阿拉木斯，任德辰

·臨床醫(yī)學(xué)·

·論著·

三種藥物對(duì)全身麻醉外科手術(shù)后惡心嘔吐的預(yù)防作用

阿拉木斯，任德辰

目的 評(píng)估和比較昂丹司瓊、格拉司瓊和雷莫司瓊對(duì)全身麻醉下進(jìn)行的外科手術(shù)后的惡心嘔吐(postoperative nausea and vomiting, PONV)的預(yù)防作用。方法 90例被確診為美國麻醉師協(xié)會(huì)(ASA)分級(jí)為I和II級(jí)患者，年齡20～65歲，預(yù)定在全身麻醉下進(jìn)行外科手術(shù)。經(jīng)患者知情同意，并簽署知情同意書后，將全部患者分成3組，每組30例。昂丹司瓊組：昂丹司瓊0.1 mg/kg，格拉司瓊組：格拉司瓊40 μg/kg，雷莫司瓊組：雷莫司瓊0.3 mg，用5 ml生理鹽水稀釋藥物后在麻醉前5 min通過靜脈給藥。在術(shù)后的第1個(gè)24 h，記錄所發(fā)生的惡心、嘔吐和干嘔等癥狀情況。如沒有發(fā)生惡心、嘔吐、干嘔和使用緊急止吐藥則為完全發(fā)揮藥效，以此評(píng)估藥物的作用。用單因素方差分析和卡方檢驗(yàn)對(duì)獲得的數(shù)據(jù)進(jìn)行觀察。結(jié)果 術(shù)后0～3 h期間，所有實(shí)驗(yàn)組之間沒有明顯區(qū)別(P>0.05)；在術(shù)后3～24 h期間，雷莫司瓊和昂丹司瓊有明顯的區(qū)別，昂丹司瓊組70%的患者無惡心、嘔吐和干嘔，雷莫司瓊組93%的患者無惡心、嘔吐和干嘔，2組比較差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。然而，在同樣的時(shí)期格拉司瓊和雷莫司瓊之間沒有區(qū)別(P>0.05)。結(jié)論 術(shù)后0～3 h內(nèi)，所有的研究藥物對(duì)預(yù)防惡心、嘔吐和干嘔的作用沒有明顯的區(qū)別。在術(shù)后3～24 h階段，格拉司瓊和雷莫司瓊與昂丹司瓊相比能更好的預(yù)防PONV。

全身麻醉；外科手術(shù)；惡心嘔吐； 昂丹司瓊；格拉司瓊；雷莫司瓊

外科手術(shù)后的惡心嘔吐(postoperative nausea and vomiting, PONV)是施行全身麻醉的外科手術(shù)中最有危險(xiǎn)性的副作用。PONV導(dǎo)致傷口裂開、出血、誤吸、電解質(zhì)紊亂、延長出院時(shí)間和減少患者的安全性等并發(fā)癥。導(dǎo)致PONV發(fā)生的因素較多，包括患者、手術(shù)和麻醉相關(guān)因素?；颊呦嚓P(guān)的因素有年齡、體質(zhì)量、性別、術(shù)前存在的疾病、術(shù)后惡心、嘔吐、干嘔病史和吸煙史。有趣的是，不吸煙者發(fā)生PONV的傾向性是吸煙者的2倍[1]。預(yù)防PONV的藥物有很多種，包括傳統(tǒng)止吐藥，如胃復(fù)安(多巴胺受體拮抗劑)；最近引進(jìn)的止吐藥，如昂丹司瓊、格拉司瓊和雷莫司瓊(5-羥色胺受體阻斷劑)。探索這些藥物在接受全身麻醉患者中預(yù)防PONV的潛力及其臨床效果是本實(shí)驗(yàn)的目的。因此，可以通過實(shí)驗(yàn)評(píng)估比較昂丹司瓊、格拉司瓊和雷莫司瓊在實(shí)施全身麻醉的外科手術(shù)后預(yù)防PONV的作用。

1 資料與方法

1.1 研究對(duì)象 本試驗(yàn)選擇90例被確診為美國麻醉師協(xié)會(huì)(ASA)分級(jí)I級(jí)和II級(jí)，年齡20～65歲，預(yù)定施行全身麻醉進(jìn)行外科手術(shù)的患者。實(shí)驗(yàn)排除標(biāo)準(zhǔn)為：有暈動(dòng)癥病史，曾經(jīng)發(fā)生術(shù)后惡心嘔吐史，前庭病變，體質(zhì)量指數(shù)(body mass index， BMI)>30和圍術(shù)期24 h內(nèi)使用過止吐藥的患者。經(jīng)醫(yī)院倫理委員會(huì)的允許并通過書面形式告知患者。經(jīng)患者知情同意，并簽署知情同意書后，將全部患者分為3組，每組平均30人。

1.2 方法 所有的藥物均用5 ml的生理鹽水稀釋后通過靜脈給藥，昂丹司瓊0.1 mg/kg(昂丹司瓊組)、格拉司瓊40 μg/kg(格拉司瓊組)和雷莫司瓊0.3 mg(雷莫司瓊組)。實(shí)驗(yàn)藥物由單人準(zhǔn)備，要求其不知道實(shí)驗(yàn)藥物的使用情況?；颊咴谛g(shù)前建立好靜脈通道后，進(jìn)入手術(shù)室并且連接監(jiān)護(hù)儀，在麻醉誘導(dǎo)前5 min對(duì)每個(gè)患者注射5 ml的實(shí)驗(yàn)藥物。所有患者通過標(biāo)準(zhǔn)的麻醉誘導(dǎo)，使用曲馬多(0.5 mg/kg)、丙泊酚(2 mg/kg)、羅庫溴銨(0.6 mg/kg)進(jìn)行氣管插管。保持氧流量2 L/min，麻醉維持使用0.5%～2.0%的七氟醚和瑞芬太尼[0.25～2.0 μg/(kg·h)]根據(jù)手術(shù)進(jìn)程和肌松情況追加羅庫溴銨。術(shù)前監(jiān)測(cè)包括持續(xù)的心電圖、血壓、心率、呼吸頻率、血氧飽和度等生命體征。在手術(shù)結(jié)束時(shí)所有患者靜脈注射新斯的明50 μg/kg拮抗殘余的神經(jīng)肌肉阻滯作用。在患者恢復(fù)自主呼吸后拔出氣管導(dǎo)管，并送往恢復(fù)室。由同一實(shí)驗(yàn)者記錄患者術(shù)后的惡心、嘔吐和干嘔的發(fā)生情況。緊急止吐藥為從靜脈注射0.2 mg/kg的胃復(fù)安。惡心的定義為令人不愉快的感覺聯(lián)合嘔吐的沖動(dòng)。干嘔是腹部肌肉不自主的有節(jié)律的收縮，但沒有胃內(nèi)容物排出。沒有發(fā)生惡心、嘔吐、干嘔和不使用緊急止吐藥則稱為完全發(fā)揮藥效。結(jié)果制作成表使用單因素方差分析或者使用卡方檢驗(yàn)進(jìn)行統(tǒng)計(jì)學(xué)分析。

2 結(jié)果

在昂丹司瓊、格拉司瓊和雷莫司瓊3組患者中，年齡、體質(zhì)量指數(shù)和麻醉時(shí)間沒明顯區(qū)別(P>0.05)。術(shù)后的0～3 h內(nèi)，3組的PONV發(fā)生率差異無統(tǒng)計(jì)學(xué)意義(P>0.05)。見表1。昂丹司瓊組：惡心13.3%，嘔吐13.3%；格拉司瓊組：惡心10%，嘔吐13.3%；雷莫司瓊組：惡心3.3%，嘔吐6.7%。在昂丹司瓊、格拉司瓊和雷莫司瓊3組中需要緊急止吐藥患者的百分比分別為13.3%、13.3%和3.3%，而在術(shù)后3～24 h內(nèi)分別為23.3%、10.0%和6.7%(表2)。術(shù)后0～3 h期間，3組之間藥物對(duì)于預(yù)防惡心、嘔吐、干嘔和緊急止吐藥的使用結(jié)果比較差異無統(tǒng)計(jì)學(xué)意義(P>0.05)。雖然無統(tǒng)計(jì)學(xué)意義，但在雷莫司瓊組中僅有3.3%的患者使用了緊急止吐藥。在術(shù)后的3～24 h期間，雷莫司瓊與格拉司瓊相比和昂丹司瓊與格拉司瓊相比，對(duì)于預(yù)防惡心、嘔吐、干嘔和緊急止吐藥的使用結(jié)果比較差異無統(tǒng)計(jì)學(xué)意義(P>0.05)。然而，在術(shù)后的3～24 h期間，昂丹司瓊與雷莫司瓊的使用結(jié)果相比差異有統(tǒng)計(jì)學(xué)意義(P<0.05)(表3)。

表1 昂丹司瓊組、格拉司瓊組和雷莫司瓊組術(shù)后0～3 h發(fā)生惡心嘔吐的情況(每組n=30)

3 討論

PONV的病因是多因素的，與患者自身、外科手術(shù)和麻醉有著多種相關(guān)因素?；颊呦嚓P(guān)的因素包括年齡、體質(zhì)量、性別、存在的疾病、曾經(jīng)有惡心嘔吐病史、焦慮和吸煙。高發(fā)生率的外科手術(shù)如斜視手術(shù)、中耳手術(shù)，而使用阿片類藥物，氯胺酮和新斯的明等藥物也增加PONV的發(fā)生率?；颊呋顒?dòng)、血容量不足和過早的進(jìn)行交流都可能增加患者發(fā)生PONV的風(fēng)險(xiǎn)?？诜?.5 mg阿普唑侖保證晚上有好的睡眠，丙泊酚快速誘導(dǎo)麻醉和靜脈注射75 mg雙氫滅痛有助于減緩術(shù)前的焦慮和術(shù)后疼痛。本實(shí)驗(yàn)中藥物使用的劑量是基于之前發(fā)表的文獻(xiàn)。3組藥物都是選擇性的5-羥色胺-3受體拮抗劑對(duì)治療患者的PONV是有效的[2]。5-羥色胺-3受體拮抗劑被視為預(yù)防化療和放療引起的嘔吐的金標(biāo)準(zhǔn)。眾所周知，在相同的有效劑量下5-羥色胺-3拮抗劑具有更明顯的臨床止吐作用和安全性。發(fā)現(xiàn)昂丹司瓊、格拉司瓊和雷莫司瓊這3種藥物明顯減少術(shù)后3 h內(nèi)的PONV發(fā)生率。然而，在術(shù)后3～24 h期間，昂丹司瓊組和雷莫司瓊組之間出現(xiàn)明顯的不同。2010年Choi等[3]報(bào)道了相似的結(jié)果，證明在術(shù)后的6～24 h期間，雷莫司瓊預(yù)防PONV的效果優(yōu)于昂丹司瓊。這一發(fā)現(xiàn)與Hahm等的研究一致[4]。在術(shù)后24 h期間，昂丹司瓊和格拉司瓊之間沒有明顯的區(qū)別，有些實(shí)驗(yàn)同樣支持這一觀點(diǎn)[5-7]。本研究未能在昂丹司瓊組和格拉司瓊組之間發(fā)現(xiàn)區(qū)別，可能與僅僅限制在24 h有關(guān)?？傊?，預(yù)防性的使用昂丹司瓊、格拉司瓊和雷莫司瓊都能減少術(shù)后3 h內(nèi)惡心和嘔吐的發(fā)生率。然而，在術(shù)后的24 h內(nèi)，雷莫司瓊能夠更有效地預(yù)防PONV的發(fā)生。

表2 昂丹司瓊組、格拉司瓊組和雷莫司瓊組術(shù)后3～24 h發(fā)生惡心嘔吐的情況(每組n=30)

表3 術(shù)后昂丹司瓊組、格拉司瓊組和雷莫司瓊組無惡心、嘔吐和干嘔的情況(每組n=30)

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[3] Choi YS, Shim JK, Yoon DH, et al. Effect of ramosetron on patient-controlled analgesia related nausea and vomiting after spine surgery in highly susceptible patients: comparison with ondansetron[J]. Spine, 2008, 33(17): E602-E606. DOI:10.1097/BRS.0b013e31817c6bde.

[4] Hahm TS, Ko JS, Choi SJ, et al. Comparison of the prophylactic anti-emetic efficacy of ramosetron and ondansetron in patients at high-risk for postoperative nausea and vomiting after total knee replacement[J]. Anaesthesia, 2010, 65(5): 500-504. DOI:10.1111/j.1365-2044.2010.06310.x.

[5] Fujii Y, Tanaka H, Ito M. Ramosetron compared with granisetron for the prevention of vomiting following strabismus surgery in children[J]. Br J Ophthalmol, 2001, 85(6): 670-672. DOI:10.1136/bjo.85.6.670.

[6] Schwartzberg L, Barbour SY, Morrow GR, et al. Pooled analysis of phase III clinical studies of palonosetron versus ondansetron, dolasetron, and granisetron in the prevention of chemotherapy-induced nausea and vomiting (CINV)[J]. Support Care Cancer, 2014, 22(2): 469-477. DOI:10.1007/s00520-013-1999-9.

[7] Lee WS, Lee KB, Lim S, et al. Comparison of palonosetron, granisetron, and ramosetron for the prevention of postoperative nausea and vomiting after laparoscopic gynecologic surgery: a prospective randomized trial[J]. BMC Anesthesiology, 2015, 15(1)： 121-125. DOI:10.1186/s12871-015-0102-0.

(本文編輯：林永麗)

Protective effects of the 3 drugs on postsurgical nausea and vomiting under general anesthesia

Alamus,RenDechen

(HospitalofOnshoreServiceDepartmentofNavalVessels,Dalian161041,China)

Objective To evaluate and compare the preventive effects of ondansetron, granisetron and ramosetron on postsurgical nausea and vomiting under general anesthesia.Methods Ninety patients of ASA grade I and II with an age range of 20-65 years were scheduled for surgery under general anesthesia. With the knowledge and consent of the patients and following the signing of the letter of agreement, the patients were divided into 3 groups, each consisting of 30. The patients

the following drugs intravenously. The ondansetron group received 0.1 mg/kg ondansetron, the granisetron group was given granisetron at a dose of 40 μg/kg, and the ramosetron group had 0.3 mg ramosetron, which was diluted with 5 ml physiological saline and transfused intravenously 5 minute before surgery. Episodes of nausea, vomiting and retching were recorded in the first 24 hours after surgery. If there were no nausea, retching or vomiting or if acute antiemetic drug was used, it showed that the drugs had produced certain effect upon which the drugs were evaluated. Observation results were assessed and analyzed by using analysis of variance (ANOVA) and chi-square test.Results Within 0-3 hours after surgery, no statistical significance could be noted in all the study groups (P>0.05). Within the period of 3-24 hours, significant differences could be shown, when comparisons were made between the ramosetron group and the ondansetron group. Seventy per cent of the patients in the ondansetron group had no nausea and vomiting or retching, while 93% of the patients in the ramosetron group had no nausea and vomiting or retching. Statistical significance could be noted, when comparisons were made between them (P<0.05). However, during the period, no significant statistical differences could be seen between the granisetron and the ramosetron groups (P>0.05).Conclusion Within 0-3 hours after surgery, all the study drugs were not significantly different in the prevention of nausea, retching and vomiting. However, both ramosetron and granisatron were superior to ondansetron in the prevention of PONV within the period of 3-24 hours after surgery.

General anesthesia; Surgery; Nausea and vomiting; Ondansetron; Granisetron; Ramosetron

161041 遼寧 大連，解放軍92538部隊(duì)衛(wèi)生處

任德辰，電子信箱：rendecheng1988927@163.com

R975.4

A

10.3969/j.issn.1009-0754.2017.04.021

2016-05-31)