Fig. 32.1
Functional anatomy of the liver
Fig. 32.2
A hepatic lobule
Liver anatomy and function are intricately related. Liver functions include regulation of blood coagulation, synthesis of hormones, erythrocyte breakdown, carbohydrate metabolism, lipid and amino acid metabolism, and immunologic function. Corticosteroids, aldosterone, estrogen, androgens, insulin, and antidiuretic hormone are all inactivated by the liver. The unique structure of the hepatic lobule, and a hepatocyte location within the liver, is critical to its function. Periportal hepatocytes, in what is termed zone 1, are located close to the terminal vascular branches of the portal vein and hepatic artery. These hepatocytes are supplied by blood with a high nutritional content returning from the GI circulation. These zone 1 hepatocytes contain large mitochondria and have high concentrations of Krebs cycle enzymes. They are involved in gluconeogenesis, beta-oxidation of fatty acids, amino acid catabolism, ureagenesis, synthesis of cholesterol, and bile acid secretion. Hepatocytes in the centrilobular or perivenular area (zone 3) are most distant from the terminal vascular branches. Because of their location, these hepatocytes are involved in anaerobic work: glycolysis and lipogenesis. They are involved in general detoxification and biotransformation of drugs. These cells are most sensitive to injury from systemic hypoperfusion, hypoxemia, and accumulation of toxic by-products.
Preoperative Examination of the Patient with Liver Disease
Currently, endstage liver disease affects more than three million individuals in the United States. Liver dysfunction has historically been due to chronic viral (B or C) or alcoholic hepatitis. Alcohol is the most common cause of cirrhosis of liver. However, the incidence of nonalcoholic fatty liver disease is increasing due to the obesity epidemic. Though the overall presence of cirrhosis in this population is low, it does increase the number of patients with liver disease that are encountered in routine anesthetics. Patients presenting to the operating room should be screened for the possibility of liver disease with questions of prior blood transfusion, illicit drug use, alcohol intake, and family history of liver disease (Table 32.1). Physical examination can identify signs of liver disease such as jaundice, spider telangiectasia, ascites, or dilated abdominal veins. Preoperative workup includes blood count, coagulation studies, and a complete metabolic panel (Table 32.2). Two primary indicators of liver dysfunction are a serum albumin <2.5 mg/dl and a prolonged prothrombin time >14 s/INR > 1.5. However, some centers also use prealbumin as a marker for liver disease, since it has a short half-life of just 2 days.
Table 32.1
Key aspects of history and physical examination to consider in liver disease
History of alcohol use and alcoholic hepatitis |
Features of portal hypertension |
Ascites |
Esophageal or gastric varices |
Renal function |
Hepatic encephalopathy |
Presence of acute liver failure |
Calculated Child–Turcotte–Pugh and/or MELD score |
Prior liver biopsy—cirrhosis present? |
Liver transplantation evaluation |
Table 32.2
Liver function tests
Serum bilirubin | Normal < 1.5 mg/dl Jaundice with > 3.5 mg/dl Postoperative jaundice most commonly due to production of bilirubin as a result of resorption of large hematoma/red cell breakdown following transfusion |
Serum ALT and AST | ALT is more liver specific, while AST is also found in the heart, kidneys, and skeletal muscle |
Serum alkaline phosphatase (AP) | AP is also found in the bones, small bowel, and kidneys. Mild elevation, hepatocellular injury; high elevation, biliary obstruction |
Serum albumin | Normal 3.5–5.5 mg/dl, half-life 2–3 weeks |
Blood ammonia | Elevations with hepatocellular damage |
Prothrombin time | Normal 11–14 s |
Acute hepatitis is viewed as a strict contraindication to elective surgery because of the associated high complication and mortality rate. Delay of urgent surgery should also be considered until an episode of acute liver injury resolves, such as in acute alcoholic hepatitis. Patients with mild chronic hepatitis with no evidence of portal hypertension and well-preserved hepatic function generally may proceed with elective surgery. However, patients with significant portal hypertension may be at higher risk of postoperative complications.
Classification of Liver Dysfunction
There are two main classification systems for liver disease that aim to stratify patients with liver dysfunction. The Child–Turcotte–Pugh system (CTP), initially developed in 1964, assesses patients using serum albumin level, serum bilirubin level, ascites, encephalopathy, and prothrombin time (Table 32.3). This value is then assigned as a Class A (good, 4 % 3-month mortality), B (intermediate, 14 % 3-month mortality), or C (poor, 51 % 3-month mortality). The CTP is easy to calculate and is historically verified. It was a key consideration in the transplant algorithm, until it became supplanted by the Model for End-Stage Liver Disease (MELD) score in 2002. The MELD score is calculated from the objective values for the serum bilirubin level, serum creatinine level, and INR. The values are weighted by relative mortality influence, with greatest weight given to renal function.
Table 32.3
Child–Turcotte–Pugh score
Characteristic | 1 point | 2 points | 3 points |
|---|---|---|---|
Ascites | None | Controlled | Refractory |
Encephalopathy | None | Controlled | Dense |
Albumin (g/L) | >3.5 | 2.8–3.5 | <2.8 |
Bilirubin (mg/dL) | <2 | 2–3 | >3 |
INR | <1.7 | 1.7–2.3 | >2.3 |
Class A, 5–6 points; Class B, 7–9 points; Class C, 10–15 points | |||
Anesthetic Considerations in End-Stage Liver Disease
It is important to understand the physiology behind liver disease and minimize the risks when surgery is necessary in the presence of liver disease.
Cardiovascular: Patients with end-stage liver disease typically have a hyperdynamic circulation characterized by an elevated heart rate, increased stroke volume, and low peripheral vascular resistance. This combination of factors leads to a high cardiac output. Though the total blood volume is increased, the central “effective” volume is decreased. Some causes of cirrhosis are also associated with disease-induced cardiomyopathy, such as alcoholic liver disease. These patients may have atypical cardiovascular presentations in the face of their chronic liver disease. They present with congestive heart failure and decreased peripheral blood flow.
Pulmonary Dysfunction: This complication of end-stage liver disease is due to intrapulmonary vascular dilations. There is a decrease in oxygenation with a PaO2 < 70 mmHg (hypoxemia) or PAO2–PaO2 gradient >22 mmHg on room air that is associated with intrapulmonary vascular dilation. Patients may hyperventilate producing a respiratory alkalosis. The triad of increased alveolar–arterial oxygen gradient, and evidence of intrapulmonary vascular dilations is defined as the hepatopulmonary syndrome (HPS). Supplemental oxygen is unable to increase PaO2 significantly when large arteriovenous communications are the primary cause of hypoxemia. Survival of patients with HPS compared with cirrhotic patients of the same CTP class without HPS is dramatically lower. In addition, the presence of significant ascites causes elevation of the diaphragm leading to decreased lung volumes (FRC) and a restrictive ventilatory defect.
Electrolyte Abnormalities: Hyponatremia is common, due to a relative water overload rather than total body sodium depletion. Water restriction may help regain normal serum sodium levels. Diuretics that increase free water clearance are used in severe cases. Saline solution is infused in cases of severe hyponatremia complicated by seizures. Infusion of saline solution temporarily increases serum Na+ levels but can worsen ascites and increase fluid retention. Hypokalemia is seen frequently due to urinary potassium excretion, secondary to an increase in circulating aldosterone. Diuretic therapy may also contribute to hypokalemia. Management consists of oral KCl supplementation and withholding K-wasting diuretics. It is important that renal function be preserved perioperatively and excessive diuresis avoided.
Endocrine: Glucose intolerance and insulin resistance are often seen. This is usually due to the liver’s impaired ability to degrade insulin. Abnormal thyroid function tests may be discovered. This usually reflects altered hepatic metabolism of the thyroid hormones and a decreased production of plasma binding proteins.
Coagulation Defects: In chronic and acute liver diseases, many changes in the coagulation pathway occur. This can be due to a number of factors including abnormal platelet numbers and function, decreased synthesis of coagulation factors, and vitamin K deficiency. There is a decrease in the levels of factors II, V, VII, IX, and X, protein C, protein S, and antithrombin III. Thrombocytopenia commonly occurs due to increased platelet sequestration. Decreased thrombopoietin synthesis by the disease liver also contributes. Decreased platelet adhesiveness and impaired aggregation are also well described, with unknown etiology. It is unclear if these changes actually increase the bleeding risk, as the decrease in the procoagulant system is mirrored by a simultaneous decrease of the fibrinolytic system. Thus, despite significant coagulation abnormalities as assessed by standard laboratory tests, clinical bleeding may not be evident. Surgical procedures are performed on cirrhotic patients often without the need for any blood products, despite the presence of end-stage liver disease with significant thrombocytopenia and platelet abnormalities.
Portal Hypertension this complication results from an increased hepatic vascular resistance to portal blood flow, typically occurring in the hepatic sinusoids. Hepatic vascular changes are due to cirrhotic changes in the liver and a reaction to the hyperdynamic state caused by systemic vasodilation and volume expansion. Over time, this resistance gradient leads to the formation of portosystemic collaterals (sites—gastroesophageal, periumbilical, retroperitoneal, hemorrhoidal). These develop by dilation and hypertrophy of vascular channels. This is the root cause of the development of esophageal varices.
Ascites: Ascites is the accumulation of fluid in the peritoneal cavity. It is a common consequence of many forms of cirrhosis, due to a combination of portal hypertension, hypoalbuminemia, and sodium/water retention. Three theories underlie its pathogenesis:
The underfill hypothesis states that cirrhosis-related hepatic venous drainage is blocked due to portal hypertension leading to the ascitic fluid formation. This fluid formation decreases the effective intravascular volume, leading to further sodium and water retention by the kidney, perpetuating the cycle.
The overflow hypothesis states that portal hypertension leads to sodium and water retention despite an overfilled vasculature, increasing the total plasma volume. This increased intravascular volume leads to portal hypertension via increased portal hydrostatic pressure. The lower plasma oncotic pressure leads to translocation of fluid from the splanchnic circulation.
The theory of peripheral vasodilation states that splanchnic arterial vasodilation occurs secondary to the production of vasodilatory mediators in the setting of liver failure. In order to maintain systemic perfusion in the face of an enlarged intravascular compartment, the kidney retains sodium and water, thus increasing the total ascitic fluid volume.
In spite of differences in proposed etiology, ascites is treated with sodium- and fluid-restrictive diets. Aldosterone antagonists (potassium-sparing spironolactone) allow for diuresis and volume reduction. Large-volume (4–6 L) paracentesis is effective in removal of large amounts of ascitic fluid in the setting of refractory ascites. This allows for an immediate improvement in cardiac output, as pressure on the inferior vena cava and right atria is released. Subsequent circulatory dysfunction, however, may occur up to 24 h later with relative hypovolemia occurring due to progressive reaccumulation of ascites with a resultant decrease in filling pressures. Administration of a plasma expander, such as albumin, may prevent the relative hypovolemia. Re-equilibration of the intravascular volume occurs 6–8 h after the removal of a large volume of ascitic fluid.
The clinical implications of the ascites vary. Ascites may impede the patient’s respiratory function and increase the patient’s risk for aspiration. Patients with acute deterioration of pulmonary function or tense ascites may benefit from preoperative drainage in an elective or semi-urgent situation. In an emergency, laparotomy itself will lead to release of ascites fluid.
Hepatorenal Syndrome: This is a prerenal failure that is characterized by intense vasoconstriction of the renal circulation and low glomerular filtration (oliguria), with preserved renal tubular function and normal renal histology. HRS can be brought about by gastrointestinal bleeding, dieresis, sepsis, or major surgery. There are two types of hepatorenal syndrome. Type I develops rapidly over a few weeks and is progressive with a high mortality rate, and often needing a liver transplantation. Type II follows a less acute course and is mainly seen in patients that are resistant to diuretic therapy.
Hepatic Encephalopathy: Severe hepatocellular damage can lead to accumulation of toxins such as ammonia, mercaptans, and phenols, which are normally metabolized by the liver. This can lead to hepatic encephalopathy characterized by mental status changes, asterixis, hyperreflexia, and an inverted plantar reflex. Hepatic encephalopathy can be precipitated by GI bleeding, sepsis, vomiting, and excessive diuresis. Treatment should be aggressive and consists of supportive care, lactulose (osmotic laxative), and neomycin (inhibits ammonia production by intestinal bacteria).
Anesthetic Management of End-Stage Liver Disease
Patients with advanced liver disease have alterations in pharmacokinetics and pharmacodynamics of all medications. For example, cerebral uptake of benzodiazepines is increased, due to a leaky blood brain barrier. By contrast, pharmacologic responses to catecholamines and other vasoconstrictors are decreased. Induction drugs and muscle relaxants have increased dose requirements due to increased volume of distribution.
Intraoperative Monitoring: Depending on the surgery performed, it may warrant consideration of an arterial line and central line in addition to standard ASA monitors. An arterial line provides immediate measurement of the patient’s hemodynamic status in the setting of large volume shifts. It also provides access for intra- and postoperative lab draws. A central line provides an indication of cardiac filling pressures. The ability to monitor intravascular fluid volume is especially important in situations of underlying cardiovascular instability, hepatorenal syndrome, dehydration, and anticipated intercompartmental fluid shifts.
Induction of Anesthesia: Rapid sequence induction is typically recommended for patients with increased intra-abdominal pressure due to the presence of ascites. Although severe liver dysfunction can decrease cholinesterase activity and may prolong the effect of succinylcholine, this is rarely clinically significant. In hepatorenal syndrome, however, plasma potassium levels may preclude the use of succinylcholine. Cisatracurium and rocuronium may be beneficial to use for muscle relaxation, in order to avoid prolongation of muscle paralysis due to dysfunction of hepatic metabolism.
Maintenance of Anesthesia: One must be aware that liver injury can be worsened with hypoxia, the stress response, drug toxicity, and infection. Therefore, adequate hepatic oxygenation must be ensured throughout the procedure. In addition, anemia should be avoided. Arterial hypotension should be prevented by adequate blood and volume replacement and by avoiding relative overdoses of anesthetics or other blood pressure-lowering agents.
Postoperative Care: The management of the patient with liver disease is very challenging, affecting all major organ systems. Operations on CPT Class B or C patients should only be performed if the benefit–risk ratio is deemed absolutely necessary. The patient’s cardiovascular status must be assessed preoperatively and considered separately in risk stratification for anesthesia. Finally, intensive care unit observation is recommended for the first postoperative night, due to the many hemodynamic shifts that may be expected to occur in the first 6–12 h after surgery.
Liver Transplantation
Candidates for a liver transplant undergo a rigorous preoperative evaluation with multiple specialists including: a transplant surgeon, hepatologist, transplant anesthesiologist, psychiatrist, dietitian, and social worker. The appropriateness of liver transplant for each candidate is determined, and then a formal transplant listing is submitted to the national transplantation organization. Organ allocation priority is based on the MELD score with additional points awarded for specific indications. This is an effort to maintain an equitable system of allocation. Nationwide, the 3-year patient survival rate after transplantation is about 73 %. Contraindications to liver transplantation include but are not limited to: significant coronary artery disease, cardiac dysfunction, moderate to severe pulmonary hypertension, uncontrolled infection or sepsis, active alcohol abuse, advanced malignant hepatic disease or metastatic disease, and markedly elevated intracerebral pressure in the presence of acute hepatic failure.
Preoperative Preparation: Immediately prior to transplant, preoperative labs should include a hematocrit, electrolytes, bilirubin, albumin, prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, and a blood type and cross. The blood bank should be notified immediately with a massive transfusion protocol available: 10–20 units of red blood cells, 5–10 units of fresh frozen plasma, 4–10 units of single donor platelets, and 10 units of cryoprecipitate. Rapid sequence induction is often performed due to the emergency nature of the procedure, plus the significant ascites that is usually present. Monitors required for the procedure are: 2–3 large-bore IV catheters, a radial arterial line, a rapid transfusion catheter, and a central venous pressure monitor. In a patient with known pulmonary hypertension, either a preinduction or pre-incision pulmonary artery catheter should be placed, or transesophageal echocardiography can be used. Every patient must have a Foley bladder catheter to aid in volume status monitoring. Normothermia is maintained with fluid warmers and forced-air heating blankets.
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