陳劉芳， 肖 翔， 陳中剛， 吳 云， 劉友坦*

1. 南方醫(yī)科大學(xué)深圳醫(yī)院麻醉科，深圳 518000 2. 武漢大學(xué)中南醫(yī)院麻醉科，武漢 430071

·短篇論著·

胃癌根治患者術(shù)后應(yīng)用鹽酸羥考酮的鎮(zhèn)痛效果觀察

陳劉芳1,2， 肖 翔1， 陳中剛1， 吳 云2， 劉友坦1*

1. 南方醫(yī)科大學(xué)深圳醫(yī)院麻醉科，深圳 518000 2. 武漢大學(xué)中南醫(yī)院麻醉科，武漢 430071

目的： 觀察胃癌根治切除術(shù)患者術(shù)后應(yīng)用鹽酸羥考酮的鎮(zhèn)痛效果。方法： 選取本院2014年4月至2015年6月進(jìn)行胃癌切除術(shù)患者90例作為主要觀察對(duì)象，術(shù)后均進(jìn)行鎮(zhèn)痛泵治療，采用隨機(jī)數(shù)字表法將患者分為觀察組(采用鹽酸羥考酮進(jìn)行止痛，n=45)和對(duì)照組(采用舒芬太尼進(jìn)行止痛，n=45)，比較兩組患者術(shù)后不同時(shí)間點(diǎn)鎮(zhèn)痛效果(疼痛視覺(jué)模擬評(píng)分法)、嗎啡補(bǔ)充應(yīng)用劑量、鎮(zhèn)靜評(píng)分變化及不良反應(yīng)情況。結(jié)果： 觀察組患者在術(shù)后2 h及術(shù)后48 h鎮(zhèn)痛效果與對(duì)照組比較差異無(wú)統(tǒng)計(jì)學(xué)意義；觀察組患者在術(shù)后6、12、24 h鎮(zhèn)痛效果均低于對(duì)照組(P<0.05)；觀察組患者術(shù)后48 h內(nèi)共2例患者補(bǔ)充應(yīng)用嗎啡肌注(40 mg)，低于對(duì)照組補(bǔ)充用藥患者數(shù)(9例)和用藥總量(150 mg)，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。觀察組患者自控按壓藥物次數(shù)低于對(duì)照組(P<0.05)；觀察組患者在術(shù)后2 h及術(shù)后48 h鎮(zhèn)靜評(píng)分與對(duì)照組比較差異無(wú)統(tǒng)計(jì)學(xué)意義；觀察組患者Ramsay鎮(zhèn)靜評(píng)分在術(shù)后6、12、24 h均高于對(duì)照組(P<0.05)。觀察組患者術(shù)后48 h內(nèi)患者中有2例出現(xiàn)惡心及嘔吐，低于對(duì)照組的10例(P<0.05)。結(jié)論： 采用鹽酸羥考酮進(jìn)行胃癌根治切除術(shù)患者術(shù)后鎮(zhèn)痛效果滿意，不良反應(yīng)小，值得臨床推廣。

鹽酸羥考酮；胃癌；疼痛；鎮(zhèn)痛

隨著現(xiàn)代醫(yī)學(xué)模式的深入發(fā)展，臨床對(duì)患者的生理及心理的關(guān)注程度明顯提高。胃癌根治術(shù)術(shù)后的急性疼痛雖然具有自限性，但治療不及時(shí)會(huì)遷延為慢性疼痛。目前臨床主要通過(guò)嗎啡或舒芬太尼對(duì)胃癌患者術(shù)后疼痛進(jìn)行鎮(zhèn)痛[1]。研究[2]表明，鹽酸羥考酮能夠明顯緩解乳腺癌改良根治手術(shù)后急性疼痛。因此，本研究嘗試將其應(yīng)用于胃癌根治切除術(shù)術(shù)后患者鎮(zhèn)痛，探討其鎮(zhèn)痛效果，為后續(xù)臨床應(yīng)用提供支持。

1 資料與方法

1.1 一般資料 選擇從2014年4月至2015年6月入住本院進(jìn)行胃癌切除術(shù)患者90例，術(shù)后均進(jìn)行鎮(zhèn)痛泵治療，采用隨機(jī)數(shù)字表法將患者分為觀察組(采用鹽酸羥考酮進(jìn)行止痛)45例，對(duì)照組(采用舒芬太尼進(jìn)行止痛)45例。納入標(biāo)準(zhǔn)：患者經(jīng)胃鏡檢查確診胃癌，診斷符合《中華人民共和國(guó)衛(wèi)生行業(yè)標(biāo)準(zhǔn):胃癌診斷標(biāo)準(zhǔn)(WS 316-2010)》；患者年齡50～60歲；患者對(duì)羥考酮及舒芬太尼均無(wú)變態(tài)反應(yīng)；患者癌癥分期為0期或ⅠA期；符合美國(guó)麻醉師協(xié)會(huì)(ASA)麻醉分級(jí)Ⅰ～Ⅱ級(jí)。排除標(biāo)準(zhǔn)：除外患者伴發(fā)機(jī)體其他部位腫瘤；嚴(yán)重肝腎損傷患者；精神異?；颊?；手術(shù)不成功及術(shù)后手術(shù)切口難愈合者。本研究經(jīng)醫(yī)院醫(yī)學(xué)倫理委員會(huì)審核通過(guò)，所有患者均知情同意并簽署知情同意書(shū)。

1.2 麻醉方法

1.2.1 術(shù)前準(zhǔn)備 術(shù)前兩組患者均禁食水8 h。入手術(shù)室后，進(jìn)行吸氧、心電監(jiān)護(hù)等措施，實(shí)時(shí)監(jiān)護(hù)患者脈搏、血氧飽和度、開(kāi)放2條或2條以上靜脈通路，穿刺橈動(dòng)脈并監(jiān)測(cè)有創(chuàng)動(dòng)脈血壓及中心靜脈壓。

1.2.2 手術(shù)麻醉 對(duì)兩組患者進(jìn)行靜脈注射，包括咪達(dá)唑侖0.05 mg/kg，阿托品0.5 mg，芬太尼4 μg/kg，依托咪酯0.3 mg/kg，羅庫(kù)溴銨0.9 mg/kg；術(shù)中兩組患者均給予丙泊酚注射液，注射用鹽酸瑞芬太尼0.2～0.4 μg/(kg·min)進(jìn)行麻醉維持，間斷注射順阿曲庫(kù)銨維持肌肉松弛。手術(shù)結(jié)束前，停止丙泊酚注射，對(duì)照組應(yīng)用枸櫞酸舒芬太尼注射液0.1 μg/(kg·min)，觀察組應(yīng)用鹽酸羥考酮注射液0.1 mg/(kg·min)，手術(shù)結(jié)束時(shí)可短期應(yīng)用預(yù)防惡心、嘔吐的藥物。

1.2.3 術(shù)后鎮(zhèn)痛 患者術(shù)后開(kāi)啟靜脈止痛泵，靜脈泵容量100 mL，對(duì)照組術(shù)后采用舒芬太尼鎮(zhèn)痛，靜脈泵含舒芬太尼2 μg/kg；觀察組患者以鹽酸羥考酮為主，靜脈泵含羥考酮1 mg/kg；注射速率為2 mL/h，單次按壓劑量為0.5 mL，鎖定時(shí)間設(shè)置在15 min，患者鎮(zhèn)痛效果不理想，可以采用嗎啡肌肉注射10 mg/次。

1.3 疼痛程度評(píng)價(jià)標(biāo)準(zhǔn) 患者術(shù)后鎮(zhèn)痛效果(疼痛視覺(jué)模擬評(píng)分法)[3]：讓患者自己進(jìn)行痛感評(píng)價(jià)，以0～10分為標(biāo)準(zhǔn)，0分為無(wú)痛感，10分為極度疼痛；臨床評(píng)定以“0～2”分為“優(yōu)”，“3～5”分為“良”，“6～8”分為“可”，“>8”分為“差”。根據(jù)兩組患者術(shù)后不同時(shí)期疼痛感覺(jué)進(jìn)行分類(lèi)統(tǒng)計(jì)。Ramsay鎮(zhèn)靜評(píng)分變化[4]：按照患者鎮(zhèn)靜程度分為6個(gè)層次，以1～6進(jìn)行分級(jí)，1級(jí)煩躁不安，2級(jí)清醒且能安靜合作，3級(jí)嗜睡并對(duì)指令反應(yīng)敏捷，4級(jí)處于淺睡眠狀態(tài)仍可迅速喚醒，5級(jí)入睡狀態(tài)對(duì)呼叫反應(yīng)遲鈍，6級(jí)處于深睡狀態(tài)且對(duì)呼叫無(wú)反應(yīng)。按照患者所處層次計(jì)分，即1級(jí)計(jì)為1分，統(tǒng)計(jì)兩組患者的各時(shí)段總分進(jìn)行比較。

1.4 觀察指標(biāo) 記錄患者在術(shù)后2 h(T0)、術(shù)后6 h(T1)、術(shù)后12 h(T2)、術(shù)后24 h(T3)、術(shù)后48 h(T4)的鎮(zhèn)痛效果及嗎啡補(bǔ)充應(yīng)用劑量、患者自控按壓藥物的次數(shù)以及手術(shù)后不良反應(yīng)的發(fā)生情況。

2 結(jié) 果

2.1 一般資料 對(duì)照組患者男30例、女15例，年齡51～60歲、平均(57.36±4.13)歲，體質(zhì)量(78.25±10.43) kg；觀察組男29例、女16例，年齡52～60歲、平均(58.41±5.13)歲，體質(zhì)量(80.15±9.86)kg。兩組患者一般資料差異無(wú)統(tǒng)計(jì)學(xué)意義。

2.2 兩組患者術(shù)后不同時(shí)間點(diǎn)鎮(zhèn)痛效果的對(duì)比 結(jié)果(表1)表明：觀察組患者在術(shù)后2 h及術(shù)后48 h鎮(zhèn)痛效果與對(duì)照組比較差異無(wú)統(tǒng)計(jì)學(xué)意義；觀察組患者在術(shù)后6 h、12 h、24 h疼痛評(píng)分均低于對(duì)照組(P<0.05)。

表1 兩組患者術(shù)后不同時(shí)間點(diǎn)鎮(zhèn)痛效果(疼痛評(píng)分)的比較 n=45,

*P<0.05與對(duì)照組相比

2.3 患者嗎啡補(bǔ)充情況及自控按壓藥物次數(shù)的對(duì)比 結(jié)果(表2)表明：觀察組患者術(shù)后48 h內(nèi)共2例患者補(bǔ)充應(yīng)用嗎啡，共注射40 mg，低于對(duì)照組補(bǔ)充用藥患者數(shù)(9例)和用藥總量150 mg(P<0.05)；觀察組患者自控按壓藥物次數(shù)顯著低于對(duì)照組(P<0.05)。

表2 患者嗎啡補(bǔ)充情況及患者自控按壓藥物次數(shù)

**P<0.01，*P<0.05與對(duì)照組相比

2.4 鎮(zhèn)靜評(píng)分變化以及不良反應(yīng)情況 結(jié)果(表3)表明：觀察組患者在術(shù)后2 h及術(shù)后48 h鎮(zhèn)靜評(píng)分與對(duì)照組比較差異無(wú)統(tǒng)計(jì)學(xué)意義；觀察組患者Ramsay鎮(zhèn)靜評(píng)分在術(shù)后6 h、12 h、24 h均高于對(duì)照組(P<0.05)；觀察組患者術(shù)后48 h內(nèi)患者中有2例(4.44%)出現(xiàn)惡心及嘔吐，低于對(duì)照組10例(22.22%，P<0.05)。

表3 Ramsay鎮(zhèn)靜評(píng)分變化情況的比較 n=45,

*P<0.05與對(duì)照組相比

3 討 論

胃癌屬于常見(jiàn)惡性腫瘤，會(huì)造成機(jī)體嚴(yán)重影響[5]。而胃癌患者主要以手術(shù)根治為主，作為腹部手術(shù)其術(shù)后疼痛非常明顯，且疼痛會(huì)引起機(jī)體出現(xiàn)多種并發(fā)癥。臨床常見(jiàn)術(shù)后鎮(zhèn)痛藥物主要以舒芬太尼和羥考酮為主[6]。舒芬太尼是臨床常用的阿片類(lèi)鎮(zhèn)痛藥物，鎮(zhèn)痛效果良好，但如果劑量過(guò)大會(huì)引起呼吸抑制、嗜睡、惡心等不良反應(yīng)，甚至可能會(huì)出現(xiàn)心動(dòng)過(guò)緩等情況[7]。與之相比，羥考酮不僅能夠減輕手術(shù)疼痛，還能夠降低患者的不良反應(yīng)發(fā)生情況[8]，極大提升手術(shù)后的鎮(zhèn)痛效果，并且預(yù)防不良反應(yīng)發(fā)生，使患者能夠更快康復(fù)，提高預(yù)后效果。因此，在臨床上通常使用不同鎮(zhèn)痛方法或多種鎮(zhèn)痛聯(lián)合應(yīng)用來(lái)進(jìn)行術(shù)后鎮(zhèn)痛[9]。

本研究發(fā)現(xiàn)，觀察組患者在術(shù)后6、12、24 h疼痛評(píng)分均低于對(duì)照組(P<0.05)。舒芬太尼是一種高選擇性的阿片受體激動(dòng)劑，通過(guò)影響患者延髓、脊髓等痛覺(jué)傳導(dǎo)區(qū)的阿片受體來(lái)產(chǎn)生作用，并且跟其有效結(jié)合[10]。但對(duì)于患者的內(nèi)臟痛，該藥難以取得較好的鎮(zhèn)痛效果，且劑量過(guò)大還會(huì)造成患者嘔吐、惡心等不良反應(yīng)[11]。羥考酮是目前臨床上唯一使用的純阿片雙受體激動(dòng)劑，能夠同時(shí)激動(dòng)κ、μ受體，相比舒芬太尼，該藥能夠起到更好的鎮(zhèn)痛效果[12]。因此，術(shù)后鎮(zhèn)痛應(yīng)用鹽酸羥考酮鎮(zhèn)痛效果起效更快，效果更佳。本研究觀察組患者術(shù)后48 h內(nèi)共2例患者補(bǔ)充應(yīng)用嗎啡，共注射40 mg，低于對(duì)照組補(bǔ)充用藥患者數(shù)和用藥總量(P<0.05)。有研究[13-15]表明，羥考酮具有極高的生物利用度，靜脈注射該藥可以在2～3 min內(nèi)起到鎮(zhèn)痛效果，在5 min時(shí)血藥濃度會(huì)達(dá)到最大值，具有較長(zhǎng)的鎮(zhèn)痛時(shí)間，所以靜脈注射該藥品可起到更好的鎮(zhèn)痛效果[16-17]。多項(xiàng)研究[18-20]表明，應(yīng)用羥考酮的患者補(bǔ)救鎮(zhèn)痛率更低，與本研究結(jié)果一致。觀察組患者自控按壓藥物次數(shù)低于對(duì)照組(P<0.05)；Ramsay鎮(zhèn)靜評(píng)分在術(shù)后6 h、12 h、24 h均高于對(duì)照組(P<0.05)。應(yīng)用羥考酮患者術(shù)后48 h內(nèi)2例出現(xiàn)惡心嘔吐，低于對(duì)照組(P<0.05)。本研究發(fā)現(xiàn)術(shù)后鎮(zhèn)痛藥物不良反應(yīng)主要以胃腸道反應(yīng)為主，患者惡心及嘔吐發(fā)生率越低，其影響越小，對(duì)臨床康復(fù)越有利。

綜上所述，采用鹽酸羥考酮進(jìn)行胃癌根治切除術(shù)患者術(shù)后鎮(zhèn)痛效果滿意，比照應(yīng)用舒芬太尼不良反應(yīng)小，鎮(zhèn)痛效果滿意度高，值得臨床推廣。

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[本文編輯] 廖曉瑜， 賈澤軍

Clinical efficacy of oxycodone hydrochloride in treatment with postoperative analgesia in patients with radical gastrectomy

CHEN Liu-fang1,2, XIAO Xiang1, CHEN Zhong-gang1, WU Yun2, LIU You-tan1*

1. Department of Anesthesiology, Shenzhen Hospital of Southern Medical University, Shenzhen 518000, Guangdong, China2. Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China

Objective： To observe the effect of oxycodone hydrochloride on postoperative analgesic in patients with radical resection of gastric cancer. Methods： Totally 90 cases with gastric cancer resection in hospital April 2014 and 2015 June were selected and divided into observation group (treated with oxycodone hydrochloride for pain) in 45 cases, control group (treated with sufentanil for pain) in 45 cases. The analgesia effect (pain visual analogue score) at different time, morphina supplement dosage, changes of sedation scores and adverse reactions were compared. Results： The patients in the observation group after operation and postoperative analgesic effect of 2 h and 48 h compared with the control group had no significant difference; the patients in the observation group after operation 6 h, 12 h and 24 h analgesic effect was significantly lower than the control group (P<0.05); the patients in the observation group after 48 h in patients with a total of 2 cases of application of intramuscular injection of morphine, 40 mg was significantly lower than the control group of patients (9 cases) and the number of the total dosage of 150 mg (P<0.05); the number of drug automatic pressing in the observation group was significantly lower than the control group (P<0.05); patients in the observation group after the surgery and postoperative 2 h and 48 h score compared with the control group. The Ramsay sedation score in postoperative 6 h, 12 h, 24 h in observation group were significantly higher than control group (P<0.05); Two cases in observation group had nausea and vomiting after 48h of operation, which was lower than the control group of 10 cases (P<0.05). Conclusions： The oxycodone hydrochloride has satisfied effect on analgesia for gastric cancer radical resection with few adverse effect, which is worth of clinical promotion.

oxycodone hydrochloride; gastric cancer; pain; analgesia

2017-02-28 [接受日期] 2017-06-15

深圳市衛(wèi)生計(jì)生系統(tǒng)科研項(xiàng)目(201607037). Supported by Research Project of Health Planning System of Shenzhen (201607037).

陳劉芳，碩士，講師、主治醫(yī)師. E-mail: chenliufang48@163.com

*通信作者(Corresponding author). Tel: 0755-23329999, E-mail: 785433277@qq.com

10.12025/j.issn.1008-6358.2017.20170154

R 614

A