant cardiopulmonary resuscitation measures in cases of severe toxicity.FundingThis study was funded by grants awarded in 2011 by the Carlos III Health Institute III.Conflict of interestsThe authors declare no conflict of interest relating to the content of this study." "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres594478" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec609420" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres594479" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y método" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec609421" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study design" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Preparation of animals" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Experimental protocol" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Determination of bupivacaine levels" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Times and measurements" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Statistical analysis" ] 6 => array:2 [ "identificador" => "sec0045" "titulo" => "Sample size" ] ] ] 6 => array:2 [ "identificador" => "sec0050" "titulo" => "Results" ] 7 => array:3 [ "identificador" => "sec0055" "titulo" => "Discussion" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0060" "titulo" => "Clinical considerations" ] ] ] 8 => array:2 [ "identificador" => "sec0065" "titulo" => "Limitations" ] 9 => array:2 [ "identificador" => "sec0070" "titulo" => "Conclusions" ] 10 => array:2 [ "identificador" => "sec0075" "titulo" => "Funding" ] 11 => array:2 [ "identificador" => "sec0080" "titulo" => "Conflict of interests" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-11-24" "fechaAceptado" => "2015-02-10" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec609420" "palabras" => array:5 [ 0 => "Bupivacaine" 1 => "Cardiac toxicity" 2 => "QRS interval" 3 => "Intralipid" 4 => "Antidote" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec609421" "palabras" => array:5 [ 0 => "Bupivacaína" 1 => "Toxicidad cardiaca" 2 => "Intervalo QRS" 3 => "Intralipid" 4 => "Antídoto" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveThe principal mechanism of cardiac toxicity of bupivacaine relates to the blockade of myocardial sodium channels, which leads to an increase in the QRS duration. Recently, experimental studies suggest that lipid emulsion is effective in reversing bupivacaine cardiac toxicity. We aimed to evaluate the temporal evolution of the QRS widening induced by bupivacaine with the administration of Intralipid. Material and methodsTwelve pigs were anesthetized with intravenous sodium thiopental 5mgkg−1 and sevoflurane 1 MAC (2.6%). Femoral artery and vein were canalized for invasive monitoring, analysis of blood gases and determination of bupivacaine levels. After instrumentation and monitoring, a bupivacaine bolus of 4–6mgkg−1 was administered in order to induce a 150% increase in QRS duration (defined as the toxic point). The pigs were randomized into two groups of six individuals. Intralipid group (IL) received 1.5mLkg−1 of IL over 1min, followed by an infusion of 0.25mLkgmin−1. Control group (C) received the same volume of a saline solution. The electrocardiographic parameters were recorded, and blood samples were taken after bupivacaine and 1, 5, 10 and 30min after Intralipid/saline administration. ResultsBupivacaine (4.33±0.81mg/kg in IL group and 4.66±1.15mg/kg in C group) induced similar electrocardiographic changes in both groups; mean maximal percent increase in QRS interval was 184±62% in IL group, and 230±56% in control group (NS). Lipid administration reversed the QRS widening previously impaired by bupivacaine. After 10min of the administration of IL, the mean QRS interval decreased to 132±56% vs. 15±76% relative to the maximum widening induced by bupivacaine, in IL and C group, respectively. ConclusionIntralipid reversed the lengthening of QRS interval induced by the injection of bupivacaine. Time to normalization of electrocardiographic parameters can last more than 10min. While the phenomena of cardiac toxicity persist, resuscitation measures and adequate monitoring should be continued until adequate heart conduction parameters are restored." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoLa toxicidad cardiaca inducida por la bupivacaína (B) se relaciona con el bloqueo de los canales de sodio, que se traduce por un ensanchamiento del intervalo QRS. Estudios experimentales recientes, sugieren que el Intralipid (IL) es eficaz en revertir la toxicidad cardiaca de la B. Nuestro objetivo fue analizar la evolución temporal del ensanchamiento del QRS inducido por la B con la administración de IL. Material y métodoDoce cerdos fueron anestesiados con tiopental sódico, 5mgkg−1, y sevoflurano a concentración alveolar mínima de 2,6%. Tras la instrumentalización se administró un bolo de B de 4–6mgkg−1 con el objetivo de inducir un aumento de 150% en la duración del QRS. El grupo IL recibió 1,5mLkg−1 de IL seguido de 0,25mLkg min−1; el grupo control (C) recibió salino. Se registraron los parámetros electrocardiográficos tras la infusión de B y a 1, 5,10 y 30min de la administración de Intralipid/salino. ResultadosLa administración de B (4,33±0,81mg/kg en el grupo IL y 4,66±1,15mg/kg en el grupo C) indujo cambios electrocardiográficos similares en ambos grupos; el porcentaje medio de incremento máximo en el QRS fue de 184±62% en el grupo IL, y de 230±56% en el grupo C. El IL revirtió el ensanchamiento del QRS inducido por la B, a los 10min de su administración el intervalo QRS disminuyó 132±56% vs. 15±76%, en relación al máximo incremento inducido por la B, en el grupo IL y grupo C respectivamente. ConclusiónEl IL revirtió eficazmente el ensanchamiento del intervalo QRS inducido por la B. El tiempo hasta la normalización de los parámetros electrocardiográficos puede prolongarse más de 10min. Mientras persistan los fenómenos de toxicidad cardíaca, las medidas de resucitación y monitorización deben continuarse hasta que los parámetros de conducción cardíaca se hayan restaurado de forma adecuada." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y método" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Zaballos M, Sevilla R, González J, Callejo D, de Diego C, Almendral J, et al. Análisis de la regresión temporal en el ensanchamiento del intervalo QRS inducido por bupivacaína con la administración de Intralipid. Estudio en un modelo experimental porcino. Rev Esp Anestesiol Reanim. 2016;63:13–21." ] 1 => array:2 [ "etiqueta" => "☆☆" "nota" => "This study received an award at the 19th annual ESRA-ESPAÑA, 2013 meeting." ] ] "multimedia" => array:8 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 667 "Ancho" => 1637 "Tamanyo" => 64908 ] ] "descripcion" => array:1 [ "en" => "Experimental design." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1070 "Ancho" => 1646 "Tamanyo" => 91922 ] ] "descripcion" => array:1 [ "en" => "Bupivacaine levels in venous blood. Values expressed as median and interquartile range." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1463 "Ancho" => 2167 "Tamanyo" => 426985 ] ] "descripcion" => array:1 [ "en" => "Example of QRS interval widening following bupivacaine administration. The baseline QRS interval of 50ms extended to 200ms following bupivacaine administration." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1005 "Ancho" => 1624 "Tamanyo" => 77900 ] ] "descripcion" => array:1 [ "en" => "Evolution of the QRS interval in both groups over the study period. Pre-IL, 1, 5, 10, 30min post-IL: QRS interval prior to Intralipid administration and at 1-min intervals post administration. Values expressed as median and interquartile range." ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 2235 "Ancho" => 3250 "Tamanyo" => 648035 ] ] "descripcion" => array:1 [ "en" => "Example of the effect of intralipid on the QRS interval. The start line of the graph shows a sinus rhythm of 75bpm, with a QRS complex duration of 140ms. The arrow indicates the effect of Intralipid administration, showing P blocked by a Wenckebach nodal block, following by narrow QRS complexes of 80ms." ] ] 5 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "DAP, diastolic arterial pressure; HR, heart rate; bpm, beats per minute; SAP, systolic arterial pressure. Data are expressed as median and interquartile range." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Intralipid group \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Control group \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Baseline HR, bpm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">106 (93–107) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">102(80–108) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.39 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Baseline SAP (mm Hg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">111(101–120) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">101 (88–111) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.35 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Baseline DAP (mm Hg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">62 (55–80) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">63 (55–69) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.91 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Bupivacaine HR, bpm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">92 (81–99) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">83 (69–97) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.31 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Bupivacaine SAP (mm Hg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">73 (56–96) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">76 (62–90) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.76 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Bupivacaine DAP (mm Hg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">34(27–61) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40 (33–51) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.76 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">HR 10min intralipid/saline, bpm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">87(61–103) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">98 (68–114) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.69 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">SAP 10min intralipid/saline (mm Hg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">94 (69–100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 (83–107) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.71 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">DAP 10min intralipid/saline (mm Hg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">47(36–62) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">55(45–63) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.54 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">HR 30min intralipid/saline, bpm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 (54–102) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 (84–113) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.54 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">SAP 30min intralipid/saline (mm Hg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">130 (83–140) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">113 (101–130) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">DAP 30min intralipid/saline (mm Hg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">82 (45–90) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67(60–74) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab972098.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Haemodynamic parameters at different study time points." ] ] 6 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Data are expressed as median and interquartile range." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Intralipid group \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Control group \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Baseline pH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.52 (7.42–7.53) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.49 (7.44–7.55) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.93 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Baseline pO2 (mm Hg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">506 (347–545) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">445 (316–542) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.69 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Baseline pCO2 (mm Hg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">34 (31–46) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41 (34–47) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.48 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Baseline CO3H− (mmolL−1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">28 (21–37) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 (28–35) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.60 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Baseline BE (mmolL−1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (−3 to 16) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (4–12) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.74 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Baseline SaO2 (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Bupivacaine pH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.48 (7.41–7.50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.48 (7.45–7.53) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.61 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Bupivacaine pO2 (mm Hg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">542 (531–545) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">488 (474–520) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.03 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Bupivacaine pCO2 (mm Hg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42 (40–46) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38 (34–40) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Bupivacaine CO3H− (mmol litre−1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29 (27–37) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">28 (27–29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.24 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Bupivacaine BE (mmol litre−1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (2.7–10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (4–6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.38 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Bupivacaine SaO2 (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Intralipid/saline pH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.44 (7.38–7.52) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.46 (7.43–7.55) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.53 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Intralipid/saline pO2 (mm Hg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">526 (254–577) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">483 (422–499) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.87 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Intralipid/saline pCO2 (mm Hg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">39 (35–44) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40 (32–47) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.91 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Intralipid/salineCO3H− (mmolL−1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27 (21–35) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29 (27–30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.80 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Intralipid/saline BE (mmolL−1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3±(−4 to 11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (4–8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.53 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Intralipid/saline SaO2 (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab972100.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Arterial blood gas obtained at different study time points." ] ] 7 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "HR: heart rate; bpm: beats per minute; PR: atrioventricular conduction time; QRS: duration of QRS interval; Qtc: duration of corrected QT interval.The table shows post-bupivacaine intoxication electrocardiographic parameters immediately before Intralipid administration, and the same parameters at 10 and 30min post intralipid administration. Data are expressed as median and interquartile range." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Intralipid group \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Control group \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Baseline HR, bpm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">106 (93–107) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">102 (80–108) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.39 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Baseline PR (ms) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 (80–128) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">119 (98–135) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.37 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Baseline QRS (ms) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60 (58–71) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">56 (50–68) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.43 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Baseline QTc (ms) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">502 (489–523) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">515 (455–550) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.96 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Bupivacaine HR, bpm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">92 (81–99) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">83 (69–97) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.31 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Bupivacaine PR (ms) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">160 (146–170) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">200 (178–206) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Bupivacaine QRS (ms) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">171 (155–206) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">198 (176–207) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.43 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Bupivacaine QTc (ms) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">579 (531–625) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">590 (563–635) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.63 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">HR 10min intralipid/saline, bpm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">87 (61–103) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">98 (68–114) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.69 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">PR 10min intralipid/saline (ms) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">130 (120–155) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">200 (185–230) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">QRS 10min intralipid/saline (ms) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">88 (75–128) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">170 (144–219) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.03 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">QTc 10min intralipid/saline (ms) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">560 (439–597) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">569 (486–620) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.63 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">HR 30min intralipid/saline, bpm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 (54–102) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 (84–113) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.54 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">PR 30min intralipid/saline (ms) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">126 (114–140) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">157 (113–185) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.34 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">QRS 30min intralipid/saline (ms) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">74 (60–77) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">92 (88–128) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.04 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">QTc 30min intralipid/saline (ms) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">550 (530–560) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">550 (525–590) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.78 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] 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Original article

Analysis of the temporal regression of the QRS widening induced by bupivacaine after intralipid administration. Study in an experimental porcine model

Análisis de la regresión temporal en el ensanchamiento del intervalo QRS inducido por bupivacaína con la administración de Intralipid. Estudio en un modelo experimental porcino

M. Zaballosa,

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mati@plagaro.net

Corresponding author.

, R. Sevillaa, J. Gonzálezb, D. Callejoa, C. de Diegoc, J. Almendrald, O. Quintelae, M.J. Anadónf

a Servicio de Anestesiología, Reanimación y Terapéutica del Dolor, Hospital Universitario Gregorio Marañón, Universidad Complutense de Madrid, Madrid, Spain

b Servicio de Cardiología, Hospital Universitario de Getafe, Madrid, Spain

c Servicio de Cardiología, Hospital de Torrejón, Torrejón de Ardoz, Madrid, Spain

d Unidad de Electrofisiología Cardíaca y Arritmología Clínica, Grupo HM Hospitales, Universidad CEU-San Pablo, Madrid, Spain

e Instituto Nacional de Toxicología y Ciencias Forenses, Universidad Complutense de Madrid, Madrid, Spain

f Departamento de Toxicología y Legislación Sanitaria, Universidad Complutense de Madrid, Madrid, Spain

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        "titulo" => "An&#225;lisis de la regresi&#243;n temporal en el ensanchamiento del intervalo QRS inducido por bupivaca&#237;na con la administraci&#243;n de Intralipid&#46; Estudio en un modelo experimental porcino"
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Example of QRS interval widening following bupivacaine administration&#46; The baseline QRS interval of 50<span class="elsevierStyleHsp" style=""></span>ms extended to 200<span class="elsevierStyleHsp" style=""></span>ms following bupivacaine administration&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Bupivacaine&#44; due to its effectiveness&#44; low cost and prolonged action&#44; is still one of the most widely used local anaesthetics &#40;LA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> However&#44; it has been associated with cardiac arrest following administration&#44; involving practically simultaneous presentation of seizures and asystole that require prolonged&#44; fruitless&#44; cardiopulmonary resuscitation&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The cardiac toxicity of bupivacaine is due to the combination of acute depression of myocardial contractility and a severe decrease in ventricular conduction&#44; which in turn causes reentrant arrhythmias&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> Various electrophysiological mechanisms can explain this phenomenon&#44; one of the most relevant being sodium channel block&#44; followed by calcium and potassium channel block to a lesser extent&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Electrocardiographically&#44; this sodium channel inhibition manifests as a distinct QRS widening&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">In recent years&#44; laboratory studies and individual case reports have suggested that administration of lipids&#44; such as Intralipid &#40;IL&#41;&#44; during LA-induced cardiac toxicity can act as an antidote to bupivacaine and potentially reduce morbidity&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a> One of the suggested mechanisms behind this effect is the capacity of this lipid to absorb the LA&#46; This is known as the &#8220;lipid sink&#8221; effect&#44; and is a consequence of the lipophilicity of bupivacaine&#44; which reduces the tissue content of the drug&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Preliminary studies have suggested that IL can modify the toxic action of bupivacaine&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> However&#44; there is scant information on the effect of IL on bupivacaine-induced cardiac conduction alterations&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The aim of this study is to evaluate whether bupivacaine-induced cardiac alterations can be reversed by administration of IL at a dose that is non-lethal but capable of causing severe impairment of the cardiac conduction system&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">We based our study on the hypothesis that IL administration would reverse bupivacaine-induced depression of myocardial conduction velocity&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study design</span><p id="par0035" class="elsevierStylePara elsevierViewall">This is a randomized&#44; case&#8211;control experimental study&#46; The protocol was approved by the Animal Research Ethics Committee of the Gregorio Mara&#241;&#243;n teaching hospital &#40;ACTA CEEA no&#46; 1&#46; 2013&#41;&#46; Twelve large-white pigs of both sexes weighing between 28 and 52<span class="elsevierStyleHsp" style=""></span>kg &#40;mean 37<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>kg&#41; were used&#46; Animals were randomized to one of the two groups using the online randomizing programme Research-randomizer&#46; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> shows the study design sequence&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Preparation of animals</span><p id="par0040" class="elsevierStylePara elsevierViewall">The animals fasted for 10<span class="elsevierStyleHsp" style=""></span>h prior to the start of the study&#44; but were given unlimited water&#46; The animals were premedicated with 20<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span> intramuscular ketamine 20<span class="elsevierStyleHsp" style=""></span>min before transfer to the operating room&#46; When the desired level of sedation had been reached&#44; the animals were transferred to the operating room where intravenous access was obtained from a vein in the outer ear&#46; Anaesthesia was induced with 5<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span> sodium thiopental &#40;Tiobarbital Braun&#44; B Braun medical S&#46;A&#46;&#41;&#46; Following this&#44; the animal was intubated without the use of muscle relaxants in order to avoid drug conflict that could interfere with the study&#46; The animal received mechanical ventilation with pure oxygen&#44; and the minute volume was adjusted to maintain partial pressure of CO<span class="elsevierStyleInf">2</span> at around 35&#8211;40<span class="elsevierStyleHsp" style=""></span>mm Hg &#40;Respirador Dr&#228;ger SA1&#44; Dr&#228;ger Medical Hispania S&#46;A&#46;&#44; Spain&#41;&#46; A warming blanket was used to maintain the animal&#39;s temperature at around 38<span class="elsevierStyleHsp" style=""></span>&#176;C &#40;Warm Touch&#44; Patient Warming System&#44; Mallinckrodt Medica&#41;&#46; During the intervention&#44; a saline solution &#40;0&#46;9&#37;&#41; was infused at a rate of between 2 and 5<span class="elsevierStyleHsp" style=""></span>mL<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span><span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleSup">&#8722;1</span>&#46; Anaesthesia was maintained with 2&#46;6&#37; sevoflurane&#44; the MAC described for pigs&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">An ultrasound-guided &#40;Vivid S5 &#8211; GE Healthcare&#41; arterial line was placed in the femoral artery and vein for invasive monitoring and intraoperative determinations&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Continuous 12-lead echocardiography recordings were obtained &#40;ECG Lab 3&#46;0&#46; Tecnomed 2000 S&#46; L&#46; Madrid&#41;&#44; together with recording from the standard <span class="elsevierStyleSmallCaps">II</span> lead &#40;PowerLab 16&#47;30&#44; AD Instruments&#41;&#46; The continuous recordings were saved to a laptop computer&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Experimental protocol</span><p id="par0055" class="elsevierStylePara elsevierViewall">When the monitoring instruments had been placed and the animal had been stabilized&#44; baseline measurements were taken and a preliminary dose of 4<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span> bupivacaine &#40;bupivacaine hydrochloride&#44; Inibsacain&#44; Inibsa&#41;&#44; was administered over 30<span class="elsevierStyleHsp" style=""></span>s&#46; The toxic target in our animal model was the induction of cardiac toxicity&#44; which we defined as a 150&#37; increase in the QRS interval&#46; If this was not achieved within 3<span class="elsevierStyleHsp" style=""></span>min of bupivacaine administration&#44; an additional dose of 1<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span> was administered&#46; If the toxic target was not achieved&#44; further doses of 1<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>kg were administered&#44; up to a total of 6<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span>&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">An initial dose of 1<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>kg was chosen because this had been shown to give a plasma level of 2000<span class="elsevierStyleHsp" style=""></span>ng<span class="elsevierStyleHsp" style=""></span>mL<span class="elsevierStyleSup">&#8722;1</span> in other bupivacaine-induced cardiac toxicity models&#46; This is usually sufficient to induce severe electrophysiological alterations without causing asystole and the subsequent deterioration of the animal&#44; thus avoiding confounding factors&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;10</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">When the target toxic effect had been achieved&#44; we proceeded to administer a loading dose of 1&#46;5<span class="elsevierStyleHsp" style=""></span>mL<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span> IL &#40;supplied by the hospital&#39;s pharmacy&#41; injected over 1<span class="elsevierStyleHsp" style=""></span>min&#44; followed by infusion of 0&#46;25<span class="elsevierStyleHsp" style=""></span>mL<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span><span class="elsevierStyleHsp" style=""></span>min<span class="elsevierStyleSup">&#8722;1</span>&#46; We used the IL infusion recommended in guidelines published by various anaesthesiology associations for the treatment of local anaesthetic-induced toxicity&#46; In the control group&#44; IL was replaced by saline solution&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">We took samples of venous and arterial blood to measure blood gases and bupivacaine levels at the different study time points &#40;GEM<span class="elsevierStyleSup">&#174;</span> Premier 3000 Blood Gas analyser Model 5700&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Determination of bupivacaine levels</span><p id="par0075" class="elsevierStylePara elsevierViewall">Determination of plasma bupivacaine levels was performed with liquid chromatography-tandem mass spectroscopy &#40;LC&#8211;MS&#47;MS&#41;&#44; following the method used with other local anaesthetics&#46; For this purpose&#44; a 2<span class="elsevierStyleHsp" style=""></span>mL sample of venous blood from the femoral vein was centrifuged a 4000<span class="elsevierStyleHsp" style=""></span>rpm for 10<span class="elsevierStyleHsp" style=""></span>min&#46; All samples were stored frozen at &#8722;20<span class="elsevierStyleHsp" style=""></span>&#176;C until needed for analysis&#46; The analysis was performed with 50<span class="elsevierStyleHsp" style=""></span>&#956;L of plasma &#40;previously brought up to room temperature&#41; to which mepivacaine was added as an internal standard&#46; We used solid phase extraction &#40;Strata-X columns &#91;3<span class="elsevierStyleHsp" style=""></span>mL&#47;60<span class="elsevierStyleHsp" style=""></span>mg&#93;&#41; to eliminate any matrix interference&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Bupivacaine was separated from its internal standard within 1&#46;5<span class="elsevierStyleHsp" style=""></span>min and quantified using the LC&#8211;MS&#47;MS system equipped with an electrospray ionization source in positive ionization mode&#46; The mass spectrometry method used was MRM &#40;multiple reaction monitoring&#41;&#44; in which two phases for both bupivacaine &#40;289&#46;3<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>149&#46;2 and 289&#46;3<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>84&#46;2&#41; and its internal standard &#40;247<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>98 and 247<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>70&#46;1&#41; were monitored&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Times and measurements</span><p id="par0085" class="elsevierStylePara elsevierViewall">Echocardiographic parameters were measured at baseline&#44; following administration of bupivacaine&#44; and then every minute until the toxic target was reached &#40;usually within the first 5<span class="elsevierStyleHsp" style=""></span>min&#41;&#46; After administration of IL&#44; echocardiographic parameters were determined at 1&#44; 5&#44; 10 and 30<span class="elsevierStyleHsp" style=""></span>min&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">QRS interval duration</span>&#58; following the standard criteria recommended by the American Heart Association&#44; we considered global intervals in all 12 leads&#46; QRS duration was measured in the lead of earliest onset and up to the lead of latest offset&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">PR interval&#58;</span> measured from the beginning of the P wave to the beginning of the Q wave&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">QT interval&#58;</span> from the beginning of the QRS complex to the end of the T wave&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Corrected QT interval</span> &#40;Qtc<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>QT&#47;&#8730;RR&#44; Bazett&#39;s formula&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0110" class="elsevierStylePara elsevierViewall">Statistical analysis was performed using SPSS version 20&#46;0&#46; &#40;SPSS Inc&#46;&#44; Chicago&#44; IL&#44; USA&#41;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Results are expressed as median and interquartile range&#46; The general study data and characteristics of study animals were analyzed descriptively&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">QRS values&#44; bupivacaine levels&#44; haemodynamic and blood gas parameters were compared between the IL and control groups using the Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test for independent samples&#46; QRS values prior to bupivacaine administration&#44; at the moment of maximum toxicity&#44; and following administration of IL were compared using the Wilcoxon test for related samples&#46; Significance levels were not adjusted for multiple comparisons&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Sample size</span><p id="par0125" class="elsevierStylePara elsevierViewall">We estimated that mean QRS widening&#44; on the basis of the bupivacaine dose administered&#44; would be greater the 150&#37; of the baseline value&#46; We considered that a difference of over 50&#37; in the reversal of the QRS value in the Intralipid group vs control would be clinically relevant&#46; We estimated that 6 animals in each group would be sufficient&#44; considering an alpha risk of 0&#46;05 and a beta risk of 0&#46;2&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Results</span><p id="par0130" class="elsevierStylePara elsevierViewall">The mean bupivacaine dose required to produce the QRS interval target was 4&#46;33<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;81<span class="elsevierStyleHsp" style=""></span>mg&#47;kg in the IL group and 4&#46;66<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;15<span class="elsevierStyleHsp" style=""></span>mg&#47;kg in the control &#40;C&#41; group&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;59&#46; Haemodynamic and blood gas measurements over the study period are shown in <a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a>&#46; No significant differences were observed between groups in either of these parameters&#44; except for pO<span class="elsevierStyleInf">2</span> following bupivacaine administration&#44; when this parameter was slightly lower in controls &#40;540<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;6<span class="elsevierStyleHsp" style=""></span>mm Hg IL group vs 495<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>28<span class="elsevierStyleHsp" style=""></span>mm Hg C group&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">The evolution of bupivacaine levels over the study period is shown in <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#46; Toxic levels in excess of 2000<span class="elsevierStyleHsp" style=""></span>ng<span class="elsevierStyleHsp" style=""></span>mL<span class="elsevierStyleSup">&#8722;1</span> were observed in all animals&#46; Plasma levels did not differ between groups&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0140" class="elsevierStylePara elsevierViewall">A significant increase in the QRS interval following administration of bupivacaine was observed&#46; This widened from baseline values of 63<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7<span class="elsevierStyleHsp" style=""></span>ms and 59<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11<span class="elsevierStyleHsp" style=""></span>ms in the IL and C groups&#44; respectively&#44; to 175<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>29<span class="elsevierStyleHsp" style=""></span>ms &#40;&#916;177&#37;&#41; in the IL group and 192<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>29<span class="elsevierStyleHsp" style=""></span>ms in the C group &#40;&#916;228&#37;&#41;&#59; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;43&#41;&#46; <a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a> shows an example of the effect of bupivacaine on the QRS interval&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">Following infusion of IL&#44; QRS widening was reversed in the IL group&#44; but remained the same in the C group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#44; &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46; At 10<span class="elsevierStyleHsp" style=""></span>min after IL administration&#44; the QRS interval decreased to 132<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>56&#37; vs 15<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>76&#37;&#44; relative to the maximum bupivacaine-induced increase observed&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#46; The QRS interval remained significantly widened in the C group at 30<span class="elsevierStyleHsp" style=""></span>min vs the IL group &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46; Other electrocardiographic changes are shows in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46; The PR interval was prolonged with administration of bupivacaine and partially corrected following IL administration&#46; At 10<span class="elsevierStyleHsp" style=""></span>min it remained significantly prolonged in the C group &#40;135<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19<span class="elsevierStyleHsp" style=""></span>ms IL group vs 206<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>24<span class="elsevierStyleHsp" style=""></span>C group&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41;&#46; The QTc interval also increased following bupivacaine infusion&#46; However&#44; it did not return to baseline following administration of IL&#44; and at 30<span class="elsevierStyleHsp" style=""></span>min both groups showed similar values&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">Arrhythmias were induced in 3 animals from each group&#46; The most common type was complete AV block &#40;1 animal in the IL group and 2 in the C group&#41;&#46; Other arrhythmias included nonsustained ventricular tachycardia in 2 animals from the IL group&#44; and 1 episode of sustained ventricular tachycardia in the C group&#46; IL administration reversed the arrhythmia in all animals except for 1&#44; which developed a high-grade AV block with severe hypotension that ended in asystole&#46; This animal received external cardiac massage and 30<span class="elsevierStyleHsp" style=""></span>&#956;g<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span>&#44; after which its haemodynamic and electrocardiographic parameters were recovered&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Discussion</span><p id="par0155" class="elsevierStylePara elsevierViewall">The main finding in this study is that IL was effective in rapidly correcting bupivacaine-induced cardiac conduction toxicity&#44; and in particular in reversing prolongation of the QRS interval&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Bupivacaine-induced depression of cardiac conduction is a well-known phenomenon that manifests on ECG as a widening of the QRS interval&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;13</span></a> This widening correlates in turn with plasma bupivacaine levels&#44; and is caused by sodium channel block&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Reports from clinical practice have described post-local anaesthesia plasma bupivacaine levels that are high enough to trigger major electrophysiological and haemodynamic alterations&#46; Therefore&#44; a widening of the QRS interval observed in a patient receiving local anaesthetic should prompt clinicians to suspect anaesthetic toxicity&#44; and to take appropriate monitoring and therapeutic measures&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">In an earlier study of bupivacaine toxicity in a porcine model similar to ours&#44; the authors compared the effects of early administration of two lipid preparations vs saline solution on cardiac conduction&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> This study showed that early &#40;30<span class="elsevierStyleHsp" style=""></span>s post-bupivacaine&#41; infusion of lipids can reverse bupivacaine-induced electrophysiological and electrocardiographic alterations&#46; In contrast to this study&#44; in our bupivacaine toxicity model we specifically sought to reproduce a situation of severe cardiac toxicity with a mean widening of the QRS interval of over 150&#37; over baseline&#46; Once this target toxicity had been achieved&#44; we administered IL&#46; This cardiac conduction delay impairs the electrical and mechanical activation of the left ventricle&#44; a depolarisation that could in turn trigger reentrant arrhythmia&#46; In our study&#44; IL successfully restored electrical conduction after the toxic effects of bupivacaine administration had been confirmed&#44; thus adding further evidence to support the administration of lipid solutions in the event of accidental bupivacaine intoxication&#46; However&#44; it is important to note that the effect of bupivacaine on the QRS interval persists 10<span class="elsevierStyleHsp" style=""></span>min after IL administration&#46; This finding&#44; together with the persistence of other electrocardiographic alterations up to 30<span class="elsevierStyleHsp" style=""></span>min after IL infusion&#44; suggests the need for continued clinical monitoring due to the continued vulnerability of the heart&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Our findings are consistent with those of earlier studies showing that IL reverses bupivacaine-induced cardiac arrest and myocardial depression&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7&#44;14&#44;15</span></a> In dogs given higher toxic doses of bupivacaine that those used in our study&#44; IL infusion associated with other cardiopulmonary resuscitation measures increased the survival rate in the treatment group vs controls not receiving lipids&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Similarly&#44; pre-treatment with lipids in rats receiving bupivacaine increased the dose of bupivacaine required to cause death in 50&#37; of animals by 48&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Generally speaking&#44; most authors have found that lipid administration improve both survival and the effectiveness of resuscitation measures in in vivo models&#44; and facilitates the restoration of cardiac parameters in isolated heart models&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;17</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Several reports concerning patients presenting severe LA intoxication have shown that lipid administration facilitated patient recovery&#44; often when other resuscitation measures had failed&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#8211;20</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">The protective mechanism of lipids against toxicity from long acting LA suggests they are lipophilic&#44; and shows the excellent capacity of lipid emulsions to bind with LAs&#46; The most widely accepted theory in this regard is Weinberg&#39;s lipid sink phenomenon&#44; which suggests that a tissue-blood concentration gradient is established that drives the LA drug from the heart and other tissues into the newly formed &#8216;lipid sink&#46; Other mechanisms suggested involve an increase in intracellular fatty acid content that overcomes the reduced ATP production caused by LA-induced blockade of fatty acid transport and oxidation&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Despite these theories&#44; further research is needed to definitively explain the mechanism responsible for the anti-LA toxicity action of lipid emulsions&#46;</p><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Clinical considerations</span><p id="par0185" class="elsevierStylePara elsevierViewall">Extraordinary progress has been made in recent years in local anaesthesia techniques in response to a growing demand from both patients and surgeons&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> Despite their proven efficacy&#44; however&#44; the risk of systemic toxicity has been a recurring problem since LAs were first introduced into clinical practice&#46; The findings of our study support those of earlier authors who showed that IL reverses the cardiac conduction alternations induced by bupivacaine toxicity&#46; We also found that cardiac toxicity persists for at least 10<span class="elsevierStyleHsp" style=""></span>min after IL infusion&#44; suggesting that patients should remain under observation until they are stabilized and out of danger&#46; It is essential to take precaution to avoid adverse events when administering local anaesthesia&#46; However&#44; should cardiac toxicity occur&#44; administration of a lipid emulsion should be considered to reverse the toxic effects of bupivacaine on cardiac electrical conduction&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Limitations</span><p id="par0190" class="elsevierStylePara elsevierViewall">In our study&#44; we did not evaluate the mechanism of action of Intralipid&#44; and therefore we cannot specifically confirm the action of this emulsion&#46; However&#44; the existence of a control group in which cardiac toxicity was not reversed would corroborate the effectiveness of the antidote&#46; Likewise&#44; we cannot be sure whether cardiac recovery can be extrapolated to a model with a higher dose of bupivacaine and higher level of cardiac toxicity&#46; However&#44; the electrocardiographic parameters obtained showed that the levels obtained in this study were sufficiently toxic&#44; and this in our opinion justifies our conclusions&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conclusions</span><p id="par0195" class="elsevierStylePara elsevierViewall">This study has shown that administration of Intralipid effectively reverses the cardiac toxicity induced by non-lethal doses of bupivacaine&#46; These findings justify the use of Intralipid in situations of bupivacaine toxicity&#44; and supports the recommendations made in toxicity management guidelines&#46; This does not rule out&#44; however&#44; the need for concomitant cardiopulmonary resuscitation measures in cases of severe toxicity&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Funding</span><p id="par0200" class="elsevierStylePara elsevierViewall">This study was funded by grants awarded in 2011 by the <span class="elsevierStyleGrantSponsor" id="gs1">Carlos III Health Institute III</span>&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conflict of interests</span><p id="par0205" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest relating to the content of this study&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The principal mechanism of cardiac toxicity of bupivacaine relates to the blockade of myocardial sodium channels&#44; which leads to an increase in the QRS duration&#46; Recently&#44; experimental studies suggest that lipid emulsion is effective in reversing bupivacaine cardiac toxicity&#46; We aimed to evaluate the temporal evolution of the QRS widening induced by bupivacaine with the administration of Intralipid&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Twelve pigs were anesthetized with intravenous sodium thiopental 5<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span> and sevoflurane 1 MAC &#40;2&#46;6&#37;&#41;&#46; Femoral artery and vein were canalized for invasive monitoring&#44; analysis of blood gases and determination of bupivacaine levels&#46; After instrumentation and monitoring&#44; a bupivacaine bolus of 4&#8211;6<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span> was administered in order to induce a 150&#37; increase in QRS duration &#40;defined as the toxic point&#41;&#46; The pigs were randomized into two groups of six individuals&#46; Intralipid group &#40;IL&#41; received 1&#46;5<span class="elsevierStyleHsp" style=""></span>mL<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span> of IL over 1<span class="elsevierStyleHsp" style=""></span>min&#44; followed by an infusion of 0&#46;25<span class="elsevierStyleHsp" style=""></span>mL<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleHsp" style=""></span>min<span class="elsevierStyleSup">&#8722;1</span>&#46; Control group &#40;C&#41; received the same volume of a saline solution&#46; The electrocardiographic parameters were recorded&#44; and blood samples were taken after bupivacaine and 1&#44; 5&#44; 10 and 30<span class="elsevierStyleHsp" style=""></span>min after Intralipid&#47;saline administration&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Bupivacaine &#40;4&#46;33<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;81<span class="elsevierStyleHsp" style=""></span>mg&#47;kg in IL group and 4&#46;66<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;15<span class="elsevierStyleHsp" style=""></span>mg&#47;kg in C group&#41; induced similar electrocardiographic changes in both groups&#59; mean maximal percent increase in QRS interval was 184<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>62&#37; in IL group&#44; and 230<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>56&#37; in control group &#40;NS&#41;&#46; Lipid administration reversed the QRS widening previously impaired by bupivacaine&#46; After 10<span class="elsevierStyleHsp" style=""></span>min of the administration of IL&#44; the mean QRS interval decreased to 132<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>56&#37; vs&#46; 15<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>76&#37; relative to the maximum widening induced by bupivacaine&#44; in IL and C group&#44; respectively&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Intralipid reversed the lengthening of QRS interval induced by the injection of bupivacaine&#46; Time to normalization of electrocardiographic parameters can last more than 10<span class="elsevierStyleHsp" style=""></span>min&#46; While the phenomena of cardiac toxicity persist&#44; resuscitation measures and adequate monitoring should be continued until adequate heart conduction parameters are restored&#46;</p></span>"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La toxicidad cardiaca inducida por la bupivaca&#237;na &#40;B&#41; se relaciona con el bloqueo de los canales de sodio&#44; que se traduce por un ensanchamiento del intervalo QRS&#46; Estudios experimentales recientes&#44; sugieren que el Intralipid &#40;IL&#41; es eficaz en revertir la toxicidad cardiaca de la B&#46; Nuestro objetivo fue analizar la evoluci&#243;n temporal del ensanchamiento del QRS inducido por la B con la administraci&#243;n de IL&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Doce cerdos fueron anestesiados con tiopental s&#243;dico&#44; 5<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span>&#44; y sevoflurano a concentraci&#243;n alveolar m&#237;nima de 2&#44;6&#37;&#46; Tras la instrumentalizaci&#243;n se administr&#243; un bolo de B de 4&#8211;6<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span> con el objetivo de inducir un aumento de 150&#37; en la duraci&#243;n del QRS&#46; El grupo IL recibi&#243; 1&#44;5<span class="elsevierStyleHsp" style=""></span>mL<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span> de IL seguido de 0&#44;25<span class="elsevierStyleHsp" style=""></span>mL<span class="elsevierStyleHsp" style=""></span>kg min<span class="elsevierStyleSup">&#8722;1</span>&#59; el grupo control &#40;C&#41; recibi&#243; salino&#46; Se registraron los par&#225;metros electrocardiogr&#225;ficos tras la infusi&#243;n de B y a 1&#44; 5&#44;10 y 30<span class="elsevierStyleHsp" style=""></span>min de la administraci&#243;n de Intralipid&#47;salino&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La administraci&#243;n de B &#40;4&#44;33<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;81<span class="elsevierStyleHsp" style=""></span>mg&#47;kg en el grupo IL y 4&#44;66<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;15<span class="elsevierStyleHsp" style=""></span>mg&#47;kg en el grupo C&#41; indujo cambios electrocardiogr&#225;ficos similares en ambos grupos&#59; el porcentaje medio de incremento m&#225;ximo en el QRS fue de 184<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>62&#37; en el grupo IL&#44; y de 230<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>56&#37; en el grupo C&#46; El IL revirti&#243; el ensanchamiento del QRS inducido por la B&#44; a los 10<span class="elsevierStyleHsp" style=""></span>min de su administraci&#243;n el intervalo QRS disminuy&#243; 132<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>56&#37; vs&#46; 15<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>76&#37;&#44; en relaci&#243;n al m&#225;ximo incremento inducido por la B&#44; en el grupo IL y grupo C respectivamente&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El IL revirti&#243; eficazmente el ensanchamiento del intervalo QRS inducido por la B&#46; El tiempo hasta la normalizaci&#243;n de los par&#225;metros electrocardiogr&#225;ficos puede prolongarse m&#225;s de 10<span class="elsevierStyleHsp" style=""></span>min&#46; Mientras persistan los fen&#243;menos de toxicidad card&#237;aca&#44; las medidas de resucitaci&#243;n y monitorizaci&#243;n deben continuarse hasta que los par&#225;metros de conducci&#243;n card&#237;aca se hayan restaurado de forma adecuada&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Objetivo"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Material y m&#233;todo"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusi&#243;n"
          ]
        ]
      ]
    ]
    "NotaPie" => array:2 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Zaballos M&#44; Sevilla R&#44; Gonz&#225;lez J&#44; Callejo D&#44; de Diego C&#44; Almendral J&#44; et al&#46; An&#225;lisis de la regresi&#243;n temporal en el ensanchamiento del intervalo QRS inducido por bupivaca&#237;na con la administraci&#243;n de Intralipid&#46; Estudio en un modelo experimental porcino&#46; Rev Esp Anestesiol Reanim&#46; 2016&#59;63&#58;13&#8211;21&#46;</p>"
      ]
      1 => array:2 [
        "etiqueta" => "&#9734;&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">This study received an award at the 19th annual ESRA-ESPA&#209;A&#44; 2013 meeting&#46;</p>"
      ]
    ]
    "multimedia" => array:8 [
      0 => array:7 [
        "identificador" => "fig0005"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Experimental design&#46;</p>"
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      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Bupivacaine levels in venous blood&#46; Values expressed as median and interquartile range&#46;</p>"
        ]
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      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Figure 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Example of QRS interval widening following bupivacaine administration&#46; The baseline QRS interval of 50<span class="elsevierStyleHsp" style=""></span>ms extended to 200<span class="elsevierStyleHsp" style=""></span>ms following bupivacaine administration&#46;</p>"
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      3 => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Figure 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Evolution of the QRS interval in both groups over the study period&#46; Pre-IL&#44; 1&#44; 5&#44; 10&#44; 30<span class="elsevierStyleHsp" style=""></span>min post-IL&#58; QRS interval prior to Intralipid administration and at 1-min intervals post administration&#46; Values expressed as median and interquartile range&#46;</p>"
        ]
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      4 => array:7 [
        "identificador" => "fig0025"
        "etiqueta" => "Figure 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
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        "figura" => array:1 [
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Example of the effect of intralipid on the QRS interval&#46; The start line of the graph shows a sinus rhythm of 75<span class="elsevierStyleHsp" style=""></span>bpm&#44; with a QRS complex duration of 140<span class="elsevierStyleHsp" style=""></span>ms&#46; The arrow indicates the effect of Intralipid administration&#44; showing P blocked by a Wenckebach nodal block&#44; following by narrow QRS complexes of 80<span class="elsevierStyleHsp" style=""></span>ms&#46;</p>"
        ]
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      5 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">DAP&#44; diastolic arterial pressure&#59; HR&#44; heart rate&#59; bpm&#44; beats per minute&#59; SAP&#44; systolic arterial pressure&#46; Data are expressed as median and interquartile range&#46;</p>"
          "tablatextoimagen" => array:1 [
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Intralipid group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Control group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Baseline HR&#44; bpm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">106 &#40;93&#8211;107&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">102&#40;80&#8211;108&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Baseline SAP &#40;mm Hg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">111&#40;101&#8211;120&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">101 &#40;88&#8211;111&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Baseline DAP &#40;mm Hg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">62 &#40;55&#8211;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">63 &#40;55&#8211;69&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Bupivacaine HR&#44; bpm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">92 &#40;81&#8211;99&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">83 &#40;69&#8211;97&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Bupivacaine SAP &#40;mm Hg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">73 &#40;56&#8211;96&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">76 &#40;62&#8211;90&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Bupivacaine DAP &#40;mm Hg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">34&#40;27&#8211;61&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40 &#40;33&#8211;51&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">HR 10<span class="elsevierStyleHsp" style=""></span>min intralipid&#47;saline&#44; bpm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">87&#40;61&#8211;103&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">98 &#40;68&#8211;114&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;69&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">SAP 10<span class="elsevierStyleHsp" style=""></span>min intralipid&#47;saline &#40;mm Hg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">94 &#40;69&#8211;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">97 &#40;83&#8211;107&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">DAP 10<span class="elsevierStyleHsp" style=""></span>min intralipid&#47;saline &#40;mm Hg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">47&#40;36&#8211;62&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">55&#40;45&#8211;63&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">HR 30<span class="elsevierStyleHsp" style=""></span>min intralipid&#47;saline&#44; bpm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">97 &#40;54&#8211;102&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100 &#40;84&#8211;113&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">SAP 30<span class="elsevierStyleHsp" style=""></span>min intralipid&#47;saline &#40;mm Hg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">130 &#40;83&#8211;140&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">113 &#40;101&#8211;130&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">DAP 30<span class="elsevierStyleHsp" style=""></span>min intralipid&#47;saline &#40;mm Hg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">82 &#40;45&#8211;90&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">67&#40;60&#8211;74&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Haemodynamic parameters at different study time points&#46;</p>"
        ]
      ]
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        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Data are expressed as median and interquartile range&#46;</p>"
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Intralipid group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Control group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Baseline pH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;52 &#40;7&#46;42&#8211;7&#46;53&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;49 &#40;7&#46;44&#8211;7&#46;55&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Baseline pO<span class="elsevierStyleInf">2</span> &#40;mm Hg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">506 &#40;347&#8211;545&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">445 &#40;316&#8211;542&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;69&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Baseline pCO<span class="elsevierStyleInf">2</span> &#40;mm Hg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">34 &#40;31&#8211;46&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">41 &#40;34&#8211;47&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Baseline CO<span class="elsevierStyleInf">3</span>H<span class="elsevierStyleSup">&#8722;</span> &#40;mmol<span class="elsevierStyleHsp" style=""></span>L<span class="elsevierStyleSup">&#8722;1</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">28 &#40;21&#8211;37&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30 &#40;28&#8211;35&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Baseline BE &#40;mmol<span class="elsevierStyleHsp" style=""></span>L<span class="elsevierStyleSup">&#8722;1</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6 &#40;&#8722;3 to 16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7 &#40;4&#8211;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;74&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Baseline SaO<span class="elsevierStyleInf">2</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Bupivacaine pH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;48 &#40;7&#46;41&#8211;7&#46;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;48 &#40;7&#46;45&#8211;7&#46;53&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Bupivacaine pO<span class="elsevierStyleInf">2</span> &#40;mm Hg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">542 &#40;531&#8211;545&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">488 &#40;474&#8211;520&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Bupivacaine pCO<span class="elsevierStyleInf">2</span> &#40;mm Hg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">42 &#40;40&#8211;46&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38 &#40;34&#8211;40&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Bupivacaine CO<span class="elsevierStyleInf">3</span>H<span class="elsevierStyleSup">&#8722;</span> &#40;mmol litre<span class="elsevierStyleSup">&#8722;1</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">29 &#40;27&#8211;37&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">28 &#40;27&#8211;29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Bupivacaine BE &#40;mmol litre<span class="elsevierStyleSup">&#8722;1</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6 &#40;2&#46;7&#8211;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;4&#8211;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Bupivacaine SaO<span class="elsevierStyleInf">2</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Intralipid&#47;saline pH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;44 &#40;7&#46;38&#8211;7&#46;52&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;46 &#40;7&#46;43&#8211;7&#46;55&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Intralipid&#47;saline pO<span class="elsevierStyleInf">2</span> &#40;mm Hg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">526 &#40;254&#8211;577&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">483 &#40;422&#8211;499&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Intralipid&#47;saline pCO2 &#40;mm Hg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">39 &#40;35&#8211;44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40 &#40;32&#8211;47&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Intralipid&#47;salineCO<span class="elsevierStyleInf">3</span>H<span class="elsevierStyleSup">&#8722;</span> &#40;mmol<span class="elsevierStyleHsp" style=""></span>L<span class="elsevierStyleSup">&#8722;1</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27 &#40;21&#8211;35&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">29 &#40;27&#8211;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Intralipid&#47;saline BE &#40;mmol<span class="elsevierStyleHsp" style=""></span>L<span class="elsevierStyleSup">&#8722;1</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>&#40;&#8722;4 to 11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6 &#40;4&#8211;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Intralipid&#47;saline SaO<span class="elsevierStyleInf">2</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab972100.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Arterial blood gas obtained at different study time points&#46;</p>"
        ]
      ]
      7 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">HR&#58; heart rate&#59; bpm&#58; beats per minute&#59; PR&#58; atrioventricular conduction time&#59; QRS&#58; duration of QRS interval&#59; Qtc&#58; duration of corrected QT interval&#46;</p><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">The table shows post-bupivacaine intoxication electrocardiographic parameters immediately before Intralipid administration&#44; and the same parameters at 10 and 30<span class="elsevierStyleHsp" style=""></span>min post intralipid administration&#46; Data are expressed as median and interquartile range&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Intralipid group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Control group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Baseline HR&#44; bpm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">106 &#40;93&#8211;107&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">102 &#40;80&#8211;108&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Baseline PR &#40;ms&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100 &#40;80&#8211;128&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">119 &#40;98&#8211;135&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Baseline QRS &#40;ms&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60 &#40;58&#8211;71&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">56 &#40;50&#8211;68&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Baseline QTc &#40;ms&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">502 &#40;489&#8211;523&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">515 &#40;455&#8211;550&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;96&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Bupivacaine HR&#44; bpm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">92 &#40;81&#8211;99&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">83 &#40;69&#8211;97&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Bupivacaine PR &#40;ms&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">160 &#40;146&#8211;170&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">200 &#40;178&#8211;206&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Bupivacaine QRS &#40;ms&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">171 &#40;155&#8211;206&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">198 &#40;176&#8211;207&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Bupivacaine QTc &#40;ms&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">579 &#40;531&#8211;625&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">590 &#40;563&#8211;635&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">HR 10<span class="elsevierStyleHsp" style=""></span>min intralipid&#47;saline&#44; bpm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">87 &#40;61&#8211;103&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">98 &#40;68&#8211;114&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;69&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">PR 10<span class="elsevierStyleHsp" style=""></span>min intralipid&#47;saline &#40;ms&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">130 &#40;120&#8211;155&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">200 &#40;185&#8211;230&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">QRS 10<span class="elsevierStyleHsp" style=""></span>min intralipid&#47;saline &#40;ms&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">88 &#40;75&#8211;128&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">170 &#40;144&#8211;219&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">QTc 10<span class="elsevierStyleHsp" style=""></span>min intralipid&#47;saline &#40;ms&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">550 &#40;530&#8211;560&#41;&nbsp;\t\t\t\t\t\t\n
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Article information

ISSN: 23411929
Original language: English

DOI:10.1016/j.redare.2015.08.002

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