王婷婷 孫 申 王 琦 黃紹強(qiáng)
(復(fù)旦大學(xué)附屬婦產(chǎn)科醫(yī)院麻醉科 上海 200090)
腹腔鏡與開腹手術(shù)中單次輸注羅庫溴銨或順式阿曲庫銨后神經(jīng)肌肉阻滯時(shí)間的比較
王婷婷 孫 申 王 琦 黃紹強(qiáng)△
(復(fù)旦大學(xué)附屬婦產(chǎn)科醫(yī)院麻醉科 上海 200090)
目的 比較腹腔鏡與開腹手術(shù)中單次輸注羅庫溴銨或順式阿曲庫銨后神經(jīng)肌肉阻滯時(shí)間。方法 100例全麻下行擇期婦科手術(shù)的女性患者根據(jù)手術(shù)方式分為2組,各組再隨機(jī)分為羅庫溴銨組和順式阿曲庫銨組,共計(jì)4組,分別為羅庫溴銨開腹組(OR組)、順式阿曲庫銨開腹組(OC組)、羅庫溴銨腹腔鏡組(LR組)和順式阿曲庫銨腹腔鏡組(LC組),每組25例。每位患者均靜脈推注舒芬太尼0.5 μg/kg和丙泊酚2 mg/kg,待意識(shí)消失后按組別分別靜脈推注羅庫溴銨0.9 mg/kg或順式阿曲庫銨組0.15 mg/kg。記錄羅庫溴銨或順式阿曲庫銨注射后第1個(gè)成串刺激(T1)出現(xiàn)的時(shí)間及T1恢復(fù)到基礎(chǔ)值的5%和25%的時(shí)間。結(jié)果 OC組和LC組相比,神經(jīng)肌肉阻滯時(shí)間的差異無統(tǒng)計(jì)學(xué)意義。LR組與OR組相比,推注羅庫溴銨后T1出現(xiàn)的時(shí)間、T1恢復(fù)到基礎(chǔ)值的5%及25%的時(shí)間均顯著延長(P<0.05)[(36.2±4.0)minvs.(44.8±10.7)min,(41.8±6.8)minvs.(52.8±11.2)min,(49.5±7.5)minvs.(62.6±13.5)min]。結(jié)論 需警惕羅庫溴銨用于腹腔鏡手術(shù)時(shí)神經(jīng)肌肉阻滯時(shí)間的延長,必要時(shí)進(jìn)行肌松監(jiān)測。
氣腹; 神經(jīng)肌肉阻滯; 腹腔鏡; 肌松藥
腹腔鏡手術(shù)較傳統(tǒng)開腹手術(shù)有縮短住院天數(shù)、改善預(yù)后、美觀等優(yōu)點(diǎn)[1-3]。我們研究發(fā)現(xiàn)腹腔鏡手術(shù)較傳統(tǒng)開腹手術(shù)顯著延長單次劑量羅庫溴銨的神經(jīng)阻滯時(shí)間[4],推測這一現(xiàn)象與腹腔鏡對(duì)肝血流的影響有關(guān)。腹腔鏡手術(shù)時(shí)的頭低腳高截石位和氣腹會(huì)增加腹內(nèi)壓,使血液從腹部流向胸部,可能會(huì)減少肝臟血流量[5-7],從而影響主要通過肝攝取和膽汁排泄的羅庫溴銨的代謝[8]。
臨床上使用的不同種類的肌松藥有不同的代謝途徑,如順式阿曲庫銨主要通過非器官依賴的Hoffman反應(yīng)降解,受肝血流的影響較小[9],因此我們推測順式阿曲庫銨的代謝受腹腔鏡手術(shù)的影響較小。由于直接測量肝血流往往難以實(shí)現(xiàn),因此本研究比較腹腔鏡和傳統(tǒng)開腹手術(shù)時(shí),測量單次輸注3倍ED95劑量的羅庫溴銨和順式阿曲庫銨的神經(jīng)肌肉阻滯作用時(shí)間,以期為臨床工作提供參考。
研究對(duì)象 本研究已獲得復(fù)旦大學(xué)附屬婦產(chǎn)科醫(yī)院倫理委員會(huì)批準(zhǔn)(批號(hào):2014-34)。所有患者均簽署了知情同意書。選擇全麻下行擇期婦科手術(shù)的女性患者100例,手術(shù)時(shí)間預(yù)計(jì)約1 h,ASAⅠ~Ⅱ級(jí),年齡18~60歲,體質(zhì)指數(shù)(body mass index,BMI)18~30 kg/m2,無肝炎、肝硬化、肝癌,無心衰、哮喘、腎功能不全(肌酐清除率≤30 mL/min),無水電解質(zhì)、酸堿平衡紊亂,未服用過可能對(duì)神經(jīng)肌肉阻滯藥有影響的藥物,如抗生素、抗驚厥藥等,無預(yù)期插管困難(Mallampati評(píng)分[10]≥Ⅲ級(jí))。根據(jù)不同的手術(shù)方式分為開腹組和腹腔鏡組,各組再由隨機(jī)數(shù)字法隨機(jī)分為羅庫溴銨組和順式阿曲庫銨組,共計(jì)4組,每組25例,分別為開腹羅庫溴銨組(OR組)、開腹順式阿曲庫銨組(OC組)、腹腔鏡羅庫溴銨組(LR組)和腹腔鏡順式阿曲庫銨組(LC組)。
病例納入時(shí)間從2015年1月1日至2016年6月1日,手術(shù)時(shí)間為晨8:00—10:00。所有患者術(shù)前均未用藥,禁食至少8 h?;颊呷胧液箝_放手背部靜脈,以8 mL·kg-1·h-1的速度輸注乳酸鈉林格式液,監(jiān)測心電圖、血壓、氧飽和度和腦電雙頻指數(shù)(BIS,美國Aspect Medical Systems公司)。開腹組患者維持平臥位,腹腔鏡組患者維持頭低腳高20°截石位。所有患者靜脈推注舒芬太尼0.5 μg/kg和丙泊酚 2 mg/kg,待意識(shí)消失后按組別分別靜脈推注羅庫溴銨0.9 mg/kg (批號(hào):160105,浙江仙居醫(yī)藥股份有限公司)或順式阿曲庫銨0.15 mg/kg (批號(hào):16051118,江蘇恒瑞醫(yī)藥股份有限公司)。氣管插管后麻醉維持采用丙泊酚6~12 mg·kg-1·h-1和瑞芬太尼0.25 μg·kg-1·min-1,使腦電雙頻指數(shù)(bispectral index,BIS)值維持在40~60,調(diào)整呼吸參數(shù)使ETCO2維持在30~35 mmHg (1 mmHg=0.013 kPa,下同),監(jiān)測食道體溫,輸液維持體溫在36~37 ℃。腹腔鏡組患者氣腹內(nèi)壓力維持在12~15 mmHg。手術(shù)結(jié)束時(shí)停止輸注異丙酚和瑞芬太尼,待肌松阻滯完全恢復(fù)后,即第4個(gè)肌顫搐/第1個(gè)肌顫搐>0.9 (T4/T1>0.9)時(shí)拔除氣管導(dǎo)管。
記錄各組術(shù)前及術(shù)后24 h的谷草轉(zhuǎn)氨酶(glutamic-oxaloacetic transaminase,AST)、谷丙轉(zhuǎn)氨酶(glutamic-pyruvic transaminase,ALT)、尿素氮(blood urea nitrogen,BUN)、肌酐(creatinine,Cr)值。
肌松監(jiān)測 神經(jīng)肌肉傳導(dǎo)功能監(jiān)測采用肌張力定量神經(jīng)肌肉傳導(dǎo)監(jiān)測儀(型號(hào):HXD-1CO28,黑龍江華翔有限公司)。將患者前臂固定,醫(yī)用酒精消毒腕部皮膚,連接肌松監(jiān)測儀,陽性電極置于尺側(cè)腕屈肌的橈側(cè),距腕橫紋1 cm,陰性電極置于陽性電極近心端2~3 cm處,連接導(dǎo)線固定。拇指外展并以250 g的前負(fù)荷握住傳感器。推注舒芬太尼和丙泊酚后,開啟肌松監(jiān)測儀,啟動(dòng)4個(gè)成串刺激(TOF)模式(刺激電流50 mA,刺激頻率0.1 Hz,脈沖寬度200 μs,每組TOF間隔12 s),監(jiān)測拇內(nèi)收肌顫搐程度。當(dāng)肌松監(jiān)測達(dá)到穩(wěn)定狀態(tài),即第1個(gè)肌顫搐/單刺激顫搐(T1/Tc)和T4/T1的差異<5%,進(jìn)行定標(biāo)。定標(biāo)完成后快速推注(5 s內(nèi))各組指定的肌松藥(羅庫溴銨或順式阿曲庫銨組),當(dāng)神經(jīng)肌肉阻滯達(dá)到最大程度時(shí)進(jìn)行氣管插管。記錄靜脈注射羅庫溴銨或順式阿曲庫銨組后T1出現(xiàn)的時(shí)間、T1恢復(fù)到基礎(chǔ)值的5%及25%的時(shí)間。為了減少誤差,選擇連續(xù)3次超過設(shè)定水平的平均時(shí)間為最終時(shí)間。當(dāng)T1恢復(fù)到基礎(chǔ)值的25%時(shí)研究終止。
若發(fā)生低血壓(平均動(dòng)脈壓低于基礎(chǔ)值的30%或低于60 mmHg),靜推去氧腎上腺素50 μg;若出現(xiàn)心動(dòng)過緩(心率<50次/分),靜推阿托品0.5 mg。如果術(shù)中發(fā)生異常體動(dòng)或手術(shù)醫(yī)師要求加深肌肉松弛程度,則追加推注肌松藥。剔除追加肌松藥的患者。
最初入組100例患者,每組25例,LC組有2例患者在T1恢復(fù)至基礎(chǔ)值的5%~25%時(shí),應(yīng)手術(shù)醫(yī)師要求加深神經(jīng)肌肉阻滯程度而追加了肌松藥,故被剔除。最終98例患者納入研究。
羅庫溴銨兩組間及順式阿曲庫銨兩組間比較,在年齡、身高、BMI、ASA分級(jí)、氣管插管至手術(shù)開始的時(shí)間、手術(shù)持續(xù)時(shí)間、手術(shù)類型等方面的差異無統(tǒng)計(jì)學(xué)意義(表1)。
表1 LR、OR、LC和OC組的一般情況Tab 1 Baseline characteristics for the four groups of LR,OR,LC and OC
OR:Rocuronium administered in open surgery;OC:Cisatracurium administered in open surgery;LR:Rocuronium administered in laparoscopic surgery;LC:Cisatracurium administered in laparoscopic surgery.
4組間丙泊酚和瑞芬太尼消耗量的差異無統(tǒng)計(jì)學(xué)意義,腹腔鏡手術(shù)兩組間手術(shù)過程中腹內(nèi)壓變化差異無統(tǒng)計(jì)學(xué)意義。OC組與LC組相比,神經(jīng)肌肉阻滯時(shí)間的差異無統(tǒng)計(jì)學(xué)意義(表2)。LR組與OR組相比,推注羅庫溴銨后T1出現(xiàn)的時(shí)間、T1恢復(fù)到基礎(chǔ)值的5%及25%的時(shí)間顯著延長(P<0.05,表3):(36.2±4.0)minvs.(44.8±10.7)min,(41.8±6.8)minvs.(52.8±11.2)min,(49.5±7.5)minvs.(62.6±13.5)min。
表2 LC組和OC組神經(jīng)肌肉阻滯作用時(shí)間的比較Tab 2 Changes in the duration of neuromuscular blockade in OC group and LC group
OC:Cisatracurium administered in open surgery;LC:Cisatracurium administered in laparoscopic surgery;T1:The first twitch.(1)From the injection to T1 occurrence;(2)From T1 recovered to 5% or 25% of baseline.
LC組有1例患者在插管即刻出現(xiàn)心動(dòng)過緩,OC組有1例患者在插管后40 min發(fā)生心動(dòng)過緩,推注阿托品后心率均恢復(fù)至50次/min以上。4組患者比較,低血壓和心動(dòng)過緩發(fā)生率的差異無統(tǒng)計(jì)學(xué)意義。4組患者在研究過程中心率、平均動(dòng)脈壓、體溫、ETCO2的變化差異無統(tǒng)計(jì)學(xué)意義。4組患者在術(shù)前及術(shù)后肝腎功能的差異無統(tǒng)計(jì)學(xué)意義(表4)。
表3 LR和OR組神經(jīng)肌肉阻滯作用時(shí)間的比較Tab 3 Changes in the duration of neuromuscular blockade in OR group and LR group
OR:Rocuronium administered in open surgery; LR:Rocuronium administered in laparoscopic surgery;T1:The first twitch.(1)From the injection to T1 occurrence;(2)From T1 recovered to 5% or 25% of baseline.
表4 LR、OR、LC和OC組術(shù)前及術(shù)后24 h肝腎功能的比較Tab 4 Changes in the function of liver and kidney in the 4 groups of LR,OR,LC and OC before and after the operation
AST:Serum aspartate aminotransferase; ALT:Alanine aminotransferase;BUN:Blood urea nitrogen;Cr:Creatinine;PRE:Pre-operation; POST:Post-operation;OR:Rocuronium administered in open surgery;OC:Cisatracurium administered in open surgery; LR:Rocuronium administered in laparoscopic surgery;LC:Cisatracurium administered in laparoscopic surgery.
本研究結(jié)果表明,腹腔鏡和開腹手術(shù)相比,推注羅庫溴銨后T1出現(xiàn)的時(shí)間、T1恢復(fù)到基礎(chǔ)值的5%、25%的時(shí)間顯著延長,而順式阿曲庫銨的神經(jīng)肌肉阻滯時(shí)間則不受影響。
靜脈注射肌松藥后,血藥濃度迅速升高并分布到血供豐富的臟器,血藥濃度的降低有兩個(gè)明顯的時(shí)相,即分布相與消除相。非去極化肌松藥的分布半衰期在2~10 min之間,而消除半衰期受藥物消除及代謝途徑的影響。羅庫溴銨主要經(jīng)肝臟代謝,膽道排泄,9%原型經(jīng)腎臟排泄,因此肝血流和肝灌注的變化可能會(huì)影響其神經(jīng)肌肉的阻滯時(shí)間。而順式阿曲庫銨主要通過Hoffmann反應(yīng)消除,經(jīng)腎臟排泄,因此肝血流和肝灌注的變化可能對(duì)其沒有顯著影響。
氣腹對(duì)肝灌注和肝臟總血流存在有一定影響。Junghans等[12]發(fā)現(xiàn)豬的腹內(nèi)壓≥12 mmHg時(shí)肝灌注顯著降低。本研究通過比較腹腔鏡手術(shù)和開腹手術(shù)對(duì)羅庫溴銨和順式阿曲庫銨的神經(jīng)肌肉阻滯時(shí)間的不同影響,進(jìn)一步證實(shí)了腹腔鏡手術(shù)時(shí)的氣腹可能通過降低肝血流及肝臟微循環(huán)灌注,延長羅庫溴銨的神經(jīng)肌肉阻滯時(shí)間。頭低腳高的手術(shù)體位可能會(huì)加重這種影響。
無論腹腔鏡還是開腹手術(shù),術(shù)中都需要維持臨床所需的神經(jīng)肌肉阻滯程度,以利于手術(shù)視野暴露[13]。然而麻醉醫(yī)師有時(shí)會(huì)碰到這樣的問題:開腹手術(shù)的患者推注單次劑量羅庫溴銨后神經(jīng)肌肉阻滯已經(jīng)完全恢復(fù),而相同時(shí)間內(nèi)進(jìn)行腹腔鏡手術(shù)的患者神經(jīng)肌肉阻滯程度仍然較深。因此腹腔鏡手術(shù)輸注羅庫溴銨時(shí),需要警惕藥物蓄積所引起的神經(jīng)肌肉阻滯時(shí)間的延長,有必要在腹腔鏡手術(shù)使用羅庫溴銨時(shí)使用神經(jīng)肌肉監(jiān)測儀。
目前臨床上常用的神經(jīng)肌肉監(jiān)測儀包括肌張力肌松監(jiān)測儀(mechanomyography,MMG)、肌電圖肌松監(jiān)測儀(eletromyography,EMG)和加速度肌松監(jiān)測儀(acceleromyography,AMG)。雖然AMG已經(jīng)越來越多使用于臨床,但MMG仍然是神經(jīng)肌肉監(jiān)測的金標(biāo)準(zhǔn),且AMG和MMG之間不能互換[14-15],因此本研究采用MMG監(jiān)測。
本研究存在一定的局限性。首先,本研究不是一項(xiàng)隨機(jī)和雙盲的研究。然而手術(shù)方式在術(shù)前已經(jīng)決定,多種可能影響肌松藥藥效學(xué)的因素如性別[16]、年齡[17]、BMI[18]、體溫[19]、缺氧[20],復(fù)合吸入麻醉藥[21-23]及近日節(jié)律[24]等盡量控制在相同的水平,因此設(shè)計(jì)的缺陷已經(jīng)降到最低。其次,我們僅比較了術(shù)前及術(shù)后24 h患者的肝腎功能,而未收集更長時(shí)間的數(shù)據(jù)。陳繼業(yè)等[25]研究證實(shí),肝缺血90 min后復(fù)流,術(shù)后1 h時(shí)ALT較術(shù)前無顯著差異,而至術(shù)后2、3天顯著高于術(shù)前(P<0.05),術(shù)后4天與術(shù)前無顯著差異。而復(fù)流后1 h AST水平達(dá)到峰值,術(shù)后3天與術(shù)前無顯著差異。因此術(shù)后24 h是測量肝功能變化最佳的時(shí)間點(diǎn)。最后,我們的研究終點(diǎn)選擇在T1/Tc恢復(fù)至基礎(chǔ)值25%的時(shí)點(diǎn),而未測量之后的T1/Tc恢復(fù)至基礎(chǔ)值75%的時(shí)間和恢復(fù)指數(shù)等指標(biāo)。 T1/Tc恢復(fù)到基礎(chǔ)值的25%的時(shí)間為臨床神經(jīng)肌肉阻滯作用的時(shí)間,之后肌松逐漸恢復(fù)而不利于臨床手術(shù)操作,因此這個(gè)終點(diǎn)的選擇更貼近于真實(shí)的臨床實(shí)踐。
本研究提示,與開腹手術(shù)相比,羅庫溴銨用于腹腔鏡手術(shù)時(shí)神經(jīng)肌肉阻滯時(shí)間顯著延長;而順式阿曲庫銨對(duì)開腹手術(shù)和腹腔鏡手術(shù)神經(jīng)肌肉阻滯時(shí)間的影響未見差異,這可能與腹腔鏡手術(shù)的氣腹導(dǎo)致肝血流減少有關(guān)。麻醉醫(yī)師在使用羅庫溴銨進(jìn)行腹腔鏡手術(shù)神經(jīng)肌肉阻滯時(shí),需要警惕神經(jīng)肌肉阻滯時(shí)間的延長,必要時(shí)進(jìn)行肌松監(jiān)測。
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Comparison of the duration of neuromuscular blockade following a single bolus dose of rocuronium or cisatracurium in laparoscopic gynaecological surgery and conventional open surgery
WANG Ting-ting, SUN Shen, WANG Qi, HUANG Shao-qiang△
(DepartmentofAnaesthesia,ObstetricsandGynecologyHospital,FudanUniversity,Shanghai200090,China)
Objective To compare the duration of neuromuscular blockade in laparoscopic and open surgical approaches following a single bolus dose of rocuronium or cisatracurium. Methods One hundred female patients underwent either laparoscopic or open gynaecological surgery were randomly and equally divided into OR group (rocuronium administered in open surgery),OC group (cisatracurium administered in open surgery),LR group (rocuronium administered in laparoscopic surgery) and LC group (cisatracurium administered in laparoscopic surgery).Anaesthesia was induced with sufentanil of 0.5 μg/kg and propofol of 2 mg/kg,and neuromuscular blockade was induced with rocuronium of 0.9 mg/kg or cisatracurium of 0.15 mg/kg,intravenously.Then adductor pollicis train-of-four responses following ulnar nerve stimulation were monitored with mechanomyography.We recorded the duration of the first twitch (T1) occurrence after the injection of rocuronium or cisatracurium,and the duration from T1 recovered to 5% and 25% of baseline. Results The mean time from the end of injection of rocuronium until spontaneous recovery to T1,and to recovery to 5% and 25% of baseline,was significantly prolonged in LR group [(44.8±10.7) min,(52.8±11.2) min and (62.6±13.5) min] compared with OR group [(36.2±4.0) min,(41.8±6.8) min and (49.5±7.5) min](Pall<0.05) On the other hand,there was no significant difference on the duration of neuromuscular blockade between LC group and OC group. Conclusions Neuromuscular blockade may be prolonged following a single bolus dose of rocuronium given during laparoscopic procedures,which should be on the alert,and assess neuromuscular function to ensure safe recovery.
pneumoperitoneum; neuromuscular blockade; laparoscopy; muscle relaxant
R614.2+4
A
10.3969/j.issn.1672-8467.2017.02.004
2016-06-23;編輯:段佳)
上海市衛(wèi)計(jì)委青年局級(jí)課題(201344196)
△Corresponding author E-mail:timrobbins@163.com
* This work was supported by the Youth Foundation from Shanghai Municipal Commission of Health and Family Planning (201344196).
復(fù)旦學(xué)報(bào)(醫(yī)學(xué)版)2017年2期