Hepatopulmonary Syndrome and Hepatopulmonary Syndrome and Portopulmonary Hypertension in the Portopulmonary Hypertension in the MELD Era MELD Era M. Susan Mandell MD PhD M. Susan Mandell MD PhD Professor of Anesthesiology Professor of Anesthesiology Liver Transplant Program Liver Transplant Program University of Colorado University 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
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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)
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
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
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
Criteria for PPHTNCriteria for PPHTNPressure MeasurementsPressure Measurements
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
Criteria for PPHTNCriteria for PPHTNPressure MeasurementsPressure Measurements
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
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