evaluation of surgical risk in patients with liver disease · evaluation of surgical risk in...

Evaluation of Surgical Risk in Evaluation of Surgical Risk in Patients with Liver DiseasePatients with Liver Disease

Stefano FagiuoliStefano FagiuoliUSC Gastroenterologia

Ospedali Riuniti di Bergamo

There is no such thingThere is no such thing

as a good cirrhotic patientas a good cirrhotic patient……..

Cirrhosis and SurgeryCirrhosis and Surgery

Frequency of elective surgery on pts with and without cirrhosisFrequency of elective surgery on pts with and without cirrhosis19981998--20052005

Cholecystectomy

Colectomy

Abdominal Aortic Aneurism Repair

Coronary Atery By-pass Surgery

Cholecystectomy

Colectomy

Abdominal Aortic Aneurism Repair

Coronary Atery By-pass Surgery

Stable over study periodStable over study period


Lenght of StayLenght of Stay Total ChargesTotal Charges

Mortality Rate %Mortality Rate %

Normal

Cirrhosis

Cirrhosi + PH

Dysfunctions in cirrhosisDysfunctions in cirrhosis

CoagulopathyRisk of Bleeding

Impaired Reticoloendotelial System Risk of Infections

Portal HypertensionBleeding, Hypotension, Infections

Impaired Metabolism /DetossificationDrug Toxicity

CoagulopathyCoagulopathyRisk of BleedingRisk of Bleeding

Impaired Reticoloendotelial System Impaired Reticoloendotelial System Risk of Infections Risk of Infections

Portal HypertensionPortal HypertensionBleeding, Hypotension, InfectionsBleeding, Hypotension, Infections

Impaired Metabolism /DetossificationImpaired Metabolism /DetossificationDrug ToxicityDrug Toxicity



ComorbidityNutritional status

Assessment prior to Surgery in CirrhoticsAssessment prior to Surgery in Cirrhotics

Type of Surgery

Assessment of Liver Dysfunction


Is it really Necessary ?

Timing ?

Experience of Clinical Team

Type of SurgeryType of Surgery

URGENT HIGH RISK• Abdominal Surgery

Cholecistectomy, Gastrectomy, Colectomy

• CardioThoracic• Hepatic Resection

LOW-RISKExtra Toracic-Abdominal

Cirrhosis and Surgery : ELECTIVE vs URGENTCirrhosis and Surgery : ELECTIVE vs URGENT

30 –day Mortality30 30 ––day Mortalityday Mortality

Cirrhosis and Surgery : ELECTIVE vs URGENTCirrhosis and Surgery : ELECTIVE vs URGENT

Combined effect of Risk FactorsCombined effect of Risk FactorsCombined effect of Risk Factors

Mansour, Surgery 1997

Mean Mean 18%18%

Mean Mean 50%50%

Mor

talit

y


SurgerySurgerySurgery Abdominal Abdominal SurgerySurgery

Postoperative MortalityPostoperative MortalityMELDMELD

Northup, Ann. Surg. 2005Northup, Ann. Surg. 2005

Blood Flow ReciprocityBlood Flow Reciprocity

0022 Portal SupplyPortal Supply

50%50%

O2

0022 Arterial SupplyArterial Supply

50%50%

Hepatic Artery Hepatic Artery Blood FlowBlood Flow

30%30%

Portal Blood FlowPortal Blood Flow70%70%

ImpairedImpairedautoregulationautoregulation

Reduced due toReduced due toPortal HypertensionPortal HypertensionArterovenous shuntingArterovenous shunting

In cirrhosisIn cirrhosisHyperdinamic CirculationHyperdinamic Circulation

Cardiac output Cardiac output Vascular resistanceVascular resistanceDECREASED BASELINE DECREASED BASELINE HEPATIC PERFUSION HEPATIC PERFUSION

Manipolation during splancnic Manipolation during splancnic surgerysurgery

Type of Anesthetic Type of Anesthetic (alothane)(alothane)Anesthetic ConcentrationAnesthetic Concentration

INCREASED Susceptibility to ISCHEMIAINCREASED Susceptibility to ISCHEMIA

Abdominal SURGERYAbdominal SURGERY

Can Increase over Can Increase over 50%50%via Compensatory Vasodilation via Compensatory Vasodilation

Rischio Operatorio nel Cirrotico

CHOLECYSTECTOMY: Laparoscopy vs LaparotomyCHOLECYSTECTOMY: Laparoscopy vs LaparotomyCHOLECYSTECTOMY: Laparoscopy vs Laparotomy

Tuech, 2002Tuech, 2002

Laparoscopy:Less

• Bleeding• Morbidity• Hospital Stay

Laparoscopy:Laparoscopy:LessLess

•• BleedingBleeding•• MorbidityMorbidity•• Hospital StayHospital Stay




Type of Surgery

Assessment of Liver DysfunctionPrognostic ScoresEvaluation of Functional ReserveHepatic VolumetryDynamic “Functional Volumetry”


Prognostic ScoreChild-PughMELD

Synthetic Hepatic Function

Biotrasformation Capacity (Xenobiotics)

Metabolic Activity

Hepatic Volumetry

Prognostic ScoreChild-PughMELD

Synthetic Hepatic Function

Biotrasformation Capacity (Xenobiotics)

Metabolic Activity

Hepatic Volumetry

Hepatic EvaluationHepatic Evaluation

Extra-Hepatic Diseases

Immunitary Status

Renal Function

Portal Hypertension

Neurologic Function

Nutritional Status

Extra-Hepatic Diseases

Immunitary Status

Renal Function

Portal Hypertension

Neurologic Function

Nutritional Status

General EvaluationGeneral Evaluation

Child-Turcotte:

Developed in 1964 (Modified by Pugh in 1973) : Death risk after surgical porto-caval procedure in cirrhotics

MELD:

Developed in 1999 for TIPS procedure in cirrhotics

ChildChild--Turcotte:Turcotte:

Developed in 1964 Developed in 1964 (Modified by Pugh in 1973)(Modified by Pugh in 1973) :: Death risk after Death risk after surgical portosurgical porto--caval procedure in cirrhoticscaval procedure in cirrhotics

MELDMELD: :

Developed in 1999 for TIPS procedure in cirrhotics Developed in 1999 for TIPS procedure in cirrhotics

CPT & MELD classification systemsCPT & MELD classification systems

CPT & MELD classification systemsCPT & MELD classification systems

Child-Pugh Classificationuseful as a general assessment of the severity of liver disease

ChildChild--Pugh ClassificationPugh Classificationuseful as a general assessment of the severity of liver diseaseuseful as a general assessment of the severity of liver disease

The MELD Model, UNOS ModificationThe MELD Model, UNOS Modification

http://www.mayoclinic.org/gihttp://www.mayoclinic.org/gi--rst/mayomodel.htmlrst/mayomodel.html

MELD score:

What is the INR?

What is the bilirubin? (mg/dl)

What is the creatinine? (mg/dl)

Has the patient had dialysis at least twice in the past week? No

Yes

MELD Score 3-month Mortality ≥ 40 100% 30-39 83% 20-29 76% 10-19 27% <10 4%

C o m p u t e

Reimposta


3030--day Mortalityday Mortality 9090--day Mortalityday Mortality

For MELD > 8 each one-point increase in MELD

14% increase in both 30- and 90-day mortality

For MELD > 8 each one-point increase in MELD

14% increase in both 30- and 90-day mortality

772 patients with Cirrhosis who underwent Surgery (1980-2004)

Teh SH et Al. Gastroenterology, 132:1261-9, 2007

End-point:•DEATH•DECOMPENSATION

EndEnd--point:point:•DEATH•DECOMPENSATION

195 Pts195 PtsSurgery in CirrhosisSurgery in Cirrhosis::

MELDMELD CTPCTP



ChildChild--Pugh ScorePugh Score MELD ScoreMELD Score


Telem, Gastroent & Hepatol. 2010Telem, Gastroent & Hepatol. 2010

Operatory Risk in CirrhosisOperatory Risk in Cirrhosis

9090--days Mortalitydays Mortality

72%72%76%76%77%77%

190 Cases (Urgent + Elective)190 Cases (Urgent + Elective)


113 Cases (Elective Surgery)113 Cases (Elective Surgery)


CABG and CirrhosisCABG and Cirrhosis

MELD > 13.5

Predictive of Post-Operative In-Hospital Mortality

MELD > 13.5MELD > 13.5

Predictive of Post-Operative In-Hospital Mortality

MELD better than CTP and EUROScore

AUCAUC

MELD:MELD: 85,185,1CTPCTP: 75,7: 75,7EUROScoreEUROScore: 65,9: 65,9




Type of Surgery

Assessment of Liver DysfunctionPrognostic ScoresPrognostic ScoresEvaluation of Functional ReserveHepatic VolumetryDynamic “Functional Volumetry”

Hepatic VolumetryHepatic Volumetry

In Healthy Individuals:In Healthy Individuals:70-75% Hepatectomy = No Consequences > 87.5% Hepatectomy = Inevitable Death

When synthetic alterations are present in a cirrhotic patient, >75% of the liver is

dysfunctional

ASSUMPTION(?!):ASSUMPTION(?!):

Liver VolumetryLiver Volumetry MEVISMEVIS--CTCTVirtual ResectionVirtual Resection

RLV = 27%RLV = 27% RLV = 34%RLV = 34% RLV = 61%RLV = 61%

33--DD--reconstruction of functional liver anatomyreconstruction of functional liver anatomyVolume calculation of portal vein segments and hepatic artery seVolume calculation of portal vein segments and hepatic artery segmentsgments

Selle D et al. IEEE Trans Med Imaging 2002;21(11):1344Selle D et al. IEEE Trans Med Imaging 2002;21(11):1344--5757

Resection on cirrhosis: even in compensated patients, a minimum of 40% of the whole liver must remain…

Resection on cirrhosis: even in compensated patients, a minimum of 40% of the whole liver must remain…

Clearance TestsClearance Tests

Indocyanin Green Dye

Jaluronic acid

Galactose elimination Capacity (GEC)

Lidocaine/Monoethylglycinexylide (MEGx)

Redox tolerance Index

Arterial Ketone Body Ratio

Breath TestsAminopyrine, Methionine, Caffeine, Methacetine, Chetoisocaproic, Galactose

Indocyanin Green DyeIndocyanin Green Dye

Jaluronic acid

Galactose elimination Capacity (GEC)

Lidocaine/Monoethylglycinexylide (MEGx)

Redox tolerance Index

Arterial Ketone Body Ratio

Breath TestsAminopyrine, Methionine, Caffeine, Methacetine, Chetoisocaproic, Galactose

ICGICG--R14 Pulse Dye DensitometryR14 Pulse Dye Densitometry

I.V. ICG is eliminated into the bileCorrelating with liver cell function without enterohepatic recirculation

Noninvasive methodArterial ICG concentration: by pulse-dye densitometry (Pulse Oximetry)

Based on difference in absorbance between oxyhemoglobin (940 WL) and ICG (805 WL)

I.V. ICG is eliminated into the bileCorrelating with liver cell function without enterohepatic recirculation

Noninvasive methodArterial ICG concentration: by pulse-dye densitometry (Pulse Oximetry)

Based on difference in absorbance between oxyhemoglobin (940 WL) and ICG (805 WL)

METHODMETHOD

Set System with Height, Body weight, Hemoglobin level of patientI.V. Bolus of 25 mg of ICG and flushingBlood ICG Concentration monitored every pulse via optical probe (patient’ nose)ICG-R15 is automatically calculated within 5’ (decay curve)

Normal function: Retention < 10%Retention < 10%

Indocyanin Green (ICG)Indocyanin Green (ICG)

2 Segments or until 30% 2 Segments or until 30%

1 Segment until 15% 1 Segment until 15%

NO SegmentectomyNO Segmentectomy

NO SubNO Sub--segmentectomy segmentectomy

Prediction of Resecability in CirrhoticsPrediction of Resecability in Cirrhotics

Hasegawa, 1987 - Watanabe, 1999

at 15 minat 15 min. from 0,5 mg/Kg i.v. bolus

Cirrhosis and Liver ResectionCirrhosis and Liver Resection

Relationship between ICG R15 and parenchymal hepatic resection rate relative to outcomeRelationship between ICG R15 and parenchymal hepatic resection rRelationship between ICG R15 and parenchymal hepatic resection rate relative to outcomeate relative to outcome

Survivors

NonSurvivors

Non Cirrhotics


Valuable Tool to plan Intraoperative decisions on extent of Resection


PostPost--operative Stayoperative StayPostPost--operative Bilirubin increaseoperative Bilirubin increase


FRL Dynamic EvaluationFRL Dynamic Evaluation

GSA-Scintigraphy99mTc-labeled diethylenetriaminepentaacetic acid

Galactosyl Human Serum Albumin

GSAGSA--ScintigraphyScintigraphy99mTc-labeled diethylenetriaminepentaacetic acid

Galactosyl Human Serum Albumin

HBSHepatobiliary Scintigraphy 99mTc-labeled Mebrofenin

HBSHBSHepatobiliary Scintigraphy 99mTc-labeled Mebrofenin

Receptor-mediatedAsialoglycoprotein Receptors only on Hepatocytes

ReceptorReceptor--mediatedmediatedAsialoglycoprotein Receptors only on HepatocytesAsialoglycoprotein Receptors only on Hepatocytes

Hepatic Uptake & ExcretionHepatic + Biliary System

Hepatic Uptake & ExcretionHepatic Uptake & ExcretionHepatic + Biliary SystemHepatic + Biliary System

Uptake Reduced by↓HepatocytesCirrhosisCholestasis

Uptake/Excretion Reduced by↓Blood flowHypoalbuminemiaLiver Function

Combined with SPECT/CT cameras

for 3-dimensional Evaluation

Combined with SPECT/CT camerasCombined with SPECT/CT cameras

for 3for 3--dimensional Evaluationdimensional Evaluation

FRL Dynamic EvaluationFRL Dynamic Evaluation

Anterior projection of CeCT reconstruction

Planar dynamic 99mTc-mebrofenin HBS images

Portal/hepatic veins used as landmarks for FRL &

CeCT scans

Delineated FRL of CeCT scans was used as constant reference

On SPECT image, FRL manually outlined on CTlow scans linked to SPECT images

SPECT image


p < 0,0001p < 0,0001

FRL-V= Future Remnant Liver – VolumeFRL-F= Future Remnant Liver – Uptake Function

At 3At 3°° postpost--op dayop day

p < 0,0001p < 0,0001

p < 0,0003p < 0,0003

Correlation FRLCorrelation FRL--F/FRLF/FRL--V V in Normal & cirrhoticsin Normal & cirrhotics


ROC curveROC curveFRL-F cut-off

2,69%min/m22,69%min/m2Identified Pts with Significant Risk of

Post-op Liver Failure

AUC=0,916

FORMULA:FORMULA:

Alb is albumin (g/dl); HPT, hepaplastin test (%); GOT, (U/l);KICG, K, value of indocyanine green clearance test;OGTT. LI, 60-min/120-min glucose level in 75-g OGTT;RW, weight of resected liver (g).

AlbAlb is albumin (g/dl); HPTHPT, hepaplastin test (%); GOTGOT, (U/l);KICGKICG, K, value of indocyanine green clearance test;OGTTOGTT. LI, 60-min/120-min glucose level in 75-g OGTT;RWRW, weight of resected liver (g).

Original data: 28 pts from 1981-1984Training data set: 207 pts between 1985-1999Pre-operative evaluation: 145 pts between 2000-2006

New Formula ??New Formula ??


No Hepatectomy if score > 50No Hepatectomy if score > 50


MELDMELD--Matched Study PopulationMatched Study Population

p = 0,453

ALL 241 PatientsALL 241 Patients

p < 0,008p < 0,008

Mayo Model 9Mayo Model 9

To determine the risk of post-operative mortality for all types of major surgery, especially gastro-intestinal, orthopedic and cardiac surgery (includes open-heart procedures), please enter the following variables:

What is the age?What is the ASA score? (use 1-5)What is the bilirubin? (mg/dl)What is the creatinine? (mg/dl)What is the INR?

What is the etiology of cirrhosis? Alcoholic or CholestaticViral/Other

To determine the risk of post-operative mortality for all types of major surgery, especially gastro-intestinal, orthopedic and cardiac surgery (includes open-heart procedures), please enter the following variables:

What is the age?What is the ASA score? (use 1-5)What is the bilirubin? (mg/dl)What is the creatinine? (mg/dl)What is the INR?

What is the etiology of cirrhosis? Alcoholic or CholestaticViral/Other

Compute Reset Form

PROBABILITY OF MORTALITYPOST-OPERATIVE INTERVAL

7 days7 days 30 days30 days 90 days90 days 1 year1 year 5 years5 years

http://www.mayoclinic.org/meld/mayomodel9.html




Type of Surgery

Assessment of Liver Dysfunction


Child-PughAscitesCreatinineCirrhosis # da CBPBPCOInfectionsPrevious G.I. BleedingASA physical statusIntraoperative HypotensionSurgery Severity Score

Child-PughAscitesCreatinineCirrhosis # da CBPBPCOInfectionsPrevious G.I. BleedingASA physical statusIntraoperative HypotensionSurgery Severity Score

Perioperative ComplicationsPerioperative ComplicationsRisk FactorsRisk Factors

Ziser, anesthesiology, 1999


Male SexChild-PughAscitesCreatinineCryptogenic CirrhosisPreoperative InfectionsASA physical statusThoracic Surgery

Male SexChild-PughAscitesCreatinineCryptogenic CirrhosisPreoperative InfectionsASA physical statusThoracic Surgery

Ziser, anesthesiology, 1999

Postoperative MORTALITYPostoperative MORTALITYRisk FactorsRisk Factors

Malnutrition and Surgery in CirrhotcsMalnutrition and Surgery in Cirrhotcs

Matsumata, 1990

The Assessment of Surgical Risk in

Cirrhosis Represents a Stimulating Challenge

Limits of prognostic Scores Limits of prognostic Scores

Lack of an “all-inclusive”Validated Score

Type of surgeryRole of PHNutritional Status

Hepatic FunctionComorbidityTeam experience

Standard MELD performs less at lower numbers

Modified MELD scores are better

Dynamic Scores are the answer ?

Grazie dell’attenzione

Classe di Child e morbidità/mortalità perioperatoria(interventi chirurgici addominali)

Classe di Child e morbiditClasse di Child e morbiditàà/mortalit/mortalitàà perioperatoriaperioperatoria(interventi chirurgici addominali(interventi chirurgici addominali))

Garrison, Ann Surg 1984Garrison, Ann Surg 1984

ChildChild--Pugh classification system e Rischio Operatorio nel Pugh classification system e Rischio Operatorio nel cirroticocirrotico

ChildChild--PughPugh RischioRischio ChirurgiaChirurgia

AA 77--10%10%(rischio basso)(rischio basso)

Ben tollerataBen tollerata

BB 2323--30%30%(rischio moderato)(rischio moderato)

Possibile*

CC 7575--84%84%(rischio elevato)

Generalmente Generalmente ControindicataControindicata

* * solo dopo adeguata preparazionesolo dopo adeguata preparazione

Malnutrizione Malnutrizione èè un significativo fattore di rischio di morbiditun significativo fattore di rischio di morbiditàà e e mortalitmortalitàà postpost--operatoria nel cirroticooperatoria nel cirrotico

Maggiore frequenza di Maggiore frequenza di complicanzecomplicanze postpost--operatorie operatorie (17 vs 7%; (17 vs 7%; p<0.01)p<0.01)

Merli, Nutrition 2002Merli, Nutrition 2002

Aumentato rischio di Aumentato rischio di mortalitmortalitàà operatoria precoce o tardiva operatoria precoce o tardiva (62 (62 vs 22%; p<0.01)vs 22%; p<0.01)

Cello, Am J Surg 1981Cello, Am J Surg 1981Garrison, Ann Surg 1984Garrison, Ann Surg 1984

Malnutrizione e Rischio OperatorioMalnutrizione e Rischio Operatorio

……mama

Merli, Nutrition 2002Merli, Nutrition 2002

LL’’effetto della malnutrizione può essere mascherato da altri fattoeffetto della malnutrizione può essere mascherato da altri fattori associati a danno ri associati a danno epatico che possono svolgere un epatico che possono svolgere un ruolo predominateruolo predominate in tale condizionein tale condizione

La malnutrizione eLa malnutrizione e’’ stata valutata con metodi eterogenei e spesso non confrontabilistata valutata con metodi eterogenei e spesso non confrontabili::

Parametri antropometriciParametri antropometrici (massa magra: circonferenza muscolo braccio; massa grassa: spessore pieghe cutanee)Bioelectrical impedenceBioelectrical impedenceCalorimetria indirettaCalorimetria indirettaSubjective Global AssessmentSubjective Global Assessment (parametri clinici e di laboratorio)

Height z scoreHeight z score (x eta’ pediatrica: differenza tra altezza paziente e altezza media diviso SD)

……ll’’utilizzo della malnutrizione come unico fattore di rischio utilizzo della malnutrizione come unico fattore di rischio operatorio nel cirrotico ha dei limiti:operatorio nel cirrotico ha dei limiti:

Chirurgia nel CirroticoChirurgia nel Cirrotico

AnestesiaAnestesiaAnestesia

LaparotomiaLaparotomia

ToracotomiaToracotomia

IpotensioneIpotensione

Perdite ematichePerdite ematicheTrasfusioniTrasfusioni

Circolazione ExtraCircolazione Extra--corporeacorporea

Chirurgia cardiovascolare nel cirrotico Chirurgia cardiovascolare nel cirrotico

Hayashida, Ann Thorac Car Sur 2004Hayashida, Ann Thorac Car Sur 2004

MortalitMortalitàà (%)(%)AutoreAutore n CBP (bypass cardiop) An CBP (bypass cardiop) A BB CC

Klemperer, 1998Klemperer, 1998 1313 sisi 00 80 80 --Bizouarn, 1999Bizouarn, 1999 1212 sisi 00 50 50 --Kaplan, 2002Kaplan, 2002 88 sisi 00 50 50 --Hayashida, 2004 Hayashida, 2004 1515 sisi 00 5050 100100

Classe ChildClasse Child--PughPugh IC con CPB IC senza CPBIC con CPB IC senza CPB

AA AccetabileAccetabile AccetabileAccetabile

BB Controindicato*Controindicato* AccetabileAccetabile

CC ControindicatoControindicato ??

* Se non strettamente necessario* Se non strettamente necessario


Stadiation/Type of Hepatopaty

Screening of Complications

Surgical Risk Factors

Evaluation of Hepatic Function

Nutritional Evaluation

Stadiation/Type of Hepatopaty

Screening of Complications

Surgical Risk Factors

Evaluation of Hepatic Function

Nutritional Evaluation

PrePre--operative Evaluationoperative Evaluation

Rischio Operatorio nel Cirrotico

Two-step strategyTIPS 15-30 giorni pre-intervento chirurgico:

TwoTwo--step strategystep strategyTIPS 15TIPS 15--30 giorni pre30 giorni pre--intervento chirurgico:intervento chirurgico:

Potrebbe comportarePotrebbe comportare

Riduzione rischio di sanguinamentoRiduzione rischio di sanguinamentoRiduzione emotrasfusioniRiduzione emotrasfusioniRiduzione ipotensione intraoperatoriaRiduzione ipotensione intraoperatoriaRiduzione tempi operatoriRiduzione tempi operatoriRiduzione mortalitRiduzione mortalitàà

Tipo di anestetico e fegato cirroticoTipo di anestetico e fegato cirrotico

Alotano ed EnfluoranoAlotano ed EnfluoranoMetabolizzati dal fegato (alotano: 20%; enfluorano:3%)Metabolizzati dal fegato (alotano: 20%; enfluorano:3%)Riducono flusso attraverso lRiducono flusso attraverso l’’arteria epatica (vasodilatazione sistemica)arteria epatica (vasodilatazione sistemica)Hanno debole effetto inotropo negativoHanno debole effetto inotropo negativo

IsofluoranoIsofluoranoMetabolizzato dal fegato solo in minima parte (0.2%)Metabolizzato dal fegato solo in minima parte (0.2%)AAumenta il flusso attraverso lumenta il flusso attraverso l’’arteria epaticaarteria epaticaRappresenta lRappresenta l’’anestetico di scelta nei pazienti con malattie anestetico di scelta nei pazienti con malattie epaticheepatiche

Anestetici VolatiliAnestetici Volatili

Agenti bloccanti neuromuscolari:Agenti bloccanti neuromuscolari:Effetto prolungato nellEffetto prolungato nell’’epatopatico per:epatopatico per:

riduzione dellriduzione dell’’attiattiììvitvitàà pseudocolinesterasicapseudocolinesterasicaridotta escrezione biliareridotta escrezione biliareaumentato volume di distribuzioneaumentato volume di distribuzione

Atracurio:Atracurio:Metabolismo indipendente dal fegatoMetabolismo indipendente dal fegatoAgente di scelta nei pazienti epatopaticiAgente di scelta nei pazienti epatopatici

Doxacurio:Doxacurio:Miorilassante a lunga durata dMiorilassante a lunga durata d’’azioneazioneRaccomandato per interventi chirurgici prolungati (OLTx)Raccomandato per interventi chirurgici prolungati (OLTx)


Narcotici:Narcotici:Morfina e meperidina: riducono il flusso epaticoMorfina e meperidina: riducono il flusso epaticoFentanil: narcotico di scelta nei pazienti epatopaticiFentanil: narcotico di scelta nei pazienti epatopatici

Sedativi:Sedativi:Diazepam: metabolismo prolungato in pazienti epatopatici (totalmDiazepam: metabolismo prolungato in pazienti epatopatici (totalmente ente epatico)epatico)Lorazepam: agente di scelta (non ha metabolismo epatico)Lorazepam: agente di scelta (non ha metabolismo epatico)



Cirrhosis “per se” is NOT a Contraindication to

SurgeryBUT

Mandate a Rigorous Selection to prevent

Morbidity and Mortality

Cirrhosis “per se” is NOT a Contraindication to

SurgeryBUT

Mandate a Rigorous Selection to prevent

Morbidity and Mortality

MEGx test

Lydocaine 1 mg/Kg i.v. bolusSamples at 0, 15, 30, 45 min.

Serum levels of mono-etil-glicine-xilodide (MEGX)

Reflects cit. p450 Activity and Hepatic FlowUSE (?):

Prognostic Evaluation in cirrhosisFunctonal reserve in pts with liver metastasisEvaluation of graft functionalityPre/post-operative assessment

Lydocaine 1 mg/Kg i.v. bolusSamples at 0, 15, 30, 45 min.

Serum levels of mono-etil-glicine-xilodide (MEGX)

Reflects cit. p450 Activity and Hepatic FlowUSE (?):

Prognostic Evaluation in cirrhosisFunctonal reserve in pts with liver metastasisEvaluation of graft functionalityPre/post-operative assessment

MEGx testMEGx test

p<0.05p<0.05A vs CA vs CB vs CB vs C

Persistent Hep.Persistent Hep.

Chronic ActiveChronic Active

CirrhosisCirrhosis

MinMin

Aminopirina Breath Test (13C)

Dose orale 2 mg/Kg (e.v.)

Distribuzione: UniformeMetabolismo:

Esclusivo epatico (c. p450)NON correlato a flusso portaleNON influenzato da colestasi

Dose orale 2 mg/Kg (e.v.)

Distribuzione: UniformeMetabolismo:

Esclusivo epatico (c. p450)NON correlato a flusso portaleNON influenzato da colestasi

Riflette Massa Epatica Funzionale

Riflette Massa Riflette Massa Epatica FunzionaleEpatica Funzionale

1313COCO22% Dose cumulativa% Dose cumulativa

LIMITIEnzimi inducibili

AlcolFarmaci

Stato nutrizionaleFolatiGlutatione

Età?Produzione endogena CO2

FebbreAlimenti

LIMITIEnzimi inducibili

AlcolFarmaci

Stato nutrizionaleFolatiGlutatione

Età?Produzione endogena CO2

FebbreAlimenti

F. Perri

Aminopirina Breath Test (13C)

Normale

Child A

Child C

Minuti

F. Perri

13CO2 Espirato

% Dose Cumulativa a 2 ore

>8,4%Normale

< 8,4% - >2.3%Epatopatia / Cirrosi

< 2,3%Alta Mortalità Chirurgica

13CO2 Espirato

% Dose Cumulativa a 2 ore

>8,4%Normale

< 8,4% - >2.3%Epatopatia / Cirrosi

< 2,3%Alta Mortalità Chirurgica

Cirrhosis and Nutritional StatusCirrhosis and Nutritional Status

Compensated CirrhosisNormal Energetic Requests

25-35 Kcal/Kg

Decompensated CirrhosisIncreased Energetic Requests

Up to 40-45 Kcal/Kg

Compensated CirrhosisCompensated CirrhosisNormal Energetic Requests

25-35 Kcal/Kg

Decompensated CirrhosisDecompensated CirrhosisIncreased Energetic Requests

Up to 4040--45 Kcal/Kg45 Kcal/Kg

GrazieIl Bacio, Klimt

Rischio Operatorio nel CirroticoRischio Operatorio nel Cirrotico

Del Olmo, 2003Del Olmo, 2003

NonNon--Hepatic SurgeryHepatic Surgery

15,1%15,1% 37,4%37,4% 41,5%41,5% 45,5%45,5%




Cirrhosis and Type of Surgery (Hepatic resection)Cirrhosis and Type of Surgery (Hepatic resection)

Reduction ofReduction ofFunctional MassFunctional Mass

SyntesisSyntesisDetossificationDetossification

AlbuminAlbuminPTPTComplementComplement

HemorragicRisk

HemorragicHemorragicRiskRisk

ResistanceResistancePortal FlowPortal Flow

ASCITESASCITES

ENCEPHALOPATENCEPHALOPATYY

INFECTIONSINFECTIONSINFECTIONS

Portal Portal HypertensionHypertension

Operative Risk in cirrhosisOperative Risk in cirrhosis

Blood Flow ReciprocityBlood Flow ReciprocityBlood Flow Reciprocity

0022 Portal SupplyPortal Supply

50%50%

O20022 Arterial SupplyArterial Supply

50%50%

Increase over Increase over 50%50%via Compensatory Vasodilation via Compensatory Vasodilation (( Portal flowPortal flow))

Reduced by:Reduced by:Cardiac Cardiac Output Output Systemic Systemic Pressure (intraoperative)Pressure (intraoperative)Manipolation due to splancnic surgeryManipolation due to splancnic surgery

Portal Blood FlowPortal Blood Flow70%70%

Hepatic Artery Blood FlowHepatic Artery Blood Flow30%30%

Operative Risk in cirrhosisOperative Risk in cirrhosis

Blood Flow Blood Flow ReciprocityReciprocity

O2 Compensatory Compensatory Splancnic Arterial Splancnic Arterial

Vasodilation :Vasodilation :

REDUCED BY:REDUCED BY:Type of Anesthetic Type of Anesthetic (alothane)(alothane)Anesthetic ConcentrationAnesthetic Concentration

COMPROMIZEDCOMPROMIZEDin cirrhosisin cirrhosis

INCREASEDINCREASEDSusceptibility to ISCHEMIASusceptibility to ISCHEMIA

…Any degree of clinically

evident liver dysfunction in

a prospective surgical patient

should raise concern

……Any Any degree of clinically

evident liver dysfunction in

a prospective surgical patient

should raise concern

Cirrhosis and Type of SurgeryCirrhosis and Type of Surgery

LAPAROTOMY

Hepatic Arterial Flow• Visceral Traction induces reflexive hypotension

Hemorragic Risk• Portal Hypertension• Previous Operations

ABDOMINAL SURGERY


Causes of DeathCauses of Death

Abdominal Sepsis

G.I. Complications

No cardiac deaths

MortalityMortality

Klemperer, Ann Thor. Surg. 1993Klemperer, Ann Thor. Surg. 1993

CARDIAC SurgeryCARDIAC Surgery

Commonly Used Commonly Used 1313COCO22 BREATH TESTSBREATH TESTS

Aminopirine P450 N-demetylationMethacetine P450 O-demetylationFenacetinae P450 1A2 O-demetylationCaffeine P450 1A2 N-demetylationEritromycine P450 IIIA N-demetylationFenylalanine Cyitoplasmic Hydroxylasis Galactose Membrane EsokinasisChetoisocaproic Acid Mitocondrial DecarboxilationMethionine Mitocondrial OxidationNa-Ottanoate (MCFA) Mitocondrial Beta-oxidation

Aminopirine P450 N-demetylationMethacetine P450 O-demetylationFenacetinae P450 1A2 O-demetylationCaffeine P450 1A2 N-demetylationEritromycine P450 IIIA N-demetylationFenylalanine Cyitoplasmic Hydroxylasis Galactose Membrane EsokinasisChetoisocaproic Acid Mitocondrial DecarboxilationMethionine Mitocondrial OxidationNa-Ottanoate (MCFA) Mitocondrial Beta-oxidation


Predictive Factors p

Child Score 0,001

Ascites 0,006

Encephalopathy 0,002

PT 0,02

MortalityMortality

p < 0,001p < 0,001

Mansour, Surgery 1997Mansour, Surgery 1997Abdominal SurgeryAbdominal Surgery

URGENTURGENT

Liver VolumetryLiver Volumetry


FRL-V= Future Remnant Liver – VolumeFRL-F= Future Remnant Liver – Uptake Function

Real Operative Risk in Cirrhotic Patient is Difficult to AssessReal Operative Risk in Cirrhotic Patient is Difficult to Assess

Few Few ““GoodGood”” DataData

Mostly RetrospectiveMostly Retrospective

Confounding factors Confounding factors (type of surgery, underlying diesease, anesthesiology(type of surgery, underlying diesease, anesthesiology……..)..)

Friedman, Hepatology 1999Friedman, Hepatology 1999

Operative Risk in CirrhosisOperative Risk in Cirrhosis

evaluation of surgical risk in patients with liver disease · evaluation of surgical risk in...

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