What is the importance of understanding liver physiology and liver function tests for a fellow in liver transplant anesthesia?

Liver Physiology and Liver Function Tests in Liver Transplant Anesthesia

Core Liver Physiology Relevant to Transplant Anesthesia

Hepatic Blood Flow and Vascular Anatomy

The liver receives approximately 25% of cardiac output through dual blood supply: 75% via the portal vein (deoxygenated, nutrient-rich) and 25% via the hepatic artery (oxygenated). 1 This unique vascular arrangement is critical because hepatic artery thrombosis occurs in 5-10% of liver transplant recipients, usually within the first month, causing dramatic increases in serum transaminases and potentially requiring retransplantation. 1 Portal and hepatic vein thrombosis can manifest as recurrent ascites or variceal hemorrhage, requiring urgent vascular stenting or anastomotic revision. 1

Metabolic Functions Critical to Anesthetic Management

• Protein synthesis: The liver produces albumin, coagulation factors (II, VII, IX, X), and cholinesterase, all of which directly impact drug binding, coagulation status, and metabolism of anesthetic agents. 2
• Drug metabolism: Hepatic dysfunction alters both Phase I (cytochrome P450) and Phase II (conjugation) reactions, fundamentally changing pharmacokinetics of most anesthetic drugs. 2, 3
• Glucose homeostasis: End-stage liver disease impairs gluconeogenesis and glycogen storage, predisposing patients to hypoglycemia during prolonged procedures. 2

Pathophysiologic Changes in End-Stage Liver Disease

Patients with end-stage liver disease develop hyperdynamic circulation with increased cardiac output, decreased systemic vascular resistance, and relative hypovolemia despite total body fluid overload. 2 This creates a unique hemodynamic profile requiring careful fluid management and vasopressor selection during transplantation. 4

• Portosystemic shunting leads to hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPHN), both life-threatening conditions requiring specific screening. 1
• Coagulopathy results from decreased synthesis of clotting factors, thrombocytopenia from splenic sequestration, and enhanced fibrinolysis. 1

Liver Function Tests: Interpretation and Clinical Significance

Hepatocellular Injury Pattern

Elevated transaminases (AST/ALT) indicate hepatocellular damage, with AST:ALT ratio >2 suggesting alcohol-induced injury. 5 In the immediate post-transplant period, acute dramatic increases in transaminases within the first week suggest hepatic artery thrombosis requiring urgent intervention. 1

• AST (aspartate aminotransferase): Less specific than ALT; found in liver, heart, muscle, and kidneys. 5
• ALT (alanine aminotransferase): More liver-specific; elevations indicate hepatocyte injury. 5
• Timing matters: Serial monitoring is essential post-transplant, as evolving patterns distinguish preservation injury from rejection or vascular complications. 5

Cholestatic Injury Pattern

Elevated alkaline phosphatase and bilirubin indicate biliary obstruction or cholestasis, with GGT confirming hepatic origin of alkaline phosphatase elevation. 5 Biliary complications occur in 10-25% of deceased donor transplants and 28-32% of right-lobe living donor transplants. 1

• Bilirubin elevation post-transplant may indicate bile leaks, anastomotic strictures, or hepatic artery thrombosis leading to biliary ischemia. 1
• Alkaline phosphatase: Confirm hepatic origin with GGT before pursuing biliary imaging. 5

Synthetic Function Assessment

Prothrombin time (PT/INR) and albumin levels reflect hepatic synthetic capacity and are more reliable indicators of liver function than transaminases. 6 These parameters remain stable in successful transplants but deteriorate with graft dysfunction. 6

• PT/INR: Prolongation indicates deficiency of vitamin K-dependent factors (II, VII, IX, X). 6
• Albumin: Half-life of 20 days makes it useful for assessing chronic synthetic function but not acute changes. 1

Preoperative Assessment for Liver Transplant Anesthesia

Cardiovascular Evaluation

Two-dimensional echocardiography with Doppler must be performed in all liver transplant candidates to screen for cirrhotic cardiomyopathy and portopulmonary hypertension. 1 If right ventricular systolic pressure exceeds 50 mmHg on 2-DE, right-heart catheterization is mandatory to confirm PPHN diagnosis. 1

• Cirrhotic cardiomyopathy presents with diastolic dysfunction, prolonged QT interval, and blunted response to stress despite hyperdynamic baseline state. 1
• PPHN is defined as mean pulmonary artery pressure >25 mmHg with normal pulmonary capillary wedge pressure in the setting of portal hypertension. 1

Pulmonary Assessment

Screening transcutaneous oxygen saturation in the upright position must be performed in all patients with possible portosystemic shunting; pulse oximetry <97% on room air warrants further evaluation for hepatopulmonary syndrome. 1 HPS is confirmed with 2-DE during agitated saline infusion showing bubbles in the left atrium within 3-6 cardiac cycles. 1

• 99mTechnetium-MAA perfusion lung scan quantifies intrapulmonary shunting; MAA shunt fraction of 27.8% is highly specific for shunting associated with hypoxia. 1
• Cystic fibrosis patients require pulmonary function tests (FEV1 and FVC) as CF-related lung disease severity impacts transplant outcomes. 1

Renal Function Assessment

Serum creatinine alone cannot estimate GFR in liver disease patients; use the revised Schwartz Formula (0.413 × height[cm] / sCr[mg/dL]) or cystatin C for accurate assessment. 1 Cystatin C level of 1.06 mg/L predicts GFR <80 mL/min/1.73 m² with 91% sensitivity and 81% specificity. 1

• Modified RIFLE criteria (Risk, Injury, Failure, Loss, End-stage) should be used to assess acute renal injury severity using estimated creatinine clearance and urine output. 1
• Hepatorenal syndrome represents functional renal failure in advanced liver disease and may reverse post-transplant. 1

Intraoperative Monitoring During Liver Transplantation

Essential Hemodynamic Monitoring

Continuous arterial blood pressure monitoring via arterial line, central venous pressure monitoring, and pulmonary artery catheter (in selected cases) are standard for liver transplantation. 4 The anhepatic phase and reperfusion create dramatic hemodynamic shifts requiring real-time assessment. 4

• Transesophageal echocardiography provides superior assessment of cardiac function, volume status, and detection of air embolism during the procedure. 4
• Cardiac output monitoring guides fluid resuscitation and vasopressor therapy during the hyperdynamic state of liver failure. 4

Metabolic and Coagulation Monitoring

Serial arterial blood gases, lactate, glucose, electrolytes (especially potassium and ionized calcium), and thromboelastography must be monitored throughout the procedure. 4 Lactate clearance post-reperfusion indicates graft function. 1

• Thromboelastography (TEG) provides real-time assessment of coagulation status and guides targeted blood product therapy more effectively than conventional coagulation tests. 4
• Ionized calcium drops precipitously with citrated blood product administration and requires aggressive replacement. 4
• Glucose monitoring every 30-60 minutes prevents hypoglycemia during anhepatic phase and hyperglycemia from steroid administration. 4

Graft Function Assessment

Post-reperfusion, daily liver profile tests (bilirubin, AST/ALT, INR, platelets, lactate) and weekly volumetric imaging are recommended for graft monitoring. 1 Bilirubin, PT/INR, and lactate trends indicate early graft dysfunction or small-for-size syndrome. 1

Anesthetic Pharmacology in Liver Disease

Induction Agents

Propofol, thiopental, or ketamine can be used for induction, but doses must be reduced by 30-50% due to decreased protein binding and altered volume of distribution in liver disease. 6, 3 Propofol has minimal hepatic metabolism and is preferred despite hemodynamic effects. 3

• Etomidate provides hemodynamic stability but suppresses adrenal function, which is already compromised in liver failure. 3
• Ketamine maintains hemodynamic stability and is useful in hemodynamically unstable patients. 6

Maintenance Agents

Isoflurane, desflurane, or sevoflurane, alone or combined with small doses of fentanyl, represent reasonable maintenance regimens for liver transplant anesthesia. 6, 3 These volatile agents undergo minimal hepatic metabolism and maintain hepatic blood flow better than older agents. 3

• Sevoflurane and desflurane have the lowest hepatic metabolism (<5%) and fastest emergence profiles. 3
• Avoid halothane due to risk of hepatotoxicity and reduced hepatic blood flow. 3

Neuromuscular Blocking Agents

Cisatracurium is the preferred neuromuscular blocker as it undergoes Hofmann elimination independent of hepatic or renal function. 2, 3 Rocuronium and vecuronium have prolonged duration in liver disease due to decreased hepatic clearance. 2

• Succinylcholine has unpredictable effects due to decreased pseudocholinesterase production in liver failure. 2
• Reversal agents: Sugammadex is safe in liver disease; neostigmine requires adequate cholinesterase activity. 3

Opioid Selection

Fentanyl is preferred over morphine or meperidine due to more predictable pharmacokinetics in liver disease, though clearance is still reduced requiring dose adjustment. 2, 3 Remifentanil undergoes plasma esterase metabolism independent of hepatic function. 2

Post-Transplant Complications Affecting Liver Function

Vascular Complications

Hepatic artery thrombosis within the first week manifests as acute dramatic transaminase elevation and requires immediate thrombectomy or thrombolytic therapy for potential graft salvage. 1 After the first week, it typically causes biliary strictures or bilomas requiring retransplantation. 1

• Portal vein thrombosis presents with recurrent ascites or variceal hemorrhage and may require vascular stenting. 1
• Doppler ultrasound should be performed immediately when vascular thrombosis is suspected. 7

Biliary Complications

Biliary complications occur in 10-25% of deceased donor transplants, presenting with elevated liver tests, jaundice, or fever. 1 Anastomotic strictures respond to ERCP or PTC, while nonanastomotic strictures (often from hepatic artery thrombosis) are more difficult to treat. 1

• Bile leaks occur in 5-15% of patients at the anastomosis, T-tube site, or cystic duct stump. 1
• MRCP is the preferred imaging modality for detailed biliary tree evaluation with high sensitivity for biliary complications. 5, 8

Rejection and Infection

Liver biopsy is essential for diagnosing allograft rejection, preservation injury, drug-induced injury, or recurrent viral infection when liver tests are abnormal post-transplant. 1 Histological assessment at 1 year post-transplant predicts fibrosis progression and clinical decompensation risk. 1

Critical Pitfalls to Avoid

Preoperative Pitfalls

• Failing to screen for PPHN and HPS can lead to catastrophic intraoperative events; both conditions require specific screening protocols. 1
• Relying on serum creatinine alone underestimates renal dysfunction in liver disease; use cystatin C or revised Schwartz Formula. 1
• Inadequate dental assessment can lead to post-transplant sepsis; 27% of transplant centers report sepsis from suspected dental sources. 1

Intraoperative Pitfalls

• Inadequate monitoring during reperfusion misses critical hemodynamic changes, hyperkalemia, and metabolic acidosis that occur within minutes. 4
• Over-reliance on conventional coagulation tests rather than TEG leads to inappropriate blood product administration. 4
• Failure to maintain hepatic perfusion pressure during anesthesia compromises graft function; mean arterial pressure should be maintained >65 mmHg. 6

Post-Transplant Pitfalls

• Delaying contact with transplant center when LFTs are >1.5 times normal can have significant consequences for graft survival. 7
• Overlooking drug interactions affecting immunosuppressant levels leads to rejection or toxicity. 7
• Failing to consider small-for-size syndrome in living donor transplants with GRWR <0.8% leads to delayed recognition of graft dysfunction. 1

Specialized Anesthesia Team Requirements

The United Network for Organ Sharing requires liver transplant programs to designate a Director of Liver Transplant Anesthesia with expertise in perioperative care of liver transplant patients. 1 A specialized liver transplant anesthesia team has been associated with more favorable patient outcomes. 1

• Disease-specific assessments must be performed for conditions like Alagille syndrome (cardiac disease, vascular abnormalities), biliary atresia with splenic malformation (complex heart disease), and primary hyperoxaluria (renal and cardiac dysfunction). 1
• Expertise in managing coagulopathy, massive transfusion, and hemodynamic instability during the anhepatic phase and reperfusion is essential. 4