吲哚美辛栓聯(lián)合氨酚羥考酮片治療老年原發(fā)性肝癌TACE術(shù)后疼痛的臨床觀察

朱昆喜沈春華吳偉本馬占龍郗鳴

目的觀察吲哚美辛栓聯(lián)合氨酚羥考酮片對(duì)老年原發(fā)性肝癌經(jīng)導(dǎo)管肝動(dòng)脈化療栓塞(TACE)術(shù)后疼痛的治療效果,為老年原發(fā)性肝癌TACE術(shù)后疼痛的臨床治療提供幫助。方法選取我院收治的90例行TACE術(shù)的老年原發(fā)性肝癌病人,按隨機(jī)數(shù)字表法將病人分為研究組和對(duì)照組,每組各45例,對(duì)照組病人TACE術(shù)前后采用吲哚美辛栓治療,研究組病人TACE術(shù)前后采用吲哚美辛栓聯(lián)合氨酚羥考酮片治療。觀察治療前后2組病人疼痛程度及評(píng)分、疼痛持續(xù)時(shí)間、血壓、脈搏及不良反應(yīng)情況。結(jié)果研究組病人經(jīng)過(guò)聯(lián)合治療后術(shù)中疼痛評(píng)分、術(shù)后疼痛評(píng)分以及術(shù)后疼痛持續(xù)時(shí)間均顯著低于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);研究組病人血壓以及脈搏頻率顯著低于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);研究組病人總不良反應(yīng)發(fā)生率明顯低于對(duì)照組,輕度疼痛以下人數(shù)比例明顯高于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。結(jié)論吲哚美辛栓與氨酚羥考酮片的聯(lián)合治療止痛效果明顯、不良反應(yīng)少,有利于老年原發(fā)性肝癌病人TACE術(shù)后疼痛的治療。

吲哚美辛栓; 氨酚羥考酮片; 經(jīng)導(dǎo)管肝動(dòng)脈化療栓塞術(shù); 原發(fā)性肝癌; 疼痛

原發(fā)性肝癌是一種常見(jiàn)的肝臟惡性腫瘤,具有很高的發(fā)病率以及死亡率,經(jīng)導(dǎo)管肝動(dòng)脈化療栓塞(TACE)術(shù)是中晚期肝癌病人除手術(shù)以外的最佳治療方法之一,但卻會(huì)引起持續(xù)的、嚴(yán)重的疼痛,影響了癌癥病人的治療[1-2]。吲哚美辛栓是一種非甾體類(lèi)的鎮(zhèn)痛消炎藥,具有緩解TACE術(shù)引起的疼痛以及消炎的作用[3];氨酚羥考酮片是一種由對(duì)乙酰氨基酚組成的復(fù)方制劑,具有中樞神經(jīng)止痛以及周?chē)窠?jīng)止痛作用[4]。二者能夠從不同層面達(dá)到緩解疼痛的作用。本研究探究了吲哚美辛栓聯(lián)合氨酚羥考酮片對(duì)老年原發(fā)性肝癌病人TACE術(shù)引起的疼痛的治療效果以及不良反應(yīng)情況,為老年原發(fā)性肝癌病人TACE術(shù)后的疼痛治療提供幫助。

1 資料方法

1.1 一般資料 收集我院本部2014年1月至2016年1月期間收治的90例原發(fā)性肝癌病人。按隨機(jī)數(shù)字表法將90例病人分為研究組和對(duì)照組,其中研究組病人45例,男25例、女20例,年齡60～80歲,平均(67.9±6.2)歲,其中肝癌Ⅰ期23例、肝癌Ⅱ期14例、肝癌Ⅲ期8例;對(duì)照組病人45例,男24例、女21例,年齡60～80歲,平均(68.5±6.6)歲,其中肝癌Ⅰ期22例、肝癌Ⅱ期13例、肝癌Ⅲ期10例;2組病人在年齡、性別、疾病嚴(yán)重程度、病程、分期、身體狀況等方面比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。

1.2 納入和排除標(biāo)準(zhǔn) 本研究經(jīng)我院倫理委員會(huì)批準(zhǔn)同意,并且經(jīng)病人簽署知情同意書(shū)后開(kāi)展實(shí)施;所有病人的預(yù)計(jì)生存期均超過(guò)4月;所有病人均符合2001年中國(guó)抗癌協(xié)會(huì)制定的原發(fā)性肝癌診斷標(biāo)準(zhǔn);所有病人均符合相關(guān)治療要求;所有病人均能夠積極配合相關(guān)治療且治療前均有詳細(xì)的資料;排除存在其他心、腸、腎、肺、內(nèi)分泌、門(mén)靜脈高壓及脂肪肝等疾病的病人;排除對(duì)相關(guān)治療藥物存在過(guò)敏現(xiàn)象的病人。

1.3 治療方法 2組病人均采用TACE術(shù)治療,對(duì)照組術(shù)前3 d開(kāi)始及術(shù)后應(yīng)用吲哚美辛栓(馬應(yīng)龍藥業(yè)集團(tuán)股份有限公司,國(guó)藥準(zhǔn)字:H42020377),肛門(mén)給藥，1粒/次，1次/d;研究組病人在對(duì)照組基礎(chǔ)上同時(shí)服用氨酚羥考酮片(Mallinckrodt Inc,國(guó)藥準(zhǔn)字:J20140037),每隔6 h口服1粒;2組病人術(shù)后治療時(shí)間為10 d。

1.4 術(shù)中和術(shù)后疼痛評(píng)估 2組病人術(shù)中采用Wong-Baker臉譜疼痛評(píng)分:由病人確定術(shù)中疼痛最嚴(yán)重時(shí)間點(diǎn),然后進(jìn)行打分,疼痛程度由輕到重按0～10分進(jìn)行打分;術(shù)后采用視覺(jué)模擬疼痛量表(VAS)評(píng)分:由病人根據(jù)疼痛感覺(jué)自行打分;根據(jù)《內(nèi)科腫瘤學(xué)》進(jìn)行疼痛分級(jí)：(1)無(wú)痛;(2)輕度疼痛:病人疼痛可以忍受且不影響睡眠;(3)中度疼痛:病人不能忍受疼痛,需采用止痛措施,病人睡眠受影響;(4)重度疼痛:病人出現(xiàn)痙攣、出汗等癥狀,病人難以入睡。

1.5 血壓、脈搏監(jiān)測(cè) 采用CMS50IW型脈搏血氧儀(康泰醫(yī)學(xué)系統(tǒng)(秦皇島)股份有限公司)測(cè)定2組病人治療前后脈搏情況,操作流程嚴(yán)格按照說(shuō)明書(shū)進(jìn)行;采用立柱式血壓計(jì)測(cè)定2組病人治療前后收縮壓和舒張壓水平。

1.6 不良反應(yīng)情況觀察 觀察2組病人治療后出汗、休克和動(dòng)脈痙攣等不良反應(yīng)的發(fā)生情況,總不良反應(yīng)發(fā)生率=不良反應(yīng)人數(shù)/總?cè)藬?shù)×100%。

2 結(jié)果

2.1 2組病人術(shù)中、術(shù)后疼痛評(píng)分以及術(shù)后疼痛持續(xù)時(shí)間比較 研究組病人經(jīng)過(guò)聯(lián)合治療后術(shù)中與術(shù)后疼痛評(píng)分顯著低于對(duì)照組(P<0.05);與治療后對(duì)照組相比,研究組病人的術(shù)后疼痛持續(xù)時(shí)間顯著降低,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)，見(jiàn)表1。

組別術(shù)中疼痛評(píng)分(分)術(shù)后疼痛評(píng)分(分)術(shù)后疼痛持續(xù)時(shí)間(d)對(duì)照組4.73±0.545.76±0.623.86±0.74研究組3.22±0.33*4.09±0.37*1.61±0.45*

注：與對(duì)照組比較，*P<0.05

2.2 2組病人治療后疼痛程度比較 2組病人術(shù)后疼痛程度差異有統(tǒng)計(jì)學(xué)意義(Z=2.7,P=0.007)。研究組無(wú)痛及輕度疼痛病人比例明顯高于對(duì)照組,見(jiàn)表2。

2.3 2組病人治療前后血壓、脈率比較 治療前2組病人收縮壓、舒張壓和脈率比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05);與本組治療前相比,研究組治療后收縮壓、舒張壓和脈率顯著降低,差異有統(tǒng)計(jì)學(xué)意義(t=5.50、4.83、4.95,均P<0.05);對(duì)照組病人治療后收縮壓、舒張壓和脈率顯著降低,差異有統(tǒng)計(jì)學(xué)意義(t=2.98、2.60、3.43,均P<0.05);治療后研究組收縮壓、舒張壓和脈率顯著低于對(duì)照組，差異有統(tǒng)計(jì)學(xué)意義(t=2.90、2.39、2.07,均P<0.05),見(jiàn)表3。

表2 2組病人治療后疼痛程度比較(n,%,n=45)

2.4 2組病人術(shù)中及術(shù)后不良反應(yīng)情況比較 研究組治療后出汗、休克和動(dòng)脈痙攣比例明顯少于對(duì)照組,總不良反應(yīng)發(fā)生率明顯低于對(duì)照組(P<0.05);見(jiàn)表4。

表3 2組病人治療前后血壓、脈率比較

注:與本組治療前比較,*P<0.05;與對(duì)照組治療后比較,#P<0.05。

表4 2組病人術(shù)中及術(shù)后不良反應(yīng)發(fā)生率比較(n,%,n=45)

注:與對(duì)照組比較,*P<0.05

3 討論

3.1 原發(fā)性肝癌TACE術(shù)治療 原發(fā)性肝癌具有發(fā)病率高、隱匿性強(qiáng)以及預(yù)后效果差的特點(diǎn)[5]。由于原發(fā)性肝癌被發(fā)現(xiàn)時(shí)常處于中晚期,因此原發(fā)性肝癌治療方式的選擇尤為重要。TACE術(shù)是中晚期病人除手術(shù)以外的最佳治療方法之一,已被廣泛應(yīng)用于臨床,并取得了令人滿意的治療效果[6]。TACE術(shù)切斷腫瘤的供血致使高濃度的化療藥局限于腫瘤細(xì)胞,栓塞劑栓塞了腫瘤的供血血管,引起了該血管供血區(qū)缺血,肝區(qū)出現(xiàn)組織缺血性疼痛;藥物注入后腫瘤腫脹壞死,使包膜緊張引起繼發(fā)性疼痛,抗腫瘤藥物及碘油混合劑作為刺激物刺激血管內(nèi)膜,引起血管痙攣,因而會(huì)導(dǎo)致原發(fā)性肝癌病人TACE術(shù)中、術(shù)后疼痛[7]。持續(xù)嚴(yán)重的疼痛易引起肝癌病人出現(xiàn)交感神經(jīng)興奮或者肌肉收縮,影響了病人的身體狀況,因病人疼痛或手術(shù)操作困難而使得治療失敗[8]。因此,及時(shí)有效地控制原發(fā)性肝癌病人TACE術(shù)疼痛對(duì)癌癥的治療具有重要的臨床意義。

3.2 鎮(zhèn)痛機(jī)制分析 本研究發(fā)現(xiàn),吲哚美辛栓聯(lián)合氨酚羥考酮片能夠降低老年原發(fā)性肝癌TACE術(shù)中、術(shù)后疼痛評(píng)分以及術(shù)后疼痛持續(xù)時(shí)間;同時(shí)降低原發(fā)性肝癌TACE術(shù)病人血壓、脈率以及總不良反應(yīng)發(fā)生率;增加輕度疼痛以下人數(shù)比例。TACE術(shù)導(dǎo)致肝臟組織缺血缺氧、小動(dòng)脈痙攣、微循環(huán)血流阻滯以及血小板激活凝集等,使得肝臟及腫瘤組織腫脹增大以及緊張度增加,從而壓迫牽拉神經(jīng)導(dǎo)致疼痛,同時(shí)TACE術(shù)引起炎癥反應(yīng),組織胺、5羥色胺以及緩激肽等大量釋放,使得前列腺素釋放量增加,進(jìn)一步加重疼痛[9-11]。吲哚美辛栓是一種非甾體類(lèi)的鎮(zhèn)痛消炎藥,能夠非選擇性地抑制老年原發(fā)性肝癌TACE術(shù)病人體內(nèi)環(huán)氧化酶1和2的活性,從而抑制前列腺素的合成,同時(shí)吲哚美辛栓能夠緩解TACE術(shù)導(dǎo)致的小動(dòng)脈痙攣、組織腫脹以及血小板激活凝集,從而減輕炎癥反應(yīng),達(dá)到鎮(zhèn)痛的作用[12-13]。吲哚美辛栓通過(guò)肛門(mén)用藥,藥物直接通過(guò)腸黏膜進(jìn)入血液,增加了藥物的利用度、減少了對(duì)胃腸道的影響,從而減少了不良反應(yīng)的發(fā)生[14]。氨酚羥考酮片是一種對(duì)乙酰氨基酚組成的復(fù)方制劑,羥考酮具有中樞神經(jīng)止痛作用,而對(duì)乙酰氨基酚則具有周?chē)窠?jīng)止痛作用[15]。氨酚羥考酮片具有鎮(zhèn)痛效果強(qiáng)、作用時(shí)間長(zhǎng)以及成癮性小的特點(diǎn),其鎮(zhèn)痛效果隨劑量的增加而增加,鎮(zhèn)痛最高限度只能由不良反應(yīng)決定[16]。氨酚羥考酮片與吲哚美辛栓的鎮(zhèn)痛作用互補(bǔ),能夠從不同層面達(dá)到鎮(zhèn)痛的作用,因此吲哚美辛栓聯(lián)合氨酚羥考酮片能夠更好地緩解TACE術(shù)引起的疼痛,同時(shí)改善病人的血壓以及心率。重要的是,二種藥物作用時(shí)間較長(zhǎng),因此能夠減少術(shù)后疼痛持續(xù)時(shí)間。由于吲哚美辛栓與氨酚羥考酮片能夠緩解炎癥反應(yīng)以及具有有效的鎮(zhèn)痛作用,因此研究組病人TACE術(shù)后不良反應(yīng)發(fā)生率較低。吲哚美辛栓聯(lián)合氨酚羥考酮片對(duì)老年原發(fā)性肝癌TACE術(shù)引起的疼痛具有良好的治療效果。

[1] 徐麗麗, 李春暉, 張冰. 超聲引導(dǎo)下射頻消融聯(lián)合TACE治療進(jìn)展期原發(fā)性肝癌療效及并發(fā)癥分析[J]. 貴州醫(yī)藥, 2016,40(3):265-267.

[2] 倪宏, 王林, 李波. 老年乙肝相關(guān)性原發(fā)性肝癌早期檢測(cè)的標(biāo)志物研究[J]. 實(shí)用老年醫(yī)學(xué), 2016,30(7):578-581.

[3] Delaram M, Dadkhah NK, Jafarzadeh L. Comparison of indomethacin suppository and lidocaine cream on post-episiotomy pain: A randomized trial[J]. Ira J Nur Midwif Res, 2015,20(4):450-453.

[4] MS AKCM, Bijur PE, Lynne Holden MD, et al. Comparative analgesic efficacy of oxycodone/acetaminophen versus hydrocodone/acetaminophen for short-term pain management in adults following ED discharge[J]. Acad Emer Med, 2015,9(2):27-36.

[5] 劉典勛, 郭玉軍. 精準(zhǔn)肝切除術(shù)治療原發(fā)性肝癌對(duì)血清惡性生物學(xué)指標(biāo)的影響[J]. 海南醫(yī)學(xué)院學(xué)報(bào), 2015,21(6):822-824.

[6] 劉堯, 王宇, 雷光焰, 等. TACE聯(lián)合放射性粒子組織間放療對(duì)原發(fā)性肝癌患者惡性生物學(xué)指標(biāo)的影響[J]. 海南醫(yī)學(xué)院學(xué)報(bào), 2016,22(12):1303-1306.

[7] Jin W, Han H, Zhou S, et al. Therapeutic efficacy of brucea javanica oil emulsion (BJOE) combined with transcatheter hepatic arterial chemoembolization (TACE) in patients with primary liver cancer[J]. Int J Clin Exp Med, 2015,8(10):18954-18962.

[8] Wang Y, Deng T, Zeng L, et al. Unresectable hepatocellular carcinomas by MRI monitoring after transcatheter hepatic arterial chemoembolization[J]. Hepatol Res, 2015,16(3):389-397.

[9] Lin YY, Lee RC, Tseng HS, et al. Objective measurement of arterial flow before and after transcatheter arterial chemoembolization: A feasibility study using quantitative color-coding analysis[J]. Cardiovasc Inter Rad, 2015,38(6):1494-1501.

[10]Li XH, Wang YF, Sun GM. Transcatheter arterial chemoembolization combined with microwave coagulation therapy and the perioperative care for patients with hepatocellural carcinoma[J]. J Buon Off, 2015,20(4):1037-1041.

[11]Wu H, Zhao W, Liu S, et al. Pure transcatheter arterial chemoembolization therapy for intrahepatic tumors causes a shrink in pulmonary metastases of hepatocellular carcinoma[J]. Int J Cli Expl Med, 2015,8(1):1035-1042.

[12]Freeman ML, Kozarek RA. Take 2 indomethacin (suppositories) and call me in the morning? The evolving role of nonsteroidal antiinflammatory drugs in protection against post-endoscopic retrograde cholangiopancreatography pancreatitis[J]. Gastroenterology, 2016, 150(4):805-808.

[13]Zamanian F, Jalili M, Moradi-Lakeh M, et al. Morphine suppository versus indomethacin suppository in the management of renal colic: Randomized clinical trial[J]. Pain Res Treat, 2016,2016(2):1-6.

[14]Siddiqui AA, Patel D, Kaplan J, et al. A trial of rectal indomethacin to prevent post-ERCP pancreatitis in patients with suspected type 3 sphincter of oddi dysfunction[J]. Dig Dis Sci, 2015,60(8):2509-2515.

[15]Morton T, Franke R, Devarakonda K. Pooled post hoc analysis of population pharmacokinetics of oxycodone and acetaminophen following multiple oral doses of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets[J]. Pain Pra, 2016,16(6):730-736.

[16]Deveaughgeiss A, Kadakia A, Chilcoat H, et al. A retrospective cohort study of long-term immediate-release hydrocodone/acetaminophen use and acetaminophen dosing above the FDA recommended maximum daily limit among commercially insured individuals in the United States (2008-2013)[J]. J Pain Off, 2015,6(6):569-579.

ClinicalobservationofindometacinsuppositoriescombinedwithoxycodoneandacetaminophentabletsonpostoperativepainofTACEinelderlypatientswithhepatocellularcarcinoma

ZHUKun-xi,SHENChun-hua,WUWei-ben,MAZhan-long.

DepartmentofRadiology,ShengzeHospital,Suzhou215228,China;XIMing.DepartmentofAnesthesia,BenQHospital,Suzhou215000,China

ObjectiveTo observe the effect of indometacin suppositories combined with oxycodone and acetaminophen tablets on postoperative pain of transcatheter arterial chemoembolization((TACE) in elderly patients with hepatocellular carcinoma, and to offer help for postoperative pain in elderly patients with hepatocellular carcinoma TACE treatment.MethodsA total of 90 elderly patients with postoperative pain after hepatocellular carcinoma TACE were selected and randomly divided into control group and research group, with 45 cases in each group. The elderly patients in the control group were treated with indometacin suppositories. The elderly patients in the research group were treated with indometacin suppositories combined with oxycodone and acetaminophen tablets. Before and after therapy, pain severity and score, duration of pain, blood pressure, pulse and adverse reactions were recorded and compared between two groups.ResultsThe pain score, postoperative pain score, and the duration of postoperative pain in the research group were significantly lower than those in the control group (P<0.05). Blood pressure and pulse rate in the research group were significantly lower than those in the control group (P<0.05). The total adverse reaction rate of research group was significantly lower than that of the control group, and the proportion of patients with mild pain was significantly higher than that of the control group (P<0.05).ConclusionsIndomethacin suppositories combined with oxycodone and acetaminophen tablets have obvious analgesic effect and low side effect, which is beneficial to the treatment of TACE in elderly patients with primary liver cancer.

indomethacin suppositories; oxycodone and acetaminophen tablets; transcatheter arterial chemoembolization; hepatocellular carcinoma; postoperative pain

215228江蘇省蘇州市,江蘇盛澤醫(yī)院放射科(朱昆喜,沈春華,吳偉本,馬占龍);215000江蘇省蘇州市,蘇州明基醫(yī)院麻醉科(郗鳴)

郗鳴,Email:kiki39918@sina.com

R 735.7

A

10.3969/j.issn.1003-9198.2017.09.012

2016-10-19)