ARDS进展（急性呼吸窘迫综合征）-施焕中

1、急性呼吸窘迫综合征广西医科大学第一附属医院呼吸内科施焕中广西医科大学第一附属医院危重症中心N EnglJMed2003;348:683-693.N EnglJMed2003;348:683-693.N EnglJMed2003;348:683-693.MethodsWeevaluated109 survivorsoftheacuterespiratorydistresssyndrome3,6,and12months after dischargefrom theintensivecareunit.Ateach visit,patientswere interviewedandunderwent

2、 aphysicalexamination, pulmonary-functiontesting,a six-minutewalktest,andaquality-of-lifeevaluation.ResultsPatientswhosurvivedthe acute respiratory distresssyndromewere young (medianage,45years)and severely ill(median Acute Physiology, Age,and ChronicHealth Evaluationscore,23) andhadalong stayinthe

3、intensivecare unit(median,25days).Patientshad lost18percentoftheirbase-linebodyweightbythe timetheywere dischargedfromtheintensive careunit andstatedthatmuscleweaknessand fatiguewerethereasonsfortheirfunctionallimitation.Lung volumeandspirometricmeasurementswerenormalby6months, butcarbonmonoxidediff

4、usioncapacityremainedlowthroughoutthe12-monthfollow-up.Nopatientsrequiredsupplementaloxygen at 12 months,but 6percentofpatientshadarterialoxygen saturationvalues below 88 percentduringexercise. Themedianscorefor thephysicalrole domainoftheMedicalOutcomesStudy36-item Short-FormGeneralHealthSurvey(ahe

5、alth-relatedquality-of-life measure) increasedfrom 0at3monthsto25at12months (scoreinthenormal population,84). Thedistancewalkedinsix minutesincreased fromamedianof281mat3 monthsto422mat12months; allvalueswerelowerthan predicted.The absenceofsystemiccorticosteroidtreatment, theabsence of illnessacqui

6、redduring theintensivecare unitstay,and rapid resolutionoflunginjuryandmultiorgandysfunctionwere associatedwithbetterfunctionalstatusduringtheone-yearfollow-up.ConclusionsSurvivorsofthe acute respiratory distress syndromehave persistentfunctionaldisability oneyear after dischargefrom theintensivecar

7、eunit.Most patients haveextrapulmonaryconditions,with musclewasting andweaknessbeingmost prominent.N EnglJMed2003;348:683-693.定义ALI/ARDS是指由心心源性以以外的各各种肺内内外致病病因素导导致的急急性、进进行性缺缺氧性呼呼吸衰竭竭。ALI/ARDS具有性质质相同的的病理生生理改变变，严重重的ALI即被定义为ARDS。ALI/ARDS以肺微血血管通透透性增加加、肺气气容积减减少、肺肺顺应性性降低和和严重肺肺内分流流及通气气/血流比例例失调为为病理生生理特点点，临床床

8、表现为为不易缓缓解的急急性进行行性缺氧氧性呼吸吸衰竭，胸部X线可见肺肺部浸润润征象。高危因素素一、直接接肺损伤伤因素严重肺部部感染、胃内容容物吸入入、溺水水、吸入入有毒气气体、肺肺挫伤、氧中毒毒等。二、间接接肺损伤伤因素脓毒症、休克、严重非非胸部创创伤、重重症胰腺腺炎、大大量输血血、输液液、体外外循环、DIC等。发病机制制一、血管管内皮和和气道上上皮损伤伤二、中性性粒细胞胞介导的的肺损伤伤三、其他他炎症机机制细胞因子子表面活性性物质呼吸机引引起的肺肺损伤其他损伤伤机制四、机化化性肺泡泡炎发病机制制TheNormal Alveolus (Left-HandSide)and theInjured

9、Alveolus in theAcutePhaseofAcuteLung Injuryandthe Acute Respiratory Distress Syndrome (Right-Hand Side).Intheacutephaseofthe syndrome (right-hand side),thereissloughingofboththebronchial andalveolarepithelial cells,with theformationofprotein-rich hyalinemembranes on thedenuded basement membrane.Neut

10、rophilsareshownadheringtothe injuredcapillary endothelium andmarginatingthrough theinterstitiuminto theairspace, which is filledwith protein-richedemafluid.Inthe airspace,analveloarmacrophage is secretingcytokines, interleukin-1, 6, 8, and10,(IL-1, 6, 8, and10)and tumor necrosis factor(TNF- ), which

11、 actlocally to stimulatechemotaxis andactivateneutrophils.Macrophagesalsosecrete other cytokines,including interleukin-1, 6, and10.Interleukin-1canalsostimulatethe productionofextracellularmatrixbyfibroblasts. Neutrophils canrelease oxidants,proteases,leukotrienes, andotherproinflammatorymolecules,s

12、uch as platelet-activatingfactor (PAF).A numberofantiinflammatorymediatorsare alsopresentinthealveolarmilieu,includinginterleukin-1receptorantagonist,soluble tumor necrosis factorreceptor,autoantibodiesagainst interleukin-8, andcytokinessuchasinterleukin-10and11(notshown). Theinfluxofprotein-rich ed

13、ema fluid intothe alveolus hasledtothe inactivationofsurfactant.MIFdenotesmacrophage inhibitoryfactor.发病机制制管状髓磷磷脂发病机制制Surfactant Productionand RecyclingintheNormal Alveolus (PanelA)andChangesinSurfactant MetabolisminAcuteLungInjury(Panel B).Inthenormal alveolus,surfactant is synthesized andpackagedi

14、nto lamellar bodiesinthecellcytoplasm. These lamellar bodiesthen migratetothe cellmembrane, withwhichtheyfuse,andthenarereleasedintotheairfluid interfacewithinthe alveolus.They subsequentlyform an intermediatetubular stage of surfactantcalled tubularmyelin,whichfinally produces thefunctional coating

15、layer. Surfactantproteinsare alsoinvolvedinthe coatingprocess.Surfactantrecyclingoccurs throughtheendocytosisofsmallvesicles.Alterationsinsurfactantmetabolism (PanelB)mayoccuratany of these steps.Theexactpathophysiologyofsurfactant metabolisminARDShasnot beenfullyestablished, butitislikelytoconsisto

16、fboth thedestructionandthe structuralalterationofsurfactant lipidsandproteincausedbythe inflammatorymilieuofthe injuredair space.Inaddition,synthesis andrecyclingofsurfactantarelikely to be reducedand itsfunctionimpairedbytheaccumulation ofproteinaceousmaterialwithinthe alveolus.TNFdenotestumornecro

17、sisfactor.病理2 d14d14d病理4 d14dPanelA shows alung-biopsyspecimenobtainedfroma patienttwo daysafterthe onset of thesyndromeasa resultoftheaspirationofgastric contents.Characteristichyaline membranesareevident(arrow),with associatedintraalveolarredcellsand neutrophils,findingsthat areconsistent withthe

18、pathologicaldiagnosisofdiffusealveolardamage(hematoxylinandeosin, x90). PanelsB andC showlung-biopsyspecimens obtained 14 daysafterthe onset of sepsis-associated acute lunginjury andtheacuterespiratorydistresssyndrome. Panel Bshowsgranulationtissue in thedistalair spaceswith achronicinflammatory-cel

19、linfiltrate (hematoxylinandeosin, x60).TrichromestaininginPanelC revealscollagendeposition(darkblue areas)inthegranulationtissue,a findingthatisconsistent withthe depositionofextracellularmatrixinthe alveolar compartment (x60).PanelD shows aspecimenoflungtissuefroma patientwho diedfourdays after the

20、onsetofacutelung injuryandthe acute respiratory distress syndrome;thereisinjurytoboththecapillary endothelium andthealveolarepithelium.Thereisanintravascularneutrophil (LC)inthe capillary(C). Vacuolizationand swelling of theendothelium(EN) areapparent.Lossofalveolarepithelial cells is alsoapparent,

21、withthe formationofhyaline membranesontheepithelialside of thebasementmembrane(BM*).PanelEshowsa specimen of lungtissue obtained fromapatient duringthefibrosing-alveolitisphaseinwhichthereisevidenceofreepithelializationoftheepithelialbarrier withalveolarepithelialtype II cells.Thearrowindicates atyp

22、icaltype II cellwithmicrovilliandlamellarbodies containingsurfactant.The epithelialcellimmediatelyadjacenttothis cellisinthe processofchangingtoatype Icell,withflattening,loss of lamellar bodies,andmicrovilli. Theinterstitiumisthickened, withdepositionofcollagen(C).临床表现现一、大多多起病急急剧，进进展快。二、呼吸吸困难、窘迫，一般

23、氧氧疗难以以纠正。三、体格格检查：早期可可无明显显异常，较多见见呼吸频频数。唇唇指发绀绀，心率率增加，肺部听听诊可闻闻及于罗罗音或哮哮鸣音，后期出出现湿罗罗音并呈呈肺实变变体征。四、胸部部X线表现：早期可可无异常常,或呈轻度度间质改改变，表表现为纹纹理增多多、边缘缘模糊，继之出出现斑片片状或大大片状阴阴影，后后期两肺肺可出现现广泛实实变。X线PanelA shows ananteroposteriorchestradiograph froma42-year-oldmanwiththeacuterespiratorydistresssyndromeassociatedwith gram-nega

24、tivesepsis whowasreceiving mechanicalventilation. Thepulmonary-artery wedge pressure,measuredwith apulmonary-arterycatheter,was 4mmHg. There arediffuse bilateralalveolaropacitiesconsistentwith thepresenceofpulmonaryedema. Panel Bshowsananteroposteriorchestradiograph froma60-year-oldmanwithacutelung

25、injuryandthe acute respiratory distress syndrome whohadbeenreceivingmechanicalventilationforsevendays.Reticular opacitiesarepresentthroughout bothlungfields, afindingsuggestive of thedevelopmentoffibrosingalveolitis. Panel CshowsaCTscan of thechestobtainedduringthe acute phase.Thebilateral alveolar

26、opacitiesaredenser in thedependent, posteriorlung zones,with sparingofthe anterior lungfields.Thearrows indicate thickenedinterlobularsepta, consistentwiththepresenceofpulmonary edema.Thebilateral pleuraleffusions area commonfinding.PanelD shows aCTscanofthechestobtainedduring thefibrosing-alveoliti

27、sphase.Thereare reticularopacitiesand diffuseground-glass opacitiesthroughout bothlungfields, anda large bulla is presentinthe leftanteriorhemithorax.诊断标准准一、有发发病的高高危因素素。二、急性性起病，呼吸频频数和（或）呼呼吸窘迫迫。三、低氧氧血症：ALI时PaO2/FiO2300 mmHg；ARDS时PaO2/FiO2200 mmHg。四、胸部部X线检查两两肺浸润润影响。五、PCWP18 mmHg或临床上上能除外外心源性性肺水肿肿。返符合以以

28、上5项者可诊诊断为ALI或ARDS。一、不把把是否行行机械通通气和行行机械通通气的时时间纳入入诊断标标准。二、不强强调PEEP对氧合的的影响。三、为了了动态观观察病情情变化，对上机机患者应应尽量在在相同的的通气条条件下进进行前后后比较。四、PaO2/FiO2难于排除除通气功功能障碍碍对氧合合的影响响。在临临床应用用中以PAAO2可以更好好地反映映ARDS的病理生生理特点点，从而而提高ARDS诊断的特特异性，应用时时宜注意意氧浓度度的影响响。诊断时应应注意以以下各项项五、ARDS胸片的表表现缺少少特异性性，在不不同的原原发病和和不同的的时期可可有不同同的表现现，可以以为间质质或实质质，散在在或弥

29、漫漫，可轻轻可重，但进展展迅速。六、若能能除外左左房压高高，PAWP对诊断ARDS并非必须须，但对对无典型型胸片或或不能完完全从临临床表现现除外左左房高压压的患者者，必须须有PAWP作为诊断断条件。七、有慢慢性肺病病者（如如肺间质质纤维化化、结节节病等），即使使达到ARDS的诊断标标准也不不纳入ARDS。诊断时应应注意以以下各项项治疗一、原发发病的治治疗应积极寻寻找原发发病灶并并予以彻彻底治疗疗。感染染是导致致ARDS的常见原原因，而而且ARDS易并发感感染，所所以对于于所有的的病人都都应怀疑疑感染的的可能，除非有有明确的的其他导导致ARDS的原因存存在。宜宜选择广广谱抗生生素。2004-07

30、-272004-08-122004-08-142004-08-152004-08-172004-08-182004-08-202004-08-232004-08-252004-08-272004-08-302004-08-312004-09-012004-09-032004-09-072004-09-152004-09-202004-09-232004-09-272004-09-302004-10-082004-10-172004-10-24治疗二、机械械通气机械通气气是ARDS最为重要要的支持持治疗手手段。在在掌握ARDS呼吸力学学改变特特点的基基础上，合理的的使用机机械通气气技术对对于提高

31、高ARDS的抢救成成功率具具有重要要意义。详见下述述。治疗三、液体体管理保持循环环系统较较低的前前负荷可可减少肺水水的含量量，有报报道可以以缩短上机时间间和降低低死亡率率。建议议在早期可给予予高渗晶晶体液，此后可可给予胶体液，同时限限制入量量，辅以以利尿剂剂，使出出入量保保持一定定水平的的负平衡衡，有条条件可监监测PAWP，在不影响响心输出出量和血血压的情情况下尽尽量降低低PAWP。必要时可可使用多多巴胺和和多巴酚酚丁胺等等血管活活性药物物。Crit CareMed 2002; 30:2175-2182.Figure1. Changeinserumtotalprotein duringthes

32、tudy, withthe treatmentperiodidentifiedbytheshadedarea.Pointsrepresentmean,witherrorbarsindicatingsem.Figure3. Changeinoxygenation,asmeasuredbythe Pao2/Fio2ratio(meansem),with thetreatmentperiod identifiedbytheshadedarea. *Significantwithin-groupchange frombaseline; time pointswith significant betwe

33、en-groupdifferences. Amaximumof25%ofdatapointsmay be absentfrom calculationsrepresentedafterday5.Figure4. Changeinthemeanarterialpressure(mmHg)/heart rate(beats/min)ratio(MAP/HRratio)frombaseline.The treatmentperiodisindicated by theshadedarea.Pointsrepresentmeanvalues, witherrorbarsdepictingsem(mea

34、nsem) at eachtimepoint.Figure5. Kaplan-Meierplot depictingthepercentageofpatientsrequiringmechanicalventilationduringthe 30-dayfollow-upperiod.Differencesbetween groupsarenot statisticallysignificant.Crit CareMed 2002; 30:2175-2182.Patients:Thirty-seven mechanically-ventilated patients withacutelung

35、injuryand serum total protein=5.0g/dL.Interventions:Five-dayprotocolizedregimen of 25 gofhumanserumalbuminevery8 hrswith continuousinfusionfurosemide, or dualplacebo,targetedtodiuresis, weightloss,andserumtotalprotein.Measurementsand MainResults:Measuredoutcomesincludedchange in weight,serumtotalpro

36、tein,fluidbalance,hemodynamics, respiratory systemcompliance,andoxygenation. Baseline characteristicswere similarbetweengroups(treatment,n= 19;control,n =18),with traumabeingthemajorcauseofacutelunginjury.Diuresisandweight lossover5 days(5.3kgmore in thetreatmentgroup,p= .04)was accompanied by impro

37、vementsinthePao2/Fio2ratiointhetreatment group within24hrs(from171 to 236,p= .02). Respiratory mechanicswere unchanged.Meanarterialpressureincreasedfrom80to88mmHg(p= .10), andheartrate decreasedfrom 110to95beats/min(p= .008) overtimeinthetreatment group.Nodifference in mortalitywasobserved, withfavo

38、rable trendsinmeasuresofintensivecare.Conclusions:Albuminandfurosemidetherapy improves fluid balance, oxygenation,andhemodynamicsinhypoproteinemicpatientswith acute lunginjury.Determiningtheeffect of thissimple therapyoncost,outcomes, andotherpatient populations requires furtherstudy.N EnglJMed2004;

39、350:2247-2256.6997 patientsBackgroundItremains uncertainwhether thechoiceofresuscitationfluidforpatientsinintensive careunits(ICUs) affectssurvival.Weconductedamulticenter, randomized, double-blindtrialtocompare theeffectoffluidresuscitationwith albuminorsalineonmortalityinaheterogeneous populationo

40、fpatientsintheICU.ResultsOfthe6997patientswhounderwent randomization, 3497were assigned to receivealbuminand3500toreceive saline;thetwo groupshadsimilarbaselinecharacteristics. There were726deaths in thealbumin group,ascomparedwith 729deathsinthesaline group (relativerisk of death,0.99;95percentconf

41、idence interval,0.91 to 1.09; P=0.87). Theproportion ofpatientswith newsingle-organand multiple-organ failurewassimilar in thetwogroups (P=0.85).Therewere no significantdifferencesbetween thegroupsinthe mean(SD)numbersofdays spent in theICU(6.56.6inthe albumingroupand6.26.2inthesaline group,P=0.44),

42、days spentinthehospital(15.39.6 and15.69.6,respectively;P=0.30),days of mechanicalventilation(4.56.1and4.35.7,respectively; P=0.74), or daysofrenal-replacementtherapy (0.52.3 and0.42.0,respectively; P=0.41).ConclusionsInpatientsintheICU,useofeither 4percentalbumin or normalsalinefor fluid resuscitat

43、ionresultsinsimilar outcomes at 28 days.N EnglJMed2004;350:2247-2256.治疗四、氧运运输呼吸、循循环和血血液系统统的功能能状态共共同决定定氧运输输量的大大小。应应通过合合理的液液体疗法法、氧疗疗、机械械通气、使用血血管活性性药物使使氧运输输量达最最佳水平平，而不不应只着着眼于某某一个脏脏器的功功能状态态。目前前尚无充充分证据据表明使使氧运输输量达到到一个超超常水平平能降低低ARDS的死亡率率 。治疗五、肺外外脏器功功能的支支持和营营养支持持近年来，呼吸支支持技术术的进步步可使多多数ARDS患者不再再死于低低氧血症症，而主主要死于

44、于MODS。ARDS可使肺外外脏器功功能受损损，而肺肺外脏器器功能受损又又能反过过来加重重ARDS。因此，加强液体体管理，尽早开开始肠内内营养，注意循环环功能、肾功能能和肝功功能的支持对对于防止止MODS的发生有有重要意义。AmJ RespirCrit CareMed,2004,169: 638-644.Theaim of thisstudywas to evaluate theeffectofparenteralnutritioncontainingmedium- andlong-chain triglyceridesonthefunctionofthe respiratory system

45、andtoinvestigatemechanismsinvolvedinthis process. We studied13patientswithacuterespiratorydistresssyndrome(ARDS), 8receiving lipid and5 placebo, and6 withoutARDS,receiving lipid.Bronchoalveolarlavage(BAL)was performedbeforeand 1hourafteradministrationoflipidorplacebo.Inpatientswith ARDS, lipid admin

46、istrationresultedindeterioration of oxygenation (PaO2/FIO2: from129 37 to 95 42),compliance of respiratory system(from39.2 12to33.1 9.2ml/cmH2O),andpulmonaryvascularresistance(from25847to32158dynescm-5).IntheBAL fluid of thesamegroup,anincreaseintotalproteinandphospholipid concentrations,phospholipa

47、se activities, platelet-activatingfactor andneutrophils,aswell as alterations in BALlipidprofile wereobserved. Nosignificantchanges wereobservedinthe controlorinthe ARDS-Placebogroups. In conclusion, thisstudyindicates thatadministrationofmedium- andlong-chain triglyceridesinpatientswithARDScausesal

48、terationsinlungfunctionandhemodynamics.Inflammatorycells,possiblyactivated by lipids,releasephospholipase A2andplatelet-activatingfactor, enhancingedemaformation, inflammation,andsurfactantalterations.AmJ RespirCrit CareMed,2004,169: 638-644.治疗六、其他他药物治治疗皮质激素素在中晚晚期应用用可能对对防止肺肺纤维化化有一定定作用。对于脂脂肪栓塞塞综合征征和卡

49、氏氏肺囊虫虫肺炎有有预防和和治疗作作用。其其他抗炎炎制剂，如PGE1抗内毒素素抗体、IL-1受体抗体体、PAF受体拮抗抗剂、抗抗TNF抗体等，均需进进一步研研究。N EnglJMed2004;351:884-892.N EnglJMed2004;351:884-892.Figure1.Mean (SE) PaO2:FiO2Valuesinthe ControlGroupand theSurfactant Group.ThemeanPaO2:FiO2value,ameasure of theblood-oxygenatingability of thelung,wassignificantlyg

50、reater from4to24hoursaftertreatmentinthe surfactantgroupthaninthecontrolgroup.Figure2.NumberofVentilator-free Daysinthe ControlGroupand theSurfactant Group.Patientswith 0ventilator-free daysincludedthosewho wereneverfreefrom mechanicalventilationand those whodied within28days after treatment,regardl

51、essoftheirneed formechanical ventilation.Therewere no significant differences betweenthe twogroups.Figure3.Nonpulmonary-OrganFailureduringthe 28 DaysafterTreatment among Patients withARDSasa ResultofDirectorIndirectLungInjury. DirectARDS wasdefined as ARDSdue to pneumonia,aspiration,orboth.The numbe

52、rofnonpulmonaryorgansthatfailed(withfailureofanorgandefined as ascoreof3or4 SOFA) wassignificantly greateramongpatientswithindirectARDS thanamongthosewithdirectARDS(P=0.02).N EnglJMed2004;351:884-892.MethodsIntwomulticenter, randomized, double-blindtrialsinvolving448 patients withARDSfrom variouscau

53、ses,wecomparedstandardtherapy alone withstandardtherapyplus up to fourintratrachealdosesofa recombinant surfactantproteinCbasedsurfactant given withina periodof24hours.ResultsTheoverallsurvivalrate was66percent 28 daysaftertreatment, andthemedian numberofventilator-freedayswas0 (68percent range,0 to

54、 26);therewas no significant differencebetween thegroupsintermsofmortality or theneed formechanicalventilation.Patientsreceiving surfactanthad asignificantlygreater improvement in blood oxygenation duringtheinitial24hoursoftreatmentthanpatientsreceivingstandardtherapy,accordingtobothunivariateandmul

55、tivariate analyses.ConclusionsTheuse of exogenoussurfactant in aheterogeneouspopulation of patients withARDSdidnot improvesurvival. Patientswhoreceivedsurfactanthadagreater improvement in gasexchangeduringthe 24-hourtreatment periodthan patients whoreceivedstandardtherapy alone,suggesting thepotenti

56、albenefitofa longertreatmentcourse.N EnglJMed2004;351:884-892.ARDS的机械通通气一、ARDS的呼吸力力学特点点 1肺气容容积减少少2病变的的非均一一性3肺顺应应性降低低 心脏SPARDS的机械通通气二、呼吸吸机所致致肺损伤伤 1肺气压压伤(barotrauma)2肺容积伤伤(volutrauma)3肺萎陷伤伤(atelectauma)4肺生物伤伤(biotrauma)ARDS的机械通通气三、机械械通气的的策略 1高呼气气末正压压策略2小潮气气量策略略3长吸气气策略4肺开放放策略ARDS的机械通通气四、通气气参数的的调节 1吸氧浓浓

57、度(FiO2)2PEEP3潮气量4呼吸频频率的调调节5吸呼比比(IE)的调节0204060VT（L）LIPUIPN EnglJMed1998;338:347-354.N EnglJMed1998;338:347-354.BackgroundInpatientswith theacuterespiratorydistresssyndrome,massive alveolar collapse andcycliclungreopeningandoverdistentionduringmechanicalventilationmayperpetuatealveolarinjury.

58、Wedetermined whetheraventilatorystrategydesignedtominimizesuch lunginjuriescouldreduce notonly pulmonarycomplicationsbutalsomortalityat28daysinpatientswith theacuterespiratorydistresssyndrome.MethodsWerandomlyassigned53patientswith early acute respiratorydistresssyndrome(including 28 describedprevio

59、usly),all ofwhom werereceiving identicalhemodynamicandgeneralsupport,toconventionalorprotectivemechanical ventilation.Conventionalventilationwasbasedonthe strategy of maintaining thelowestpositiveend-expiratorypressure(PEEP)for acceptableoxygenation,with atidalvolume of 12 ml perkilogramofbody weigh

60、tandnormalarterialcarbon dioxidelevels (35to38mmHg). Protectiveventilationinvolvedend-expiratorypressuresabovethe lowerinflection point on thestaticpressurevolume curve,a tidal volumeofless than6mlperkilogram, drivingpressuresofless than20cmofwaterabovethe PEEPvalue, permissivehypercapnia, andprefer