2004 aasld annual meeting hepatopulmonary syndrome and portopulmonary hypertension … ·...

Hepatopulmonary Syndrome and Hepatopulmonary Syndrome and Portopulmonary Hypertension in the Portopulmonary Hypertension in the

MELD EraMELD Era

M. Susan Mandell MD PhDM. Susan Mandell MD PhDProfessor of AnesthesiologyProfessor of AnesthesiologyLiver Transplant ProgramLiver Transplant Program

University of ColoradoUniversity of Colorado

2004 AASLD Annual Meeting

I have no relationships with commercial entities that might be perceived as having a connection with this presentation and the content of my presentation including the discussion of off-label/investigative use of

medicine(s) medical devices or procedures

Principles of MELDPrinciples of MELD

Allocate organs according to mortality riskAllocate organs according to mortality risk

Allocate organs to patients who will benefit Allocate organs to patients who will benefit from liver transplantationfrom liver transplantation

MELD and Pulmonary Vascular MELD and Pulmonary Vascular DiseaseDisease

Do candidates with pulmonary vascular disease Do candidates with pulmonary vascular disease have an increased risk of mortality? have an increased risk of mortality?

Will recipients with pulmonary vascular disease Will recipients with pulmonary vascular disease benefit from liver transplantation?benefit from liver transplantation?

ContentsContents

1.1. Criteria for disease diagnosisCriteria for disease diagnosis2.2. Diagnostic testsDiagnostic tests3.3. Pre transplant morbidity/mortalityPre transplant morbidity/mortality4.4. Post transplant morbidity/mortalityPost transplant morbidity/mortality5.5. What priority should these patient have?What priority should these patient have?

Definition of Hepatopulmonary Definition of Hepatopulmonary Syndrome (HPS)Syndrome (HPS)

Liver DiseaseLiver DiseaseArterial deoxygenationArterial deoxygenationIntrapulmonary ShuntingIntrapulmonary Shunting

Kennedy T Chest 1977;72:305

Criteria for HPSCriteria for HPSDeoxygenationDeoxygenation

Diagnosis of HPS in 98 subjects with positive Diagnosis of HPS in 98 subjects with positive contrast echocardiographycontrast echocardiography

ArterialArterial--alveolar difference > 15 mm Hg 32%alveolar difference > 15 mm Hg 32%ArterialArterial--alveolar difference > 20 mm Hg 31%alveolar difference > 20 mm Hg 31%Age Corrected Age Corrected 28%28%Partial pressure of arterial oxygen < 80 mm Hg 19%Partial pressure of arterial oxygen < 80 mm Hg 19%Partial pressure of arterial oxygen < 70 mm Hg 15%Partial pressure of arterial oxygen < 70 mm Hg 15%Age corrected Age corrected 15% 15%

Schenk P. Gut 2002;51:853

Criteria for HPSCriteria for HPSIntrapulmonary ShuntIntrapulmonary Shunt

40 patients with biopsy proven cirrhosis40 patients with biopsy proven cirrhosis

15/40 positive contrast echo 38%15/40 positive contrast echo 38%

3 positive Tc MAA lung scan 8% 3 positive Tc MAA lung scan 8% ((99mTc macroaggregated albumin perfusion lung scan)99mTc macroaggregated albumin perfusion lung scan)

Abrams G, Gastroenterology 1995;109:1283

Criteria for HPSCriteria for HPSIntrapulmonary ShuntIntrapulmonary Shunt

Diagnosis of HPS in Diagnosis of HPS in 7 patients with hypoxemia7 patients with hypoxemia

Test Test % HPS % HPS% HPS % HPS((n=40) n=40) ((n= 7n= 7))

Contrast echo 17.5% 100%Contrast echo 17.5% 100%Lung scan 8% 43% Lung scan 8% 43%

Abrams G, Gastroenterology 1995;109:1283

Criteria for HPSCriteria for HPS

Other causes of hypoxemia in patients with liver Other causes of hypoxemia in patients with liver diseasedisease

Fluid retention (V/Q mismatch)Fluid retention (V/Q mismatch)Pleural effusionPleural effusionAscitesAscitesCardiopulmonary diseaseCardiopulmonary disease

Are Patients with HPS at Increased Are Patients with HPS at Increased Risk of Mortality?Risk of Mortality?

Mortality increased in HPS defined byMortality increased in HPS defined by(age corrected A(age corrected A--aDO2)aDO2)Contrast echocardiographyContrast echocardiography

Median survival of 10.6 mo in HPS vs. 40.8 mo without Median survival of 10.6 mo in HPS vs. 40.8 mo without HPS. HPS. Causes of death were primarily non pulmonaryCauses of death were primarily non pulmonary

Schenk P et al. Gastroenterology 2003;125:1042Schenk P et al. Gastroenterology 2003;125:1042

Will Patients Benefit from Liver Will Patients Benefit from Liver Transplantation Transplantation

Time to recovery (125% of preoperative PaO2) ranges Time to recovery (125% of preoperative PaO2) ranges from 10 to 24 monthsfrom 10 to 24 months

29% mortality rate within 10 weeks of surgery 29% mortality rate within 10 weeks of surgery compared to 15% 1 year mortality for all liver compared to 15% 1 year mortality for all liver transplants in the United Statestransplants in the United States

30.5% mortality over 10 yr study period30.5% mortality over 10 yr study periodTaille C. Transplantation 2003;75:1482

Argueda M. Hepatology 2003;37:192; www.UNOS.org national data

Egawa H. Transplantation 1999;67:712

Will Patients Benefit from Liver Will Patients Benefit from Liver TransplantationTransplantation

What predicts early mortality in HPS patients?What predicts early mortality in HPS patients?

1.1. Tc MAA brain uptake Tc MAA brain uptake >> 20%20%

2.2. PaO2 PaO2 << 50 mm Hg RA50 mm Hg RA

Arguedas M. Hepatology 2003;37:192Krowka M. Chest 2000;118:615

Morbidity of HPS following Morbidity of HPS following Liver TransplantationLiver Transplantation

Increase in Increase in

Cerebral hemorrhageCerebral hemorrhageBiliary leaksBiliary leaksWound infectionWound infection

complications correlate with the degree of complications correlate with the degree of hypoxemia and pulmonary shunthypoxemia and pulmonary shunt

Taille C. Transplantation 2003;75:1482Egawa H. Transplantation 1999:67:712

UNOS Policy forUNOS Policy forHPSHPS

3.6.4.5.13.6.4.5.1 Liver Candidates with Liver Candidates with Hepatopulmonary Syndrome (HPS).Hepatopulmonary Syndrome (HPS).

1.1. Evidence of a shunt Evidence of a shunt 2.2. Patients with a clinical evidence of portal Patients with a clinical evidence of portal

hypertension hypertension 3.3. PaO2 < 60 on room air PaO2 < 60 on room air

may be referred to the RRB for consideration of a MELD score thamay be referred to the RRB for consideration of a MELD score that would provide t would provide them a reasonable probability of being transplanted within 3 monthem a reasonable probability of being transplanted within 3 months.ths.Patients should have no significant clinical evidence of underlyPatients should have no significant clinical evidence of underlying primary ing primary pulmonary disease.pulmonary disease.

Definition of Portopulmonary Definition of Portopulmonary Hypertension (PPHTN)Hypertension (PPHTN)

mPAP mPAP >> 25 mm Hg25 mm HgPCWP PCWP << 15 mm Hg15 mm HgPVR PVR >> 120 120 dynes.s.cmdynes.s.cm--55

Evidence of portal hypertensionEvidence of portal hypertension

Mandell M. Anesthesiology 1997;87:450

Criteria for PPHTNCriteria for PPHTNPressure MeasurementsPressure Measurements

Pulmonary pressure measurements and resistance Pulmonary pressure measurements and resistance affected byaffected by

Central hyperdynamic flowCentral hyperdynamic flowAscites Ascites Pleural EffusionPleural Effusion


EchocardiographyEchocardiographyEstimated systolic pressure Estimated systolic pressure >> 40 mm Hg40 mm Hg

RequiresRequires

Cardiac CatheterizationCardiac Catheterization

Cotton C. Liver Transpl 2002;8:1051Torregrosa M. Transplantation 2001;71:572Colle I Hepatology 2003;37:401


91.9%91.9%99%99%Negative Negative predictive predictive valuevalue

37%37%31%31%Positive Positive predictive predictive valuevalue

estest SPAPSPAP>>5050

est est SPAPSPAP>> 4040

Cotton C. Liver Transpl 2002;8:1051Torregrosa M. Transplantation 2001;71:572

Are Patients with PPHTN at Are Patients with PPHTN at Increased Risk of Mortality?Increased Risk of Mortality?

50% mortality within 6 months of diagnosis with 50% mortality within 6 months of diagnosis with 2/3 of deaths due to PPHTN2/3 of deaths due to PPHTN

Robalino B. J Am Coll Cardiol 1991;17:492

Will Patients Benefit from Liver Will Patients Benefit from Liver TransplantationTransplantation

Significantly increased postoperative mortalitySignificantly increased postoperative mortality

35% mortality rate for all patients with PPHTN35% mortality rate for all patients with PPHTN71% mortality during transplant hospitalization71% mortality during transplant hospitalization93% due to cardiopulmonary cause93% due to cardiopulmonary cause

Ramsay M. Liver Transpl 1997;3:494Krowka M. Liver Transpl 2000;6:443

Predictors of Liver Transplant OutcomePredictors of Liver Transplant Outcome

Is mPAP a marker of disease severity?Is mPAP a marker of disease severity?Meta analysisMeta analysis

Krowka M. Liver Transpl 2000;6:443

100%100%SevereSevere> 50 mm Hg> 50 mm Hg

50%50%ModerateModerate3535--50 mm Hg50 mm Hg

0%0%MildMild< 35 mm Hg< 35 mm Hg

MortalityMortalityDisease Disease SeveritySeverity

mPAPmPAP

Predictors of Liver Transplant Outcome Predictors of Liver Transplant Outcome in PPHTNin PPHTN

mPAP in survivors of liver transplantationmPAP in survivors of liver transplantationProspective studyProspective study

322 322 ++ 12912945 45 ++ 88DeathDeathnn = 13= 13

341 341 ++1811814545++ 1414SurvivorSurvivornn = 23= 23

PVR PVR dynes.sec.cmdynes.sec.cm--55mPAP mPAP

mm Hgmm HgStatusStatus

Krowka M. Mandell M. Liver Transplantation 2004;10:174


Survival distributed by “severity of disease”Survival distributed by “severity of disease”

4 (40%)4 (40%)66SevereSevere

8 (40%)8 (40%)1212ModerateModerate

1 (16%)1 (16%)55MildMild

DeathDeathnn =13=13

SurvivorSurvivornn =23=23

SeveritySeverity

Krowka M. Mandell Liver Transplantation 2004;10:174

mPAP of 35 may signal a change in risk


Survival distributed by severity of diseaseSurvival distributed by severity of disease

13 (61%)13 (61%)((nn = 21)= 21)

8 (66%)8 (66%)((nn = 12)= 12)

Dismissed Dismissed OLTOLT

8 (17%)8 (17%)((nn = 21)= 21)

4 (28%)4 (28%)((nn = 12)= 12)

Died OLTDied OLT25 (54%)25 (54%)2 (14%)2 (14%)Denied OLTDenied OLT

PVR PVR >> 250250nn = 46= 46

PVR < 250 PVR < 250 nn =14=14

StatusStatus

Krowka M. Mandell M Liver Transplantation 2004;10:174

No significant difference

Will Patients Benefit from Liver Will Patients Benefit from Liver Transplantation?Transplantation?

0

10

20

30

40

50

60

70

BeforeProstacylcin

AfterProstacyclin

CHD

CVD

PPHTN

0

2

4

6

8

10

12

14

BeforeProstacyclin

AfterProstacyclin

CHD

CHD

PPHTN

Treatment with pulmonary vasodilatorsProstacyclin (12 = 5.6 Prostacyclin (12 = 5.6 ++ mo) mo)

31 31 ++ 16 ng/kg16 ng/kg

mPAP PVR

McLaughlin V. Ann Intern Med 1999;130:740

Will Patients Benefit from Liver Will Patients Benefit from Liver Transplantation?Transplantation?

Outcome of PPTHN following liver Outcome of PPTHN following liver transplantationtransplantation

1.1. ImprovedImproved2.2. Persistence Persistence 3.3. WorsenedWorsened4.4. De NovoDe Novo

Predictive Variables?Predictive Variables?Unknown effect of pulmonary vasodilatorsUnknown effect of pulmonary vasodilators

SummarySummary

Both HPS and PPHTN are poorly defined diseases.Both HPS and PPHTN are poorly defined diseases.Variability in study subjects calls for a consensus Variability in study subjects calls for a consensus agreement on disease criteriaagreement on disease criteriaPatients with HPS and PPHTN experience increased Patients with HPS and PPHTN experience increased mortality waiting for liver transplantationmortality waiting for liver transplantationPatients with severe hypoxemia and/or shunting do Patients with severe hypoxemia and/or shunting do not appear to benefit from transplantation and not appear to benefit from transplantation and therefore may not benefit from additional MELD therefore may not benefit from additional MELD pointspoints

SummarySummary

mPAP and PVR are not simple surrogates of disease mPAP and PVR are not simple surrogates of disease severity in patients with PPTHNseverity in patients with PPTHNThe effects of pulmonary vasodilators on PPHTN The effects of pulmonary vasodilators on PPHTN outcome are unknownoutcome are unknownNo variable identifies which PPHTN patients benefit No variable identifies which PPHTN patients benefit from liver transplantationfrom liver transplantation

2004 aasld annual meeting hepatopulmonary syndrome and portopulmonary hypertension … ·...

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