药物治疗no医学课件

ARDS的药物治疗 NO的历史 1998年的诺贝尔医学奖被三名药学家分享 RobertFurchgott FeridMurad和LouisIgnarro各自独立研究NO如何在内皮细胞生成 调节其它细胞的功能 NO的基本概念 血管内皮细胞 平滑肌细胞 血小板 肥大细胞以及血流中的白细胞等都有NO生成活性 气道内NO主要由上皮细胞iNOS合成 正常量NO可维持肺血管处于适当舒张状态 抑制PLT聚集和WBC贴壁黏附 过量的NO可杀伤正常细胞组织 外源性NO的实质 外源性的NO是一种有潜在细胞毒性的气体 小剂量 5 80ppm 吸入可避免细胞毒性 而选择性的舒张肺血管 iNO可选择性舒张肺血管 由于NO与Hb结合而迅速失活 因此iNO仅有局部效应 即对通气肺区的血管有扩张作用 这对于改善病理状态下的通气血流比 VA Q 失调有重要意义 而对体循环影响小 iNO可选择性舒张肺血管 Berger等在10头乳猪中作细菌性肺损伤模型 1小时内肺动脉压升高 VA Q失调 2小时后并发有肺血管受损 进行iNO150ppm30min后 在1小时和2小时后均能有效降低肺动脉压而不影响体循环 但未逆转VA Q失调 iNO的一些研究 一个回顾性研究 iNO的一些研究 EfficacyofinhalednitricoxideinpatientswithsevereARDS SETTING UniversitysurgicalICU Eighty sevenpatientswithsevereARDS 30of87patientswithARDSinhaledlowconcentrationsofNOformorethan48hinadditiontothestandardtreatment Chest1995Apr 107 4 1107 15 iNO的一些研究 ResultIn83 ofthepatients NOincreasedPaO2 FIO2by 10mmHg In87 NOreducedvenousadmixture QVA QT by 10 In63 NOdecreasedmeanpulmonaryarterypressure PAP by 3mmHg Chest1995Apr 107 4 1107 15 iNO的一些研究 ResultSurvivalratesinpatientstreatedwithNOdidnotdifferfromsurvivalratesinpatientsnottreatedwithNO Chest1995Apr 107 4 1107 15 iNO的一些研究 四个前瞻RCT iNO的一些研究 EffectsofinhalednitricoxideinpatientswithacuterespiratorydistresssyndromeProspective multicenter randomized double blind placebo controlledstudy SETTING Intensivecareunitsof30academic teaching andcommunityhospitalsintheUnitedStates Atotalof177patientswereenrolledovera14 monthperiod CritCareMed1998Jan 26 1 15 23 iNO的一些研究 PATIENTS PatientswithARDS asdefinedbytheAmerican EuropeanConsensusConference wereenrolledintothestudyiftheonsetofdiseasewaswithin72hrsofrandomization INTERVENTIONS Patientswererandomizedtoreceiveplacebo nitrogengas orinhaledNOatconcentrationsof1 25 5 20 40 or80ppm CritCareMed1998Jan 26 1 15 23 iNO的一些研究 ResultAnacuteresponsetotreatmentgas definedasaPaO2increase 20 wasseenin60 ofthepatientsreceivinginhaledNOwithnosignificantdifferencesbetweendosegroups Twenty fourpercentofplacebopatientsalsohadanacuteresponsetotreatmentgasduringthefirst4hrs CritCareMed1998Jan 26 1 15 23 iNO的一些研究 ResultIn5ppminhaledNOdosegroup thepercentageofpatientsaliveandoffmechanicalventilationatday28 aposthocanalysis washigher 62 vs 44 P 0 05 thantheplacebogroup CritCareMed1998Jan 26 1 15 23 iNO的一些研究 ResultTherewerenodifferencesamongthepooledinhaledNOgroupsandplacebowithrespecttomortalityrate thenumberofdaysaliveandoffmechanicalventilation orthenumberofdaysaliveaftermeetingoxygenationcriteriaforextubation CritCareMed1998Jan 26 1 15 23 iNO的一些研究 ResultTherewerenodifferencesamongthepooledinhaledNOgroupsandplacebowithrespecttomortalityrate thenumberofdaysaliveandoffmechanicalventilation orthenumberofdaysaliveaftermeetingoxygenationcriteriaforextubation CritCareMed1998Jan 26 1 15 23 iNO的一些研究 InhalationofnitricoxideinacutelunginjuryDESIGN Prospective open randomised multicentre parallelgroupphaseIIItrial SETTING GeneralICUsin43universityandregionalhospitalsinEurope PATIENTS 268adultpatientswithearlyALI IntensiveCareMed1999Sep iNO的一些研究 InterventionsNOResponderswererandomlyallocatedtoconventionaltreatmentwithorwithoutINO iNO 1 40ppm wasgivenatthelowesteffectivedoseforupto30daysoruntilanendpointwasreached IntensiveCareMed1999Sep iNO的一些研究 ResultFrequencyofreversalofALIwasnodifferentinINOpatients 61 andcontrols 54 p 0 2 Themortalityat30dayswas44 foriNOpatients 40 forcontrolpatients p 0 2vsiNO and45 innon responders IntensiveCareMed1999Sep iNO的一些研究 Inhalednitricoxideversusconventionaltherapy effectonoxygenationinARDS DepartmentofMedicine UniversityofUtahSchoolofMedicine SaltLakeCity USA Arandomized controlledclinicaltrialn 20 11patientswithiNOversus9patientswithconventionaltherapy AmJRespirCritCareMed1998May iNO的一些研究 ConclusionsIndicatethatiNOdoesnotleadtoasustainedimprovementinoxygenationascomparedwithconventionaltherapyInpatientswithsevereARDS AmJRespirCritCareMed1998May iNO的一些研究 Inhalednitricoxideinacuterespiratorydistresssyndromen 30ARDSresultedmainlyfromsepsis 25ofthe30 TheoptimaldoseofiNOwasdeterminedtobebetween0 5 40ppm d AmJRespirCritCareMed1998May iNO的一些研究 ResultDuringthefirst24h thehypoxiascoreincreasedgreatlyinpatientstreatedwithiNO 70 4mmHg 59 versus 14 2mmHg 9 3 forthecontrolgroup p 0 02 AmJRespirCritCareMed1998May iNO的一些研究 Result40 ofthepatientstreatedwithiNOwerealiveandweanedfrommechanicalventilationwithin30dcomparedwith33 3 inthecontrolgroup p 0 83 The30 dmortalityratewassimilarinthetwogroups AmJRespirCritCareMed1998May iNO的一些研究 关于在新生儿呼吸衰竭中的应用 iNO的一些研究 Inhalednitricoxideinfull termandnearlyfull terminfantswithhypoxicrespiratoryfailure Theinfantswererandomlyassignedtoreceivenitricoxideataconcentrationof20ppmor100percentoxygen asacontrol NEnglJMed1997Feb iNO的一些研究 ResultThe121infantsinthecontrolgroupandthe114inthenitricoxidegrouphadsimilarbase lineclinicalcharacteristics 64 ofthecontrolgroupand46 ofthenitricoxidegroupdiedwithin120daysorweretreatedwithextracorporealmembraneoxygenation P 0 006 NEnglJMed1997Feb iNO的一些研究 Result17 ofthecontrolgroupand14 oftheiNOgroupdied Pnotsignificant Butsignificantlyfewerinthenitricoxidegroupreceivedextracorporealmembraneoxygenation 39 vs 54 P 0 014 NEnglJMed1997Feb iNO的一些研究 Low dosenitricoxidetherapyforpersistentpulmonaryhypertensionofthenewborn n 248 Theneonateswhoreceivednitricoxideweretreatedwith20ppmforamaximumof24hours followedby5ppmfornomorethan96hours TheprimaryendpointofthestudywastheuseofECMO NEnglJMed2000Feb iNO的一些研究 ResultECMOwasusedin78neonatesinthecontrolgroup 64 andin48neonatesinthenitricoxidegroup 38 P 0 001 The30 daymortalityrateinthetwogroupswassimilar 8 inthecontrolgroupand7 inthenitricoxidegroup NEnglJMed2000Feb iNO的一些研究 Discussion由于新生儿循环的特点以及引起呼吸衰竭的原因不同 使得新生儿的相关研究结果不能用于临床 NEnglJMed2000Feb iNO的一些研究 CochraneReviews iNO的一些研究 InhalednitricoxideforacutehypoxemicrespiratoryfailureinchildrenandadultsTherewasnosignificantdifferen