Anaesthesia for Acute Anaesthesia for Acute Liver FailureLiver Failure

Dr C P Snowden Dr C P Snowden Consultant Consultant AnaesthetistAnaesthetist

Freeman Hospital Freeman Hospital Newcastle Upon TyneNewcastle Upon Tyne

European Liver Transplant Registry

Transplantation and ALF: OutcomesTransplantation and ALF: Outcomes

France France Bismuth et al Ann Bismuth et al Ann SurgSurg 1995 1995 68% 1 yr68% 1 yr; 62% 5yr; 62% 5yr

UKUKBernal et al Hep 1998Bernal et al Hep 199866% 1 yr66% 1 yr

SpainSpainFernandez et al Gastro Hep 2003 Fernandez et al Gastro Hep 2003 68% 1 yr68% 1 yr; 59% 5 yr ; 59% 5 yr

USAUSAHoofnagleHoofnagle et al 1995 et al 1995 63% 1 yr63% 1 yr(Included children)(Included children)

Farmer et al Ann Farmer et al Ann SurgSurg 2003200373% 1 yr;73% 1 yr; 67% 5yr 67% 5yr (200 pts over 17yrs; (200 pts over 17yrs; Included children)Included children) UK & Ireland LT Audit 2003-04

90 day Mortality 15.5 (9.3-25.2)

Anaesthesia and ALFAnaesthesia and ALFPaucity of LiteraturePaucity of Literature

Continuation of ITU care ?Continuation of ITU care ?•• Operative stresses Operative stresses

Small Numbers ?Small Numbers ?•• 5% 5% --12% of all liver transplants12% of all liver transplants•• 86/566 in UK (200386/566 in UK (2003--4)4)

Poor Poor PerioperativePerioperative outcomes ?outcomes ?•• Intraoperative deaths Intraoperative deaths -- 1.3% 1.3% -- USA USA (Farmer et al 2003)(Farmer et al 2003)

•• 85% 90 day survival85% 90 day survival

Anaesthesia has no outcome relevance ? Anaesthesia has no outcome relevance ? •• Early postoperative deaths Early postoperative deaths •• 10% ALF patients are brain dead during/after 10% ALF patients are brain dead during/after OLTxOLTx•• Intraoperative variables not included in prediction modelsIntraoperative variables not included in prediction models

Newcastle ExperienceNewcastle ExperienceAdults onlyAdults only1993 1993 -- to dateto date456 456 OLTxOLTx (38/yr)(38/yr)90 (20%) 90 (20%) -- SuperurgentSuperurgent OLTxOLTx50% POD50% POD11% 11% -- 90 day mortality (0390 day mortality (03--04) 04)

AnaesthesiaAnaesthesia2/3/52/3/5 anaesthetistsanaesthetistsNo dedicated liver CCUNo dedicated liver CCUEarly involvementEarly involvementICP boltingICP boltingConventional OLT with VVBConventional OLT with VVBTrained ODP/ANTrained ODP/AN for VVBfor VVB

Anaesthetic ConsiderationsAnaesthetic Considerations

Preoperative issuesPreoperative issuesCerebral CareCerebral CareFluid “Challenges” Fluid “Challenges” Postoperative expectationsPostoperative expectations

Population CharacteristicsPopulation Characteristics

Younger age Younger age -- 35yr (Range:1935yr (Range:19--67)67)No complications of chronic liver diseaseNo complications of chronic liver diseaseLimited coexisting comorbidityLimited coexisting comorbidityEarly retention of compensatory mechanisms Early retention of compensatory mechanisms “Self selecting”“Self selecting”•• Contraindications (e.g. HIV, malignancy)Contraindications (e.g. HIV, malignancy)•• Removal from Removal from superurgentsuperurgent list for deterioration list for deterioration •• Limited organ availabilityLimited organ availability

19901990--9696n=124 (London) n=124 (London) 35% of those 35% of those listedlisted did not have did not have OLTxOLTx(Bernal et al 1995)(Bernal et al 1995)

19961996--0505n=102 (Newcastle)n=102 (Newcastle)25% of those 25% of those listedlisted did not have did not have OLTxOLTx

ALF: Acute Model of MSOFALF: Acute Model of MSOF

Acute MOFAcute MOFCVS dysfunctionCVS dysfunctionPulmonary failurePulmonary failureRenal failure Renal failure •• 7070--75% (paracetamol)75% (paracetamol)•• 30% (others)30% (others)

CNS failureCNS failurehyperacutehyperacute 70%70%subacutesubacute <4%<4%

Incidence reducing ?Incidence reducing ?61% to 45% (8761% to 45% (87--93)93)

MakinMakin et al Gastro 1995et al Gastro 1995

Mortality without Mortality without OLTxOLTx

Preoperative InvolvementPreoperative Involvement

Early anaesthetic Early anaesthetic involvement involvement

PracticalitiesPracticalities•• ProtocolsProtocols•• “Appropriate” vascular “Appropriate” vascular

access access •• ICP monitoringICP monitoring•• Renal supportRenal support

StabilityStability•• CNS CNS –– therapy, responsetherapy, response•• CVS CVS –– inotropesinotropes, VC , VC •• RS RS –– ventilation, oxygen ventilation, oxygen •• Coagulation Coagulation •• Fluid balanceFluid balance

Preoperative factors for Preoperative factors for OLTxOLTxoutcome outcome •• CreatinineCreatinine >200>200µµmol/lmol/l•• Jaundice Jaundice –– encephalopathy encephalopathy

<3.5 days <3.5 days

Preoperative UrgencyPreoperative UrgencyDonor LikelihoodDonor Likelihood•• Australia Australia -- 5 days 5 days

(Holt et al 1999)(Holt et al 1999)•• USA USA -- 2 days (02 days (0--72)72)

(Farmer 2003)(Farmer 2003)•• Newcastle (1993Newcastle (1993--2005) 2005)

1 day (01 day (0--11)11)75% listed have 75% listed have OLTxOLTx

Appropriate, available supportAppropriate, available support•• “Bridging” systems“Bridging” systems•• Live related donorsLive related donors

Recipient stabilityRecipient stability•• Cerebral/CVSCerebral/CVS•• Ammonia level >150 Ammonia level >150 µµmol/lmol/l

Relative contraindicationsRelative contraindications Acquired Acquired Immunodeficiency Immunodeficiency Syndrome Syndrome

NonNon--compliance with compliance with medical therapy medical therapy

Severe coexistent Severe coexistent CVS/RS diseaseCVS/RS disease

Alcohol dependenceAlcohol dependenceFixed, dilated pupils > 1 Fixed, dilated pupils > 1 hr in absence of STPhr in absence of STP

Acute drug abuseAcute drug abuseSignificant ARDSSignificant ARDS

DementiaDementiaProgressive Hypotension Progressive Hypotension resistant to therapyresistant to therapy

Chronic refractory Chronic refractory mental illnessmental illness

MalignancyMalignancy

Multiple episodes of self Multiple episodes of self harmharm

Untreated/Progressive Untreated/Progressive InfectionInfection

PsychiatricPsychiatricMedical Medical

Total Total HepatectomyHepatectomy

DilemmaDilemma“No liver better than bad one”“No liver better than bad one”No chance of hepatic recoveryNo chance of hepatic recoveryNewer transplantation bridgesNewer transplantation bridgesDonor availability/stateDonor availability/state

Stability Stability CerebrovascularCerebrovascular stability stability Cardiovascular supportCardiovascular support

Total Total HepatectomyHepatectomyEarly 1990’sEarly 1990’s“Toxic liver syndrome” “Toxic liver syndrome” --hepatic necrosis with hepatic necrosis with shock, renal and shock, renal and respiratory failurerespiratory failureRingeRinge et al 1993et al 1993•• Overall survival rate 9/30 Overall survival rate 9/30

(30%)(30%)

Cerebral Care during TransplantationCerebral Care during Transplantation

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ANHEPATICDISSECTIONTRANSFER REPERFUSION

Intraoperative ICP ChangesIntraoperative ICP ChangesLidofskyLidofsky 1992 (USA)1992 (USA)12 pts: 12 pts: OLTxOLTx -- No VVBNo VVB

Dissection Dissection AnhepaticAnhepatic (minimal)(minimal)Reperfusion Reperfusion

JalanJalan 2003 (UK)2003 (UK)11 pts; Piggyback 11 pts; Piggyback -- PSSPSS

Dissection Dissection ReperfusionReperfusion

PredictablePredictable

DetryDetry 1999 (USA)1999 (USA)12 pts; 12 pts; OLTxOLTx -- VVBVVB

Dissection Dissection ReperfusionReperfusion

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ANHEPATICDISSECTIONTRANSFER REPERFUSION

Cerebral “Calming”Cerebral “Calming”

HA/PV Clamp

IVCClamp

Liver “Liver “DevascularisationDevascularisation””Improvement of:Improvement of:

Systemic “hyperkinetic syndrome”Systemic “hyperkinetic syndrome”Noun et al Trans Proc 1995Noun et al Trans Proc 1995

Middle cerebral artery Flow relation to MAP after liver devascularisation

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Cerebral hyperperfusionCerebral hyperperfusionEjlersenEjlersen et al Trans Proc 1994et al Trans Proc 1994

•• Use of Use of TranscranialTranscranial dopplerdoppler•• HepatectomyHepatectomy vsvs devascularisationdevascularisation

ICP: Temporal changeICP: Temporal change

ALF: ICP/ CBFALF: ICP/ CBFICP surges related to CBF surges

CPP = CBF x CVR

CBF/CMRO2 “uncoupling”50% reduction in CMR “Luxury” perfusion stateIncreasing MABP (to maintain CPP) ?detrimental ? Role of inflammation

JalanJalan et al 2004 J Hepet al 2004 J Hep

CytokinesCytokines

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DissectionDissection• Cytokine Release• Surgical stimulation

ReperfusionReperfusion• Cytokine release • CBF increased; CVR decreased• Artificially elevated BP – VC use• pCO2 rise

Adapted from “Adapted from “JalanJalan et al 2003 Transplantation”et al 2003 Transplantation”

Intraoperative ICP Changes Intraoperative ICP Changes 11/12 required treatment11/12 required treatment6/12 6/12 5/12 5/12 3/123/12

LidofskyLidofsky 1992 (USA)1992 (USA)12 pts: 12 pts: OLTxOLTx -- No VVBNo VVB

Dissection Dissection AnhepaticAnhepatic (minimal)(minimal)Reperfusion Reperfusion

4/6 required treatment 4/6 required treatment 11/11 required treatment 11/11 required treatment

JalanJalan 2003 (UK)2003 (UK)11 pts; Piggyback 11 pts; Piggyback -- PSSPSS

Dissection Dissection ReperfusionReperfusion

PreopPreop predictability ?predictability ?PreopPreop no treatmentno treatmentPreopPreop standard treatmentstandard treatment

UnpredictableUnpredictablePredictablePredictable

4/12 required treatment 4/12 required treatment

0/4 pts had 0/4 pts had intraopintraop increaseincrease4/8 pts had 4/8 pts had intraopintraop increaseincrease

DetryDetry 1999 (USA)1999 (USA)12 pts; 12 pts; OLTxOLTx -- VVBVVB

Dissection Dissection ReperfusionReperfusion

PreopPreop predictability ?predictability ?<20mmHg<20mmHg>20mmHg>20mmHg

ICP: Individual variationICP: Individual variation

JalanJalan et al 2004 J Hepet al 2004 J Hep

ICP: Individual variationICP: Individual variation

ALFComplex MABP/CBF relationship Degrees of impaired autoregulationIndividual baseline CBF is variable Unknown MABP ischaemic threshold CPP >50mmHg; 100% survival

AnaesthesiaAutoregulation maintained <1.6 MAC Intraoperative opioids reduce MAC

HyperventilationHyperventilation

Short term hypocapnia (3.5kPa)with hyperventilation

• Improves BP autoregulation• Increases CO2 sensitivity • Prevents rise in CBF above

anhepatic levels at reperfusion

DoblarDoblar et al 1995; et al 1995; AnesAnes AnalgAnalgLarsen FS et al 1996; J Larsen FS et al 1996; J HepatolHepatol

ALF

16 ptsAge 29 yr (28-54)

Paracetamol(13)Non A Non B (2)

Other (1)

No Preoptreatment

(<15 mmHg)(n=6)

Episodes of ICP controlled by

standard therapy(n=5)

Uncontrolled ICP(>25 mmHg for > 1 hr

despite CVVH and mannitol)Cooled to 33.4oC

(31.9-33.8)(n=5)

OLTxNo VVB35.9OC

(35.5-37.1

Temp

OLTxNo VVB36.4OC

(35.8 – 37.3)

OLTxNo VVB33.4OC

(31.9 – 33.8)

Transplantation 2003; 75; 12; 2034-2039

Results: Results: HaemodynamicsHaemodynamics

Results: ICP/CBFResults: ICP/CBFRise in ICP concomitant with Rise in ICP concomitant with CBF increaseCBF increase

Hypothermia negates changes Hypothermia negates changes in ICP/CBFin ICP/CBF

? Cause and effect? Cause and effect

? Mechanism:? Mechanism:•• Reinstitutes autoregulationReinstitutes autoregulation•• Cytokine reduction Cytokine reduction

Hypothermia considerations Hypothermia considerations Intraoperative Safety ValveIntraoperative Safety Valve•• ? Return of autoregulation ? Return of autoregulation •• Other modalities might work betterOther modalities might work better

Questions?Questions?•• What is optimal temp ?What is optimal temp ?•• When and how long to institute ?When and how long to institute ?•• Effect in different preoperative risk groups ?Effect in different preoperative risk groups ?•• Need for RCT and survival data ?Need for RCT and survival data ?

Mild Intraoperative hypothermia (34.5Mild Intraoperative hypothermia (34.5ooC)C)•• Reperfusion difficultiesReperfusion difficulties•• Coagulation problemsCoagulation problems•• Drug metabolismDrug metabolism•• Postoperative cardiac eventsPostoperative cardiac events•• Infection ratesInfection rates

Cerebral CareCerebral CareStandard CareStandard Care•• 1515oo head up tilt,head up tilt, no venous constriction no venous constriction •• Sedation/paralysis Sedation/paralysis •• Ventilated (pCOVentilated (pCO22) during transfer ) during transfer •• CVS stability CVS stability -- Full drug syringes Full drug syringes espesp inotropesinotropes•• Theatre monitoring Theatre monitoring -- duplicate ITU duplicate ITU

HypothermiaHypothermia

Dissection phase Dissection phase -- ShortenShorten•• Rapid Rapid hepatectomyhepatectomy•• Early Early devascularisationdevascularisation (HA/PV/Bile duct transection)(HA/PV/Bile duct transection)

AnhepaticAnhepatic•• PreemptivePreemptive hyperventilation (3.5kPa)hyperventilation (3.5kPa)

ReperfusionReperfusionAvoid:Avoid:•• IschaemiaIschaemia (CPP>50 mmHg) (CPP>50 mmHg) •• Hyperperfusion (Careful use of vasoconstrictors)Hyperperfusion (Careful use of vasoconstrictors)

Cerebral Care: Further ConsiderationsCerebral Care: Further Considerations

CVS StabilityCVS Stability•• Hypothermia Hypothermia •• AprotininAprotinin (Regular dose) (Regular dose) -- AntiAnti--inflammatoryinflammatory•• Vasopressin caution Vasopressin caution –– ICP exacerbation during bolusICP exacerbation during bolus•• Vessel release Vessel release -- HA HA vsvs PV reperfusionPV reperfusion

Cerebral Monitoring Cerebral Monitoring •• ICP ICP –– cerebral hyperperfusion marker cerebral hyperperfusion marker •• Other modalities Other modalities –– NIRS, Transcranial NIRS, Transcranial dopplerdoppler, SjO2, SjO2

ICP therapyICP therapy (e.g. (e.g. MannitolMannitol, STP), STP)•• Unresponsive Unresponsive •• May not need itMay not need it•• Adverse effectsAdverse effects

HypotensionHypotensionFluid overload Fluid overload

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ANHEPATICDISSECTIONTRANSFER REPERFUSION

Case: Fluid “Challenges” Case: Fluid “Challenges” VVBIVC

Clamp

Overt Fluid “Challenges”Overt Fluid “Challenges”Retention of Venous ReturnRetention of Venous Return

VenovenousVenovenous BypassBypass

No VVBNo VVB3 litre replacement 3 litre replacement ((CheemaCheema et al 1995)et al 1995)

VVBVVBElectiveElective

No renal benefit No renal benefit CVS stability CVS stability No PRS benefit No PRS benefit

Urgent Urgent Prevents prePrevents pre--anhepaticanhepatic fluid loadingfluid loading? CVS stability? CVS stabilityMesenteric congestion Mesenteric congestion –– ACSACS

Surgery Surgery -- Vena Cava SparingVena Cava Sparing• Conventional OLTx with VVB• Piggyback with/without VVB• Piggyback with PCS• Cavocavoplasty without either

Overt Fluid “Challenges”Overt Fluid “Challenges”

Factor Factor VIIaVIIa

2 FHF pts 2 FHF pts ((KalicinskiKalicinski et al 1999 Trans Proc)et al 1999 Trans Proc)

Rapid correction of PT Rapid correction of PT ((ShamiShami et al 2003 Liver Trans)et al 2003 Liver Trans)

? Thrombosis risk? Thrombosis risk

0%0%43.6%43.6%100%100%Use of VVB Use of VVB

CavocavoCavocavo(n=39)(n=39)

PBT PBT (n=39)(n=39)

OLTxOLTx(n=38)(n=38)

1522.81522.8±1878.9**±1878.9**

3889.13889.1±5688.1±5688.1

84188418±7728.4±7728.4

Intraoperative Intraoperative Blood UsageBlood Usage

31/39 31/39 (79.5%)**(79.5%)**

25/39 25/39 (64.1%)(64.1%)

9/38 9/38 (23.7%)(23.7%)

Blood loss < Blood loss < 3litres3litres

Factor CorrectionFactor Correction

Role of surgical methodsRole of surgical methods? ? PreopPreop correction correction Volume load Volume load

Lerut et al 1997 Trans Int

Covert Fluid “Challenges”Covert Fluid “Challenges”

Renal FailureRenal Failure

High incidence in ALFHigh incidence in ALF

Intraoperative RRTIntraoperative RRT

Endothelial Leak Endothelial Leak

Pulmonary oedemaPulmonary oedemaCerebral oedema Cerebral oedema Mesenteric oedemaMesenteric oedema

Considerations for Renal ReplacementConsiderations for Renal Replacement

Vascular accessVascular access

Drug UseDrug Use•• RemifentanylRemifentanyl•• CisatracuriumCisatracurium

Combined VVB and filtrationCombined VVB and filtration•• HypervolemiaHypervolemia

Tobias M et al; 1999 Anesth

•• LifeLife--threatening threatening hyperkalemiahyperkalemiaZiemann-Gimmel,P et al; 2003 Anes anal

High exchange CVVHHigh exchange CVVH•• Continuous regimesContinuous regimes

Davenport 1993 CCM

Intraoperative CVVH strategiesIntraoperative CVVH strategies

AdvantagesAdvantages

Single venous accessSingle venous access

Temperature control Temperature control

Accurate fluid removalAccurate fluid removal

Lactate/Acid balanceLactate/Acid balance

KK++ regulationregulation

DisadvantagesDisadvantages

Discontinuation in ITUDiscontinuation in ITU

Experienced nurse Experienced nurse

Filter clottingFilter clotting

VVB “steal”VVB “steal”

? best regimes? best regimes

Realistic Postoperative ExpectationsRealistic Postoperative Expectations

Early RecoveryEarly Recovery

Preoperative statePreoperative stateCerebralCerebral•• 10% failure to recover10% failure to recover•• Autoregulation returnAutoregulation return

MOF MOF –– endothelial leakendothelial leak•• PulmonaryPulmonary

WeaningWeaningInfectionInfection

•• Mesenteric congestionMesenteric congestionACSACS

Return of liver functionReturn of liver functionDrug metabolismDrug metabolism“Marginal” donors“Marginal” donors•• Fatty liver Fatty liver •• Size Size

abdominal closureabdominal closureReRe--laparotomylaparotomy

Realistic Postoperative ExpectationsRealistic Postoperative Expectations

Continual CareContinual Care

InfectionInfection

Nutrition Nutrition

Renal failureRenal failure•• ImmunosuppressiveImmunosuppressive•• Anaesthetic drugs Anaesthetic drugs

% 1 yr survival 1996 to 1999% 1 yr survival 1996 to 1999

SurvivalSurvivalSurvivalSurvivalPtsPtsTiming of Timing of RRTRRT

41.841.818184343PostPost

73.673.614141919Pre/PostPre/Post

Gonwa et al 2001 Trans

Summary Summary Paucity of literaturePaucity of literature

Preoperative Preoperative •• Different population Different population •• Acute MOFAcute MOF•• HepatectomyHepatectomy

Fluid challengesFluid challenges•• Overt Overt

venous returnvenous returncoagulation coagulation

•• Covert Covert oedemaoedemarenal failure renal failure

•• CVVH use CVVH use

Cerebral IssuesCerebral Issues•• Temporal consistencyTemporal consistency•• Define risk groupsDefine risk groups•• HypothermiaHypothermia•• MonitoringMonitoring•• Cytokine removal Cytokine removal

liver support/CVVHliver support/CVVH•• Other measures Other measures

surgical/hyperventilationsurgical/hyperventilation

Delayed Postoperative Delayed Postoperative RecoveryRecovery•• AcceptanceAcceptance