帕瑞昔布鈉給藥時(shí)機(jī)對(duì)腹腔鏡下急性化膿性闌尾炎切除術(shù)患者術(shù)后炎性因子的影響

蔣永，譚憶，張世勇，林慧雯

(內(nèi)江市第一人民醫(yī)院麻醉科，四川 內(nèi)江　641000)

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帕瑞昔布鈉給藥時(shí)機(jī)對(duì)腹腔鏡下急性化膿性闌尾炎切除術(shù)患者術(shù)后炎性因子的影響

蔣永，譚憶，張世勇，林慧雯

(內(nèi)江市第一人民醫(yī)院麻醉科，四川 內(nèi)江641000)

目的探討帕瑞昔布鈉給藥時(shí)機(jī)對(duì)腹腔鏡下急性化膿性闌尾炎切除術(shù)患者術(shù)后炎性因子的影響，為預(yù)防及減輕急性化膿性闌尾炎手術(shù)圍術(shù)期應(yīng)激反應(yīng)方法的選擇提供參考。方法選取急性化膿性闌尾炎患者100例，按隨機(jī)數(shù)字表法分為A組與B組，每組各50例，兩組患者在入院后均急診手術(shù)，芬太尼、依托咪酯、咪達(dá)唑侖及維庫溴銨進(jìn)行麻醉誘導(dǎo)，丙泊酚、瑞芬太尼麻醉維持，A組患者在麻醉誘導(dǎo)前靜脈注射帕瑞昔布鈉，B組患者在術(shù)畢時(shí)靜脈注射帕瑞昔布鈉。觀察指標(biāo)圍手術(shù)期相關(guān)指標(biāo)變化。結(jié)果兩組患者手術(shù)時(shí)間、出血量、阿托品及麻黃堿使用率比較差異無統(tǒng)計(jì)學(xué)意義；白細(xì)胞介素-6(IL-6)、白細(xì)胞介素-8(IL-8)、白細(xì)胞介素-10(IL-10)及腫瘤壞死因子α(TNF-α)水平，A組術(shù)前分別為(7.84±2.80)、(8.12±2.97)、(47.11±12.93)ng·L-1、(0.97±0.30)mg·L-1，術(shù)后24 h分別為(24.11±10.73)、(20.95±14.61)、(113.26±23.85)ng·L-1、(1.45±0.39)mg·L-1，B組術(shù)前分別為(7.91±2.45)、(8.04±3.05)、(44.72±13.65)ng·L-1、(0.99±0.37)mg·L-1，術(shù)后24 h分別為(32.73±13.64)、(33.47±23.74)、(95.60±21.39)ng·L-1、(1.94±0.86)mg·L-1，兩組術(shù)后24 h時(shí)以上指標(biāo)水平較術(shù)前升高(P<0.05)，術(shù)后24 h時(shí)IL-6、IL-8及TNF-α水平低于B組(P<0.05)，IL-10水平高于B組(P<0.05)；兩組術(shù)后24 h時(shí)VAS評(píng)分及24 h內(nèi)自控鎮(zhèn)痛泵按壓次數(shù)比較差異無統(tǒng)計(jì)學(xué)意義。結(jié)論腹腔鏡下急性化膿性闌尾炎切除術(shù)患者帕瑞昔布鈉在麻醉誘導(dǎo)前給藥較術(shù)畢給藥更有利于降低術(shù)后炎性因子水平，提高抑炎因子濃度，用藥時(shí)機(jī)對(duì)術(shù)后鎮(zhèn)痛無影響。

闌尾炎;藥物時(shí)間療法;帕瑞昔布;白細(xì)胞介素6 ;白細(xì)胞介素8;白細(xì)胞介素10;腫瘤壞死因子α

急性闌尾炎是普外科最常見疾病之一，闌尾炎的發(fā)病與自身免疫力下降、腸道局部感染等有關(guān)，根據(jù)病情發(fā)展可分為急性單純性闌尾炎、急性化膿性闌尾炎、壞疽及闌尾穿孔等，均需進(jìn)行急診手術(shù)治療。手術(shù)自身的應(yīng)激反應(yīng)及機(jī)體代謝會(huì)對(duì)免疫功能形成一定程度的抑制，帕瑞昔布鈉是選擇性環(huán)氧化酶-2(COX-2)抑制劑，有較強(qiáng)的抗炎及鎮(zhèn)痛作用[1-2]，本文對(duì)帕瑞昔布鈉給藥時(shí)機(jī)對(duì)腹腔鏡下急性化膿性闌尾炎切除術(shù)患者術(shù)后炎性因子的影響進(jìn)行了研究，為預(yù)防及減輕急性化膿性闌尾炎手術(shù)圍術(shù)期應(yīng)激反應(yīng)方法選擇提供參考，現(xiàn)報(bào)道如下。

1　資料與方法

1.1臨床資料選取2014年6月至2015年6月四川省內(nèi)江市第一人民醫(yī)院收治的急性化膿性闌尾炎患者100例，納入標(biāo)準(zhǔn)：(1)術(shù)前診斷為急性闌尾炎，術(shù)后病理確診為急性化膿性闌尾炎；(2)未合并其他急慢性感染性疾??；(3)擬行腹腔鏡下闌尾切除術(shù)；(4)麻醉(ASA)分級(jí)I～I(xiàn)I級(jí)；(5)無腹腔鏡手術(shù)治療禁忌證。排除標(biāo)準(zhǔn)：(1)合并嚴(yán)重的心、肝、腎等重要臟器功能障礙性疾?。?2)合并免疫功能異常性疾?。?3)在近3個(gè)月內(nèi)有使用免疫抑制劑或免疫增強(qiáng)劑治療史者，阿司匹林哮喘史，近1周有使用非甾體類藥物(NSAIDs)治療史；(4)嚴(yán)重高血壓或NSAIDs過敏史。將患者按隨機(jī)數(shù)字表法分為A組與B組，每組各50例，A組中男28例、女22例，年齡(32.37±3.11)歲，ASA分級(jí)Ⅰ級(jí)21例、Ⅱ級(jí)29例，病程(7.42±3.11)h，白細(xì)胞計(jì)數(shù)WBC(14 028±3 249)×109·L-1，體質(zhì)量指數(shù)BMI(23.19±0.73)kg·m-2；A組中男30例、女20例，年齡(32.08±8.46)歲，ASA分級(jí)Ⅰ級(jí)18例、Ⅱ級(jí)32例，病程(7.50±3.19)h，WBC(13 984±3 102)×109·L-1，BMI(23.04±0.78)kg·m-2；兩組患兒在性別、年齡、病程、WBC、ASA分級(jí)、BMI等方面比較差異無統(tǒng)計(jì)學(xué)意義。本研究經(jīng)四川省內(nèi)江市第一人民醫(yī)院倫理委員會(huì)審核通過，患者均知情同意并簽署知情同意書。

1.2方法兩組患者在入院后均急診手術(shù)，在術(shù)前30 min給予0.5 mg阿托品及0.1 g苯巴比妥鈉肌注，入手術(shù)室后開通靜脈通道，進(jìn)行血壓、血氧飽和度(SpO2)心電圖等監(jiān)測(cè)，40 mg帕瑞昔布鈉用生理鹽水2 mL稀釋備用。采用3 μg·kg-1芬太尼、0.3 mg·kg-1依托咪酯、0.03 mg·kg-1咪達(dá)唑侖及0.1 mg·kg-1維庫溴銨進(jìn)行麻醉誘導(dǎo)，4～8 mg·kg-1·h-1丙泊酚、0.1～0.3 μg·kg-1·min-1瑞芬太尼及4 mg維庫溴銨進(jìn)行麻醉維持，根據(jù)血壓及心率可給予麻黃堿及阿托品等藥物。A組患者在麻醉誘導(dǎo)前靜脈注射帕瑞昔布鈉，B組患者在術(shù)畢時(shí)靜脈注射帕瑞昔布鈉。術(shù)后常規(guī)給予鎮(zhèn)痛泵鎮(zhèn)痛，鎮(zhèn)痛藥物為嗎啡1 g·L-1，負(fù)荷劑量2 mg，單次給藥劑量設(shè)定1 mg，背景量0.5 mg·h-1，鎖定時(shí)間10 min。

1.3觀察指標(biāo)(1)手術(shù)時(shí)間、出血量，阿托品及麻黃堿使用率;(2)術(shù)前、術(shù)后24 h時(shí)白細(xì)胞介素-6(IL-6)、白細(xì)胞介素-8(IL-8)、白細(xì)胞介素-10(IL-10)及腫瘤壞死因子α(TNF-α)水平，檢測(cè)采用放射免疫法，試劑盒購自美國(guó)eBioscience公司;(3)術(shù)后24 h時(shí)疼痛程度(VAS)評(píng)分，自控鎮(zhèn)痛泵按壓次數(shù)。

1.4統(tǒng)計(jì)學(xué)方法采用SPSS19.0軟件進(jìn)行統(tǒng)計(jì)分析，計(jì)數(shù)資料采用χ2檢驗(yàn)，計(jì)量資料采用t檢驗(yàn)，P<0.05為差異有統(tǒng)計(jì)學(xué)意義。

2　結(jié)果

2.1兩組患者術(shù)中瑞芬太尼及丙泊酚用量、手術(shù)時(shí)間、出血量、阿托品及麻黃堿使用率比較兩組患者丙泊酚用量、手術(shù)時(shí)間、出血量、阿托品及麻黃堿使用率比較差異無統(tǒng)計(jì)學(xué)意義(P>0.05)，A組術(shù)中瑞芬太尼用量少于B組，兩組比較差異有統(tǒng)計(jì)學(xué)意義(P<0.05)，見表1。

表1　兩組患者手術(shù)時(shí)間、出血量、阿托品及麻黃堿使用率比較

2.2兩組術(shù)前、術(shù)后24 h時(shí)IL-6、IL-8、IL-10及TNF-α水平變化比較IL-6、IL-8、IL-10及TNF-α水平兩組術(shù)前比較差異無統(tǒng)計(jì)學(xué)意義(P>0.05)，術(shù)后24 h時(shí)較術(shù)前升高，組內(nèi)比較差異有統(tǒng)計(jì)學(xué)意義(A組：t=10.37、t=6.09、t=17.24、t=4.90，B組：t=12.66、t=7.51、t=14.18、t=7.18；P<0.05)，術(shù)后24 h時(shí)IL-6、IL-8及TNF-α水平低于B組(t=3.51、t=3.18、t=3.67，P<0.05)，IL-10水平高于B組(t=3.90，P<0.05)，組間比較差異有統(tǒng)計(jì)學(xué)意義(P<0.05)，見表2。

表2　兩組術(shù)前、術(shù)后24 h時(shí)IL-6、IL-8、IL-10及TNF-α水平變化比較

注：與組內(nèi)術(shù)前比較，aP<0.05；與B組術(shù)后比較，bP<0.05。

2.3兩組術(shù)后24 h時(shí)VAS評(píng)分及24 h內(nèi)自控鎮(zhèn)痛泵按壓次數(shù)比較兩組術(shù)后24 h時(shí)VAS評(píng)分及24 h內(nèi)自控鎮(zhèn)痛泵按壓次數(shù)比較差異無統(tǒng)計(jì)學(xué)意義(P>0.05)，見表3。

表3　兩組術(shù)后24 h時(shí)VAS評(píng)分及24 h內(nèi)自控鎮(zhèn)痛泵按壓次數(shù)比較±s

3　討論

急性闌尾炎是普外科常見急腹癥，患者可表現(xiàn)為腹痛、發(fā)熱、惡心嘔吐等，進(jìn)行體格檢查可發(fā)現(xiàn)有右下腹部麥?zhǔn)宵c(diǎn)壓痛、反跳痛及肌緊張等陽性體征，實(shí)驗(yàn)室檢查可發(fā)現(xiàn)白細(xì)胞及C-反應(yīng)蛋白等炎性細(xì)胞因子升高[3-5]。急性闌尾炎的發(fā)病因素尚不完全清楚，一般認(rèn)為是闌尾梗阻、感染、闌尾畸形等因素共同作用所致，在急性闌尾炎發(fā)病早期多為單純性闌尾炎，如病情進(jìn)一步發(fā)展闌尾由于缺血壞死導(dǎo)致細(xì)菌在局部繁殖發(fā)生化膿，此時(shí)如不能及時(shí)手術(shù)可進(jìn)一步發(fā)展為闌尾穿孔。

手術(shù)作為一種創(chuàng)傷性操作，可導(dǎo)致機(jī)體發(fā)生應(yīng)激反應(yīng)，出現(xiàn)IL-6等炎性因子的異常升高，其升高水平與機(jī)體免疫應(yīng)答、麻醉用藥、疾病自身等均有關(guān)，而這種應(yīng)激反應(yīng)雖然是機(jī)體保護(hù)性反應(yīng)，但是如應(yīng)激反應(yīng)過度可對(duì)免疫功能形成一定程度的抑制。腹腔鏡手術(shù)作為一種微創(chuàng)手術(shù)，相對(duì)于開腹手術(shù)對(duì)患者應(yīng)激反應(yīng)輕，但無法完全避免這種反應(yīng)。如應(yīng)激反應(yīng)強(qiáng)烈，炎癥因子會(huì)大量釋放[6]，引起組織細(xì)胞的過度損傷，甚至于發(fā)生全身炎性反應(yīng)綜合征等圍術(shù)期炎癥并發(fā)癥，不利于患者康復(fù)。帕瑞昔布鈉是COX-2抑制藥，在體內(nèi)可通過肝酶作用轉(zhuǎn)化為伐地昔布，伐地昔布具有藥理活性可對(duì)COX-2起到特異性抑制作用，從而阻斷前列腺素等致炎、致痛因子的合成，有效的減輕痛覺及抑制炎性反應(yīng)，起到良好的鎮(zhèn)痛效果[1-2]。IL-6、IL-8、TNF-α是致炎因子，可促進(jìn)炎性反應(yīng)加強(qiáng)，IL-10是抑炎因子，升高可減輕致炎因子對(duì)組織細(xì)胞的炎癥損傷反應(yīng)，臨床研究發(fā)現(xiàn)如對(duì)在手術(shù)前后給與帕瑞昔布鈉進(jìn)行靜脈用藥，可有助于降低患者術(shù)后IL-6、IL-8、TNF-α水平，減輕炎性反應(yīng)及起到良好鎮(zhèn)痛作用[7-12]，但是帕瑞昔布鈉的用藥時(shí)機(jī)是否對(duì)患者術(shù)后炎癥因子水平存在影響，臨床研究較少。本研究對(duì)帕瑞昔布鈉給藥時(shí)機(jī)對(duì)腹腔鏡下急性化膿性闌尾炎切除術(shù)患者術(shù)后炎性因子的影響進(jìn)行了研究，A組患者在麻醉誘導(dǎo)前靜脈注射帕瑞昔布鈉，B組患者在術(shù)畢時(shí)靜脈注射帕瑞昔布鈉，觀察指標(biāo)圍術(shù)期相關(guān)指標(biāo)變化，結(jié)果顯示無論何時(shí)用藥均不對(duì)患者手術(shù)時(shí)間、出血量、阿托品及麻黃堿使用率形成影響。分析患者手術(shù)前后IL-6、IL-8、IL-10及TNF-α水平變化，兩組術(shù)后24 h時(shí)以上指標(biāo)水平較術(shù)前升高，這主要是手術(shù)創(chuàng)傷及闌尾炎局部感染的雙重影響所致，但是A組患者術(shù)后24h時(shí)IL-6、IL-8及TNF-α水平低于B組，IL-10水平高于B組，表明在麻醉誘導(dǎo)前應(yīng)用帕瑞昔布鈉對(duì)術(shù)后致炎因子抑制作用強(qiáng)于術(shù)畢用藥，這可能是由于炎癥因子的合成、釋放、代謝及滅火等存在一定程度的時(shí)間差，麻醉誘導(dǎo)前用藥對(duì)術(shù)中手術(shù)創(chuàng)傷所致炎性反應(yīng)可起到早期抑制作用，因此效果會(huì)更為明顯。

綜上所述，腹腔鏡下急性化膿性闌尾炎切除術(shù)患者帕瑞昔布鈉在麻醉誘導(dǎo)前給藥較術(shù)畢給藥可減少瑞芬太尼術(shù)中用量，更有利于降低術(shù)后炎性因子水平，提高抑炎因子濃度，用藥時(shí)機(jī)對(duì)術(shù)后鎮(zhèn)痛無影響。

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Effect of the administration timing of parecoxib sodium on postoperative inflammatory factors of patients undergoing acute suppurative appendicitis surgery with laparoscopy

JIANG Yong,TAN Yi,ZHANG Shiyong,et al

(DepartmentofAnesthesiology,FirstRenminHospital,Neijiang,Sichuan641000,China)

ObjectiveTo investigate the effect of the administration timing of parecoxib sodium on postoperative inflammatory factors of patients undergoing acute suppurative appendicitis surgery with laparoscopy,so as to provide reference for choosing methods of prevention and mitigation of perioperative stress response to acute suppurative appendicitis surgery.MethodsA hundred patients of acute suppurative appendicitis were randomized intogroup A (n=50)and group B (n=50).All of the patients underwent emergency surgery after admission.Fentanyl,etomidate,midazolam and vecuronium were taken for induction of anesthesia,and propofol and remifentanil were for the keeping of anesthesia.Group A received intravenous parecoxib sodium before induction of anesthesia,while group B received intravenous parecoxib sodium after surgery.The changes of relevant indicators of perioperative period were observed.ResultsThere were no significant differences between the two groups in the operative time,blood loss,atropine and ephedrine usage.The Interleukin-6 (IL-6),interleukin-8 (IL-8),interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) levels in group A and group B were (7.84±2.80)vs(7.91±2.45),(8.12±2.97)vs(8.04±3.05),(47.11±12.93) ng · L-1vs(44.72±13.65) ng·L-1,(0.97±0.30) mg·L-1vs(0.99±0.37) mg·L-1before surgery,(24.11±10.73)vs(32.73±13.64),(20.95±14.61)vs(33.47±23.74),(113.26±23.85) ng·L-1vs(95.60±21.39) ng·L-1,(1.45±0.39) mg·L-1vs(1.94±0.86) mg·L-124 h after surgery.The above indicators in both groups were significantly increased 24 h after surgery compared to those before surgery (P<0.05).The IL-6,IL-8 and TNF-α levels 24 hours after surgery were lower in group A than in group B (P<0.05),while IL-10 was higher in group A than in group B (P<0.05).There were no significant differences in 24 h VAS score and pressing times of controlled analgesia pump within 24 hours.ConclusionsAdministration of parecoxib sodium before surgery for patients with acute suppurative appendicitis surgery with laparoscopy is more conducive to reduce postoperative inflammatory cytokines,increase the concentration of anti-inflammatory factor,and the timing of administration has no effect on pain after surgery.

Appendicitis;Drug chronotherapy;Parecoxib;Interleukin-6;Interleukin-8;Interleukin-10;Tumor necrosis factor-alpha

10.3969/j.issn.1009-6469.2016.08.053

2016-02-14，

2016-07-12)