劉紅升,蘇 琴,趙曉東,果應(yīng)菲,姚詠明,張慶紅
中國(guó)人民解放軍總醫(yī)院第一附屬醫(yī)院急救部,北京100048
神經(jīng)源性肺水腫早期形式的急診識(shí)別及治療
劉紅升,蘇 琴,趙曉東,果應(yīng)菲,姚詠明,張慶紅
中國(guó)人民解放軍總醫(yī)院第一附屬醫(yī)院急救部,北京100048
目的 提高急診臨床對(duì)非創(chuàng)傷性腦出血患者發(fā)生神經(jīng)源性肺水腫(NPE)的早期診治水平。方法 將2008 年10月至2014年10月中國(guó)人民解放軍總醫(yī)院第一附屬醫(yī)院急救部收治的非創(chuàng)傷性急性腦出血患者中符合入選標(biāo)準(zhǔn)的140例患者分為發(fā)病后發(fā)生NPE組(n=25)及未發(fā)生NPE(n=115),對(duì)兩組患者診治過程中的臨床資料進(jìn)行分析和比較。結(jié)果 雖然NPE組與非NPE組患者平均動(dòng)脈壓相似,但兩組患者動(dòng)脈血?dú)庵械膒H值(pH 7.32比7.39,P=0.002)及HCO3-濃度(20.6 mmol/L比22.7 mmol/L,P=0.01)差異均有統(tǒng)計(jì)學(xué)意義。NPE組與非NPE組患者的年齡(50.1歲比65.1歲,P=0.0008)和血糖水平(15.4 mmol/L比10.78 mmol/L,P=0.001)差異也有統(tǒng)計(jì)學(xué)意義。急診救治24 h時(shí),NPE組25例患者中20例有效;5例死亡,其中3例暴發(fā)性NPE(均在1 h內(nèi)發(fā)病)死于急性呼吸窘迫綜合征并發(fā)全身多系統(tǒng)器官功能衰竭,2例死于腦疝。結(jié)論 NPE是腦出血患者中少見且預(yù)后差的嚴(yán)重并發(fā)癥之一。對(duì)相對(duì)年輕、高血糖及血?dú)馄岬哪X出血患者要警惕早期NPE的發(fā)生,積極預(yù)防和及時(shí)治療可以提高該病救治成功率。
腦出血;早期神經(jīng)源性肺水腫;急診室;診治
Acta Acad Med Sin,2015,37(3):343-347
神經(jīng)源性肺水腫(neurogenic pulmonary edema,NPE)是指在沒有心、肺原發(fā)疾病情況下,由于顱腦損傷或中樞神經(jīng)系統(tǒng)疾病引起的急性肺間質(zhì)和肺泡液體滲出導(dǎo)致急性肺水腫的臨床綜合征,病因被認(rèn)為是大量?jī)翰璺影穼?dǎo)致心肺功能障礙[1-3]。NPE的臨床表現(xiàn)分為兩種截然不同的類型,其中早期形式最常見,其發(fā)展特點(diǎn)是肺水腫癥狀在神經(jīng)損傷后幾分鐘到幾小時(shí)后即出現(xiàn);另一種為延遲形式,是中杻神經(jīng)系統(tǒng)(central nerve system,CNS)損傷后12~24 h出現(xiàn)NPE[4-5]。盡管這兩種類型的NPE在臨床上都很重要,但是預(yù)測(cè)早期形式特別是早期暴發(fā)性NPE在急診臨床中更加重要,因其臨床表現(xiàn)更加兇險(xiǎn),起病非常急劇,進(jìn)展快速,臨床預(yù)后極差,是一種罕見但致命的肺部并發(fā)癥[1-2]。本研究回顧性分析了140例非創(chuàng)傷性腦出血患者的臨床資料,對(duì)NPE組和非NPE組患者進(jìn)行了比較,分析了NPE患者臨床發(fā)病及診治過程的特征,以期提高急診臨床對(duì)非創(chuàng)傷性腦出血患者發(fā)生NPE的早期診治水平。
資料來源 2008年10月至2014年月10月中國(guó)人民解放軍總醫(yī)院第一附屬醫(yī)院急救部收治的非創(chuàng)傷性腦出血患者140例。排除標(biāo)準(zhǔn):(1)年齡<15歲,入院前心跳驟停、呼吸驟?;騼烧呔?(2)既往有嚴(yán)重心臟病,肺、腦疾病病史;(3)以往發(fā)現(xiàn)胸部X線片異常; (4)入院12 h后出現(xiàn)急性發(fā)作性肺水腫;(5)有跌倒致頭部外傷史。
方法 以患者出現(xiàn)癥狀呼叫緊急救助時(shí)間作為發(fā)病時(shí)間,所有患者均在來診后最短時(shí)間內(nèi)行頭顱CT檢查,并立即在急診室完成胸部X線片、血?dú)夥治龊统曅膭?dòng)圖。一旦確診為腦出血,立即按照現(xiàn)行指南的搶救預(yù)案進(jìn)行處置[6]。早期急診處置為立即給予循環(huán)和呼吸支持。早期腦出血處置為控制血壓、降顱壓(存在高顱壓時(shí))、維持正常循環(huán)血量,并在后序給予外科治療。所有患者均在入院后72 h時(shí)給予格拉斯哥預(yù)后評(píng)分: (1)5分:恢復(fù)良好; (2)4分:輕度殘疾;(3)3分:重度殘疾;(4)2分:植物生存;(5) 1分:死亡[7]。
早期NPE定義:確診為腦出血的患者,發(fā)病后12 h內(nèi)出現(xiàn)急性發(fā)作性肺水腫,除外心源性肺水腫及輸液過快過量等原因?qū)е碌淖笮乃ソ?。同時(shí)伴有:(1)雙肺浸潤(rùn)(除外誤吸導(dǎo)致的吸入性肺炎); (2)氧合指數(shù)<300 mmHg(1 mmHg=0.133 kPa); (3)無左心房高壓的證據(jù);(4)無其他常見急性呼吸窘迫綜合征(acute respiratory distress syndrome,ARDS)的原因(如誤吸、大量輸血、膿毒癥)。暴發(fā)性NPE的上述臨床癥狀更加兇險(xiǎn),病情進(jìn)展極為迅速[8-10]。
統(tǒng)計(jì)學(xué)處理 采用SPSS 16.0統(tǒng)計(jì)軟件,分類比較采用卡方檢驗(yàn),組間比較采用曼-惠特尼U檢驗(yàn),對(duì)患者的年齡、性別、平均動(dòng)脈壓、腦出血部位、血糖水平等采用多變量Logistic回歸分析,P<0.05為差異有統(tǒng)計(jì)學(xué)意義。
一般情況 NPE組25例患者中,男8例,女7例; 非NPE組115例患者中,男38例,女75例;兩組間差異無統(tǒng)計(jì)學(xué)意義(P=0.92)。NPE組患者的中位年齡為50.1歲(48.3~68.4歲),明顯低于非NPE組的65.1歲(58.6~84.2歲)(P=0.001)。NPE組25例患者中,基底節(jié)、丘腦、腦葉和腦干的出血例數(shù)分別為12(48.0%)、6(24.0%)、3(12.0%)和4(16.0%);非NPE 組115例患者中,基底節(jié)、丘腦、腦葉和腦干的出血例數(shù)分別為56(48.6%)、25(21.7%)、14(12.2%) 和20(17.4%);兩組間差異無統(tǒng)計(jì)學(xué)意義(P=0.42)。NPE組25例患者中,高血壓和糖尿病的例數(shù)分別為11(44.0%)和1(4.0%);非NPE組115例患者中,高血壓和糖尿病的例數(shù)分別為53(46.0%)(P=0.63)和55(4.8%) (P=0.75),差異均無統(tǒng)計(jì)學(xué)意義。
格拉斯哥預(yù)后評(píng)分 NPE組25例患者中,格拉斯哥預(yù)后評(píng)分為5分、4分、3分、2分和1分的例數(shù)分別為 8(32.0%)、8(32.0%)、2(8.0%)、2(8.0%)和5(20.0%);非 NPE組115例患者中,格拉斯哥預(yù)后評(píng)分為5分、4分、3分、2分和1分的例數(shù)分別為20(17.4%)、21(18.3%)、20(17.4%)、14(12.1%)和40(34.8%);兩組間差異無統(tǒng)計(jì)學(xué)意義(χ2=6.75,P=0.17)。
兩組患者治療過程中觀察數(shù)據(jù)的比較 NPE組和非NPE組患者的平均動(dòng)脈壓[120.8 mmHg(109.0~145.6 mmHg)比123.6 mmHg(110.7~142.8 mmHg),P=0.96]和體溫[36.0℃(35.2~36.6℃)比35.9℃(35.0~36.4℃),P=0.87]差異無統(tǒng)計(jì)學(xué)意義;NPE組患者的PaO2/FiO2[110.0(67.2~146.3)比321.5(158.5~478.6),P=0.001]、pH值 [7.32(7.26~7.38)比7.39(7.35~7.43),P=0.002]、HCO3-濃度[20.6 mmol/L(18.6~22.6 mmol/L)比22.7 mmol/L(20.8~24.6 mmol/L),P=0.01] 和血糖水平[15.4 mmol/L(11.8~17.7 mmol/L)比10.8 mmol/L(9.3~13.1 mmol/L),P=0.001]差異均有統(tǒng)計(jì)學(xué)意義。
Logistic回歸分析結(jié)果 多變量邏輯回歸分析與早期NPE相關(guān)的變量,包括年齡、性別、體溫、平均動(dòng)脈壓和血糖水平,結(jié)果顯示,年齡(P=0.004)和血糖水平(P=0.001)與發(fā)生早期NPE顯著相關(guān)(表1)。
預(yù)后 NPE組25例患者中,14例治療后6 h內(nèi)肺水腫癥狀糾正或大部分緩解,6例于72 h內(nèi)緩解。5 例(20.0%)于治療后24 h內(nèi)死亡,其中3例暴發(fā)性NPE于12 h內(nèi)均死亡,死因?yàn)锳RDS并發(fā)MOF;另外2例死于腦疝。
表1 多元回歸分析發(fā)生神經(jīng)源性肺水腫的相關(guān)因素Table 1 Logistic regression analysis of the risk factors of the early form of neurogenic pulmonary edema
急性腦血管疾病并發(fā)NPE的機(jī)制目前尚不十分清楚[11-12],對(duì)NPE的診斷和管理仍存在爭(zhēng)議和挑戰(zhàn),在實(shí)際工作中出現(xiàn)的各種臨床情況都可能混淆診斷。尤其是在急診救治各種CNS損傷患者時(shí),NPE的不定時(shí)發(fā)生、相對(duì)不可預(yù)測(cè)性和缺乏特殊病原學(xué)診斷標(biāo)記物和治療方法都令急診醫(yī)師感到困擾。目前NPE的發(fā)病機(jī)制存在沖擊傷理論和滲透缺陷理論兩種理論[13]。沖擊傷理論認(rèn)為,中樞神經(jīng)系統(tǒng)損傷可導(dǎo)致交感神經(jīng)沖動(dòng)釋放增加,引發(fā)短暫而劇烈地體循環(huán)血管收縮,使大量靜脈血回流,造成肺循環(huán)發(fā)生短暫而嚴(yán)重高壓,一方面導(dǎo)致壓力性肺水腫,另一方面肺毛細(xì)血管由于沖擊傷作用,內(nèi)皮細(xì)胞損傷,導(dǎo)致大量血漿蛋白外滲,這種改變?cè)趬毫ο陆岛笕匀淮嬖凇B透缺陷理論則認(rèn)為交感神經(jīng)系統(tǒng)起主導(dǎo)作用,介導(dǎo)了NPE的血管通透性改變。
NPE的肺水腫臨床表現(xiàn)并無特異性,特別是早期形式的NPE,因?yàn)榘Y狀出現(xiàn)通常幾分鐘到幾小時(shí),所以有時(shí)可迅速消退,故有些患者不顯示所有預(yù)期的癥狀,如呼吸困難、呼吸急促、心動(dòng)過速等,還有很多患者由于延誤治療時(shí)機(jī)或者處于昏迷狀態(tài),常見不到肺水腫的早期表現(xiàn),常在咳出粉紅色泡沫痰或呼吸困難雙肺出現(xiàn)哮鳴音時(shí)才被發(fā)現(xiàn),從而造成急診臨床上被誤診及漏診,暴發(fā)性NPE則發(fā)病更是極為迅猛,臨床表現(xiàn)更加兇險(xiǎn),本研究中3例暴發(fā)性NPE患者均在來診1 h內(nèi)突然出現(xiàn)呼吸窘迫、極度呼吸困難、呼吸過速及嚴(yán)重低血癥(SpO2<50%);兩肺聽診時(shí)細(xì)爆裂聲,水泡音迅速出現(xiàn)并進(jìn)行性加重,布滿雙肺,立即行氣管插管后有大量洗肉水樣、粉紅色、泡沫樣分泌物涌出氣道,并持續(xù)加重。3例暴發(fā)性NPE的胸片均為高密度浸潤(rùn)符合ARDS,發(fā)病前均無心、肺、腦等慢性疾病史[14]。由于暴發(fā)性NPE臨床發(fā)病率較少,6年來我院只診斷3例,故本研究入選病例數(shù)較少,這也是本研究局限之處。
在本研究臨床診治過程中筆者發(fā)現(xiàn),性別、血壓、腦出血部位及出血量的多少并不能夠?qū)υ\斷NPE有所幫助,但值得注意的是,NPE組動(dòng)脈血?dú)庵械膒H值及HCO3-濃度均較非NPE組顯著降低,但該結(jié)果尚需更多的病例進(jìn)一步證實(shí)。多變量回歸分析結(jié)果則顯示,相對(duì)小的年齡和高血糖狀態(tài)與早期形式NPE的發(fā)生具有統(tǒng)計(jì)學(xué)意義的相關(guān)性,提示該指標(biāo)對(duì)預(yù)測(cè)早期形式NPE的發(fā)生可能具有一定意義。本研究中3例暴發(fā)性NPE較非暴發(fā)性NPE患者臨床癥狀出現(xiàn)時(shí)間更早、癥狀更嚴(yán)重,并均死亡,但因?yàn)椴±龜?shù)太少,因此僅能做一描述,沒有得出統(tǒng)計(jì)學(xué)結(jié)論。
NPE的治療目前主要集中在平息交感神經(jīng)過度活躍導(dǎo)致肺損傷及對(duì)癥處理,治療方法從對(duì)抗交感神經(jīng)沖動(dòng)增加、降低肺毛細(xì)血管壓力和穩(wěn)定肺毛細(xì)血管通透性這兩方面入手,以利減少NPE的發(fā)生,改善預(yù)后,提高生存率[15-16]。本研究NPE組除對(duì)腦出血給予常規(guī)治療外,還立即實(shí)施階梯性呼吸支持法,及時(shí)行氣管插管等有效氣道管理方法,以保持PaO2>60 mmHg;在使用呼吸機(jī)通氣時(shí),20例行呼氣末正壓通氣(positive end expiratory pressure,PEEP)的患者中,3例暴發(fā)性NPE均行6~15個(gè)PEEP治療,但其經(jīng)皮血氧飽合度SpO2仍不能夠維持,波動(dòng)在40%~75%。此外,應(yīng)大劑量聯(lián)合應(yīng)用脫水劑,甘露醇與速尿交替使用,盡快降低顱內(nèi)壓;同時(shí)給予甲潑尼松龍80 mg靜脈滴注降低毛細(xì)血管通透性,輔助治療腦水腫和肺水腫[17-19]。采用血管活性藥物西地蘭或酚妥拉明降低心臟負(fù)荷,調(diào)整循環(huán),及時(shí)監(jiān)測(cè)電解質(zhì)水平,保持電解質(zhì)和酸堿平衡等。并常規(guī)應(yīng)用有效抗生素、防治上消化道出血、肺部感染及加強(qiáng)護(hù)理等[20]。
本研究不足之處在于,入組病例數(shù)較少;患者發(fā)病時(shí)間,特別是昏迷患者不能準(zhǔn)確界定;僅為單中心、回顧性研究,因此不能確定發(fā)生NPE的因果關(guān)系。但本研究最主要目的是為了拋磚引玉,引起急診同仁對(duì)NPE的重視,特別是對(duì)暴發(fā)性NPE,在急救工作中能夠快速識(shí)別,從而提高該類疾病患者的預(yù)后。
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Identification and Treatment of the Early Form of Neurogenic Pulmonary Edema in Emergency Room
LIU Hong-sheng,SU Qin,ZHAO Xiao-dong,GUO Ying-fei,YAO Yong-ming,ZHANG Qing-hong
Emergency Department,the First Affiliated Hospital of Chinese PLA General Hospital,Beijing 100048,China
Objective To improve the management of the early neurogenic pulmonary edema(NPE) in patients with non-traumatic cerebral hemorrhage.Methods Totally 140 eligible patients with non-traumatic cerebral hemorrhage who were treated in the emergency department of our hospital from October 2008 to October 2014 were divided into two groups:NPE group(n=25)and non-NPE group(n=115).The clinical data were analyzed and compared.Results Although the mean arterial pressure was similar between these two groups,the median pH and the bicarbonate ion(HCO3-)were significantly lower in the NPE group than in the non-NPE group(pH:7.32 vs.7.39,P=0.002;HCO3-,20.6 mmol/L vs.22.7 mmol/L,P=0.01).Multivariate regression analysis indicated that younger age and higher glucose level were significantly correlated with the early onset of NPE in the NPE group than in the non-NPE group(age:50.1 years vs.65.1 years,P= 0.0008;glucose,15.4 mmol/L vs.10.78 mmol/L,P=0.001).There were only 3 patients in all with non-traumatic cerebral hemorrhage happened the fulminant NPE in 1 hour.Within 24 hours after patients visited the emergency room,the condition was improved in 20 of 25 patients in the NPE group.However,5 patients died,among whom 3 patients with fulminant NPE(onset within 1 hour)died due to acute respiratory distress syndrome and complicated with multiple organ failure,and 2 died of cerebral hernia.Conclusions NPE is a rare and severe complication in patients with non traumatic cerebral hemorrhage.The possibility of NPE should be considered in relatively young patients with higher glucose and lower blood pH value.Timely prevention and treatment can improve the outcomes.
cerebral hemorrhage;the early form neurogenic pulmonary;emergency room;diagnosis and treatment
SU Qin Tel:010-33556740,E-mail:suqin1117@126.com
R743.3
A
1000-503X(2015)03-0343-05
10.3881/j.issn.1000-503X.2015.03.019
2015-01-04)
蘇 琴 電話:010-33556740,電子郵件:suqin1117@126.com
國(guó)家自然科學(xué)基金(81272089)Supported by the National Natural Sciences Foundation of China(81272089)