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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">ETM</journal-id>
<journal-title-group>
<journal-title>Experimental and Therapeutic Medicine</journal-title>
</journal-title-group>
<issn pub-type="ppub">1792-0981</issn>
<issn pub-type="epub">1792-1015</issn>
<publisher>
<publisher-name>D.A. Spandidos</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3892/etm.2018.6355</article-id>
<article-id pub-id-type="publisher-id">ETM-0-0-6355</article-id>
<article-categories>
<subj-group>
<subject>Articles</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Effects of different doses of dexmedetomidine on analgesic efficacy and inflammatory cytokines in patients undergoing laparoscopic surgery</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author"><name><surname>Wan</surname><given-names>Zhigang</given-names></name>
<xref rid="af1-etm-0-0-6355" ref-type="aff"/></contrib>
<contrib contrib-type="author"><name><surname>Wang</surname><given-names>Jie</given-names></name>
<xref rid="af1-etm-0-0-6355" ref-type="aff"/></contrib>
<contrib contrib-type="author"><name><surname>Cao</surname><given-names>Hui</given-names></name>
<xref rid="af1-etm-0-0-6355" ref-type="aff"/></contrib>
<contrib contrib-type="author"><name><surname>Wu</surname><given-names>Lili</given-names></name>
<xref rid="af1-etm-0-0-6355" ref-type="aff"/>
<xref rid="c1-etm-0-0-6355" ref-type="corresp"/></contrib>
</contrib-group>
<aff id="af1-etm-0-0-6355">Department of Anesthesiology, The First People&#x0027;s Hospital of Wujiang District, Suzhou, Jiangsu 215200, P.R. China</aff>
<author-notes>
<corresp id="c1-etm-0-0-6355"><italic>Correspondence to</italic>: Dr Lili Wu, Department of Anesthesiology, The First People&#x0027;s Hospital of Wujiang District, 169 Gongyuan Road, Songling, Wujiang, Suzhou, Jiangsu 215200, P.R. China, E-mail: <email>lhoxr032@163.com</email></corresp>
</author-notes>
<pub-date pub-type="ppub">
<month>09</month>
<year>2018</year></pub-date>
<pub-date pub-type="epub">
<day>26</day>
<month>06</month>
<year>2018</year></pub-date>
<volume>16</volume>
<issue>3</issue>
<fpage>1743</fpage>
<lpage>1746</lpage>
<history>
<date date-type="received"><day>08</day><month>01</month><year>2018</year></date>
<date date-type="accepted"><day>21</day><month>06</month><year>2018</year></date>
</history>
<permissions>
<copyright-statement>Copyright: &#x00A9; Wan et al.</copyright-statement>
<copyright-year>2018</copyright-year>
<license license-type="open-access">
<license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by-nc-nd/4.0/">Creative Commons Attribution-NonCommercial-NoDerivs License</ext-link>, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.</license-p></license>
</permissions>
<abstract>
<p>The effects of different doses of dexmedetomidine on analgesic efficacy and inflammatory cytokines in patients with laparoscopic surgery were investigated. A total of 179 laparoscopic patients from March 2015 to May 2017 were enrolled and randomly divided into the control group (group A) and three experimental groups with different doses of dexmedetomidine (group B: 0.25; group C: 0.5 and group D: 1 &#x00B5;g/kg). Results showed that there was no significant difference between the four groups in the operation time, the amount of surgical bleeding and intraoperative fluid infusion. The VAS score of group A was significantly higher than the other three groups. In addition, the VAS score of group D at each time-point was the lowest. There was no significant difference regarding the agitation score and sedation score between group A and group B. Furthermore, the restlessness score and sedation score in group C were significantly lower than those in group A and group B. Next we found that CRP and TNF-&#x03B1; in group A and group B were significantly higher than those in groups C and D. In addition, IL-10 in group D was significantly higher than that in group C. Moreover, patients in group C had the least adverse reaction effects. In conclusion, medium dosage of dexmedetomidine cannot only effectively relieve the pain of laparoscopic patients but also regulate the secretion of inflammatory cytokines.</p>
</abstract>
<kwd-group>
<kwd>dexmedetomidine</kwd>
<kwd>laparoscopy</kwd>
<kwd>analgesia</kwd>
<kwd>inflammatory factors</kwd>
</kwd-group>
</article-meta>
</front>
<body>
<sec sec-type="intro">
<title>Introduction</title>
<p>Patients receiving hysteroscopic and laparoscopic surgery commonly experience severe pain during surgery. In addition, there is a relatively great impact on the nervous system at the same time (<xref rid="b1-etm-0-0-6355" ref-type="bibr">1</xref>,<xref rid="b2-etm-0-0-6355" ref-type="bibr">2</xref>). As an anesthetic adjuvant drug, dexmedetomidine has a good sedative effect in surgery. Also, dexmedetomidine is an adrenergic receptor agonist with good efficacy on sedation, anti-anxiety and neuroprotection (<xref rid="b3-etm-0-0-6355" ref-type="bibr">3</xref>&#x2013;<xref rid="b5-etm-0-0-6355" ref-type="bibr">5</xref>).</p>
<p>In this study, patients receiving hysteroscopic and laparoscopic surgery in our hospital were selected and given different doses of dexmedetomidine, respectively, to explore the anesthetic effects of the drug in the process of surgery and determine the optimal dose for achieving the best efficacy.</p>
</sec>
<sec sec-type="subjects|methods">
<title>Patients and methods</title>
<sec>
<title/>
<sec>
<title>Objects of study</title>
<p>A total of 179 patients who received laparoscopic surgery in The First People&#x0027;s Hospital of Wujiang District (Suzhou, China) from March 2015 to May 2017 were selected and randomly divided into the control group and three groups with different doses of dexmedetomidine. Among them, the control group (group A) included 42 patients aged 23&#x2013;43 years, with an average age of 34.4&#x00B1;7.3 years; the low-dose group (group B) included 47 patients, aged 22&#x2013;44 years, with a mean age of 35.4&#x00B1;6.8 years; the middle-dose group (group C) had 45 patients, aged 22&#x2013;45 years, with a mean age of 34.9&#x00B1;6.4 years; and the high-dose group (group D) had 45 patients, aged 23&#x2013;44 years, with a mean age of 36.9&#x00B1;6.8 years. There were no significant differences in age and pathogenetic condition of the patients among the four groups (p&#x003E;0.05), and the data were comparable. All patients were aware of the clinical protocol before the study and signed the informed consent. This study was approved by the Ethics Committee of The First People&#x0027;s Hospital of Wujiang District (Suzhou, China). Inclusion criteria were: female patients aged 20&#x2013;45 years and rated as class 1 based on the America society of Anesthesiologist (ASA) classification. Exclusion criteria were: patients with mental disease or with injury in the heart, liver, kidney and other vital organs.</p>
</sec>
<sec>
<title>Methods</title>
<p>The four groups of patients received anesthesia induction, in which, the medication dosages were 0.6 mg&#x00B7;kg<sup>&#x2212;1</sup>, 2 mg&#x00B7;kg<sup>&#x2212;1</sup> and 2 &#x00B5;g&#x00B7;kg<sup>&#x2212;1</sup> for rocuronium bromide, propofol and fentanyl, respectively, and tracheal intubation was also performed. Patients in groups B, C and D were given 0.25, 0.5 and 1 &#x00B5;g/kg dexmedetomidine, respectively, while those in group A were administered with the same dose of 0.9&#x0025; NaCl solution. Patients in each group received intravenous infusion for 10 min. After incubation, mechanical ventilation was carried out with tidal volume set at 8 ml/kg and respiratory rate at 8 breaths per minute. During surgery, doses of propofol and fentanyl were adjusted according to the patient&#x0027;s condition. When the endoscope was withdrawn, medication was stopped immediately.</p>
</sec>
<sec>
<title>Observation indicators and efficacy evaluation</title>
<p>The operation duration, intraoperative bleeding volume and intraoperative transfusion volume of each patient were recorded. Serum inflammatory cytokines [C-reactive protein (CRP), tumor necrosis factor-&#x03B1; (TNF-&#x03B1;) and interleukin-10 (IL-10)] of patients were detected. Visual analogue scale (VAS) scoring. Agitation scoring and Sedation scoring were also recorded for each patient (<xref rid="b6-etm-0-0-6355" ref-type="bibr">6</xref>&#x2013;<xref rid="b10-etm-0-0-6355" ref-type="bibr">10</xref>).</p>
</sec>
<sec>
<title>Statistical analysis</title>
<p>SPSS 19.0 software (IBM, Armonk, NY, USA) was used for statistical analysis. All quantitative data were expressed as mean &#x00B1; standard deviation (SD). Comparison between groups was done using one-way ANOVA test followed by post hoc test (Least Significant Difference). P-values &#x003C;0.05 were considered statistically significant.</p>
</sec>
</sec>
</sec>
<sec sec-type="results">
<title>Results</title>
<sec>
<title/>
<sec>
<title>Surgical situations of patients in four groups</title>
<p>The operation duration, intraoperative bleeding volume and intraoperative transfusion volume of the four groups of patients showed no differences (p&#x003E;0.05) (<xref rid="tI-etm-0-0-6355" ref-type="table">Table I</xref>).</p>
</sec>
<sec>
<title>Postoperative VAS scores of patients in four groups</title>
<p>It was found that the VAS scores at all time-points in the control group were significantly higher than those in the other three treatment groups after operation, and the scores in group D were the lowest (<xref rid="tII-etm-0-0-6355" ref-type="table">Table II</xref>).</p>
</sec>
<sec>
<title>Comparison of agitation score and sedation score in patients among four groups</title>
<p>In comparison with group A, group C had obviously decreased agitation score and sedation score (p&#x003C;0.05); there were no evident differences in agitation score and sedation score between groups A and B; sedation score in group D was clearly higher than that in group C (<xref rid="tIII-etm-0-0-6355" ref-type="table">Table III</xref>).</p>
</sec>
<sec>
<title>Comparison of serum inflammatory cytokines in patients among the four groups</title>
<p>The levels of CRP, TNF-&#x03B1; and IL-10 in groups A, B and C were significantly increased at T2, T3 and T4, while the levels of IL-10 at T2, T3 and T4 in group D were overtly higher than that at T1 (p&#x003C;0.05), while the levels of inflammatory cytokines in groups A and B had no significant differences. In addition, the levels of CRP and TNF-&#x03B1; in patients in groups A and B were clearly higher than those in groups C and D, while the increases in levels of IL-10 in groups C and D were significantly higher than those in the first two groups (p&#x003C;0.05) (<xref rid="tIV-etm-0-0-6355" ref-type="table">Table IV</xref>).</p>
</sec>
<sec>
<title>Comparison of adverse reactions in patients among four groups</title>
<p>Adverse reactions of patients in the four groups were compared, and it was found that group C had significantly fewer cases in tachycardia, bradycardia and hypertension compared with those in groups A and B. Finally, patients in group D had symptoms of bradycardia and hypotension, and sometimes hypertension and delayed recovery (<xref rid="tV-etm-0-0-6355" ref-type="table">Table V</xref>).</p>
</sec>
</sec>
</sec>
<sec sec-type="discussion">
<title>Discussion</title>
<p>With the development of medical devices, hysteroscope combined with laparoscope has been applied in a variety of gynecological diseases, such as uterine fibroids and uterus septum, and the use can improve the accuracy of diagnosis and cure rate, with an easy operation (<xref rid="b11-etm-0-0-6355" ref-type="bibr">11</xref>). However, during the operation, the patient may have pain and have adverse reaction effects on inflammation and nerves at the same time. Therefore, the application of an effective anesthetic method is especially important. The use of an appropriate dose of anesthetic in the operation can relieve the pain of the patient, and is also able to reduce the damage to the patient tissue (<xref rid="b12-etm-0-0-6355" ref-type="bibr">12</xref>,<xref rid="b13-etm-0-0-6355" ref-type="bibr">13</xref>).</p>
<p>Among anesthetics, dexmedetomidine is an adrenergic receptor agonist, which is widely used in anesthesiology. It suppresses the central and sympathetic nerves so as to reduce the tension on the sympathetic nerve and increase the activity of vagas nerve, thereby lowering the release of noradrenaline in the body and achieving the sedation effect on the patient (<xref rid="b14-etm-0-0-6355" ref-type="bibr">14</xref>,<xref rid="b15-etm-0-0-6355" ref-type="bibr">15</xref>).</p>
<p>Important factors for the assessment of inflammation are CRP, TNF-&#x03B1; and IL-10. A stress response in the body can stimulate the secretion of CRP (an acute phase protein). A trauma or an infection of the body is sure to result in a sharp increase in TNF-&#x03B1;, and hypersecretion of this factor can trigger an inflammatory response (<xref rid="b16-etm-0-0-6355" ref-type="bibr">16</xref>). However, IL-10 inhibits TNF-&#x03B1; in the body. Therefore, its increased secretion will relieve the inflammatory condition when inflammation occurs (<xref rid="b17-etm-0-0-6355" ref-type="bibr">17</xref>&#x2013;<xref rid="b20-etm-0-0-6355" ref-type="bibr">20</xref>).</p>
<p>In this study, it was found that the cellular inflammatory cytokines CRP and TNF-&#x03B1; in dexmedetomidine groups were significantly lower than those in the control group, and IL-10 in groups C and D were overtly higher than those in the other two groups, indicating that the use of dexmedetomidine is able to relieve the body&#x0027;s inflammation and protect it from invasion of pathogens. The agitation, sedation and VAS scoring carried out on patients revealed that the control group had increased agitation and VAS scores in comparison with dexmedetomidine groups, and reduced sedation score compared with those in groups C and D. Among the three dexmedetomidine groups, the situation of agitation and sedation of patients were the best in group C, so the dose of 0.5 &#x00B5;g/kg was the optimal dose. It was also found that the number of patients with adverse reactions was the minimum in group C and significantly lower than those in groups A and B, and there was a greater number of cases with symptoms of bradycardia and hypotension in group D, which also well proved that the dose of 0.5 &#x00B5;g/kg was the best choice. This study found that the patients in the three dexmedetomidine groups had few effects on T-lymphocyte subsets, which could ensure stable T-lymphocyte subsets in patients.</p>
<p>In conclusion, the use of dexmedetomidine in patients undergoing hysteroscopic surgery can relieve the patient&#x0027;s pain, decrease the release of inflammatory cytokines <italic>in vivo</italic> and protect cellular immunity. Dexmedetomidine has a high clinical therapeutic value, which is worth promoting and applying in clinical practice.</p>
</sec>
</body>
<back>
<ack>
<title>Acknowledgements</title>
<p>Not applicable.</p>
</ack>
<sec>
<title>Funding</title>
<p>No funding was received.</p>
</sec>
<sec>
<title>Availability of data and materials</title>
<p>All data generated or analyzed during this study are included in this published article.</p>
</sec>
<sec>
<title>Authors&#x0027; contributions</title>
<p>ZW and JW designed the study. HC and LW collected the patient data. ZW and JW analyzed the patient data. All authors have read and approved the final manuscript.</p>
</sec>
<sec>
<title>Ethics approval and consent to participate</title>
<p>This study was approved by the Ethics Committee of The First People&#x0027;s Hospital of Wujiang District (Suzhou, China). All patients were aware of the clinical protocol before the study and signed the informed consent.</p>
</sec>
<sec>
<title>Patient consent for publication</title>
<p>Not applicable.</p>
</sec>
<sec>
<title>Competing interests</title>
<p>The authors declare that they have no competing interests.</p>
</sec>
<ref-list>
<title>References</title>
<ref id="b1-etm-0-0-6355"><label>1</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Adams</surname><given-names>R</given-names></name><name><surname>Brown</surname><given-names>GT</given-names></name><name><surname>Davidson</surname><given-names>M</given-names></name><name><surname>Fisher</surname><given-names>E</given-names></name><name><surname>Mathisen</surname><given-names>J</given-names></name><name><surname>Thomson</surname><given-names>G</given-names></name><name><surname>Webster</surname><given-names>NR</given-names></name></person-group><article-title>Efficacy of dexmedetomidine compared with midazolam for sedation in adult intensive care patients: A systematic review</article-title><source>Br J Anaesth</source><volume>111</volume><fpage>703</fpage><lpage>710</lpage><year>2013</year><pub-id pub-id-type="doi">10.1093/bja/aet194</pub-id><pub-id pub-id-type="pmid">23748199</pub-id></element-citation></ref>
<ref id="b2-etm-0-0-6355"><label>2</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Muzii</surname><given-names>L</given-names></name><name><surname>Domenici</surname><given-names>L</given-names></name><name><surname>Lecce</surname><given-names>F</given-names></name><name><surname>Di Feliciantonio</surname><given-names>M</given-names></name><name><surname>Frantellizzi</surname><given-names>R</given-names></name><name><surname>Marchetti</surname><given-names>C</given-names></name><name><surname>Monti</surname><given-names>M</given-names></name><name><surname>Panici</surname><given-names>Benedetti P</given-names></name></person-group><article-title>Clinical outcomes after resectoscopic treatment of cesarean-induced isthmocele: A prospective case-control study</article-title><source>Eur Rev Med Pharmacol Sci</source><volume>21</volume><fpage>3341</fpage><lpage>3346</lpage><year>2017</year><pub-id pub-id-type="pmid">28829510</pub-id></element-citation></ref>
<ref id="b3-etm-0-0-6355"><label>3</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Banga</surname><given-names>A</given-names></name><name><surname>Sahoo</surname><given-names>D</given-names></name><name><surname>Budev</surname><given-names>M</given-names></name><name><surname>Akindipe</surname><given-names>O</given-names></name><name><surname>Lane</surname><given-names>C</given-names></name><name><surname>Garcha</surname><given-names>P</given-names></name><name><surname>Sasidhar</surname><given-names>M</given-names></name></person-group><article-title>Functional status at discharge predicts 6-month survival among lung transplant patients admitted to the medical intensive care unit</article-title><source>Chest</source><volume>144</volume><fpage>1021A</fpage><year>2013</year><pub-id pub-id-type="doi">10.1378/chest.1699114</pub-id></element-citation></ref>
<ref id="b4-etm-0-0-6355"><label>4</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Clini</surname><given-names>EM</given-names></name><name><surname>Crisafulli</surname><given-names>E</given-names></name><name><surname>Antoni</surname><given-names>FD</given-names></name><name><surname>Beneventi</surname><given-names>C</given-names></name><name><surname>Trianni</surname><given-names>L</given-names></name><name><surname>Costi</surname><given-names>S</given-names></name><name><surname>Fabbri</surname><given-names>LM</given-names></name><name><surname>Nava</surname><given-names>S</given-names></name></person-group><article-title>Functional recovery following physical training in tracheotomized and chronically ventilated patients</article-title><source>Respir Care</source><volume>56</volume><fpage>306</fpage><lpage>313</lpage><year>2011</year><pub-id pub-id-type="doi">10.4187/respcare.00956</pub-id><pub-id pub-id-type="pmid">21235844</pub-id></element-citation></ref>
<ref id="b5-etm-0-0-6355"><label>5</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mo</surname><given-names>Y</given-names></name><name><surname>Zimmermann</surname><given-names>AE</given-names></name></person-group><article-title>Role of dexmedetomidine for the prevention and treatment of delirium in intensive care unit patients</article-title><source>Ann Pharmacother</source><volume>47</volume><fpage>869</fpage><lpage>876</lpage><year>2013</year><pub-id pub-id-type="doi">10.1345/aph.1AR708</pub-id><pub-id pub-id-type="pmid">23719785</pub-id></element-citation></ref>
<ref id="b6-etm-0-0-6355"><label>6</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rouve</surname><given-names>S</given-names></name><name><surname>Didier</surname><given-names>A</given-names></name><name><surname>Demoly</surname><given-names>P</given-names></name><name><surname>Jankowsky</surname><given-names>R</given-names></name><name><surname>Klossek</surname><given-names>JM</given-names></name><name><surname>Annesi-Maesano</surname><given-names>I</given-names></name></person-group><article-title>Numeric score and visual analog scale in assessing seasonal allergic rhinitis severity</article-title><source>Rhinology</source><volume>48</volume><fpage>285</fpage><lpage>291</lpage><year>2010</year><pub-id pub-id-type="pmid">21038018</pub-id></element-citation></ref>
<ref id="b7-etm-0-0-6355"><label>7</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Demoly</surname><given-names>P</given-names></name><name><surname>Bousquet</surname><given-names>PJ</given-names></name><name><surname>Mesbah</surname><given-names>K</given-names></name><name><surname>Bousquet</surname><given-names>J</given-names></name><name><surname>Devillier</surname><given-names>P</given-names></name></person-group><article-title>Visual analogue scale in patients treated for allergic rhinitis: an observational prospective study in primary care: asthma and rhinitis</article-title><source>Clin Exp Allergy</source><volume>43</volume><fpage>881</fpage><lpage>888</lpage><year>2013</year><pub-id pub-id-type="doi">10.1111/cea.12121</pub-id><pub-id pub-id-type="pmid">23889242</pub-id></element-citation></ref>
<ref id="b8-etm-0-0-6355"><label>8</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Aretha</surname><given-names>D</given-names></name><name><surname>Kiekkas</surname><given-names>P</given-names></name><name><surname>Eleftheria</surname><given-names>P</given-names></name></person-group><article-title>Anesthesia awareness and the bispectral index</article-title><source>N Engl J Med</source><volume>359</volume><fpage>429</fpage><lpage>431</lpage><year>2008</year><pub-id pub-id-type="pmid">18655250</pub-id></element-citation></ref>
<ref id="b9-etm-0-0-6355"><label>9</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dahaba</surname><given-names>AA</given-names></name><name><surname>Worm</surname><given-names>HC</given-names></name><name><surname>Zhu</surname><given-names>SM</given-names></name><name><surname>Bao</surname><given-names>FP</given-names></name><name><surname>Salah</surname><given-names>A</given-names></name><name><surname>Zakaria</surname><given-names>S</given-names></name><name><surname>Bornemann</surname><given-names>H</given-names></name><name><surname>Stadlbauer</surname><given-names>V</given-names></name><name><surname>Rehak</surname><given-names>PH</given-names></name><name><surname>Metzler</surname><given-names>H</given-names></name><etal/></person-group><article-title>Sensitivity and specificity of bispectral index for classification of overt hepatic encephalopathy: A multicentre, observer blinded, validation study</article-title><source>Gut</source><volume>57</volume><fpage>77</fpage><lpage>83</lpage><year>2008</year><pub-id pub-id-type="doi">10.1136/gut.2007.129130</pub-id><pub-id pub-id-type="pmid">17698861</pub-id></element-citation></ref>
<ref id="b10-etm-0-0-6355"><label>10</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wisor</surname><given-names>JP</given-names></name><name><surname>Eriksson</surname><given-names>KS</given-names></name></person-group><article-title>Dopaminergic-adrenergic interactions in the wake promoting mechanism of modafinil</article-title><source>Neuroscience</source><volume>132</volume><fpage>1027</fpage><lpage>1034</lpage><year>2005</year><pub-id pub-id-type="doi">10.1016/j.neuroscience.2005.02.003</pub-id><pub-id pub-id-type="pmid">15857707</pub-id></element-citation></ref>
<ref id="b11-etm-0-0-6355"><label>11</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mantz</surname><given-names>J</given-names></name><name><surname>Josserand</surname><given-names>J</given-names></name><name><surname>Hamada</surname><given-names>S</given-names></name></person-group><article-title>Dexmedetomidine: New insights</article-title><source>Eur J Anaesthesiol</source><volume>28</volume><fpage>3</fpage><lpage>6</lpage><year>2011</year><pub-id pub-id-type="doi">10.1097/EJA.0b013e32833e266d</pub-id><pub-id pub-id-type="pmid">20881501</pub-id></element-citation></ref>
<ref id="b12-etm-0-0-6355"><label>12</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Feng</surname><given-names>XJ</given-names></name><name><surname>Hu</surname><given-names>XY</given-names></name><name><surname>Zhang</surname><given-names>S</given-names></name><name><surname>Li</surname><given-names>JN</given-names></name><name><surname>Fan</surname><given-names>HG</given-names></name></person-group><article-title>Effects of the dexmedetomidine, midazolam, butorphanol, and atropine combination on plasma oxidative status and cardiorespiratory parameters in raccoon dogs (<italic>Nyctereutes procyonoides</italic>)</article-title><source>Vet Med (Praha)</source><volume>60</volume><fpage>450</fpage><lpage>455</lpage><year>2015</year><pub-id pub-id-type="doi">10.17221/8420-VETMED</pub-id></element-citation></ref>
<ref id="b13-etm-0-0-6355"><label>13</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Asl</surname><given-names>ME</given-names></name><name><surname>Isazadefar</surname><given-names>K</given-names></name><name><surname>Mohammadian</surname><given-names>A</given-names></name><name><surname>Khoshbaten</surname><given-names>M</given-names></name></person-group><article-title>Ondansetron and meperidine prevent postoperative shivering after general anesthesia</article-title><source>Middle East J Anaesthesiol</source><volume>21</volume><fpage>67</fpage><lpage>70</lpage><year>2011</year><pub-id pub-id-type="pmid">21991735</pub-id></element-citation></ref>
<ref id="b14-etm-0-0-6355"><label>14</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Martin</surname><given-names>E</given-names></name><name><surname>Ramsay</surname><given-names>G</given-names></name><name><surname>Mantz</surname><given-names>J</given-names></name><name><surname>Sum-Ping</surname><given-names>ST</given-names></name></person-group><article-title>The role of the alpha2-adrenoceptor agonist dexmedetomidine in postsurgical sedation in the intensive care unit</article-title><source>J Intensive Care Med</source><volume>18</volume><fpage>29</fpage><lpage>41</lpage><year>2003</year><pub-id pub-id-type="doi">10.1177/0885066602239122</pub-id><pub-id pub-id-type="pmid">15189665</pub-id></element-citation></ref>
<ref id="b15-etm-0-0-6355"><label>15</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Coull</surname><given-names>JT</given-names></name><name><surname>Jones</surname><given-names>ME</given-names></name><name><surname>Egan</surname><given-names>TD</given-names></name><name><surname>Frith</surname><given-names>CD</given-names></name><name><surname>Maze</surname><given-names>M</given-names></name></person-group><article-title>Attentional effects of noradrenaline vary with arousal level: Selective activation of thalamic pulvinar in humans</article-title><source>Neuroimage</source><volume>22</volume><fpage>315</fpage><lpage>322</lpage><year>2004</year><pub-id pub-id-type="doi">10.1016/j.neuroimage.2003.12.022</pub-id><pub-id pub-id-type="pmid">15110021</pub-id></element-citation></ref>
<ref id="b16-etm-0-0-6355"><label>16</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ryan</surname><given-names>S</given-names></name><name><surname>Taylor</surname><given-names>CT</given-names></name><name><surname>McNicholas</surname><given-names>WT</given-names></name></person-group><article-title>Predictors of elevated nuclear factor-kappaB-dependent genes in obstructive sleep apnea syndrome</article-title><source>Am J Respir Crit Care Med</source><volume>174</volume><fpage>824</fpage><lpage>830</lpage><year>2006</year><pub-id pub-id-type="doi">10.1164/rccm.200601-066OC</pub-id><pub-id pub-id-type="pmid">16840748</pub-id></element-citation></ref>
<ref id="b17-etm-0-0-6355"><label>17</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Urschitz</surname><given-names>MS</given-names></name><name><surname>Poets</surname><given-names>CF</given-names></name><name><surname>Stuck</surname><given-names>BA</given-names></name><name><surname>Wiater</surname><given-names>A</given-names></name><name><surname>Kirchhoff</surname><given-names>F</given-names></name></person-group><article-title>Mitglieder der Steuerungsgruppe der AG P&#x00E4;diatrie der Deutschen Gesellschaft f&#x00FC;r Schlafforschung und Schlafmedizin (DGSM). Medicinal treatment of breathing disorders in adenotonsillar hyperplasia</article-title><source>HNO</source><volume>62</volume><fpage>582</fpage><lpage>585</lpage><year>2014</year><comment>(In German)</comment><pub-id pub-id-type="doi">10.1007/s00106-014-2906-5</pub-id><pub-id pub-id-type="pmid">25052895</pub-id></element-citation></ref>
<ref id="b18-etm-0-0-6355"><label>18</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Garaud</surname><given-names>S</given-names></name><name><surname>Roufosse</surname><given-names>F</given-names></name><name><surname>De Silva</surname><given-names>P</given-names></name><name><surname>Gu-Trantien</surname><given-names>C</given-names></name><name><surname>Lodewyckx</surname><given-names>JN</given-names></name><name><surname>Duvillier</surname><given-names>H</given-names></name><name><surname>Dedeurwaerder</surname><given-names>S</given-names></name><name><surname>Bizet</surname><given-names>M</given-names></name><name><surname>Defrance</surname><given-names>M</given-names></name><name><surname>Fuks</surname><given-names>F</given-names></name><etal/></person-group><article-title>FOXP1 is a regulator of quiescence in healthy human CD4<sup>&#x002B;</sup> T cells and is constitutively repressed in T cells from patients with lymphoproliferative disorders</article-title><source>Eur J Immunol</source><volume>47</volume><fpage>168</fpage><lpage>179</lpage><year>2017</year><pub-id pub-id-type="doi">10.1002/eji.201646373</pub-id><pub-id pub-id-type="pmid">27861791</pub-id></element-citation></ref>
<ref id="b19-etm-0-0-6355"><label>19</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>den Otter</surname><given-names>I</given-names></name><name><surname>Willems</surname><given-names>LN</given-names></name><name><surname>van Schadewijk</surname><given-names>A</given-names></name><name><surname>van Wijngaarden</surname><given-names>S</given-names></name><name><surname>Janssen</surname><given-names>K</given-names></name><name><surname>de Jeu</surname><given-names>RC</given-names></name><name><surname>Sont</surname><given-names>JK</given-names></name><name><surname>Sterk</surname><given-names>PJ</given-names></name><name><surname>Hiemstra</surname><given-names>PS</given-names></name></person-group><article-title>Lung function decline in asthma patients with elevated bronchial CD8, CD4 and CD3 cells</article-title><source>Eur Respir J</source><volume>48</volume><fpage>393</fpage><lpage>402</lpage><year>2016</year><pub-id pub-id-type="doi">10.1183/13993003.01525-2015</pub-id><pub-id pub-id-type="pmid">27230446</pub-id></element-citation></ref>
<ref id="b20-etm-0-0-6355"><label>20</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dauffenbach</surname><given-names>LM</given-names></name><name><surname>Sia</surname><given-names>GC</given-names></name><name><surname>Zheng</surname><given-names>J</given-names></name><name><surname>Jun</surname><given-names>N</given-names></name><name><surname>Olsen</surname><given-names>EP</given-names></name><name><surname>Kerfoot</surname><given-names>CA</given-names></name></person-group><article-title>Abstract 1669: Multiplex immunohistochemical staining of PD-L1, PD-1, CD3, CD4, CD8, CD68, FoxP3, and Ki-67 and image analysis of tumor and invasive margin in human FFPE NSCLC tissue</article-title><source>Cancer Res</source><volume>77</volume><supplement>Suppl. 13</supplement><fpage>1669</fpage><year>2017</year><pub-id pub-id-type="doi">10.1158/1538-7445.AM2017-1669</pub-id></element-citation></ref>
</ref-list>
</back>
<floats-group>
<table-wrap id="tI-etm-0-0-6355" position="float">
<label>Table I.</label>
<caption><p>Surgical situations of patients in four groups (mean &#x00B1; SD).</p></caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="bottom">Group</th>
<th align="center" valign="bottom">n</th>
<th align="center" valign="bottom">Operation duration (min)</th>
<th align="center" valign="bottom">Intraoperative bleeding volume (ml)</th>
<th align="center" valign="bottom">Intraoperative transfusion volume (ml)</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">A</td>
<td align="center" valign="top">42</td>
<td align="center" valign="top">181.2&#x00B1;4.5<sup><xref rid="tfn1-etm-0-0-6355" ref-type="table-fn">a</xref></sup></td>
<td align="center" valign="top">109.3&#x00B1;5.2<sup><xref rid="tfn1-etm-0-0-6355" ref-type="table-fn">a</xref></sup></td>
<td align="center" valign="top">2,299&#x00B1;102.3<sup><xref rid="tfn1-etm-0-0-6355" ref-type="table-fn">a</xref></sup></td>
</tr>
<tr>
<td align="left" valign="top">B</td>
<td align="center" valign="top">47</td>
<td align="center" valign="top">179.5&#x00B1;6.4</td>
<td align="center" valign="top">110.2&#x00B1;6.3</td>
<td align="center" valign="top">2,208&#x00B1;130.4</td>
</tr>
<tr>
<td align="left" valign="top">C</td>
<td align="center" valign="top">45</td>
<td align="center" valign="top">180.9&#x00B1;7.3</td>
<td align="center" valign="top">108.9&#x00B1;4.8</td>
<td align="center" valign="top">2,219&#x00B1;128.6</td>
</tr>
<tr>
<td align="left" valign="top">D</td>
<td align="center" valign="top">45</td>
<td align="center" valign="top">180.1&#x00B1;6.9</td>
<td align="center" valign="top">109.4&#x00B1;5.8</td>
<td align="center" valign="top">2,297&#x00B1;185.8</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="tfn1-etm-0-0-6355"><label>a</label><p>Compared with those in the other three groups, p&#x003E;0.05.</p></fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tII-etm-0-0-6355" position="float">
<label>Table II.</label>
<caption><p>VAS scores of patients in four groups after operation (mean &#x00B1; SD).</p></caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th/>
<th align="center" valign="bottom" colspan="4">Time (h)</th>
</tr>
<tr>
<th/>
<th align="center" valign="bottom" colspan="4"><hr/></th>
</tr>
<tr>
<th align="left" valign="bottom">Group</th>
<th align="center" valign="bottom">2</th>
<th align="center" valign="bottom">4</th>
<th align="center" valign="bottom">12</th>
<th align="center" valign="bottom">24</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">A</td>
<td align="center" valign="top">4.2&#x00B1;0.9<sup><xref rid="tfn2-etm-0-0-6355" ref-type="table-fn">a</xref></sup></td>
<td align="center" valign="top">2.9&#x00B1;0.3<sup><xref rid="tfn2-etm-0-0-6355" ref-type="table-fn">a</xref></sup></td>
<td align="center" valign="top">2.4&#x00B1;0.3<sup><xref rid="tfn2-etm-0-0-6355" ref-type="table-fn">a</xref></sup></td>
<td align="center" valign="top">1.4&#x00B1;0.2<sup><xref rid="tfn2-etm-0-0-6355" ref-type="table-fn">a</xref></sup></td>
</tr>
<tr>
<td align="left" valign="top">B</td>
<td align="center" valign="top">2.9&#x00B1;0.4</td>
<td align="center" valign="top">2.1&#x00B1;0.2</td>
<td align="center" valign="top">1.7&#x00B1;0.2</td>
<td align="center" valign="top">0.9&#x00B1;0.1</td>
</tr>
<tr>
<td align="left" valign="top">C</td>
<td align="center" valign="top">2.7&#x00B1;0.3</td>
<td align="center" valign="top">2.0&#x00B1;0.2</td>
<td align="center" valign="top">1.6&#x00B1;0.1</td>
<td align="center" valign="top">0.7&#x00B1;0.1</td>
</tr>
<tr>
<td align="left" valign="top">D</td>
<td align="center" valign="top">2.4&#x00B1;0.2</td>
<td align="center" valign="top">1.9&#x00B1;0.1</td>
<td align="center" valign="top">1.3&#x00B1;0.2</td>
<td align="center" valign="top">0.6&#x00B1;0.1</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="tfn2-etm-0-0-6355"><label>a</label><p>Compared with those in groups B, C and D, p&#x003C;0.05.</p></fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tIII-etm-0-0-6355" position="float">
<label>Table III.</label>
<caption><p>Comparison of agitation score and sedation score in patients among four groups (mean &#x00B1; SD).</p></caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="bottom">Group</th>
<th align="center" valign="bottom">Agitation score</th>
<th align="center" valign="bottom">Sedation score</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">A</td>
<td align="center" valign="top">2.7&#x00B1;0.2</td>
<td align="center" valign="top">1.1&#x00B1;0.1</td>
</tr>
<tr>
<td align="left" valign="top">B</td>
<td align="center" valign="top">2.2&#x00B1;0.2</td>
<td align="center" valign="top">1.1&#x00B1;0.1</td>
</tr>
<tr>
<td align="left" valign="top">C</td>
<td align="center" valign="top">1.2&#x00B1;0.1<sup><xref rid="tfn3-etm-0-0-6355" ref-type="table-fn">a</xref></sup></td>
<td align="center" valign="top">1.9&#x00B1;0.2<sup><xref rid="tfn3-etm-0-0-6355" ref-type="table-fn">a</xref></sup></td>
</tr>
<tr>
<td align="left" valign="top">D</td>
<td align="center" valign="top">2.2&#x00B1;0.1</td>
<td align="center" valign="top">5.5&#x00B1;0.2<sup><xref rid="tfn3-etm-0-0-6355" ref-type="table-fn">a</xref>,<xref rid="tfn4-etm-0-0-6355" ref-type="table-fn">b</xref></sup></td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="tfn3-etm-0-0-6355"><label>a</label><p>Compared with group A, p&#x003C;0.05.</p></fn>
<fn id="tfn4-etm-0-0-6355"><label>b</label><p>Compared with group C, p&#x003C;0.05.</p></fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tIV-etm-0-0-6355" position="float">
<label>Table IV.</label>
<caption><p>Comparison of serum inflammatory cytokines in patients among four groups (mean &#x00B1; SD).</p></caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="bottom">Group</th>
<th align="center" valign="bottom">Time</th>
<th align="center" valign="bottom">CRP (mg/l)</th>
<th align="center" valign="bottom">TNF-&#x03B1; (ng/l)</th>
<th align="center" valign="bottom">IL-10 (ng/l)</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">A</td>
<td align="center" valign="top">T1</td>
<td align="center" valign="top">11.45&#x00B1;2.12<sup><xref rid="tfn5-etm-0-0-6355" ref-type="table-fn">a</xref></sup></td>
<td align="center" valign="top">19.25&#x00B1;3.32</td>
<td align="center" valign="top">12.57&#x00B1;1.78</td>
</tr>
<tr>
<td/>
<td align="center" valign="top">T2</td>
<td align="center" valign="top">36.71&#x00B1;6.32</td>
<td align="center" valign="top">32.45&#x00B1;6.43</td>
<td align="center" valign="top">16.79&#x00B1;1.98</td>
</tr>
<tr>
<td/>
<td align="center" valign="top">T3</td>
<td align="center" valign="top">64.98&#x00B1;4.75</td>
<td align="center" valign="top">56.39&#x00B1;6.43</td>
<td align="center" valign="top">18.69&#x00B1;2.09</td>
</tr>
<tr>
<td/>
<td align="center" valign="top">T4</td>
<td align="center" valign="top">44.62&#x00B1;4.53</td>
<td align="center" valign="top">46.21&#x00B1;6.78</td>
<td align="center" valign="top">19.79&#x00B1;2.34</td>
</tr>
<tr>
<td align="left" valign="top">B</td>
<td align="center" valign="top">T1</td>
<td align="center" valign="top">11.50&#x00B1;1.64<sup><xref rid="tfn5-etm-0-0-6355" ref-type="table-fn">a</xref></sup></td>
<td align="center" valign="top">18.29&#x00B1;3.45</td>
<td align="center" valign="top">12.10&#x00B1;2.12</td>
</tr>
<tr>
<td/>
<td align="center" valign="top">T2</td>
<td align="center" valign="top">34.26&#x00B1;7.43</td>
<td align="center" valign="top">31.20&#x00B1;6.43</td>
<td align="center" valign="top">12.21&#x00B1;1.97</td>
</tr>
<tr>
<td/>
<td align="center" valign="top">T3</td>
<td align="center" valign="top">64.98&#x00B1;7.54</td>
<td align="center" valign="top">53.96&#x00B1;4.77</td>
<td align="center" valign="top">16.92&#x00B1;2.32</td>
</tr>
<tr>
<td/>
<td align="center" valign="top">T4</td>
<td align="center" valign="top">43.21&#x00B1;6.78</td>
<td align="center" valign="top">44.05&#x00B1;4.56</td>
<td align="center" valign="top">19.41&#x00B1;1.98</td>
</tr>
<tr>
<td align="left" valign="top">C</td>
<td align="center" valign="top">T1</td>
<td align="center" valign="top">11.27&#x00B1;2.43<sup><xref rid="tfn5-etm-0-0-6355" ref-type="table-fn">a</xref></sup></td>
<td align="center" valign="top">18.56&#x00B1;2.43</td>
<td align="center" valign="top">12.31&#x00B1;1.02</td>
</tr>
<tr>
<td/>
<td align="center" valign="top">T2</td>
<td align="center" valign="top">24.07&#x00B1;3.43<sup><xref rid="tfn6-etm-0-0-6355" ref-type="table-fn">b</xref></sup></td>
<td align="center" valign="top">24.15&#x00B1;3.45<sup><xref rid="tfn6-etm-0-0-6355" ref-type="table-fn">b</xref></sup></td>
<td align="center" valign="top">21.09&#x00B1;2.98</td>
</tr>
<tr>
<td/>
<td align="center" valign="top">T3</td>
<td align="center" valign="top">43.52&#x00B1;4.32<sup><xref rid="tfn6-etm-0-0-6355" ref-type="table-fn">b</xref></sup></td>
<td align="center" valign="top">36.21&#x00B1;3.75<sup><xref rid="tfn6-etm-0-0-6355" ref-type="table-fn">b</xref></sup></td>
<td align="center" valign="top">24.69&#x00B1;2.0<sup><xref rid="tfn6-etm-0-0-6355" ref-type="table-fn">b</xref></sup></td>
</tr>
<tr>
<td/>
<td align="center" valign="top">T4</td>
<td align="center" valign="top">33.21&#x00B1;3.86<sup><xref rid="tfn6-etm-0-0-6355" ref-type="table-fn">b</xref></sup></td>
<td align="center" valign="top">28.42&#x00B1;4.32<sup><xref rid="tfn6-etm-0-0-6355" ref-type="table-fn">b</xref></sup></td>
<td align="center" valign="top">25.76&#x00B1;2.21<sup><xref rid="tfn6-etm-0-0-6355" ref-type="table-fn">b</xref></sup></td>
</tr>
<tr>
<td align="left" valign="top">D</td>
<td align="center" valign="top">T1</td>
<td align="center" valign="top">11.72&#x00B1;2.43</td>
<td align="center" valign="top">18.26&#x00B1;4.21</td>
<td align="center" valign="top">12.09&#x00B1;1.09<sup><xref rid="tfn5-etm-0-0-6355" ref-type="table-fn">a</xref></sup></td>
</tr>
<tr>
<td/>
<td align="center" valign="top">T2</td>
<td align="center" valign="top">16.21&#x00B1;4.54<sup><xref rid="tfn6-etm-0-0-6355" ref-type="table-fn">b</xref></sup></td>
<td align="center" valign="top">19.45&#x00B1;2.11<sup><xref rid="tfn6-etm-0-0-6355" ref-type="table-fn">b</xref></sup></td>
<td align="center" valign="top">23.21&#x00B1;2.02</td>
</tr>
<tr>
<td/>
<td align="center" valign="top">T3</td>
<td align="center" valign="top">18.21&#x00B1;4.52<sup><xref rid="tfn6-etm-0-0-6355" ref-type="table-fn">b</xref></sup></td>
<td align="center" valign="top">22.45&#x00B1;2.31<sup><xref rid="tfn6-etm-0-0-6355" ref-type="table-fn">b</xref></sup></td>
<td align="center" valign="top">25.76&#x00B1;2.01<sup><xref rid="tfn6-etm-0-0-6355" ref-type="table-fn">b</xref></sup></td>
</tr>
<tr>
<td/>
<td align="center" valign="top">T4</td>
<td align="center" valign="top">16.52&#x00B1;3.87<sup><xref rid="tfn6-etm-0-0-6355" ref-type="table-fn">b</xref></sup></td>
<td align="center" valign="top">21.69&#x00B1;2.67<sup><xref rid="tfn6-etm-0-0-6355" ref-type="table-fn">b</xref></sup></td>
<td align="center" valign="top">24.5&#x00B1;62.78<sup><xref rid="tfn6-etm-0-0-6355" ref-type="table-fn">b</xref></sup></td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="tfn5-etm-0-0-6355"><label>a</label><p>Compared with those at T2, T3 and T4, p&#x003C;0.05.</p></fn>
<fn id="tfn6-etm-0-0-6355"><label>b</label><p>Compared with those in groups A and B, p&#x003C;0.05.</p></fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tV-etm-0-0-6355" position="float">
<label>Table V.</label>
<caption><p>Comparisons of adverse reactions in patients among four groups (n).</p></caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="bottom">Adverse reaction</th>
<th align="center" valign="bottom">A</th>
<th align="center" valign="bottom">B</th>
<th align="center" valign="bottom">C</th>
<th align="center" valign="bottom">D</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">Tachycardia</td>
<td align="center" valign="top">9</td>
<td align="center" valign="top">7</td>
<td align="center" valign="top">0<sup><xref rid="tfn7-etm-0-0-6355" ref-type="table-fn">a</xref></sup></td>
<td align="center" valign="top">0</td>
</tr>
<tr>
<td align="left" valign="top">Bradycardia</td>
<td align="center" valign="top">7</td>
<td align="center" valign="top">7</td>
<td align="center" valign="top">0<sup><xref rid="tfn7-etm-0-0-6355" ref-type="table-fn">a</xref></sup></td>
<td align="center" valign="top">5</td>
</tr>
<tr>
<td align="left" valign="top">Hypertension</td>
<td align="center" valign="top">7</td>
<td align="center" valign="top">2</td>
<td align="center" valign="top">1<sup><xref rid="tfn7-etm-0-0-6355" ref-type="table-fn">a</xref></sup></td>
<td align="center" valign="top">2</td>
</tr>
<tr>
<td align="left" valign="top">Hypotension</td>
<td align="center" valign="top">2</td>
<td align="center" valign="top">0</td>
<td align="center" valign="top">1</td>
<td align="center" valign="top">4</td>
</tr>
<tr>
<td align="left" valign="top">Nausea and vomiting</td>
<td align="center" valign="top">0</td>
<td align="center" valign="top">1</td>
<td align="center" valign="top">0</td>
<td align="center" valign="top">0</td>
</tr>
<tr>
<td align="left" valign="top">Respiratory depression</td>
<td align="center" valign="top">1</td>
<td align="center" valign="top">1</td>
<td align="center" valign="top">0</td>
<td align="center" valign="top">0</td>
</tr>
<tr>
<td align="left" valign="top">Delayed recovery</td>
<td align="center" valign="top">1</td>
<td align="center" valign="top">0</td>
<td align="center" valign="top">0</td>
<td align="center" valign="top">1</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="tfn7-etm-0-0-6355"><label>a</label><p>Compared with those in groups A and B, p&#x003C;0.05.</p></fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</article>
