急性肝功能衰竭1急性肝功能衰竭1急性肝功能衰竭的定義Acuteliverfailure(ALF)isdefinedaslife-threateningliverinjuryintheabsenceofpreexistingliverdiseasewithcoagulopathy(prothrombintime>15secondsorinternationalnormalizedratio[INR]1.5)andhepaticencephalopathy(HE)thatdevelopswithin26weeksofinitialsymptomsTheterm‘‘fulminanthepaticfailure’’(FHF)isusedwhenHEdevelopswithin8weeksofjaundice2急性肝功能衰竭的定義AcuteliverfailureEtiologyofacuteliverfailure3Etiologyofacuteliverfailur44肝性腦病的分期臨床上按神經精神癥狀的輕重把肝性腦病分為四期：一期(前驅期):輕微的神經精神癥狀,可表現出欣快、反應遲鈍、睡眠節律的變化。二期(昏迷前期):一期癥狀加重,可出現:行為異常、嗜睡、精神錯亂.經常出現撲翼樣震顫等.三期(昏睡期):有明顯的精神錯亂、昏睡、肌張力↑等癥狀.四期(昏迷期):神志喪失,不能喚醒,沒有撲翼樣震顫等.5肝性腦病的分期臨床上按神經精神癥狀的輕重把肝性腦病分為四期：肝性腦病分期6肝性腦病分期6肝性腦病發病機制

氨中毒學說假性神經遞質學說血漿氨基酸失衡學說

GABA學說其他神經毒質在肝性腦病發病中的作用7肝性腦病發病機制氨中毒學說7氨中毒(ammoniaintoxication)學說血氨增高的原因：氨清除不足（主要）圖肝臟合成尿素的鳥氨酸循環

OCT：鳥氨酸氨基甲酰轉移酶

CPS：氨基甲酰磷酸合成酶氨的清除：8氨中毒(ammoniaintoxication)學說血氨增proteinNH3NH3ureaNormalmetabolism9proteinNH3NH3ureaNormal9Liverfailure肝衰竭proteinNH3NH3urea×BloodNH3↑10LiverfailureproteinNH3NH3ureaLiverfailure肝衰竭proteinNH3NH3urea×血NH3↑ShuntingCirculation門-體分流↑11LiverfailureproteinNH3NH3ureaCerebralEdemaandIntracranialHypertensionHepaticencephalopathyammoniainflammationalteredneurotransmissionpathwayscerebralhemodynamicdysautoregulation12CerebralEdemaandIntracraniaCerebralEdemaandIntracranialHypertensionOthercommontriggersforICPelevation:volumeoverloadhyponatremiaseverehypercarbiasevereacidosisincreasedthoracicandabdominalcompartmentpressures13CerebralEdemaandIntracraniaNeuromonitoringstrategiesInvasiveneuromonitoringstrategiesNoninvasiveneuromonitoringstrategiesserialheadcomputedtomography(CT)transcranialDopplerjugularbulboximetrypupillometry14NeuromonitoringstrategiesInvaAlgorithmforthediagnosticandtherapeuticmanagementofacuteliverfailurewithadvancedhepatic

encephalopathyandintracranialhypertensionEmergingstrategiesforthetreatmentofpatientswithacutehepaticfailure,CurrOpinCritCare2016,22:000–00015AlgorithmforthediagnosticaAlgorithmforthediagnosticandtherapeuticmanagementofacuteliverfailurewithadvancedhepatic

encephalopathyandintracranialhypertensionEmergingstrategiesforthetreatmentofpatientswithacutehepaticfailure,CurrOpinCritCare2016,22:000–00016AlgorithmforthediagnosticaAnnualUpdateinIntensiveCareandEmergencyMedicine201517AnnualUpdateinIntensiveCarIntensivecaresupportivestrategiesdirectedatcerebraledemainacuteliverfailureEmergingstrategiesforthetreatmentofpatientswithacutehepaticfailure,CurrOpinCritCare2016,22:000–00018IntensivecaresupportivestraIntensivecaresupportivestrategiesdirectedatcerebraledemainacuteliverfailureEmergingstrategiesforthetreatmentofpatientswithacutehepaticfailure,CurrOpinCritCare2016,22:000–00019IntensivecaresupportivestraAKIinALFAcuterenalfailuredevelopsin55–68%ofallpatientswhopresentwithALFandinthevastmajorityofcasesreverseswithresolutionofliverinjuryorwithtransplantationmechanismdirectrenaltoxicityfunctionalimpairmentasseeninthehepatorenalsyndromeMooreK.Renalfailureinacuteliverfailure.EurJGastroenterolHepatol1999;11:967–975.LeitheadJA,FergusonJW,BatesCM,etal.Thesystemicinflammatoryresponsesyndromeispredictiveofrenaldysfunctioninpatientswithnonparacetamol-inducedacuteliverfailure.Gut2009;58:443–449.20AKIinALFAcuterenalfailure2121臨床問題該患者無明顯活動性出血征象，監測凝血功能：INR3.2，APTT65s，FIB1.2g/L，PLT40109/L需要輸注血制品（血漿、冷沉淀、血小板）以糾正凝血功能障礙？22臨床問題該患者無明顯活動性出血征象，監測凝血功能：INR3ProthrombinTime,PT23ProthrombinTime,PT232424252526262727凝血功能再平衡健康人VS肝功能不全28凝血功能再平衡健康人VSPeripheral-VeinThrombosisArterialThrombosisPortal-VeinThrombosis：等待肝移植的患者中發生率8-25%FrancozC,BelghitiJ,VilgrainV,etal.Splanchnicveinthrombosisincandidatesforlivertransplantation:usefulnessofscreeningandanticoagulation.Gut2005;54:691-7.29Peripheral-VeinThrombosisFranHematologicalSupportHb>7.0g/dlINR<6Plateletcount>20109/LFibrinogen>1.0g/lAnnualUpdateinIntensiveCareandEmergencyMedicine201530HematologicalSupportHb>7.0臨床問題對于肝功能衰竭需要進行CRRT的患者，監測其凝血功能顯著異常（APTT、INR顯著升高），怎樣開展CRRT治療？無抗凝？枸櫞酸抗凝？31臨床問題對于肝功能衰竭需要進行CRRT的患者，監測其凝血功能該試驗共納入71例患者，共更換539次濾器管路。平均的濾器壽命為9(6–16)小時。其中51例患者接受完全無抗凝CRRT，其濾器壽命為12(7-24)小時。余下20例患者開始也行無抗凝CRRT，其濾器壽命為7(5-11)小時，但其后即使予以全身肝素抗凝或局部肝素抗凝使得APTT顯著延長，也并不增加其濾器的壽命32該試驗共納入71例患者，共更換539次濾器管路。平均的濾器壽所有43個濾器壽命均超過24小時，其中32個(74%)的濾器壽命達到72小時在提前更換濾器的事件中，只有3例是因為總鈣/游離鈣>2.5盡管在嚴重肝功能衰竭患者中進行局部枸櫞酸抗凝的CVVHD治療會造成體內枸櫞酸蓄積，但并沒有造成酸堿平衡紊亂及電解質紊亂在嚴重肝功能衰竭患者中進行局部枸櫞酸抗凝的血液凈化治療是安全、可行的，但仍有必要密切監測總鈣/游離鈣以保障患者安全33所有43個濾器壽命均超過24小時，其中32個(74%)的濾器目的：研究心臟術后并發肝、腎功能不全患者進行局部枸櫞酸抗凝的CRRT治療的安全性及有效性結果：共納入15例心臟外科術后并發肝、腎功能不全患者，在治療過程中肝酶（AST、ALT）、膽紅素、r-GT均沒有顯著改變。濾器后游離鈣、患者體內游離鈣及患者體內總鈣/游離鈣水平均穩定，未發現枸櫞酸中毒結論：在急性肝功能衰竭患者中進行局部枸櫞酸抗凝是有效、安全的34目的：研究心臟術后并發肝、腎功能不全患者進行局部枸櫞酸抗凝的急性肝功能衰竭35急性肝功能衰竭1急性肝功能衰竭的定義Acuteliverfailure(ALF)isdefinedaslife-threateningliverinjuryintheabsenceofpreexistingliverdiseasewithcoagulopathy(prothrombintime>15secondsorinternationalnormalizedratio[INR]1.5)andhepaticencephalopathy(HE)thatdevelopswithin26weeksofinitialsymptomsTheterm‘‘fulminanthepaticfailure’’(FHF)isusedwhenHEdevelopswithin8weeksofjaundice36急性肝功能衰竭的定義AcuteliverfailureEtiologyofacuteliverfailure37Etiologyofacuteliverfailur384肝性腦病的分期臨床上按神經精神癥狀的輕重把肝性腦病分為四期：一期(前驅期):輕微的神經精神癥狀,可表現出欣快、反應遲鈍、睡眠節律的變化。二期(昏迷前期):一期癥狀加重,可出現:行為異常、嗜睡、精神錯亂.經常出現撲翼樣震顫等.三期(昏睡期):有明顯的精神錯亂、昏睡、肌張力↑等癥狀.四期(昏迷期):神志喪失,不能喚醒,沒有撲翼樣震顫等.39肝性腦病的分期臨床上按神經精神癥狀的輕重把肝性腦病分為四期：肝性腦病分期40肝性腦病分期6肝性腦病發病機制

氨中毒學說假性神經遞質學說血漿氨基酸失衡學說

GABA學說其他神經毒質在肝性腦病發病中的作用41肝性腦病發病機制氨中毒學說7氨中毒(ammoniaintoxication)學說血氨增高的原因：氨清除不足（主要）圖肝臟合成尿素的鳥氨酸循環

OCT：鳥氨酸氨基甲酰轉移酶

CPS：氨基甲酰磷酸合成酶氨的清除：42氨中毒(ammoniaintoxication)學說血氨增proteinNH3NH3ureaNormalmetabolism43proteinNH3NH3ureaNormal9Liverfailure肝衰竭proteinNH3NH3urea×BloodNH3↑44LiverfailureproteinNH3NH3ureaLiverfailure肝衰竭proteinNH3NH3urea×血NH3↑ShuntingCirculation門-體分流↑45LiverfailureproteinNH3NH3ureaCerebralEdemaandIntracranialHypertensionHepaticencephalopathyammoniainflammationalteredneurotransmissionpathwayscerebralhemodynamicdysautoregulation46CerebralEdemaandIntracraniaCerebralEdemaandIntracranialHypertensionOthercommontriggersforICPelevation:volumeoverloadhyponatremiaseverehypercarbiasevereacidosisincreasedthoracicandabdominalcompartmentpressures47CerebralEdemaandIntracraniaNeuromonitoringstrategiesInvasiveneuromonitoringstrategiesNoninvasiveneuromonitoringstrategiesserialheadcomputedtomography(CT)transcranialDopplerjugularbulboximetrypupillometry48NeuromonitoringstrategiesInvaAlgorithmforthediagnosticandtherapeuticmanagementofacuteliverfailurewithadvancedhepatic

encephalopathyandintracranialhypertensionEmergingstrategiesforthetreatmentofpatientswithacutehepaticfailure,CurrOpinCritCare2016,22:000–00049AlgorithmforthediagnosticaAlgorithmforthediagnosticandtherapeuticmanagementofacuteliverfailurewithadvancedhepatic

encephalopathyandintracranialhypertensionEmergingstrategiesforthetreatmentofpatientswithacutehepaticfailure,CurrOpinCritCare2016,22:000–00050AlgorithmforthediagnosticaAnnualUpdateinIntensiveCareandEmergencyMedicine201551AnnualUpdateinIntensiveCarIntensivecaresupportivestrategiesdirectedatcerebraledemainacuteliverfailureEmergingstrategiesforthetreatmentofpatientswithacutehepaticfailure,CurrOpinCritCare2016,22:000–00052IntensivecaresupportivestraIntensivecaresupportivestrategiesdirectedatcerebraledemainacuteliverfailureEmergingstrategiesforthetreatmentofpatientswithacutehepaticfailure,CurrOpinCritCare2016,22:000–00053IntensivecaresupportivestraAKIinALFAcuterenalfailuredevelopsin55–68%ofallpatientswhopresentwithALFandinthevastmajorityofcasesreverseswithresolutionofliverinjuryorwithtransplantationmechanismdirectrenaltoxicityfunctionalimpairmentasseeninthehepatorenalsyndromeMooreK.Renalfailureinacuteliverfailure.EurJGastroenterolHepatol1999;11:967–975.LeitheadJA,FergusonJW,BatesCM,etal.Thesystemicinflammatoryresponsesyndromeispredictiveofrenaldysfunctioninpatientswithnonparacetamol-inducedacuteliverfailure.Gut2009;58:443–449.54AKIinALFAcuterenalfailure5521臨床問題該患者無明顯活動性出血征象，監測凝血功能：INR3.2，APTT65s，FIB1.2g/L，PLT40109/L需要輸注血制品（血漿、冷沉淀、血小板）以糾正凝血功能障礙？56臨床問題該患者無明顯活動性出血征象，監測凝血功能：INR3ProthrombinTime,PT57ProthrombinTime,PT235824592560266127凝血功能再平衡健康人VS肝功能不全62凝血功能再平衡健康人VSPeripheral-VeinThrombosisArterialThrombosisPortal-VeinThrombosis：等待肝移植的患者中發生率8-25%FrancozC,BelghitiJ,VilgrainV,etal.Splanchnicveinthrombosisincandidatesforlivertransplantation:usefulnes