劉麗平，李斌，朱磊，竇志敏，李玉民

硝酸甘油對(duì)感染性休克合并ARDS患者的臨床療效觀察

劉麗平，李斌，朱磊，竇志敏，李玉民

目的評(píng)價(jià)硝酸甘油對(duì)感染性休克合并急性呼吸窘迫綜合征(ARDS)患者的臨床療效，并探討其可能的作用機(jī)制。方法納入2013年1月－2014年1月蘭州大學(xué)第一醫(yī)院重癥醫(yī)學(xué)科收治的感染性休克合并ARDS患者，將符合標(biāo)準(zhǔn)者隨機(jī)分為對(duì)照組和硝酸甘油組。對(duì)照組給予標(biāo)準(zhǔn)治療，硝酸甘油組在標(biāo)準(zhǔn)治療基礎(chǔ)上，給予硝酸甘油0.5～1.0mg/h靜脈泵入。入組后0、6、24、72h記錄兩組各項(xiàng)監(jiān)測(cè)指標(biāo)，包括一般情況、APACHE Ⅱ評(píng)分、血流動(dòng)力學(xué)指標(biāo)、呼吸功能監(jiān)測(cè)指標(biāo)、呼吸機(jī)使用時(shí)間、ICU停留時(shí)間、住院及28d病死率、免疫指標(biāo)(CD4+/CD8+)及炎癥指標(biāo)等。結(jié)果共43位患者入選，其中對(duì)照組21例，硝酸甘油組22例。在治療24、72h時(shí)點(diǎn)兩組患者APACHE Ⅱ評(píng)分、心率、肺動(dòng)脈壓(PAP)、乳酸及多巴胺、去甲腎上腺素、呼吸頻率(RR)、吸入氧濃度(FiO2)、氣道阻力、C反應(yīng)蛋白(CRP)、降鈣素原(PCT)、白介素-6(IL-6)、白細(xì)胞(WBC)均較入組時(shí)及治療6h時(shí)下降，且72h時(shí)硝酸甘油組明顯低于對(duì)照組(P<0.05)；同時(shí)，外周血管阻力指數(shù)(SVRI)、pH值、動(dòng)脈氧分壓(PaO2)、潮氣量(VT)、肺順應(yīng)性、氧合指數(shù)、CD4+/CD8+在治療24h、72h時(shí)較入組時(shí)及6h時(shí)明顯升高，且72h時(shí)硝酸甘油組明顯高于對(duì)照組(P<0.05)。硝酸甘油組機(jī)械通氣(MV)時(shí)間為4.3±0.6d，明顯低于對(duì)照組(6.1±0.7d，P<0.05)；ICU住院時(shí)間及總住院時(shí)間分別為7.8±0.8d、9.3±0.6d，明顯低于對(duì)照組(分別為9.2±0.9d、12.9±1.3d，P<0.05)；住院病死率及28d病死率均明顯低于對(duì)照組(P<0.05)。結(jié)論對(duì)感染性休克合并ARDS患者使用硝酸甘油可以使呼吸機(jī)條件改善，降低機(jī)械通氣、ICU停留及總住院時(shí)間，降低病死率。這可能與硝酸甘油可改善微循環(huán)，降低肺循環(huán)阻力及全身炎性反應(yīng)，提高免疫力有關(guān)。

硝酸甘油；休克，膿毒性；急性呼吸窘迫綜合征

膿毒癥(sepsis)是由微生物侵入人體而誘發(fā)的全身炎癥反應(yīng)綜合征(SIRS)，最終可引發(fā)多器官功能障礙(MODS)[1-3]。急性呼吸窘迫綜合征(ARDS)是MODS的一個(gè)重要組成部分，病死率高達(dá)48%～75%[4-5]。微循環(huán)障礙是膿毒癥的主要病理生理基礎(chǔ)之一，而ARDS發(fā)病機(jī)制中毛細(xì)血管內(nèi)皮細(xì)胞的損害必然導(dǎo)致微循環(huán)障礙。有研究指出硝酸甘油可改善微循環(huán)[6-7]，但其在感染性休克所致的ARDS中作用如何鮮見報(bào)道。本研究采用前瞻性隨機(jī)對(duì)照方法觀察小劑量硝酸甘油是否可以改善感染性休克合并ARDS患者的肺功能，并探討其可能的作用機(jī)制，從而為感染性休克及ARDS的救治提供新的依據(jù)。

1 資料與方法

1.1 研究對(duì)象 以蘭州大學(xué)第一醫(yī)院重癥醫(yī)學(xué)科2013年1月－2014年1月接診的感染性休克合并ARDS患者為研究對(duì)象。

1.2 入選及排除標(biāo)準(zhǔn) 入選標(biāo)準(zhǔn)：(1)年齡≥18歲，性別不限。(2)符合感染性休克的診斷標(biāo)準(zhǔn)[8]。①有明確感染灶；②有全身炎癥反應(yīng)存在；③收縮壓(SBP)低于90mmHg或較原來基礎(chǔ)值下降40mmHg，經(jīng)液體復(fù)蘇后1h不能恢復(fù)或需血管活性藥維持；④伴有器官組織的低灌注如尿量小于30ml/h，或有急性意識(shí)障礙等；⑤血培養(yǎng)可能有致病微生物生長(zhǎng)。(3)符合ARDS的診斷標(biāo)準(zhǔn)[9]。根據(jù)1992年歐美ARDS聯(lián)席會(huì)議標(biāo)準(zhǔn)診斷：①急性起病；②氧合指數(shù)(PO2/FiO2)<200mmHg；③X線胸片顯示雙肺斑片狀陰影；④肺動(dòng)脈嵌頓壓<18mmHg或無(wú)左房壓升高證據(jù)。所有患者或其家屬均簽署知情同意書。

排除標(biāo)準(zhǔn)：①年齡<18歲、妊娠；②合并神經(jīng)源性休克、腦血管意外、顱腦外傷患者；③入選24h內(nèi)應(yīng)用硝酸鹽衍生物；④存在靜脈應(yīng)用硝酸甘油的絕對(duì)適應(yīng)證(不穩(wěn)定冠狀動(dòng)脈綜合征)；⑤存在治療禁忌證：疾病終末期預(yù)計(jì)24h內(nèi)死亡的患者。

1.3 方法

1.3.1 分組及治療 符合感染性休克診斷的患者常規(guī)放置肺動(dòng)脈漂浮導(dǎo)管，嚴(yán)格按照EGDT 方案維持血流動(dòng)力學(xué)參數(shù)穩(wěn)定，酌情應(yīng)用液體和血管活性藥物以使平均動(dòng)脈壓(MAP)達(dá)到65mmHg。將符合ARDS診斷的患者隨機(jī)分為對(duì)照組和硝酸甘油組。對(duì)照組給予標(biāo)準(zhǔn)治療，包括小潮氣量、高PEEP的有創(chuàng)機(jī)械通氣，肺復(fù)張，限制性液體管理，抗炎，抑酸，營(yíng)養(yǎng)支持，化痰霧化及胸部物理治療等。硝酸甘油組在標(biāo)準(zhǔn)治療的基礎(chǔ)上，給予硝酸甘油0.5～1.0mg/h靜脈泵入，調(diào)整MAP＞65mmHg；用藥過程中若MAP持續(xù)<65mmHg，立即并永久性終止用藥。分別于入組后0、6、24、72h記錄兩組監(jiān)測(cè)指標(biāo)，抽取靜脈血送中心實(shí)驗(yàn)室檢測(cè)炎癥及免疫因子。

1.3.2 監(jiān)測(cè)指標(biāo) 記錄兩組年齡、性別、體重、APACHEⅡ評(píng)分；血流動(dòng)力學(xué)指標(biāo)包括心率(HR)、MAP、中心靜脈壓(CVP)、心臟指數(shù)(CI)、外周血管阻力指數(shù)(SVRI)、肺動(dòng)脈嵌壓(PAWP)、肺動(dòng)脈壓(PAP)、乳酸(Lac)水平等；復(fù)蘇液體量及升壓藥使用量；呼吸機(jī)條件監(jiān)測(cè)[pH、動(dòng)脈氧分壓(PaO2)、PCO2、呼吸頻率(RR)、呼氣末氣道正壓(PEEP)、潮氣量(VT)、吸入氧濃度(FiO2)、氧合指數(shù)、氣道阻力、肺順應(yīng)性]；機(jī)械通氣(MV)時(shí)間；ICU停留時(shí)間；住院及隨訪28d病死率；免疫指標(biāo)(CD4+/CD8+，流式細(xì)胞法)；炎癥指標(biāo)[C反應(yīng)蛋白(CRP)，速率散射比濁法；降鈣素原(PCT)，化學(xué)發(fā)光法；白介素-6(IL-6)，酶聯(lián)免疫法]。

1.4 統(tǒng)計(jì)學(xué)處理 采用SPSS 13.0軟件進(jìn)行統(tǒng)計(jì)分析，將所有數(shù)據(jù)進(jìn)行正態(tài)性檢驗(yàn)，正態(tài)分布的計(jì)量資料以表示，兩組均數(shù)比較采用t檢驗(yàn)；分類計(jì)數(shù)資料如28d病死率以百分?jǐn)?shù)表示，組間比較采用χ2檢驗(yàn)。P<0.05為差異有統(tǒng)計(jì)學(xué)意義。

2 結(jié) 果

2.1 兩組基本資料比較 2013年1月－2014年1月蘭州大學(xué)第一醫(yī)院重癥醫(yī)學(xué)科共收治216例感染性休克患者，其中符合ARDS的患者43例，隨機(jī)分為對(duì)照組(n=21)和硝酸甘油組(n=22)。兩組年齡、性別、體重及APACHE Ⅱ評(píng)分等差異均無(wú)統(tǒng)計(jì)學(xué)意義(P＞0.05)。

2.2 血流動(dòng)力學(xué)監(jiān)測(cè)指標(biāo)變化 治療過程中兩組患者M(jìn)AP、CVP、PAWP、CI無(wú)明顯差異(P>0.05)；治療24、72h時(shí)兩組患者APACHE Ⅱ評(píng)分、HR、PAP、乳酸水平及多巴胺(DA)、去甲腎上腺素(NE)用量均較入組時(shí)及治療6h時(shí)下降，且72h時(shí)硝酸甘油組均明顯低于對(duì)照組(P<0.05)；同時(shí)，SVRI在治療24、72h時(shí)較入組及6h明顯升高，且72h時(shí)硝酸甘油組明顯高于對(duì)照組(P<0.05)；兩組的液體平衡量隨著治療時(shí)間延長(zhǎng)逐漸較少，72h時(shí)兩組均達(dá)液體負(fù)平衡，且硝酸甘油組液體負(fù)平衡明顯多于對(duì)照組(P<0.05，表1)。

2.3 呼吸功能監(jiān)測(cè)指標(biāo)變化 治療過程中兩組患者PEEP無(wú)明顯差異(P>0.05)；治療24h、72h兩組患者RR、FiO2、氣道阻力均較入組時(shí)及治療6h時(shí)下降，且72h時(shí)硝酸甘油組均明顯低于對(duì)照組(P<0.05)；同時(shí)，pH值、PaO2、VT、肺順應(yīng)性、氧合指數(shù)在治療24h、72h較入組時(shí)及6h明顯升高，且72h時(shí)硝酸甘油組明顯高于對(duì)照組(P<0.05，表2)。

表1 兩組患者血流動(dòng)力學(xué)監(jiān)測(cè)指標(biāo)比較(±s)Tab.1 Comparison of hemodynamics indexes between the two groups (±s)

表1 兩組患者血流動(dòng)力學(xué)監(jiān)測(cè)指標(biāo)比較(±s)Tab.1 Comparison of hemodynamics indexes between the two groups (±s)

(1)P<0.05 compared with 0h; (2)P<0.05 compared with 6h; (3)P<0.05 compared with 24h; (4)P<0.05 compared with control group; –. No data

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表2 兩組患者呼吸功能監(jiān)測(cè)指標(biāo)比較(±s)Tab.2 Comparison of respiratory function indexes between the two groups (±s)

表2 兩組患者呼吸功能監(jiān)測(cè)指標(biāo)比較(±s)Tab.2 Comparison of respiratory function indexes between the two groups (±s)

(1)P<0.05 compared with 0h; (2)P<0.05 compared with 6h; (3)P<0.05 compared with 24h; (4)P<0.05 compared with control group

Item Control group (n=21) Nitroglycerin group (n=22) 0h 6h 24h 72h 0h 6h 24h 72h pH 7.2±0.4 7.2±0.6 7.3±0.5(1)(2) 7.4±0.4(1)(2) 7.2±0.8 7.3±0.7 7.4±0.6(1)(2) 7.4±0.8(1)(2)(3)RR (/min) 30.1±1.4 31.0±1.6(1) 28.2±3.1(1)(2) 21.1±2.4(1)(2)(3) 29.3±1.7 29.2±1.2(1) 22.4±1.4(1)(2) 19.3±1.7(1)(2)(3)PaO2(mmHg) 56.7±2.2 58.5±1.9 66.2±3.1(1)(2) 73.7±3.2(1)(2)(3) 58.6±2.7 59.2±2.1 68.6±3.6(1)(2) 82.7±7.6(1)(2)(3)PaCO2(mmHg) 32.3±1.9 32.2±1.8 33.0±2.1 36.3±2.8(1)(2) 31.3±1.8 32.4±1.7 34.5±2.2 39.5±3.1(1)(2)(3)PEEP (cmH2O) 9.2±1.2 9.2±1.3 8.1±1.1 6.1±1.2 8.9±1.1 9.1±1.2 8.2±1.3 5.9±1.1 VT (ml) 380±98 392±101 450±123(1)(2) 490±113(1)(2) 398±102 412±99 480±134(1)(2) 580±128(1)(2)(3)FiO2(%) 78.4±6.8 76.3±7.1 63.2±5.7(1)(2) 53.0±4.1(1)(2)(3) 76.0±7.5 74.5±8.4 58.5±5.3(1)(2) 46.2±3.9(1)(2)(3)Lung compliance (ml/cmH2O) 22.0±2.1 29.2±3.1 39.4±3.5(1)(2) 56.6±4.9(1)(2)(3) 23.0±2.5 31.1±3.2 49.3±3.7(1)(2) 82.2±5.6(1)(2)(3)Airway resistance [cmH2O/(L.s)] 24.2±3.5 22.1±3.1 16.4±3.5(1)(2) 10.2±2.6(1)(2)(3) 26.2±3.3 23.4±3.2 11.3±3.5(1)(2) 6.6±2.1(1)(2)(3)Oxygenation index (mmHg) 74.4±13.5 76.3±13.3 106.5±18.5(1)(2)148.6±25.6(1)(2)(3) 76.8±13.2 78.6±13.4 143.2±16.8(1)(2) 216.6±22.1(1)(2)(3)

2.4 炎性因子及免疫指標(biāo)變化 治療24、72h兩組患者CRP、PCT、IL-6、WBC均較入組時(shí)及治療6h下降，且在24、72h時(shí)硝酸甘油組均明顯低于對(duì)照組(P<0.05)；同時(shí)，CD4+/CD8+在治療24、72h較入組時(shí)及6h明顯升高，且24、72h時(shí)硝酸甘油組明顯高于對(duì)照組(P<0.05，表3)。

2.5 其他 硝酸甘油組MV時(shí)間(4.3±0.6d)明顯低于對(duì)照組(6.1±0.7d，P<0.05)；ICU住院時(shí)間及總住院時(shí)間(分別為7.8±0.8d、9.3±0.6d)明顯低于對(duì)照組(分別為9.2±0.9d、12.9±1.3d，P<0.05)；住院病死率及28d病死率分別為9%、13%，明顯低于對(duì)照組(19%、23%，P<0.05)。

表3 兩組患者炎性因子及免疫指標(biāo)變化比較(±s)Tab.3 Comparison of inflammatory cytokines and immune indexes between the two groups (±s)

表3 兩組患者炎性因子及免疫指標(biāo)變化比較(±s)Tab.3 Comparison of inflammatory cytokines and immune indexes between the two groups (±s)

(1)P<0.05 compared with 0h; (2)P<0.05 compared with 6h; (3)P<0.05 compared with 24h; (4)P<0.05 compared with control group

Group Control group (n=21) Nitroglycerin group (n=22) 0h 6h 24h 72h 0h 6h 24h 72h CRP(mg/L) 136.6±26.2 126.4±21.6(1) 81.3±14.3(1)(2) 36.8±11.2(1)(2)(3) 132.3±22.3 125.4±21.6(1)38.5±10.2(1)(2)(4)16.5±11.1(1)(2)(3)(4)PCT(ng/L) 0.025±0.003 0.023±0.002 0.018±0.002(1)(2)0.012±0.002(1)(2)(3) 26.0±2.8 24.2±1.6 12.4±1.2(1)(2)(4) 3.3±1.1(1)(2)(3)(4)IL-6(μg/L) 12.9±1.5 12.1±1.2 9.2±1.4 6.3±1.3(1)(2) 13.2±1.7 12.4±1.3 5.9±1.3(1)(2)(4) 2.3±0.5(1)(2)(3)(4)WBC(×109/L) 26.6±2.5 23.5±2.1 18.4±2.2 16.2±2.1(1)(2) 25.5±2.4 23.4±2.3 15.6±2.1(1)(2)(4) 11.4±1.8(1)(2)(3)(4)CD4+/CD8+ 0.5±0.1 0.6±0.1 1.2±0.3(1)(2) 1.9±0.4(1)(2)(3) 0.6±0.1 0.7±0.2 1.9±0.4(1)(2)(4) 2.8±0.6(1)(2)(3)(4)

3 討 論

ARDS的基本病理生理改變是血管內(nèi)皮細(xì)胞和肺泡上皮細(xì)胞受損、通透性亢進(jìn)所致的肺水腫。血管內(nèi)皮細(xì)胞受損，膠原組織暴露，刺激血小板附著和聚集，從而激活凝血反應(yīng)鏈，纖維蛋白及免疫球蛋白也應(yīng)激性增高，終致血栓形成和微循環(huán)障礙。重癥感染、感染性休克易釋放大量炎性因子，從而損傷血管內(nèi)皮細(xì)胞，易合并ARDS。本研究應(yīng)用硝酸甘油治療感染性休克合并ARDS患者，結(jié)果顯示，硝酸甘油可以減輕炎癥反應(yīng)，提高免疫力，改善肺功能，降低病死率。

硝酸甘油通過一氧化氮合酶產(chǎn)生一氧化氮，一氧化氮使血管平滑肌松弛，減少白細(xì)胞和血小板黏附，減輕組織水腫，降低微循環(huán)通透性，從而改善微循環(huán)血流[10]。研究表明，硝酸甘油可以明顯改善動(dòng)脈波形，且并不影響心輸出量和全身血管阻力[11-12]。低劑量硝酸甘油可導(dǎo)致靜脈擴(kuò)張，從而降低心臟充盈壓，提高心肌灌注壓，降低心肌氧耗[13-15]。本研究發(fā)現(xiàn)，硝酸甘油組患者M(jìn)AP、CVP、PAWP、CI與對(duì)照組比較無(wú)明顯差異，說明小劑量硝酸甘油對(duì)體循環(huán)的影響不大；但在治療過程中硝酸甘油組患者APACHEⅡ評(píng)分、心率、乳酸水平及多巴胺、去甲腎上腺素用量均較對(duì)照組明顯下降，而SVRI較對(duì)照組明顯升高(P<0.05)，提示硝酸甘油可以提高感染性休克患者的氧輸送，降低氧耗，改善病情；同時(shí)我們也發(fā)現(xiàn)，兩組患者入組時(shí)肺動(dòng)脈壓(PAP)均高于正常，這可能是由于缺氧導(dǎo)致肺動(dòng)脈血管痙攣，肺循環(huán)阻力增加，同時(shí)ARDS時(shí)肺毛細(xì)血管微循環(huán)障礙，從而導(dǎo)致肺動(dòng)脈壓力升高，而硝酸甘油可以降低肺動(dòng)脈壓力。

既往對(duì)于ARDS的治療及研究主要集中在呼吸機(jī)及液體管理等方面，關(guān)于改善微循環(huán)是否可以改善肺功能的研究少見。本研究結(jié)果顯示硝酸甘油可以使感染性休克合并ARDS患者的呼吸機(jī)應(yīng)用條件降低，如硝酸甘油組患者RR、FiO2、氣道阻力較對(duì)照組明顯下降，而pH值、PaO2、VT、肺順應(yīng)性、氧合指數(shù)明顯高于對(duì)照組(P<0.05)，這可能與硝酸甘油改善肺血管微循環(huán)、降低肺循環(huán)阻力有關(guān)，而呼吸機(jī)條件的改善導(dǎo)致硝酸甘油組機(jī)械通氣時(shí)間、住ICU時(shí)間及總住院時(shí)間縮短。

感染性休克所致ARDS的發(fā)病機(jī)制是感染介導(dǎo)的全身炎性反應(yīng)綜合征激活巨噬細(xì)胞和中性粒細(xì)胞等炎癥細(xì)胞釋放細(xì)胞因子等化學(xué)介質(zhì)。本研究發(fā)現(xiàn)，兩組患者入組時(shí)炎癥因子(CRP、PCT、WBC、IL-6)明顯升高，隨著綜合治療的進(jìn)行，兩組炎癥因子均下降，且硝酸甘油組較對(duì)照組同時(shí)間點(diǎn)下降明顯，這可能與硝酸甘油使血管平滑肌松弛，減少白細(xì)胞和血小板黏附，減輕組織水腫，改善微循環(huán)，從而減少炎癥因子釋放有關(guān)。另外，有研究認(rèn)為影響ARDS預(yù)后的危險(xiǎn)因素主要是全身炎癥反應(yīng)和免疫功能低下[16]。本研究觀察了CD4+/ CD8+比值，發(fā)現(xiàn)兩組患者入組時(shí)CD4+/CD8+均較低，隨著綜合治療的進(jìn)行逐漸升高，且硝酸甘油組較對(duì)照組同時(shí)間點(diǎn)升高明顯，提示硝酸甘油可以提高患者的免疫力。同時(shí)我們發(fā)現(xiàn)，硝酸甘油的給予可以降低病死率。

綜上所述，感染性休克合并ARDS患者給予硝酸甘油可以改善呼吸機(jī)條件，降低機(jī)械通氣時(shí)間、ICU停留時(shí)間及總住院時(shí)間，降低病死率，改善全身氧輸送/氧耗平衡，使得體循環(huán)更易維持，這可能與硝酸甘油通過改善微循環(huán)，降低肺循環(huán)阻力及全身炎性反應(yīng)，提高免疫力有關(guān)。因此，臨床上可以嘗試給予此類患者硝酸甘油。當(dāng)然，本研究樣本量較小，尚需更大規(guī)模的臨床研究來證實(shí)，同時(shí)也需要進(jìn)一步探討其具體機(jī)制。

[1]Vincent JL, Sakr Y, Sprung CL,et al. Sepsis in European intensive care units: results of the SOAP study[J]. Crit Care Med, 2006, 34(2): 344-353.

[2]Blanco J, Muriel-Bombín A, Sagredo V,et al. Incidence, organ dysfunction and mortality in severe sepsis: A Spanish multicenter study[J]. Crit Care, 2008, 12(6): R158.

[3]Wang CJ, Liu HX, Wang YM,et al. Changes of accompanying femoral artery and vein blood gas analysis in patients with burnsepsis[J]. Tianjin Med J, 2015, 43(1): 72-74. [王車江, 劉洪霞,王宜民, 等. 燒傷膿毒癥患者伴行股動(dòng)脈、股靜脈血?dú)庾兓芯縖J]. 天津醫(yī)藥, 2015, 43(1): 72-74.]

[4]Zhang ZG, Liu J, Zhang CY. Clinical observation on effects of high frequency oscillating ventilation on patients with early acute respiratory distress syndrome[J]. Med J Chin PLA, 2013, 38(1): 58-61. [張志剛, 劉健, 張彩云. 高頻振蕩通氣對(duì)早期急性呼吸窘迫綜合征患者的治療作用[J]. 解放軍醫(yī)學(xué)雜志, 2013, 38(1): 58-61.]

[5]Yang Y, Qiu HB. Acute respiratory distress syndrome in the past present and future[J]. Chin J Pract Intern Med, 2013, 33(11): 833-837. [楊毅, 邱海波. 急性呼吸窘迫綜合征過去 現(xiàn)在 未來[J]. 中國(guó)實(shí)用內(nèi)科雜志, 2013, 33(11): 833-837.]

[6]Spronk PE, Ince C, Gardien MJ,et al. Nitroglycerin in septic shock after intravascular volume resuscitation[J]. Lancet, 2002, 360(9343): 1395-1396.

[7]Kleschyov AL, Oelze M, Daiber A,et al. Does nitric oxide mediate the vasodilatory activity of nitroglycerin[J]? Circ Res, 2003, 93(9): e104-e112.

[8]Levy MM, Fink MP, Marshall JC,et al. 2001 SCCM/ESICM/ ACCP/ATS/SIS International Sepsis Definitions Conference[J]. Crit Care Med, 2003, 31(4): 1250-1256.

[9]Bernard GR, Artigas A, Brigharn KL,et al. The American-European Consensus Conference of ARDS: definition, mechanisms, relevant outcomes and clinical tri al coordination[J]. Am J Respir Crit Care Med, 1994, 149(3Pt1): 814-818.

[10] Kurose I, Wolf R, Grisham MB,et al. Modulation of ischemia/ reperfusion-induced microvascular dysfunction by nitric oxide[J]. Circ Res, 1994, 74(3): 376-382.

[11] McVeigh GE, Allen PB, Morgan DR,et al. Nitric oxide modulation of blood vessel tone identified by arterial waveform analysis[J]. Clin Sci, 2001, 100(4): 387-393.

[12] Jiang XJ, O'Rourke MF, Jin WQ,et al. Quantification of glyceryl trinitrate effect through analysis of the synthesised ascending aortic pressure waveform[J]. Heart, 2002, 88(2): 143-148.

[13] Hollenberg SM. Vasodilators in acute heart failure[J]. Heart Fail Rev, 2007, 12(2): 143-147.

[14] Elkayam U, Bitar F, Akhter M,et al. Intravenous nitroglycerin in the treatment of decompensated heart failure: potential benefits and limitations[J]. J Cardiovasc Pharmacol Ther, 2004, 9(4): 227-241.

[15] Shin DD, Brandimarte F, De Luca L,et al. Review of current and investigational pharmacologic agents for acute heart failure syndromes[J]. Am J Cardiol, 2007, 99(2A): 4A-23A.

[16] Qiu HB, Dai JH, Yang Y,et al. Clinical epidemiology of acute respiratory distress syndrome from 1991 to 2001[J]. Chin Crit Care Med, 2003, 7(23): 489-491. [邱海波, 代靜泓, 楊毅, 等. 1991-2001年急性呼吸窘迫綜合癥的臨床流行病學(xué)調(diào)查[J].中國(guó)急救醫(yī)學(xué), 2003, 7(23):489-491.]

Clinical efficacy of nitroglycerin in patients with septic shock with ARDS

LIU Li-ping1, LI Bin1, ZHU Lei1, DOU Zhi-min1, LI Yu-min2*1Department of Critical Care Medicine, First Hospital of Lanzhou University, Lanzhou 730000, China
2Department of General Surgery, Second Hospital of Lanzhou University, Lanzhou 730030, China
*< class="emphasis_italic">Corresponding author, E-mail: lym19621225@hotmail.com

, E-mail: lym19621225@hotmail.com
This work was supported by the Hospital Fund of First Hospital of Lanzhou University (ldyyynlc201110)

ObjectiveTo evaluate the clinical efficacy of nitroglycerin in patients with septic shock with ARDS, and explore its possible mechanism.MethodsFrom January 2013 to January 2014, patients with septic shock with ARDS were included in the study in the department of critical care medicine in our hospital. Patients who met the criteria were randomly divided into the control group and the nitroglycerin group. The standard treatment was given in control group, and nitroglycerin 0.5-1.0mg/h was given in nitroglycerin group on basis of standard treatment. Monitoring indexes were recorded at 0, 6, 24 and 72h, including general condition, APACHE Ⅱ score, hemodynamic indexes (HR, MAP, CVP, CI, SVRI, PAWP, PAP, Lac), volume of fluid resuscitation, quantity of vasopressor drugs, ventilator condition (PH, PO2, PCO2, RR, PEEP, VT, FiO2, oxygenation index, airway resistance, lung compliance), mechanical ventilation time, ICU stay time, hospital follow-up, 28-day follow-up, immune index (CD4+/CD8+), inflammatory markers (CRP, PCT, IL-6, WBC).ResultsForty-three patients were included in this study, with 21 in control group and 22 in nitroglycerin group. At 24 and 72h after the treatment, APACHEⅡ score, heart rate, pulmonary artery pressure (PAP), lactic acid and dopamine, norepinephrine, respiratory rate (RR), inspired oxygen concentration (FiO2), airway resistance, C reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), white blood cell count (WBC) significantly decreased as compared with those at 0 and 6 h, and these parameters in nitroglycerin group were lower than these in the control group at the 72h (P<0.05); at thesame time, those indexes such as peripheral vascular resistance index (SVRI), pH value, arterial partial pressure of oxygen (PaO2), tidal volume (VT), lung compliance, oxygenation index, CD4+/CD8+more significantly increased in the treatment group at 24 and 72h than those at 0 and 6h, especially at 72h, and these values were significantly higher than that of control group (P<0.05). Time of mechanical ventilation, ICU stay and hospital stay in nitroglycerin group was respectively lower than those of the control group (P<0.05); the hospital mortality and 28-day mortality rate in nitroglycerin group were significantly lower than that of control group (P<0.05).ConclusionNitroglycerin in the patients with septic shock complicated by ARDS can improve the ventilator condition, shorten the time for mechanical ventilation, ICU stay and hospital stay, and reduce the mortality rate, as nitroglycerin can reduce the resistance of pulmonary circulation and systemic inflammatory reaction, and enhance immunity by improving microcirculation.

nitroglycerin; shock, septic; acute respiratory distress syndrome

R631.4

A

0577-7402(2015)08-0647-05

10.11855/j.issn.0577-7402.2015.08.09

2014-12-27；

2015-06-23)

(責(zé)任編輯：熊曉然)

蘭州大學(xué)第一醫(yī)院院內(nèi)基金(ldyyynlc201110)

劉麗平，副主任醫(yī)師，博士研究生。主要從事重癥醫(yī)學(xué)的臨床與基礎(chǔ)研究

730000 蘭州 蘭州大學(xué)第一醫(yī)院重癥醫(yī)學(xué)科(劉麗平、李斌、朱磊、竇志敏)；730030 蘭州 蘭州大學(xué)第二醫(yī)院普外科(李玉民)

李玉民，E-mail: lym19621225@hotmail.com