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
0
20
40
60
80
100
120
08:4
5:00
09:4
5:00
10:4
5:00
11:4
5:00
12:4
5:00
13:4
5:00
14:4
5:00
15:4
5:00
16:4
5:00
17:4
5:00
0
10
20
30
40
50
60
70
80
90
MABPICPCPP
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
0
20
40
60
80
100
12008
:45:
00
09:4
5:00
10:4
5:00
11:4
5:00
12:4
5:00
13:4
5:00
14:4
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15:4
5:00
16:4
5:00
17:4
5:00
0
10
20
30
40
50
60
70
80
90
MABPICPCPP
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
0
50
100
150
200
40 50 60 70 80 90 100 110MAP (mmHg)
CB
F (V
mea
n - c
m/s
ec)
Anhepatic
Dissection
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
0
25
50
75
100
Pre OLT Dissection Anhepatic Reperfusion Post OLT
Con
cent
ratio
n IL
-1B
(pg/
ml)
CBF during CBF during OLTxOLTx
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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12008
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17:4
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MABPICPCPP
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
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