硬膜外麻醉復(fù)合全身麻醉對(duì)老年腹部手術(shù)患者心肌損傷及凝血纖溶系統(tǒng)的影響

李彬子 韓文東 王瑞娟 王珍

·臨床論著·

硬膜外麻醉復(fù)合全身麻醉對(duì)老年腹部手術(shù)患者心肌損傷及凝血纖溶系統(tǒng)的影響

李彬子*韓文東 王瑞娟 王珍

（安陽(yáng)市第六人民醫(yī)院麻醉科，河南 安陽(yáng) 455000）

分析老年腹部手術(shù)患者應(yīng)用硬膜外麻醉復(fù)合全身麻醉后心肌損傷情況及凝血纖溶系統(tǒng)變化。選取我院2018年3月至2019年3月期間收治的103例老年腹部手術(shù)患者，依據(jù)隨機(jī)單雙號(hào)抽簽法分為對(duì)照組（n=51）及觀察組（n=52）。對(duì)照組患者應(yīng)用舒芬太尼、咪唑安定、羅庫(kù)溴銨、丙泊酚進(jìn)行全身麻醉，觀察組患者先于T10-T12椎間隙穿刺置管，注入5 mL利多卡因，5 min后給予利多卡因、布比卡因混合液10 mL間斷注入，感覺(jué)阻滯達(dá)T6平面后，給予舒芬太尼、咪唑安定、羅庫(kù)溴銨、丙泊酚進(jìn)行全身麻醉。觀察兩組患者麻醉前、后凝血纖溶系統(tǒng)指標(biāo)水平及心肌損傷指標(biāo)水平變化，并對(duì)比兩組患者麻醉中麻醉藥物用量及不良事件發(fā)生率。觀察組術(shù)后6 h 心肌肌鈣蛋白I（Cardiac troponin I，cTnI）、凝血酶時(shí)間（Thrombin time，TT）、肌酸激酶同工酶（Creatine kinase isoenzymes，CK-MB）水平明顯低于對(duì)照組（P<0.05），術(shù)后12 h cTnI、纖維蛋白原（Fibrinogen，F(xiàn)IB）、CK-MB水平低于對(duì)照組（P<0.05）。丙泊酚、維庫(kù)溴銨、舒芬太尼用量及不良事件發(fā)生率低于對(duì)照組（P<0.05）。硬膜外麻醉復(fù)合全身麻醉能夠有效降低老年腹部手術(shù)患者凝血纖溶系統(tǒng)的影響，減輕心肌損傷，減少麻醉用藥，術(shù)后并發(fā)癥發(fā)生率低。

硬膜外麻醉；全身麻醉；老年；腹部手術(shù)；心肌損傷；凝血纖溶系統(tǒng)

手術(shù)是臨床上治療疾病的重要方法，治療時(shí)能夠快速而有效的直達(dá)病灶，消除疾病病因，其療效得到臨床一致肯定[1]。隨著手術(shù)在臨床上的廣泛應(yīng)用，有研究指出[2]，患者在手術(shù)期間由于手術(shù)的創(chuàng)傷，會(huì)導(dǎo)致患者出現(xiàn)不同程度的應(yīng)激反應(yīng)，而手術(shù)應(yīng)激的出現(xiàn)會(huì)導(dǎo)致患者機(jī)體器官、組織、臟器功能發(fā)生一系列改變，以保證機(jī)體維持穩(wěn)定的內(nèi)環(huán)境，促使患者生理功能正常，若應(yīng)激反應(yīng)長(zhǎng)時(shí)間存在，會(huì)導(dǎo)致機(jī)體內(nèi)氨基酸、游離脂肪酸、血糖等能源物質(zhì)大量消耗，引起不良反應(yīng)發(fā)生，處于圍術(shù)期的手術(shù)患者，應(yīng)激反應(yīng)的出現(xiàn)會(huì)引起凝血纖溶系統(tǒng)水平發(fā)生異常表達(dá)，嚴(yán)重時(shí)甚至導(dǎo)致肺栓塞、深靜脈血栓等情況發(fā)生，除此之外，神經(jīng)系統(tǒng)變化主要表現(xiàn)為交感神經(jīng)過(guò)度興奮，極易引起心肌損傷發(fā)生，提升患者術(shù)后心血管并發(fā)癥發(fā)生率，老年患者機(jī)體體質(zhì)較差，且合并多種慢性疾病，機(jī)體的臟器組織功能減弱，在生理因素的影響下表現(xiàn)更為明顯。圍術(shù)期應(yīng)激反應(yīng)影響因素較多，常見(jiàn)的有精神、禁食、手術(shù)創(chuàng)傷、血容量、疼痛、麻醉、術(shù)后不適等，麻醉是手術(shù)過(guò)程中必不可缺步驟，麻醉質(zhì)量對(duì)于手術(shù)效果及患者預(yù)后均有著重要影響，同時(shí)麻醉方法的選擇對(duì)于術(shù)中機(jī)體組織器官各功能變化亦有著調(diào)節(jié)效用[3]。該研究旨在觀察硬膜外麻醉復(fù)合全身麻醉在老年腹部手術(shù)中的麻醉效果，現(xiàn)報(bào)道如下。

1 資料與方法

1.1 一般資料

選取2018年3月至2019年3月期間來(lái)我院就診的103例老年腹部手術(shù)患者，采用隨機(jī)單雙號(hào)抽簽法分為對(duì)照組和觀察組。

對(duì)照組51例，男30例，女21例；年齡65~81歲，平均72.93±7.01歲；美國(guó)紐約心臟病學(xué)會(huì)（New York Heart Association，NYHA）心功能分級(jí)Ⅰ級(jí)28例，Ⅱ級(jí)23例；美國(guó)麻醉醫(yī)師協(xié)會(huì)（American Society of Anesthesiologists，ASA）分級(jí)Ⅱ級(jí)36例，Ⅲ級(jí)15例；體質(zhì)量53~71 kg，平均61.93±5.11 kg；手術(shù)類(lèi)型：膽總管切開(kāi)取石術(shù)8例，膽囊切除術(shù)15例，胃癌根治術(shù)28例。

觀察組52例，男29例，女23例；年齡66~82歲，平均73.01±6.99歲；NYHA心功能分級(jí)Ⅰ級(jí)27例，Ⅱ級(jí)25例；ASA分級(jí)Ⅱ級(jí)35例，Ⅲ級(jí)17例；體質(zhì)量52~72kg，平均61.96±5.08 kg；手術(shù)類(lèi)型：膽總管切開(kāi)取石術(shù)11例，膽囊切除術(shù)16例，胃癌根治術(shù)25例。兩組患者資料無(wú)統(tǒng)計(jì)學(xué)意義（P>0.05），有可比性。納入標(biāo)準(zhǔn)：符合手術(shù)指征，ASA分級(jí)Ⅱ-Ⅲ級(jí)，NYHA分級(jí)Ⅰ-Ⅱ級(jí)，年齡≥65歲，患者知情，經(jīng)我院倫理委員會(huì)批準(zhǔn)。排除標(biāo)準(zhǔn)：合并血液系統(tǒng)疾病者，嚴(yán)重肝腎功能障礙者，術(shù)前30 d使用免疫抑制劑者。

1.2 方法

進(jìn)入手術(shù)室后，均給予生命體征監(jiān)護(hù)儀連接，建立靜脈通道，術(shù)前禁用其他藥物，對(duì)照組患者給予全身麻醉誘導(dǎo)，麻醉藥物舒芬太尼0.4 μg·kg-1、咪唑安定0.03 mg·kg-1、羅庫(kù)溴銨0.8 mg·kg-1、丙泊酚3 mg·kg-1，插管后連接呼吸機(jī)，丙泊酚3 mg·（kg·h）-1、順阿曲庫(kù)溴銨0.2 mg·（kg·h）-1、瑞芬太尼0.01 mg·（kg·h）-1持續(xù)泵入，1.5%七氟醚吸入維持麻醉；觀察組患者先于T10-T12椎間隙穿刺置管，注入5 mL利多卡因，5 min后給予利多卡因、布比卡因混合液10 mL間斷注入，感覺(jué)阻滯達(dá)T6平面后行全身麻醉，麻醉方法同對(duì)照組。

1.3 觀察指標(biāo)

1.3.1 凝血纖溶系統(tǒng)指標(biāo)水平比較

于患者麻醉前、術(shù)后6、12 h檢測(cè)并對(duì)比凝血酶時(shí)間（Thrombin time，TT）、活化部分凝血活酶時(shí)間（Activated partial thromboplastin time，APTT）、血小板（Platelet count，PLT）、纖維蛋白原（Fibrinogen，F(xiàn)IB）、凝血酶原時(shí)間（Prothrombin time，PT）水平變化。

1.3.2 心肌損傷指標(biāo)水平

于患者麻醉前、術(shù)后即刻、術(shù)后6、12 h檢測(cè)并對(duì)比心肌肌鈣蛋白I（Cardiac troponin I，cTnI）、肌酸激酶同工酶（Creatine kinase isoenzymes，CK-MB）水平變化。

1.3.3 麻醉藥物用量比較

對(duì)比兩組患者手術(shù)麻醉期間維庫(kù)溴銨、丙泊酚及舒芬太尼用量。

1.3.4 對(duì)比手術(shù)期間不良事件發(fā)生情況。

觀察記錄并比較兩組患者手術(shù)期間不良反應(yīng)發(fā)生。

1.4 統(tǒng)計(jì)方法

2 結(jié)果

2.1 凝血纖溶系統(tǒng)指標(biāo)水平比較

術(shù)后6 h ，對(duì)照組患者TT水平高于觀察組，術(shù)后12 h，F(xiàn)IB水平高于觀察組（P<0.05），見(jiàn)表1。

表1 凝血纖溶系統(tǒng)水平對(duì)比（±SD）

注：與麻醉前比較，*P<0.05；與對(duì)照組比較，#P<0.05。

2.2 心肌損傷指標(biāo)水平比較

兩組患者術(shù)后即刻、6 h及術(shù)后12 h cTnI、CK-MB水平均較麻醉前升高。對(duì)照組術(shù)后6 h及術(shù)后12 h cTnI、CK-MB水平高于觀察組患者（P<0.05），見(jiàn)表2。

2.3 麻醉藥物用量比較

對(duì)照組患者麻醉過(guò)程中維庫(kù)溴銨、丙泊酚、舒芬太尼用量均高于觀察組（P<0.05），見(jiàn)表3。

2.4 不良事件發(fā)生率

觀察組出現(xiàn)心絞痛2例，心律失常1例，不良事件發(fā)生率5.77%（3/52），對(duì)照組出現(xiàn)心肌梗死2例，心律失常2例，心力衰竭1例，心絞痛5例，不良事件發(fā)生率19.61%（10/51），有統(tǒng)計(jì)學(xué)意義（=4.4711，P<0.05）。

3 討論

手術(shù)是臨床上重要的治療手段之一，由于創(chuàng)傷的刺激，患者在圍術(shù)期間多伴有不同程度的應(yīng)激反應(yīng)，老年患者由于生理功能退化，合并多重基礎(chǔ)疾病等因素影響，在圍術(shù)期應(yīng)激反應(yīng)更為明顯[4]。臨床分析認(rèn)為[5]，圍術(shù)期應(yīng)激反應(yīng)的發(fā)生與手術(shù)創(chuàng)傷及麻醉均有著重要關(guān)聯(lián)。

近年來(lái)，隨著微創(chuàng)醫(yī)學(xué)在臨床的廣泛開(kāi)展，當(dāng)前手術(shù)方式對(duì)于機(jī)體的損傷已降至最小范圍，短時(shí)間內(nèi)手術(shù)方式的優(yōu)化希望較小，因此，對(duì)于麻醉方式的優(yōu)化以引起臨床的重視。

全身麻醉是老年腹部手術(shù)患者較為常用的麻醉方式，其具有維持患者術(shù)中氧氣供應(yīng)，抑制迷走神經(jīng)興奮，保證手術(shù)順利進(jìn)行效用。隨著臨床研究的不斷深入，有研究表明[6]，單純?nèi)砺樽黼m能夠維持手術(shù)順利進(jìn)行，但是，其對(duì)術(shù)中患者機(jī)體血流動(dòng)力學(xué)水平并無(wú)明顯調(diào)節(jié)效用，不能夠預(yù)防改善圍術(shù)期患者機(jī)體應(yīng)激反應(yīng)，影響整體麻醉質(zhì)量及手術(shù)效果[7]。

表2 心肌損傷指標(biāo)水平對(duì)比（±SD）

注：與麻醉前比較，*P<0.05；與對(duì)照組比較，#P<0.05。

表3 兩組患者麻醉藥物用量對(duì)比（±SD，mg）

注：與對(duì)照組比較，#P<0.05。

本文研究顯示，對(duì)照組患者在術(shù)后6 h、12 h患者的TT、APTT、PLT、FIB、PT水平均較麻醉前明顯改變，而觀察組患者僅有APTT在術(shù)后明顯提升，表明手術(shù)對(duì)機(jī)體的損傷能夠引起患者在圍術(shù)期間凝血纖溶系統(tǒng)異常改變，通過(guò)改善麻醉方式能夠有效降低手術(shù)應(yīng)激對(duì)于機(jī)體的影響。同時(shí)，觀察組患者術(shù)后6 h、12 h cTnI、CK-MB改變幅度均顯著低于對(duì)照組患者，提示硬膜外阻滯麻醉復(fù)合全身麻醉應(yīng)用于老年腹部手術(shù)患者，能夠有效減輕患者心肌損傷，且效果優(yōu)于單純?nèi)砺樽砘颊?。在保持同樣麻醉效果前提下，能夠進(jìn)一步減少患者在麻醉期間藥物使用量，更利于老年患者術(shù)后機(jī)體代謝，同時(shí)能夠有效降低患者術(shù)后并發(fā)癥發(fā)生率，該研究?jī)?nèi)，觀察組患者術(shù)中麻醉藥物用量及術(shù)后并發(fā)癥發(fā)生率亦證明這一觀點(diǎn)。

臨床分析認(rèn)為，硬膜外阻滯復(fù)合全身麻醉結(jié)合兩種麻醉方式的優(yōu)點(diǎn)，聯(lián)合應(yīng)用，優(yōu)勢(shì)互補(bǔ)，能夠通過(guò)抑制凝血機(jī)制激活，調(diào)節(jié)組織纖維蛋白溶酶原、纖溶酶原水平，擴(kuò)張血管，提升血管流量，降低血液黏度，改善微循環(huán)障礙及外周血管阻力，緩解心臟氧耗，調(diào)節(jié)心率，減輕心肌損傷，產(chǎn)生減輕應(yīng)激反應(yīng)，保護(hù)心臟功能的效用，進(jìn)而有效降低患者術(shù)后并發(fā)癥發(fā)生率[8]。

羅小剛[9]等學(xué)者研究證實(shí)，對(duì)老年腹部手術(shù)患者應(yīng)用硬膜外麻醉復(fù)合全身麻醉后，顯著降低對(duì)老年腹部手術(shù)患者凝血功能的影響，與該研究結(jié)果一致。

綜上所述，硬膜外麻醉復(fù)合全身麻醉通過(guò)抑制凝血機(jī)制激活，降低血液黏度，改善微循環(huán)障礙等應(yīng)用于老年腹部手術(shù)患者效果顯著，有效降低對(duì)患者凝血纖溶系統(tǒng)的影響，減輕心肌損傷及術(shù)后并發(fā)癥發(fā)生率，值得臨床推廣應(yīng)用。

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Effects of epidural anesthesia combined with general anesthesia on myocardial injury and coagulation and fibrinolysis system in elderly patients undergoing abdominal surgery

Li Bin-zi*, Han Wen-dong, Wang Rui-juan, Wang Zhen

(Department of Anesthesiology, The Sixth People's Hospital of Anyang, Anyang 455000, Henan)

To investigate the effects of epidural anesthesia combined with general anesthesia on the myocardial injury and the changes of the coagulation and fibrinolysis system in elderly patients undergoing abdominal surgery.All together, 103 elderly patients with abdominal surgery admitted to our hospital from March 2018 to March 2019 were randomly divided into the control group (n=51) and the observation group (n=52). Patients in the control group underwent general anesthesia with sufentanil, midazolam, rocuronium bromide, and propofol. Patients in the observation group were treated with T10-T12 intervertebral space puncture. And lidocaine 5 mL was given 5 min later. 10 mL of lidocaine and bupivacaine mixture was injected intermittently. After the sensory block reached the T6 plane, general anesthesia was induced with sufentanil, midazolam, rocuronium bromide and propofol. The level of post-coagulation, fibrinolysis system, myocardial injury index, the anesthetic dosage, and adverse event rate in anesthesia was compared between the two groups.Cardiac troponin I (cTnI), thrombin time (TT), and creatine kinase isoenzymes (CK-MB) levels in the observation group were significantly lower than those in the control group (P<0.05). The levels of cTnI, fibrinogen (FIB) and CK-MB in the observation group were less than the control group at 12 h after operation (P<0.05). The amount of Propofol, vecuronium bromide and sufentanil, and the incidence of adverse events in the observation group were lower than those of the control group (P<0.05).Epidural anesthesia combined with general anesthesia effectively reduces the influence of the coagulation and fibrinolysis system in elderly patients with abdominal surgery, decrease myocardial damage, and has a low incidence of postoperative complications.

Epidural anesthesia; General anesthesia; Aged; Abdominal surgery; Myocardial injury; Coagulation and fibrinolysis system

Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

Lu R, Zhao X, Li J, et al.

BACKGROUND: In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed.

METHODS: We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus.

FINDINGS: The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues.

INTERPRETATION: 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation.

(From Lancet. 2020, pii: S0140-6736(20)30251-8.)

李彬子，男，主治醫(yī)師，主要從事臨床麻醉，Email：lbzzyd@163. com。

（2019-11-1）