Perioperative Management Perioperative Management of Liver Transplant Patientsof Liver Transplant Patients

January 22, 2007January 22, 2007

Geoffrey Schultz, MDGeoffrey Schultz, MD

Topic ObjectivesTopic Objectives

1. Overview of indications & selection for liver 1. Overview of indications & selection for liver transplantation.transplantation.

2. Identification & treatment of complications 2. Identification & treatment of complications associated with liver disease in the preoperative associated with liver disease in the preoperative period.period.

3. Identification & treatment of complications 3. Identification & treatment of complications following orthotopic liver transplantation.following orthotopic liver transplantation.

4. Induction of immunosuppressive 4. Induction of immunosuppressive pharmacotherapy following transplantation.pharmacotherapy following transplantation.

5. Diagnosis & treatment of graft rejection.5. Diagnosis & treatment of graft rejection.

Orthotopic Liver TransplantationOrthotopic Liver Transplantation

11stst orthotopic liver orthotopic liver transplantation 1963.transplantation 1963.

Approximately 5,000 Approximately 5,000 orthotopic liver orthotopic liver transplantations transplantations annually for 17,000 in annually for 17,000 in need.need.

Indications for Liver Transplantation in Adults:Indications for Liver Transplantation in Adults:Etiologies of End-Stage Liver DiseaseEtiologies of End-Stage Liver Disease

1. Fulminant Hepatic Failure1. Fulminant Hepatic Failure 2. Alcoholic Liver Disease2. Alcoholic Liver Disease 3. Chronic Hepatitis C3. Chronic Hepatitis C 4. Chronic Hepatitis B4. Chronic Hepatitis B 5. Non-alcoholic steatohepatitis5. Non-alcoholic steatohepatitis 6. Autoimmune Hepatitis6. Autoimmune Hepatitis 7. Primary Biliary Cirrhosis7. Primary Biliary Cirrhosis 8. Primary Sclerosing Cholangitis8. Primary Sclerosing Cholangitis 9. Hepatic tumors 9. Hepatic tumors 10. Metabolic and genetic disorders10. Metabolic and genetic disorders

Indications for Liver Transplantation in AdultsIndications for Liver Transplantation in Adults

Presence of irreversible liver disease and a life Presence of irreversible liver disease and a life expectancy of less than 12 months with no expectancy of less than 12 months with no effective medical or surgical alternatives to effective medical or surgical alternatives to transplantation transplantation

Chronic liver disease that has progressed to the Chronic liver disease that has progressed to the point of significant interference with the patient's point of significant interference with the patient's ability to work or with his/her quality of life ability to work or with his/her quality of life

Progression of liver disease that will predictably Progression of liver disease that will predictably result in mortality exceeding that of result in mortality exceeding that of transplantation (85% one-year patient survival transplantation (85% one-year patient survival and 70% five-year survival) and 70% five-year survival)

Manifestations of End-Stage Liver DiseaseManifestations of End-Stage Liver Disease

Progressive jaundice Progressive jaundice Intractable ascites Intractable ascites Spontaneous bacterial peritonitis Spontaneous bacterial peritonitis Hepatorenal Syndrome Hepatorenal Syndrome Encephalopathy Encephalopathy Variceal bleeding Variceal bleeding Intractable pruritus Intractable pruritus Chronic fatigue (such as resulting in loss of Chronic fatigue (such as resulting in loss of

gainful employment) gainful employment) Bleeding diathesis or coagulopathy Bleeding diathesis or coagulopathy

Selection Criteria for Organ AllocationSelection Criteria for Organ Allocation

United Network for Organ Sharing United Network for Organ Sharing (UNOS) governing body for organ (UNOS) governing body for organ allocation utilizes MELD score.allocation utilizes MELD score.

Model for End Stage Liver Disease Model for End Stage Liver Disease (MELD) Score(MELD) Score• 0.957 x loge (creatinine) + 0.378 x loge (bilirubin mg/dL) + 1.12 x loge 0.957 x loge (creatinine) + 0.378 x loge (bilirubin mg/dL) + 1.12 x loge

(INR) + 0.643 x 10 (INR) + 0.643 x 10

• Range from 10 to 40Range from 10 to 40• Special considerations, amendments for Special considerations, amendments for

HCC, renal failure.HCC, renal failure.

Preoperative management of complications Preoperative management of complications associated with hepatic failure & associated with hepatic failure &

decompensated cirrhosisdecompensated cirrhosis Hepatic EncephalopathyHepatic Encephalopathy Cerebral EdemaCerebral Edema Acute Renal FailureAcute Renal Failure Infection & SepsisInfection & Sepsis Metabolic DerangementsMetabolic Derangements MalnutritionMalnutrition CoagulopathyCoagulopathy Portal HypertensionPortal Hypertension

Hepatic EncephalopathyHepatic Encephalopathy

Etiology: Attributed to increased Etiology: Attributed to increased serum ammonia levels secondary to serum ammonia levels secondary to metabolism of nitrogenous metabolism of nitrogenous substances in the gut.substances in the gut.

Symptoms: Range from euphoria to Symptoms: Range from euphoria to coma.coma.

Treatment: lactulose, decreased Treatment: lactulose, decreased intake of nitrogen containing intake of nitrogen containing compounds, oral neomycin.compounds, oral neomycin.

Cerebral EdemaCerebral Edema

Etiology: UnknownEtiology: Unknown Swelling of brain results in increased ICP & Swelling of brain results in increased ICP &

herniation. herniation. Invasive monitoring with goal of ICP < 20 Invasive monitoring with goal of ICP < 20

mmHg & CPP > 50 mmHg.mmHg & CPP > 50 mmHg. Treatment: Anxiolysis, HOB elevation, Treatment: Anxiolysis, HOB elevation,

hyperventilation, avoidance of hyperventilation, avoidance of overhydration, mannitol diuresis, HD if overhydration, mannitol diuresis, HD if compromised renal function. compromised renal function.

Acute Renal FailureAcute Renal Failure

Etiology: Toxin induced, Derangements in Etiology: Toxin induced, Derangements in systemic & intrarenal hemodynamics.systemic & intrarenal hemodynamics.

Treatment: Prevention of hypotension, Treatment: Prevention of hypotension, treatment of infection, avoidance of treatment of infection, avoidance of nephrotoxic agents. nephrotoxic agents.

Once established, renal failure in this Once established, renal failure in this setting is often irreversible. Early setting is often irreversible. Early utilization of renal replacement therapy is utilization of renal replacement therapy is indicated.indicated.

Infection & SepsisInfection & Sepsis

Etiology: Immunologic derangements Etiology: Immunologic derangements including complement deficiency, including complement deficiency, reduced opsonins, WBC dysfunction.reduced opsonins, WBC dysfunction.

Treatment: Frequent cultures, Treatment: Frequent cultures, including ascites. Broad spectrum including ascites. Broad spectrum antibiotics, including anti-fungals.antibiotics, including anti-fungals.

Metabolic DerangementsMetabolic Derangements

1. Hypokalemia1. Hypokalemia• Increased sympathetic tone promotes Increased sympathetic tone promotes

cellular uptake of K. Decreased serum K cellular uptake of K. Decreased serum K promotes production of ammonia by the promotes production of ammonia by the kidney.kidney.

2. Hyponatremia2. Hyponatremia 3. Hypoglycemia3. Hypoglycemia

• Secondary to decreased hepatic Secondary to decreased hepatic glycogen stores & decreased glycogen stores & decreased gluconeogenesis.gluconeogenesis.

CoagulopathyCoagulopathy

Etiology: Compromised synthetic Etiology: Compromised synthetic function, deficiency of coagulation function, deficiency of coagulation factors, platelet dysfunction.factors, platelet dysfunction.

Contribute to GI bleeding in Contribute to GI bleeding in conjunction with portal hypertension.conjunction with portal hypertension.

Treatment: Prevention with H2 Treatment: Prevention with H2 blockers, PPI. Judicious use of Factor blockers, PPI. Judicious use of Factor VIIa & FFP.VIIa & FFP.

Post-operative complications & Post-operative complications & management of liver transplant patientsmanagement of liver transplant patients Right pleural effusionRight pleural effusion

• May affect ventilation, necessitating May affect ventilation, necessitating drainage.drainage.

Hepatic edema secondary to Hepatic edema secondary to aggressive resuscitation & increased aggressive resuscitation & increased intravascular volume.intravascular volume.• Goal CVP 6-10. Minimize increased Goal CVP 6-10. Minimize increased

hepatic vein pressures, sinusoidal hepatic vein pressures, sinusoidal congestion that impair graft perfusion & congestion that impair graft perfusion & exacerbate reperfusion injury.exacerbate reperfusion injury.

Post-operative complications & Post-operative complications & management of liver transplant patientsmanagement of liver transplant patients

Renal failureRenal failure• Elevation of creatinine & BUN observed Elevation of creatinine & BUN observed

in nearly all transplant patients in nearly all transplant patients secondary to ATN, hepatorenal secondary to ATN, hepatorenal syndrome. Usually self-limiting. May syndrome. Usually self-limiting. May necessitate therapy with loop diuretics, necessitate therapy with loop diuretics, renal replacement therapy.renal replacement therapy.

Post-operative complications & Post-operative complications & management of liver transplant patientsmanagement of liver transplant patients Electrolyte DerangementsElectrolyte Derangements

• Recovering graft increases demand for Recovering graft increases demand for magnesium & phosphorous.magnesium & phosphorous.

• Transfusion of citrate rich blood products Transfusion of citrate rich blood products results in decreased serum magnesium & results in decreased serum magnesium & calcium.calcium.

• Rapid correction of chronic hyponatremia with Rapid correction of chronic hyponatremia with isotonic solution can have severe neurological isotonic solution can have severe neurological consequence. Judicious use of hypotonic consequence. Judicious use of hypotonic solutions with goal of serum Na 125-130 solutions with goal of serum Na 125-130 advised.advised.

Post-operative complications & Post-operative complications & management of liver transplant patientsmanagement of liver transplant patients ThrombocytopeniaThrombocytopenia

• Preoperative portal hypertension results in Preoperative portal hypertension results in splenomegaly & platelet sequestration. splenomegaly & platelet sequestration. Generally improves as graft recovers. May Generally improves as graft recovers. May necessitate replacement if bleeding is necessitate replacement if bleeding is encountered or invasive procedures are encountered or invasive procedures are planned. Splenectomy is rarely indicated.planned. Splenectomy is rarely indicated.

• Platelet dysfunction secondary to renal & Platelet dysfunction secondary to renal & hepatic failure may be improved acutely with hepatic failure may be improved acutely with DDAVP.DDAVP.

Post-operative complications & Post-operative complications & management of liver transplant patientsmanagement of liver transplant patients Biliary leakBiliary leak

• RUQ pain, fever, persistent elevation of RUQ pain, fever, persistent elevation of bilirubin, liver enzymes. Biloma on CT. Treated bilirubin, liver enzymes. Biloma on CT. Treated with endoscopic stent, percutaneous drainage. with endoscopic stent, percutaneous drainage. Possible surgical revision if duct is ischemic.Possible surgical revision if duct is ischemic.

Hepatic artery thrombosisHepatic artery thrombosis• Persistent elevation or increasing liver Persistent elevation or increasing liver

enzymes, poor graft function. Diagnosed with enzymes, poor graft function. Diagnosed with U/S, CT angiography, MRA. Treated with U/S, CT angiography, MRA. Treated with immediate revascularization.immediate revascularization.

Induction of ImmunosuppressionInduction of Immunosuppression

Triple therapyTriple therapy• Calcineurin inhibitor (tacrolimus, cyclosporine), anti-Calcineurin inhibitor (tacrolimus, cyclosporine), anti-

proliferative agent (mycophenolate), corticosteroid proliferative agent (mycophenolate), corticosteroid taper.taper.

• Initiated immediately following transplantation.Initiated immediately following transplantation.• Levels followed daily in immediate post-operative period Levels followed daily in immediate post-operative period

& with decreasing frequency once stabilized in desired & with decreasing frequency once stabilized in desired range.range.

Agents vary according to etiology of liver disease.Agents vary according to etiology of liver disease.• Thymoglobulin & Hb Ig utilized in hepatitis patients Thymoglobulin & Hb Ig utilized in hepatitis patients

along with entecavir & prograf to limit viral replication & along with entecavir & prograf to limit viral replication & to avoid coritocsteroid usage.to avoid coritocsteroid usage.

Allograft rejectionAllograft rejection

Hyperacute rejectionHyperacute rejection• Secondary to preformed Ab to graft antigen. Secondary to preformed Ab to graft antigen.

Extremely rare. Necessitates retransplantation.Extremely rare. Necessitates retransplantation. Acute Cellular RejectionAcute Cellular Rejection

• 70% of patients 5 to 14 days following 70% of patients 5 to 14 days following transplant.transplant.

• Heralded by fever, jaundice, elevation of liver Heralded by fever, jaundice, elevation of liver enzymes.enzymes.

• Diagnosed by liver biopsy. Demonstrates Diagnosed by liver biopsy. Demonstrates endothelialitis & non-suppurative cholangitis.endothelialitis & non-suppurative cholangitis.

                                                                      

Althaus SJ, Perkins JD, Soltes G, Glickerman D.Althaus SJ, Perkins JD, Soltes G, Glickerman D. Use of a Wallstent in successful Use of a Wallstent in successful treatment of IVC obstruction following liver transplantation. Transplantation. 1996 treatment of IVC obstruction following liver transplantation. Transplantation. 1996 Feb 27;61(4):669-72. Feb 27;61(4):669-72.

Kim BW, Won JH, Lee BM, Kim BW, Won JH, Lee BM, KoKo BH, Wang BH, Wang HJ, Kim MW. HJ, Kim MW. Intraarterial thrombolytic Intraarterial thrombolytic treatment for hepatic artery thrombosis immediately after living donor liver treatment for hepatic artery thrombosis immediately after living donor liver transplantation. Transplant Proc. 2006 Nov;38(9):3128-31. transplantation. Transplant Proc. 2006 Nov;38(9):3128-31.

Cotler, Scott J, MD UptoDate Treatment of acute cellular rejection in liver Cotler, Scott J, MD UptoDate Treatment of acute cellular rejection in liver transplantationtransplantation

Brown, Robert S., MD, MPH, Dove, Lorna M, MD, MPH UptoDate Patient selection for Brown, Robert S., MD, MPH, Dove, Lorna M, MD, MPH UptoDate Patient selection for liver transplantationliver transplantation

Eric Goldberg, MD, Sanjiv Chopra, MD UptoDate Overview of the treatment of Eric Goldberg, MD, Sanjiv Chopra, MD UptoDate Overview of the treatment of fulminant hepatic failurefulminant hepatic failure

Bussutil RW, Klintmalm GB, Transplantation of the Liver, WB Saunders Company, Bussutil RW, Klintmalm GB, Transplantation of the Liver, WB Saunders Company, Philadelphia. 1996Philadelphia. 1996

Peter J. Friend; Charles J. Imber Transplantation Immunology. Current Status of Liver Peter J. Friend; Charles J. Imber Transplantation Immunology. Current Status of Liver Transplantation pp. 29 – 46, MAR 2006Transplantation pp. 29 – 46, MAR 2006

http://med.stanford.edu/shs/txp/livertxphttp://med.stanford.edu/shs/txp/livertxp