Whether preventive low dose magnesium sulphate infusion has an influence on postoperative pain perception and the level of serum beta-endorphin throughout the total abdominal hysterectomy | Revista Española de Anestesiología y Reanimación (English Edition)

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"apellidos" => "Mohammad Zadeh" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "e" "identificador" => "aff0025" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Department of Anesthesiology, Reproductive Health Research Center, Guilan University of Medical Sciences, Rasht, Iran" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Physiology, Medical Biotechnology Research Center, Faculty of Paramedical Sciences, Guilan University of Medical Science, Rasht, Iran" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Department of Clinical Biochemistry, Medical Biotechnology Research Center, Faculty of Paramedical Sciences, Guilan University of Medical Sciences, Rasht, Iran" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Department of Gynaecology, Reproductive Health Research Center, Guilan University of Medical Sciences, Rasht, Iran" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Bachelor of Science, Department of Anesthesiology, Reproductive Health Research Center, Faculty of Paramedical Sciences, Guilan University of Medical Sciences, Rasht, Iran" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Por qué la infusión preventiva de una dosis baja de sulfato de magnesio influye en la percepción del dolor postoperatorio y el nivel sérico de beta-endorfinas en las histerectomías abdominales totales" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1669 "Ancho" => 1617 "Tamanyo" => 127194 ] ] "descripcion" => array:1 [ "en" => "Study flow chart." ] ] ] "textoCompleto" => "IntroductionPain is one of the most common fears of patients scheduled for all types of surgeries, and can influence postoperative recovery and patient satisfaction. For many years, opioids have been used to alleviate intra- and postoperative pain<a class="elsevierStyleCrossRef" href="#bib0165">1</a>; however, because of their side effects, much research has been done to find less harmful pain relief alternatives.<a class="elsevierStyleCrossRef" href="#bib0170">2</a> Pain perception is multi-factorial, and can be modified by environmental factors, individuality, socioeconomic status, prior pain perception, etc.,<a class="elsevierStyleCrossRef" href="#bib0175">3</a> and these factors seem to complicate postoperative pain management.<a class="elsevierStyleCrossRef" href="#bib0170">2</a>In the recent years, attention has focused on adjuvant analgesics for postoperative pain management, one of these being magnesium, which is known to be an analgesic due to its calcium channel blocking action and N-methyl-d-aspartate (NMDA) receptor antagonism (possibly by preventing nociceptive central sensitization). Furthermore, the role of magnesium in decreasing catecholamine release has been shown to improve management of adrenergic response during surgery.<a class="elsevierStyleCrossRefs" href="#bib0180">4,5</a> As an intravenous (IV) adjuvant, magnesium sulphate can be used in multiple ways, including preventive low-dose infusion.<a class="elsevierStyleCrossRefs" href="#bib0175">3,6</a> Nevertheless, the beneficial effect of IV magnesium sulphate on postoperative pain management is still controversial,<a class="elsevierStyleCrossRefs" href="#bib0185">5,7–9</a> and outcomes can be affected by the anaesthesia technique use or magnesium dosage administered.<a class="elsevierStyleCrossRef" href="#bib0210">10</a>Endogenous opioids, which are generated in response to noxious stimulation, are closely related to pain. Beta-endorphins are potent endogenous opioid peptides that are synthesized primarily by the anterior pituitary gland and the hypothalamus.<a class="elsevierStyleCrossRef" href="#bib0215">11</a>Beta-endorphins, as a hormonal stress response, help control pain by binding to opioid receptors, and have maximum affinity for the μ1-opioid receptor at the presynaptic nerve terminal. Beta-endorphins inhibit GABA release, leading to increased dopamine release.<a class="elsevierStyleCrossRefs" href="#bib0220">12–14</a> Opioid medications function by mimicking natural endorphins, competing for receptor binding.<a class="elsevierStyleCrossRef" href="#bib0165">1</a>Major surgical procedures have been shown to increase secretion of stress hormones, such as beta-endorphins.<a class="elsevierStyleCrossRefs" href="#bib0235">15–17</a> Some studies have shown a correlation between serum beta-endorphin levels and postoperative pain.<a class="elsevierStyleCrossRefs" href="#bib0250">18,19</a>We investigated the effect of single-dose magnesium sulphate on postoperative pain control in total abdominal hysterectomy (TAH) under balanced general anaesthesia.<a class="elsevierStyleCrossRef" href="#bib0170">2</a> Low-dose intraoperative magnesium sulphate infusion appears to have lower toxicity and a better safety margin, and it was this characteristic, together with certain controversies surrounding this approach,<a class="elsevierStyleCrossRefs" href="#bib0200">8,9,20</a> that prompted us to investigate the possible relationship between low-dose magnesium sulphate and postoperative pain management by measuring serum beta-endorphin levels in patients receiving this analgesia during TAH.The main aim of this study was to evaluate the effect of low dose intra-operative magnesium sulphate infusion on postoperative pain management and stress hormones, such as beta-endorphins, in patients undergoing TAH.Patients and methodsStudy design and settingThe study was approved by the ethics committee of Guilan University of Medical Sciences (IRCT number 2014012316325N1) and designed as a parallel double-blinded, placebo-controlled study using equal randomization (1:1). It was conducted at the obstetrics and gynaecology ward of Al-Zahra maternity hospital (Rasht, Iran) during 2013–2014.Forty patients undergoing elective TAH with physical status I and II were included in the study after giving their informed consent. The physical status of the patients was diagnosed according to American Society of Anaesthesiologists (ASA) criteria. None of the patients had undergone prior abdominal surgeries and none presented major organ dysfunction, such as renal dysfunction, neuropathy or myopathy, hypersensitivity or allergy to magnesium, other drugs or food products. None reported opioid addiction or calcium channel blockers consumption.In order to ensure that prolonged manipulation did not influence postoperative pain scores, patients undergoing surgery lasting more than 2h or needing additional surgery (anterior-posterior repair, hernia repair) were excluded.Randomization and interventionsPatients were randomized to 2 groups; the test group, receiving magnesium (n=20) and controls, receiving placebo (n=20).<a class="elsevierStyleCrossRefs" href="#bib0265">21,22</a> The randomized list was prepared using the block randomization method. Patients were allocated to groups according to their surgical schedule, and were informed by ward nurses who were given an envelope at admission time. The test group received continuous intraoperative IV infusion of 15mg/kg/h magnesium sulphate dissolved in 100ml of isotonic saline (as a preventive low dose); controls received the same volume of isotonic saline without magnesium.Standard balanced general anaesthesia was performed as described above.<a class="elsevierStyleCrossRef" href="#bib0170">2</a> Anaesthesia was performed in all cases using IV injection of sodium thiopental (5mg/kg), fentanyl (1μg/kg) and succinylcholine (1mg/kg). After intubation, anaesthesia was maintained using balanced N2O/O2 (50%/50%), isoflurane (0.5%), atracurium (0.5mg/kg), and fentanyl (1μg/kg). Incremental doses of fentanyl (1μg/kg) were used if the patients showed any sign of sweating, lacrimation, or 20% increase in heart rate or blood pressure. Electrocardiography, heart rate, pulse oximetry, noninvasive blood pressure and level of neuromuscular junction block monitoring was performed. At the end of the surgery, neostigmine (0.05mg/kg) and atropine (0.02mg/kg) were administered to reverse neuromuscular blockade. Heart rate and noninvasive blood pressure were measured over the first 24 postoperative hours. Patients, surgeons, the outcome evaluator, and nursing staff were blinded to group assignment. The operating room nurses handed the envelopes to the anaesthetist. All procedures were performed by the same gynaecological surgeon and the same anaesthetist.Data collection and outcomesThe primary outcome measure was pain score reported at 0, 6, 12, and 24h after surgery. The secondary outcome was serum levels of beta-endorphins measured 15min before induction and at the end of surgery.Pain scores were evaluated using the verbal numeric rating scale (VNRS) (0=no pain; 10=worst pain). Before surgery, all subjects were instructed on how to use VNRS. Age, weight, and duration of surgery were noted. Pethidine consumption and side effects such as nausea, vomiting, hypotension or hypermagnesaemia in the first 24 postoperative hours were documented. Patients reporting a VNRS of more than 4 received pethidine 20mg.To evaluate the beta-endorphin level, venous blood samples were taken using anticoagulant-free tubes and centrifuged at 800×g for 5min. The resulting sera were kept at −20°C until measurement. Analysis of serum beta-endorphins was performed using an enzyme-linked immunosorbent assay (ELISA) kit (Hangzhou Eastbiopharm Co., China) and ELISA reader (Stat Fax, USA). The detection limit for beta-endorphin was 2.59ng/L. Serum levels of magnesium were measured before and 10min after surgery by colorimetry, using the Pars Azmoon kit (Tehran, Iran). The analysis was performed by a laboratory technician who was not involved in the study in any way. Hypermagnesaemia was defined as serum magnesium levels of more than 5mEq/L (when signs appeared).Statistical analysisValues are presented as mean±SD. The Student's t-test was used to compare means between groups. Preoperative and end-of-surgery levels of beta-endorphin and magnesium in each group were compared using the paired-samples t-test. Significance was set at p<0.05. Statistical analysis was performed on SPSS v. 21 software.ResultsForty women completed the study (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The groups were well matched for age, weight and duration of surgery (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). No significant differences were observed in systolic and diastolic blood pressure between the groups in the preoperative and postoperative period (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). No cases of postoperative hypotension were observed.<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>At the end of surgery, VNRS scores in the control group were significantly lower than those in the test group (p=0.0001); however, at 6 and 12h, VNRS score in the test group was significantly lower than controls (p=0.0001). At 24h, there was no significant difference in scores between groups (p=0.83). At 24h, the test group required less pethidine than controls (p=0.0001) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). No patients presented postoperative nausea or vomiting.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Serum beta-endorphin level was 100.32±35.07ng/L in the test group and 85.62±7.19ng/L in controls 15min before induction. No significant difference was observed between groups (p=0.23) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Our results show that at the end of the surgery, serum beta-endorphin levels (test group [83.71±24.46ng/L] and control group [92.30±56.02ng/L]) did not differ significantly between groups (p=0.73) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). In the test group, end-of-surgery serum beta-endorphin levels were significantly lower than pre-induction levels (p=0.04) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). In controls, no significant difference was observed between pre-induction and end-of-surgery serum beta-endorphin levels (p=0.77) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). In addition, in the test group, serum magnesium levels before infusion of magnesium sulphate and 10min after surgery were 2.19±0.54mEq/L and 3.08±0.77mEq/L, respectively (p=0.001); therefore, no hypermagnesaemia was observed.DiscussionWe found that infusion of low-dose magnesium sulphate leads to improved postoperative pain scores at 6, and 12h after surgery and reduces the need for opioid analgesics in the first 24 postoperative hours.Kahraman and Eroglu (2014)<a class="elsevierStyleCrossRef" href="#bib0275">23</a> showed that pain scores were considerably lower at 2 and 4h after hysterectomy in patients receiving IV infusion of magnesium sulphate, which differs slightly from our findings. It has been suggested that differences in anaesthesia technique<a class="elsevierStyleCrossRef" href="#bib0210">10</a> and magnesium dose could affect postoperative pain perception. In our study, lower doses of magnesium (15 vs 65mg/kg) were used, and postoperative pain scores were lower even at 12h after TAH. This could be due to differences in the anaesthesia technique (balanced general anaesthesia vs spinal anaesthesia).Our results contrast with the findings of Wilder-Smith et al.,<a class="elsevierStyleCrossRef" href="#bib0260">20</a> who found perioperative magnesium infusion to have no significant effect on postoperative analgesia and cumulative morphine consumption. The foregoing study, however, had a small sample size (total 24 patients undergoing hysterectomy), and received magnesium levulinate infusion at different dosages (initial bolus 8mmol followed by 8mmol/h, starting at induction).A meta-analysis of 20 randomized controlled trials with 1257 subjects<a class="elsevierStyleCrossRef" href="#bib0280">24</a> assessed the effect of perioperative systemic magnesium on postoperative pain. It was concluded that systemic perioperative magnesium might be useful for postoperative pain and opioid use. Although all the studies included in this meta-analysis were limited to subjects aged over 18 years receiving general anaesthesia, some limitations were observed, such as differences in the duration of magnesium infusion (only intraoperative compared with intraoperative and postoperative), different surgeries and small sample sizes (5 studies with less than 20 patients in each group).Lysakowski et al.<a class="elsevierStyleCrossRef" href="#bib0205">9</a> in a systematic review of 14 randomized trials with 778 subjects (2007), evaluated the role of magnesium on postoperative analgesia. They found that conclusions varied among the studies analyzed, but none provided convincing evidence that perioperative magnesium may have favourable effects on postoperative pain intensity and analgesic requirements. However; it should be noted that most of the studies included in this review were small and differed in terms of magnesium infusion strategy, age group, and surgical and anaesthetic technique.In our study, total serum levels of magnesium rather than ionized magnesium (Mg2+) were determined due to instrumental limitations. Overall, our results show that preventive low-dose infusion of magnesium sulphate during TAH under balanced general anaesthesia carries a lower risk of adverse effects, and might be beneficial for postoperative pain and opioid consumption. Given the antinociceptive potential, excellent safety profile and low cost of magnesium, more research to explore its adjuvant effect on postoperative analgesia would be justified.Our study shows that preventive low-dose magnesium sulphate infusion could have an opioid sparing-effect on postoperative pain and significantly reduce serum beta-endorphin levels during TAH.Our results contrast with the findings of Liu et al.,<a class="elsevierStyleCrossRef" href="#bib0285">25</a> in which preoperative analgesia with IV flurbiprofen in patients undergoing eosophagectomy (n=15 in each group) had no significant effect on plasma beta-endorphin levels at the end of the surgery compared with pre-induction levels. The authors concluded that general anaesthesia combined with perioperative flurbiprofen infusion to reduce nociceptive stress did not affect baseline beta-endorphin levels. In our study, however, preventive analgesia with low-dose infusion of magnesium sulphate led to a decrease in serum beta-endorphin levels at the end of the surgery.Wu et al.<a class="elsevierStyleCrossRef" href="#bib0290">26</a> examined the effect of ketamine combined with morphine and morphine alone (15 women in each group) on plasma beta-endorphin levels in patients scheduled for radical surgery under general anaesthesia. In contrast to our study, plasma beta-endorphin levels increased significantly in both groups at the end of the intervention compared with pre-induction levels.Caba et al.,<a class="elsevierStyleCrossRef" href="#bib0295">27</a> comparing general anaesthesia vs general anaesthesia plus epidural block, determined plasma levels of beta-endorphin and ACTH during cholecystectomy. Despite the small sample size, they showed that general anaesthesia was more potent in reducing beta-endorphin and ACTH levels compared with anaesthesia plus epidural block. In our study, we found that intraoperative magnesium sulphate administration during TAH under general anaesthesia mitigated end-of-surgery serum beta-endorphin levels.Mirilas et al.<a class="elsevierStyleCrossRef" href="#bib0300">28</a> studied the role of fentanyl anaesthesia on serum levels of beta-endorphin before surgery and at 2h after surgery and found no significant change in beta-endorphins 2h after surgery. In our study, however, mean patient age was higher, and beta-endorphin levels were evaluated at the end of surgery.Aho et al.<a class="elsevierStyleCrossRef" href="#bib0305">29</a> found that women receiving intramuscular clonidine (as pre-anaesthetic) showed significantly less increase in plasma beta-endorphin levels during laparoscopy. They concluded that the blunting effect of clonidine on plasma levels of beta-endorphin might reflect a deeper level of anaesthesia or could be due to the interaction of clonidine with endogenous opiates. It should be noted that the sample size (ten women in each group) of this study was particularly low.It appears that low-dose intraoperative magnesium sulphate infusion, by attenuating central sensitization<a class="elsevierStyleCrossRefs" href="#bib0180">4,5</a> due to its mild analgesic effect, could reduce the acute beta-endorphin response to surgical noxious stimuli.<a class="elsevierStyleCrossRef" href="#bib0310">30</a>In our study, we found no significant differences in end-of-surgery serum beta-endorphin levels between test and control groups. The reasons for this are not entirely clear, but the following hypotheses have been put forward (1) inter-individual differences in ovarian hormone levels, or the timing of the surgery in respect of the menstrual cycle, since pain sensation might be influenced by the luteal or follicular phase of menstruation,<a class="elsevierStyleCrossRef" href="#bib0315">31</a> (2) genetics, (3) the timing of beta-endorphin quantification (diurnal variation of beta-endorphin),<a class="elsevierStyleCrossRef" href="#bib0320">32</a> (4) small sample size.ConclusionIn summary, low-dose intra-operative magnesium sulphate infusion reduces postoperative pain, opioid consumption, and serum beta-endorphin levels during TAH. However, in view of the conflicting results in the literature and the limitations of our study, further studies in larger series or with longer postoperative follow-up are needed to determine beta-endorphin levels and confirm our findings.Ethical disclosureProtection of people and animalsThe authors declare that the procedures followed conformed to the ethical standards of the responsible human experimentation committee and in agreement with the World Medical Association and the Helsinki Declaration.Confidentiality of the dataThe authors state that they have followed the protocols of their work center on the publication of patient data.Right to privacy and informed consentThe authors have obtained the informed consent of the patients and/or subjects referred to in the article. This document is in the possession of the author of correspondenceAuthors’ contributionsAuthors A and C designed the study, drafted the protocol, interpreted the data and authored the first draft of the manuscript. Authors B, D, and E collected the data. Author C performed the critical revision of the manuscript and conducted the literature searches. Authors B and C performed the analyses and provided administrative, technical and material support. All authors read and approved the final manuscript.Conflicts of interestAll authors state that there is no conflict of interest in the present study." "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres867814" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec856881" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres867813" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec856882" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Patients and methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study design and setting" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Randomization and interventions" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Data collection and outcomes" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0045" "titulo" => "Conclusion" ] 9 => array:3 [ "identificador" => "sec0055" "titulo" => "Ethical disclosure" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0060" "titulo" => "Protection of people and animals" ] 1 => array:2 [ "identificador" => "sec0065" "titulo" => "Confidentiality of the data" ] 2 => array:2 [ "identificador" => "sec0070" "titulo" => "Right to privacy and informed consent" ] ] ] 10 => array:2 [ "identificador" => "sec0050" "titulo" => "Authors’ contributions" ] 11 => array:2 [ "identificador" => "sec0075" "titulo" => "Conflicts of interest" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-08-02" "fechaAceptado" => "2016-11-09" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec856881" "palabras" => array:4 [ 0 => "Magnesium sulphate" 1 => "Serum beta-endorphin" 2 => "Total abdominal hysterectomy" 3 => "Postoperative pain management" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec856882" "palabras" => array:4 [ 0 => "Sulfato de magnesio" 1 => "Beta-endorfinas séricas" 2 => "Histerectomía abdominal total" 3 => "Tratamiento del dolor postoperatorio" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveDue to the known role of preventive low dose magnesium sulphate on postoperative pain management, in this randomized, double-blinded, placebo-controlled study, we tried to investigate the possible relationship between low dose intra-operative magnesium sulphate infusion, postoperative analgesia and the level of serum beta-endorphin during total abdominal hysterectomy under general anaesthesia. MethodsForty women undergoing total abdominal hysterectomy were randomly allocated into 2 groups (20 in each arm). Fifteen minutes before induction of anaesthesia, the case group received a continuous intravenous infusion of magnesium sulphate (15mg/kg/h) and placebo control group received the same volume of isotonic saline. Pain scores were assessed at 0, 6, 12, and 24h after operations using Verbal Numeric Rating Scale. Pethidine consumption was recorded precisely. Serum level of beta-endorphin just 15min before the induction and at the end of the operations was determined by ELISA technique. ResultsAt 6 and 12h after the operations, Verbal Numeric Rating Scale in the case group was significantly lower than that of placebo control group (p=0.0001). Over 24h after the operations, pethidine consumption was significantly lower in the case group compared with control group (p=0.0001). In the case group, serum level of beta-endorphin was significantly decreased at the end of the operations compared with before the induction (p=0.04). ConclusionWe illustrated that preventive low dose intra-operative magnesium sulphate infusion reduces postoperative pain, has opioid sparing effect and declines serum beta-endorphin concentration during total abdominal hysterectomy." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoDebido al conocido papel preventivo que juegan las bajas dosis de sulfato de magnesio en el tratamiento del dolor postoperatorio, en este estudio aleatorizado a doble ciego y controlado con placebo tratamos de investigar la posible relación entre la infusión intraoperatoria de sulfato de magnesio, la analgesia postoperatoria y el nivel de beta-endorfinas séricas en las histerectomías abdominales totales realizadas bajo anestesia general. MétodosSe distribuyó aleatoriamente a 40 mujeres sometidas a histerectomía abdominal total en 2 grupos (20 en cada uno de ellos). Quince minutos antes de la inducción de anestesia, al grupo de estudio se le administró una infusión intravenosa de sulfato de magnesio (15mg/kg/h), y al grupo control con placebo se le administró el mismo volumen de solución salina isotónica. Las puntuaciones del dolor se evaluaron a las 0, 6, 12 y 24h posteriores a la intervención, utilizando la escala de calificación numérica verbal. Se registró de manera precisa el consumo de petidina. Se determinó el nivel sérico de beta-endorfinas 15min antes de la inducción y al finalizar las intervenciones, utilizando el método ELISA. ResultadosA las 6 y 12h posteriores a las intervenciones, el valor de la escala de calificación numérica verbal en el grupo de estudio fue considerablemente menor que en el grupo control con placebo (p=0,0001). A las 24h de la intervención, el consumo de petidina fue significativamente inferior en el grupo de estudio en comparación con el grupo control (p=0,0001). En el grupo de estudio, el nivel sérico de beta-endorfinas descendió considerablemente al final de las intervenciones, en comparación con el momento anterior a la inducción (p=0,04). ConclusiónDemostramos que la baja dosis preventiva e intraoperatoria de sulfato de magnesio reduce el dolor postoperatorio, tiene un efecto opioide moderado y disminuye la concentración sérica de beta-endorfinas en las histerectomías abdominales totales." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Haryalchi K, Abedinzade M, Khanaki K, Mansour Ghanaie M, Mohammad Zadeh F. Por qué la infusión preventiva de una dosis baja de sulfato de magnesio influye en la percepción del dolor postoperatorio y el nivel sérico de beta-endorfinas en las histerectomías abdominales totales. Rev Esp Anestesiol Reanim. 2017;64:384–390." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1669 "Ancho" => 1617 "Tamanyo" => 127194 ] ] "descripcion" => array:1 [ "en" => "Study flow chart." ] ] 1 => 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:3 [ "leyenda" => "DBP: diastolic blood pressure; SBP: systolic blood pressure.Values are presented as mean±SD." "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable \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">Test group (n=20) \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">Controls (n=20) \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<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \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">Age (yr) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48.30±5.66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50.70±2.20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.089 \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">Weight (kg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">72.65±8.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">76.85±9.87 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.149 \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">Duration of surgery (h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.52±0.12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.58±0.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.126 \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">Preoperative SBP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">126.50±18.43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">118.25±7.83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.07 \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">Preoperative DBP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">74.95±10.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">76.20±6.07 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.64 \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">Postoperative SBP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">126.75±10.04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">130.25±10.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.28 \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">Postoperative DBP \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><td class="td" title="table-entry " align="char" valign="top">74.25±4.38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">74.00±5.03 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1459509.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Comparison between groups." ] ] ] "descripcion" => array:1 [ "en" => "Baseline characteristics and arterial pressure of patients in the test and control groups." ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "Values are presented as mean±SD." "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables (h) \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">Test group (n=20) \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">Controls (n=20) \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<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \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">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.70±1.34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.20±0.41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.0001 \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">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.30±0.73 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.80±0.62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.0001 \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">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.30±0.98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.75±1.12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.0001 \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">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.95±0.94 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.90±0.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.83 \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">Pethidine consumption (mg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.00±18.92 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">68.00±17.42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1459510.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "Comparison between groups." ] ] ] "descripcion" => array:1 [ "en" => "Comparison of pain severity based on verbal numeric rating scale scores at different time points and 24-hour postoperative pethidine use between test and control groups." ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "Values are given as mean±SD." "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Beta-endorphin level (ng/L) \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">Test group (n=20) \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">Controls (n=20) \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<a class="elsevierStyleCrossRef" href="#tblfn0015">a</a> \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">Pre-induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100.32±35.07 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">85.62±7.19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.23 \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">End of surgery \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">83.71±24.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">92.30±56.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.73 \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">p<a class="elsevierStyleCrossRef" href="#tblfn0020">b</a> \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><td class="td" title="table-entry " align="char" valign="top">0.77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1459511.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "a" "nota" => "Comparison between groups." ] 1 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "b" "nota" => "Comparison between pre-induction and end-of-surgery levels in each group." ] ] ] "descripcion" => array:1 [ "en" => "Comparison of pre-induction and end-of-surgery serum levels of beta-endorphin between study groups." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:32 [ 0 => array:3 [ "identificador" => "bib0165" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Understanding endorphins and their importance in pain management" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A.S. Sprouse-Blum" 1 => "G. Smith" 2 => "D. Sugai" 3 => "F.D. Parsa" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Hawaii Med J" "fecha" => "2010" "volumen" => "69" "paginaInicial" => "70" "paginaFinal" => "71" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20397507" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0170" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of low-dose (single-dose) magnesium sulfate on postoperative analgesia in hysterectomy patients receiving balanced general anesthesia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Taheri" 1 => "K. Haryalchi" 2 => "M. Mansour Ghanaie" 3 => "N. 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Granry" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/BF03018719" "Revista" => array:6 [ "tituloSerie" => "Can J Anaesth" "fecha" => "2003" "volumen" => "50" "paginaInicial" => "732" "paginaFinal" => "746" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12944451" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0185" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of magnesium sulphate on intraoperative anaesthetic requirements and postoperative analgesia in gynaecology patients receiving total intravenous anaesthesia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.H. Ryu" 1 => "M.H. Kang" 2 => "K.S. Park" 3 => "S.H. Do" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/bja/aem407" "Revista" => array:6 [ "tituloSerie" => "Br J Anaesth" "fecha" => "2008" "volumen" => "100" "paginaInicial" => "397" "paginaFinal" => "403" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18276652" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0190" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of continuous magnesium sulfate infusion on spinal block characteristics: a prospective study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. Agrawal" 1 => "S. Agrawal" 2 => "A.S. 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Whether preventive low dose magnesium sulphate infusion has an influence on postoperative pain perception and the level of serum beta-endorphin throughout the total abdominal hysterectomy

Por qué la infusión preventiva de una dosis baja de sulfato de magnesio influye en la percepción del dolor postoperatorio y el nivel sérico de beta-endorfinas en las histerectomías abdominales totales

K. Haryalchia, M. Abedinzadeb, K. Khanakic,

Corresponding author

khanaki@gums.ac.ir
khanaki_korosh_bio@yahoo.com

Corresponding author.

, M. Mansour Ghanaied, F. Mohammad Zadehe

a Department of Anesthesiology, Reproductive Health Research Center, Guilan University of Medical Sciences, Rasht, Iran

b Department of Physiology, Medical Biotechnology Research Center, Faculty of Paramedical Sciences, Guilan University of Medical Science, Rasht, Iran

c Department of Clinical Biochemistry, Medical Biotechnology Research Center, Faculty of Paramedical Sciences, Guilan University of Medical Sciences, Rasht, Iran

d Department of Gynaecology, Reproductive Health Research Center, Guilan University of Medical Sciences, Rasht, Iran

e Bachelor of Science, Department of Anesthesiology, Reproductive Health Research Center, Faculty of Paramedical Sciences, Guilan University of Medical Sciences, Rasht, Iran

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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">Pain is one of the most common fears of patients scheduled for all types of surgeries&#44; and can influence postoperative recovery and patient satisfaction&#46; For many years&#44; opioids have been used to alleviate intra- and postoperative pain<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">1</span></a>&#59; however&#44; because of their side effects&#44; much research has been done to find less harmful pain relief alternatives&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">2</span></a> Pain perception is multi-factorial&#44; and can be modified by environmental factors&#44; individuality&#44; socioeconomic status&#44; prior pain perception&#44; etc&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">3</span></a> and these factors seem to complicate postoperative pain management&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In the recent years&#44; attention has focused on adjuvant analgesics for postoperative pain management&#44; one of these being magnesium&#44; which is known to be an analgesic due to its calcium channel blocking action and N-methyl-<span class="elsevierStyleSmallCaps">d</span>-aspartate &#40;NMDA&#41; receptor antagonism &#40;possibly by preventing nociceptive central sensitization&#41;&#46; Furthermore&#44; the role of magnesium in decreasing catecholamine release has been shown to improve management of adrenergic response during surgery&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">4&#44;5</span></a> As an intravenous &#40;IV&#41; adjuvant&#44; magnesium sulphate can be used in multiple ways&#44; including preventive low-dose infusion&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">3&#44;6</span></a> Nevertheless&#44; the beneficial effect of IV magnesium sulphate on postoperative pain management is still controversial&#44;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">5&#44;7&#8211;9</span></a> and outcomes can be affected by the anaesthesia technique use or magnesium dosage administered&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">10</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Endogenous opioids&#44; which are generated in response to noxious stimulation&#44; are closely related to pain&#46; Beta-endorphins are potent endogenous opioid peptides that are synthesized primarily by the anterior pituitary gland and the hypothalamus&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">11</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Beta-endorphins&#44; as a hormonal stress response&#44; help control pain by binding to opioid receptors&#44; and have maximum affinity for the &#956;1-opioid receptor at the presynaptic nerve terminal&#46; Beta-endorphins inhibit GABA release&#44; leading to increased dopamine release&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">12&#8211;14</span></a> Opioid medications function by mimicking natural endorphins&#44; competing for receptor binding&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">1</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Major surgical procedures have been shown to increase secretion of stress hormones&#44; such as beta-endorphins&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">15&#8211;17</span></a> Some studies have shown a correlation between serum beta-endorphin levels and postoperative pain&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">18&#44;19</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">We investigated the effect of single-dose magnesium sulphate on postoperative pain control in total abdominal hysterectomy &#40;TAH&#41; under balanced general anaesthesia&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">2</span></a> Low-dose intraoperative magnesium sulphate infusion appears to have lower toxicity and a better safety margin&#44; and it was this characteristic&#44; together with certain controversies surrounding this approach&#44;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">8&#44;9&#44;20</span></a> that prompted us to investigate the possible relationship between low-dose magnesium sulphate and postoperative pain management by measuring serum beta-endorphin levels in patients receiving this analgesia during TAH&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The main aim of this study was to evaluate the effect of low dose intra-operative magnesium sulphate infusion on postoperative pain management and stress hormones&#44; such as beta-endorphins&#44; in patients undergoing TAH&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study design and setting</span><p id="par0040" class="elsevierStylePara elsevierViewall">The study was approved by the ethics committee of Guilan University of Medical Sciences &#40;IRCT number 2014012316325N1&#41; and designed as a parallel double-blinded&#44; placebo-controlled study using equal randomization &#40;1&#58;1&#41;&#46; It was conducted at the obstetrics and gynaecology ward of Al-Zahra maternity hospital &#40;Rasht&#44; Iran&#41; during 2013&#8211;2014&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Forty patients undergoing elective TAH with physical status I and II were included in the study after giving their informed consent&#46; The physical status of the patients was diagnosed according to American Society of Anaesthesiologists &#40;ASA&#41; criteria&#46; None of the patients had undergone prior abdominal surgeries and none presented major organ dysfunction&#44; such as renal dysfunction&#44; neuropathy or myopathy&#44; hypersensitivity or allergy to magnesium&#44; other drugs or food products&#46; None reported opioid addiction or calcium channel blockers consumption&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">In order to ensure that prolonged manipulation did not influence postoperative pain scores&#44; patients undergoing surgery lasting more than 2<span class="elsevierStyleHsp" style=""></span>h or needing additional surgery &#40;anterior-posterior repair&#44; hernia repair&#41; were excluded&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Randomization and interventions</span><p id="par0055" class="elsevierStylePara elsevierViewall">Patients were randomized to 2 groups&#59; the test group&#44; receiving magnesium &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&#41; and controls&#44; receiving placebo &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">21&#44;22</span></a> The randomized list was prepared using the block randomization method&#46; Patients were allocated to groups according to their surgical schedule&#44; and were informed by ward nurses who were given an envelope at admission time&#46; The test group received continuous intraoperative IV infusion of 15<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;h magnesium sulphate dissolved in 100<span class="elsevierStyleHsp" style=""></span>ml of isotonic saline &#40;as a preventive low dose&#41;&#59; controls received the same volume of isotonic saline without magnesium&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Standard balanced general anaesthesia was performed as described above&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">2</span></a> Anaesthesia was performed in all cases using IV injection of sodium thiopental &#40;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41;&#44; fentanyl &#40;1<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg&#41; and succinylcholine &#40;1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41;&#46; After intubation&#44; anaesthesia was maintained using balanced N<span class="elsevierStyleInf">2</span>O&#47;O<span class="elsevierStyleInf">2</span> &#40;50&#37;&#47;50&#37;&#41;&#44; isoflurane &#40;0&#46;5&#37;&#41;&#44; atracurium &#40;0&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41;&#44; and fentanyl &#40;1<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg&#41;&#46; Incremental doses of fentanyl &#40;1<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg&#41; were used if the patients showed any sign of sweating&#44; lacrimation&#44; or 20&#37; increase in heart rate or blood pressure&#46; Electrocardiography&#44; heart rate&#44; pulse oximetry&#44; noninvasive blood pressure and level of neuromuscular junction block monitoring was performed&#46; At the end of the surgery&#44; neostigmine &#40;0&#46;05<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41; and atropine &#40;0&#46;02<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41; were administered to reverse neuromuscular blockade&#46; Heart rate and noninvasive blood pressure were measured over the first 24 postoperative hours&#46; Patients&#44; surgeons&#44; the outcome evaluator&#44; and nursing staff were blinded to group assignment&#46; The operating room nurses handed the envelopes to the anaesthetist&#46; All procedures were performed by the same gynaecological surgeon and the same anaesthetist&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Data collection and outcomes</span><p id="par0065" class="elsevierStylePara elsevierViewall">The primary outcome measure was pain score reported at 0&#44; 6&#44; 12&#44; and 24<span class="elsevierStyleHsp" style=""></span>h after surgery&#46; The secondary outcome was serum levels of beta-endorphins measured 15<span class="elsevierStyleHsp" style=""></span>min before induction and at the end of surgery&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Pain scores were evaluated using the verbal numeric rating scale &#40;VNRS&#41; &#40;0<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>no pain&#59; 10<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>worst pain&#41;&#46; Before surgery&#44; all subjects were instructed on how to use VNRS&#46; Age&#44; weight&#44; and duration of surgery were noted&#46; Pethidine consumption and side effects such as nausea&#44; vomiting&#44; hypotension or hypermagnesaemia in the first 24 postoperative hours were documented&#46; Patients reporting a VNRS of more than 4 received pethidine 20<span class="elsevierStyleHsp" style=""></span>mg&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">To evaluate the beta-endorphin level&#44; venous blood samples were taken using anticoagulant-free tubes and centrifuged at 800<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">g</span> for 5<span class="elsevierStyleHsp" style=""></span>min&#46; The resulting sera were kept at &#8722;20<span class="elsevierStyleHsp" style=""></span>&#176;C until measurement&#46; Analysis of serum beta-endorphins was performed using an enzyme-linked immunosorbent assay &#40;ELISA&#41; kit &#40;Hangzhou Eastbiopharm Co&#46;&#44; China&#41; and ELISA reader &#40;Stat Fax&#44; USA&#41;&#46; The detection limit for beta-endorphin was 2&#46;59<span class="elsevierStyleHsp" style=""></span>ng&#47;L&#46; Serum levels of magnesium were measured before and 10<span class="elsevierStyleHsp" style=""></span>min after surgery by colorimetry&#44; using the Pars Azmoon kit &#40;Tehran&#44; Iran&#41;&#46; The analysis was performed by a laboratory technician who was not involved in the study in any way&#46; Hypermagnesaemia was defined as serum magnesium levels of more than 5mEq&#47;L &#40;when signs appeared&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0080" class="elsevierStylePara elsevierViewall">Values are presented as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#46; The Student&#39;s <span class="elsevierStyleItalic">t</span>-test was used to compare means between groups&#46; Preoperative and end-of-surgery levels of beta-endorphin and magnesium in each group were compared using the paired-samples <span class="elsevierStyleItalic">t</span>-test&#46; Significance was set at <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46; Statistical analysis was performed on SPSS v&#46; 21 software&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0085" class="elsevierStylePara elsevierViewall">Forty women completed the study &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The groups were well matched for age&#44; weight and duration of surgery &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; No significant differences were observed in systolic and diastolic blood pressure between the groups in the preoperative and postoperative period &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; No cases of postoperative hypotension were observed&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">At the end of surgery&#44; VNRS scores in the control group were significantly lower than those in the test group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#59; however&#44; at 6 and 12<span class="elsevierStyleHsp" style=""></span>h&#44; VNRS score in the test group was significantly lower than controls &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#46; At 24<span class="elsevierStyleHsp" style=""></span>h&#44; there was no significant difference in scores between groups &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;83&#41;&#46; At 24<span class="elsevierStyleHsp" style=""></span>h&#44; the test group required less pethidine than controls &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; No patients presented postoperative nausea or vomiting&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">Serum beta-endorphin level was 100&#46;32<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>35&#46;07<span class="elsevierStyleHsp" style=""></span>ng&#47;L in the test group and 85&#46;62<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;19<span class="elsevierStyleHsp" style=""></span>ng&#47;L in controls 15<span class="elsevierStyleHsp" style=""></span>min before induction&#46; No significant difference was observed between groups &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;23&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">Our results show that at the end of the surgery&#44; serum beta-endorphin levels &#40;test group &#91;83&#46;71<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>24&#46;46<span class="elsevierStyleHsp" style=""></span>ng&#47;L&#93; and control group &#91;92&#46;30<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>56&#46;02<span class="elsevierStyleHsp" style=""></span>ng&#47;L&#93;&#41; did not differ significantly between groups &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;73&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; In the test group&#44; end-of-surgery serum beta-endorphin levels were significantly lower than pre-induction levels &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; In controls&#44; no significant difference was observed between pre-induction and end-of-surgery serum beta-endorphin levels &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;77&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; In addition&#44; in the test group&#44; serum magnesium levels before infusion of magnesium sulphate and 10<span class="elsevierStyleHsp" style=""></span>min after surgery were 2&#46;19<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;54<span class="elsevierStyleHsp" style=""></span>mEq&#47;L and 3&#46;08<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;77<span class="elsevierStyleHsp" style=""></span>mEq&#47;L&#44; respectively &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#59; therefore&#44; no hypermagnesaemia was observed&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0105" class="elsevierStylePara elsevierViewall">We found that infusion of low-dose magnesium sulphate leads to improved postoperative pain scores at 6&#44; and 12<span class="elsevierStyleHsp" style=""></span>h after surgery and reduces the need for opioid analgesics in the first 24 postoperative hours&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Kahraman and Eroglu &#40;2014&#41;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">23</span></a> showed that pain scores were considerably lower at 2 and 4<span class="elsevierStyleHsp" style=""></span>h after hysterectomy in patients receiving IV infusion of magnesium sulphate&#44; which differs slightly from our findings&#46; It has been suggested that differences in anaesthesia technique<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">10</span></a> and magnesium dose could affect postoperative pain perception&#46; In our study&#44; lower doses of magnesium &#40;15 vs 65<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#41; were used&#44; and postoperative pain scores were lower even at 12<span class="elsevierStyleHsp" style=""></span>h after TAH&#46; This could be due to differences in the anaesthesia technique &#40;balanced general anaesthesia vs spinal anaesthesia&#41;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Our results contrast with the findings of Wilder-Smith et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">20</span></a> who found perioperative magnesium infusion to have no significant effect on postoperative analgesia and cumulative morphine consumption&#46; The foregoing study&#44; however&#44; had a small sample size &#40;total 24 patients undergoing hysterectomy&#41;&#44; and received magnesium levulinate infusion at different dosages &#40;initial bolus 8<span class="elsevierStyleHsp" style=""></span>mmol followed by 8<span class="elsevierStyleHsp" style=""></span>mmol&#47;h&#44; starting at induction&#41;&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">A meta-analysis of 20 randomized controlled trials with 1257 subjects<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">24</span></a> assessed the effect of perioperative systemic magnesium on postoperative pain&#46; It was concluded that systemic perioperative magnesium might be useful for postoperative pain and opioid use&#46; Although all the studies included in this meta-analysis were limited to subjects aged over 18 years receiving general anaesthesia&#44; some limitations were observed&#44; such as differences in the duration of magnesium infusion &#40;only intraoperative compared with intraoperative and postoperative&#41;&#44; different surgeries and small sample sizes &#40;5 studies with less than 20 patients in each group&#41;&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Lysakowski et al&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">9</span></a> in a systematic review of 14 randomized trials with 778 subjects &#40;2007&#41;&#44; evaluated the role of magnesium on postoperative analgesia&#46; They found that conclusions varied among the studies analyzed&#44; but none provided convincing evidence that perioperative magnesium may have favourable effects on postoperative pain intensity and analgesic requirements&#46; However&#59; it should be noted that most of the studies included in this review were small and differed in terms of magnesium infusion strategy&#44; age group&#44; and surgical and anaesthetic technique&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">In our study&#44; total serum levels of magnesium rather than ionized magnesium &#40;Mg<span class="elsevierStyleSup">2&#43;</span>&#41; were determined due to instrumental limitations&#46; Overall&#44; our results show that preventive low-dose infusion of magnesium sulphate during TAH under balanced general anaesthesia carries a lower risk of adverse effects&#44; and might be beneficial for postoperative pain and opioid consumption&#46; Given the antinociceptive potential&#44; excellent safety profile and low cost of magnesium&#44; more research to explore its adjuvant effect on postoperative analgesia would be justified&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Our study shows that preventive low-dose magnesium sulphate infusion could have an opioid sparing-effect on postoperative pain and significantly reduce serum beta-endorphin levels during TAH&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Our results contrast with the findings of Liu et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">25</span></a> in which preoperative analgesia with IV flurbiprofen in patients undergoing eosophagectomy &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>15 in each group&#41; had no significant effect on plasma beta-endorphin levels at the end of the surgery compared with pre-induction levels&#46; The authors concluded that general anaesthesia combined with perioperative flurbiprofen infusion to reduce nociceptive stress did not affect baseline beta-endorphin levels&#46; In our study&#44; however&#44; preventive analgesia with low-dose infusion of magnesium sulphate led to a decrease in serum beta-endorphin levels at the end of the surgery&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Wu et al&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">26</span></a> examined the effect of ketamine combined with morphine and morphine alone &#40;15 women in each group&#41; on plasma beta-endorphin levels in patients scheduled for radical surgery under general anaesthesia&#46; In contrast to our study&#44; plasma beta-endorphin levels increased significantly in both groups at the end of the intervention compared with pre-induction levels&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Caba et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">27</span></a> comparing general anaesthesia vs general anaesthesia plus epidural block&#44; determined plasma levels of beta-endorphin and ACTH during cholecystectomy&#46; Despite the small sample size&#44; they showed that general anaesthesia was more potent in reducing beta-endorphin and ACTH levels compared with anaesthesia plus epidural block&#46; In our study&#44; we found that intraoperative magnesium sulphate administration during TAH under general anaesthesia mitigated end-of-surgery serum beta-endorphin levels&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Mirilas et al&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">28</span></a> studied the role of fentanyl anaesthesia on serum levels of beta-endorphin before surgery and at 2<span class="elsevierStyleHsp" style=""></span>h after surgery and found no significant change in beta-endorphins 2<span class="elsevierStyleHsp" style=""></span>h after surgery&#46; In our study&#44; however&#44; mean patient age was higher&#44; and beta-endorphin levels were evaluated at the end of surgery&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Aho et al&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">29</span></a> found that women receiving intramuscular clonidine &#40;as pre-anaesthetic&#41; showed significantly less increase in plasma beta-endorphin levels during laparoscopy&#46; They concluded that the blunting effect of clonidine on plasma levels of beta-endorphin might reflect a deeper level of anaesthesia or could be due to the interaction of clonidine with endogenous opiates&#46; It should be noted that the sample size &#40;ten women in each group&#41; of this study was particularly low&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">It appears that low-dose intraoperative magnesium sulphate infusion&#44; by attenuating central sensitization<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">4&#44;5</span></a> due to its mild analgesic effect&#44; could reduce the acute beta-endorphin response to surgical noxious stimuli&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">30</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">In our study&#44; we found no significant differences in end-of-surgery serum beta-endorphin levels between test and control groups&#46; The reasons for this are not entirely clear&#44; but the following hypotheses have been put forward &#40;1&#41; inter-individual differences in ovarian hormone levels&#44; or the timing of the surgery in respect of the menstrual cycle&#44; since pain sensation might be influenced by the luteal or follicular phase of menstruation&#44;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">31</span></a> &#40;2&#41; genetics&#44; &#40;3&#41; the timing of beta-endorphin quantification &#40;diurnal variation of beta-endorphin&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">32</span></a> &#40;4&#41; small sample size&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conclusion</span><p id="par0175" class="elsevierStylePara elsevierViewall">In summary&#44; low-dose intra-operative magnesium sulphate infusion reduces postoperative pain&#44; opioid consumption&#44; and serum beta-endorphin levels during TAH&#46; However&#44; in view of the conflicting results in the literature and the limitations of our study&#44; further studies in larger series or with longer postoperative follow-up are needed to determine beta-endorphin levels and confirm our findings&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Ethical disclosure</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Protection of people and animals</span><p id="par0185" class="elsevierStylePara elsevierViewall">The authors declare that the procedures followed conformed to the ethical standards of the responsible human experimentation committee and in agreement with the World Medical Association and the Helsinki Declaration&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Confidentiality of the data</span><p id="par0190" class="elsevierStylePara elsevierViewall">The authors state that they have followed the protocols of their work center on the publication of patient data&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Right to privacy and informed consent</span><p id="par0195" class="elsevierStylePara elsevierViewall">The authors have obtained the informed consent of the patients and&#47;or subjects referred to in the article&#46; This document is in the possession of the author of correspondence</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Authors&#8217; contributions</span><p id="par0180" class="elsevierStylePara elsevierViewall">Authors A and C designed the study&#44; drafted the protocol&#44; interpreted the data and authored the first draft of the manuscript&#46; Authors B&#44; D&#44; and E collected the data&#46; Author C performed the critical revision of the manuscript and conducted the literature searches&#46; Authors B and C performed the analyses and provided administrative&#44; technical and material support&#46; All authors read and approved the final manuscript&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflicts of interest</span><p id="par0200" class="elsevierStylePara elsevierViewall">All authors state that there is no conflict of interest in the present study&#46;</p></span></span>"
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              "titulo" => "Confidentiality of the data"
            ]
            2 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Right to privacy and informed consent"
            ]
          ]
        ]
        10 => array:2 [
          "identificador" => "sec0050"
          "titulo" => "Authors&#8217; contributions"
        ]
        11 => array:2 [
          "identificador" => "sec0075"
          "titulo" => "Conflicts of interest"
        ]
        12 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2016-08-02"
    "fechaAceptado" => "2016-11-09"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec856881"
          "palabras" => array:4 [
            0 => "Magnesium sulphate"
            1 => "Serum beta-endorphin"
            2 => "Total abdominal hysterectomy"
            3 => "Postoperative pain management"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec856882"
          "palabras" => array:4 [
            0 => "Sulfato de magnesio"
            1 => "Beta-endorfinas s&#233;ricas"
            2 => "Histerectom&#237;a abdominal total"
            3 => "Tratamiento del dolor postoperatorio"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Due to the known role of preventive low dose magnesium sulphate on postoperative pain management&#44; in this randomized&#44; double-blinded&#44; placebo-controlled study&#44; we tried to investigate the possible relationship between low dose intra-operative magnesium sulphate infusion&#44; postoperative analgesia and the level of serum beta-endorphin during total abdominal hysterectomy under general anaesthesia&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Forty women undergoing total abdominal hysterectomy were randomly allocated into 2 groups &#40;20 in each arm&#41;&#46; Fifteen minutes before induction of anaesthesia&#44; the case group received a continuous intravenous infusion of magnesium sulphate &#40;15<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;h&#41; and placebo control group received the same volume of isotonic saline&#46; Pain scores were assessed at 0&#44; 6&#44; 12&#44; and 24<span class="elsevierStyleHsp" style=""></span>h after operations using Verbal Numeric Rating Scale&#46; Pethidine consumption was recorded precisely&#46; Serum level of beta-endorphin just 15<span class="elsevierStyleHsp" style=""></span>min before the induction and at the end of the operations was determined by ELISA technique&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">At 6 and 12<span class="elsevierStyleHsp" style=""></span>h after the operations&#44; Verbal Numeric Rating Scale in the case group was significantly lower than that of placebo control group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#46; Over 24<span class="elsevierStyleHsp" style=""></span>h after the operations&#44; pethidine consumption was significantly lower in the case group compared with control group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#46; In the case group&#44; serum level of beta-endorphin was significantly decreased at the end of the operations compared with before the induction &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">We illustrated that preventive low dose intra-operative magnesium sulphate infusion reduces postoperative pain&#44; has opioid sparing effect and declines serum beta-endorphin concentration during total abdominal hysterectomy&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objective"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusion"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Debido al conocido papel preventivo que juegan las bajas dosis de sulfato de magnesio en el tratamiento del dolor postoperatorio&#44; en este estudio aleatorizado a doble ciego y controlado con placebo tratamos de investigar la posible relaci&#243;n entre la infusi&#243;n intraoperatoria de sulfato de magnesio&#44; la analgesia postoperatoria y el nivel de beta-endorfinas s&#233;ricas en las histerectom&#237;as abdominales totales realizadas bajo anestesia general&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se distribuy&#243; aleatoriamente a 40 mujeres sometidas a histerectom&#237;a abdominal total en 2 grupos &#40;20 en cada uno de ellos&#41;&#46; Quince minutos antes de la inducci&#243;n de anestesia&#44; al grupo de estudio se le administr&#243; una infusi&#243;n intravenosa de sulfato de magnesio &#40;15<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;h&#41;&#44; y al grupo control con placebo se le administr&#243; el mismo volumen de soluci&#243;n salina isot&#243;nica&#46; Las puntuaciones del dolor se evaluaron a las 0&#44; 6&#44; 12 y 24<span class="elsevierStyleHsp" style=""></span>h posteriores a la intervenci&#243;n&#44; utilizando la escala de calificaci&#243;n num&#233;rica verbal&#46; Se registr&#243; de manera precisa el consumo de petidina&#46; Se determin&#243; el nivel s&#233;rico de beta-endorfinas 15<span class="elsevierStyleHsp" style=""></span>min antes de la inducci&#243;n y al finalizar las intervenciones&#44; utilizando el m&#233;todo ELISA&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A las 6 y 12<span class="elsevierStyleHsp" style=""></span>h posteriores a las intervenciones&#44; el valor de la escala de calificaci&#243;n num&#233;rica verbal en el grupo de estudio fue considerablemente menor que en el grupo control con placebo &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0001&#41;&#46; A las 24<span class="elsevierStyleHsp" style=""></span>h de la intervenci&#243;n&#44; el consumo de petidina fue significativamente inferior en el grupo de estudio en comparaci&#243;n con el grupo control &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0001&#41;&#46; En el grupo de estudio&#44; el nivel s&#233;rico de beta-endorfinas descendi&#243; considerablemente al final de las intervenciones&#44; en comparaci&#243;n con el momento anterior a la inducci&#243;n &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;04&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Demostramos que la baja dosis preventiva e intraoperatoria de sulfato de magnesio reduce el dolor postoperatorio&#44; tiene un efecto opioide moderado y disminuye la concentraci&#243;n s&#233;rica de beta-endorfinas en las histerectom&#237;as abdominales totales&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Objetivo"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusi&#243;n"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Please cite this article as&#58; Haryalchi K&#44; Abedinzade M&#44; Khanaki K&#44; Mansour Ghanaie M&#44; Mohammad Zadeh F&#46; Por qu&#233; la infusi&#243;n preventiva de una dosis baja de sulfato de magnesio influye en la percepci&#243;n del dolor postoperatorio y el nivel s&#233;rico de beta-endorfinas en las histerectom&#237;as abdominales totales&#46; Rev Esp Anestesiol Reanim&#46; 2017&#59;64&#58;384&#8211;390&#46;</p>"
      ]
    ]
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        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
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        "mostrarDisplay" => false
        "figura" => array:1 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Study flow chart&#46;</p>"
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">DBP&#58; diastolic blood pressure&#59; SBP&#58; systolic blood pressure&#46;</p><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Values are presented as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#46;</p>"
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                  <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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable&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">Test group &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&#41;&nbsp;\t\t\t\t\t\t\n
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                  \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><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age &#40;yr&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">48&#46;30<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">50&#46;70<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;20&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;089&nbsp;\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">Weight &#40;kg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">72&#46;65<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">76&#46;85<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;87&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;149&nbsp;\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">Duration of surgery &#40;h&#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&#46;52<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;58<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;15&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;126&nbsp;\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">Preoperative SBP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">126&#46;50<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#46;43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">118&#46;25<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;83&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;07&nbsp;\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">Preoperative DBP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">74&#46;95<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">76&#46;20<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;07&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;64&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">130&#46;25<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;32&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">0&#46;87&nbsp;\t\t\t\t\t\t\n
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Comparison between groups&#46;</p>"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Baseline characteristics and arterial pressure of patients in the test and control groups&#46;</p>"
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        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Values are presented as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#46;</p>"
          "tablatextoimagen" => array:1 [
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                  <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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables &#40;h&#41;&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">Test group &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&#41;&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">Controls &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&#41;&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><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;70<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;20<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;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">6&#46;30<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;73&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#46;80<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;62&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;0001&nbsp;\t\t\t\t\t\t\n
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