Brief report
Neuroprotective effect of sevoflurane in general anaesthesia
Efecto neuroprotector del sevoflurano en anestesia general
Victoria Ramos Ramosa, Pablo Mesa Suárezb, José Diego Santotoribioc,d,
, María Ángela González Garcíae, Antonio Muñoz Hoyosf
Corresponding author
a Unidad de Gestión Clínica de Pediatría, Hospital de Jerez de la Frontera, Jerez de la Frontera, Cádiz, Spain
b Unidad de Gestión Clínica de Anestesiología, Hospital Universitario Puerto Real, Puerto Real, Cádiz, Spain
c Unidad de Gestión Clínica de Laboratorio, Hospital Universitario Puerto Real, Puerto Real, Cádiz, Spain
d Departamento de Biomedicina, Biotecnología y Salud Pública, Universidad de Cádiz, Cádiz, Spain
e Unidad de Gestión Clínica de Análisis Clínicos, Hospital de Jerez de la Frontera, Jerez de la Frontera, Cádiz, Spain
f Departamento de Pediatría, Universidad de Granada, Granada, Spain
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It is commonly used in anaesthesia as an induction and hypnotic maintenance agent. The studies published on the effect of sevoflurane on the central nervous system (CNS) have been conducted in animals and have contradictory conclusions. Some studies have shown that exposure to sevoflurane produces a neurotoxic effect, increasing neuronal apoptosis (neuronal death)<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">1–4</span></a>; however, other studies achieve a neuroprotective or antiapoptotic effect.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">5,6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In a paper recently published in <span class="elsevierStyleSmallCaps">Medicina Clínica</span>, serum S100B protein is suggested as a biomarker of overall post-anaesthesia brain damage. S100B protein is a calcium binding protein found in CNS cells, part of the structure of astrocytes and <span class="elsevierStyleItalic">Schwann</span> cells, which increases in patients with brain damage.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">7</span></a> The aim of this study was to assess brain damage from inhaled sevoflurane by determination of serum S100B protein before and after exposure to this drug as the sole anaesthetic agent in children scheduled for magnetic resonance imaging (MRI).</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and method</span><p id="par0015" class="elsevierStylePara elsevierViewall">Quasi-experimental study, before-and-after type, after exposure to sevoflurane as sole anaesthetic agent. This work has been authorized by the Clinical Research Ethics Committee of the Puerto Real University Hospital, and all participants signed an informed consent.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients</span><p id="par0020" class="elsevierStylePara elsevierViewall">Paediatric patients up to 13 years of age scheduled for a brain MRI who were being assessed for headaches were consecutively included from April 2015 to April 2016. Children with known neurological disorders, history of prematurity, emergency procedures, blood dyscrasias, liver or kidney disorders, soft tissue and cartilage tumours, or extensive trauma injuries in a previous period of 3 months were excluded. Children whose MRI's were reported with some kind of abnormality were also excluded.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Method</span><p id="par0025" class="elsevierStylePara elsevierViewall">A sample of peripheral venous blood was obtained from each of the patients included in this study and stored in a gel separator tube (Vacuette<span class="elsevierStyleSup">®</span>) during the pre-anaesthesia consultation (baseline sample). All patients underwent MRI under general anaesthesia with sevoflurane as the sole anaesthetic agent. The induction was performed with sevoflurane inhaled at an inspiratory fraction (FiAA) of 8% for a few seconds. FiAA was decreased to 2.5–3.5% after the loss of consciousness. After the imaging test, during anaesthetic recovery, the supply of inhalational agent was discontinued, and with the patient still in the MRI room, another peripheral venous blood sample (post-exposure sample) was taken. Blood samples (baseline and post-exposure) were centrifuged for 4<span class="elsevierStyleHsp" style=""></span>min at 4000<span class="elsevierStyleHsp" style=""></span>rpm to obtain serum. The concentration of serum S100B protein was determined in both samples by electrochemiluminescence immunoassay by MODULAR E-170 autoanalyzer (Roche Diagnostics) with reference values for normality between 5 and 105<span class="elsevierStyleHsp" style=""></span>ng/L.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical analysis</span><p id="par0030" class="elsevierStylePara elsevierViewall">The obtained data were processed by the MedCalc<span class="elsevierStyleSup">®</span> statistical programme. Descriptive statistics were performed with the frequency of qualitative variables; with the minimum/maximum value, the arithmetic mean and the standard deviation of quantitative variables with normal distribution; and the minimum/maximum value, median and interquartile range of quantitative variables with non-Gaussian distribution. The correlation between variables with normal distribution were analyzed using <span class="elsevierStyleItalic">Pearson</span>'s correlation coefficient, and the <span class="elsevierStyleItalic">Spearman's rho</span> or rank correlation coefficient was used for the correlation between variables with non-Gaussian distribution. The comparison between groups was performed by analysis of variance test for variables with normal distribution; and for variables with non-Gaussian distribution, the <span class="elsevierStyleItalic">Mann–Whitney</span> nonparametric test was used for independent data and the <span class="elsevierStyleItalic">Wilcoxon</span> test for paired data.</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0035" class="elsevierStylePara elsevierViewall">A total of 72 patients were included, aged between 2 and 13 years (median<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6), 28 boys and 44 girls. All variables studied followed a non-Gaussian distribution. No statistically significant differences were found between sexes regarding serum S100B protein levels in the baseline sample (S100BB) or postexposure sample (S100Bp) using the <span class="elsevierStyleItalic">Mann–Whitney</span> test. There was no significant correlation between patient age and S100BB or S100Bp values (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.05) using <span class="elsevierStyleItalic">Spearman's rho</span> correlation rank analysis. The time elapsed from baseline sampling during the pre-anaesthesia consultation to the post-exposure sampling at the MRI room was between 7 and 12 days (median<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>8). Maintenance anaesthesia during the MRI lasted between 20 and 45<span class="elsevierStyleHsp" style=""></span>min (median<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>27).</p><p id="par0040" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows descriptive statistics of the values obtained from S100BB, S100Bp and the difference between the two (S100Bp-b). In 58 of 72 patients (80.56%), serum S100B protein levels decreased after exposure to inhaled sevoflurane, obtaining statistically significant differences between S100BB and S100Bp by the <span class="elsevierStyleItalic">Wilcoxon</span> test (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.0059). Between S100Bp-b and the duration of anaesthesia there was an inverse correlation, <span class="elsevierStyleItalic">Spearman's rho rank correlation</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>−0.522 (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.0049).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0045" class="elsevierStylePara elsevierViewall">Low concentrations of serum S100B protein are associated with a neurotrophic effect; on the contrary, its elevation is associated with an increased neuronal apoptosis (neuronal death).<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">8</span></a> In this study, S100Bp values (median<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>66.5<span class="elsevierStyleHsp" style=""></span>ng/L) were significantly lower than S100BB (median<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>84.0<span class="elsevierStyleHsp" style=""></span>ng/L), resulting in a decrease in serum S100B protein levels after general anaesthesia with sevoflurane inhalation; in addition, the increased time exposure to sevoflurane was associated with a greater decrease in serum S100B protein, therefore, sevoflurane could have an antiapoptotic or neuroprotective effect on the CNS. It should be noted that, in this study, the children were anesthetized with sevoflurane at low concentrations (2.5–3.5%), because animal studies have shown a neurotoxic or neuroprotective effect according to the concentration of the drug administered: at high doses (8%) it has been related to an increased neuronal apoptosis; however, at low (2%) doses it has been associated with decreased neuronal apoptosis (neuronal death).<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">9</span></a> Decreased neuronal apoptosis was also found by caspase 3 determination in the brains of rats that had suffered a brain ischaemic injury and were treated with 2.4% sevoflurane.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In a paper recently published by our group,<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">7</span></a> a significant increase in serum S100B protein after exposure to a combination of intravenous anaesthetic drugs (propofol, midazolam and fentanyl) and inhaled sevoflurane was observed, therefore, a brain damage association with a specific drug could not be established, but rather, with the general anaesthesia as a whole. In the same study, an inversely proportional relationship of low intensity between the time of the procedure and increased serum S100B protein was demonstrated, i.e., the longer the patient was anesthetized, the smaller the brain damage was from anaesthesia, which indicated that increased time of exposure to anaesthetic drugs may be protective. In these patients, anaesthesia maintenance was performed by sevoflurane inhalation at 2%, which may explain the neuroprotective effect, because longer anaesthesia times meant increased exposure time to sevoflurane at low doses.</p><p id="par0055" class="elsevierStylePara elsevierViewall">This supposed antiapoptotic effect of sevoflurane could consolidate its use in general anaesthesia. In addition, it raises the possibility of its application as treatment in diseases with CNS involvement, opening new lines of research to evaluate the clinical relevance of this anti-apoptotic or neuroprotective effect and analyze the relationship between the decrease in serum S100B protein and the patient's neurological symptoms.</p><p id="par0060" class="elsevierStylePara elsevierViewall">In conclusion, serum S100B protein concentration significantly decreased after general anaesthesia with inhaled sevoflurane at low doses, therefore, this drug could have a antiapoptotic or neuroprotective effect on the CNS, although further studies are necessary in order to confirm it.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflict of interests</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare that there is no conflict of interest in connection with the results obtained in this study.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres821193" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and method" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec818195" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres821194" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y método" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec818196" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Patients and method" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Method" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0030" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflict of interests" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-07-19" "fechaAceptado" => "2016-10-20" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec818195" "palabras" => array:4 [ 0 => "S100B protein" 1 => "General anaesthesia" 2 => "Brain damage" 3 => "Sevoflurane" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec818196" "palabras" => array:4 [ 0 => "Proteína S100B" 1 => "Anestesia general" 2 => "Daño cerebral" 3 => "Sevoflurano" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The aim of this study was to evaluate the brain damage caused by inhaled sevoflurane, by determining the concentration of serum S100B protein before and after the exposure to this drug as the only anaesthetic agent.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and method</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Paediatric patients undergoing general anaesthesia for the conduct of a nuclear magnetic resonance were included in the study. A venous blood sample was taken from each patient before (basal sample) and after (post-exposure sample) administering the general anaesthesia. The concentration of serum S100B protein was determined in the basal (S100Bb) and post-exposure sample (S100Bp).</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A total of 72 patients were included in the study, with a mean patient age of 2–13 years (median<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6), 28 males and 44 females. S100Bp values (median<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>66.5<span class="elsevierStyleHsp" style=""></span>ng/L) were significantly lower (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.0059) than those of S100Bb (median<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>84.0<span class="elsevierStyleHsp" style=""></span>ng/L). The median of the difference between S100Bp and S100Bb was −11.0<span class="elsevierStyleHsp" style=""></span>ng/L.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Inhaled sevoflurane at low doses causes a decrease of serum S100B protein levels, hence, this drug could have a neuroprotective effect in the central nervous system.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and method" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción y objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El objetivo fue evaluar el daño cerebral producido por el sevoflurano inhalado mediante la determinación de la proteína S100B sérica antes y después de una exposición a este fármaco como único agente anestésico.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y método</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron pacientes pediátricos sometidos a resonancia magnética nuclear bajo anestesia general con sevoflurano inhalado a dosis baja. A todos los pacientes se les extrajo una muestra de sangre venosa, antes (muestra basal) y después de la anestesia general (muestra postexposición). Se determinó la concentración de la proteína S100B sérica en la muestra basal (S100Bb) y en la muestra postexposición (S100Bp).</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 72 pacientes entre 2 y 13 años (mediana<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6), 28 niños y 44 niñas. Los valores de S100Bp (mediana<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>66,5<span class="elsevierStyleHsp" style=""></span>ng/l) fueron significativamente inferiores (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,0059) a los de S100Bb (mediana<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>84,0<span class="elsevierStyleHsp" style=""></span>ng/l). La mediana de las diferencias entre S100Bp y S100Bb resultó −11,0<span class="elsevierStyleHsp" style=""></span>ng/l.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El sevoflurano inhalado a dosis bajas produce un descenso de la proteína S100B sérica, por lo que este fármaco podría tener un efecto neuroprotector a nivel del sistema nervioso central.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y método" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Ramos Ramos V, Mesa Suárez P, Santotoribio JD, González García MÁ, Muñoz Hoyos A. Efecto neuroprotector del sevoflurano en anestesia general. Med Clin (Barc). 2017;148:158–160.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">CI: confidence interval; IR: interquartile range; S100Bb: serum S100B protein in the baseline sample; S100Bp: serum S100B protein in the postexposure sample.</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"> \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">Minimum \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">Maximum \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">Median (95% CI) \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">IR \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">S100BB (ng/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">453.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">84.0 (71.7–98.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">S100Bp (ng/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">424.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">66.5 (56.5–90.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">S100Bp-b (ng/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−190.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">80.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−11.0 (−27.1 to −6.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1380554.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Descriptive statistics of serum S100B protein concentration in the baseline sample and postexposure sample, and the difference between the two.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0050" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "[Chinese]" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of sevoflurane on brain neuroapoptosis and ability of long-term learning and memory in newborn rats" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S.Q. 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