LIVER DiSEASE AND ANESTHESiA
The liver is the largest internal organ in the body and it plays a critical role in the homeostasis of many physiologic systems, including nutrient and drug metabolism, synthesis of plasma proteins and critical hemostatic factors, and detoxification and elimination of many endogenous and exogenous substances. Patients with advanced liver disease are at high risk for excessive morbidity and mortality following surgery because of failure of one or more of these essential functions. For example, the normal liver moderates the hypotensive response to acute blood loss and hypovolemia through its reservoir function, and helps minimize blood loss through synthesis of coagulation factors and degradation of fibrinolytic substances. Failure of these functions contributes to intraoperative and postoperative hypoperfusion, tissue ischemia, and activation of the systemic inflammatory response, setting the stage for the postoperative development of multisystem organ failure. Acute or chronic liver dysfunction can impair the response to anesthesia and surgery in several critical ways, whereas certain anesthetics and hemodynamic disturbances can induce unique and serious alterations in postoperative hepatic function.
The spectrum of liver dysfunction ranges from mild diffuse inflammation seen in early hepatitis or infiltration of the liver with fat seen in hepatic steatosis to the development of the histologic changes associated with cirrhosis. The varied metabolic derangements that develop over time in a patient as hepatocyte function declines manifest pathologic changes in every organ system and pose a formidable problem to the surgeon and anesthesiologist during surgery. Identification of the surgical risk is imperative in the care of any patient. Patients with liver disease are at particularly high risk for morbidity and mortality in the postoperative period due to both the stress of surgery and the effects of general anesthesia.
Surgical Risk Assessment
Secondary to the loss of hepatic reserve capacity and because of other systemic derangements that are the result of liver dysfunction (such as hemodynamic impairments), patients with liver disease have an inappropriate response to surgical stress. These individuals are accordingly at an increased risk of bleeding, infection, postoperative hepatic decompensation, including hepatic coma or death. Therefore, the decision to perform surgery in these patients must be heavily weighed.
Prediction of surgical risk is based on the degree of liver dysfunction, the type of surgery, and the preclinical status of the patient. The extent of liver dysfunction and type of surgery play key roles in determining a patient’s specific
risk. In addition, liver disease can affect almost every organ and system in the body, including the cardiorespiratory and circulatory systems, the brain, the kidneys, and the immune system.
The extent to which secondary manifestations of liver disease affect these systems may be just as important as the manifestations of primary liver dysfunction in predicting the outcome after surgery. Such comorbid conditions responsible for perioperative morbidity and mortality (e.g. coagulopathy, intravascular volume, renal function, electrolytes, cardiovascular status, and nutritional status) should be identified and addressed before surgery. Optimal preparation may decrease death and complications after surgery. Issues to anticipate and address include manifestations of acute liver decompensation including encephalopathy, acute renal failure, coagulopathy, adult respiratory distress syndrome, and sepsis.
Classification of Liver Dysfunction
Two main classification systems have been developed to stratify patients with liver dysfunction —
Child-Turcotte- Pugh (CTP) score and
Model for End-Stage Liver Disease (MELD) score.
Child-Turcotte-Pugh (CTP) system
The Child-Turcotte-Pugh (CTP) system, initially developed in 1964 as the Child-Turcott system, characterized the degree of liver disease in patients undergoing portosystemic shunting procedures.3 Patients were assessed using serum albumin level, serum bilirubin level, ascites, encephalopathy, and nutritional status, and then assigned to a class: A (good, 4% 3 month mortality), B (intermediate, 14% 3 month mortality), or C (poor, 51% 3 month mortality). The category of nutritional status was replaced with prothrombin time by Pugh in 1970 to decrease the subjectivity of the score (Table 9.1). The system evolved into a widely accepted stratification method for all patients with liver dysfunction and became a common term in medical language when discussing a patient with liver disease.
Surgeons have long used the CTP score to predict operative mortality for hepatic and nonhepatic surgery in patients with liver disease. The benefits of the CTP score lie in its ease of calculation, which can be performed at the bedside, and its familiarity across fields of medicine. The system has withstood the test of time, with multiple studies showing independent prognostic value across varied clinical settings, medical and surgical. The main weakness of the CTP score stems from the subjective measurements of ascites and encephalopathy that can skew the scoring system significantly between individuals. Further, concomitant renal dysfunction is not accounted for in the CTP system but has important prognostic significance in cirrhosis.
Model for End-Stage Liver Disease (MELD) score
The MELD score is calculated from the objective values of serum bilirubin level, serum creatinine level, and international normalized ratio (INR), which were determined by statistical analysis to be highly predictive of mortality in cirrhosis. The values are weighted by logarithmic calculations to reflect their relative influence on mortality, giving the most weight to renal function as this has been shown to be a key component of predicting survival in cirrhosis.
Note: The United Network for Organ Sharing (UNOS) has made the following modifications to the score:
If the patient has been dialyzed twice within the last 7 days, then the value for serum creatinine used should be 4.0
Any value less than one is given a value of 1 (i.e. if bilirubin is 0.8, a value of 1.0 is used) to prevent the occurrence of scores below 0 (The natural logarithm of 1 is 0, and any value below 1 would yield a negative result).
MELD was originally developed at the Mayo Clinic, and at that point was called the “Mayo End-stage Liver Disease” score. The original version also included a variable based on the underlying etiology (cause) of the liver disease, but this criterion was subsequently dropped from the equation because it was proved prognostically insignificant.
With regard to its original utilization, a MELD score <8 predicts good outcome after TIPS and a score >18 predicts poor outcome. Avoidance of TIPS is generally recommended in patients with a MELD score >24, unless the procedure is used as a measure of last resort to control active variceal bleeding. Since its implementation, the MELD score’s use has also been expanded to predict the risk of mortality and morbidity after other procedures. A MELD score of at least 8 predicts an increased risk of postoperative complications, including death in patients undergoing cholecystectomy and cardiac surgery requiring cardiopulmonary bypass.
Mortality interpretation using MELD
In interpreting the MELD Score in hospitalized patients, the 3 month mortality is:
40 or more — 71.3% mortality
30–39 — 52.6% mortality
20–29 — 19.6% mortality
10–19 — 6.0% mortality
<9 — 1.9% mortality.
Other Risk-Stratification Systems
The ASA physical status class risk stratification system is based on comorbid conditions that are a threat to life or that limit activity and thus helps in predicting preoperative risks. In general, an ASA class greater than 2 increases the risk 1.5 to 3.2 fold. The ASA class independently predicted postoperative mortality in patients undergoing hepatic resection for hepatocellular carcinoma. Teh et al also found the ASA class significantly predicts increased mortality and morbidity among patients with cirrhosis undergoing major surgery, with ASA class V the strongest predictor of postoperative mortality at 7 days.
It is also important not to overlook the preoperative cardiopulmonary evaluation. This is required of any patient, regardless of the functional status of their liver. Cardiac risk stratification should potentially include an assessment of functional capacity (metabolic equivalent [MET] or exercise duration) and stress testing (exercise electrocardiography [ECG], dipyridamole thallium test, or dobutamine stress echocardiography),ifitisperformed. Surgery-specificrisk also has a pivotal role in cardiac risk assessment.
The evaluation of any patient undergoing surgery should include thorough history taking and physical
examination. In asymptomatic patients, this is an extremely valuable screening tool. Risk factors (e.g. pervious blood transfusions, tattoos, illicit drug use, sexual history, alcohol use, personal history of adverse reaction to anesthesia, and personal or family history of jaundice) for liver disease should be explored.
A complete medication review including over-the- counter and herbal agents should be performed. Symptoms or physical signs suggestive of liver dysfunction/disease (e.g. hepatosplenomegaly, spider angioma, jaundice, gynecomastia, palmar erythema, scleral icterus, asterixis, encephalopathy) should prompt further examination with liver function tests, coagulation studies, complete blood cell (CBC) counts and metabolic panels. However, routine preoperative testing of liver function is not recommended because of the low prevalence of liver abnormalities in clinically asymptomatic patients.
Asymptomatic patients with significantly abnormal liver function should have their elective surgery postponed and their liver disease investigated; their perioperative risk should be reassessed after their liver dysfunction is characterized.
Acuity of Liver Disease
Although most studies have focused on patients with end- stage liver disease or cirrhosis, patients with acute hepatitis have been associated with an increased risk of surgical morbidity and mortality. This also applies to patients with acute alcoholic hepatitis. Patients with these conditions tend to have morbidity rates higher than those with chronic cholestatic disease. Therefore, it is prudent to postpone surgery, especially elective surgery, until liver enzymes level normalizes. Patients with chronic liver disease but with preserved hepatic function may not have an increased operative risk, but these individuals need to be closely evaluated nonetheless.
Severity and Specific Derangements of Known Chronic Liver Disease
In patients with known liver disease, especially with cirrhosis, optimal preparation for surgery, that appropriately addresses the primary features and secondary manifestations of liver disease may decrease the risk of complications or death after surgery. This includes laboratory tests to assess blood counts, coagulopathy, electrolyte abnormalities, and markers of hepatic synthetic function.
Ascites is the most common complication of cirrhosis and is associated with increased infections, increased incidence of renal failure, increased complication rate, poor quality of life, and worse long-term outcome. Ascites develops as hepatic resistance to portal blood flow increases, causing the gradual development of portal hypertension, collateral vein formation, and shunting of blood to the systemic circulation. Increased local production of vasodilators like nitric oxide leads to splanchnic arterial vasodilation, which, combined with portal hypertension, results in abdominal lymph production exceeding lymph resorption and accumulation of intraabdominal fluid. In the later stages of cirrhosis, the splanchnic vasodilation becomes so profound that it overcomes the compensatory cardiovascular and renal responses, decreasing effective circulating volume and ultimately leading to the hepatorenal syndrome. Sodium restriction is the cornerstone of preoperative therapy of ascites. Diuretic therapy has its aim blocking the sodium retention seen with cirrhosis and increasing urinary water and sodium excretion. Spironolactone is a weak diuretic which inhibits sodium reabsorption in the distal renal tubules and collecting ducts by inhibiting the action of aldosterone. Frusemide may not be well-tolerated in patients with liver dysfunction for two reasons. The first is that the natriuretic effect of frusemide seems to be proportional to its urinary concentration and a reduced renal clearance could lessen effectiveness. The other reason is that frusemide, unlike spironolactone, fosters hypokalemia, which can worsen hepatic encephalopathy. Paracentesis can also be employed to reduce ascites. It is recommended that sufficient ascitic fluid be removed to make the patient comfortable. Peritoneovenous shunts (i.e. LeVeen, Denver shunts) move ascetic fluid into the vascular tree, expanding vascular volume, producing natriuresis.
The presence of symptomatic ascitis presents a significant problem for intraabdominal surgery. The sudden release of many liters of ascites at laparotomy can result in paracentesis-induced circulatory dysfunction (PICD), which involves activation of the renin-angiotensin- aldosterone system (RAAS) by an acute increase in splanchnic vasodilation, although the exact mechanism is not known. The incidence of PICD is reduced by pre- emptive administration of volume expanders, namely intravenous albumin at 8 g/L of ascites removed. Most patients with symptomatic, large-volume ascites will benefit from preoperative paracentesis, diuretic therapy, and stringent limitation of salt intake to 1.5 to 2 g/d to minimize reaccumulation of the ascetic fluid. This regimen prevents PICD from appearing in the intra and postoperative period, compounding the already complex care of a cirrhotic patient. In the case of emergent surgery when preoperative paracentesis is not possible, intravenous volume expansion before and during laparotomy should help to alleviate the effect of the rapid ascites removal. An alternative to large-volume paracentesis in patients with severe, refractory ascites is the TIPS procedure, which is effective in decreasing portal hypertension and splanchnic vasodilation, thereby reducing ascites formation.
Hyponatremia can complicate the treatment of ascites significantly, as the patient may have low total body sodium secondary to hypersecretion of antidiuretic hormone (ADH), which is in response to activation of the RAAS by a low effective circulating volume. The initial treatment of hyponatremia is fluid restriction but this can be difficult to accomplish because the inciting cause in this case is an effective low-volume state, prompting RAAS activation and leading ultimately to development of the hepatorenal syndrome. Thus, in this setting volume restriction may hasten the development of renal impairment.
A new class of drugs, known as vaptans or aquaretics, selectively inhibits V2 receptors in the renal collecting tubules, increasing free water clearance and showing some promise in treating hyponatremia of cirrhosis in preliminary clinical studies.
Coagulopathy and Thrombocytopenia
A cardinal feature of cirrhosis is the development of coagulopathy secondary to the declining synthetic function of the liver, leading to prolongation of the prothrombin time (PT) and easy bruising or excessive bleeding. Although coagulopathy is usually due to poor hepatic function, concomitant poor nutrition or malabsorption can lead to vitamin K deficiency, which can exacerbate the problem. Additionally, portal hypertension leads to hypersplenism with resultant platelet trapping and peripheral thrombocytopenia. Table 9.2 enumerates the major coagulation factor deficits and platelet deficiencies seen in liver dysfunction. Vitamin K supplementation and administration of fresh frozen plasma (FFP) are recommended to correct coagulopathy before surgery. Vitamin K must be given parenterally for at least 72 hour before an observable effect. The infusion of 500 ml FFP acutely raises the levels of most essential clotting factors by 20%. Because factor VII has such a short half-life (4-8 hour), the response to FFP measured by the prothrombin time (PT) may not be long-lasting, thus repeated doses of FFP may be required if there is persistent hepatic dysfunction. Hence continuous infusion of FFP at 6–12 hour intervals, according to repeated PT values may be considered. Cryoprecipitate might also be required to reduce the prothrombin time. Finally, recombinant factor VII is highly effective at rapidly providing temporary correction of cirrhotic coagulopathy, but due to exorbitant cost and limited availability it should be reserved for emergency surgery in patients with severe coagulopathy or concomitant intracranial bleeding.
Platelet counts are often low in patients with cirrhosis secondary to sequestration due to portal hypertension and splenomegaly. Significant thrombocytopenia (<20,000) should prompt platelet transfusion preoperatively, but not with more moderate levels of thrombocytopenia as the platelets function normally. The presence of coexisting renal failure and uremia may alter this decision as intrinsic platelet function may be compromised. Administration of 1 Deamino-8-D-arginine vasopressin, which causes a transient increase in expression of the von Willebrand factor, can improve clotting temporarily.
Table 9.2: Major coagulation factor deficits and platelet deficiencies seen in liver disease
Decreased synthesis of plasma coagulation factors
Single factor reduction
Reduced vitamin K—dependent factors (factors II, VII, IX, X)
Reduced nonvitamin K—dependent factors (factors V, XIII, fibrinogen)
Shortened half-lives of plasma coagulation factors
Increased utilization (due to disseminated intravascularvcoagulation; hyperfibrinolysis)
Loss from bleeding (variceal)
Platelet abnormalities—quantitative and qualitative
Hypersplenism in portal hypertension (platelet trapping)
Coexisting renal failure and uremia (platelet dysfunction)
Hepatic encephalopathy is the decrease in consciousness seen in severe liver disease. In its most severe form, it produces hepatic coma. Generally, this is a lethal syndrome, with over 90% mortality. Many patients with cirrhosis may have portosystemic encephalopathy at baseline, which increases their risk of postoperative encephalopathy. As the liver’s metabolic capacity diminishes with advancing disease, its ability to clear the portal blood of nitrogenous compounds generated by intestinal bacteria fails. Several such compounds have been implicated in hepatic encephalopathy, but ammonia has the most supporting evidence for a causative role. It should be emphasized that hepatic encephalopathy is a diagnosis of exclusion and all other possible causes for a patient’s confusion should be examined. Multiple factors in the preoperative and postoperative periods may precipitate encephalopathy, such as infection and/or sepsis, diuretics, hypokalemia, metabolic alkalosis, constipation, use of central nervous system (CNS) depressants such narcotics and benzodiazepines, hypoxia, azotemia, and gastrointestinal bleeding. Addressing the underlying precipitant through correction of electrolyte abnormalities, treatment of infection, management of gastrointestinal bleeding, and restriction of sedatives may help prevent or decrease encephalopathy. With the onset of acute encephalopathy, protein intake may be held for 24 hours, but should be reinstated thereafter with a goal of 1 to 1.5 g/kg/d. Patients with zinc deficiency should receive supplementation. Hepatic encephalopathy is also often treated by administering lactulose or poorly absorbed antibiotics such as rifaximin.
There are two issues concerning hepatic encephalopathy and hepatic coma which are of interest to the anesthe-siologist. First is the fact that hyperventilation with attendant respiratory alkalosis strongly fosters conversion of ammonium ion (NH4+)
to ammonia (NH3). Ammonia is the form that crosses the blood-brain barrier, and may produce adverse CNS events. The second is that hepatic encephalopathy may involve the GABA receptor system of the brain. Hence, many CNS depressants such as benzodiazepines, narcotics and barbiturates can precipitate hepatic encephalopathy, hepatic coma and death. The mechanism apparently is increased CNS susceptibility to these drugs, amplified by other altered drug handling phenomena seen in liver disease (decrease biotransformation, decreased albumin binding, renal dysfunction, etc).
Close communication with the patient’s hepatologist preoperatively is crucial to optimize the patient’s medical care before surgery if they show signs of encephalopathy. Postoperatively, special care should be directed to limiting medications that may affect mental status as patients with preoperative encephalopathy are likely to manifest severe delirium postoperatively due to the stresses of surgery.
Patients with chronic liver disease are at risk for renal dysfunction at baseline due to the propensity for hemodynamic derangements that increase the risk of renal hypoperfusion. This risk is increased by diuretics, nephrotoxic agents including nonsteroidal anti-inflammatory drugs (NSAIDs), large-volume paracentesis performed without albumin supplementation, infections, and gastrointestinal bleeding.
Hepatorenal syndrome is a unique pathology seen only in advanced liver disease. Basically it results in progressive oliguria and is functional. No anatomical pathology can be found in the microanatomy of the kidney. In fact, the ability to concentrate urine may be retained. The hallmark of this syndrome is an avid sodium retention. The cirrhotic patient can also develop acute oliguric renal failure due to hemorrhage, infections, hypotension, etc. A third type of renal failure not confined to liver disease is prerenal azotemia.
The risk of renal dysfunction in the postoperative period is increased because of hemodynamic changes and fluid shifts or losses, particularly if ascites fluid is removed at laparotomy. Renal function should be closely monitored pre and postoperatively, with appropriate measures taken to address or eliminate potential insults.
The predominant feature of a cirrhotic patient’s cardiovascular system is a generalized hyperdynamic state, consisting of increased heart rate, cardiac output, and plasma volume, with reduced systemic vascular resistance and blood pressure. Baroreceptor reflexes tend to be blunted. There appears to be both decreased numbers and downregulation of adrenergic receptors in patients with cirrhosis. Early in cirrhosis these changes are subtle but they increase with disease progression, aided by the development of arteriovenous communications and autonomic dysfunction. From a practical standpoint, the hemodynamic changes described earlier cause patients with cirrhosis to have increased total blood volume but decreased central and effective arterial volume, and are therefore functionally hypovolemic. Their peripheral circulation is increased, however, which can be deceptive on physical examination. Their hemodynamic compensatory systems are maximized, and their renal perfusion is already decreased at baseline, so acute volume depletion or hemorrhage is not well tolerated. It is advisable to obtain central venous access before commencing any intra-abdominal surgery to reliably monitor the volume status of the central vasculature.
Cirrhotic cardiomyopathy has recently been recognized and classified as a separate entity.8 Systolic dysfunction, consisting of a blunted contractility response, and diastolic dysfunction are present, as well as electromechanical abnormalities. Although the penetrance of cardiac dysfunction in cirrhosis is variable, routine preoperative cardiac testing is advisable to identify patients with limited cardiac reserve. Electrocardiography can identify a characteristic increase in the Q-T interval, reflecting a prolonged repolarization time, which has been shown to significantly correlate with severity of liver disease, elevated brain natriuretic peptide (BNP) level, and decreased survival. A preoperative stress echocardiogram can identify systolic dysfunction, as the expected increases in stroke volume and ejection fraction will be diminished or absent, reflecting an inadequate contractility response to increased ventricular filling pressure. Diastolic dysfunction can be detected on Doppler echocardiogram as an abnormally low ratio of early to late (atrial) left ventricular filling, representing impaired left ventricular relaxation.
Pulmonary complications of end-stage liver disease include hepatopulmonary syndrome, portopulmonary hypertension, and hepatic hydrothorax.
The hepatopulmonary syndrome (HPS) is defined as an arterial oxygenation defect induced by intrapulmonary vascular dilatations associated with hepatic disease. Increased pulmonary nitric oxide production is implicated in the pathogenesis of this condition, similar to that of splanchnic vasodilatation. This produces an increase in the shunt fraction, resulting in a ventilation-perfusion mismatch. It is presumed that the middle core of the capillary blood column does not receive sufficient oxygen. (This particular hypoxemia can be partially corrected with high inspired oxygen concentration and hence is not a true shunt). Dyspnoea and hypoxemia are worse in the upright position (called platypnea and orthodeoxia, respectively). [Note: Platypnea may also be caused by an anatomical cardiovascular defect increasing positional right-to-left shunting. In these rare syndromes, the venous blood from liver does not pass through the lungs, or venous blood from the portal circulation reaches the inferior vena cava without passing through the liver.] Physical examination findings indicating chronic hypoxia, such as digital clubbing, spider nevi, and cyanotic lips and nail beds, are seen in advanced HPS although they are not specific to this condition.
There are no effective perioperative therapies to improve the pulmonary vascular abnormalities, hypoxemia, and ventilation-perfusion mismatches associated with HPS. Liver transplantation is the only treatment shown to be effective in improving this condition. Patients with significant hypoxemia require long-term supplemental oxygen therapy. The prognosis with HPS is poor.
Pleural effusion (hepatic hydrothorax), usually unilateral and in the right hemithorax, can occur and impair ventilation. However, the associated hypoxemia is usually not severe. Drainage is usually not recommended because the effusion often rapidly reaccumulates. Finally, the risk of chronic obstructive pulmonary disease (COPD) should be assessed in any patient who has previously smoked tobacco or who has alpha-1 antitrypsin deficiency. Pulmonary infections (e.g. pneumonia) are also common in chronic liver disease.
Nutritional status is frequently poor in patients with cirrhosis. Serum albumin, prealbumin, and triglyceride levels are helpful to objectively quantify the patient’s nutritional status, in addition to observing physical signs of cachexia and wasting. If the patient is undergoing elective surgery, every effort should be made to improve their nutritional status before surgery. Patients with encephalopathy may be limited by enteral protein restriction, particularly if they have had a portosystemic shunt procedure, as hyperammonemia has been demonstrated following enteral glutamine administration in this population. This specific group of patients may benefit from parenteral nutrition preoperatively if their malnutrition is severe. Patients with alcoholic liver disease and Wernicke encephalopathy benefit from preoperative vitamin B1 supplementation. Advanced liver disease can also predispose to hypoglycemia.
Severe malnutrition is associated with an increased need for packed red blood cells, FFP, and cryoprecipitate during liver transplantation. It is also associated with a prolonged postoperative stay.
Gastric and Esophageal Varices
Depending on the type of surgery anticipated, a preoperative esophagogastroduodenoscopy may be useful to evaluate the extent of the varices present in a cirrhotic patient’s esophagus and stomach. This especially applies if the patient is to undergo foregut surgery, as this will better delineate the anatomy of interest preoperatively. If the patient has a history of prior upper gastrointestinal bleeding, it is prudent to perform endoscopy before surgery if not recently done already.
Patients with autoimmune hepatitis on daily steroids should receive stress-dosed steroids before surgery. D-penicillamide can impair wound healing; patients taking it for Wilson disease should decrease their dose for 1–2 weeks pre and postoperatively. Wilson disease might predispose to an increased risk of neurologic changes postoperatively. In addition, it is worth noting that patients with a history of alcohol abuse are at increased risk of other complications, including poor wound healing, bleeding, delirium, and infections. Patients who have continued to actively drink are at risk for withdrawal.
The type of surgery is potentially an important determinant of postoperative hepatic dysfunction. Because of traction on abdominal viscera, intraabdominal operations are more likely than extraabdominal surgeries to cause reflex systemic hypotension and to subsequently reduce hepatic blood flow. Surgeries that result in a large amount of blood loss increase the risk for ischemic hepatic injury. Sufficient surgical hemostasis and autologous platelet-rich plasma have been demonstrated to be useful for prevention of massive hemorrhage.
Patients undergoing emergency surgery are at substantial risk for liver dysfunction. The more urgent the surgery, the less opportunity that is available to correct reversible factors, such as electrolyte abnormalities, coagulopathy, and clinical manifestations of portal hypertension (e.g. ascites, hepatic encephalopathy).
Factors Associated with Perioperative Mortality and Morbidity
Higher American Society of Anesthesiologists (ASA) physical status
Higher Child-Pugh class dysfunction
Coexisting respiratory disease
Higher surgical score
Emergent vs Elective Surgery
Numerous studies have shown increased mortality in cirrhotic patients undergoing emergent surgery. Franzetta and colleagues concluded that the emergency nature of the procedure, in combination with Child class, was a significant factor in predicting perioperative mortality. Friedman proposed the following list of contraindications to elective surgery in patients with liver disease:
Acute viral hepatitis
Acute alcoholic hepatitis
Fulminant hepatic failure
Severe chronic hepatitis
Child class C cirrhosis
Severe coagulopathy (prolongation of the PT of >3s despite vitamin K administration; platelet count < 50,000/mm3)
Severe extrahepatic complications (hypoxemia, cardiomyopathy, heart failure, acute renal failure)
Patients with advanced liver disease are much more likely to suffer from hepatic decompensation due to anesthesia and surgery. Administration of anesthesia reduces blood flow to the liver during all surgical procedures. In patients with normal liver function, the reduction in blood flow can result in asymptomatic elevation in the results of serum liver biochemical tests postoperatively; in patients with compromised liver function preoperatively, hepatic decompensation can occur intra and postoperatively, leading to morbidity and mortality. Because liver disease is common and patients with liver disease are frequently asymptomatic, the preoperative assessment of all patients undergoing surgery must include a careful history and physical examination to uncover risk factors for and evidence of liver dysfunction. If liver disease is present, elective surgery should be deferred until the patient has been evaluated or recovered.
Most surgical procedures, whether performed under general or conduction (spinal or epidural) anesthesia, are followed by minor elevations in the results of serum liver biochemical tests. Minor postoperative elevations of serum aminotransferase, alkaline phosphatase, or bilirubin levels in patients without underlying cirrhosis are not clinically significant. However, in patients with underlying liver disease, and especially those with compromised hepatic synthetic function, surgery can precipitate frank hepatic decompensation.
Not only chronic liver impairment but also acute hepatitis increases the susceptibility for ischemia following hypoperfusio, perhaps because of the hypermetabolic state. Interaction of the different anesthetic agents with microcirculatory mediators responsible for the ‘hepartic arterial buffer response’ might partly explain the varying hepatotoxic effects of volatile anesthetics and the subsequent perioperative liver insults. General anesthesia aggravates the already dysfunctional cardiovascular status present in many patients with chronic liver disease, further reducing the hepatic blood flow, especially that of the hepatic artery.
It is commonly accepted that all volatile anesthetics have the potential to impair liver function.
Halothane is the most likely of the clinically used vapors to produce, or exacerbate, hepatic hypoxia when blood flow to the liver is critically limited and the adequacy of the oxygen supply-to-demand balance is in question. Halothane is associated with a risk for autoimmune hepatitis following exposure, with a reported incidence of about 1:6000–1:35000. A mild hepatic reaction is characterized bymoderately increased liver enzymes, transient jaundice and a low mortality. Fulminant halothane-associatedhepatitis, however, is associated with repeated exposure to halothane and the development of severe liver failure with high mortality. Specific circulating IgG antibodies were found in patients with fulminant hepatic failure after halothane exposure and these antibodies were shown to react with cell surface antigens of hepatocytes making them more susceptible to antibody dependent cell-mediated toxicity. In addition, a genetic susceptibility factor has been proposed, which would predispose certain patients to halothane hepatitis and thus makes an individual prediction about the safety of halothane very difficult.
Isoflurane, an isomer of enflurane, undergoes only a minimal biotransformation of 0.2% and preserves hepatic blood flow and oxygen delivery even during open laparotomy.
Sevoflurane anesthesia usually preserves blood flow and oxygen delivery to the liver, even in the presence of positive- pressure ventilation. Patients having elective operations under sevoflurane anesthesia (1 or 2 MAC) experience significant reductions in mean arterial blood pressure, but maintain the hepatic blood flow at preanesthetic levels. Animal data suggest that the hepatic arterial buffer response remains intact. Sevoflurane appears to be the most effective of the inhaled anesthetics for maintaining both blood flow and oxygen delivery to the liver. Thus, it is less likely in theory than either halothane or enflurane to induce liver injury and is no more toxic than desflurane or isoflurane. Its metabolic products are less reactive, and therefore probably less injurious.
Other than sevoflurane, desflurane is the least likely of the halogenated vapors to cause severe hepatic injury, based on the immune theory of anesthesia-induced hepatitis. Nonetheless, desflurane produces a greater reduction of hepatic blood flow and oxygen delivery than either isoflurane or sevoflurane. Hence, it may be more likely than the latter agents to cause liver injury in the setting of marginal hepatic oxygenation.
The extent of biotransformation with regard to the volatile anesthetics is given in the Table 9.3.
Other anesthetic drugs and hepatic function
Nitrous oxide (N2O) produces a mild increase in sympathetic nervous system tone. Consequently, one would expect mild vasoconstriction of the splanchnic vasculature, leading to a decrease in portal blood flow, and mild vasoconstriction of the hepatic arterial system. In addition, N2O is a known inhibitor of the enzyme methionine synthase, which could potentially produce toxic hepatic effects. Even brief exposures to N2O at concentrations used clinically are sufficient to produce time-related decreases in methionine synthase activity in the livers of animals and humans, and prolonged exposure will induce a functional vitamin B12 deficiency. Whether the resultant abnormalities in folate and methionine metabolism actually injure the liver is unclear. There is no convincing evidence that nitrous oxide per se causes hepatotoxicity in the absence of a precarious oxygen supply-demand ratio in the liver.
Nonopioid Sedative-hypnotic Agents
Based on limited clinical and experimental data, intravenous anesthetics have only a modest impact on hepatic blood flow and no significant adverse influence on postoperative liver function when arterial blood pressure is adequately maintained. Because it is a sympathomimetic agent, ketamine may produce a moderate increase in serum concentrations of some liver enzymes. Other intravenous agents, such as propofol, etomidate, and midazolam, have not been shown to alter hepatic function significantly in patients undergoing minor operative procedures. Although very large doses of thiopental (>750 mg) may cause hepatic dysfunction, usual induction doses have little effect on the liver.
Elimination of benzodiazepines that undergo glucur- onidation (e.g. oxazepam, lorazepam) is unaffected by liver disease, whereas the elimination of those that do not undergo glucuronidation (e.g. diazepam, chlordiazepoxide) is prolonged in liver disease.
Opioids have little effect on hepatic function, provided they do not impair hepatic blood flow and oxygen supply. All opioids increase tone of the common bile duct and the sphincter of Oddi, as well as the frequency of phasic contractions, leading to increases in biliary tract pressure and biliary spasm. The effect on the sphincter of Oddi does not favor one opioid over another and is not considered an absolute contraindication to narcotic analgesia, even in cases of pancreatitis. Small doses of an appropriate opioid have an important role in the management of most cases, as they can reduce the need for volatile anesthetics (particularly helpful if there are cardiovascular or hypovolemic problems) and also cause slowing of cardiac rate via vagal stimulation. Large doses of long acting opioids are best avoided because of the limited metabolism and elimination due to liver disease.
With regard to succinylcholine, there is theoretical speculation that this drug could have a prolonged duration in liver disease because of deficiencies of plasma cholinesterase in patients with hepatic disease. But clinically it is not seen to be significant. If duration of succinlycholine single-dose is prolonged from 8 to 14 minutes, it is rare that this will present a problem of overwhelming magnitude.
The volume of distribution of nondepolarizing muscle relaxants is increased in patients with liver disease,
and therefore larger doses may be required to achieve adequate neuromuscular blockade. Atracurium and cisatracurium are metabolized independent of the liver and are therefore preferred in patients with liver disease. Vecuronium seems an ideal drug for longer procedures. Except for some problems in dose requirements due to volume of distribution changes, these drugs have been determined to possess fairly normal kinetics in liver- disease patients. Pancuronium is best avoided as it is long-acting and therefore, it can precipitate residual neuromuscular blockade. Further, pancuronium can amplify the preinduction tachycardia due to a variety of reasons (hyperdynamic circulation, fever, pain, blood loss, etc).
These patients seem to respond to neostigmine in an appropriate fashion. Glycopyrrolate is preferable to atropine as a muscarinic receptor blocker because it does not cross the blood-brain barrier.
Both general and regional anesthesia cause reversible sympathectomy with peripheral vasodilatation and exacerbation of hypotension. These adverse changes may be reversed and hepatic blood flow may be maintained with the administration of vasopressor drugs (e.g. dopamine or ephedrine) to restore splanchnic blood flow or fluid administration to maintain normal arterial blood pressure. No significant difference in liver function and hepatic perfusion was seen between general anesthesia using isoflurane and spinal anesthesia, provided the mean arterial pressure was maintained within normal limits. However, because of the increased risk for spinal hematoma in patients with liver dysfunction and the better titration of volatile anesthetics, isoflurane, sevoflurane or desflurane might be the more appropriate agents for anesthesia in patients with preexisting liver impairment. Due to the altered biotransformation local anesthetic doses should be carefully titrated. (Average half-life of lignocaine in liver dysfunction may be as high as 5 hours compared to 1.5 hours in normal state.)
Patients with chronic liver disease have a reduced functional reserve capacity and are at greater risk of ischemia and hypoperfusion, and therefore require tighter control of arterial blood pressure. However, macrohemodynamic variables, such as mean arterial pressure and systemic vascular resistance, do not necessarily reflect nutritional organ blood supply, and oxygenation as well as microcirculatory blood flow cannot be reliably predicted from those variables. Euvolemia should be targeted by fluid replacement, as the low central venous pressure (CVP) exposes the patient to the risk of inadequate organ perfusion and reduces the volume reserve for meeting hemorrhagic challenges. The use of norepinephrine and dobutamine, when required for the maintenance of perfusion pressure may potentially provide benefits.
Elective surgery is contraindicated in patients with CTP class C, high MELD score, ASA class V, acute hepatitis, severe coagulopathy, or severe extrahepatic manifestations of liver disease (e.g. acute renal failure, hypoxia, cardiomyopathy). Postpone elective surgery until acute hepatitis resolves.
Avoid surgery if possible in patients with a MELD score of greater than or equal to 8 or CTP class B unless they have undergone a thorough preoperative evaluation and preparation.
Universal precautions are mandatory given the high incidence of viral disease in this patient population. The ultimate goal of intraoperative management is to minimize perturbations of the hepatic oxygen supply and demand ratio.
There is no difference in clinical outcomes related to the anesthetic technique.
These patients may have a full stomach, even if they have not taken food or fluid for several hours, because of hiatal hernia, massive ascites, and decreased gastric and intestinal motility. Therefore, premedication may include an H -receptor blocker, metoclopramide, as well as sodium citrate.
Choose anesthetic drugs keeping in mind the changes in pharmacokinetics in liver dysfunction as well as the possible deleterious effects of the drug on liver function.
Airway management is dictated by physical evaluation, gastric aspiration risk, and nature of surgery. In general, nasal intubation is avoided in the presence of coagulopathy.
Esophageal and gastric instrumentation should be minimized due to the risk of bleeding.
Correct coagulation defects before inserting invasive vascular lines and taking up for neuraxial techniques.
Hemodynamic monitoring is dependent on the physiologic state of the patient and magnitude of the proposed surgery.
The normal compensatory baroreceptor mechanism and the regulatory systems of cardiovascular homeostasis are impaired.
Intraoperative fluid management can be difficult, as many patients are already functionally hypovolemic and the anesthetics cause hypotension, yet the blood pressure must be kept adequate to perfuse the liver and sympathomimetics are often counterproductive.
Preoperative fasting can lead to hypoglycemia necessitating periodic plasma glucose monitoring and infusion of glucose-containing fluids.
Positive pressure ventilation and positive end-expiratory pressure may cause deleterious effects in hepatic venous pressure, resulting in decreased cardiac output and total hepatic blood flow. Hyperventilation should be avoided because hypocarbia can independently reduce hepatic blood flow.
Measures to avoid hepatorenal syndrome should be instituted and closely monitored.
Coagulopathy and other bleeding disorders should be corrected.
Postoperative monitoring: Admission to the ICU may be appropriate after prolonged surgeries, intraoperative hypotension, excessive blood loss, or cardiac and/or pulmonary surgery.
Enteral nutrition is more conducive to hepatic recovery than parenteral nutrition, and oral intake or tube feedings should be started as soon as possible. Oral feeding also reduces the risk of spontaneous bacterial peritonitis in the postoperative period.
Two postoperative problems that apply particularly to the patient with liver disease are postoperative ascites leak and postoperative jaundice.
Preoperative Approach to a Patient with Known or Suspected Liver Disease
While obtaining the history, inquiry should be made about risk factors and the presence of symptoms attributable to chronic liver disease. The history should include questions about prior episodes of jaundice and their relationship to surgical procedures and the anesthetic techniques used, blood product transfusions, use of alcohol and other recreational drugs, current medications (including herbal preparations), family history of jaundice or liver disease, travel history, and an occupational history (exposure to hepatotoxins). In the review of systems, the patient should be asked about easy bruising, anorexia, weight loss or gain, fatigue, nausea, vomiting, pain with fatty meals, pruritus, abdominal distention, and episodes of gastrointestinal bleeding.
The physical examination of the patient with chronic liver disease is particularly valuable because the patient may appear ill before there is laboratory evidence of hepatic dysfunction. The examination should focus on signs such as scleral icterus, jaundice, ascites, splenomegaly, palmar erythema, gynecomastia, asterixis, testicular atrophy, spider angiomata, petechiae, and ecchymosis. The liver may be enlarged with a tender soft and smooth edge if the patient has hepatitis, or firm and nodular with presence of cirrhosis or malignancy. Patients with chronic hepatitis often have extrahepatic manifestations, including arthritis, skin rashes, and thyroiditis. Acute liver failure has a distinct clinical presentation. Typically, nonspecific symptoms such as nausea and malaise are followed by the rapid onset of jaundice and subsequently altered mental status, which may progress to coma with clinical and radiologic evidence of cerebral edema.
If no suspicion of liver dysfunction arises from a thorough history and physical examination, then laboratory tests for liver function do not need to be routinely obtained because of the low prevalence of disease. If, however, hepatic dysfunction is known or suspected, then the degree of dysfunction should be quantified by applying either the Child-Pugh or Model of End-stage Liver Disease (MELD) scoring system.
Acute hepatitis (viral, alcoholic, ischemic, or drug- related) is associated with increased perioperative risk and mortality. For nonemergent procedures, supportive care allowing an improvement in the overall condition will diminish the perioperative risk. Therefore, in the presence of acute hepatic disease, elective surgery should be postponed. For patients with fulminant hepatic failure, consider liver transplantation.
In case of chronic liver disease, the decision making is usually based on Child-Turcotte-Pugh classification. Patients belonging to class A (as well as noncirrhotic patients) may be taken up for elective surgery. Class C patients may be taken up only for emergency life-saving procedures as the perioperative adverse events are significantly high. Alternatives to surgery may be always considered in such cases. Class B patients require preoperative optimization and close perioperative monitoring. The algorithm for perioperative decision making is given in Figure 9.1.
The preoperative optimization strategies are discussed under the following headings:
a. Correction of coagulopathy
b. Control of ascites
c. Prevention of hepatorenal syndrome
d. Prevention/control of hepatic encephalopathy
e. Correction of acid-base/electrolyte disturbances
a) Correction of Coagulopathy
Subcutaneous administration of vitamin K, 10 mg/d for 1 to 3 days, will correct coagulopathy due to nutritional or bile salt deficiency but not due to hepatic synthetic dysfunction.
A rational approach to the liver-disease patient with excess bleeding and a prolonged PT is to administer 2–6 units (12–15ml/kg) of FFP in a attempt to bring the PT to within 2–3 seconds of control. Continued infusion at 6–12 hours is recommended. If surgery is progressing with ongoing bleeding, FFP requirements may certainly be greater.
If the platelet count is less than 40,000–50,000/mm3, platelet transfusions may be required.
Cryoprecipitate, which contains large quantities of von Willebrand multimers and is rich in fibrinogen, should be considered when hemorrhage cannot be controlled.
A prolonged bleeding time also can be treated with diamino-8-D-arginine vasopressin.
Recombinant factor VIIa has been introduced as an additional option for the treatment of bleeding due to coagulopathy in cirrhotic patients undergoing surgery.
There would appear to be no problem with insertion of an epidural catheter for postoperative pain control if the PT has been corrected to within 2.5-3 seconds of control and the platelet count is > 40,000 /mm3 with normal bleeding times.
b) Control of Ascites
Sodium restriction is the corner-stone of preoperative therapy of ascites.
Diuretic therapy: Spironolactone 100–500 mg.
Paracentesis: It is recommended that sufficient ascites fluid be removed to make the patient comfortable.
Peritoneovenous shunts (i.e. LeVeen, Denver shunts). Complications include sepsis, venous thrombosis, disseminated intravascular coagulation, congestive heart failure, etc.
c) Prevention of Hepatorenal Syndrome
Adequate preoperative evaluation of fluid, electrolyte and renal status so that a rational approach to fluid management during surgery can be planned.
Quantification of urinary output via a bladder catheter and central venous pressure measurements are strongly advised during extensive operative procedures.
Ideally urine output should be maintained in adults at 1ml/kg/hour.
Mannitol may be a helpful diuretic.
Clinician should be alert that cases with preoperative circulatory imbalance, high bilirubin serum levels (>18mg/dl) and ongoing infection (endotoxemia) are more prone to postoperative renal insufficiency.
Close monitoring should extend 24 to 48 hours postoperatively in cases of major surgeries.
d) Prevention/Control of hepatic Encephalopathy
CNS depressants such as benzodiazepines, narcotics and barbiturates can precipitate hepatic encephalopathy. The mechanism apparently is increased CNS susceptibility to these drugs, amplified by other altered drug-handling phenomena seen in liver disease (i.e. decreased biotransformation, decreased albumin- binding, renal failure, etc).
Judicious use of CNS depressant and avoidance of large doses of these drugs are recommended.
Addressing the underlying precipitant through correction of electrolyte abnormalities, treatment of infection, management of gastrointestinal bleeding, and restriction of sedatives may help prevent or decrease encephalopathy.
Hepatic encephalopathy is also often treated by administering lactulose or poorly absorbed antibiotics such as rifaximin.
e) Correction of acid-base/electrolyte disturbances
Correct the metabolic parameters, which can worsen hepatic blood flow or precipitate hepatic encephalopathy.
Fluid Management in Anesthesia for Liver Disease
Fluid management in a patient with liver failure is complicated by several interacting problems. These patients seem to be simultaneously hypervolemic and hypovolemic. Most infused fluid is retained, but renal function deteriorates, along with avid sodium retention and arterial underfilling. Neither sodium retention nor arterial underfilling explains all the clinical findings or leads to consistently successful therapy.
The goals in these patients are to avoid increasing interstitial fluid overload, maintain normal potassium concentration, and maintain intravascular volume. The contents of infused solutions should be initially selected and then adjusted based on periodic determinations of serum electrolyte concentrations. Fluid administration must be carefully titrated to an endpoint such as central venous pressure, pulmonary artery occlusion pressure, and urine output. Intravascular colloid oncotic pressure (COP) should be restored by infusion of 25% albumin when possible. If the patient is acutely hypovolemic, 5% albumin solutions should be preferred to crystalloids, which tend to expand further the already overexpanded ECF volume (i.e. produce more edema and ascites). Intraabdominal pressure should be estimated from urinary bladder pressure, and paracentesis should be performed whenever it increases to greater than 20 to 25 mm Hg. If cardiac failure is present,
treatment must include administration of inotropic drugs and diuretics when filling pressures are increased. Trials of dopamine, norepinephrine, phenylephrine, or vasopressin may be performed in hypotensive patients with low vascular resistance and hypotension to increase renal perfusion pressure and renal blood flow.
Intraoperative maintenance of an acceptable urine output may help decrease the risk of postoperative acute renal failure. When blood replacement is necessary, the stored blood should be administered as slowly as possible to compensate for the decreased clearance of citrate by the cirrhotic liver. Infusion of glucose may be necessary during the perioperative period to prevent hypoglycemia.
Anesthesiologist needs to anticipate the following intraoperative complications:
Electrolyte abnormalities: Hypocalcemia may occur when citrated blood or FFP is transfused.
Elective postoperative mechanical ventilation is preferred in the following situations:
Severe liver disease
Associated cardiac or pulmonary disease
Fluid or electrolyte disturbance
Oxygen saturation <90% with 40% oxygen
If the patient is extubated, continuous monitoring is imperative in the postanesthesia care unit (PACU). Oxygen supplementation should be continued.
Adequate analgesia should be provided using small intermittent doses of opioids, local anesthesia or regional anesthetic techniques.
Maintain urine output > 1-2ml/kg/hr.
Continue mannitol and dopamine, if used intraoperatively.
Fluid and electrolyte management should be taken care of with frequent assessment.
Minimize the use of sedatives or narcotics in the postoperative period.
Commonly encountered postoperative complications include: